%A Philip Tarasi %T An Exploration of the Experiences of LGBTQ International Students: The Case of the University of Pittsburgh %X This doctoral dissertation aimed to explore the unique experiences of a very specific, yet quite diverse segment of the student body population in higher education: International students who also identify as Lesbian, Gay, Bisexual, Transgender, and Queer or Questioning (LGBTQ). The experiences of this subset of the student population have not been extensively examined in scholarly research (Rankin, 2006). Oba and Pope (2013) indicate that these students might confront many difficulties in their academic and personal lives on American campuses as they grapple with factors related to their multiple identities. In light of these findings, this dissertation strove to explore the experiences of these students on one college campus in a city in the United States, the University of Pittsburgh. Sixty-nine students completed a survey which was created specifically for this study. Thirteen of the survey respondents also participated in individual interviews. Results indicated that students? experiences were quite varied whereby some students reported more positive experiences than others. Furthermore, many participants indicated that they were not open about their LGBTQ identities to others on campus. Negative encounters with homophobia and racism were also reported by various participants. Recommendations are presented for higher education professionals regarding implementing services to assist this diverse student population with a myriad of potential difficulties in their new surroundings. %D 2016 %K LGBTQ International Students in Higher Education %I University of Pittsburgh %L pittir30632 %A Stephanie M. Romero %T THE AWAKENED HEART OF THE MINDFUL TEACHER: A CONTEMPLATIVE EXPLORATION %X This dissertation is a contemplative narration of my lived experience of bringing mindfulness into my teaching. The dissertation first portrays the process of entering into the dialogic space of mindfulness as a Buddhist concept intersecting with the scientific, educational, and public domains. I then describe the contemplative reflection process I used to explore my incorporation of mindfulness into my teaching praxis. From this, I wrote contemplative reflections during a year and half. In this way, I tried to embody mindfulness in my methodology. I used the same process to contemplate these reflections to deepen my understanding and identify themes. The two main themes I arrived at are an openhearted quality (bodhichitta) and a newfound openness that resulted from bringing mindfulness to my professional spaces. I illustrate these themes through six contemplative narratives that portray my heightened consciousness of how my embodiment of mindfulness has influenced my classroom presence and opened my heart. Each contemplative reflection narrates the quality of open awareness towards my own and others? emotions ? good and bad. Each narrative also includes a reflective aspect that explores the themes that emerged. My contemplative reflections illustrate how mindfulness helped me stay open to both the joy and the pain of teaching. Mindfulness practices also provided me with the social and emotional awareness and tools to confront the highly emotional and sometimes volatile space of public schools. My contemplative reflections depict the lived experience of mindfully working through the positive and negative experiences of daily life in public school. Coming from the place of an open heart makes teaching much more rich and full of joy, but at the same time also makes the painful parts of teaching and working in a public, bureaucratic institution more palpable. However, by using my mindfulness practices to delve into that pain, I felt my connection to others, which brought about compassion and a desire to help. %D 2016 %K Mindfulness in education, contemplative inquiry, meditation, qualitative research, secular mindfulness, interpretive research, classroom teaching, Buddhist inquiry, self-study, social and emotional competency %I University of Pittsburgh %L pittir30543 %A delsaz sultan %T Evaluation of CAD/CAM Generated Ceramic Post & Core %X Objective The purpose of this study was to evaluate the use of CAD/CAM technology as a method to fabricate a single-unit, all-ceramic Post & Core restoration. Materials and Methods Three master dies were fabricated from polymer material (Acadental T Endo TM series RT _AE401_08 ?). The coronal part of the die simulated an ideal core preparation with a 1.5 to 2mm ferrule. The intracanal space of the first die was prepared for a post length of 5mm. The intracanal space for the second die was prepared for a post length of 10mm. Finally, the intracanal space for the third die was prepared to a length of 14mm. Each die was scanned 20 times using the Sirona CEREC AC BlueCam?. A total of sixty e.max? CAD/CAM post and core restorations were milled using Sirona CEREC three compact milling unit?. The restorations were evaluated for precision of fit using 2 methods: 1. The marginal gap was measured for each Post & Core restoration using scanning electron microscopy to determine the accuracy of fit of the core to the die. Measurements were made at three points: mesial, buccal and distal of each sample. The mean marginal gap for the three groups was 38 um. 2. A radiograph was taken of each of the 60 samples to determine the post length. The mean post length for the group that was calibrated for 5mm was 6.3mm. Mean post length for the group that was calibrated for 10mm was 10.0mm. Mean post length for the group that was calibrated for 14mm was 11.0mm. Overall, there was no pattern of relationship between marginal gap and post length among the three groups. Conclusion This study concluded that the focal working length of Sirona CEREC?AC? BlueCam is accurate up to 13.7mm. However, the technology is not able to consistently produce accurate milled post and core restorations beyond 11mm. The mean marginal gap for the three groups was 38 um. Future studies are needed to evaluate the biomechanical properties of ceramic Post & Core restorations. %D 2016 %K Evaluation of CAD/CAM Generated Ceramic Post & Core %I University of Pittsburgh %L pittir30630 %A Andrew Surloff %T INTERVIEWING FOR GREAT TEACHERS: A STUDY OF THE PREPARATION AND PRACTICES OF K-12 SCHOOL PRINCIPALS RESPONSIBLE FOR INTERVIEWING AND HIRING TEACHERS %X The purpose of this study was to survey K-12 school principals from across Southwestern Pennsylvania to investigate the schooling and other forms of preparation that these school principals received with respect to conducting employment interviews for teaching vacancies. Further, this study also sought to examine the practices that these school principals use during these teacher employment interviews to determine if these practices used in the field are aligned with the suggested best practices from the peer-reviewed research on this topic. This study was guided by three research questions. The Tri-State School Study Council housed at the University of Pittsburgh granted the researcher permission to survey their member principals. Each principal received an electronic survey sent from the researcher that was comprised of items that asked principals to register demographic data, and data regarding interview preparation and interview practices. The survey had 27 items and took about ten minutes to complete. One hundred fourteen principals completed the survey with a total response rate of 36%, and a net rate of 32.2% that was usable for analysis and inclusion in this study. Quantitative data was analyzed using descriptive statistics and qualitative data, though minimal, was used to interpret data from open-ended questions. INTERVIEWING FOR GREAT TEACHERS: A STUDY OF THE PREPARATION AND PRACTICES OF K-12 SCHOOL PRINCIPALS RESPONSIBLE FOR INTERVIEWING AND HIRING TEACHERS Andrew L. Surloff, EdD University of Pittsburgh, 2016 v The results of the study indicated that fewer than 20% of the principals had received a formal education (university coursework or professional development) on how to prepare and conduct interviews for teaching vacancies. This lack of preparation may be the reason that these principals reportedly use only a basic set of best practices with great frequency when conducting interviews. Finally, the K-12 principal sample reported that approximately 80% of them are the primary or secondary decision makers with respect to making final hiring decisions regarding teaching vacancies. %D 2016 %K Interviews Principals Teachers %I University of Pittsburgh %L pittir30602 %A Mary Ann Steiner %T Climate Change Education in Informal Settings: Using Boundary Objects to Frame Network Dissemination %X This study of climate change education dissemination takes place in the context of a larger project where institutions in four cities worked together to develop a linked set of informal learning experiences about climate change. Each city developed an organizational network to explore new ways to connect urban audiences with climate change education. The four city-specific networks shared tools, resources, and knowledge with each other. The networks were related in mission and goals, but were structured and functioned differently depending on the city context. This study illustrates how the tools, resources, and knowledge developed in one network were shared with networks in two additional cities. Boundary crossing theory frames the study to describe the role of objects and processes in sharing between networks. Findings suggest that the goals, capacity and composition of networks resulted in a different emphasis in dissemination efforts, in one case to push the approach out to partners for their own work and in the other to pull partners into a more collaborative stance. Learning experiences developed in each city as a result of the dissemination reflected these differences in the city-specific emphasis with the push city diving into messy examples of the approach to make their own examples, and the pull city offering polished experiences to partners in order to build confidence in the climate change messaging. The networks themselves underwent different kinds of growth and change as a result of dissemination. The emphasis on push and use of messy examples resulted in active use of the principles of the approach and the pull emphasis with polished examples resulted in the cultivation of partnerships with the hub and the potential to engage in the educational approach. These findings have implications for boundary object theory as a useful grounding for dissemination designs in the context of networks of informal learning organizations to support a shift in communication approach, particularly?when developing interventions for wicked?socio-scientific issues such as climate change. %D 2016 %K Boundary object, networked learning, climate change education %I University of Pittsburgh %L pittir30584 %A li zhou %T IGNORING MULTILEVEL DATA STRUCTURE IN COMFIRMATORY FACTOR ANALYSIS WITH ORDINAL ITEMS %X This study used the Monte Carlo method to compare multilevel and single-level models in confirmatory factor analysis (CFA) of ordinal items with clustered data. Specifically, model fit indices, estimates of factor loading and standard error were compared among three models, two-level CFA, single-level CFA with adjusted standard error, and single-level CFA with normal standard error. Two different factorial structures were considered, 2 factors at both the within- and between-level (W2B2) and 2 factors at the within-level and 1 factor at the between-level (W2B1). All model fit indices indicated that the two-level CFA model fitted the clustered data well. The model fit of the two-level CFA model was better than that of the single-level CFA model with adjusted standard error, which was better than that of the normal single-level CFA model. Chi-square p value and RMSEA were not as sensitive as CFI and TLI in the small sample size to the misspecification of factorial structure. When factor loadings across levels were the same in the true model, factor loadings estimated from the single-level models were acceptable. The standard error of the within-level factor loading estimated by the normal model was significantly smaller than the complex model, which was smaller than the two-level model, suggesting that standard errors are underestimated when the single-level model is used to estimate the two-level data. The effect of design factors on the relative bias of the factor loading and standard errors between W2B2 model and W2B1 model were similar in most conditions. These results suggest applied researchers consider the interest of the study first when selecting CFA models of clustered data. The single-level CFA with adjusted standard error is preferred when the interest of the study is at the individual level, while multilevel CFA is recommended when the interest is at the cluster level. However, in either case, the recommendation is to compare both models to prevent the spurious clustering effect. If there truly exists a multilevel data structure, standard errors estimated from the two-level CFA model are expected to be significantly larger than adjusted standard errors in the single-level model. %D 2016 %K ignoring multilevel confirmatory factor analysis ordinal items %I University of Pittsburgh %L pittir30609 %A Joshua Williams %T AN EXAMINATION OF THE POTENTIAL OF SECONDARY MATHEMATICS CURRICULUM MATERIALS TO SUPPORT TEACHER AND STUDENT LEARNING OF PROBABIILITY AND STATISTICS %X The Common Core State Standards for Mathematics (CCSSSM) suggest many changes to secondary mathematics education including an increased focus on conceptual understanding and the inclusion of content and processes that are beyond what is currently taught to most high school students. To facilitate these changes, students will need opportunities to engage in tasks that are cognitively demanding in order to develop this conceptual understanding and to engage in such tasks over a breadth of content areas including probability and statistics. However, teachers may have a difficult time facilitating a change from traditional mathematics instruction to instruction that centers around the use of high-level tasks and a focus on conceptual understanding and that include content from the areas of probability and statistics that may go beyond their expertise and experience. Therefore, curriculum materials that promote teacher learning, as well as student learning, may be a critical element in supporting teachers? enactment of the CCSSM. This study examines three secondary mathematics curriculum materials with the intention of determining both the opportunities they provide for students to engage in high-level tasks and the opportunities for teacher learning. Tasks in the written curriculum materials involving probability and statistics as defined by the CCSSM will be examined for evidence of these opportunities. The results of this examination suggest that one of the three secondary mathematics curriculum materials, Core-Plus Mathematics Project (CPMP), contains high-level tasks addressing many of the probability and statistics standards from the CCSSM. A second curriculum, Interactive Mathematics Program, also contains high-level tasks but has far fewer high-level tasks than CPMP. The third curriculum, Glencoe Mathematics (GM), addresses many of the probability and statistics standards from CCSSM but does so with low-level tasks. None of the three curricula provides ample opportunities for teacher learning in the areas of anticipating student thinking and providing transparency of the pedagogical decisions made by the authors when designing the materials. %D 2016 %K Mathematics Education %I University of Pittsburgh %L pittir30592 %A Francis J. Pokrywka %T Pandemic Planning: Are Universities Really Prepared? %X Planning for a pandemic influenza outbreak at a college or university cannot be done in a vacuum. Like any emergency plan, it needs to be a coordinated effort by a dedicated and unselfish group of individuals at the university pulling together a multitude of people and resources focused on a common goal. There is an ongoing struggle among emergency preparedness coordinators at colleges and universities to know when they have done ?enough? in preparing their campus to respond to and recover from a pandemic influenza or some other infectious disease outbreak. Every year new ideas emerge from various governmental, health or emergency response organizations on improved methods to assess the threat of a pandemic and updating response plans. The need to add to or modify existing plans to better ready their institutions of higher learning for such an emergency is ongoing. In this dissertation, an effort was made to survey key individuals from emergency planning groups at colleges and universities in the U.S. to gather information on what is important in their pandemic flu plans and how they are structured. This survey evaluated whether these collective college or university plans are in substantial agreement with current CDC and WHO guidelines for effectively and comprehensively anticipating, preparing for, responding to and recovering from pandemic emergencies at their institution and in the nearby community. The data generated from this research study can provide pandemic flu planners with tools for evaluating when their plans are sufficiently robust to meet a pandemic threat and to minimize the impact on their campus in the face of rising costs, shifting university priorities and increasing demands on their time. %D 2016 %K Pandemic Influenza, Planning Methodology, University Committee Organization, Emergency Preparedness, University Emergency Planning %I University of Pittsburgh %L pittir30457 %A Taylor Mulcahey %T The internet as a tool for feminist development in post-revolutionary Tunisia %X This project analyzes the role of the internet in the development of grassroots feminism in Tunisia following the 2011 revolution that toppled the longstanding regime, and sparked a wave of protest throughout the Middle East and North Africa. Following the collapse of the regime, and its program of state feminism, Tunisian women had the opportunity to develop new forms of grassroots feminism, and they did so using a variety of tools, including the internet. The internet is free, and widely accessible, and it offers new ways of facilitating social movements. It is changing the way that women react to sexism and oppression in their societies, and is therefore becoming a key piece in contemporary feminist development, as was the case in Tunisia. In order to understand how Tunisian women are utilizing this tool, I conducted an in-depth analysis of three online entities, including the blog A Tunisian Girl, the Chaml Collective, and the topless images of Amina Sboui. Through online ethnography and cultural visual analysis, I discovered that there were a number of development methods that these entities held in common. Each source utilized the internet to create transnational feminist connections and promote feminine agency, and through their ability to affect offline spaces, they each challenged the idea that the online social movements are ineffective. I also found that the type of entity is important, as different sources were better suited to achieve specific goals, including the use of images in order to quickly share a message across diverse online platforms, and Chaml?s use of Facebook to facilitate discussions. My research into the specific use of these online entities to aid in the development of a grassroots feminist movement in Tunisia contributes to a growing body of scholarship on the intersection of online and offline spaces, and the role of new technologies in the development and facilitation of social movements, including contemporary feminism. %D 2016 %K Tunisia, Feminism, Cyberfeminism, Internet, Mulcahey %I University of Pittsburgh %L pittir30531 %A Rebecca Glucksman %T Development of the Bamboo Test Kit-in-a-Backpack %X This thesis documents the fabrication and use of the ?Bamboo Test-Kit-in-a-Backpack?. The ?kit? is intended for rapid in-the-field assessment of bamboo material properties. Presently the kit supports full-culm compression, longitudinal shear (?bowtie? test), edge bearing, and culm flexural tests. Additionally, it could be further adapted for pin shear tests and a number of small clear specimen tests. The thesis documents proof of concept and validation testing ensuring that results from the test kit are comparable to those of a standard testing machine. A key objective of this work is to endure that tests and sample preparation are practical and simple to conduct on a remote construction site. One critical issue of test specimen tolerance ? permitted out-of-squareness of specimen ends is also addressed. %D 2016 %K bamboo, field test, standardization, global housing problem, test methods, test kit, end squareness %I University of Pittsburgh %L pittir26696 %A Devin Q. Rutan %T Legacies of the Residential Security Maps: measuring the persistent effects of redlining in Pittsburgh, Pennsylvania %X In the late 1930?s, the Home Owners? Loan Corporation, under the direction of the Federal Home Loan Bank Board, constructed Residential Security Maps that graded the housing markets of over 200 cities according to a variety of criteria, including some based in harsh racial, ethnic, and class prejudice. Explanations for urban development have progressed over the course of the twentieth century to reflect not only changing urban conditions but changing ideology and, simultaneously, have the capacity to create the conditions that they describe. Burgess?s ecological model was influential in the 1930?s and shaped real estate officials? and policy makers? notions of neighborhood quality and risk. Policymakers? approach to measuring risk with Residential Security Maps has generated much debate. Critiques to Jackson?s traditional argument, that the physical maps were used by lenders to redline urban areas, have challenged the feasibility of his theory. Using primary government documents from the National Archives and various publications, I argue that the FHLBB was an influential voice in the development of neighborhood appraisal practices and in the normalization and legitimatization of racialized assessments of lending risk. Also, because of the conceptualization of real estate practices, the development of similar lending maps, and the sensitivity of the HOLC to local influences and conditions, the Residential Security Maps are an appropriate way to assess urban real estate practices in the 1930?s. I ground the discussion of neighborhood risk onto Pittsburgh?s stratified and segregated geography of the 1930?s. I developed a GIS-based framework to assess the impact of neighborhood appraisal practices on the social geography of Pittsburgh. I find that neighborhood appraisal had lasting and persistent impacts on the social geography of Pittsburgh as more positive conditions were concentrated in green and blue areas and more negative conditions were concentrated in red and yellow areas. I discuss the implications of these findings for urban housing, the complicity debate, neighborhood development policy, and the prospects for neighborhood equality. %D 2016 %K Pittsburgh Pennsylvania Residential Security Maps Redlining Mortgage Lending Discrimination Housing GIS HOLC FHLBB FHA Census Racism Development Inequality %I University of Pittsburgh %L pittir30503 %A Eleanor/ET Turi %T Psychosocial comorbidities related to return to work following aneurysmal subarachnoid hemorrhage %X Ability to return to work after stroke has been proven to have positive psychosocial benefits on survivors and caregivers. Even though one-fifth of aSAH survivors suffer from poor psychosocial outcomes, the relationship between such outcomes and ability to work post-stroke is limited in the literature. This project seeks to define the relationship between age, gender, race, marital status, household income, anxiety and depression and ability to return to work 3 and 12 months post aSAH. 121 subjects were included in this retrospective analysis. Anxiety was scored via the State-Trait Anxiety Inventory (STAI) while depression was measured using Becks Depression Inventory-II (BDI-II). Both variables were assessed at 3 and 12 months post-aSAH. Ability to return to work was dichotomized into ability to return or not and was measured at the same time points. The categorical variables - gender, race, and household income - were analyzed using chi-squares or Fisher?s exact test, while continuous variables including age, BDI, State & Trait anxiety scores were analyzed using independent t-tests. Age was significantly associated with failure to return to work 3 and 12 months post-aSAH in both adjusted and unadjusted analysis. High scores of depression, State anxiety, and Trait anxiety 3 and 12 months post-aSAH all had significant or trending associations with failure to return to work 12 months post-aSAH in both adjusted and unadjusted analysis. Female gender had a trending association with failure to return to work 12 months post-stroke. The interactive variables of older age and high State anxiety, older age and high Trait anxiety, and older age and high rates of depression 3 and 12 months post-aSAH also were significantly associated with failure to return to work 12 months post-aSAH. Patients who are older, female, and suffer from poor psychological outcomes such as depression or anxiety are at an increased risk of failing to return to work 1-year post-aSAH. The interactive results of this study give us information about which patients are at risk for poor outcomes and therefore can be streamlined for therapy that targets such psychosocial needs. %D 2016 %K aSAH, return to work, psychosocial %I University of Pittsburgh %L pittir30569 %A Heather Newell %T Beliefs and Practices of Providing Formative Feedback to Teachers: A Study of Principals' Understandings, Experiences, and Purposes %X In Pennsylvania, Act 82 of 2012 introduced the Educator Effectiveness system and its foundational belief that student achievement is the result of teachers? high quality instruction and principals? high quality school leadership. With the heightened expectations of principal and teacher accountability for student achievement, principals positively impact student achievement through the day-to-day work of teachers. Principals intentionally design and communicate formative feedback so that teachers learn and grow. This study explored the current practices and beliefs of principals who provide formative feedback to teachers. Principals and assistant principals were surveyed to gather evidence of their self-reported use of effective formative feedback qualities. They were asked to rank order research-based highly effective formative feedback qualities in order of perceived value in leading to teacher learning. Next, seven principals were interviewed regarding the methods they use to provide formative feedback to teachers. The principals were chosen to be interviewed because they reported similar feedback beliefs and practices as those reported in the literature on formative feedback. This study found that principals and assistant principals value different qualities than the ones they use in their daily feedback practices. Additionally, principals and assistant principals believe that certain feedback qualities have an impact on teachers? practices that are different from those supported in the literature as being effective and are also different from those that they use in their own feedback messages to teachers. Principals who report beliefs that reflect the research on formative feedback are better able to defend and explain their feedback practices. When principals intentionally incorporate highly effective formative feedback qualities in their feedback messages to teachers, they contribute to the professional learning of teachers. They also learn and grow themselves, sustaining a professional learning culture. %D 2016 %K Educator Effectiveness Teacher Professional Development Teacher Learning Principal Learning Principal Formative Feedback %I University of Pittsburgh %L pittir30497 %A Sarah Quesen %T DIFFERENTIAL ITEM FUNCTIONING FOR ACCOMMODATED STUDENTS WITH DISABILITIES: EFFECT OF DIFFERENCES IN PROFICIENCY DISTRIBUTIONS %X When studying differential item functioning (DIF) with students with disabilities (SWD) focal groups typically suffer from small sample size, whereas the reference group population is usually large. This makes it possible for a researcher to select a sample from the reference population to be similar to the focal group on the ability scale. Doing so may improve the accuracy of DIF detection. Using scores from a 60-item multiple choice math assessment administered statewide to eighth graders, this study examined the effect of similar vs. dissimilar proficiency distributions on uniform DIF detection. Results from testing the similar- and different-ability reference groups with a SWD focal group were compared for four models: logistic regression, hierarchical generalized linear model, the Wald-1 IRT-based test, and the Mantel-Haenszel procedure. A DIF-free-then-DIF strategy, using a Wald-2 test to identify DIF-free anchor items, was used with these methods. The rate of DIF detection was examined for both similar and dissimilar distribution groups among all accommodated scores and the most common accommodation subcategories (extended time, frequent breaks, some/all items read aloud) to see if type of accommodation changed the rate of items flagged for DIF. The difference in item difficulty (delta DIF) was used to compare results among models, using the ETS? classification system, which served both as a measure of effect size and allowed for comparisons between models. No items were detected for DIF using the similar distribution reference group, regardless of method. No items were detected for DIF with either reference group when the IRT-based Wald-1 test was used. With the dissimilar reference group, logistic regression had the lowest rate of items flagged for DIF (<5%), Mantel Haenszel flagged 8-15% of items, and hierarchical generalized linear model flagged 23-38% of items for DIF. Forming focal groups by accommodation type did not alter the pattern of DIF detection observed among models. This study found that creating a reference group to be similar in ability to the focal group by purposefully sampling from the reference population might control the rate of erroneous DIF detection for SWD. %D 2016 %K Differential Item Functioning, DIF, Students with Disabilities %I University of Pittsburgh %L pittir35979 %A Yuqiao Zhou %T INACTIVATION OF IRE1? IN OSTERIX-CRE EXPRESSING DENTAL MESENCHYME DISRUPTS DENTIN FORMATION %X Endoplasmic reticulum (ER) stress signaling is a cellular adaptive mechanism that is activated in response to the accumulation of misfolded and/or unfolded proteins in the ER lumen, a cellular stress termed ER stress. Inositol requiring enzyme 1? (IRE1?) is an ER membrane-resident proximal sensor for ER stress. Herein, we aim to determine the biological role of IRE? in regulating dentinogenesis in vivo, by selectively deleting IRE1? in Osterix-expressing cells, including odontoblasts. Isolated molars from IRE1? conditional knockout (Ire1a CKO) mice displayed a significantly (p < 0.05) reduced mRNA expression of genes involved in the ER biogenesis and clearance of mal-folded/misfolded proteins, e.g., endoplasmic reticulum?localized DnaJ 4 (ERdj4), compared with their control littermates. Consequently, IRE1? deficiency leads to heightened ER stress, as evidenced by increased protein expression of ER stress markers, e.g., phosphorylated PKR-like kinase (p-PERK) and phosphorylated eukaryotic initiation factor 2? (p-eIF2?), in IRE1?-deficient odontoblasts, compared with WT odontoblasts shown by Immunohistochemistry staining. Odontoblast deficiency of IRE1? resulted in significantly decreased dentin matrix deposition rate, and consequently reduced dentin thickness and an increased ratio of predentin vs. dentin thickness, as shown by calcein double labeling and H&E staining respectively (p < 0.05). Micro-computed tomography analysis demonstrated a significantly reduced root dentin volume in the IRE1?-deficient molars, compared with control counterparts. Furthermore, it was found that odontoblast deficiency of IRE1? resulted in compromised odontoblastic differentiation and/or function, as reflected by significantly reduced gene and/or protein expression of odontoblast differentiation markers, e.g., dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), and alpha-1 type I collage (COL1), in the odontoblasts of IRE1?-deficient molars, compared with control counterparts. In addition, IRE1?-deficiency in odontoblast leads to a decrease of ?-catenin protein expression in the pulp and odontoblast cell layer of Ire1a CKO mice. Collectively, these data demonstrate that IRE1? is a critical physiological regulator for dentinogenesis. %D 2016 %K Dentinogenesis;Odontoblast;ER stress signaling; IRE1; XBP1 %I University of Pittsburgh %L pittir30505 %A Jamie M Zelazny %T The Effects of Childhood Maltreatment and Genomic Variation in the Hypothalamic-Pituitary-Adrenal (HPA) Axis on Neuropsychological Functioning in Offspring of Depressed Parents %X Childhood maltreatment has been associated with an increased risk for psychiatric disorders and suicide. The primary role of the hypothalamic-adrenal-pituitary (HPA) axis is to maintain homeostasis when challenged with stress. Genomic variation in genes of the HPA axis may play a role in the effects of maltreatment on neuropsychological functioning. The aims of the dissertation study were: (1) to examine the effect of childhood maltreatment on neuropsychological functioning; (2) to examine the effects polymorphisms in genes of the HPA axis (CRH, CRHBP, CRHR1, CRHR2, and NR3C1) with neuropsychological functioning; and (3) to explore gene environment interactions between genes of the HPA axis and exposure to childhood maltreatment on neuropsychological function. This was a secondary data analysis of neuropsychological testing, psychiatric assessments, and genomic data from the Familial Pathways to Early Onset Suicide Attempt Study. A total of 369 subjects were included in Aim 1 and 145 subjects in Aims 2 and 3. Multiple linear regression was used to analyze the effects of maltreatment, genotype, and their interactions on neuropsychological functioning. Physical abuse was associated with poorer performance in the memory domain (p=.006). While no longer significant after controlling for multiple comparisons, results trended trend toward significance (q=.088). Emotional abuse was associated with better scores on measures of verbal fluency (p=.03), but the results were no longer significant after false discovery rate (FDR) correction. Before FDR testing, significant protective effects were detected for two SNPs in the CRHBP gene and one single nucleotide polymorphisms (SNPs) in the CRHR2 gene; and significant risk effects were detected for two SNPs in the CRHR1 gene and one SNP in the NR3C2 gene. However, after FDR corrections, only one result remained significant, a protective effect for CRHBP rs7704995 on the Impulse Control Domain. No significant gene environment interactions were detected. These findings are consistent with the literature showing that exposure to physical abuse is associated with deficits in memory. Further studies are needed with larger sample sizes and all the relevant genes of the HPA axis to determine whether genomic variation in genes of the HPA axis have a direct effect on neuropsychological functioning. %D 2016 %K Child Abuse Genetics Executive Function %I University of Pittsburgh %L pittir30530 %A Madhav Sachar %T NOVEL INSIGHTS INTO PROTOPORPHYRIN IX-INDUCED LIVER INJURY %X Protoporphyrin IX (PPIX) is an endogenous hepatotoxin produced by all the cells as an intermediate in the heme biosynthesis pathway. In normal conditions, PPIX is efficiently converted into heme. However, genetic disease or xenobiotics can disrupt homeostasis in the heme biosynthesis pathway to cause PPIX accumulation. The first part of my thesis research revealed the mechanism by which isoniazid dysregulates the heme biosynthesis pathway. Isoniazid is an anti-tuberculosis drug known to cause liver injury when used with rifampicin. Here, I showed that isoniazid treatment independently induced the accumulation of PPIX in the liver of wild-type mice. Isoniazid dysregulates the heme biosynthesis pathway in the liver in part through the induction of delta-aminolevulinate synthase 1 protein as well as by the downregulation of ferrochelatase protein. Results from this study established the porphyrinogenic properties of isoniazid and explained how isoniazid can potentiate toxicity when administered with rifampicin. In the second part of this thesis, I showed that the ATP-binding cassette sub family G member 2 (ABCG2) is a key facilitator in the PPIX-mediated liver injury. ABCG2 is an ATP dependent transporter present in the liver which excretes PPIX from hepatocytes into the bile. Using genetic and chemical PPIX-mediated liver injury mouse models, I showed that Abcg2 deficiency abolished liver injury. In the genetic mouse model, I showed that the deficiency of Abcg2 in bone marrow cells redistributed PPIX produced by bone marrow into the spleen and decreased PPIX available in the serum to be collected by the liver. Also, Abcg2-deficiency in hepatocytes reduced the excretion of PPIX into the bile duct thus preventing PPIX-induced bile-duct blockage and consequently averting colestatic liver injury. I further showed that accumulated PPIX in the hepatocytes with Abcg2 deficiency was metabolized into detoxified metabolite which was excreted easily into the bile for fecal elimination. This study is important as it provides a novel therapeutic approach for the management of PPIX-mediated liver injury. Collectively, this work has provided greater insights into drug-induced PPIX accumulation and mechanism of PPIX-mediated liver injury. In addition, it is hoped that this work can help to develop strategies for preventing PPIX-mediated liver injury. %D 2016 %K ABCG2, LIVER INJURY, Protoporphyrin IX, Isonaizid, BCRP, Cholestasis %I University of Pittsburgh %L pittir30502 %A Jennifer Zerbato %T ESTABLISHMENT AND REVERSAL OF HIV-1 LATENCY IN PRIMARY CD4+ NAIVE AND CENTRAL MEMORY T CELLS %X Human immunodeficiency virus type 1 (HIV-1) persists as a lifelong infection, due to the establishment of a latent viral reservoir in rCD4+ T cells, representing a major barrier to eradication of HIV-1 infection. Therapeutic approaches to eliminate this latent reservoir have included the ?kick and kill? strategy, which involves the administration of a latency reversing agent (LRA) to ?kick? HIV-1 out of latency and ?kill? the HIV-1-infected cells by cytolytic or viral cytopathic effects. rCD4+ T cells are heterogeneous, consisting of na?ve (TN), stem cell-like memory (TSCM), central memory (TCM), transitional memory (TTM), effector memory (TEM), and terminally differentiated (TTD) cells. Preliminary studies demonstrated that the TCM and TTM cell subsets constitute the major proportion of the latent HIV-1 reservoir in infected individuals on ART, while HIV-1 DNA is consistently lower in TN cells. Consequently, there has been little emphasis on studying HIV-1 latency in TN cells. The primary goal of this thesis was to understand latent HIV-1 infection in TN cells in comparison to TCM cells, through the development of an appropriate in vitro primary cell model of HIV-1 latency in TN and TCM cells, as well as in ex vivo patient-derived cells. Employing the ?kick and kill? approach to TN and TCM cells in our in vitro primary cell model revealed that although TN cells contained significantly less HIV-1 DNA than TCM cells, following reactivation, they produced as much, if not more, virus than TCM cells when normalized for infection frequency. This finding was also observed using ex vivo cells from 4 of 7 donors. Furthermore, we found that similar levels of replication-competent virus were recovered from TN and TCM cells when corrected for infection frequency. These findings suggest that quantifying HIV-1 DNA alone may not be predictive of the size of the inducible latent reservoir in different CD4+ T cell subsets. Furthermore, although TN cells constitute only a fraction of the HIV-1 DNA reservoir, they may contribute significantly to viral rebound following treatment interruption or failure. Thus, a greater attention should be given to the latent viral reservoir in TN cells in HIV-1-infected individuals on ART. %D 2016 %K Naive CD4+ T cells CD4+ T cell subsets HIV-1 latency HIV-1 latency reversal "kick and kill" NNRTIs %I University of Pittsburgh %L pittir30329 %A Nishank Bhalla %T Evasion and Resistance of Host Antiviral Defense pathways by Alphaviruses %X The Alphavirus genus consists of positive-sense single stranded RNA viruses which cause millions of annual infections, and are classified as arthritogenic (Sindbis (SINV) and Chikungunya virus (CHIKV)) or encephalitic (Venezuelan (VEEV) and eastern equine encephalitis viruses (EEEV)) based on disease phenotype. The nature, severity and outcome of disease following infection by a particular alphavirus are primarily dependent on evasion of or resistance to the Interferon-?/? (IFN-?/?) upregulated antiviral state. In mice, induced serum IFN-?/? levels are highest following VEEV infection, lower following SINV infection, and negligible after EEEV or CHIKV infection. SINV or CHIKV cause a self-limiting, non-fatal infection in mice with functional IFN ?/? responses, suggesting limited antagonism of the IFN-?/? response, while infection with EEEV or VEEV is lethal. Whereas EEEV avoids both IFN-?/? and antiviral state induction via suppression of myeloid cell replication and lymphoid tissue dissemination, VEEV infection is associated with extensive systemic replication that occurs despite rapid induction of serum IFN-?/?, suggesting successful replication despite upregulation of antiviral effectors. However, viral determinants of this differential sensitivity of various alphaviruses to IFN-?/? are unknown. In this study I have investigated the relative sensitivity of SINV, CHIKV, EEEV and VEEV to the IFN-?/? induced antiviral state, and found that VEEV is most resistant to the activities of antiviral effectors expressed either collectively or individually. I mapped this activity to the nonstructural protein-expressing region of the genome, and determined that VEEV nonstructural protein 2 (nsP2) induced translation shutoff is critical for the antiviral state resistance of VEEV. I definitively separated virus induced transcription and translation shutoff as independent activities, and identified the viral proteins mediating these activities for multiple alphaviruses. Furthermore, I demonstrated that expression of nsP2 alone is sufficient to block Signal Transducer and Activator of Transcription 1 (STAT1) phosphorylation, and that viral infection induces proteasome-mediated degradation of Janus Kinase 1 (JAK1). Additionally, I demonstrate the role of IRF7 in host antiviral response induction following alphavirus infection. Overall, I have delineated the interactions of multiple alphaviruses with host antiviral mechanisms, and illustrated the different strategies that closely related alphaviruses can use to successfully overcome the IFN-?/? response. %D 2016 %K Alphaviruses, Interferon, Translation shutoff, Transcription shutoff, Nonstructural protein 2 %I University of Pittsburgh %L pittir29757 %A Avraham Bayer %T Pathways deployed by human placental trophoblasts to confer viral resistance %X During pregnancy, the placenta plays a vital role in protecting the developing fetus from microbial infections. The multinucleated and terminally differentiated syncytiotrophoblasts actively coordinate host defense through a multitude of mechanisms. In addition to forming a cellular barrier, the syncytiotrophoblasts release extracellular vesicles containing microRNAs from the chromosome 19 microRNA cluster (C19MC). These vesicle-packaged miRNAs, upon uptake by recipient cells, induce autophagy and limit viral infection, acting against a diverse panel of both DNA and RNA viruses. We have shown that medium conditioned by primary human trophoblast (PHT) cells, which contain these vesicles, confers resistance from pathogens associated with congenital infections to recipient non-placental cells. Furthermore, we have demonstrated that primary human trophoblasts constitutively produce interferon lambda 1 (IFN?1), leading to a robust induction of interferon stimulated genes in an autocrine and paracrine manner. These parallel pathways, actively coordinated by PHT cells, contribute to the barrier function of the placenta, protecting the developing fetus from viral infections. %D 2016 %K Placenta, Trophoblast, C19MC, miRNAs, IFN lambda %I University of Pittsburgh %L pittir30296 %A Wen-Chi Wang %T social support and parental stress among parents of young children with autism spectrum disorder: an international comparison of United States and China %X Parents of young children with autism spectrum disorder (ASD) are more likely to experience high parental stress compared to other parents, and social support has been identified in previous research as an effective buffer against stress. However, limited research has evaluated the associations between different types of social support and stress in parents of young children with ASD, the possible impact of cultural background on parents? stress levels, and their use and experience of social support. The goal of this study was to examine the association between perceived, received, informal, and formal social support and parental stress level among U.S. and Chinese parents of young children (ages 0-6) suspected or diagnosed with ASD. Results showed that a high percentage of parents in both samples experienced high levels of parental stress: 81% in the U.S. sample and 96% in the Chinese sample. U.S. parents? (n = 64, mean age = 35 years) stress levels decreased as their perceived support increased. However, none of the four types of social support, individually or combined, were significantly associated with parental stress among Chinese parents (n = 45, mean age = 32 years). The results implied that ASD programs in the United States and China need to include parental stress as one of the foci of intervention. Additionally, due to the growing foreign and immigrant populations in the United States, ASD programs need to have a service delivery model that can accommodate to the needs of families with diverse cultural backgrounds. %D 2016 %K autism spectrum disorder, early intervention, parent support, parental stress, Chinese parents, U.S. parents %I University of Pittsburgh %L pittir30475 %A John Walters %T TReg, CD4 Tem, and CD8 Temra fail to predict acute cellular rejection in living-donor renal allograft recipients %X Since it was pioneered successfully, renal transplantation remains the only option for patients with stage-5 chronic, severe, and end-stage renal disease for whom dialysis treatment complications preclude its continued use. Currently, and historically, the supply of suitable living-donor allografts is far less than their clinical need, and this gap cannot be offset by transplanting available cadaveric kidneys. Immuno-suppressive and -induction therapies have been used to impair the recipients? immune response against the allograft. Without such therapies many recipients? immune systems would reject the organ, causing the patient to again experience renal failure. It is therefore incumbent upon the public health community to ascertain the most effective treatment modality for transplanted organs to ensure that these limited resources are utilized in the most efficient manner possible. Thymoglobulin and Basiliximab induction therapies are two induction treatments available clinically for kidney transplantation. Within this study, patients undergoing treatment using either of these induction-agents had their circulating T cell phenotypes analyzed and compared. The goal of this study was to produce a statistical model, based on Generalized Estimating Equation methodology, that would predict episodes of acute cellular rejection (ACR) between the day of the transplant and up to one year after transplantation. The selection of potential covariates was based upon previously identified T cell markers. Due to small sample size, missing data, and both left- and right-truncation of the data, the model was not able discriminate between patients that underwent ACR from those that did not based upon the a priori markers of interest. However, the analysis did identify different memory T cell proportions that may be predictive of ACR in patients treated with Thymoglobulin or Basiliximab and warrants further study. The public health impact of a predictive model would be to increase the quality and duration of life in individual patients and reduce the burden of End Stage Renal Disease (ESRD) within the US population as a whole. %D 2016 %K Renal Kidney Transplant Thymoglobulin Basiliximab GEE Generalized Estimating Equations Acute Cellular Rejection ACR %I University of Pittsburgh %L pittir28692 %A Sarah Zelazny %T "It's All in the How": adolescent and young adult women's recommendations for establishing comfort within family planning providers' communication about and assessment for intimate partner violence %X Context and Public Health Importance: Intimate partner violence (IPV) is a serious public health problem that disproportionately affects adolescent women seeking family planning services compared to general population estimates. Current clinical guidelines recommend routine assessment to identify and respond to IPV to prevent and attend to the negative health outcomes that are caused by violence victimization. There are gaps in the literature on how providers should communicate with their patients about sensitive issues like IPV and how to establish comfort for their patients. Methods: Clinic staff at 5 western Pennsylvania family planning clinics received communication skill-based and knowledge-based training as part of an exploratory study of lPV assessment. We audio recorded clinic encounters for participating providers and patients. We interviewed patient participants about their experiences with the providers' IPV assessment and they reflected on their audio-recorded clinic encounters. Results: The mean age for the 44 participants was 22.8 years old. Participants named "comfort" as a main component for discussing and disclosing IPV in the clinical setting. The sub-themes associated with how to create patient comfort include: Build the patient-provider relationship, Provider should communicate like a friend/be on the patient level, Patient needs to feel cared for by provider, and Appropriate timing and space. Conclusion: Methods for establishing patient comfort via communication should be incorporated into and examined within sensitive healthcare areas such as IPV and can be extended to HIV, palliative, and oncological care to improve patient health outcomes. Further research on the subthemes of comfort and how they differ in patient populations and settings should be conducted. %D 2016 %K intimate partner violence, adolescent and young adult health, patient-provider communication, clinical communication %I University of Pittsburgh %L pittir30386 %A Kali Stull %T Vectors of risk, bodies that breathe %X Fogging pyrethroid-based pesticides is a routine component of vector management strategies in Jakarta, Indonesia with the aim to kill the Aedes aegypti mosquito and reduce Dengue infections. As more mosquitoes become resistant to pesticide, fogging is an ineffective technology to reduce mosquito populations. This thesis tells a historical epidemiological multi-species narrative about Dengue in a megacity. Power and agency are noticed as dynamic forces that shape the illness experience and the choice to continue fogging. The thesis brings forth questions: ?how do mosquitoes, viruses, and humans co-create one another?, how do power differentials shape public health intervention decisions?, how do nonhumans and technology act in ways that are disparate from humans intelligence and intention?, and how might affirming the inseparability of nature and culture resign humans to live together with mosquitoes in a way that reduces harmful viral mixing? Public Health statement: By discussing mosquitoes?, virus?, and residents? response to fogging and tracking the ways pyrethroid risks are made invisible, the author suggests that fogging itself is a risk. As 60% of infectious diseases that affect humans spend part of their life course in a nonhuman animal, this considered approach toward the vector?s ability to make meaning and exercise agency inspires illuminating questions about zoonotic diseases. %D 2016 %K new materialism, Dengue, Jakarta, mosquito, Aedes aegypti, pesticide, intra-action, natureculture, risks, affect %I University of Pittsburgh %L pittir30372 %A Kanyin Ong %T Application of grocery purchase data to understanding patterns of Salmonella enteritidis illnesses in the United States, 2004-2006 %X Introduction: Salmonellosis, caused by infection with Salmonella species, is a significant public health problem, both in the disease burden and economic costs. Over 1 million illnesses every year are due to Salmonella infections. Salmonella enteritidis accounts for approximately 20% of reported illnesses. It has been estimated that approximately 90% of illnesses are acquired from exposure to contaminated foods in the home. This is a study to determine the association between household-reported grocery purchases and Salmonella enteritidis. Methods: This is a retrospective, ecological, cross-sectional study that analyzed Homescan market as unique geographic areas. Food data comes from Homescan, and illness data comes from National Salmonella Surveillance System (NSSS). Food data was standardized and a per-capita annual Purchase-Weight was calculated for each Food Category. A risk score for each Homescan market was calculated which identifies the average relative risk of foods reported by households in the Homescan market. A negative binomial model was applied to the Homescan market risk score as the independent variable and the incidence rate of Salmonella enteritidis illnesses as the dependent variable with the size of each Homescan market population included as an offset. Results: From 2004 to 2006 there were 12,589 cases of Salmonella enteritidis reported in the United States. The Homescan market incidence rate varied from <1 to 7 cases per 100,000 persons. In the same time period, 21,124 households reported 19,152,019 food observations which were grouped into 1 of 62 Food Categories. The population-weighted risk score varied between Homescan markets from 1.47 (San Diego) to 2.36 (Birmingham). There was no association between rates of salmonellosis and relative high-risk food exposure in Homescan market areas. Discussion: This is the first attempt to utilize grocery purchases as a proxy for food exposure and sporadic salmonellosis. Differences in relative amounts of high-risk food exposure were found at a population-level, demonstrating variation in food exposure throughout the United States. While there was no association with rates of salmonellosis, this may have been because there was not sufficient heterogeneity between the geographic units due to their size. As a result, a replication of this approach among smaller geographic units should be considered. %D 2016 %K foodborne disease, ecologic study, grocery, salmonellosis, salmonella, enteritidis %I University of Pittsburgh %L pittir30395 %A Matthew J. Kesterke %T The Effects of In-utero Thyroxine Exposure On Mandibular Shape in Mice %X An estimated 3% of U.S. pregnancies are affected by maternal thyroid dysfunction, with between one and three of every 1,000 pregnancies being complicated by overactive maternal thyroid levels. Overactive maternal thyroid hormones have been linked to neurological impairment and craniofacial development dysmorphogenesis, affecting both endochondral and intramembranous bone. Using both Euclidean Distance Matrix Analysis (EDMA) and geometric morphometric approach, this study evaluates the role of in utero thyroxine overexposure on the growth of offspring mandibles in a sample of 241 mice. Principle component analysis (PCA) and canonical variate analysis (CVA) utilized 16 unilateral mandibular landmarks obtained from 3D microCT to assess shape changes between unexposed controls (n=63) and exposed mice (n=178). By evaluating shape changes in the mandible between different age groups (15, 20, and 25 days postnatal) and different dosage levels (low, medium, and high), this study found that maternal thyroxine alters offspring mandibular shape in both age- and dosage-dependent manners, particularly within the high dosage individuals in the oldest age group. The EDMA results demonstrate marked shape changes throughout the mandible, with the gonial angle and alveolus undergoing significant (p <0.10) changes. Geometric morphometric analysis revealed that group differences in overall shape were significant (p <0.001 for both PCA and CVA) and showed major changes in regions of the mandible associated with muscle attachment (coronoid process, gonial angle) and regions of growth largely governed by articulation with the cranial base (condyle) and occlusion (alveolus). These results compliment recent studies demonstrating that maternal thyroxine levels can alter the cranial base and cranial vault of offspring, contributing to a better understanding of both normal and abnormal mandibular development and facilitating a fuller understanding of evolutionary and medical implications of craniofacial growth and development. %D 2016 %K Craniofacial Growth and Development, Maternal Environment, Mandible, Thyroxine, Bone Growth %I University of Pittsburgh %L pittir30345 %A Meghan Mattos %T MILD COGNITIVE IMPAIRMENT IN OLDER, RURAL-DWELLING ADULTS %X Introduction: Rural-dwelling adults are particularly vulnerable to cognitive problems given known higher rates of associated risk factors and limited resources and access to care. Early cognitive changes remain understudied in this population. Objective: To determine if and how rural residence is a unique risk factor for delayed detection of early-stage cognitive impairment. Methods: Studies 1 and 2 involved secondary data analyses of the National Alzheimer?s Coordinating Center Uniform Data Set and compared older rural- and urban-dwelling adults on key characteristics and cognitive symptom severity. Study 1 used a cross-sectional design to examine sociodemographic factors, comorbid conditions and cognitive symptom severity between groups. Study 2 used the same variables from Study 1, to examine possible differences in results using two geographic classification schemes. Studies 3 and 4 used qualitative methods including semi-structured, in-home interviews with participants with early cognitive changes and care partners. Study 3 explored perceived determinants of health in these rural-dwelling dyads using thematic content analysis. Study 4 described their subjective experiences at three time periods around a specialty research center visit. Results: Study 1. Rural and urban groups differed significantly in mean (?SD) years since onset of cognitive symptoms (2.98?1.91 in rural and 3.89?2.70 in urban adults, t[260]= -2.23, P = .03), but they did not differ across sociodemographic features, comorbid conditions, or cognitive symptom severity. Study 2. Results varied both in magnitude and direction of odds ratio differences between two geographic classification schemes for outcome variables. Study 3. Six themes emerged about perceived determinants of health: 1) Staying active, 2) Eating well, 3) Living with cognitive changes, 4) Living rural, 5) Connecting with neighbors and community, and 6) Relying on children. Study 4. Dyad experiences varied across the three time periods. Dyads sought to learn more about cognitive symptoms and described the impact of cognitive changes on everyday life. Conclusions: There were no significant differences in cognitive symptom severity between rural- and urban-dwelling participants. Qualitative findings highlight critical aspects of rural adults? perceived determinants of health and reactions to cognitive symptoms and diagnosis, which may be used to help target earlier diagnosis and improve long-term disease management. %D 2016 %K Alzheimer's disease, health disparities, Mild Cognitive Impairment, qualitative methods, rural health %I University of Pittsburgh %L pittir30103 %A Lea Martin %T CONTRASTING TOP-DOWN AND BOTTOM-UP RETRIEVAL METHODS FOR ASSESSING AUTOBIOGRAPHICAL MEMORY %X Autobiographical memory (AM) is a unique type of memory for storing personally relevant information. AM specificity has been linked to a variety of psychological functions and mental health outcomes. Researchers have relied on two approaches to measure AM specificity: generative retrieval, wherein individuals are cued to initiate a top-down search for a memory, and direct retrieval, wherein a highly specific cue induces bottom-up activation of a memory. AM has almost always been assessed via generative retrieval measures, which fail to fully measure AM access as they exclude instances of bottom-up AM retrieval. Consequently, generative retrieval measures may confound AM specificity with executive functioning because generative retrieval engages working memory to a greater extent than direct retrieval. This study compared direct retrieval (odor-elicited) and generative retrieval (sentence-completion) measures of AM access and contrasted working memory?s association with both types of retrieval in 87 community-dwelling adult smokers. Analyses revealed no correlation between generative and direct retrieval measures. In addition, neither type of retrieval was significantly associated with working memory capacity. Concerns about measurement validity for the study sample limited the conclusions that could be drawn from the data, but highlighted the need for increased prudence when selecting memory measures. Future work using a broad and multimodal approach to AM assessment should continue to investigate the relationship between top-down and bottom-up approaches to measuring AM access, as this holds promise for understanding AM structure and its relation to a host of psychologically meaningful constructs. %D 2016 %K autobiographical memory, odor, working memory %I University of Pittsburgh %L pittir29979 %A Bethany Nugent %T Cognitive and Occupational Function in Survivors of Adolescent Cancer %X The number of cancer survivors living in the U.S. is dramatically increasing. Cognitive decline is a commonly reported and burdensome symptom of cancer survivors. In addition, many cancer survivors experience difficulty maintaining employment. This dissertation addresses gaps in the literature of cognitive and occupational function of cancer survivors, with particular emphasis on the understudied population of cancer survivors diagnosed as an adolescent or young adult (AYA). For this dissertation, a series of studies were conducted to 1) explore the association between occupation and symptom burden in breast cancer survivors, 2) synthesize the evidence of cognitive outcomes in survivors of AYA cancer, and 3) describe cognitive and occupational function in survivors of adolescent cancer compared to healthy controls. To address aim one, a secondary analysis of data from early-stage breast cancer survivors explored the relationship between occupation and symptom burden. Breast cancer survivors employed in lower skill level jobs reported greater symptom burden over the first year of anastrozole treatment than women employed at the higher skill level. Survivors employed at lower skill levels had higher levels of fatigue and worse depressive, musculoskeletal, vasomotor, and gastrointestinal symptoms. To address aim two, an integrative review synthesized the current state of science in terms of cognitive outcomes of those diagnosed with cancer as an AYA. Survivors of AYA cancer tended to experience cognitive difficulties; however, to date, no study has focused exclusively on those diagnosed as an AYA or encompassed the entirety of the AYA age range. Future studies are needed because cognitive outcomes of survivors of AYA cancer have been largely neglected. Lastly, a cross-sectional, descriptive comparative study described cognitive and occupational function in survivors of adolescent cancer compared to healthy controls. Survivors of adolescent cancer perceived greater cognitive difficulty than healthy peers, although there were not significant measurable differences in performance on neuropsychological tests. Survivors of adolescent cancer also reported poorer work output than healthy controls. This dissertation contributes to the growing body of literature pertaining to health and well-being of cancer survivors, in particular cognitive and occupational function, and unique considerations needed for those diagnosed with cancer as an AYA. %D 2016 %K cancer survivorship; adolescent and young adult; neuropsychological function; cognitive function; occupational function %I University of Pittsburgh %L pittir29722 %A Claire Syler %T Actor Coaching: Talking Performance into Being %X What does it mean to coach actor(s) on a monologue or scene? Directors and teachers of acting have long referred to the practice of ?actor coaching,? yet, despite an omnipresence in the field, there is virtually no theorization of the activity. So, how do coaches use language, dramatic text, and embodiment to communicate knowledge and develop performance? This study forges an interdisciplinary framework that uses theatre and performance studies scholarship and Vygotskian-based sociocultural learning theory, a subfield of the learning sciences, to examine the multimodal talk of a seasoned acting instructor over the course of a university-level acting class. Employing ethnographic methods, data drew from observations, written fieldnotes, analytical memos, interviews with the participants, and roughly twenty-five hours of digital video footage, which formed the chief data set. To examine the video corpus, and to locate the instructor?s coaching register, the study relied on interaction analysis, sociolinguistic methods of register analysis, and prior research on the language of sports coaching. Analyzing the instructor?s talk, as it emerged over time and interactivity, revealed four gross registers of actor coaching, which were enacted in varying participatory frames and coalesced to create implicit participatory norms. In turn, these norms served to reduce the asymmetrical power dynamics inherent in actor coaching and teaching, reify the constitutive ?rules? of realistic performance, and cultivate dialogic interactions that required a partial perspective taking from the coach, character, and/or student standpoint. Linguistic analysis of the coaching register yielded a repertoire of discursive moves (questions of knowing, eventcasts, telegraphic utterances) the instructor contingently issued to challenge and develop performance, as well as maintain student motivation. Functionally, actor coaching demanded the student reside within a space of public attention, communicational interplay, affect, metacognition, performance, and revision. The study concludes by theorizing actor coaching as situated in cultural-historical settings that privilege particular performance traditions and texts, dialogically dependent upon communicative interaction and co-perspective taking, and guided by a coach?s scaffolded language use. As a theory-building project, the study suggests that actor coaching is a significant disciplinary resource for theatre studies and worthy of future analysis. %D 2016 %K theatre, pedagogy, actor coaching, sociolinguistics %I University of Pittsburgh %L pittir27980 %A Xiaodan Zhou %T Analysis and PDE on metric measure spaces: Sobolev functions and Viscosity solutions %X We study analysis and partial differential equations on metric measure spaces by investigating the property of Sobolev functions or Sobolev mappings and studying the viscosity solutions to some partial differential equations. This manuscript consists of two parts. The first part is focused on the theory of Sobolev spaces on metric measure spaces. We investigate the continuity of Sobolev functions in the critical case in some general metric spaces including compact connected one-dimensional spaces and fractals. We also constructe a large class of pathological $n$-dimensional spheres in $\mathbb{R}^{n+1}$ by showing that for any Cantor set $C\subset\mathbb{R}^{n+1}$ there is a topological embedding $f:\mathbb{S}^n\to\mathbb{R}^{n+1}$ of the Sobolev class $W^{1,n}$ whose image contains the Cantor set $C$. The second part is focused on the theory of viscosity solutions for nonlinear partial differential equations in metric spaces, including the Heisenberg group as an important special case. We study Hamilton-Jacobi equations on the Heisenberg group $\mathbb{H}$ and show uniqueness of viscosity solutions with exponential growth at infinity. Lipschitz and horizontal convexity preserving properties of these equations under appropriate assumptions are also investigated. In this part, we also study a recent game-theoretic approach to the viscosity solutions of various equations, including deterministic and stochastic games. Based on this interpretation, we give new proofs of convexity preserving properties of the mean curvature flow equations and normalized $p$-Laplace equations in the Euclidean space. %D 2016 %K Sobolev spaces, metric measure spaces, Heisenberg group, viscosity solution, convexity preserving, game-theoretic methods %I University of Pittsburgh %L pittir29165 %A Yangyang Wang %T Analysis of Complex Bursting Patterns in Multiple Timescale Respiratory Neuron Models %X Many physical systems feature interacting components that evolve on disparate timescales. Significant insights about the dynamics of such systems have resulted from grouping timescales into two classes and exploiting the timescale separation between classes through the use of geometric singular perturbation theory. It is natural to expect, however, that some dynamic phenomena cannot be captured by a two timescale decomposition. One example is the mixed burst firing mode, observed in both recordings and model pre-B\"{o}tzinger neurons, which appears to involve at least three timescales based on its time course. With this motivation, we construct a model system consisting of a pair of Morris-Lecar systems coupled so that there are three timescales in the full system. We demonstrate that the approach previously developed in the context of geometric singular perturbation theory for the analysis of two timescale systems extends naturally to the three timescale setting. To elucidate which characteristics truly represent three timescale features, we investigate certain reductions to two timescales and the parameter dependence of solution features in the three timescale framework. Furthermore, these analyses and methods are extended and applied to understand multiple timescale bursting dynamics in a realistic single pre-B\"{o}tzinger complex neuron and a heterogeneous population of these neurons, both of which can generate a novel mixed bursting (MB) solution, also observed in pre-B\"{o}tC neuron recordings. Rather surprisingly, we discover that a third timescale is not actually required to generate mixed bursting solution in the single neuron model, whereas at least three timescales should be involved in the latter model to yield a similar mixed bursting pattern. Through our analysis of timescales, we also elucidate how the single pre-B\"{o}tC neuron model can be tuned to improve the robustness of the MB solution. %D 2016 %K fast-slow systems, multiple timescales, oscillations, geometric singular perturbation theory, bursting, respiratory neuron, persistent sodium, calcium %I University of Pittsburgh %L pittir29247 %A An-kwok Ian Wong %O Final draft %T Biomarker Discovery in Exome Data %X Current DNA sequencing technology enables inexpensive sequencing of the exome or the protein-coding regions of the genome. The primary goal of the analyses of exome data is to identify sequence variants, such as single nucleotide variations (SNVs), that will help elucidate the genetic causes of common polygenic diseases such as Alzheimer's disease and chronic pancreatitis. Exome data analysis presents several challenges. These challenges include the large number of SNVs compared to the relatively small sample size, the rarity of many of the SNVs, and potential interactions among SNVs on their effect on disease. In this work, I develop, implement, and evaluate a new multivariate biomarker ranking algorithm called Bayesian averaged probabilistic rules (BAPR) that has several novel characteristics. It (1) learns probabilistic rule models from data, (2) performs Bayesian model averaging to rank biomarkers like SNVs, and (3) incorporates biological knowledge as structure priors of biomarkers. The BAPR algorithm was evaluated on several exome datasets with both synthetic outcomes and real outcomes, and using a range of variant deleteriousness scores as structure priors. The quality of SNV rankings was evaluated with biomarker recovery plots, area under the Receiver Operating Characteristic curves, and evidence of biological validity as supported by the literature. The BAPR algorithm performed statistically significantly better in identifying previously known disease-associated SNVs and biologically meaningful SNVs when compared to chi-square and random forests. BAPR with uniform and expected number of predictors priors performed better than priors that were derived from variant deleteriousness scores. Also, combining several variant deleteriousness scores performed at least as well as the best performing single deleteriousness score. The variant deleteriousness scores have sparse coverage and typically scores are available only for a small proportion of SNVs that are measured in an exome dataset. The encouraging results obtained with these scores suggests that as coverage of the scores increases the performance of algorithms like BAPR that incorporate them will also improve. %D 2016 %K BAPR, biomarker discovery, exome, exome data, biomarker recovery %I University of Pittsburgh %L pittir28415 %A Abigail Snyder %T COMPUTATIONAL ANALYSIS OF PATTERN GENERATION IN REDUCED VERTEBRATE MOTOR CIRCUIT MODELS %X Rhythmic behaviors such as breathing, walking, and scratching are vital to many species. Such behaviors can emerge from groups of neurons, called central pattern generators (CPGs), in the absence of rhythmic inputs. In vertebrates, the identification of the cells that consti- tute the CPG for particular rhythmic behaviors is difficult, and often, its existence has only been inferred. In the second and third chapters of this thesis, we use two reduced mathemat- ical models to investigate the capability of a proposed network to generate multiple scratch rhythms observed in turtles. Under experimental conditions, intact turtles generate sev- eral rhythmic scratch motor patterns corresponding to non-rhythmic stimulation of different body regions. These patterns feature alternating phases of motoneuron activation that occur repeatedly, with different patterns distinguished by the relative timing and duration of activ- ity of hip extensor, hip flexor, and knee extensor motoneurons. We show through simulation that the proposed network can achieve the desired multi-functionality, even though it relies on hip unit generators to recruit appropriately timed knee extensor motoneuron activity. We develop a phase space representation which we use to derive sufficient conditions for the network to realize each rhythm and which illustrates the role of a saddle-node bifurcation in achieving the knee extensor delay. This framework is harnessed to consider bistability and to make predictions about the responses of the scratch rhythms to input changes for future experimental testing. We also consider a stochastic spiking model to reproduce firing rate changes observed in experiment, explore the relative contributions of different parameters in the model to the observed changes, support our collaborators? hypothesis regarding these changes, and provide our collaborators with predictions for future experiments. In the fourth chapter of this thesis, we present a theoretical study examining whether three mechanisms suggested by deletion experiments can operate in the same CPG for an extensor-flexor pair in the mammalian central nervous system during locomotion. We arrive at unique solution properties produced by each of the three mechanisms for use in future experiments. Our findings propose explanations for the coexistence of the three experimentally suggested yet seemingly contradictory mechanisms for rhythmogenesis. %D 2016 %K rhythmogensis, central pattern generators %I University of Pittsburgh %L pittir29075 %A Shaghayegh Sahebi %T Canonical Correlation Analysis in Cross-Domain Recommendation %X Cross-domain recommendation has recently emerged as a hot topic in the field of recommender systems. The idea is to use rating information accumulated in one domain (known as a source or auxiliary domain) to improve the quality of recommendations in another domain (known as a target domain). One of the important problems in cross-domain recommendation is the selection of source domains appropriate for a target domain. Previous works mostly assume that the best domain pairs can be decided based on similarity of their nature (such as books and movies), or simulate domain pairs by splitting the same dataset into multiple domains. We argue that the success of cross-domain recommendations depends on domain characteristics and shared (latent) information among domains; therefore posing new questions: What makes a good auxiliary domain? How should we choose the best auxiliary domain for a specific target domain? In this dissertation we examine the success and failure of cross-domain collaborative filtering across three different datasets with various characteristics of domains. Our goals are to explore the added value of cross-domain recommendations in comparison with traditional within-domain recommendations, and to achieve some progress in uncovering the main mystery of cross-domain recommendation: how can we determine whether a pair of domains is a good candidate for applying cross-domain recommendation techniques? For the former goal, we propose a cross-domain collaborative filtering approach based on canonical correlation analysis. In order to address the latter goal, we investigate a canonical correlation approach as a possible predictor of successful domain pairs and examine a range of features of a single domain and domain pairs in order to see how they could be used to improve predictions. Eventually, we propose a domain-pair classifier that can distinguish between the beneficial and non-beneficial domain pairs before performing the recommendations. %D 2016 %K Recommender Systems Cross Domain Collaborative Filtering Domain Analysis Algorithm Canonical Correlation Analysis %I University of Pittsburgh %L pittir29220 %A Xun Wang %T Computational study of proton-disordered ice Ih %X Water is the most important liquid on the earth, yet the physics behind many properties of water is still poorly understood. Particular interesting are the condensed phases of water: ice and liquid water, that both possess anomalous properties. In this thesis, I focus on using different methods, including force fields as well as DFT calculations, to predict several key properties of proton-disordered ice Ih and liquid water. The focus of my study of ice Ih is on its comparable dielectric constant ?_s with liquid water, which directly results from its proton-disorder nature. Predictions of the dielectric constant of ice Ih from pairwise additive force fields fall appreciably below than the experimental values, with significant improvement being achieved by polarizable force fields. I examined the performance of different force fields, and confirmed that the polarizable AMOEBA models with three polarizable sites per molecule outperform polarizable models such as DC97 with a single polarizable site. Since it is difficult to resolve the subtle energetic difference of different proton ordering arrangements in ice Ih with force fields, I studied the energetics of ice Ih, from DFT calculations using the BLYP functional as well as several dispersion-corrected BLYP functionals. As shown in my study, the dispersion-corrected functionals not only give better energy predictions but also get better lattice parameters and equilibrium volumes for the optimized ice Ih unit cells. I also predicted the structural as well as dynamical properties of liquid water from ab initio molecular dynamics simulations with several dispersion-corrected BLYP functionals. The results of calculations all confirmed that including dispersion corrections in functionals is essential to get faster water rotational dynamics and a ?softer? structure of liquid water. Finally I parametrized a two-channel dispersion-corrected atom-centered pseudopotential (DCACP2) based on the BLYP functional to correct for the long-range dispersion force for three rare gas elements: helium, neon and argon. By fitting the interaction energy of three homonuclear dimers against CCSD(T) calculations, the resulting DCACP2-BLYP method performs significantly better than the one-channel DCACP approach for the two-body binding energies of the dimers. I also explore the factor responsible for the success of DCACP2 method. %D 2016 %K molecular dynamics, density functional theory, proton disorder, ice, dispersion %I University of Pittsburgh %L pittir29282 %A Seth Walters %T DEVELOPMENT, VALIDATION, AND USE OF A QUANTITATIVE THEORY OF IN VIVO DOPAMINE DYNAMICS %X Since the early 1980s, fast scan cyclic voltammetry (FSCV) has been used to detect changes in dopamine's presence in the brain's extracellular space. The dopamine signals detected result from several simultaneous biophysical processes. Because these processes currently cannot be directly measured, a mathematical model which quantitatively explains FSCV data is necessary to describe their natures and magnitudes. I have created a simple mathematical model which posits that diffusion of dopamine in the brain follows a unidirectional first order kinetic scheme from its source. The model, using just three parameters, produces excellent fits to dopamine responses evoked by short electrical stimuli. These parameters are: Rp (release), kU (fuptake) and kT (mass transport). When longer stimulations are performed, the addition of a term kR, which modifies Rp by an exponential, is adequate to fit nearly all observed dopamine responses in the anaesthesized rat brain. To complement this work, I have determined that the ubiquitous failure of dopamine concentration changes as measured by FSCV to return to baseline, called hang-up, is an artifact caused by a form of long duration adsorption to the carbon fiber electrodes commonly used to measure dopamine. I have developed a mathematical correction for this artifact. In addition, I have experimentally determined that the observed first order behavior of the mass transport parameter kT arises essentially entirely from the brain itself, rather than the adsorption kinetics of dopamine at the electrode. Finally, having established a sound theoretical framework for understanding the biological and instrumental origins of dopamine signals in the brain, I have used this model to study both anatomical differences in dopamine signaling, as well as the biophysical effects of the drug buproprion, an antidepressant. These studies have found that the density of dopamine signaling is greatest in the dorsolateral striatum, and that this high density of signaling is enabled by high rates of dopamine uptake, which attenuate the spatial range of dopamine signaling. I anticipate that this work is a necessary step towards the comprehensive mechanistic dissection of cellular signaling, and I hope it will prove invaluable to future progress. %D 2016 %K dopamine, "mathematical model", model, "fast scan cyclic voltammetry" %I University of Pittsburgh %L pittir29297 %A BASAK GEMICI AY %T DYNAMICS OF COLLECTIVE ACYION IN TURKISH PRISONS:COMPARATIVE ANALYSIS OF MAMAK AND DIYARBAKIR PRISONS BETWEEN 1980 AND 1985 %X Historically, one of the most significant periods in which incarceration was used as a tool to manage political opponents of the regime in Turkey was the 1980s, specifically during and after the 1980 military coup. This study investigates the high-risk environments of the two notorious military prisons: Mamak and Diyarbakir Prisons between 1980 and 1985. These two military prisons: Mamak Prison, where Turkish revolutionaries were incarcerated and Diyarbakir Prison, where Kurdish revolutionaries were incarcerated, were infamous for the torture and level of repression implemented by the military junta. The aim of the military junta was to dissolve revolutionary organizations and military prisons were one of the state institutions that were used to realize this aim. Thus, while comparing the dynamics of collective action of the political prisoners in two prisons, I also consider how different prisons/ prison contexts affect the success a regime has in demobilizing dissident groups.Using in-depth interviews I conducted, along with contemporary writings from former political prisoners, my research will demonstrate how the development of solidary interpersonal relations and shared identity were solidified during prison life and facilitated formation of collective action. Moreover, the risk-taking ability of the leaders appear as contingently interconnected themes to identity and relations in explaining how political prisoners in Diyarbakir Prison formed more frequent and sustainable collective actions than the political prisoners in Mamak Prison. This thesis contributes to the discussions of different mobilization processes under high-risk contexts in undemocratic environments and addresses the understudied aspect of collective action in Turkish prisons. %D 2016 %K Turkish Prisons, leadership in high-risk collective action, military coup, prisons, high-risk collective action, Diyarbakir Prison, Mamak Prison, Kurdish insurgents, Turkish insurgents, political prisoners, torture, humour, mobilisation, demobilisation, state repression %I University of Pittsburgh %L pittir29071 %A Yongzhao Yan %T ENANTIOSELECTIVE SYNTHESIS AND CYCLOISOMERIZATION OF 1-BICYCLO[1.1.0]BUTAN-1-YL ALKYLAMINES %X This dissertation demonstrates the synthesis and application studies of 1-bicyclo[1.1.0]butyl alkylamines. The enantioselective synthesis of 1-bicyclo[1.1.0]butyl alkylamines was achieved by dicarbene addition to enantiomerically enriched propargyl amides. The enantioselective addition of alkynes to imines proceeded well for most N-DPP amides. But the carbene addition suffered from the formation of cyclopropane byproducts. However, a series of silyl-substituted bicyclo[1.1.0]butanes could be synthesized by this methodology in high, reproducible yields. When tethered to an activated alkyne, the silyl-substituted bicyclo[1.1.0]butane undergoes cyclization to form pyrrolidines. In the application of the 1-bicyclo[1.1.0]butyl alkylamines, a palladium(0)-catalyzed cycloisomerization of bicyclo[1.1.0]butanes and methylenecyclopropanes has been developed. 3-Azaspiro[bicyclo[3.1.0] hexane-6,1'-cyclopropane] is obtained with excellent stereoselectivity. Novel 2,3,3a,6a- tetrahydrocyclopenta[c]pyrrol-4(1H)-one is the product of the cycloisomerization and carbonylation sequence. %D 2016 %K Cycloisomerization, Bicyclo[1.1.0]butane, Palladium, Synthetic Method, %I University of Pittsburgh %L pittir26163 %A Ling Yang %T Essays on Information Economics %X This dissertation comprises three essays on information economics. I study the role of information in various decision making environments. In the first chapter, I propose an alternative way to study the value of information in a game. A decision problem is similar to another if the optimal decision rule for the latter, when applied to the former, is better than making a decision without any information in the former. In a game, if the induced decision problem by a change in the strategies of other players is similar to the problem originally faced by the player, the player benefits more from her own information after the change. Using the concept of similarity, I study the value of information in various games, even when a closed form solution is unavailable. The second chapter studies a persuasion game between a decision maker (DM) and an expert. Prior to the communication stage, the expert exerts costly effort to obtain decisive information about the state of nature. The expert may feign ignorance but cannot misreport. We show that monitoring of information acquisition hampers the expert's incentives to acquire information. Contrary to everyday experiences, monitoring is always suboptimal if the expert's bias is large, yet sometimes optimal if the expert's bias is small. The third chapter studies a model in which partisan voting is rationalized by Knightian decision theory under uncertainty (Bewley, 2002). When uncertainty is large, some voters become hard-core supporters of their current party due to status quo bias. I characterize equilibria of the model that are robust to electorate size. With costly information acquisition, partisan behaviors arise naturally from status quo biases in large elections. In the selected informative voting equilibrium, swing voters rationally mix between two alternatives: either they acquire information and vote informatively or they do not acquire information and vote to cancel the partisans' votes. %D 2016 %K Similarity, Value of Information, Partisan Voting, Uncertainty, Persuasion Game %I University of Pittsburgh %L pittir29194 %A Irina Navrotskaya %T Inverse problem in classical statistical mechanics %X This thesis concentrates on the inverse problem in classical statistical mechanics and its applications. Let us consider a system of identical particles with the total energy W + U, where W is a fixed scalar function, and V is an additional internal or external potential in the form of a sum of m-particle interactions u. The inverse conjecture states that any positive, integrable function ?(m) is the equilibrium m-particle density corresponding to some unique potential u. It has been proved for all m ? 1 in the grand canonical ensemble by Chayes and Chayes in 1984. Chapter 2 of this thesis contains the proof of the inverse conjecture for m ? 1 in the canonical formulation. For m = 1, the inverse problem lies at the foundation of density functional theory for inhomogeneous fluids. More generally, existence and differentiability of the inverse map for m ? 1 provides the basis for the variational principle on which generalizations to density functional theory can be formulated. Differentiability of the inverse map in the grand canonical ensemble for m ? 1 is proved here in Section 3.2. In particular, this result leads to the existence of a hierarchy of generalized Ornstein-Zernike equations connecting the 2m-,...,m-particle densities and generalized direct correlation functions. This hierarchy is constructed in Section 3.3. %D 2016 %K statistical mechanics, measure theory, functional analysis %I University of Pittsburgh %L pittir28992 %A Hyo Kyung Woo %T Korean Englishes, Uneven Asias, and Global Circulation, 1895-1945 %X This dissertation investigates the role of English as a global mediatory language and English literature as a global reading material for a group of Korean writers during the Japanese colonization of Korea, roughly from 1895 to 1945. The primary argument of this dissertation is that Korean intellectuals of the colonial period appropriated the privilege accorded to the English language, and to Anglophone literature, as an anti-colonial tool against the Japanese rule, incorporating their anti-colonial aspirations into their own Anglophone literary practices. First, ?Korean Englishes? traces the complex and unexplored local history of English and its intersection with other local languages under Japanese colonial rule. Colonial Korea was a symbolic translingual zone. English, a secondary but global language, was positioned within the multivalent linguistic conflicts: English, as a language of modernity, gradually subverted the dominance of classical Chinese, the learned language of pre-modern Korea, while disturbing the new imperial imposition of Japanese language education in Korea. These four languages, Chinese, Japanese, Korean, and English, were all in contact and conflict in multi-sited ways. As a result of this positioning, the political power of English provided Koreans with a voice situated within multiple colonial legacies. Second, ?Korean Englishes? examines the local reception and production of English literature and how Korean writers borrowed the cultural capital of English-language literature for their own literary practices. During the Japanese colonial era, Korean writers indirectly translated a variety of English literary works, from Victorian sensational fictions to the poetry of Yeats, via Japanese translations, and produced their Anglophone writings. These translators and writers constantly discovered and created new meanings of the texts and utilized their interpretations as a resources for the self-expression of the colonized, at a time when their own language and literature were censored under Japanese colonial policies. By examining English-based, anti-colonial linguistic and literary practices in colonial Korea, this project argues that Korean Englishes were a product of the triangular interplay between the local, the regional, and the global, changing existing postcolonial studies? perception of English. %D 2016 %K Englishes, colonial Korea, translation, English literature in Korea, global circulation, world literature %I University of Pittsburgh %L pittir29160 %A Jiaqing / J.X. Xu %T Modeling Defaults In Banking & Real Estate %X In this thesis, we study two topics related to defaults. First, we provide a Probability of Default (PD) calculation method for privately-held U.S. regional banks, using free and transparent data from the Federal Deposit Insurance Corporation (FDIC). Our method is efficient and useful for both investors and regulators. We have improved Moody's proprietary RiskCalc PD model [17] by creating a new cautionary index, which is able to capture default behaviors very well and has a very high predictive power over both one-year and six-month time horizons as shown by our numerical results. We also find that this performance is robust over different historical periods. We describe the factors we chose, the modeling methodology, and the model's accuracy in detail. Second, we propose two strategies to reduce the frequency of defaults in home mortgages (foreclosures). The first is a new mortgage insurance contract (American put option with the house as the underlying asset). Our analysis differs from that for the standard put option in equity markets in that our strike (the remaining value of the mortgage) is time dependent, and the drift and volatility in the Geometric Brownian Motion are time dependent (step functions) due to a regime switch from declining to increasing house prices. Both theoretical derivations and numerical results will be obtained. We will also analyze the Adjustable Balance Mortgage (ABM) in continuous time as a second alternative to avoiding foreclosures. Here the mortgage payments are reduced if the house price falls below the remaining value of the mortgage. %D 2016 %K Logistic Regression, Model Selection, ROC Curve, AUC, KS Statistic, American Put Option, Integral Equation, Early Exercise Boundary, Default Probability, Adjustable Balance Mortgage %I University of Pittsburgh %L pittir28708 %A David Punihaole %T Molecular Structural Insights of Polyglutamine-Rich Amyloid-like Fibrils Using UV Resonance Raman Spectroscopy %X There is currently little that is known about the structure of polyglutamine (polyQ) fibrils, which are involved in at least ten neurodegenerative diseases, including Huntington's. Given the difficulty of studying these aggregates, new and incisive biophysical methods need to be developed in order to obtain high-resolution structural information of polyQ and other amyloid-like fibrils. Here, we present our recent advances in UV resonance Raman (UVRR) spectroscopy that enable the elucidation of molecular-level structural information of amyloid-like fibrils. We show, for example, how the primary amide UVRR bands report on the local hydrogen bonding and dielectric environment of glutamine side chains. We also discuss a newly discovered spectroscopic marker, the Amide III$^{\textrm{P}}$ vibration, which sensitively reports on the OCCC dihedral angle of glutamine (Gln) and asparagine (Asn) side chains. These and other spectroscopic markers are used to gain insights into the peptide backbone and side chain structures of polyQ peptides in solution-state and in fibrils. Finally, we demonstrate how the structural information obtained from UVRR can be utilized to guide Molecular Dynamics simulations in order to obtain experimentally validated structural models of polyQ fibrils. %D 2016 %K none %I University of Pittsburgh %L pittir28138 %A Justin Ross Sevenker %T Old English Composition: Literacy and the History of English in the United States %X This dissertation is a critical history of ?the history of the English language? as a school subject in the United States. I recover the subject as a formative component of literacy instruction and the early field of composition in the nineteenth century. I also trace its development as a teacher education requirement in the twentieth century and propose an alternative, progressive approach to teaching it today. To do so, I examine numerous, underexplored instructional texts on the history of English, including over three hundred dictionary, grammar, rhetoric, and composition textbook titles published repeatedly during the eighteenth and nineteenth centuries. By charting the circulation of this material, I establish that the history of English was a pervasive component of the period?s cultures of literacy. Moreover, I show how it was used to advance theories about standardization, ?Anglo-Saxon? style, and linguistic exceptionalism that linger as unexamined assumptions among beginning writers, new teachers, and even in current composition scholarship. In this way, I call into question contemporary practices that silently sustain the subject?s once raced and nationalist politics. Specifically, I argue that by underwriting composition?s tacit policy of English monolingualism, traditional histories of English have constrained how the field prepares literacy educators to work with new populations of multilingual and non-standard English users entering U.S. schools. I propose that a more historically self-aware history of English, recentered on the availability of diverse Englishes and the multilingual reality of communication, can equip teachers with more productive, inclusive instructional practices today. I theorize my approach using the CCCC?s ?Students? Right to Their Own Language? statement as well as later scholarship on critical language awareness. Drawing on my own ?History and Politics of the English Language? course at the University of Pittsburgh, I then demonstrate how the history of English can remain an active component of teacher preparation, composition studies, and English education more broadly. The version of the course I outline emphasizes historical topics that impinge on present literate concerns. Moreover, it incorporates student-directed research projects that enable new teachers to reflect on entrenched attitudes that inform their work with diverse populations of English users. %D 2016 %K history of literacy, book history, history of instruction, teacher education, Students' Right to Their Own Language, language difference, mulitlingual writing, critical language awareness %I University of Pittsburgh %L pittir29114 %A Jiannan Ouyang %T Operating System Mechanisms for Performance Isolation between Co-Located Applications %X The efficient sharing of a single server node between multiple co-located applications is increasingly important in modern large-scale datacenters and supercomputers. However, existing operating system (OS) architectures fall short in ensuring the performance isolation between co-located applications, which impedes the efficiency of large-scale computing infrastructures as well as the scalability of large-scale applications. The goal of this research is to improve the performance isolation capability of existing OS kernels, as well as to develop novel OS architectures aiming to provide isolated and optimized execution environments for workloads with disparate runtime requirements. We first studied the performance interference problem between time-shared virtual machines as seen in the cloud. We conducted comprehensive performance analyses to identify the root causes of the kernel performance degradation problem in shared virtual environments. To address this problem, we designed and implemented two synchronization techniques optimized for shared virtual environments: the preemptable ticket spinlock (pmtlock) algorithm and the Shoot4U paravirtual TLB shootdown scheme. Our evaluation demonstrates that both techniques significantly reduce the performance interference between co-located virtual machines. Besides improving existing OS kernels, we also looked at the design of operating systems aiming to provide isolated and optimized execution environments for in-situ analysis applications as seen in modern high performance computing (HPC). We designed and implemented the Pisces lightweight co-kernel architecture, which allows multiple independent lightweight co-kernels to be deployed side-by-side with Linux on isolated hardware partitions. Each co-kernel can be optimized for the local HPC workload, while the performance isolation between co-kernels is enforced at both the software and hardware level. Our evaluation shows better application scalability on the co-kernel architecture compared with native Linux. Finally, to support high performance I/O on lightweight co-kernels, we developed HobbesIO: an I/O delegation service on lightweight co-kernels that allows the application transparent I/O delegation from a co-kernel process to an I/O service processes deployed on arbitrary native or virtual Linux enclaves. Our evaluation shows that HobbesIO achieves comparable performance with native Linux. %D 2016 %K performance isolation, synchronization, multi-kernel, high performance computing, cloud computing %I University of Pittsburgh %L pittir29307 %A Shelby Stanhope %T Parameter estimation for dynamical systems %X Parameter estimation is a vital component of model development. Making use of data, one aims to determine the parameters for which the model behaves in the same way as the system observations. In the setting of differential equation models, the available data often consists of time course measurements of the system. We begin by examining the parameter estimation problem in an idealized setting with complete knowledge of an entire single trajectory of data which is free from error. This addresses the question of uniqueness of the parameters, i.e. identifiability. We derive novel, interrelated conditions that are necessary and sufficient for identifiability for linear and linear-in-parameters dynamical systems. One result provides information about identifiability based solely on the geometric structure of an observed trajectory. Then, we look at identifiability from a discrete collection of data points along a trajectory. By considering data that are observed at equally spaced time intervals, we define a matrix whose Jordan structure determines the identifiability. We further extend the investigation to consider the case of uncertainty in the data. Our results establish regions in data space that give inverse problem solutions with particular properties, such as uniqueness or stability, and give bounds on the maximal allowable uncertainty in the data set that can be tolerated while maintaining these characteristics. Finally, the practical problem of parameter estimation from a collection of data for the system is addressed. In the setting of Bayesian parameter inference, we aim to improve the accuracy of the Metropolis-Hastings algorithm by introducing a new informative prior density called the Jacobian prior, which exploits knowledge of the fixed model structure. Two approaches are developed to systematically analyze the accuracy of the posterior density obtained using this prior. %D 2016 %K parameter estimation, identifiability, Metropolis-Hastings, inverse problems, Bayesian inference, linear dynamical systems %I University of Pittsburgh %L pittir28592 %A Glenn Young %T Pathogen dynamics: modeling and analysis of competition, organization, and vaccination %X The work presented in this thesis is motivated by questions arising about pathogen dynamics. The effects of pathogens can be observed on a variety of spatial scales, from within-host interactions with the immune system on the microscopic level, to the spread of communicable disease on the population level. We present analyses of three common pathogens on three different scales. In Chapter 2, we derive and study a system of ordinary differential equations modeling the competition for space and resources between a mammalian host's native intestinal microbiota and an invasive species of Salmonella Typhimurium. We use our model to discuss optimal invasion strategies that maximize the salmonella's likelihood of successfully displacing the microbiota for a spot on the intestinal wall. In Chapter 3, we analyze an anomalous behavior observed in which two interacting pulses of E. coli in a one-dimensional nutrient gradient will turn around move away from one another rather than combine. To this end, we derive a novel system of ordinary differential equations approximating the dynamics of the classic Keller-Segel partial differential equations model for bacterial chemotaxis, and use this approximation to make testable predictions about mechanisms driving the turn around behavior. Finally, in Chapter 4, we use a two-strain SIR-type model of rotavirus transmission to study the effects of vaccination on a population exposed to multiple endemic strains. %D 2016 %K Mathematical biology, pathogen dynamics %I University of Pittsburgh %L pittir28720 %A Robert Steel %T Planning For Failure %X Sometimes I not only judge that P, but I also have some further ?higher?-order? evidence about my reliability when it comes to this sort of judgment. Perhaps I make an arithmetical judgment, but at the same time I have evidence that I am drunk and so arithmetically unreliable. I argue that the rational response in such a situation is to calibrate one?s confidence in P to the level suggested by one?s higher-?order evidence?in this particular case, however confident I would be in P just given the description ?I judged that P, drunkenly.? As a special case, this ?calibrationist? doctrine entails a conciliatory view of peer disagreement. Some have found conciliatory views to be disturbing, taking them to collapse into psychologism and, at the limit, skepticism. I develop a conciliatory view which need be neither of these things, which is fortunate, since I also argue it is correct. %D 2016 %K Epistemology, Higher Order Evidence, Peer Disagreement, Calibrationism, Epistemic Planning %I University of Pittsburgh %L pittir28590 %A Ryan Sayer %T REPLICATING EFFECTIVE PEDAGOGICAL APPROACHES FROM INTRODUCTORY PHYSICS TO IMPROVE STUDENT LEARNING OF QUANTUM MECHANICS %X Upper-level undergraduate students entering a quantum mechanics (QM) course are in many ways similar to students entering an introductory physics course. Numerous studies have investigated the difficulties that novices face in introductory physics as well as the pedagogical approaches that are effective in helping them overcome those difficulties. My research focuses on replicating effective approaches and instructional strategies used in introductory physics courses to help advanced students in an upper-level QM course. I have investigated the use of Just-in-time Teaching (JiTT) and peer discussion involving clicker questions in an upper-level quantum mechanics course. The JiTT approach including peer discussions was effective in helping students overcome their difficulties and improve their understanding of QM concepts. Learning tools, such as a Quantum Interactive Learning Tutorial (QuILT) based on the Double-slit Experiment (DSE) which I helped develop, have been successful in helping upper-level undergraduate students improve their understanding of QM. Many students have also demonstrated the ability to transfer knowledge from a QuILT based on the Mach-Zehnder interferometer while working on the DSE QuILT. In addition, I have been involved in implementing research-based activities during our semester-long professional development course for teaching assistants (TAs). In one intervention, TAs were asked to grade student solutions to introductory physics problems first using their choice of method, then again using a rubric designed to promote effective problem-solving approaches, then once more at the end of the semester using their choice of method. This intervention found that many TAs have ingrained beliefs about the purposes of grading which include placing the burden of proof on the instructor as well as a belief that grading cannot serve as a formative assessment. I also compared TAs grading practices and considerations when grading student solutions to QM problems versus when grading student solutions to introductory physics. Many TAs penalized students for not explicating the problem solving process more often in the QM context than in the introductory physics context. The implications of these interventions for promoting student learning in QM are discussed. %D 2016 %K physics education research, quantum mechanics, introductory physics, pedagogy %I University of Pittsburgh %L pittir28558 %A Sharon Quinsaat %T REVOLUTION FROM AFAR: MOBILIZATIONS FOR HOMELAND REGIME CHANGE AND THE MAKING OF THE FILIPINO DIASPORA, 1965-1992 %X From the late 1970s to the early 1990s, Filipinos in the U.S. and the Netherlands became key players in international efforts to overthrow an oppressive regime and institute democracy in the Philippines. When Philippine dictator Ferdinand Marcos declared martial law on September 21, 1972, Filipino student and political organizations in the U.S. immediately convened in San Francisco and launched a national campaign to oppose authoritarian rule. In less than a year, the movement spread as new organizations of diverse political orientations emerged and took root in long-established Filipino communities in the U.S. Activists focused on lobbying Congress for the withdrawal of military and economic support to Marcos. In the Netherlands, Filipino exile and solidarity organizations in Europe organized the Permanent People?s Tribunal on the Philippines in 1980 to expose and isolate the Marcos dictatorship and recognize the national liberation movements as the genuine representatives of the Filipino people. While much is known about why migrants maintain homeland ties, information on how they become engaged in organizations involved in political struggles remains scant. Through a comparative case study of homeland-directed activism among Filipinos in the U.S. and the Netherlands from the period of authoritarian rule (1965-1986) to the early years of democratic transition (1986-1992) in the Philippines, the project analyzes how political structures in both the host and home societies, resources in the migrant communities, and formation of oppositional consciousness interact and influence mobilization. Research findings show that variations in the emergence, growth, and outcomes of the movement in the two countries were due to dissimilar host-country conditions and the manner by which the interaction of economic, political, and social structures in the homeland and hostland provided opportunities and disincentives for mobilization. However, similar mechanisms and processes occurred in both the U.S. and Netherlands, although these differed with regard to actors and outcomes, depending on the historical context. Overall, the formation of diasporas is a consequence of strategic social construction by political entrepreneurs in periods of heightened contention in the homeland such as during dictatorship and regime change. Thus, diasporas are outcomes, rather than causes or agents, of transnational mobilization. %D 2016 %K Social Movement, Diaspora, Anti-Dictatorship, Philippines, Filipinos %I University of Pittsburgh %L pittir28561 %A Matthew Wheeler %T Rational Structures and Fractional Differential Refinements %X In the following thesis, we explore the notion of rational Fivebrane structures. This is done through a combination of obstruction theory and rational homotopy theory. We show that these structures can be classified to some degree by the underlying Spin bundle. From there we turn our focus to the differential setting. Using this relation to the Spin bundle, we apply the classical machinery of Cheeger and Simons to understand differential rational Fivebrane classes. Finally we use these classes to obtain information for differential trivializations in the integral case. In doing this we introduce the exact braid diagram. %D 2016 %K string and fivebrane structures, rational homotopy theory, differential cohomology, differential braid diagram, fractional differential characters %I University of Pittsburgh %L pittir28594 %A LINGQING XU %T Regulation of Focal Adhesion Dynamics by a Kinesin Motor Kid/KIF22/Kinesin-10 %X Cell adhesion is one of the fundamental mechanisms cells use to interact with their surrounding environment. It is mediated by multiprotein structures termed focal adhesions (FAs). The formation of FAs and the regulation of their assembly and disassembly dynamics are crucial to cell structure and viability. In my dissertation study, I explored the role of a kinesin motor Kid/kinesin-10/KIF22 in adhesion dynamics. I found that Kid localizes to the sites of FAs and functions as an adhesion disassembly factor by modulating the phosphorylation of two important components of FAs, focal adhesion kinase (FAK) and paxillin. Loss of Kid caused changes in the density, distribution, and size of FAs leading to defects in cell adhesion and migration. This study discovered a novel function of Kid during interphase and expanded our knowledge on how motor proteins play significant roles in adhesion dynamics. %D 2016 %K KIF22, Focal Adhesions, Adhesion Dynamics, Focal Adhesion Kinase %I University of Pittsburgh %L pittir29238 %A Amy L. Short %T Sequenced copolymers with controlled molecular weights prepared via entropy-driven ring-opening metathesis polymerization %X A segmer-based approach towards monomer synthesis was successfully carried out to produce a series of linear ?,?-diolefinic species with varying linker lengths. Ring-closing metathesis (RCM) using a cis-selective ruthenium catalyst yielded a large strainless macrocycle that then underwent entropy-driven ring-opening metathesis polymerization (ED-ROMP). When compared to the same polymerization carried out with the complementary trans-monomer, the ED-ROMP of cis-monomer demonstrated a significantly higher degree of molecular weight control. The narrow dispersity exhibited by this process suggests that a new regime of selectivity enhanced ED-ROMP (SEED-ROMP) has been achieved. Reaction kinetics for this process were probed and the process was compared to alternative polymerization methods. Finally, the high degree of control was exemplified in a series of chain extension and block copolymerization experiments. Ultimately, SEED-ROMP represents a novel method to obtain well-defined copolymers of precise molecular weights. %D 2016 %K Sequenced copolymer, entropy-driven ring-opening metathesis polymerization (ED-ROMP), thermodynamic and kinetic enhancement, molecular weight control, controlled polymerization, cis-selective ring closing metathesis (RCM), poly-(lactic-co-glycolic) acid (PLGA), well-defined block copolymer formation, chain extension polymerization, selectivity-enhanced entropy-driven ring-opening metathesis polymerization (SEED-ROMP), deactivation entropy-driven ring-opening metathesis polymerization (DED-ROMP) %I University of Pittsburgh %L pittir29287 %A Christopher Myers %T Steering the Seas of Reform: Education, Empirical Science, and Royal Naval Medicine, 1815-1860 %X As medical and imperial actors, early-nineteenth-century British naval surgeons navigated the sweeping changes that occurred within the Royal Navy, the medical profession, and British society. They embraced and applied empirical natural and medical scientific approaches between the 1810s and 1850s. Their attempts to employ science as they negotiated naval service?s realities and experiences, pursued their scientific and medical interests and duties, and confronted tropical fevers transformed the naval service. Scottish and Scottish-trained medical officers and leaders, who dominated the service through mid-century, spearheaded these efforts. In the process, surgeons? practical utility to the Navy?s global-imperial duties became an increasingly important consideration, and their professional status and respectability rose. This dissertation culminates with a case study of surgeons? efforts to confront tropical fevers encountered off the West African coast. These later chapters analyze the changes in medical and strategic thought, approaches, and practices that led to a shift in practices related to fevers and the widespread use of quinine. This account builds on efforts to integrate military and colonial medicine and science into narratives of British history, and the histories of empire, medicine, and science. It draws from medical course and student records, naval papers, reports and correspondence, university and parliamentary committees, and medical and scientific manuscripts and journals. This approach sheds analytical, statistical, and demographic light on naval medicine?s place in broader imperial and professional contexts, highlighting the convergence of educational, professional, institutional, and practical reforms with the necessities of service at sea. It portrays the early nineteenth century as a period of turmoil and transition in medicine and science? often labeled the Age of Reform. Professionalization and the rise of science within the medical profession led to educational, professional, and practical upheaval, as well as rising qualifications, authority, and ambitions. Bringing multiple literatures on medical and scientific education, professionalization, and practice into dialogue, this project presents an inclusive but focused view of these developments, and their relations to naval medicine. Naval surgeons emerge as an important group that had to negotiate the myriad professional and societal changes that shaped British science, medicine, and society during this formative period. %D 2016 %K naval medical officers, medical education, tropical medicine, Royal Navy, naturalists, prosopography %I University of Pittsburgh %L pittir28191 %A Sarah M. Wells %T The Synthesis of 6,12-Guaianolide Analogs and Related Chemical Tools for Probing their Mechanism of NF-?B Inhibition %X Guaianolides, the largest class of sesquiterpene lactones, possess a wide range of biological activities, particularly in the areas of anti-inflammation and anticancer. The allenic Pauson-Khand reaction (APKR) is a rhodium (I) catalyzed [2 + 2 + 1] cyclocarbonylation reaction of allene-ynes and has been established as a viable methodology for accessing the guaianolide 5,7,5-tricyclic framework. However, allene-yne precursors with methyl substituted allenes and alkynes have been poorly tolerated. Optimization of high dilution APKR conditions is described for these methyl substituted allene-ynes, which give direct access to C4 and C10 methyl substituted bicycle[5.3.0]decadienones, consistent with the guaianolide framework. This APKR approach was also applied to continuing the synthesis of highly oxygenated guaianolide analogs, capable of inhibiting NF-?B. The ?-methylene-?-butyrolactone moiety is incorporated into allene-yne tether prior to the APKR. Given the potent NF-?B inhibitory properties demonstrated by our analogs, derivatives were synthesized in effort to examine the biological mechanism of inhibition. Installation of alkyne ligation handles onto the base-sensitive guaianolide analogs, for use in biomechanistic studies, was achieved using the acid mediated Nicholas reaction. This method was also established for the general installation of alkyne ligation handles onto hydroxyl, sulfhydryl, amino, and carboxyl groups. Synthesis and biological evaluation of an ?-methyl-?-butyrolactone guaianolide analog established the importance of the ?-methylene-?-butyrolactone moiety for potent NF-?B inhibition. %D 2016 %K guaianolides allenic Pauson-Khand reaction alkyne probes NF-?B Inhibition %I University of Pittsburgh %L pittir28636 %A Jeremiah Morgan %T Tukey quotients, pre-ideals, and neighborhood filters with calibre (omega 1, omega) %X This work seeks to extract topological information from the order-properties of certain pre-ideals and pre-filters associated with topological spaces. In particular, we investigate the neighborhood filter of a subset of a space, the pre-ideal of all compact subsets of a space, and the ideal of all locally finite subcollections of an open cover of a space. The class of directed sets with calibre (omega 1, omega) (i.e. those whose uncountable subsets each contain an infinite subset with an upper bound) play a crucial role throughout our results. For example, we prove two optimal generalizations of Schneider's classic theorem that a compact space with a G_delta diagonal is metrizable. The first of these can be stated as: if X is (countably) compact and the neighborhood filter of the diagonal in X^2 has calibre (omega 1, omega) with respect to reverse set inclusion, then X is metrizable. Tukey quotients are used extensively and provide a unifying language for expressing many of the concepts studied here. %D 2016 %K topology, directed sets, calibres, Tukey quotients, compact covers, P-paracompactness, metrizability, productivity, Lindelof Sigma-spaces, neighborhood filters, strong Pytkeev property, function spaces %I University of Pittsburgh %L pittir28129 %A Oana Adelina Stefan %T Vacationing in the Cold War: Foreign Tourists to Socialist Romania and Franco's Spain, 1960s-1970s %X My dissertation examines the politics and effects of international tourism in socialist Romania and Francoist Spain in the postwar era. Despite the sharp economic and political differences between the two dictatorial regimes at the time of the Cold War, I argue that significant similarities existed in the way that they aimed to take advantage of international tourism in order to improve their image abroad and to acquire hard currencies, which were sorely needed as both states wanted to pursue a process of economic modernization. This dissertation also attempts to provide an explanation for why, by the end of the 1970s, the two countries achieved rather different results in terms of tourism development, despite the fact that both shared many features in the 1940s and 1950s. Most English-language scholarly literature examines relations between and transfers from western to eastern Europe, but pays little attention to the relationships between southern or eastern parts of the continent and the ?West.? Moreover, most scholarly work silently integrates, often by implication, southern Europe into the amorphous ?West.? This study takes a different approach. By comparing the rise and evolution of international tourism in two countries on different sides of the Iron Curtain, it reassesses the geopolitics of postwar Europe by showing the developmental similarities between eastern and southern Europe. It thereby suggests that the Cold War view of a bipolar Europe needs refining. The bulk of my dissertation analyzes the two governments? policies?and the discussions and debates leading up to those policies?regarding tourism, how and why the policies were implemented, as well as the anticipated and unanticipated results. To provide a more in-depth analysis of the ways in which tourists, their behaviors, and their preferences (be they in attire, morals, diet and the like) influenced policies, I compare the Romanian Black Sea coast and Spain?s Costa del Sol during the 1960s and 1970s. I focus in particular on the interactions between foreign tourists and locals, and how intended policies were applied and received. %D 2016 %K Cold War, international tourism, socialist Romania, Franco's Spain, dictatorship, socialism, Francoism, everyday life, consumption %I University of Pittsburgh %L pittir28005 %A Swathi Sreerangarajan %T Working Around Ethnographic Entanglements: South Asian American Literature and Popular Culture %X This dissertation identifies the significant demands on ethnic American artists to narrate their identities, and it analyzes specific literary texts and cultural practices that attempt to work around such imperatives. Interpreting the work of South Asian American authors and performers, I depart from two main strains of reading/viewing habits that entail expectations for ethnic people to explore and represent their (ethnic) identities. Building on the scholarship of Rey Chow, Jack Halberstam, and several Asian American literary critics, I argue that publishers and a range of readers often demand autoethnographic representations?i.e. cultural representations that correct or disrupt mainstream narratives?from ethnic authors. The dissertation?s introductory chapter elaborates on these expectations as part of what I call ethnographic entanglements, or the biopolitical situation of artists who must ethnographize themselves in order to be published. The remaining chapters focus on workarounds produced by authors and artists, frustrating readers who expect cultural representation. Drawing attention to how South Asian diasporic authors have addressed ethnographic demands in their use of child characters, Chapter 2 takes up Bapsi Sidhwa?s novel An American Brat to explore the formal potential of the ?brat? as an uncooperative figure allowing authors to circumvent readerly expectations of ethnography. Chapter 3 considers ?identity confusion? among second-generation immigrants in the context of the cultural self-consciousness demanded of ethnic youth and analyzes fictional representations of a distinctive kind of nightclub event, the ?desi party,? from the 1990s that offered temporary relief from the everyday demands of legible self-representation. Chapter 4 argues that the Indian Canadian standup artist Russell Peters produced a form of accent comedy that rejected both the performance of stereotypical ethnic identity thrust upon brown actors on the screen throughout the 1990s and the alternative task of providing an autoethnographic corrective. The coda to the dissertation returns to the question of the ethnographic packaging of South Asian American print and media narratives and the ways in which contemporary media convergence allows artists to de-privilege ?outsider? audiences. %D 2016 %K "Ethnographic Entanglements," Autoethnography, "Burden of Representation," "Politics of Representation," Workarounds, "South Asian American" %I University of Pittsburgh %L pittir29254 %A Joseph / B McCaffrey %T Mental Function and Cerebral Cartography: Functional Localization in fMRI Research %X This dissertation advances a novel philosophical account of the relationship between brain mapping and cognitive theorizing in functional magnetic resonance imaging (fMRI) research. I argue that testing hypotheses about human cognition and behavior with fMRI critically depends on bridging assumptions about how cognitive functions map onto the brain. I demonstrate that in light of recent theoretical (e.g., network thinking) and methodological (e.g., resting state fMRI) advancements, these bridging assumptions are often problematic. I conclude that at this stage of scientific development, fMRI research should focus on articulating and testing new bridging assumptions rather than testing psychological theories. %D 2016 %K Philosophy Neuroimaging Philosophy of Science Brain Mapping fMRI %I University of Pittsburgh %L pittir29153 %A Travis J Hurst %T Astrophysical Probes of Dark Matter %X In the ?CDM model, ? 