Digital Commons Network^™

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 …

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 …

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 …

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) …

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 …

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 …

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 …

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.

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, …

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 …

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 …

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 …

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, …

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 …

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 …

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. …

Identifying Quantitative Trait Loci Of Genetically Regulated Molecules To Reveal Biological Mechanisms In Complex Traits, Chen Lin

Yale Graduate School of Arts and Sciences Dissertations

Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with complex traits and diseases, but most of these variants reside in non-coding regions, making their biological functions challenging to study and interpret. To investigate the potential roles of these variants, expression quantitative trait locus (eQTL) analyses associate genetic variants with gene expression, providing insights into their regulatory roles. Integrating eQTL results with GWAS summary statistics has motivated transcriptome-wide association studies (TWAS), which focus on testing associations between imputed genetically regulated gene expression (GReX) and complex traits, offering a powerful gene-level view of genetic contributions to disease. Despite substantial …

Exploration Of The Mechanisms Regulating Genomic Stability In Plants, Wenxin Yuan

Yale Graduate School of Arts and Sciences Dissertations

Genomic stability is a cornerstone of cellular integrity, with implications spanning genetic engineering, epigenetic regulation, and disease modeling. However, most studies rely on yeast or mammalian models, leaving significant gaps in our understanding of plant chromatin biology and genome stability mechanisms. Exploring the conserved and divergent processes regulating genome stability in plants has become increasingly important, especially as global climate change threatens crop yields and biodiversity. Furthermore, the developmental resilience of plants provides a unique opportunity to study genes essential in mammals, offering translational insights for agriculture and human health. This dissertation investigates the molecular and genetic mechanisms underpinning T-DNA …

Scalable Real-Time Decoding System For Quantum Error Correction, Namitha Godawatte Liyanage

Yale Graduate School of Arts and Sciences Dissertations

A real-time decoder capable of meeting the stringent requirements for accuracy, latency, and throughput is essential for fault-tolerant quantum computing. While prior work has demonstrated progress in decoding isolated logical qubits, scaling to interacting logical qubits introduces significantly greater challenges, as all logical qubits in the system must be decoded collectively. This thesis addresses these challenges through the design and implementation of DECOARC, a vertex-level parallel decoding architecture based on the decoding graph abstraction. DECOARC organizes parallel computing resources using a hybrid tree-grid topology. We instantiate DECOARC in this work through two complementary systems: HELIOS, for single logical qubits, and …

Investigating The Seasonal And Interannual Evolution Of Dissolved Oxygen In The Arctic Ocean’S Canada Basin, Ashley Arroyo

Yale Graduate School of Arts and Sciences Dissertations

This dissertation examines the evolution of dissolved oxygen in the waters of the Arctic Ocean's Canada Basin. Dissolved oxygen concentrations in the ocean are initially set at the surface through air-sea exchange and subsequently modified by physical and biogeochemical processes as waters circulate and mix. The variability of dissolved oxygen in the Arctic Ocean across seasonal and interannual timescales provides valuable insight into the broader evolution of water masses in the Arctic Ocean. As dissolved oxygen concentrations are gradually depleted in deeper waters via biological consumption, and only replenished when waters return to the surface, their distribution provides a valuable …

Learning Randomized Reductions For Security, Privacy, And Side-Channel Resilience, Ferhat Erata

Yale Graduate School of Arts and Sciences Dissertations

Modern computing systems face multifaceted challenges in security, privacy, and leakage resilience. This dissertation makes four key contributions to addressing these challenges through novel combinations of symbolic reasoning, machine learning, and neurosymbolic techniques. First, it develops symbolic AI techniques for analyzing side-channel vulnerabilities in low-level code and quantum computers. I introduce novel symbolic register analyses to automatically detect power side-channel vulnerabilities in constant-time cryptographic implementations. Additionally, I demonstrate an algebraic reconstruction method using Mixed-Integer Linear Programming (MILP) optimization to reverse-engineer quantum circuits from power traces, enabling extraction of proprietary circuit information. Second, my research pioneers automated learning of randomized self-reductions …

Sermon Rhetoric And White Evangelical Support For The Republican Party, Stephan Paul Lendway

Yale Graduate School of Arts and Sciences Dissertations

One of the most notable political shifts in American politics over the past fifty years has been the sorting of political and religious elites to produce the partisan “God Gap.” Among religious voters, evangelicals, especially White evangelicals, support Republican presidential candidates at higher levels than other religious voters. I argue that may partly be because of evangelical sermon content. In particular, I posit that, relative to Catholic and mainline Protestant sermons,evangelical Protestant sermons are more likely to consist of cultural and elite threats and that these threats consist of more sin, politicization on the ideological right, and mobilizing rhetoric. First, …

Revising The Nation: Tribal Sovereignty And The American History Textbook, 1929-2002, Grace R. Ellis

Library Map Prize

This thesis examines Indigenous representation in twentieth-century American history textbooks. Chapter One contends that the most popular U.S. history textbook of the late twentieth century, The American Pageant, erased tribal nations from its narrative and its maps. Across twelve editions (1956-2002), The Pageant taught generations of students that “Indians” served only as barriers to building the modern American nation-state. While Indigenous erasure can be traced back to specific passages in The Pageant, erasure can better be understood as an iterative process, both textual and cartographic in nature. Beginning in 1983, The Pageant added new maps that depicted tribes …

