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Limbic Circuit Control Of Stress And Neuroinflammation, Alexa Renee Soares Jan 2025

Limbic Circuit Control Of Stress And Neuroinflammation, Alexa Renee Soares

Yale Graduate School of Arts and Sciences Dissertations

Individuals are constantly subjected to various forms of stress, which shape the brain in different ways. The brain, in turn, must coordinate a response to adapt to the demands of the stressor. This response is coordinated via interactions between several neuromodulatory and neuroinflammatory signaling pathways. The limbic system, particularly the amygdala and hippocampus, has been highlighted as an important site for integration of these signals. These areas are critical for engaging neural, autonomic, and behavioral responses to acute stress and for plasticity-driven learning that can shape future responses to stress through a process called allostasis. Chronic exposure to stress can …

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Building Certified Systems With Compositional Semantics, Yu Zhang Jan 2025

Building Certified Systems With Compositional Semantics, Yu Zhang

Yale Graduate School of Arts and Sciences Dissertations

Formal verification has emerged as the most rigorous approach for building reliable computer systems. Certified systems, in particular, are accompanied by a formal specification and a machine-checkable proof of correctness, enabling independent verification by third parties. However, verifying large-scale, heterogeneous systems presents significant challenges that current techniques cannot adequately address. Such systems require compositional methods that can flexibly integrate diverse verification approaches, including program logic, certified compilation, and data abstraction. While compositional semantics offers a promising foundation, existing frameworks are typically built on specialized operational models that resist integration with one another. This dissertation presents a three-dimensional algebraic compositional structure …

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Building Intelligent Robots For Social Regulation Therapy, Rebecca Ramnauth Jan 2025

Building Intelligent Robots For Social Regulation Therapy, Rebecca Ramnauth

Yale Graduate School of Arts and Sciences Dissertations

Throughout life, we learn the rules of social behavior by observing others, by exposure to diverse social contexts, and, in some cases, through targeted intervention. More than learning the rules and expectations on how to behave, social regulation involves the dynamic, real-time coordination of one's internal states and outward behaviors to meet those expectations. Regulation becomes challenging when internal states conflict with external demands, such as in moments of heightened emotion, sensory overload, or social ambiguity. In certain contexts (such as isolation during a global pandemic) or for some individuals (such as those with autism), social regulation can be difficult …

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Documentary Opera: Twenty-First Century American Performances Of Race And The Archive, Allison Chen-Xing Chu Jan 2025

Documentary Opera: Twenty-First Century American Performances Of Race And The Archive, Allison Chen-Xing Chu

Yale Graduate School of Arts and Sciences Dissertations

“Documentary Opera: Twenty-First Century American Performances of Race and the Archive” explores how embracing the documentary impulse has transformed American opera in the twenty-first century. Amidst the current renaissance of American opera, I identify a trend that I call “documentary opera,” namely operas that engage documentary source materials, techniques, and aesthetics to reimagine narratives of historical figures or current events. Like documentary works in other genres such as film and theater, these operas rely on an interrogation of, and relationship to, the archive; however, they also harness the affordances of opera’s heavily stylized aesthetics to unsettle the notion of the …

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Reducing Dementia Risk By Identifying And Promoting Social Determinants: A Multi-Site And Multi-Method Study, Jose M. Aravena Jan 2025

Reducing Dementia Risk By Identifying And Promoting Social Determinants: A Multi-Site And Multi-Method Study, Jose M. Aravena

Yale Graduate School of Arts and Sciences Dissertations

Background: Dementia is one of the leading causes of disability and death, and the most feared condition by older adults. Although encouraging evidence has shown that lifestyle can play a pivotal role in dementia prevention, dementia incidence is still increasing in those groups that are at most risk. A largely unexplored explanation for this phenomenon in high-risk groups is the effect of social determinants of health (SDH), a range of structural (i.e., social position, healthcare services) and psychosocial determinants (ageism, social perceptions of dementia) that can be a major modifiable driver of brain and cognitive health. Thus, by using three …

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Neurocognition In Youth With Prediabetes, Jade Ivey Quillian Jan 2025