26% of the matter-energy content of the Universe is in the form of an unidentified Cold Dark Matter. Observations indicate that the Dark Matter is a new exotic particle not accounted for in the Standard Model of particle physics. Identifying the Dark Matter particle is one of the most pressing problems in cosmology and particle physics. In this thesis we investigate several possible astrophysical signatures of Dark Matter: Dark Matter annihilations in cold White Dwarfs provide a source of luminosity that could halt their cooling. This effect can be used to constrain the Dark Matter density local to the White Dwarf. In the case of the coldest White Dwarf in a Globular Cluster, a constraint on the maximum Dark Matter content is derived. Globular Clusters do not appear to have Dark Matter halos today, but could have possessed them in the past. We investigate whether Globular Clusters could have lost their halos through multi-body gravitational interactions? we find that this scenario is unlikely. Finally, we explore the effects of Asymmetric Dark Matter on stellar evolution. Asymmetric Dark Matter can alter the transport of energy in the cores of stars. We show that this has potentially observable effects on low mass Main Sequence and post-Main Sequence stars. Our main conclusion is that astrophysical observations can potentially rule out some Dark Matter models. On the other hand, if the properties of the Dark Matter particle become known, then its astrophysical effects must be taken into account when evaluating observations. %D 2016 %K Dark Matter %I University of Pittsburgh %L pittir29009 %A Darcy Mandell %T Autonomic Stress Recovery and Habituation in Migraine %X Migraine sufferers have been characterized as particularly ?stress-sensitive,? and they tend to experience headaches following periods of increased psychological stress. The biological mechanisms responsible for this unusual stress response are poorly understood. In particular, it is unclear why migraineurs suffer from headaches in response to stress while others do not. Several theories have implicated autonomic dysfunction?and in particular, sympathetic hyper-reactivity to stress? as a way of explaining increased psychological stress reactivity found in migraineurs. Despite efforts to capture these patterns in laboratory stress settings, researchers have been largely unable to provide reliable evidence of autonomic hyper-reactivity to acute stress in this population. The present study pursued the alternative hypothesis that migraineurs have prolonged autonomic recovery following stress, along with decreased habituation to repeated stressors. We compared patterns of autonomic stress recovery and habituation in a sample of young adult migraineurs and healthy controls using a repeated intermittent stressor task and separate measures of sympathetic and parasympathetic function. In contrast to our predictions, which posited sustained sympathetic engagement and a possibly blunted parasympathetic rebound upon stressor cessation, we found that individuals with episodic migraine were largely indistinguishable from controls in their sustained stress responses. Unexpectedly, migraineurs demonstrated consistently stronger vagal withdrawal to repeated stressors than healthy controls. They also showed evidence of greater cognitive and emotional reactions than controls, primarily in the form of higher subjective stress and more negative appraisals of the stressor task itself. While this is not the first study to report altered parasympathetic function in migraineurs, it is one of only a handful to assess these patterns in the context of acute laboratory stress exposure, and the only known study to report exaggerated parasympathetic withdrawal alongside reports of increased subjective stress and negative stress appraisals. %D 2016 %K Stress, Migraine, Autonomic, Sympathetic, Parasympathetic %I University of Pittsburgh %L pittir28920 %A David Burstein %T CHALLENGES IN RANDOM GRAPH MODELS WITH DEGREE HETEROGENEITY: EXISTENCE, ENUMERATION AND ASYMPTOTICS OF THE SPECTRAL RADIUS %X In order to understand how the network structure impacts the underlying dynamics, we seek an assortment of methods for efficiently constructing graphs of interest that resemble their empirically observed counterparts. Since many real world networks obey degree heterogeneity, where different nodes have varying numbers of connections, we consider some challenges in constructing random graphs that emulate the property. Initially we focus on the Uniform Model, where we would like to uniformly sample from all graphs that realize a given bi-degree sequence. We provide easy to implement, sufficient criteria to guarantee that a bi-degree sequence corresponds to a graph. Consequently, we construct novel results regarding asymptotics of the number of graphs that realize a given degree sequence, where knowledge of the aforementioned enumeration result will assist us in constructing realizations from the Uni- form Model. Finally, we consider another random directed graph model that exhibits degree heterogeneity, the Chung-Lu random graph model and prove concentration results regarding the dominating eigenvalue of the corresponding adjacency matrix. We extend our analysis to a more generalized model that allows for intricate community structure and demonstrate the impact of the community structure in networks with Kuramoto and SIS epidemiological dynamics. %D 2016 %K degree sequence, directed graph, Chung-Lu, random graphs, contingency table, digraph %I University of Pittsburgh %L pittir29302 %A Katherine Anne Kidd %T THE (CLASS) STRUGGLE IS REAL(LY QUEER): A BILATERAL INTERVENTION INTO WORKING-CLASS STUDIES AND QUEER THEORY %X Class issues have become more prescient in media and literary studies, as the gap between the upper and lower classes has widened. Meanwhile, scholars in the growing field of working-class studies attempt to define what working-class literature is by formulating criteria for what kinds of people count as working-class, based on moralism supposedly held by working-class people. Usually, working-class people are envisioned as white, heteronormative, and dignified legitimate workers. Working-class studies seldom engages with queer theory or conventional forms of identity politics. Conversely, queer theorists often reference class, but abandon it in favor of other topics. This dissertation argues that working-class studies needs a queering, and queer theory needs a more pointed class analysis. I begin with a close look at queer people of color in media, first revisiting the 1990 documentary film Paris is Burning. I examine how failure relates to the lives of the queens portrayed, and how class complicates failure?s potential resistance, and how drag performances comprise highly class-critical social commentary. Ru Paul?s Drag Race and the photography of Pittsburgh artist Caldwell Linker are compared with the film. In my second chapter, I analyze the television series Breaking Bad and argue that the limited scope of working-class character in working-class studies obscures the exploitation of non-normative Others by Walter White, who is not a working-class hero, but a high capitalist rising to power in the economy of illicit drug manufacturing. In my last chapter, I explore the issues of class and abjection in three contemporary novels, Bastard out of Carolina, by Dorothy Allison, The Beans of Egypt, Maine, by Carolyn Chute, and Push, by Sapphire. This chapter asks questions about extremes of class and queer failure, and the impact of intersectionality on the ostensible resistance in claiming failure and indignity argued in contemporary queer theories that take up abjection. %D 2016 %K Class, work, queer, drag, abjection, failure, race, morality, drugs %I University of Pittsburgh %L pittir29339 %A William J Kowallis %T Computational Studies of Biological Ion Channels %X Structural and functional characteristics of three biological ion channels were studied. First, current-voltage characteristics were calculated using non-equilibrium molecular dynamics (NEMD), Brownian Dynamics (BD), and Poisson-Nernst-Planck theory (PNP) for the ion channel alpha-hemolysin, comparing and contrasting the results among each other and experimental values. Results show that all methods produce qualitatively accurate results in terms of selectivity, where quantitave accuracy increases with more atomistic detailed simulation methodology. Results from NEMD simulations show that a specific location within the pore may account for selectivity of the channel, and point mutation of one residue (lys147) would likely result in a change in selectivity. The residue was mutated to serine, structural viability was tested with all-atom molecular dynamics, and PNP and BD calculations of the mutated structure show that selectivity is changed via this mutation. Second, pH dependence of current-voltage characteristics of alpha-hemolysin were studied using PNP and compared to experimental data, applying pH-dependent charge states determined from calculated pKa values for all titratable residues in the structure. Results indicate that altered charge states of both internal and external residues most accurately described experimental data. Third, Poisson-Boltzmann and (PNP) calculations were performed to determine the functional state of the crystallographic structure of the mitochondrial channel VDAC1, finding that the current-voltage properties indicated that structure represents the open conformation of the channel. Calculations were repeated using mutant channel structures, reflecting experimental results showing changes in selectivity. Two proposed gating motions of the channel were explored, with calculated current-voltage results from the gated structures not reflecting experimental changes in current-voltage properties, suggesting that the two proposed gating methods were not correct for this channel. Last, Poisson-Nernst-Planck calculations were performed of the influx of ferrous ions (Fe2+) into human H-ferritin protein. All-atom molecular dynamics simulation was used to determine both the equilibrium pore structure as well as the diffusion constant profile through the channel, using Force-Force Autocorrelation Function methodology. Results show relatively slow (compared to other channels) transit of Fe2+ ions through the channel due to greatly reduced internal diffusion constants (from bulk values) within the ferritin pore as well as low physiological concentration of Fe2+. %D 2016 %K ion channels, poisson-nernst-planck, brownian dynamics, molecular dynamics, alpha-hemolysin, ferritin, VDAC %I University of Pittsburgh %L pittir29172 %A Jennifer/S Jhun %T A Defense of Equilibrium Reasoning in Economics %X Critics both within and outside of philosophy have challenged economics wholesale as unscientific. In particular, economics seems unable to predict future events because it relies on assumptions like equilibrium conditions, which stipulate that the economy tends to stay in its current state absent external forces. The popular background view that gives rise to this criticism is that the job of science is to uncover laws of nature, by appeal to which we can determine (usually deductively) the future behavior of a dynamical system as it evolves. I argue that lawlike statements in economics have a very different role than this: they provide a means of understanding in terms of how efficient a particular system is. This account is more faithful to the history and the practice of economics. Perhaps surprisingly, it also accounts better for the explanatory power of some laws of physics. By reinterpreting ceteris paribus assumptions, and equilibrium assumptions more generally, as tools both for articulating constraints on a system as well as for identifying opportunities for a system, I am able to take into consideration the ways in which both engineers and policy makers aim to design or test such complex systems for stability. Macroscopic properties such as stability cannot be reduced to details about the individual atoms that make up bulk material or the individual agents that make up the economy. Yet, the behaviors of the micro-constituents and of the macroscopic aggregate are related. In order to address this lacuna between the micro and the macro, I explore the possibility of exploiting newer methods in the material sciences, namely multi-scale modeling, that have been useful in talking about these interesting and desirable macroscopic properties. These methods use not one but multiple models at different temporal and spatial scales to describe a system, without prioritizing any particular one. Given the substantial methodological and formal analogies between thermodynamics and economics, the success of the multi-scale framework in the former suggests it will be similarly useful for the latter. %D 2016 %K Philosophy of Science, Philosophy of Economics, Modeling, Idealization, Ceteris Paribus, Equilibrium %I University of Pittsburgh %L pittir29164 %A DONGDONG LI %T THE EMERGENCE OF WALLED TOWNS AND SOCIAL COMPLEXITY IN THE TAOJIAHU-XIAOCHENG REGION OF JIANGHAN PLAIN CHINA %X The especially early emergence of Neolithic walled towns in the Jianghan Plain is widely used as an indicator of social complexity. In recent decades, research on walled towns has focused on their role in the origin of Chinese civilization and in the formation of early states in China. Several models have been suggested to explain the emergence of walled towns: inter-regional conflicts between the Central Plain and the Jianghan Plain, intra-regional conflicts among walled towns in the Jianghan Plain, and control of flooding in the Neolithic period. The trajectories of developing social complexity of these earliest walled towns and the relationships that existed among them have not previously been systematically investigated from the perspective of demographic distributions. The full-coverage systematic regional survey presented here included two of the earliest walled towns in the Jianghan Plain: Taojiahu and Xiaocheng. It was designed to illuminate their social trajectories and by extension those of their counterparts elsewhere in the Jianghan Plain and areas adjacent to it. The regional survey revealed spatial and temporal variations in the settlement patterns of an area of 58 km2 from 3900 BCE to 600 CE. Population distribution patterns were documented for each period in this time span to investigate the dynamic forces behind social and settlement changes. Different approaches to understanding the emergence of early walled towns were evaluated through the analysis of population distribution and its relationships to environmental variables. The conclusions of the research include the following. First, the emergence of the Taojiahu and Xiaocheng walled towns was a process of the in situ population increase from initial small communities rather than pulling together people spread throughout the landscape in different communities. Second, throughout their histories, Taojiahu and Xiaocheng contained the vast majority of the population of their territories; there was little or no hinterland population or settlement hierarchy around them. Third, economic activities and the development of economic interdependence involving both subsistence and non-subsistence products were of particular importance at Taojiahu and Xiaocheng. Fourth, Xiaocheng might have served as an economic outpost of Taojiahu focused on the production of rice and other goods. %D 2016 %K WALLED TOWNS, SOCIAL COMPLEXITY, JIANGHAN PLAIN, XIAOCHENG, TAOJIAHU %I University of Pittsburgh %L pittir29347 %A HAKKI LEE %T ESSAYS ON LABOR AND PRODUCT MARKETS %X This dissertation is a collection of three essays on labor economics and industrial organization. In the first essay, I study how and to what extent labor market frictions, which are defined as the inability to costlessly find jobs or move between jobs, affect workers' schooling decisions. In order to study this link, I use an on-the-job search model. Consistent with the data, the model economy predicts that a higher job-to-job transition rate increases the opportunity cost of a college education, reducing the incentives for schooling. Instead, a higher job separation rate decreases the opportunity cost, leading to more schooling. In addition, a higher job finding rate increases employment duration, which can help college educated workers enjoy higher skill prices for a longer time and lead to more investment in schooling. In the second essay, I explore whether the number and types of people who attend college affect the college wage premium, which is defined as the wage of college graduates relative to high school graduates. I estimate the return to schooling by exploiting all of the variation or only the exogenous variation in educational attainment as the instrumental variable. The result reveals that composition effects account for nearly one half of the observed return to schooling. In addition, I find strong evidence that sudden short-run changes in educational attainment lowered education wage premiums for the affected cohorts, but only weak evidence that long-run trend changes in educational attainment lowered education wage premiums. The third essay analyzes a monopolistic supplier's optimal decision of input prices when two downstream sellers simultaneously choose their advertisement efforts and their output levels. The independent advertisement decision by each seller causes the free-rider problem by its rivals. The supplier uses price-discrimination to alleviate the free-riding problem associated with the advertisement decision. Therefore, allowing price-discrimination may increase aggregate output-- and social surplus-- the reverse of the welfare implications in the previous literature. %D 2016 %K Labor Market Friction, Schooling Decision, College Wage Premium, Composition Effect, Price Discrimination, Advertisement %I University of Pittsburgh %L pittir28132 %A Conor Lennon %T Essays in Empirical Labor Economics %X This dissertation focuses on furthering our understanding of how labor markets work. Each essay sheds light on how individual, governmental, and institutional factors combine to determine economic outcomes within specific labor markets. The first chapter uses the Affordable Care Act's employer mandate to ask if variation in health expenses at the individual level can affect labor market outcomes. Using a difference-in-difference estimation strategy the essay shows that higher cost workers face lower wages and increased unemployment as a result of the employer mandate. Specifically, each dollar of annual medical expenses is associated with a $0.30 to $0.40 wage penalty. The negative changes in labor market outcomes for higher cost workers highlight that firms face the same incentives as an insurer to limit access and price discriminate. The second chapter focuses on why antebellum slave prices were higher in the deep South. Existing research suggests price differences were due to productivity differences. This essay shows that the chance of escape was a complementary source of price differences. To do so, the paper examines the consequences of the Fugitive Slave Act of 1850. The Act was designed to reduce the chance of successful escape and the paper shows it caused slave prices in northern slave states to increase by between 15 and 30 percent relative to the deeper South. In 1854, reinstated loopholes reverse the effects of the Act. These findings are backed up by advertisements for runaways collected from antebellum newspapers. The third chapter uses a correspondence study to examine how employers view degrees earned online. Many major universities in the US have online programs that claim to be comparable to a traditional degree. The essay uses fictional resumes to apply for real jobs but randomly varies the degree held. Estimates suggest employers do not value these programs equally: After controlling for co-variates a traditional degree-holder is twice as likely to be called for interview compared to an individual with an online degree. %D 2016 %K Lennon, dissertation, Economics %I University of Pittsburgh %L pittir27734 %A Martin Marinos %T FROM SOCIALIST HUMANISM TO NEOLIBERAL POPULISM: TWO REGIMES OF MEDIA IN LATE AND POST-SOCIALIST EUROPE %X This dissertation explores the central role media played in the redefinition of socialist culture following Stalin?s death and explains how Bulgaria?s transition from socialist to post-socialist media has hindered the emergence of a democratic civil society. Through a multi-method approach that engages with both primary sources in print and interviews with local journalists, politicians, and media experts, this project uses Bulgaria as a case study in order to offer a historical account of the post-1989 (neo)liberalization of media and its role in the proliferation of xenophobic, far-right discourses. The first part of the project seeks to explain how and why mass communication and especially the new medium of television intervened in the cultural and political changes that accompanied post-Stalinist socialism. I trace how, starting in the 1960s, high culture became a major feature of Bulgarian media. Through the television screen, opera, ballet, poetry and theatre entered the Bulgarian home. The goal of this ambitious endeavor was first to assist the population, rural for the most part, to achieve the socialist humanist vision of a holistically developed personality and second, to frame socialist consumption not simply as the accumulation of material goods, but also as the enjoyment of high cultural products. The second part of the dissertation, examines the construction of the media sphere after 1989. It shows that the conceptualization of civil society as separate from the sphere of the economy obscures the multitude of ways through which neoliberal capitalism subsumes mass media and corrupts the public sphere. The dissertation argues that one of the most detrimental outcomes of this degenerated media field is the ongoing growth of the far-right political parties and movements. %D 2016 %K political economy of media, neoliberalism, socialist humanism, television, Bulgaria, Eastern Europe %I University of Pittsburgh %L pittir28017 %A Carl N Keiser %T GROUP COMPOSITION IN SOCIAL SPIDERS: COLLECTIVE BEHAVIOR, KEYSTONE INDIVIDUALS, AND BACTERIAL TRANSMISSION DYNAMICS %X The global success of animal societies is due, in part, on the ability of groups of animals to perform collective behaviors that would be unachievable by a single individual. One major determinant of collective behavior is the composition of different types of individuals within the group. For example, individuals often differ consistently in their behavioral traits and the tasks in which they participate, and a group?s composition of individuals expressing different behavioral phenotypes (i.e., ?personalities?) can be a fundamental driver of collective behaviors. Though, the same compositions that excel in one aspect of collective behavior may also incur costs in other, opposing patterns of social interactions. Here, I use the social spider Stegodyphus dumicola to test how group personality composition explains patterns of collective behaviors, social interactions, and bacterial transmission. Stegodyphus dumicola is an African social spider that lives in colonies of several dozen to many hundreds of individuals whose collective behaviors are determined by the composition of ?bold? and ?shy? spiders present in the colony. I found that group personality composition is a more important predictor of the execution of collective behaviors than more conspicuous colony traits like group size. Then, using social network analyses I found that colony contact networks are disassortive, where individuals preferentially interact with others of opposing personality types. Using experimental exposures to a fluorescence-transformed cuticular bacterium (Pantoea sp.), I found that horizontal bacterial transmission is predominantly directional, occurring more so from ?bolder? to ?shyer? spiders. Thus, it could be reasoned that animal groups containing diverse personality types may experience augmented success during collective tasks, but may also incur costs in the context of horizontal bacterial transmission. Taken together, it appears that personality compositions may impose constraints on the social organization of animal societies. %D 2016 %K Bacterial transmission Collective behavior Social spider Stegodyphus dumicola %I University of Pittsburgh %L pittir28354 %A Mengchen Huang %T LOCAL PROBE INVESTIGATION OF EMERGENT PHENOMENA IN COMPLEX OXIDE HETEROINTERFACES %X Complex oxide heterointerfaces exhibit rich physics as well as many veiled puzzles. LaAlO3/SrTiO3 (LAO/STO) is one of the prototype of such heterointerfaces. In 2004, Ohtomo and Hwang first reported a conducing interface emerged between perovskite oxide insulators LaAlO3 and SrTiO3. Following this seminal discovery, many emergent phenomena like metal-insulator transition, piezoresponse, superconductivity, magnetism, strong spin-orbit coupling and coexistence of superconductivity and magnetism were reported in the fascinating LAO/STO system. However, the origin of the conducting interface is still the subject of intense debate, and the physics behind these emergent phenomena remains a wild space to be explored. My Ph.D. study focused on the emergent phenomena in LAO/STO by using ?local probes? ? nanostructures created by conductive atomic force microscope (c-AFM) lithography and the AFM itself. I used piezoresponse force microscope (PFM) to study the electromechanical response in LAO/STO and developed a high-resolution, non-destructive PFM imaging technique to visualize nanostructures at LAO/STO interface. The results indicate that the PFM signal is related to a carrier density mediated interfacial lattice distortion, and surface adsorbates can affect the PFM signal via coupling to the electrons at the interface. I integrated graphene on LAO/STO, created field-effect devices in graphene/LAO/STO and collaborated with Dr. Giriraj Jnawali to investigate the transport properties. The high quality single layer graphene on LAO/STO exhibited the half-integer quantum Hall effect and room temperature weak antilocalization behavior. I performed transport measurements in (110)-oriented LAO/STO to investigate anisotropic quasi one-dimensional superconductivity in nanowires. Based on the results I proposed a plausible explanation related to the Lifshitz transition and anisotropic band structures of nanowires in (110)-oriented LAO/STO. Co-worked with Dr. Keith Brown, I studied the conductivity switching of LAO/STO interface by solvent immersion and light exposure. We reported a fully reversible, more than four order of magnitude conductance modulation and proposed a surface protonation model. Besides these main research projects that are discussed in this thesis, I also contributed in many other research projects by optimizing the proper sample preparation methods, performing nanostructures fabrication and characterization, and being actively involved in the measurements, data analysis and manuscript preparation. %D 2016 %K local probes, complex oxides, emergent phenomena %I University of Pittsburgh %L pittir26863 %A Lauren Marbella %T NMR Characterization of Metal Nanoparticle Formation, Structure, and Performance %X Analytical methods with high chemical, spatial, and temporal resolution are crucial to understanding and controlling nanoparticle properties as well as translating these discoveries into society-shaping technologies. However, approaches for the characterization of solid inorganic materials and solution phase molecular species are often disparate. One powerful technique to address this gap is nuclear magnetic resonance (NMR) spectroscopy, which can facilitate routine, direct, molecular-scale analysis of nanoparticle formation and morphology in situ, in both the solution and solid phase. This dissertation describes the application of NMR to study metal nanoparticle formation, structure, and performance with unprecedented chemical detail. In Chapter 1, the dissertation is introduced by highlighting recent developments in the application of NMR spectroscopy to the study of noble metal nanoparticle growth, surface chemistry, and physical properties. In Chapter 2, the formation of bimetallic Au-Cu nanoparticles is studied by solution NMR techniques (in conjunction with mass spectrometry and X-ray absorption spectroscopy) to reveal the chemical mechanisms driving metal atom distribution in the final particle. Building on hypotheses tested in Chapter 2, Chapter 3 describes one of the first syntheses of Au-Co alloys at any length scale with fully tunable compositions. The magnetic and optical properties of the resulting Au-Co nanoparticle alloys are evaluated with NMR and photoluminescence spectroscopies, respectively, and are found to exhibit both high relaxivity and high brightness, making them ideal bimodal imaging agents. Building on these studies of nanoparticle formation, NMR spectroscopy is then used to study final particle structure and physical properties. In Chapter 4, NMR is used to probe ligand shell architectures on phosphine-terminated Au nanoparticles and allow the identification of 31P-197Au coupling for the first time in nanoparticle systems ? a feature which may ultimately be used to study previously NMR-inaccessible nuclei such as 197Au. This utility is highlighted in Chapter 5 where the impact of local and global crystallographic environments in Au nanoclusters are probed using 31P NMR. In Chapter 6, solid-state NMR is used to characterize the emergence of metallic behavior in degenerately doped Cu2-xSe nanoparticles as well as to reveal the structural evolution of the particle as a function of this doping. %D 2016 %K NMR, metal nanoparticle %I University of Pittsburgh %L pittir29096 %A David Klinowski %T Non-Monetary Incentives for Economic Behavior %X This dissertation studies the effectiveness of various non-monetary incentives in encouraging economically-relevant behavior. Chapter 1 looks at the provision of information about others? donations as a way to increase contributions to charity. Results from a laboratory experiment show that when individuals donate out of image concerns, informing them in the early stages of a solicitation campaign about small contributions from others increases the extensive and intensive margins of giving. A central contribution is to demonstrate that the timing of the information?and not just its content?greatly affects donation behavior. Chapter 2 delves into the recent and booming phenomenon of crowdfunding to study the effect of goal setting on charitable giving. Using a dataset from a nation wide crowdfunding platform, it is shown that donors make larger contributions, at a faster pace, in order to be the ones who reach the recipients? fundraising targets. Results indicate that the behavior is motivated by donors deriving a heightened feeling of impact during completion. The Chapter thus provides insight into what mechanisms work and why in the understudied environment that is crowdfunding for charity. Finally, Chapter 3 shifts gears and studies the exertion of effort in the workplace. It explores in a laboratory experiment whether giving workers autonomy through delegation of contract choice intrinsically motivates effort. The Chapter finds a null result under several specifications, casting doubt on an intrinsic link between autonomy and motivation of effort. Altogether this dissertation contributes to the understanding of how and why non-monetary incentives serve?or fail to serve?as powerful means of directing economic behavior. %D 2016 %K Charitable giving, behavioral economics, experimental economics %I University of Pittsburgh %L pittir28545 %A Daniel Lamont %T Optical and Mechanical Characterization and Analysis of Nanoscale Systems %X Optical and Mechanical Characterization and Analysis of Nanoscale Systems ABSTRACT Daniel N. Lamont, Ph.D. University of Pittsburgh, 2016 This thesis discusses research focused on the analysis and characterization of nanoscale systems. These studies are organized into three sections based on the research topic and methodology: Part I describes research using scanning probe microscopy, Part II describes research using photonic crystals and Part III describes research using spectroscopy. A brief description of the studies contained in each part follows. Part I discusses our work using scanning probe microscopy. In Chapter 3, we present our work using apertureless scanning near-field optical microscopy to study the optical properties of an isolated subwavelength slit in a gold film, while in chapter 4 atomic force microscopy and a three point bending model are used to explore the mechanical properties of individual multiwall boron nitride nanotubes. Part II includes our studies of photonic crystals. In Chapter 6 we discuss the fabrication and characterization of a photonic crystal material that utilizes electrostatic colloidal crystal array self assembly to form a highly ordered, non closed packed template; and in Chapter 7 we discuss the fabrication and characterization of a novel, simple and efficient approach to rapidly fabricate large-area 2D particle arrays on water surfaces. Finally, in Part III we present our spectroscopic studies. In Chapter 9 we use fluorescence quenching and fluorescence lifetime measurements to study electron transfer in aggregates of cadmium selenide and cadmium telluride nanoparticles assemblies. Chapter 10 features our work using the electronic structure of zinc sulfide semiconductor nanoparticles to sensitize the luminescence of Tb3+ and Eu3+ lanthanide cations, and Chapter 11 presents our recent work studying photo-induced electron transfer between donor and acceptor moieties attached to a cleft-forming bridge. %D 2016 %K nanoscience, spectroscopy, "photonic crystals", "charge transfer", "energy transfer" %I University of Pittsburgh %L pittir29294 %A CHONG LIU %T POSTSYNTHETIC CONTROL OF FUNCTIONALITY AND POROSITY IN METAL-ORGANIC FRAMEWORKS USING COVALENT, COORDINATIVE, AND ELECTROSTATIC INTERACTIONS %X Metal-organic frameworks (MOFs) are a versatile family of hybrid materials. Research attention and industrial interest have focused on MOFs because of their diverse properties and their tunable host-guest interactions/chemistry. MOFs are intrinsically porous, and the porosity underlies many of their properties and applications. Methods for systematically controlling MOF porosity and functionality provide a gateway to new frontiers of MOF research. In this dissertation, I present four research projects aimed at fine-tuning MOF porosity and functionality in order to create materials with functionally- and structurally-complex pore environments. Specifically, in Chapter 2, a versatile and nearly quantitative method is presented to covalently modify MOFs, especially mesoporous MOFs, with organic and biological molecules via strain-promoted click chemistry. In Chapter 3, a sequential postsynthetic ligand exchange protocol is presented for introducing up to three orthogonal functional groups into the MOF pore space. Subsequently, a new fluorescence-based method is implemented to experimentally reveal the macroscopic distribution of functional groups within individual MOF crystals by introducing fluorophore and quencher molecules. In Chapter 4, construction of porosity gradients within individual mesoporous MOF crystals via ligand exchange-based partial pore expansion is described. The product MOF crystals, bearing a hierarchical distribution of domains having differential porosity, are used to organize nano-sized molecules in a heterogeneous fashion. In Chapter 5, a series of isoreticular rare earth MOFs having the well-known fcu topology is introduced. Based on their anionic nature, cation exchange experiments are applied to incorporate chromophore guest molecules. One of the incorporated dye compounds is used as an antenna molecule to sensitize Yb3+ in the MOF. The research described represents a significant step forward in the development of MOF chemistry and will enable new studies that focus on using MOFs as platform materials for precisely organizing complex molecules and nanoscale materials in three-dimensional space. %D 2016 %K metal-organic frameworks, postsynthetic modification, ligand exchange, porosity gradient, cation exchange, lanthanide photoluminescence, %I University of Pittsburgh %L pittir28994 %A Natthapong Liamcharoen %T Performance analysis of a proposed hybrid optical network %X This dissertation discusses a novel Hybrid Optical Network (HON) that can provide service differentiation based on traffic characteristics (i.e., packet, burst, and long-lived flow) with QoS guarantee not only in network layer, but also in physical layer. The DHON consists of sophisticated edge-nodes, which can classify, monitor, and dynamically adjust optical channels in the core layer as traffic variation. The edge nodes aggregate traffic, identifying end-to-end delay by ingress queuing delay or burst timeout. The network can estimate number of channels by arriving traffic intensity and distribution with estimated upper-bound delay. The core layer employs two parallel optical switches (OCS, OBS) in the same platform. Thanks to the overflow system, the proposed network enhances utilization with fewer long distance premium channels. The premium channel can quickly handle burst traffic without new channel assignment. With less overprovisioning capacity design, the premium channel enhances utilization and decrease number of costly premium channels. This research also proposes mathematic models to represent particular DHON channels (i.e., circuit, packet, and burst). We employ method of moments based on overflow theory to forecast irregular traffic pattern from circuit-based channel (i.e., M/M/c/c) to overflow channel, in which G/G/1 model based on Ph/Ph/1 matrix can represent the overflow channel. Moreover, secondary channel supports packet-based traffic over wavelength channel with two service classes: Class I based on delay sensitive traffic (i.e., long flow) and Class II for non-delay sensitive traffic (e.g., best effort). In addition, mixture of traffic in the wavelength channels is investigated based on M/G/1 and M/G/2 with specific service time distribution for particular class. Finally, we show our DHON based on (O-O-O) switching paradigm has improved the performance over typical (O-E-O) switching network architecture based on NSF topology. %D 2016 %K "hybrid optical network", "performance analysis", overflow, "QoS in optical network" %I University of Pittsburgh %L pittir29019 %A Nina Leezenbaum %T Posture Development and Vocalization Production in Infants at Heightened Risk for Autism Spectrum Disorder %X During the first 14 months of life, typically-developing (TD) infants demonstrate rapid advances in posture and vocal development. There is a striking synchronization in the emergence of important milestones in these two domains (e.g., Oller, 1980; Piper & Darrah, 1994). For example, between the ages of 6 and 8 months, TD infants begin to sit independently without relying on external support for balance. Around this same time, they begin to produce syllabic vocalizations, which are defined as consonant-vowel (CV) sounds that are characteristic of babbling (e.g., [ba]; Oller, 2000). Between approximately 10 and 12 months, most TD infants can stand unsupported and say their first words, and by the time they reach 14 months they are walking long distances and producing nearly 20 words (Fenson et al., 1994). Although posture and vocal development were once considered unrelated, there is mounting evidence demonstrating a developmental pathway linking behaviors in these domains (see Iverson, 2010, for a review). Specifically, the emergence of new postures as well as increased postural control (i.e., the ability to maintain a stable posture over time) dramatically change infants? experiences with objects, people, and their own bodies in ways that are relevant not only for motor development (e.g., reaching and manual exploration; Rochat & Goubet, 1995), but for development in other domains (e.g., vocalizations; Yingling, 1981). One implication of this framework is that even seemingly small disruptions in posture development can have cascading effects that lead to delays outside of the motor domain (see Iverson, 2010, for additional discussion). %D 2016 %K autism spectrum disorders, posture development, and vocalization development %I University of Pittsburgh %L pittir29103 %A Timothy Licquia %T STUDYING THE MILKY WAY THROUGH ITS EXTRAGALACTIC ANALOGS %X The Universe is teeming with galaxies, which are complex structures with a broad range of colors, shapes, and sizes. We reside within the Milky Way (MW), just one example of this population, allowing us to study its stars and gas, and hence the physical mechanisms that shape galactic properties, in intimate detail. Unfortunately, our inside-out view prohibits us from measuring the MW's light as an integrated source, and perhaps more problematic is that dust in the interstellar medium shrouds most its light from view. Consequently, our knowledge of the global characteristics of the MW, and hence how fits among the galaxy population, has remained very limited. This thesis is focused on employing modern statistical techniques as well as preexisting Galactic and extragalactic data to overcome these challenges. A key aspect of this work is the development of a hierarchical Bayesian meta-analysis technique for better constraining properties of our Galaxy that have been studied by many authors and for which there exist extensive observational data, but may be prone to large systematic uncertainties. Applying this machinery yields new estimates of the MW's mass properties, including its star formation rate and total stellar mass, as well as its exponential disk scale length measured from both visible and infrared starlight. Additionally, this thesis presents a new method for identifying a sample of MW analog galaxies from extragalactic data in order to determine properties of our Galaxy that are all but impossible to observe directly. Herein, this technique yields new estimates of the MW's photometric properties ? i.e., its global color and luminosity at visible wavelengths, as measured from across cosmic distances. This work culminates with new, accurate investigations of how the MW fits into a variety of extragalactic contexts, which quantitatively demonstrates that in several ways the MW is not the prototypical spiral galaxy it was recently thought to be. Notably, the MW most likely lies in the sparsely populated ?green-valley? region of the galaxy color-magnitude diagram. Furthermore, comparing the MW to spiral galaxy scaling relations reveals that it is extraordinarily compact versus its peers. %D 2016 %K Milky Way, Astronomy, Galaxies, Galaxy Properties, Galaxy Evolution, Stellar Mass, Star Formation Rate, Disk Scale Length, Scaling Relations, Color Index, Absolute Magnitude, Luminosity, Eddington Bias, Inclination Reddening, Mixture Models, Meta-Analysis, Bayesian Model Averaging, Information Criteria, Principal Component Analysis, Multivariate Regression, Statistical Inference %I University of Pittsburgh %L pittir28351 %A Yong Li %T TIME FILTERS FOR NUMERICAL WEATHER PREDICTION %X The Robert-Asselin (RA) time filter combined with leapfrog scheme is widely used in numerical models of weather and climate. The RA filter suppresses the spurious computational mode associated with the leapfrog method, and successfully stabilizes the numerical solution. However, it also weakly dampens the physical mode and degrades the formal second-order accuracy of the leapfrog scheme to first order. There is a natural intention to reduce the time-stepping error as it has proven to be a substantial part of the total forecast error. Yet a new scheme must be non-intrusive, i.e., easily implementable in legacy codes in order to avoid significant programming undertaking. The object of this work is the development, analysis and validation of novel Robert-Asselin type time filters, addressing both of the above problems. Specifically, we first propose and analyze a higher-order Robert-Asselin (hoRA) type time filter. The analysis reveals that the filtered leapfrog scheme exhibits second- or third-order accuracy depending on the filter parameter. We then investigate its behavior when used in conjunction with the implicit-explicit integration, which is commonly used in weather and climate models to relieve the severe time step restriction induced by unimportant high-frequency waves. Next, we build a framework of constructing a family of hoRA filters with any pre-determined order of accuracy. In particular, we focus on the fourth-order time filter. Finally, we present supplemental analysis for several filters developed by Williams. For each direction, we present comprehensive error and stability analysis, and perform numerical tests to verify theoretical results. %D 2016 %K numerical weather prediction, time filters, Robert-Asselin-Williams, higher-order Robert-Asselin, leapfrog scheme, Crank-Nicolson, G-stability %I University of Pittsburgh %L pittir28208 %A Zitao Liu %T Time Series Modeling of Irregularly Sampled Multivariate Clinical Data %X Building of an accurate predictive model of clinical time series for a patient is critical for understanding of the patient condition, its dynamics, and optimal patient management. Unfortunately, this process is challenging because of: (1) multivariate behaviors: the real-world dynamics is multivariate and it is better described by multivariate time series (MTS); (2) irregular samples: sequential observations are collected at different times, and the time elapsed between two consecutive observations may vary; and (3) patient variability: clinical MTS vary from patient to patient and an individual patient may exhibit short-term variability reflecting the different events affecting the care and patient state. In this dissertation, we investigate the different ways of developing and refining forecasting models from the irregularly sampled clinical MTS data collection. First, we focus on the refinements of a popular model for MTS analysis: the linear dynamical system (LDS) (a.k.a Kalman filter) and its application to MTS forecasting. We propose (1) a regularized LDS learning framework which automatically shuts down LDSs' spurious and unnecessary dimensions, and consequently, prevents the overfitting problem given a small amount of data; and (2) a generalized LDS learning framework via matrix factorization, which allows various constraints can be easily incorporated to guide the learning process. Second, we study ways of modeling irregularly sampled univariate clinical time series. We develop a new two-layer hierarchical dynamical system model for irregularly sampled clinical time series prediction. We demonstrate that our new system adapts better to irregular samples and it supports more accurate predictions. Finally, we propose, develop and experiment with two personalized forecasting frameworks for modeling and predicting clinical MTS of an individual patient. The first approach relies on model adaptation techniques. It calibrates the population based model's predictions with patient specific residual models, which are learned from the difference between the patient observations and the population based model's predictions. The second framework relies on adaptive model selection strategies to combine advantages of the population based, patient specific and short-term individualized predictive models. We demonstrate the benefits and advantages of the aforementioned frameworks on synthetic data sets, public time series data sets and clinical data extracted from EHRs. %D 2016 %K "Time Series", Forecasting, "Gaussian Process", "Linear Dynamical Systems" %I University of Pittsburgh %L pittir29316 %A Peter Adelman %T Transcriptionally Defined Subpopulations of Cutaneous Neurons: Effects of Nerve Injury and Regeneration %X Primary sensory neurons are responsible for cutaneous somatosensory transduction. These neurons can transduce mechanical force, temperature, and chemical sensitivity, which we perceive as pressure, position, heat, cold, itch, and pain. It has long been recognized that different afferents are specific for distinct modalities, but it has not been clear if afferent sensitivities represent a continuum or unique populations of afferents with common properties. I found that mouse dorsal root ganglion afferents can be clearly divided into groups by their transcriptional expression and that these groups share common modality sensitivities and functional properties. Further investigation revealed that the levels of some individual transduction channels may be an even more accurate way to track modality sensitivity, giving a potential molecular signature for function in murine afferents. These findings imply that recognized histological projection bands in the spinal cord (Substance P, CGRP, IB4, etc.) reflect subpopulations of afferents with unique properties that are projecting to unique areas of the spinal cord. This is relevant to sensory coding models, but may also be very important for the development of neuropathic pain after nerve injury. Nerve injury and regeneration alters mRNA and protein expression, and causes parallel changes in afferent properties. These functional changes in afferents could cause unusual activity in corresponding spinal cord circuits (e.g. a spinal cord circuit that is normally mechanically insensitive would receive mechanical input). I investigated this possibility and discovered population-specific regulation of transcripts. This included a mechanotransducer, Piezo2, which is upregulated in the small peptidergic subpopulation. Subsequent knockdown using Piezo2 siRNA reduced the number of mechanically sensitive afferents. These findings suggest that Piezo2 is necessary for mechanotransduction in injured afferents and could be responsible for induced neuropathic pain. %D 2016 %K nerve injury, DRG, regeneration, single cell qPCR, electrophysiology %I University of Pittsburgh %L pittir29706 %A Torrey Gallagher %T Averaging and fixed points in Banach spaces. %X We use various averaging techniques to obtain results in different aspects of functional analysis and Banach space theory, particularly in fixed point theory. Specifically, in the second chapter, we discuss the class of so-called mean nonexpansive maps, introduced in 2007 by Goebel and Japon Pineda, and we prove that mean isometries must be isometries in the usual sense. We further generalize this class of mappings to what we call the affine combination maps, give many examples, and study some preliminary properties of this class. In the third chapter, we extend Browder's and Opial's famous Demiclosedness Principles to the class of mean nonexpansive mappings in the setting of uniformly convex spaces and spaces satisfying Opial's property. Using this new demiclosedness principle, we prove that the iterates of a mean nonexpansive map converge weakly to a fixed point in the presence of asymptotic regularity at a point. In the fourth chapter, we investigate the geometry and fixed point properties of some equivalent renormings of the classical Banach space c0. In doing so, we prove that all norms on `1 which have a certain form must fail to contain asymptotically isometric copies of c0. %D 2016 %K Fixed point; functional analysis; demiclosedness; Opial; mean nonexpansive %I University of Pittsburgh %L pittir28750 %A Jen-Feng Hsu %T Cooling the Center-of-Mass Motion of a Diamond Nanocrystal in a Magneto-Gravitational Trap %X A magneto-gravitational trap for micro/nanometer sized diamagnetic particles, such as diamond nanocrystals, is tested and characterized. After exploring various other systems, such as a suspended graphene beam and an optical trap, this magneto-gravitational nanomechanical trapping system for diamond with nitrogen-vacancy (NV) centers presents unique advantages for experiments in fundamental quantum mechanics. Those include, for example, the generation of large quantum superposition states and tests of quantum gravity. Features are demonstrated for this system, such as stable and passive levitation from atmospheric pressure to high vacuum, low resonant frequencies and damping rates, and cooling of the center-of-mass motions to below 1 K. The construction of the trap, vacuum system, optics, and motion detection electronics are described in detail. %D 2016 %K Magnetic trapping, nanomechanical oscillator, feedback cooling, quantum ground state, and diamond nanocrystal %I University of Pittsburgh %L pittir29178 %A Liqing Gu %T DEVELOPMENT OF PROTEOMICS APPROACHES TOWARDS CHARACTERIZING OXIDATIVE MODIFICATIONS %X Mass spectrometry (MS) is an analytical technique allowing the investigation of a single protein or the entire complement of proteins from biomatrices for understanding attributes such as sequences, modifications, structures, abundances and interactions. Protein oxidative modifications, such as carbonylation and cysteine reversible oxidations, have important roles in physiological processes, including redox signaling, homeostasis, enzymatic catalysis and protein degradation. MS-based redox proteomics can identify and quantify oxidized protein modifications within the proteome. However it is challenging to globally investigate cysteine reversible modifications, due to the low abundance (~ < 1%) and diversity (e.g., S-nitrosylation, S-glutathionylation, sulfenic acid, disulfide bonds) of these modifications. Novel proteomics approaches are needed to better understand cysteine-related redox signaling and oxidative stress in disease. This dissertation presents studies of protein oxidative modifications using MS-based approaches. First, proteomics methodologies to study protein carbonylation and cysteine reversible modifications are reviewed, including the relevant applications in neurodegenerative disease. Next, a MS-based characterization of a whole protein is described by studying oxidative modifications generated through treatment of a model protein with oxidants. Novel methods towards characterizing endogenous cysteine oxidations in disease are then presented, including inexpensive and high-throughput approaches. The first approach utilizes low-cost isotopic dimethyl peptide labeling for comparing two proteome samples. This methodology has the ability to isolate and quantify total cysteinyl peptides or oxidized cysteinyl peptides from complex samples, and is employed to characterize the liver proteome of an Alzheimer?s disease (AD) mouse model. The second approach is cysteine-selective combined precursor isotopic labeling and isobaric tagging (cysteine-selective cPILOT), which incorporates isobaric tags to achieve 12-plex multiplexing capability. Cysteine-selective cPILOT is used to isolate total cysteinyl peptides from liver proteins and S-nitrosylated peptides from brain proteins of an AD mouse model. Overall the novel proteomics approaches developed herein lower experimental costs and improve the throughput of cysteine redox proteomics studies. %D 2016 %K Quantitative Proteomics; Redox Proteomics; Oxidative Modifications %I University of Pittsburgh %L pittir27770 %A John Galante %T DISTANT LOYALTIES: WORLD WAR I AND THE ITALIAN SOUTH ATLANTIC %X This dissertation focuses on the impacts of World War I on Italian immigrant communities in the metropolitan areas of Buenos Aires, Montevideo and S?o Paulo. It uses the period of the war, and the diverse responses to the conflict by immigrants and their institutions of civil society, to highlight patterns of social cohesion and division within Italian overseas communities. It centers its analysis on a pro-war immigrant mobilization influenced by Italian nationalism and an anti-war movement shaped by working-class ideologies that emphasized Internationalism. It therefore considers the tangible connections and sentimental relationships that existed between Italian immigrants in South America and political and intellectual leaders in Italy, a nation-state that existed only from the mid-nineteenth century. Moreover, through its study of three immigrant communities, this dissertation reviews interactions and comparisons among those communities as they related to the pro- and anti-war efforts. It uses the transformative period of World War I to trace and track patterns of interaction and ?distant loyalties? in an area it refers to as the Italian South Atlantic. %D 2016 %K Latin American History, Migration History, Italian Immigration %I University of Pittsburgh %L pittir28973 %A Nathan Frink %T Dancing in His Head: The Evolution of Ornette Coleman's Music and Compositional Philosophy %X Ornette Coleman (1930-2015) is frequently referred to as not only a great visionary in jazz music but as also the father of the jazz avant-garde movement. As such, his work has been a topic of discussion for nearly five decades among jazz theorists, musicians, scholars and aficionados. While this music was once controversial and divisive, it eventually found a wealth of supporters within the artistic community and has been incorporated into the jazz narrative and canon. Coleman?s musical practices found their greatest acceptance among the following generations of improvisers who embraced the message of ?free jazz? as a natural evolution in style. Performers such as Jamaaladeen Tacuma, David Murray, Pat Metheny and John Zorn incorporated the techniques of spontaneous group improvisation and what Coleman described as ?harmolodic? organization into their own performance. This dissertation traces Coleman?s rise from relative obscurity to a place of greater celebrity in jazz and other musical circles. Coleman?s acceptance by the academy, other composers, notable jazz musicians, and the public is discussed in terms of how these shifts were made, and in what ways Coleman?who often felt victimized and mistreated by record company executives, critics, and musical establishments? transcended the gaps in his musical training in order to create his own distinctive and influential compositional style. This ?harmolodic theory? was then refined over a period of nearly 55 years. v The work discusses harmolodics in detail by building on the taxonomic models described by Ekkard Jost and Peter N. Wilson. It describes the variations in compositional practice as Coleman?s style evolved from 1980 until his death in 2015. The analysis supplements transcriptions and harmonic analyses with spectrograms and waveforms in order to illuminate specific areas of Coleman?s work. These graphic representations clarify observations made through transcription and reinforce some of the concepts embodied in Coleman?s unique philosophy of music. %D 2016 %K Coleman, Ornette, Denard, Denardo, Cortez, Jayne, Tacuma, Jamaaladeen, Allen, Geri, Metheny, Pat, Prime Time, Harmolodic, Harmolodics, Musical, Music, Composition, Free Jazz, avant-garde, black music, jazz, improvisation, Nix, Bern, %I University of Pittsburgh %L pittir27686 %A Jing He %T From Gene Expression to Behavior: A Study in Bacterial Cells %X Gene expression plays an important role in cell metabolism, motility, and replications. Using fluorescence microscopy, I found that the expression profile of LamB, an Escherichia coli outer membrane protein, is unimodal in cell cytosol. The bimodal distribution of lambda phage, which binds to LamB receptors on the outer membrane, should result from the heterogeneity in protein export and assembly processes. The study also estimates the burst-like LamB expression to have a mean bursting rate of 9.4 bursts per cell-cycle and a mean bursting number of 82 copies per burst. In another study on bacterial growth curves, I unexpectedly discovered that depletion of 4 amino acids (arginine, methionine, isoleucine, and glycine) can cause diauxie-like growth arrests, which last for 5 to 30 minutes depending on the amino acids used. As a quantitative measure of response times of gene regulations upon starvation, this technique could potentially provide a simple and robust means to determine the time constants in metabolic networks of a variety of bacteria. Normal expression of genes is also significant for robust bacterial swimming and chemotaxis. I observed strikingly that very small Vibrio alginolyticus cells are able to reorient by a pi-flip (180 degrees) in around 60 ms, but this ability is gradually lost when the cell size becomes larger. I also observed that in a cheY deletion mutant of V. alginolyticus, over expression of CheY, or its phosphorylated form CheY-p, significantly diminishes the mutant's ability to change swimming directions. To understand how Vibrio alginolyticus reorients during a flick, H. Fu came up with a dynamic model incorporating flagellar off-axial rotation during a flick and I performed the calculation. Comparing the model prediction with the experiment, my observations are consistent with the physical picture that V. alginolyticus' flagellum follows some closed path on the surface of a unisphere characterized by the polar and azimuthal angles. Fitting the data of cheY deletion mutant using this model suggests the possibility of motor remodeling and "stiffening" when CheY concentration is increased. %D 2016 %K "Gene Expression Noise","Stringent Response", "Growth Arrest", "Bacterial Motility", "Reorientation Mechanism" %I University of Pittsburgh %L pittir29292 %A Eric Griffin %T THE GREATER UNSEEN: ON THE IDENTITIES, DISTRIBUTIONS, AND IMPACTS OF FOLIAR BACTERIA ON TROPICAL ARBOREAL SPECIES %X Bacteria have been called the ?unseen majority? in nature. Leaves of higher plants comprise perhaps the largest bacterial substrate on earth, yet we know surprisingly little about the bacteria that occupy these spaces. The shaded understory of tropical forests is likely a ?hotspot? for bacteria because water availability and humidity are high and UV radiation is low. Ultimately, these communities may be critical mediators of plant performance among co-occurring woody species and ultimately contribute to plant species distributions at the community level. In this dissertation, I (Chapter 2) review the ecology and behavior of bacteria that reside on the phyllosphere (on and inside leaves) and outline testable hypotheses to empirically evaluate the potential ecological implications of foliar bacteria. Moreover, I conducted a major effort to test interrelated hypotheses regarding the distribution, impact, and identity of foliar bacteria with replicated manipulations of N, P, and K in large experimental forest plots in Panama. To determine the net effect of foliar bacteria, I experimentally reduced bacterial in situ via the application of standard antibiotics for nearly three years. Specifically, I (Chapter 3) evaluated the degree to which soil nutrients and foliar bacteria impacted seedling growth among co-occurring woody species. Additionally, I (Chapter 4) evaluated the degree to which soil nutrients and foliar bacteria mediated leaf traits and enemy impacts among species and soil nutrient additions. Finally, I (Chapter 5) conducted a major sequencing effort to determine the degree to which host species, soil nutrients, and commercial antibiotics caused variation in bacterial endophyte community structure. Overall, my results demonstrate that there are frequent interactions between soil nutrient and foliar bacteria on plant performance and enemy impacts, which differ among host species. Further, metagenomic sequencing revealed that host species, soil nutrient additions, and antibiotics caused significant variations in bacterial community composition. For every metric, plant-bacterial interactions are largely dependent on host species and soil resource supply, a classic niche axis for species coexistence. Ultimately, my work provides evidence that foliar bacteria are an entirely independent plant functional trait that can cause critical species-specific performance outcomes, which may have important implications for plant diversity maintenance. %D 2016 %K diversity maintenance, tropical forest, plant-microbe interactions, community ecology, soil nutrient availability, foliar bacteria, next-generation sequencing %I University of Pittsburgh %L pittir27914 %A Richard Beach Gray %T Global Russian Cinema in the Digital Age: The Films of Timur Bekmambetov %X This dissertation analyzes the films of director and producer Timur Bekmambetov, who works in both Hollywood and Russia. He has contributed to the stabilization of the contemporary Russian film industry, and this dissertation focuses on the digital techniques present in his otherwise live-action films. One such technique is a new way of cinematic representation that I term ?object perspective.? Digital sequences often feature an inanimate, everyday object that acts as a focal point, taking the spectator on a ?ride? through cinematic space that rivals video games and the real-world amusement park. ?Object perspective? is a device that challenges ideas about point of view, cinematic pleasure, and the way in which even everyday objects may be gendered by cinematic means of representation. This effect is analyzed with attention to product placement and scopophilia within his films. Other techniques, such as virtual kinetic subtitles and digital dubbing, transform his films to cater to local audiences. These techniques are themselves a form of branding that sends a message to the audience: they are special and deserve a localized form of the product. Other effects?such as digital composites of fan extras?are contextualized in a post-Soviet cinema. These films meet both global commercial demands and the ideological framework of Putin?s state cinema industry. Bekmambetov?s work struggles to reach local audiences separated by linguistic and cultural differences in a way that attempts to erase past trauma and to project an image of the present as available to social and economic advancement for all. I conclude that the organizing principle for these digital techniques is the attempt to garner greater participation for spectators. These films draw on the techniques of the avant-garde (such as revealing the device), but in an effort that does not alienate the viewer. Rather, they function as an opportunity for further immersion, or as an endorsement for a real-world product or a real-world political regime. %D 2016 %K Global, Russian cinema, digital cinema, Timur Bekmambetov, Bazelevs, ideology, object perspective, dubbing, subtitles, virtual, index, Hollywood cinema, Night Watch, Day Watch, Elki, Wanted, Irony of Fate. The Continuation, Osobo opasen %I University of Pittsburgh %L pittir28353 %A William J. Glassford %T Investigating the Evolutionary Origins and Modification of Novel Morphologies and their Developmental Networks %X The nature of the origin of morphological characters has long been a central subject of interest in the field of evolutionary developmental biology. Currently, many morphologies are known to be underscored by vast gene regulatory networks (GRNs) such that GRNs are anticipated for any feature of anatomy. Hence, if networks drive anatomical development, how do they evolve? The co-option of networks, a phenomenon in which cohorts of pre-existing transcriptional circuits are redeployed to new developmental settings, has been proposed to facilitate the rapid evolution of GRNs. Although several examples suggest the contribution of network co-option to the evolution of novel structures, examples that demonstrate and explore this process in molecular detail are currently lacking. In this dissertation I investigate the posterior lobe as a model of network co-option. A cuticular outgrowth on the genitalia of male fruit flies, this morphology is unique to the Drosophila melanogaster clade. By studying the ancestry of one gene?s posterior lobe activity, I discovered that it existed before the evolution of the posterior lobe, and had been redeployed from a network active during embryonic life. I next investigate the origin of the posterior lobe by studying the intercellular signaling pathways that contribute to its specification, discovering that a drastically altered pattern of the Notch ligand Delta is necessary for the development and evolution of the posterior lobe. I then explore how an embryonic circuit that was co-opted to the posterior lobe was subsequently modified to alter its shape. Finally, I study the origins of novelty at the level of an individual transcriptional circuit, analyzing all possible intermediate states along its evolutionary path. These studies demonstrate the value of an approach focused on understanding the co-option and origination of regulatory circuitry for the study of the evolution of novel characters. %D 2016 %K Evolution, Development, enhancer, gene regulatory network %I University of Pittsburgh %L pittir29093 %A Nathan G Glasgow %T Mechanisms of NMDA receptor inhibition by memantine and ketamine %X NMDA receptors (NMDARs), a subfamily of ionotropic glutamate receptors, have unique biophysical properties including high permeability to Ca2+. Activation of NMDARs increases the concentration of intracellular Ca2+ that can activate a vast array of signaling pathways. NMDARs are necessary for many processes including synaptic plasticity, dendritic integration, and cell survival. Aberrant NMDAR activation is implicated in many central nervous system disorders including neurodegenerative disorders, neuronal loss following ischemia, and neuropsychiatric disorders. Hope that NMDARs may serve as useful therapeutic targets is bolstered by the clinical success of two NMDAR antagonists, memantine and ketamine. Memantine and ketamine act as open channel blockers of the NMDAR-associated ion channel, and exhibit similar IC50 values and kinetics. Memantine is approved for treatment of Alzheimer's disease and shows promise in treatments of Huntington's disease, and ischemia. Ketamine was initially approved for use as a general anesthetic, but has recently shown efficacy in treatment of depression and of pain. Notably, memantine is not effective in treatment of depression or pain. In addition, memantine is well tolerated, whereas ketamine induces psychotomimetic side effects. The basis for the divergent clinical profiles of memantine and ketamine is not clear. One recently-proposed hypothesis is that memantine and ketamine inhibit overlapping but distinct subpopulations of NMDARs. However, mechanisms underlying inhibition of distinct NMDAR subpopulations by memantine or by ketamine are not fully understood. We therefore examined and compared mechanisms of inhibition by memantine and by ketamine. We also describe a novel fast perfusion system optimized for brief synaptic-like glutamate applications to lifted cells. We found that: (1) inhibition by memantine and ketamine exhibit differential dependence on duration of receptor activation and on NMDAR subtype; (2) the dependence of memantine inhibition on duration of NMDAR activation results from stabilization of a Ca2+-dependent desensitized state; (3) the endogenous NMDAR open channel blocker Mg2+ slows the binding kinetics of both memantine and ketamine, and, unexpectedly, speeds recovery from memantine inhibition; (4) although inhibition by memantine was thought to be mediated by only the charged form of memantine, the uncharged form of memantine also binds to and inhibits NMDARs, and exhibits surprisingly slow unbinding kinetics. %D 2016 %K NMDA receptor; channel block; memantine; ketamine; desensitization; inactivation %I University of Pittsburgh %L pittir28135 %A Sebastian Fajardo %T PREHISPANIC AND COLONIAL SETTLEMENT PATTERNS OF THE SOGAMOSO VALLEY %X This research documents the social trajectory developed in the Sogamoso valley with the aim of comparing its nature with other trajectories in the Colombian high plain and exploring whether economic and non-economic attractors produced similarities or dissimilarities in their social outputs. The initial sedentary occupation (400 BC to 800 AD) consisted of few small hamlets as well as a small number of widely dispersed farmsteads. There was no indication that these communities were integrated under any regional-scale sociopolitical authority. The population increased dramatically after 800 AD and it was organized in three supra-local communities. The largest of these regional polities was focused on a central place at Sogamoso that likely included a major temple described in Spanish accounts. Demographic estimates for the pre-contact period (1200-1600 AD) and for the Colonial times indicate a density similar to the demographic estimates calculated for 800-1200 AD. Regional-scale political organization shifted, however, without sign of overall political integration of the entire survey area. This scenario suggested political dynamics with only moderate levels of sociopolitical differentiation. The strongest and most intensive social interaction occurred in the local community around which the largest regional polity gravitated. This interaction responded to social and religious activities related to burial practices and the use of large communal structures where people from across the valley gathered regularly in the central place at Sogamoso, but did not live there as permanent residents. Economic activities were also probably at play as centripetal forces that attracted population to different places of the survey area but they seemed less important than social activities and religious practices. This evidence indicates that the polity centered in Sogamoso during prehispanic times was demographically smaller and less central than indicated by interpretations based on the historic accounts. This data suggests that the Spaniards classified as important prehispanic communities that were both large and small and based on varied centralizing forces affecting daily and supra-local interaction. The comparison of the Sogamoso valley with other trajectories in the Eastern Highlands suggests that economic and non-economic centralizing forces acting on human interaction create different degrees of nucleation, inequality and system survivability. %D 2016 %K Settlement Patterns, Muisca, Colombia and Early Human Communities %I University of Pittsburgh %L pittir29329 %A Matthew Geramita %T Parallel processing in the mammalian olfactory bulb %X Splitting sensory information into parallel pathways is a common strategy in sensory systems. Yet, it is not well understood how circuits in these parallel pathways are composed to maintain or even enhance the encoding of specific stimulus features. In this dissertation, we investigate the parallel pathways formed by mitral and tufted cells (MCs and TCs) of the olfactory system and characterize the emergence of feature selectivity in these cell types via distinct patterns of connectivity to local inhibitory interneurons. Chapter 2 explores differences in feedforward circuitry onto MCs and TCs. We find that MCs display longer latency spiking that is more strongly dependent on stimulus intensity than TCs. Longer latency spiking in MCs is a consequence of weaker excitatory and stronger inhibitory currents, mediated by periglomerular cells, onto MCs compared to TCs. Chapter 3 describes the causes and consequences of lateral inhibition differences between MCs and TCs. We find that MCs are affected by lateral inhibition at intermediate firing rates, while TCs are affected at lower firing rates. These differences arise, in part, due to differential recruitment of morphologically distinct classes of granule cells by MCs and TCs. Using simulations, we show that these differences in lateral inhibition allow TCs and MCs to perform odor discriminations best in separate concentration ranges. Together, the experiments described here suggest that differences in odor-evoked responses between MCs and TCs are a consequence of distinct patterns of connectivity to multiple populations of inhibitory interneurons. %D 2016 %K olfaction computational neuroscience %I University of Pittsburgh %L pittir28389 %A Marie-Odile N. Hobeika %T Recovered Beginnings: Rhetoric's Disaffiliation from Homer %X This dissertation presents a history of rhetoric in relation to Homer?s poetry, as well as the beginning of a theoretical account of the rhetorical life of poiesis. Rather than recount the Socratic counter-claims on Sophistical teachings, this dissertation recovers classical theories of rhetoric as they demonstrate techniques of extrication from Homeric epos, the source of poetic institutions of classical Greek life. If Homer is understood, not as a poet, but as an uninterrupted afterlife in the imaginations of rhetors, then the material of this dissertation is a grammar of attitudes that rhetors had about what they imagined to be ?Homer?. In the first chapter I attribute the continuity of Homer?s afterlife (nachleben) to traditional and democratic forums of education, where Homer?s poetry was seminal. In the second chapter, I enter into Plato?s exile of Homer in Republic as a disaffiliation from father Homer mirroring rhetoric?s extrication from the decay of patrilineal culture. In the third, I argue that Aristotle?s imaginary associations of Homer as stranger (xenos) indicate that the philosopher never settled a difference of kind between rhetoric and poetry in the Rhetoric. Though he loved epic dignity, he also feared the strangeness of Homeric style, paradoxically teaching young rhetors to disambiguate epical arrangements in speech. In the fourth chapter on Longinus? Sublime, I read his emulation of Homer as a para-religious move that sought to resurrect faith in the republic of letters at a time when eloquence had evidently reached its dearth. In the fifth and final chapter, I argue that the Homeric afterlife in rhetoric continues on today, as contemporary scholars carry the conceit that rhetoric was a more advanced technological form than poetry. Treating developmentalist conceits as symptoms of change rather than inherent truisms has two implications. First, it shifts the object of study of re-covered beginnings away from formal arts, either epic poetry, or rhetoric individually; to the modes of extraction affecting the treatment of those arts as autonomous. Second, it contributes to contemporary scholarship a sequence of modes (disaffiliation, disambiguation, and emulation) in the light of which other cultural formations may be considered going forward. %D 2016 %K Homer, poetry, rhetoric, disaffiliation, disambiguation, zeal %I University of Pittsburgh %L pittir29003 %A Ashley/ ARH Hall %T THEORIZING RIVAL RHETORICS OF BLACK MATERNITIES: IMAGINING (RE)PRODUCTIVE LIFE IN SOCIAL DEATH %X This dissertation considers the ways that Black women navigate the anti-black violence that constrains them, creating social life within social death via their (re)production. The narratives of racial difference embedded within cultural pathology criminalizing Black women?s attempts to ?produce properly? has meant that they have had to find creative ways to mother and empower themselves. In de-centering a concern for mothering as biological, this study primarily focuses on the ways Black women mother self via their strategies of self-care. Ashley draws from and speak to the history of Black women?s particular (re)productive struggles to imagine a different kind of rhetorical framework, Black Maternal Futurism (BMF). Black Feminist Studies, Black Queer Studies, and Afro-pessimism & Afro-futurism constitute the theoretical landscape in which she positions this project on Black mothering, sexual expression, and (re)production. In imagining rhetoric as ?something different,? this project analyzes rhetorics produced by Black women about their mothering to gain a deeper understanding as to how they negotiate a violent, anti-black world. %D 2016 %K Black women,Black mothering, Reproduction, gendered blackness, state violence, rhetoric, Black Maternal Futurism, Black girl magic, Self-care, anti-blackness %I University of Pittsburgh %L pittir28251 %A Andrea Juliana Enciso Mancilla %T VARIACIONES EN TORNO A LA RIQUEZA DE LA NADA: INFLUENCIA DEL PENSAMIENTO CHINO CL?SICO Y EL BUDISMO ZEN EN LA POESIA DE JUAN L. ORTIZ, HUGO PADELETTI Y ARTURO CARRERA VARIACIONES EN TORNO A LA RIQUEZA DE LA NADA: INFLUENCIA DEL PENSAMIENTO CHINO CL?SICO Y EL BUDISMO ZEN EN LA POESIA DE JUAN L. ORTIZ, HUGO PADELETTI Y ARTURO CARRERA %X This dissertation investigates how Juan L Ortiz (1896-1978), Hugo Padeletti (1928), and Arturo Carrera (1948), interpret and represent Chinese classical and Zen Buddhist systems of thinking in their poetry, in 20th century Argentina. I argue that these authors share a common aesthetical and philosophical goal in their interpretations of Chinese, and Japanese systems of thinking portrayed in their poetry. They are seeking philosophical and aesthetical alternatives to Eurocentric Modernity. In order to achieve this, these three authors lean in their poetry towards the dissolution of the self, passivity, contemplation, silence and exposure to the outside. Nonetheless, their interpretations of these Chinese and Japanese systems of thinking change relative to the way in which they react to historical, social, cultural and political events that shaped their cultural contexts. My investigation involves a close reading of the poetry of each author in the context of contemporary literary currents in 20th Century Argentina, in order to trace differences, and similarities, as well as individual specificities in their interpretations and representations of classical Chinese and Zen Buddhist verbal aesthetics and thought. The purpose of this research is to explore how, alongside during the 20th century, these Argentinian poets critique European Modernity in Argentina, through recurring to orientalism, as an alternative model to the Cartesian Rationalism and the other ideologies associated to the dominant discourse of progress. %D 2016 %K 20th Century Argentinian poetry, Juan L. Ort?z, Hugo Padeletti, Arturo Carrera, Eastern Philosophy, Zen Buddhism, Taoism, Classical Chinese poetry, Cultural studies, Trans-pacific Hispanic Studies %I University of Pittsburgh %L pittir29332 %A Ulf Hlobil %T What Is Inference? Or the Force of Reasoning %X Abstract What are we doing when we make inferences? I argue that to make an inference is to attach inferential force to an argument. Inferential force must be understood in analogy to assertoric force, and an argument is a structure of contents. I call this the ?Force Account of inference.? I develop this account by first establishing two criteria of adequacy for accounts of inference. First, such accounts must explain why it is absurd to make an inference one believes to be bad. The upshot is that if someone makes an inference, she must take her inference to be good. Second, accounts of inference must explain why we cannot take our inferences to be good---in the sense that matters for inference---by merely accepting testimony to the effect that they are good. Next, I spell out the Force Account in detail, and I show that it meets these two criteria of adequacy. According to the Force Account, we make an inference by reflectively endorsing the inference as good. That allows us to understand in what sense inference is a self-conscious and active manifestation of reason. I then demonstrate that the account can be fruitfully applied to debates in epistemology and practical philosophy. In particular, I show that the Force Account gives us the resources to settle debates about inferential internalism and pure moral testimony. %D 2016 %K inference, reasoning, mental action, self-consciousness, moral testimony, Moorean absurdity %I University of Pittsburgh %L pittir28130 %A Amy Cymbala %T 'Dearest Wife, Most Famous Woman': Gender, Commemoration, and Women's Funerary Monuments in Rome, 1550-1750 %X This dissertation examines women?s funerary memorials produced in Rome from 1550 to 1750. Their numbers represent only a small share of the surviving funerary monuments made in these two centuries. They survive as proof that some women?s achievements and characters were considered worthy of public recognition at a time and place where women?s activities have been assumed to be domestic and negligible. Some of these memorials were modest floor plaques and slabs, others framed tributes attached to walls and pillars, and a few were grand structures dominating entire walls in a family chapel or in prominent locations in the aisle of Rome?s most prestigious church: St. Peter?s. These memorials represent almost all social classes, except of course wealthy individuals of both genders who chose to give to charity instead, or those too poor to afford this public record of their lives. In order to understand these memorials, my first task was to find them and account for their prevalence. My database (Appendix A) now contains over five hundred examples, from which major patterns relative to their location, commission, and commemorative programs can be observed and analyzed. With selected case studies, I then show that the design of individual memorials both celebrated women?s roles in the private sphere, and praised their contributions to cultural and religious life in the city. As such, this thesis adds to the expanding body of scholarship on women patrons of Roman architecture, and adds a significant new dimension by considering the female patrons and subjects of public sculpture. This dissertation demonstrates for the first time that Roman women?s funerary monuments were part of complex (and sometimes conflicting) dialogues about the role of women in the papal city. Moreover, it revises traditional assumptions about gender tensions in Rome, revealing the ways women and their memorials provided desirable models of female accomplishment in the name of religious reform. %D 2016 %K Women's tombs, Renaissance, Early Modern, sculpture, gender, Italy %I University of Pittsburgh %L pittir29249 %A Jorge Cely %T MOTIVIC INTEGRATION, THE SATAKE TRANSFORM AND THE FUNDAMENTAL LEMMA. %X The purpose of this work is to use motivic integration for the study of reductive groups over p-adic fields (towards applications of the fundamental lemma for groups). We study spherical Hecke algebras from a motivic point of view. We get a field independent description of the spherical Hecke algebra of a reductive group and its structure. We investigate the Satake isomorphism from the motivic point of view. We prove that some data of the Satake isomorphism is motivic. %D 2016 %K MOTIVIC INTEGRATION, THE SATAKE TRANSFORM AND THE FUNDAMENTAL LEMMA. %I University of Pittsburgh %L pittir28611 %A Daniel Chung %T ROLE OF ERBB4 SPLICING IN PARVALBUMIN INTERNEURON MATURATION AND SCHIZOPHRENIA %X Cognitive dysfunction is a core and clinically-critical feature of schizophrenia. Certain cognitive deficits, such as impaired working memory, appear to emerge from altered gamma oscillations in the dorsolateral prefrontal cortex (DLPFC). Cortical gamma oscillations require the activity of parvalbumin (PV) interneurons and reduced PV interneuron activity in schizophrenia has been proposed to be due to deficient excitatory drive to these neurons. Synaptic pruning coincides with the period in which individuals with schizophrenia typically present their first clinical symptoms and thus an excessive pruning of excitatory inputs to PV interneurons in the DLPFC during development could provide the neural substrate for altered prefrontal gamma oscillations and working memory dysfunction in schizophrenia. However, evidence for pruning or pathogenic loss of excitatory inputs to PV interneurons in development and schizophrenia, respectively, and molecular mechanisms underlying these processes have not been identified. The formation of excitatory synapses on PV interneurons is mediated by ErbB4 signaling pathway. ErbB4 transcript is alternatively spliced and each splice variant is associated with different functional effects. In schizophrenia, the total ErbB4 expression is unaltered, but alternative splicing of ErbB4 is dysregulated, suggesting that ErbB4 splicing shifts may provide molecular mechanisms for modulating the excitatory synapse number on PV interneurons. Using a top-down translational approach, I first characterized the association between dysregulated ErbB4 splicing shifts and fewer excitatory inputs to PV interneurons in a human cohort of comparison subjects and schizophrenia subjects. Then I assessed the developmental context of this relationship in a cohort of non-human primates with different ages. Finally, I investigated the cause-and-effect relationship between ErbB4 splicing shifts and excitatory synapse number on PV interneurons using rat primary neuronal culture. Data from these different experimental systems converge onto the hypothesis that developmental shifts in ErbB4 splicing induce pruning of excitatory synapses on PV interneurons and deficits in this process result in a loss of excitatory inputs to PV interneurons in schizophrenia. Therefore, work from this dissertation reinforces the view that schizophrenia is a neurodevelopmental disorder with disturbances in the maturation of prefrontal cortical circuitry. %D 2016 %K Schizophrenia, Development, Dorsolateral prefrontal cortex, Parvalbumin interneuron, ErbB4 signaling, Alternative splicing %I University of Pittsburgh %L pittir29076 %A Jonas Gamso %T South-South Trade, Trade-Based Policy Diffusion, And Political Autonomy In Countries Of The Global South %X The tremendous growth of South-South trade is among the key trends in international economics, yet it has received surprisingly little attention from scholars of international political economy. This dissertation helps to fill this void by providing the first systematic analysis of the political effects of South-South trade. Such analysis is appropriate given the foreign policy norm that uniquely characterizes South-South relations, including South-South trade: countries of the South espouse the practice of non-interference in the domestic affairs of their partners. In contrast, countries of the North typically seek to promote certain domestic policies among their partners in the Global South, such as human rights, democratic governance, certain foreign policy behaviors, and labor and environmental standards. In light of Southern non-interference and its contrast to the foreign policy norms of countries of the North, this dissertation assesses the effects of South-South trade on trade-based diffusion processes associated with labor laws, environmental standards, and voting within international organizations. In assessing each of these policy areas, the analysis considers three issues: first, whether the policy diffusion patterns associated with South-South are different from those associated with other types of trade flows; second, whether high levels of South-South trade weaken the effectiveness of trade-based policy promotion efforts by countries of the North; and third, whether variation in South-South trade levels moderates the relationships between domestic political variables and policy outcomes. These hypotheses correspond to a novel theory positing that trade-based efforts by Northern countries to promote the adoption of their favored policies by partners in the South are weaker where those Southern partners engage in high levels of South-South trade. In Southern countries where Northern efforts are rendered weak by high levels of South-South trade, it is further theorized that domestic level interests and institutions play a larger role in the policy process, as these interests and institutions are less constrained by interference from the North and not subject to comparable interference efforts from the South. The results provide mixed support for this theory, but they do clarify that South-South trade is accompanied by different policy diffusion patterns than other types of trade. %D 2016 %K South-South trade; Labor Rights; Environmental Policy; Political Autonomy; Political Dependency; The Global South; Race to the Top %I University of Pittsburgh %L pittir28011 %A Ervin Dyer %T Two Paths Forward: An Ethnographic Study of Somali Bantu Refugees Living in a Northeastern City Public Housing Community %X In 1991, civil war struck the Northeastern African nation of Somalia. In the nation?s collapse, thousands of Somali Bantu were displaced from southern Somalia. An estimated 14,000 were eventually relocated to the United States, making them the largest refugee group ever resettled in the United States. When they arrived, the Somali Bantu, one of the most persecuted ethnic groups in Somalia, became a rural people thrust into a post-industrial global American society. They are one of the most culturally dissimilar groups to come to the U.S: they arrived with very little formal education, a language barrier; are Muslims in a predominantly Christian space; and are agrarians placed amid an urban social mosaic. There are about 50 Somali Bantu families living in this Northeastern city and socioeconomic factors have pushed one-third of these families into an isolated, impoverished and nearly all-Black American public housing project. This ethnographic study is focused on 13 Somali Bantu male heads of household who live in this community. I ask two primary research questions: How do Somali Bantu men, who live in an impoverished, segregated public housing community, access and maintain employment? And, despite challenges of race and class, what resources do they deploy to assimilate toward the larger society? Over a three-year period, I used informal and structured interviews, more than 700 hours of participant and non-obtrusive observation, and census research to investigate how Somali Bantu male heads of household are ?survivors? who build beneficial social networks with middle-income white volunteers from faith-based and refugee support groups and that they also rely upon a set of friendly neighbors to settle into the public housing space. %D 2016 %K Race, class, immigration, refugees, urban, ethnography %I University of Pittsburgh %L pittir28205 %A Titas Chakraborty %T Work and Society in the East India Company Settlements in Bengal, 1650-1757 %X This dissertation examines the history of work in the Dutch East India Company (VOC) and the English East India Company (EIC) settlements in Bengal between 1650 and 1757. By 1650, both companies had firmly established trading networks in Bengal, and by the early years of the eighteenth century, the profitability of trade in Bengal had become very clear to both companies. The volume and value of trade grew steadily until 1757, when the EIC defeated the Nawab of Bengal, Siraj-ud-Daulah, at the Battle of Plassey, thereby inaugurating direct colonial conquest of the region. During this period of trade, when neither company had political sway over the region and very little intrusion into the producing hinterland, they employed hundreds, sometimes thousands, of workers each year. How did these corporate entities manage labor in time and place, where their political control over workers was severely challenged? To answer this question, this dissertation specifically looks at workers who were directly employed by the companies. In doing so, it brings to light the lives and work of laboring people?boatmen, cartmen, coolies, silk reelers, slaves, sailors and soldiers?thus far ignored by social and economic historians of South Asia and the Indian Ocean. Most importantly, it reveals a world of work marked by the workers? assertion of their right to mobility and ?customary? payments. By emphasizing workers? agency, I argue that the European companies? control over the workers was far from total. Building on the rich body of work on the economic, social and labor histories of Mughal India and the Indian Ocean, this work proposes to shift the focus of eighteenth-century South Asian history from economic histories of trade and the history of both European and Asian mercantile and political elites to the social history of working people. It also brings labor history into the pre-colonial history of South Asia. %D 2016 %K labor, East India company, Bengal, Mobility, %I University of Pittsburgh %L pittir29080 %A Magda Gabriela Sava %T CONTRIBUTIONS TO THE THEORY OF SENSITIVITY AND STABILITY ANALYSIS OF MULTI-CRITERIA DECISION MODELS, WITH APPLICATIONS TO MEDICAL DECISION MAKING %X Patients are faced with multiple alternatives when selecting the preferred method for colorectal cancer screening, and there are multiple criteria to be considered in the decision process. We model patients? choices using a multi-criteria decision model, and propose a new approach for characterizing the idiosyncratic preference regions for individuals and for groups of similar patients. We propose an extension of the sensitivity and stability analyses for Analytic Network Models developed by May et al. (2013). We study ANP models to understand how preference regions are created, and how boundaries can be characterized, as the number of criteria increases. For the two-criteria and three-criteria sensitivity and stability analyses, piecewise linear functions and triangular mesh generation, respectively, are used to approximate the boundaries between two adjacent preference regions. We use optimization methods to find the best approximations for the core stability and solution stability regions for cases where two and three criteria are perturbed simultaneously, and there exist an arbitrary number of alternatives. We define sensitivity and stability measures that can be implemented in practice, and that can be considered as a starting point in any medical decision making process. We apply our newly developed methodology to randomly chosen patients, and show how insights derived from the sensitivity and stability of patients? preferences might be used within the medical decision making process. Individualized stability analysis is informative, but the generalization to groups of similar patients may be even more important for healthcare providers. Our comparisons reveal that a patient?s age may be an effective discriminating factor that should be taken into consideration when extending the individualized sensitivity and stability analysis to groups of patients with similar characteristics. %D 2016 %K Multi-criteria decision making; AHP/ANP models; medical decision making %I University of Pittsburgh %L pittir29011 %A Shannon Harris %T Essays in Appointment Management %X Patients who no-show or who cancel their outpatient clinic appointments can be disruptive to clinic operations. Scheduling strategies, such as slot overbooking or servicing patients during overtime slots, may assist with mitigating such disruptions. In the majority of scheduling models, no-shows and cancellations are considered together, or cancellations are not considered at all. In this dissertation, I propose novel prediction models to forecast the probability of no-show and cancellation for patients. I present analyses to show that no-shows and cancellations are two different types of patient behavior, and should be treated separately when scheduling a patient. Additionally, I develop a multi-day, online, overbooking model that incorporates no-show and cancellation probabilities, and outlines how patients should be optimally overbooked in an outpatient clinic schedule to increase clinic service reward. I find that past history is an indicator of future no-show behavior for patients attending outpatient clinics, and that only a limited look-back window is needed in order to gain insight into patient?s future behavior. Advance appointment cancellations are more challenging to predict, and tend to occur at the beginning or at the end of an appointment?s lifecycle. The optimal overbooking strategy is a function of both the no-show and the cancellation probabilities, and affects both the day on which an overbooking may occur, and the appointment slot in which the patient is overbooked. %D 2016 %K outpatient scheduling, no-show, cancellation, overbooking %I University of Pittsburgh %L pittir28960 %A Feihong Xia %T Marketing in the Internet Age %X The Internet has changed the landscape of marketing, and presented us with new marketing phenomena and challenges. In this dissertation, I focus on two emerging research topics at the frontier of marketing research ?capturing consumer purchase patterns from big data and online groupbuy. Marketers have recognized that the probability of a consumer?s (or household?s) purchase in a particular product category may be influenced by past purchases in the same category, and also by purchases in other, related categories. Past studies of cross-category effects have focused on a limited number of product categories, and have often ignored intertemporal effects in their analyses. The availability of such enormous consumer shopping data sets, and the value of analyzing the complex relationships across categories and over time (for example, for personalized promotions) suggest the need for computationally efficient modeling and estimation methods. We explore the nature of intertemporal cross-product patterns in an enormous consumer purchase data set, using a model that adopts the structure of conditional restricted Boltzmann machines (CRBM). Our empirical results demonstrate that our proposed approach, employing the efficient estimation algorithm embodied in the CRBM, enables us to process very large data sets, and to capture the consumer decision patterns, for both predictive and descriptive purposes, that might not otherwise be apparent. Online group buying, under which the seller offers discounts based on the size of the pool of buyers, is rapidly growing in popularity in both developed and emerging markets. Our study categorizes the diverse mechanisms across group buying sites into three main types ? volume strategy (e.g., Groupon), collective buying (e.g., Mercata), and referral reward (e.g., LivingSocial) ? and associated subtypes. Our seller faces a market comprising four segments of consumers who are heterogeneous in their product knowledge or intrinsic valuation or both. Informed consumers may inform and raise the valuation of their less informed peers. Consideration of a broader strategy space combined with a richer consumer behavior model, relative to the extant literature, provides new insights on when and how specific strategies or subtypes are optimal. Collective buying emerges with the largest domain of optimality, followed by referral reward strategy and then the volume strategy. Within collective buying, its subtypes favoring limited penetration are often optimal. %D 2016 %K Marketing, Pricing, Groupbuy, Big Data %I University of Pittsburgh %L pittir28951 %A Subhara Raveendran %T Combination immunotherapy targeting HSP90 DNA repair client proteins overexpressed in melanoma %X DNA repair protein (DNA-RP) overexpression in tumor cells has been reported to involve post- translational protein stabilization mediated by the molecular chaperone, Heat shock protein 90 (HSP90), thereby preventing proteasome-dependent degradation of these HSP90 ?client? proteins. This overexpression of DNA-RP in a cancer-stage associated manner has also been correlated to chemotherapy resistance and poor overall prognosis. Hence, HSP90 inhibitors (HSP90i) have been heralded as cotherapy agents for cancer patients that have developed resistance to first-line treatments such as temozolomide (TMZ). Under conditions in which HSP90 function is blocked by HSP90i, HSP90 client proteins rapidly become polyubiquinated and undergo cytosolic degradation, resulting in sensitization of cancer cells to chemotherapy. We observed that HSP90i promote the proteasome-dependent degradation of a range of DNA repair client proteins, from which, we were able to define nine H-2Kb/Db-presented peptide epitopes that could be recognized by Type-1 CD8+ T cells after specific vaccination. When combined with an adoptive cell therapy (ACT) using anti-DNA-RP CD8+ T cells, HSP90i-cotreatment yielded superior anti-tumor efficacy against TMZ-resistant B16 melanomas established in the dermis of syngenic C57BL/6 mice. Innovation. This is the first study to focus on the use of HSP90i to conditionally promote the degradation and subsequent presentation of DNA-RP-derived peptides in MHC class I complexes, allowing for improved recognition of chemotherapy-refractory tumor cells by the adaptive (T cell) immune system in vitro and in vivo. Public health significance. Melanoma is the deadliest form of skin cancer, with increasing incidence worldwide. This study defines a novel approach that may be translated into the clinic for the treatment of patients with advanced-stage melanomas or alternate chemotherapy-resistant forms of cancer. This approach could be readily combined with a range of synergistic immunotherapies as a novel first- or second-line treatment option for patients that have previously developed (genotoxic or targeted) therapy-specific resistance. %D 2016 %K cancer, chemotherapy, immunology, adoptive cell therapy,vaccine, HSO90 %I University of Pittsburgh %L pittir30381 %A Jerod Caligiuri %T CONSTRAINING INFLATION THROUGH JOINT OBSERVATIONS OF THE PRIMORDIAL GRAVITATIONAL WAVE BACKGROUND %X The standard cosmological model leaves many questions unanswered. An early period of accelerated expansion of the Universe, referred to as inflation, resolves these issues. It provides a means to generate perturbations in matter and density that lead to the formation of structure as well as in gravitational waves. Inflation preserves fluctuations by driving them beyond the causal horizon. Their wavelengths trace the time they exit and their amplitude reveals the expansion rate and inflationary potential energy at exit. Measurements of these fluctuations is therefore a powerful probe of the inflationary Universe. After providing the necessary overview of background cosmology and inflation, I explore our ability to constrain viable models using joint measurements at vastly separated length scales and frequencies. Particular attention is paid to observations of the tensor power spectrum at large scales through measurements of the B-mode polarization of the cosmic microwave background and at small scales by direct detection using interferometric gravitational wave detectors. First, I consider a simple test of the inflationary consistency relation and discuss a simple means to constrain the running of the tensor spectral index. Secondly, I investigate more generally how joint observations can restrict viable models and reveal a highly constrained class of likely expansion histories and potential energies driving the expansion. Within these remaining classes of models, subsets are revealed by their spectral tilts at small scales. Thus, the addition of a measure of the tensor spectral tilt at solar system scales amplifies the restrictive power to identify valid inflationary models. I conclude with a discussion of the possible addition of constraints of both the tensor and scalar power spectrum at intermediate scales and some for the challenges that future experiments will need to overcome. %D 2016 %K inflation, cosmology, gravitational waves, primordial power spectrum %I University of Pittsburgh %L pittir29145 %A Sean Carney %T Characterizing Excluded Strand DNA Interactions with Hexameric Helicases and Determining Roles in Unwinding Mechanisms %X DNA replication is an essential process for all living organisms, and errors in this process can lead to genetic mutations and disease. An assembly of protein machinery, termed the replisome, coordinates enzymatic activities at the replication fork. The DNA helicase is the heart of the replisome unwinding double-strand DNA at the head of the progressing replisome and providing single-strand templates for DNA polymerases. Replicative helicases are composed of six subunits, and arranged in a ring-like structure where ATP hydrolysis events provide the energy to translocate upon and unwind the DNA. The mechanism of helicase unwinding has been widely studied, but there are still many aspects that remain unknown. It is generally thought that these helicases encircle one strand of DNA while the other is excluded from the central channel of the helicase. Our lab has previously identified an interaction between the excluded strand and the helicase exterior that was important for unwinding in the archaeal MCM helicase. The steric exclusion model of replicative helicase unwinding was expanded to include the excluded strand interactions in this newly proposed steric exclusion and wrapping (SEW) model. Here, we present work that expands on the SEW model by revealing that the bacterial DnaB and mitochondrial Twinkle replicative helicases also interact with the excluded strand. We have also developed a new single-molecule FRET analysis program to characterize these excluded strand interactions. Although the excluded strand interaction is seen in multiple replicative helicases, we propose distinct roles for the interaction based on functional assays and known differences in replisome architecture across the various organisms. We have also begun to characterize the helicase-excluded strand wrapping interaction in the presence of other replisome components, namely the single-strand binding (SSB) protein. We further characterized the archaeal SSB protein from Sulfolobus solfataricus and provide evidence for a novel DNA-helicase-SSB ternary complex. Overall, this thesis makes significant contributions to the understanding of replicative helicase unwinding mechanisms by expanding upon the current steric exclusion and wrapping model and introduces a novel single-molecule FRET analysis program that we anticipate will be adopted and utilized by others in the field. %D 2016 %K DNA Replication Single-molecule FRET Hexameric Helicase E.coli DnaB Mitochondrial Twinkle Single strand binding protein %I University of Pittsburgh %L pittir29147 %A Jesse Horst %T Sleeping on the Ashes: Slum Clearance in Havana in an Age of Revolution, 1930-1965 %X This dissertation examines the relationship between poor, informally housed communities and the state in Havana, Cuba, from 1930 to 1965, before and after the first socialist revolution in the Western Hemisphere. It challenges the notion of a ?great divide? between Republic and Revolution by tracing contentious interactions between technocrats, politicians, and financial elites on one hand, and mobilized, mostly-Afro-descended tenants and shantytown residents on the other hand. The dynamics of housing inequality in Havana not only reflected existing socio-racial hierarchies but also produced and reconfigured them in ways that have not been systematically researched. As the urban poor resisted evictions, they utilized the legal and political systems to draw their neighborhoods into contact with the welfare state. Not merely co-opted by politicians, tenants and shantytown residents claimed housing as a citizenship right and played a decisive role in centralizing and expanding state institutions before and after the 1959 Revolution. Far from giving the urban poor free rein over their destinies, however, their tight relationships with the Cuban state impelled officials to implement new policies drawn from abroad. Public debates over slum clearance reinforced the social-scientific discourse of a ?culture of poverty? in ways that ultimately blended with the incipient socialist system. This discourse was embedded in the most beneficial interventions of the revolutionary welfare state but in ways that perpetuated racism and social exclusion. By the early 1960s, then, slum policy in Havana represented a dynamic interaction between residents, social scientists, and state bureaucrats. The urban poor shaped the Revolution, even as the Revolution sought to manage them. %D 2016 %K Cuban Revolution, Urban Informality, Shantytowns %I University of Pittsburgh %L pittir29364 %A Jonathan A. Buttaci %T THINKING FORMS IN IMAGES: ARISTOTLE ON INTELLECTUAL CAPACITIES, ACTIVITIES, AND VIRTUES %X Aristotle?s active intellect has been a subject of much interpretive controversy over the centuries. Some have said it is the divine mind, others a god-like power of the human soul. Most begin by asking what the active intellect is; instead, I first ask what it does. Upon a close reading of de Anima III.5, I conclude that the active intellect activates or actualizes potentially intelligible objects, making them to be actually or actively intelligible for thinking. Accordingly, on my view, the active intellect is not responsible for initiating particular episodes of thinking for an individual, nor is it responsible for the intelligibility of the world in general. Rather, as I go on to argue, the active intellect plays a distinctive role in learning and discovery by making intelligible objects available for individual knowers. To understand this role more precisely, I consider Aristotle?s idea that we learn by doing: not only do we become builders by building and brave by doing brave things, but we also get knowledge of triangles by thinking about triangles. In my investigation into his account of intellectual learning I draw on the Posterior Analytics and Metaphysics. I conclude that Aristotle distinguishes two sorts of intellectual activity when students are learning about triangles: they think about specific proofs in order to gradually grasp them, but they can also manipulate diagrams to discover proofs not yet considered, perhaps by drawing parallel lines or bisecting angles. This latter activity, by which students search for and uncover intelligible content in perceptual particulars, is the distinctive function of the active intellect. It is productive, then, like light, which does not create the color of things but rather reveals colored things as they already are. In doing so, however, the active intellect does not act as some intellectual spotlight, but rather as the familiar capacity to explore and move about one?s world, a capacity to inquire that is shared by the toddler and the scientist alike. The active intellect therefore directs our perceptual engagement in inquiry, so that we may hunt down, discover, and consider the correct intelligible forms in the images. %D 2016 %K Aristotle, de Anima, Posterior Analytics, intellect, active intellect, learning, teaching, discovery %I University of Pittsburgh %L pittir28529 %A Philip Fournier %T The Catalytic Degradation of Carbon Nanomaterials %X The explosion of research into carbon-based nanomaterials has been driven by their possible application to a wide range of fields. While materials such as graphene and cellulose nanostructures show great potential due to their physical qualities, understanding of their stability and toxicity is still not well-defined. This report explores the result of exposing new and familiar nano-sized carbon architectures to oxidative environments, with the intent of furthering the safe and effective implementation of them. First, intentional degradation of graphene oxide is exhibited through the use of iron oxide nanoparticles as a component in the Fenton reaction. Next, the morphologies of different nanocellulose sources are thoroughly characterized using microscopy techniques. The interaction between myeloperoxidase and one of these nanocellulose samples, which results in acute aggregation, is then investigated. An additional degradation system utilizing DNA origami and horseradish peroxidase is also introduced as a possible approach for graphene oxide degradation. Finally, two emerging nanomaterials, carbon nanofibers and chitin, are analyzed and their pulmonary toxicity assessed in collaboration with the National Institute of Occupational Safety and Health. %D 2016 %K graphene, graphene oxide, iron oxide nanoparticles, holey, nanocellulose, carbon nanofiber, chitin, oxidation, degradation %I University of Pittsburgh %L pittir28171 %A Brian P. Bloom %T Using Inorganic Nanoparticle Surface Passivation as a Tool for New Approaches in Photovoltaics %X Colloidal semiconductor nanoparticles (NPs) are an attractive alternative for optoelectronic devices owing to their low cost, solution processability, and interesting quantum confinement properties. Much progress has been made towards the development of semiconductor NP based devices, however, only recently have researchers begun to understand and utilize the role of the NP surface capping ligands in these systems. The fundamental studies in this dissertation focus on the ligand-NP interaction and the interesting properties that become manifest. The first series of experiments discussed herein explore the influence of the ligand on the size dependent electronic state energies of CdSe NPs. The second study shows how Fermi-level pinning of PbS NPs on a gold substrate inhibits the size and ligand dependent changes in the electronic states. It was found that the insertion of an alumina layer decouples the NPs from the substrate and the size and ligand dependent energy shifts are restored. The third study in this dissertation shows how capping CdSe NPs with chiral ligands can lead to spin specific conduction pathways. The last study investigates charge transport in donor bridge acceptor NP dyads on a microbead template. By changing the size of the acceptor and its ligand length, charge transport could be studied as a function of driving force and bridge length. The findings in these studies elucidate the importance of capping ligand on the physical properties of semiconductor NPs and may guide the development for future advances in optoelectronic devices. %D 2016 %K Nanoparticle, Quantum Dot, Ligand Exchange, Chiral induced Spin Selectivity, Fermi-level pinning %I University of Pittsburgh %L pittir28978 %A Simone Aiola %T New Probes of Cosmic Microwave Background Large-Scale Anomalies %X Fifty years of Cosmic Microwave Background (CMB) data played a crucial role in constraining the parameters of the ?CDM model, where Dark Energy, Dark Matter, and Inflation are the three most important pillars not yet understood. Inflation prescribes an isotropic universe on large scales, and it generates spatially-correlated density fluctuations over the whole Hubble volume. CMB temperature fluctuations on scales bigger than a degree in the sky, affected by modes on super-horizon scale at the time of recombination, are a clean snapshot of the universe after inflation. In addition, the accelerated expansion of the universe, driven by Dark Energy, leaves a hardly detectable imprint in the large-scale temperature sky at late times. Such fundamental predictions have been tested with current CMB data and found to be in tension with what we expect from our simple ?CDM model. Is this tension just a random fluke or a fundamental issue with the present model? In this thesis, we present a new framework to probe the lack of large-scale correlations in the temperature sky using CMB polarization data. Our analysis shows that if a suppression in the CMB polarization correlations is detected, it will provide compelling evidence for new physics on super-horizon scale. To further analyze the statistical properties of the CMB temperature sky, we constrain the degree of statistical anisotropy of the CMB in the context of the observed large-scale dipole power asymmetry. We find evidence for a scale-dependent dipolar modulation at 2.5?. To isolate late-time signals from the primordial ones, we test the anomalously high Integrated Sachs-Wolfe effect signal generated by superstructures in the universe. We find that the detected signal is in tension with the expectations from ?CDM at the 2.5? level, which is somewhat smaller than what has been previously argued. To conclude, we describe the current status of CMB observations on small scales, highlighting the tensions between Planck, WMAP, and SPT temperature data and how the upcoming data release of the ACTpol experiment will contribute to this matter. We provide a description of the current status of the data-analysis pipeline and discuss its ability to recover large-scale modes. %D 2016 %K Cosmology, "Cosmic Microwave Background", "Temperature Anisotropies" %I University of Pittsburgh %L pittir29047 %A Lauren, N. Ross %T Stem Cell Development and the Pathway Model: Scientific Puzzles and Bioethical Issues %X This thesis examines various scientific puzzles and bioethical issues that are related to the pathway model of stem cell development. This model has been criticized in the bioethics and philosophy of science literature by those who claim that it: (1) oversimplifies development in ways that misrepresent scientific understanding,1 (2) leads to poorly informed scientific and clinical decision-making,2 and (3) lacks appropriate justification.3 Robert et al (2006) rely on these points to claim that scientists who rely on this model are acting ?unethically,? because the model inaccurately oversimplifies development and suggests unrealistic future therapies.4 In this project I provide an analysis of the rationale that underlies the pathway model in the context of hematopoietic stem cell biology. I suggest that this model is representative of current scientific understanding and that it can be used to appropriately inform decision- making. In order for this model to appropriately figure in various decision-making processes, the assumptions and reasoning strategies that it depends on must be appreciated, as these clarify the scope and limits of the model. %D 2016 %K bioethics; causation, explanation %I University of Pittsburgh %L pittir29081 %A Christopher Hortert %T CONTAMINATED GROUNDWATER FLOW CONTROL ACROSS AN INVERTED GROUNDWATER DIVIDE WITH THREE GROUNDWATER CONTROL SYSTEMS %X The potential impacts from legacy, unlined landfills to surrounding hydrological systems are substantial challenges in the management of waste and water quality. Because these landfills do not have passive controls (i.e. liners), groundwater controls (pumping wells, trenches, etc.) can be necessary to minimize impacts. However, the function and interaction of multiple groundwater control devices in combination with complicated hydrogeologic settings are poorly characterized. Most research on groundwater control device interactions relies on simulation experiments and either measures the effectiveness of a system using a limited set of groundwater control devices or focuses on a single aquifer. This thesis examines three groundwater control devices (a slurry wall, a pumping trench, and a pumping well) installed near an active legacy landfill to evaluate changes in the flow of contaminated groundwater off site. This system of control devices was evaluated using monthly water quality data from a spring where changes in water quality were observed prior to installation of the groundwater control system. The water geochemical results indicate that the contaminated groundwater flows primarily through the fractured rock in the ridge (contrary to expectations), and therefore the collection trench is more effective in contaminant flux reductions. The groundwater pumping well, designed to capture contaminated groundwater flow through the coal seams and sandstone, is less effective, likely due to limited transport through the coal aquifers. Although the groundwater control system reduces the amount of contaminated groundwater flow off site, these controls must operate until the landfill is closed and a permanent control (i.e. installation of a clay cap which will reduce infiltration and should result in reduced groundwater elevations) can be installed which may take decades. The results provide fundamental information for future application of groundwater control in complicated field sites. %D 2016 %K groundwater control through a ridge using three groundwater control devices %I University of Pittsburgh %L pittir27588 %A Rana Zakerzadeh %T A Computational model for fluid-porous structure interaction %X This work utilizes numerical models to investigate the importance of poroelasticity in Fluid- Structure Interaction, and to establish a connection between the apparent viscoelastic behavior of the structure part and the intramural filtration flow. We discuss a loosely coupled computational framework for modeling multiphysics systems of coupled flow and mechanics via finite element method. Fluid is modeled as an incompressible, viscous, Newtonian fluid using the Navier-Stokes equations and the structure domain consists of a thick poroelastic material, which is modeled by the Biot system. Physically meaningful interface conditions are imposed on the discrete level via mortar finite elements or Nitsche's coupling. We further discuss the use of our loosely coupled non-iterative time-split formulation as a preconditioner for the monolithic scheme. We further investigate the interaction of an incompressible fluid with a poroelastic structure featuring possibly large deformations, where the assumption of large deformations is taken into account by including the full strain tensor. We use this model to study the influence of different parameters on energy dissipation in a poroelastic medium. The numerical results investigate the effects of poroelastic parameters on the pressure wave propagation, filtration of the incompressible fluid through the porous media, and the structure displacement. %D 2016 %K Fluid-structure interaction, Poroelasticity, Finite elasticity, Energy dissipation %I University of Pittsburgh %L pittir28595 %A Ashley Ace %T Documenting the Geometry and Magnitude of Shortening at the Allegheny Front: Lycoming County, Pennsylvania %X The Appalachian Mountain belt extends through the eastern United States and into southeastern Canada, and is expressed as elongated topographic ridges and valleys of folded and thrust faulted sedimentary and crystalline rock. The Appalachian Plateau (AP) in northwest Pennsylvania, and the Appalachian Valley and Ridge in southeastern Pennsylvania have pronounced differences in geologic structure and topographic expression. The AP consists of gentle folds and low relief (but higher elevation) topography, and 10-15 percent layer parallel shortening (LPS) in rocks sampled at the surface. In contrast, the Valley and Ridge province is a blind fold and thrust belt. The duplexing sequence in the Valley and Ridge is bound by a deep decollement surface within shales of the Cambrian Waynesboro Formation, underlying a detachment at the base of the Ordovician Reedsville shale. Twenty-four kilometers of shortening in the Cambrian ? Ordovician sequence is expressed as LPS in the AP. Due to the deficiency of geophysical and outcrop data, all the strata in the AP above the Silurian salt detachment has been assumed to be shortening via LPS plus very gentle folding. Increased hydrocarbon exploration has led to the acquisition of new high quality 3-D seismic and well log data which reveal that the strata from Silurian Salina Group through the Devonian Marcellus shale is shortening through a variety of mechanisms including wedge-style thrust faulting and folding. Through kinematically restored and balanced cross sections we show that the magnitude of microscale shortening calculated from the rocks exposed at the surface of the AP is equal to the magnitude of macroscale shortening in the Silurian-lower Devonian units immediately above the salt detachment. Comparing our interpretations with previously published seismic throughout the AP allows us to extend our model of how shortening in the Salina Group through Marcellus shale is balanced by LPS in the rocks above the Marcellus shale to include the extent of the previously published studies. As the hydrocarbon-rich Marcellus shale is a part of this uniquely deforming Silurian-Devonian package, understanding the geometries of these structures has a potential impact on the quality and quantity of hydrocarbon recovery. %D 2016 %K Appalachian Plateau, Valley and Ridge, Seismic, Marcellus Shale, Geologic Structure %I University of Pittsburgh %L pittir28655 %A Qinghao Zhang %T Enhancing the Solubility of Calcium Phosphate Ceramics by Calcium Salt Infiltration for the Purpose of Hematopoietic Stem Cell Culturing %X The hematopoietic stem cells (HSCs) have been unquestionably important to therapies that involve blood and immune system replacement. However, the in-vitro culture and the expansion of HSCs inhibit their application. This work aims to develop a composite biodegradable 3D scaffold that would simulate key aspects of the in-vivo microenvironment (niche) in which expansion of the hematopoietic stem cells takes place in human bone marrow. Hydroxyapatite (HA) has been chosen as a scaffold material because of its biocompatibility and the ability to create an osteogenic scaffold and thereby simulate trabecular bone that is known to be important to the HSC niche in bone marrow. It is hypothesized that the use of a Ca-rich HA scaffold will create a three dimensional, protective environment for HSCs and further promote their in-vitro expansion by releasing Ca ions into the culture medium. The first part of this study examined the processing of Ca-rich HA and the release of calcium ions into saline over time. The Ca-rich phase was introduced into the HA by an infiltration process and has been shown to release calcium into the culture medium over 42 days. The second part of this study examined the effect of the scaffold material on the fate of human umbilical vein endothelial cells (HUVECS), a well-known endothelial progenitor model. The results showed, for the first time, that at least some HUVEC cells have hematopoietic potential and that the scaffold promoted differentiation down the hematopoietic cell lineage. This is thought to be due to hemangioblast character in the HUVEC cells which is also shared by HSCs. Finally the effects of the scaffold on the in-vitro co-culture of an osteoblast cell line and primary human bone marrow derived HSCs was studied. The infiltrated scaffolds were shown to stimulate the HSC population to differentiate down the hematopoietic lineage and also showed greater potential to differentiate down the HSC lineage in consequent CFU assays. %D 2016 %K Hydroxyapatite, Hematopoietic stem cell, infiltration %I University of Pittsburgh %L pittir28563 %A Michael A. Freeman %T The Ethical Implications of Emerging Genetic Predictors of Poor Organ Transplant Outcomes %X Emerging research is beginning to identify genetic risk factors which may predict an increased likelihood of rejection following transplantation. The identification of these predictors prompt us to consider how we should incorporate this information into the process of transplant candidate evaluation and organ allocation, as well as the ethical implications of such incorporation. In order to ground this analysis, this thesis begins with an examination of how we consider other predictors of poor transplant outcomes currently, as interpreted in concordance with the US transplant system?s dual goals of efficacious and just organ allocation. It then proceeds with a brief summary of the current research on genetic predictors of poor transplant outcome, followed by a specific examination of the mechanisms by which these genes are investigated. This allows an examination of the challenges of appropriately applying the data gained through common methods of genetic research. Next, it examines the complex ethical and social conflicts which may arise from a decision to incorporate genetic predictors within the current US transplantation system. It then concludes with a proposal for a mechanism for including genetic risk profiles into the transplant evaluation process on a national level that will seek to mitigate these conflicts and support both a just allocation system and ongoing research into this area of medicine. %D 2016 %K Bioethics, Genetic, Organ Transplantation, Medicine %I University of Pittsburgh %L pittir28659 %A Rongzhang Chen %T Fiber-Optic Sensing for High-Temperature and Energy Applications %X Fiber-optic sensors act as important roles in many of today's industrial sectors. It provides vital information for a large number of applications such as process controls, fossil fuel and nuclear electrical power generation, transportation, and environment monitoring. Compared with their electronic counterparts, fiber-optic sensors truly stand out where extreme operation environments leave almost all the electronic sensors unusable. Derived from the superior properties of optical fibers such as high-temperature stability, immunity to electromagnetic interference and strong resistance to most chemicals, fiber-optic sensors can be engineered to deliver sensing performance under various adverse conditions. Recently numerous research efforts have been put to leverage those merits of optical fibers to achieve sensing capabilities under high-temperature environments (> 600 deg C). In this thesis, five fiber-optic sensing schemes are demonstrated to explore and validate the potential of fiber-optic sensors for high-temperature and energy applications. The first scheme manifests itself as a high-temperature-stable distributed Bragg reflector (DBR) fiber laser which intrinsically is able to operate and measure ambient temperatures up to 750 deg C. The second scheme is based on self-heated high-attenuation fibers (HAFs). Thanks to HAFs and regenerated fiber Bragg gratings, a hot-wire flow meter with ambient temperature compensation was realized with all-optical fiber construction with maximum operational temperature at 800 deg C. In the third sensing scheme, the other kind of fiber grating laser, the distributed feedback (DFB) fiber laser as strain sensor is presented to monitor acoustic emissions for a lab-induced hydraulic fracturing process. The fourth scheme covers a 3D strain field imaging technique for hydraulic fracturing study, enabled by Rayleigh backscatter based optical frequency domain reflectometry (OFDR). In the fifth scheme, we are aiming at increasing the measurement accuracy of the OFDR system by reducing the system measurement noise level. Via cavity ring down method, the system noise is demonstrated to reduce by over 52%. All these technologies and devices offer reliable and flexible sensing solutions for high-temperature and energy industrials, which were not previously possible. %D 2016 %K fiber optic, energy, high-temperature, distributed Bragg reflector, fiber laser, hot-wire anemometer, flow meter, distributed feedback, acoustic measurement, strain monitoring, hydraulic fracturing, Rayleigh scattering, distributed measurement, cavity ring down %I University of Pittsburgh %L pittir23464 %A Leitao Chen %T Finite Volume Discrete Boltzmann Method on a Cell-Centered Triangular Unstructured Mesh %X Due to its basis in kinetics, the lattice Boltzmann method (LBM) has been shown to be superior to conventional computational fluid dynamic (CFD) tools that solve the Navier-Stokes (NS) equation for complex flow problems, such as multiphase and/or multicomponent flows. However, after development for decades, the LBM still has not gained prominence over other CFD tools for a number of reasons, one of which is its unsatisfactory ability to handle complex boundary geometries. The goal of the current work is to overcome this difficulty. In order to fully integrate the unstructured mesh for treating complex boundary geometries, the discrete Boltzmann equation (DBE), which is the Eulerian counterpart of the lattice Boltzmann equation (LBE), is chosen for the study. The finite volume (FV) method is selected to solve the governing equation due to its outstanding performance in handling an unstructured mesh and its built-in conservation. Therefore, the method in the current work is called the finite volume discrete Boltzmann method (FVDBM). A FVDBM platform, both for isothermal and thermal models, is developed in the current work, which consists of three parts: the cell-centered (CC) triangular unstructured mesh, the FVDBM solver, and the boundary treatment, among which the latter two are the main areas of contribution. In the FVDBM solver, there are three components: the time marching scheme, the flux scheme, and the collision calculator. The flux schemes are the major area of study because of their significance in the overall FVDBM model (they control the spatial order of accuracy) and their complexity (they calculate the spatial gradient term) on the unstructured mesh. A universal stencil is developed on the arbitrary CC triangular unstructured mesh, with which two categories of flux schemes are developed systematically: the Godunov type and the non-Godunov type. As a result, a total of five schemes (three Godunov schemes and two non-Godunov schemes) with different orders of accuracy are formulated, numerically validated and analyzed. Two major conclusions can be drawn. First, for any flux scheme, Godunov or non-Godunov, its actual order is roughly one order lower than its theoretical order for velocity solutions, due to the diffusion error introduced by the unstructured mesh and the Eulerian nature of the solver. Second, a Godunov scheme is less diffusive and more stable than a non-Godunov one if they are of the same order of accuracy. Furthermore, a unique three-step boundary treatment is developed in detail for the current model. With the proposed boundary treatment, a variety of physical boundary conditions (velocity, density, and temperature, etc.) can be realized on the complex boundaries with the triangular unstructured mesh in a unified way. It can also incorporate different lattice models indiscriminately. With sufficient numerical testing, it is found that the boundary treatment is at least second-order accurate in space, and it can accurately preserve Dirichlet boundary conditions up to machine accuracy under different scenarios. %D 2016 %K lattice Boltzmann; BGK collision; finite volume method; flux schemes; order of accuracy; numerical viscosity; unstructured mesh; boundary treatment; Dirichlet Boundary %I University of Pittsburgh %L pittir28066 %A Sung Jae Chung %T Fundamental study of the design and development of iron based alloys for biodegradable implant device applications %X Biodegradable metals have been widely studied in recent years as potential biomedical implant materials which exhibit higher mechanical properties than degradable polymers while corroding over time to alleviate known complications such as stress-shielding, infection, permanent physical irritation and secondary removal/revision surgeries that is inherent to permanent and bio-inert metallic biomaterials. Specifically, iron (Fe), magnesium (Mg), and their alloys are the two main classes of metals that have been considered as promising candidates for degradable load and non-load bearing bone implants, cardiovascular stents, and other implantable medical devices. However, most of the research on Fe and Fe based alloys have reported very slow degradation rate in physiological environments while Mg and Mg based alloys under rapid degradation. Hence, controlling the degradation rates of these metals has been a key challenge limiting the technological development and implementation of these systems requiring more fundamental studies to be conducted. There is therefore the need to modify the chemical composition and microstructural characteristics through the appropriate alloying techniques with suitable alloying elements. Some studies have been conducted to overcome these limitations but the degradation rates and cytocompatibility of the two main classes of metals are still far from levels necessary for implementation in clinical applications. An alternative approach is therefore needed to develp metallic materials with improved degradation behavior wihle maintaining ithe desired biocompatibility. Although Fe and Mg have been studied separately as degradable implants, there are no reports on the Fe-Mg binary alloy system for use as biodegradable metallic materilas because of the thermodynamic immiscibility of Fe and Mg under ambient conditions. In this dissertation, novel non-equilibrium alloys, particularly in the Fe-Mg binary system with additional elements, have been proposed and studied for their desirable corrosion and cytocompatible properties. The first part of this dissertation focuses on the formation of amorphous alloys in the Fe-Mg binary alloy system through the process of high energy mechanical alloying (HEMA) followed by pulsed laser deposition (PLD) in order to overcome the limitations of the immiscibility of Fe-Mg. In the second part of this dissertation, an alloy development strategy to accomplish high degradation rates, antiferromagnetic behavior and good cytocompatibility is presented. Thus, manganese (Mn), calcium (Ca) and zirconium (Zr) were selected and added as alloying elements, which include the following two aspects: (i) Electrochemical considerations to increase the corrosion rates by electrochemical modification of the Fe matrix; (ii) addition of Mn to introduce anti-ferromagnetic characteristics to the alloy for exploring biological applications. Powders and thin layers were characterized for their composition/structure and evaluated potential for biomedical applications using preliminary in vitro cytocompatibility and corrosion experiments. For Fe-Mg binary alloy, uniform corrosion of Fe70Mg30 amorphous thin layer was observed and the corrosion current density value was approximately 8 fold higher than pure Fe. The direct and indirect cytotoxicity results indicated that Fe70Mg30 amorphous thin layer has no cytotoxicity to MC3T3-E1, hMSCs, HUVECs and NIH3T3 cell lines. Similarly, addition of Ca, Zr and Mn indicate good cytocompatibility with suitable modifications in the corrosion rates %D 2016 %K Iron alloys, Biodegradable metals, High energy mechanical alloying, Pulsed laser deposition, Amorphous, Biomaterials %I University of Pittsburgh %L pittir28914 %A Injung Ko %T IMPACT OF SELF- AND GROUP-AFFIRMATION ON RESPONSE TO INGROUP AND OUTGROUP OSTRACISM %X Two studies examined the effectiveness of self- and group-affirmation in reducing the aversiveness of ingroup and outgroup ostracism. It was hypothesized that in the case of ingroup ostracism, self-affirmation (but not group-affirmation) would be more effective in buffering against negative reactions than no-affirmation, whereas in the case of outgroup ostracism, group-affirmation (but not self-affirmation) would be more effective than no-affirmation. Both studies employed a 3 (affirmation: self vs. group vs. no) ? 