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    Situating Racialized Genders: An Analysis of Identity Development, Cultural Influences, and State-level Policy Impact on the Health of Transgender People of Color

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    This research provides an in-depth exploration and definition of the multifaceted experiences of transgender (trans and nonbinary) individuals of color in the United States (US), balancing both a broad legislative analysis and a focused qualitative perspective. This dissertation explores how to more rigorously define the epidemiological concept of “exposure” to impact upon health inequities for individuals who experience oppression on multiple axes (e.g., race and gender). Initially, this research employs a polytomous latent class analysis to classify US states into three categories—Mostly Protective, Mixed, and Mostly Harmful—based on trans rights and structural racism policies. By drawing upon data from the Movement Advancement Project’s Gender Identity Tally and a structural racism legal database, the analysis reveals that even within seemingly inclusive states, protective measures are not uniformly applied, pointing to the necessity of comprehensive, intersectional policy evaluations. These insights underscore the variable impacts of state policies, advocating for more inclusive legislative frameworks that adequately consider the intersecting identities of race and gender. The second study shifts to a qualitative focus, examining the experiences of 8 Black transmasculine individuals in the Black culturally rich and historically significant city of Detroit, Michigan—a pivotal site during the Great Migration – and surrounding counties in Southeastern Michigan. Using Interpretative Phenomenological Analysis and object elicitation, the study investigates how participants, aged 25-35 years, navigate the tapestry of Black gender norms, family belonging, and community interactions in shaping their masculine and Black identities. A key finding is the role of alcohol serving not only as a medium for gender affirmation and personal identity exploration but also as a crucial element in familial and community bonding and coping with structural anti-Black oppression. Amid structural discrimination, alcohol emerges as a tool for coping and solidarity, facilitating connections and collective support within the family and community. Together, these quantitative and qualitative insights offer a holistic view of how historical, cultural, and political determinants intersect with localized, cultural dynamics to influence the well-being and identity development of marginalized communities. The research stresses the importance of crafting policy solutions that are both broad in scope and finely attuned to the specific needs and challenges faced by these communities. By detailing the interplay between legislation and lived experience, the study advocates for interventions and policies that are both inclusive and sensitive to the diverse realities of trans individuals of color, particularly those identifying as Black and transmasculine.Population Health Science

    2055 年に向けた体制の立て直し――ラオス人民革命党第12 回大会

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    GeopoliticalStrength in Religious Ties: How Diplomatic Relations Between the Vatican and Post-Revolutionary Iran have Bolstered Iranian Resilience

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    Numerous players influence those at the helm of the global political stage. Yet dominant state powers, especially democratic ones, remain at the forefront. They set the tone, reshape borders, dictate trade, and attempt to instill peace in times of instability and turmoil. In the today’s world, where information is immediate and no global event is “unsearchable,” traditional rules are no longer uniplanar as to what international relations and diplomatic means may drive intrastate dialogue and change. Unlikely players can hold immense power. This thesis outlines one salient example of significant impact relating to relations between two unique, noncentral players: the Islamic Republic of Iran, and the Holy See (herein referred to as “the Vatican”). At face value, most would not think that these two bodies share much in common. Beliefs, social norms, and political disposition vis-à-vis the rest of the world, are vastly different. Yet, upon deeper inspection we find many similarities, shared beliefs, common causes, and appreciation for what each represents. Importantly, both entities hold significant political and spiritual power over their citizens and adherents. Contrast this with the most powerful political authority on Earth, the United States. Hailed for democracy and freedom fighting, feared for its mighty military, and envied for its development and wealth, the U.S. sits at the top of all global powers. But this position comes with immense responsibility and expectations. Not only is the U.S. expected to assist in maintaining global stability, but the democratic values of the country’s leadership and its citizens empower it to export democracy to all who will listen and even to those who will not. While sentiments had been building for decades, the terror attacks of September 11 exacerbated intolerance for dissimilar players. If you are not democratic, it is difficult to be viewed positively by the U.S., however it is the right of individual nations to determine what political structure will bind them and that democracy is not always the choice. Some nondemocratic entities are benign, such as the Vatican, while others present an adversarial threat to democracy, for example, postrevolutionary Iran. Ironically, these two are similar politically in that they both follow theocratic principles. But one heads a list of top five foreign policy priorities and threats to the U.S., and the other heads a list of friends, eager to be engaged in times of needed counsel. Through this thesis, I will show how the U.S. and the Western world find relations with the Vatican useful when convenient. On the other hand, I will outline how a deeper, religious bond between the Vatican and Iran has come to supersede the mere diplomatic relationship between the U.S. and the Vatican. I will explain how Vatican– Iranian relations have yielded unexpected gains for Iran and have bolstered their political body when most of the world has stood against them.Extension Studie