Neurocognition In Youth With Prediabetes, Jade Ivey Quillian

Yale Graduate School of Arts and Sciences Dissertations

The association between type 2 diabetes (T2D) and cognitive impairment has been well established. This is critical because T2D is a key risk factor for Alzheimer’s disease. However, these studies often fail to account for adiposity and other co-morbid conditions that accompany T2D in older adults. As a result, the mechanisms linking connecting T2D and cognitive impairment consequently remain unclear. The overall aim of this dissertation is to understand the precise effects of dysfunctional glucose metabolism on neurocognition. To do this I capitalized on a unique opportunity to study dysregulated glucose in youth from the Pathogenesis of Youth Onset Diabetes …

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Functional Roles Of Histone H3 Lysine 4 Methylation At Regulatory Elements, Haoming Yu Jan 2025

Functional Roles Of Histone H3 Lysine 4 Methylation At Regulatory Elements, Haoming Yu

Yale Graduate School of Arts and Sciences Dissertations

Histone H3 lysine 4 methylation (H3K4me) is a highly conserved histone post-translational modification linked to active transcription. Although the enzymes that regulate this mark are essential for development, the direct functional role of H3K4me itself remains unclear. To provide a comprehensive overview, I first reviewed evidence from histone residue mutations, histone modifier perturbations, and epigenetic editing studies in yeast, Drosophila, and mammalian systems. This analysis highlights that H3K4me3 instructs transcription initiation and Pol II pause-release at promoters, and H3K4me1 and H3K4me3 may have convergent functions in establishing open chromatin. However, the functional role of H3K4me3 at intergenic site remains poorly …

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Exploring Communication In Pediatric Oncology And Parental Bereavement Outcomes: A Mixed Methods Study, Na Ouyang Jan 2025

Exploring Communication In Pediatric Oncology And Parental Bereavement Outcomes: A Mixed Methods Study, Na Ouyang

Yale Graduate School of Arts and Sciences Dissertations

The first two years after a child’s death, defined by parents as early bereavement, are a particularly vulnerable period for parents. More than 40% of bereaved parents report severe, prolonged grief symptoms during early bereavement. High-quality parent-clinician communication, which is delivered honestly, clearly, and with sensitivity, helps parents make informed decisions about medical care, address their complex needs during their child’s end-of-life (EOL), and is related to lower severity of prolonged grief symptoms many years after a child’s death. However, research rarely focuses on the parent experience in early bereavement, and little is known about which specific components of parent-clinician …

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Integrating Life History And Ecological Adaptation: Evolution In The Desert-Alpine Plant Lineage Cistantheae, Anri Chomentowska Jan 2025

Integrating Life History And Ecological Adaptation: Evolution In The Desert-Alpine Plant Lineage Cistantheae, Anri Chomentowska

Yale Graduate School of Arts and Sciences Dissertations

Understanding the mechanisms underlying evolution and adaptation - particularly among traits that evolve correlatively, like those that make up life history strategies - requires an integrative approach across evolutionary, ecological, and genomic scales. This dissertation focuses on the desert-alpine lineage Cistantheae (Montiaceae), a clade of herbaceous plants distributed across arid and montane habitats in western North and South America. The three chapters, at different scales, explore how climate niche, mating system, and photosynthetic physiology are correlated to life history strategies through evolutionary history. Chapter 1 presents the first densely-sampled molecular phylogeny of Cistantheae, inferred using reduced-representation genome sequencing (ddRADSeq). This …

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Understanding The Double-Itcz Bias: From Ocean-Atmosphere Interactions To Future Climate Projections, Zhiyuan Li Jan 2025

Understanding The Double-Itcz Bias: From Ocean-Atmosphere Interactions To Future Climate Projections, Zhiyuan Li

Yale Graduate School of Arts and Sciences Dissertations

The double-ITCZ bias is one of the most persistent and long-standing model deficiencies in General Circulation Models (GCMs), affecting simulations of tropical precipitation patterns and future climate projections. This bias manifests as an unrealistic secondary Intertropical Convergence Zone (ITCZ) forming south of the equator, particularly in coupled ocean-atmosphere models. Since the ITCZ plays a crucial role in shaping global precipitation patterns, addressing this bias is essential for improving climate model reliability. CMIP6 projections indicate that the double-ITCZ feature may become more pronounced under global warming, raising the question of whether this enhancement represents a true climate change response or a …