2 (ostracism: ingroup vs. outgroup) between-participants design. After completing a self-affirming, group-affirming, or non-affirming writing task, undergraduates were ostracized by either ingroup or outgroup members in a three-person Cyberball game. Participants in Study 1 (strong ostracism) and Study 2 (moderate ostracism) received the ball on 6.7% and 16.7% out of thirty tosses, respectively. In Study 1, participants reported uniformly high levels of aversiveness and negative emotions across the six conditions. In Study 2, in the ingroup ostracism condition, self-affirmed participants, but not group-affirmed participants, reported significantly lower aversiveness and less negative emotion than did non-affirmed participants. In the outgroup ostracism condition, neither self- nor group-affirmation reduced negative responses relative to no affirmation. Implications and suggestions for future studies are discussed. %D 2016 %K Ostracism, Social exclusion, Self-affirmation, Group-affirmation, ingroup/outgroup %I University of Pittsburgh %L pittir29342 %A Yihong Kang %T IN-SITU AND EX-SITU STUDIES ON EARLY-STAGE SCALE ESTABLISHMENT %X This thesis study is divided into two parts. In the first part, competitive oxidation during the nucleation-and-growth stage was investigated based on studies on Cu-Ni and Ni-Cr alloys. Two competing oxidation mechanisms were proposed to interpret the competitive oxidation behavior of a dilute Cu-Ni alloy during the nucleation-and-growth stage of oxidation under 10-4 Torr oxygen pressure at a temperature range from 350? to 600?. NiO was found to be the preferred oxide phase to form initially on the Cu-Ni alloy surface rather than a copper oxide product. Depending on the time of the growth process, an individual NiO island could be limited by oxygen surface diffusion, diffusion of Ni in the Cu-Ni matrix towards the surface, or a combination of these two processes. In the competitive oxidation of dilute Ni-Cr alloys under low oxygen partial pressures (10-7 to 10-5 Torr) at 600?, it was found that Cr2O3 is the preferred oxide to form on the alloy surface, with the growth of Cr2O3 being limited by diffusion of Cr in the alloy towards the surface. Only when the amount of Cr2O3 formed initially on the surface was sufficiently high that the oxygen inward diffusion into alloy could be reduced to the extent that establishment of a continuous Cr2-O3 scale was possible. The second part of this study investigated the third-element effect on Al2O3-scale formation on Ni-based alloys. Two new perspectives of the third-element effect were proposed. The Cr addition to a relatively dilute Ni-Al alloy resulted in the formation of much coarser internal oxides, and decreased the internal oxidation rate significantly; on the contrary, Mn addition, which has the similar affinity to oxygen as Cr, to a similar Ni-Al alloy led to the formation of much finer rod-like internal oxides, and increased the internal oxidation rate significantly. Based on this experimental observation, it was proposed that the addition of a third element may change the internal oxide phase and morphology, such that the diffusion path of oxygen in the internal oxidation zone could be significantly affected, which in turn could affect the internal-to-external oxidation transition. The Cr addition into a relative dilute Ni-Al alloy was also found to enhance the Al grain-boundary diffusion at lower temperature (below 1000?), which consequently enhanced the Al2O3-scale establishment during the heating process. Surface recrystallization, which occurs during the heating of alloys prepared with an abraded surface finish (i.e., 500-grit), could result in the formation of fine sub grains around 1 ?m in size near the alloy surface, and provide necessary fast diffusion paths for Al. This Cr effect on the Al grain-boundary diffusion was much more evident during the oxidation of surface-abraded Ni-Al-Cr alloys than on the same alloys with a polished surface finish. %D 2016 %K oxidation, alloy, high-temperature, thin film, third-element effect, alumina %I University of Pittsburgh %L pittir29007 %A Jung Lim %T Improving the design and operation of WHO-EPI vaccine distribution networks %X Vaccines have contributed significantly to the prevention of diseases. Yet millions of children, especially in low and middle income countries, remain unvaccinated and are exposed to preventable diseases such as typhoid, measles and tuberculosis. There are many reasons for this including personal belief systems, vaccine safety concerns, problems with vaccine availability, failures in the healthcare system, social barriers and economic constraints. International organizations are making continual efforts to increase vaccine coverage in these countries using various strategies. In this research we focus on the problems associated with poor design and operation of vaccine delivery systems and address these issues via four broad contributions. First, we present four quantitative models that can be used to optimize the selection of locations for vaccine outreach (where teams from clinics go to relatively remote places to administer vaccines), in order to maximize the number of residents that can be reached; each model addresses a different type of coverage possibility. The models are analyzed and contrasted using an example and adapted to address the situation when the coverage assumptions and demands are uncertain. Second, we propose modular vaccine packaging as an alternative to current packaging, which is not standardized and leads to inefficiencies when packing vaccines into a storage device; this in turn can result in vaccine shortages. We illustrate the benefits of modular packaging over current packaging schemes and storage devices that are commonly used in the field. Third, we suggest alternative ordering policies at the clinic level that are based on secondary vaccine packaging. The policies draw upon lean concepts that have been used in the manufacturing sector to simplify and improve inventory management. Since the ordering units are larger, storage space issues may occur at clinics or during vaccine transportation and the new ordering polices are analyzed in terms of their effect on storage. Lastly, we propose a mathematical model to redesign the vaccine distribution network from a central warehouse to individual health clinics and study algorithms to solve this difficult problem. We propose a hybrid algorithm based on mixed integer programming and an evolutionary strategy. We also describe how to improve the performance of the evolutionary strategy and how to use the results of the evolutionary strategy to reduce the calculation time of the integer programming model. %D 2016 %K Vaccine, Supply chain, Network design, packaging, coverage model, Evolutionary strategy %I University of Pittsburgh %L pittir28696 %A Gabriel Lopez Zenarosa %T Integrating Proactive and Reactive Decision-making in Surgery Scheduling %X Aggregate surgical expenditures in the US amounted to about 5.2% of the Gross Domestic Product in 2010, and are projected to increase. About 42% of hospitals' revenues are generated by their operation rooms (ORs), yet the average OR runs at only 68% capacity. While OR management has many aspects, the most important and challenging issues are centered on surgery scheduling. Advance surgery schedules improve OR efficiency; however, days of surgeries rarely go as planned, and rescheduling is performed in practice as uncertainties unravel. Surgery scheduling involves sequential decision-making; advance scheduling and day-of-surgery rescheduling must account for subsequent rescheduling to achieve better OR efficiencies over myopic decision-making. This dissertation focuses on the integration of proactive and reactive decision-making in surgery scheduling. We present stochastic programs with chance-constrained recourse for surgery scheduling and rescheduling: minimizing the total expected OR underutilization subject to probabilistic overtime constraints, where surgery durations and occurrences are random. We demonstrate how our approach outperforms the surgery scheduling and rescheduling policies used in practice at a hospital, and we provide some insights on further improvements that can be made at the operational, tactical, and strategic decision-making levels. %D 2016 %K surgery scheduling, advance scheduling, day-of-surgery rescheduling, stochastic programming, chance-constrained programming, chance-constrained recourse, probabilistic constraints, integer programming, optimization, optimization software, modeling systems, parallel algorithms %I University of Pittsburgh %L pittir28900 %A Hillary C. Cleveland-Rubeor %T A MINIMAL CONSERVED REGION OF SHROOM2 AND SHROOM3 MEDIATES ACTIN BINDING AND BUNDLING %X Changes in cell morphology are essential for generating the complex tissues that make up all organisms. Regulation of the cell?s morphology is dynamic and is achieved through the coordinated activity of numerous signaling pathways and proteins that converge on the cytoskeleton at many levels. In epithelial cells, the Shroom family of proteins drives anisotropic changes to morphology such as apical constriction and convergent extension in the formation of such structures as the neural tube, vasculature, gut, and eye. Shroom proteins are a class of actin-binding proteins that recruit Rho-associated coiled-coil Kinase (or Rock), to the cytoskeleton to induce contraction of the actin network and effect change. Recent work in this field has focused on understanding the direct interaction of Shroom and Rock, but little work has been done to understand how Shroom proteins directly interact with actin. The actin-binding ability of these proteins has been localized to Shroom Domain 1, a domain unique to Shroom proteins. My work has centered on better understanding the interaction between the SD1 and actin. I have identified small, conserved regions of both Shroom2 and Shroom3 that are capable of binding and bundling actin with similar affinity. With the use of Transmission Electron Microscopy, I observed that both proteins organize actin filaments into similar tightly packed parallel or anti-parallel bundles. While Shroom proteins localize to different populations of actin within the cell, it appears that the ability to bind and bundle actin has been conserved, and that other region of the proteins must drive their unique localization patterns. %D 2016 %K Shroom, Shroom2, Shroom3, Shroom Domain 1, SD1, Actin, Actin-binding proteins, Actin-bundling proteins, TEM, Transmission Electron Microscopy %I University of Pittsburgh %L pittir29174 %A Qingcheng Yang %T MULTIRESOLUTION MOLECULAR MECHANICS: THEORY AND APPLICATIONS %X A general mathematical framework, Multiresolution Molecular Mechanics (MMM), is proposed to consistently coarse-grain molecular mechanics at different resolutions in order to extend the length scale of nanoscale modeling of crystalline materials. MMM is consistent with molecular mechanics in the sense that the constitutive description such as energy and force calculations is exactly the same as molecular mechanics and no empirical and phenomenological constitutive relationships in continuum mechanics are employed. As such, MMM can converge to full molecular mechanics naturally. As many coarse-graining approaches, MMM is based on approximating the total potential energy of a full atomistic model. Analogous to quadrature rules employed to evaluate energy integrals in finite element method (FEM), a summation rule is required to evaluate finite energy summations. Most existing summation rules are specifically designed for the linear interpolation shape function and their extensions to high order shape functions are currently not clear. What distinguishes MMM from existing works is that MMM proposes a novel summation rule framework SRMMM that is valid and consistent for general shape functions. The key idea is to analytically derive the energy distribution of the coarse-grained atomistic model and then choose some quadrature-type (sampling) atoms to accurately represent the derived energy distribution for a given shape function. The optimal number, weight and position of sampling atoms are also determined accordingly, similar to the Gauss quadrature in FEM. The governing equations are then derived following the variational principle. The proposed SRMMM is verified and validated numerically and compared against many other summation rules such as Gauss-quadrature-like rule. And SRMMM demonstrates better performance in terms of accuracy and computational cost. The convergence property of MMM is also studied numerically and MMM shows FEM-like behavior under certain circumstance. In addition, MMM has been applied to solve problems such as crack propagation, atomic sheet shear, beam bending and surface relaxations by employing high order interpolation shape functions in one (1D), two (2D) and three dimensions (3D) . %D 2016 %K MULTIRESOLUTION MOLECULAR MECHANICS; SUMMATION RULE; GENERALIZED QUASICONTINUUM METHOD; COARSE-GRAINED ATOMISTICS; ATOMISTIC-TO-CONTINUUM COUPLING; MULTISCALE MODELING %I University of Pittsburgh %L pittir28638 %A Justin Proto %T Microwave Assisted Intramolecular Dehydrogenative Dehydro-Diels Alder Approach to Substituted Benzofused Heterocycles %X The emergence of benzo[b]thiophenes and benzo[b]furans as biologically useful scaffolds is of growing attention in medicine as natural products and pharmaceutical drugs. The means to produce these synthetic cores quickly and from economic starting materials has garnered much attention. Much of the current methodology is focused on formation of the heterocyclic ring annulation from benzene derivatives. However, the mechanistic restraints ofthis chemistry narrows the substitutional scope of the resulting benzo-fused heterocycles. Presented here is a simple methodology to produce uniquely substituted benzo[b]thiophenes and benzo[b]furans via the intramolecular dehydro-Diels-Alder reaction induced by microwave heating. Starting from aromatic heterocycles and focusing on a strategy of benzene annulation from heterocyclic-diene alkynyl-dienophile pairs forming tricyclic fused heterocycles were readily synthesized. The allowance of major product selection was demonstrated by solvent choice during heating; fully aromatic heterocycles were favored when PhNO2 was chosen, in as little as 10% by volume. The use of DMF favored the formation of dihydroheterocycles. The reaction showed a tolerance of terminal alkyne substitution and generally produced good yields. %D 2016 %K Benzofused Heterocycles, Diels Alder, intramolecular, microwave assisted %I University of Pittsburgh %L pittir28562 %A Mahdis Shayan %T Novel Surface Modification Techniques to Enhance Biocompatibility of Metallic Materials for Medical Implants %X Four different novel surface modification techniques have been investigated to enhance the cell growth behavior in metallic implantable materials. The potential of each technique has been studied for improving current treatments in a target disease. The first surface modification technique is the creation of nanoscale grain surfaces on stainless steel 316L material via linear plane-strain machining. The in vitro cell adhesion study demonstrates the enhanced osteoblast adhesion and growth on the native oxide layer formed on the material with the smallest grain size (i.e., created by 0? rake angle). This result represents a high potential of nanoscale grain surface in stainless steel for improving the bone bonding for orthopedic biomaterials. The second surface modification technique is a rapid endothelialization of thin film nitinol through electrostatic cell seeding process. This technique utilizes dielectrophoresis supplying for temporarily created positive surface charges on thin film nitinol. In vitro cell adhesion assays have demonstrated the enhanced seeding of endothelial cells on thin film nitinol under the optimal electrical conditions (i.e., 5V applied voltage for 30 minutes) which shows the potential use of the technique for thin film nitinol based low-profile endovascular graft. In the third technique, a thin layer of silk is deposited on the thin film nitinol substrate using electrospinning technique to facilitate the surface endothelialization and to enhance the hemocompatibility. The proof-of-concept in vitro test results have demonstrated that the integrated thin film nitinol and electrospun silk represents a high-potential candidate material for small-diameter vascular grafts owning to favorable properties of thin film nitinol and silk. The last technique introduces the micropatterned thin film nitinol as a novel low-profile cover for stents in treating carotid artery stenosis disease. A sputter deposition technique along with a lift-off process was used to create various microscale features in thin film nitinol. The micropatterned thin film nitinol effectively captured the embolic particles dislodged from the carotid artery stenosis in vitro model. Besides, the micropatterned thin film nitinol has significantly enhanced endothelial cell adhesion and growth. Therefore, four surface modification techniques showed advancement in cellular behavior with the various metallic biomaterials used in treating critical diseases. %D 2016 %K BIOCOMPATIBILITY, BIOMATERIALS, METALLIC IMPLANTS, SURFACE MODIFICATION %I University of Pittsburgh %L pittir28925 %A Justin Coughlin %T REACTIVE NITROGEN EMISSIONS AND DEPOSITION FROM UNCONVENTIONAL NATURAL GAS EXTRACTION IN THE MARCELLUS SHALE BASIN %X Emissions of nitrogen oxides (NOx = NO + NO2) in the United States (U.S.) from large stationary sources, such as electric generating units, have decreased since 1995 and resulted in the associated decreases in nitrogen (N) deposition, ambient ozone and nitrogen dioxide (NO2) concentrations. However, increasing NOx emissions from emerging industries, such as unconventional natural gas (UNG) extraction, could potentially offset gains in stationary source emission reductions in shale gas producing regions of the U.S. The Marcellus Shale in the northeastern U.S. has seen dramatic increases in the development of wells over the past ten years, and it is currently unknown whether NOx emissions from UNG extraction are having an effect on ecosystems or air quality. In our study, modeling, experimental, and field studies were used to investigate the influence of Marcellus Shale UNG extraction activities on local and regional fluctuations in N emissions, ambient concentrations, and deposition fluxes. In one study, we determined that federal deposition monitoring networks do not effectively capture regional well pad NOx emissions, despite the high well pad density areas of northeastern and southwestern Pennsylvania where NOx emissions densities can reach 21 kg NOx ha-1 year-1. In another study, passive samplers were deployed at a collaborative research well in the Marcellus Formation, the Marcellus Shale Energy and Environment Laboratory (MSEEL) located in Morgantown, West Virginia (WV) to assess spatio-temporal changes in ambient concentrations, deposition, and isotopic composition of key reactive nitrogen species over a transect spanning the research well pad and access road. NO2, nitric acid (HNO3), ozone (O3), and ammonia (NH3) were measured over the entire well cycle from site development through production. Using an isotopic mixing model, we determined that the N deposition attributable to well pad activities ranged from 0.16 to 0.55 kg N ha-1 within 400 m of the well pad. This research demonstrates that even though well pad activities are not effectively being monitored on a regional scale, the activities are having an effect on local N deposition dynamics and are high enough to impact local ecosystems in high well pad density areas. %D 2016 %K Nitrogen oxides, natural gas extraction, Marcellus Shale, nitrogen deposition %I University of Pittsburgh %L pittir29256 %A Erkan Bayir %T ROLE OF HNRNP H IN A REVERSIBLE FINE-TUNING MECHANISM OF SPLICING RESPONSE UPON TRANSCRIPTIONAL PAUSING %X Alternative splicing is a common way of diversifying the proteome and regulating protein functions without increasing genome size. Chemotherapeutic agents, such as cisplatin, cause changes in the splicing of proliferation-associated exons, which contribute to the overall proliferative phenotype of cancer cells. Transcriptional pausing, which is seen in embryonic stem cells as a timing regulator of gene expression, also impacts splicing. The mechanisms by which transcriptional pausing and pause-release alter the functions of splicing machinery are largely unknown. Thus, I tested the effects of the transcription elongation inhibitor DRB (5,6-dichloro-1-?-D-ribofuranosylbenzimidazole) on the splicing of a set of inducible exons with a common UAGG-GGGG splicing code. These exons were previously identified through a genomewide search for the transcripts sensitive to hnRNP A1 and hnRNP H. I found that the endogenous human HNRNPH1 Exon 4 and its paralog HNRNPH3 Exon 3 had increased skipping upon DRB treatment, as did the pA+ reporter-cloned GRIN1 CI, a brain-region-specific rat exon with this splicing code, previously studied in our lab. I used single and combined mutations to monitor the effect of DRB-induced transcriptional pausing and pause-release on splicing, since the shared motifs include two exonic UAGG motifs and a GGGG close to 5? splice site. GGGG mutants had increased skipping, compared to wild type, upon DRB treatment. UAGG-GGGG code is necessary for the response, as the triple mutant lost its ability to respond to DRB. These data point to a role of hnRNP H in response to transcription stress. %D 2016 %K splicing, transcription, stress, pause-release, DRB %I University of Pittsburgh %L pittir29176 %A Xiang Chen %T Smartphone Power Consumption Characterization and Dynamic Optimization Techniques for OLED Display %X Smartphones have emerged as the most popular and frequently used platform for the consumption of multimedia. Following the rapid growth of application number and the explosion of cellular network bandwidth, high power consumption, and limited battery capacity remain as the major challenges in smartphone designs. Therefore, lots of research is made to characterize and optimize the smartphone power performance. However, the existing research approaches on smartphone power characterization generally ignore the impact from the components' varying performance in different applications, as well as users' behavior during the practical usage. Hence, the power optimization techniques in the modern smartphone are inflexible to adapt to different application scenarios and user behaviors. In this dissertation, I first proposed a new smartphone power consumption characterization and analysis approach -- ``SEER'', which was associated with both user ethological and smartphone evolutionary perspectives. The real-time power consumption is measured with a set of the most popular applications on different generations of Samsung Galaxy smartphones. And deep analysis is made to find how each smartphone component is utilized in different applications, and how the users' daily usage patterns impact on final energy consumption. The experiments show that some traditional power-hungry components, such as Wi-Fi and CPU, actually consume much less energy in practical daily usage. Meanwhile, OLED display panel is still the biggest power consumer in the whole smartphone system; even it's considered the most promising low power display technology. To further optimize the display power consumption with OLED. I further proposed a set of dynamic power optimization techniques for OLED display, balancing the real-time power performance and the user visual perception experience. In this dissertation, the optimization is full-filled at three different levels: 1) Hardware based Optimization: Based on the traditional AMOLED display pixel driver, a novel DVS-friendly OLED driver design is proposed, which can minimize the display color distortion under aggressive supply voltage scaling. Correlated fine-grained DVS schemes (DiViCi) are also proposed to utilize the DVS-friendly driver into video streaming applications. 2) Software based Optimization: Despite the hardware modification, a dynamic OLED power model is built to evaluate the OLED panel power consumption and human visual perception quality assessment. A novel video category based dynamic tone mapping (DaTuM) technique is proposed for video streaming; 3) User Interaction based Optimization: The user interaction and visual perception during the display content capture phase are also taken into consideration, a novel OLED power friendly video recording application (MORPh) was also proposed. Dedicated real-time management and reliability enhancement schemes are explored to promote the applicability of the proposed approaches . Experiments show that, with these power optimization techniques, the OLED display panel power performance on smartphone device is significantly improved with reasonable visual quality controllability. %D 2016 %K Displays, Power Measurement, Optimization Methods, Real-time Systems, Application Software, User Centered Design %I University of Pittsburgh %L pittir28086 %A Michael Cook %T Towards the Total Synthesis and Stereochemistry Determination of Stresgenin B %X The natural product stresgenin B has been shown to inhibit the up-regulation of HSPs in vivo. Since HSPs are known to protect cancerous cells from a variety of internal and applied stress (such as drug treatments and radiation), this makes stresgenin B a potentially new chemotherapeutic agent. Herein is described the development and application of a new synthetic method that efficiently installs a primary amide-bearing acetonide group. Based on extensive Reaxys and SciFinder searching, we have found this to be only the second example of such a moiety, and the first in the class of 5,5-bicyclic systems. This methodology has the potential to be expanded to include esters, carboxylic acids, and other more exotically functionalized acetonides. In addition, we have held in reserve analogous compounds (synthesized during the course of this work), very similar in structure and composition to the natural product, for future SAR studies. %D 2016 %K Stresgenin B Synthesis Natural Product HSP %I University of Pittsburgh %L pittir29241 %A Lu Zhang %T UNDERSTANDING MEMRISTORS AND SELECTORS FOR FUTURE STORAGE AND COMPUTING APPLICATIONS: MODELING AND ANALYSIS %X The memristor and selector devices are the most promising candidates in the research of emerging memory technologies and neuromorphic computing applications. To understand the device properties and guide for future applications, models for those devices based on physical mechanisms are essential. We developed models for two popular memristors and a selector. We developed a SPICE-compatible compact model of TiO2-TiO2-x memristors based on classic ion transportation theory. Our model is shown to simulate important dynamic memristive properties like real-time memristance switching, which are critical in memristor-based analog circuit designs. The model, as well as its analytical approximation, is validated with the experimentally obtained data from real devices. Minor deviations of our model from the measured data are also analyzed and discussed. We illustrate a heuristic two-state-variable memristor model of charged O vacancy drift resistive switches that includes the effects of internal Joule heating on both the electronic transport and the drift velocity (i.e. switching speed) of vacancies in the switching material. The dynamical state variables correspond to the cross-sectional area of a conducting channel in the device and the gap between the end of the channel and one of the electrodes. The model was calibrated against low voltage pulse-sweep and state-test data collected from a TaOx memristor so that the contributions of the channel gap, area and temperature to switching can be analyzed. The model agrees well with experimental results for long switching times and low-to-intermediate voltage operation. A selector device that demonstrates high nonlinearity, low switching voltage and volatility was fabricated using HfOx materials with Ag electrodes. The electronic conductance of such volatile selector device was studied under both static and dynamic conditions, with DC and AC measurements respectively. From experimental observations, a compact model is developed in this study to illustrate the physical process of the formation and dissipation of Ag filament for electron transport through the device. A dynamic capacitance model is used to fit the transient current traces under different voltage bias through the device and allow the extraction of parameters associated with the various parasitic components in the device. %D 2016 %K memristor, selector, modeling, ion transport theory, state variable, dynamic conductance and capacitance %I University of Pittsburgh %L pittir28634 %A Robert M. Miller %T Biomechanical Factors Influencing the Successful Non-Operative Treatment of Rotator Cuff Tears %X The risk of developing a degenerative rotator cuff tear increases dramatically with age, reaching over 50% in the 7th decade of life. The severe pain and loss of function brought on by rotator cuff tears underscores the importance of swift and effective treatment. Unfortunately, failure rates for treating rotator cuff tears remain high. Unsuccessful treatment may relate to failure to restore joint kinematics or propagation of the rotator cuff tear. Furthermore, it is not clear which types of tears (i.e. geometry and amount of degeneration) will result in propagation. Therefore, the objective of this work was to investigate the effects of exercise therapy and initial tear characteristics on alteration of glenohumeral kinematics and tear propagation. Glenohumeral joint kinematics were measured in subjects with an isolated supraspinatus tear before and after 12 weeks of therapy. Although exercise therapy does not increase sub-acromial space, therapy decreases the overall joint contact path length by 36%, indicating a more stable joint. Cadaveric experiments measured tear propagation for increasing levels of loading using a novel cyclic loading protocol. Anterior supraspinatus tears propagate at lower loads than tears in the middle third (389 ? 237 N vs 714 ? 168 N). Mechanical testing also showed that tendons with pre-existing rotator cuff tears are not more likely to propagate than artificial tears representative of a ?traumatic? rotator cuff tear (408 ? 86 N vs 580 ? 181). Histological analysis on cadavers (age 50-80) found no differences in degeneration between intact and torn supraspinatus tendons, indicating that age-related degeneration is a wide-spread phenomenon that can lead to the initiation of rotator cuff tears. Using experimental data, finite element models of supraspinatus tendon were validated and used to predict effects of tear size, location, and degeneration on propagation. Overall, the model found that larger, more degenerative tears in the anterior third of the supraspinatus tendon are most at risk for propagation. These results provide valuable information to improve treatment of rotator cuff tears based on tear characteristics at diagnosis, by focusing on improving joint kinematics and advocating for early treatment of degenerative tears that interrupt the rotator cable structure. %D 2016 %K Rotator cuff, kinematics, tear propagation, finite element modeling %I University of Pittsburgh %L pittir28190 %A Timothy Keane %T Extracellular Matrix for Repair of Gastrointestinal Mucosa %X Extracellular matrix (ECM) bioscaffolds have been shown to promote site-appropriate functional tissue remodeling in multiple anatomic sites, including the gastrointestinal (GI) tract. Discovery work over the past 2 decades has identified contributing mechanistic factors of ECM-induced tissue remodeling to be the modulation of the innate immune response by the action of embedded signaling molecules while naturally occurring cryptic peptide motifs released or exposed during ECM degradation and remodeling simultaneously promote stem/progenitor cell chemotaxis, proliferation, and differentiation. This immune stimulatory approach, paired with rapid restoration of the GI mucosal tissue, represents a novel therapeutic strategy for treating disease of the GI tract such as inflammatory bowel disease (IBD). The objective of the present thesis was to determine the efficacy of ECM for the repair of GI mucosal tissue. First, ECM was isolated from the proximal (esophagus) and distal (colon) of the GI tract to characterize spatial differences in the biochemical and mechanical properties of GI ECM. Next, we measured the effect of GI-ECM on epithelial cell remodeling and the inflammatory response. Finally, the efficacy of ECM for treating colonic mucosal tissue was tested in a rat model of IBD. Results show expected spatial changes in ECM along the GI tract with esophageal and colonic ECM having unique properties. Exposure of intestinal epithelial cells to GI ECM in-vitro led to enhanced epithelial cell remodeling and an increased barrier function. Macrophages exposed to degradation products of GI-ECM in-vitro were shown to exhibit an immunoregulatory and antiinflammatory phenotype. Finally, an enema hydrogel composed of GI ECM was shown effectively treat a rodent model of IBD. We defined effective therapy according to two essential physiologic processes that were positively directed by ECMH treatment. First, the colonic epithelial barrier function, which protects the host from the relentless barrage of proinflammatory luminal contents, was restored. Second, the pro-inflammatory state of tissue macrophages, which propagate inflammation by releasing inflammatory cytokines, was resolved. Together, this strategy represents a proactive therapeutic approach and is a distinct departure from the immunosuppressive (defensive) and surgical (salvage) methods currently used to treat IBD. %D 2016 %K Extracellular matrix, inflammatory bowel disease, macrophage activation, barrier function %I University of Pittsburgh %L pittir28126 %A Annuli Okoye %T Liquid-Liquid Extraction Process for High Efficiency Rapid Purification of Copper Radionuclides %X According to a new market report published by Transparency Market Research, the global market for radiopharmaceuticals was valued at approximately 3.8 billion USD in 2011 and is expected to reach 12.2 billion USD by 2018 (2013). Usually, these radiopharmaceuticals consist of three major components: 1) a biomolecule (BM) responsible for receptor targeting; 2) a bifunctional chelate (BFC) for radionuclide coordination; and 3) a radionuclide for imaging and/or radiotherapy. Specific activity (SA) is one of the most important parameters for characterizing the quality of radionuclides or radiotracers. In many cases, it is the limiting factor for using radiotracers in biological systems, especially when targeting low capacity receptors, or when there is a risk of inducing pharmacological side effects. Competition for the low abundance receptors can arise not only from unlabeled versions of the tracer molecule, but also from other molecules of related structures, such as byproducts from radiolabeling procedures. Therefore, achieving high SA is extremely important for radiopharmaceuticals that target proteins, such as tumor receptors, that are present in very low (nM or less) concentrations in vivo (Woods, Wiseman et al. 1980, Velikyan, Beyer et al. 2004, Velikyan, Beyer et al. 2008, Patil, Gada et al. 2012, Zeng, Lee et al. 2012). However, one of the major barriers to improving the effective Specific Activity of radiometals is contamination from a variety of non-radioactive metal contaminants. In addition to optimizing radiolabeling reactions and/or separation methods, removing the metal contaminants from radiometals is a direct and efficient approach to increasing the effective SA of metal-based radiotracers. A water oil separation device was created for the purpose of purifying Cu-64, for the application of the preparation of promising radiopharmaceutical compounds for diagnosis and radiotherapy. The membrane utilized in the device is capable of separating the aqueous solution from the organic solvent. Based on the data obtained from UV-Vis spectroscopy of the separated two phases that contain different colored dyes, the purity of either the water or the organic phase separated by the membrane is greater than 99 %. %D 2016 %K radopharmaceuticals, radiometals, copper-64 purification, Positron Emission Tomography %I University of Pittsburgh %L pittir29184 %A Kasey Catt %T Multifunctional Conducting Polymer Coatings for Magnesium Implants %X Magnesium?s potential to degrade completely in vivo with safe corrosion byproducts make it a promising biomaterial for use in a wide array of implants from orthopedic fixation devices that do not require a removal surgery to peripheral nerve guides that degrade away after regeneration. However, a few issues need to be addressed before widespread clinical use can be realized. Firstly, Mg often degrades too rapidly in vivo. Rapid degradation can result in the mechanical instability and gas bubbles that may separate the implant from the tissue. Secondly, Mg implants lack the ability to combat potential infection and the inflammatory foreign body response. Lastly, Mg alone lacks a versatile functionalization method to incorporate tissue specific cues that better guide tissue growth and regeneration. To overcome these issues, conducting polymer based coatings with a combination of functionalities in corrosion control, drug release, and biofunctionalization are investigated in this thesis. A composite coating of conducting polymer poly 3,4-ethylene dioxythiophene (PEDOT) doped with Graphene Oxide (GO) has been developed for improving Mg implant performance for applications such as orthopedic fixation, stents, and peripheral nerve regeneration. The PEDOT/GO coating decreased Mg corrosion throughout 22days of immersion in a phosphate buffered solution. Corrosion protection is attributed to an initial passive barrier followed by electrochemical coupling of the coating with the Mg to from a more protective Mg phosphate layer. Additionally, anti-inflammatory drug Dexamethasone was incorporated into the PEDOT/GO film and it was shown that Mg corrosion current could drive drug release. Lastly, the carboxylic acid groups of the GO sheets exposed at the surface of the PEDOT/GO coating were used to immobilize multiple bioactive molecules. Specifically, immobilized poly ethylene glycol (PEG) prevented both bacterial and fibroblast attachment, while nerve growth factor (NGF) attachment increased neurite sprouting from PC12 cells. These results suggest that the PEDOT/GO coating has the potential to be a versatile coating that can provide corrosion protection and add biologically relevant cues to the Mg implant %D 2016 %K Magnesium, Corrosion, Conducting Polymer %I University of Pittsburgh %L pittir28976 %A Andrew Whitford %T Patterns of population activity associated with the intentional control of single neuron firing rates in primate motor cortex %X Although it is firmly established that the primate motor cortex contributes to intentional behavior, the exact relationship between patterns of cortical activity and effected action is not well-understood. A particular matter of controversy is the degree to which such patterns subserve a singular function in the control of behavior, and are constrained by this specific role. The reported capability of nearby motor cortical neurons to vary independently of one another -- and to be dissociated from overt movement -- has often been cited as evidence that patterns of cortical activity are rather labile; that they are readily adjusted to suit varied behavioral demands. Such claims are rooted in evidence from neurophysiology experiments that entail direct reinforcement of variation in the firing rates of single cortical neurons -- that is, single unit operant conditioning experiments. However, such investigations have largely been limited to the consideration of relationships among neurons recorded on the same electrode, or among small populations (N<5) of nearby neurons. Here, we explore cortical flexibility by characterizing patterns of population (N>20) activity as single neurons are targeted for conditioning. We find that a substantial percentage of the populations tend to co-vary, even though behavioral goals (i.e., reward) depend only on the activity of single neurons. Further, stable patterns of covariation can change with those goals. We conclude that cortical activity can be reshaped to suit behavioral demands, but that intrinsic structure -- perhaps due to network connectivity patterns -- likely constrains the flexibility of population activity. %D 2016 %K motor cortex, behavioral neurophysiology, brain interface, operant conditioning, behavior %I University of Pittsburgh %L pittir28927 %A Xuan Ding %T Towards Non-invasive Ultrasonic Characterization of Carotid Atherosclerotic Plaque %X Vulnerable atherosclerotic plaques are thought to be prone to rupture due to various compositional and morphological factors. One key characteristic is thought to be the presence of a soft, lipid rich core in the plaque. Acoustic radiation force impulse (ARFI) and thermal strain imaging (TSI) are non-invasive ultrasound-based imaging modalities. ARFI imaging measures the tissue response to an ultrasonically generated mechanical perturbation. In TSI, the tissue temperature is increased and image contrast is a result of the temperature and composition dependence of the speed of sound. Initial efforts to develop a TSI system utilized two separate ultrasound transducers for heating and imaging. We developed signal processing to improve estimates of thermal strain obtained from this system and showed that TSI could be used to detect lipids in ex vivo human arterial tissue samples. However, the translational obstacles encountered by this system outweighed the potential imaging utility. In order to address these challenges, we developed temporally interleaved multi-foci beamforming which could be implemented on a standard imaging array to generate a broad, homogeneous ultrasound beam for either ARFI pushing or TSI heating. We showed that this beamforming approach could enable simultaneous acquisition of ARFI and thermal strain data while substantially improving the frame rate for ARFI imaging. In order to better understand the factors that affect signal quality in TSI and ARFI imaging, we conducted separate phantom studies for each imaging modality. We showed that with a temperature rise <1oC, TSI could differentiate between phantoms with different lipid percentages. Additionally, we showed that pulse inversion harmonic imaging could be used to improve TSI signal quality in the presence of clutter. Finally, we showed that high frame rate ARFI imaging was able to achieve a 45-fold improvement in frame rate at the cost of increased estimation bias and jitter, and decreased image contrast. These studies indicate that multi-foci beamforming can be used to enable simultaneous TSI and ARFI imaging on current clinical systems. This imaging sequences developed in this dissertation facilitate non-invasive assessment of both the composition and mechanical properties of tissue which might be especially useful for characterization of vulnerable plaques. %D 2016 %K Ultrasound, Carotid Artery, Atherosclerosis, Non-invasive, Thermal Strain, Acoustic Radiation Force Impulse %I University of Pittsburgh %L pittir28967 %A Ye Zhan %T Acoustic Powered Micro Swimmer and Its Bidirectional Propulsion %X Micro-robots have great potential in biomedical aspects. However, there are no detailed experiments results for micro-swimmer (a micro-channel contains an air bubble inside it) propelling into the human body environment. This thesis describes the micro-swimmer propelling in blood environments, and testing in real blood. Demonstrated through bubble vibration, micro-swimmer can push forward in the blood environment. Meanwhile, I found the phenomenon of the micro-swimmer moving backward in the blood environment. The velocity of stream speed and position of the bubble interface have effect on the micro-swimmer propulsion direction. One the other hand, I find out the micro-swimmer is harder to propel in the blood environment. In order to improve the efficiency of acoustic transmission, I also made the liquid lens to focus sound, which can improve the transfer efficiency of acoustic wave. %D 2016 %K micro-swimmer, bubble vibration, propulsion direction %I University of Pittsburgh %L pittir29074 %A Brandon Jennings %T An Analysis of Oscillator-Based Computations for Image Processing %X Although there has been a vast amount of research into improving CMOS technology and computer architecture to make more powerful and efficient systems, the trends of decreasing sizes and energy and increasing power and speed are plateauing. Major roadblocks hindering the progression of Boolean logic based computing are transistor size, heat dissipation, clock speed, and computation power. This has inspired investigation into new methods for performing, complex operations not based on logic gates, or non-Boolean computations. One such method is coupled oscillator arrays. Instead of a logic gates to compute complex functions, the intrinsic physical properties of the oscillators can be used for computation making them more efficient for non-Boolean computations. This thesis will explore the use of coupled oscillator arrays to perform convolution, a primitive operation that plays a central role in many signal and image processing algorithms. Real-world circuit model parameters will be discussed and their impact on the circuit will be analyzed. In addition, this thesis will show the use of oscillators in Degree of Match (template matching), discrete cosine transform, discrete Fourier transform, Gabor filtering, and image compression. The effects of the model parameters on the will be examined on these implementations. %D 2016 %K oscillators, discrete fourier transform, dct, convolution, dft, discrete cosine transform, degree of match, template matching, compression, gabor filter, filter, coupled oscillators %I University of Pittsburgh %L pittir28308 %A Nithin Reddy Karna %T Effect of Ligament Geometry on the Stress at the Bone Insertion Sites %X Objective: The focus of this study is to identify the significance of the ligament shape at the bone insertion sites and how it affects the stresses at the locations. A ligament is a dense bundle of connective tissues made up of fibers that connects one bone and another bone to control joint motion and transfer load. This study was focused on stress at the bone insertion site where the ligament attaches to the bone. The present study was done to determine the importance of using nonlinear elastic properties and non-uniform geometry of the ligament when analyzed under a tensile load. A 2D axis-symmetry model was considered for the ligament and the bone was chosen to be a rigid material body and a non- linear static analysis was performed to assess the stress at the bone- ligament interface. Results: The von Mises stresses at the insertion sites were predicted. Effect of different ligament geometry shapes was studied by comparing the stress results. Clinical or Engineering Relevance: The results allow a better understanding of the shape of ligament morphology due to the load. %D 2016 %K ligaments, bone insertion sites, finite element analysis %I University of Pittsburgh %L pittir29039 %A Matthew Grasinger %T Evaluating the Capabilities of Lattice Boltzmann Method for Non-Newtonian and Free-Surface Flows towards Applications in Wellbore Cementing %X When oil and gas wellbores are drilled, barriers must be put in place to ensure that fluids do not leak out of the wellbore. Wellbore leakage can lead to environmental damage, loss of pressure at the wellhead, and consequently, loss of production. An important yet vulnerable barrier is the cement annulus. Creating the cement annulus, a process known as primary cementing, is difficult to perform optimally. Every well has unique subsurface conditions, and so no cement slurry mix design both performs well and is economical for all wells. Although some general guidelines and analytical techniques exist for approximating the performance of a cement slurry mix, the mechanics of primary cementing are complex. Computational methods can help better understand primary cementing and aid designers in determining the optimal mix. The lattice Boltzmann method (LBM) is a promising technique for simulating primary cementing because it is well-suited for efficiently simulating non-Newtonian flows, multiphase multicomponent flows, and flows through complex geometries--namely, some of the complexities associated with the mechanics of primary cementing. Despite the advantages of LBM, there are considerations that must be made, as with all computational methods, in regards to the accuracy and numerical stability of the solution. Issues with accuracy and numerical stability are especially prevalent in non-Newtonian flows because of the nonlinear constitutive relationship. Chapter 1 is a numerical investigation of the accuracy, stability, and computational efficiency of different LBM models in simulating non-Newtonian flows. %D 2016 %K Lattice Boltzmann Method; Non-Newtonian Flow; Free-Surface Flow; Primary Cementing %I University of Pittsburgh %L pittir28664 %A Mohammad Taghi Sharbati %T GRAPHENE QUANTUM DOT-BASED ORGANIC LOGHT EMITTING DIODES %X Graphene quantum dots (GQDs) have received a great deal of attention due to their unique optical properties, potentially useful for various applications such as display technology, optoelectronics, photovoltaics, sensing, and bioimaging. In this thesis we have investigated GQDs for an emissive layer in all-solution-processed organic light emitting diodes (OLEDs). Our GQD-based OLEDs are designed and fabricated as two different structures: bottom emission configuration on ITO substrate and top emission configuration on p-Si substrate. For both structures, GQDs show multiple emission peaks in blue, green and red regions. This multi-wavelength emission in the visible spectral range suggests presence and involvement of different-sized GQDs. In the case of GQD-OLEDs on silicon substrate, we have applied a SiO2 buffer layer with various thickness (2-150nm) and investigated the effects on carrier injection and confinement. With thin layers (< 10nm) of SiO2 it is found that the oxide layer well serves as a barrier blocking the direct tunneling of holes from the substrate. With thick layers (20-150nm) of SiO2 a band bending occurs enabling the Fowler-Nordheim (FN) tunneling of holes into the p-type transport layer. The FN-tunneling-enabled hole injection is found to allow varying the GQD excitation level (carrier energy and concentration), as demonstrated by the spectral change for different oxide thickness. %D 2016 %K OLED, Organic Light Emitting Diode, GQD, Graphene Quantum Dot, GQD-OLED, Top-Emitting OLED, Bottom-Emitting OLED, Silicon based OLED, GQD Photoluminescence, GQD Electroluminescence, Photoluminescence (PL), Electroluminescence (EL), Red Emitting GQD %I University of Pittsburgh %L pittir29260 %A Qiao Lu %T Hydraulic Fracture Initiation in Limestone %X Carbonate-rich rocks such as limestone comprise commonly encountered reservoir rocks in the oil and gas industry. This thesis is aimed at showing the impact of acidic fluid on hydraulic fracture initiation through laboratory experimentation. The results show that, compared to water injection, acid injection results in more rapid initiation of the hydraulic fractures under so-called static fatigue or pressure-delay conditions wherein a certain pressure, insufficient to instantaneously generate a hydraulic fracture, is maintained until a hydraulic fracture grows. Acid injection also is shown to generate a dissolution cavity in the vicinity of the wellbore. The breakdown of the specimen is also explosive in the case of acid injection, probably due to generate of carbon dioxide as a part of the dissolution reaction. Finally, the time to breakdown, or specimen lifetime, is shown to be related not only to the magnitude of the wellbore pressure but also, to the apparent permeability of the specimen. Taken together, the results indicate firstly that acid injection can be expected to improve initiation of multiple hydraulic fractures within multistage hydraulic fracturing of horizontal wells by decreasing the time required for initiation at subcritical wellbore pressures. The results also show that the current theoretical framework can capture the overall negative exponential relationship between the time to breakdown and the wellbore pressure, but it is insufficient to account for the secondary dependence on rock permeability. %D 2016 %K Hydraulic fracture limestone pressure delayed %I University of Pittsburgh %L pittir28188 %A Fabiana Arias Pinto %T Investigating Microchannel Reactors for Fischer-Tropsch Synthesis %X Microchannel reactors (MCRs) exemplify significant miniaturization of the physical dimensions and process intensification when compared with conventional industrial reactors, allowing for linear scaleup, flexible manipulations, and substantial capital cost reductions. MCRs have promising applications in Gas-to-Liquid (GTL) technologies, such as the Fischer-Tropsch (F-T) synthesis, particularly for monetizing small onshore and offshore gas fields, which is economically unfeasible with other conventional industrial F-T technologies. Even though MCRs were proposed for commercial implementations and demonstration plans have already been built, adequate literature publications on the use of MCRs in F-T synthesis is scanty and to the best of our knowledge many details concerning the hydrodynamics, mass transfer, heat transfer, and reactor performance are not available. The overall objective of this study is to investigate the performance and the flow distribution of a MCR, using one-dimensional (1-D) and Computational Fluid Dynamics (CFD) models. A MCR consisting of 50 channels, each packed with 100-micron cobalt catalyst, operating under the low temperature F-T synthesis (500 K and 25 bar) was used to study the reactor performance. The inlet flow distribution was investigated using another CFD model with air at 298 K and 1.01325 bar. A 50-channel MCR was used in this investigation. The modeling results led to the following conclusions: 1. The 1-D model systematically predicted steeper hydrocarbon flow rate profiles when compared with those of the CFD model, however, both models converge to the same values at the channel outlet. 2. For one channel of the MCR, both the 1-D and CFD models indicated that increasing the H2/CO ratio in the feed increased CO conversion, C5+ yield, pressure drop, F-T reaction rate, and the heat transfer requirements. Increasing the inlet syngas velocity decreased CO conversion and increased the pressure drop. Also, increasing temperature, increased the F-T reaction rate, CO conversion and the C5+ yield, and decreased the pressure drop. Furthermore, under the conditions investigated, the F-T process in the MCR used was kinetically-controlled. 3. The CFD model used to investigate the flow distribution in the MCR showed that using a flow distributor resulted in a homogenous flow distribution and eliminated the strong gas recirculation. %D 2016 %K Microchannel Reactor, Fischer-Tropsch, CFD Simulation %I University of Pittsburgh %L pittir29089 %A YONGTAI LI %T Modeling of Isobutylene Polymerization Process in Agitated Reactors %X In this study, a comprehensive model for the IBP process in agitated reactors was developed based on the reaction mechanism by Vasilenko et al. 2010, and takes into account the reaction rate kinetics for initiation, propagation, chain transfer, and chain termination steps as well as the mixing effects. The model coupled the mass balance equations for each reaction step with those of the segregated zones model for micro- and macro-mixing effects by Villermaux 1989, and was numerically solved by Matlab. The model was then used to predict the effect of various operating variables on the IBP process performance, in terms of the three main metrics: monomer conversion (X), number average molecular weight (Mn) and polydispersity index (PDI). In the absence of mixing, our model was used to carry out sensitivity analyses to quantify the effects of the reaction rate constants of the initiation (ki), propagation (kp), chain-transfer (ktr) and chain termination (kt) steps on the three main performance metrics. The model predictions led to: (1) Increasing ki was found to have negligible effect on the three main IBP process performance metrics; (2) Increasing kp increased X and Mn and decreased PDI; (3) increasing ktr the increased X, but decreased Mn and PDI; and (4) Increasing kt deceased X and Mn, and increased PDI. In the presence of mixing, and at given kinetic rate constant, the model was used to conduct a parametric study to determine the effect of mixing on the IBP process performance. Eight different cases, four poor and four good mixing conditions, reactor type, and impeller type as well as design, were considered, and their effects on the three main IBP process performance metrics were investigated. The model predictions led to: (1) Mixing controls the IBP process performance due to its inherently fast reaction kinetics; (2) Mixing time and impeller type significantly affected the required mixing speed; (3) all model predictions underscored the importance of good mixing in the cationic IBP process; and (4) our model was able to predict the IBP process performance metrics and the required mixing speed in agitated reactors provided with different impellers. %D 2016 %K Isobutylene polymer, cationic polymerization, mixing effect, impeller geometry %I University of Pittsburgh %L pittir29042 %A zhang zhenwei %T Most suitable mother wavelet for the analysis of fractal properties of stride interval via the average wavelet coefficient method %X The human gait is a complex interaction of many nonlinear systems and stride intervals that can be modeled as a stochastic $1/f^\beta$ process, where the spectral index $\beta$ can be interpreted as a ?biomarker? of diseases. The previous study showed that the average wavelet method provides the most accurate results when applied to stride interval time series. The purpose of this paper is to determine the most suitable mother wavelet for analysis of the fractal characteristics of the stride interval time series. This paper presents a comparative numerical analysis of sixteen mother wavelets applied to the average wavelet coefficient method with different simulated signal lengths and $\beta$ values. Five candidates were chosen due to their good performance on the mean square error test for both short and long signals. Next, we comparatively analyzed these five mother wavelets for physiologically relevant stride time series lengths . Our analysis showed that the symlet 2 mother wavelet provides a low mean square error and low variance for long time intervals and relatively low errors for short signal lengths. It can be considered as the most suitable mother function without the burden of considering the signal length. %D 2016 %K fractals,time series analysis, self similarity, gait, stride intervals, wavelets , 1/f process, mother wavelet %I University of Pittsburgh %L pittir28714 %A Alvaro Cardoza %T Power Source Buffering using a Triangular Modular Multilevel Converter with Energy Storage %X As power systems throughout the world continue to utilize DC infrastructure within distributed generation solutions and microgrid designs, an effective DC-DC interfacing power electronic device must be developed for managing power flow and power quality levels between a system?s increasingly diversified array of sources and loads. DC-DC power electronic interfaces are continuing to gain increased attention throughout many distribution applications, including the information and communication technology (ICT), electric vehicle, and renewable generation industries. The research effort described herein explores the use of a multi-port DC-DC modular multilevel converter interfacing a dual-input connection of a 380 VDC system and a 42.9 VDC/ 40.7 A photovoltaic panel with a 96 VDC output resistive load. Ultracapacitors are used to power-buffer the input signal and in this application, the inherently intermittent solar panel output. This technology represents the merits of utilizing a singular interfacing device to consolidate the flows between joint generation and load, while maintaining stable output power through the use of a modular energy storage solution. This work will detail the operation and control of the DC-DC converter and its module-interfaced power buffering solution, as well as provide design methodologies for the system described. %D 2016 %K Power Electronics, Energy Storage, Ultracapacitors, Photovoltaic, Modular Multilevel Converter, Power Smoothing %I University of Pittsburgh %L pittir28955 %A Etienne Zahnd %A Ervin Sejdi? %T Prediction methods for 1/f^? processes with application to the analysis of stride interval time series %X The power law in the frequency spectrum S(f)=1/f^? allows for a good representation of the various time evolutions and complex interactions of many physiological processes. The spectral exponent ? can be interpreted as the degree of fractal characteristic which in turn makes it some sort of biomarker that gives an idea of the relative health of an individual. This thesis presents a thorough investigation of prediction of the fractal nature of the process with specific consideration given to experimentally measured gait stride interval time series. The goal is to consider the accuracy of several time series prediction methods such as the neural networks, regression trees and bagged regression trees learning method. To test these methods we simulated stride intervals time series as 1/f^? processes. This investigation is to complement previous analyses on predicting the process with which this study compared. It was shown as result of the research that the greatest number of points one can accurately predict is between five and fifteen using the regression tree, the feedforward neural network and the AR model. %D 2016 %K prediction, stride interval, time series, 1/f^? process, human gait, neural networks, regression trees, autoregressive model %I University of Pittsburgh %L pittir28667 %A Victor Manrique %T STUDY ON THE SIMULTANEOUS HYDROPHILICITY/OLEOPHOBICITY OF AN IONIC LIQUID THIN FILM %X Simultaneous hydrophilic/oleophobic materials are desired for various applications where anti-fogging is required. The ideal coating would be one that can be applied physically, such as an ionic liquid (IL) thin film. This thesis project explores the simultaneous hydrophilic/oleophobic wetting behavior of of a thin film of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIIm) on silica substrate. First, atomic force microscopy revealed that EMIIm forms a complete film on silica substrate with film dewetting occurring at 0.84 nm thickness. Next the molecular arrangement was analyzed with angle-resolved x-ray spectroscopy, by calculating the atomic ratio of nitrogen from the anion to nitrogen from the cation (N-/N+). For the three samples tested the ratio was above 0.5, indicating that the anion was organized over the cation even when the film was dewetted. This was determined to be due to the planar structure of the EMI cation. Further analysis done by changing the takeoff angle revealed a change in N-/N+ for 0.43 nm thin film; N-/N+ for the film bulk and the film surface was 0.8 and 0.9 respectively. This meant that for 0.43 nm film the ions are in a layered arrangement with the fluorinated anion layer at the surface. Finally, it was found that while the water contact angle (WCA) was low for all film thickness values tested (avg. 5.33? ? 3.91) the hexadecane contact angle (HCA) plateaued to 41.15? for samples greater than 0.55 nm thickness. Time-dependent HCA trials were conducted, for 24 hours and 3 hours. The trials confirmed that film penetration was occurring, as the HCA reached a final equilibrium value after 3 hours. The contact liquid is drawn to the high energy silica, so the liquid will pass through the intermolecular holes in the film to get to the substrate. Given that the WCA is low and constant, and the size difference between water and hexadecane, the hole size must be between 0.27 nm and 0.78 nm. In addition, the final HCA had a positive correlation to the film thickness. %D 2016 %K Ionic Liquid, Thin Film, Wetting %I University of Pittsburgh %L pittir28966 %A Yuwen Yang %T A Study of Shale Gas Production and Its Supply Chain %X Over the last few years, shale gas has become one of the most important energy sources in the United States, and advances in related technologies have led to an unprecedented economic boom in several parts of the country. On the other hand, the shale gas sector and its unique extraction technologies are still relatively young, and there are a number of concerns from the public about several aspects of the shale gas industry such as hydraulic fracturing, methane emission and waste management. The objective of this thesis is to present a comprehensive and objective study of shale gas and its entire supply chain, including the various material flows within it, in order to motivate safety, cost-savings and operational efficiency improvement. The study begins with an introduction to the basic background of the petroleum, natural gas and shale gas industry and goes on to describe the process of shale gas production and map its supply chain, starting with initial exploration to identify a potential drilling location and ending with the delivery of the natural gas to end-use customers. We present detailed flow of various materials and when possible, costs in the shale gas supply chain as a first step toward planning for its efficient operation. We also span a wide range of topics including environmental effects and safety, public health implications of unconventional gas extraction, the upgraded equipment and techniques to reduce environmental pollution, the use pattern of shale gas, fluctuations in its price, and its implications on sustainable energy. We end with a detailed case study of distributed power generation from Marcellus shale, and discuss how natural gas can play a key role in bridging the gap between coal/petroleum based energy and renewable energy. As a more reliable and cheaper alternative to renewable energy today, and as a more environmentally friendly alternative to other fossil fuels such as coal and petroleum, shale gas has the potential to be a solution to the energy gap in the near future. %D 2016 %K Shale Gas, Natural Gas, Supply Chain, Hydraulic Fracturing %I University of Pittsburgh %L pittir28465 %A louis J vuga %T POTENTIAL DIAGNOSTIC AND PROGNOSTIC BIOMARKERS OF IDIOPATHIC PULMONARY FIBROSIS AND THE IMPACT OF E2F8 IN COLLAGEN 1 SYNTHESIS %X Idiopathic pulmonary Fibrosis (IPF) is a chronic lung disease with median survival about 2-3.5 years (1). Lung transplant is the most effective therapy although pirfenidone (2) and nintetanib (3) delay mortality or disease progression. Biomarkers are used for diagnosis and management of diseases (4) but for IPF, a reliable biomarker is not established (5, 6). In this project, we proposed to investigate lung transcript expressions and plasma proteins as diagnostic or prognostic biomarkers and their implication in Pathogenesis of IPF. First, we found 44 transcripts qualified after t-test, Benjamini and Hochberg multiple correction, and 1.5-fold change cutoff. We observed 33 transcripts that commonly distinguished IPF from control or COPD. The scoring coefficients of the principal components (COMP) distinguished IPF from control or COPD by using Classification Tree model. The receiver operating characteristic (ROC) curves for scoring coefficients of COMP of IPF vs control was with Area Under Curve (AUC) = 0.90 (95% CI), sensitivity 85% and specificity 91% and IPF or COPD was AUC= 0.88 (95% CI), sensitivity 86 % and specificity 90%. Second, we measured 24 biomarkers in IPF plasma using Searchlight Protein Array. In cross-sectional study, intercellular adhesion molecule 1 (ICAM), vascular cell adhesion molecule 1 (VCAM1), and S100 calcium binding protein A12 (S100A12), and surfactant protein D (SFTPD) were predictors of IPF mortality (P < 0.05). In serial studies, previously identified proteins ICAM1, VCAM1, S100A12, interleukin 8 (IL8) and novel proteins matrix metallopeptidase 10 (MMP10) and tissue inhibitor of metalloproteinase 1 (TIMP1) were predictors of IPF mortality. Third, we discovered in lung fibroblasts from IPF a deficiency of E2F transcription factor 8 (E2F8), which is eliminated by an F-box protein 16 (FBXO16). Biologically, E2F8 reduces fibroblast proliferation, and E2F8 also decreases collagen 1A1 mRNA synthesis. Hence, we found a model of lung fibrosis focusing on two novel molecular inputs (E2F8 and FBXO16) linked to fibroblast behavior in subjects with IPF. In summary, our transcriptomic and plasma proteins analyses revealed the utility of biomarker discovery in advancing precision medicine in IPF. Together these finding provide novel insights that may improve IPF diagnosis, prognostic and potential drug discovery. %D 2016 %K IPF, Biomarkers, E2F8, Fibroblasts, Transcripts, lung %I University of Pittsburgh %L pittir29520 %A Ricardo Jose Ferrari %T THE EFFECT OF ELECTRICAL STIMULATION ON AGED SKELETAL MUSCLE REGENERATIVE POTENTIAL %X Increasing age typically results in a decreased skeletal muscle regenerative capacity after injury, a decreased muscle mass and weakness, ultimately resulting in an increased likelihood for falls, susceptibility to recurrent injury, and a prolonged recovery. In response to injury, aged muscle displays a decreased capacity to regenerate damaged myofibers. Instead, the repair response is characterized by fibrotic accumulation, a response that has been attributed to dysfunction of the muscle stem cell (MuSC) population. MuSCs are a reserve cell population that plays a central role in dictating muscle regeneration. Muscle contractile activity, elicited by exercise or electrical stimulation, for example, has been suggested to be an important intervention to increase blood flow to the injury area and to promote the activation of muscle MuSCs. The purpose of this study is to test the hypothesis that neuromuscular electrical stimulation (Estim) inhibits activation of the muscle progenitor cell (MPC) fibrogenic molecular program to enhance skeletal muscle regeneration in aged animals. MPCs represent a heterogenous myogenic cell population, the majority of which are MuSCs. Our in vivo studies demonstrate that two weeks of Estim enhances myofiber regeneration and increases tetanic force recovery in aged muscles after an acute injury. In vitro, we find that improved muscle regeneration in aged muscle following the application of Estim is concomitant with a rejuvenated MPC phenotype. Our results further suggest that the beneficial effect of Estim on MPC regenerative potential may be mediated by up-regulation of the anti-aging protein, Klotho. Taken together, these data provide evidence that Estim is a safe and effective method and to improve functional recovery after an acute injury in aged muscle. It is anticipated that findings from this study will aid in the development of clinically relevant rehabilitation programs to enhance the muscle healing response in a geriatric population. %D 2016 %K Electrical Stimulation, Aging, Satellite Cells, Skeletal Muscle, Klotho, Wnt Signaling %I University of Pittsburgh %L pittir28094 %A Szu-Han Kay Chen %T EFFECTS OF VOICE OUTPUT AND DOSE ON AUGMENTATIVE AND ALTERNATIVE COMMUNICATION TREATMENT FOR PEOPLE WITH APHASIA %X Introduction: Aphasia frequently occurs after a stroke and may become a chronic communication/language disorder. Not all people with aphasia (PWA) fully recover to their premorbid language functioning. Many will face life-long communication difficulties impacting their quality of life. Despite Augmentative and Alternative Communication (AAC) intervention being used to improve the language and communication functioning for PWA, the effects of AAC intervention are obscured, because many variables, such as voice output and treatment dose, have not been investigated systematically. Method: This dissertation includes a pair of studies that aim to determine the effects of two voice outputs (synthesized voice vs. human voice) and doses of computerized AAC training on naming performance with able-bodied individuals and PWA. The dissertation uses a single-subject combined 2 by 2 factorial design to investigate the impact of the two variables. A mixed model trajectory analysis (MMTA) is used to evaluate how single variables affect the treatment outcomes. Pre-and-Post standardized assessments are used for evaluating the outcomes. Results: The results indicate that both able-bodied people and PWA learned to name words under the synthesized and human voice conditions using an AAC system. Overall, people learned better with human voice than synthesized voice. Both groups learned to name pictures by exposure only. The results also show that adding one self-paced practice in the same session did not facilitate improvement of able-bodied individuals? performance. Additionally, the results show the performance of PWA is varied both within participant and across participants. All participants were satisfied with the training program. Conclusion: This dissertation is the first study to test voice output and treatment dose as AAC intervention variables for PWA. Evidence supporting the value of voice output features in AAC intervention was found that may facilitate the naming skills of PWA. It also demonstrates MMTA, as an innovative way to evaluate the effects of an individual variable at the personal-level and group-level in AAC aphasia intervention. Future AAC studies can draw upon the findings to systematically investigate the numerous variables of AAC technology and treatment that are effective in improving language and communication performance. %D 2016 %K Augmentative and Alternative Communication, Aphasia, Small sample, Mixed model analysis, Speech generating device %I University of Pittsburgh %L pittir28309 %A Samannaaz S Khoja %T FAT DEPOTS WITHIN AND AROUND THE SKELETAL MUSCLE IN RHEUMATOID ARTHRITIS AND THEIR ROLE IN PHYSICAL FUNCTION %X Altered body composition towards greater body fat mass and lower lean mass is a well-known manifestation of Rheumatoid Arthritis (RA). However, there is limited information on fat accumulation in and around the skeletal muscles, and whether they contribute to functional limitations and low physical activity levels that persist in this population despite well-controlled disease. The main objectives of this dissertation were to 1) characterize accumulation of skeletal muscle fat (SMF), intermuscular adipose tissue (IMAT) and subcutaneous adipose tissue (SAT) in individuals with RA and determine the associations of SMF, IMAT and SAT with physical function and physical activity measures; and 2) compare SMF, IMAT and SAT between individuals with RA and healthy individuals. This cross-sectional ancillary study used data from previously conducted studies in adults with RA and healthy adults. SMF, IMAT and SAT were measured from computed tomography images of the mid-thigh region. Physical function in the RA cohort was measured using self-report and performance-based tests, and physical activity was assessed using an accelerometer-based activity monitor. Associations between each fat depot, and physical function and activity were assessed by multiple linear regression models. To compare SMF, IMAT and SAT in RA and non-RA subjects, those with RA were matched in sex and BMI to healthy adults of same age and to older healthy adults who were 10-20 years older. The differences between groups were assessed using related samples tests. In subjects with RA, higher SMF significantly contributed to lower physical function and activity (R2? range=.08-.25, p<0.05), whereas IMAT and SAT accumulation were not associated with physical function or activity. Individuals with RA had significantly higher SMF (10% difference, p < 0.05) whereas IMAT and SAT accumulation were similar to healthy individuals of same age. There were no differences in SMF, IMAT and SAT between the RA and matched older healthy groups. Study findings demonstrate that SMF accumulation is an important contributor to low physical function and activity, and accumulates more in RA. These results provide preliminary evidence for future longitudinal studies to investigate the impact of SMF on disability and promote health in individuals with RA. %D 2016 %K "rheumatoid arthritis", "disability", "physical function", "skeletal muscle", "fat" %I University of Pittsburgh %L pittir29323 %A Joel Stevans %T IDENTIFYING FACTORS ASSOCIATED WITH PHYSICAL THERAPISTS? ADHERENCE TO LOW BACK PAIN GUIDELINES ACROSS THE DOMAINS OF THE CONSOLIDATED FRAMEWORK FOR IMPLEMENTATION RESEARCH: A MIXED METHODS STUDY %X In 2007 a regional physical therapy (PT) organization implemented low back pain (LBP) guidelines throughout its 50 outpatient clinical sites. Despite multiple improvement efforts since that time guideline adherence is suboptimal (38%). In this study the Consolidated Framework for Implementation Research (CFIR) guided an evaluation to identify determinants of adherence. A sequential, mixed methods design was used to identify determinants of adherence to LBP guidelines. We surveyed PTs using instruments pertinent to LBP management and implementation success to explore factors associated with guideline adherence across three CFIR domains: Individual, Innovation, and Inner Setting. Instruments included the Pain Attitudes and Beliefs Scale, Intolerance of Uncertainty Scale, Ottawa Acceptability of Decision Rules Instrument, and Alberta Context Tool. Survey responses, provider demographics and professional characteristics were merged with risk-adjusted measures of guideline adherence using data from the organization?s database. Generalized linear models (GLM) were first used to assess univariate associations, then main effects and 2x2 interactions were evaluated using GLM with forced, backward stepwise elimination. The sample was stratified by quartile using the risk-adjusted adherence measure. Purposive maximum variation sampling identified 15 high and 15 low performing providers for semi-structured telephonic interviews. One hundred and twelve survey completers (74%) had a risk-adjusted guideline adherence measure and were included in the study. There was no association between PT?s acceptability of individual guideline recommendations and adherence. There were significant interactions between Professional Certification (PC) and Uncertainty Paralysis (?=-0.06, p>0.05), PC and Time to Deliver Quality Care (?=0.26, p=0.03), and PC and Connections with Colleagues (?=0.36, p=0.01). Qualitative interviews identified barriers to adherence resulting from the complexity of the guidelines and limited skills required to carry out some of the recommendations. The interviews also revealed that perceived support for the initiative was stronger from senior management compared to front line supervisors. This study addresses three gaps in the dissemination and implementation literature: 1) it describes one method to identify determinants for tailoring interventions; 2) it quantifies interaction effects within and between CFIR domains; and 3) it assesses determinants of sustainability in a mature implementation initiative. %D 2016 %K implementation Science, low back pain, guidelines, physical therapy %I University of Pittsburgh %L pittir29355 %A Mahender Arjun Mandala %T PEER REVIEW IN DESIGN: UNDERSTANDING THE IMPACT OF COLLABORATION ON THE REVIEW PROCESS AND STUDENT PERCEPTION %X A cornerstone of design and design education is frequent situated feedback. With increasing class sizes, and shrinking financial and human resources, providing rich feedback to students becomes increasingly difficult. In the field of writing, web-based peer review?the process of utilizing equal status learners within a class to provide feedback to each other on their work using networked computing systems?has been shown to be a reliable and valid source of feedback in addition to improving student learning. Designers communicate in myriad ways, using the many languages of design and combining visual and descriptive information. This complex discourse of design intent makes peer reviews by design students ambiguous and often not helpful to the receivers of this feedback. Furthermore, engaging students in the review process itself is often difficult. Teams can complement individual diversity and may assist novice designers collectively resolve complex task. However, teams often incur production losses and may be impacted by individual biases. In the current work, we look at utilizing a collaborative team of reviewers, working collectively and synchronously, in generating web based peer reviews in a sophomore engineering design class. Students participated in a cross-over design, conducting peer reviews as individuals and collaborative teams in parallel sequences. Raters coded the feedback generated on the basis of their appropriateness and accuracy. Self-report surveys and passive observation of teams conducting reviews captured student opinion on the process, its value, and the contrasting experience they had conducting team and individual reviews. We found team reviews generated better quality feedback in comparison to individual reviews. Furthermore, students preferred conducting reviews in teams, finding the process ?fun? and engaging. We observed several learning benefits of using collaboration in reviewing including improved understanding of the assessment criteria, roles, expectations, and increased team reflection. These results provide insight into how to improve the review process for instructors and researchers, and forms a basis for future research work in this area. With respect to facilitating peer review process in design based classrooms, we also present recommendations for creating effective review system design and implementation in classroom supported by research and practical experience. %D 2016 %K peer review, feedback, collaboration, team work, collective review, critique, design, learning, education, engineering, creative, web-based %I University of Pittsburgh %L pittir28637 %A Maha Almarwani %T TIMING AND COORDINATION OF GAIT: IMPACT OF AGING, GAIT SPEED AND RHYTHMIC AUDITORY CUEING %X Purpose: The aims of this dissertation were to: 1) compare the test-retest reliability and determine minimal detectable change (MDC) of spatial and temporal gait variability in younger and older adults 2) examine the impact of challenging walking conditions (slower and faster speeds) on gait variability in younger and older adults and 3) examine the impact of rhythmic auditory cueing (metronome) on the walk ratio as an indicator of the spatial and temporal coordination of gait at different walking speeds in healthy adults. Subjects: Forty younger (mean age = 26.6 ? 6.0 years) and 120 older adults (mean age = 78.1 ? 6.2 years) independent in ambulation were studied. Methods: Gait characteristics were collected using a computerized walkway (GaitMat II?). Step length, step width, step time, swing time, stance time and double support time variability were derived as the standard deviation of all steps across the 4 passes. Cadence and walk ratio were also calculated. Analyses: Test-retest reliability was calculated using Intra-class correlation coefficients (ICCs(2,1) ), relative limits of agreement (LoA%) and standard error of measurement (SEM). The MDC at 90% and 95% level were also calculated. Mixed linear models were used to determine differences in gait variability between younger and older by walking conditions and with metronome cues. Results and Clinical Relevance: Younger adults had greater test-retest reliability and smaller MDC of spatial and temporal gait variability compared to older adults. In older adults, walking slowly is more challenging to the motor control of gait and may be more sensitive to age-related declines in gait than usual and faster speed walks. Finally, a metronome-cue, commonly used in gait rehabilitation, may have been detrimental to the walking pattern. It is possible that the metronome-cue disrupts gait timing by increasing the attentional demand of walking at non-ideal speeds such as slower and faster speeds. Future research should further investigate inconsistency of gait variability as a potential early indicator of a decline in mobility. Also, future longitudinal studies are needed to determine if changes in gait variability on challenging gait conditions predict future mobility disability in older adults with near normal gait. %D 2016 %K Reliability; Gait variability; Motor control; Faster; Slower; Metronome-cued; Walk ratio; Walking pattern; Healthy adults; Older adults; %I University of Pittsburgh %L pittir28172 %A Victoria Scharp %T Temporal Processing of Ongoing Event Representations %X Time cues are ubiquitous in language and the ability to interpret them is essential for understanding events during discourse comprehension. Temporal markers that signal ongoing versus completed events, like the progressive and simple past tense, prompt distinct mental event representations. However, the detailed properties of ongoing event representations remain unexplored. Drawing from both the simulation and semantic association approaches to knowledge representation, this study examines the novel prediction that ongoing events engender incremental discourse representation updating processes. Experimental sentences cued either early or late phases of an ongoing event (e.g. Alice had recently started/almost finished baking a cake). Targets in a post-sentential lexical decision task were strongly associated with either early or late event phases (e.g. EGGS/AROMA). Facilitation priming was predicted for congruent sentence-target pairs, however, priming was found for the early event phase exclusively. The results have implications for models of knowledge representation, theories of semantic priming, and discourse model updating. %D 2016 %K temporal processing, event processing, language comprehension %I University of Pittsburgh %L pittir29038 %A Rachel G Miller %T Cardiovascular disease in Type 1 diabetes: quantifying risk and addressing limitations in the analysis of longitudinal cohort studies %X Cardiovascular disease (CVD) has historically been increased in type 1 diabetes compared to the general population, but no contemporary estimates of risk are available in the United States. Additionally, the reasons for this increased risk are not fully understood, as the hyperglycemia that characterizes type 1 diabetes is itself an inconsistent predictor of CVD incidence. Thus, the objective of this dissertation is to quantify the contemporary incidence and excess risk of CVD in young adults <45 years old with type 1 diabetes and to utilize novel statistical methods to address limitations in the analyses of longitudinal cohort studies, in an effort to better understand the risk factor patterns that lead to CVD in this population. Data are from the Pittsburgh Epidemiology of Diabetes Complications study, a prospective cohort study of childhood-onset type 1 diabetes diagnosed at Children?s Hospital of Pittsburgh between 1950 and 1980. CVD data from the background Allegheny County, Pennsylvania population were used to calculate age- and sex-matched standardized mortality (SMR) and incidence rate ratios (IRR). Using tree-structured survival analysis (TSSA), formal subgroup analysis was performed to identify groups at varying levels of risk for CVD, based on threshold effects of continuous risk factors. Joint models were used to simultaneously model the longitudinal trajectory of HbA1c and time to CVD incidence. CVD risk was shown remain significantly increased in this type 1 diabetes cohort. TSSA identified a range of risk groups, which were defined by combinations of diabetes duration, non- HDL cholesterol, albumin excretion rate, and white blood cell count. The longitudinal trajectory of HbA1c was associated with CVD risk, similarly across all manifestations of CVD, including coronary artery disease, stroke, and lower extremity arterial disease, which is a new finding in this cohort. This work has important impacts on public health, as it confirms that individuals with type 1 diabetes continue to be at increased risk for CVD and demonstrates that novel statistical methods should be utilized as a complement to traditional methods to increase understanding of disease etiology. %D 2016 %K Type 1 Diabetes, Cardiovascular Disease, Risk Stratification, Tree-Structured Survival Analysis, Joint Models, Longitudinal Data, Cohort Studies, Glycemic Control %I University of Pittsburgh %L pittir28541 %A Proma Paul %T Comprehensive cervical cancer prevention and control: Potential strategies at different stages of cervical cancer progression %X Advancements in the continuum of cervical cancer care, including risk factor assessment, human papillomavirus (HPV) vaccines, and screening programs, have reduced the cervical cancer burden. However, cervical cancer remains an important public health issue, particularly in developing countries. This research investigated three potential prevention opportunities along the cervical cancer continuum, including: factors associated with HPV natural history in middle-aged women which may influence current vaccination and screening recommendations; testing for carcinogenic HPV serotypes to assess the feasibility of ?catchup? HPV vaccination in populations who missed the conventional adolescent vaccination window; and protective dietary patterns. First, we measured the incidence and clearance of HPV, and associated risk factors, in the HIP (HPV in Perimenopause) Study, a U.S. clinic-based cohort of women aged 35-60 years old. Next, we measured the quadrivalent vaccine-specific HPV seroprevalence in a population-based, cross-sectional analysis of young, married, postpartum, rural Indian women. Lastly, we evaluated the associations of soy and tea consumption on risk of cervical cancer in a large Singapore population of women aged 45-74. Each of these studies yielded findings of public health significance. First, the majority of new HPV detections in U.S. older women occurred during periods of sexual abstinence or monogamy, lifetime number of sexual partners modified incident HPV risk, and the majority of incident HPV cleared within 18 months. Our findings suggest that although HPV vaccination may provide some protection the overall benefit may be limited and considering a risk-based approach to cervical cancer screening may be valuable. Second, we found that seroprevalence of HPV-6, HPV-11, HPV-16, and HPV-18 was relatively low in the postpartum Indian women, 6.6%, 10.1%, 10.1%, and 3.9%, respectively, suggesting that ?catchup? HPV vaccination in this population may be effective in preventing cervical cancer. Third, we found that high soy intake was associated with a decrease cervical cancer risk among Chinese green tea drinkers, but not among non-drinkers of green tea. Developing nutritional interventions utilizing soy and tea components may disrupt cervical carcinogenesis. Further research is needed to continue to develop and implement effective cervical cancer interventions at various points on the cancer continuum. %D 2016 %K cervical cancer, HPV %I University of Pittsburgh %L pittir29045 %A Megan Weber %T EXAMINING THE RELATIONSHIP BETWEEN THE GENOTYPE AND REDEFINED PHENOTYPE OF DENTAL CARIES %X Dental caries is a multifactorial infectious disease and is a major public health problem estimated to affect 60 to 90 percent of school children as well as a vast number of adults. At this time, the best predictor of dental caries for a patient is whether or not they have had caries in the past. We have eight hundred seventy-six whole saliva samples collected from Norwegian patients from one of five primary care dental centers in Rogaland County. The University of Pittsburgh IRB under protocol #12110620 approved these study samples. dmft/DMFT scores were collected at ages 5, 12, 14, 16, 17, and 18 according to World Health Organization (WHO) Protocols. DNA was extracted from whole saliva using Oragene kits and an established protocol. Our objective was to use the dmft/DMFT scores over time to redefine the phenotype of caries and look for patterns of the disease in order to assist in the identification of individuals at risk for caries and aid in the development of new strategies of prevention. We aimed to categorize the patients according to characteristics such as more or less acute increases in their dmft/DMFT scores. We also aimed to compare our newly formed definitions with definitions based on dmft/DMFT cutoffs we have been using in our studies. We generated genotyping data using Taqman chemistry in SNPs involved in processes such as enamel formation and salivary contributions and test for association with caries defined using longitudinal caries experience scores. We compared dmft/DMFT data to diet data and dental erosion scores to determine the role of diet within our population and determine if dental caries and dental erosion scores are associated. Funding for this study came from NIH/NIDCR R01-DE18914 and graduate support from the University of Pittsburgh School of Dental Medicine. %D 2016 %K Dental Caries, Dental Erosion, Genetics, Genotyping %I University of Pittsburgh %L pittir29516 %A Benjamin Rothrauff %T Extracellular Matrix-Enhanced Biomimetic Scaffolds for Tissue-Specific Orthopaedic Tissue Engineering %X The work contained herein sought to combine soluble extracellular matrices (ECMs) derived from decellularized musculoskeletal tissues with biomimetic scaffolds for the purpose of orthopaedic tissue engineering. More broadly, tissue engineering combines cells, scaffolds, and biomolecules (e.g., growth factors and cytokines) to restore or replace biological tissues. Scaffolds derived from decellularized tissues provide cells with the biophysical and biochemical motifs that constitute the ECM of the native tissue, in turn promoting homologous (i.e., tissue-specific) cell phenotypes. However, decellularized whole tissues are limited in clinical use due to poor cell infiltration and constrained geometries. On the other hand, decellularized tissues can be pulverized or solubilized to theoretically provide a tissue-specific supplement that, in combination with biomimetic scaffolds, promotes homologous neotissue formation in a tissue defect regardless of shape or size. Nevertheless, the retention of tissue-specific bioactivity following solubilization of ECMs remains uncertain. In particular, few studies have explored the tissue-specific bioactivity of soluble ECM derived from decellularized musculoskeletal tissues. In this thesis, tendon, hyaline cartilage, and knee menisci were decellularized and solubilized through one of two methods ? (1) urea extraction or (2) pepsin digestion. When added as medium supplements to in vitro cultures of human mesenchymal stem cells (MSCs) grown on two-dimensional (2D) plastic or as 3D MSC pellets, only urea-extracted ECM fractions promoted tissue-specific differentiation. Urea-extracted fractions of ECM derived from the inner and outer halves of the meniscus exerted region-specific effects, in agreement with the regional variations in ultrastructure, biochemical composition, and cell phenotype seen in native menisci. The soluble ECMs further enhanced tissue-specific differentiation when combined with biomimetic scaffolds, including aligned electrospun nanofibers to mimic tendon and photocrosslinkable hydrogels to mimic hyaline cartilage and inner meniscus. Additionally, soluble ECMs interacted synergistically with transforming growth factor beta (TGF-?) when provided as an exogenous supplement. Taken together, the work contained herein begins to elucidate the mechanisms by which soluble ECMs promote tissue specific effects and provides support for their use in orthopaedic tissue engineering. %D 2016 %K Extracellular Matrix, Tissue Engineering, Stem Cell, Tendon, Cartilage, Meniscus %I University of Pittsburgh %L pittir29517 %A Tri Q. Le %T Inpatient post-acute care utilization patterns and outcomes in Pennsylvania medicaid %X The Medicaid expansion, one of the key provisions under the Affordable Care Act (ACA), has turned Medicaid into a larger player in the US healthcare system. The intent of the expansion was to increase access to essential healthcare services such as post-acute care (PAC) for low-income individuals. Studies have shown that variation in Medicare spending is attributed to the variation in post-acute care (PAC) utilization which includes care in home health, skilled nursing facilities (SNF), inpatient rehabilitation facilities (IRF), and long-term acute care hospitals (LTACH). However, very little is known about PAC utilization in the Medicaid population. For instance, Pennsylvania expanded Medicaid in January 2015, initially under a 1115 waiver and then under the original terms of the ACA. Many more individuals and families of low socioeconomic status were able to enroll in the Medicaid program as a result of the expansion. With studies pointing to PAC utilization and spending as the driver of variation in Medicare healthcare costs, the same may pertain to the Medicaid population. Chapter 1 provides the purpose, findings, and implications of the dissertation. Chapter 2 is a retrospective cohort study that determines the association between insurance type, either enrolled in Medicaid or commercial insurance, and the likelihood of being admitted to an inpatient PAC facility. The study found that hospitalized Medicaid beneficiaries were as likely as similar patients with commercial insurance to be admitted to any PAC facility but less likely to be admitted to an inpatient PAC facility (SNF, IRF, LTACH). This would inform policymakers that new Medicaid enrollees, which tend to be low-income and nondisabled adults, will certainly increase the cost of the Medicaid program. Chapter 3 is a retrospective cohort study that determines whether Medicaid managed care utilizes inpatient PAC differently than its FFS counterpart. The study found that Medicaid managed care beneficiaries were more likely to be admitted to an inpatient PAC than their FFS counterparts. This has significant cost implications since the majority of all Medicaid beneficiaries in the United States were enrolled in an MCO. Chapter 4 is a retrospective cohort study that determines the degree to which patient outcomes observed among Medicaid beneficiaries was mediated by variation in the intensity of PAC utilization. The study found that PAC utilization patterns for hospitalized Medicaid beneficiaries impacted readmissions and mortality to a degree. While we could not determine whether more PAC utilization would result in better quality of care, the effect of these patterns on outcomes should encourage states to standardize their approach to PAC and take necessary steps to improve patient management and care coordination among providers. Public Health Significance This dissertation addressed the three tenets of the healthcare iron triangle: access, cost, and quality. It will inform policymakers on how new Medicaid enrollees due to the expansion can potentially affect future cost to the program and impact the outcomes of Medicaid beneficiaries. %D 2016 %K post-acute; medicaid; irf; ltch; snf; pennsylvania; utilization %I University of Pittsburgh %L pittir28043 %A Sevinc Akcay %T Molecular consequences of elastin gene mutations in autosomal dominant cutis laxa and supravalvular aortic stenosis %X Elastic fibers are components of the extracellular matrix(ECM) that contribute resilience to tissues and bind and regulate transforming growth factor beta (TGF?). Elastin gene (ELN) mutations cause several phenotypes including Williams-Beuren Syndrome (WBS), supravalvular aortic stenosis (SVAS) and autosomal dominant cutis laxa (ADCL). This work focused on the molecular consequences of the ELN gene mutations in ADCL and SVAS. ADCL is characterized by loose and inelastic skin, pulmonary emphysema, aortic root dilation, and peripheral pulmonary aortic stenosis. Our goal was to evaluate the impact of ELN mutations on TGF? signaling and molecular pathology of ADCL. Dermal fibroblasts from four patients with ELN mutations in exon 34 or exon 30 and controls were used. Increased intracellular TGF? signaling was found in patients with exon 30 mutations, despite unchanged extracellular TGF? activity. TGFBR1 levels were increased at the protein and the RNA level. Patients with exon 34 mutations had normal TGF? signaling. Our results indicate mutation-specific TGF? signaling changes in ELN-related cutis laxa patients, which may influence to disease severity. Elastin assay showed decreased elastin deposition in ADCL cells and long-term TGF? treatment improved elastin deposition. Semi-quantitative RT-PCR experiments showed increased expression of the mutant compared to the wild-type allele in ADCL cells under baseline conditions. Long-term TGF? treatment normalized this allelic imbalance in expression. Therefore, we conclude that increased TGF? signaling is a protective mechanism in ADCL at the molecular level. SVAS is characterized by narrowing of the ascending aorta. An SVAS family with a duplication in the ELN gene was analyzed genetically and functionally. Gene-dosage analysis showed that a tetranucleotide repeat in intron 1 was within the duplicated region. RT-PCR of pre-mRNA showed that a SNP in intron 23 of the mutant allele was not expressed. Decreased elastin deposition was found in affected individuals, supporting that this partial duplication yielded a null allele. Uncovering the nature of connections between elastin and TGF? may help developing treatments for cutis laxa. Our findings are relevant to complex diseases characterized by elastin degradation and TGF? dysregulation, including aneurysms and chronic obstructive pulmonary disease that have major public health impact. %D 2016 %K autosomal dominant cutis laxa, supravalvular aortic stenosis %I University of Pittsburgh %L pittir28102 %A Carrie Hanley %T Quantity and quality of cardiovascular fat in women at midlife: associations with various markers of cardiovascular disease risk %X Background: Cardiovascular fat (CF) is a complex metabolically active organ and a cardiovascular disease (CVD) risk factor. Postmenopausal women have more CF compared to premenopausal women that may partly contribute to their increased risk of CVD. Objectives: Our objectives were to determine whether CF quantities differed by race; whether CF quantities were associated with adipokines and coronary artery calcification (CAC) progression; and whether the quality of CF depots, measured via radiodensity, were associated with CVD risk measures in women at midlife. Methods: We evaluated participants from the SWAN Cardiovascular Fat Ancillary Study (n=562 midlife women; mean age 50.9 ? 2.9 years; 62% White; 38% Black) who had cross-sectional measures (volumes and/or radiodensity) of CF depots (epicardial fat (EAT), paracardial fat (PAT), total heart fat (TAT), and aortic perivascular fat (PVAT)). Sample sizes varied for each study aim based on applied exclusion criteria (range 524 to 222). Multivariable linear or logistic regression models were used for analyses. Results: Whites had higher quantities of CF for all depots compared to Blacks, independent of cardiovascular risk factors and abdominal visceral fat (VAT). Race modified the associations between adiposity measures and CF quantities such that Whites had more PAT for higher levels of BMI than Blacks; whereas, Blacks had more EAT for higher levels of VAT than Whites. PAT was positively associated with leptin independent of cardiovascular risk factors and VAT, with stronger associations among Whites compared with Blacks. Lastly, we found that lower TAT radiodensity (poorer quality) was associated with a less favorable cardiometabolic profile and women with mid-range radiodensity values had significantly lower odds of CAC presence compared to low radiodensity values, independent of cardiovascular risk factors and BMI. Conclusions: These analyses contribute to public health significance by enhancing our understanding of potential contributions of the quantity and quality of separate CF depots to CVD risk in midlife women. We found that the quantity of the mostly overlooked PAT depot may be especially important among midlife women with independent associations with leptin. Future studies should evaluate CF depots separately and further explore CF radiodensity as a marker of fat quality. %D 2016 %K cardiovascular fat menopause %I University of Pittsburgh %L pittir29061 %A Ying Shan %T Statistical methods for genetic risk confidence intervals, Bayesian disease risk prediction, and estimating mutation screening saturation %X Genetic information can be used to improve disease risk estimation as well as to estimate the number of genes influencing a trait. Here we explore these issues in three parts. 1) For an informed understanding of a disease risk prediction, the confidence interval of the risk estimate should be taken into account. But few previous studies have considered it. We propose a better risk prediction model and provide a better screening strategy considering the confidence intervals. Risk models are built with varying numbers of genetic risk variants known as single nucleotide polymorphisms (SNPs). Inclusion in the risk model of SNPs, sorted in decreasing order by effect size, with smaller effects modestly, shifts the risk but also increases the confidence intervals. The more appropriate risk prediction model should not include the small effect SNPs. The newly proposed screening method is superior to the traditional one as evaluated by net benefit quantity. 2) Many methods have been developed for associated SNP selection, SNP effect estimation, and risk prediction. A Bayesian method designed for continuous phenotypes, BayesR, shows good characteristics. Here, we developed an extension of BayesR (BayesRB), so that the method can be used for binary phenotypes. For SNP effect estimation, BayesRB shows the unbiasedness and sparseness for the big and small effect SNPs, respectively. It also performs well on risk prediction, but not on associated SNP selection. 