    Characterization of Factors that Regulate Cell Envelope Synthesis in Staphylococcus aureus

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    Bacteria are separated from their environment by a cell envelope, an essential structure composed of multiple polymers and proteins. To grow and divide, the existing structure needs to be remodeled then expanded with new material. These processes are inextricably linked: the degradation and synthesis of the cell envelope must be balanced to maintain its integrity. To accomplish this, cells have evolved a series of regulators in the cell envelope which can (i) directly modify the activities of cell envelope synthesis proteins or (ii) signal transduction proteins that can direct intracellular processes to respond to extracellular events. This thesis is split across two projects, each elucidating a regulatory complex in the membrane of S. aureus. In the first project, I describe a physical and genetic interaction between SpsB and SpbR (backgrounds for each protein are provided in Chapter 1.3). This project was undertaken with two other graduate students, Madeleine Stone and Youngseon Park, and together we describe how SpbR controls processing of LtaS to terminate lipoteichoic acid synthesis and maintain appropriate length LTAs in the membrane. In the second project, I describe a physical and genetic interaction between AuxB, PknB, and GpsB (backgrounds for each protein are provided in Chapter 1.4, Chapter 1.6, and Chapter 1.7). I show that AuxB forms independent interactions with GpsB and PknB; by altering the interaction between AuxB and PknB, I induce phenotypes that indicate the former regulates the latter. I also describe how the features of PknB and AuxB confer intrinsic resistance to various antibiotic compounds and have unique genetic relationships to cell envelope polymers. Finally, I present models for the possible physiological roles of AuxB in complex with PknB and GpsB. In Chapter 2, I characterize SpbR as an interacting partner of the signal peptidase SpsB and show that it regulates lipoteichoic acid synthesis by controlling cleavage of lipoteichoic acid synthase. In Chapter 3, I report and characterize AuxB-GpsB and AuxB-PknB interactions and present evidence that AuxB antagonizes PknB through its direct association. I further show that S. aureus becomes sensitive to various disruptions in cell envelope synthesis when the AuxBPknB complex is too abundant or lacking from the cell. In Chapter 4, I discuss unpublished work on AuxB and PknB that provides exciting hypothesis for future work. In Chapter 5, I discuss future directions and implications for this workChemical Biolog

    Evolutionary motif swapping of human dihydrofolate reductase rewires the enzymatic cycle

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    Despite common descent, enzymes often rescue poorly when expressed across domains of life. Causes include factors external to the enzyme, such as differences in codon usage, sensitivity to proteases, and transcriptional or post-translational regulatory differences, yet often the underlying cause remains unclear. Dihydrofolate reductase (DHFR) catalyzes the same metabolic conversion across the tree of life. Nevertheless, human DHFR (hsDHFR) does not effectively rescue growth of DHFR-deficient E. coli despite similar in vitro kinetics. This phenomenon has been previously attributed to inhibition of hsDHFR by its oxidized cofactor, NADP+. To understand this phenomenon, we designed mutants based on deep sequence divergences across the tree of life, yielding variants which outperform both wild-type enzymes in vitro and which rescue growth of E. coli. Remarkably, a single, ancient sequence insertion underlies gain of function, not by modulating product inhibition, but by redirecting ligand flux – the non-equilibrium sequence of steps binding and unbinding product, cofactor, and substrate. We find that deleting this insertion decouples the dynamics of a substrate binding loop from subdomain motion, thereby controlling a critical enzymatic parameter orthogonal to catalytic proficiency.Biology, Molecular and Cellula