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Unwanted Transitions Of A Superconducting Qubit Induced By Microwave Drives, Pavel Kurilovich Jan 2025

Unwanted Transitions Of A Superconducting Qubit Induced By Microwave Drives, Pavel Kurilovich

Yale Graduate School of Arts and Sciences Dissertations

Quantum bits built from microwave superconducting circuit components such as capacitors, inductors, and tunnel junctions are one of the leading platforms for realizing a fault-tolerant quantum computer. A roadblock towards this goal is the insufficient fidelity of operations -- single-qubit gates, two-qubit gates, and readout measurements -- performed on the quantum bits via microwave pulses. The main limitation of operation fidelity comes from decoherence. If the operation is performed too slowly compared to the decoherence time, a qubit error will happen. Usually, it is possible to speed up the operations by increasing the power of the microwave pulse. However, reducing …

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Light Sheet Microscopy For 3d Nanoscale Imaging, Hannahmariam Mekbib Jan 2025

Light Sheet Microscopy For 3d Nanoscale Imaging, Hannahmariam Mekbib

Yale Graduate School of Arts and Sciences Dissertations

Advances in expansion microscopy, a super resolution microscopy technique in which samplesare expanded up to ~8,000 times their original volume, require new microscope modalities to image the large sample sizes. These new techniques should be suitable for imaging large sample volumes, yet need to maintain the high 3D resolution of 250-500 nm of high-end confocal microscopy to provide the maximum level of detail and thereby reveal nanoscale cellular ultrastructure. Axially Swept Light Sheet Microscopy (ASLM) has emerged as a promising technique for generating high-resolution images at high-throughput. However, current designs struggle with the trade-off between limited resolution and field-of-view (FOV) …

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The Independent And Redundant Roles Of Tbx16 And Msgn1 In Mesodermal Differentiation, Guoyu Zhu Jan 2025

The Independent And Redundant Roles Of Tbx16 And Msgn1 In Mesodermal Differentiation, Guoyu Zhu

Yale Graduate School of Arts and Sciences Dissertations

Tbx16 and msgn1 genes are key genes responsible for the mesodermal progenitor cells to undergo mesodermal fate transition during zebrafish embryonic body elongation. Here we elucidated their previously unclear independent and redundant roles of mesodermal fate regulation. Using heat-shock induced tbx16 and msgn1 overexpression, in situ hybridization, quantitative PCR, RNA sequencing, and systematic analysis of differentially expressed genes, we found that tbx16 and msgn1 promotes mesodermal differentiation by repressing the progenitor niche that maintains the mesodermal progenitor cell state. Tbx16 and msgn1 repress the expression of many of the same genes in the mesodermal progenitor niche, but tbx16 also represses …

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Programming Cell States With Emage And Engineered Allosteric Crispr Effectors In Saccharomyces Cerevisiae, Peter Ciaccia Jan 2025

Programming Cell States With Emage And Engineered Allosteric Crispr Effectors In Saccharomyces Cerevisiae, Peter Ciaccia

Yale Graduate School of Arts and Sciences Dissertations

Cells are self-replicating information processing systems that maintain control of internal state by gathering and expending chemical energy. Programming these cellular states requires complementary technological paradigms: genome editing methods define the phase space of possible cellular behaviors by modifying an underlying genetic blueprint, and transcriptional and allosteric control systems enable precise navigation within that defined space through spatiotemporal and environmentally responsive regulation. In this sense, genome editing and gene regulation tools work synergistically to expand ability to perturb, control, and monitor cellular function. No single genome editing or control paradigm optimally addresses all applications: eukaryotic MAGE (eMAGE) excels at generating …

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Mediating Power: How Hybrid Media Disrupts Elite Messaging In Japan, Colin Moreshead Jan 2025

Mediating Power: How Hybrid Media Disrupts Elite Messaging In Japan, Colin Moreshead

Yale Graduate School of Arts and Sciences Dissertations

How does political communication function when the channels between elites, media, and the public become fragmented and unpredictable? This dissertation investigates how influence is exercised in a shifting media environment, where traditional broadcast-era assumptions about information flow and audience exposure no longer hold. Rather than assuming stable pathways from elite messaging to public response, the projects examine how political actors, media institutions, and citizens operate under new constraints and opportunities for choice. It asks whether elites can still shape media tone in ways that affect public support, whether media outlets retain agenda-setting power in a competitive landscape, and how citizens …