3) When a recessive forward genetic screening study (RFGSS) is carried out to detect disease mutations, it is important to estimate the screening saturation so as to guide the screening strategy. Here, we develop a simulation-based "unseen species" method to estimate the screening saturation in a RFGSS. We simulated a RFGSS process based on a real study and compared our method to both nonparametric methods and parametric methods. The proposed method performs better than all the other methods, except an existing "unseen species" method. The above three newly proposed methods are helpful for constructing better risk prediction models and for estimating the number of disease contributing genes. These methods can be applied to different disease studies and may make contributions to public health. %D 2016 %K Risk prediction, Conffidence intervals, Bayesian models, Screening saturation %I University of Pittsburgh %L pittir28629 %A Matthew Johnson %T Analysis of racial differences in ICD shock burden using Cox proportional hazards regression %X Background/Research Aims: Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) are major public health issues that most often result in death and affect a significant number of adults. Implantable cardiac defibrillators (ICDs) are an important tool used in SCA/SCD prevention. Racial differences with respect to ICD firings have not been very well explored with only limited previous research on the topic. This study seeks to analyze a large dataset of patients with defibrillators by race and also build a risk model for ICD shock using Cox proportional hazards regression. Methods: Using data from the GRADE study, N= 1770 patients (1449 Whites and 321 African Americans) were initially compared by race for almost 80 baseline variables. N= 1524 patients (1275 Whites and 249 African Americans) had information on ICD shocks and were compared by race via Kaplan-Meier survival curves. A Cox proportional hazard regression analysis was performed to produce hazard ratios and evaluate each baseline characteristic with respect to defibrillator shock over time individually, followed by a multivariable model building process to examine race in the context of other significant covariates. Missing data was also examined in the terms comprising the final model and multiple imputations were performed for any variables deemed to have excessive missingness. Results: Overall, African Americans were younger, had more nonischemic cardiomyopathy, had a higher prevalence of hypertension, smoked more, and had a lower ejection fraction than whites in the study. In comparing Kaplan-Meier survival curves, African Americans had a higher burden of shocks over time than whites by the end of the 5 year time period (p<0.01). Over 20 variables were individually related to shock at 60 months in a Cox regression setting (including race). The final multivariable model consisted of seven terms: race (not statistically significant but forced into the model), ejection fraction, history of NSVT, antiarrhythmic medication, diagnosis, age, and BUN. One variable was found to have excessive missingness (BUN) and after performing multiple imputations, results were overall similar in the second analysis except race became statistically significant (p= 0.04, HR= 1.385) while BUN went from statistically significant to not. Conclusions: The public health impact of this study is in trying to build on the limited previous research and paint a more complete portrait of the relationship between race and appropriate defibrillator firings. After accounting for data missingness, race was found to be statistically significant in its relationship to ICD shock over time when adjusting for several additional covariates in the final multivariable model. %D 2016 %K ICD, defibrillator, race, Cox %I University of Pittsburgh %L pittir28090 %A Inmaculada Hernandez %T Evaluating the safety and effectiveness of non-vitamin K antagonist oral anticoagulants in the medicare population %X For decades, warfarin was the only oral anticoagulant available for the prevention of stroke and systemic embolism in atrial fibrillation. Since 2010, four non-vitamin K antagonist oral anticoagulant agents have gained Food and Drug Administration approval for this indication: dabigatran, rivaroxaban, apixaban and edoxaban. Chapter 1 provides an introduction to the three research manuscripts that constitute this dissertation. It reviews the use of anticoagulation therapy in atrial fibrillation and especially the evidence on non-vitamin K antagonist oral anticoagulants. Chapter 2 (Manuscript 1) is a retrospective cohort study that compares the risk of stroke and bleeding with rivaroxaban 20mg/dabigatran 150mg, and rivaroxaban 15mg/dabigatran 75mg. This study found no difference in the risk of stroke between dabigatran and rivaroxaban; however, rivaroxaban 20mg and rivaroxaban 15mg were associated with higher risk of thromboembolic events other than stroke, death, major bleeding, and any bleeding events than dabigatran 150mg and dabigatran 75mg. Chapter 3 (Manuscript 2) evaluates the patterns of anticoagulation use after a first major bleeding on dabigatran or warfarin, and compares the thromboembolic and bleeding risk between post-hemorrhage treatment groups. In this study, post-hemorrhage resumption of anticoagulation with either dabigatran or warfarin was associated with increased survival and stroke-free survival, as compared to discontinuing anticoagulation. In addition, this paper revealed that the risk of recurrent major hemorrhage was higher with warfarin than dabigatran. Chapter 4 (Manuscript 3) is a cost-effectiveness study that compares edoxaban 60mg, apixaban 5mg, dabigatran 150mg, dabigatran 110mg, rivaroxaban 20mg and dose-adjusted warfarin in the prevention of stroke in atrial fibrillation patients with high risk of bleeding, as defined by HAS-BLED score ?3. This study found that, while apixaban 5mg was the most effective strategy, its incremental cost-effectiveness ratio when compared to edoxaban was slightly above the $100,000 per quality-adjusted life year threshold. Public Health Significance The investigations reported in this dissertation will guide clinicians in the prescription of the most appropriate anticoagulation agent according to the clinical characteristics of atrial fibrillation patients. This will ultimately lead to the prevention of strokes, the second leading cause of mortality worldwide, and bleeding events, the most common complication of anticoagulation therapy. %D 2016 %K Anticoagulation; Atrial fibrillation; Hemorrhage; Non-vitamin K antagonist oral anticoagulants; Stroke; Warfarin. %I University of Pittsburgh %L pittir28084 %A Rebecca Vanderwall %T Evaluation of communication skills in genetic counseling training programs: A needs assessment %X Communication skills are a necessary part of training and education for medical professionals and a key element of genetic counseling practice. These skills include both educating patients and addressing psychosocial needs. Although the types of communication that genetic counselors should master have been expressed in the literature, significantly less is known about effective ways to assess communication skills. This study was designed as a needs assessment to gain an understanding of how communication skills are currently being assessed in genetic counseling programs across the United States and Canada and to evaluate if a new communication assessment tool would be beneficial to these programs. Semi-structured phone interviews were conducted with directors of 14 of the 35 accredited programs and thematic analysis was performed on the notes generated from the interviews. It was discovered that all of the programs assess communication skills in some way, but no program uses the exact same methods. Most of the evaluation methods used in genetic counseling programs are not based on relevant literature or a known theoretical framework. Program directors are mostly interested in the creation of a new assessment tool, which may improve students? communication skills and assist supervisors in identifying and addressing deficiencies. This study has public health significance because good communication contributes to better patient satisfaction, more teamwork within the medical team, better patient compliance, more cost-effective medicine, and better health in general. Assessing communication skills effectively would better ensure that genetic counselors are competent in the necessary skills when they complete their training. %D 2016 %K genetic counseling; communication; communication skills; assessment %I University of Pittsburgh %L pittir27215 %A Allison Saras %T FROM FAMILY BACKGROUND TO SOCIALIZATION TO POST GRADUATE PLANS: A CASE STUDY EXAMINING THE MCCARL CENTER FOR NONTRADITIONAL STUDENT SUCCESS %X This case study examines the McCarl Center for Nontraditional Student Success at the University of Pittsburgh and studies how the socialization processes of nontraditional undergraduate students? influences their plans, career and academic, upon graduation. Within the study, my research questions focus on how the individual attributes and family background, socialization processes (interaction, integration and learning), normative contexts (majors, peer groups and co-curriculum) and personal communities (family, friends and employers) contribute and influence a nontraditional student?s motivations and aspirations upon graduation. The conceptual framework used to structure this study was Vincent Tinto?s (1975, 1993) student integration theory and John Weidman?s (1984, 1989) socialization model. To study this particular phenomenon, I used a case study (Yin, 2013) as my methodological approach and the tool for collecting my data was phenomenological interviewing (Seidman, 2013). I conducted 19 personal interviews with nontraditional students associated with the McCarl Center at the University of Pittsburgh. After analyzing the interview data collected, I found that nontraditional students have individualized situations that influence their socialization processes on and off campus and the aspirations to continue onto graduate study is a strong and likely possibility. However, after graduation nontraditional students first want to enter the workforce before enrolling in a graduate study program to ease student debt, gain work experience or to simply take a break from higher education. In conclusion, my study has several implications on today?s nontraditional student experience, existing policy and procedures, and the setting in which this study was conducted, the McCarl Center. %D 2016 %K Nontraditional, veterans, graduate study, socialization, ambitions, motivations, social integration, academic integration %I University of Pittsburgh %L pittir29452 %A Anwesha Sanyal %T Identification of cellular factors involved in Neisseria gonorrhoea induced enhanced HIV-1 transmission in a cervical tissue based organ culture model %X The presence of sexually transmitted infections (STI) such as Neisseria gonorrhoeae (NG) can enhance the transmission of HIV-1. Our goal in this study is to elucidate mechanism by which NG induces enhanced HIV-1 transmission. A cervical tissue based organ culture system was developed to study the interaction between NG and HIV-1 which provided a unique opportunity to elucidate mechanism of NG induced enhanced HIV-1 transmission across cervical mucosa. We demonstrated that the NG exposure on the cervical tissue in the organ culture model showed physical characteristics of NG infection and induced high levels of inflammatory cytokines IL1-? and TNF-? that have been observed during in-vivo NG infection in the cervix. In elucidating the mechanism of NG induced enhancement of HIV-1 transmission, we demonstrated that NG not by itself but the culture fluids from NG exposed tissues (reminiscent of cervical milieu) increased HIV-1 transcription from the HIV- LTR in TZM-bl cells, induced full length HIV-1 from latently infected U1 and ACH2 cells and increased transmission of HIV-1 across cervical mucosa. The whole genome transcriptome analysis using second-generation sequencing of the micro-dissected epithelial layer of the tissues exposed to NG and HIV-1 identified with high statistical significance differentially expressed genes in NG exposed and HIV-1 exposed tissues, and identified common cellular factors as well as pathways involved in cell activation, migration and stimulation expressed in the epithelia. Out of these only two differentially expressed genes that were common between tissues exposed to both NG and HIV-1 are CXCL10 and IL8. Addition of inhibitors of CXCL10 and IL8 suppressed HIV-1 transmission, while addition of CXCL10 and IL8 increased HIV-1 transmission indicating that CXCL10 and IL8 could be involved in HIV-1 transmission across cervical epithelia. IL-1? also increased CXCL10 and IL8 expression in cervical tissues and enhanced HIV-1 transmission Altogether these data are consistent with a model (Figure 42) for NG induced enhanced HIV-1 transmission: NG infection secretes IL-1? which induces increased production of epithelial CXCL10 and IL-8 causing the migration of HIV-1 target cells CD3+T cells and macrophages towards intraepithelial region that fuels HIV-1 replication in submucosa and consequently enhances HIV-1 transmission. Taken together, our results confirm that the risk of acquisition of HIV-1 infection in the ecto-cervical region increases with prior NG infection. From the public health perspective, identification of IL-1? and its target cellular proteins in NG induced enhanced HIV-1 transmission could be useful in development of drugs that impair HIV transmission. Further work in nonhuman primates or humanized mouse models could provide confirmation of the role of CXCL10 and IL-8 in HIV transmission and its modulation by NG secreted proteins like IL-1? in vivo. %D 2016 %K NG, HIV-1 TRANSMISSION, CYTOKINES, MUCOSA, EPITHELIUM %I University of Pittsburgh %L pittir28095 %A Jia-Yuh Chen %T Joint modeling of bivariate longitudinal and survival data in spouse pairs %X Joint modeling of longitudinal and survival data has become increasingly useful for analyzing clinical trials data. Recent multivariate joint models relate one or more longitudinal outcomes to one or more failure times (e.g., competing risks) in the same subject. We consider a case where longitudinal and survival outcomes are measured in subject pairs (e.g., married couples). In this dissertation, we propose a joint model incorporating within-pair correlations, both in the longitudinal and survival processes. We use a bivariate linear mixed-effects model for the longitudinal process, where the random effects are used to model the temporal correlation among longitudinal outcomes and the correlation between different outcomes. For the survival process, we incorporate a gamma frailty into a Weibull proportional hazards model to account for the correlation between survival times within pairs. The two sub-models are then linked through the shared random effects, where the longitudinal and survival processes are conditionally independent given the random effects. Parameter estimates are obtained by maximizing the joint likelihood for the bivariate longitudinal and bivariate survival data using the EM algorithm. The proposed methodology is applied to the spouse data from the Cardiovascular Health Study (CHS) to investigate the association of both longitudinal depression scores and survival times between husbands and wives, and to quantify the association of mortality and longitudinal depression with other covariates in husbands and wives after accounting for the within-spouse correlation. Public Heath Significance: Spouse studies seek to reveal the importance of both environmental and genetic influences on individuals. The analysis of such information is useful in assessing long term health effects in spouse pairs and/or individuals living together. The methodology we propose provides a valid statistical inference on the association of longitudinal measurements and the time-to-events among paired subjects. This methodology will contribute to the analysis of public health studies by ensuring that proper prediction and inference are made when pairs of individuals are measured longitudinally. %D 2016 %K Joint models, spouse pairs, bivariate longitudinal data, bivariate survival data, bivariate linear mixed-effects model, Weibull proportional hazards model with gamma frailty, depression, mortality %I University of Pittsburgh %L pittir28112 %A Chendi Cui %T Marine n-3 fatty acid intake, glutathione s-transfrases (GST) polymorphisms and colorectal cancer risk: the Singapore Chinese Health Study %X The role of marine n-3 polyunsaturated fatty acids (PUFAs) in colorectal carcinogenesis has been investigated in many epidemiological studies; however, the epidemiological evidence is inconclusive. A potential explanation is due to competing products of n-3 PUFAs metabolism. Anti-inflammatory eicosanoids, products of n-3 PUFAs metabolism through cyclooxygenase (COX) enzymes, could inhibit inflammatory responses, which have a protective effect against colorectal cancer. Alternatively, malondialdehyde (MDA) and 4-hydroxy-2-hexenal (4-HHE), lipid peroxidation products of marine n-3 PUFAs, could be mutagenic. It has been suggested that glutathione S-transferases (GSTs) are involved in removing lipid peroxidation products. Therefore, we investigated whether GST genotypes (i.e., GSTT1, GSTM1) modified the marine n-3 PUFAs-colorectal cancer association using a nested case-control study within the Singapore Chinese Health Study. With 469 incident colorectal cancer cases and 1,167 noncases, we observed the effect modification of combined GSTT1 and GSTM1 positive genotypes with marine n-3 PUFAs on colorectal cancer (p for interaction < 0.01), and with the ratio of marine n-3 to n-6 PUFAs on colorectal cancer (p for interaction = 0.01). An inverse association of marine n-3 PUFAs with colorectal cancer was observed among those with high activity GST genotypes (i.e., combined GSTM1 and GSTT1 positive genotype) [Odds ratio (OR) for Q4 vs. Q1 = 0.57, 95% CI = 0.32-1.01, p for trend <0.05]; however, a positive association was observed among those with one or more GST null genotypes [OR for Q4 vs. Q1 = 1.49, 95% CI = 1.00-2.23, p for trend = 0.01]. Among those with one or more GST null genotypes, a positive association was also shown for the ratio of marine n-3 to n-6 PUFAs and colorectal cancer [OR for Q4 vs. Q1 = 1.64, 95% CI = 1.09-2.37, p for trend < 0.01], although no statistically significant association was observed for high activity GST genotypes. Our results suggest the role of GSTT1 and GSTM1 in the association between marine n-3 PUFAs and colorectal cancer. This finding provided a point to consider GST genotypes in the marine n-3 PUFAs-colorectal cancer association in the population. It is important for further public health intervention program to consider this interaction while intervening on the population. %D 2016 %K colorectal cancer, diet, marine n-3 polyunsaturated fatty acids, glutathione S-transferase %I University of Pittsburgh %L pittir28111 %A Geoffrey Johnson %T Quality adjusted Q-learning and conditional structural mean models for optimizing dynamic treatment regimes %X The focus of this work is to investigate a form of Q-learning using estimating equations for quality adjusted survival time, and to generalize these methods to quality adjust other outcomes. We use the m-out-of-n bootstrap and threshold utility analysis to show how the patient-specific optimal regime varies according to treatment characteristics (e.g. cost, side effects). Methodologies investigated are demonstrated to construct optimal treatment regimes for the treatment of children's neuroblastoma. We also propose a new method for optimizing dynamic treatment regimes using conditional structural mean models. The inverse-probability-of-treatment weighted (IPTW) or g-computation estimator is used at each stage to estimate what we call the `preliminary' optimal treatment regime, given patient information up to the current stage and prior treatment assignment. Essentially this tailors the optimal treatment assignment at the current stage, and provides an optimal strategy for the remaining stages given the information currently available. We compare this method for optimizing a dynamic treatment regime to Q-learning. Additionally, we propose a two step prescriptive variable selection procedure that supports the tailored optimization of dynamic treatment regimes using conditional structural mean models by eliminating from consideration any suboptimal treatment regimes and sifting out the covariates that prescribe the optimal treatment regimes. The methods described herein are meant to advance the field of dynamic treatment regimes, a field that has a substantial impact on public health. The treatment policies that come from DTRs, whether determined for the population as a whole or tailored for specific subgroups, can be used to guide and shape health policies that will ultimately lead to greater public health and safety. %D 2016 %K Dynamic Treatment Regime, Adaptive Treatment Strategy, Quality Adjusted Lifetime, Potential Outcomes, Counterfactuals, Inverse Probability Weighting, m-out-of-n Bootstrap, Structural Mean Model, Q-learning, g-computation %I University of Pittsburgh %L pittir28101 %A Christopher Freyder %T Using linear regression and mixed models to predict health care costs after an inpatient event %X Gateway Health Plan? wanted to compare the before and after costs of a member who had an inpatient stay in a hospital which will allow them to evaluate costs in comparison trials. As part of my internship with Gateway Health Plan?, I was able to estimate a formula to evaluate difference in costs. Using Gateway Health Plan?s? internal data from the past three years, I used regression to evaluate the difference in cost for members before and after an inpatient event. I ran a simple linear regression model as well as a mixed effects model in order to look at the comparison of the before and after costs. Age and gender were also considered at as possible covariates in the prediction process because both of those factors are known to be associated with healthcare costs. The results showed that average cost before an inpatient event as well as gender were significant in estimating the average cost after an inpatient event. I found that females tend to cost less than males, and female patients cost less after the inpatient event compared to before the inpatient event, while men cost more after the event. Public health significance: This research will help Gateway Health Plan to evaluate interventions to assess whether they lower health care costs. Being able to evaluate if interventions are cost efficient will improve healthcare leading to an improvement in population health. %D 2016 %K Mixed Models, Health Care, Patient as their own Control %I University of Pittsburgh %L pittir28089 %A Amie DiTomasso %T The black female leadership development institute programs year one evaluation %X The objective of this thesis is to evaluate the first year of the Black Female Leadership Development Institute (BFLDI) program of the Urban League of Greater Pittsburgh (ULPGH) and to provide the organization with program recommendations. The BFLDI aims to increase self-efficacy, knowledge about reproductive sexual health information, dating abuse recognition, how to reduce high-risk behaviors, increase social supports, and facilitate healthy psychosocial development through a variety of program activities conducted over eight months. Evaluation information was collected from 36 minority adolescent females. A pre and post survey measuring self-efficacy, self-image, gender norm beliefs, reproductive sexual health attitudes, dating abuse recognition, and reproductive sexual health knowledge was conducted with study participants. The analysis included calculating descriptive statistics, construct averages, and cross tabulations in order to evaluate the BFLDI program. Participants reported high levels of program satisfaction. There was no significant difference observed in knowledge, attitudes, or beliefs between the pre and post surveys. However, a positive association between self-efficacy and gender norm beliefs (p = .023) was observed. Two trends were observed in the associations between age and reproductive sexual health attitudes and age and dating abuse recognition. Recommendations for year two include modifications in activities such as topics focused more directly on program goals and increased evaluation measurements such as collection of behavioral data. This program is relevant to public health as it serves as an intervention to reduce the health problems of sexually transmitted infection, teenage pregnancy, and dating abuse among minority adolescent females. %D 2016 %K evaluation, adolescents, females, program, sexual health %I University of Pittsburgh %L pittir29177 %A Megan Beck %T The regulation and function of long-chain acyl-CoA dehydrogenase and the effect of the single Nucleotide polymorphism K333Q %X Nine acyl-CoA dehydrogenases (ACADs) are involved in mitochondrial fatty acid ?-oxidation (FAO), an important energy-producing pathway. Disorders of FAO are common inborn errors of metabolism and genetic deficiencies have been identified for all ACADs except long-chain acyl-CoA dehydrogenase (LCAD). Understanding the function of LCAD and the phenotype of LCAD deficiency may enable identification of unrecognized cases of LCAD deficiency, and eventual treatment, and improve public health. I hypothesized that human LCAD (hLCAD) and mouse LCAD (mLCAD) are biochemically equivalent, but that hLCAD functions in tissues not normally reliant upon FAO, such as the lung. Additionally, I hypothesized that a missense polymorphism (K333Q), linked to an absence of LCAD antigen in human lung, is deleterious. Recombinant mLCAD, hLCAD, and hLCAD K333Q proteins were purified and biochemically characterized. Recombinant mLCAD was more stable and demonstrated higher catalytic efficiency than hLCAD. Additionally, recombinant hLCAD bearing the K333Q substitution demonstrated lower activity, impaired substrate binding, and reduced stability compared to wild-type hLCAD. Based on these findings and on western blotting experiments demonstrating higher LCAD expression in human lung than other long-chain ACAD enzymes, I hypothesized that LCAD K333Q may be associated with lung disease. Primary alveolar type II (ATII) cells from individuals homozygous for the minor Q allele had five-fold less LCAD antigen than ATII cells from individuals homozygous for the major K allele, consistent with lower protein stability. Cohorts of neonates with respiratory distress syndrome and children hospitalized for pneumonia were genotyped for LCAD K333Q. Association of lung function with different genotypes at the K333Q locus was examined in the Long Life Family Study (LLFS) (N=4953). Contrary to the hypothesis, the LCAD K333Q locus was not associated with lung disease. Heterozygotes for the Q allele were under-represented among children hospitalized with pneumonia, whereas homozygotes for the K allele were over-represented, suggesting that carrier status for K333Q confers some benefit. Individuals in the LLFS who carried the Q-allele at the K333Q locus had increased lung function. In conclusion, recombinant mLCAD was biochemically superior to hLCAD, which was superior to hLCAD K333Q. However, the K333Q polymorphism was not associated with respiratory distress or pneuomonia-induced complications. %D 2016 %K Long-chain acyl-CoA dehydrogenase, Fatty Acid Oxidation, Single Nucleotide Polymorphism K333Q %I University of Pittsburgh %L pittir28080 %A Robert Sheehan %T Closing the loop: A combined computational modeling and experimental approach provides novel insights into immune cell signaling systems and their global effects. %X Systems biology is an approach that marries complimentary disciplines, encouraging the use of quantitative methods to help define, explain, and predict biological processes. By building computational models of biological systems, we can pose new biologically motivated questions and make falsifiable, quantitative predictions. In this thesis I will discuss the cycle of model building and experimental validation, and how it has provided insight into poorly and understood systems and allowed us to predict the effects of perturbations on these systems, which could have real and significant effects in human health and medicine. First, we model the activation of neutrophils in sepsis. By fitting a single model to two sets of data, coming from animals that survive and succumb to the same bacterial challenge, we create a realistic representation of biological variation, showing how a single network architecture can lead to different outcomes. Additionally, this method allows us to identify markers for sepsis susceptibility and identify and optimize a potential treatment option to lead to improved outcomes. Next, we model signaling downstream of the T cell receptor, and how this leads to differentiation decision making in CD4 T cells. By modeling the dynamics of this signaling network under varying antigen doses, we are able to identify network elements critical to dose discrimination, leading to the production of Treg cells following low dose stimulation and Th cells following high dose stimulation. We can then perturb these elements of the network, to potentially fine tune mature T cell populations to alter the trajectories of autoimmune disorders or cancer. Finally, we model the dynamics of IL-17 signaling. This allows us to understand how ubiquitin scaffolds form following cytokine stimulation, leading to the activation of NF-?B, and how the ubiquitin editing enzyme A20 acts as a negative feedback regulator by breaking these chains. This allows us to better understand ubiquitin oligomerization as a fulcrum in the system, and how changes in A20 and ubiquitin binding proteins lead to different profiles of NF-?B activation and could play a role in inflammatory disorders. %D 2016 %K "computational biology", modeling, "rule-based modeling", immunology, sepsis, "T cell differentiation", IL-17, NF-kB %I University of Pittsburgh %L pittir29440 %A Mark Weir %T SIMULTANEOUS INHIBITION OF DRIVER AND EFFECTOR KINASES PROMOTES POTENT GROWTH ARREST OF AML CELLS IN VITRO AND IN VIVO %X Acute myelogenous leukemia (AML) is caused by successive mutations acquired in hematopoietic progenitor cells that lead to the overpopulation of the bone marrow and peripheral blood by immature myeloid cells. The overall survival rate with current therapy is 25%, which decreases steadily with patient age. While numerous genetic alterations occur in AML, mutations to the FMS-like tyrosine kinase 3 (FLT3) are the most common, occurring in 30% of patients. Two types of FLT3 mutations occur in AML: internal tandem duplications (ITDs) and tyrosine kinase domain point mutations. FLT3 mutations drive AML pathogenesis and numerous small molecule kinase inhibitors have been designed as therapeutics for FLT3-mutated AML. However, these FLT3 inhibitors have had limited clinical success owing to lack of potency in vivo, toxicity, or short duration of response due to the development of resistance. Constitutively active FLT3 links to multiple downstream tyrosine kinases that are critical for AML cell survival and proliferation. Gene silencing studies have shown that several of these FLT3-associated kinases are individually crucial for FLT3 oncogenic potential, including SYK, FES, and the myeloid Src-family kinase, HCK. These previous observations raised the hypothesis that a small molecule inhibitor with a selectivity profile targeting FLT3 plus these associated kinases may be a potent AML drug lead with reduced propensity for acquired resistance. To test this hypothesis, we screened a library of N-phenylbenzamide compounds and identified a compound with three-digit nanomolar activity against each of these AML-associated kinases in vitro. Remarkably, this compound (TL02-59) inhibited FLT3-ITD+ cell growth in the picomolar range. Furthermore, TL02-59 demonstrated efficacy against primary AML bone marrow samples and a mouse xenograft model of AML. To explore the full range of targets for TL02-59, we performed a KINOMEscan assay and determined the expression of the TL02-59 target kinases in primary AML bone marrow samples. We discovered that while myeloid Src-family kinases HCK, LYN and FGR are critical to TL02-59 efficacy, inhibition of SYK, FES and the Ser/Thr kinases p38? and TAOK3 also plays a role. Future work will explore the advantages of this potent, multi-targeted kinase inhibitor in combating acquired resistance in AML. %D 2016 %K AML, Leukemia, FLT3, Src-Family Kinase, Kinase inhibitor, FES, SYK %I University of Pittsburgh %L pittir29333 %A Kevin Zitelli %T Cell-type specific plasticity at intrapallidal synapses in a mouse model of Parkinson's Disease %X The cell types that comprise neural networks are critical in determining their function. Within the globus pallidus externa (GPe), a nucleus of the basal ganglia implicated in Parkinsonism, several neuronal subpopulations have been described genetically and anatomically, but functional and physiological studies have been limited. This study examines the previously undescribed collateral connections between two key cell types in the GPe, defined by the genetic expression of parvalbumin (PV) or LIM homeobox 6 (Lhx6). Further investigation of this network in a mouse model of Parkinson?s Disease reveals a selective weakening of synaptic input from PV to Lhx6 neurons following dopamine lesions. This study builds on recent literature elucidating the roles of specific GPe cell types to basal ganglia function in health and disease. %D 2016 %K globus pallidus externa, GPe, Parkinson's Disease, synaptic plasticity, slice electrophysiology, lateral inhibition %I University of Pittsburgh %L pittir29401 %A Rory Donovan-Maiye %T Efficient Sampling in Stochastic Biological Models %X Even when the underlying dynamics are known, studying the emergent behavior of stochastic biological systems in silico can be computationally intractable, due to the difficulty of comprehensively sampling these models. This thesis presents the study of two techniques for efficiently sampling models of complex biological systems. First, the weighted ensemble enhanced sampling technique is adapted for use in sampling chemical kinetics simulations, as well as spatially resolved stochastic reaction-diffusion kinetics. The technique is shown to scale to large, cell-scale simulations, and to accelerate the sampling of observables by orders of magnitude in some cases. Second, I study the free energy estimates of peptides and proteins using Markov random fields. These graphical models are constructed from physics-based forcefields, uniformly sampled at different densities in dihedral angle space, and free energy estimates are computed using loopy belief propagation. The effect of sample density on the free energy estimates provided by loopy belief propagation is assessed, and it is found that in most cases a modest increase in sample density leads to significant improvement in convergence. Additionally, the approximate free energies from loopy belief propagation are compared to statistically exact computations and are confirmed to be both accurate and orders of magnitude faster than traditional methods in the models assessed. %D 2016 %K Stochastic Systems Biology Computational Biophysics Graphical Models Weighted Ensemble %I University of Pittsburgh %L pittir29315 %A Andrew Sedgewick %T Graphical models for de novo and pathway-based network prediction over multi-modal high-throughput biological data %X It is now a standard practice in the study of complex disease to perform many high-throughput -omic experiments (genome wide SNP, copy number, mRNA and miRNA expression) on the same set of patient samples. These multi-modal data should allow researchers to form a more complete, systems-level picture of a sample, but this is only possible if they have a suitable model for integrating the data. Due to the variety of data modalities and possible combinations of data, general, flexible integration methods that will be widely applicable in many settings are desirable. In this dissertation I will present my work using graphical models for de novo structure learning of both undirected and directed sparse graphs over a mixture of Gaussian and categorical variables. Using synthetic and biological data I will show that these models are useful for both variable selection and inference. Selecting the regularization parameters is an important challenge for these models so I will also cover stability based methods for efficiently setting these parameters, and for controlling the false discovery rate of edge predictions. I will also show results from a biological application to data from metastatic melanoma patients where our methods identified a PARP1 slice site variant that is predictive of response to chemotherapy. Finally, I present work incorporating miRNA into a pathway based graphical model called PARADIGM. This extension of the model allows us to study patient-specific changes in miRNA induced silencing in cancer. %D 2016 %K "Graphical Models", "Pathway Models", cancer, "Machine Learning" %I University of Pittsburgh %L pittir29404 %A Kelly A Koral %T LEUKOCYTE SPECIFIC PROTEIN-1: A NOVEL REGULATOR OF HEPATOCELLULAR MIGRATION AND PROLIFERATION IN LIVER REGENERATION AND CANCER %X Hepatocellular carcinoma (HCC) is the most commonly diagnosed form of liver cancer with high morbidity and mortality. Copy number variation analysis (CNV) of human HCC revealed that over 50% of the HCC samples examined had CNV in the gene leukocyte specific protein-1 (LSP1). LSP1, a F-actin binding protein, is expressed in hematopoietic cells and interacts with Kinase Suppressor of Ras (KSR), a scaffold for the ERK/MAPK pathway. The expression of LSP1 in liver and its role in normal hepatocellular function and carcinogenesis remains unknown. Therefore, LSP1 mRNA and protein levels were analyzed in normal hepatocytes in culture, rat liver following partial hepatectomy (PHx), and hepatoma cell lines. In culture and after PHx, LSP1 increased after the termination of hepatocyte proliferation and migration. To investigate LSP1 function in HCC, shRNA was utilized to stably knock down LSP1 expression in the JM1 rat hepatoma cell line. Loss of LSP1 in JM1 cells resulted in dramatic upregulation of cyclin D1 and pERK2, as well as increased cell proliferation and migration. Co-immunoprecipitation and immunofluorescence analysis displayed an interaction and co-localization between LSP1, KSR and F-actin in the JM1 cells and liver during regeneration. Conversely, expression of LSP1 in JM2 rat hepatoma cell line led to decreased proliferation. Enhanced expression of LSP1 in mouse hepatocytes during liver regeneration following injection of an LSP1 expression plasmid also led to decreased hepatocyte proliferation, cyclin D1 and pERK expression. LSP1 knockout mice subjected to PHx displayed increased hepatocellular proliferation on day 4 when compared to control livers as well as increased pERK expression, whereas LSP1 overexpressing transgenic mice (TG) livers displayed a decrease in Ki67 positive hepatocytes on day 4 following PHx and decreased pERK expression. Hepatocytes from KO mice displayed increased proliferation in the absence of growth factors in culture whereas TG hepatocytes proliferated significantly less than WT control hepatocytes. Conclusion: LSP1 is expressed in normal hepatocytes and liver following PHx after the termination of proliferation. In rat hepatoma cell lines and mouse liver in vivo, LSP1 functions as a negative regulator of proliferation and migration. Given the high frequency of LSP1 CNV in human HCC, LSP1 may be a novel target for diagnosis and treatment of HCC. %D 2016 %K Hepatocellular Carcinoma, partial hepatectomy, LSP1 %I University of Pittsburgh %L pittir29318 %A Josiah E Radder %T Novel insights into the genetic basis of chronic obstructive pulmonary disease %X Chronic obstructive pulmonary disease (COPD), defined as irreversible airflow limitation, is caused by a complex interaction of environmental exposures, most commonly cigarette smoke, and genetic factors. Genetic studies of COPD have used tests of genome-wide linkage and association to identify loci that contribute to disease susceptibility. However, as seen in other chronic diseases, the best-replicated loci associated with COPD only account for a small portion of disease heritability. Identifying additional genetic determinants of chronic diseases offers the opportunity to better understand their biology as well as the promise of better disease prediction and patient stratification, first steps in the development of precision medicine. The genetic architecture underlying chronic disease is complex, and it is likely that there is still common variation contributing to COPD that has been masked from association studies by phenotypic and genotypic heterogeneity. Further, there is evidence that rare variation contributes to chronic disease susceptibility, and rare variants in SERPINA1 leading to alpha-1 antitrypsin deficiency support this in COPD. The trio of studies presented in this work aim to detect both of these types of variation. In the first, we employ an extreme-trait study design to detect rare variants in the first whole genome sequencing study of COPD. Using this approach, we identify a previously unreported non-synonymous variant associated with COPD, and two suggestively associated candidate genes, PTPRO and ZNF816. In the second and third studies, we integrate mouse and human genetic data to identify undetected common variants associated with human disease and mouse models of disease. The first study uses a mouse model of cigarette smoke-induced emphysema and identifies the gene ABI3BP as a potential candidate gene. The second looks at early life determinants of chronic disease by measuring airspace size in mice at maturity, leading to identification of IL1R2, which plays a previously undescribed role in lung development. Finally, we demonstrate that by integrating the results of genetic studies, it is possible to gather additional information about the genetic architecture of chronic diseases like COPD. %D 2016 %K "chronic obstructive pulmonary disease", "whole genome sequencing", "pulmonary disease", "lung disease", genetics, sequencing %I University of Pittsburgh %L pittir29369 %A Johannes Kutten %T Role of TSP1-CD47 Signaling in Tracheal Repair and Regeneration %X BACKGROUND: Loss of the trachea and proximal airway from congenital disorders, acute injury or chronic disease is a life-threatening complication. The lack of suitable native replacements has led to attempts to bioengineer tracheas. Recent clinical cases of bioengineered tracheal transplants have been hampered by an inability to maintain growing cell populations. The majority of cases have ended in significant acute and chronic complications, morbidity and death. A growing body of literature has found that a ligand-receptor interaction between the secreted protein thrombospodin-1 (TSP1) and its high affinity receptor CD47, which is upregulated in tissue injury, constitutively restricts multiple transcription factors that modulate self-renewal and pluripotency. HYPOTHESIS: TSP1-CD47 signaling is maladaptively induced in injured airways and bioengineered tracheas to inhibit cellular dedifferentiation, proliferation and restoration of engineered tracheal transplants. METHODS: This dissertation first describes a murine orthotopic tracheal transplant model and second describes methods to characterize the effects of TSP1-CD47 signaling on airway epithelial cells. In vitro, airway epithelial cell wound healing and tissue angiogenic capacity was assessed using a variety of techniques. In vivo, naphthalene injury and orthotopic transplantation of decellularized tracheal grafts was performed in wild-type mice or in mice that lacked TSP1-CD47 signaling, and epithelial restoration was assessed. RESULTS: Decellularized tracheal grafts support re-epithelization within seven days and epithelial differentiation within eight weeks after transplantation. Disruption of TSP1-CD47 signaling restores self-renewal gene expression in tracheal epithelial cells exposed to hypoxic stress and stimulates more rapid wound healing in an in vitro model of airway injury. TSP1 inhibits proliferation of airway epithelial cells while antibody blockade of CD47 restores cell proliferation. Further, TSP1 is upregulated following airway epithelial cell seeding onto decellularized tracheal scaffolds. TSP1-CD47 signaling is induced in the airways of WT mice after injury. CD47 null mice displayed enhanced tracheal healing of both chemically injured airways and following orthotopic transplantation of decellularized tracheal grafts. CONCLUSION: TSP1-CD47 signaling is maladaptively upregulated in stressed tracheal epithelial cells, in injured airways, in cells seeded on decellularized tracheal grafts, and in engineered tracheal transplants to limit self-renewal gene expression and inhibit cell proliferation, airway healing and cellular incorporation of bioengineered tracheal transplants. %D 2016 %K tissue engineering, regenerative medicine, pathology, trachea, decellularization, CD47, TSP1, thrombospondin-1, extracellular matrix %I University of Pittsburgh %L pittir29327 %A Eser Yilmaz %T SENSORY NEURON SUBPOPULATION-SPECIFIC REGULATION OF INTRACELLULAR CALCIUM IN A RAT MODEL OF CHEMOTHERAPY- INDUCED PERIPHERAL NEUROPATHY %X Chemotherapeutic-induced peripheral neuropathy (CIPN) is associated with a unique stocking-glove distribution of signs and symptoms. CIPN starts with numbness and tingling and proceeds to ongoing pain. The potential impact of target of innervation on CIPN has been largely ignored despite the tremendous heterogeneity among sensory neurons regarding their resting and injury-induced properties. Moreover, there is compelling evidence from other neuropathy models indicating that dysregulation of intracellular Ca2+ in sensory neurons contributes to the signs and symptoms of the neuropathy. Therefore, the central hypothesis I pursued in this thesis was that both the positive and negative signs of CIPN are due to subpopulation-specific changes in Ca2+ regulation, which I tested in a paclitaxel-induced peripheral neuropathy model. Paclitaxel was associated with a persistent decrease in mechanical nociceptive threshold in response to stimuli applied to the glabrous hindpaw skin, but not the other areas that were tested. While paclitaxel had no detectable influence on either resting or depolarization-evoked Ca2+ transients in putative non-nociceptive neurons, there was a significant paclitaxel-induced decrease in the evoked Ca2+ transient duration in putative nociceptive glabrous neurons, which correlated with the paclitaxel-induced nociceptive behavior. This paclitaxel-induced change in Ca2+ regulation was not due to increased activity of Na+-Ca2+-exchanger (NCX), which contributes to the regulation of evoked Ca2+ transient durations in this subpopulation of neurons. However, the paclitaxel-induced decrease in the duration of the evoked Ca2+ transient did appear to be due to both direct and indirect influences of mitochondria. The direct influence reflected an increase in mitochondria volume, enabling an increase in total Ca2+ uptake, while the indirect influence reflected an increase in the activity of ATP-dependent Ca2+ regulatory mechanisms, such as the sarco-endoplasmic-reticulum-ATPase (SERCA). The results generated in this dissertation expand the current view of CIPN mechanisms and constitute an important step towards understanding the roles of intracellular Ca2+ as well as mitochondrial changes to the pain associated with CIPN, paving the road for novel therapeutic strategies to limit the side effects of chemotherapy. %D 2016 %K paclitaxel, dorsal root ganglia, pain, mitochondria, NCX %I University of Pittsburgh %L pittir28554 %A Jose Juan Tapia Valenzuela %T A study on systems modeling frameworks and their interoperability %X 'What is in a model?' is a question that any systems modeler has asked at least once when working with a biological system. To answer this question we must understand how every species and reaction in a model are biologically related to each other, which in the case of cellular systems requires an understanding of local protein and gene interactions at the domain level. Typical modeling approaches like reaction-networks do not explicitly encode this information, which can obfuscate the assumptions made by a model and limit their further analysis, comparison and re-use. Additionally, the multi-state nature of the elements in a model can lead to a combinatorial explosion of the interactions in the model, pushing reaction-networks to their limits. Rule-based modeling is a modeling paradigm that addresses these issues through the use of a graph-based representation of each species's interaction domains and their local interactions. In this paradigm, reaction \emph{rules} describe a class of reactions and are represented as graph rewriting operations that encode biological processes like bond formation and post-translational modification. This allows for a concise, explicit encoding of how species interact, modify and are related to each other while at the same time managing the enormous number of potential molecular interactions in a multi-state system. In this work I present two different approaches that aim to bring the benefits of rule-based modeling's graph representation to other modeling paradigms: \emph{Atomizer} and \emph{MCell-R}. Atomizer is an algorithm for the extraction of structural and process information from reaction-network models, which I use to encode the model in a rule-based format. Once we have an explicit understanding of what is in a model and how entities in a model interact, we can then perform meta-modeling operations like model analysis, alignment, comparison and visualization, which I demonstrate through the application of Atomizer to a large dataset of reaction network models. MCell-R is a framework for the efficient modeling and simulation of multi-state, multi-component spatial systems. The framework consists of an integration of the NFsim rule-based simulation engine together with the MCell spatial modeling system, which highlights the utility of bringing rule-based paradigms into reaction based platforms. %D 2016 %K systems modeling, SBML, BioNetGen, MCell, spatial modeling, Monte Carlo %I University of Pittsburgh %L pittir29367 %A Henry A Ogoe %T ROBUST PREDICTIVE MODELING OF RELATED GENE EXPRESSION DATA VIA MULTI-SOURCE TRANSFER RULE LEARNING %X The advent of high-throughput genomics has led to the accumulation of copious amounts of biomedical data such as gene expression, made available through public repositories like the NCBI?s GEO. Meanwhile, the digitization of biomedical literature into repositories such as PubMed, have motivated the creation of curated knowledge bases like the Gene Ontology. Pooling information from such repositories and integrating it with predictive modeling of similar biomedical data from multiple studies, could lead to models that are more robust. Most current methods are unable to leverage background knowledge, referred to herein as catastrophic forgetting, and often produce black-box models that are difficult for humans to interpret. In this era of precision medicine, there is thus a critical need for effective methods that could incorporate background knowledge from multiple sources, and yet produce simple to understand models from biomedical datasets. This dissertation develops four novel frame-works: (i) TRL-FM, (ii) KARL, (iii) MS-TRL, and (iv) iTRL, which use transfer rule learning to incorporate background knowledge from multiple sources for predictive modeling of gene expression datasets. They provide significant extensions to an existing method, TRL that leveraged background knowledge from single sources. This work tests the hypothesis that ?incorporating background knowledge from multiple sources into predictive modeling via the transfer rule learning approach leads to models that contain more robust propositional rule patterns than learning without any background knowledge or just from a single source.? To test this hypothesis, I compared the accuracy and coverage of predictive models that were produced with the methods developed herein, to the baseline models, using 25 gene expression datasets from 5 studies of brain, breast, colon, lung, and prostate cancers. The results showed that the former, produce on average, statistically significantly more robust models than the latter. Also, KARL, MS-TRL, and iTRL provide mechanisms that could be used to discover both domain-specific and domain-independent robust rule patterns. The methods developed herein augment extant capabilities of predictive modeling techniques to utilize and build robust, easy-to-interpret rule models from sparse, single, diverse sources of biomedical data and knowledge. These methods can be easily extended to other application domains beyond biomedicine. %D 2016 %K predictive modeling, transfer learning, gene expression, multiple sources, knowledge discovery, rule learning %I University of Pittsburgh %L pittir29428 %A Jason Boone %T Exploring the Relationship of Teacher Evaluation and Professional Development in Southwestern Pennsylvania %X This study examined the effects of Section 1123 of Act 82 of 2012, a section of an omnibus bill relating to the Public School Code of 1949 (P.L. 30, No. 14), on selected school districts in Southwestern Pennsylvania. This specific section of the omnibus bill of amendments, commonly known as the Educator Effectiveness Model, relates to educator effectiveness and included policies and procedures relating to rating forms for and suspension of professional educators in the Commonwealth of Pennsylvania. School administrators, union presidents, and classroom teachers have all been affected by this legislation over the past four years, be it through trainings regarding the legislation or the actual implementation of the legislation at the local level. The purpose of this study is to examine the effects the legislation has had in these selected school districts relating to evaluation and supervision processes, and whether or not these changes have had any effect on professional development offerings that have been occurring in any of these districts. Based on the findings of this study, the legislation has had a profound effect in these selected districts in Southwestern Pennsylvania. Many school administrators and union presidents report the additional paperwork, protocols, and focus on data (both student-level and observation-based) have helped to increase stress levels in the schools, both in administrators and teachers. These participants also report that the use of evaluation and supervision data is inconsistent amongst these districts, and amongst the buildings in each of these districts. Although some of the union presidents responded favorably to aligning professional development opportunities with data collected through the evaluation and supervision processes, the manner in which this would occur, or how to best implement the process, was not consistently reported by the participants in the study. %D 2016 %K Teacher Evaluation, Teacher Supervision, Adult Learning, Professional Development %I University of Pittsburgh %L pittir29314 %A Courtney Queen %T Female Genital Cutting/Mutilation: An Exploratory Study of the Psychological Health Outcomes in Tanzania %X Female Genital Cutting/Mutilation (FGC/M) is a practice that involves the partial or total removal of various portions of the external female genitalia for non-medically necessary reasons. This tradition has been passed through generations and is still very much present today. While the practice is adhered to for the social and cultural benefits it engenders, many negative outcomes have been associated with the practice. The harmful physical and sexual outcomes of FGC/M have been examined; however, very little research has focused on the psychological impact of FGC/M. The purpose of this study was to narrow the gap in the research by examining the mental health and emotional outcomes of FGC/M among women in the East African country of Tanzania. Tanzania is home to the Maasai, a tribe with strong historical and cultural roots who have held on to many tribal practices over the years, including FGC/M. I used a qualitative methodological approach which included in-depth, semi-structured interviews with women from the Maasai tribe who have undergone FGC/M. Given that mental health is not a developed field in Tanzania, this study sought to elicit participants? feelings toward the practice of FGC/M including how the procedure made them feel emotionally both at the time it occurred and today. During the interviews Maasai women described their personal experiences with and feelings toward FGC/M. Their responses were categorized in the following ways: 1) their view of the logic behind why FGC/M is practiced; 2) psychological health outcomes; 3) women?s general opinions and attitudes about FGC/M; and 4) women?s personal journey and experience with FGC/M. This study suggests that while FGC/M provides symbolic importance for Maasai women. They associate the procedure with pain, fear and shock at the time of undergoing FGC/M. FGC/M marks a significant turning-point in a young girls? life that includes both positive and negative outcomes. Many women wanted this practice to end because of their own negative consequences; however, they still had plans to continue this among their own daughters and granddaughters. This indicates that this practice, however traumatic it may seem, is attached to the strength and pride of what it means to be a Maasai woman. These findings provide the impetus for a number of social work practice, policy, and research implications to follow. %D 2016 %K Maasai, Tanzania, Female Genital Cutting, Female Genital Mutilation, mental health %I University of Pittsburgh %L pittir29344 %A Amanda Chan %T Cultural frontiers: women directors in post-revolutionary New Wave Iranian cinema %X Iranian New Wave Cinema (1969 to present) has risen to international fame, especially in post-revolutionary years, for its social realist themes and contribution to national identity. This film movement boasts a number of successful women directors, whose films have impressed audiences and film festivals worldwide. This study examines the works of three Iranian women directors, Rakhshan Bani-Etemad, Tamineh Milani, and Samira Makhmalbaf, for their films? social, political, and cultural themes and commentary while also investigating the directors? techniques in managing censorship codes that regulate their production and content. Importantly, these women directors must also navigate the Islamic Republic?s Ministry of Culture and Islamic Guidance?s censorship laws, which dictate that challenging the government?s law or Islamic law is illegal and punishable. These women directors make films that highlight the issues and social status of Iranian women, the working class, and the under-privileged; they touch upon motherhood, love, marriage, abuse, war, and more. Moreover, they are social films that compose the genre of ?women?s films,? though the characters and filmmakers are both men and women. While scholars have looked at the way Iranian women directors challenging both the traditional, one-dimensional representations of women in cinema, such as those in filmfarsi, this research draws upon feminist theory to argue that women directors utilize a number of strategies to elude or challenge censorship codes, which range from creative shooting to simply skipping the censorship review process altogether. Films by Iranian women directors reject the Orientalist conception of Iranian women as Muslim women who are prisoners of their culture and society. %D 2016 %K iran, feminism, new wave, directors, film, cinema, tamineh milani, tahmineh milani, rakhshan, bani-etemad, bani etemad, samira, makhmalbaf, the apple, the hidden half, two women, the fifth reaction, at five in the afternoon, blackboards, the blue veil, the may lady, under the skin of the city %I University of Pittsburgh %L pittir27767 %A Elizabeth Hoadley %T Discrimination and modern Paganism: a study of religion and contemporary social climate %X This work investigates attitudes of religious discrimination against Paganism and how the faith is lived as a culture. It closely examines how discriminatory attitudes against Paganism are translated into actions and how they have affect Pagan lives on an individual basis. This project also investigates the origins of discriminatory attitudes for non-Pagans, in order to better understand them. The research problem includes two basic parts: distinguishing discriminative actions and attitudes, and observing their effects on Pagans? daily lives. The cycle of action and information involved in discrimination against Pagans is discussed in detail, including an analysis of the defense mechanisms employed by Pagans to mitigate the adverse effects of discrimination in their lives. The goal of this research is to add to current understandings of religious discrimination and how it can greatly influence Pagan practice and culture. The use of the results of this research will include but not be limited to: further studies on the cultural power of religious discrimination, the formation of greater public understanding of nontraditional religions and how they are affected by modern social climates, and the addition of a seldom heard voice into current conversations surrounding religious tensions in the modern world. %D 2016 %K Paganism Religion Anthropology Discrimination Witchcraft Neo-Paganism Wicca %I University of Pittsburgh %L pittir28559 %A Christina Fulponi %T The uses of Italian identity to advance political agendas: harnessing the media to influence the parameters of immigration discourse %X The State?s construction of Italian identity during the Diaspora informs the way the Italian population perceives non-Italians as incompatible with certain elements of Italian culture, specifically Catholicism, Whiteness, and ties to the land. The discourse of the Lega Nord has tried to capitalize on recent immigration to advance their own agenda by using the media to promote specific aspects of this Italian identity. Lega Nord discourse, broadcast by the media, was able to influence the parameters of the immigration debate. This was achieved by the media constructing images of migrants as ?others within? the Italian nation through differentiating them based on certain fixed and exclusive elements of identity emphasized in the LN?s rhetoric. By stressing certain elements of identity, the LN has created a political discourse that is hostile to migrants, which serves their political agenda in achieving homogeneity and reinforces their stance on Northern autonomy. Italian identity is not absolute and can be reimagined to emphasize components that create a more inclusive discourse. %D 2016 %K Italian Identity, Identity, Italianit?, Migration, Media, Immigration discourse, Italian politics, Lega Nord, Silvio Berlusconi %I University of Pittsburgh %L pittir29295 %A Meghan Bathgate %T EXAMINING MOTIVATIONAL SHIFTS IN MIDDLE SCHOOL: WHAT DEEPENS SCIENCE MOTIVATION AND WHAT ATTENUATES ITS DECLINE? %X While motivational decline towards science is common during adolescence, this dissertation asks if there are beneficial science experiences that buffer against the loss of motivation and even promote its growth. The dissertation consists of two papers (Chapter 2 & 3) with additional analyses in Chapter 4 and a summary of findings in Chapter 5. The first paper examines whether classroom science experiences are differentially associated with motivational change and science content knowledge. Using self-reports from a sample of approximately 3,000 middle school students, this study investigates the influence of perceived science classroom experiences (student engagement & perceived success), on motivational change (fascination, values, competency belief) and content learning. Controlling for demographic information, school effects, and initial levels of motivation and content knowledge, we find that dimensions of engagement (affect, behavioral-cognitive) and perceived success are differentially associated with changes in particular motivational constructs and learning. The second paper examines one of these motivational outcomes (value) in more detail. Valuing science is associated with positive learning outcomes and is often used to motivate engagement in the sciences, but less is known about what influences its development and maintenance, particularly during the critical middle school years. Using multinomial regression applied to longitudinal data from approximately 2,600 middle-school students, I test the relationship of the perceived science experiences examined in Paper 1 (affective engagement, behavioral-cognitive engagement, & perceived success) and optional formal and optional informal experiences to changes in science utility value. Furthermore, we address whether the same factors that predict growth in science value also predict absence of decline. Overall, we find that all five factors are associated with changes in value, but some have different relationships with growth vs. decline outcomes. Chapter 4 extends these findings to examine drivers of growth and decline for fascination and competency beliefs. Together, these findings provide a more nuanced view of the factors associated with science motivation and learning (both in and out of the science classroom), as well as the practical implications for educational practice. %D 2016 %K motivation engagment science learning middle-school %I University of Pittsburgh %L pittir28460 %A Buket Kisac %T The Effects of Transfer of Stimulus Control Procedures and Peer-Mediated Intervention on the Acquisition and Generalization of Intraverbals for Children with Autism Spectrum Disorders %X Intraverbals are a type of verbal behavior that occurs when a verbal stimulus evokes a verbal response that has no point-to-point correspondence or formal similarity with the verbal stimulus (Skinner, 1957). One teaching procedure used to establish intraverbal skills is transfer of stimulus control procedure. Although a number of research studies have shown that transfer of stimulus control procedures appeared to be effective in teaching intraverbals for children with ASD, the gains observed in the training did not transfer, or generalize, to other people and settings. That is, merely the use of transfer of stimulus control procedures did not yield the generalization of intraverbal responses. The literature on generalization has emphasized that generalization does not occur unless specific procedures such as programming common stimuli are also provided (Stokes & Osnes, 1989; Stokes & Baer, 1977). In this study, the researcher investigated the effects of transfer of stimulus control procedures and a peer prompting procedure on the acquisition and generalization of intraverbals across peers without disabilities using a multiple baseline across three conversation scripts design. Two children with ASD and four typically-developing children participated in this study. Upon the intervention, both participants demonstrated increased contextually-appropriate intraverbal responses in a few sessions. Results also indicated that the combined approach showed promising generalization outcomes related to increases in correct intraverbals. Additionally, both participants required decreased number of adult-delivered prompts to converse with their peers during peer prompting sessions, indicating that they would maintain social interaction in the teacher?s absence. Considerations for interpretation and recommendations for future directions of this study are also discussed. %D 2016 %K Keywords: Transfer of stimulus control procedures, peer-mediated intervention intraverbals, and children with autism spectrum disorder. %I University of Pittsburgh %L pittir29237 %A Mary Catherine Reljac %T The Motivations, Relationships, and Decision-Making of Western Pennsylvania Public School Board Members %X The local control of public schools in the United States provides opportunities for everyday citizens to participate in governance and shape educational programs (Tyack, 2003). This study surveyed the people who volunteered to serve on Western Pennsylvania school boards, specifically examining their motivations for service including the recruitment process, experiences or interactions that motivated board service, interests, and socialization methods once on the board. The study also uncovered information regarding the decision-making processes employed by school board members and their relationships and patterns of communication with others in the school community. Additionally, the study collected information on the challenges of school board leadership and what would help board members in their service. The study found that the majority of respondents were self-motivated to seek election and were interested in giving back to the community, being most often interested in curricular issues or financial issues. Respondents chiefly used resources provided by the district to gather information for decision-making and learned about their roles primarily from other school board members or through state organizations. Respondents regularly communicated with other school board members and the superintendent, primarily in face-to-face conversations %D 2016 %K school board, motivations, relationships, decision-making, Western Pennsylvania, education %I University of Pittsburgh %L pittir29146 %A Anna Peluso %T COMPARISON OF MINDFUL AND SLOW EATING STRATEGIES ON ACUTE ENERGY INTAKE %X Introduction:Mindfulness and slow eating techniques are commonly recommended to aid in weight loss within behavioral weight management programs; yet, the role of these eating strategies on acute energy intake (EI) and satiety are not clear. Purpose: The purpose of this study was to investigate the effects of mindful and slow eating strategies on acute EI and satiety. Methods: 24 subjects (median BMI: 29.1 (24.3 ? 36.7), median age: 24.0 (21.0 ? 31.8)) were randomized to one of three eating conditions (EAT, SLOW, or MIND). For the EAT condition, subjects were instructed to eat as they normally would for both test meal sessions. For the SLOW condition, subjects were instructed to eat as they normally would for their first test meal session and to slow their eating for their second test meal session. For the MIND condition, subjects were instructed to eat as they normally would during their first test meal session and were given brief instructions on mindful eating for their second test meal session. For each condition, subjects were provided ad-libitum access to a test meal and EI was calculated based upon food consumed during this period. Subjects rated their level of satiety following each meal. Results: There were no significant differences in EI between eating strategy conditions (EAT: 848 (704-1071) kcals, MIND: 673 (485- 846) kcals, SLOW: 756 (611-1076) kcals) (p = 0.786). There was a trend toward a decrease in energy intake in the MIND condition (mean change in energy intake: -64.4 ? 178.4 kcals) compared with the EAT (mean change in energy intake: 98.3 ? 169.6 kcals) condition and a prevention of increased intake in the SLOW (mean change in energy intake: 2.6 ? 107.9 kcals) condition (p = 0.133). There were no significant differences in ratings of satiety between conditions. Conclusion: Neither mindful nor slow eating strategies significantly decreased acute EI or satiety, although a decrease in EI achieved through a brief mindfulness practice and prevention of increased intake through slow eating may be clinically meaningful for weight management. Future studies should aim to investigate the potential benefits of slow eating and mindfulness for weight management. %D 2016 %K mindful eating, mindfulness, satiety, slow eating, energy intake %I University of Pittsburgh %L pittir29112 %A Kristie Rupp %T HOUSEHOLD SUPPORT AND PHYSICAL ACTIVITY IN ADOLESCENT FEMALES FROM LOWER SOCIOECONOMIC STATUS HOUSEHOLDS %X BACKGROUND: Parental support for physical activity has been demonstrated to be associated with physical activity levels of low socioeconomic status adolescent females. While research show that adult facilitation and encouragement of physical activity engagement is valued by this group, limited research has been done examining the associations between household support and physical activity levels in this population. PURPOSE: The purpose of this study was to examine the association between the perception of household support and physical activity levels of low socioeconomic status adolescent girls. METHODS: Thirty-six girls, between the ages of 13-17 years, were recruited from lower socioeconomic geographic areas. Recruitment strategies included boy low-touch (e.g., flyers, mailings) and high-touch (e.g., face to face) methods. During a study visit, participants completed two questionnaires as well as had their height and weight measured. The 3DPAR was used to assess participant physical activity and the household support questionnaire was used to collect demographic information as well as measure support for physical activity from the adult in the household the participant perceived themselves as being closest with and each additional adult in the household. RESULTS: There were no significant associations between the perception of household support for physical activity and physical activity levels. There were negative significant associations between the BMI of low socioeconomic status adolescent girls and both the total household support (p=0.001) and the support provided by the closest adult to the participant in the household (p<0.001). The most frequently reported priorities were family and friends, school, and being the best version of oneself. The most frequently reported facilitators of physical activity were family/ friend support, types of physical activities, and school. The most frequently reported barriers to physical activity were school, transportation, and pain/injury. CONCLUSIONS: These findings suggest that household support for physical activity is not associated with physical activity engagement in adolescent girls living in low socioeconomic geographic areas. Thus, other factors may be associated with physical activity participation in this population group, and this warrants further investigation. %D 2016 %K physical activity, adolescents, parental support, socioeconomic status, BMI %I University of Pittsburgh %L pittir29134 %A Stephanie McCoy %T Objectively Measured Physical Activity and Sedentary Behavior in Children with Autism Spectrum Disorder %X Low levels of physical activity and high levels of sedentary behavior are of public health concern in children. However, little is known about the patterns of physical activity and sedentary behavior in 6-11-year-old children with autism spectrum disorder (ASD). PURPOSE: To examine patterns of physical activity and sedentary behavior in children with ASD. To examine relationships between moderate-to-vigorous physical activity (MVPA) and sedentary behavior and potential determinants of these behaviors. METHODS: Nineteen children 6-11-year-olds with ASD were recruited. Height and weight were objectively measured and used to determine BMI for age, and participants wore an ActiGraph GT3X activity monitor for 7 consecutive days to measure physical activity and sedentary time. Parents answered questions on demographics, perceptions of physical activity, barriers to child?s physical activity, child?s autism severity, and functional disability. RESULTS: Fifty percent of children achieved the guidelines for physical activity in children. Participants spent on average 76 ? 48 minutes per day engaged in MVPA, and 332 ? 65 minutes per day sedentary. There no differences between weekday and weekend MVPA, nor weekday and weekend sedentary time. Twelve participants were classified as normal weight, 4 participants were classified as overweight, and 3 participants were classified as obese. There were no differences between prevalence rates of overweight or obesity in our sample compared to national averages. No relationships were found between MVPA and sedentary time and any independent variables examined. However, qualitatively, the most common parent-reported barriers to children?s physical activity were child?s lack of interest, inadequate community physical activity programs, behavioral problems, not being able to find a community program that accommodates their child?s physical disability, and child is too developmentally disabled. CONCLUSIONS: Findings suggest that barriers commonly reported by parents of children with ASD may serve as targets for creating physical activity programs adapted for this population. Further, over 90% of participants wore the monitor over 12 hours on 7 days. Thus, these findings suggest that an activity monitor worn around the waist for one week is a feasible option for the measurement of physical activity and sedentary behavior in this population. %D 2016 %K physical activity, autism spectrum disorder, autism, sedentary behavior, obesity, children %I University of Pittsburgh %L pittir29152 %A Yafei Lyu %T Development of Tenofovir Prodrugs as Rectal Microbicides for HIV Prevention %X Receptive anal intercourse is common among men who have sex with men (MSM), transgender women, and practiced by women around the world. The risk of becoming infected with HIV through receptive anal intercourse is 20 times greater than vaginal intercourse. Hence, there is an urgent need for the development of rectal specific topical pre-exposure prophylaxis (PrEP) products. In the current study, our lab developed enemas containing tenofovir (TFV) for rectal application, which may provide some advantages with respect to user acceptability and compliance. In addition to evaluation of TFV in enemas, prodrugs of TFV: tenofovir alafenamide fumarate (TAF) and hexadecyloxypropyl (HDP)-tenofovir (CMX157) were evaluated due to their increased potency and better safety profile. In this project, a high performance liquid chromatography (HPLC) method for TAF was developed and qualified. Preformulation studies for TAF including solubility, hydrolytic, thermal, photolytic, and oxidative stability and preservative compatibility were conducted. TAF was found to be susceptible to hydrolytic degradation in acidic pH (pH?4) and degraded when exposed in an aqueous solution to temperatures greater than 25?C. TAF hypotonic and isotonic enema formulations (1.76 mg/mL) were developed and characterized with respect to pH, osmolality, and drug content. One-week stability of these enemas was assessed in 40?C/75% RH, 30?C/65% RH and 25?C/60% RH environmental chambers. TAF enemas were stable for one week. In addition to the TAF enema, formulation efforts were initiated with CMX157. A preliminary HPLC method for CMX157 was developed. Prototype CMX157 enemas were prepared and pH and osmolality testing conducted. Additional formulation optimization is required to enhance TAF stability in an enema format. Further investigation of the prototype CMX157 enema developed with respect to its physiochemical characteristics and stability is needed. %D 2016 %K Enema, TAF, CMX157, rectal microbicide %I University of Pittsburgh %L pittir29219 %A Mostafa Shehabeldin %T INVESTIGATING THE MECHANISM OF INTRACELLULAR SIGNALING OF MAGNESIUM IN HUMAN BONE MARROW STROMAL CELLS (hBMSCs): POTENTIAL ROLE IN OSTEOGENESIS %X Magnesium metal and its alloys have been investigated as promising biomaterials for internal bone fixation devices. Previous reports have shown that magnesium fixation devices enhance fracture healing in animal models while exhibiting biocompatibility and biodegradability. Moreover, mechanistic studies have indicated that mesenchymal stem cells (MSCs) display an osteogenic response to increased magnesium (Mg2+) concentrations in culture medium. We sought to study the signaling pathways underlying Mg-mediated osteogenesis in human bone marrow stromal cells (hBMSCs). We hypothesized that Mg2+ could be inducing the osteogenic response of hBMSCs in a calcium sensing receptor (CaSR) dependent manner. In the present study, hBMSCs were stimulated with basal medium (BM) supplemented with 10 mM MgSO4 (10-Mg), 4 mM CaCl2 (4-Ca) or 10 mM CaCl2 (10-Ca) at different time points. Western blot results showed a similar trend of CaSR phosphorylation in response to 10-Mg and 4-Ca media. Although this phosphorylation peaked at 15 minutes with both 10-Mg and 4-Ca media, it was not significantly higher than with BM alone. PKC-? and Erk 1/2 are two downstream kinases of the CaSR. Both kinases have been reported to play a pivotal role in the differentiation of osteoprogenitors by regulating the expression of key osteogenic markers. We showed that hBMSCs exposure to 10-Mg medium resulted in significant phosphorylation of PKC-? relative to BM. In contrast, Erk1/2 did not exhibit significant changes in its activity with 10-Mg medium. In addition, qPCR data showed upregulation of Cx43, ALPL and Col10A1 following hBMSCs treatment with 10-Mg medium. Similarly, a trend of upregulation of Runx2 mRNA was seen with 10-Mg medium; however, this upregulation was not statistically significant. VEGFA, a key angiogenic marker, was downregulated at the mRNA level by 10-Mg medium at a late time point (3 weeks). Chemical blocking of CaSR by its selective antagonist NPS2143 only potentiated ALPL expression, but did not have any effect on VEGFA or Col10A1. In conclusion, we propose a potential mechanism by which PKC-? and Cx43 could mediate the osteogenic response of hBMSCs to increased Mg2+ concentrations. The suggested functional activity of PKC-? might be regulated by a CaSR upstream signaling mechanism. %D 2016 %K Magnesium Signaling, PKC-?, Calcium sensing receptor, Bone regeneration, fixation devices. %I University of Pittsburgh %L pittir29106 %A Feng Shan %T Investigation of cancer drug penetration in 2D and 3D tumor cell culture models %X Limited drug penetration into solid tumors may prevent cancer agents from achieving sufficient concentrations to exert their therapeutic effects. However, most pre-clinical in vitro drug discovery studies utilize two dimensional (2D) growth inhibition assays, which do not closely recapitulate either the three dimensional (3D) morphology or cellular microenvironments of solid tumors. In this study, we investigated the penetration of cancer drugs into 2D and 3D head and neck squamous cell carcinoma (HNSCC) cell culture models to determine whether differences in drug penetration might contribute to differences in growth inhibition in the two models. Ellipticine, idarubicin, daunorubicin and doxorubicin were selected as the test drugs because they are fluorescent and a linear relationship exists between fluorescent intensity and drug concentration. Cal33 and FaDu HNSCC cell lines were seeded into normal tissue culture microplates to generate 2D monolayers or Ultra Low Attachment microplates to generate spheroids. We used the Cell Titer Glo? reagent to measure cellular ATP levels as an indicator of cell viability and proliferation. The ImageXpress Micro automated high content platform was used to acquire fluorescent images of 2D and 3D cell cultures exposed to the four fluorescent drugs and the Hoechst DNA stain. We used the multi-wavelength cell scoring image analysis module to quantify the accumulation and distribution of fluorescent drugs in 2D and 3D cell cultures. Although 2D Cal33 cultures were more sensitive than 3D cultures to growth inhibition by all four drugs, both models exhibited similar concentration and time dependent drug accumulation characteristics. In 2D, the distribution of compounds within cells was uniform and independent of the cell numbers seeded into the wells. In Cal33 spheroids however, the compounds exhibited an apparent distribution gradient from high in cells in the outer layers to low in cells in the interior. We speculate that the enhanced cell-cell and cell-ECM contacts in spheroids forms a barrier through which therapeutic agents must penetrate, and that the lower drug concentrations experienced by tumor cells in the interior of spheroids combines with their diminished proliferative capacity to confer the apparent resistance of 3D cultures to cancer drug induced growth inhibition and cell death. %D 2016 %K 3D tumor cell culture, drug penetration %I University of Pittsburgh %L pittir29068 %A Harini Venkata Krishnan %T ENGINEERED IN VITRO BREAST CANCER MODELS SHOW PHENOTYPIC DIFFERENTIATION CHARACTERISTICS OF EARLY VS. LATE-STAGE DISEASE %X Cancer drug discovery and development is challenged by poor prediction of drug responses in in vitro disease models. Results from clinical trials suggest that just 5% of drugs tested are successful in patients. Currently used disease models such as two-dimensional (2D) cell monolayers and in vivo animal models fail to recapitulate the human tumor microenvironment. Further, disease progression from the non-invasive to metastatic stage needs models that can recapitulate each stage. Hence, there is an unmet need to develop three-dimensional (3D) models that capture natural tumor progression for better understanding of disease biology as well as screening of drug regimens acting on different disease stages. In this work, we have characterized 3D breast microtumors ranging from 150 to 600 ?m diameters using non-invasive T47D cells with precise control over physicochemical microenvironmental factors. In this study, we test the hypothesis that the size-controlled microtumors will exhibit differential biochemical features and drug response arising from unique molecular signatures created by variable tumor microenvironments. To test this hypothesis, we studied the physicochemical features such as hypoxia, reactive oxygen species, metabolic activity, and cell cycle status. Additionally, the expression of key regulators of growth/proliferation pathways in breast cancer progression such as estrogen receptor alpha (ER-?) and growth factor receptor/s was studied and efficacy of clinically used inhibitors such as 4-hydroxytamoxifen (4-OHT) was evaluated. The results indicated that large T47D microtumors (600 ?m) exhibited traits of clinically advanced tumors such as collective cell migration, mesenchymal marker upregulation, loss of ER-? and endocrine resistance in contrast to the small microtumors (150 ?m). Thus, the engineered in vitro models could successfully recapitulate phenotypic differentiation characteristics of early vs. late disease stage in the same non-invasive T47D cells just by precisely controlling the microtumor size, which further regulated the tumor microenvironmental factors. The large microtumors (600 ?m) were found to resemble features of advanced stage breast cancer whereas the small microtumors (150 ?m) recapitulated features of early stage breast cancer. Hence, such disease stage-specific microtumor models could help in the evaluation of crucial mechanisms in breast tumor progression correlated to tumor size and in the screening of therapeutic candidate/s. %D 2016 %K 3D cell culture, stage specific model, breast cancer progression %I University of Pittsburgh %L pittir29199 %A Brian Kiesel %T The Toxicology, Pharmacokinetics and Metabolism of a Novel IL-6 Induced STAT3 Inhibitor %X Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and annually an approximate 46,000 Americans are diagnosed and 8,600 Americans die from the disease. The oncogenic transcription factor STAT3 is frequently hyper-activated in HNSCC and promotes gene transcription involved in cancer development, maintenance and progression. Several selective small molecule inhibitors of IL-6-induced STAT3 activation were identified in a screening campaign, and four analogs from a lead optimization series were analyzed to promote one to test in vivo. To choose a lead compound for in vivo experimentation, the four compounds were incubated with mouse liver microsomes to select a lead based on enhanced metabolic stability. From this experiment compound UPCDC-10205 was prioritized for in vivo testing to evaluate its toxicity, pharmacokinetics (PK) and metabolism. Both single and multiple IV dose toxicity studies determined that the maximum soluble dose at 4 mg/kg of compound UPCDC-10205 in 10% Solutol? was not toxic to mice. To evaluate PK, single doses of UPCDC-10205 IV 4 mg/kg, PO 4 mg/kg, or PO 30 mg/kg UPCDC-10205 suspension in 1% carboxymethyl cellulose were administered to groups of female mice that were euthanized from 5 min to 24 h after dosing. Plasma, urine and various tissues were analyzed using LC-MS to quantitate UPCDC-10205. PK parameters were determined non-compartmentally. Potential metabolites were monitored in plasma and urine using LC-MS. PK analysis showed rapid plasma clearance and extensive distribution of UPCDC-10205. Comparisons of plasma exposure between 4 mg/kg PO and IV showed a bioavailability of ~5%. Little UPCDC-10205 was observed in urine, leading to the hypothesis that metabolism was the major contributor to clearance. Metabolic investigations revealed direct glucuronidation as the major metabolite, explaining why microsomal stability (reflective of phase I metabolism) did not translate to in vivo metabolic stability. %D 2016 %K STAT3, Pharmacokinetics %I University of Pittsburgh %L pittir29170 %A Seth Creasy %T Comparison of Supervised and Unsupervised Physical Activity Programs during a Standard Behavioral Weight Loss Intervention for Adults who are Overweight or Obese %X Both supervised and unsupervised physical activity programs have successfully increased physical activity and reduced body weight when combined with a standard behavioral weight management program. However, it remains unclear if supervised and unsupervised physical activity programs with similar activity prescriptions change physical activity behavior and physiological responses comparably. Purpose: The primary aim of this study was to examine changes in moderate-to-vigorous physical activity (MVPA) in response to a supervised physical activity program prescribed in minutes/week (SUP-PA), an unsupervised physical activity program prescribed in minutes/week (UNSUP-PA), and an unsupervised physical activity program prescribed in steps/day (STEP) during a standard behavioral weight loss intervention. Methods: Fifty-two overweight and obese adults (age: 43.5 ? 10.1 years, BMI: 31.5 ? 3.5 kg/m2) were randomized to STEP (n=18), UNSUP-PA (n=17), and SUP-PA (n=17). Subjects were prescribed a calorie-restricted diet (1200-1800 kcals/day) and increased physical activity (150 min/week or 10,000 steps/day with 2,500 brisk steps/day). All three groups attended weekly in-person group intervention sessions for 12 weeks. Results: All three groups significantly increased MVPA in bouts of ?10 minutes over the 12-week intervention (STEP: 11.5 ? 31.2 min/day, UNSUP-PA: 16.1 ? 25.8 min/day, and SUP-PA: 21.6 ? 24.9 min/day, p<0.001) with no differences between groups (p=0.94) or group by time interaction (p=0.81). In addition, there were no significant differences in weight loss between the groups (p=0.81). Conclusions: This study provides evidence that unsupervised physical activity prescribed in minutes/week and an unsupervised physical activity program prescribed in steps/day can increase physical activity equally compared to a supervised physical activity program during a standard behavioral weight loss program eliciting similar physiological responses in adults who are overweight or obese. %D 2016 %K Physical activity, obesity, exercise %I University of Pittsburgh %L pittir29029 %A Joshua Centor %T DECISION-MAKING IN HIGHER EDUCATION: STRATEGIC PLANNING AND RESOURCE ALLOCATION AT ELITE PRIVATE UNIVERSITIES IN THE UNITED STATES %X There are a multitude of challenges facing American higher education in the 21st century and no shortage of pressing topics that administrators must address at their respective institutions on a daily basis. This dissertation utilizes qualitative interview research methodology to connect with some of the leaders of American higher education to understand how institutions define priorities, allocate scarce resources and develop strategic plans that move their institutions forward. Five institutions were selected as part of the sample based on their inclusion among the top 30 private universities in the annual U.S. News and World Report rankings. A semi-structured telephonic interview approach was employed with 22 senior administrators from Duke University, Emory University, Georgetown University, Stanford University and Yale University, including all five presidents. The subjects discussed the major challenges facing elite private universities in the United States, including access and affordability, influence of government on research and financial constraints. The dissertation provides context for the alignment between strategic plans and annual operating plans, as well as the alignment between institutional mission and resource allocation decisions. Despite the similarities shared by the five elite universities, there are also differences that emerged through the research with regard to institutional approach to strategic planning, investment in intercollegiate athletics and overall alignment in decentralized financial environments. This dissertation shares the perspectives of American higher education leaders regarding the myriad of challenges and opportunities facing this sector of academe. %D 2016 %K strategic planning higher education resource allocation intercollegiate athletics sports qualitative interviews access affordability private universities presidents research decentralization mission statement %I University of Pittsburgh %L pittir28651 %A Richard Regelski %T THE EFFECTIVENESS OF PEER-ASSISTED LEARNING STRATEGIES ON READING COMPREHENSION FOR STUDENTS WITH AUTISM SPECTRUM DISORDER %X Individuals with autism spectrum disorder (ASD) demonstrate strengths in word recognition and decoding, but comprehension skills are not well developed. If reading problems are not quickly addressed, they will continue to affect academic progress. Unless an effective reading intervention is established early, the outcome for struggling readers is not positive. There is little research in the area of reading comprehension for students with ASD. However, one instructional approach that has benefited many beginning readers and has improved reading comprehension skills is Peer-Assisted Learning Strategies (PALS). The current study investigated the effects of PALS on reading fluency and reading comprehension for students with ASD. A single-subject multiple baseline design across participants was used for three students with ASD. Results from the current study demonstrated that students with ASD can improve reading comprehension and reading fluency when using PALS. More specifically, all three students increased their reading comprehension and two students increased their reading fluency. Directions for future research and implications follow a discussion of findings. %D 2016 %K Peer-Assisted Learning Strategies PALS Reading Comprehension Strategies for Students with Autism PALS + Reading Comprehension PALS + Autism %I University of Pittsburgh %L pittir29102 %A ANITA SCHUCHARDT %T LEARNING BIOLOGY THROUGH CONNECTING MATHEMATICS TO SCIENTIFIC MECHANISMS: STUDENT OUTCOMES AND TEACHER SUPPORTS %X Integrating mathematics into science classrooms has been part of the conversation in science education for a long time. However, studies on student learning after incorporating mathematics in to the science classroom have shown mixed results. Understanding the mixed effects of including mathematics in science has been hindered by a historical focus on characteristics of integration tangential to student learning (e.g., shared elements, extent of integration). A new framework is presented emphasizing the epistemic role of mathematics in science. An epistemic role of mathematics missing from the current literature is identified: use of mathematics to represent scientific mechanisms, Mechanism Connected Mathematics (MCM). Building on prior theoretical work, it is proposed that having students develop mathematical equations that represent scientific mechanisms could elevate their conceptual understanding and quantitative problem solving. Following design and implementation of an MCM unit in inheritance, a large-scale quantitative analysis of pre and post implementation test results showed MCM students, compared to traditionally instructed students) had significantly greater gains in conceptual understanding of mathematically modeled scientific mechanisms, and their ability to solve complex quantitative problems. To gain insight into the mechanism behind the gain in quantitative problem solving, a small-scale qualitative study was conducted of two contrasting groups: 1) within-MCM instruction: competent versus struggling problem solvers, and 2) within-competent problem solvers: MCM instructed versus traditionally instructed. Competent MCM students tended to connect their mathematical inscriptions to the scientific phenomenon and to switch between mathematical and scientifically productive approaches during problem solving in potentially productive ways. The other two groups did not. To address concerns about teacher capacity presenting barriers to scalability of MCM approaches, the types and amount of teacher support needed to achieve these types of student learning gains were investigated. In the context of providing teachers with access to educative materials, students achieved learning gains in both areas in the absence of face-to-face teacher professional development. However, maximal student learning gains required the investment of face-to-face professional development. This finding can govern distribution of scarce resources, but does not preclude implementation of MCM instruction even where resource availability does not allow for face-to-face professional development. %D 2016 %K science education, problem solving, mathematics, student learning, professional development %I University of Pittsburgh %L pittir29104 %A Taylor Eddens %T HOST-PATHOGEN INTERACTIONS IN PNEUMOCYSTIS INFECTION %X Pneumocystis remains the most common opportunistic infection in patients with HIV/AIDS and can cause a life-threatening fulminant pneumonia. Pneumocystis pneumonia is re-emerging in the HIV-negative population, as immunosuppressive medications have greater use clinically. As the at-risk population increases, understanding the underlying host responses that can lead to protection against Pneumocystis becomes imperative. To that end, we characterized the early CD4+ T-cell dependent eosinophilic response to Pneumocystis murina. Importantly, we demonstrated that eosinophils have potent anti-Pneumocystis activity both in vitro and in vivo. However, eosinophils in the lung can also lead to pathology as seen in allergic airway inflammation in asthma. We therefore compared Pneumocystis to the common airway allergen, house dust mite, and demonstrated that the immune response to both pathogens was highly similar. Pneumocystis antigen exposure resulted in increased airway hyperresponsiveness and mucus production in a Th2-dependent and eosinophil-independent manner. From a translational standpoint, a subset of patients with severe asthma had increased anti-Pneumocystis IgG and IgE antibodies. Patients with high anti-Pneumocystis IgG levels had worsened cough and lung function as measured by spirometry, suggesting that Pneumocystis exposure may be correlated with worsened disease. As Pneumocystis infection induces such a potent adaptive immune response, we next examined local immunity to Pneumocystis. Inducible bronchus associated lymphoid tissue (iBALT) has been characterized in several models of lung infection and contributes to protection. Pneumocystis infection and exposure in a co-housing model resulted in the formation of iBALT structures in a CXCL13-dependent manner. Importantly, CXCL13 regulation appeared to be dependent on both Th2 and Th17 CD4+ T-cells in vivo and in pulmonary fibroblasts in vitro. The host response to Pneumocystis is limited in patients with global immunosuppression and the identification of novel drug and vaccine targets is lacking. Towards that end, we annotated the Pneumocystis genome and as proof-of-principle, demonstrated that the kinome (specifically VPS34) was druggable in vitro. Additionally, we utilized various ?omics techniques to identify Meu10 and GSC-1 as novel vaccine targets capable of providing partial protection against Pneumocystis. Together, these studies identified novel protective and pathologic immune responses to Pneumocystis and enabled a top-down approach of anti-Pneumocystis therapeutic development. %D 2016 %K Pneumocystis, vaccine, kinome, eosinophil, asthma, lymphoid tissue %I University of Pittsburgh %L pittir28236 %A Minlu Hu %T THE ROLE OF EPITHELIAL INTEGRITY AND METABOLIZING ENZYMES IN TOPICAL MICROBICIDE EFFICACY FOR THE PREVENTION OF HIV SEXUAL TRANSMISSION %X In order to further reduce the number of HIV-1 infections, efforts must be made to prevent new acquisition of HIV in healthy population. Although the antiretroviral-based topical (microbicides) and oral pre-exposure prophylaxis (PrEP) products have been evaluated in a number of clinical trials, the results from these studies have been inconsistent. The aim of my dissertation study is to examine whether the modulators of tissue integrity and metabolizing enzymes could affect antiretroviral drug exposure and efficacy in cervicovaginal tissues. First of all, we demonstrated that the several commonly used excipients which increased paracellular permeability of cervicovaginal tissue did not significantly reduce tenofovir (TFV) activity in HIV-1 prevention in an ex vivo explant tissue model. In addition, TEER, morphology, permeability, and MTT-based tissue viability do not necessarily change in parallel with each other and the use of a single measurement cannot accurately reflect the effect of excipients on cervicovaginal tissue integrity. Also, we found that the mRNA of several Phase I and II metabolizing enzyme isoforms, such as CYP1A1, CYP1B1 and UGT1A1, are highly expressed in the human female genital tract. In phosphorylating enzymes study, we found that the majority of TFV-related phosphorylating enzymes showed significantly decreased mRNA level in T cells as compared to their levels in cervicovaginal tissues. Furthermore, our results indicated that medroxyprogesterone acetate and progestone treatments changed the activity of phosphorylating enzymes toward different directions in cervicovaginal epithelial cell line (VK2) and a T cell line (PM1). Additionally, we found that medroxyprogesterone acetate, progestone, IL1? and IL8 treatment resulted in altered tenofovir diphosphate level in a vaginal epithelial cell line and a T cell line. Taken together, these studies provide valuable information on the excipients? effect on multiple aspects of cervicovaginal tissue integrity, as well as what biological factors may affect the effectiveness of TFV and its clinical potential. Such information will facilitate the efforts toward optimized vaginal PrEP products for HIV-1 prevention. %D 2016 %K Microbicides, HIV, excipient, tenofovir, Vaginal epithelium, phosphorylating enzymes %I University of Pittsburgh %L pittir28694 %A xiaolan zhang %T PEG-DERIVATIZED FTS-BASED MICELLES FOR COMBINATION CANCER THERAPY %X Polymeric micelles represent a promising drug carrier system that has gained considerable attention due to its simplicity, small sizes, and ability to solubilize water-insoluble drugs and accumulate specifically in the tumors. However, most of them do not possess any biological activity by themselves. One interesting approach in the design of a carrier is to incorporate components in the carrier system itself that exhibit favorable biological activity, either counteracting the side effects caused by the loaded anticancer drugs, or promoting synergistic effect with the incorporated drug. We first developed a dual function carrier that is based on PEG-derivatized S-trans, trans-farnesylthiosalicylic acid (FTS) (PEG5k-FTS2). FTS is a synthetic farnesylcysteine mimetic that acts as a potent and especially nontoxic Ras antagonist. In addition to retention of anti-Ras activity, PEG5k-FTS2 forms small-sized micelles that are capable of synergistic delivery of various hydrophobic agents. A further structure activity relationship (SAR) study was conducted in four PEG-FTS conjugates that vary in the molecular weight of PEG (PEG2K vs PEG5K) and the molar ratio of PEG/FTS (1/2 vs 1/4). We demonstrated that PEG5k-FTS4 formed the most stable mixed micelles with PTX among the four PEG-FTS conjugates. Next, we examined whether the performance of PEG5k-FTS2 can be further improved via incorporation of Fmoc, based on our recent discovery of Fmoc as a novel and potent drug-interactive motif. Our data showed that introduction of an Fmoc at the interfacial region of PEG5k-FTS2 led to a significant improvement in the drug loading capacity for a number of anticancer agents including paclitaxel (PTX), doxorubicin (DOX), curcumin, and etoposide. Finally, we established a reduction-sensitive delivery system by incorporation of an additional cleavable linkage (disulfide bond) into PEG5k-FTS2. We demonstrated that the incorporation of a disulfide linkage led to an enhanced release of FTS inside tumor cells, which was associated with an improved cytotoxicity against tumor cells. In summary, our data demonstrated that PEG-derivatized FTS can serve as dual functional carrier for the targeted delivery of therapeutic agents and contribute additional effects with the loaded anticancer drug. Our improved dual function carrier represents a simple and effective targeted drug delivery system for cancer. %D 2016 %K dual function; farnesyl thiosalicylic acid; nanomicelles; paclitaxel; targeted delivery %I University of Pittsburgh %L pittir28560 %A PEIPEI LU %T THE ROLE OF HEPATIC ARYL HYDROCARBON RECEPTOR IN METABOLIC HOMEOSTASIS AND HEPATIC CARCINOGENESIS %X The aryl hydrocarbon receptor (AHR), also known as the dioxin receptor, was originally characterized as a xenobiotic receptor that senses xenotoxicants. In the first part of my thesis research, I have uncovered an unexpected endobiotic and hepatic role of AHR in fatty liver and energy metabolism. Despite causing severe fatty liver, transgenic activation of AHR protected mice from diet-induced obesity and type 2 diabetes. The endocrine hormone fibroblast growth factor 21 (FGF21) was established as a novel transcriptional target of AHR and mediates the metabolic benefit of AHR. Moreover, the transactivation of FGF21 by AHR contributed to both hepatic steatosis and systemic insulin hypersensitivity, both of which were largely abolished upon FGF21 knockdown. Results from this study may help to establish AHR as a pivotal environmental modifier that integrates signals from chemical exposure in the regulation of lipid and energy metabolism. The second part of my thesis research is to investigate the function of AHR in promoting hepatic carcinogenesis and to study the mechanisms of its tumor-promoting effect. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or dioxin, is a potent liver cancer promoter through sustained activation of AHR in rodents, but its carcinogenic effect in human has been controversial. This inter-species difference is largely due to different ligand affinity and distinct gene transactivation selectivity and potency. Here I report the oncogenic potential of human AHR in promoting hepatic carcinogenesis. Constitutive activation of human AHR was as efficiently as mouse Ahr in promoting diethylnitrosamine (DEN)-initiated hepatic carcinogenesis in transgenic mice. The growth arrest and DNA damage-inducible gene 45 beta (Gadd45b), a signal molecule inducible to external stress and UV irradiation, is highly induced upon AHR activation and acts as a transcriptional target of AHR. In addition, as an intrinsic coactivator, Gadd45b facilitates the AHR transcription activity, which might play a role in potentiating the tumor promoting effect of AHR. Taken together, my work has revealed critical functions of AHR in energy homeostasis and hepatic carcinogenesis. It is hoped that understandings of the functions of AHR may help develop AHR-based novel therapeutics in the treatment of metabolic diseases and hepatic carcinogenesis. %D 2016 %K Xenobiotic receptor, transcriptional regulation, transcription factor, diabetes, obesity, fatty liver, hepatic carcinogenesis %I University of Pittsburgh %L pittir28685 %A Chenxiao Tang %T SCREENING 20-HETE INHIBITORS IN MICROSOMAL INCUBATES USING UPLC-MS/MS %X 20-hydroxyeicosatetraenoic acid (20-HETE) is a metabolite of arachidonic acid (AA) formed by cytochrome P450 (CYP) 4A11 and CYP4F2 in humans, with potent microvascular constriction activity. Inhibition of 20-HETE formation is neuroprotective in subarachnoid hemorrhage, cardiac arrest and thromboembolic stroke preclinical models. These findings suggest that inhibition of 20-HETE formation is a potential therapeutic strategy for neuroprotection after brain injury. At this point, a clinically relevant 20-HETE inhibitor is not available to be evaluated as a therapeutic intervention. Our goal is to identify a selective, metabolically stable, and potent 20-HETE inhibitor. Test compounds were obtained either via virtual screening against a CYP4F2 homology model or from scaffold hopping from structures of known inhibitors. Four different types of microsomes including human liver microsome (HLM), recombinant CYP4F2 (rCYP4F2), rat liver microsome (RLM) and rat kidney microsome (RKM) were used. AA was incubated in microsomes with/without compound for 20 min. 20-HETE formation rate was quantified using a validated UPLC-MS/MS assay and normalized by vehicle control group. Other eicosanoids including 15-, 12-HETEs, epoxyeicosatrienoic acids (EETs),and dihydroxyeicosatrienoic acids (DiHETs) were monitored simultaneously. Selected compounds were tested in HLM for metabolic stability over 60 minutes. Remaining amount of compound was quantified using UPLC-MS/MS and normalized to corresponding 0-min values. Among 26 compounds, compounds 10 and 26 both inhibited 20-HETE formation in a dosedependent manner. At 2500nM, compound 10 reduced 20-HETE formation to 19.9?1.8%, 24.0?5.5% in rCYP4F2 and HLM compared with control; compound 26 decreased 20-HETE formation to 32.4?6.5%, 34.8?5.1% in rCYP4F2 and HLM, respectively. After structure modification, compound 19 and its hydrochloride salt compound 18 were the most potent and dose-dependently inhibited 20-HETE formation. At 2500nM, compound 19 decreased 20-HETE formation to 4.4?0.4%, 8.6?1.3% in rCYP4F2 and HLM, respectively without inhibitory effects on 15-, 12-HETE, EETs or DiHETS formation. Compounds 10 and 19 were more stable with 91.4?11.0% and 100.4?1.7% remaining compound at 30min in HLM compared to 35.1?5.7% of 3-(4-n-butoxyphenyl)pyrazole. These results suggested that compounds 10, 19 and 26 are potent 20-HETE formation inhibitors, compounds 10 and 19 have improved microsomal stability, and these three compounds can serve as lead compounds for further structure modifications that may lead to novel 20-HETE formation inhibitors. %D 2016 %K 20-hydroxyeicosatetraenoic acid; epoxyeicosatrienoic acid; UPLC-MS/MS; microsome incubation; inhibitor %I University of Pittsburgh %L pittir28767 %A Yuan Wei %T CO-DELIVERY OF PACLITAXEL AND IMATINIB BY PEG DERIVATIZED NLG CARRIER AS ENHANCED IMMUNOCHEMOTHERAPY %X Indoleamine 2,3-dioxygenase (IDO), which catalyzes the initial and rate-limiting step in the tryptophan catabolism along the kynurenine pathway, is an immunosuppressive enzyme that can lead to T cell anergy, apoptosis and potential induction of regulatory T cells (Treg cells). This discovery has led to the development of several IDO inhibitors including NLG919, an immunotherapy drug that targets IDO with high efficacy, into the clinical trial for treating solid tumor. Our goal is to develop PEG derivatized NLG as a functional carrier for specifically delivering anticancer agents to the tumor site to stimulate immune response and eliminate systemic toxicity. Previously, our group has developed a PEG2K-Fmoc-NLG micellar system that can effectively deliver anticancer drug Paclitaxel (PTX) and synergize with chemotherapy to reduce tumor growth. One major limitation with this approach is the feedback mechanism following NLG-mediated inhibition of IDO, which subsequently leads to the up-regulation of IDO expression. In addition, the mRNA expression of IDO can be further enhanced by PTX treatment. For long-term treatment, increased dose of this formulation would be necessary to maintain the same effect for treating cancer. The focus of our study is to identify a compound that can effectively inhibit the expression of IDO at transcriptional level and develop an improved PEG-NLG-based carrier for codelivery of the compound and a chemotherapeutic agent such as PTX. %D 2016 %K co-delivery, ido, immunotherapy, immunochemotherapy %I University of Pittsburgh %L pittir29062 %A Qian Zhao %T Epidemiology of general, regional and ectopic skeletal muscle fat in aging African ancestry men %X OBJECTIVE: We aim to study on the epidemiology of general, regional and ectopic skeletal muscle fat in aging African ancestry men. To be specific, we described the natural changes and identified correlates to the longitudinal changes of these adiposity measures, and evaluated their association with hypertension and mortality. METHOD: We use Tobago Health Study to achieve the objectives. The demographic characteristics, lifestyle factors, medical history and medication use were self-reported and collected with interviewer-administered questionnaire. Total body fat percentage, trunk fat percentage and leg fat percentage were assessed with Dual-Energy X-ray Absorptiometry (DXA). Ectopic skeletal muscle fat (inter- and intra- muscular fat) was examined by Quantitative Computed Tomography (QCT). The hypertension status was defined as diastolic blood pressure over 90 mmHg or systolic blood pressure over 140 mmHg or having antihypertensive treatment. The date of death was obtained from death certificate and/or proxy. Linear regression was used to identify the potential correlates for the changes in these adiposity measures. Logistic regression was performed to evaluate the association with newly developed hypertension. Cox hazard proportional model was used to assess the association with mortality risks. RESULTS: Baseline hypertension was associated with greater decline in the muscle attenuation and leg fat. Furthermore, intramuscular fat (reflecting by decreased muscle attenuation) was associated with newly developed hypertension after adjustment for the baseline and the change in BMI (OR (95% CI) per SD: 1.32 (1.06,1.64)) or WC measurements (OR (95% CI) per SD: 1.35 (1.08, 1.68)). Both intermuscular fat (HR (95% CI) per SD: 1.29 (1.06-1.57)) and intramuscular fat (HR (95% CI) per SD: 1.37 (1.08-1.75)) were significant associated with elevated morality risk in fully adjusted models. None of the other adiposity measures were associated with newly developed hypertension or elevated morality risks. CONCLUSION: These novel findings confirmed that ectopic fat, though with a small amount, may be more crucial in driving cardiometabolic diseases than general body fat per se, highlighted the importance of maintaining muscle attenuation in healthy aging, and was with great public health significance. Further studies are needed to establish if these associations are independent of inflammation, visceral or other ectopic fat depots, to identify possible biological mechanisms underlying theses relationship, and to replicate our findings in other populations. %D 2016 %K "African ancestry men", "general body fat", "regional body fat", "ectopic skeletal muscle fat" %I University of Pittsburgh %L pittir28691 %A Nicole Danielle Osier %T Characterization of the melatonergic system after brain injury %X Traumatic brain injury (TBI) affects individuals of all ages, races, and geographies and is often associated with expensive clinical management. Melatonin (MEL) has been trialed as a TBI therapeutic with mixed results, due in part to a lack of understanding of the mechanism. This study characterizes endogenous changes in melatonergic receptors (MT1 and MT2) after experimental TBI induced using pneumatic CCI (2.8 mm depth) in young adult Sprague Dawley rats. Half the rats were exposed to sham surgery to control for the effects of anesthesia and craniectomy. In total, 25 rats were enrolled in the study, with 6-7 rats per group. Test animals were sacrificed at 2 post-surgery time points, either 6 hours (hr) or 24 hr post-surgery. Following sacrifice, the test animal?s brain was harvested, dissected, and flash frozen until analysis. Whole cell lysates were prepared, aliquoted, and used for western blot analysis, probing for cytochrome C (to validate injury severity), MT1, MT2, and beta actin (to control for protein loading). ImageJ and Image Lab software were used to quantify protein data; SPSS software was used to run t-tests to compare group means on a single variable and correlation testing was used to explore the relationship between outcomes of interest. Melatonin receptors were down-regulated in a brain region- and time point- dependent manner. MT1 was downregulated in the frontal cortex at 24 hr and in the hippocampus at both 6 hr and 24 hr post-TBI. Similarly, MT2 was downregulated in the frontal cortex at 24 hr and in the hippocampus at both 6 and 24 hr post-TBI. This is the first study to report downregulation of MT1 and MT2 after neurotrauma; receptor downregulation may affect the efficacy of MEL therapy. Additional research to characterize these changes after TBI are necessary including efforts to establish the time course and regional patterns, replication in more diverse samples, as well as inclusion of additional cellular, histological, and behavioral endpoints. TBI in rats modeled using CCI results in acute downregulation of MEL-specific receptors (subtypes MT1 and MT2); replication of these findings is necessary as are evaluations of the implications of lower receptor levels. %D 2016 %K Traumatic brain injury; brain trauma; controlled cortical impact; rat; pre-clinical; melatonin %I University of Pittsburgh %L pittir28630 %A Megan Crilly %T Antibiotic development and the pharmaceutical industry: an examination of the 2012 Generating Antibiotic Incentives Now Act, the counterintuitive market for antibiotics research and development and the need for profit maximizing policy solutions %X There is growing concern within the public health community that the rapid decline of new antibiotics over the last two decades, coupled with the adaptive nature of bacterial infections, could lead to widespread disease without effective treatments. It is difficult for pharmaceutical companies to recoup the billions of dollars invested in the research and development (R&D) of new antibiotics because bacterial infections are treated with older antibiotics first and for short dosage periods to stymie antibiotic resistance. Without a means to recoup their R&D costs and enduring shareholder demands for profit-maximizing endeavors, many companies shut down their antibiotics labs in favor of more profitable medications, like those for chronic illnesses that require continual administration for extended periods. In an effort to stimulate more antibiotic R&D, the United States passed the Generating Antibiotic Incentives Now (GAIN) Act in 2012 to motivate companies to bring more antibiotic treatments to market. This paper aims to explain the supply and demand problems of the current market for antibiotics and analyze GAIN?s impact on R&D investment. After examining the amount of antibiotics in clinical trials before and after the GAIN Act, there was insufficient statistical evidence to support the hypothesis that GAIN altered the behavior of companies. This Act does not offer enough incentives to counteract the unique market anomaly antibiotics present. Without a continual robust antibiotic pipeline, bacterial infections, including new strains of antibiotic-resistant infections, will be untreatable. This study has public health significance because highlights the urgent nature of providing additional incentives to companies that invest in antibiotics R&D, without which, there will be few options to treat bacterial infections in the future. %D 2016 %K Antibiotics, Antibiotic Resistance, Pharmaceutical Industry, Antibiotics Industry, 2012 Generating Antibiotics Now Act %I University of Pittsburgh %L pittir27786 %A Michael R Zeleny %T Assessing Neural Network Prediction in Kidney Disease Data %X Neural networks can be used as a potential way to predict continuous and binary outcomes. With their ability to model complex non-linear relationships between variables and outcomes, they may be better at prognosis than more traditional regression methods such as logistic regression. In this thesis, the prognostic abilities of neural networks will be assessed using data from the Consortium for Radiological Imaging Studies of Polycystic Kidney Disease (CRISP) using clinically signi?cant variables such as BMI, Blood Urea Nitrogen (BUN), Height Adjusted Total Kidney Volume (htTKV), baseline estimated glomeruler ?ltration rate (eGFR), and type of PKD. Both a logisitic regression and variations of neural networks were modeled. The neural networks had hidden units from 2 to 10, and weight decays from 0.01 to 0.05. Each of these models was assessed by looking at Receiver Operator Characteristic (ROC) curves, speci?cally the area under the curve (AUC). The complexity of these models was also looked at by calculating the degrees of freedom for each model. More complex models could lead to an over?tting of the data, and were therefore examined in this study. The study showed that neural networks have the capability to predict the outcome of stage 3 kidney disease better than a more traditional logistic regression, however, the models become increasingly complex as the predictive ability increases. These ?ndings could have a great impact on public health in the future. They could greatly impact the methods that are used for prognosis. The use of neural networks might lead to better prognosis and earlier treatment for kidney disease based on an individuals baseline measurements of the aforementioned variables, or any other new biomarkers that are discovered in the future. %D 2016 %K Neural Networks, Chronic Kidney Disease, Prediction Modeling %I University of Pittsburgh %L pittir27531 %A Linxi Liu %T Assessment of intermediate (process) outcomes in the BARI 2D clinical trial %X BARI 2D is a 2-by-2 factorial clinical trial identifying optimal therapies for patients with documented stable coronary artery disease and Type 2 Diabetes. Previous results of the BARI 2D study indicated that there was a non-significant association between the therapies and 5-year survival outcomes. Our study hypothesizes that several intermediate variables may exist whose trajectories of improving or worsening in response to treatments act against each other leading to the previous non-significant associations. Before randomization, the participants were stratified to two types of revascularization - PCI or CABG. Then each participant was randomized to receive one cardiac therapy (prompt revascularization plus intensive medicine or intensive medicine alone), and also one glycemic therapy (insulin-sensitization or insulin-provision). Five intermediate outcomes BMI, SBP, HDL, LDL and Hba1c were studied. Linear regression was conducted to assess the difference of each intermediate outcome between therapies at Year 1 and at Year 3. Also conducted was a comparison of the trajectories over time by therapies using longitudinal repeated measures mixed models. In 2368 patients (mean age 62.4 years), the improvement of the intermediate outcomes was generally notable over the first year, and then slowly diminished over time. At both Year 1 and 3, insulin-provision resulted in higher BMI and Hba1c, and lower HDL than insulin-sensitization, irrespective of the assigned cardiac therapy and revascularization stratum. Longitudinally, insulin-provision resulted in higher Hba1c, irrespective of the assigned cardiac therapy and revascularization stratum; and an interaction effect of the cardiac and glycemic therapies on BMI was found in CABG stratum. These results suggested that insulin-sensitization therapy is superior to insulin-provision therapy generally. In CABG stratum, the effect of cardiac therapy on BMI depends on the assignment of glycemic therapy. The public health significance of this study is that, though the cancelling-out hypotheses for these five intermediate variables may be overly optimistic, it involves a potentially illuminating perspective to explain the mechanisms through which the BARI 2D treatment therapies affect multiple intermediate outcomes. This in turn could also help inform and enhance the targeted adjuvant therapies, thus resulting in improved survival outcomes by better focusing on controlling the harmful intermediate variables. %D 2016 %K Coronary Artery Disease; Type 2 Diabetes; Intermediate; Risk Factors; BMI; HDL; LDL; SBP; Hba1c %I University of Pittsburgh %L pittir28006 %A Kathryn Bethea %T CAPITAL GATEKEEPING OR COMMUNITY ADVOCACY: A QUALITATIVE STUDY OF DIVERSITY COLLEGE ADMISSION PROFESSIONALS? PERSEPCTIVES OF COLLEGE ACCESS IN A LOCAL URBAN CONTEXT %X Race/ethnicity plays an important role in college access for urban students of color. This study explores how race/ethnicity influences college admission policies and practices, which, in turn, impacts college access. The main research question is how institutions of higher education, specifically diversity college admission professionals (DCAPs), play a crucial role in college access for local underrepresented students of color in a northeast local city school district. Using a descriptive study design, I utilize cultural capital theory and critical race theory in a combined theoretical framework to analyze the DCAPs? narratives. The present study is a qualitative look at DCAPs? perspectives of the interplay between sociocultural context, cultural capital, and institutional race-conscious admissions policies that impacts college access. Findings show that DCAPs are an authority on college access and have a unique perspective on local diversity recruitment and college access outreach. The DCAPs? cultural habitus of ?critical gatekeeping advocates? portrays their narrative as bicultural middle managers in college admissions. Although DCAPs are concerned about admitting students of color, they are constrained by socio-racial stratification in the P-16 educational system. Furthermore, college admission perpetuates the cultural capital and racialization in higher education. Through sharing the DCAPs? recommendations for improving college access, I discuss ways to develop policy, programming, and praxis to promote college access and institutional diversity initiatives. The implications of the current research study will further inform how college admission impacts the college access gap. %D 2016 %K college access, diversity recruitment, CRT, cultural capital, qualitative narrative analysis, college admissions %I University of Pittsburgh %L pittir27998 %A Jennifer Bowling %T Challenging the gold standard: alternatives to the collison for aerosol generation in research %X Animal studies to demonstrate efficacy of medical countermeasures against respiratory disease or biodefense threats require exposure of animals to aerosolized viruses and bacteria. Prior studies have shown that the choice of culture media and relative humidity in the aerosol chamber can impact the dose of infectious agent delivered to animals. Most infectious aerosol studies have involved the use of Collison jet nebulizers which create a small, relatively monodisperse aerosol that targets the deep lung. Collison nebulizers require a relatively large volume of infectious agent and the jets that create the aerosol may damage the agent being aerosolized. Damage resulting from the nebulizer can impact agent infectivity and virulence as well as study reproducibility. We compared the Blaustein Atomizing Module (BLAM) and the Aeroneb, a vibrating-mesh nebulizer, to the existing ?gold standard? Collison nebulizer for generation of small particle aerosols containing either a bacterium, F. tularensis, or a virus, influenza or Rift Valley Fever Virus (RVFV) in different exposure chambers. Aerosol performance was assessed by comparing the spray factor (the ratio between the aerosol concentration of an agent and the concentration of the agent in the nebulizer), the reduction in pathogen viability, and the aerosol efficiency (the ratio of the actual aerosol concentration to the theoretical aerosol concentration. In the NOT, the Collison had superior aerosol performance compared to the BLAM and the Aeroneb, while the Aeroneb had superior aerosol performance comparted to the Collison in the whole-body and head-only chambers. Regression analysis revealed increased humidity was associated with improved aerosol performance of F. tularensis, but no environmental factors were associated with improved aerosol performance of influenza or RVFV. This data demonstrates that there is no ?one size fits all? choice for aerosol generators, and that further characterization of aerosol generators and factors that affect aerosol performance are needed to improve selection of aerosol equipment. The public health significance of this research is to contribute to the characterization of available aerosol generators to optimize aerosol experiments for a more robust experimental design for developing animal models of respiratory infections and developing therapeutics and vaccines against potential biological weapons. %D 2016 %K Aerosol generator, respiratory transmission, influenza, Francisella, Rift Valley Fever Virus %I University of Pittsburgh %L pittir27455 %A Jocelyn Shoemake %T Characteristics of diabetes prevention translation programs targeted towards African American populations through the lens of the CDC's recognition program %X Reducing type 2 diabetes (T2D) is currently of public health significance since diabetes is considered to be a major national epidemic in the United States. While diabetes affects all racial/ethnic groups, African Americans are disproportionately diagnosed with T2D when compared to Non-Hispanic whites. With such pronounced disparities, it is crucial that effective interventions are critically developed and examined for their impact on populations considered to be at high risk for T2D. The CDC?s National Diabetes Prevention Program (NDPP) aims to reduce diabetes incidence rates by working with public and private partners to translate the effective and evidence-based lifestyle intervention for individuals with prediabetes into community settings. In order to ensure the standardization and fidelity of translated programs, the CDC created the Diabetes Prevention Recognition Program (DPRP). The DPRP highlights standard guidelines that are considered key components of the DPP curriculum and offers organizations/programs implementing the intervention an opportunity to be nationally recognized. Many individuals aiming to translate the DPP for their targeted populations use current research as a guide for program development and implementation. However, the DPRP?s standard guidelines have not been assessed systematically for translational research components and outcomes of published studies. This thesis, therefore, aimed to understand the characteristics of translational research through the lens of the DPRP. Two previously published systematic reviews were analyzed for this article. The first systematic review explored DPP translational research among the general population, whereas the second systematic review explored translations of the DPP specifically among African American populations. Overall, the results indicate that for both systematic reviews, only 15.4% of the articles met all of the assessed DPRP variables. However, studies among the general population were more likely to meet curriculum components, short-term weight loss goals and program eligibility requirements when compared to studies among African Americans. In conclusion, this thesis highlights the importance of assessing and reporting the DPRP standards in translational DPP research, particularly studies among racial and ethnic minorities. Assessing standard guidelines in research may increase the number of nationally recognized DPP programs that are translated and implemented into high-risk communities, hence, making a broader public health impact. %D 2016 %K Diabetes Prevention Program, Type 2 Diabetes, Translations, African American, Black, CDC Diabetes Prevention Recognition Program %I University of Pittsburgh %L pittir27543 %A Lauren Chubb %T Characterization of silica content in gold mine dust with respect to particle size %X Globally, silicosis is responsible for thousands of deaths each year and is a major public health concern in industries like mining. Silicosis is caused by exposure to respirable crystalline silica, and while incidence of silicosis has declined in recent decades, its continued occurrence in young workers indicates that high crystalline silica exposures in the contemporary workforce persist despite monitoring efforts and regulatory enforcement. Crystalline silica exposure is monitored in the mining industry via collection of respirable dust samples, from which both dust and crystalline silica concentrations are determined. Accurate quantification of crystalline silica is vital to assessing workers? exposure, and to limiting exposure through selection of appropriate engineering controls and personal protective equipment. To quantify crystalline silica in a sample, one of two analytic methods is used: X-ray diffraction and infrared spectroscopy. Previously, confounding effects of mineral composition and size distribution of dust were assumed to have only minor impact on the accuracy of both methods; however, as mining technologies evolve, so do the characteristics of the dust generated in mines, and such effects may no longer be negligible. Evaluating the characteristics of mine dust with respect to particle size and crystalline silica content is imperative to understanding how crystalline silica analysis may be affected by these characteristics. To date, few studies have investigated particle size-related crystalline silica content in occupational dusts, and while some efforts have been made to characterize coal mine dusts, there has been no such effort to characterize metal/non-metal mine dusts. This study undertakes detailed characterization of dusts from three gold mine operations, via analysis of size distribution using particle sizers and a cascade impactor; crystalline silica content by infrared and X-ray diffraction methods; and single-particle composition via scanning electron microscopy. Results indicate that the size distribution of crystalline silica within a particular dust is not equivalent to the dust?s size distribution; the abundance of crystalline silica in a dust varies with particle size; the two methods of quantifying crystalline silica yield variable results depending on particle size; and, like crystalline silica, particle types of different elemental composition vary in abundance with respect to particle size. %D 2016 %K occupational exposure, respirable crystalline-silica, particle size %I University of Pittsburgh %L pittir26877 %A Dushani Palliyaguru %T Characterizing Withaferin A as a novel NRF2 inducer: implications for liver disease prevention %X Intercepting the rising rates of non-communicable diseases is currently one of the most exigent public health challenges faced by all nations around the world. Prevention of these diseases using molecules that have dietary origin may be most attractive because of their safety, cost-effectiveness and feasibility of oral administration. However, the mechanism of action of such plant-based agents remains largely unknown. In recent years, the stress responsive transcription factor Nrf2, has been validated as a target for disease chemoprevention with several small molecules. Withania somnifera (WS) is a plant that has been used in Ayurveda (an ancient form of medicine in South Asia) for millennia. In the recent past, withanolides isolated from WS, such as Withaferin A (WA) have been demonstrated to be preventive and therapeutic against multiple diseases in experimental models. While scientific research performed on WS and WA has exploded in the past decade, much regarding the mode of action and molecular targets involved remain unknown. The goal of this dissertation was to determine if WA is an inducer of Nrf2 signaling and to explore whether the cytoprotective response elicited by WA resulted in prevention of liver toxicity. Here, WA has been characterized as a potent inducer of Nrf2 signaling that profoundly protects mice against acetaminophen hepatotoxicity but not against non-alcoholic fatty liver disease caused by methionine-choline deficient diet. Further, it was shown that WA pharmacologically induces Nrf2 signaling in a Keap1-independent, PI3K-dependent manner. Public health significance: the identification of an agent isolated from a medicinal plant abundantly used in traditional medicine, as a novel Nrf2 inducer provides an opportunity to expand the current repertoire of Nrf2 inducers so that culturally-appropriate chemoprevention programs can be designed to fight the global burden of non-communicable disease. %D 2016 %K Withaferin A, Nrf2, liver toxicity, Disease prevention %I University of Pittsburgh %L pittir27459 %A Crystal Archibald %T Comparing the immunogenicity of influenza vaccines LAIV and IIV in pediatric patients during the 2014-2015 season %X Influenza virus causes a contagious respiratory illness in humans that poses a major public health threat, especially to vulnerable populations such as children and adolescents, who have less mature immune systems. Influenza infections are responsible for over 200,000 hospitalizations and over 3,600 deaths a year. The influenza vaccine is the best form of prevention from influenza illness due to the vaccines ability to elicit an antibody response without causing illness. Currently, there are two types of influenza vaccines available to children and adolescents, the inactivated influenza vaccine (IIV) and the live attenuated influenza vaccine (LAIV). The present study was designed to compare the immunogenicity of the two vaccines in pediatric participant?s ages 3 to 17 years. We hypothesized that the LAIV vaccine would produce an increased breath and enhanced antibody response to influenza vaccination compared to the IIV vaccine. Results from this study suggest that IIV was superior compared to LAIV at eliciting immune responses following vaccination. However, potential limitations include the fact that current assays measure immune responses in peripheral blood only and may not reflect mucosal immunity. Further, due to issues with the H1N1 virus strain in the LAIV vaccine, these results need to be confirmed in a season where LAIV vaccine is immunogenic (2015-16). %D 2016 %K Influenza Vaccine %I University of Pittsburgh %L pittir27887 %A Tianyuan Xu %T Comparison of utilization and complications of peripherally inserted central catheters versus peripheral midline catheters in a large academic medical center %X Background: Peripherally inserted central catheters (PICCs) are a commonly used central intravenous (IV) access device, which sometimes cause severe complications. Midline catheters (MC) are peripheral IV access devices that may reduce the need for central lines, and hence central line associated blood stream infection (CLABSI). The objective of this study is to compare the utilization and safety of PICC and MC. Methods: This was a retrospective quality improvement study. Data were collected using electronic medical records and IV team insertion data. SAS v9.3 was used for analysis. Means and standard deviations were calculated to describe central tendencies and variation. Fisher?s Exact Tests were used to describe strength of associations between variables. Results: From January to May 2015, a total of 206 PICCs and 200 MCs were inserted in 367 individual patients. There was a total of 12 individual PICCs and 39 individual MCs involved with complications. MCs are associated with higher rate of non-serious complications as compared to PICCs. However, the severe complications were not significantly different between PICCs and MCs (4.9% vs. 9.0%, P=0.1182). Among the 206 PICCs, four readmissions were related to PICC issues, while among the 200 MCs, no readmission was caused by MC issues. Conclusions: The reduction of CLABSIs could be a reasonable trade off for the increased non-severe complications associated with MCs. As technology of these devices is evolving, longer-term data will be essential to assure safety of MCs. Additional prospective studies could more objectively assess the safety and efficacy of these two devices. Public Health Importance: A CLABSI is one of the most costly health care-associated infections (HAIs), and can cause prolonged hospital stays, increased costs and risk of mortality. %D 2016 %K CLABSI, PICC, midline catheter (MC), and safety %I University of Pittsburgh %L pittir27484 %A Nandita Mukhopadhyay %T Computational methods for calculating meiotic recombination from nuclear pedigrees %X Meiotic recombination is increasingly an important area for research in genetics. Recombination is critical for the proper segregation of chromosomes, and errors in recombination may result in chromosomal abnormalities and non-disjunction. Both the total number and the pattern of recombination events are known to vary genome-wide and from person to person. Using genome-wide genotype data to detect locations of recombination in individuals is the first necessary tool to study recombination. Earlier methods, e.g. CRI-MAP, used linkage-style modeling on three-generation families and sparse microsatellite markers to detect recombination events. More recently, methods using ?streaks? of SNPs showing IBD status on dense GWAS SNP data have been used to score recombination locations in sibships. Here, I have developed a new SNP streak method to score recombination locations in pedigree types not previously handled, such as half-sibling pedigrees, and pedigrees with one or more ungenotyped individuals. We implemented our new method as a Python software package, MBFam. This package analyzes family-based genome-wide association datasets, accepting input data as PLINK binary files, a widely used input format for genetic data. The computation steps involve extraction of recombination probands, detection of recombination events, computation of recombination breakpoint locations and the offspring inheriting each recombination event, while accounting for Mendelian inheritance inconsistency errors and proximate double recombinations. MBFam has been extensively tested on the Mac OSX and Linux platforms. For demonstration purposes, this new method was applied to two family-based GWAS datasets. Recombination intervals scored were used to create sex-specific average recombination counts (ARC) using all new pedigree structures and only the full-sibships. GWASs were conducted for male and female probands for both sets of ARCs. In one of the datasets, the added pedigree structures increased the female proband sample. This new method has the potential to significantly improve sample sizes for recombination studies, eventually leading to a better understanding of the biology of recombination and fertility, and benefitting the design of medical and public health interventions for improving maternal and child health. %D 2016 %K Recombination Pedigree Genomewide recombination rate Recombination phenotype Genomewide association study SNP association panel %I University of Pittsburgh %L pittir27997 %A Alexandra Nowalk %T Depression and somatization in Bhutanese-Nepali refugees %X The number of Bhutanese-Nepali refugees entering Allegheny County has exceeded 4,500 over the last several years. Local physicians who work with this population have reported patients exhibiting symptoms of various mental disorders. This phenomenon is of grave concern, as various studies have found a suicide rate among Bhutanese-Nepali refugees that is significantly higher than the suicide rates for the general US population and other refugee groups. This research will determine if Bhutanese-Nepali cultural conceptualizations of mental health correlate to mental disorders classified in the Diagnostic Statistical Manual of Mental Disorders (DSM-V) through a series of individual interviews and a single focus group. By determining and improving the correlations between Bhutanese-Nepali culturally specific disease and western mental health diagnoses physicians will be able to provide informed, culturally-appropriate healthcare for refugees. As a result, public health practitioners will be able to better develop interventions that effectively address the mental health needs of Bhutanese-Nepali refugees and the quality of mental healthcare refugees receive will improve. %D 2016 %K Depression; Somatization; Refugees %I University of Pittsburgh %L pittir27549 %A Luis Duran %T Disgust, conservatism and influenza prevention: An embodied cognition approach to health attitudes and intentions %X Background: Recent studies demonstrated that a disgust reaction, which evolved as an instinctive response to protect one?s body from potential contaminants, affects judgments about morality and sexuality through embodied linkages between the concepts of cleanliness, physical purity, and moral purity. Therefore, disgust sensitivity and sexual and social conservatism ? favoring traditional social norms in the face of external forces for change ? might affect attitudes towards protective health behaviors and political support for health protection efforts. However, no studies have looked at these linkages in a public health context like infectious disease prevention. Statement of public health relevance: Intentionally triggering a disgust reaction might prove an effective communication strategy for health behavior change interventions. Future research might focus on testing the fit between different disgust triggers and specific public health issues. Methods: Forty-three literate, English-speaking adults were randomized (1:1) to cleanliness prime ? exposure to hand sanitizer ? or control and shown publicly available influenza statistics illustrated with graphs and figures. The hypotheses were: (1) disgust sensitivity and sexual and social conservatism are positively associated with disgust, perceptions of influenza risk/severity/costs and likelihood of taking preventive measures against influenza, but negatively associated with trust of influenza-related information and likelihood of supporting taxes for influenza prevention; (2) disgust is similarly associated with the other four variables; and (3) hand sanitizer exposure is similarly associated with disgust and the other four variables. Results: Statistically significant results at ? = 0.05 were observed for the first two of the three study hypotheses with the pilot sample size (N = 43). Post hoc analyses showed significant results for: (1) correlations between indexes for disgust sensitivity with disgust, perceptions of influenza risk/severity/costs and likelihood of taking preventive action against influenza; and (2) correlations between indexes for sexual and social conservatism with disgust and likelihood of supporting taxes for influenza prevention. Conclusions: Disgust sensitivity and sexual and social conservatism were both correlated with disgust, while disgust sensitivity was correlated with perceptions of influenza risk/severity/costs and likelihood of taking preventive action against influenza, and sexual and social conservatism was correlated with likelihood of supporting influenza prevention taxes. However, exposure to hand sanitizer did not produce the hypothesized responses. %D 2016 %K embodied cognition, influenza prevention, health communication, disgust sensitivity, moral contagion %I University of Pittsburgh %L pittir27193 %A Robin Pokrzywinski %T Disparities in body mass index of women by sexual orientation %X Background: Obesity is a leading health indicator with larger body size associated with increased all-cause mortality. Sexual minority women (SMW) are reported to have higher body mass index (BMI) than heterosexual women. Aims: The three aims of our research were to: 1) identify if, and what, differences exist in dietary intake of women by sexual orientation (SO); 2) investigate dietary consumption as a potential mediator between SO and BMI; and 3) explore current depression as a mediator with the sample stratified by lifetime history of depression. Methods: This secondary analysis utilized Epidemiologic STudy of HEalth Risk in Women (ESTHER) Project data. Group comparisons were made between the SO groups for dietary intake from three-day food diary data. With SO as the predictor and BMI as the outcome, three models were tested: 1) total caloric intake as a mediator; 2) macronutrients (mean daily grams of: fat, carbohydrates, protein, and alcohol) as parallel mediators; and 3) current depression as a mediator with the ESTHER sample stratified by lifetime history of depression. Results: SMW had significantly higher BMI than heterosexual women. Even after adjusting for education level and parity, SMW had higher daily consumption than heterosexual women of: caloric intake; total fat; total monounsaturated fatty acid; and total polyunsaturated fatty acid. Alcohol intake was significantly higher for SMW than heterosexual women but not after adjusting for education and parity. Total caloric intake and fat intake partially mediate the association between SO and BMI even when covariates are held constant (age, education, smoking status, physical activity). SMW had significantly higher rates of lifetime history of depression than heterosexual women. We did not find evidence that current depression mediates the relationship between the SO of women and BMI. We found that women with no lifetime history of depression did not have a significant association between the sexual orientation of women and BMI. Conclusion: Our findings are of public health significance to this minority population. Research has traditionally concluded that SMW are disproportionately more overweight and obese than heterosexual women. We explored the influence of dietary intake and depression to help explain BMI differences. %D 2016 %K sexual minority women, body mass index, dietary intake, depression %I University of Pittsburgh %L pittir27524 %A Taylor Ball %T Effect of Influenza vaccination on outcome of hospitalized adults: case control study %X Background: Influenza is a respiratory illness caused by three different viruses: type A, B, or C. Influenza has a large impact on morbidity and mortality globally with an estimated attack rate at 5-10% in adults and 20-30% in children. The Influenza vaccine is the most effective way to prevent Influenza. The purpose of this epidemiologic study is to determine the efficacy of the Influenza vaccines administered between 2013 and 2015, and to address public misconceptions concerning the safety of the vaccine. Methods: This case control study of adult patients took place at University of Pittsburgh Medical Center Mercy Hospital. The study included 306 adult patients with respiratory illnesses who were admitted to the hospital during 2013-2015 Influenza seasons. Of these admitted patients, 206 tested positive for Influenza while the other 100 patients tested negative and therefore served as case controls. Data on each patient were collected via medical records, which included vaccination status, demographics such as gender, and outcomes such as length of stay. The data were statistically analyzed using SAS v 9.3 software. Results: Among Influenza positive cases during the 2013-2014 Influenza season, 34.4% were vaccinated and 55.6% were between the ages 51 and 79. Among Influenza positive cases during the 2014-2015 season, 64.6% were vaccinated and 57% were between the ages 51 and 79. Among Influenza negative cases during both Influenza seasons, 66.7% were vaccinated and 56.3% were between the ages 51 and 79. Importantly, as a general finding, those patients who received Influenza vaccination prior to admission were significantly less likely to have Influenza (p = 0.0132). Patients who were vaccinated prior to admission were statistically significantly older (p = 0.0001) and had higher comorbidity scores (p = 0.0001). Conclusions: Influenza vaccination significantly reduces the rate of Influenza positivity among inpatients. Patients who are older and have higher comorbidity scores are more likely to be vaccinated. The Influenza vaccine is significant to public health because it is cost effective and reduces hospitalizations and mortality due to Influenza. This information can be used to educate patients and health care workers about the Influenza vaccine and its benefits. %D 2016 %K Influenza vaccine %I University of Pittsburgh %L pittir27425 %A Junyao Wang %T Effect of overweight status at onset on C-peptide levels during first 2 years since diagnosis in children with type 1 diabetes %X Background: Recently, the growing epidemic of obesity is mirrored in the increasing incidence rate of T1D in children. However, the role of overweight in the progress of T1D is still unknown. Objective: To assess the relationship between the overweight status at onset and the insulin reserve in the first two years since diagnosis in children with T1D. Methods: One hundred sixty-eight children newly diagnosed with T1D, aged from 1.5 to 18.9 years, with 2-years of follow-up, ?4 autoantibodies measured at baseline, and onset C-peptide plus 3 or more follow-up measures were included in this study from the Children?s Hospital of Pittsburgh Registry (2004-2006). Baseline demographic and clinical characteristics were compared between overweight and non-overweight subjects. The change and the rate of change of C-peptide were evaluated. The contribution of being overweight to C-peptide levels and change in C-peptide from onset over time were estimated using linear mixed models adjusting for other covariates. Results: Among the 168 subjects with mean age at 9.7 years and mean onset C-peptide of 0.76ng/mL, 22% (36) were overweight at onset with BMI ? 