    Development of an exosome-based tagging method to label CD8+ T effector cells that immune surveil arteriolar endothelium for transcriptional characterization

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    T cell function is highly regulated during acute viral infection to ensure an effective immune response. Upon antigen exposure, T cells experience a unidirectional differentiation that can be studied based on the increased expression of CX3CR1. Previous work from our group has identified a subset of CX3CR1hi CD8+ T effector cells that patrol along vessel walls, mostly on arterioles, enabling a rapid response to endothelial viral infections. In an attempt to isolate and characterize patrolling CD8+ effector T cells, we used Kaede (a photoconvertible protein) to specifically label intravascular T cells interacting with the endothelium at a given time point. However, this method can neither distinguish patrolling cells interacting with the endothelial wall for different periods of time nor the signal strength they receive, thus producing a heterogenous outcome with cells at various stages of patrolling. To further study patrolling T cells, we have developed a complementary approach using endothelium-derived fluorescent exosomes to tag T cells actively interacting with arterioles. This technique allows us to obtain a sizable amount of better synchronized T effectors for in depth characterization. In this regard, bulk RNA-seq unveiled a proliferating transcriptional gene signature for patrolling CD8+ T cells. This result is in agreement with the scRNA-seq data obtained with the Kaede model. Moreover, we also detected multiple Trav, Traj, Trbv and Trbj genes specifically upregulated in either patrolling or circulating T cells in both transcriptional analyses. However, by analyzing the VJ combinations and CDR regions of individual cells detected by TCR clonotyping, minor differences were identified. Finally, using a predictive software for transcriptional regulators (BART, Binding Analysis for Regulation of Transcription), we found a striking amount of epigenetic modulators upregulated preferentially in patrolling CD8+ effector T cells, indicating that these effector cells might be experiencing active epigenetic regulation. These findings suggest that CD8+ effector T cells interacting with arteriolar endothelium during the anti-viral immune response receive signals that shape them at transcriptional and epigenetic level.Graduate Educatio

    Navigating Digital Worlds: Empirical Studies of Choice and Behavior in Sociotechnical Systems

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    This dissertation empirically examines the nature and consequences of three types of choices that individuals, firms, and communities make (or might make) against the background of complex sociotechnical environments, new technologies, and competing goals. First, in Chapter 1, I present research about consumer choice and price comparison behavior in the context of the market for ridesharing services Uber and Lyft. Combining several novel data sources along with benchmark evidence from existing literature, the work calibrates a simple sequential search model to benchmark observed search behavior against theoretical predictions. The work finds that consumers compare prices substanially less than canonical models would predict given observed levels of price dispersion and benchmark estimates of consumer search costs. While the individual benefits of searching are modest, the aggregate implications are large; in a back-of-the-envelope calculation, we find that New York City-based rideshare customers collectively leave over \$300 million per year on the table by not comparing prices (about 6\% of platforms' gross booking volume), illustrating how small frictions can have substantial aggregate implications for the distribution of surplus in digital markets. Second, in Chapter 2, I present research that studies conflict and disagreement in online conversations. The study develops and experimentally tests a novel AI-based mediation tool designed to facilitate constructive online dialogue across political divides. Powered by a large language model (LLM), the tool automates mediation interventions grounded in communication and conflict resolution principles such as paraphrasing, identifying agreement, and encouraging perspective-taking. In a randomized controlled trial, the system successfully generated context-sensitive interventions in contentious conversations; however, effects on participants' attitudes towards people they disagree with were limited. The findings highlight both the promise and the challenges of using LLMs to promote healthier online discourse at scale. Note that results presented in the present chapter are based on a partial sample of data from the study; future drafts of this work will include results from the full sample of data. Finally, in Chapter 3, I present emerging research that studies workers' beliefs about the future labor market impact of emerging digital technologies, with a focus on AI and large language models (LLMs). As AI tools like LLMs become increasingly capable, workers must make decisions about how to respond. Importantly, these decisions are shaped not only by the actual rate and direction of technological change, but also by workers' beliefs about these future trajectories. Importantly, these beliefs may differ across workers and may not align with expert forecasts about the likely impact of AI, while nonetheless shaping economic behavior. In this research, we design and conduct a survey and randomized experiment to study the role of worker beliefs in shaping labor market responses to generative AI, with a focus on two professional fields: law and management consulting. There are three main findings. First, we find that beliefs vary substantially within and across professions. Second, we find that workers expecting larger AI impacts are somewhat more likely to report AI training, degree enrollment and workplace LLM use (though results are noisy and not significant based on current sample). Third, we find that exposure to contrasting expert narratives shifts stated beliefs about the likely impact of AI on the labor market; we do not find evidence of a significant impact on behavioral outcomes in current sample (small effects possible with more data). The findings in this chapter are based on preliminary pilot data from an ongoing project; findings may change as additional data collection continues. The title of this dissertation, "Navigating Digital Worlds", emphasizes that, at least collectively, we have agency in the digital worlds that we create and inhabit. Sociotechnical spaces are not fixed or inevitable, but are instead imagined, constructed, and shaped by people, technologists, experts, and policymakers. The choices we make about the structure of these spaces then shapes the opportunities, constraints, and consequences we face in subsequently navigating them.Business Administratio

