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Advances In Synthetic Data Generation And Causal Inference, Shinpei Nakamura Sakai

Yale Graduate School of Arts and Sciences Dissertations

Synthetic data generation has become essential for addressing data scarcity, privacy concerns, and generalization problems when applying machine learning in various domains. Hence, data is the main ingredient of any machine learning model. If synthetic data is too similar to real data, the risk of privacy breaches is significantly higher; if it is too different, its practical applicability is undermined. This dissertation proposes two approaches to enhance synthetic data generation. Chapter 2 develops SC-GOAT, a framework that integrates a supervised component tailored to the specific downstream task and employs a meta-learning approach to learn the optimal mixture distribution of existing …

Reciprocal Relationships Between Musical Expectation And Repetition Structure, Aditya Chander

Yale Graduate School of Arts and Sciences Dissertations

This dissertation examines several ways in which listeners' expectations for musical structure are related to the usage of repetition across and within pieces of music in a range of different styles. In particular, it examines the relative role of long-term expectations (acquired from a lifetime of exposure to music) and short-term expectations (acquired in real time as a piece of music unfolds) in music listening. Throughout the dissertation, I assume that listeners acquire musical expectations via statistical learning, a cognitive mechanism that automatically extracts distributional properties of sensory input without explicit instruction. Part I of this project, comprising the first …

Growth Indicators And Conformal Measures For Transverse Groups And Ergodic Dichotomy For Subspace Flows In Higher Rank, Yahui Wang

Yale Graduate School of Arts and Sciences Dissertations

Let G be a connected semisimple real algebraic group. The class of transverse subgroups of G includes all discrete subgroups of rank one Lie groups and any subgroups of Anosov or relatively Anosov subgroups. Given a transverse subgroup Gamma, we show that the Gamma-action on the Weyl chamber flow space determined by its limit set is properly discontinuous. This allows us to consider the quotient space and define Bowen-Margulis-Sullivan measures. We then study the ergodicity of a one-parameter diagonalizable subgroup of G acting on the aforementioned quotient space, equipped with a Bowen-Margulis-Sullivan measure. We obtain an ergodicity criterion similar to …

Dysregulation Of Transcription And Mrna Processing In Splicing Factor Mutant States: Mechanistic Insights And Implications, Prajwal Chaitanya Boddu

Yale Graduate School of Arts and Sciences Dissertations

Recurrent mutations in RNA splicing factor (SF) genes, such as SF3B1, U2AF1, SRSF2, and ZRSR2, are key drivers of oncogenesis in various cancers, particularly clonal myeloid disorders like Myelodysplastic syndromes (MDS) and Acute Myeloid Leukemia (AML). Over the past decade, significant insights have been gained into their molecular mechanisms and effects on RNA splicing. These mutations are typically heterozygous and non-synonymous (except ZRSR2, which involves single-allele loss-of-function mutations) and are largely mutually exclusive, suggesting shared downstream mechanisms that prevent co-occurrence. Given their pre-eminent roles in splicing, most studies to date have primarily focused on the effects of SF mutations on …

Spatial Control Of Nonlinear Interactions In Multimode Fibers, Kabish Wisal

Yale Graduate School of Arts and Sciences Dissertations

In recent years, there has been significant advancement in controlling optical scattering by structuring the wavefront of the incident light, or `wavefront shaping'. Most applications of wavefront shaping have focused on linear scattering, but there is a growing interest in tailoring nonlinear scattering. In this thesis, we explore a new approach based on wavefront shaping for suppressing certain instabilities induced by nonlinear scattering in passive and active multimode fibers (MMFs). Specifically, we focus on suppressing stimulated Brillouin scattering (SBS) and transverse mode instability (TMI). A key motivation for our work is power scaling in high power fiber lasers and amplifiers, …

Elucidating Cell Intrinsic Regulators Of Cd8 T Cell Differentiation: Klf2 Maintains Effector Cd8 Lineage Fidelity, Eric Quinn Fagerberg

Yale Graduate School of Arts and Sciences Dissertations

CD8 T cells are an integral part of the immune system, principally responsible for the cytolytic clearance of virally infected and cancerous cells. They adapt to the nature of the immune response they are partaking in by adopting distinct cell fates through a process of highly coordinated differentiation. These fates are characterized by the activation and suppression of functional programs under the control of transcription factors and epigenetic machinery, which integrate cell extrinsic signals to drive differentiation. Here we elucidate the function of a group of transcription factors in dictating CD8 T cell differentiation in infection. We go on to …

Deep Learning For Large-Scale Harmonic Analysis: A Corpus Study Of Western Harmony From 1700-1900, Malcolm Sailor

Yale Graduate School of Arts and Sciences Dissertations

This dissertation trains deep learning models for the Roman numeral analysis and applies these to the analysis of a corpus of over 12,000 movements of Classical music composed between 1700 and 1900. The Roman numeral analysis models obtain performance that is, as of this writing, state of the art. At the same time, this is the first work of scholarship to employ such models at scale for a music-theoretic corpus study. Consistent with music-historical expectations, this corpus study shows that, along many dimensions, such as the distribution of keys employed or the proportion of chromatic scale degrees, harmonic complexity rose …

Spink1-Col18a1 Crosstalk Shapes Epigenome And Drives Cancer Stemness In Pancreatic Ductal Adenocarcinoma, Haoyu Tang