85th percentile. Onset C-peptide level of overweight subjects was higher than that of non-overweight (median: 0.88ng/mL vs. 0.50ng/mL, P<0.0001). The highest C-peptide levels (median: 1.86ng/mL vs. 1.47ng/mL, P=0.30) were observed a 3 months, followed by a continuous decline reaching the lowest level at 24 months (median: 0.29ng/mL vs. 0.18ng/mL, P=0.13). Linear mixed models suggest that the overall mean rate of change of the overweight subjects was 0.7865ng/mL/months (95% C.I.: (0.2277, 1.3452), P=0.0062) compared to the non-overweight subjects adjusting for other baseline covariates. The differences of mean C-peptide levels between these two groups decreased as time passed and reached similar levels at the end of the second year. Conclusion: Compared to the non-overweight T1D children, overweight children had higher C-peptide levels at 3, 6, 12, and 18 months after diagnosis; however, at 24 months, this difference was not statistically significant. Public health significance: Children with T1D who are overweight can benefit from the potential related target interventions to help them maintain or extend the duration of high C-peptide level after receiving treatment. %D 2016 %K Type 1 diabetes, C-peptide, Overweight %I University of Pittsburgh %L pittir27470 %A Garry Smyda %T Efficiency of current diabetic retinopathy screening recommendations in a pediatric population %X Diabetic retinopathy (DR) is a microvascular complication that typically occurs with greater frequency as disease duration increases. Both the American Diabetes Association and the International Society for Pediatric and Adolescent Diabetes make recommendations that patients be screened for retinopathy starting at age 10 and after a disease duration of greater than 2 years. Because it is important to catch DR early to prevent vision loss to the patient, sensitive screening techniques such as digital fundus photography are in important tool in this effort. The public health cost of DR complications can be effectively reduced by instituting smarter screening recommendations, not screening those who are at very low risk, and preventing vision loss by early identi?cation and treatment of DR. In this study, patients attending a large pediatric diabetes clinic that met the screening recommendations were offered DR screening using digital fundus photography. A total of 440 patients both met screening criteria and had retinopathy screening data. Of the 440, 203 were screened in-clinic by an opthalmologist, and 236 had already been screened by an outside practitioner. 5.4% of those screened in-clinic were positive for DR, while 0.42%of those screened elsewhere were found to be DR+. Those with retinopathy had significantly longer disease duration, were older at the time of screening, had higher HbA1c, and higher triglycerides. All of the cases had measures exceeding the screening guidelines, with a minimum age at screening of 13.4 years, and a minimum diabetes duration of 6.5 years. It is unknown if the difference in prevalence between the two screening locations is due to a true difference in prevalence, or a systematic underreporting of DR in the outside-screened group, or a combination of these factors. The screening method of the 236 screened outside was not reported, and cases may have been missed in this cohort. Further study will need to be done to better quantify who would bene?t most from screening, but building a risk model will require a much larger, comprehensive study. While it appears that the current screening guidelines may be revised without decreasing sensitivity, when screening is done it must be done using the most accurate methods in order to be most effective in catching DR in early stages when treatment is still effective. This study emphasizes the public health benefit to screening for diabetic retinopathy as a routine element of diabetes management. In fact, the patients who took advantage of screening o?ered by the clinic showed over 10 times the prevalence of those who had already received screening by an outside practice, and most of these patients would have not otherwise completed screening, even though they were within the guidelines. The benefit to state-of-the-art digital fundus photography DR screening in this at-risk cohort is clear. %D 2016 %K diabetic retinopathy screening pediatric %I University of Pittsburgh %L pittir27435 %A Christopher Hoffmann %T Enhancing PrEP uptake among MSM: Findings from interviews with researchers and practitioners %X BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is a prescription antiretroviral medication that an HIV-negative person who is at high risk for HIV infection takes once per day to prevent infection. The most recent National HIV/AIDS Strategy identifies increasing PrEP uptake among men who have sex with men (MSM) as a pillar of ending the AIDS epidemic. Extant literature suggests that barriers to PrEP uptake among MSM are related to access, stigma, and knowledge/attitudes. METHODS: From February-March 2016, semi-structured interviews were conducted with researchers and practitioners in the HIV prevention field who work with MSM in Pittsburgh, Pennsylvania (n=11). An interview guide was used that asked about PrEP barriers and ways to mitigate these barriers. Interview recordings were transcribed and analyzed for key themes using ATLAS.ti software. RESULTS: The original list of 39 codes was condensed into five key themes. The five key themes are that PrEP is empowering; PrEP barriers are multidimensional and overlapping; episodic PrEP is viewed favorably; PrEP needs, access, and perceptions differ by race and age; and risk compensation is real, but it should not be used to prohibit PrEP uptake. A list of all PrEP barriers identified in the interviews is presented. PUBLIC HEALTH SIGNIFICANCE: For public health practice, participants in these interviews identified stigma as more significant of a barrier to PrEP uptake for MSM than its discussion in the existing literature would suggest. PrEP enhancement efforts should simultaneously target multiple barriers across constructs for maximum effectiveness, avoid shaming overtones, and be inclusive of black MSM. A table is presented that may serve as a map to intervention design. Research is needed to test the association of PrEP use and STI incidence in US-based samples, to fine-tune local PrEP uptake efforts in other regions, and to monitor unintended consequences of PrEP uptake in the near or distant future. %D 2016 %K pre-exposure prophylaxis, prep, HIV, AIDS, HIV/AIDS, MSM, men who have sex with men %I University of Pittsburgh %L pittir27530 %A Anne C. Ritter %T The Epidemiology of post-traumatic seizures following moderate to severe traumatic brain injury %X Though death rates due to traumatic brain injury (TBI) are decreasing in the United Statues, TBI remains a significant public health problem. Individuals who survive moderate and severe TBI become at risk of developing secondary complications, including post-traumatic seizures (PTS). PTS are well-recognized sequelae of TBI. Despite previous research, there remains a high degree of variability in who will develop PTS and no approved prophylactic medications to prevent late PTS exist. Late PTS is associated with significant morbidity and worse outcomes following TBI. Therefore, it is of public health importance to understand the characteristics of individuals with PTS, identify factors to improve prognostication, and explore novel risk factors to support a personalized medicine approach. Using the Traumatic Brain Injury Model Systems, we examined the incidence of immediate (<24hours), early (1?7 days), and late (>7 days post-injury) PTS. Incidence of new onset seizures was highest immediately (8.9%) and one-year (9.2%) post-injury. Late PTS prevalence surpassed 20% at five-years post-injury. Incidence was stratified by potential risk factors and relative risk calculated. Individuals with immediate but not early seizures had a significantly greater incidence of late PTS compared to individuals not seizing during acute hospitalization. We then developed and internally validated prognostic models for PTS during acute hospitalization, at one-year, and two-years post-TBI. We identified multiple variables, including novel factors such as pre-injury mental health conditions, predictive of PTS. Year one and two models showed fair-to-good ability to discriminate PTS, supporting the idea that more accurate prognostication of late PTS can be accomplished. Lastly, we examined genetic variation in neuronal glutamate transporter genes as risk factors for PTS. We identified genetic variants significantly associated with increased PTS risk, after controlling for known risk factors. The relative effect size of the genetic markers suggests these variants may be significant predictors of PTS and may improve prognostic model reliability and validity. Classifying subpopulations at high-risk for PTS could facilitate research regarding the effectiveness of tiered prophylaxis and novel pharmacological interventions, improving prevention and treatment. Together, findings from the current work may affect future research and programmatic decisions, positively impacting those at risk for PTS. %D 2016 %K post-traumatic seizure traumatic brain injury %I University of Pittsburgh %L pittir27835 %A Allison Brichacek %T Evaluation of a novel antiviral for influenza infection in the ferret model %X Influenza viruses, although common, cause thousands of deaths worldwide and remain a prominent public health issue, especially with the growing population of elderly and immune-compromised individuals. Currently, the influenza vaccine is the best tool available at protecting against infection, but the correct strains are hard to predict and the vaccines do not always work. Therefore, it is necessary to explore more effective antiviral drugs. New antivirals like these are of public health importance because they can help reduce morbidity and mortality related to influenza infection. Our collaborators from the University of Washington have computationally designed a small protein, HB36.6, which interferes with influenza infection by binding the virus? hemagglutinin surface protein. This thesis has tested the novel antiviral using the influenza A/California/07/09 (H1N1) strain in a ferret model by looking at the effects of low and high doses of HB36.6, and comparing it to untreated controls or against the current standard antiviral, Tamiflu. Antiviral effectiveness was evaluated using a combination of clinical and viral parameters. First, the animals were monitored and scored using a detailed clinical scoring system for onset of clinical signs of disease, as well as tracked through daily measurements of weights and temperatures. Second, viral titers were quantitated using RT-PCR in tissue samples obtained at necropsy and the untreated controls were compared to HB36.6-treated animals or those treated with Tamiflu. The overall hypothesis for this study was that HB36.6 will be effective in reducing viral loads and limiting disease following aerosolized influenza infection in the ferret model, and this reduction in viral loads/disease would be more effective than the currently used antiviral, Tamiflu. The results of these studies show that HB36.6-treated animals display fewer clinical symptoms when a low dose of the treatment is used, but there appears to be no reduction in viral loads. Higher doses appear to be toxic to the animals, especially when taken over multiple days throughout the course of infection. These studies have yielded important information on a new class of influenza therapeutics that should be further evaluated using larger sample sizes. %D 2016 %K influenza, antivirals, ferrets %I University of Pittsburgh %L pittir27886 %A Melissa Gregory %T Exploring postpartum weight management techniques to decrease proportion of overweight and obese women %X Obesity is a major public health problem in the United States. A subgroup of obese individuals with particular health concerns is women of childbearing age. Although there is an extensive amount of research on excessive gestational weight gain and its adverse health effects, there is limited research about weight gain and management during the postpartum period. While weight management interventions have targeted women within the prenatal stage of pregnancy, few have focused on the postpartum period. A focus on the postpartum period is therefore important because 1) a unique opportunity exists during this period to intervene to improve the health of women, and 2) many childbearing women will become pregnant again and so intervening during this period may improve the outcomes of future pregnancies. This thesis therefore provides data to inform the development of more effective weight management interventions targeting women during the postpartum period. Specifically, this thesis provides preliminary data about overweight and obese postpartum women and their preferences and views surrounding weight management, data that can be used to strengthen the development and implementation of interventions. A sample of postpartum women was assessed to describe their attitudes about and preferences with respect to interventions. Results found that women were most interested in individualized, phone-based interventions that focus on dietary intake and ways to reduce postpartum weight gain. Women were also asked about potential barriers impacting their ability to complete weight management interventions. Socio-demographic factors were assessed to determine whether these factors were potential predictors of interest. Multigravida and primigravida were the only statistically significant predictors of interest, with women undergoing their second pregnancy being most interested in participating in weight management programs. Few weight intervention studies have looked into the psychosocial context of women participating in weight management. The findings of this thesis suggest approaches to reduce weight gain postpartum capturing preferences and potential barriers to treatment. %D 2016 %K overweight, obesity, postpartum, pregnancy, weight interventions, weight management %I University of Pittsburgh %L pittir27403 %A Jacquelynn Jones %T Exploring the associations between internet-based professional social networking and emotional distress %X Young professionals commonly use professional social networking websites. In light of emerging concerns regarding social networking use and emotional distress, the purpose of this study was to investigate the association between frequency of use of LinkedIn, the most commonly used professional social networking website, and depression and anxiety among young adults. In October 2014, we assessed a nationally-representative sample of 1,787 U.S. young adults between the ages of 19 to 32 regarding frequency of LinkedIn use, depression and anxiety, and socio-demographic covariates. We measured depression and anxiety using validated Patient-Reported Outcomes Measurement Information System measures. We used bivariable and multivariable logistic regression to assess the association between LinkedIn use and depression and anxiety while controlling for age, sex, race, relationship status, living situation, household income, education level, and overall social media use. In weighted analyses, 72% of participants did not report the use of LinkedIn, 16% reported at least some use but less than once each week, and 12% reported use at least once per week. In multivariable analyses controlling for all covariates, compared with those who did not use LinkedIn, participants using LinkedIn at least once per week had significantly greater odds of increased depression (adjusted odds ratio [AOR] = 2.10, 95% confidence interval [CI] =1.31-3.38) and increased anxiety (AOR = 2.79, 95% CI = 1.72-4.53). LinkedIn use was significantly related to both outcomes in a dose-response fashion. As depression and anxiety become leading contributors to disability adjusted life years, it is important to recognize the implications of these disorders and acknowledge them as major public health problems. Future research should investigate directionality of the found association and possible reasons to better address the burden associated with depression and anxiety. %D 2016 %K social networking, depression, anxiety, LinkedIn %I University of Pittsburgh %L pittir27542 %A Amy Kunz %T Expression of alk1 is regulated by a positive feedback mechanism involving blood flow and circulating ligand %X ALK1, a TGF-? type I receptor serine/threonine kinase, is critical for proper vascular development. Heterozygous loss of ALK1 results in the vascular disorder, hereditary hemorrhagic telangiectasia type 2 (HHT2), which is characterized by the development of arteriovenous malformations (AVMs) and affects 1 in 5,000 people worldwide. HHT is thought to be caused by a haploinsufficiency and therefore delineating how ALK1 is regulated could provide avenues for targeted and effective clinical interventions. In the zebrafish model organism, alk1 is expressed in arterial endothelial cells of vessels leading away from the heart. We have learned that alk1 expression closely correlates with the presence of blood flow, but which component of blood flow is responsible for regulation is unknown. I propose that flow is required for activation of a positive feedback mechanism by which Bmp10 ? a circulating ligand of Alk1 receptors that is produced by the heart and secreted into the bloodstream ? through Alk1 activation maintains arterial alk1 expression at the level of transcription. In this work, I define the spatiotemporal relationship between cessation and restoration of blood flow and alk1 expression and show that flow-mediated alk1 expression is regulated at the transcriptional level. Finally, I provide evidence that intact Bmp10/Alk1 signaling is required to maintain alk1 mRNA expression. I hypothesize that this effect is driven by a gradient of Bmp10 ligand established by blood flow that triggers a positive feedback mechanism initiated by Bmp10/Alk1 signaling. The goal of my work is to understand the mechanism of ALK1 regulation in order to progress toward the goal of targets and effective clinical management for HHT patients. HHT is a relatively common genetic disease that often goes underdiagnosed due to its variable presentation even among members of the same family, hence studying this complex disease is significant for practice of public health. %D 2016 %K Alk1, zebrafish, vasculature, HHT %I University of Pittsburgh %L pittir27513 %A Kara Peters %T Facilitators of and Barriers to Mental Health Treatment among Adolescents in an Integrated HealthCare Setting %X Background: The high incidence of mental health disorders among adolescents, accompanied by low treatment utilization, is a major public health problem. Including mental health treatment in primary care medical settings through an integrated health care model offers an opportunity for early intervention and easier treatment uptake for adolescents with mental health diagnoses. Methods: This thesis examined the barriers to and facilitators of implementing a mental health referral system with the support of a quality improvement project within a single clinic. Results: Qualitative analysis revealed key facilitators to be provider education; communication among team members; a shared EHR and electronic referral orderset; ongoing monitoring, evaluation, and improvement of the system; and social workers. Barriers included workflow challenges; lack of protocols; and fewer available services. Quantitative data analyses showed significant improvement in mental health utilization rates since the implementation of the project. Conclusion: The findings from this thesis can be used to inform future integrated models for adolescent mental health care in primary care settings. Expanding integrated models has public health implications for increasing treatment utilization among adolescents in need of mental health services, ultimately leading to improved quality of life throughout adulthood. %D 2016 %K adolescents integrated healthcare mental health treatment social work %I University of Pittsburgh %L pittir27765 %A Nicolette Walano %T Familial clustering of suicide and major depressive disorder: an observational analysis %X Depression is considered the third most important burden of disease globally; further, it is ranked first in middle and high-income countries. It is well understood that depression is has a heritability of 31-43%, but no genetic associations predisposing individuals to depression have been found. A small group of individuals have previously been identified with treatment resistant major depressive disorder (TR-MDD), suicidality and a myriad of metabolic alterations. This is considered a neuropsychiatric inborn error of metabolism that initially presents with psychiatric manifestation. The most common metabolic finding is cerebral folate deficiency. Supplementation of folinic acid has been shown to result in a reduction of symptoms. Understanding this group of individuals, particularly with the knowledge that metabolic disease commonly manifests with psychiatric illness, has implications for the way depression may be diagnosed and treated in the future. This study captured and analyzed the family histories of 36 individuals in an attempt to discern whether the transmission of depression and suicide in these families fits known Mendelian inheritance patterns. By using segregation analysis in addition to an observational analysis this study has assessed autosomal recessive and autosomal dominant inheritance patterns. Observation of family histories showed male-to-male transmission and thus excluded the possibility of X-linked or mitochondrial inheritance in this group. The observational study identified that 6/36 families (16.7%) met all criteria for autosomal dominant inheritance and no families met all criteria for autosomal recessive inheritance. The just over 30% of families met a few, but not all of the criteria for autosomal dominant inheritance (11/36) and 33 of 36 families or 91.67% met only one criterion for autosomal recessive inheritance. This suggests that these families are transmitting depression and suicidality in a polygenic or multifactorial pattern. The statistical analysis supports this conclusion finding that the families fit a non-Mendelian pattern of inheritance. Understanding the way depression is being transmitted in these families has significant public health relevance as it may inform our understanding and future studies of the genetics of depression, a significant health burden. %D 2016 %K Depression, Suicide, Family, Metabolic, Cerebral Folate Deficiency, Genetics %I University of Pittsburgh %L pittir27547 %A Natalie Fiato %T Family planning in Sub-Saharan Africa: a review of interventions in promotion of long-acting reversible contraception %X International non-governmental organizations (INGOs) in the field of sexual and reproductive health (SRH) consider access to family planning services a universal human right. Family planning programs should strive to effectively provide information, counseling, and contraceptive services to allow women and men the ability to freely determine when and how many children they desire to have. In developing regions of the world, women are often unable to obtain or use modern contraception (mC) for many reasons relating to both supply and demand side factors. Use of mC is lowest in Sub-Saharan Africa (SSA). Unmet need (i.e., women who desire to delay childbearing but are not using any methods to do so) is highest in this region as well. Higher rates of unintended pregnancy are directly related to low mC use and high unmet need. The public health significance of this relationship is great: unintended pregnancy has grave health implications for maternal and child morbidity and mortality in the developing world. Women of reproductive age in SSA rely primarily on traditional and short-acting reversible contraception, which are prone to incorrect or inconsistent usage and failure. By contrast, long-acting reversible contraception (LARC) provides up to ten years of highly effective protection against pregnancy. LARC methods are among the safest, most cost-effective, and reliable forms of contraception available today. LARC includes the copper intrauterine device (IUD), levonorgestrel intrauterine system (LNG-IUS), and contraceptive implant. These methods are appropriate for most women, and can be used to space or limit childbearing until the user is ready to have children. LARC methods have historically been underutilized in SSA, where they could benefit millions of women seeking to control their fertility. Relatively few interventions exist within the international development field where LARC has been sustainably introduced into the mC method mix in SSA. This paper reviews and examines the literature on published interventions, and provides international development practitioners with useful recommendations for LARC promotion in family planning programs moving forward. These recommendations include decentralizing health care networks, building capacity in service delivery and skills training, and conducting advocacy and education through social and behavioral change communication (SBCC). %D 2016 %K Family planning, Sub-Saharan Africa, long-acting reversible contraception, contraception %I University of Pittsburgh %L pittir27371 %A Hollis Laird %T Garden-based nutrition education programs: a review of impact and evaluation methods %X The goal of this paper is to examine the effects of garden-based nutrition education programs and their methods of evaluation. Current literature shows that garden-based nutrition education programs have positive effects on children including: increased knowledge about fruits and vegetables, increased knowledge about science, increased preference for fruits and vegetables, increased consumption of fruits and vegetables, and increased self-efficacy. The first objective of this paper is to review the extant literature regarding garden-based nutrition education programs in order to identify effective programs. The second objective is to review current methods used to evaluate of garden-based nutrition education programs in order to identify the limitations. Examining the evaluation methods for these interventions is vital as there are currently no standardized evaluation methods for garden-based nutrition education programs. By developing standardized evaluation tools we will be better able to study the impact of programs, but first these methods need to be examined. Lastly, this paper describes the evaluation of an existing community garden with a garden-based nutrition education component aimed at children, Enright Community Garden. The public health significance of this paper is that with disproportionate levels of childhood obesity in marginalized communities characterized by little to no access to healthy foods, we must identify effective interventions that increase knowledge, exposure, and access to fresh fruits and vegetables. %D 2016 %K Garden-based nutrition education, evaluation %I University of Pittsburgh %L pittir27815 %A Tricia Zion %T Genetic counselors' views and opinions regarding the possible implementation of prenatal exome sequencing %X The utility and effectiveness of whole exome sequencing (WES) have been demonstrated in a pediatric setting, and for this reason, it has recently begun being offered in in the prenatal setting. The scope of exome sequencing and the possibility for incidental findings raises ethical concerns and challenges current resources available to prenatal genetic counselors to implement this testing. This creates a need to understand genetic counselors? opinions toward such a test prior to its implementation. For this reason, a survey focusing on clinical scenarios and factors influencing genetic counselors? opinions on prenatal WES was distributed to clinical prenatal counselors and laboratory counselors through the National Society of Genetic Counselors? student research survey program. One hundred and sixty respondents met criteria for and completed the survey. Results of this survey were analyzed for descriptive statistics as well as comparison of responses using nonparametric analysis. Responses showed that 59.4% of respondents were comfortable with prenatal WES as a diagnostic tool after other diagnostic testing had come back negative or inconclusive. Support for use of prenatal exome sequencing increased significantly (p=0.0088) in the context of targeted prenatal exome (TES), with 74.4% of counselors supporting TES after other diagnostic testing was negative or inconclusive. The two largest factors influencing opinions and support of prenatal exome sequencing were the perceived ability of patients to handle the amount of information provided by the testing (n=125) and the clinical utility of exome sequencing in the prenatal setting (n=123). Most genetic counselors (70.7%) were more likely to support prenatal exome sequencing if educational resources were provided to aid in the implementation of the testing. Overall, 46.9% of genetic counselors would support this testing if it were restricted to cases with clear clinical indications, while an additional 31.9% would support prenatal TES only. The public health significance of this study is that, because prenatal WES/TES will likely be clinically available in the near future, understanding genetic counselors? perceptions of testing and barriers to uptake will help to more seamlessly integrate this testing into the clinic to provide the most benefit and least harm to prenatal patients. %D 2016 %K exome, WES, exome sequencing, genetic counseling, survey, TES, targeted exome, prenatal, prenatal exome %I University of Pittsburgh %L pittir27359 %A Kelly Johnson %T Genome-wide association studies of childhood bone health %X Osteoporosis is a major public health concern characterized by low bone mineral density (BMD) and deterioration of bone tissue, causing increased bone fragility and risk of fracture. Though current research has focused primarily on bone health in the elderly, early bone health, including peak BMD attainment, is a strong predictor of bone health later in life. Twin and family studies have demonstrated a strong genetic component in peak BMD, though the specific genes influencing variation in bone development are largely unknown. Moreover, the question of whether the genes influencing bone health during childhood are the same as those influencing bone health later in life is currently unknown. Therefore, to identify variants and genes implicated in childhood bone health, we performed separate genome-wide association studies (GWAS) for ten bone health phenotypes (bone mineral content [BMC] and BMD of the hip, spine, and head, BMC of the whole body, and four measures of hip geometry) in 296 Caucasian children aged 5 years (mean = 5.3) who were enrolled in the Iowa Bone Development Study. Linear regression while adjusting for sex, height, and weight was used to test 548,051 genetic polymorphisms and 7.4 million imputed variants for evidence of association. Genomic regions showing statistical association were scrutinized for relevant gene functions related to bone biology. Five genome- wide significant (P?5x10-8) and 30 suggestive (P<10-6) loci were identified in total. Implicated genes may represent significant roles in the converging pathways that regulate BMD, embryonic bone development, and bone remodeling. Furthermore, understanding the genetic determinants of bone health during childhood may have implications across the lifespan. Though osteoporosis is usually viewed as an age-related disorder, risk of osteoporosis is impacted much earlier in life, including phases of bone mineral acquisition during youth. Therefore, the public health significance of this study is that identifying the genetic factors contributing to early skeletal health may ultimately lead to screening programs, which identify children with a genetic predisposition to bone disease. This allows for targeted interventions to optimize bone health in adolescence, promote management of bone health across the lifespan, and lower risk for osteoporosis later in life. %D 2016 %K GWAS, bone, genetics, childhood %I University of Pittsburgh %L pittir27893 %A Lora McClain %T HSV-1 infection in human induced pluripotent stem cell-derived neurons: cellular models for quiescence and drug discovery %X Background: Herpes simplex virus, type 1 (HSV-1) establishes latency in human sensory ganglia following primary infection through mucosal tissues. Once latent, the virus persists for the host?s lifetime, with periodic reactivations that cause lytic lesions. First-line medications like acyclovir (ACV) abort lytic reactivations, but drug resistance has been reported and second line drugs may cause serious side effects. These facts, together with inefficacy of antivirals against latency, compel new drug screens; human neural tissues that model aspects of latency are arguably well-suited for such screens. Studies: Study 1. Human induced pluripotent stem cell-derived neurons (iPSC-neurons) were used to model HSV-1 infection employing an HSV-1 construct that incorporates dual fluorescent reporter genes from different kinetic expression groups. Lytic infection was demonstrated initially. ?Quiescent? infection was next established using protocols from animal models of latent infection. The quiescent infection fulfilled most criteria for latency, including viral gene expression and heterochromatization patterns. Studies 2 and 3: The antiviral activity of two series of compounds was investigated using monkey epithelial cells and iPSC-neurons. Anti-lytic activity that reduced viral copy number and protein levels was induced by four compounds, of which two compounds also inhibited reactivation of HSV-1 from quiescence/latency. Four compounds were also efficacious against varicella zoster virus and/or human cytomegalovirus infections. Study 4: Moderate throughput platforms for antiviral drug screens based on iPSC-neurons were designed, with readouts based on high content analysis and flow cytometry. Conclusions: Lytic and latent HSV-1 infection was modeled in human iPSC-neurons, with features similar to animal models. Compounds with novel effects against HSV-1 infections were identified using the iPSC-neuron model. Platforms for moderate throughput drug screens are feasible using human iPSC-neuron models. Public Health Significance: Herpesviruses are highly prevalent, with rates exceeding 95% in some populations. Recurrent HSV-1 eye infections are the leading cause of infectious corneal blindness in the USA. HSV-1 encephalitis that is particularly devastating to neonates can be fatal. Associations between HSV-1 seropositivity and cognitive impairment have been reported even without encephalitis. There are no effective HSV-1 vaccines and there are growing concerns about antiviral drug efficacy. In view of the enormous burden, there is a compelling need for novel drug screens. %D 2016 %K HSV-1, VZV, HCMV, antiviral, iPSC, neuron, drug discovery, gene expression %I University of Pittsburgh %L pittir27447 %A Blandine Victor %T Human and microbial genetic factors contributions to the development of HIV-associated neurocognitive disorder %X Years of research and the development of effective therapeutic treatments, have dramatically improved the life expectancy rates for HIV-infected individuals. However, there is a subpopulation of aging, infected individuals who have experienced an adverse impact on their long-term health and quality of life, the mechanism of which has become an increasing concern of public health importance. The counteractive outcomes of aging within the infected population leaves many susceptible to developing age related morbidities in the form of cognitive impairment, brain atrophy, and other neurocognitive disorders at an earlier age then those within the non-infected population. These symptoms manifest in the form of HIV-associated Neurocognitive Disorder or HAND in infected individuals. Fully understanding the process in which HAND can occur has been a striving goal within the Public Health community. Our goal is to determine if there are specific genetic and/or microbial factors within individuals that may be contributing to their development of cognitive decline. All these efforts could provide comprehensive insight at an endophenotypic level into the pathological mechanism of HAND, and a better understanding of how diversity in the gut microbiome can affect health and aging. Subsequently, this information could lead to the identification of genetic biomarkers, development of treatments, and therapeutic options for regulating chronic HIV infection and neuropathology. We hypothesize that inherited SNPs in genes of the folate metabolism pathway affect the availability of methyl groups within the cell, and consequently influence DNA methylation, leading to the development of HAND in seropositive individuals, and neurocognitive decline in seronegative individuals. We also hypothesize that there is an altered composition of the microbiome within the gut of infected individuals, the presence of which directs the level of HIV pathogenesis and HAND development. In comparing HIV+ and Cognitive Decline groups against control groups, we do not have sufficient evidence to conclude that there is an increased risk of adverse outcome in association with any of the folate genes that we observed. Isolation of bacterial genome produced expected PCR product, and data interpretation following 16S rRNA sequencing will soon yield definitive microbial composition analysis. %D 2016 %K HAND, DNA Methylation, Microbial Composition, Accelerated Aging %I University of Pittsburgh %L pittir27466 %A Juliann Hudak %T Human trafficking: globally, nationally, and in the Commonwealth of Pennsylvania %X Background: Human trafficking has no geographic boundaries and affects a large number of people across the globe. Human trafficking is of significant public health relevance because it negatively affects the health of men, women, and children of many races, ethnicities, and social classes. The crime of human trafficking has been occurring for many years, but was addressed by policy only recently. Despite the creation of anti-trafficking legislation, human trafficking still occurs globally, nationally, and in the Commonwealth of Pennsylvania. Methods: For this paper, anti-trafficking policies in Pennsylvania were reviewed along with the primary international and national anti-trafficking policies. The key concepts that inform anti-trafficking policies were also reviewed and compared. Results: The US and the UN adopted a three-tiered approach to anti-trafficking policy, which includes protecting victims, prosecuting offenders, and preventing trafficking in the source country. Following the creation of national anti-trafficking legislation, several states developed policy to combat trafficking, including the Commonwealth of Pennsylvania. Despite international, national, and state adoption of anti-trafficking policy, the key concepts that inform these policies differ greatly. Additionally, there is inconsistency across policies about what acts constitute human trafficking. Furthermore, anti-trafficking policies still lack provisions important for protecting victims, prosecuting traffickers, and preventing human trafficking. Summary: Human trafficking is a global problem with a significant health burden. As a result, there is a need for the creation and implementation of comprehensive, evidence-based anti-trafficking policies, specifically global policies with a standard definition of human trafficking. US policies and state policies, such as those in Pennsylvania, also need to be expanded to include comprehensive definitions and explicit victim protections. By improving anti-trafficking policy at the global, national, and state levels, victims will be protected and progress will be made towards the end goal of eradicating human trafficking. %D 2016 %K human trafficking, Pennsylvania, policy %I University of Pittsburgh %L pittir27374 %A Elizabeth M Stinson %T Humoral response to Type-A derived genetically modified live attenuated Francisella tularensis in rabbits %X Francisella tularensis is a gram negative, non-motile, coccobacillus that is the causative agent of tularemia. There is concern that F. tularensis could be used as a biological weapon and development of vaccines is a high priority. Type A strains are highly virulent but the current live vaccine strain (LVS) is based on a type B strain which is only partially protective against aerosol challenge with SCHU S4 (S4), a type A strain. Historically mice have been the most commonly used model to study vaccines and pathogenesis of F. tularensis. However, mice are acutely sensitive to tularemia such that strains that are attenuated or avirulent in other mammals cause lethal disease in mice. Therefore, the rabbit model has been used in these studies because New Zealand White rabbits have a disease course and susceptibility similar to humans. The data presented here will demonstrate that the humoral immune response plays a role in the protection and survival from a F. tularensis infection. A novel ELISA assay has been used to examine antibody titers against F. tularensis in the plasma of rabbits post vaccination and analyzed to determine if there is a correlation to survival against challenge with SCHU S4. In addition, data was analyzed to compare various vaccines, vaccination routes, and vaccine doses to determine if one provided better protection and higher survival rate. %D 2016 %K humoral immunity, Francisella tularensis, vaccine, SCHU S4, LVS, bio-weapon, ELISA, vaccination routes, antibody, antibody titers %I University of Pittsburgh %L pittir26430 %A Seyed Amir Bahreini %T Identification of DNA sequence variants in the estrogen receptor pathway in breast cancer %X Breast cancer is of public health importance with an increasing incidence over the past decade. Estrogen Receptor (ER) activity is critical for promoting majority of breast cancers. Inhibiting ER is one of the most successful targeted therapies in oncology. Studies have suggested that genomic variation in ER binding sites and ESR1 gene may be responsible for endocrine treatment response and cancer progression. We investigated the role of single nucleotide variants (SNVs) in the ER pathway in breast cancer, including clinically relevant mutations in ER gene and regulatory variants in ER binding sites. First, we developed a computational pipeline to identify SNVs in ER binding sites, using chromatin immunoprecipitation-sequencing (ChIP-seq) data from hormone responsive breast cancer cells and tumors. Analysis of ER ChIP-seq data from multiple MCF7 studies characterized a SNV within intron 2 of the IGF1R gene, rs62022087, predicted to increase the affinity for ER binding. By integrating 43 ER ChIP-seq data sets, multi-omics and clinical data, we identified SNVs regulating downstream target genes which may contribute to patients? survival. Second, we used sensitive detection methods to detect mutations and identified high frequencies ESR1 mutations in primary tumors, metastatic lesions and cell-free DNA samples. This result may be due to higher sensitivity of our study in detecting mutations at very low allele frequency. Finally, we generated appropriate knock-in cell lines through CRISPR technology to study ER mutations. RNA-seq studies revealed ER mutations are can activate estrogen regulated genes in a ligand independent manner and also may induce/repress a set of novel targets. Cell adhesion assays demonstrated mutants are less adhesive to Collagen I which may be a marker of metastasis. Taken together, our findings indicate that SNVs in ER pathway are clinically important and may predict drug response in ER+ breast cancer. From the public health perspective, screening for these impactful variants will be soon part of the genetic testing as our knowledge of genome improves. This will eventually help initiatives to reduce public health burden by choosing the right treatment for breast cancer patients in personalized manner. %D 2016 %K Breast cancer, genetics, single nucleotide variants, estrogen receptor, regulatory variants, endocrine resistance, metastasis, circulating free DNA %I University of Pittsburgh %L pittir27486 %A Kevin Urda %O This is my final version. %T LGBT aging: the approaching silver wave %X Over the next twenty to thirty years, nearly four million LGBT Baby Boomers will be retiring and begin using the aging services in the United States. This thesis presents a critical literature synthesis that examines the public health significance of LGBT seniors? health disparities and health protectors, the historical framework that has shaped their lives, and the structural issues that create health disparities. Unique aspects of subgroups within the LGBT population are extrapolated as well. The three major recommendations to support LGBT seniors are: 1) Improve LGBT research to gather more nuanced information on LGBT seniors including the intersection of sexuality with other minority statuses, 2) Support aging-in-place for LGBT seniors to give them a safe, supportive environment surrounded by self-selected friends and family, and 3) Improve and implement LGBT sensitivity training for medical and support groups working with LGBT seniors. %D 2016 %K LGBT Aging, LGBT Seniors, LGBT Elders, LGBT Baby Boomers %I University of Pittsburgh %L pittir27546 %A Brianna Heath %T MT1 receptor mediated neuroprotection in R6/2 mouse model of Huntington?s disease %X Huntington?s Disease (HD) is a fatal, autosomal dominant, neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The disease is characterized by chorea, as well as psychiatric and cognitive symptoms. At present, no treatment able to modify the disease progression is available. HD is characterized by the death of medium striatal spiny neurons within the brain. Melatonin is a hormone which acts as a neuroprotectant in a variety of neurodegenerative diseases. While most endogenous melatonin is produced by the pineal gland and circulated in the bloodstream, melatonin is also present in neurons. Here I use a novel method of detecting site specific melatonin synthesis to show melatonin is synthesized in neuronal mitochondria, where melatonin receptors are also localized. Previous research shows the melatonin receptor MT1 to be the mechanism of melatonin?s neuroprotection in cell and mouse models of HD. Here I measure the expression of MT1 in the R6/2 mouse model of HD to compare with literature reported decrease in expression, and test the effects of the R6/2 phenotype on overexpression of MT1 in a transgenic MT1 mouse model (NSE-MT1). Further, I use the cross of the NSE-MT1 mouse model and R6/2 to assess the effects of overexpression of MT1 in increasing melatonin?s neuroprotective properties to ameliorate disease phenotypes including caspase activation, neuronal density, rotarod behavioral testing, and survival. Together, these data show overexpression of MT1 produces small increases in melatonin?s neuroprotective properties with regard to caspase activation, but this protective effect does not cause corresponding increases in behavioral deficits or survival. Neuroprotection by melatonin is partially mediated by the MT1-receptor in an HD mouse model, but may additionally function by alternate pathways or be modulated by regulatory mechanisms. Understanding melatonin?s role as a neuroprotectant can help with the development of melatonergic therapeutics to treat HD and other neurodegenerative diseases to significantly impact public health outcomes. %D 2016 %K huntington's disease, melatonin, mt1, neuroprotection %I University of Pittsburgh %L pittir27756 %A Ethan Blum %T Maternal sources of stress within her combined individual and neighborhood environment and the risk of preeclampsia %X Preeclampsia is one of the leading contributors to morbidity and mortality for both the mother and fetus. Risk factors include African-American ancestry, obesity, and high levels of allostatic load. Low socioeconomic status is associated with high allostatic load. We assessed the relationship between socioeconomic status and race in efforts to obtain an accurate estimation of the African-American risk of preeclampsia. This study is significant to public health because it may identify reasons behind the differences in preeclampsia risk of preeclampsia between African-American women and Caucasian women to reveal points of intervention to reduce this risk. Nulliparous Pittsburgh women who delivered singleton births at UPMC Magee Women 19s Hospital between Jan 1st 2007-Dec 31st 2014 were randomly sampled. Women with preexisting hypertension, diabetes, and thyroid disorder were excluded. Our final sample consisted of 527 cases and 1713 controls. We created multi-level regression models to assess the risk of preeclampsia. We included neighborhood level information provided by the 2009-2013 American Community Survey, 2000, Decennial Census, and other Pittsburgh-wide organizations. UPMC Magee-Women 19s Hospital Obstetrical Maternal and Infant database provided individual level indicators. The neighborhood indicators included; percentage of households on SNAP, poverty rate, unemployment, median household income, percent greenery, crime rate, and economic and demographic growth between 2000-2009. Together these multi-level models could potentially illuminate the driving forces behind both neighborhood characteristics and individual qualities on the observed racial disparities in preeclampsia. Univariate analysis showed that African-Americans were more likely to have preeclampsia than Caucasians. When applying a multi-level model, the African-Americans odds decreased 16%. Under conditional regressions where neighborhoods were matched on similar quartiles of SNAP, poverty status, unemployment, and median household income, African-Americans odds of preeclampsia declined by 39-41%. The matched analysis explained more of the variability in risk of preeclampsia that was independent of race. Analysis of African-Americans compared to Caucasians indicated disparities among several neighborhood-level indicators. We discovered that the inclusion of the neighborhood environment explained some of the African-American risk of preeclampsia. We also noticed neighborhood-level disparities between Caucasians and African-Americans in Pittsburgh. We speculate the frequency of preeclampsia in African-Americans may be reduced by lowering these economic disparities. %D 2016 %K multi-level model, socioeconomic status, SES, preeclampisa, disparity, African-American %I University of Pittsburgh %L pittir27850 %A Alexander Kovalik %T Measuring generalized anxiety disorder (GAS) using the DSM-V severity measure assessment among resettled Bhutanese-Nepali refugees %X Public Health Relevance: Mental illness affects refugees who settle all over the world; however, Bhutanese refugees who settle in western societies are at higher risk. These high rates affect local communities, health systems, and economies, while highlighting the importance of refugee health services. Objective: The aim of this study was to measure generalized anxiety disorder (GAD) in a sample of Bhutanese-Nepali refugees experiencing mental health symptoms in Pittsburgh, Pennsylvania, and explore their attitudes about mental health and treatment options. Methods: Six participants volunteered for in-home interviews where GAD status was assessed using the mean DSM-V Severity Measure for Generalized Anxiety Disorder questionnaires. A review of literature, in-home interviews and a single focus group with four participants were conducted to gain information on attitudes about mental health, culturally specific events or experiences related to mental health, and treatments available and utilized by this community. Results: A moderate level of GAD was found in the sample. Traditional medicine (meditation, yoga, dhamis) and clinical medicine (pharmaceuticals) were reportedly used to treat anxiety in this sample, with a combination of both reportedly working best. Stress associated with relocation and resettlement has been suggested as a cause of GAD among the sample. Conclusion: In a small sample of Bhutanese-Nepali refugees in Pittsburgh, Pennsylvania; moderate levels of GAD were reported; however, due to a small sample size an alternative diagnosis such as a culture-bound syndrome should not be excluded. Future evaluations should be done to expand treatment regimens for mental health in the international refugee population, as well as evaluate diagnostic measuring tools. %D 2016 %K Bhutanese-Nepali refugee, mental health, GAD %I University of Pittsburgh %L pittir27899 %A Amy E Davis %T Non-genetic specialists' experiences ordering chromosomal microarrays %X Chromosomal microarray (CMA) is a first-tier clinical diagnostic test for individuals with developmental delay or intellectual disability, autism spectrum disorder, or multiple congenital anomalies. Due to the limited number of genetics professionals in the United States, non-genetic specialists often find themselves in situations where a CMA is indicated for their patient, but an evaluation by a clinical geneticist is not required. Many studies have identified barriers that non-genetic specialists experience when ordering genetic testing such as poor knowledge of genetics, cost of testing, uncertainty of genetic testing issues, and fear of discrimination. There are currently no studies investigating barriers that non-genetic specialists? encounter when ordering CMA. A survey was distributed to neurologists, developmental pediatricians, cardiologists, and endocrinologists at the Children?s Hospital of Pittsburgh of UPMC. The results of this survey were analyzed using descriptive statistics. Results showed that 43.8% of participants were ordering CMAs less often than they believe would be beneficial for their patients. The majority of participants (93.8%) indicated that the most significant barrier to ordering CMA was lack of insurance coverage. Participants indicated that on average, 48.1% of insurance pre-authorization requests get approved, regardless of insurance policy. Approximately 50-70% of participants indicated that they order CMA for the patient indications outlined in the 2010 American College of Medical Genetics consensus guidelines. Most respondents (88.9%) reported being comfortable ordering a CMA. Respondents indicated that they were comfortable providing pre-test counseling (83.3%) and routinely discuss some, but not all issues relevant to CMA. Although not every study participant reported working with a genetic counselor, almost all respondents agreed that genetic counselors would be valuable or very valuable throughout all aspects of ordering a CMA. The public health significance of this study is that CMA plays an important role in the diagnostic evaluation of a significant number of patients. Given the limited supply of genetic professionals, non-genetic specialists may increasingly be expected to order CMA, and may experience barriers that prevent the effective use of this test in relevant clinical situations. Therefore, it is important to understand potential barriers to allow for appropriate implementation of CMA. %D 2016 %K microarray genetic testing barriers %I University of Pittsburgh %L pittir27441 %A Kerrianne Morrow %T Non-invasive prenatal testing: provider knowledge and future directions %X Non-Invasive Prenatal Testing (NIPT) is a commercially available technology that analyzes cell-free fetal DNA circulating in maternal blood with the purpose of detecting specific fetal aneuploidies. Currently, this technology can be ordered by any prenatal medical professional including genetic counselors, obstetricians, and midwives. Professional societies recommend that NIPT be used as a screening method that is followed up with diagnostic testing and also that testing be accompanied with genetic counseling. With the increasing accessibility and relatively low cost of NIPT, prenatal medical professionals and labs are considering offering NIPT to all pregnant women. A questionnaire focusing on knowledge and views of NIPT was distributed to genetic counselors via the National Society of Genetic Counselors. Results were analyzed using descriptive statistics. Results showed that a total of 95% of genetic counselors agreed/strongly agreed with being familiar with NIPT clinical data. 99% are mostly confident/very confident when interpreting or explaining NIPT results to their patients. 89% agreed/strongly agreed they are familiar with microdeletion and microduplication conditions analyzed via NIPT. Although there is a strong understanding of microdeletions and microduplications, 26% agreed that they should be analyzed via NIPT while 35% did not agree. 95% of genetic counselors currently order NIPT for high-risk pregnancies, while 36% order NIPT for average-risk pregnancies. Regarding monogenic disorder analysis, 32% approved of this addition to NIPT, 47% remained neutral, and 21% disapproved. In the future, it is likely that NIPT will be offered via a public health-based model to all pregnancies rather than only pregnancies meeting high-risk criteria. This study aims to assess current opinions of genetic counselors regarding their knowledge and comfort level of genetic testing regarding NIPT in order to identify advantages, limitations, concerns, and gaps in knowledge. The public health significance of this research is that it will allow for the creation of appropriate educational materials regarding NIPT. Therefore, providers will become informed and skilled in their interactions with patients. This will in turn lead to a greater level of competency and education among all prenatal providers. Understanding these factors will help streamline patient interaction with the most benefit to the patient. %D 2016 %K genetic counseling, non-invasive prenatal testing, cell-free fetal DNA %I University of Pittsburgh %L pittir27508 %A Chunyan Wang %T Nonparametric estimation of the association between liver transplantation waiting time and posttransplant graft failure %X Liver transplantation is the most effective treatment for patients with end-stage liver disease. While many factors are associated with posttransplant graft failure, it has been suspected that liver transplant waiting time is negatively associated with posttransplant survival. Due to the suspicion, efforts have been made to reduce wait time for patients. There were some studies investigating this relationship recently. However, these studies were performed either with restricted samples or using data from a single center, and the results were inconclusive. For example, a study showed that after the Model for End-Stage Liver Disease (MELD) era, a longer waiting time predicts longer posttransplant survival for adult patients with hepatocellular carcinoma, whereas another study found no significant relationship between waiting time and posttransplant survival. In this study, we quantified the time-varying association (time-varying odds ratio) between liver transplant waiting time and posttransplant mortality in the presence of retransplantation as a competing risk. We also applied two different methods to estimate the cumulative incidence of posttransplant mortality. In the first method, the univariate cumulative incidence function method, we assume independence between the liver transplant waiting time and posttransplant survival. The second method, the bivariate cumulative incidence function method, takes into account the association between transplant waiting time and posttransplant survival. Our analytic dataset was extracted from the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) database. The subjects in our study included 1,265 transplant candidates who were first on the liver transplant waiting list from 2002 to 2012 and were 1-11 years old. Our analysis showed that liver transplant waiting time is positively associated with posttransplant survival. Further investigation is needed to understand whether this finding was because of survivor bias; that is, those who were able to wait longer were healthier. Our analysis also indicated that retransplantation has a weak association with liver transplant waiting time. PUBLIC HEALTH SIGNIFICANCE: We applied two different methods to pediatric liver transplant data in estimating cumulative incidence of posttransplant mortality. The findings will be the first step to help the liver transplant community understand the impact of liver transplant waiting time on posttransplant survival, and will help researchers further identify indicators of liver transplantation for reducing posttransplant mortality thus have a significant impact on future public health research. %D 2016 %K Liver transplant; Successive events; Competing risks; Cumulative incidence function; Odds ratio %I University of Pittsburgh %L pittir27353 %A Sally Caine Leathers %T Obesity uncovered: diagnosis without treatment in plans offered on the 2015 health insurance marketplace %X Background: Obesity is a public health problem that currently affects more than one-third of American adults. The Patient Protection and Affordable Care Act (ACA) requires all private health plans to cover diagnostic screening and counseling for obesity. However, the ACA does not guarantee access to effective treatment for obesity. Objective: To examine the health plans sold on the 2015 Health Insurance Marketplace (Marketplace) by describing the coverage and access barriers for surgical and non-surgical treatments for obesity. Methods: Using data from the 2015 Marketplace Public Use Files that consist of a census of all health plans sold on the 2015 Marketplace in 37 states, which excludes plans sold on the 14 State-based Marketplaces. Descriptive statistics are employed to characterize the plans? coverage, exclusions, limitations, and out-of-pocket costs for bariatric surgery (surgical category), dietician services, nutritional counseling, gym access, gym membership, gym membership reimbursement, and weight loss programs (non-surgical category). Results: Bariatric surgery was covered by 30.4% of plans. Of these plans, over one-third applied a limit on the coverage amount. Of the plans covering bariatric surgery with a copayment, 60.3% of these plans had a copayment of $1,000 or more. In contrast, the non-surgical treatments were covered by more than 80% of plans. Of these plans with a copayment, 71.6% had a copayment between $1 and $49. Of the plans covering treatments in the surgical or non-surgical categories, coinsurance rates were more prevalent than copayments, with almost two-thirds of plans having a coinsurance rate of 50% or more. Conclusions: A majority of plans on the 2015 Marketplace covered non-surgical obesity treatments. However, bariatric surgery, the treatment that results in the greatest amount of weight loss, was covered by less than one-third of plans. Furthermore, bariatric surgery, even when covered, may be less accessible to patients with a Marketplace plan due to high cost sharing and limits on the coverage amount. This study is significant to public health because it provides an early description of the coverage and access barriers to obesity treatments available to Marketplace enrollees, highlighting the importance of promoting policy that expands coverage of and access to obesity treatments given the high prevalence of obesity in the U.S. %D 2016 %K obesity, Health Insurance Marketplace, Marketplace, and health insurance %I University of Pittsburgh %L pittir27285 %A Stephanie Pikula %T Observing the effects of an educational intervention on MRSA screening compliance in an acute healthcare facility %X BACKGROUND: Healthcare-associated infections, particularly methicillin-resistant Staphylococcus aureus (MRSA), have been an on-going public health problem for several years. Cases of MRSA are often missed due to non-compliance with MRSA screening procedures, which has been attributed to many factors. However, one of the most influential factors is a lack of knowledge regarding screening. Therefore, it is important to consider the benefits of providing education to physicians regarding MRSA screening. METHODS: A total of 34 primary care physicians (PCPs) at Western Psychiatric Institute and Clinic in Pittsburgh, PA were identified as the PCPs mainly responsible for swabbing incoming patients for MRSA. An intervention was developed that highlighted the appropriate swabbing procedure and MRSA surveillance measures, as well as a form of acknowledgement that the PCPs were required to sign and return to confirm that they participated. Baseline data of patients? swab status was collected for one month before the intervention. Following the intervention, swab status data was collected for one and a half months. RESULTS: Of the 34 PCPs that were contacted for the study, 18 returned the form of acknowledgement. In order to determine if the intervention was effective, compliance rates were calculated for each month. The baseline compliance rate was 66.67%. After the intervention, the first month?s data yielded a compliance rate of 74.07%, and the remaining half month of data yielded a compliance rate of 80%. CONCLUSION: An educational intervention regarding MRSA screening had a significant impact on screening compliance. This suggests that with regular interventions, compliance could continue to improve and in the future, regular educational interventions should be considered in healthcare settings in order to promote screening compliance. %D 2016 %K methicillin-resistant Staphylococcus aureus, MRSA, educational intervention, intervention, education, acute healthcare facility %I University of Pittsburgh %L pittir27863 %A Zhongying Xu %T Optimal sample size determination in adaptive seamless phase II/III design %X The adaptive seamless phase II/III design combines the conventional separate phases II and III trials into a single trial, and it allows for adaptations (e.g. sample size reassessment and early stopping for futility or success) after the interim analysis. In this study, we propose a simulation-based method to determine the optimal sample size for the adaptive seamless phase II/III design. We assume that a power law relationship exists between the overall sample size and statistical power of the final test. The optimal sample size is defined as the minimum sample size that provides adequate power with overall type I error rate under control. To find the optimal size, we also take correlations between the early and the final outcomes into consideration. The methodology is applied to determining sample sizes in a study for a candidate treatment that can avoid renal damage during cardiac operations while the most effective dose of the treatment will be selected at the interim analysis. PUBLIC HEALTH SIGNIFICANCE Adaptive seamless phase II/III design eliminates the time between the traditional separate trials and better utilizes the data collected before the interim analysis, thus will result in faster clinical trials. Treatment effect can be confirmed at the final test if adequate power is achieved and the overall type I error rate is under control. Using these faster clinical trials, effective treatment can be approved sooner to benefit more patients. In addition, in an adaptive seamless phase II/III design more patients will be allocated to the more effective treatment than they would in conventional clinical trials. %D 2016 %K adaptive seamless design; closed testing principle; combination test; sample size determination; treatment selection %I University of Pittsburgh %L pittir27481 %A Kristin F Gambin %T Patient experiences at a high-risk pancreatic cancer clinic: A thematic analysis of focus groups %X Pancreatic cancer is a rare, occurring in less than 2% of the population, but high mortality disease with a survival rate of less than 6%. Approximately 5-10% of pancreatic cancer is due to a hereditary predisposition. A hereditary predisposition may be due to a pathogenic variant within a gene related to cancer syndromes, or some individuals may also be at risk due to having two or more first-degree relatives or three or more close family members who have been diagnosed with pancreatic cancer, which is considered Familial Pancreatic Cancer. This study focuses on these individuals who are at an increased risk of developing pancreatic cancer and their caregivers. The goal of this study is to identify patients? experiences at a high-risk pancreatic cancer center in Pittsburgh, Pennsylvania, and their experiences of living with a family history of pancreatic cancer. Participants of the larger Pancreatic Adenocarcinoma Gene Environment Risk (PAGER) Study and their caregivers were invited to attend one of two focus groups where they were able to provide their opinions and comments about the clinic and their feelings of living with an increased risk of pancreatic cancer. Transcripts of the focus groups were analyzed by qualitative thematic analysis, which identified five major themes. The main themes identified were: 1. Attributes study participants noted about the clinic staff; 2. Barriers individuals faced to receiving care; 3. The fear participants described related to being at an increased risk to develop pancreatic cancer; 4. The family dynamics surrounding the increased risk for pancreatic cancer; and 5. Areas of improvement identified by participants for the clinic and pancreatic cancer research in general. The results of this study identified overwhelming satisfaction with the UPMC High-Risk Pancreas Clinic and the care that is provided to the patients in the clinic. Public Health Significance: This study has public health significance because it has been shown that patients who are satisfied with their care experience better health outcomes. %D 2016 %K Pancreatic cancer focus groups thematic analysis high-risk cancer %I University of Pittsburgh %L pittir27442 %A Ifeoma Okafor %T Perception of patients and healthcare workers (HCWS) of contact precautions (CP) for multidrug resistant organisms (MDRO) %X Background: Contact precautions (CP) for multi-drug resistant organisms (MDRO) have and continue to be a controversial topic in the health-care setting. To control the spread of such organisms within hospitals, interventions involving patient isolation or patient quarantine are utilized. The aim of this study was to evaluate the quality of care for patients under CP isolation as well as healthcare worker perception of modified CP control to ultimately decrease the risks that are encountered from CP and to provide a more effective CP policy that serves patients and healthcare workers better. Methods: A mixed method study within an academic University-affiliated medical system was conducted. Patient care perception and healthcare worker perception were evaluated qualitatively via surveys for eight weeks (June2015-August 2015) with all ICUs assigned to the same strategy. Data was collected using anonymous, self-administered surveys. Four different surveys were distributed between the two groups: 100 patients under CP as well as 100 non-CP patients. A total of 100 health care workers were divided into two sub-categories based on expertise: physicians and nurses and then individuals who specialize in infection control. Results: A total of 200 patients and 100 healthcare workers were interviewed for this study. Using qualitative contact analyses, the interview transcripts showed no significant difference in the quality of care for patients under CP compared to non-CP patients. The average rate for healthcare worker compliance with PPE was 40-70%. Healthcare worker perception of modified CP protocol was evaluated and showed that PPE does not inhibit or limit the quality of care they provide to patients under CP. If contact isolation were to be removed, majority would feel comfortable caring for patients with only the utilization of hand hygiene (HH). Conclusion: Patient care and satisfaction for those under CP was not limited compared to that of non-CP patients. Proposed changes in CP protocol coupled with the comprehensive data collection detected no significant changes in MRDO acquisition and infection. This is important to public health because modifying CP protocol could facilitate and make the work of health care workers more efficient. Further research needs to be done to determine the cost effectiveness as well as waste management (gloves/gowns) of CP to determine its overall usefulness that may inhibit or enhance these findings. (Sponsored by Infection Control Department and Quality Departments UPMC Hospital System) %D 2016 %K Contact Precautions, Multi-Drug Resistant Organisms, Healthcare Workers %I University of Pittsburgh %L pittir27504 %A Tomoko Fujii %T Physical activity, body composition, thigh composition and structural changes in the knees of older adults %X Osteoarthritis of the knee (knee OA) is a major cause of disability. The effect of physical activity and sedentary time on knee structural changes in older adults has not been established. Recent studies highlight the metabolic aspect of knee OA, but whether higher weight or metabolic mechanisms are more important is unknown. First, physical activity level was defined based on subjectively measured energy expenditure in total and for exercise in the Health, Aging and Body Composition Study. In older adults without knee pain, being lifestyle active or an exerciser was associated with two times higher odds of severe cartilage damage in the medial tibiofemoral joint compared with being inactive, suggesting vulnerability of knee cartilage to higher physical activity levels. In older adults with knee pain, those watching TV for ?7 hours/week had over two times higher odds of bone marrow lesion (BML) in the whole knee, and ?14 hours/week with 2.6 times higher odds of severe cartilage damage in the medial compartment compared with <7 hours/week. Next, body composition from DXA, and abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) areas on CT were examined. Higher appendicular lean mass rather than total body fat mass was associated with knee structural changes. Greater VAT area per weight was not positively associated with knee outcomes. Significant associations between greater SAT area and higher odds of knee structural changes found only in women were not explained by inflammatory markers, adipokines, or cardiometabolic risk factors. Lastly, thigh fat composition on CT and knee extensor strength were examined. Higher thigh density reflecting lower intramuscular fat, specifically quadriceps in men and hamstring in women, and higher knee extensor strength per quadriceps area in women were associated with lower odds of structural changes. Generally, no association with structural change was found for thigh intermuscular adipose tissue area or thigh SAT area. These findings support the importance of mechanical mechanisms rather than metabolic mechanisms. This dissertation has the important public health implication that weight control, good muscle quality and proper levels of physical activity are recommended for knee OA prevention and control in older adults. %D 2016 %K knee osteoarthritis, MRI, physical activity, body composition, intramuscular fat, older adults %I University of Pittsburgh %L pittir27306 %A Erin Winchester %T Physician knowledge and attitudes concerning breast cancer genetics %X The discovery of the breast and ovarian cancer predisposition genes, BRCA1 and BRCA2, has led to the development of lifesaving treatments and cancer risk reduction strategies in families who carry pathogenic variants. Genetic testing techniques have improved over the years and decreased in cost so that many who meet widely accepted testing guidelines based on family and personal histories of cancer are able to afford testing after appropriate counseling. It has been suggested that all women should be offered genetic testing for these genes, regardless of family or personal cancer history. To implement a population-based screening program, primary care physicians would need to know about the BRCA genes as well as understand how best to use genetic test results based on an individual?s medical history; these providers would also need to be willing to incorporate an additional service into their practice. A questionnaire was developed to assess the knowledge and opinions of individuals, within the UPMC network, in the medical specialties of obstetrics/gynecology and family medicine with regard to BRCA1/2 and offering BRCA1/2 testing to patients. The average number of knowledge questions that were answered correctly, across all 64 participants was 9.5 correct out of 13 questions, for an average score of 73.4%; only one individual correctly answered all 13 questions. The question that providers most often answered incorrectly concerned testing policies for variants of uncertain significance; only 29.8% (25/84) correctly answered that they would not test a patient for an unclear genetic finding that was found in a relative. With regard to what would motivate those surveyed to incorporate population-based BRCA1/2 testing into their practice, 70.2% (59/84) indicated that evidence-based professional society guidelines would be their greatest motivator, while only 4.8% (4/86) indicated they were not interested or motivated to offer BRCA1/2 testing to their patients. The results of this study will help to guide future educational programs for physicians as the BRCA genes are considered for population-based screening. The public health significance of this work is that the public will receive proper counseling and consistent care with regard to their BRCA testing, if physicians are trained properly. %D 2016 %K breast cancer, genetics, knowledge, physicians, population screening, BRCA1/2 %I University of Pittsburgh %L pittir27789 %A Amber Blackwood %T The Pittsburgh parks prescription: a school-based approach to preventing childhood obesity %X School-based, park-focused obesity prevention programs can be a creative solution to the rise in childhood and adolescent obesity rates in the last three decades. Studies have identified numerous physical and mental health benefits connected to physical activity and the outdoors. Several parks prescription programs have been developed and implemented to encourage youth to become more physically active by using their local parks. The Pittsburgh Parks Prescription (Rx) is a school-based pilot program delivered in two gym class settings in Pittsburgh?s Arsenal Elementary and Middle Schools. The program is significant to public health in its aims at increasing knowledge of local parks, desire to utilize park systems, and self-reported physical activity in parks. A review of successful school-based obesity prevention and parks prescription programs revealed a common ecological design. Interviews and small group discussions were held with key program informants to inform improvements for the Pittsburgh Parks Rx program. In response, proposed modifications were made to expand reach, increase flexibility, enhance sustainability, and integrate the Pittsburgh Parks Rx into existing programs. %D 2016 %K Childhood obesity, parks prescription, preliminary program evaluation %I University of Pittsburgh %L pittir27407 %A Laura Cross %T Population screening for hereditary cancer syndromes: opinions from Amazon Mechanical Turks %X The current standard of care in genetic testing for hereditary cancer syndromes is to offer genetic testing to individuals who meet certain criteria based on personal and/or family history of cancer. With the recent advances in testing technology, it has become feasible to consider genetic testing on a wider scale. There has been a debate by experts in the field of cancer genetics of whether the family history-based approach should be supplemented or replaced with a population-screening based approach. The purpose of this study was to examine the interest level and motivations of individuals in the general population for genetic testing of genes associated with hereditary cancer as well as identify psychosocial implications. This study surveyed individuals in the dominant market of crowdsourcing used by researchers in the academic setting, Amazon Mechanical Turks. The majority of the participants in this study (73%, n = 861) indicated that they would currently be interested in taking a genetic test for cancer. After this initial interest question, the participants were presented with six possible result scenarios. After the scenarios were presented, the participants were again asked a question regarding interest level in genetic testing for hereditary cancer. Of the 861 participants who answered this question, 40 (4.9%) of those who initially indicated an interest on having genetic testing for hereditary cancer at some point in life, stated that they would never take such a genetic test. This data suggests that the need for informed consent and patient understanding of the test is needed. The survey responses indicated a wide variety of emotional and psychological stresses may occur as a result of genetic testing and indicates the need for additional support and resources to be in place before the implementation of a population-screening program for any genes related to hereditary cancer. A population-screening program for hereditary cancer would be a public health intervention with the goal of identifying all mutation-carriers. However, there could possibly be serious medical, psychosocial, ethical and legal ramifications should such a program like this be implemented before more research and serious thought is given into the proper infrastructure. %D 2016 %K cancer, genetics, genetic testing, hboc, population screening, brca, hereditary cancer syndromes %I University of Pittsburgh %L pittir27860 %A Peng Liu %T Power analysis for stepped wedge trials with delayed treatment initiation and longitudinal measurements %X Stepped wedge trials (SWT) is a special type of crossover cluster randomized trials (CRT) in which clusters are randomized to initiate treatment at different points in time. This design is proposed for a future trial that aims to study the effectiveness of a population health management (PHM) intervention based on Electronic Health Record (EHR) among patients with CKD. This study will collect multi-level data with longitudinal kidney function measurements from patients nested within practices. There are two challenges in powering this trial: (1) existing literature to power SWTs focus on cross-sectional design and single level of clustering; and (2) patients enrolled in the EHR-PHM trial may experience delayed treatment initiation in which they receive treatment later than expected. The effect of delayed treatment initiation to power has not been discussed in the current literature. The goal of this thesis is to develop a simulation-based method for power and sample size analysis for SWTs with longitudinal outcomes and delayed treatment initiation. We assumed random effects mixed models to account for correlation introduced by multiple levels of clustering. Simulation parameters are acquired from preliminary EHR data and verified by nephrologists. We determined the power and sample size requirements with varying levels of delayed treatment initiation. We have found that delayed treatment initiation results in slight loss of power. The impact of varying levels of subject delay for a fixed time delay is similar to the impact of varying levels of time delay for a fixed subject delay. Simulation-based power calculation is a flexible and practical tool in designing SWT with longitudinal measurements. Public health significance: In clinical trials, the simulation-based power calculation method provides a practical and flexible approach for power calculation and sample size determination in designing SWTs with longitudinal outcomes while incorporating the effect of delayed treatment initiation. This method will be useful in the design of the EHR-PHM trial which could potentially improve care for and outcomes of high risk CKD patients. %D 2016 %K Stepped Wedge Trials, Power, Delayed Treatment Initiation, Longitudinal Measurements %I University of Pittsburgh %L pittir27501 %A Janet Truebig %T Prevalence of Neurocognitive Disorders and Potential Correlates in the Pitt Men?s Study Cohort %X Background: While people living with HIV (PLWH) are able to enjoy relatively good health due to the advent of combination antiretroviral therapy (cART), some aging HIV-positive individuals have demonstrated neurocognitive impairments which are not associated with other comorbidities. This condition, classified as HIV-associated neurocognitive disorder (HAND), has a spectrum of severity consisting of asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). Objective: The purpose of this study is to investigate the prevalence of neurocognitive disorders within the Pitt Men?s Study cohort, and identify correlating variables that could be potential risk factors for the disease. Methods: The Pitt Men?s Study is a sub-cohort of the Multicenter AIDS Cohort Study, and is a prospective study of gay and bisexual men. Neuropsychological impairment is diagnosed through the use of an algorithm developed by the HIV Neurobehavioral Research Center, which classifies disease based on an individual?s scores in a series of neuropsychological function tests. SAS Statistical Software 9.4 was utilized for data analysis. Results: There was no significant difference in frequency of neurocognitive disorders between HIV-negative and HIV-positive individuals. The rate of HAND in HIV-negative individuals was 31.89% while the rate in HIV-positive individuals was 31.82%. In individuals under 50 years old, ever having been infected with Hepatitis C virus was significantly higher in the neurocognitive disorder group than the normal group. Conclusion: There is no evidence of HAND in the PMS cohort; rates of neurocognitive disorder are higher in the HIV-negative group than expected. The only significant risk factor for neurocognitive disorder found in the cohort was Hepatitis C virus infection in individuals under 50 years old. Public Health Significance: Neurocognitive disorders have the potential to cause a reduction in quality of life. While there was no evidence of HAND in the PMS cohort, a large proportion of HIV-positive and HIV-negative MSM demonstrate neurocognitive disorders. This study may indicate a high prevalence of neurocognitive disorders in MSM due to an unknown risk factor. Further investigation is critical to identify risk factors of neurocognitive disorders. %D 2016 %K HIV neurocognitive MSM HAND %I University of Pittsburgh %L pittir26722 %A Yifeng Lu %T Prevalence, risk factors and outcomes of multidrug resistant Tuberculosis identified by GeneXpert MTB/RIF Assay in Bukavu, Democratic Republic of the Congo %X Background: Tuberculosis (TB) has been the top-ranked infectious disease in human history for a very long time. According to World Health Organization (WHO), Democratic Republic of the Congo (DRC) has been high HIV/TB co-infection burden area for decades. However, MDR-TB were underreported in DRC due to the incompetent healthcare infrastructure and the lack of diagnostic method. Method: This study aims to provide more epidemiological information on the prevalence of multidrug resistant tuberculosis (MDR-TB) infection identified by GeneXpert MTB/RIF assay, which is a new diagnostic method. The data were collected at the General Referral Hospital of Bukavu, DRC. Subject population was the suspected TB patients who visited the hospital of Bukavu, DRC. Retrospective analyses were done based on those data to identify risk factors. In addition, multiple statistical analyses, including multivariate logistic regression, Pearson Chi-square test were performed to investigate how the TB prevalence and treatment outcomes relate to risk factors and GeneXpert assay. Results: The Prevalence of all TB in the study population is 15.6% as identified by GeneXpert Assay. MDR-TB prevalence is 3.2% among the whole study population and 20% among TB positive subgroup. Logistic regression showed that previous TB episode and HIV known status are risk factors for developing MDR-TB. However, no risk factor for treatment failure was found in this study. Conclusions: GeneXpert Assay provided reliable TB and MDR-TB prevalence data in the resource limited area Bukavu, DRC. We noticed that MDR-TB prevalence from our study is significantly higher than national level, which suggests severe underestimation of MDR-TB burden in DRC. However, loss to follow-up of treatment outcome and high proportion of HIV status unknown are significantly affecting the data validity of this study. Public Health Significance: The control of MDR-TB in DR Congo requires diagnostic methods that are not only easy to implement in resource limited area, but also fast in turnaround time for both TB infection and drug resistance detection. GeneXpert MTB/RIF assay is an ideal test, but lack of field test. This study provides solid evidence of the performance of GeneXpert assay in the field as a solution of MDR-TB underreported issue. %D 2016 %K Tuberculosis; Democratic Republic of the Congo; Bukuva; HIV; Multi-drug Resistant tuberculosis; GeneXpert; %I University of Pittsburgh %L pittir27408 %A Melissa Knorr %T Promoting gender equality within family planning programs: An analysis of USAID projects %X Gender norms present barriers to contraceptive use and contribute to high rates of unmet need for contraceptives. In the developing world, complications arising from pregnancy and childbirth present the leading threat to the health and lives of women of reproductive age. Mortalities and morbidities resulting from unintended pregnancies are a significant public health issue. Meeting women?s need for contraception could prevent 53 million unintended pregnancies, 15 million unsafe abortions, and 90,000 maternal deaths each year. International family planning programs actively address gender inequality as a means of decreasing unmet need for contraception. The United States Agency for International Development conducts family planning and reproductive health projects in more than 45 countries and positions gender equality at the center of its development work. This paper is a gender analysis of 19 United States Agency for International Development projects initiated between 2009 and 2015, and is based on publicly available project reports and website descriptions. Projects are classified using the Gender Equality Continuum Tool, case studies are reviewed, and common approaches to promote gender equality are discussed. Key findings, limitations, and promising paths forward are presented. %D 2016 %K gender equality; family planning; reproductive health; international family planning; barriers to contraceptive use %I University of Pittsburgh %L pittir27333 %A Bess Wayburn %T Psychosocial impact of targeted exome sequencing on parents of chronically ill children %X Whole exome sequencing (WES) is a relatively new testing option, currently offered primarily in the pediatric setting, that is open to more uncertainty than single gene or gene panel testing. This uncertainty makes pre-test counseling challenging yet critical to ensure informed consent. Adaptation of counseling strategies for this type of testing requires a better understanding of parents' experiences throughout the WES testing process. However, the experience of parents of chronically ill children who have actually gone through the entire WES testing process has not been widely reported in the literature. Currently, analysis of exome test results at Children?s Hospital of Pittsburgh does not include the incidental findings that are typically reported in WES results (i.e. variants in genes that are not associated with the child?s present condition) and is, therefore, referred to as ?targeted exome sequencing? (TES). This study was designed to gain an understanding of the psychosocial impact on parents of the TES testing process for chronically ill children in order to improve test education, consent and results disclosure processes and to better help parents cope with the results. Semi-structured interviews were conducted with 11 parents of children who received targeted exome sequencing results and thematic analysis was performed on transcripts generated from the interviews. The experiences and opinions of parents whose children received positive, likely negative or uncertain results were analyzed, in order to develop a robust understanding of the full TES process. This study has Public Health significance because the results may contribute to the development of updated recommendations for optimizing informed consent and results disclosure for TES. %D 2016 %K whole exome sequencing; targeted exome sequencing %I University of Pittsburgh %L pittir27311 %A Hatem Kaseb %T Spheroid-enriched cancer stem-like cells as a model for targeted therapy in oral cancer with distal 11Q loss %X Oral squamous cell carcinoma (OSCC) has a poor prognosis due to multiple factors including local recurrence, distant metastasis and therapeutic resistance. Our laboratory has demonstrated that the ATR-CHEK1 pathway is a critical modulator of radioresistance in OSCC; we evaluated the effectiveness of targeted CHEK1 inhibition in OSCC cancer stem-like cells (CSLC). To this end, we analyzed CSLC properties and the effect of ionizing radiation (IR) and CHEK1 inhibition on CSLCs isolated from OSCC (parental) cell lines with and without distal 11q loss. The CSLCs, propagated in enriched serum-free medium, demonstrated stem-cell like characteristics including asymmetrical and symmetrical cell division, self-renewal, re-differentiation, colony forming capacity at extreme (limiting) dilutions, and radioresistance. CHEK1 inhibitors affected the functional CSLC properties, resulting in significant reduction in proliferation, survival, colony initiation, growth, migration. The most drastically affected CSLC property was extracellular matrix migration. As determined by dose-response curves, a drug level ?100-fold higher than the dose that was effective on parental OSCC cell lines was required to inhibit CSLC migration. Overall, our results suggest that distal 11q loss may predict radioresistance in CSLC; however, the CSLC response to IR-CHEK1 inhibition is not distal 11q loss-driven. CHEK1 inhibitors increase the radiosensitivity of oral CSLC as they do for OSCC cell lines. Thus, we propose that CHEK1 inhibition may be a useful adjuvant therapy for advanced and/or metastatic OSCC. PUBLIC HEALTH SIGNIFICANCE: Our results increased the understanding of cancer stem-like cells in oral cancers and establish these cells as a contributing factor to radioresistance that could be potentially reversed in as many as 25% of cancers by CHEK1 inhibitors. %D 2016 %K Oral squamous cell carcinoma, cancer stem-like cells %I University of Pittsburgh %L pittir27518 %A Michael Kujawa %T Understanding the neuropathogenesis of Rift Valley Fever using in vitro and in vivo models %X Rift Valley Fever Virus (RFVF) is a mosquito-borne pathogen found primarily within Africa that is capable of causing both human and animal illness. In humans, RVFV can cause different clinical diseases, with encephalitis being one of the more severe outcomes. In order to study the neuropathogenic mechanisms of RVFV, our laboratory developed the Lewis rat model. When exposed to RVFV via the aerosol route, Lewis rats develop a uniformly lethal encephalitic disease with neurological symptoms. The goal of this research study is to compare in vitro brain cell culture systems to the in vivo brain environment of rats infected with RVFV, further define the systemic (serum) and regional (CNS) cytokine dysregulation that occurs in infected rats, and explore the neuropathogenesis using an animal model. The results presented here demonstrate that SH-SY5Y neuronal cells and HBMEC cells were as permissive for viral replication as Vero E6 and BHK-21 cells, two cell lines that are defective in the antiviral response. The high permissivity of these cells for RVFV replication suggests both cell types may be targeted in vivo and play a role in disease progression. Cytokines produced from SH-SY5Y and HBMEC cells in vitro are similar to the cytokine storm produced in infected rats during the encephalitic stage of disease. MMP-9 may be a potential factor in compromising brain vasculature, and current studies are continuing to evaluate the effect of virus infection on blood brain barrier integrity. Experiments examining the blood brain barrier integrity in infected rats suggest that virus arrives in the CNS via the olfactory bulb prior to breakdown of the blood brain barrier. Taken together, the neuropathological route of infection appears to enter through the olfactory epithelium early after exposure and progresses directly into the brain tissue. The public health significance of this project is supported by the creation of a novel Rift Valley Fever in vitro neuronal model, as well as the exploration of the neuropathogenesis during infection that has previously been unknown. %D 2016 %K Rift Valley Fever Virus, RVFV, Encephalitis, SH-SY5Y, HBMEC, Neuronal Cells, MMP-9, Lewis Rats %I University of Pittsburgh %L pittir27497 %A Kelsey Leonard %T The association of selenium levels with markers of cardiovascular disease %X Background: Oxidative stress is a key precursor to atherosclerosis, endothelial dysfunction and arterial stiffness, which are three mechanisms of the progression of cardiovascular disease (CVD). Selenium (Se) is an essential mineral that comprises at least 25 selenoproteins in humans. Many of these selenoproteins play antioxidant roles that are crucial to arterial health and endothelial function. A 2015 meta-analysis of observational studies proposed that CVD risk is significantly decreased only within the narrow selenium range of 55 to 145 ?g/L. Methods: Data were previously collected from the Women and Infant Study of Healthy Hearts (WISH). Serum samples from this study were analyzed to determine Se concentrations using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The distribution of Se in this sample was examined as were linear and quadratic associations with carotid intima-media thickness (cIMT), pulse wave velocity (PWV) and flow mediated dilation (FMD). Sub-group analyses were performed to examine these relationships within and outside of the reported beneficial range of Se status. Results: Se concentrations ranged from 58 to 598 ?g/L, with a median of 172 ?g/L. No participants were deficient in Se, but 74% had selenium levels higher than 145 ?g/L. The distribution of Se was skewed left, so Se levels were natural log transformed for the analyses. Quadratic relationships between Se level and cIMT, FMD and PWV had better fit compared to linear relationships. There were no significant associations between Se status and cIMT (p=0.14), PWV (p=0.51) or FMD (p=0.51). There was a significant linear relationship between Se levels greater than 145 ?g/L and PWV (p=0.006). Conclusions: On average, the sample had good cardiovascular health and was relatively young to observe subclinical CVD progression. There may be an inverse association between selenium status and pulse wave velocity, a marker of arterial stiffness. This novel finding may lead to a greater understanding of the mechanisms of arterial stiffness, a major risk factor for CVD, which has great public health importance. %D 2016 %K selenium imt fmd pwv cardiovascular disease %I University of Pittsburgh %L pittir27885 %A Amy L. Ashbridge %T The impact of a theory-driven flu vaccine compliance communications campaign: a multiyear evaluation %X Achieving full participation in a flu vaccination program for health care workers remains a persistent challenge. While previous studies in the literature have looked at the theoretical background surrounding flu vaccination, few studies have looked at the efficacy and effectiveness of flu vaccination communications campaigns that have been used to encourage populations to become vaccinated. Over three years, a novel flu vaccine compliance communications campaign was developed and implemented at two pilot sites, Western Psychiatric Institute and Clinic of UPMC (WPIC), and Magee-Womens Hospital of UPMC (Magee). Pilot sites received the intervention as a rolled-out approach, with UPMC Presbyterian Shadyside serving as a control arm for all three years of the intervention. In the third year of the program, a policy mandate was introduced across UPMC. Moderate increases compared to the initial baseline data, and then year-to-year increases within the individual hospital campus, were seen when a risk-based communications campaign was introduced at Magee and WPIC, with no significant changes when a social-norms component was added. In this population, a social-norms-based approach is unlikely to deliver measurable results with employee vaccination. The largest increases came during the final year of the policy mandate, with no significant changes across the three populations. This indicates that policy is the strongest influencer in employee influenza vaccination, but moderate increases can be achieved with the adoption of a risk-based approach to vaccine communications if such a policy is not feasible. Additionally, employees demonstrated greater engagement with communications materials when theory-driven campaigns were introduced, compared to employee response to communications materials used in the control hospital. This communications approach and campaign carries public health significance by shaping future campaigns and programs, and delivering lessons learned regarding application of motivators, related to routine influenza vaccination, and the expansion of vaccination to other HCW and general adult populations. By developing a novel practice that can be applicable toward a range of vaccination practices, this project carries public health significance in filling a gap toward best practices for encouraging vaccination when organizational or other mandates are not available. %D 2016 %K worksite health, influenza, vaccination %I University of Pittsburgh %L pittir27471 %A Katie Baric %T An overview of the multidimensional poverty in Honduras: gaps, barriers,and opportunities for growth %X INTRODUCTION: The Multidimensional Poverty Index (MPI) is a systematic measurement of the tools and resources an individual or a community has at its disposal to increase their public health capacity and promote Human Development (HD). This thesis seeks to describe the social, cultural, political, and governmental barriers to overcoming Multidimensional Poverty (MP) and to providing vulnerable populations with the necessary resources to reduce the burden of poverty and disease, particularly in the setting of rural Honduras. METHODS: This thesis provides a review of the extant literature on this topic, focusing specifically on systematic reviews and citation snowball sampling for each of the MPI indicators. The databases Pubmed, Google Scholar, and JSTOR were used. RESULTS: The ten indicators of the MPI are categorized into three main sections that are essential for poverty reduction: health, education, and standard of living. Health is measured by nutrition and child mortality, education is measured by years of schooling and attendance, and standard of living by sanitation, hygiene, floor, assets, cooking fuel, and electricity. Each of these components and subcomponents have adverse health effects as well as potential public health intervention strategies that have been evidentially supported in the literature. DISCUSSION: Solutions to improve each of the indicated dimensions of multidimensional poverty are holistic and multifaceted, and interventions that are targeted to only one dimension can have spillover effects and affect another dimension. The importance of well-rounded growth and development is absolutely essential for the elimination of MP, particularly for those in rural Honduras who many times fight against barriers like corruption and environmental duress. The sister parish mission between Nuestra Se?ora de Suyapa in Honduras and St. Michael the Archangel Catholic Church in North Carolina, USA, is an applied example of how a third party institution can reduce MP; a solution that deserves further exploration. CONCLUSION: There is plenty of evidence in the literature that suggests possibilities for reducing the MPI as measured by the indicators of health, education, and livelihood. While there are limitations to this thesis study design, it is apparent that, given one-fifth of Honduras remains in MP, the recommendations provided herein suggest intervention points that bear further exploration in the effort to reduce multidimensional poverty in Honduras. %D 2016 %K multidimensional poverty, human development, Honduras, Catholic Church, public health %I University of Pittsburgh %L pittir27858 %A Nikita Saoji %T The psychometrics of the children's depression inventory when used with children who are chronically ill and matched community comparisons %X The Children?s Depression Inventory (CDI) can be used to screen for childhood depression in children ages seven to sixteen. While the scale has exhibited reliability and validity with typically developing children, the psychometrics have not been examined in a large cohort of children who are chronically ill. The purpose of this study is to measure the psychometrics (reliability and validity) of the CDI when used with children who are chronically ill (N=350) and matched community comparison peers (N=357). This study endeavors to determine if the psychometrics of the CDI are similar in children who are chronically ill compared to children without a chronic illness. Data were aggregated from previous reports examining social and emotional functioning of children with six chronic diseases (cancer, sickle cell, hemophilia, juvenile rheumatoid arthritis, chronic migraine, and neurofibromatosis) and matched comparisons. CDI scores were collected in the homes of chronically ill children and in the homes of matched community comparison peers. Results showed no significant differences between groups on CDI scores, shapes of distributions, reliability, or validity. Findings suggest that the psychometrics of the CDI are similar for children with chronic diseases and typically developing children. The public health significance of this work suggests the CDI may be an effective screening tool for use in tertiary care pediatric settings, which could increase screening rates and improve mental health in children who are chronically ill. %D 2016 %K psychometrics, reliability, validity, CDI, depression, chronic disease, pediatrics %I University of Pittsburgh %L pittir27290 %A Ann Piccirillo %T The role of lipid transporter MFSD2A in innate and adaptive effector T cells %X Major facilitator superfamily domain containing 2a (MFSD2A) is a protein expressed by endothelial cells. It functions as a long chain fatty acid transporter, carrying fatty acids in the chemical form of lysophosphaditylcholine (LPC). It has recently been discovered that MFSD2A is the lipid transporter that carries docosahexaenoic acid (DHA) across the blood brain barrier into the brain. A role for MFSD2A in innate and adaptive T cells remains unclear. This is important to public health relevance because an understanding of how lipids are taken up and used during an activated effector T cell response is critical to fighting infection, immune disease, and even cancer. A search of the Immunological Genome Project (IMMGEN) Database reveals MFSD2A is upregulated in activated CD8 effector T cells exposed to Listeria monocytogenes, peaking at 12 hours post infection and decreasing over 48 hours. Preliminary microarray results of invariant natural killer T cells (iNKT), a form of innate cell, shows high upregulation of MFSD2A transcript upon in vitro activation with alpha-galactosylceramide. Results were validated using a real-time PCR approach in both activated iNKT and CD8 T cells. This was further supported by probing for MFSD2A protein analysis via western blot. In vitro activation studies using isolated CD8 T cells from C57BL/6 mice further support results by showing increased MFSD2A and LPC by flow cytometry analysis. Finally, a working in vivo congenic CD45.1 OT-I mouse infection model of Listeria monocytogenes tagged to OVA-peptide recapitulates IMMGEN findings as MFSD2A is higher expressed at 12-72 hours post infection compared to wildtype OT-I control mice. These data all support the claim that MFSD2A and LPC play a critical role for lipid metabolism within the innate and adaptive effector T cell. %D 2016 %K MFSD2A, T cells, NKT cells, LPC, immunology, lipid metabolism, T cell activation %I University of Pittsburgh %L pittir27218 %A Ashlee McKeon %T PHYSIOLOGICAL PREDICTORS OF BEHAVIORAL DYSREGULATION IN ADULTS WITH TRAUMATIC BRAIN INJURY: A NOVEL ECOLOGICAL MOMENTARY ASSESSMENT METHOD %X Each year in the United States 2.5 million people sustain a traumatic brain injury (TBI), making TBI one of the leading causes of death and disability. Difficulty self-regulating behavior is considered a hallmark deficit of TBI and can impede positive rehabilitation outcomes. Traditional clinic-based assessments with TBI cohorts are often compromised due to inaccurate self-reporting caused by self-awareness and/or memory challenges. This project developed out of the need for more adequate and objective assessment methods of behavior after TBI. The aim of this study was to identify physiological states that may serve as real world, real-time prodromes of behavioral dysregulation when compared to direct behavioral observation during task performance. Adults with TBI (N=14) were asked to complete a protocol of challenging, problem-solving tasks selected due to their potential to elicit negative responses believed to be indicative of dysregulation and result in task breakdown behaviors. Participants wore a portable biosensor band throughout the completion of all research tasks, which allowed for continuous physiological recordings of heart rate, breathing rate, and heart rate variability. Physiology was then synchronized with post hoc behavioral ratings conducted by trained clinicians from video recordings and analyzed through hierarchical linear mixed model methods to assess both between- and within-subject contribution related to the outcome. Testing was conducted at ReMed of Pittsburgh, a community-based brain injury rehabilitation program. This study was funded in part through the National Science Foundation?s Integrative Graduate Education & Research Traineeship (IGERT) Program in the Department of Rehabilitation Science & Technology and the School of Health & Rehabilitation Sciences Dean?s Research Development Fund, all at the University of Pittsburgh. %D 2016 %K behavioral dysregulation, self regulation, traumatic brain injury, ecological momentary assessment, physiology %I University of Pittsburgh %L pittir28182 %A Caitlin C. Corrigan %T The Politics of Privatizing Governance: The Political and Institutional Determinants of Corporate Social Responsibility in Africa %X Companies often go above and beyond business requirements to promote development in the communities where they work. These efforts are frequently thought of as philanthropic acts aimed at generating good will for a company. However, previous findings, and the findings from this study, show that company efforts to promote what is often termed corporate social responsibility (CSR) cannot really be considered fully voluntary or philanthropic. CSR is shaped by economic, normative and institutional circumstances where a company is headquartered and, as this research will show, the institutional and political contexts where a company operates. While political and regulatory pressure for CSR in developing countries has previously been considered low, this research demonstrates the ways in which formal and informal political institutions do actually influence the CSR process in the African context. This dissertation uses a comparative case study methodology to understand CSR processes. The case studies focus on comparing operations within mineral mining companies, using De Beers and Anglo Gold Ashanti (AGA) operations in three countries, Botswana, Ghana and South Africa. This is done in order to compare how CSR varies within an individual company, isolating the effect of operational location. The research is structured into three empirical sections based mainly on fieldwork in Southern Africa and CSR spending data collected from De Beers and AGA. In the first section, an adapted institutional analysis and development framework is used to display how initial conditions at mining locations, community attributes and national and local institutions influence the CSR processes at each mining operation. The second section examines the varying ways governments and politicians can control, influence or structure CSR. How these various forms of control effect CSR projects and spending is analyzed by comparing mining operations in Botswana, South Africa and Ghana and in South Africa over time. The final research section focuses on the role of local institutions in the CSR process and the importance of the relationships between communities, local governments and mining companies, drawing on fieldwork in South Africa and Botswana. %D 2016 %K Corporate Social Responsibility; Mining; South Africa; Botswana; Diamonds; Governance %I University of Pittsburgh %L pittir27665 %A Frances Loustau-Williams %T The Relationship Between Migration and Development in Morocco %X The relationship between migration and development can be volatile. While movement can lead to a more appropriate allocation of human resources within an economy, an unstable population distribution can lead to toxic concentrations of people. This is a potential risk factor as many people respond to the changes inherent to societal transformation through movement. As such, excess movement can disrupt the population distribution of a country. More comprehensive models of migration in developing countries are necessary in order to understand how rural populations are affected by development. The following study explores the relationship between migration and development in Morocco, with a particular focus on movement in the interior and predominantly rural areas. The analysis observes movement to small population centers in the rural areas. This observed