    Perceived Value of Bioacoustics dMRV in Nature-Based Carbon Solutions

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    The carbon credit market is forecasted to grow significantly in both size and complexity, driven by continued global efforts to mitigate climate change. To facilitate the marketplace, carbon serves as the anchor of value for each credit regardless of the capture or reduction method. Nature-based credits (NbC) depend on the natural systems that provide not only carbon sequestration, but also ecosystem services. Carbon credits created through project-level interventions in natural systems (Nature-based solutions, NbS) with added benefits, such as biodiversity, tend to trade at a price premium; nevertheless, questions about durability and the lack of standardized monitoring, reporting, and verification (MRV) plague consumer confidence in NbS. Demand for MRV quality improvements in NbS has inspired advancements in digital Monitoring, Reporting, and Verification (dMRV) technology; however, there is insufficient exploration of the sector’s perceived value of these tools. I investigated the linkages between perceived value and willingness to pay among stakeholders in the NbS carbon market. My research focused on bioacoustics dMRV as one such potential solution, whose application is relatively nascent in NbS carbon projects. Advancements in hardware and software have rapidly expanded the utility of this technology by increasing audio sensitivity beneath ecosystem canopies and expediting signal processing with new AI software. Bioacoustics is an underutilized tool that may help satisfy demand for improved MRV quality in NbS projects by enabling robust biodiversity data collection where field studies have previously been prohibitive. My goal was to inform stakeholders about this rapidly evolving tool, as NbS project quality, MRV, best practices, protocols and standards are under review for revision. I used a mixed-methods exploratory sequential design to gather both qualitative and quantitative data. My stakeholder sampling approach was holistic, including not only those directly involved with NbS projects (such as developers and buyers), but also secondary stakeholders who shape the broader carbon project sector (such as technology service providers, insurance and ratings providers, corporate strategists, and ecosystem specialists). Stakeholders were interviewed and surveyed to assess themes, including perceived value and willingness to pay for bioacoustics dMRV. Triangulation of qualitative and quantitative data revealed both opportunities and barriers to adoption. Results confirmed hypotheses 1, 2, and 3. Hypothesis 4 uncovered a semantic caveat (willingness for ‘price premium’ is supported, willingness for ‘additional budget’ is not). The averages of quantitative survey responses aligned with interviews and background research; however, the high response disparity suggests a lack of consensus across the sector as a whole. A notable link between price, value, and risk was identified as an opportunity to reframe the cost of bioacoustics dMRV not only in terms of co- benefits but also as an indicator of carbon durability risk. These results indicated that stakeholders see value in more robust biodiversity MRV data; it can significantly boost consumer confidence in NbS, increase investment volume, and command price premiums, thereby enabling not only carbon mitigation but also the preservation and improvement of ecosystems. When quality improvements become standardized, quality credits will become the standard, not the exception, and every NbS investment will work harder and better for nature and humanity.Extension Studie