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Circuit And Cell Class Specific Effects Of Psilocybin And Serotonergic Psychedelics, Pasha Davoudian Jan 2025

Circuit And Cell Class Specific Effects Of Psilocybin And Serotonergic Psychedelics, Pasha Davoudian

Yale Graduate School of Arts and Sciences Dissertations

Psychedelics are compounds that can alter perception and cognition and are being explored as treatments for depression, anxiety, and substance-use disorders. Yet, the mechanisms by which they reshape brain function remain poorly understood. This dissertation presents four studies in rodent models examining how psychedelics act across synapses, microcircuits, and whole-brain networks. Chapter 1 shows that a single dose of psilocybin promotes plasticity in the frontal cortex. Chapter 2 maps brain-wide activity induced by psilocybin and ketamine, linking shared and distinct effects to gene expression. Chapter 3 extends this approach to multiple psychiatric drugs, using machine learning to classify drug-specific circuit …

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In Terms Of Theory, Samuel Steinmetz Jan 2025

In Terms Of Theory, Samuel Steinmetz

Yale Graduate School of Arts and Sciences Dissertations

In Terms of Theory attends to theory in relation to the eighteenth-century novel and to early twentieth-century film, primarily as the taking account of the possibility of form—of the novel, of film, and of theory. The overarching argument of the dissertation, developed in chapter 1, is that the novel and film, as modern forms unknown to classical aesthetics, present particularly rich cases for exploring what theory does, what it looks like, how it relates to its subject, and what kind of knowledge it offers. The rest of the dissertation presents independent case studies: chapter 2 analyzes and contextualizes the style …

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Evaluation Of Passive Sampling And Emerging Bulk Air Disinfection Technologies To Monitor And Mitigate Airborne Viral Exposure In Indoor Environments, Darryl Marissa Angel Jan 2025

Evaluation Of Passive Sampling And Emerging Bulk Air Disinfection Technologies To Monitor And Mitigate Airborne Viral Exposure In Indoor Environments, Darryl Marissa Angel

Yale Graduate School of Arts and Sciences Dissertations

The COVID-19 pandemic demonstrated the significance of understanding the airborne route of transmission for respiratory viruses and clarified the need to monitor and mitigate the presence of respiratory viral aerosols in indoor congregate settings. The goal of this dissertation is to evaluate the ability of emerging technologies to detect and reduce infectious viral aerosols within occupied indoor spaces. This work first explores the ability of a wearable passive sampler to collect viral aerosols for personal exposure assessments to SARS-CoV-2. The sampling material, polydimethylsiloxane (PDMS), efficiently collected enveloped viral aerosols, with a calculated uptake rate commensurate with previously developed passive aerosol …

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Moral Uncertainty And Bargaining, Harry Reginald Lloyd Jan 2025

Moral Uncertainty And Bargaining, Harry Reginald Lloyd

Yale Graduate School of Arts and Sciences Dissertations

I develop and defend an original answer to the problem of moral uncertainty - the question of how to behave when one has at least some credence in more than one moral theory. My marketplace response to this problem models the moral theories in which one has credence using "theory representatives," who bargain with each other to determine how the morally uncertain decision maker is to behave. This marketplace approach gives plausible recommendations in a wide range of cases, and also escapes the various objections that have been levelled against other proposed solutions to the problem of moral uncertainty.

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Trade Unions And The Challenge Of Technological Displacement, Alexander Trubowitz Jan 2025

Trade Unions And The Challenge Of Technological Displacement, Alexander Trubowitz

Yale Graduate School of Arts and Sciences Dissertations

This dissertation examines trade unions' responses to the employment risks generated by labor-saving technological change in British and West German manufacturing during the third quarter of the twentieth century, an era of rapid technological advance and the period during which British manufacturing fell behind the German competition. Drawing on previously untapped archival evidence from both countries, this dissertation challenges existing views in comparative political economy and economic history regarding unions' attitudes toward technological change and the welfare state as well as received contrasts between coordinated capitalism in West Germany and its supposed opposite in Britain. Focusing on the engineering industry, …

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Roles For The Planar Cell Polarity Pathway In Postnatal Intestinal Patterning And Architecture, Rebecca Frances Lee Jan 2025