Cryo-Em Reveals The Mechanochemical Cycle Of Reactive Full-Length Human Dynein-1, Pengxin Chai

Yale Graduate School of Arts and Sciences Dissertations

Dynein is a microtubule-based motor protein complex that generates force and drives movement toward the minus ends of microtubules. Despite extensive structural, biochemical, and biophysical studies, key questions remain about how dynein achieves its unidirectional stepping and force-generating powerstroke through its ATP-dependent mechanochemical cycle. In this dissertation, I leverage recent advances in cryo-electron microscopy (cryo-EM) and develop novel cryo-EM image processing methods to elucidate the atomic-level details of the mechanochemical cycle of full-length cytoplasmic dynein-1. I directly visualize the conformational landscape of dynein both on and off microtubules, uncovering several novel and important reactive intermediates. These findings include the discovery …

A Commitment To Health For All: Reimagining Representation And Participation In The Who Beyond State-Centrism, Yen-Wen Liao

Public Health Theses

Despite its stated commitment to “health for all,” the World Health Organization (WHO) has long been subject to the influence of Member State politics. Specifically, the Organization’s state-based membership model and governance structure have continuously enabled powerful Member States to advance their political interests, leading to the exclusion and marginalization of populations based on the recognition or political status of their representatives. One such example is Taiwan, which has been repeatedly denied membership in the Organization despite the functional independence of its public health authority, leaving over 23 million people neglected amid two major health crises. These forms of exclusion …

Defining The Genetic Basis Of Autosomal Dominant Polycystic Liver Disease With Whole Exome Sequencing, Xinmiao Meng

Public Health Theses

Polycystic liver and kidney diseases are inherited disorders marked by progressive cyst formation in hepatic and renal tissues, leading to significant morbidity through organ enlargement, impaired function, and eventual kidney failure or painful hepatic enlargement. While several genes—including PKD1, PKD2, GANAB, and PRKCSH—are implicated, a substantial proportion of cases remain genetically unexplained, limiting diagnostic precision and therapeutic development. This thesis aims to refine the genetic understanding of polycystic liver diseases through whole exome sequencing of 292 individuals with liver and/or kidney cysts. We first identify pathogenic variants in known disease genes in 133 individuals (46%), confirming the recurrent involvement of …

Beyond Vulnerability: Climate Change And The Moral Authority Of Youth, Amber Acquaye

Yale Medicine Thesis Digital Library

Young people worldwide demand a voice in climate governance, yet their perspectives remain largely excluded from the moral frameworks that shape climate policy. This exclusion not only marginalizes children’s lived experiences and ethical reasoning but also perpetuates paternalistic norms and dangerous marginalization. To counter this, this thesis study shows that youth are not just passive stakeholders but moral agents whose perspectives yield a more just and comprehensive understanding of climate responsibility. Recognizing their ethical insights is crucial for medicine, especially pediatrics and child psychiatry, given how climate change amplifies health risks like respiratory illnesses, heat-related conditions, and eco-anxiety. Understanding how …

Effect Of Constraining Underdilated Transjugular Intrahepatic Portosystemic Shunts, Ishan Ayyalasomayajula

Yale Medicine Thesis Digital Library

Transjugular intrahepatic portosystemic shunt (TIPS) placement remains a primary treatment option for managing the sequelae of portal hypertension. However, the degree of decompression must be balanced to avoid complications of overshunting, such as hepatic encephalopathy (HE), liver failure, and heart failure. Currently, the most utilized device for TIPS creation, the Viatorr endoprosthesis shunt can be dilated to between 8 and 10 mm. However, dilating to the minimal size can decrease the hepatic-venous pressure gradient (HVPG) below goal. However, shunts that were underdilated at placement can self-expand to their minimal diameter. Placing a constraining stent around the endograft theoretically precludes such …

Quantitative Assessment Of Facial Ptosis In Face Transplantation, Sam Boroumand

Yale Medicine Thesis Digital Library

As a transformative surgical procedure, face transplantation restores form and function to patients with severe facial disfigurements, yet the long-term aging dynamics of transplanted tissues remain poorly characterized. This study aimed to investigate the progression of facial ptosis in transplanted facial allografts over time, addressing a critical gap in the understanding of long-term outcomes following face transplantation. Specific aims include quantifying ptosis progression using cephalometric measurements, identifying regional variations in the degree of ptosis across the face, and comparing changes between face transplant recipients and a non-face transplanted control cohort to contextualize findings.

To assess these aims, standardized frontal headshots …

Effectiveness Of Interventions For Depressive Symptoms After Spinal Cord Injury: A Systematic Review, Robert Cotter

Yale Medicine Thesis Digital Library

Our aims were to summarize and evaluate evidence regarding the efficacy ofinterventions for depressive symptoms in adults living with spinal cord injury (SCI) and comorbid major depressive disorder or significant depressive symptoms to inform the development of clinical practice guidelines. Articles published since 2013 and available in Medline, The Cochrane Library, Embase, Scopus, CINAHL, or PsycINFO were evaluated. Databases were searched in June 2022 and updated November 2023. Inclusion criteria: age 18 years or older, traumatic SCI, and clinically significant depression (Population), mental health interventions including behavioral, pharmacological, and complementary and alternative medicine (Intervention), inclusion of a control group (Comparator), …