phenomenon is henceforth referred to as ?rural urbanization.? A mixed methods, multi-level analysis was conducted. An initial geographically weighted regression was performed using macro-level data as to identify the variation unexplained by pre-existing models. The statistical analysis was followed up by a case study of an example of rural urbanization in a town called Guigou, located in the Middle Atlas Mountains of Morocco. A survey was conducted in order to identify the reasons people migrated to Guigou and from where they migrated. Finally, qualitative interviews with representatives of the various migrant types in Guigou were conducted. The analysis observes an emergent economy in a small town in the Middle Atlas Mountains that evolved over several decades, beginning with farmers travelling short distances to take advantage of job opportunities in the agricultural sector and improved social services. The data indicate that as the economy grew and diversified, more and more people were drawn to Guigou, engaging in a variety of non-agricultural jobs. Over time the migrants came from increasingly diverse backgrounds. These origins included a large proportion of people coming from the large cities. It is concluded that migration occurs incrementally based on relative positioning in economy, leading to heterogeneous outcomes. It is asserted that migration mirrors economic patterns and should thus be treated as a complex phenomenon. %D 2016 %K Migration, Development, Rural Development, Agrarian Transformation, Societal Transformation %I University of Pittsburgh %L pittir27954 %A Godfreyb Ssekajja %T State Stretch: Intrastate identities and the promotion of interstate integration %X In attempting to explicate why leaders of sovereign states promote inter-state integration (ISI), most literature emphasizes the economic benefits involved. But economic explanations are sometimes insufficient because regional unions not only involve economic losses; they are also eminently political constructs. Where political motivations are identified, the focus is on the distribution of power and the relative gains among states. Thus, these power theories cannot explicate why leaders of states that incur relative losses, and those that are less powerful, would promote ISI. In much of this literature, domestic conflict is largely ignored despite its usefulness in understanding the factors that shape policy preferences. Even in the analyses that point to domestic political processes, the focus is on economic and geopolitical interests. Therefore, certain crucial intrastate tensions that impact government decision-making are usually not identified. This thesis identifies one such tension ? ethnic sub-nationalism ? and attempts to establish its relationship to the promotion of ISI in Africa. Realizing the threat posed to state sovereignty when ethnicity is expressed in the form of sub-nationalism, I demonstrate how a threatened state?s leadership is more likely to promote ISI. My argument is that the need to discourage and replace a threatening subnational identity with a supranational identity causes the leadership to promote ISI. This allusion to the construction of social identities implies that the causal process is best contextualized within the constructivist theory. For evidence, I focus on Uganda and link Buganda?s ethnic identity to Museveni?s promotion of ISI in East Africa through congruence & content analyses of his speeches. By presenting Uganda?s ISI policy as an externalization of the country?s internal weaknesses, my research underscores the importance of examining threats to a state?s sovereignty from within in order to comprehend why that sovereignty is diminished from without. More crucially, I attempt to establish a causal link between the intrastate ethnic identities that threaten many African states and ISI promotion by the leaders of those states. However, my findings are largely exploratory and thus should be approached cautiously: they only provide an entr?e into a subject that, I hope, will be subsequently studied more profoundly. %D 2016 %K Inter State Integration (ISI), Pan-African identity, Ethnic identity, %I University of Pittsburgh %L pittir27675 %A Yven Destin %T Modifying Haitian Images in the Miami Media from 1979 through 2010 in Advent of Social Media %X This study analyzes the racialization of the immigrant Other in the American media by exploring the images of Haitians deployed in three different newspapers?Miami Herald, Miami Times, and Haiti-Observateur?that are directed to racially/ethnically distinct readers. I examine the positive and negative images of Haitians in these papers and trace their development over time. Specifically, I examine the reportage of Haitians over three events: the boatlift crisis of 1979, the AIDS epidemic crisis of 1983, and the earthquake of 2010. This study asks, is there an existing hegemonic view of Haitians in which race is a primary signifier in the American media? My study applies the concept of controlling images, the idea that racialized images are commonly deployed in the American media, to shed light on the production and reproduction of racism toward Haitians. This dissertation therefore sets out to investigate the presence, absence, and degree of racialized illustrations of Haitians among three newspapers in a city where many Haitian immigrants reside. My analysis reveals that before the 2010 earthquake, the controlling images of Haitians changed from negative to positive. Furthermore, the newspapers constructed and modified the controlling images according to racialized and political journalistic practices, especially after the earthquake because of social media. During the 1979 boatlift crisis and the 1983 AIDS epidemic, the mainstream newspaper, the Herald, offered more negative images of Haitians than the black newspaper, the Times, and the Haitian newspaper, Observateur. However, the Observateur mostly operated outside the racial framework of the American newspapers during these periods preceding the earthquake. After the 2010 earthquake, in an era of social media, the Herald changed its images of Haitians. The mainstream newspaper offered more positive images of this group than the other newspapers. During this time, the black newspaper reflected a reduced interest in race in the coverage of the Haiti disaster when compared to coverage of earlier crises. The Haitian newspaper was more closely engaged with the earthquake disaster, more than its coverage of the previous crises, though less engaged than the American newspapers. %D 2016 %K Haitians images media newspapers social controlling boat people AIDS Haiti earthquake victims grounded theory frames Atlas.ti Herald Times Observateur Miami Florida modified primitive polluted poor qualitative research stigma diaspora journalism journalistic practices race dictatorship national security coding %I University of Pittsburgh %L pittir27361 %A Eunjoo Yi %T ANALYSTS? ROLE IN M&A ANNOUNCEMENTS: THE MODERATING EFFECT OF ANALYST SCRUTINY AT THE EVENT-LEVEL %X Although much is known regarding the antecedents and consequences of analyst scrutiny, very little attention has been paid to how analyst scrutiny is stimulated in a firm?s announcement and subsequently influences the market response to the announcement. Adopting a behavioral perspective of analyst scrutiny in M&A context, I examine how analyst scrutiny moderates the effects of deal attributes on the market response to deal announcements. To test this moderating effect on M&A performance, I decompose analyst scrutiny into two levels: the firm-level and the event-level, and suggest that event-level scrutiny occurs based on specific event attributes. Treating deal-level scrutiny as event-level scrutiny triggered by a firm?s rich media use for an M&A announcement, I propose that deal-level scrutiny will magnify the effects of both value-positive and value-negative deal attributes on an acquirer?s market performance. A dataset of 783 M&A announcements by S&P 500 companies from 2005 to 2011 supported the moderating effect of rich media use only on the relationship between a negative deal attribute, such as relative deal size, and an acquirer?s performance, but not on the relationship between two positive attributes, cash payment for a deal and industry relatedness, and performance. %D 2016 %K M&A, Analyst scrutiny, Event announcement, Conference call %I University of Pittsburgh %L pittir28067 %A Yangyang Fan %T Auditor-client relationship, audit process and audit quality %X This study examines how the auditor-client relationship affects the audit process and audit quality. Chapter 2 examines the likelihood of auditor dismissal following financial statement restatements at companies where at least one of the audit committee members works on the audit committee of another company that is audited by the same audit firm (?AC-auditor interlocking?). Empirical evidence shows that companies with AC-auditor interlocking relationships are less likely to dismiss their auditors after a restatement occurs. Further evidence suggests that interlocking companies that retain their auditors after a restatement have lower subsequent audit quality compared to interlocking companies that dismiss their auditors. These findings raise concerns about the audit committee?s role in auditor termination when audit quality is relatively low and suggest that AC-auditor interlocking may impair audit quality. Chapter 3 explores the pricing and client acceptance strategies of audit offices following litigations related to clients? misconduct. Using a hand-collected sample of auditor litigation events, I find that audit offices involved in litigation increase their audit fees following the filing of the lawsuit. Further analyses indicate that the increase in audit fees charged by litigation offices is driven by clients? high switching cost and low bargaining power. I also find that both litigation and non-litigation offices of audit firms involved in litigation are less likely to have new engagements following the start of the litigation, and that new engagements of litigation offices after litigation are likely to be less risky than the new engagements before litigation. %D 2016 %K Auditor-client relationship, audit process, audit quality %I University of Pittsburgh %L pittir28063 %A James Gaugler %T Enzymatic Degradation of Carbon Nanotubes and Mechanical Separation of Carbon Nanocups %X In this work, single-walled carbon nanotubes and nitrogen-doped multi-walled carbon nanotubes are introduced and studied in the contexts of biodegradation and drug delivery, respectively. Single-walled carbon nanotubes have been shown to degrade in the myeloperoxidase enzyme system, and in Chapter 2, the mitigating effects of antioxidants and polyethylene glycol coating on nanotube biodegradation are examined. In Chapter 3, a simple method for the separation of nitrogen-doped multi-walled carbon nanotubes by grinding in a mortar and pestle is reported. %D 2016 %K carbon nanotube, nitrogen-doped carbon nanotube, nitrogen-doped carbon nanocup, bioddegradation, drug delivery %I University of Pittsburgh %L pittir26545 %A Daniel Burridge %T Movement Territories and Logics from Below: The Struggle for Critical Collaboration in El Salvador %X In this thesis, I use ethnographic research methods to interrogate the understandings, practices, and demands of four distinct social movements on the left in El Salvador's novel political context in which the leftist Frente Farabundo Marti para la Liberacion Nacional (FMLN) has been in control of the executive branch of government since 2009. I deploy the analytic frame of the ?movement territory? to reflect the localized and territorially contingent understandings of my research participants, as well as to capture the similarities and differences across geographically, socially, and ideologically diverse spaces in which movements act. I find that Salvadoran movements have employed diverse modes of interaction with FMLN-controlled state institutions that can be divided into three tendencies: emergence, pacification, and critical collaboration. In broad strokes however, I contend that movements on the left have been weakened in the post-war period by a neoliberal state logic that contradicts a community-based logic from below based on historical movement traditions (typically associated with, and coordinated by the FMLN) of community organizing, social solidarity, and militant public mobilization. Neoliberal state logic has also led to epidemic social violence, massive emigration, and the ?NGOization? of social struggle, factors which have further weakened movements on the left. Finally, the FMLN?s assumption of state power itself, and its instrumental use of social movements, has served to relegate movements to a marginal status in the current context. %D 2016 %K El Salvador, Social Movements, Latin American Studies, Community Studies, State and Civil Society, Neoliberalism, Movement Territories, Critical Collaboration %I University of Pittsburgh %L pittir26724 %A Mark Bender %T Strategic Platforms in the Digital Age %X Platforms, or intermediaries that serve two distinct user groups in a market, are becoming increasingly common in ecommerce and digital marketing since the advent of web 2.0. This dissertation examines the role of three platforms that facilitate marketing interactions between two distinct user groups. In the first essay, Daily Deal Websites as Matchmakers, I examine the role that daily deal websites (e.g., Groupon, LivingSocial) serve in matching consumers and vendors. Specifically, I am interested in how competition between multiple platforms may segment both sides of the markets and allow each daily deal website to play the role of matchmaker. However, I also show that segmenting both sides of the market is difficult and this may explain the demise of many of these websites. In the second essay, Crowdfunding as a Vehicle for Raising Capital and for Price Discrimination, I investigate an entrepreneur?s optimal decision to set instruments available in a crowdfunding (e.g., Kickstarter, Indiegogo) campaign (campaign goal and funder reward). I find that conditional upon market conditions, consumers? interest in the proposed product, and the entrepreneur?s need to fund the product through crowdfunding, that the entrepreneur may choose to set his instruments to either raise capital or to price discriminate. In the third essay, Setting Artist Royalties on Music Streaming Platforms, I investigate how a streaming platform (e.g., Spotify, Apple Music) may choose to set its royalty to attract artists to the platform. I explore when the streaming platform may choose to exclude high valuation artists. %D 2016 %K Marketing, Platforms, Game Theory, Crowdfunding, Daily Deals, Streaming %I University of Pittsburgh %L pittir28027 %A Gregory J Morgan %T The Use of Graphene and its Derivatives in Chemical and Biological Sensing %X Abstract A chemical sensor is defined as a transducer comprised of, or coated with, a layer that responds to changes in its local chemical environment. Chemical sensors convert various forms of energy into a measurable signal. For instance, the chemical energy involved with bonds breaking or forming can change the electronic properties of the transducer, creating an observable signal such as an increase or decrease in electrical resistance. Chemical sensing is important in many facets of research including environmental, bio-medical/pharmaceutical, industrial, automotive, and human safety. For a sensor to be practical it must interact preferentially with the target chemical analyte. A sensor should be precise, accurate, robust, cost efficient to manufacture, low in power consumption, portable otherwise the sensor is undesirable. Another key value of chemical sensors is it must exhibit rapid detection. Prior to portable sensors chemical analysis was performed in a laboratory on large, expensive instruments, which is costly in time, equipment fees, and personnel wages to operate. These sophisticated instruments are accurate and precise, however, it is far more beneficial to have a miniature, on-site detection apparatus. The first environmental, on-site sensor was used by the mining industry to monitor subterranean air quality; the canary. Carbon monoxide and methane (colorless, odorless gases) are large iv problems in the mining industry; smaller life forms are more susceptible to being poisoned by toxic gases. Today sensor constructs are far different from that of a canary, however, they serve the same purpose. Carbon nanomaterials such as graphene and single-walled carbon nanotubes and other derivatives prove to be of great importance in sensor research due to their unique electronic properties, and they?re high aspect ratio allowing them to be highly sensitive to small perturbations in local electronic environments. %D 2016 %K graphene, sensors, holey graphene, field-effect transistors, chemiresistors %I University of Pittsburgh %L pittir27255 %A Jamie L. Amemiya %T CORRELATES AND CONSEQUENCES OF FUTURE EXPECTATIONS AT THE TRANSITION TO ADULTHOOD AMONG HIGH-RISK ADOLESCENTS %X Little is known about how future expectations at the transition to adulthood are formed and whether these beliefs forecast young adult outcomes among high-risk adolescents involved in the juvenile justice system. Using a sample of 989 serious adolescent offenders (Mage = 15.96 years, SD = 1.13; 86.7% male), the present study examined (a) if there were distinct, multivariate profiles of future expectations at the transition to adulthood at 18 years (i.e., future expectations for educational attainment, occupational success, and law-abiding behavior), (b) the correlates (i.e., socioeconomic status, demographic, and social factors) of future expectations, and (c) whether future expectations mediated the relation between socioeconomic status and young adult outcomes (i.e., educational attainment, occupational attainment, and law-abiding conduct at age 21 years). There was no support for multivariate profiles of future expectations in this high-risk sample. Analyses that examined each domain of future expectations separately revealed that socioeconomic status was not a robust correlate of young offenders? future expectations in any domain. With respect to demographic correlates, males and ethnic minority youth reported lower expectations for adulthood success in comparison to their female and White counterparts. With respect to social correlates, higher parental expectations and greater bonding to teachers were associated with higher adolescent future expectations, although these relations varied by the domain of expectations. Finally, although there was not robust evidence that future expectations mediated the relation between socioeconomic status and young adult outcomes in any domain, both educational and law-abiding future expectations were associated with prospective outcomes in the respective domains, with educational expectations associated with educational achievements and law-abiding expectations related to antisocial behavior in early adulthood. %D 2016 %K future expectations, juvenile justice, transition to adulthood %I University of Pittsburgh %L pittir27688 %A Rongqian Ma %T CUI HU?S MURAL POEM AND ITS RESONANCE IN THE STORY OF ?RENMIAN TAOHUA?: A DIALOGIC ANALYSIS %X This thesis studies the poetry-story relationship with an analysis of Cui Hu?s?? poem and its resonance in the story of ?renmian taohua? ???? (Beauty and Peach Blossoms). More specifically, I discuss how a Tang Dynasty poem inspired the formation of ?renmian taohua? as a literary trope while various forms of adaptation of Cui Hu?s romance shaped the cultural implications of it from late Tang Dynasty to the present. First appearing in Benshi shi (Storied Poems) ???, a late Tang anthology of anecdotes edited by Meng Qi ??, Cui Hu?s poem was represented in a romantic story, which evolved into different genres across different periods. By tracing the evolution of the romance and particularly focusing on one drama adaptation by the playwright Meng Chengshun ??? (1598 ? 1684) in late Ming Dynasty, I argue that the interaction between poetry and story narratives contextualized a dialogic context where a ?collective memory? of the poem was shaped and represented in the form of a commonly used literary trope. Drawing upon Bakhtin?s notion of dialogism, I follow two threads in this study: one is the phrase ?renmian taohua? as a multi-cultural discourse of romance and women; the other is the significance of a poetic genre that was popularized in the Ming-Qing period, which I define as ?embedded poems? in this essay. %D 2016 %K Chinese Literature, Ming-Qing Poetry, Cui Hu, Renmian taohua %I University of Pittsburgh %L pittir27995 %A Kevin Soo %T Elemental Causal Learning From Transitions %X Much research on elemental causal learning has focused on how causal strength is learned from the states of variables. In longitudinal contexts, the way a cause and effect change over time can be informative of the underlying causal relationship. We propose a framework for inferring the causal strength from different observed transitions, and compare the predictions to existing models of causal induction. According to this framework, transitions where the cause and effect change simultaneously are the most informative about the underlying causal strength. The predictions of this framework are tested in an experiment where subjects observe a cause and effect over time, updating their judgments of causal strength after observing different transitions. The results are largely consistent with the proposed framework, showing that causal learning in longitudinal contexts relies on patterns of transitions ? a previously overlooked source of information from which causal strength can be learned. %D 2016 %K Causal learning, causal reasoning, time %I University of Pittsburgh %L pittir27642 %A Emily J. Braham %T INTERGENERATIONAL ASSOCIATIONS IN NUMERICAL APPROXIMATION AND MATHEMATICAL ABILITIES %X Although growing evidence suggests a link between children's math skills and their ability to estimate numerical quantities using the approximate number system (ANS), little is known about the sources underlying individual differences in ANS acuity and their relation with specific mathematical skills. To examine the role of intergenerational transmission of these abilities from parents to children, the current study assessed the ANS acuities and math abilities of 54 children (5-8 years old) and their parents, as well as parents? expectations about children?s math skills. Children?s ANS acuity positively correlated with their parents? ANS acuity, and children?s math abilities were predicted by unique combinations of parents? ANS acuity and math ability depending on the specific math skill in question. These findings provide the first evidence of intergenerational transmission of an unlearned, non-verbal numerical competence and are an important step toward understanding the multifaceted parental influences on children?s math abilities. %D 2016 %K math ability, approximate number system, intergenerational transmission %I University of Pittsburgh %L pittir27601 %A Regina Calloway %T Integrative and predictive processes in text reading: The N400 across a sentence boundary %X In the present study we used two experiments to test whether readers use integrative (retrospective), predictive (prospective), or both processes when reading words across a sentence boundary. We used Experiment 1 to determine whether prediction and integration could be measured as distinct processes. Response times (RTs) to determining whether probe words occurred in a previous sentence were measured. Critical probes were either high or low predictable words, given a context sentence. Both word types were easy to integrate, fitting well with the previous sentence. Results showed high predictable words had longer RTs than low predictable words, demonstrating that prediction and integration are distinct processes. In Experiment 2 we aimed to determine which processes were used when reading across a sentence boundary using event-related potentials (ERPs). The ERP component of interest was the N400, an indicator of semantic fit. We measured processing differences for high and low predictable words that were matched for integrability in sentence pairs. In a control condition, words were unpredictable and difficult to integrate. There was no difference in word processing (indicated by N400 amplitudes) between high and low predictable words across a sentence boundary. However, both word types were easier to process (reduced N400s) than control conditions. Findings show semantic overlap from word- and sentence-level activations facilitate integration in cross-sentence boundary reading. %D 2016 %K ERP, prediction, integration, text processing %I University of Pittsburgh %L pittir27256 %A Elizabeth M. Dahlburg %T Primary Amide Raman Vibrations as Environmental and Structural Markers of Glutamine and Asparagine Protein Side Chains %X UV resonance Raman (UVRR) is a powerful spectroscopic technique for the study of protein conformation and dynamics. Excitation at ~200 nm selectively enhances secondary amide vibrations, which are sensitive to the peptide backbone secondary structure and local environment. Primary amide bands are also resonance enhanced in UVRR spectra and could be used to report on glutamine and asparagine side chains in biophysical studies of proteins and peptides. IR absorption, visible Raman, and UVRR were used to investigate the small primary amide molecule propanamide. Dramatic spectral changes in the primary amide vibrations were observed upon aqueous solvation. Aqueous solvation impacts the dielectric and hydrogen bonding environment of the primary amide group resonance structures. This leads to a decrease in C--O and increase in C--N bond order of the primary amide group and therefore alters the resonance enhancement and vibrational frequencies of the primary amide vibrations substantially. Due to this significant response, several primary amide bands can be used as sensitive environmental markers for the glutamine and asparagine side chains. Visible Raman and UVRR spectra of L-glutamine and five derivative molecules, D-glutamine, N-Acetyl-L-glutamine, L-glutamine t-butyl ester, Glycyl-L-glutamine, and L-seryl-L-asparagine, were collected and assigned in the 950-1200 cm-1 region. The OCCC dihedral angle of each was determined from X-ray crystal structures. An empirical relationship between the AmIIIP vibrational frequency and the OCCC dihedral angle was observed. This dependence can be explained by hyperconjugation that occurs between the Cbeta--Cgamma sigma orbital and the C=O pi* orbital of the primary amide group. This interaction induces an increase in the Cbeta--Cgamma bond length. As the Cbeta--Cgamma bond length increases, the stretching force constant decreases, downshifting the AmIIIP band. Due to this sensitivity, the AmIIIP can be used as a structural marker diagnostic of the OCCC dihedral angle, such as in the side chains glutamine and asparagine in peptide and protein conformational studies. %D 2016 %K Raman, UV resonance Raman, glutamine, protein structure, side chain %I University of Pittsburgh %L pittir27554 %A Tammy Pappert-Outly %T Serum Troponin I levels and all cause mortality and incident myocardial infarction: analysis of the Pittsburgh veteran's healthcare system %X Cardiovascular disease (CVD) is the leading cause of death in both men and women. Although rates of CVD have declined, the overall number of people who will develop CVD is substantial. Given current demographic trends and the future ?silver tsunami?, the number of deaths due to CVD and incident CVD events will increase. Circulating levels of cardiac troponin have been shown to predict subsequent cardiac events. In addition, the predictive value of cardiac troponin I (cTnI) may extend beyond death and myocardial infarction. Most of the data come from observational studies of community dwelling subjects with relatively short follow-up period. It is important to systematically evaluate whether serum levels of cTnI predict CVD outcomes over the long term. In this dissertation, we evaluated a policy implemented at the Veteran?s Affair (VA) Healthcare System in Pittsburgh. This policy required that serum cTnI levels be drawn on all patients admitted to the hospital with pain between their ears and hips. After excluding patients who had an acute myocardial infarction or who died in the hospital, we identified 2901 patients with a serum cTnI level drawn in fiscal 2010. Follow-up continued for 365 days after their initial admission. Patients with elevated troponin I levels were more likely to die, odds ratio (OR)=2.31;95% confidence interval (CI), 1.52-3.52; to have a myocardial infarction, OR=5.46; 95% CI, 2.70-11.04; to develop heart failure OR=2.15;95% CI, 1.35-3.42; and left ventricular hypertrophy, OR=2.11; 95% CI, 1.18-3.77. The association with one year mortality was consistent in patients with and without acute coronary syndrome. We found no association with diabetes or hypertension. Serum cTn1 predicted chronic kidney disease in models that did not adjusted for baseline renal function, OR=2.06; 95% CI, 1.54-2.75. Given the public health importance of CVD, our results show the value in a single measure of troponin in predicting future CVD events over one year of follow-up.. Our results suggest that the Pittsburgh VA Health System should continue measuring troponin on these patients. Patients with elevated levels could be targeted for interventions aimed at preventing CVD events. %D 2016 %K Serum Troponin I, myocardial infarction, Pittsburgh Veteran's Healthcare System %I University of Pittsburgh %L pittir28252 %A Brendan Barstow %T Supporting Students? Research Writing in Psychology through Argument Diagramming %X Arguing for the need for a scientific research study (i.e. writing an introduction to a research paper) poses significant challenges for students. When faced with these challenges, students often generate overly ?safe? studies, or replications, or in contrast include no strong support for their hypothesis. Additionally, instruction on argumentation has been slow to integrate into scientific education and discourse. This raises the question?how can we support novice scientists in generating and defending high quality hypotheses? A long history of research supports the affordances provided by spatial representations of complex information, particularly in the sciences. More recently, argument diagramming? the process of spatially representing an argument by its component parts and their relationships? has gained traction in instruction for philosophy, social studies, and law. However, its effectiveness for supporting students in science is relatively untested. Additionally, many of these studies have focused on basic contrasts between diagramming and no diagramming. The purpose of these studies was to test the effectiveness of argument diagrams for supporting students? resear %D 2016 %K Science instruction, Writing instruction, Diagramming, Argument Diagramming, science education, psychology education, classroom study %I University of Pittsburgh %L pittir28012 %A Dylan Reilly %T TRANSCREATION: INTERSECTIONS OF CULTURE AND COMMERCE IN JAPANESE TRANSLATION AND LOCALIZATION %X This study looks at text-heavy examples of translated Japanese popular media, such as recent video games and manga (Japanese comics) to explore the recent evolution of Japanese-English translation and localization methods. While acknowledging localization?s existence as a facet of the larger concept of translation itself, the work examines ?translation? and ?localization? as if they were two ends of a spectrum; through this contrast, the unique techniques and goals of each method as seen in translated media can be more effectively highlighted. After establishing these working definitions, they can then be applied as a rubric to media examples to determine which ?translative? or ?localizing? techniques were employed in the translation process. The media examples chosen as case studies for this examination were selected on the merits of their specific interplays of ?translative? and ?localizing? factors, such as cultural authenticity versus commercial palatability, the values of unofficial translation versus official localization, and the impact of globalization on what is or is not ?translatable.? Ultimately, the goal of this project is not only to shed light on the varied motivations and methods of translating Japanese media, but to potentially provide a frame of reference for new efforts in bringing Japanese media to English-speaking shores: once these techniques have been clarified, they can be synthesized in novel ways to create more effective translations ? or localizations ? in the future. %D 2016 %K translation, localization, globalization, Japan, video games, anime, manga %I University of Pittsburgh %L pittir27683 %A Timothy Hogge %T Turning Crisis into Blessings: The Evolution of Japanese Culture Through Disaster %X The purpose of this thesis is to examine three major turning points in Japanese history and the evolution of Japanese culture as a result of disaster, as well as the evolution of disaster narratives. The 1923 Kant? Earthquake, the post-World War II era, and the 3.11 triple disasters will be examined to show not only how Japanese culture has evolved over time in response to these disasters, but also how some aspects of the culture have remained the same. The Kant? earthquake and the post-World War II years will be examined to give a historical context of the culture of disaster in Japan so as to show how they informed the narratives and culture that arose in the aftermath of 3.11. Responses from the government, the general population, cinematic, and literary responses to 3.11 will be examined in more detail than the other disasters since it is the main focus of this thesis. Using Jeffrey Alexander?s theory on the creation of cultural trauma, we will examine these disasters as socially mediated rather than purely psychological experiences shedding new light and new ways of thinking about the experience of disaster and the creation of cultures of disaster. %D 2016 %K Japan, Culture of Disaster, Fukushima, Kanto, Nuclear, Earthquake, Disaster %I University of Pittsburgh %L pittir28061 %A Wan-chun Huang %T The Voice of a New China: Democratic Behaviors in Chinese Reality Shows Super Girl and Happy Girls %X China?s media have long served the Communist Party?s political purposes, and China?s television has always been under government censorship. One of China?s first reality shows, Super Girl, showed too much of the ?democratic? idea according to the Communist Party, which then banned it in 2006. Nevertheless, the show, in effect, introduced the participatory audience, and Chinese audiences became consumers who not only actively sought new information but also actively participated in a given show. Now, because of today?s new media technologies and their convergence, the relationship between producers and consumers has been both reshaped and consolidated, empowering the rights of the participatory audience and spurring democratic ideas in Chinese society. The Chinese consumers nowadays are thus able to participate in both creating the media text and at the same time collectively making their own meaning in that text. Because of such an empowered audience, China?s reality shows have become a powerful platform and conduit that allow the voice of the Chinese people to be heard. Therefore, in this paper, I will examine four aspects of the Chinese reality shows in an era of ?media convergence?: first, the new relationship between China?s government and media producers; second, the intense cooperation between Chinese new media producers and consumers; third, the public voice created by new Chinese audiences on new media platforms on the Internet; and fourth, the limitations and possibilities of democratic participation in Chinese reality shows. %D 2016 %K China's reality shows; Democracy; Media convergence %I University of Pittsburgh %L pittir27684 %A Andrew J. Brown %T Development and Characterization of a Magnesium/Polymer Composite for Guided Bone Regeneration %X Every year in the United States, 2 million implant supported dental prostheses are placed in order to restore the functionality and cosmetic appearance of missing teeth. In over half of these cases, a bone grafting procedure must be performed to build the bony foundation necessary for implant survival. Unfortunately, the current gold-standard bone graft substitutes impart limited osteoconductivity and exhibit long degradation times leading to unpredictable outcomes. Thus, there exists a significant need for degradable dental bone graft substitutes capable of enhancing the bone regeneration process. The overall goal of this work was to design guided bone regeneration devices that address the limitations of current bone graft substitutes and barrier membranes. First, bone graft substitutes were synthesized from metallic magnesium (Mg) particles and poly-(lactic-co-glycolic acid) (PLGA) and subsequently characterized. These Mg/PLGA scaffolds were found to release magnesium at a controllable rate that ameliorated the acidic degradation profile of PLGA and enhanced bone marrow stromal cell proliferation in vitro. Next, we evaluated the Mg/PLGA scaffolds in a canine socket preservation model and found that the scaffolds increased bone height and bone volume regenerated relative to controls. Other groups have demonstrated enhanced osteogenic activity surrounding magnesium implants in orthopedic applications. However, the cellular mechanisms underlying these observations have not been well defined. Our next objective was to assess these cellular mechanisms in vitro, following exposure of bone marrow stromal cells (BMSCs) to varying concentrations of magnesium ion, simulating device degradation. We found that certain magnesium concentrations enhanced cell proliferation and matrix mineralization and impacted gene pathways associated with increased osteogenic activity. Finally, we designed and evaluated a Mg/PLGA barrier membrane and magnesium micromesh in a canine vertical ridge augmentation model which showed promise for a fully degradable and osteoconductive magnesium-based guided bone regeneration therapy. This work established the use of degradable magnesium devices for enhancing dental bone regeneration while expanding knowledge of the cellular mechanisms impacted by magnesium?s degradation. %D 2016 %K Magnesium, PLGA, Alveolar Bone Grafting, Guided Tissue Regeneration, Bone Regeneration, Tissue Engineering, Bone Substitutes, %I University of Pittsburgh %L pittir26714 %A Amy Chaya %T Development and Testing of Degradable Magnesium Alloys for Bone Fracture Healing %X Bone fractures are an extremely common injury, with over six million occurring each year in the U.S. Roughly one third of these fractures require internal fixation devices, such as plates and screws, to facilitate bone healing. Traditionally, internal fixation devices have been made with permanent metals like titanium alloys, which can cause long-term complications and even require surgical removal. To circumvent these problems, resorbable polymeric devices have been developed; however their mechanical limitations render them inadequate for many load bearing applications. Unlike permanent metals and resorbable polymers, degradable magnesium alloys provide a balance of degradation and strength. Recent investigations with magnesium alloys have begun demonstrating their promise as orthopedic biomaterials; however, additional work remains to fully assess their efficacy. For these reasons, we conducted in vivo studies to better understand the biological effects of magnesium degradation. To begin, two subcutaneous implant models were developed incorporating human stem cells and magnesium implants. Using these models, we measured gradual magnesium degradation, and observed human cells and osteogenic protein expression around the implant-tissue interface. These results supported subsequent assessments of magnesium as fixation plates and screws using an ulna fracture model. With pure magnesium devices, we observed gradual implant degradation and fracture healing similar to that of clinically-used titanium devices. In addition, we observed abundant new bone formation around the degrading magnesium devices. Interestingly however, when testing faster degrading magnesium alloy devices, we observed localized cortical bone loss. This dichotomy in observations emphasizes the biological sensitivity to magnesium implants based on their degradation rate and composition. Taken together, our results demonstrate preliminary efficacy of pure magnesium fixation devices and support their continued development; however, additional investigations should be conducted to fully understand the mechanisms of magnesium?s effect on bone biology and long-term safety. %D 2016 %K Magnesium, bone fracture fixation, degradable metal %I University of Pittsburgh %L pittir27304 %A Yuning Cao %T Examining the development of pragmatics of Chinese JFL students %X The field of interlanguage pragmatics has burgeoned since late 20th century. Requests, as a part of speech act theory, have been investigated by many scholars. This cross-sectional study explores the acquisition of pragmatics of Chinese learners of Japanese in foreign language contexts (JFL) by examining their request usages, which incorporates pragmatic transfer as a tool to interpret data. Discourse completion task (DCT) questionnaires were distributed to first-year, second-year and fourth-year Japanese learners at a university in China, as well as to native speakers in the U.S. to elicit requests. Requests were analyzed according to the following six categories: perspectives, speech levels, strategies, syntactic downgraders, semantic downgraders, and supportive moves. Based on data analysis, the preliminary findings are: 1) Significant improvement from the first- year group to the second-year group can be observed. 2) In general, the fourth-year group performed similar to or less native-like than the second-year group. 3) Regardless of the advancement, a gap still exists between learners and native speakers regarding pragmatics proficiency. The study not only sheds light on the evolution of learners? interlanguage from a perspective of pragmatics, but can also reveal part of the current teaching and learning situations of Japanese pragmatics at universities in China. By discussing learners' success and potential areas that need developing, the findings could provide some meaningful implications for Japanese pedagogy. %D 2016 %K SLA, pragmatics, DCT, requests %I University of Pittsburgh %L pittir28074 %A Eliot George %T Investigation of Variable Stiffness Based Polymer Morphing Structures %X Morphing structures have a multitude of potential applications in many engineering fields. Control surfaces for aircraft, pumps and valves for artificial organs or any application where a complex motion is required and can benefit from incorporating a morphing structure. The ability of a morphing structure to change its shape or configuration can potentially allow designs and functionality that would be impossible to realize without morphing. The focus of this thesis is to investigate the feasibility and operation of a structural shape morphing structure. Structural shape morphing is defined as shape change through material modulus changes. This allows fewer actuators, fewer moving parts and lower energy consumption to effect the same change in configuration as a traditional shape change structure. The morphing structure examined was designed and created specifically for this work and is composed almost entirely of polymer materials. The design utilizes electrical voltage to control the structural stiffness and motion of the structure independently. A review of literature covering fabrication and modeling in morphing structures, polymer actuators, variable modulus materials and variable stiffness structures is presented. A conceptual design for a shape morphing structure is fabricated and refined and an analytical model is developed for the structure to predict its response to applied voltages. The morphing structure?s capabilities are measured through experimental testing and the predictions of the analytical model are compared to the results. We demonstrate shape morphing by deforming the structure with an actuator, increasing the effective structural modulus and then removing the actuation force. Our tests show a fixed shape change in the structure of up to 20% of the total deformation. Feasibility is also discussed for real-world applications and suggested areas for further exploration on the topic are presented. %D 2016 %K Structural shape morphing, variable modulus structures, smart materials and structures, electroactive polymer materials and Ionomers %I University of Pittsburgh %L pittir25288 %A Kent Nixon %T Invisible Shield: Gesture-Based Mobile Authentication %X Intelligent mobile devices have become the focus of the electronics industry in recent years. These devices, e.g., smartphones and internet connected handheld devices, enable quick and efficient access of users to both business and personal data, but also allow the same data to be easily accessed by an intruder if the device is lost or stolen. Existing mobile security solutions attempt to solve this problem by forcing a user to authenticate to a device before being granted access to any data. However, such checks are often easily bypassed or hacked due to their simplistic nature. In this work, we demonstrate Invisible Shield, a gesture-based authentication scheme for mobile devices that is far more resilient to attack than existing security solutions and requires neither additional nor visible effort from user perspective. In this work, we design methods that efficiently record and preprocess gesture data. Two classification problems, "one vs. many" and "one vs. all," are then mathematically formulated and examined using the gesture data collected from 20 individuals. Classification algorithms specialized for each case are developed, achieving a classification accuracy as high as 90.7% in the former case, and an equal error rate as low as 7.7% in the latter using real Android systems. Finally, the system resource requirements of different classification algorithms are compared. %D 2016 %K invisible, shield, mobile, gesture, security, touchscreen %I University of Pittsburgh %L pittir27233 %A Hassan Awada %T Spatiotemporal Delivery of Complementary Proteins for Repair of the Infarcted Myocardium %X Ischemic heart disease is a leading cause of morbidity and mortality worldwide. After the onset of myocardial infarction, multiple pathologies develop and progress the disease towards heart failure. Pathologies such as ischemia, inflammation, cardiomyocyte death, ventricular remodeling and dilation, and interstitial fibrosis, develop and involve the signaling of many proteins. Therapeutic proteins can play important roles in limiting or countering pathological changes after infarction. However, they typically have low retention rate and short half-lives in vivo in their free form and can benefit from the advantages offered by controlled release systems to overcome their challenges. Protein-based therapies can be more effective when concerns such as spatiotemporal presentation, bioactivity, and retention are addressed. We tested the efficacy of controlled delivery of different combinations of cardiac-implicated proteins such as VEGF, HGF, PDGF, FGF-2, IL-10, TIMP-3, and SDF-1?. The controlled delivery of an optimal combination of proteins per their physiologic spatiotemporal cues to the infarcted myocardium holds great potential to repair and regenerate the damaged heart muscle. To address this issue, we developed a spatiotemporal delivery vehicle comprised of fibrin gel and heparin-based coacervates. Proteins that should be released relatively quickly are embedded in the fibrin gel, while proteins that should be released over a longer period are embedded in the coacervate and distributed in the same gel. This dissertation describes the process of developing the fibrin gel-coacervate composite for spatiotemporal delivery of therapeutic proteins and demonstrates its potential in triggering a significant cardiac repair process. It explores the ability of the coacervate to co-release different proteins, the development of the fibrin gel-coacervate system to achieve sequential delivery of different proteins, and the optimization of protein combinations and doses, paving the way for a potential comprehensive strategy to treat myocardial infarction. %D 2016 %K coacervate; fibrin; proteins; myocardial infarction; controlled release; growth factors; cardiac repair; angiogenesis; ecm; remodeling; heart; delivery system; spatiotemporal; fibrosis; cardiomyocyte %I University of Pittsburgh %L pittir27380 %A Marie Skoczylas %T ANARCHISM AND PREFIGURATIVE POLITICS IN THE OCCUPY MOVEMENT: A STUDY OF OCCUPIED SPACE, HORIZONTAL STRUCTURE, AND ANARCHIST THEORY IN PRACTICE %X Occupy Wall Street began on September 17, 2011, when hundreds of people with grievances regarding the current political and economic system in the United States, and inspired by the Arab Spring and anti-austerity protests overseas, occupied a park in the financial district in New York City. Over the next several weeks, Occupy groups formed in cities across the U.S. and around the world as tens of thousands of people joined the movement. Participants used horizontal organizing structures and carried out practices in the occupied spaces meant to deconstruct concentrations of power and forge new economic, political, and interpersonal relations. These approaches characterize anarchist theory in practice today. Anarchists established the Occupy model but the majority of participants did not identify with the philosophical tradition. Participants struggled with making the non-hierarchical structures work, and most occupations were evicted by winter 2012, foreclosing the possibility of using the spaces as laboratories for further social experimentation with small-scale solutions for societal transformation. However, the member-led, space-taking approaches of the Occupy model continue to inspire anti-austerity protesters today. In this dissertation, I examine what happens when a mass movement uses anarchist approaches. I interviewed 57 participants of the Occupy Movement in three cities: New York City; Pittsburgh, Pennsylvania; and Oakland, California. Analyzing conflicts revealed deep political disagreements among participants about the way society should work. I argue that participants must have political affinity and a commitment to the practices meant to enact shared values, including: a willingness to engage in ongoing experimentation, which requires a suspension of static, authoritative knowledge about the best way to struggle; a desire for harmony instead of unity; and an embrace of conflict as part of a culture that accepts a fluid and unstable existence, desiring liberation through continuous negotiation. I find both prefigurative and instrumental approaches were present and strategic, and that conflict centered on trying to maintain their co-existence. I challenge scholars? misrepresentations of anarchism, and examine what constitutes anarchism today, discovering it is better described as a balancing act between prefigurative aims and a desire for autonomy. %D 2016 %K Prefiguration, prefigurative politics, horizontalism, anarchism, anarchist theory, anarchist practice, occupation, Occupy Movement, Occupy Wall Street, Occupy Pittsburgh, Occupy Oakland, social movement %I University of Pittsburgh %L pittir27602 %A Burcin Simsek %T APPLICATIONS OF POINT PROCESS MODELS TO IMAGING AND BIOLOGY %X This dissertation deals with point process models and their applications to imaging and messenger RNA (mRNA) transcription. We address three problems. The first problem arises in two-photon laser scanning microscopy. We model the process by which photons are counted by a detector which suffers from a dead period upon registration of a photon. In this model, we assume that there are a Poisson (?) number of excited molecules, with exponentially distributed waiting times for the emissions of photons. We derive the exact distribution of all observed counts, rather than grouped counts which were used earlier. We use it to get improved estimates of the Poisson intensity, which leads to images with higher signal-to-noise ratio. This improvement is because grouping of count data results in loss of information. We illustrate this improvement on imaging data of paper fibers. Next, we study two variants of this model: the first uses a finite time horizon and the second considers gamma waiting times for the emissions. The second problem concerns the Conway-Maxwell-Poisson distribution for count data. This family has been proposed as a generalization of the Poisson for handling overdispersion and underdisperson. Because the normalizing constant of this family is hard to compute, good approximations for it are needed. We provide a statistical approach to derive an existing approximation more simply. However, this approximation does not perform well across all the parameter ranges. Therefore, we introduce correction terms to improve its performance. For other parts of the parameter space, we use the geometric and Bernoulli distributions, with correction terms based on Taylor expansions. Using numerical examples, we show that our approximations are much better than earlier proposed methods. In the last problem, we present a new application for Conway-Maxwell-Poisson family. We use the generalized linear model setting of this family to study mRNA counts. We then compare its performance with the existing methods used for modeling mRNAs, such as the negative binomial. This empirical model can be a good modeling tool for dispersed mRNA count data when a biophysically based model is not available. %D 2016 %K Greek alphabet %I University of Pittsburgh %L pittir27381 %A Yuko E. Wright %T THE ARTS OF THE GEISHA: UNRAVELING THE ARTISTIC TRADITIONS AND THE AESTHETICS OF IROKE THROUGH AN ANALYSIS OF THEIR MUSIC AND DANCE %X This dissertation investigates the aesthetic concept of iroke (roughly, sexiness or eroticism, but literally, the love-sex atmosphere) through the performing arts practiced by geisha: kouta (small songs) and koutaburi (dance of small songs). Historically, the geisha?female performing artists?came into existence by separating the arts (gei) from sex (iro). However, since they closely worked within the vicinity of theatres and pleasure quarters, they have been misinterpreted as sex workers rather than accomplished multi-talented artists. By studying kouta and koutaburi under two former geisha, Kasuga Toyo Seiyoshi and Asaji Yoshie, I found that such misconceptions are deeply rooted in what geisha embody and express through their arts? iroke. Drawing on my own experiences of geisha arts and through detailed analyses, I illustrate the expressions of iroke in kouta and koutaburi performances and delineate the nature of iroke aesthetics. By mastering iroke and performing arts associated with iroke, the geisha were able to pioneer a new field of performing arts as preservers, teachers, and headmasters. Positioning geisha arts and aesthetics at the core, I explore the meaning and value of arts as well as geisha?s raison d??tre in the modern Japan. %D 2016 %K geisha, japan, iroke, kouta, koutaburi, shamisen %I University of Pittsburgh %L pittir27723 %A Qinhao Zhang %T Adaptive Control for Solar Energy Based DC Microgrid System Development %X During the upgrading of current electric power grid, it is expected to develop smarter, more robust and more reliable power systems integrated with distributed generations. To realize these objectives, traditional control techniques are no longer effective in either stabilizing systems or delivering optimal and robust performances. Therefore, development of advanced control methods has received increasing attention in power engineering. This work addresses two specific problems in the control of solar panel based microgrid systems. First, a new control scheme is proposed for the microgrid systems to achieve optimal energy conversion ratio in the solar panels. The control system can optimize the efficiency of the maximum power point tracking (MPPT) algorithm by implementing two layers of adaptive control. Such a hierarchical control architecture has greatly improved the system performance, which is validated through both mathematical analysis and computer simulation. Second, in the development of the microgrid transmission system, the issues related to the tele-communication delay and constant power load (CPL)?s negative incremental impedance are investigated. A reference model based method is proposed for pole and zero placements that address the challenges of the time delay and CPL in closed-loop control. The effectiveness of the proposed modeling and control design methods are demonstrated in a simulation testbed. Practical aspects of the proposed methods for general microgrid systems are also discussed. %D 2016 %K Adaptive Control, MPPT, Medium Voltage Microgrid %I University of Pittsburgh %L pittir27409 %A Konstantin Tourkov %T Analysis of total solar efficiency of biomass, solar thermal, and photovoltaic technologies and evaluation of potential improvements via combination of the technologies %X This work examines several renewable energy resources on the basis of total solar energy efficiency and a detailed thermodynamic analysis of potential hybrid operation of several renewable energy technologies. The first part of the investigation focuses on creating a comparison between biomass, photovoltaic, and solar thermal renewable energy technologies alongside coal from the perspective of the energy pathway that originates from the energy received from the sun. This method accounts for the total energy pathway from the sun to electricity, as well as the energy investment required over the lifetime of a power plant. The second step in the investigation is an analysis of a combination of photovoltaic technology and solar thermal technology via the use of concentrated photovoltaic cells and an organic Rankine cycle. The organic Rankine cycle is optimized by examining several configurations and working fluids with the goal of achieving highest performance for a constant temperature operating range. The behavior of the combined system is then analyzed for potential improvements. A similar combination is then sought in the use of biomass gasification and solar thermal technology. A solar gasifier is proposed as the method of such a combination. A numerical investigation is carried out to more thoroughly examine the behavior of the solar gasifier. A CFD model is developed, utilizing a two-fluid approximation with reaction modeling for devolatilization, heterogeneous, and homogeneous chemical reactions. The results of the composition of product synthesis gas are compared to experimental work done by other groups. The final section of the investigation is focused on utilizing results from the aforementioned numerical investigation to examine a potential molten salt solar gasification plant that produces electricity via a solid oxide fuel combined with a microturbine. A second law analysis of the system is carried out and several configurations for the fuel cell/micro-turbine system are examined for improvements in performance under various operating pressures. An overall system exergy efficiency is established and potential improvements are identified. %D 2016 %K Organic Rankine cycle, photovoltaic, combined cycle, total solar efficiency, solar gasification, solid oxide fuel cell %I University of Pittsburgh %L pittir27426 %A Matthew Barry %T Analytical and Experimental Studies of Thermoelectric Devices and Materials %X Interest in thermoelectric devices (TEDs) for waste-heat recovery applications has recently increased due to a growing global environmental consciousness and the potential economic benefits of increasing cycle efficiency. Unlike conventional waste-heat recovery systems like the organic Rankine cycle, TEDs are steady-state, scalable apparatus that directly convert a temperature difference into electricity using the Seebeck effect. The benefits of TEDS, namely steady-state operation and scalability, are often outweighed by their low performance in terms of thermal conversion efficiency and power output. To address the issue of poor device performance, this dissertation takes a multi-faceted approach focusing on device modeling, analysis and design and material processing. First, a complete one-dimensional thermal resistance network is developed to analytically model a TED, including heat exchangers, support structures and thermal and electrical contact resistances. The purpose of analytical modeling is twofold: to introduce an optimization algorithm of the thermoelectric material geometry based upon the realized temperature difference to maximize thermal conversion efficiency and power output; and to identify areas within the conventional TED that can be restructured to allow for a greater temperature difference across the junction and hence increased performance. Additionally, this model incorporates a component on the numerical resolution of radiation view factors within a TED cavity to properly model radiation heat transfer. Results indicate that geometric optimization increases performance upwards of 30\% and the hot-side ceramic diminishes realized temperature difference. The resulting analytical model is validated with published numerical and comparable analytical models, and serves as a basis for experimental studies. Second, an integrated thermoelectric device is presented. The integrated TED is a restructured TED that eliminates the hot-side ceramic and directly incorporates the hot-side heat exchanger into the hot-side interconnector, reducing the thermal resistance between source and hot-side junction. A single-state and multi-stage pin-fin integrated TED are developed and tested experimentally, and the performance characteristics are shown for a wide range of operating fluid temperatures and flow rates. Due to the eliminated to thermal restriction, the integrated TED shows unique performance characteristics in comparison to conventional TED, indicating increased performance. Finally, a grain-boundary engineering approach to material processing of bulk bismuth telluride (Bi$_{2}$Te$_{3}$) is presented. Using uniaxial compaction and sintering techniques, the preferred crystallographic orientation (PCO) and coherency of grains, respectively, are controlled. The effect of sintering temperature on thermoelectric properties, specifically Seebeck coefficient, thermal conductivity and electrical resistivity, are determined for samples which exhibited the highest PCO. It is shown the performance of bulk Bi$_{2}$Te$_{3}$ produced by the presented method is comparable to that of nano-structured materials, with a maximum figure of merit of 0.40 attained at 383 K. %D 2016 %K Thermoelectric Device, Integrated Thermoelectric Device, Radiation View Factor, Geometric Optimization %I University of Pittsburgh %L pittir27214 %A jiapeng Qi %T Comparison of Effects of Mixing and Infiltration of Hydroxyapatite with Calcium Nitrate %X Aimed to enhance the release of calcium ions to promote the cell expansion and growth of HSCs, a controlled gradient of CaO close to the exterior surface is designed in this study by infiltration. To establish a comparison with infiltration, an experiment of direct mixing HA with CaO is also conducted. XRD result revealed that the extra CaO incorporated into HA caused the formation of tetracalcium phosphate (Tetcp), which played a significant part in the formation of a surface precipitate and weight gain of the samples during immersion of the samples in saline. Infiltrated materials that showed less Tetcp formation showed weight loss and less surface precipitation. %D 2016 %K Hydroxyapatite HA CaO mixing infiltration %I University of Pittsburgh %L pittir27564 %A Dariush Mohammadyani %T Computational Studies of Lipid Oxidation and Signaling %X Introduction: Lipid signaling refers to events involving lipid messengers that bind proteins, which in turn mediate the effects of these lipids on specific cellular responses. The identification of lipid messengers and mechanisms of their interactions with the target proteins are the main pillars of understanding lipid signaling. Lipids function as signals in two ways: (i) chemical modifications of lipids, and (ii) asymmetric distribution of lipids. Methodology: We utilized computational approaches, including molecular docking, molecular dynamics simulations and bioinformatics, to explore the mechanism of lipid signaling in several cellular pathways. Oxygenated (ox-)lipid signaling in anti-cancer immunity: Oxygenation is the major metabolic modification generating numerous new molecular species of lipids, which can be involved in signaling processes. The structural role of ox-lipids in lipid droplets (LDs) present in tumor environments was examined. The presence of polar oxygenated functional group(s) in oxygenated lipids (ox-lipids) resulted in to their localization in the LD surface. We then explored possible interactions of ox-lipids with the heat shock protein 70 (HSP70), one of the key-proteins in antigen-cross presentation. Our data revealed that HSP70 specifically recognizes the neutral ox-lipids on the LD surface leading to tight binding and deep penetration into the phospholipid monolayer of the LD. Lipoxygenase-driven phospholipid peroxidation signaling: we explored the catalytic and inhibition mechanisms of lipoxygenases (LOX?s), the main generators of ox-lipids in ferroptosis iv cell death. We revealed the mechanism of peroxidation of esterified fatty acid via LOX?s and provided a possible mechanism of inhibition of LOX?s, particularly by vitamin E?s. Lipid signaling due to asymmetric distribution of cardiolipin: The mitochondrial signature phospholipid, cardiolipin (CL), is asymmetrically distributed in the inner mitochondrial membrane. CL asymmetry is disrupted through a process called ?CL externalization?, which can be recognized by many proteins. We described the molecular details of cardiolipin interactions with cytochrome c and LC3, the key players of apoptosis and mitophagy pathways, respectively. The CL-binding site(s) on these proteins were identified. Our data suggested that the strong interactions of cyt-c/LC3 with CL-containing membranes lead to CL clustering. This clustering in turn induces a negative curvature on the membrane surface. %D 2016 %K Lipid Oxidation, Lipid Signaling, Computational Methods, Coarse-grained %I University of Pittsburgh %L pittir27219 %A Nicholas Kirsch %T Control Methods for Compensation and Inhibition of Muscle Fatigue in Neuroprosthetic Devices %X For individuals that suffer from paraplegia activities of daily life are greatly inhibited. With over 5,000 new cases of paraplegia each year in the United States alone there is a clear need to develop technologies to restore lower extremity function to these individuals. One method that has shown promise for restoring functional movement to paralyzed limbs is the use of functional electrical stimulation (FES), which is the application of electrical stimulation to produce a muscle contraction and create a functional movement. This technique has been shown to be able to restore numerous motor functions in persons with disability; however, the application of the electrical stimulation can cause rapid muscle fatigue, limiting the duration that these devices may be used. As an alternative some research has developed fully actuated orthoses to restore motor function via electric motors. These devices have been shown to be capable of achieving greater walking durations than FES systems; however, these systems can be significantly larger and heavier. To develop smaller and more efficient systems some research has explored hybrid neuroprostheses that use both FES and electric motors. However, these hybrid systems present new research challenges. In this dissertation novel control methods to compensate/inhibit muscle fatigue in neuroprosthetic and hybrid neuroprosthetic devices are developed. Some of these methods seek to compensate for the effects of fatigue by using fatigue dynamics in the control development or by minimizing the amount of stimulation used to produce a desired movement. Other control methods presented here seek to inhibit the effects of muscle fatigue by adding an electric motor as additional actuation. These control methods use either switching or cooperative control of FES and an electric motor to achieve longer durations of use than systems that strictly use FES. Finally, the necessity for the continued study of hybrid gait restoration systems is facilitated through simulations of walking with a hybrid neuroprosthesis. The results of these simulations demonstrate the potential for hybrid neuroprosthesis gait restoration devices to be more efficient and achieve greater walking durations than systems that use strictly FES or strictly electric motors. %D 2016 %K Neuroprosthesis, Functional Electrical Stimulation, Musculoskeletal Modeling, Nonlinear Controls, Optimal Control, Model Predictive Control, Dynamic Optimization %I University of Pittsburgh %L pittir27316 %A qiang zhong %T Development and Experimental Evaluation of a State Dependent Coefficient Based State Estimator for Functional Electrical Stimulation-Elicited Tasks %X Functional electrical stimulation (FES) is an application of low-level electrical current to the motor nerves to produce muscle contractions. FES-induced limb motion can be used to reproduce gait in persons with paraplegia. The biggest limitation of using FES for gait restoration is the rapid onset of muscle fatigue. Unlike FES, powered exoskeletons don?t suffer from this limitation but need batteries and large actuators to generate enough torque to restore gait motion. However, a hybrid neuroprosthesis that combines these two technologies may be a promising direction to achieve walking for long durations. Our ultimate goal is to develop a wearable hybrid neuroprosthesis that can be conveniently used in daily life. In order to use closed loop feedback control for a wearable walking hybrid neuroprosthesis, accurate estimates of lower limb angles need to be determined. This thesis presents a nonlinear estimator that utilized a single joint knee model to estimate the knee joint angle based on wearable sensors. Two inertial measurement units (IMUs) were used to measure kinematic data of the thigh and shank segments. A new class of state estimator called State-Dependent Riccati Equation (SDRE) based estimator was developed to estimate the knee joint angle during FES of the quadriceps muscle. The SDRE estimator is robust to uncertainties in the modeling and sensor bias/noise of the IMUs. To prove that the SDRE estimator is feasible for this application, it was compared with an Extended Kalman Filter (EKF) and a rotation matrix method (RMX). Each estimator's performance was evaluated using a rotary encoder, which was assumed as the true value of the joint angle. The error for each estimator was calculated through the root mean square error (RMSE), in which the experimental results showed that the SDRE estimator had the most accurate knee joint estimation with a mean RMSE of 1.77 degrees. The EKF and rotation matrix gave a mean RMSE of 2.04 degrees and 2.79 degrees, respectively. Further, a two limb joint angle simulation study was performed to explore the performance of the SDC estimator during multi-DOF limb movements. In another simulation, this novel estimator was combined with the synergy-inspired controller scheme for tracking control of hip and knee joint angles. A discussion on stability analysis of this estimator-controller scheme is also presented in this thesis. %D 2016 %K State-Dependent Riccati Equation, nonlinear estimation, IMU, EKF, FES %I University of Pittsburgh %L pittir27418 %A Diana M Lievano Ortegon %T Dynamics of rate-based separation methods for granular materials and the solid-liquid interaction %X Processing of granular materials is a costly endeavor that spans across a variety of industries ranging from pharmaceutical, food, and cosmetics to construction and metal extraction. Devices commonly used in granular processing however, lack a fundamental understanding of granular behavior - implementing outdated technologies based on heuristics. Separation units for dry mixture, in particular, are highly energy intensive and environmentally unfriendly. For wet or damp mixtures, less is understood about the liquid-solid particle interactions that govern mixture behavior, which has limited development of advanced separation units for wet mixtures in industry. The work herein implements discrete element method (DEM) simulations along with experimental work to present two energy-efficient (green), granular separation unit prototypes, designed to rationally exploit the properties of particulate materials that naturally result in segregation. This work also describes an analytical method that yielded a deeper and novel characterization of solid-liquid interactions among two- or three-particles simultaneously. Taken together, the work presented in this dissertation seeks to advance the current state of knowledge of solid-solid and solid-liquid interactions, and has furthered the development of rationale separation systems with applications in industry. Herein, segregation of granular mixtures with two newly developed systems was successfully demonstrated. Each prototype potentiates the effects of physical differences among particles to achieve separation via a kinetic differential, known as rate-based separation. In the first case, a passive separation system ? analogous to sieving ? was developed to successfully induce segregation among size-disperse granular mixtures, without being encumbered by issues with material accumulation or fouling. In the second case, separation of density-disperse mixtures was successfully demonstrated using a fluid coated vibrating system. The unique features of these systems make each an attractive option for further development as a unit operation in manufacturing settings, particularly given the rising interest in green technology. Further study of the rupture forces of complex liquid bridges is presented to advance the understanding of liquid-solid interactions in particle processing. Using a custom-built micromechanical force microscope, the rupture force of bridges conjoining two or three particles were analytically measured. Direct characterization of three-particle interactions in the funicular regime is a novel achievement. Results indicate that the maximum force and rupture distance are the effect of surface characteristics, straining mechanism and effective liquid volume. These insights may encourage new solutions to achieve wet mixture separation. This work utilizes powerful computational simulations and experimental methods to reveal novel insights of granular behavior, which drive innovation of new, rational separation devices that are attractive to industry applications. %D 2016 %K granular flow, rate-based separation, mixing, discrete element method, particle dynamics, capillarity, viscosity, lubrication, cohesion, pendular saturation, funicular saturation, liquid bridge rupture. %I University of Pittsburgh %L pittir26346 %A Yafei Wei %T ESTIMATION, MODEL SELECTION, AND RESILIENCE OF POWER-LAW DISTRIBUTIONS %X This thesis includes a series studies on power-law distribution, which is a widely used distribution in vast areas such as biology, economy, social science and information science. There are three parts in the thesis. The first part is parameter estimation of power-law distributions. We categorize variants of power-law distributions into six types. We proposed improvements on the estimation for some types, either decreasing bias or standard deviation of the estimates. We also proposed methods for some types if there is no corresponding estimation method yet. The second part is model selection between non-truncated and truncated power-law distributions. We evaluated both criterion based methods and test based methods on the model selection, by calculating sensitivity and specificity of each method from simulation studies. We also proved some properties of the calculation to extend the result of the simulation study with a particular parameter setting to more general parameter settings. The third part is exploring resilience of the power-law degree distribution of scale-free networks. We explored how the degree distribution changes if the network receives attacks to lose vertices and corresponding edges under random removal, normal curve removal and high degree removal strategies. We derived the form of expected degree distribution, which is not power law any more even one vertex is removed. We also conducted a simulation study by using goodness of fit test to see the validity of power law, which shows that power law is very resilient for random removal but fragile for high degree removal. We conducted simulation study to observe the change of parameters when the goodness of fit test shows that power law is a good fit. %D 2016 %K power-law distribution, parameter estimation, bootstrap, starting point, model selection, truncated, resilience, degree distribution, scale-free network %I University of Pittsburgh %L pittir27667 %A Jorge Tapia-Ortiz %T Educaci?n, comunidad y literatura: condiciones para la emergencia de una literatura ind?gena contempor?nea (caso br?ran-t?rraba en Costa Rica) %X In the last decade indigenous narratives and poetry in Latin America have received much attention. There has been a broader understanding and appreciation of the need to investigate the importance of indigenous development of literary studies. As a result, researchers have broken through pre-existing notions and beliefs that have kept indigenous narratives from becoming part of the literary canon. In many indigenous communities, individuals are taking charge of producing written works based on their rich oral traditions by becoming authors, translators and editors of a growing stream of literary and scholarly works published in native languages and Spanish (or Portuguese, in the case of Brazil). In recent years, the Br?ran-T?rraba community, in southern Costa Rica, has gone through a series of social changes aimed at gaining a better education to improve the structural conditions of their school and community. A reform of the education system also passed to improve conditions for the indigenous communities by giving autonomy to the elders and leaders to form and design their academic curricula more independently, allowing new experiences to fortify their culture by venturing in literary workshops. Here, I analyze the emergence of their writing related to the introduction of indigenous authors into the education system and how it triggers the creation of local literatures to promote and help create the emergence and recognition of these narratives. We proved that the role that literature and literary studies plays in this process is an important one with the publication of the first anthology of contemporary indigenous writers in Costa Rica, which is included in Chapter V. This anthology is the result of literary workshops where I used the methodological insights provided by Colombian sociologist Orlando Fals Borda, whose basic principle is to obtain the appropriate concepts and analysis from the actors involved to describe their actions. A second basic principle takes into account that the researcher himself inevitably becomes an actor in this study. The main goal with this work is to become an example to other researchers interested in indigenous communities and aid in the promotion of indigenous literatures and cultures. %D 2016 %K Educaci?n, literatura ind?gena, Costa Rica, Abya Yala %I University of Pittsburgh %L pittir27721 %A Mark Steger %T Enhancing microcavity polaritons for technological applications %X Microcavity exciton-polaritons, semiconductor quasiparticles that are a unique mixture of light and matter, are routinely used to study quantum many-body phenomena. Due to the light mass of the polariton, $\sim 10^{-4}$ times the bare electron mass, polaritons manifest noticeable quantum effects even at room temperature. As solid state systems, microcavity polaritons are generally robust and compatible with current semiconductor technology. Microcavity chips could be integrated into electronic or optical circuits. I present a demonstration of microcavity polaritons as an all-optical transistor, where the strong nonlinearity of the system leads to a change in the reflectivity for a signal light-ray from high to low. I also discuss the promise of using strongly coupled microcavities as low-threshold polariton lasers, which could replace traditional lasers in some cases. The last two decades have seen great strides in the material systems used in microcavities, even demonstrating strong coupling at room temperature. GaN, CdZnSe, organic semiconductors and more recently, MoS$_2$ have supported strong coupling at ambient conditions. This makes technological applications more promising. I present our current progress in this field. Also, the general quality of microcavities has advanced steadily over this time. I demonstrate that our long-lifetime polaritons persist for an order of magnitude longer than in similar samples. This opens up new regimes of study and technological application as these particles thermalize better and carry quantum coherence over macroscopic distances. %D 2016 %K Microcavity; Exciton-polaritons; Optical Switch %I University of Pittsburgh %L pittir26368 %A Holly A. Yanacek %T Feeling Differently at the Fin de Si?cle: Representations of Emotion and Cultural Change in German Literature, 1890-1901 %X This dissertation examines the representation of emotion in German literature of the fin de si?cle, which I identify as a period of rapid cultural change when emotional codes and social mores were disputed. Compassion, honor, shame, love, pride, and pity were topics of contested public and intellectual debate around 1900, and I argue that the renegotiation of these emotional codes happened in part through literary works and other media. Building upon Bakhtinian discourse analysis and informed by current history of emotions research, my dissertation contributes the theoretical concept ?heteropathia,? which I define as the co-presence of differing ways of feeling represented in a single literary work or cultural object. I propose a methodology of reading for heteropathia that considers three aspects of a novel: the narrative situation, the depiction of emotional styles, and the reference to theoretical models of emotion. Chapter 2 analyzes compassion and honor as emotional antipodes associated with different moral systems in Theodor Fontane?s Effi Briest (1895). Although the novel depicts honor as an emotional practice that has lost its relevance in late nineteenth-century society, it ultimately admits the need for both compassion and self-regulatory emotions. Chapter 3 examines the subversion of nineteenth-century gendered emotional imperatives of feminine shame and romantic love in Lou Andreas-Salom??s Fenitschka (1898). Fenitschka champions self-realization and validates alternate ways of feeling and gender roles, albeit not without admitting the difficulty in challenging familiar cultural narratives. Chapter 4 reads Thomas Mann?s Buddenbrooks (1901) as a critique of a range of emotions, from unreflective bourgeois pride to life-negating decadent sensibility, across four generations. Through its figure of the young writer Kai, who exemplifies both life-affirming pride and artistic sensibility, Buddenbrooks self-reflexively refers to its own mediation of emotions and thus highlights the role of literature in renegotiating emotions and social mores. I conclude that these three novels feature a heteropathic impulse that recalls the transitional status of the fin de si?cle. These works acknowledge emotional alterity yet resist embracing any way of feeling uncritically. Instead, they mediate between diverse affective perspectives and create spaces for critical analysis and dialogue. %D 2016 %K German realism; history of emotions; fin de si?cle; Theodor Fontane; Lou Andreas-Salom?; Thomas Mann %I University of Pittsburgh %L pittir27660 %A Hanju Sun %T First principles calculation of charged vacancy diffusion in nickel oxide %X We studied the diffusion of charged vacancies in nickel oxide (NiO) crystal using the first-principles calculation method. We determined the formation energy and migration energy of vacancies with various charge states in NiO. Detailed diffusion paths on atomic scale of various charged vacancies in NiO crystal were investigated. Further analysis about physical origin of charge-dependent vacancy diffusion has been done. Our results reveal that the number of electrons occupying defect level and defect level shift have an important impact on migration energy of the vacancy, especially for charged O vacancies in intrinsic NiO crystal. %D 2016 %K NiO; Vacancy; Diffusion; First-principles %I University of Pittsburgh %L pittir27315 %A Kevin Sapp %T From Bottom to Top: Identification to Precision Measurement of 3rd Generation Quarks with the ATLAS Detector %X The 3rd-generation quarks, bottom (b) and top (t), are recent additions to the Standard Model of particle physics, and precise characterization of their properties have important implications to searching for new physics phenomena. This thesis presents two analyses which use 4.6 fb?1 of pp collision data at ?s = 7 TeV collected by the ATLAS detector at the Large Hadron Collider (LHC) to measure their properties. The first is an analysis which measures our ability to identify jets originating from b quarks with machine-learning algorithms applied to simulated and real data, so the result in simulation can be corrected to match that in data. This measurement has implications for our ability to identify processes with b quarks in their final state; t quarks decay to a b quark and a weak vector boson W more than 99% of the time. The second analysis presented measures properties of the t ? Wb decay channel associated with phenomena not predicted by the Standard Model, through a set of effective couplings which preserve Lorentz covariance. The kinematic information of the final-state particles is used to construct an event-specific coordinate system, and probability density is estimated as a function of solid angle in these coordinates. A parameterization of the effective couplings is extracted via a novel unfolding method, finding their values consistent with the Standard Model expectation, contributing the first measurement of the correlation between the parameters, and improving on previous limits. %D 2016 %K LHC, ATLAS Experiment, Top Quark, b-tagging, Electroweak Physics, Heavy-flavor Physics %I University of Pittsburgh %L pittir26732 %A Sameer Damle %T Fundamental Study of the Mechanical Failure of Silicon Based Electrodes for Li-Ion Batteries Using a Novel Multi-Physics Computational Modeling Framework %X Li-ion batteries are the currently accepted flagship energy storage system with several cathode systems identified over the years. However, graphite has always remained the commercial anode material of choice. Silicon has been identified as the next-generation anode for Li-ion systems with a high theoretical capacity (4200 mAhg-1) compared to graphite (372 mAhg-1) and has been the focus of much research over the past decade. Silicon unfortunately, undergoes large volumetric expansion (312%) upon Li diffusion generating considerable diffusion-induced stresses. Presence of high stress leads to mechanical failure of Si resulting in capacity fade due to loss of electrical contact with the current collector impeding commercialization. The mechanical response of the electrode depends on the electrode properties comprising the active (Si) and passive components (current collector, mechanical supports). The objective of this thesis is to gain a mechanistic understanding of the interactions between the electrode components and their effect on the overall mechanical integrity of the Si based anode assembly, which can aid in the design of failure resistant, next-generation, high capacity anodes. To achieve this objective, a custom nonlinear finite element modeling software that can model coupled diffusion induced large elasto-plastic deformation of Si, surface electrochemical reaction kinetics and eventual mechanical failure response of the electrode system was utilized. This modeling framework is first used to understand the effect of passive components (current collector and Si-Cu interface properties) on the mechanical stability of an a-Si thin film anode system. To unlock the mechanisms behind the gradual interfacial delamination of the Si film from the underlying Cu current collector in an a-Si thin film anode system, a detailed parametric study is performed to analyze effect of the mechanical properties of the current collector and the Si-Cu interface on the delamination at Si-Cu interface. The knowledge gained from these studies is further bolstered by examining the mechanical stability of a-Si patterned thin film anodes upon insertion of a thin elastic buffer layer between a square Si thin film pattern and the current collector. Finally, the modeling framework is utilized to understand the effect of active material geometry in Si-carbon nanotube (CNT) heterostructured anodes. %D 2016 %K Li-ion battery, Silicon anode, Silicon thin film anode, Si-CNT heterostructured anode, Multi-physics modeling, Finite element method, Mechanical degradation %I University of Pittsburgh %L pittir27056 %A Shijing Luo %T Graphene-Polyimide Nanocomposite Piezoresistive Thin Film Device for Strain and Pressure Measurement %X In this thesis, piezoresistive thin film strain/pressure sensors made of graphene-polyimide (PI) nanocomposites with graphene concentration varies from 1.0wt% to 1.8wt% were fabricated, and their piezoresistive properties were characterized. The range of the graphene concentration is determined by percolation threshold theory, so the nanocomposites remain as semiconductors. The graphene-PI nanocomposites suspension were fabricated by blending method and was put into an ultrasonic water bath for a few hours to fully disperse the solution and avoid agglomeration of graphene nano-fillers. The graphene-PI nanocomposite thin film strain sensors were fabricated by depositing the suspensions on the polyimide substrate through a drop-on-demand piezoelectric inkjet printer, and electrodes were coated by sputter coater. The electrical impedance with respect to the strain that the nanocomposite thin films suffered under uniaxial tension and uniform pressure were monitored, and the gauge factor of these sensors under two experimental circumstances were calculated and compared. The respond of these strain sensor to pressure was also directly related. The temperature effect was evaluated, and the temperature coefficients of these graphene-PI nanocomposites devices were determined, and a feasible method to eliminate the temperature effect by temperature compensation was proposed. Finally, the most sensitive strain gauge represented by the largest gauge factor was found, proving that graphene-PI nanocomposites are superior materials than metals to fabricate high sensitive strain sensors, and inkjet printing technique is a desirable method to achieve this. %D 2016 %K Piezoresistive strain sensor, Graphene-polyimide nanocomposites,Inkjet printing technology, Gauge factor %I University of Pittsburgh %L pittir27461 %A DaShanne Stokes %T How an Entity Becomes a State: Tibet, Taiwan, Palestine, and the Quest for Recognition %X The question, ?Why are some entities politically recognized as states while others are not?? is central to the conflicts faced by the peoples of Tibet, Taiwan, and Palestine, and indeed the entire world. It is a question whose answer defines the contours of the international arena and helps to decide the rights, obligations, and fates of people everywhere. Despite the plethora of research on the state, however, little is known about how the political recognition of states may operate as part of a larger international recognition structure. Such unknowns raise questions about the outcomes faced by entities like Tibet, Taiwan, and Palestine. Why, for example, have Tibet, Taiwan, and Palestine achieved the varying levels of political recognition that they have? How and why did opportunities to politically recognize Tibet (1913), Taiwan (1971), and Palestine (1948, 1988, and 2012) as states emerge when they did? And is there any validity to claims that there have been ?missed opportunities? for Tibet, Taiwan, and Palestine to have been politically recognized as states? I address these questions using original comparative-historical data to conceptualize the ?opportunity structure for recognition? as an overarching framework by which to synthesize the theory and practice of recognizing states and would-be states. In this way, recognition or non-recognition are more than the outcome of the complex interactions between states, would-be states, the international system, and the sometimes-competing, sometimes-aligning interests and goals of each. I argue that ?opportunities for recognition? tend to emerge during times when political opportunities and state interests are in strong alignment, favoring an entity?s political recognition as a state. The patronage of strong states can be a critical factor in the emergence and success of opportunities for recognition, but such patronage is not strictly necessary or sufficient to generate opportunities for recognition or for those opportunities to result in widespread recognition. Additionally, the study finds that claims about missed opportunities for recognizing Tibet, Taiwan, and Palestine are without merit. %D 2016 %K political recognition, diplomatic recognition, Tibet, Taiwan, Palestine %I University of Pittsburgh %L pittir27209 %A Jing Zhang %T IN VIVO MONITORING OF NEUROTRANSMITTER SEROTONIN AND DOPAMINE IN THE STRIATUM OF FREELY-MOVING RATS WITH ONE MINUTE TEMPORAL RESOLUTION BY ONLINE MICRODIALYSIS COUPLED WITH CAPIILARY HPLC %X Dopamine and serotonin are widely studied monoamine neurotransmitters which are heavily involved in many physiological functions and pathological conditions. One of the methods used to investigate the normal or abnormal functioning of the monoaminergic systems is to monitor the extracellular dopamine and serotonin: normal and altered resting levels and neurotransmission process by using microdialysis coupled with high performance liquid chromatography (HPLC) system. Traditional microdialysis/HPLC systems are usually done offline with low 5-30 minutes temporal resolution. Here we developed an online microdialysis/HPLC system with one minute temporal resolution to monitor dopamine and serotonin in the striatum of freely-moving rats. One minute HPLC separations of dopamine and serotonin were achieved by using columns packed with sub-2 ?m particles, ultrahigh pressures and elevated temperatures. Parameters of the HPLC-electrochemical detection system were optimized towards high speed and high sensitivity. On-column preconcentration was taken into account in the overall optimization and it was found that column diameter played a key role in the optimization process. To control zone dispersion during solute transportation, capillary tubing (75 ?m inside diameter, 70 cm long) was used as microdialysis probe inlet and outlet. In vitro assessment by step function showed that the solute dispersion was well within one minute (46.4 s from -2? to 2?). In vivo monitoring of basal levels and fast changes of the extracellular serotonin in the striatum of freely-moving rats was performed. The longest monitoring lasted for 16.7 hours with one minute temporal resolution. The superior temporal resolution revealed dynamic details in response to stimulation by 120 mM K+ and fluoxetine intake. In vivo monitoring of the dopaminergic system with one minute temporal resolution was carried out with slightly altered HPLC conditions. Dopamine maximum release and stimulus K+ concentration showed exponential correlation before the threshold of spreading depression, 100 mM K+. Repetitive dopamine maximum concentration with a 4.5 ? 0.3 min time interval during the 20 minutes 120 mM K+ administration each represented a neuron depolarization process. Perfusing dexamethasone, a neuroprotective drug, enabled the increase of dopamine basal levels and the reduction of the frequency of complete neuron depolarization under the same stimulation conditions. %D 2016 %K serotonin, dopamine, microdialysis, capillary HPLC, online, temporal resolution %I University of Pittsburgh %L pittir26283 %A Erich Zorn %T INTEGRATED ANALYSIS AND INTERPRETATION OF MICROSEISMIC MONITORING OF HYDRAULIC FRACTURING IN THE MARCELLUS SHALE %X In 2012 and 2013, hydraulic fracturing was performed at two Marcellus Shale well pads, under the supervision of the Energy Corporation of America. Six lateral wells were hydraulically fractured in Greene County in southwestern Pennsylvania and one lateral well was fractured in Clearfield County in north-central Pennsylvania. During hydraulic fracturing operations, microseismic monitoring by strings of downhole geophones detected a combination of >16,000 microseismic events at the two sites. High quality traditional and geomechanical well logs were acquired at Clearfield County, as well as tomographic velocity profiles before and after stimulation. In partnership with the US Department of Energy?s National Energy Technology Laboratory, I completed detailed analysis of these geophysical datasets to maximize the understanding of the engineering and geological conditions in the reservoir, the connection between hydraulic input and microseismic expression, and the geomechanical factors that control microseismic properties. Additionally, one broad-band surface seismometer was deployed at Greene County and left to passively monitor site acoustics for the duration of hydraulic fracturing. Data from this instrument shows the presence of slow-slip or long period/long duration (LPLD) seismicity. In years prior to our investigation, lab-scale fracturing studies and broadband seismic monitoring of hydraulic fracturing had been completed by other researchers in unconventional shale and tight sand in Texas and Canada. This is the first study of LPLD seismicity in the Marcellus Shale and reveals aseismic deformation during hydraulic fracturing that could account for a large portion of ?lost? hydraulic energy input. Key accomplishments of the studies contained in this dissertation include interpreting microseismic data in terms of hydraulic pumping data and vice versa, verifying the presence of LPLD seismicity during fracturing, establishing important geomechanical controls on the character of induced microseismicity, and extensive data integration toward locating a previously unmapped fault that appears to have exhibited significant control over well stimulation efforts at Clearfield. %D 2016 %K Marcellus Shale, Microseismic, Fracture, Hydraulic Fracturing, Geomechanics, Slow Slip %I University of Pittsburgh %L pittir27687 %A Yuan Hu %T Improving Coordinated Traffic Signal Timing through Connected Vehicle Technology %X For coordinated traffic control systems of traffic signals, timing offset is an important parameter that should account for the effect of queued vehicles at signals, travel speeds between intersections and the roadway geographic characteristics. In order to improve coordinated signal timing in the short term, this dissertation research developed an approach to optimize timing offset based on queue length information that will soon be available from connected vehicles (CVs) in the near future. The benefits of this approach were measured in an urban street corridor network and a suburban highway corridor network using the simulation program VISSIM. The simulation results shows that using the queue measurements in signal retiming provided a better optimized signal coordination during the peak hours. Up to 21.6% less delay and 13.9% less stops when compared to the current signal retiming approach. Based on multiple runs of simulation under different connected vehicle market penetration rates, at least 60% penetration rate was required for this approach. %D 2016 %K Connected vehicle technology, Coordinated traffic signal system, Corridor network %I University of Pittsburgh %L pittir27309 %A Jie Guo %T Improving Reliability and Performance of NAND Flash Based Storage System %X High seek and rotation overhead of magnetic hard disk drive (HDD) motivates development of storage devices, which can offer good random performance. As an alternative technology, NAND flash memory demonstrates low power consumption, microsecond-order access latency and good scalability. Thanks to these advantages, NAND flash based solid state disks (SSD) show many promising applications in enterprise servers. With multi-level cell (MLC) technique, the per-bit fabrication cost is reduced and low production cost enables NAND flash memory to extend its application to the consumer electronics. Despite these advantages, limited memory endurance, long data protection latency and write amplification continue to be the major challenges in the designs of NAND flash storage systems. The limited memory endurance and long data protection latency issue derive from memory bit errors. High bit error rate (BER) severely impairs data integrity and reduces memory durance. The limited endurance is a major obstacle to apply NAND flash memory to the application with high reliability requirement. To protect data integrity, hard-decision error correction codes (ECC) such as Bose-Chaudhuri-Hocquenghem (BCH) are employed. However, the hardware cost becomes prohibitively with the increase of BER when the BCH ECC is employed to extend system lifetime. To extend system lifespan without high hardware cost, we has proposed data pattern aware (DPA) error prevention system design. DPA realizes BER reduction by minimizing the occurrence of data patterns vulnerable to high BER with simple linear feedback shift register circuits. Experimental results show that DPA can increase the system lifetime by up to 4? with marginal hardware cost. With the technology node scaling down to 2Xnm, BER increases up to 0.01. Hard-decision ECCs and DPA are no longer applicable to guarantee data integrity due to either prohibitively high hardware cost or high storage overhead. Soft-decision ECC, such as lowdensity parity check (LDPC) code, has been introduced to provide more powerful error correction capability. However, LDPC code demands extra memory sensing operations, directly leading to long read latency. To reduce LDPC code induced read latency without adverse impact on system reliability, we has proposed FlexLevel NAND flash storage system design. The FlexLevel design reduces BER by broadening the noise margin via threshold voltage (Vth) level reduction. Under relatively low BER, no extra sensing level is required and therefore read performance can be improved. To balance Vth level reduction induced capacity loss and the read speedup, the FlexLevel design identifies the data with high LDPC overhead and only performs Vth reduction to these data. Experimental results show that compared with the best existing works, the proposed design achieves up to 11% read speedup with negligible capacity loss. Write amplification is a major cause to performance and endurance degradation of the NAND flash based storage system. In the object-based NAND flash device (ONFD), write amplification partially results from onode partial update and cascading update. Onode partial update only over-writes partial data of a NAND flash page and incurs unnecessary data migration of the un-updated data. Cascading update is update to object metadata in a cascading manner due to object data update or migration. Even through only several bytes in the object metadata are updated, one or more page has to be re-written, significantly degrading write performance. To minimize write operations incurred by onode partial update and cascading update, we has proposed a Data Migration Minimizing (DMM) device design. The DMM device incorporates 1) the multi-level garbage collection technique to minimize the unnecessary data migration of onode partial update and 2) the virtual B+ tree and diff cache to reduce the write operations incurred by cascading update. The experiment results demonstrate that the DMM device can offer up to 20% write reduction compared with the best state-of-art works. %D 2016 %K NAND flash, error pattern, object-based interface %I University of Pittsburgh %L pittir26805 %A Bo Wang %T In Vivo Assessment of Lamina Cribrosa Microstructure in Glaucoma %X Glaucoma is an optic neuropathy that is the second leading cause of blindness worldwide. The disease is characterized by damage to the retinal ganglion cells, resulting in irreversible vision loss. While the exact pathogenesis remains unclear, damage due to glaucoma is believed to first occur at the lamina cribrosa (LC), a collagenous meshwork in the optic nerve head through which all retinal ganglion cell axons pass on their way to the brain. The mechanical theory of glaucoma postulates that elevated intraocular pressure deforms the LC, leading to a biological cascade resulting in retinal ganglion cell death. However, the interaction between intraocular pressure and glaucoma is complex; a substantial heterogeneity exists in the intraocular pressure at which a given patient experiences glaucoma. Recent studies have identified that perhaps intracranial pressure, which acts posterior to the LC, may play an important role in the disease process. Given the complex 3D microstructure of the LC, in vivo studies thus far have been limited to assessment of changes in its surface. However, because the axons are traversing through the entire volume of the LC, the axonal damage can occur at any level of the LC, rather than only at its surface. Therefore, full understanding of the damage caused by glaucoma requires systematic characterization of the 3D LC microstructure. In order to better characterize the 3D LC microstructure, we demonstrate here a novel automated 3D LC segmentation method that is reproducible and capable of accurately detecting the LC microstructural component. Using our segmentation analysis, we find in a primate model that the LC microstructure deforms according to both intraocular pressure as well as intracranial pressure, with significant interaction between the two. We then move to the translational aspect of our study to characterize the healthy LC in human eyes and identify a number of structural and biomechanical differences in the LC microstructure compared to glaucoma eyes. Our findings demonstrate that a novel automated 3D assessment of the LC microstructure is capable of 1) identifying in vivo difference in the LC microstructure and LC biomechanics in glaucoma eyes and 2) improving our understanding of glaucoma pathogenesis. %D 2016 %K Glaucoma, Imaging, Optical Coherence Tomography, Lamina Cribrosa %I University of Pittsburgh %L pittir27212 %A Junyu Duan %T Influence of Composition and Thermomechanical Processing Conditions on the Microstructure and Properties of Hot Rolled Microalloyed Steels %X This study investigated the effects of selected chemical compositions and processing conditions on the microstructures and mechanical properties of microalloyed hot rolled band. Also, the comparisons have been made between hot rolled band and QT steel. The microstructures of all the specimens were characterized by optical microscopy, scanning microscopy, electron back-scattered diffraction pattern techniques, and the stored energy was calculated by the subgrain method. The mechanical properties including microhardness, tensile and Charpy V-notch impact properties were measured. The relationship between microstructure and mechanical property behaviors has been made. The results show that vanadium can significantly improve strength at high coiling temperatures, but the effectiveness decreased with the lower coiling temperatures. Vanadium also played a very important role in tempering resistance. The relationship between the relative concentration of vanadium and nitrogen has been discussed. It showed that increasing concentration of nitrogen and decreasing concentration of aluminum would not help to improve the final strength and would increase the grain size. Coiling temperature is another important parameter in the hot rolling process since the OM, SEM and EBSD results showed that with different coiling temperatures, the microstructures and mechanical properties of the materials exhibited great difference. The experiment results confirmed the phase transformation predictions made by using the JmatPro thermo-kinetic software. %D 2016 %K HSLA steels, Vanadium, Thermomechanical processing, Stored energy %I University of Pittsburgh %L pittir27373 %A Gregory Wojaczynski %T Integration of the Microcircuitry of the Deep Cerebellar Nuclei into Canonical Cerebellar Circuits %X Defining the anatomical organization of cerebellar circuits has been the pursuit of neuroanatomists for over a century. The regular, repeated cytoarchitecture across the entire extent of the cerebellar cortex has led to an alluring promise that by understanding how a small patch of cortex processes information, we can generalize this finding to understand how the cortex functions as a whole. While great progress has been made to characterize cortical circuits, there has been a relative paucity of studies examining the microcircuitry of the deep cerebellar nuclei. Recent studies have shown that the deep nuclei are not passive relays of cortical processing but rather are highly sophisticated nodes within the cerebellum that have the capacity to both store memory traces and function without cortical input. The local network of the deep nuclei consists of at least six cell types and to date little information is known as to how these cells are synaptically linked, and how the cortex feeds into this network. The heterogeneity of the deep nuclei and the limitations of monosynaptic tracing techniques have hindered efforts to fully define the microcircuitry that supports nuclear processing. The advent of viral transneuronal tracing gives us the opportunity to probe the multisynaptic networks that are so characteristic of cerebellar circuits. The studies in this dissertation were designed to define the microcircuitry of the deep nuclei by utilizing monosynaptic and viral transneuronal tracing. First we provide evidence for largely non-collateralized projections from Purkinje cells onto principal or nucleo-olivary projection neurons using a dual viral tracing paradigm. In the second study we combine classical and viral tracing to provide strong evidence supporting the longstanding hypothesis that the inferior olive and cerebellum form a series of parallel, closed-loop circuits. Lastly we demonstrate, using monosynaptic tracing, a novel excitatory nucleo-cortical projection from the parvocellular interpositus nucleus targeting the Purkinje cell layer of the paraflocculus. Our studies, while confirming some aspects of cerebellar dogma, cast serious doubt onto the long held assumptions that the deep cerebellar nuclei are relay nuclei. These new findings suggest a substantial revision to cerebellar functional theories is necessary. %D 2016 %K cerebellum, viral tracing, PRV, interpositus, microcircuitry %I University of Pittsburgh %L pittir27655 %A Alejandro Sanchez Lopera %T Jos? Revueltas y Roberto Bola?o: Formas gen?ricas de la experiencia %X My dissertation investigates the ways in which Jos? Revueltas (M?xico, 1914-1976) and Roberto Bola?o (Chile, 1953-2003) strive to communicate anti-humanistic social experiences in Chile and Mexico through three episodes: the Mexican Revolution; the 1968 revolts in Mexico; and the 1973 Chilean coup. I argue that Revueltas and Bola?o share a common project of recovering experiences, forgotten or ostracized, stigmatized as marginal to the history of nation-state consolidation often because of their cruelty. Both writers challenge us to confront these abject histories as a way of reimagining Latin American societies without self-indulgence or pity, signaling the exit from perennial debates about originality and deficit. In short, Revueltas and Bola?o offer an anti-exceptionalist literature for re-thinking Latin America in a global context. Each chapter of the dissertation is guided and modeled by a problem, and the criteria used for the texts chosen is hinged on their relationship to each problem. My inquiry was based on six problems: generic and non-territorial sovereignty; images of thought; right to cruelty and the arts of memory in Revueltas? texts; non-psicological memory and thought; fascism and sadism; the transition from the letrado to the calculista, in Bola?o?s case. %D 2016 %K Experience; memory; sovereignty; sadism; truth; Jos? Revueltas; Roberto Bola?o; Latin American Literature %I University of Pittsburgh %L pittir26333 %A Baomin Wang %T Light Management in Silicon Nanostructures for Photovoltaics %X The main challenge with the use of silicon for photovoltaics is that silicon is not a strong absorber of sunlight in the near-infrared region. Conventional silicon photovoltaics are thus typically of thicknesses 200 to 300 _m to ensure the absorption of most sunlight. However, single crystalline silicon solar cells require expensive manufacturing methods. So current solar cell technology is not as competitive as that of traditional energy sources. To promote and increase the silicon solar cell capacity, costs need to drop below $1/W. Increasing absorption of light in the absorber layers is critical issue for achieving high efficiency silicon solar cells. Various light trapping methods have been developed, experimentally and computationally. Light trapping with sub-wavelength nanostructures involves coupling light into localized resonant modes and guided resonance modes in active region to increase absorption. Nanophotonic light trapping strategies have used structuring of the silicon itself or patterning of dielectric materials on front and back of silicon. In order to continue developing cheap and high efficiency silicon solar cells, we studied several anti-reflection and light trapping structures with lower cost and higher absorption. First of all, tapered nanocone structure was proposed and studied and then fabricated via Bosch process. Secondly, high refractive index nanosphere scheme was investigated as a light trapping strategy which does not create new surface or interface and is easy to fabricate. Then inverse woodpile and woodpile photonic crystal structures were studied and proven to have superior light trapping ability due to the ability to engineer the photonic density of states. Finally, ultrathin silicon was fabricated via wet etching method, and then high refractive index nanosphere layers were coated and the power conversion efficiency was increased by 26.5%. Furthermore, metal nanomesh was used as front contact to substitute traditional indium tin oxide, and the power conversion efficiency was increased by 53% due to high haze factor and lower sheet resistance of the metal nanomesh. More importantly, with the metal nanomesh as front contact, the ultrathin silicon solar cells showed superior flexibility. %D 2016 %K silicon, nanostructures, photovoltaics, light management %I University of Pittsburgh %L pittir27318 %A Xinjie Duan %T The Link between Hemodynamics and Wall Structure in Cerebral Aneurysms %X Intracranial aneurysms (IAs) are pathological enlargements of the walls of cerebral arteries. Rupture of aneurysms causes 80% of subarachnoid hemorrhages. It is generally accepted that the abnormal hemodynamics within the aneurysm sac can lead to a breakdown in the normal process of collagen renewal and remodeling leaving the aneurysm vulnerable to rupture. However, the link between hemodynamics and wall integrity, as well as the underlying mechanisms governing the aneurysm pathophysiology remain poorly understood. To investigate the variability of wall structure and mechanical properties within the human unruptured aneurysms, we performed uniaxial mechanical testing on samples resected from aneurysm walls with simultaneous multiphoton microscopy imaging of collagen structure. Significant variations in collagen architecture and mechanical response were found in unruptured aneurysms. Factor of Safety (FoS) was used to quantitatively assess the structural integrity of aneurysms, and subcategorize the unruptured population. In order to further improve the assessment of the structural integrity of the unruptured population, intramural stresses were obtained from FEA with patient-specific models and used for FoS estimation. In this case study, histological investigation of ECM suggests that aneurysms with high FoS are capable of bearing biaxial loading with collagen fibers in two main directions inside the wall and dispersed on the abluminal side. The robust IAs display a rich cell content that is distributed into distinct layers. The collagen architecture in these layers displays similar functional roles to the medial and adventitial layers of the control basilar artery. To study the connection between aneurysmal hemodynamic conditions and the mechanical properties of the aneurysms wall, we constructed computational fluid dynamics models from 3DRA images. Statistically significant correlations between hemodynamic quantities and failure characteristics and high strain stiffness of the wall were found. In order to assess the correlation between local hemodynamics and local wall structure, we developed a methodology for mapping the resected aneurysm sample onto a reconstruction of the lumen. Local collagen structure was accessed at multiple areas, and was correlated with the local hemodynamics. In the case study used to illustrate this methodology, high wall shear stress was found to be associated with sparse, inhomogeneous fiber architectures. %D 2016 %K cerebral aneurysm, remodeling, structural integrity, hemodynamics, rupture risk, correlation %I University of Pittsburgh %L pittir26734 %A Ari Pritchard-Bell %T Mathematical Modeling in Systems Medicine: New Paradigms for Glucose Control in Critical Care %X Stress hyperglycemia occurs frequently in critical care patients and many of the harmful repercussions may be mitigated by maintaining glucose within a ``healthy'' zone. While the exact range of the zone varies, glucose below 80 $mg/dl$ or above 130 $mg/dl$ increases risk of mortality. Zone glucose control (ZGC) is accomplished primarily using insulin administration to reduce hyperglycemia. Alternatively, we propose also allowing glucose administration to be used to raise blood glucose and avoid hypoglycemia. While there have been attempts to create improved paradigms for treatment of stress hyperglycemia, inconsistencies in glycemic control protocols as well as variation in outcomes for different ICU subpopulations has contributed to the mixed success of glucose control in critical care and subsequent disagreement regarding treatment protocols. Therefore, a more accurate, personalized treatment that is tailored to an individual may significantly improve patient outcome. The most promising method to achieve better control using a personalized strategy is through the use of a model-based decision support system (DSS), wherein a mathematical patient model is coupled with a controller and user interface that provides for semi-automatic control under the supervision of a clinician. Much of the error and subsequent failure to control blood glucose comes from the failure to resolve inter- and intrapatient variations in glucose dynamics following insulin administration. The observed variation arises from the many biologically pathways that affect insulin signaling for patients in the ICU. Mathematical modeling of the biological pathways of stress hyperglycemia can improve understanding and treatment. Trauma and infection lead to the development of systemic insulin resistance and elevated blood glucose levels associated with stress hyperglycemia. We develop mathematical models of the biological signaling pathways driving fluctuations in insulin sensitivity and resistance. Key metabolic mediators from the inflammatory response and counterregulatory response are mathematically represented acting on insulin-mediated effects causing increases or decreases in blood glucose concentration. Data from published human studies are used to calibrate a composite model of glucose and insulin dynamics augmented with biomarkers relevant to critical care. The resulting mathematical description of the underlying mechanisms of insulin resistance could be used in a model-based decision support system to estimate patient-specific metabolic status and provide more accurate insulin treatment and glucose control for critical care patients. %D 2016 %K Biomedical Systems, Insulin Sensitivity, Critical Care, Mathematical Modeling, Parameter Estimation, Virtual Patient, Glucose Control %I University of Pittsburgh %L pittir26769 %A Pedro Henrique Casa Grande Rosa %T Mathematical Modeling of Flowback Water Treatment Using Reverse Osmosis and Nanofiltration Technologies %X The main objective of this study is to assess, through mathematical modeling, the potential use and feasibility of deploying nanofiltration and reverse osmosis technologies in the treatment of flowback water. Field data of flowback water flow rates and chemical composition were used in the models in order to provide an accurate assessment of each technology. Operating conditions based on the current commercial reverse osmosis and nanofiltration membranes for water treatment were also considered. Mathematical models for the reverse osmosis and nanofiltration processes were developed to assess the performance of these processes in the treatment of flowback water produced during the hydraulic fracturing for natural gas production from shale plays. The models, based on the mass balance and thermodynamics, were verified and implemented in Matlab version R2015. The models were used to perform a sensitivity analysis for the two processes in order to determine the effect of the operating variables on the membrane performance in terms of solute concentration and filtration time. For the reverse osmosis, it was found that pressure drop, inlet flow rate and membrane area were the major parameters governing the process. For nanofiltration, on the other hand, pressure drop, reflection coefficient and membrane area were the most important parameters affecting the process performance. The models were also used to assess and compare the performance of four different commercial reverse osmosis and three nanofiltration membranes using actual field data, such as inlet flowrate and flowback water composition. The predictions of the two models showed that the reverse osmosis was significantly superior to the nanofiltration membranes in the removal of Na+ and Ca2+. Nanofiltration membranes, however, exhibited higher removal efficiencies for Cl- than that of the reverse osmosis membranes. This behavior was attributed primarily to the nature of both processes; since the reverse osmosis is mainly driven by the chemical potential of chlorine, whereas, the nanofiltration is controlled by the molecule size. %D 2016 %K water hydraulic fracturing flowback membrane reverse osmosis nanofiltration modeling %I University of Pittsburgh %L pittir27854 %A Jian Feng %T Micro Propulsion in Liquid by Oscillating Bubbles %X A number of attempts have been made to fabricate microswimmers that possibly navigate in vivo including the artificial magnetic bacteria flagella, chemical microswimmers and natural organism based microswimmers. This paper presents another propelling mechanism in micron scale that works by oscillating microbubbles in acoustic field. First of all, the propulsion mechanism is proven by two-dimensional computational fluid dynamics (CFD) simulations. Then, the microswimmer device is made on a parylene structure by photolithography. The underwater propulsion in one-dimensional is demonstrated and the propulsion mechanism is also confirmed by experiments. The relation of the propulsion speed/bubble oscillation amplitude and the input acoustic signal is measured. It is shown that the propulsion will happen when the bubble oscillation amplitude (or Reynolds number) gets large enough which is close to the system acoustic resonance. Around this resonance frequency (about 11 kHz), the measured propulsion speed is up to 45 mm/s and payload-carrying ability is realized. The one-directional rotation acoustic turbo is also made with a speed of about 75 rpm. This acoustic frequency dependence also becomes the foundation for two-dimensional propulsion. Then, the bi-directional motion and two-dimensional steering motion are realized by microbubbles with different lengths based on their different acoustic resonances. First of all, the frequency behavior for long (about 760 ?m average length) and short (about 300 ?m average length) bubbles at about 6 kHz and 11 kHz are measured, including oscillation amplitude and generated microstreaming. By adjusting input acoustic frequency, specific bubbles could be activated selectively. Then, when the different microbubbles are arranged into opposite directions, the bi-directional propulsion can be realized, including back/forth motion and clockwise/counter-clockwise rotation. The bi-directional motion mechanism is also confirmed by three-dimensional CFD simulations and the net force is calculated. The concept is further developed into two-dimensional propulsion by arranging long and short bubbles into orthogonal directions on the same device. By switching the input acoustic frequency, the controlled steering propulsion is illustrated on a two-dimensional plane. Carrying of objects in a T-junction microchannel is shown as well. The last part of this thesis is focused on developing the microswimmer into a biodegradable device, including long- and short-tem. The long-term biodegradable device is fabricated by polycaprolactone (PCL) by a simple dipping method, and propulsion in a minitube is shown. The short-term biodegradable device is fabricated by rolling up magnesium film based on building stress mismatch mechanically with help of a stretcher. The method could also be applied to aluminium and parylene film rollups. At last, the propulsion and biodegradable abilities of magnesium microtube are demonstrated. %D 2016 %K Microelectromechanical Systems (MEMS), Microfabrication, Microfluidics, Acoustics, Bubbles %I University of Pittsburgh %L pittir27303 %A Carolyn Zook %T Military Experience and the Shaping of Nationalism in the U.S. Armed Forces %X This study examines the agency of individuals, their understanding of nationalist messages, and how these messages are then incorporated back into the everyday. Specifically, I ask: What combat experiences explain a soldier?s critical, nationalistic, or mixed attitude toward the U.S. following their combat deployment? What structural factors resonate at the individual level? How are broad messages of national unity, sacrifice, and patriotism interpreted and consequently incorporated into everyday lives? Sociological work on nationalism has largely ignored the American case, as well as individual level data in current research on nationalism; gaps this dissertation aims to fill. To answer these questions, I used a mixed methods approach to collect and analyze two data sets: 1) a quantitative survey on nationalistic attitudes of soldiers, and 2) in-depth, semi-structured interviews with U.S. soldiers who served in combat zones of the Iraq or Afghanistan wars. These questions were conceptualized by focusing on three key areas of solders? combat experiences: 1) Recruitment: Soldiers who enlisted because of 9/11 will view their combat experiences with a more nationalistic view than those who enlisted prior to 9/11. Findings showed that 9/11 was not as important of a factor as initially thought, but rather that soldiers are committed to service in general; 2) Combat: Soldiers who served in a combat zone will rationalize significant experiences with a more nationalistic view than those who report no experience of significant or difficult events. Findings suggest that soldiers did not overtly make a connection with their significant experiences using national rhetoric, but they do maintain ideals rooted in the values and beliefs of the country; 3) Returning Home Post-Deployment: Soldiers who return home to widely accessible resources and support networks will have a more favorable view of their military experience and a more nationalistic narrative than soldiers who return home to limited or difficult to navigate resources. Findings suggest that social networks made for both an ease of transition to civilian life, but also complicated it in terms of strained family dynamics. %D 2016 %K nationalism; patriotism; military; combat %I University of Pittsburgh %L pittir27715 %A Hao Wang %T Multiple-Resonator Wireless Power Transmission System Design and Integrated Data Path %X With the rapid development of mobile and implantable devices, the wireless power transfer (WPT) technology has become increasingly attractive because it frees numerous electronic systems from power cords or batteries. Recently, the WPT method based on the magnetic resonant coupling has gained popularity both in research and applications. This dissertation contributes to the magnetic resonant WPT system design by addressing three important problems. The first problem deals with the design of multiple-resonator systems. In order to power objects over a longer distance, a multiple-resonator system is usually needed. However, most existing multiple-resonator systems are designed experimentally with a strict requirement on the position of the resonators. We propose to optimize multiple-resonator systems by investigating the transfer function from the transmitter to the receiver. An equivalent circuit model is developed to maximize the power output. This method is then utilized to find the optimal position for the relay resonator in a three-resonator wireless power transfer system. The second problem is to power a device which is mobile within a certain field. The Biot-Savart law and a concentric model of a spiral coil are utilized to simulate the magnetic field distribution of a multiple-transmitter WPT platform. The vertical component of the magnetic field of the coil is optimized to achieve an evenly distributed magnetic field over the field. As a result, a position-free powering of mobile sensors or devices is achieved. The third problem deals with integration of wireless power transfer and wireless data communication. This problem is especially importation in implanted medical sensors where power must be delivered to the implants and measured data must be transmitted to the outside of the human body. Currently, most implementations of power and communication systems utilize a separated data channel, which requires not only substantial power consumption but also a high complexity of the implanted circuit. In this work, a unified data and power channel is developed in which data are processed by an asynchronous sigma-delta pulse conversion. The resulting pulses are transmitted using load modulation. %D 2016 %K Resonant, Coupling, Wireless, Multiple-resonator, Transfer function, Asynchronous Sigma Delta Modulation, Load Modulation, Data Transmission. %I University of Pittsburgh %L pittir27384 %A Beiye Liu %T Neuromorphic System Design and Application %X With the booming of large scale data related applications, cognitive systems that leverage modern data processing technologies, e.g., machine learning and data mining, are widely used in various industry fields. These application bring challenges to conventional computer systems on both semiconductor manufacturing and computing architecture. The invention of neuromorphic computing system (NCS) is inspired by the working mechanism of human-brain. It is a promising architecture to combat the well-known memory bottleneck in Von Neumann architecture. The recent breakthrough on memristor devices and crossbar structure made an important step toward realizing a low-power, small-footprint NCS on-a-chip. However, the currently low manufacturing reliability of nano-devices and circuit level constrains, .e.g., the voltage IR-drop along metal wires and analog signal noise from the peripheral circuits, bring challenges on scalability, precision and robustness of memristor crossbar based NCS. In this dissertation, we quantitatively analyzed the robustness of memristor crossbar based NCS when considering the device process variations, signal fluctuation and IR-drop. Based on our analysis, we will explore deep understanding on hardware training methods, e.g., on-device training and off-device training. Then, new technologies, e.g., noise-eliminating training, variation-aware training and adaptive mapping, specifically designed to improve the training quality on memristor crossbar hardware will be proposed in this dissertation. A digital initialization step for hardware training is also introduced to reduce training time. The circuit level constrains will also limit the scalability of a single memristor crossbar, which will decrease the efficiency of implementation of NCS. We also leverage system reduction/compression techniques to reduce the required crossbar size for certain applications. Besides, running machine learning algorithms on embedded systems bring new security concerns to the service providers and the users. In this dissertation, we will first explore the security concerns by using examples from real applications. These examples will demonstrate how attackers can access confidential user data, replicate a sensitive data processing model without any access to model details and how expose some key features of training data by using the service as a normal user. Based on our understanding of these security concerns, we will use unique property of memristor device to build a secured NCS. %D 2016 %K memristor, neuromorphic %I University of Pittsburgh %L pittir27362 %A Petch Janbanjong %T New Observations on Flash Bainite %X Flash bainite is a new type of microstructure developed from new heat treatment process called ?Flash Processing?. Using less treatment time, the result is the high performance steel with mixed microstructure of bainite and martensite. This research aimed to study the characteristics of this process using typical low carbon steel, with 0.1-wt% C. The experiments have been done with two similar types of steels, one with vanadium and one without. Two rates of heat treatment and 3 different heating temperatures have been set up and experiments were conducted to twelve samples. The results show 2 groups of different samples, with and without bainite in the final microstructure. The samples that were heat-treated to 950 ?C resulted in fractions of bainite in the end. The microstructures and characteristics of flash bainite have been studied morphologically using OM, SEM and EBSD. OM results and SEM results confirmed that the formation of bainite in flash processed steel was because of the incomplete carbides dissolution and carbon concentration gradients. SEM results showed that flash bainite samples showed characteristics of upper-bainite morphology, specifically bainitic ferrite type. EBSD results also confirmed the characteristics of bainite and the contribution to mechanical properties of the microstructures. The hardness test showed outstandingly high value in the range of 380-390 HV, even when compared to typical bainite and martensite. The comparisons of typical flash bainite and flash bainite developed in the research have been made and concluded. Also, the comparisons between typical bainite and flash bainite have been made to confirm the type of bainite developed in this research in morphological aspect. The results showed that flash bainite could be considered as a valuable option of steels in the future. However, further experiments should be made to confirm mechanical properties of this type of steels. %D 2016 %K Flash Bainite, Bainite, Martensite %I University of Pittsburgh %L pittir27445 %A Shibin Mathew %T On Signal Transduction in Human Embryonic Stem Cells: Towards a Systems View %X Human embryonic stem cells (hESC) have been a major cell source for research in regenerative medicine due to the demonstration of properties of self-renewal and efficient lineage specific differentiation, both on additions of external cues. Self-renewal provides the potential to extract large quantities of na?ve cells that can then be differentiated to clinically relevant mature lineages. While there exists significant proof-of-concept to transform stem cells to the desired lineage, generating fully functional cell types is still an unmet challenge. A major reason for this is our limited understanding of the complexity of the transformation process. The overarching goal of this PhD research was to provide strategies to bring mathematical modeling into the realm of stem cell research, particularly to analyze the complex regulatory network of signaling events controlling cell fate. This work focused on the signaling pathways that in concert control the balance of self-renewal and endoderm differentiation of hESCs. We proposed a framework for developing mechanistic understanding from disparate signaling pathways using combinations of data-driven and equation based models. As a first step, we analyzed growth factor mediated PI3K/AKT pathway that must remain highly active to inhibit differentiation in self-renewal state. Using an integrated approach of mechanistic modeling, systems analysis and experimental validation we identified the role of a regulatory process (negative feedback) in maintaining signal amplitudes and controlling the propagation of parameter uncertainty down the pathway in the self-renewal state. To analyze endoderm differentiation, biclustering with bootstrapping formulation was used to identify co-regulated transcription factor patterns under a combinatorial modulation of endoderm inducing signaling pathways. In the final step, a detailed mechanistic analysis was done to characterize the dynamic features of TGF-?