Roles For The Planar Cell Polarity Pathway In Postnatal Intestinal Patterning And Architecture, Rebecca Frances Lee

Yale Graduate School of Arts and Sciences Dissertations

The coordination and patterning of cells required for proper tissue architecture play a critical role in organ development and function. This process is especially important in the small intestine, which relies heavily on its unique architecture of “hills” (villi) and “valleys” (crypts) to maximize nutrient absorption. Stem cells from a single crypt generate daughter cells that migrate up the villus in a linear ribbon pattern to form villus ribbons, while progressively differentiating into zonated cell states. This differentiation is tightly correlated to distinct digestive functions through compartmentalized expression of nutrient transporters. Despite the implicit reliance of intestinal tissue physiology on …

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The Science Of Not Knowing: Systems Thinking Between Vienna And The United States, 1900-1972, Libby S. O'Neil Jan 2025

The Science Of Not Knowing: Systems Thinking Between Vienna And The United States, 1900-1972, Libby S. O'Neil

Yale Graduate School of Arts and Sciences Dissertations

This dissertation is a history of the interdisciplinary field of systems theory from the perspective of Central European scientists and intellectuals who migrated to North America during the 20th century. It is a story about how people, ideas, and techniques circulated in new ways across a period of global upheaval, about how the philosophy of science became a stage for urgent political questions, and about how scientists tried to grasp the whole without surrendering authority over its constituent parts. This project reveals how European interwar debates were encoded into technical practices of control and communication in the postwar United States, …

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Cross-Stack Design Space Exploration For Energy-Efficient Ai Systems, Abhishek Moitra Jan 2025

Cross-Stack Design Space Exploration For Energy-Efficient Ai Systems, Abhishek Moitra

Yale Graduate School of Arts and Sciences Dissertations

The growing complexity of neural networks—from spiking neural networks (SNNs) to vision transformers (ViTs) and large language models (LLMs)—has posed major challenges for deployment on edge devices with limited compute and memory resources. This thesis addresses these challenges by proposing a suite of co-optimization strategies that span device, circuit, architecture, and algorithm layers to enable efficient AI inference on both analog and digital compute-in-memory (CiM) platforms. The first contribution, SpikeSim, presents an end-to-end simulation framework for evaluating SNNs on CiM hardware, uncovering key tradeoffs in neuronal memory, latency, and crossbar mapping. XPert introduces a differentiable co-search framework that jointly optimizes …

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Inference Of Somatic Selection In Cancer: Methods And Applications, Jeffrey Mandell Jan 2025

Inference Of Somatic Selection In Cancer: Methods And Applications, Jeffrey Mandell

Yale Graduate School of Arts and Sciences Dissertations

Cancers are predominantly understood as diseases in which somatic tissue lineagesacquire genetic or epigenetic alterations that confer traits which lead to aberrant cell growth. Such phenotypes include maintenance of proliferative signaling, resistance of apoptotic signaling, and immune suppression. In a microcosm of classical evolution, which progresses via random genetic drift and natural selection, somatic cells accumulate mutations throughout the life course. The small subset of mutations (or other heritable alterations) that provide proliferative advantages to the cells in which they occur tend to gain prevalence in subsequent generations, which may eventually lead to clonal evolution of cancer cell traits. While …

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The Dynamics And Composition Of The Middle Atmosphere Of Titan, Nicholas Lombardo Jan 2025

The Dynamics And Composition Of The Middle Atmosphere Of Titan, Nicholas Lombardo

Yale Graduate School of Arts and Sciences Dissertations

Titan, the largest moon of Saturn, is the only world apart from Earth known to have a thick nitrogen dominated atmosphere which supports stable liquid on its surface. High in Titan's atmosphere, the destruction of nitrogen and methane (Titan's second most abundant molecule) initiates an intricate web of chemical reactions that produce a suite of large hydrocarbon and nitrile species, and ultimately lead to Titan's characteristic orange haze. The aerosols in Titan's atmosphere strongly absorb solar shortwave radiation, which leads to the development of a stratopause (akin to the development of Earth's stratopause by the absorption of solar ultraviolet light …

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Unveiling The Spatial Cellular Dynamics And Regulatory Network In Glioblastoma, Shuozhen Bao Jan 2025