    Studies of Ubiquitin Activation and Chain Synthesis

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    The Ubiquitin Proteasome System (UPS) is among the most extensive cellular pathways, with over 1200 components, and it has profound implications for cellular homeostasis and disease. In this dissertation, we will discuss in vitro studies of its mechanism. We will begin in Chapter Two by characterizing a computationally derived small molecule library to target the ubiquitin fold domain of UBE1 for enzymatic inhibition. This work will describe a screen conducted to test a library generated in silico and discuss alternative methods for targeting E1. Next, we will transition to investigating free ubiquitin chain formation by the E3 ligase Hul5 in Chapter Three. We will describe rapid di-ubiquitin formation by Hul5 and the suppression of this reaction by calcium, which is mediated by calcium binding to calmodulin. Characterization of di-ubiquitin identified a preference for K48-linkages and formation by an acceptor site on Hul5. Lastly, we will conclude by discussing the role of Hul5 as the only identified processivity factor of the proteasome. In Chapter Four, we will establish a framework and method for the in vitro characterization of Hul5 as a processivity factor to uncover its mechanism of action. Together, this body of work elucidates therapeutic and mechanistic features of the UPS to contribute to our biological understanding of the pathway.Chemical Biolog

    Agrarian Developmentalism: The Politics of Development Strategies in Latin America

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    The conventional wisdom holds that governments extract from agriculture to promote industrialization. However, development strategies are not uniform. While some governments did extract from agriculture, others actively supported the sector in what I call agrarian developmentalism. Why do some governments support agriculture while others extract from the sector during industrialization? I argue that this variation is explained by the structure of the party system and rural producers’ legislative strength. Integrative party systems—where parties rely on mixed rural-urban constituencies for electoral support—are more favorable to agriculture. In these systems, politicians from different parties are more likely to endorse pro-rural programs, include rural producers in governing coalitions, and craft intersectoral bargains to solve urban-rural distributional conflicts. In contrast, segmented party systems—where politicians specialize in representing either urban or rural constituencies—foster intersectoral conflict, making generous government support for agriculture less likely. Additionally, rural producers’ legislative strength determines the level of extraction. This formal power allows them to systematically constrain extraction from agriculture. The combination of an integrative party system and rural legislative strength leads to agrarian developmentalism. I develop the argument through a comparative historical analysis of two countries with divergent development strategies crafted during World War II: Colombia and Chile. In Colombia, the government supported agriculture generously through price support, tariff protection, and public spending. By contrast, the Chilean government sidelined agriculture to promote industrialization. Drawing on original data collected over twelve months of fieldwork from a range of historical sources, I show how variation in the type of party system and rural producers’ legislative strength shaped agricultural policy. I also demonstrate that alternative approaches focusing on the structural or instrumental power of rural producers have limited leverage to explain whether development strategies favor agriculture. The main contribution of this study is to show that patterns of political representation through the party system matter for economic policy outcomes. Against the literature portraying landowners as very powerful actors, my findings reveal that they were mainly reacting to rather than shaping economic policy. Second, I offer a new perspective on Latin American party systems. Parties in integrative party systems are often dismissed as “catch-all” clientelistic machines that lack programmatic commitments. I demonstrate that these parties do have programmatic agendas that influence how politicians govern and how development strategies unfold. Third, my work joins recent scholarship that challenges the alignment between landowners and authoritarianism. I show that independent legislatures provide landowners with a unique institutional arena to constrain extraction, an arena absent under authoritarian regimes. Thus, I argue, democracies with broad-based coalitional parties are conducive to a pro-agricultural development strategy.Governmen

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