/SMAD pathway for inducing endoderm. Utilizing a dynamic Bayesian network formulism, AKT mediated crosstalk connections were inferred from the detailed time series data. Modeling of competing AKT-SMAD interactions followed by parametric ensemble analysis enabled identification of plausible hypotheses that could explain experimental observations. Using our integrated approach, we can now begin to rationally optimize for desirable fate of hESCs with reduced variability and accelerate the path towards therapeutic applications of hESCs. %D 2016 %K Systems Biology, Signal Transduction, Human Embryonic Stem Cells, Mathematical Modeling, Computational Biology %I University of Pittsburgh %L pittir26798 %A Giusy Mazzone %T On the Dynamics of a Rigid Body with Cavities Completely Filled by a Viscous Liquid %X This thesis deals with the dynamics of a coupled system comprised of a rigid body containing one or more cavities entirely filled with a viscous liquid. We will present a rigorous mathematical analysis of the motions about a fixed point of this system, with special regard to their asymptotic behavior in time. In the case of inertial motions and motions under the action of gravity, we will show that viscous liquids have a stabilizing effect on the motion of the solid. The long-time behavior of the coupled is characterized by a rigid body motion, and in particular a permanent rotation in the case of inertial motions, and the rest state in the case of a liquid-filled heavy pendulum. Some questions about the attainability and stability of the equilibrium configurations are also answered. Furthermore, we will investigate the time-periodic motions performed by the coupled system liquid-filled rigid body when a time-periodic torque is applied on the solid. %D 2016 %K Liquid-filled cavity, Navier-Stokes equations, rigid body, inertial motions, pendulum, attainability, stability, periodic motions. %I University of Pittsburgh %L pittir27265 %A Kaiyuan Li %T On the use of solitary waves for energy harvesting %X In the last decade there has been an increasing attention on the use of highly- and weakly- nonlinear solitary waves in engineering and physics, such as shock mitigation, acoustic imaging and nondestructive evaluation. These waves can form and travel in nonlinear systems such as one-dimensional chains of particles. One engineering application of solitary waves is the fabrication of acoustic lenses. In this dissertation, an acoustic lens based on the propagation of highly nonlinear solitary waves is proposed. The lens is part of a novel energy harvester able to focus mechanical vibrations into a single point where a piezoelectric element converts the mechanical energy into electricity. The first step of this research was to investigate numerically and experimentally a novel acoustic lens composed by one-dimensional chains of spherical particles arranged to form a circle array in contact with a linear medium. The second step of the research was to incorporate the acoustic lens into an energy harvesting that includes a wafer-type lead zirconate titanate (PZT) transducer and an object tapping the array. The PZT transducer located at the designed focal point converts the mechanical energy carried by the stress waves into electricity to power a load resistor. The performance of the designed harvester was compared to a conventional non-optimized cantilever beam, and the results showed that the power generated with the nonlinear lens has the same order of magnitude of the beam. Moreover, the performance of the proposed harvester was compared to a similar system where the chains of particles were replaced by solid rods. The results demonstrated that the granular system generates more electricity. Moreover, some parametric studies were conducted to improve the harvesting performance of the proposed system. The materials and the geometry of the harvester were considered to enhance the power output of the harvester. Numerical models were built to predict the power output from harvesters designed with different materials and geometries. The design that produces the highest power output was selected as the best design. The best design was tested experimentally to validate the enhancement in energy harvesting capability as predicted in the previous numerical model. %D 2016 %K piezoelectric, energy harvesting, solitary waves %I University of Pittsburgh %L pittir27221 %A Yen Jung Tu %T Operating Perovskite Solar Cell under Concentrated Solar Light %X A recent forecast suggested that solar cell industry will contribute nearly one third of new electricity generation capacity worldwide by the year 2030.[1] Silicon solar cell is the most widely used photovoltaic device nowadays. However, opportunities exist for technologies that advance either higher efficiencies or lower fabrication cost in the silicon solar cell. Thus, the emergence of organic?inorganic halide perovskite based solar cell has attracted much attention during the past few years. Compared with traditional silicon solar cell, the perovskite solar cell has a lower cost and is easy to fabricate. Additionally, the high potential is another feature that catches peoples? eyes. With the first perovskite solar cell reported in 2009 with power conversion efficiency of 3.8%. A record efficiency of 21.0% was achieved by researchers at EPFL in late 2015.[2] However, the instability of perovskite solar cell at high temperature reduces the performance. Modern solar cell design often uses lens to concentrate solar light in order to produce higher power from small area of solar cells. Nevertheless, part of the solar power will be converted into heat and increase the temperature of the cell. When it comes to perovskite solar cell, the concentrated solar light gives rise to considerable temperature increase of the glass substrate and causes significant degradation of the perovskite layer. Thus, figuring out the performance of perovskite solar cell under evaluated temperature and the temperature raise according to different incident light intensity are important jobs for designing concentrator solar cells. In this thesis, the transmittance and reflectance were simulated by Lumerical FDTD software to calculate the absorbance of perovskite solar cell under different incident light intensity. The temperature evaluation was then calculated by Ansys Mechanical software to find out the relation between incident light power and temperature increase. To characterize the performance of perovskite solar cell under different temperature, the I-V curve and incident photon-to-current efficiency (IPCE) were measured under various temperature conditions. By comparing the temperature-light intensity correlation, IPCE performance and I-V curve, the suitable incident solar light intensity for operating perovskite solar cell was found. %D 2016 %K Solar cell, Perovskite, IPCE, PCE, %I University of Pittsburgh %L pittir27464 %A Maryam Hasanzadeh Mofrad %T Optimizing Vaccine Clinic Operations in Low and Middle Income Countries %X This dissertation focuses on two open questions in operating vaccination clinics in low and middle income countries. First, as a result of limited ``open vial life," clinicians face difficult tradeoffs between opening a multi-dose vial to satisfy a potentially small immediate demand versus retaining the vial to satisfy a potentially large future demand. Second, in low and middle income countries, governmental health organizations face tradeoffs between locating (additional) clinics or conducting outreach trips to vaccinate patients in remote locations. To answer the first question, we formulate Markov decision process models that determine when to conserve vials as a function of the time of day, the current vial inventory, and the remaining clinic-days until the next replenishment. The objective is to minimize ``open-vial waste" while administering as many vaccinations as possible. For the base model, we analytically establish that the optimal policy is of a threshold type; conduct extensive sensitivity analysis on model parameters; develop a practical heuristic policy; suggest operational approaches that do not overly inconvenience patients; define metrics for determining appropriate operating hours and sessions per inventory replenishment cycle; and study the impact of random vial yield. We then generalize the base model by considering a positive probability of return for patients who are not vaccinated on their first visit and incorporating non-stationary arrival rates. To study these enhancements, we perform extensive numerical experiments at the clinic level for a single replenishment cycle and then extrapolate to multiple clinics and the entire world on an annual basis. The results indicate potential savings on the order of millions of doses per year. To answer the second question, given a network of population centers we develop a mixed integer linear programming model that determines clinic locations and outreach activities. The model minimizes cost over a specified period of time subject to constraints on coverage, trip distance, trip size, trip frequency and patient travel. We address demand uncertainty; perform sensitivity analysis on key model parameters; compare the performance of the optimal solution to heuristic policies; and conclude that while counterintuitive it is often suboptimal to locate clinics in the largest population centers. %D 2016 %K Markov decision process, perishable inventory model, multi-dose vial, vaccine wastage, capacitated facility location, outreach trip %I University of Pittsburgh %L pittir27262 %A Peter Wood %T Overturning Mammon: The Living Theatre & Symbolic Capital %X Overturning Mammon: The Living Theatre and Symbolic Capital focuses on the first thirteen years of the Living Theatre, founded by Judith Malina and Julian Beck. Pierre Bourdieu?s theories of cultural production provide the theoretical tools to approach the company as a cultural producer and not only as theatre artists. The Living Theatre has produced largely unpopular avant-garde and political theatre for seventy years. I argue that the company?s early years demonstrate a growing reserve of symbolic capital that helps explain the company?s longevity. Furthermore, the manner in which certain events in the company?s history have been mythologized, by company members, critics, and scholars, has led to some historically inaccurate accounts. In particular, accounts of the closing of the company?s production of The Brig in 1963 and the subsequent trial of Beck and Malina in 1964 have often been influenced by an acceptance of company member?s anecdotal, ?tall tales? approach to history rather than historical evidence and archival documents. This project redresses this lack of historical inquiry using a variety of primary and archival sources to argue that the material and historical exigencies of the Living Theatre offer theatre scholars an example of how symbolic capital can overturn economic ?reality.? %D 2016 %K theatre, theater, drama, living theatre %I University of Pittsburgh %L pittir27119 %A Cedric OFAKEM %T Overvoltages Associated With Photovoltaic Inverter Transients %X Increased penetration of solar photovoltaic (PV) can cause significant overvoltages during faults and back-fed fault current into grid while causing miss-operation of protective relaying. Transient data from four single-phase PV inverters was collected during both open-circuit and short circuit transient events. Each inverter was tested at four different output power levels and multiple tests were run for each case to account for point-on-wave effects on the transient magnitudes. Test program designs are presented to cover a range of inverter operating conditions and grid configurations. The data was used to plot the overvoltages and overcurrents associated with the transient events. In some cases, the inverters can produce transient overvoltages > 1.6 p.u. and transient overcurrents > 14 p.u. In addition, theoretical magnitudes of transient overvoltages can be compared with the laboratory result. %D 2016 %K distributed power generation grounding inverters power distribution power system modelling inverter testing smart grid %I University of Pittsburgh %L pittir26857 %A Cassilde Schwartz %T The Paradox of Confrontation: Experimental Evidence on the Audience Effects of Protest %X Do protests increase or decrease political engagement among the general public? Despite the fact that social movements so often aspire to persuade and engage civil society, scholars have largely neglected these consequences of protest activity. I argue that protest is a double-edged sword. People may become enthusiastic and engaged when they hear of protests through the news, but they disengage when faced with an actual protest. This suggestion challenges the vast majority of social movement literature, which is highly aware of the protesters? need to occupy and interrupt public life in order to capture an audience, but widely assumes that the public does not mind the interruption. This dissertation considers the possibility that the public begrudges its role as a captive audience and focuses more on the inconvenience of the event than the message. I approach this research question through a combination of two experimental designs and observational data. First, I embed a vignette experiment into a baseline phone survey in Mexico City. This experiment treats individuals with crafted news stories about protests that have randomized characteristics. The second experiment tests a different type of protest exposure, i.e., real confrontation. In this experiment, all respondents from the baseline were invited to take part in face-to-face interviews at designated times and places. Respondents in the treatment groups are interviewed during one of two protests, while respondents in the control group were interviewed on a day with no protests. All of the treatments in the vignette and field experiments take advantage of real protests that arose in opposition to the apparent killing of 43 student teachers from the Ayotzinapa teachers? college in southern Mexico. Then, using new techniques to isolate and test competing causal mechanisms, I examine the specific mediators ? emotions, conflict aversion, and political efficacy - that might link protests to political engagement. To complement the experimental results, I test the external validity of my findings with municipal-level data in Brazil, a country that shares similar patterns of protest activity with Mexico but differs in its protest geography. %D 2016 %K Latin American Politics; Mexico; Protest; Social Movements; Political Participation; Field Experiment %I University of Pittsburgh %L pittir28003 %A Roxana Elena Tanase %T Parameter estimation for partial differential equations using stochastic methods %X The aim of this thesis is to compare the efficiency of different algorithms on estimating parameters that arise in partial differential equations: Kalman Filters (Ensemble Kalman Filter, Stochastic Collocation Kalman Filter, Karhunen-Lo`eve Ensemble Kalman Filter, Karhunen- Lo`eve Stochastic Collocation Kalman Filter), Markov-Chain Monte Carlo sampling schemes and Adjoint variable-based method. We also present the theoretical results for stochastic optimal control for problems constrained by partial differential equations with random input data in a mixed finite element form. We verify experimentally with numerical simulations using Adjoint variable-based method with various identification objectives that either minimize the expectation of a tracking cost functional or minimize the difference of desired statistical quantities in the appropriate Lp norm. %D 2016 %K parameter estimation, Kalman Filter, Stochastic Collocation, Markov Chain Monte Carlo, Adjoint variable %I University of Pittsburgh %L pittir27640 %A Di Sun %T Partially Occluded Object Detection %X Object detection is a fairly important field in computer vision and image processing, and there are some domains that have been well researched, such like face detection and pedestrian detection, while these detections are based on situation that there are no shelters on objects in images or videos. But most objects are partially occluded in real world. And this becomes one major obstacle in object detection. In this paper, I utilize a state-of-art model, Deformable Part Model (DPM), which present a mixture model contains multi-scale deformable parts. And attach visibility flags to both cells and part of it. A visibility flag is used to indicate whether a specific cell or part is visible or occluded. By removing the contribution of occluded cells and parts to the whole detection score, the performance of partially occluded object detection can be significantly improved. To get the value of visibility flags, I use a mathematical method called Alternating Direction Method of Multipliers (ADMM). I experiment the model on different occlusion situation and change the occlusion conditional likelihood penalty to get better performance. %D 2016 %K Object detection, deformable part-based model, partially occluded object %I University of Pittsburgh %L pittir27366 %A Bryan S. Wright %T THE RAGTIME PIANO REVIVAL IN AMERICA: ITS ORIGINS, INSTITUTIONS, AND COMMUNITY, 1940-2015 %X Since the early 1940s, ragtime piano has been the focus of a musical revival community in the United States. Like many other music revival movements, what began as an effort by a dedicated few to revitalize and preserve a ?vanishing? musical practice?in this case, one that had flourished from the mid-1890s to the mid-1910s?soon attracted ardent enthusiasts eager to collect, compose, and perform ragtime. They celebrated its historical roots while endeavoring to re-establish ragtime as a thriving tradition. This study, drawing on original archival research, interviews with ragtime community members, and the author?s twelve years as a participant-observer in the community, examines the origins and development of the American ragtime piano revival community. Chapter 2 analyzes selected writings of the 1940s, in which the earliest revivalists sought to legitimize ragtime and forge an identity for the music distinct from jazz. Chapter 3 discusses three prominent ragtime serial publications that began in the 1960s (The RagTime Review, The Ragtimer, and The Rag Times), the people and organizations behind them, and the ways in which geographically disparate ragtime revivalists sought to organize their efforts, generating a core ragtime community while debating notions of authenticity in ragtime performance. Chapters 4 and 5 examine two prominent annual ragtime events?The Scott Joplin International Ragtime Festival and the World Championship Old-Time Piano Playing Contest)?to discuss practices through which the ragtime community has maintained and expressed itself into the twenty-first century. The dissertation argues that as the revival community has established and maintained itself, it has witnessed a shift from product-oriented to process-oriented notions of authenticity, heralding the arrival of a ?post-revival.? %D 2016 %K ragtime, revival, community, authenticity, revitalization, movement %I University of Pittsburgh %L pittir27682 %A Fen Qin %T Random silver nanowire network embedded AZO transparent and conducting films %X In this thesis, silver nanowire (Ag NW) networks are embedded into aluminum doped zinc oxide (AZO) to prepare transparent and conducting (TC) films. The nanowires are of different length and diameters according to various reaction times and temperatures. The electrical properties, such as carrier concentration, carrier mobility and resistivity are studied using Van Der Pauw Hall measurement. The optical properties such as Mie scattering, Transmission and Haze are studied from both experimental and simulating results. The best Ag NW embedded TC film shows a low resistivity ~3.6 ?10-4??cm with transmission ~ 85%. The theory of percolation is used to explain the connectivity effect of nanowires on the conductivity and transparency of TC films. Moreover, the optical improvement by adding silver nanoparticles is also discussed and showed. Small nanoparticles with diameter ~20nm can reduce the haze causing by silver nanowire networks. %D 2016 %K transparent and conducting film silver nanowire TCO %I University of Pittsburgh %L pittir27390 %A Adrienne Ronee Washington %T (Re)structuring structures, speech and selves: Yoruba language learning and redevelopment in Salvador da Bahia, Brazil %X This dissertation investigates the redevelopment of Yoruba as a curricular language in Salvador da Bahia, Brazil, and the sociohistorical and cultural dimensions of its changing form and function by drawing from the literatures on language contact and the sociosemiotics of language. Centrally, this dissertation clarifies that what drives the local study and sociolinguistic status of these linguistic practices are the social values that Yoruba carries in Salvador according to local cultural schemas. In four studies, I explore the social and historical significances attached to Yoruba linguistic forms (within local cultural schemas) in northeastern Brazil and how these socially significant language practices often serve as sites for the materialization and negotiation of cultural ideas, particularly notions about personhood (race, heritage, nation). As part of my exploration of the cultural schemas (or Yoruba language ideologies) that shape and are shaped by the local patterns and practice of Yoruba language in Salvador, I examine how these language ideologies manifest or materialize through discursive practices at different levels of the local Yoruba language learning enterprise. That is, through the distribution of Yoruba learning and the types of students (academic, career, heritage, and religious learners), the language-learning motivational orientations and perceived values attached to Yoruba learning, the evaluations of teaching and the notions of expertise or teaching qualification, and the institutions and linguistic forms or skill sets involved in teaching Yoruba. This dissertation highlights the impact of language ideologies and social context on language learning and teaching as well as language use overall, with theoretical implications for language learning and pedagogy research and language studies more generally. It contributes new scientific data on the sociolinguistic situation of Yoruba linguistic practices in Brazil, highlighting Yoruba?s functional expansion from a liturgical to a curricular language. The dissertation also demonstrates an alternate language contact trajectory and unconventional language practices overlooked by extant scholarship. It invites linguists to reframe discussions of the sociolinguistic situation of post-plantation, post-colonial societies, moving beyond a notion of ?outcomes? as the endpoint and to instead embrace ever-evolving language contact situations shaped by ever-changing cultural assumptions about language in relation to society. %D 2016 %K Yoruba, sociolinguistics, language contact, language learning, language ideologies, language redevelopment, language change, Afro-Latin, Brazil %I University of Pittsburgh %L pittir27628 %A Kristina L. Swanenburg %T Reaction to Deviates and Conformers: The Effect of Regulatory Fit %X Adherence to group norms is an important determinant of how members judge one another, with conformers typically being evaluated more positively than deviates (Levine & Kerr, 2007). This study tested predictions about reaction to conformers and deviates derived from Regulatory Fit Theory (Higgins, 2102), which takes account of people?s regulatory focus (promotion vs. prevention) and their manner of goal pursuit (eager vs. vigilant). According to the theory, because fit sustains an individual?s regulatory focus, it produces greater task engagement and intensification of affective responses to salient stimuli. The present study used a 2 (regulatory focus: promotion or prevention) x 2 (target status: deviate or conformer) x 2 (target advocacy style: eager or vigilant) between-participants design. After being induced to have either a promotion or prevention regulatory focus, male and female undergraduates in three-person groups reached consensus on a proposed senior thesis requirement, with most groups opposing the requirement (25 groups/condition). Participants then watched an ostensible student argue either for (deviate) or against (conformer) the requirement using either an eager or a vigilant advocacy style. Afterwards, participants discussed and evaluated the speaker and his message. For exploratory purposes, participants? opinion change and the content and valence of their comments during the discussion were also assessed. Major predictions were that (a) regulatory fit would produce more task engagement (longer group discussions) than nonfit; (b) conformers would be evaluated more positively than deviates; (c) fit would intensify positive evaluations of conformers and negative evaluations of deviates; and (d) task engagement would mediate the impact of fit on reaction to both targets. Only the hypothesis that conformers would be evaluated more positively than deviates was confirmed. Additional analyses found that participants were more engaged when discussing deviates than conformers. There was also some evidence of minority influence by deviates. Finally, analyses of group discussions indicated that target status influenced both the content and valence of participants? comments, and content and valence scores were related to the evaluation of the target. These results were interpreted, and directions for future research were suggested. %D 2016 %K deviance, regulatory fit %I University of Pittsburgh %L pittir27337 %A Mohammad Ahmadpoor %T Reduced-Order Modeling Toward Solving Inverse Problems in Solid Mechanics and Fluid Dynamics %X Despite great improvements in computing hardware and developments of new methodologies for solving partial differential equations (PDEs), solving PDEs numerically can still be computationally prohibitive for certain applications. This computational difficulty is especially true when the solution of PDEs is tied to characterization, control, design, or other inverse problems in general. Most of the traditional PDE solution strategies, such as the Finite Element Method or Finite Volume Method can require hundreds of thousands of degrees of freedom to accurately capture the behavior of even relatively simple physical system. The computational cost is several orders of magnitude higher for solving optimization problems (a common approach to solve inverse problems), which require obtaining several solution fields. Hence, model order reduction is necessary to enable the solution of such optimization problems with sufficient efficiency to allow practical applicability. Several approaches have been developed to create accurate reduced-order models (ROMs) of physical systems with dramatically reduced computational expense. Yet, several questions remain as to the optimal approach to create ROMs for a given physical system to ensure suitable accuracy, and even more so in relation to inverse problem applications. The objective of the present work is to address issues relating to the creation of suitably accurate ROMs that can be utilized for the solution of a variety of computational inverse mechanics problems. This work focuses on ROMs that utilize proper orthogonal decomposition (POD) to create a reduced-order basis for the PDE solution from a set of previously obtained potential solution fields (i.e., snapshots) of the system of interest. First, a generally applicable algorithm is presented to efficiently create accurate ROMs for use in solving inverse problems in material characterization (i.e., nondestructive evaluation). This algorithm is based upon a novel concept for maximizing the diversity of the system snapshots used to create the ROM. Results show that by maximizing the snapshot diversity, the accurate generalization of the resulting ROM is substantially improved, which then improves inverse problem solution capabilities. Then, a comprehensive study is presented of the capability of a set of different approaches for reduced-order modeling (all still using POD) to represent systems involving flow past bluff bodies. One of the relatively unexplored issues when creating ROMs for fluid flows is the accuracy with respect to changes in Reynolds (Re) number. The present work uses the generalized POD technique to create ROMs that are capable of predicting flow field not only at different time levels, but also at different Re numbers. Finally, the ROM strategies explored for fluid flow were extended to investigate the applicability to optimal flow control problems. The ROM of flow was used along with an optimization technique and adjoint method for gradient calculation to solve a control problem to reduce the drag force in flow past one or more cylinders. Results of the solution of this optimal control problem show that the developed ROMs are capable of solving complex optimization problems with significantly reduced computational expense. %D 2016 %K Reduced Order Model, Proper Orthogonal Decomposition, Inverse Problems, Optimal Control, Flow Control, Turbulent Flow, NDT %I University of Pittsburgh %L pittir27796 %A Tianyi Qiu %T Robust Compensation of Electromechanical Delay during Neuromuscular Electrical Stimulation of Antagonistic Muscles %X Neuromuscular electrical stimulation (NMES) can potentially be used to restore the limb function in persons with neurological disorders, such as spinal cord injury (SCI), stroke, etc. Researches on control system design has so far focused on relatively simple unidirectional NMES applications requiring stimulation of single muscle group. However, for some advanced tasks such as pedaling or walking, stimulation of multiple muscles is required. For example, to extend as well as flex a limb joint requires electrical stimulation of an antagonistic muscle pair. This is due to the fact that muscles are unidirectional actuators. The control challenge is to allocate control inputs to antagonist muscles based on the system output, usually a limb angle error to achieve a smooth and precise transition between antagonistic muscles without causing discontinuities. Furthermore, NMES input to each muscle is delayed by an electromechanical delay (EMD), which arises due to the time lag between the electrical excitation and the force development in muscle. And EMD is known to cause instability or performance loss during closed-loop control of NMES. In this thesis, a robust delay compensation controller for EMDs in antagonistic muscles is presented. A Lyapunov stability analysis yields uniformly ultimately bounded tracking for a human limb joint actuated by antagonistic muscles. The simulation results indicate that the controller is robust and effective in switching between antagonistic muscles and compensating EMDs during a simulated NMES task. Further experiments on a dual motor testbed shows its feasibility as an NMES controller for human antagonistic muscles. %D 2016 %K NMES, Lyapunov stability analysis, EMD, Delay compenstaion, Antagonist muscles %I University of Pittsburgh %L pittir27346 %A Sara L. Sumpter %T The Socio-Political Functions of Japanese "Vengeful Spirit" Handscrolls, 1150-1230 %X The second half of the twelfth century witnessed a curious boom at the Heian Court in Japan?the production of illustrated handscrolls whose narratives centered on a specific type of historical figure. Within a span of fifty years or less, three such handscroll sets were produced: the Kibi Daijin nitt? emaki, the Ban Dainagon emaki, and the Kitano Tenjin engi emaki. In each story, the protagonist is an aristocrat who had lived three-to-four-hundred years previous to the production of the handscroll set. Each of the men in question had died in exile, and each was?at one point or another?believed to have become a vengeful spirit. Moreover, in each case, the narrative presented in the handscroll differs from, or elides, the historical record. The Kibi Daijin nitt? emaki presents an entirely fictional tale based only loosely on the lives of its protagonists; the Ban Dainagon emaki records a highly embellished version of a well-documented political scandal; and the Kitano Tenjin engi emaki constructs a mythology from the details of the life and death of one of the period?s most accomplished bureaucrats. This dissertation explores the production of these three handscrolls?which I refer to as ?vengeful spirit scrolls??and focuses on the role of the re-imagining and redeployment of historical figures in these scrolls to processes of power consolidation in the late-twelfth and early-thirteenth centuries. Taking a thematic approach, I examine these handscrolls from the perspective of their role in early literary movements to reinvent historical figures, in contemporaneous perceptions of supernatural creatures, and in ritual practices such as spirit pacification rites. I also consider the scrolls from within the social context of the collapse of the traditional courtly power base at the end of the Heian period (794-1185) and beginning of the Kamakura period (1185-1333). In so doing, my project explores two main research questions: how handscrolls from this period reflect the sociopolitical changes that were ongoing during their production and how they might have been used by members of the courtier class to negotiate the intersection of temporal and non-temporal power. %D 2016 %K Japanese art, narrative art, illustrated handscrolls, folktales, monster studies, Japanese history %I University of Pittsburgh %L pittir27576 %A Elise Thorsen %T Territory and Empire in Early Soviet Poetry %X The Soviet state-building project of the 1920s and 1930s faced a number of challenges, among then reconceiving of the vast Eurasian territory and geographic relations seized from the Russian Empire as a new country. This dissertation takes as its goal the description of how civic poets sought to create a coherent sense of imagined community in which geographic and ethnic diversity was organized and enhanced by socialist ideology. As this poetic project developed over two decades, a consistent tension emerged between two positions. One, there is the necessity of constituting an imagined community that can account for the dynamism of the early Soviet decades; for example, the implicit boundaries of that community change radically over time. Two, there is a countervailing suspicion that such an imagined community will perpetuate the legacies of Russian empire and global colonialism. The methodology of this dissertation is close to the texts themselves. These include Maiakovskii?s Soviet work, the Center of Literary Constructivists, the literary brigades of the Five-Year Plans, and works dedicated to the dramatic rescue of the Cheliuskinites in 1934. In these poems, which consciously grapple with problems of geography, the prosodic and intertextual organization of space offers a basis for understanding the conceptual position of the lyric subject. This lays the groundwork for inquiry into the shifting potential roles for the civically-minded poet, and into the possibility of a community of citizens to which he could belong. %D 2016 %K Soviet Union, Russia, Russian poetry, prosody, empire, territory, imagined geographies, imagined community, Maiakovskii, Sel'vinskii %I University of Pittsburgh %L pittir27568 %A Rebecca Slavin-Phillips %T Tradition and Individualism in Suburbia: An Ethnographic Study of Orthodox Jewish Women %X This dissertation is an ethnographic study of Orthodox Jewish women in suburban New Jersey, conducted in 2013-2014. The central goal is to analyze how observant, Jewish women negotiate maintenance of religious tradition and individual choice in suburbia. The dissertation identifies religious pluralism within Orthodox Judaism that can be attributed, in part, to the suburban location. These women reside in the two Central New Jersey communities of East Brunswick and Highland Park and showcases the changes that are occurring in religious practice of the observant Jewish women how their lives reflect the changing nature of contemporary Orthodox Judaism. The study uses ethnography to examine these women?s sense of piety and how they apply Jewish law in several aspects of their lives. It examines how these women narrate their own backgrounds as Orthodox Jews or, in the case of ba?alot teshuva (newly Orthodox women), their turn to Orthodoxy as adults. It also looks at the role of feminism in their lives, their definitions of modesty, and their creation of a diversified and traditional religious environment. %D 2016 %K Jewish Studies; Religious Studies; Orthodox Jews; Ethnography of Religion; Women and Religion %I University of Pittsburgh %L pittir26786 %A Yongjin Wang %T Understanding the Mechanism of Simultaneously Oelophobic/Hydrophilic Perfluoropolyether (PFPE) Nano-Coatings %X This dissertation is focused on understanding the mechanism of simultaneously oleophobic/hydrophilic perfluoropolyether (PFPE) nano-coatings. Four specific topics are presented: 1) investigate why can a nanometer-thick polymer coated surface be more wettable to water than to oil; 2) discuss the effect of end-groups on simultaneous oleophobicity/hydrophilicity and testify the anti-fogging performance of nanometer-thick PFPEs; 3) Fabricate nanometer-thick simultaneously oleophobic/hydrophilic coatings via a cost-effective photochemical approach; 4) study the role of the interfacial interaction in the slow relaxation of nanometer-thick polymer melts on a solid surface. Specifically, chapter 2 and chapter 3 indicate that the simultaneously oleophobic/hydrophilic behavior is kinetic in nature and results from the combination of nanoscale and interfacial phenomena. The end-groups of the nanometer-thick PFPEs are critical to this peculiar wetting behavior: PFPE polymers with different end-groups can interact with the substrate in very different ways, resulting in different packing orders and thus different inter-chain distances within the polymer nanofilms. If the inter-chain distance is appropriately small, smaller water molecules penetrate the nanofilms quickly while larger oil molecules penetrate the nanofilms much more slowly. As a result, the surface shows a higher oil contact angle (OCA) than water contact angle (WCA). Moreover, the effect of simultaneous oleophobicity/hydrophilicity on the long-term anti-fogging capability has been studied by X-ray photoelectron spectroscopy (XPS) and anti-fogging tests. The results indicated that the unique simultaneous oleophobicity/hydrophilicity reduces the airborne hydrocarbon contamination and therefore improves the long-term anti-fogging performance. In chapter 4, an UV-based photochemical approach has been developed to fabricate nanometer-thick simultaneously oleophobic/hydrophilic coatings using cost-effective PFPEs without polar end-groups and the anti-fogging performance and mechanical robustness of the coating were studied. The photochemical approach established here potentially can be applied on many other polymers and greatly accelerates the development and application of simultaneously oleophobic/hydrophilic coatings. In chapter 5, the relaxation of nanometer-thick PFPE melts on a silicon wafer has been investigated by water contact angle measurement. This work reports that the relaxation of nanometer-thick polymer melts on a solid surface is much slower than in the bulk, which has been attributed to the low mobility of the anchored polymer chains and the motional cooperativity between anchored and free polymer chains in the nanometer-thick films. %D 2016 %K Simultaneously oleophobic/hydrophilic, PFPE, wetting %I University of Pittsburgh %L pittir26859 %A Andrew Kozbial %T Understanding the intrinsic water wettability of graphite %X Decades of research since the 1940s has substantiated graphite as a low surface energy material. Its chemical structure led researchers to believe that airborne hydrocarbon contamination was inconsequential and contradictory reports were not convincing. Graphite gained renewed interest when graphene was first isolated in 2004. Being an atomically thin material, the surface properties of graphene are critical to its performance, thus elucidating surface properties of graphene and graphite became important topics in fundamental and applied research. This work began with the realization that fresh graphene and graphite are mildly hydrophilic and approach their established hydrophobicity upon exposure to ambient air. Hydrocarbons in ambient air adsorb onto the fresh surface and cause it to appear hydrophobic. This work was first published in 2013 (doi: 10.1038/nmat3709) and provided the basis for further exploration of the intrinsic chemical nature of graphene, graphite, and MoS2. Fresh graphite is shown to be mildly hydrophilic and becomes hydrophobic upon exposure to ambient air. Similar behaviour was observed for graphene and MoS2. Ellipsometry showed growth of an adsorptive layer on the fresh (clean) surface and ATR-FTIR indicated that the adsorptive layer was airborne hydrocarbon. Theoretical calculation further confirmed that adsorption of only a monolayer of hydrocarbon is enough to reproduce the hydrophobic behavior previously observed on HOPG. Surface energy of fresh CVD graphene was calculated to be 62.2 ? 3.1 mJ/m2 (Fowkes), 53.0 ? 4.3 mJ/m2 (Owens-Wendt), and 63.8 ? 2.0 mJ/m2 (Neumann), which decreased to 45.6 ? 3.9 mJ/m2, 37.5 ? 2.3 mJ/m2, and 57.4 ? 2.1 mJ/m2, respectively, after 24 hours of air exposure. Similar behaviour also occurred for HOPG and MoS2. The fresh surface exhibits highest surface energy which decreases upon adsorption of airborne hydrocarbons. Results also indicate that the fresh surface is mildly polar. Analysis based on defect density and dynamic contact angle measurements determine that the intrinsic WCA of fresh sp2-hybridized carbon is 70.0? ? 1.5?. Current understanding of wetting models show that roughness and chemical heterogeneity do not cause the intrinsic hydrophilicity. This work unequivocally shows that fresh graphitic surfaces are mildly hydrophilic. %D 2016 %K Graphite; HOPG; MoS2; Molybdenum disulfide; Graphene; Wetting; Wettability; contact angle; surface energy; defect; defect density; carbon; hydrocarbon adsorption %I University of Pittsburgh %L pittir27321 %A Nana Zhang %T Variation and local adaptation in stress response using statistical analysis and bioinformatics %X Across climate regions, organisms have developed various mechanisms to their local environments. Understanding the adaptive variation and the underlying genetic basis for the variation can greatly improve our understanding on how natural selection works in nature. Organisms constantly defend with various environmental stressors. These stressors often share some pathways although also deploy stress-specific mechanisms. In this dissertation, I chose Arabidopsis thaliana natural populations across an elevation cline as a model to explore their adaptive divergence to various environmental stressors existed in their local regions. I firstly showed the constitutive adaptive variation and induced variation to multiple stressors of several key chemicals, camalexin, salicylic acid and heat shock protein 101 (Hsp101), under common garden experiments in Arabidopsis thaliana seedlings. These chemicals all showed adaptive variation in the studied populations. I then extensively explored heat stress, one of the most important stressors in nature, using a combination of phenotypic, transcriptomic and genomic approaches in the second half of the dissertation. I found out that high elevation plants adopt greater avoidance while low elevation plants adopt greater tolerance to heat stress. At the transcriptomic level, high elevation populations showed more gene expression change, both in the numbers of differentially expressed genes and the magnitude of the fold change. The genome resequencing also indicated several regions of selective sweep, which are the targets of strong selection, in comparing low and high elevation plants. Summarizing all the studies together, my dissertation provided support of the adaptive divergence in the studied Arabidopsis thaliana plants and also provided a pipeline for exploring other stressors across climate regions. %D 2016 %K Local adaptation; variation; natural selection; stress response %I University of Pittsburgh %L pittir26775 %A Mengjie Mao %T Vertical Memory Optimization for High Performance Energy-efficient GPU %X GPU heavily relies on massive multi-threading to achieve high throughput. The massive multi-threading imposes tremendous pressure on different storage components. This dissertation focuses on the optimization of memory subsystem including register file, L1 data cache and device memory, all of which are featured by the massive multi-threading and dominate the efficiency and scalability of GPU. A large register file is demanded in GPU for supporting fast thread switching. This dissertation first introduces a power-efficient GPU register file built on the newly emerged racetrack memory (RM). However, the shift operators of RM results in extra power and timing overhead. A holistic architecture-level technology set is developed to conquer the adverse impacts and guarantees its energy merit. Experiment results show that the proposed techniques can keep GPU performance stable compared to the baseline with SRAM based RF. Register file energy is significantly reduced by 48.5%. This work then proposes a versatile warp scheduler (VWS) to reduce the L1 data cache misses in GPU. VWS retains the intra-warp cache locality with a simple yet effective per-warp working set estimator, and enhances intra- and inter-thread-block cache locality using a thread block aware scheduler. VWS achieves on average 38.4% and 9.3% IPC improvement compared to a widely-used and a state-of-the-art warp schedulers, respectively. At last this work targets the off-chip DRAM based device memory. An integrated architecture substrate is introduced to improve the performance and energy efficiency of GPU through the efficient bandwidth utilization. The first part of the architecture substrate, thread batch enabled memory partitioning (TEMP) improves memory access parallelism. TEMP introduces thread batching to separate the memory access streams from SMs. The second part, Thread batch-aware scheduler (TBAS) is then designed to improve memory access locality. Experimental results show that TEMP and TBAS together can obtain up to 10.3% performance improvement and 11.3% DRAM energy reduction for GPU workloads. %D 2016 %K GPU Racetrack Memory Warp scheduler Memory partitioning %I University of Pittsburgh %L pittir27357 %A Sebasti?n Urli %T Yo, retrato. Autofiguraci?n, (i)legibilidades y poes?a l?rica. Los casos de Borges, C. Fern?ndez Moreno y Gelman %X This dissertation focuses on the self-figuration processes of Argentine writers Jorge Luis Borges, C?sar Fern?ndez Moreno and Juan Gelman. Its principal aim is to analyze the paradox of a ?lyric I? who portrays himself as constantly fragmentary, yet underlines his status as an author by using autobiographical references and remarks about his poetic practice. I argue that the figure of the author is constructed by using two modalities, or (il)legibilities. The first one includes a series of fictitious biographical references (biographemes) that are neither the coherent image of the ?self? nor a subject in constant dissemination, but that still operate within the notion of plot as a discordant concordance (Ricoeur). However, the figure of the author can also be analyzed by using theories of the image (Nancy, Didi-Huberman), ideas of language as immediate mediation (Agamben), and the ambiguity of the lyric (Culler, Combe). These all posit that poems and images can exceed narrative representation and even representation itself. The first chapter constitutes a theoretical discussion that analyzes the main concepts associated with these two (il)legibilities, while the remaining three chapters focus on the poets. In Borges?s chapter, the tension between the two (il)legibilities is shown through the construction of an ambiguous relationship of the lyric subject with Buenos Aires; through his self-figuration as a poet that desires to live different lives but limits himself to his own practice; and through a projection of his own image onto that of others. In Fern?ndez Moreno, the self-figuration process deals with the figure of his father (also a poet), and with the limits and possibilities that constant displacement in space, the inevitability of time, and irony impose on language. In Gelman, the process oscillates between the need of the subject to criticize social injustice and his use of ?fake? translations and a very personal poetic language to give account of dictatorship violence and of the disappearance of his son. By enhancing and reshaping the notion of the author, this analysis deepens our understanding of the three poets and of the challenges that the image and lyric discourse pose to self-representation. %D 2016 %K Southern Cone; Poetry; Self-figuration; Authorship; Image; Borges %I University of Pittsburgh %L pittir27696 %A Wenfu Wang %T The effect of calcium addition on the dissolution of hydroxyapatite %X Hydroxyapatite (HA) has been widely used as a scaffold material for bone tissue engineering. It has an excellent biocompatibility but a low biodegradability. The calcium content in HA is thought to have an important effect on the degradation of the scaffold. The purpose of this thesis was to fabricate a highly porous HA foam using an emulsion direct foaming method by infiltration of calcium salt solution with different calcium concentration (2mol/L and 5mol/L) and sintering process. After that foam were immersed in Tris-bufffer Saline (TBS) at several different time points. We investigated the in?uence of infiltrated calcium salt in terms of their effects on weight loss/gain, surface morphology, and microstructural-level degradation with SEM observation and micro-CT. Interestingly there were a large amount of precipitation of calcium phases and detectable weight gain for the 2M samples. And for 5M samples, weight loss with time and a better dissolution behavior were observed. %D 2016 %K hydroxyapatite infiltration degradability dissolusion foam %I University of Pittsburgh %L pittir27453 %A Iva Jestrovic %T A study of brain networks associated with swallowing via electroencephalography signals %X Swallowing and swallowing disorders have garnered continued interest over the past several decades. While physiological origins of the swallowing activity are well understood, it remains uncertain how this activity affects the central nervous system and brain activity. Electroencephalography (EEG) systems can enable our study of cerebral activation patterns during the performance of swallowing tasks, and can also possibly allow us to make inferences about the nature of abnormal neurological conditions causing swallowing difficulties. EEG also lends itself to techniques for analysis which provide insight into the interactions between brain regions, and enables the measuring and analysis of functional interactions between different brain regions by way of the graph theoretical and signal processing on graph approach. In this dissertation we provided better insight into the neurology of swallowing by focusing our research towards the three main areas of investigation. First, we showed that the EEG signals during the swallowing can be considered as non stationary. These findings provided an answer about choosing an appropriate technique for forming connectivity brain networks. Second, using graph theory and signal processing on graphs we showed that there are differences between swallowing in the neutral and chin-tuck head positions, between swallowing of different stimuli, between normal swallowing and swallowing with a distraction, and between consecutive swallows. Lastly, we improved an algorithm used to calculate the vertex-frequency information from the signals on graph that we used in our investigation. Particularly, we overcame the limitations of the computational complexity and the fixed window size associated with the windowed graph Fourier transform. %D 2016 %K Dysphagia, brain network, graph theory, signal processing on graphs %I University of Pittsburgh %L pittir27352 %A Joseph P. Kozak %T Electro-Thermal Effects of Power Transistors on Converter Performance %X In this work, a comparative study of the electrical and thermal performance of a silicon carbide (SiC) MOSFET and a silicon (Si) IGBT power transistor, operating in a DC/DC boost converter, is presented. Behavioral models of Powerex Inc. switching transistors were developed in Synopsys SaberRD and used to predict the converter electrical efficiency; ANSYS Icepak modeling software was used for thermal simulations to identify potential hot spots. This work provides an overall, electro-thermal analysis of both transistor types with respect to switching frequency in the boost converter circuit. Optimal switching frequencies for each device at a given current are observed, and thermal performance of the SiC MOSFET is quantified with comparable or greater electrical efficiency to the Si IGBT. Our SiC MOSFET temperature measurements further validated published mathematical expressions, which help, in this study, to identify the best operating frequency with respect to electrical and thermal performance. Performance analysis and design considerations from the DC/DC converter were then applied to design a 2kW, high power density, gallium nitride (GaN) based, modular multilevel converter (M2C). Half-bridge submodules for a single-phase, low voltage, high power density inverter (450 VDC, 2 kW, < 40in3 volume) were designed, constructed, and analyzed. This power density is predicted through the utilization of the EPC2014C gallium nitride (GaN) transistor into the half-bridge submodules of the M2C. These submodules are configured in series and parallel, with a switching frequency of 24 kHz, to achieve the voltage and current requirements. Each arm of the M2C was designed onto a double-sided, 6-layer, printed circuit board (PCB). The design and fabrications for these power boards are discussed as well. The design, fabrication, and analysis of all three power conversion circuits presented here also include similar analysis for their gate drive circuits. %D 2016 %K Electro-Thermal, GaN, Power Converters, SiC, Wide Bandgap Semiconductors %I University of Pittsburgh %L pittir27326 %A Zulqarnain Habib Khattak %T Evaluating the Operational and Safety Aspects of Adaptive Traffic Control Systems in Pennsylvania %X Adaptive Signal Control Technology (ASCT) is a novel Intelligent Traffic System (ITS) technology developed to optimize cycle lengths, green times or phasing sequences for traffic signals based on the changing traffic volumes collected from advanced detectors. While ASCT are considered to improve mobility and reduce congestion, they also have the potential to reduce crashes and improve traffic safety. This research explored these potential safety benefits of adaptive signal control systems through a two-step process. During the first stage, a 22 intersection corridor on Center Ave and Baum Boulevard, recently deployed with SURTRAC adaptive signals was selected and travel time runs were conducted with and without SURTRAC in operation using a GPS mobile app known as GPS tracks. The results did provide indications for safety benefits through reduced stops made along the intersections and improvement in travel time. During the second stage of the research project, 41 urban/suburban intersections from the state of Pennsylvania with SURTRAC and In-Sync ASCT deployments were selected and evaluated for their safety benefits using the Empirical Bayes (EB) before and after predictive method. National Safety Performance Functions (SPF) were selected for total and fatal & injury crash categories to calculate expected average crash frequencies for the selected intersections. The calculated expected average crash frequencies were used along with the observed crash frequencies from Pennsylvania Department of Transportation (PennDOT) crash reports in the rigorous EB method to calculate crash modification factors for adaptive signal control system. The findings, which evaluated a correlation based upon the development of Crash Modification Factor (CMF) proved the potential of ASCT to reduce crashes and improve traffic safety since the CMF values for total and fatal & injury crashes for both of the systems (SURTRAC & In-Sync) showed a significant correlation. Deploying ASCT was found to reduce total crashes by 34% with a CMF value of 0.66 and fatal & injury crashes by 45% with a CMF value of 0.55. CMF=1 means no change in safety conditions and CMF<1 indicates a reduction in crashes. The CMF correlations were found to be statistically significant at a 95% confidence level. The research findings will enable engineers and professionals to predict the potential reduction in crashes that would be expected after deploying ASCT at any new intersection. %D 2016 %K Adaptive traffic control, Empirical Bayes, Traffic safety, GPS Tracks %I University of Pittsburgh %L pittir26899 %A Sowmya Aggarwal %T Neuronal & Physiological Correlation to Hemodynamic Resting-State Fluctuations in Health and Diseases %X Low-frequency, spatially coherent fluctuations present in functional magnetic resonance imaging (fMRI) time series have had a tremendous impact on brain connectomics. To interpret the neurophysiological nature of changes in connectivity measured by hemodynamic signals, studies that investigate the dynamic relationship between neuronal and hemodynamic fluctuations are needed. Previously, our group used a transgenic animal model to simultaneously acquire bi-hemispheric images sensitive to neuronal and hemodynamic signals. We showed that hemodynamic connectivity is highly correlated with neuronal-connectivity in scans >5 min. This work used the same animal model and imaging method to calculate and compare the agreement between sliding window (SW) and dynamic conditional correlation (DCC) metrics. Transgenic GCaMP3 mice were used to simultaneously image ongoing changes in neuronal-activity (GCAMP) as well as hemodynamic measurements of blood oxygenation (OIS-BOLD, analogous to fMRI) from the same animals (n=6). Bi-hemispheric GCAMP and OIS-BOLD images were acquired at 10Hz from the exposed superior surface of the mouse brain under light ketamine anesthesia (30mg/kg/hr) for 5 to 20min periods. Pre-processing consisted of temporal band-pass filtering (0.02-0.20Hz). Then, k-means clustering was used on the GCAMP data to obtain 6 regions-of-interest. For each GCAMP and OIS-BOLD ROI time-series, we first examined the SW lengths for which the GCAMP and OIS-BOLD connectivity matrices were significantly correlated (r>0.47 corresponds to p<0.05). Over non-overlapping windows, the average SW correlation and fraction of significant windows are reported. We then examined the temporal sampling resolution for which comparisons between the GCAMP DCC and OIS-BOLD DCC connectivity matrices were significantly correlated. GCAMP (neuronal) and OIS-BOLD (hemodynamic) time-series were used to calculate SW and DCC connectivity matrices. For each non-overlapping SW window, the inter-node connectivity of the GCAMP data was compared to that of the OIS-BOLD data and tested for significance using a correlation analysis. The average correlation shows significant relationships for window lengths over 20 sec, while the average fraction of significantly correlated windows was >80% for windows >40 sec. A similar analysis of the GCAMP and OIS-BOLD DCC connectivity shows that average significant relationships were observed for temporal resolution >1.4sec, and >80% of the comparisons were significant for temporal resolution >2.2sec. %D 2016 %K Low-frequency, hemodynamic, conditional correlation, dynamic correlation, GCAMP, OIS, neuroimaging, optical imaging, mouse, brain %I University of Pittsburgh %L pittir27698 %A XIAOCONG DU %T Programming Exploration of Memristor Crossbar %X Memristor crossbar is prevailing as one of the most promising candidates to construct the neural network because of their similarity to biological synapses, favorable programmability, simple structure and high performance regarding area efficiency and power consumption. However, the performance of the memristor crossbar is limited by unideal programming and sensing process. In this thesis, the most preferred cell structure which is known as ?one-transistor-one-memristor? is investigated. Different factors that may have impacts on programming, such as the structure, the parameters and the conductance of a crossbar cell are studied using both theoretical analysis and simulation. Based on previous analysis, the programming process of the memristor crossbar deserves a deep exploration. For programming, the primary objective is to find out the relationship between the programmability of the memristor crossbar and its characteristics, such as the IR-drop and the crossbar size. The results are expected to be useful references for researchers designing the memristor crossbar. %D 2016 %K Crossbar array, memristor, programming, IR-drop, neural network, transistor %I University of Pittsburgh %L pittir27388 %A Shuangshuo Wang %T Using travel time reliability data to develop congestion management strategies in the transportation planning process %X The selection of different congestion management process (CMP) strategies for a specific corridor by a Metropolitan Planning Organization (MPO) is an important step in the transportation planning process. The selection of strategies and prediction of improvements using simple sketch planning methods based on travel time reliability data would be a useful tool. The congestion management strategies (CMS) and travel time reliability data, which are available for many MPOs including the Southwestern Pennsylvania Commission (SPC), are used to select projects to address congestion problems. A model is needed that can predict travel time reliability indices changes. Two travel time reliability indices that were used in this research are the posted speed reliability index and expected travel time reliability index, which are used by SPC. The goal of this research was to develop a CMS model that can select one or several optimum strategies for a corridor. The results are then used to calculate the changes in predicted travel time reliability indices for a corridor, which can be used to indicate the expected impact of the strategies. The research results provide a combined qualitative and quantitative method which could be used to select CMS projects and predict CMS improvements. This methodology will help MPOs to select CMS strategies and identify projects during transportation planning process. %D 2016 %K Congestion Management; Selecting strategies; Travel time reliability %I University of Pittsburgh %L pittir27100 %A Shafiq Abedin %T 3D Generalization of brain model to visualize and analyze neuroanatomical data %X Neuroscientists present data in a 3D form in order to convey a better real world visualization and understanding of the localization of data in relation to brain anatomy and structure. The problem with the visualization of cortical surface of the brain is that the brain has multiple, deep folds and the resulting structural overlap can hide data interweaved within the folds. On one hand, a 2D representation can result in a distorted view that may lead to incorrect localization and analysis of the data. On the other hand, a realistic 3D representation may interfere with our judgment or analysis by showing too many details. Alternatively, a 3D generalization can be used to simplify the model of the brain in order to visualize the hidden data and smooth some of the details. This dissertation addresses the following research question: Is 3D generalization of a brain model a viable approach for visualizing neuroanatomical data? %D 2016 %K 3D 2D Visualization Neuroscience Brain %I University of Pittsburgh %L pittir28016 %A Elizabeth Raupach %T Analysis of non-protein coding DNA transcription for roles in regulating gene expression %X During transcription, the DNA sequence encoding a gene is ?read? and copied into an RNA molecule. Many RNA molecules convey instructions for synthesizing proteins. Traditionally, proteins are thought of as molecular workhorses, which perform cellular functions. However, recent work has discovered that transcription of non-protein coding DNA is widespread in eukaryotes and plays important regulatory roles for many genes including genes mis-regulated in cancers. For example, in S. cerevisiae, the act of transcribing SRG1, a non-coding RNA (ncRNA), across the SER3 promoter positions nucleosomes over the SER3 upstream activating sequences. This creates a physical barrier preventing transcription of SER3. The pervasiveness of non-coding transcription suggests that regulatory roles for non-coding transcription may exist throughout the genome. To explore this possibility, we selected six candidate yeast genes expressing ncRNAs over their promoters and analyzed the effects of disrupting intergenic transcription on neighboring protein-coding transcript expression. Through this unbiased approach, we identified a previously unknown mechanism of transcription regulation at the ECM3 gene. Intergenic transcription seems to activate ECM3 expression. Further analyses identified roles for the Paf1 complex in ECM3 activation through methylation of histone H3 at lysine 4. Additionally, the NuA3 and SAGA chromatin modifying complexes are also required to activate ECM3 expression. These data support a model where co-transcriptional methylation of histone H3 at lysine 4 is required to recruit the NuA3 complex and other downstream modifiers to activate transcription of ECM3. Other cases of regulation by intergenic transcription had previously identified this modification in negative regulation of neighboring gene expression. Thus, ECM3 is an interesting model gene for elucidation of a novel regulatory mechanism mediated by non-coding transcription. The results presented here add to the growing number of cases where noncoding transcription has important roles in regulating gene expression. This work also indicates that the molecular mechanisms by which transcription of noncoding DNA exerts regulatory effects depend on the local chromatin environment. %D 2016 %K transcription, noncoding RNA, gene expression, chromatin %I University of Pittsburgh %L pittir27257 %A Thao Pham %T EXPLOITING THE SYNERGY BETWEEN SCHEDULING AND LOAD SHEDDING TO FACILITATE DIFFERENTIATED LEVELS OF SERVICE FOR CONTINUOUS QUERIES %X Data Stream Management Systems (DSMSs) offer the most effective solution for processing data streams by efficiently executing continuous queries (CQs) over the incoming data. CQs inherently have different levels of criticality and hence different levels of expected quality of service (QoS) and quality of data (QoD). Adhering to such expected QoS/QoD metrics is even more important in cases of multi-tenant data stream management services. In this dissertation, we propose DILoS, a framework that supports differentiated QoS and QoD for multiple classes of CQs by tightly integrating priority-based scheduling and load shedding. Unlike existing works that consider scheduling and load shedding separately, DILoS is a novel unified framework that exploits the synergy between them. For the realization of DILoS, we propose ALoMa and SEaMLeSS, two general, adaptive load managers. Our load managers can also be used standalone and outperform the state-of-the-art in three dimensions: (1)they automatically tune the headroom factor, (2) they honor the delay target, and (3) they are applicable to complex query networks with shared operators. We implemented DILoS, ALoMa and SEaMLeSS in our real DSMS prototype system (AQSIOS) and systematically evaluate their performance using real and synthetic workloads.Our experimental evaluation of ALoMa and SEaMLeSS verified their advantages over the state-of-the-art approaches. Our evaluation of DILoS showed that it (a) allows the scheduler and load shedder to consistently honor CQs? priorities, (b) significantly increases system capacity utilization by exploiting batch processing, and (c) enables operator sharing among query classes of different priorities while avoiding priority inversion. To further support differentiated QoS and QoD for CQs in distributed DSMSs, we propose ARMaDILoS, a conceptual framework for large scale adaptive resource management using DILoS. A fundamental component in ARMaDILoS is CQ migration. For this reason, we propose and implement UniMiCo, a protocol to migrate CQs without interrupting the execution of the queries. Our experiments showed that UniMiCo produced correct outputs and did not introduce any hiccup in the response time of the queries. %D 2016 %K Data stream, continuous query, scheduling, load shedding %I University of Pittsburgh %L pittir27356 %A Lauren Ross %T Explanation In Contexts of Causal Complexity %X My dissertation examines common types of causal complexity in the biological sciences, the challenges they pose for explanation, and how scientists overcome these challenges. I provide a novel distinction between two types of causal complexity and I analyze explanatory patterns that arise in these contexts. My analysis reveals how explanation in the biological sciences is more diverse than mainstream accounts suggest, which view most or all explanations in this domain as mechanistic. I examine explanations that appeal to causal pathways, dynamical models, and monocausal factors and I show how these explanations are guided by considerations that have been overlooked in the extant literature. My project explores connections between these explanatory patterns and other topics of interest in philosophy and general philosophy of science, including: reduction, multiple realizability, causal selection, and the role of pragmatics in explanation. %D 2016 %K Philosophy of Science, Philosophy of Biology, General Philosophy of Science, Causation, Explanation %I University of Pittsburgh %L pittir27571 %A Artan Salihu %T Internet Traffic and Topology Characteristics from a National ISP Perspective %X Measurement is the first step in predicting the growth of Internet. They can reveal information about traffic and topology characteristics of the Internet. Understanding traffic and topology characteristics are vital for evaluating the performance of networking protocols, creating accurate models for simulation and helping service providers to better utilize their resources. Using the data collected from a National Internet Service Provider in Kosovo, PTK, we report on traffic measurements and analyze some of the most important characteristics of Internet traffic such as self-similarity and long-range dependence. Also, we reveal information about the topology structure of Internet at IP level, from the perspective of our data. %D 2016 %K Measurements, Self-similarity, Traffic, Topology %I University of Pittsburgh %L pittir28117 %A Adriana Pitetta %T PEDAGOG?AS GRISES. SUBJETIVIDADES, MILITANCIAS Y SADISMOS EN LA PRODUCCI?N CULTURAL DEL CONO SUR %X This dissertation explores how radical militancy and State terrorism in Argentina, Chile and Uruguay in the sixties and seventies are represented in recent fictional and nonfictional films, novels, and testimonies. These texts suggest a revision from the perspective of a younger generation (my own) of the standard representation of political violence in this period as involving a strict logic of victims and victimizers. Central in my account is the idea of ?gray zone,? coined by Primo Levi, who describes the concentration camp as a site wherein victims and victimizers sometimes interchange roles. I argue that similar processes of subjective transformation occurred among the myriad actors involved in the ?Dirty Wars?. These processes are what I call, building on Levi?s concept, gray pedagogies. The first chapter, centers on the question of revolutionary militancy. I look at the ?Thou shalt not kill? (No M?taras) debate in Argentina about revolutionary violence and the documentary The Hour of Furnaces (1968) by Pino Solanas and Osvaldo Gettino. In the second chapter I analyze a group of texts centered in the idea of militant women as traitors because of their affective identification with their torturers, through a process of what I call tyrannical sexual pedagogies, specifically La vida doble (2010) by the Chilean Arturo Fontaine, El Infierno (1993) by Luz Arce, and Luisa Valenzuela?s novel La traves?a (2001). The third chapter highlights the ways in which texts by two younger Arentine artists -- the novel Los Topos (2008), by F?lix Bruzzone and Albertina Carri?s docu-film Los Rubios (2003)--address the interactions between State terror and revolutionary militancy, emphasizing issues like sexual diversity, racial questions, class or generational differences. This perspective proposes an ironic ?queer pedagogy? as an alternative to the standard testimonial representation of victimization and trauma. The last chapter deals with how the societies involved in the periods of state terror ?learn? in the process to be a willing, semi-sadistic spectator. My focus here is on the novels Par?s (1980) by the Uruguayan Mario Levrero and Historia del llanto (2007) by Alan Pauls. %D 2016 %K Southern Cone dictatorship memory gender militancy subjectivity %I University of Pittsburgh %L pittir27652 %A Kevin Andrew Reath %T THERMAL INFRARED ANALYSIS OF VOLCANIC PROCESSES %X Due to the dangerous and remote nature of many volcanoes, field-based data collection of active processes and precursory activity is problematic. Spaceborne remote sensing instruments enable these data to be recorded, monitored, and studied. The Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) is one such sensor that currently collects data in the visible near infrared (VNIR) and thermal infrared (TIR) wavelength regions and has an archive with the highest spatial resolution TIR data (90 m) currently available to the scientific community. ASTER is capable of recording precursory volcanic activity that is unidentifiable with other sensors. By combining ASTER data with those gathered from the Advanced Very High Resolution Radiometer (AVHRR) and the Moderate Resolution Imaging Spectroradiometer (MODIS), temporal resolution is improved and processes such as the cooling rate of pyroclastic flows and subtle precursory activity are able to be quantified. Rigorous modeling of these datasets further allows results such as estimation of pyroclastic flow volume, the specific eruption mechanisms and the onset of a future eruption. The work outlined in this dissertation demonstrates how data collected from the ASTER sensor greatly improves current monitoring capabilities. New methods for processing these high spatial resolution data allow scientists to understand and better evaluate the risks associated with specific volcanoes and their common eruption styles. %D 2016 %K Volcanology, Remote Sensing, Thermal Infrared, Pyroclastic, Precursory, SO2 %I University of Pittsburgh %L pittir27726 %A Michael Nardone %T Catalytic Asymmetric Alkylations of Latent Enolates %X Transition metal-catalyzed asymmetric allylic alkylations have become increasingly important in constructing highly versatile carbon-carbon and carbon-heteroatom bonds. However, diastereoselective allylic alkylations capable of setting vicinal stereocenters remain rare. The text herein describes a Ru(II)-catalyzed allylic alkylation that utilizes silyl enol ether nucleophiles to provide ?,?-substituted-?,?-unsaturated acyl pyrroles in synthetically useful diastereoselectivities. To illustrate the value of the resulting products, the methodology was exploited to construct the core of a pharmacologically active target, actinoranone. %D 2016 %K Ruthenium(II)-catalysis; Asymmetric Allylic Alkylation, Silyl Enolates, Actinoranone, Pyridyl Imidazoline, Acyl Pyrrole, %I University of Pittsburgh %L pittir26860 %A Katherine Parker %T Contentious Waters: The Creation of Pacific Geographic Knowledge in Britain, 1669-1768 %X This dissertation examines how the Pacific?covering one third of the world yet relatively new to Europeans?was portrayed prior to the famous voyages of Captain Cook. Although Pacific exploration has been extensively studied from the late eighteenth century onward, the period prior to 1770 has been largely ignored. Furthermore, exploration is usually investigated within national perspectives. This project offers a corrective to these trends; it adopts a transnational focus to investigate how societies integrated new spaces into existing geographic imaginaries. In the century prior to the Cook expeditions, the British were the main conduit of Pacific geographic knowledge to the rest of Europe. This was not because they mounted the most expeditions but because of their prolific publishing market and their particular geographic knowledge community. The Admiralty, Royal Society, and private mapmaking industry forged informal, interdependent ties to provide each other with the information necessary to make useful maps?that is, maps that could be used by navigators in foreign seas and could circulate widely. From their first commissioned expedition to the South Seas in 1669 to the first Cook expedition in 1768, the Admiralty increasingly involved themselves in the publication of voyage accounts and charts. They did so to manage their public image, but also to authenticate imperial claims. By the 1770s, exploration had become dependent on publication for its legitimation in the eyes of international diplomacy and the intellectual community. However, precisely how to create the optimum voyage account for diverse audiences was still a matter of considerable debate. Despite efforts to the contrary, the Admiralty could not monopolize Pacific geographic knowledge entirely. The resulting print wars between sailor-authors, savants, geographers, and publishers combined with geopolitical events marked the Pacific as a daunting, watery desert to be endured by Europeans. It was a place filled with giants and wandering islands and a far cry from the exotic paradise it would later become. The assimilation of geographic knowledge was just as, if not more, contentious in 1768 as it was a century earlier. %D 2016 %K Oceania, British, eighteenth century, books, cartography, discovery and exploration %I University of Pittsburgh %L pittir27729 %A Agampodi Madu Mendis %T Controlling Light in Nanoscale Dimensions %X The study of materials with nanoscale dimensions has gained wide spread research interest as these exhibit novel properties that can be used to manipulation of light for applications ranging from biosensing to optoelectronics. Metallic nanostructures coupled with light exhibit a collective oscillation of conduction band electrons leading an optical feature known as surface plasmon resonance (SPR). Quantum confinement effects in semiconductor nanoparticles allows the control over optical and electronic properties by changing size and shape of the nanoparticle. In order to fully realize the full potential of these interesting properties in nanoscale materials, this dissertation explores on fundamentals of these light matter interactions in nanoscale. The first work in this dissertation investigates on a novel plasmonic array that can be integrated into microfluidic channels to monitor real time biological interactions. The second work explores on coupling between one dimensional chains of plasmonic nanoparticles which leads delocalized surface plasmon feature which is highly sensitive local dielectric changes. The third study uses SPR to detect and quantify the interaction between the HIV capsid proteins and lipid bilayer films with the goal of establishing a potential drug target for HIV infection. The last study investigates on a general strategy to eliminate Fermi level pinning in semiconductor quantum dots using a thin film of alumina which may enhance the photoconversion efficiency in Schottky junction solar cells. The topics covered here should enable an insight into the fundamentals of light matter interactions in nanostructures which may facilitate their applications in sensing and photovoltaics. %D 2016 %K Plasmonics, Photonics, Nanoslit Arrays, Nanoparticle Chains, Quantum Dots, Fermi Level Pinning %I University of Pittsburgh %L pittir27592 %A Kaylyn Oshaben %T Modular Supramolecular Biomaterials Based on a Coiled-Coil Scaffold %X Nature uses proteins and nucleic acids to form a wide array of structural motifs. Chemists have applied these motifs to the rational design of supramolecular biomaterials. Intricate assemblies of fibers, nets and spheres have been synthesized and characterized; however, existing approaches often lack fine control over size and morphology. In an effort to address this limitation, we have developed a system based on self-assembly of a modular subunit consisting of two ?-helical peptides, which self associate to form a coiled coil, attached at their midpoints by a small organic linking group. We found that the linker identity not only impacted the flexibility of the assemblies but linker length was important to maintaining the folding of the peptides in the subunit. Our subunit design also allowed us to examine if assembly size could be controlled by changes to coiled-coil stability through sequence mutations. Supramolecular polymer growth models show assembly size can be controlled by changes in the association affinity of the monomer. We designed, synthesized and characterized a series of coiled coils with varying folded stabilities to use in the subunits and observed that assembly size increased when the stability of the coiled coil is increased. With the impact of the components of our self-assembling subunits characterized, we began examining if added functionality fluctuated with changes to the subunit. We developed a synthetic scheme for attaching a donor fluorophore and used a capping peptide labeled with an acceptor fluorophore to study F?rster resonance energy transfer in the dimeric coiled coil and larger assemblies. Finally, we observed that GCN4-p1, a well studied dimeric coiled coil, crystallized as either a dimer or trimer depending on the crystallization conditions. We carried out an extensive panel of solution-phase experiments to determine if the trimeric oligomerization state exists as measureable population. We found the solution conditions impact the preferred oligomerization state in the GCN4-p1 sequence. %D 2016 %K coiled coil, peptide, supramolecular polymer, helix, biomaterial, self assembly %I University of Pittsburgh %L pittir26730 %A Rachel Miller %T Patron Saint of a World in Crisis: Early Modern Representations of St. Francis Xavier in Europe and Asia %X Recent historical studies have focused on the vital role that Catholic saints played after the Council of Trent, investigating how these holy figures were utilized to alleviate all manner of problems besetting the Post-Tridentine Church, emerging European nation states, and individual Catholics. My dissertation, however, approaches this issue from an art historical perspective, considering how images of St. Francis Xavier, the sixteenth-century Jesuit missionary, exercised considerable agency in an early modern world rife with global crisis. Specifically, I investigate Xaverian prints and paintings created in border zones of early modern Catholicism or in territories of the Iberian empires, particularly Antwerp, Goa, and Naples. In these places, the image of Francis Xavier was consciously utilized to ameliorate crisis situations resulting from the tensions characteristic of cross-cultural interaction, the Jesuits? evangelization efforts, colonialism, and religious schism. The fundamental contention of my dissertation is that early modern images of saints do not simply reflect the historical circumstances in which they were made. Instead, institutions such as the Society of Jesus, the Portuguese or Spanish empire, and the Catholic Church enlisted the image of Xavier to quell crises globally and propagate an image of the political and spiritual triumph of Latin Christendom. %D 2016 %K St. Francis Xavier, Jesuit patronage, visual culture, Iberian empires, Post-Tridentine Church, Rome, Lisbon, Naples, Antwerp, Goa, Portuguese India %I University of Pittsburgh %L pittir27647 %A Shawn McCoy %T Natural Disasters, Risk-Salience, and Public Health %X This dissertation explores the dynamic links between natural disasters, human decision making, and risk perceptions as well as the public health implications of wildfire. In Chapter 1, we develop a model that links underlying changes in location-specific risk perceptions to housing market dynamics. We apply the model's predictions to an empirical analysis of the influence of severe wildfires on housing markets. Interpreted in the context of the model, our empirical results suggest that the evolution of risk perceptions following a natural disaster depend both on the characteristics of the property (relationship to the disaster and latent risk) and the location of the individual whose risk perceptions we are considering (potential seller vs. potential buyer). In Chapter 2, we examine the relationship between hurricanes, the salience of flood risk, and residential property investment. Utilizing a difference-in-differences estimation strategy, we find a significant increase in the probability a homeowner invests in a damaged building located in a statutorily designated flood risk area. However, we find no change in the rate of property investment in damaged homes located outside of these areas. We estimate changes in households? perceptions of risk by modeling relative changes in investment between properties in designated risk areas and properties directly outside of these zones restricting attention to the set of structures that failed to experience any damage by the storm. Model results suggest that a recent storm may elevate households' perceptions of flood risk; however, we show that the primary mechanism driving these changes is a household's exposure to storm damage. Finally, in Chapter 3 we estimate the effects of wildfire on infant health. Model results show that wildfires lead to a statistically significant 4% to 6% reduction in birthweight conditional on the mother being exposed in her second or third trimester and located inside a wildfire smoke plume or downwind of a wildfire burn area. We find no statistically significant effects of wildfire on the health of infants located more than 3 miles away from a burn scar, living outside of smoky areas, or upwind of a wildfire. %D 2016 %K Natural Disasters, Wildfire, Risk-Salience, Public Health %I University of Pittsburgh %L pittir27661 %A Shicheng Lu %T QUANTUM TRANSPORT IN SEMICONDUCTOR NANOSTRUCTURES %X Advances in complex oxide heterostructures have opened up a novel era in material sciences, and subsequently driven extensive physical research efforts to explore the underlying mechanisms. Material systems show a wide variety of phenomena such as superconductivity, magnetism, ferroelectricity, and spin-orbit coupling, all of which are gate-tunable. This facet demonstrates their significant importance, not only for science and research, but also for their substantial technological applications. One of the most promising systems is the LaAlO3/SrTiO3 heterostructure in which several unit cells of LaAlO3 are deposited on TiO2-terminated SrTiO3, giving rise to a two dimensional electron liquid (2DEL) at the interface region. In the case of 3-unit-cell (3 u.c.) LaAlO3/SrTiO3 interfaces, a conductive atomic force microscope (c-AFM) tip can be utilized to ?write? and ?erase? nanoscale devices, making LaAlO3/SrTiO3 a highly flexible platform application in novel nanoelectronics. In this thesis, the c-AFM lithography technique was employed to create various nanostructures at the LaAlO3/SrTiO3 interface. In parallel, their corresponding properties were also thoroughly investigated using quantum transport methods. Specifically, the mobility of these created nanostructures was investigated, and it was found that the mobility could be significantly enhanced in a 1D constrain configuration compared to the scenario of 2D structures. Nonlocal transport measurements were also performed on LaAlO3/SrTiO3 Hall bar structures in both normal state, and superconducting state. A novel transport property was revealed, and this property could be due to the spin and quasi-particles. Additionally, it is of note that quantum dot-like and quantum point-contact-like structures can be created via intentionally introducing barriers at the interface in LaAlO3/SrTiO3 nanowires. This can lead to various phenomena, such as electron paring without superconductivity, and conductance plateaus in transport measurements. The demonstrated c-AFM technique was also applied to a similar Al2O3/SrTiO3 material system, in which conducting channels were created at the interface. These channels show extremely high mobility at low temperature(s). %D 2016 %K Quantum transport, semiconductor, LAO/STO, LaAlO3/SrTiO3, Al2O3/SrTiO3, AFM lithography, 2DEL %I University of Pittsburgh %L pittir27502 %A Hernan Medina Jimenez %T RE-IMAGINAR LA AUTORREFERENCIALIDAD Y LA TEOR?A DEL JUEGO: A PROP?SITO DE BELLATIN, BOLA?O Y CORT?ZAR %X This dissertation contests the pervasive ?industrial reflexivity? within contemporary cultural productions by presenting how three recent cases of self-referentiality and frame narratives address this problem. The main scholarly accounts of Latin American self-referential narratives?formerly studied as ?metafiction??tend to situate such practices in relation to postmodern criticism. My guiding theoretical premise offers a significant departure from this approach by discussing self-referentiality not as a symptom but as a structural device that has historically circulated between Latin American literary traditions and Peninsular Spanish ones, and between Latin American literature and modern European epistemologies of the Other. My study thereby develops this approach by reading the works of Bellatin, Bola?o and the latest Cort?zar within the dynamics that tie them to political colonial imaginaries in Mexico, Chile, and Argentina. Locating the authors of my study within this cross-cultural exchange allows me to examine how their fictions re-structure boundaries of media and genre in response to pedagogical framing practices reified under transnational publishing industries. To address the ubiquitous status of self-referentiality across media, this study has expanded in scope to include diverse forms of textuality?a game, a novel, a happening. The second chapter examines Cort?zar?s Autonauts of the cosmoroute (1983) as a mode of self-referentiality re-structured through the premises of the narrative theory of game. In the third chapter, I argue that Bellatin?s Escritores Duplicados, a literary symposium performed by copycats, combines principles of game theory with collaborative art practices in order to frame the narrative situation as a process of reciprocal creative labor. The fourth chapter focuses on Bola?o?s 2666 in relation to the politics of the paratext as an interface that de-frames the author?s narrative system and blurs Bola?o?s self-conscious critique of both the market of interpretation and the ethos of academic culture. At its core, my dissertation acknowledges and links the politics and economy of literature with a still dependent neocolonial periphery; more specifically, it problematizes narrative framing vis-?-vis updated and new modes of self-referentiality organized in new ways, which ultimately play out a tension between highbrow literature and wider forms of cultural representation. %D 2016 %K self-referentiality, metafiction, game, paratext, Bellatin, Bolano, Cortazar %I University of Pittsburgh %L pittir27323 %A Lee Ellen Martin %T Validating the Voice In The Music of Lambert, Hendricks & Ross %X Lambert, Hendricks & Ross was an unusual vocal jazz trio. Made up of Dave Lambert, Jon Hendricks, and Annie Ross, they were one of the only interracial and mixed gender vocal jazz groups in the United States in the late 1950s. They were known for their vocalese?a style of singing in which lyrics are set to recorded instrumental melodies and improvisations. Their music revealed that the voice could fulfill its traditional role by contributing language through lyrics, and simultaneously take on the qualities of an instrument. In 1957, they set words to Count Basie big band recordings and recreated the entire ensemble with three voices. Their album Sing a Song of Basie (1957), was not only a hit, but is now considered the first foundational group recording of vocalese. In addition to their unorthodox sound, they were also a highly unusual looking group in 1950s America. Lambert, Hendricks, & Ross was a racially integrated and mixed gender trio comprised of a white vocal arranger from Boston (Lambert), an African-American vocalist and lyricist (Hendricks), and a Scottish born, former Hollywood child starlet (Ross). Together from 1957 to 1962, Lambert, Hendricks & Ross redefined vocal jazz while simultaneously reflecting changing social attitudes towards race and gender in the United States. Employing the voice as a foundation, this dissertation addresses two main questions: What does it mean to have a voice in jazz? And, who is allowed a voice? The voice is traditionally understood as either an expression of individuality or as the performance of a particular gendered, racial, or cultural identity. This dissertation examines the voice as an intersection between these two registers. In the words of Farah Jasmine Griffin, the voice is like ?a hinge, a place where things can both come together and break apart.? In this intersection, this dissertation reveals how Lambert, Hendricks, and Ross validated their subjectivities in jazz while also revealing the possibility of a more integrated and equal American society. %D 2016 %K Jazz Studies, Critical Race Theory, Gender Studies, Cultural Studies, American Studies, Voice, Lambert, Hendricks & Ross %I University of Pittsburgh %L pittir27291 %A Jianfei Hua %T Capsid Structure and DNA Packing in Jumbo Bacteriophages %X Jumbo phages, the phages with genome length larger than 200 Kbp, are extreme examples of how the capsid and genome coordinate in evolution. To learn the mechanism of capsid size change during evolutionary time, the capsid and DNA of several jumbo phages were characterized. The capsid structure and protein of a T=25 Sphingomonas paucimobilis phage PAU and a T=28 Escherichia coli phage 121Q were studied in detail. The high resolution cryo-EM structures show that the major capsid proteins (MCPs) of both phages adopt the HK97 fold which is conserved in all solved tailed phage MCP structures. The capsids contain decoration proteins with unprecedented shape and location. A pentameric protein structure is attached on the inner surface of the pentamer in both capsids. The PAU capsid has arcs of density located on hexamers surrounding the pentons, which may bend the conformation of the subunit it interacts with to improve capsid stability. 121Q capsid contains dimeric density near the local 2-fold symmetry axes and knob-like density at the middle of the hexamer, which may participate in forming the capsid shell because the 121Q MCP leaves holes at the two locations. Both capsids contain a number of internal proteins whose roles are not clear. The study on the jumbo phage DNA started with showing that partial modification of the cytosine in PAU and phage G DNA significantly slowed the phage DNA in electrophoresis. A new technique was developed to quantify the effect of base modifications in large DNA in electrophoresis, with which reliable measurements of the chromosome size of our jumbo phage collection were made. Jumbo phages have larger terminal redundancy and lower DNA packing density compared to small and mid-sized phages. The result on the DNA packing density in different sizes of phages reveals a negative correlation between the capsid size and the DNA packing density. We explain this relationship by a model based on the strength limit between the capsomers of the capsid shell. %D 2016 %K Bacteriophage, Jumbo phages, Capsid size, Triangulation Number, Capsid structure, Major capsid protein, Decoration protein, Internal protein, DNA packing density, Terminal redundancy, Capsid Evolution, PAU, 121Q, P1 %I University of Pittsburgh %L pittir27666 %A Jessica Gogan %T Curating Publics in Brazil: Experiment, Construct, Care %X Grounded in case studies at the nexus of socially engaged art, curatorship and education, each anchored in a Brazilian art institution and framework/practice pairing ? lab/experiment, school/construct, clinic/care ? this dissertation explores the artist-work-public relation as a complex and generative site requiring multifaceted and complicit curatorial approaches. Lab/experiment explores the mythic participatory happenings Domingos da Cria??o (Creation Sundays) organized by Frederico Morais at the Museum of Modern Art, Rio de Janeiro in 1971 at the height of the military dictatorship and their legacy via the minor work of the Experimental Nucleus of Education and Art (2010 ? 2013). School/construct examines modalities of social learning via the 8th Mercosul Biennial Ensaios de Geopoetica (Geopoetic Essays), 2011. Led by chief curator Jos? Roca and Pablo Helguera as pedagogic curator, the 8th edition?s regional artist residencies, neighborhood cultural center, and mediator team brought an expanded pedagogy to the center of the curatorial project. Clinic/care explores transdisciplinary practices in art and health via the Farm?cia Baldia de Boa Viagem (Baldia Pharmacy of Boa Viagem) at the Museum of Contemporary Art, Niter?i, focusing on the use and study of medicinal plants featured as part of Carlos Vergara?s exhibition Sud?rio (Shroud) in 2013-2014. Amidst the complexities of each situation a set of contingent, relational and contextual ?lessons? emerge as a possible fount for imagining a socially engaged curatorship grounded in a praxis of experiment, construct, care. One shaped by the legacies of post Neoconcrete art practices, decolonial pedagogies, Joaquin Torres Garc?a?s famous upturned map of the Americas as a gesture of radical locality, and the vital anti-colonial tradition of Oswald de Andrade?s anthropophagy. Drawing on its etymological roots of curare ? to care ? here curating affects a network of molecular learning and activism derived from a poetic and political contagion of encounters ? of ideas, practices, people and contexts ? and an ethical commitment to place. %D 2016 %K Contemporary art, curating, museums, education, Latin American Studies, Brazil, experiment, construct, care %I University of Pittsburgh %L pittir27725 %A Andrew Jeske %T The Development of English Vowels By Native Spanish Speakers %X Previous studies have shown that exposure to a second language (L2) changes one?s perception and production of L2 sounds to become more native-like (e.g., Flege, 1995; Flege & MacKay, 2004). This change has been documented most commonly among immigrants after they move to an environment where the L2 is the main means of communication (e.g., Jia & Aaronson, 2003). However, many people get introduced to a foreign language in school and it has been found that the amount of L2 exposure provided to students in a foreign language classroom is not equivalent to the amount of exposure experienced by immigrants and, therefore, will not produce the same kinds of benefits (e.g., White & Genesee, 1996). This dissertation aimed to examine the effects different amounts of L2 exposure in a classroom environment can have on the perception and production of English front vowels (/i ? e ? ?/). The participants for this study were a group 2nd, 4th, and 6th graders from two schools (one bilingual, one non-bilingual) who shared the same L1 (Spanish) and age of first exposure to L2 English, but who differed in the amount of L2 exposure they received each week (5 hours vs. 14 hours). The participants? perception was examined through a categorical discrimination task and their production of English front vowels was elicited via a picture-naming task. Predictions surrounding the relative discrimination difficulty of certain vowel pairs were made through the Perceptual Assimilation Model for Language Learners (PAM-L2) (Best & Tyler, 2007) and their production was evaluated through the Speech Learning Model (SLM) (Flege, 1995). Results from the perception task found a significant effect for school - the additional L2 exposure provided to the bilingual school students beneficially impacted their overall performance on the categorical discrimination task. However, this advantage was not clearly exhibited in their production because participants from each school were able to produce each English front vowel in a significantly distinct way. Further research will have to be conducted to see if the differences in production between the two schools affected the intelligibility of the target words. %D 2016 %K Second language acquisition, perception, production, phonetics, phonology %I University of Pittsburgh %L pittir27722 %A Tao Li %T ECONOMIC DIFFERENTIATION IN HONGSHAN CORE ZONE COMMUNITIES (NORTHEASTERN CHINA): A GEOCHEMICAL PERSPECTIVE %X Region-wide, systematic investigations were carried out in the Hongshan periphery and core zone to investigate how the earliest chiefly polities in northeastern China came into being. Possible causal factors, such as high levels of regional populations and intra-community conflict, were rejected by those regional survey projects. Economic or productive differentiation as an alternative and plausible explanation was proposed in this research background to explain the greater and more impressive material culture in the Hongshan core zone. Seeing pottery networks as a most direct indicator for economic interdependence between households, a geochemical study was carried out on 715 sherds selected from 16 Hongshan households in three residential areas (Sanjia, Dongshanzui, and Erbuchi) in the core zone. The geochemical study was complemented by a mineralogical investigation on a smaller sample from the same sherd pool. The results suggested that pottery-making was organized in different residential areas using local raw materials; non-utilitarian vessels were clearly produced with more labor investment and probably a low level of specialization, but they were no different from utilitarian ones in terms of procurement sources of pottery raw materials. Altogether, an ordinary Neolithic village economy is indicated for Hongshan core zone communities. The pottery distribution patterns suggested a wide and open pottery network crossing different neighborhoods, residential areas, and political entities. Economic connections were clearly established between Hongshan households from a few nearby districts, and the transfer of pottery created a chain of interaction that connected one end of the Hongshan zone to the other indirectly and facilitated cultural sharing of styles and other behaviors that helped create the Hongshan culture. In each residential area, a very few households stood out against others for their higher household status, and they all demonstrated a much stronger economic tie with fewer pottery producers. Yet, considering that higher-status households did not have exclusive access to certain pottery producers and nor did they rely strongly on the same producers, control over production and distribution of pottery seems not likely to be the only (or even a major) strategy that some Hongshan individuals or households employed to achieve their eliteness or power. %D 2016 %K Hongshan; Pottery; Economic differentiation; Geochemical sourcing; portable X-ray Fluorescence; X-ray diffraction; Pottery Distribution Networks; Household Status %I University of Pittsburgh %L pittir27598 %A Daniel Giraldo Pulido %T Entre l?neas: literatura marica colombiana %X This research maps a trajectory of several male Colombian writers, who informed their literary works by their own queer experiences. Poets Porfirio Barba-Jacob, Ra?l G?mez-Jattin and Harold Alvarado Tenorio, and novelists Fernando Vallejo, Bernardo Arias Trujillo and Fernando Molano Vargas are the main group of study. However, other writers and critics from Latin America and the world are taken into account to establish the relations of influence between the literary expressions from Colombia and the rest of the world. This particular group of Colombian writers are called marica, instead of queer, in order to create a productive dialogue between these two categories and the fundamental differences between a secular terminology coined by European and North American scholars, and a terminology created upon the actual Colombian context: the union of State and Catholic church that I call ?Colombian framework of traditions.? The main goal of this project is to present a coherent analysis of the most representative works of Colombian marica art from its first appearances at the end of the nineteenth century to today. Common features of this kind of art can be articulated in the form of a definition. Therefore, marica art can be defined as an ambivalent artistic expression that does not necessarily require an act of understanding, but a perception, a feeling or an affect, an act of ?reading between the lines? that is made possible by a common sensibility shared between writer and reader. This marica sensibility is the product of a collective experience of marginalization, an experience resulting from the construction, within a highly religious social context, of a subversive identity based on a male same-sex desire. My dissertation explores these common features, and considers the insights, as well as the limitations, of queer theory in this matter. I create and develop new approaches through queer theory, subsequently expanding its range of action. This project aims to make a contribution to the field and to the understanding of the Catholic/normative tradition and its mechanisms of coercion that define and shape the lives and deaths of many marica Colombian men. %D 2016 %K Porfirio Barba Jacob Bernardo Arias Trujillo Fernando Vallejo Ra?l G?mez Jattin Harold Alvarado Tenorio Fernando Molano Vargas %I University of Pittsburgh %L pittir27600 %A Regina Leckie %T Glucose control and working memory as a function of age in older type 2 diabetics: Results from the Look AHEAD Ancillary Brain Study %X Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent in the US, especially in older adults. In fact, 25.9% of adults over the age of 65 have been diagnosed with T2DM. In addition to the increased cardiovascular disease risks, cognitive and brain health impairments are also associated with T2DM. Overall lower brain volumes and poorer memory function is observed in T2DM, indicating poorer brain health than non-diabetics. While the mechanisms behind poorer cognitive function and brain health are unknown, impaired glucose control, as measured by glycated hemoglobin (HbA1c), is one aspect of T2DM that may provide insight into this ongoing inquiry. The Action for Health in Diabetes (Look AHEAD) trial was designed to longitudinally examine the cardiovascular health effects of weight-loss in older adults diagnosed with T2DM. The trial randomized participants into two conditions: Intensive Lifestyle Intervention (ILI) consisting of a physical activity regimen and caloric-restriction diet, and Diabetes Support and Education (DSE) control group offering seminars on diet, exercise, and diabetes symptoms management. At year 10 of the trial, participants (N = 237, mean age = 67 years) were recruited for a magnetic resonance imaging (MRI) ancillary study, in which participants completed a working memory task during a functional MRI (fMRI) scan and blood draw to measure HbA1c levels. Results indicate that age moderates the relationship between intervention group and cognitive function and the relationship between HbA1c and cognitive function, such that older adults in the ILI group, but not control group have the best glucose control yet worst performance. Further analyses reveal that the older adults in the ILI group with high HBA1c levels performed significantly better than those with lower HbA1c levels. Together, these results suggest that HbA1c is protective to working memory function in old age within T2DM. fMRI identifies regions in the prefrontal cortex, cingulate, insula, and hippcampus where HbA1c is associated with brain activity during the working memory task. However, no group differences in brain activity were identified. As T2DM becomes more prevalent in the population, it is critical to understand the cognitive impact this disease may have on patients, especially as they age. %D 2016 %K glucose, type 2 diabetes, HbA1c, working memory, fMRI, aging %I University of Pittsburgh %L pittir27685 %A Ericka Keef %T Interactions between the immune system, influenza A virus, and bacterial pneumonia %X Influenza and pneumonia continue to be leading causes of morbidity and mortality in the United States each year. These pathogens can be lethal on their own, but they are particularly dangerous if encountered simultaneously in an influenza-pneumonia superinfection. The severity of the infection can be controlled by the strength of the host?s immune response, which is often dependent on the age and species of the host. In this work, the intrahost immune response to respiratory infections is explored with mathematical modeling. We first examine how different species of mice react to an identical Streptococcus pneunoniae infection. A low-order ordinary differential equation (ODE) model is used to model data from four strains of mice, each of which represents a distinct phenotype in response to the infection. By changing only a small number of parameters, representing variations in the strength of the immune response, the output of the model can change significantly. We next examine the complementary study, in which the host species remains constant but the strain of bacteria administered is different. Again adjusting only a few parameters in our small ODE model, we can again reproduce several phenotypes of responses to these varied infections. We then examine the immune response to influenza infection. First, we develop a large ODE model to fit to data from mice infected with either a sublethal or lethal dose of H1N1. The model is the first of its kind to include a detailed study of the inflammatory response to infection. Next we use a Boolean network model to study data taken from adult and elderly mice infected with influenza to assess differences in the immune response that arise with age. Finally, we propose an ODE model of influenza-pneumonia superinfection. In each of these five studies, we discuss the implications of our work for further experiments and identify potential avenues for future research. %D 2016 %K influenza; pneumonia; mathematical modeling; viral kinetics; ordinary differential equations; Boolean model; rule-based model %I University of Pittsburgh %L pittir27702 %A Alexandra Klaren %T Invisible to the Eye: Rhetorics of Ethical Emotionality in Mister Rogers' Neighborhood %X This dissertation seeks to understand the success, significance, and impact of the children?s television program, Mister Rogers? Neighborhood (1968-2001). It explores the nuanced complexity of Rogers? thought, the dialogical integration of his various influences, and the intentional ethic of care behind the creation of a program that spoke to the affective, cultural, and educational needs of children (and adults) during a period of cultural and political upheaval in the United States. Despite the program?s longevity and popularity, it has received only scant attention from humanities scholars. The sole monograph to date interprets the program from a pacifist perspective. My dissertation provides the first full-fledged contextualization of the program, its vision and its enactment, as an innovative intervention into the world of children?s television. Delving into the newly available primary documents at the Fred Rogers Archive, I examined and analyzed speeches, notes, scripts, and letters written by Rogers in order to discover and understand his vision for the Neighborhood and his conception of televisual communication. Viewer mail revealed the efficacy and specificity of his heightened parasocial communication techniques and pedagogical objectives. A rhetorical analysis of the program?s first year shows how Rogers interweaves a dialogical ethos with a meticulous study of objects and play to engage young viewers in social-material culture. Drawing on dialogic theory (M. Bakhtin, P. Friere, R. Arnett, M. Buber), Roger Burggraeve?s concept of ?ethical emotionality,? and D.W. Winnicott?s theories of child development, this study shows how Rogers presciently recognized in television the parasocial possibilities for making the critical embodied social-emotional communication connections that humans need to develop and cope in the world. I argue that Rogers deployed the critical orientation of ?ethical emotionality? necessary for a ?holistic and moral education? (R. Burggraeve). I show how the success of the program revolves around Rogers? establishment of a space of ?emotional safety,? a pathos recognized by Saint-Exup?ry as ?invisible to the eye,? through rhetorics of care and connection in his televisual encounter. The dissertation?s major findings detail how the program?s success is largely owed to Rogers? effective deployment of ?ethical emotionality,? parasociality, and tele-dialogism to reach his viewers. %D 2016 %K dialogic, communication ethics, media, television, pedagogy, tele-dialogism, mass communication,interpersonal communication, Mister Rogers' Neighborhood, Fred Rogers, Mister Rogers %I University of Pittsburgh %L pittir28059 %A Tucker S. Ferda %T Jesus and the Galilean Crisis: Interpretation, Reception, and History %X 19th-century attempts to reconstruct the historical Jesus often featured the theory of a ?Galilean crisis.? The crisis theory held, in general, that Jesus? public career passed through sequential stages of friendly and hostile reception, and further contended that growing opposition to Jesus led to certain changes in his theology, outlook, or rhetorical tone. The purpose of this dissertation is to investigate the origins of this idea, its interpretive logic in the Gospels, and the historical value of the hypothesis (if any) for contemporary study of the historical Jesus. The three main contributions of the project are as follows. First, the study fills a lacuna in the history of scholarship, since the crisis theory is typically treated briefly, if at all, in surveys of Jesus research. What is more, when mention is made of it, descriptions of its background and origin are often rife with misunderstanding. This dissertation will challenge conventional periodizations of Jesus scholarship, and significantly widen the scope of research in pre-modern sources, by arguing that the crisis theory is in many ways a historical ?solution? to preexisting interpretive ?problems? in the reading of the Gospels. Second, it will be argued that the interpretive and even historical logic of the crisis theory is still very much a part of current scholarship. The notion that we posit a change in historical context to resolve certain theological tensions in the Gospel tradition?and particularly that we periodize or stratify those tensions in our sources?parallels numerous projects in New Testament studies in remarkable ways. This discussion will enable one to see continuity where histories of research have tended to stress discontinuity. Thirdly, the project will contend that, although the crisis theory is in many ways a failed hypothesis in the macro, it raises questions that current Jesus research has largely been content to ignore. The final chapters will reflect on the question of the consistency of Jesus throughout his ministry, the notion of a ?Galilean spring,? and the suggestion that the tradition is marked by a struggle to respond to growing opposition and the rejection of his message. %D 2016 %K Galilean crisis, Gospel, historical Jesus, history of scholarship, history of New Testament criticism, reception history of the Bible %I University of Pittsburgh %L pittir27112 %A Peng He %T Mathematical Analysis of Credit Default Swaps %X In this thesis, we establish a financial credit derivative pricing model for a credit default swap (CDS) contract which is subject to counterparty risks. A credit default swap is an agreement on exchange of cash flows between two parties, the buyer and the seller, about the occurrence of a credit event. The buyer makes a series of payments to the seller before the event and before the expiration date. The seller pays the buyer a fixed compensation at the moment when the event occurs, if it is before the expiry. The model arises a linear partial differential equation problem. We study this model, i.e. differential equation and show that a solution of the PDE problem from structure model can be obtained as the limit of a sequence of PDE problems which comes from intensity model. In addition, we study the infinite horizon problem of the pricing model which leads to a nonlinear ordinary differential equation problem. We obtain a implicit solution of the ODE problem and prove the solution can be converged by the solution of the PDE problem exponentially. Furthermore, the models and theoretical methods in this study get connected between two main risk frameworks: term structure model and intensity model, which greatly extend the area of applicability of structure models in financial problems. Moreover, We obtain the uniqueness, existence, and properties of the solutions of the PDE and ODE problems. Nevertheless, we implement numerical methods to calibrate the parameters of stochastic interest rate model and analyze the numerical solutions of the pricing model. %D 2016 %K Structure model, counterparty risk, linear PDE, infinite horizon, numerical analysis %I University of Pittsburgh %L pittir27289 %A Matthias Grabmair %T Modeling Purposive Legal Argumentation and Case Outcome Prediction using Argument Schemes?in the Value Judgment Formalism %X Artificial Intelligence and Law studies how legal reasoning can be formalized in order to eventually be able to develop systems that assist lawyers in the task of researching, drafting and evaluating arguments in a professional setting. To further this goal, researchers have been developing systems, which, to a limited extent, autonomously engage in legal reasoning, and argumentation on closed domains. This dissertation presents the Value Judgment Formalism and its experimental implementation in the VJAP system, which is capable of arguing about, and predicting outcomes of, a set of trade secret misappropriation cases. VJAP argues about cases by creating an argument graph for each case using a set of argument schemes. These schemes use a representation of values underlying trade secret law and effects of facts on these values. VJAP argumentatively balances effects in the given case and analogizes it to individual precedents and the value tradeoffs in those precedents. It predicts case outcomes using a confidence measure computed from the argument graph and generates textual legal arguments justifying its predictions. The confidence propagation uses quantitative weights assigned to effects of facts on values. VJAP automatically learns these weights from past cases using an iterative optimization method. The experimental evaluation shows that VJAP generates case-based legal arguments that make plausible and intelligent-appearing use of precedents to reason about a case in terms of differences and similarities to a precedent and the value tradeoffs that both contain. VJAP?s prediction performance is promising when compared to machine learning algorithms, which do not generate legal arguments. Due to the small case base, however, the assessment of prediction performance was not statistically rigorous. VJAP exhibits