Unveiling The Spatial Cellular Dynamics And Regulatory Network In Glioblastoma, Shuozhen Bao

Yale Graduate School of Arts and Sciences Dissertations

Glioblastoma (GBM) is a grade IV astrocytoma, the most common malignant brain tumor in adults, which has a poor prognosis and high recurrence. To better understand the disease's fundamental mechanism, tremendous effort has been made to investigate the molecular and cellular interactions between malignant cells and the tumor microenvironment using single-cell technology. However, the spatial intra-tumoral information of GBM, including the disease progression regulatory network and cellular dynamics, has yet to be widely constructed. Our investigation undertakes a novel approach to address the challenges. Specifically, we employ different spatial omics technologies at all levels from epigenetics, transcriptomics, post-transcriptomics, and proteomics, …

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Extending And Improving The Study Of Gene Expression Regulatory Mechanisms, Isaac William Vock Jan 2025

Extending And Improving The Study Of Gene Expression Regulatory Mechanisms, Isaac William Vock

Yale Graduate School of Arts and Sciences Dissertations

Gene expression levels are a product of RNA synthesis and degradation kinetics. In addition, the bulk rates of RNA synthesis and decay are a function of the rates of several highly regulated biochemical steps, from transcription initiation, productive elongation, RNA processing, export from the nucleus, and degradation in either the cytoplasm or nucleus. When gene expression levels need to be regulated, cells can tune any combination of these kinetic parameters to achieve the desired change. If one only studies the levels of mature RNA and their fluctuations, one misses out on understanding the intricate kinetic regulation underlying gene expression. Because …

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Elucidating Mechanisms Of Selective Ion Transport In Nanoporous Membranes, Camille Violet Jan 2025

Elucidating Mechanisms Of Selective Ion Transport In Nanoporous Membranes, Camille Violet

Yale Graduate School of Arts and Sciences Dissertations

Membranes that can separate ionic species of similar size and valency are needed to advance resource recovery for battery and electronic waste recycling, lithium harvesting, and water reuse. Insights from ion channels in biological cell membranes indicate that simultaneous confinement and preferential interactions with binding sites are critical for fast and selective ion transport. However, these specific, localized chemical interactions have yet to be translated to synthetic membrane design. This dissertation attempts to bridge the gap between molecular-level selectivity mechanisms of biological ion channels and the design of ion-selective membranes through systematic investigations of ion transport in precision-model systems. The …

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Discovery Of Direct-Acting Small-Molecule Rig-I Agonists Through Creation Of A Selective Card Activation Platform, Rong Guo Jan 2025

Discovery Of Direct-Acting Small-Molecule Rig-I Agonists Through Creation Of A Selective Card Activation Platform, Rong Guo

Yale Graduate School of Arts and Sciences Dissertations

Retinoic acid-inducible gene I (RIG-I) is a human pattern recognition receptor (PRR) that plays a key role in the innate immune response against RNA viruses, including influenza viruses, coronaviruses, and flaviviruses. As a ubiquitously expressed protein in nearly all nucleated cells, RIG-I resides primarily in the cytoplasm, where it detects foreign RNA. Although RIG-I can bind to a variety of RNA molecules, it is selectively activated by viral RNAs that have specific structural features—such as blunt-ended double-stranded regions and 5′-triphosphates. Beyond its antiviral role, RIG-I has emerged as a promising target in cancer immunotherapy, largely due to its ability to …

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Cræft-Ing The Assembly: Political Vision In The Age Of Alfred, Megan Renz Perry Jan 2025

Cræft-Ing The Assembly: Political Vision In The Age Of Alfred, Megan Renz Perry

Yale Graduate School of Arts and Sciences Dissertations

This dissertation presents an early medieval vision of pastoral education and its desired political effects through analysis of the Old English Pastoral Care, which was translated from Latin in the ninth-century Alfredian educational revival. My study is grounded in the educational formation of the clerics whom Alfred recruited in the decade prior to the initiative: men of letters from neighboring Wales, Mercia, and Francia. These grammarian-translators envisioned forming vernacular readers in prudentia, that is, practical wisdom. I read Latin and Old English sources in light of the educational (chs. I- III), linguistic (ch. IV), philosophical (ch. V), and political (ch. …

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