argumentation and prediction behavior that, to some extent, resembles phenomena in real case-based legal reasoning, such as realistically appearing citation graphs. The VJAP system and experiment demonstrate that it is possible to effectively combine symbolic knowledge and inference with quantitative confidence propagation. In AI\&Law, such systems can embrace the structure of legal reasoning and learn quantitative information about the domain from prior cases, as well as apply this information in a structurally realistic way in the context of new cases. %D 2016 %K Artificial Intelligence and Law, Argumentation, Argument Schemes, Case-based Reasoning %I University of Pittsburgh %L pittir27608 %A Courtney S Long %T Re-Categorizing Great Britain's Medieval Architecture: A Lesson in Nineteenth-Century Visual Taxonomy %X This dissertation explores the intersections of architectural history and natural science in the first half of the nineteenth century in Great Britain. Examining a set of seven British architectural historians between 1800 and 1850, an alternate approach to our contemporary understanding of Nineteenth Century architectural history writing is offered through an analysis of visual representations showing change over time. Each chapter confronts shifting notions about the developmental progress of biological and architectural species presented by some of the renowned theorists of natural science and architectural history from the eighteenth and nineteenth centuries. The theories about change over time from Carl Linnaeus, Jean-Baptiste Lamarck, Charles Lyell, and Charles Darwin, to name a few, are offered in order to contextualize pictorial arrangements of visual knowledge showing change over time in architectural histories of medieval British ecclesiastical buildings. The visual examples from works by Thomas Warton, James Storer, John Britton, Thomas Rickman, Robert Willis, Edmund Sharpe, and John Ruskin present their own narrative of progress and change over time as each new author arranged a different set of building examples for illustration that, when examined together, highlight the synchronic and diachronic relationships between space and time, text and image, and art and science. Nineteenth-century notions about vision, objectivity, and Truth to Nature are included in order to situate these often-overlooked images in the context of contemporary art historical thinking. Since its mid-nineteenth century formation as an academic discipline, the teaching of art history has been influenced by the history of science and scientific research. The correlation between natural science and architectural history, however, has been largely ignored. What is missing from recent British architectural historiographies is an investigation of theoretical and artistic production pertaining to ideas of change over time in the nineteenth century. This dissertation situates medieval British ecclesiastical architectural history within the broader framework of natural history through an analysis of nineteenth-century taxonomic systems. Examining pictures and diagrams, the following chapters investigate how natural historians and architectural historians present, in pictorial form, evolutionary descent, the typical in species, and their synchronic relations among different types and forms. %D 2016 %K Architecture-Great Britain; Art and science; Architecture, Gothic; Visualization; Windows-England; Visual taxonomy %I University of Pittsburgh %L pittir27728 %A Nathan Hall %T SHORT WAVELENGTH CONE ACTIVITY TO AND THROUGH THE SUPERIOR COLLICULUS %X A key structure for directing saccadic eye movements is the superior colliculus (SC). The SC is thought to be unresponsive to stimuli that activate only short wavelength sensitive cones (S-cones) in the retina. The apparent lack of S-cone input to the SC was recognized as an opportunity to test SC function. The assumption that S-cone stimuli are invisible to the SC has been used in numerous human clinical and psychophysical studies. The idea is that visually guided behavior dependent on the SC should be impaired when S-cone stimuli are used. Behavioral impairment to S-cone stimuli is used to infer the role of the SC in a given behavior. The goal here was to directly test this assumption by recording from single neurons in macaque SC. This hypothesis was tested in three steps. First, the perceptual reports of monkeys were used to psychophysically calibrate stimuli that activate only S-cones. Second, individual SC neurons were tested for visual sensitivity to S-cone stimuli. Finally, express saccades, a behavior known to depend on the SC, were examined physiologically and behaviorally. Both neural activity and SC-dependent behavior are present to S-cone stimuli and depend on the amount of S-cone contrast. These results demonstrate that the SC receives S-cone input, and outputs S-cone dependent behavioral commands. Together the data indicate that S-cone stimuli cannot be used to diagnose SC involvement in behavior. %D 2016 %K S-cone SC Macaque Express Saccade %I University of Pittsburgh %L pittir27375 %A Chitra Gautham %T Time-resolved two-photon absorption in quantum dots and polaritons %X We used two-photon absorption to study semiconductor samples. The energy of the photons used to excite the particle is half the energy of the electronic transition. In one set of experiments we have performed time-resolved measurements of the time scale for conversion of excitons in dark states to bright (light-emitting) states in GaAs quantum dots. The dark states are pumped using two-photon absorption, while the bright state emission is observed in single-photon emission. This conversion time is connected to the spin flip time for carriers in the quantum dots. The time scale is found to be of the order of several hundred picoseconds. In a second set of experiments, we performed time-resolved measurements of two-photon excitation directly into microcavity polariton states. Although this process is forbidden by symmetry for light at normal incidence, we observed that it is allowed at non-zero angle of incidence due to state mixing. Fermi's golden rule for bosons states that absorption into a final state is enhanced by the occupation of that state. This thesis reports experiments aimed at using a laser beam to create a condensate and modulate the two-photon absorption of a second beam. %D 2016 %K Quantum dots, Polaritons, Two-photon excitation, Excitons, Optics %I University of Pittsburgh %L pittir26693 %A Christine Debelak Neider %T "I am . . .not yet": Maxine Greene's Notion of Naming and Becoming %X I identify and study Naming, within the existential and phenomenological work of Maxine Greene, as a praxis for teachers. As a teacher, I am wondering if Naming is a useful philosophical orientation for teachers so that we can counter the data-and-expert-driven, student-as-product, teacher-as-mechanized-cog-yet-solely-accountable narrative about education and open space for ourselves to engage in teaching as human beings. Can a Naming praxis encourage our own Becoming? Can a Naming praxis help us more closely align our teaching with our ethics? I make my inquiry by writing my experiences autobiographically and critically interpreting them in dialogue (a Naming itself) with other teachers, with cultural voices, and with discourses of scholarship. Further, conducting my study ?upon myself,? I enact a Naming praxis and may therefore determine whether I find myself able to imagine alternate possibilities for Being and whether I am more closely aligned with my ethical sensibilities. In my portrayal, then, I provide an aesthetic experience for my fellow teachers to Name and Imagine their own praxis or orientation toward teaching as a human being. The work of this study demonstrates a normed understanding of the role of teacher and how that mindset might limit teachers in their ethical Becoming with their students. I offer a Naming praxis as a possible orientation countering this mindset and action toward a teacher?s ethical work and life. %D 2016 %K Maxine Greene, praxis, naming, teacher education, philosophy of education, currere, teacher lore %I University of Pittsburgh %L pittir27879 %A Vince Schiappa %T Assessment of Power Wheelchair User Satisfaction Using Seat Elevators %X The purpose of this study was to assess the difference in satisfaction of using seat elevators (SE) on power wheelchairs among individuals with disabilities through retrospective analysis of two clinical quality assurance databases that included time 1 (T1) and time 2 (T2) Functional Mobility Assessment (FMA) scores. The FMA is a validated self-report questionnaire that measures a person?s satisfaction in performing Mobility Related Activities of Daily Living (MRADL) across 10 items (Kumar, 2013). The databases collectively held 731 cases while 123 cases met the inclusion criteria of using a power wheelchair equipped with a SE at either T1, T2, or both. Three aspects of the FMA were assessed; #5 (reach), #6 (transfer), and total score. Cases were assigned to one of the three following groups; power wheelchair (PWC) users using a device with a SE at T1 but using a new device without a SE at T2 (SE ? NSE, n = 14); PWC users using a device with a SE at T1 and using a device with a SE at T2 (SE ? SE, n = 42); and PWC users using a device without a SE at T1 but using a device with a SE at T2 (NSE ? SE, n = 67). The three aspects of the FMA were analyzed within the three groups of PWC users. For the SE-NSE group, there was a significant decrease for FMA item #5 (reach) (p = .03). There were no significant changes for FMA item #6 (transfer) (p = .48) and total score (p = .57). For the SE-SE group, there were significant improvements in FMA items #5 (reach) (p < .01), #6 (transfer) (p < .01), and total score (p < .01). For the NSE-SE group, there were significant improvements for FMA items #5 (reach) (p < .01), #6 (transfer) (p < .01), and total score (p < .01). In summary, the study indicates a SE can increase satisfaction of PWC users. The lack of a statistically significant difference in FMA item #6 and FMA total for the SE ? NSE group was likely due to a small sample in that subgroup. %D 2016 %K wheelchairs, patient outcome assessment, outcome assessment, mobility %I University of Pittsburgh %L pittir27312 %A Abigail Cryan %T CHARACTERISTICS OF EPIGLOTTIC INVERSION IN CHILDREN WITH CEREBRAL PALSY %X This single cohort, retrospective, descriptive study, was conducted because of anecdotal, clinical observations that most children with cerebral palsy exhibit limited epiglottic inversion during swallowing. Puree bolus swallows from previously recorded Videofluoroscopic Swallowing Studies (VFSS) of children with cerebral palsy were analyzed with image processing software to compare the degree of the epiglottic angle before the swallow to the epiglottic angle at maximum rotation, and the competence of airway protection using the Penetration-Aspiration Scale. Data were analyzed to describe correlation between angle of epiglottic inversion and entry of material into the laryngeal vestibule. Descriptive statistics were used to describe means and standard deviation of epiglottic inversion, penetration-aspiration score, and the age and sex of the participants. A comparison was made between angle of epiglottic inversion in children with cerebral palsy and healthy norms. Findings of this study included significantly limited epiglottic inversion in children with cerebral palsy. A correlation was not demonstrated between epiglottic inversion and penetration aspiration scores. %D 2016 %K cerebral palsy, children, dysphagia, epiglottis %I University of Pittsburgh %L pittir27632 %A Valerie Williams %T Comparisons in Physical Characteristics of Professional Ballet and Collegiate Dancers %X Dancers are a group of athletes with unique physical and performance characteristics. Dance medicine and science is a growing field, as researchers and clinicians see the need for information specific to this population due to high injury rates. Comprehensive information on separate types of dancers, especially collegiate dancers, is unavailable. The purpose of this study was to describe and compare characteristics of professional ballet and collegiate dancers, as well as investigate the relationships among these characteristics. The first portion of the study investigates differences in body composition, lower extremity and trunk muscular strength, dynamic postural stability, and landing kinematics of professional ballet dancers and collegiate dance majors. The second portion of the study determines the ability of strength to predict dynamic postural stability and kinematic variables that are potential risk factors for injury including, knee valgus, ankle inversion, and foot pronation. Fifty nine dancers participated in the study (30 professional ballet and 29 collegiate). Equal proportions of males and females were in each group. Dancers completed an injury history questionnaire, followed by assessments of body composition, dynamic postural stability, kinematics during a dance jump task, and isokinetic and isometric muscular strength. Results demonstrate that professional dancers are significantly stronger than collegiate dancers for most muscle groups tested. The study found no significant differences in dynamic postural stability, and minimal differences in kinematics. No differences were found in self-reported injury histories, except that a greater proportion of professional dancers reported injuries to the ankle, and foot and toe regions. Regression analyses revealed that gender and trunk rotation strength predicted dynamic postural stability. Gender and knee flexion strength predicted maximum knee valgus angle. Gender and knee extension strength predicted ankle inversion angle at initial contact and, gender and knee flexion strength predicted maximum inversion angle. No significant predictors of foot pronation angle were found. This study provides a comprehensive assessment of professional ballet and collegiate dancers and provides insight into the relationships among their characteristics and abilities. Further research should investigate relationships in each gender separately, as well as study additional variables that explain the relationship between strength and biomechanics. %D 2016 %K dancers, physical characteristics, muscular strength, dynamic postural stability, kinematics, injury %I University of Pittsburgh %L pittir27283 %A Cristina Robles Bahm %T A Comprehensive Study of Internal Representations of Floor to Floor Transitions Points in a Large Complex Indoor Environment %X Wayfinding in complex indoor environments can be a stressful and disorienting activity. Many factors contribute to this difficulty, one reason being the number of floors paired with many different and often unpredictable ways to get from one floor to another. This dissertation focuses on providing a comprehensive analysis of how the human cognitive system represents the spatial information in floor to floor transition points. In particular, this project will focus on the internal representations formed by people familiar with a particular complex environment. In order to accomplish this, a user study was conducted at the Carnegie Museums of Art and Natural History that drew participants from the Visitor Services Department. Participants were asked to give wayfinding descriptions to and from several landmarks in the museums with the majority of the routes spanning multiple floors. Both verbal descriptions and sketch map descriptions were studied. It was found that floor to floor transition points were often represented as landmarks with two landmarks in particular being represented often as both functional as well as reorientation landmarks. This finding continues the discussion on global landmarks and their representation and salience in large complex indoor environments. %D 2016 %K wayfinding, spatial cognition %I University of Pittsburgh %L pittir28617 %A Terri Devereaux %T Condition-Specific SBAR use in Long Term Care and its Effect on Nurse Perception of Nurse-Physician Communication and Acute Care Hospitalizations: A Pilot Study %X CONDITION-SPECIFIC SBAR USE AND ITS EFFECT ON NURSE PERCEPTION OF NURSE-PHYSICIAN COMMUNICATION AND ACUTE CARE HOSPITALIZATIONS: A PILOT STUDY Terri Devereaux PhD, MPM, FNP-BC University of Pittsburgh, 2016 Ineffective communication between physicians and nurses leads to transfer of LTC residents to acute care, with up to 67% found to be avoidable. A currently used Situation, Background, Assessment, Recommendation (SBAR) communication tool requires nurses to discern and organize pertinent data to report, which may limit its usefulness and impact on communication. This study tested whether using a SBAR tool specific to changes in condition for nurses in LTC to collect and report pertinent information improves nurses? perception of nurse/physician communication and decreases the number of acute care hospitalizations. A quasi-experimental one group pre/posttest was conducted to test condition-specific SBARs (CS SBARs) for the most common reasons for transfer to acute care. All RNs (n=27) and LPNs (n=33) at a 139-bed skilled nursing/post-acute care nursing facility participated. A survey to measure nurse perception of quality of nurse-physician communication, transfers, hospitalizations, and 30-day readmissions to acute care data were collected for a 3 month period pre and post intervention. Due to high nursing turnover rates adequate power was not achievable to measure perception of quality of nurse-physician communication with confidence. Frustration was the only item with a significant change, an increase post-implementation (p=.04). A significant reduction in transfers (0.44 vs. 0.24, p<.001), hospital unplanned admissions (0.34 vs. 0.18, p=.004); 30-day readmissions (0.12 vs. 0.04, p=.011) was observed 3 months post-implementation. Avoidable transfers were significantly reduced (0.59 vs. 0.41, p=.001) as were avoidable hospital admissions (0.45 vs. 0.25, p=.003). A significant reduction in transfers due to pneumonia (0.53 vs .0.17, p=.014) was observed. No other significant condition-specific transfer reductions were observed. This study suggests that using CS SBARs when a change in resident condition occurs reduces transfers/hospitalizations/30-day readmissions and when transfers did occur, they were more likely to unavoidable, suggesting that residents were more likely to receive appropriate care in the most appropriate setting. All 30-day readmissions except one were from post-acute care suggesting that perhaps acute care transfers to LTC are not occurring at the optimal time. Estimated Medicare and Medicaid cost savings was $246,247. Limitations of the study were small sample size and study was conducted at one facility. %D 2016 %K Condition-Specific SBAR SBAR Nurse Physician Communication Long Term Care Transfers Hospitalizations 30-day Readmissions Acute Care %I University of Pittsburgh %L pittir27260 %A Dalthea Brown Beavers %T Development of the Functional Mobility Assessment - Family Centered Version %X Pediatric wheeled mobility devices require periodic updating to accommodate children?s physical growth, changing needs, and device maintenance requirements. Valid and reliable instruments are needed to facilitate the WMD assessment process and to evaluate the effect of new WMDs on clients? functional status. While the Functional Mobility Assessment (FMA) is currently available for use with adults, no similar instrument has been developed for children. In this dissertation study, the Functional Mobility Assessment-Family Centered Version (FMA-FC) was developed to fill this void in assessment technologies. Content validity of the FMA-FC was established qualitatively using interviews with parents/caregivers and therapists with expertise in WMD assessment. Using the relevance scale, quantitative content validity of the FMA-FC Beta Version 1, as rated by parents/caregivers was 92 percent and as rated by therapists was 99 percent. Parents/caregivers and therapists indicated that the meaning of items was clear and all items were easy to rate. Both test-retest reliability (ICC = .85) and internal consistency (Cronbach?s alpha = .87) of FMA-FC Beta-Version 3 were found to be acceptable. %D 2016 %K mobility, functional mobility, assessment, family-centered care, pediatrics, children %I University of Pittsburgh %L pittir27680 %A Amal Alzu'bi %T A PERSONAL GENOMIC INFORMATION ANALYSIS AND MANAGEMENT SYSTEM FOR HEALTHCARE PURPOSES %X Currently, a large amount of personal genomic data can be generated at an affordable price in a short period of time due to the improvement in the DNA sequencing technologies. Abundant research results on genetic diseases have been published in recent years. Therefore, it is eventually possible to integrate multiple types of information together and apply them into genomic-based personalized healthcare. However, this is still a very challenging task for healthcare professionals because the desired information is hidden in highly complex and heterogeneous genomic data sets and spread in various databases, which were typically created for researchers. In this research project, a personal genomic information management and analysis system is created for healthcare professionals, especially physicians. To properly design such a system, an exploratory survey was conducted to identify the current status of physicians in using genomics in their clinical practice and to collect their expectations about the features of a patient genomic information system. The results of this study indicated that physicians have sufficient knowledge in genomics and they are interested in incorporating genomics into their clinical practice. The results also indicated that a well-designed patient genomic information system with desired features can help physicians to incorporate genomics into their clinical practice. Based on the survey findings, a personal genomic information system was created for the purpose of managing and analyzing patient genomic data. In this system, we first created an integrated database, and then developed data analysis algorithms to extract clinical information from patient genetic variation data, including disease-associated genetic variations and pharmacogenomic associations. Physicians can conveniently identify the genetic reasons for diseases and determine personalized treatment options based on the information provided by the system. A usability study was conducted to obtain physicians? feedback about the system after they use it to finish some tasks such as searching the genetic variations of one patient, determining the patient?s risk of certain diseases, and identifying the corresponding pharmacogenomic results. The results of this study indicated that physicians could easily find the patient information they need and the information can be directly applied in their clinical practice. %D 2016 %K genomics, management, analysis %I University of Pittsburgh %L pittir27705 %A Sangeun Shin %T WORD FREQUENCY EFFECTS ON LEXICAL SELECTION: EVIDENCE FROM A PICTURE?WORD INTERFERENCE (PWI) TASK %X Given that a high frequency (HF) word advantage exists in lexical processing, a question arises about the locus of that frequency effect. This locus may be important for AAC research and clinical practice to provide an empirical rationale for graphic symbol-based AAC interfaces. This study?s first specific aim was to identify whether word frequency affects lexical selection using a picture-word interference (PWI) task. Fifty healthy, monolingual, Native American English speakers, between 40 and 64 years of age, participated in the study. Response times (RT) for semantic, phonological, and mixed distractor conditions served as the dependent variable during a PWI task. Data were analyzed using generalized linear mixed models (GLMMs). In all distractor conditions, participants named HF pictures significantly faster than low frequency (LF) pictures. This result revealed that the word frequency effect occurs not only with phonological encoding, but also with lexical selection and interactive processing between these two steps. This finding is at odds with the Discrete Two Stage (DTS) model that states that word frequency selectively affects the phonological encoding. The secondary aim was to determine whether the target item?s frequency interacts with the distractor item?s frequency. HF distractor words had a stronger interference effect on the retrieval of target words than LF distractor words, resulting in a more delayed RT when naming the target pictures in semantic and mixed distractor conditions. However, an interaction effect was observed between target word frequency and distractor frequency only in the mixed distractor condition. A third aim was to determine whether RT analyses provide a more sensitive measurement than error type analysis for healthy adults. No significant word-frequency effect or interaction was found for error type. A high rate of correct responses and the characteristics of the errors as the end product of inefficient word retrieval are considered as main reasons for this negative result. This finding supports the hypothesis that RT is a more sensitive measure than error type for indexing the inefficiencies that affect naming behavior in the PWI task for healthy adults. %D 2016 %K WORD PRODUCTION, WORD FREQUENCY, LEXICAL SELECTION, INTERACTIVE ACTIVATION, PICTURE?WORD INTERFERENCE, AUGMENTATIVE AND ALTERNATIVE COMMUNICATION %I University of Pittsburgh %L pittir21659 %A Jon DMC Walker %T Wisdom of the Crowd Mechanisms %X As Web 2.0 facilitates the collection of a vast amount of interactions, a phenomena, known as the wisdom of the crowd, is increasingly enlisted to justify using those interactions as surrogates for expert opinions. This dissertation explores this phenomena through an analysis of the micro elements of two wisdom of the crowd simulations: (1) Hong and Page?s (2004) Diversity trumps ability model and (2) Luan et al.?s (2012) Fast and Frugal simulation. The focus of this study is on the micro elements that contribute to those simulations? results. This focus leads to the identification of a search mechanism that favors exploitation as a first step followed by exploration as defined by March?s (1991) Exploration/Exploitation simulation. Three new methods for creating a group of experts were developed and were shown to be not only superior to the Top 10 agents but also superior to the more diverse random group of ten agents which consistently outperformed the Top 10 agents in the Hong-Page model. It was also shown that these expert groups were more efficient in incorporating the entire range of heuristics possessed by the universe of agents. The problem spaces were manipulated in various manners and the effect of such manipulations demonstrated. Additionally, group process losses were demonstrated through the simulation of a Hidden Profile scenario in which skills possessed by only one agent were ignored by the group. The effect of the dichotomization rate in the Fast and Frugal paradigm was highlighted and the effect of an alternative dichotomization rate demonstrated along with increasing the number of cues and manipulating the degree of correlation among them. Additionally, a set of perfect cue weights was developed for the Fast and Frugal paradigm and a simulation showed how a single agent executing the paradigm to choose the correct alternative saw its ability deteriorate as the cue weights progressed from the perfect order to all cues being equally weighted while groups of agents experienced increasing accuracy over the same progression. %D 2016 %K crowdsourcing %I University of Pittsburgh %L pittir28113 %A Joanna Collins %T Authors Exposed: Victorian Literary Celebrity and the Graphic Revolution %X In an effort to historicize celebrity as a phenomenon that pre-dates film, celebrity studies scholarship has, over the last three decades, taken a turn toward the literary in general and Victorian authors in particular. Most scholars point to the Graphic Revolution of the nineteenth century as celebrity?s inaugural moment, proposing that the industrialization of print, rise of the pictorial press, and advancements in photographic technologies kindled a new mode of celebration?one based less on personal achievement or service to God or state, and more on a perceived desire for proximity to the public individual. Scholars generally agree that this ?public intimacy? is one of the defining paradoxes of celebrity culture. Authors Exposed complicates the relationship between public intimacy and the printed image in Victorian literary celebrity by examining portraits of three authors?Charles Dickens, Alfred Lord Tennyson and Oscar Wilde?and by tracing how those images were produced, circulated and appropriated during each author?s lifetime. I argue that Victorian literary celebrity was characterized as much by a turn away from celebrity authors and their images as it was by audiences? desire to know more about and get closer to their favorite authors. In exploring these other attitudes towards public intimacy during the period, I challenge two key assumptions in the scholarship: first, that printed images gave audiences more intimate access to celebrities and second, that audiences always wanted more intimate knowledge about authors and their lives in the first place. In Dickens? case, his celebrity image endangered the relationship his audiences had with the characters in his early fictions, most notably Mr. Pickwick of The Pickwick Papers. For Tennyson, portraits designed to subvert celebrity and promote classical fame resulted in a kind of premature commemoration that made the Poet Laureate the object of ridicule in popular periodical series such as ?Celebrities (Very Much) at Home.? Finally, the celebrity images Wilde cultivated for his American lecture tour functioned as an artistic forgery that not only informed his later works like The Portrait of Mr. W.H., but also served as evidence of the ?gross indecency? that resulted in his incarceration. %D 2016 %K celebrity, history of fame, Victorian literature and culture, illustrated periodicals, print culture, portraits of authors %I University of Pittsburgh %L pittir27347 %A Qianheng Ma %T Behavioral failure in the process of weight regain: a data driven protocol %X Background: The prevalence of obesity is still an issue of high public health significance. Dietary self-monitoring (DSM) has been identified as the key component in standard behavioral treatment (SBT) for obesity that supports weight loss maintenance. However, little is known about the process of the weight regain in interventions using SBT. Previous research showed the temporal trend of adherence to DSM which preceded weight regain. We hypothesized that participants experienced the failure in adherence to DSM before the onset of weight regain. We then hypothesized that the adherence to daily time-contingent surveys in ecological momentary assessments (EMA) would protect people from behavioral failure and weight regain. Methods: In this study, we provided a data-driven protocol to define and analyze the weight regain and behavioral failure. With the self-weighing data, we used piecewise linear model to detect the onset of weight regain and classified participants as maintainers and regainers. We used Bai-Perron?s test to detect the failure in DSM adherence before weight regain and classified participants as collapsers and sustainers. Group-based trajectory modeling was used to cluster the longitudinal patterns of adherence to the time-contingent EMA surveys into two groups (the consistent group and the decline group). We constructed a three-state Markov transition model for the process of weight regain via a behavioral failure and used Cox models to explore the group effect on the transition intensities among states. Results: According to the self-weighing trajectories, 148 participants were classified as regainers (66.89%) and maintainers (25.68%). Among the regainers and maintainers (N=137), 62.04% was classified as collapsers versus sustainers (37.96%) for adherence to DSM. of the participants were organized as the consistent group (73.8%) versus the decline group for adherence to EMA surveys. Being consistently adherent to EMA surveys significantly was related to: (1) greater amount of percent weight loss before weight regain; (2) longer duration of weight loss and maintenance before weight regain; (3) longer duration without behavioral failure and weight regain; and (4) lower hazard of behavioral failure in DSM adherence. Conclusions: Failure in the adherence of DSM was a more hazardous state for weight regain. Consistent adherence to time-contingent EMA surveys was associated with lower hazard of failure in the adherence to DSM. %D 2016 %K weight regain;weight loss relapse;behavioral treatment;self-monitoring;Markov transition model;time series %I University of Pittsburgh %L pittir27943 %A Brita Anderson %T The Charm of Rhetoric: George Santayana and the Aesthetics of Rhetoric %X This dissertation aims to place George Santayana within the rhetorical tradition, arguing both that rhetoric helps illuminate his philosophy and that his philosophy extends rhetoric beyond its typical persuasive or oppositional frame. After situating Santayana within rhetoric?s purview and providing justification for this move, I highlight Santayana?s aesthetics as the means to view rhetoric in this novel way. In so doing, Santayana, I argue, permits us to view rhetoric aesthetically, extending its scope to achieve harmony among disparate parts. Such harmony could occur vis-?-vis beauty, which serves as the aesthetic principle underlying rhetoric. Chapter One sets out to offer an overview of Santayana?s aesthetics, focusing on his treatment of the true, the good, and the beautiful. Santayana uniquely shows an interrelationship between these concepts that has an effect on the ways in which we view relationships within and among individuals and communities, particularly as the relationship occurs as a result of their discourse. Chapter Two examines the relationship between individual and community more thoroughly, showing how an early goal of individual life was merely survival but necessarily transformed into value-laden communities. Due to the use of symbols in attaching value and meaning to objects and actions, this chapter also examines the rhetorical concept doxa. In light of circulating and competing interests, I also reconsider both dissoi logoi and phronesis because of Santayana?s comments. In Chapter Three, I focus on the imagination, emotion, epideictic rhetoric, and form. Emotions and passion influence the preferences of individuals, but so too do they connect people and experiences. In effect, rhetoric acts as a harmonizing capacity, but it also serves an instrumental purpose whereby it provides form to thought and emotion, both engendering and making articulate the imagination and the emotions. Chapter Four concludes my project, summarizing both it and Santayana?s contributions. In light of these discoveries, I ask scholars, especially rhetoricians, to consider rhetoric beyond their own rhetorical doxa, a rhetoric that departs from the focus on division and debate and encourages harmony within a beautiful life of reason. %D 2016 %K Rhetoric, Aesthetics, George Santayana, emotion, imagination, true, good, beautiful, beauty, philosophy, harmony, doxa, dissoi logoi, dialectic, phronesis, experience, form, epideictic, interests %I University of Pittsburgh %L pittir26790 %A Cynthia Popovich %T Childcare Director Leadership: A Crucial Connection to Quality Care and Education %X The purpose of this study was to explore and describe child care center directors? perceptions of their role as leaders. Survey and semi-structured interview questions were used to collect data on how child care directors describe themselves as leaders, how they are prepared and supported for leadership development, and to recognize barriers to leadership development. A survey was distributed in to 36 directors and the return rate was 23 surveys. Descriptive statistics are used to display the data. A focus group of seven directors were interviewed for 30 minutes using semi-structured interview questions. Data from this session was audio recorded, transcribed, and presented in narrative form. Directors perceive themselves to be both managers and leaders and are very relationship-based while managing their staff. Despite indicating that they have high job stress, low salaries, work long hours, and often feel isolated in their position, they agree (78%, n=18) that they do not want to leave their job and (69%, n=16) are not disillusioned with the field. Directors agree that they like dealing with broader issues in the field (87%, n=20), and (82%, n=19) that they need to become involved in the wider early childhood community, but only (30%, n=7) held any leadership positions in professional associations or groups outside of their centers. A definition of leadership collectively written by 23 directors is offered for further consideration. More than half of the directors agreed that they felt confident and self-assured when they became a director (61%, n=14), and they felt prepared for the kinds of issues that they faced (57%, n=13). Approximately 2/3 of the directors (65%, n=15) indicated that they had little leadership or administrative training before becoming a director. Directors are leaders in their centers, but not in the wider field. Early childhood training systems must respond to and provide opportunities for director leadership both in centers and in the wider early childhood community of practice where system-wide changes are needed. The voices of directors need to be included in order for any solutions to the problems in the field of early childhood care and education are to be resolved. %D 2016 %K child care, directors, leadership %I University of Pittsburgh %L pittir28065 %A Mikio S.M. Akagi %T Cognition in Practice: Conceptual Development and Disagreement in Cognitive Science %X Cognitive science has been beset for thirty years by foundational disputes about the nature and extension of cognition?e.g. whether cognition is necessarily representational, whether cognitive processes extend outside the brain or body, and whether plants or microbes have them. Whereas previous philosophical work aimed to settle these disputes, I aim to understand what conception of cognition scientists could share given that they disagree so fundamentally. To this end, I develop a number of variations on traditional conceptual explication, and defend a novel explication of cognition called the sensitive management hypothesis. Since expert judgments about the extension of ?cognition? vary so much, I argue that there is value in explication that accurately models the variance in judgments rather than taking sides or treating that variance as noise. I say of explications that accomplish this that they are ecumenically extensionally adequate. Thus, rather than adjudicating whether, say, plants can have cognitive processes like humans, an ecumenically adequate explication should classify these cases differently: human cognitive processes as paradigmatically cognitive, and plant processes as controversially cognitive. I achieve ecumenical adequacy by articulating conceptual explications with parameters, or terms that can be assigned a number of distinct interpretations based on the background commitments of participants in a discourse. For example, an explication might require that cognition cause ?behavior,? and imply that plant processes are cognitive or not depending on whether anything plants do can be considered ?behavior.? Parameterization provides a unified treatment of embattled concepts by isolating topics of disagreement in a small number of parameters. I incorporate these innovations into an account on which cognition is the ?sensitive management of organismal behavior.? The sensitive management hypothesis is ecumenically extensionally adequate, accurately classifying a broad variety of cases as paradigmatically or controversially cognitive phenomena. I also describe an extremely permissive version of the sensitive management hypothesis, arguing that it has the potential to explain several features of cognitive scientific discourse, including various facts about the way cognitive scientists ascribe representations to cognitive systems. %D 2016 %K Cognitive science Conceptual analysis Mark of the cognitive Philosophy of science Scientific practice Disagreement %I University of Pittsburgh %L pittir27590 %A Ian Cook %T Content and Context: Three Essays on Information in Politics %X This dissertation explores the implications of information asymmetries in three specific political environments: primary campaign speeches; negotiating behavior; and testimony delivered in a congressional hearing. First, dog whistling can dramatically affect the outcome of elections, despite observers never being sure it actually occurred. I build a model that addresses how a whistle operates, and explore implications on candidate competition. I find that whistling lets candidates distinguish themselves from competitors in the minds of voters. Second, political negotiation frequently looks like two sides staring each other down, where neither side wishes to concede, claiming that doing so would incur the wrath of voters. Little theory or evidence exists to explain how voters allocate blame for different outcomes. We conduct a laboratory experiment to investigate how anticipation of blame drives negotiating behavior, and how observers allocate blame. We find that the presence of an observer has little effect on standoff outcomes but appears to shorten the duration of standoffs. Third, while congressional hearings give legislators a national stage on which to score political points by publicly chastising high-level bureaucrats, and gives lobbyists a forum to demonstrate their access and importance to policymakers, less clear is how well hearings serve the purposes of oversight. I address this question through automated text analysis of hearings in the 105th ? 112th Congresses. I show that the oversight function of hearings is only effective when it is least likely to be used: when the congressional committee and the bureaucrat agree on policy %D 2016 %K politics, campaigns, dog whistling, hearings, negotiation, blame, experiment, text analysis, formal model %I University of Pittsburgh %L pittir27301 %A Rohini Chaki %T Desis in the House: South Asian American Theatre and the Politics of Belonging %X This dissertation attempts to update the traditional understanding of what constitutes American theatre by bringing into focus works by South Asian American playwrights addressing the racialization of desis - a large and diverse community of people with origins in South Asia - who have, after the events of 9/11, become questionable citizen subjects in the United States. I examine the various ways in which the plays under consideration represent the negotiation of South Asian American identity in its quest to establish belonging on the American nation-space. I look at scripts and productions to explore responses to the performance of the American desi subject?s precarious belonging in a national space that sees them variously as cultural others or even threats. These plays put the spotlight on techniques of othering as mediated by the structures of class, gender and sexuality, and religion, but they also have certain universal qualities that offer an affective staged realization of the imagined community that is America today - an ethnoracial conglomerate that transcends the conventional white/black racial binary. These plays, moreover, take ownership of and expand the representation of South Asian-origin characters in American popular culture beyond such stock types as the cab driver, the terrorist or the computer nerd. Finally, they forecast the future of the American stage and the direction that American theatre must necessarily take in order to account for the growing diversity of the lives it reflects and shapes. %D 2016 %K South Asian American Theatre - American Drama - Immigrant Identity - Racialization %I University of Pittsburgh %L pittir27822 %A Anthony Comegna %T ?The Dupes of Hope Forever:? The Loco-Foco or Equal Rights Movement, 1820s-1870s %X This dissertation illustrates the impact of the Loco-Foco movement (1820s-1870s), most notably its role in the development of ?Manifest Destiny,? the Free Soil Party, and the Republican Party. While historians have assumed that the Loco-Foco movement ended with the existence of the original third party in New York (1836-7), I pursue their philosophy and activism throughout the time and space of the late antebellum period. Loco-Focoism can be characterized as radical classical liberalism, including commitments to natural and equal rights, individualism, private property, laissez-faire, democratic republicanism, and, often, antislavery. Self-avowed and influential Loco-Focos included Herman Melville, Nathaniel Hawthorne, Walt Whitman, and countless other important figures in antebellum thought, culture, and politics ranging across the continent from New England and the northern border to the Pacific frontier zone and even the increasingly proslavery, anti-locofoco South. This study compiles the largest collection of primary sources related to the movement of any treatment to date, including dozens of newspapers, published books, poems, and pamphlets, public speeches, paintings, and private correspondence collections. This is the first and only history of the Loco-Foco Movement as such, and its conclusions offer sharp challenges to prevailing interpretations of the development of democratic-republican government, liberalism, and corporate-capitalism in the United States. While their ideology offered radical alternative models for American political and intellectual life, their efforts at practical politicking created much of the modern democratic, corporate-capitalist nation-state familiar to present-day readers. %D 2016 %K American history, locofocoism, classical liberalism, radicalism, republicanism, Young America, Civil War, slavery, abolition, Republican Party, Free Soil Party, Mexican-American War %I University of Pittsburgh %L pittir27222 %A Katie Jo Black %T Essays on Rural and Regional Economics %X This dissertation analyzes economic questions related to rural and regional economies. I specifically focus on the valuation of open space, migration patterns in the face of economic downturns, and the effects of taxation on the unconventional well industry. In Chapter 1 I explore the benefits of preserving open space. Using a difference-in-differences empirical specification, I find that there is a 23 percent increase in adjacent home values resulting from this change in institution. Further analysis suggests that this premium is being driven by the benefits from a preserved view and less so by more accessible public land. Estimates show that preserved open space acts as a complement to personal lot size. Chapter 2 evaluates the effects of Pennsylvania's Act 13 Impact Fee on energy companies. West Virginia is used as a counterfactual comparison state in the difference-in-differences approach to estimate the economic effects of the Fee. Findings show that royalty rates, leasing activity, and well drilling decline significantly, while well productivity appears to be unaffected in the short-run. There is suggestive evidence that the large effect resulting from the Fee is being driven by liquidity constraints. The results suggest minimal pass-through of the Fee to private landowners and no evidence of spillover effects into West Virginia. Lastly, in Chapter 3, I evaluate the differential migration responses to employment decline between counties with heterogeneous housing markets. Using an instrumental variables method, I provide evidence that counties with higher levels of foreclosures have a statistically smaller response to employment shocks compared to counties which have lower levels of foreclosures. After restricting my focus to a smaller time frame, I provide estimates that show that areas with higher levels of foreclosures experience an increase in small-move migrants in response to job loss. Therefore, my long run estimates suggest that there is a lock-in effect. However, my short run estimates do not suggest that rural America has experienced a lock-in effect that contributed to the decline in internal migration. Overall, my dissertation highlights the importance of understanding economic issues that rural areas face and implementing the most effective potential policy-based solutions. %D 2016 %K rural economics, regional economics, shale, open space, non-market valuation, migration, lock-in, foreclosures, employment change %I University of Pittsburgh %L pittir26878 %A Margarita A. Delgado Creamer %T THE FUNERARY BUDDHA: MATERIAL CULTURE AND RELIGIOUS CHANGE IN ?THE INTRODUCTION OF BUDDHISM TO CHINA? %X This dissertation is an inquiry into the significance of the record of the earliest objects bearing Buddhist motifs for our understanding of what is commonly known as the ?introduction of Buddhism in China. It argues that the earliest Chinese material Buddha images were innovations that both resulted from and triggered synergistic cultural interaction. This means, that far from being only a case of cultural misunderstanding or random borrowing, as has generally been stated, they gave expression to a re-envisioning of the relationship between human and supernatural beings, and contributed to transformations in the Chinese religious praxis of the period. Indeed, it has been noted that the funerary use of Buddha figures in China represented an unorthodox usage in relation to Buddhist traditions. What has not been noted, however, is that they also represented an innovation in the Chinese funerary context, since apotropaic beings were mostly represented in hybrid or animal form, while human form was generally used for mimetic or didactic purposes. In order to understand the role of the earliest Chinese objects bearing Buddhist motifs in the ?Introduction of Buddhism in China,? previous scholarship placed these objects within a historical narrative that saw them as being the outcome of cultural misinterpretation. Consequently, earlier scholarship supported the view that Buddhism was initially understood from a Daoist perspective. This dissertation argues that in order to understand the role of the funerary Buddha figures in the ?Introduction of Buddhism in China? we need to, paradoxically, first extricate the analysis from the traditional historical narrative that has shaped our thinking. %D 2016 %K Early Chinese Buddhism, material culture, Buddhism and Daoism %I University of Pittsburgh %L pittir26830 %A Mert Ertunga %T Negotiating Literary Identity during the Divide between the Philosophes and the Anti-Philosophes (1745-1765) %X This dissertation centers on the negotiation of literary identity in the philosophes vs. anti-philosophes divide during the middle decades of the eighteenth century. During that time, the ideas of the philosophes were gaining ground in readership and popularity, and, as a consequence, their enemies were beginning to perceive their ideas as pernicious threats to the traditional values upon which the French monarchy was built. Voltaire, Denis Diderot, and Jean-Jacques Rousseau squared off against anti-philosophes such as ?lie Catherine Fr?ron, Charles Palissot, and the abb? Nicolas-Sylvestre Bergier in debates concerning literature, religion, and education. Philosophes questioned the principles on which the old order rested and relentlessly called on ?reason? to challenge prejudices, while the anti-philosophes accused their adversaries of conspiring to subvert the French monarchy by rattling the foundations of the established religious practices and social peace. The careers and writings of the playwright Michel-Jean Sedaine and the literary critic ?lie Fr?ron are examined in the first two chapters as a means of analyzing the challenges faced by up-and-coming writers in order to establish legitimacy as an author in an unstable literary arena. There were also what I term the ?ecto-philosophes,? writers who belonged neither to the philosophical camp nor to the anti-philosophical one. Their writings fell into oblivion for over two centuries as most scholarly studies have focused on the writings of the philosophes and their adversaries. The third and final chapter includes a detailed study of their contribution to the literary production during the conflict between the philosophes and the anti-philosophes. %D 2016 %K Philosophes, anti-philosophes, voltaire, rousseau, marmontel, sedaine, freron, palissot, diderot, ecto-philosophes %I University of Pittsburgh %L pittir27719 %A Kalyn A Brown %T Optical Control of Signal Transduction and Other Cellular Processes %X Nature uses precise spatio-temporal control to maintain proper cellular function. Being able to replicate this control is an important step in investigating proteins. The research presented here uses photo-labile ?caging? groups and light to control protein function including signaling cascades, protein localization and dimerization. Cell signaling is an essential process that allows cells to respond to extracellular stimuli. Four kinases, ERK2, p38?, JNK1 and PAK1, were targeted to optochemically control signal transduction. ERK2, p38?, and JNK1 are MAP kinases that are implicated in cell proliferation, apoptosis, motility, and differentiation. PAK1 is a serine/threonine kinase that affects focal adhesion dynamic and action reorganization. Incorporation of a photocaged lysine into the ATP binding pocket of PAK1 allowed for optical control of PAK1 kinase activity and paxillin focal adhesions. Ras GTPases are membrane bound molecular switches involved in various pathways that convert stimuli into a cellular response. Membrane localization of Ras GTPases is determined by the C-terminal CaaX domain. Within the CaaX domain, cysteine residues are modified by the addition of a farnesyl group and two palmitoyl groups. Ultimately, photochemical control of membrane localization by CaaX domain signaling was used to determine the kinetics of CaaX domain processing. Src family tyrosine kinases are involved in cell proliferation, cytoskeletal alterations, differentiation, survival, adhesion, and migration and are localized to the membrane through the modification of a SH4 domain with myristoylation and palmitoylation. Optochemical control of SH4 domain mediated membrane localization was not achieved. Finally, the dimerization of FKBP12 and FRB was photochemically controlled by the development of a photo-cleavable rapamycin dimer. Rapamycin heterodimerizes FKBP12 and FRB and has been exploited as a research tool in a wide array of cellular processes. Photochemical control of protein localization and dimerization allows for precise spatial and temporal control over these processes, which will lend to the development of useful biological tools. %D 2016 %K Chemical Biology, Photocaging, Kinases, Localization, Conditional Control %I University of Pittsburgh %L pittir27697 %A Andrew E. Behrendt %T Travelers of an Empire That Was: Tourism, Movie-Going, and the Formation of Post-Imperial Identities in Austria and Hungary, 1918-1944 %X This dissertation investigates the history of leisure activities in order to understand how former Habsburg subjects made sense of their place in the world at empire?s end. It proposes a framework that approaches the history of Austria and Hungary in the 1920s-1930s as the history of geopolitical spaces connected by an imperial past, not simply as the divergent national stories of states insulated by new borders. I shed light on a unique moment in the region?s history: the encounter between the cultural legacy of the Habsburg Empire and a rising tide of transnational consumer culture in the form of ?democratized? travel and globalized media, both of which challenged the stability of national boundaries and identities. I demonstrate how, first, tourism culture sustained certain transnational imperial traditions and, second, the ways in which the politics of tourism engaged with an array of identities beyond nationality alone. Moreover, this thesis contributes new methodological perspectives to the field of modern European history. In addition to archival and published sources, I analyze popular films of the era as texts of ?virtual tourism,? whereby millions who could not afford to travel learned about the destinations and habits of tourism without journeying farther than their local cinema. Chapter 1 establishes the historiographical bases of the work?s post-imperial perspective and explains its multidisciplinary methodology. Chapter 2 probes the ways in which tourism promoters imagined the ?strangers? they wished to attract and, in the process, kept alive imperial connections. Chapter 3 finds that differences between the two domestic tourist industries illuminate how Austrians and Hungarians, informed by Habsburg-era cultural trends, conceived of the idea of ?homeland? in fundamentally different ways. Chapter 4 explores the promotion of rural tourism in Hungary as a mission to ?civilize? the peasantry to suit the urban visitor, with roots in the imperial past. Chapter 5 studies ?hotel movies? as virtual vacations. It focuses on the history of two prominent hotels and the way contemporary cinema mystified them as fairytale spaces where social and political problems were magically resolved. %D 2016 %K Habsburg History, Tourism History, Film History, Austrian History, Hungarian History, German History %I University of Pittsburgh %L pittir27701 %A Kathleen Davies %T WRITE TO PRIVACY: LITERATURE, LETTERS, LAW, AND THE INVIOLATE PERSONALITY IN AMERICA?S LONG NINETEENTH CENTURY %X Scholars and jurists recognize Samuel Warren and Louis Brandeis?s influential Harvard Law Review article, ?The Right to Privacy,? as the first articulation of a constitutional right to privacy, but its relatively late date (1890) in the chronology of constitutional law raises a number of questions. Why did the right to privacy become important at that particular moment? How did a concept with roots in property law come to apply to the ?inviolate personality,? in Warren and Brandeis?s memorable phrase, independent of considerations of class (or race or gender)? This dissertation proposes answers to those questions, tracing the genealogy of the right to privacy through literature and law from the end of the eighteenth century to the beginning of the twentieth. The first chapter examines the connection between privacy and the written word, especially in letters and epistolary fiction. Writers like Hector St. John de Crevecoeur and Hannah Webster Foster probe the connection between personal correspondence and national commitments, contemplating the costs and benefits of privacy, and proposing the epistolary form as a vehicle for the self. The second chapter looks closely at representations of women in literature and readings of privacy that connected women with domestic space. Works by Alcott, Hawthorne, and Poe interrogate the limitations of domesticity and conventional gender roles, while proposing the written word as an alternate, more constructive site of privacy. The third chapter considers links between literacy, deprivation, and privacy, using anti-literacy laws and narratives by Frederick Douglass and Harriet Jacobs to examine how the marginalizing experience of slavery informed discussions of privacy. The final chapter of the dissertation analyzes how societal changes create a perceived need for new rights and protections. Writers like William Dean Howells and Henry James decry newspaper culture and urbanization, warning that scrutiny and publicity endanger the self. This fear that publicity leads to privation informs Warren and Brandeis?s ?The Right to Privacy,? as it urges protections for persons rather than property. The surprising origins of the right to privacy still affect our conflicted views on the uses of this right and the measures that we take to safeguard it. %D 2016 %K Privacy, law, American Literature, domesticity, secrecy, deprivation, letters, correspondence, news paper, press, case law, Charles Brockden Brown, Hannah Webster Foster, Hector St. John de Crevecoeur, Nathanial Hawthorne, Edgar Allan Poe, Louisa May Alcott, Harriet Jacobs, Frederick Douglass, Margaret Douglass, Charles Chesnutt, William Dean Howells, Henry James, Theodore Dreiser %I University of Pittsburgh %L pittir27811 %A Brice Everett Lynn %T Culture Isn't Cutting It: Creating Study Abroad Marketing That Appeals to Men %X Despite the fact that the number of study abroad students continues to increase each year and that the types of study abroad programs continues to diversify, women still outnumber men in study abroad participation at a rate of almost three-to-one. This qualitative study seeks to understand low male participation in study abroad as a result of negative perceptions caused by the ways in which study abroad is marketed to students. I selected male study abroad alumni to participate in personal interviews through which I sought to understand the criteria, motivations, and outcomes that men had for their overseas programs. A variety of study abroad marketing materials were also collected, with a specific focus on social media. Using human, cultural, and social capital as a framework for analysis, I conducted a comparative analysis to determine whether marketing materials reflect the most compelling benefits that would motivate men to enroll. Additionally, I used normative and dialogic frameworks to understand the ways in which men?s views of their gender inform their study abroad experience. This study shows that study abroad marketing is not reflective of the practical and pragmatic motivations that men have for studying abroad. Overall, study abroad professional in charge of marketing should focus less on ?fun? and ?cultural? experiences and instead emphasize the practical and pragmatic benefits of study abroad in order to attract more men. %D 2016 %K study abroad, study abroad marketing, study abroad recruiting, study abroad diversity, marketing to men, international education, international education marketing, international education recruiting, %I University of Pittsburgh %L pittir27977 %A Mansi Shah %T ANALYSIS OF ADP RECEPTOR SIGNALING PATHWAYS IN NOCICEPTORS AND IMPLICATIONS FOR INFLAMMATORY PAIN %X Chronic pain afflicts more than 100 million Americans and significantly affects the quality of life of those suffering. Opioid receptor agonists are effective analgesics but have severe dose-limiting side effects and display drug tolerance with prolonged use. Understanding key pathways that modulate pain is critical to developing analgesics that are more effective. In my dissertation, I investigated the importance of three key purinergic receptor signaling pathways in nociception: P2Y1, P2Y12 and P2Y13. Purinergic receptors respond to nucleotides released from damaged tissue and/or immune cells and have long been implicated in modifying nociceptive responses, however, the P2Y G-protein coupled purinergic receptor family is just starting to be investigated. P2Y1, P2Y12 and P2Y13 receptors are activated by the nucleotide adenosine diphosphate (ADP), however, the receptors have opposing effects because the P2Y1 receptor is Gq/11-coupled, whereas the P2Y12 and P2Y13 receptors are Gi/o-coupled. Traditionally, Gq-coupled receptors are pro-nociceptive while Gi/o-coupled receptors are anti-nociceptive. In order to understand the implications of antagonistic signaling between the P2Y1 and P2Y12/P2Y13 receptors during inflammatory pain, the signaling cascades for each individual receptor must first be elucidated. For the first part of my dissertation, I tested the hypothesis that P2Y1 Gq-coupled receptors signal through conventional protein kinase C isoforms (cPKC) and that these isoforms mediate the behavioral effects of P2Y1 receptor activation. I discovered that the cPKC isoform PKC? is expressed predominately in the IB4+ population, similar to the P2Y1 receptor, and that antagonism of PKC? attenuates P2Y1 receptor-mediated mechanical hypersensitivity. These results demonstrate the importance of cPKCs in the P2Y1 signaling cascade and detail how P2Y1 receptors function. Next, I tested the hypothesis that P2Y12/P2Y13 Gi/o-coupled signaling is important for maintaining basal nociceptive tone and modulating pro-nociceptive signaling. I discovered that all three ADP-activated receptors, P2Y1, P2Y12 and P2Y13, are active at baseline and likely maintain basal nociceptive tone. Additionally, P2Y12 and P2Y13 receptors are capable of attenuating signaling through pro-inflammatory Gs-coupled pathways, validating the importance of P2Y12 and P2Y13 receptors as potential analgesics. These results provide insight into the signaling cascades of P2Y1, P2Y12 and P2Y13 receptors and advance our understanding of nociceptive signaling. %D 2016 %K pain, purinergic, p2y1, p2y12, p2y13, inflammation, dorsal root ganglion %I University of Pittsburgh %L pittir27511 %A Matthew Baumgartner %T IMPROVING RATIONAL DRUG DESIGN BY INCORPORATING NOVEL BIOPHYSICAL INSIGHT %X Computer-aided drug design is a valuable and effective complement to conventional experimental drug discovery methods. In this thesis, we will discuss our contributions to advancing a number of outstanding challenges in computational drug discovery: understanding protein flexibility and dynamics, the role of water in small molecule binding and using and understanding large amounts of data. First, we describe the molecular steps involved in the induced-fit binding mechanism of p53 and MDM2. We use molecular dynamics simulations to understand the key chemistry responsible for the dynamic transition between the apo and holo structures of MDM2. This chemistry involves not only the indole side chain of the anchor residue of p53, Trp23, but surprisingly, the beta-carbon as well. We demonstrate that this chemistry plays a key role in opening the binding site by coordinating the position and orientation of MDM2 residues, Val93 and His96, through a previously undescribed transition state. We confirm these findings by observing that this chemistry is preserved in all available inhibitor-bound MDM2 co-crystal structures. Second, we discuss our advances in understanding water molecules in ligand binding sites by data mining the structural information of water molecules found in X-ray crystal structures. We examine a large set of paired bound and unbound proteins and compare the water molecules found in the binding site of the unbound structure to the functional groups on the ligand that displace them upon binding. We identify a number of generalized functional groups that are associated with characteristic clusters of water molecules. This information has been utilized in several successful and ongoing virtual screens. Third, we discuss software that we have developed that allows for very efficient exploration and selection of virtual screening results. Implemented as a PyMOL plugin, ClusterMols clusters compounds based on a user-defined level of chemical similarity. The software also provides advanced visualization tools and a number of controls for quickly navigating and selecting compounds of interest, as well as the ability to check online for available vendors. Finally, we present several published examples of modeling protein-lipid and protein-small molecules interactions for a number of important targets including ABL, c-Src and 5-LOX. %D 2016 %K drug design, computational drug discovery, molecular dynamics, biophysics, MDM2, p53, crystallographic water, virtual screening, PyMOL, software %I University of Pittsburgh %L pittir28044 %A Mahlon, A Collins %T Identification of Amyotrophic Lateral Sclerosis Disease Mechanisms by Cerebrospinal Fluid Proteomic Profiling %X Amyotrophic lateral sclerosis (ALS) is the most common form of adult-onset motor neuron disease. Heterogeneity in clinical, genetic, and pathological features of ALS suggest the disease is a spectrum of disorders each resulting in motor neuron degeneration. Molecular profiling of ALS patients is, therefore, a useful means of characterizing and stratifying the ALS population. To this end, mass spectrometric proteomic profiling was performed on cerebrospinal fluid (CSF) from ALS, healthy control (HC), and other neurological disease (OND) subjects. This resulted in the identification of 1,712 CSF proteins, 123 of which exhibited altered relative abundance in ALS CSF. Biological processes related to these 123 proteins included synaptic activity, extracellular matrix, and inflammation. The application of feature selection and machine learning methods to these CSF proteomic profiles resulted in a classifier that used relative levels of WDR63, APLP1, SPARCL1, and CADM3 to predict independent ALS, HC, and OND samples with 83% sensitivity and 100% specificity. To aid in the validation of selected CSF proteins, a Western blot loading control method was developed and validated using a reversible, iodine-based total protein stain. This method improves the accuracy and sensitivity of the relative quantification of CSF proteins via Western blot. As RNA binding protein (RBP) pathology/dysfunction is common to several forms of ALS, the largest CSF RBP alteration, that of RNA binding motif 45 (RBM45) protein, was validated externally. The results demonstrated that RBM45 pathology is common to several forms of ALS, frontotemporal lobar degeneration (FTLD), and Alzheimer?s disease. To further understand the biological functions of RBM45, immunoprecipitation coupled to mass spectrometry was performed to identify RBM45 protein-protein interactions (PPIs). RBM45 PPIs and associated pathways were most strongly associated with hnRNP proteins, RNA processing, and cytoplasmic translation. RBM45 also participates in the general cellular response to stress via association with nuclear stress bodies. This association is dependent on RNA binding, is upregulated in ALS/FTLD, and is sufficient to induce the aggregation of the protein. Collectively, these results illustrate the utility of CSF proteomic profiling for characterizing mechanisms of neurological disease and provide new insights into the contributions of RNA binding protein dysregulation to ALS/FTLD. %D 2016 %K cerebrospinal fluid; amyotrophic lateral sclerosis; frontotemporal lobar degeneration; RNA binding proteins; proteomics; mass spectrometry %I University of Pittsburgh %L pittir27749 %A Rick Jordan %T LITERATURE MINING SUSTAINS AND ENHANCES KNOWLEDGE DISCOVERY FROM OMIC STUDIES %X Genomic, proteomic and other experimentally generated data from studies of biological systems aiming to discover disease biomarkers are currently analyzed without sufficient supporting evidence from the literature due to complexities associated with automated processing. Extracting prior knowledge about markers associated with biological sample types and disease states from the literature is tedious, and little research has been performed to understand how to use this knowledge to inform the generation of classification models from ?omic? data. Using pathway analysis methods to better understand the underlying biology of complex diseases such as breast and lung cancers is state-of-the-art. However, the problem of how to combine literature-mining evidence with pathway analysis evidence is an open problem in biomedical informatics research. This dissertation presents a novel semi-automated framework, named Knowledge Enhanced Data Analysis (KEDA), which incorporates the following components: 1) literature mining of text; 2) classification modeling; and 3) pathway analysis. This framework aids researchers in assigning literature-mining-based prior knowledge values to genes and proteins associated with disease biology. It incorporates prior knowledge into the modeling of experimental datasets, enriching the development process with current findings from the scientific community. New knowledge is presented in the form of lists of known disease-specific biomarkers and their accompanying scores obtained through literature mining of millions of lung and breast cancer abstracts. These scores can subsequently be used as prior knowledge values in Bayesian modeling and pathway analysis. Ranked, newly discovered biomarker-disease-biofluid relationships which identify biomarker specificity across biofluids are presented. A novel method of identifying biomarker relationships is discussed that examines the attributes from the best-performing models. Pathway analysis results from the addition of prior information, ultimately lead to more robust evidence for pathway involvement in diseases of interest based on statistically significant standard measures of impact factor and p-values. The outcome of implementing the KEDA framework is enhanced modeling and pathway analysis findings. Enhanced knowledge discovery analysis leads to new disease-specific entities and relationships that otherwise would not have been identified. Increased disease understanding, as well as identification of biomarkers for disease diagnosis, treatment, or therapy targets should ultimately lead to validation and clinical implementation. %D 2016 %K literature mining, text-mining, pathway analysis, Bayesian modeling, lung cancer, breast cancer %I University of Pittsburgh %L pittir28062 %A Margaret Wright %T Role of the Atoh1 Lineage in Merkel Cell Development and Maintenance %X Merkel cells are mechanosensory cells found in mammalian epidermis that are important for the detection of texture, size and shape. These epidermally-derived cells are present in both glabrous and hairy skin, are innervated by slowly adapting type 1 (SA1) afferents, and express the transcription factor Atoh1 from their specification into maturity. In this dissertation I sought to identify and characterize the generation and maintenance of the Atoh1+ Merkel cell lineage using transgenic mice. I found that embryonic Atoh1+ cells are proliferatively capable and unipotent, generating only mature Merkel cells. Contrary to previous estimates, these embryonic-born Merkel cells persist into late adulthood in both hairy and glabrous skin, making them the longest-lived post-mitotic cell present in mammalian epidermis. Despite this, production of Merkel cells in adulthood can be induced by mechanical abrasion caused by repeated skin shaving. Unlike embryonic Merkel cells, these de novo Merkel cells do not arise from Atoh1+ or K14+ progenitors and have a decreased probability of survival compared to original Merkel cells. Furthermore, ectopic Atoh1 expression is sufficient to induce production of ectopic Merkel cells outside the touch dome boundaries. These ectopic Merkel cells express multiple canonical Merkel cell markers and a small percentage that reside in the hair follicle bulge can persist for at least 3 months post-induction. Competency of keratinocytes to respond to Atoh1 varies by skin location, developmental age and hair cycle stage. Also, the Notch signaling pathway plays an instructive role in epidermal cell responsiveness to Atoh1 expression. Together, these experiments provide novel insight into Merkel cell genesis and maintenance as well as illustrate two mechanisms by which Merkel cells production can be initiated in adulthood. They also suggest that the skin cancer, Merkel cell carcinoma, is more likely to arise from epidermal keratinocytes than the Merkel cell lineage. %D 2016 %K Skin; Touch; Somatosensation; Mouse; Carcinoma; Development %I University of Pittsburgh %L pittir26809 %A Fernando Concha-Benavente %T Epidermal growth factor receptor and Janus Kinase 2 regulation of programmed death ligand 1 and immunoescape in head and neck cancer %X Co-inhibitory immune checkpoint receptors (ICR) are novel targets for cancer immunotherapy. Programmed death ligand 1 (PD-L1), expressed in many cancers, including head and neck cancers (HNC), interacts with its receptor, programmed death 1 (PD-1), resulting in an exhausted phenotype. As yet, the stimuli and pathways that induce PD-L1 expression in tumor cells are not fully understood. Interferon gamma (IFN?) and the epidermal growth factor receptor (EGFR) utilize Janus kinase 2 (JAK2) as a common signaling node transmitting tumor cell-mediated extrinsic or intrinsic signals, respectively. We investigated the mechanisms by which these factors upregulate PD-L1 and immunosuppressive cytokine expression in HNC cells in the context of EGFR/JAK/STAT pathway activation. We found that wild type overexpressed EGFR significantly correlated with JAK2 and PD-L1 expression. Furthermore, PD-L1 expression was induced in an EGFR- and JAK2-dependent manner, and specific JAK2 inhibition prevented PD-L1 upregulation in HNC, enhancing their immunogenicity. HNC tumors have higher expression of immunosuppressive cytokines including TGF?, IL-10, VEGF-A and IDO and lower expression of inflammatory cytokines such as IL-12A and IL-17A than controls. EGFR/JAK2 inhibition downregulated secretion of these STAT3-dependent cytokines in vitro, suggesting that targeting the EGFR/JAK2/STAT3 suppressive pathway may reverse tumor immunoescape. This view is supported by in vivo findings where HNC patients unresponsive to cetuximab therapy had significantly higher concentrations of immunosuppressive cytokines. NK cells are crucial for promoting T cell responses against cancer. However, NK cell PD-1 expression remains largely undefined. Cetuximab-activated NK cells constitute the major effector cell subset that lyses tumor targets via antibody dependent cellular cytotoxicity (ADCC). We demonstrate that expression of PD-1 in HNC tumors correlates with NK cell activation markers. HNC patients exhibit higher levels of circulating PD-1+ NK cells, which are further enriched in the tumor. Interestingly, cetuximab treatment increased this frequency in vitro and in vivo. Inhibition of the PD-L1/PD-1 axis increased cetuximab-mediated NK cell activation and cytotoxicity. Collectively, our findings suggest a novel role for JAK2 in EGFR-mediated PD-L1 upregulation and immunosuppressive cytokine secretion. Importantly, combined inhibition of the EGFR and PD-L1/PD-1 axis presents a potential strategy to reverse cetuximab-resistant immune evasion of HNC by enhancing NK cell cytotoxicity. %D 2016 %K EGFR, PD-L1, PD-1, NK cell, immunoescape %I University of Pittsburgh %L pittir27431 %A Kenneth Drombosky %T Huntington?s Disease Studies at the Interface of Chemistry, Physics, and Biology %X Huntington?s disease (HD) is a uniformly fatal genetic disease causing progressive degeneration of the central nervous system in approximately 250,000 people worldwide. Unlike other neurodegenerative diseases, such as Alzheimer?s and Parkinson?s disease, HD is explicitly caused by a single genetic defect ? a CAG codon expansion in the huntingtin gene, which codes for polyglutamine (polyQ) in the protein huntingtin (htt). People carrying 40 or more CAG/glutamine repeats will develop HD by early adulthood, while those with 36 or less are unaffected. Despite this discovery over two decades ago, there are still no treatments to cure, prevent, or delay the underlying progression of HD. The physical state of the huntingtin ?exon1? fragment responsible for triggering HD pathology (amyloid aggregates, non-? oligomers, or monomers) is a controversial roadblock that limits therapeutic discovery. Previous attempts to determine the toxic species have recently been identified as flawed or inconclusive. Herein, we describe mutated htt-exon1 analogs containing only 22-24 glutamine residues that deliver atypical aggregation: a ?hyper-amyloid? analog that ? despite its short glutamine repeat lengths ? aggregates into amyloid fibrils comparable to pathogenic huntingtin, and ?hypo-amyloid? analogs whose aggregation stops at the non-? oligomer stage. Hyper-amyloid htt-exon1 produces inclusions, cytotoxicity in rat neurons, and decreased lifespans with movement deficits in flies. Neurons and flies expressing hypo-amyloid htt-exon1 alone have no detectible HD phenotype. Our data strongly supports a toxic amyloid hypothesis, and we find no evidence of a toxic non-? oligomer. Furthermore, the non-toxic hypo-amyloid analogs are also able to inhibit amyloid formation of pathogenic repeat length htt-exon1. Co-expression of hypo-amyloid htt-exon1 with pathogenic htt-exon1 reduces aggregation in vitro, inhibits toxicity in neuron cultures, and rescues behavioral and lifespan HD phenotypes in flies. These exciting results offer novel, rationally designed approaches to HD therapeutics. %D 2016 %K Huntington, Huntingtin, Amyloid, Aggregation, Drosophila, Primary Neuron %I University of Pittsburgh %L pittir27844 %A Erin K Steer %T IMPLICATIONS OF AN INTERACTION BETWEEN PINK1 AND VCP FOR PARKINSON?S DISEASE PATHOGENESIS %X Parkinson?s disease (PD) is the most common neurodegenerative movement disorder, and affects approximately 950 per 100,000 people in North America. The etiology of PD remains unknown, but a small percentage of affected individuals have heritable forms of the disease with known genetic causes. Study of the proteins encoded by these genes has provided tremendous insight into molecular pathways that underlie PD-associated neurodegeneration. Mutations in the gene encoding PTEN-induced kinase 1 (PINK1) have been identified as the cause of an autosomal, recessively inherited parkinsonism. PINK1 is a serine/threonine kinase, uniquely localized to both the cytosol and mitochondrion. The profound effect of PINK1 on mitochondrial homeostasis has been extensively investigated, but far less is understood about its function in the cytosol. This project aimed to identify cytosolic PINK1 interacting proteins and characterize the functional consequences of the association. Using an unbiased proteomic screen, valosin-containing protein (VCP), an AAA+ ATPase, was identified as a PINK1 interactor. Upon discovery that the physical association does not require mitochondrial localization, the role of VCP in previously identified functions of the cytosolic pool of PINK1 was examined. These studies discovered a PINK1-VCP pathway that promotes neurite extension and complexity, and contributes to the maturation and maintenance of synapses. Further, PINK1 and VCP were shown to co-regulate autophagy and the accumulation of high molecular weight ubiquitination products. These results indicate that the PINK1-VCP interaction plays a key role in dendritic arbor maintenance, synapse preservation, and autophagy regulation. These three processes are commonly impaired in sporadic and familial PD as well as other neurodegenerative diseases, indicating that treatments targeting components of the PINK1-VCP signaling hub may have broad therapeutic applications. %D 2016 %K VCP, PINK, Parkinson's disease, neuronal morphology %I University of Pittsburgh %L pittir27842 %A Ankur Joshi %T INTRINSIC AND SYNAPTIC MECHANISMS CONTROLLING THE EXCITABILITY OF LAYER 5 CORTICOCALLOSAL AND CORTICOCOLLICULAR NEURONS IN AUDITORY CORTEX %X Auditory cortex (AC) layer (L) 5B contains both corticocollicular neurons, a type of pyramidal-tract neuron projecting to the inferior colliculus, and corticocallosal neurons, a type of intratelencephalic neuron projecting to contralateral AC. It is known that these neuronal types display dichotomous in vivo responses to sound. While corticocollicular neurons display robust evoked responses to wide range of sound frequencies, corticocallosal neurons are responsive to a limited range of sound frequencies. However, the intrinsic and synaptic mechanisms shaping these dichotomous responses remain unexplored. It is also known that corticocollicular neurons are critical for learning-induced plasticity involved in relearning sound localization after monaural occlusion. This learning induced-plasticity also requires the release of acetylcholine (ACh) in the AC. However, the effect of ACh release on the excitability of corticocollicular neurons is unknown. Therefore, we recorded in brain slices of mouse AC from retrogradely labeled corticocollicular and neighboring corticocallosal neurons in L5B to identify the intrinsic and synaptic mechanisms that contribute to the in vivo responses of these neurons to sound, and to examine the effect of ACh release on corticocollicular and corticocallosal neurons to identify cell-specific mechanisms that enable corticocollicular neurons to participate in relearning sound localization. In comparison to corticocallosal neurons, corticocollicular neurons display a more depolarized resting membrane potential, faster action potentials and less spike frequency adaptation. In paired recordings between single L2/3 and labeled L5B neurons, trains of EPSCs showed no synaptic depression in L2/3?corticocollicular connections, but substantial depression in L2/3?corticocallosal connections. We propose that these differences in intrinsic and synaptic properties contribute to the dichotomous in vivo responses of corticocallosal and corticocollicular neurons to sound. Additionally, ACh release generates nicotinic acetylcholine receptor (nAChR)-mediated depolarizing potentials in both corticocallosal and corticocollicular neurons, but muscarinic acetylcholine receptor (mAChR)-mediated hyperpolarizing potentials in corticocallosal neurons and mAChR-mediated prolonged depolarizing potentials in corticocollicular neurons. This prolonged mAChR-mediated depolarizing potential leads to persistent firing in corticocollicular neurons, whereas corticocallosal neurons lacking this prolonged mAChR-mediated depolarizing potential do not fire persistently. We propose that this mAChR-mediated persistent firing in corticocollicular neurons may be a mechanism required for relearning sound localization after monaural occlusion. %D 2016 %K Auditory, Cortex, Corticocallosal, Corticocollicular, Synaptic, Intrinsic %I University of Pittsburgh %L pittir26715 %A Heather Metz %T NON-CANONICAL ROLE FOR INSULIN RECEPTOR SUBSTRATE-1 IN SIGNALING PATHWAYS OF THE LUNG %X Lung cancer is the leading cause of cancer deaths worldwide. In the United States alone, lung cancer accounts for ~160,000 deaths per year while the five-year survival rate remains stagnant at ~15%. Lung can be divided into different subsets including small cell and non-small cell lung cancer. Lung Adenocarcinoma (ADCA) accounts for over 50% of non-small lung cancer cases. Within this subset, KRAS is the most common activating mutation, accounting for ~35% of cases. KRAS mutant tumors have remained a largely un-targetable subtype, and a better understanding of the signaling pathways involved in the different ADCA subtypes will be necessary for the development of therapeutics. Insulin Receptor Substrate-1 (IRS-1) is a signaling adaptor protein that interfaces with many of the pathways that are activated in lung cancer, including phosphoinositol 3-kinase (PI3K), extracellular signal regulated kinase (MEK/ERK) and Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT). The central theme of this work is to describe novel roles for IRS-1 in the lung, including its integral role in the interplay between tumor cells and the surrounding tumor microenvironment. A key player in this interaction is the neutrophil, which can have pro-host and pro-tumor roles. We have found that neutrophils present in the tumor microenvironment cause degradation of the intracellular protein IRS-1, which in turn increases PI3K pathway activation leading to increased tumor proliferation. Independent study of IRS-1 loss with an Irs-1-deficient mouse model showed that Irs-1 loss induces an increase in neutrophil recruitment to the tumor. These two observations reveal a self-perpetuating cycle that causes increased tumor burden and mortality in mice and humans. Loss of Irs-1 in our Kras mouse model of lung adenocarcinoma induced activated JAK/STAT signaling and induced recruitment of immune cells to the tumor. Since neutrophils are essential for protection against invading pathogens, an indirect method of stopping this cycle must be used. Inhibiting JAK in our mouse model reduced inflammation, which in turn reduced tumor burden and prolonged survival. Overall, this work describes a novel role for IRS-1 as a mediator of cell growth and immune cell recruitment in lung adenocarcinoma. %D 2016 %K Lung, Cancer, IRS-1 %I University of Pittsburgh %L pittir27396 %A BINH L PHONG %T REGULATION OF MAST CELL FUNCTION BY TIM-1 AND TIM-3 SIGNALING %X The T cell (or transmembrane) immunoglobulin and mucin domain (TIM) family proteins have attracted significant attention as novel immune regulators. Tim-3 is expressed on chronically stimulated, often dysfunctional, T cells. Antibodies to Tim-3 can enhance anti-viral and anti-tumor immune responses. It is also constitutively expressed by mast cells, NK cells and specific subsets of macrophages and dendritic cells. There is ample evidence for a positive role for Tim-3 in these latter cell types, which is at odds with the model of Tim-3 as an inhibitory molecule on T cells. On the other hand, polymorphisms in the TIM-1 gene, particularly in the mucin domain, have been associated with atopy and allergic diseases in mice and human. Genetic- and antibody-mediated studies revealed that Tim-1 functions as a positive regulator of Th2 responses, while certain antibodies to Tim-1 can exacerbate or reduce allergic lung inflammation. Tim-1 can also positively regulate the function of B cells, NKT cells, dendritic cells and mast cells. At this point, little is known about the molecular mechanisms by which Tim-1 and Tim-3 regulate the function of T cells or other cell types. We have focused on defining the effects of Tim-1 and Tim-3 ligation on mast cell activation, since these cells constitutively express both proteins and are activated through an ITAM-containing receptor for IgE (FcRI), using signaling pathways analogous to those in T cells. Employing a variety of gain- and loss-of-function approaches, we find that Tim-3 acts at a receptor-proximal point to enhance Lyn kinase-dependent signaling pathways that modulate both immediate-phase degranulation and late-phase cytokine production downstream of FcRI ligation. Using a Tim-1 mouse model lacking the mucin domain (Tim-1mucin), we show for the first time that the polymorphic Tim-1 mucin region is dispensable for normal mast cell activation. We further show that Tim-4 cross-linking of Tim-1 enhances select signaling pathways downstream of FcRI in mast cells, including mTOR-dependent signaling, leading to increased cytokine production but without affecting degranulation. Thus, Tim-1 and Tim-3 are promising targets in development of therapeutics against mast cell-mediated allergic and autoimmune diseases. %D 2016 %K TIM-1, TIM-3, mast cells %I University of Pittsburgh %L pittir27700 %A Erik Koppes %T The Role of Genomic Imprints in Placental Biology %X Genomic imprinting is a process by which heritable epigenetic marks at a subset of genomic loci are established in a sex-specific manner in parental gametes and then maintained in nascent offspring. This study probes the poorly understood function of genomic imprints in placental biology. Genomic imprints are responsible for the regulation of parent-of-origin specific monoallelic expression of clusters of imprinted genes. The primary epigenetic mark that distinguishes parental alleles at imprinted loci is 5-methylcytosine in the context of cytosine-guanine (CpG) dinucleotides within differentially methylated domains (DMDs). The Dnmt1 gene encodes the maintenance DNA methyltransferase, an enzyme responsible for replicating CpG methylation that is critical throughout the process of genomic imprinting. Genetic disruption of the oocyte specific isoform of Dnmt1 (Dnmt1o) results in partial and wide-spread loss of DMD methylation during preimplantation development and has strong effects on embryonic and extraembryonic development. In this dissertation the morphology of DNMT1o-deficient placentas is examined and their abnormal phenotypes correlated with loss of methylation at specific DMDs. A strong association between loss of methylation at the Kcnq1 DMD and accumulation of trophoblast giant cells was made. In addition, an association between loss of methylation at the Peg10 DMD and loss of fetal viability and placental labyrinthine volume was made. In conjunction with my study of the Dnmt1?1o model, I have engineered a novel targeted deletion of the imprinted Klf14 gene and found it has an effect on placental growth. My thesis unambiguously shows that genomic imprints are essential for placental development. %D 2016 %K Genomic Imprints, Genomic Imprinting, Placenta, Mouse, DNMT1, DNA methylation, Peg10, Kcnq1, Mest, Klf14, preimplantation, spongiotrophoblast, labyrinth, %I University of Pittsburgh %L pittir28048 %A LIZA C. VALLE %T SOCIAL CAPITAL, COLLEGE CHOICE, AND COLLEGE PERSISTENCE OF HISPANICS: A CASE OF A PUBLIC UNIVERSITY IN WESTERN PENNSYLVANIA %X The purpose of this research study is to identify the social capital factors that help Hispanics in their decision to attend a Predominantly White Institution (henceforth PWI) and those social capital factors that are significant in their college persistence. College persistence is defined as returning a second year and beyond. This case study uses a mixed methodology, specifically an explanatory sequential method. First, a cross-sectional, online survey was sent to participants who self-identified as Hispanics and who were currently enrolled during the spring of 2015 (N=365). The survey was followed-up by four individual semi-structured interviews. The target population is undergraduate Hispanic students who are 18 years old and who are attending the Indiana University of Pennsylvania (IUP). %D 2016 %K social capital, college choice, college persistence, Hispanics, Predominantly White Institutions %I University of Pittsburgh %L pittir27921 %A Courtney Andersen %T Targeting estrogen receptor as a strategy for personalized medicine in ovarian cancer %X Ovarian cancer comprises a diverse set of diseases that are difficult to detect and treat successfully. Improving outcomes for ovarian cancer patients is contingent upon identifying targeted, individualized therapeutic strategies. One promising but under-utilized target is estrogen receptor-alpha (ER). ER is expressed in ~70% of epithelial ovarian cancers and epidemiologic studies implicate a role for estrogen in ovarian tumorigenesis. Further, clinical data suggest that a subset of ovarian cancer patients benefit from endocrine therapy. We hypothesized that ER drives development and progression of a subset of ovarian tumors and that outputs of ER function would identify patients who respond to endocrine therapy. We assessed endocrine response and mechanisms of ER signaling in models and clinical samples of high-grade serous ovarian cancer (HGSOC). These studies suggested that expression of ER target genes (ERTGs) reflect active ER in HGSOC and correspond with endocrine responsiveness. In light of this, we profiled ERTG expression to evaluate changes in ER signaling during the progression from benign endometriosis to endometriosis-associated cancer (EAOC). This analysis suggested that canonical ER signaling becomes largely inactivated during this transformation and that de-repressed genes (e.g. FGF18, ESR2) may contribute to the evolution of EAOC. Finally, we compared ER and ERTG expression between serous and mucinous low malignant potential (LMP) tumors. Serous LMP tumors have high expression of ER and several ERTGs (e.g. GREB1). Taken together, our findings describe biomarkers that could identify ovarian cancer patients across multiple disease subtypes who would benefit clinically from endocrine therapy. %D 2016 %K ovarian cancer, estrogen receptor, endocrine response, endocrine therapy, personalized medicine, fulvestrant, tamoxifen, predictive biomarkers, endometriosis, gynecologic oncology %I University of Pittsburgh %L pittir27376 %A Jing Zhao %T A causal role of ATM- and NEMO-dependent NF-?B activation in DNA damage-induced senescence and aging %X The accumulation of senescent cells induced by intracellular and extracellular stress contributes to multi-organ dysfunction and aging. Persistent DNA damage chronically accumulates with aging initiating a cellular stress response termed DNA damage response (DDR). Ataxia-telangiectasia mutated (ATM) kinase, a core component of DDR signaling, is involved in p53-p21 and p16-Rb senescent effector pathways, and is essential for senescence-associated secretory phenotype (SASP). In addition, ATM activates NEMO-dependent NF-?B pathway in response to genotoxic stress. However, the underlying molecular mechanisms through which DNA damage drives senescence and aging remain poorly characterized. Here we used the Ercc1-/? mouse model of a human progeria that spontaneously develops osteoporosis, disc degeneration, glomerulonephropathy and neurodegeneration, to address the causal link between DDR-dependent NF-?B activation, cellular senescence and aging. In the first part, we demonstrated that DDR signaling, concomitant with NF-?B, was highly activated in Ercc1-/? mice. A causal role of ATM in DNA damage-induced aging was demonstrated by genetic depletion of ATM in Ercc1-/? mice, which extended health span as well as alleviated aging-related pathology. Moreover, ATM haploinsufficiency showed significantly reduced NF-?B activation and SASP. In vitro assays support an activation of ATM- and NEMO-dependent canonical NF-?B activation in response to oxidative stress. In the second part, we developed novel small molecule inhibitors to disrupt the interaction between IKK? and NEMO/IKK?. We demonstrated that novel NBD mimetics, in particular SR12343 and SR12460, efficiently inhibited both TNF-? and LPS-induced NF-?B activation in vitro. Additionally, the chronic treatment with SR12343 and SR12460 reduced LPS-induced acute inflammation in lung and liver, and improved muscle pathology in mdx mice, a murine model of Duchenne muscular dystrophy. In the third part, we demonstrated that chronic treatment of Ercc1-/? mice with SR12343 significantly improved aging symptoms and prolonged healthspan, as well as reduced the level of cellular senescence. Furthermore, suppression of IKK/NF-?B attenuated lipodystrophy and associated impaired glucose tolerance by reducing cellular senescence in fat. Taken together, these results suggest that NF-?B activation promotes cellular senescence and aging through an ATM-dependent pathway in Ercc1-/? mice and the ATM-IKK-NF-?B pathway represents a key target for the development of novel approaches for healthy aging. %D 2016 %K DNA damage, Cellular Senescence, Aging, NF-?B, Progeria and NBD peptide %I University of Pittsburgh %L pittir27841 %A Kara Denise Whitman %T WHERE DO HUMANITARIANS CONNECT TO FIND DATA? A STUDY OF ACCESSIBILITY IN ONLINE INFORMATION ABOUT ADULT REFUGEES IN EMERGENCY EDUCATION. %X There are more than 15 million refugees registered with UNHCR and an unknown unregistered number of refugees worldwide. Among these refugees are scholars, academics and adult professionals. In 2010 for instance, the largest group in the Iraqi refugee populace in Jordan, was adults 18-59 years old. Thirty percent of these adults were university graduates. Yet, according to the dominant narrative, refugees are women and children, unskilled and traumatized, terrorists and vigilantes, ineligible and queue-jumping or short-term and freeloading. Thus, refugees are framed in ways that minimize their capacity and underscore a dependency upon or threat to the host state and aid community. Subsequently, compliance tasks have precluded aid for INGOs, which in turn, have ?responsibilized? refugees through ever-restrictive eligibility criteria and rules. Adult education and livelihoods have been limited and some refugees have been denied services. As a result, the people with the least resources have been apportioned a disproportionate amount of responsibility, for an environment in which either few relevant services were provided or no accountability relationship was afforded. INGO-donor networks have published online data to increase accountability, yet it has been examined most often quantitatively. Therefore, through network perspectives and the conceptual framework of downward accountability, I analyzed program reports from humanitarian activities implemented from 2010-2015, for Iraqi and Syrian refugees in Jordan. In an open data repository, I reviewed more than 1,800 program profiles and 47 documents were selected for content analysis. The analysis suggests emergency education decreased tensions, raised awareness about diseases and hygiene, achieved child protection and gender-inclusion goals and remediated noncompliance. The information however, was most often in regard to local beneficiaries, refugees with the least skills and refugees highly dependent upon humanitarian aid. Thus, there was minimal reporting of links between accountability policies, outcomes and the livelihoods aspirations of the refugee/scholar/professional. Recommendations encompass educational policies and practices such as requalification, continuing education, professional development and certification, because they lead to sustainable livelihoods. Through comparative qualitative research, this study problematizes accountability information in open data and underscores the Iraqi and Syrian crisis as an adult education emergency ? a circumstance not often associated with refugeehood. %D 2016 %K Middle East; Humanitarian; Downward Accountability; Refugees; Adult Education; Open Data %I University of Pittsburgh %L pittir28047 %A Anna Gallagher %T The Biderbost site: exploring migration and trade on the social landscape of the Pacific Northwest %X The Biderbost site of Duvall, Washington presents an interesting archaeological case for investigating trade and migration. The extensive lithic remains contain several stylistic traits of regional groups, but incomplete excavation records hinder most traditional archaeological analyses. Instead, an analysis of tool style suggested particular tools at the Biderbost were remnants of regional trade. Additionally, a portable X-Ray Fluorescence Spectrometry study was able to accurately identify the source of several pieces of Biderbost obsidian. The results of these two analyses provided potentially conflicting conclusions regarding trade and migration in the Pacific Northwest. Ultimately, patterns in the site?s stratigraphy indicating periods of abandonment may resolve these conflicting results through the possibility of multiple site occupations. The results from this analysis hold a variety of implications for the region and emphasize the importance of combing traditional archaeological methods and archaeometric methods. %D 2016 %K Biderbost Site; migration; trade; adze; projectile point; Pacific Northwest; Archaeology; Burke Museum; Seattle; Washington; lithic; pXRF; portable x-ray florescence; obsidian; analysis; nephrite; serpentine; raw material; occupation; abandonment; social landscape; 45SN100 %I University of Pittsburgh %L pittir27735 %A ALANOUD ALOTAIBI %A Alexandre R Vieira %T Effectiveness of supportive periodontal therapy on tooth survival among patients with chronic periodontitis %X INTRODUCTION: Prevention of tooth loss and maintaining favorable periodontal status are the ultimate goals of periodontal therapy. The aim of this study was to evaluate the effectiveness of non-surgical periodontal therapy and supportive periodontal care in arresting the progression of chronic periodontitis and in preventing tooth loss. MATERIALS AND METHODS: Periodontal charts, self-reported medical history, and interleukin-1 (IL-1) polymorphism genotypes of 100 patients were obtained from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository (DRDR) after screening of 4,825 subjects. In our study we have included third molars, teeth lost during active periodontal treatment (APT), and those lost during supportive periodontal care (SPC). We used tooth loss (TL) and clinical attachment loss (CAL) as outcomes of disease affection in our analysis. Fisher?s exact test was used to investigate the association between tooth loss and different risk factors. Paired t-test was conducted to detect the difference in means of CAL between baseline and final periodontal assessments. RESULTS: There were 59 patients (36 males and 23 females with an average age of 52 years) that lost at least one tooth. Tooth mortality rate declined in patients who attended supportive periodontal program for six years compared to those who received supportive periodontal therapy for one year only (0.52 and 3.4 teeth/patient/year, respectively). Increased risk of tooth loss was found to be associated with diabetes (P=0.01), as well as high blood pressure (P<0.0001). We did not find an association between tooth loss and polymorphisms in interleukin IL-1?/IL-1? (rs1800587, P=0.36 and rs1143634, P=0.51, respectively). During the first year of supportive periodontal treatment, the clinical attachment loss showed a significant reduction (CAL gain of 0.36 mm, P=0.0697). Moreover, a significant increase in CAL was noted in the group of patients who attended regular periodontal maintenance for six years (CAL progression of 0.38mm, P=0.037). CONCLUSION: Our findings suggested that supportive periodontal therapy is effective for the long-term stability of periodontal disease in high-risk patients in our sample. %D 2016 %K Supportive periodontal therapy, Tooth loss, Chronic periodontitis. %I University of Pittsburgh %L pittir27911 %A David J Laird %T The Impact of Planning and Other Organizational Factors on the Success of Small Information Technology Projects %X While extensive empirical research has been conducted in the past to assess the value of project management and planning on large projects and to evaluate the impact of critical success factors (CSFs) and other organizational factors, little research is available on the techniques and factors used on small IT projects, and their influence on project success. This dissertation presents a research study which tests the relationship between the type and level of project planning performed on small Information Technology (IT) projects, and the success of those projects. The research considers the influence of well-documented project critical success factors (CSFs) and other project and organizational characteristics, using empirical data from 79 projects of varying complexity in which the primary objective is to upgrade the operating system on personal computers in corporate systems and networks from Windows XP to Windows 7. Data was collected via a self-directed on-line survey administered to participants on each of the projects in the study, as well as through analysis of project planning artifacts from each project. This research found that many of the factors that correlate to success on large projects also influence the success of small IT projects. However, it also identified several distinct differences between large and small projects that may inform project practitioners on techniques to apply during the execution of small IT projects to improve their probability of success. %D 2016 %K Project Management, Information Technology, Management, Critical Success Factors, Planning %I University of Pittsburgh %L pittir27819 %A Nathalie Baracaldo %T TACKLING INSIDER THREATS USING RISK-AND-TRUST AWARE ACCESS CONTROL APPROACHES %X Insider Attacks are one of the most dangerous threats organizations face today. An insider attack occurs when a person authorized to perform certain actions in an organization decides to abuse the trust, and harm the organization by causing breaches in the confidentiality, integrity or availability of the organization?s assets. These attacks may negatively impact the reputation of the organization, its productivity, and may incur heavy losses in revenue and clients. Preventing insider attacks is a daunting task. Employees need legitimate access to effectively perform their jobs; however, at any point of time they may misuse their privileges accidentally or intentionally. Hence, it is necessary to develop a system capable of finding a middle ground where the necessary privileges are provided and insider threats are mitigated. In this dissertation, we address this critical issue. We propose three adaptive risk-and-trust aware access control frameworks that aim at thwarting insider attacks by incorporating the behavior of users in the access control decision process. Our first framework is tailored towards general insider threat prevention in role-based access control systems. As part of this framework, we propose methodologies to specify risk-and-trust aware access control policies and a risk management approach that minimizes the risk exposure for each access request. Our second framework is designed to mitigate the risk of obligation-based systems which are difficult to manage and are particularly vulnerable to sabotage. As part of our obligation-based framework, we propose an insider-threat-resistant trust computation methodology. We emphasize the use of monitoring of obligation fulfillment patterns to determine some psychological precursors that have high predictive power with respect to potential insider threats. Our third framework is designed to take advantage of geo-social information to deter insider threats. We uncover some insider threats that arise when geo-social information is used to make access control decisions. Based on this analysis, we define an insider threat resilient access control approach to manage privileges that considers geo-social context. The models and methodologies presented in this dissertation can help a broad range of organizations in mitigating insider threats. %D 2016 %K Insider threats, information security, risk, trust, access control systems %I University of Pittsburgh %L pittir26802 %A Anthony R. Cillo %T Characterization of inducible reservoirs of HIV-1 %X Combination antiretroviral therapy for HIV-1 suppresses viral replication, but is not curative. HIV-1 remains detectable in those on suppressive therapy as cellular proviral DNA and cellular HIV-1 RNA in peripheral blood mononuclear cells (PBMC), and as low-level plasma viremia. A long-lived reservoir of intact proviruses is also retained in the resting CD4+ T cell population. This population of long-lived, latently infected cells is believed to cause life-long persistence of HIV-1. To deplete latently infected cells, a ?kick and kill? strategy has been proposed, in which HIV-1 is ?kicked? out of proviral latency by small molecule latency reversing agents, leading to the ?kill? from viral cytopathic effects or immune mediated clearance. Recent ex vivo and in vivo studies have concluded that histone deacetylase inhibitors, protein kinase C agonists and Brd4 inhibitors can effect HIV-1 latency reversal. We evaluated this proposed strategy at the level of individual proviruses using a limiting dilution assay, and found that currently used latency reversal agents are not potent activators of HIV-1 latency compared with T cell activation. These latency reversal agents also do not lead to significant depletions of the HIV-1 reservoir in resting CD4+ T cells. We also sought to better understand relationships between molecular biomarkers of HIV-1 persistence and the size of the inducible reservoir. We found that as the frequency of infected cells and their transcriptional activity in PBMC increases, the size of the inducible reservoir also increases. Spontaneous virion production from resting CD4+ T cells and PBMC was also associated with low-level viremia. We also found that the magnitude of the inducible reservoir, and the levels of infectious virus, were higher in total CD4+ T cells compared with resting CD4+ T cells. Finally, we also found that the size of the inducible reservoir was significantly correlated with the magnitude of viral outgrowth from total and resting CD4+ T cells. Overall, these findings demonstrate that more potent latency reversing agents will be required to reduce the size of the latent reservoir, and suggest that measures of the infectious and inducible reservoirs in those on long-term antiretroviral therapy can be greatly simplified. %D 2016 %K HIV-1 persistence, HIV-1 latency, HIV-1 latency reversal, HIV-1 reservoirs %I University of Pittsburgh %L pittir27880 %A Marko Gudic %T From demands to deliberation: participatory budgeting in Pittsburgh %X In 2015, the City of Pittsburgh partnered with several community organizations to design and pilot a unique model of PB tailored to best meet its needs. As a result of this effort, the City implemented Deliberative Community Budget Forums as a more engaging and inclusive method for soliciting public input on the 2016 Capital Budget. This paper seeks to evaluate the impact of the Deliberative Forums on the quality and level of community participation, deliberation, and engagement, as well as measure outcomes in the budget. Data collected from the 2014 Community Budget Hearings are used as a baseline for comparison. The study found the forums led to considerable quantitative and qualitative improvements in the budget process with respect to public participation and deliberation, and increased general knowledge of the budget and political engagement among participants. The study also determined areas where the forums could be improved, particularly in regards to diversity and political voice. The impact of the forums on the Capital Budget were not able to be determined. At the end, several key recommendations to address these issues are made. This paper concludes by briefly summarizing the findings of the study and discussing their positive implications for the future of the forums as an effective alternative form of PB in Pittsburgh and possibly in the United States. %D 2016 %K Participatory Budgeting, Deliberative Democracy, Pittsburgh, PB, Deliberative Forums %I University of Pittsburgh %L pittir27798 %A Lisa Wisniewski %T EXAMINATION OF THE ASSOCIATION BETWEEN PERSONAL VALUES, LIFESTYLE FACTORS, AND WEIGHT LOSS IN A BEHAVIORAL PROGRAM %X Individual level values have been suggested as a construct that may influence motivation and adherence to health behavior change. There has been limited research conducted to examine values within the context of a behavioral weight loss intervention to treat overweight and obesity. PURPOSE: The purpose of this study was to examine the association between the perception of how engagement in a weight loss intervention would influence values and actual change in weight and weight loss-related behaviors (eating and physical activity). METHODS: Data utilized within the analyses were from participants enrolled in a 6-month behavioral weight loss intervention. Baseline data were available on 67 participants (age = 44.2?9.0 years; body mass index [BMI] = 32.6?3.9 kg/m2) with 58 subjects providing data on values at 6 months (age = 43.9?9.2 years; BMI = 32.6?4.0 kg/m2). Objective measures were taken at baseline and 6 months for body weight and BMI, with questionnaires used to assess values, perceived impact that engaging in a weight loss intervention would have on values, dietary intake (kcal/day), eating behaviors for weight loss, and physical activity (kcal/week). RESULTS: Marriage/couples/intimate relationships, family, and parenting were the three highest ranked values at both baseline and 6 months, suggesting that values remained relatively stable over the course of the weight loss intervention. There was no significant relationship between participant?s perception of the impact that engaging in a weight loss intervention would have on their values (measured at baseline and 6 months) and their actual changes in body weight, and related eating and physical activity behaviors. DISCUSSION: This study found no significant association between either weight loss or weight loss related behaviors (eating, physical activity) and perception of how these efforts impacted values of participants. These findings are not consistent with theories that have suggested that values can be important to elicit health behavior changes. However, these findings do not indicate that values-based interventions will not be effective for weight loss because values were not specifically targeted within the intervention. Therefore, additional research is needed to understand how values may influence health-behavior change, specifically within the context of a weight loss intervention. %D 2016 %K Values; Weight Management; Behavior Change %I University of Pittsburgh %L pittir27972 %A Matthew Delp %T Investigating the Criteria and Processes Used in the Selection, Implementation, and Evaluation of STEM within K-12 Education %X This study utilized survey research to investigate how school districts within K-12 education select, implement, and evaluate Science, Technology, Engineering, and Mathematics (STEM) programs. Thirty school districts within the Math and Science Collaborative located in Western Pennsylvania participated in this research. In addition to characterizing the STEM programs of the participating school districts, this study also analyzed the alignment of these programs to the components of comprehensive STEM programs and critical approaches to substantiate STEM program implementation as stated in the literature (Augustine, 2005; Bybee, 2010a, 2010b; Carnevale et al., 2011; DeJarnette, 2010; Epstein & Miller, 2011b; Gardner et al., 1983; Hossain & Robinson, 2011, 2012; Kuenzi, 2008). Findings suggest that the primary goal for school districts, as it relates to STEM program implementation, is to influence students? interest and pursuit of STEM-related careers and degrees. In order to achieve this goal, results of this study indicate the focus of STEM program implementation occurs with the greatest frequency at the middle school (grades seven and eight) level, are developed as an adaptation to the curriculum, and are very diverse from one school district to the next. In addition, findings suggest that although school districts maintain they aim to promote careers and degrees in STEM, districts rely on traditional methods of evaluating STEM program implementation (i.e. standardized test scores) and do not track the longitudinal impact their STEM programs as they related to degrees and careers in STEM. Furthermore, results indicate district STEM programs are not aligned to the characteristics of comprehensive STEM programs as defined by the literature. In order to address the misalignment of school district goals and evaluation processes involved in STEM program implementation and the absence of the characteristics commensurate with comprehensive STEM programs, this study has created a framework to guide school districts in STEM program selection, implementation, and evaluation. %D 2016 %K STEM, Education %I University of Pittsburgh %L pittir27760 %A Kevin Dylan McCormick %T RIPK1 down-regulation promotes tumor progression while enhancing the apoptotic response to TLR3 ligand in head and neck squamous cell carcinoma %X Head and neck squamous cell carcinoma (HNSCC) is the most frequent malignancy of the aerodigestive tract and the limitations in current chemotherapeutic approaches have yielded a poor prognosis. Synthetic double stranded (ds) RNA, which activate toll-like receptor 3 (TLR3) and generate interferon regulatory factor 3 (IRF3)-mediated proapoptotic responses in cancer cells, are being investigated as potent adjuvants to chemotherapy. We had previously shown that cells derived from metastatic HNSCC were unable to activate prosurvival NF-?B in response to TLR3 ligand, resulting in an enhanced apoptotic response compared to cells from primary tumors. Here, we demonstrate that in metastatic tumor-derived cell lines, transcriptional downregulation of receptor interacting protein kinase 1 (RIPK1), an adaptor protein of the TLR3 pathway, enhances dsRNA-mediated apoptosis due to a loss of NF-?B activation. This is consistent with our observations supporting the reduction of RIPK1 expression during the tumor progression of HNSCC correlated with an increased promoter methylation in matched tumor samples from HNSCC patients. Treatment of metastatic tumor-derived cell lines with a hypomethylating agent rescued the expression of RIPK1, demonstrating that promoter methylation may be responsible for the downregulation of RIPK1. We show that silencing of RIPK1 enhances the tumor promoting properties in HNSCC cell lines by increasing the rate of migration, EGFR expression and anoikis resistance. As the downregulation of RIPK1 expression contributes to the metastatic phenotype of HNSCC, but is essential for TLR3-NF-?B mediated pro-survival responses, we believe the results described here may open new prospects for using synthetic dsRNA to target metastatic tumor cells. In light of these findings, RIPK1 downregulation as a treatment biomarker, or combinational therapies with NF-?B-signaling inhibitors, could be used to enhance the immunotherapeutic efficacy of synthetic dsRNA. As the downregulation of RIPK1 has been observed in additional carcinomas, our findings suggest that synthetic dsRNA could be used as a broad anti-cancer therapy and that RIPK1 expression can be a useful indicator to predict the therapy response. %D 2016 %K TLR3 dsRNA RIPK1 NF-kB poly(I):poly(C) %I University of Pittsburgh %L pittir27963 %A Otgonjargal Okhidoi %T EQUITY IN HIGHER EDUCATION: SOCIOECONOMIC STATUS AND ITS EFFECT ON ACCESS TO HIGHER EDUCATION IN POST-SOCIALIST MONGOLIA %X Higher education participation has grown worldwide in the past two decades. Mongolia is not an exception. Higher education enrollment grew twelve-fold in Mongolia after the collapse of socialism. This dissertation examines whether the higher education enrollment increase has improved the opportunity to access higher education for students from lower income families. The dissertation addressed the following research questions. To what extent does socioeconomic status influence access to higher education in post-socialist Mongolia? To what extent are government financial assistance programs reaching their target groups? And, how has the role of socioeconomic status in influencing access to higher education changed in the past two decades? Using probabilistic data from cross-sectional Household Social and Economic Survey in Mongolia from 2008 and 2011, I ran logistic regressions, multinomial regressions, age-cohort analyses, and cross-tabulations to find answers to these questions. The statistical models were based on economics and sociology of education literature and status attainment theories. Sequential model building technique was implemented. The key contribution of this study is the innovative approach in creating a composite socioeconomic status variable (SES) out of six sub-scales, taking advantage of the wealth of information on diverse household revenues and expenditures available in the household surveys. The key findings of this study include: family background (SES) is a highly significant predictor of college access in post-socialist Mongolia. As of 2012, government financial assistance programs lack strong priorities, rather demonstrating a flattened-out distribution of the limited resources among students from the entire societal spectrum. Female students have higher probability of accessing higher education than their male counterparts throughout all four locations of residence. Age-cohort analyses revealed that socioeconomic status was a significant predictor of college access for all age-cohorts whose college entrance years ranged from 1994 to 2010. The effect of family background remained relatively stable for these years. Predicted probability of attending college increased for three older age-cohorts, except the fourth?the youngest cohort. And the increase in the probability of attending college from one generation to another was less for the lower SES groups and larger for the highest SES groups. %D 2016 %K equity and access, higher education, post-socialist nations, Mongolia, socioeconomic status and access to higher education, quantitative dissertation, national Household Survey data for quantitative study %I University of Pittsburgh %L pittir27875 %A Maria T. Genest %T ?How do you think it went??: An Exploratory Study of Cooperating Teacher Feedback about Preservice Teachers' Literacy Instruction %X This study examines the nature of discourse about literacy instruction that occurs within the field placement. Using a comparative case study design within three first and second grade classrooms, participants conducted four read-aloud lessons over the duration of the study. Written and verbal post-lesson conference feedback were analyzed for evidence of discussion about high quality read-aloud instruction. The findings suggest that cooperating teachers provided limited feedback about literacy instruction; however, with the implementation of a feedback tool in the second phase of the study, post-lesson discussion with preservice teachers about the features of a high quality read-aloud lesson was more prevalent. These results suggest that cooperating teachers and preservice teachers may benefit from an explicit focus on feedback and that university supports in the form of a feedback tool may be one way to emphasize, and thus improve, knowledge about literacy instruction. %D 2016 %K literacy, teacher education, cooperating teacher, mentor teacher, read aloud, preservice teacher, feedback %I University of Pittsburgh %L pittir27902 %A Emily Sobeck %T THE EFFECTS OF DIDACTIC INSTRUCTION AND PERFORMANCE FEEDBACK ON PARAEDUCATORS? USE OF POSITIVE BEHAVIOR SUPPORT STRATEGIES IN INCLUSIVE SETTINGS %X With the shift to inclusive practices and with legislation (IDEIA, 2004; NCLB, 2001) mandating that students with disabilities be educated in the least restrictive environment (LRE), the educational service delivery for both students with disabilities and the paraeducators that provide support services has evolved. The responsibilities of paraeducators have shifted from duties that were primarily clerical in nature to now supporting students with disabilities, both instructionally and behaviorally. At the very least paraeducators are now providing academic instruction, serving as interventionists, communicating with parents, and adapting instructional materials. Although paraeducators assume a variety of roles, many paraeducators have no formal education beyond high school and are provided with minimal professional development once on the job. As more schools turn to inclusionary practices the impetus for highly qualified and trained paraeducators becomes of even more importance. Examination of the current paraeducator training literature reveals that research on paraeducator training is not only limited, but also contains several areas of methodological weakness. Although several training approaches have been investigated with paraeducators, the current paraeducator training literature does not provide evidence in support of the most effective way to provide training to paraeducators. Therefore, the following study aims to expand the research base by analyzing the general and comparative effectiveness of didactic instruction and performance feedback on paraeducators? use of positive behavior support strategies with students with disabilities in inclusive settings. Further, this study also seeks to strengthen the current literature base on paraeducator training by improving on the areas of methodological weaknesses addressed in the review. Implications for practice and future directions for research are also discussed. %D 2016 %K paraeducator training, paraprofessional training, inclusion, instructional aides special education administration, performance feedback, positive behavior support strategies %I University of Pittsburgh %L pittir27794 %A Jessica Mason %T ASSESSING THE IMPACT OF THE COLLEGE EXPERIENCE ON CIVIC ENGAGEMENT: A PROPENSITY SCORE MATCHING APPROACH %X Today?s ?millennial? undergraduate students are less politically involved than students in past generations, and voter turnout among the 18-25 age group has been on the decline since the 1970s. At the same time, however, student activism remains important on American university campuses, student opinions reflect a continued interest in the democratic process, and college freshman in 2015 were more politically involved than any of their peers in the 50 years prior. Colleges and universities are well positioned for the promotion of civic engagement, especially given the public history of the American university, many of which were involved in nation building. As such, it is important to consider the potential civic impact of higher education institutions. Using data from the NCES 2002 Education Longitudinal Study (ELS:2002), IPEDS 2006, and the 1965 Youth-Parent Socialization Panel Study, I use propensity score matching to understand the effects of various aspects of the college experience on civic engagement outcomes. I use an adaptation of Astin?s (1993) input-environment-outcome model of college impact, informed by the literature on political socialization and pre-college civic education. This study?s first key finding is that college involvement, more than the type of institution attended, has an impact on young adult civic engagement outcomes. The second key finding in this study is that the effects of the college experience on civic engagement outcomes may not persist into later adulthood. This stu