Yale Graduate School of Arts and Sciences Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with an increasing incidence and extremely dismal prognosis, due to early metastasis and the limited understanding of the mechanisms driving its progression. In this dissertation, by analyzing bulk transcriptomic profiles from PDAC patients with substantial differences in survival and deconvoluting the results using a single-cell transcriptome dataset of human PDAC, we identified serine protease inhibitor Kazal type 1 (SPINK1) as a crucial modulator of PDAC progression and patient survival. At the patient level, higher SPINK1 expression is correlated with shorter survival, and at the single cell level, SPINK1 expression showed dynamical changes …

Evaluating Clinical Outcomes And Cost-Effectiveness Of Aspirin And Clopidogrel Versus Factor Xa Inhibitors And Clopidogrel For Treatment Of Patients With Peripheral Arterial Disease After Lower Extremity Revascularization, Uday Dhanda

Public Health Theses

Introduction and Objective: Antithrombotic treatment plays a critical role in managingperipheral arterial disease (PAD) and reducing the risk of major adverse limb events (MALE) and major adverse cardiovascular events (MACE) after revascularization. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is the most commonly used regimen for medical management to prevent cardiovascular events following revascularization. Still, emerging studies suggest that dual antithrombotic pathway inhibition (DAPI), which combines a Factor Xa inhibitor with clopidogrel, may offer enhanced protection. This study evaluates the clinical outcomes and cost-effectiveness of DAPI compared to DAPT in patients undergoing lower extremity revascularization (LER).

Methods: A retrospective …

Water, Sanitation, And Hygiene (Wash) Services Among Households, Healthcare Facilities And Schools In Rural Ghana, Samantha Gillis

Public Health Theses

Introduction: Soil-transmitted helminth (STH) infections affect more than 1 billion people globally, particularly in low-income areas with poor sanitation. While mass drug administration is a common control strategy, long-term elimination requires a broader, integrated approach with an emphasis on sustainable water, sanitation and hygiene (WASH) practices, community-led initiatives, and economic development. Currently, there are critical gaps in understanding the impacts of WASH infrastructure in households, healthcare facilities, and schools on hookworm prevalence, specifically in rural Ghana. Methods: Using qualitative surveys, we characterized the current WASH landscape among households, healthcare facilities and schools in the Bono East region of Ghana. Hookworm …

Rasa3 Identified As A Potential Effector Of The Brain G Protein G⍺o By Mass Spectrometry, Halie Adesin Bell

Yale Graduate School of Arts and Sciences Dissertations

G⍺o, the alpha subunit of the most abundant heterotrimeric G protein in the brain, mediates signaling by opioids and by many neuromodulators to inhibit neural function. An open question is whether activated G⍺o-GTP directly binds to and regulates effector molecules, like all other animal G⍺ proteins, or if it signals solely by releasing Gβ�� subunits. Using mouse brain lysates as native source of G⍺o and its potential effectors, I analyzed immunopurified G⍺o protein complexes by mass spectrometry. I identified several proteins that interact preferentially with inactive or active G⍺o. I focused my analysis on proteins that are significantly upregulated in …

Mycorrhizal Type Mediates Plant-Soil Feedback And Density Dependence In A Sri Lankan Rainforest, Akshay Surendra

Yale Graduate School of Arts and Sciences Dissertations

How do so many species of trees coexist in a forest? A century of research has discovered multiple mechanisms that could maintain local-scale diversity. Chief among them, at least at early life stages, is a pattern of stronger neighborhood competition from conspecifics than heterospecifics. This pattern is driven, at least in part, by specialized natural enemies such as insects and pathogens that damage host trees more than others. Unsurprisingly, the strength of neighborhood effects varies widely among species and a current avenue of research involves understanding what explains this variation. A major axis of variation that has emerged among trees …

From Evidence To Evaluations: Explicit And Implicit Competence Impressions Of A Robot, Nicholas Surdel

Yale Graduate School of Arts and Sciences Dissertations

This dissertation presents 20 studies (N = 8,595) that focus on how people integrate inconsistent evidence when forming explicit (i.e., directly measured) versus implicit (i.e., indirectly measured) competence impressions of robots. It documents our attempts to understand explicit and implicit impressions’ sensitivity to counterattitudinal evidence, capacity to update, and susceptibility to pragmatic inferences. Although implicit impressions initially appeared insensitive to the robot’s inconsistent “oddball” performances (Chapter 2), subsequent experiments revealed implicit impressions can rapidly update when a single oddball provides sufficiently strong evidence of the robot’s true capabilities (Chapter 3). Furthermore, we found that explicit impressions’ sensitivity to relatively …

Nap-Trap Reveals 5'Utr-Mediated Translation Regulation During Zebrafish Development, Ethan C. Strayer

Yale Graduate School of Arts and Sciences Dissertations

The cis-regulatory elements encoded in an mRNA determine its stability and translational output. While there has been a considerable effort to understand the factors driving mRNA stability, the regulatory frameworks governing translational control remain more elusive. We have developed a novel massively parallel reporter assay (MPRA) to measure mRNA translation, named Nascent Peptide Translating Ribosome Affinity Purification (NaP-TRAP). NaP-TRAP measures translation in a frame-specific manner through the immunocapture of epitope tagged nascent peptides of reporter mRNAs. We benchmark NaP-TRAP to polysome profiling and use it to quantify Kozak strength and the regulatory landscapes of 5’ UTRs in the developing zebrafish …

The Death And Afterlife Of The Coptic Language In Mamluk Egypt., Ramona Teepe

Yale Graduate School of Arts and Sciences Dissertations

My dissertation, The Death and Afterlife of the Coptic Language in Mamluk Egypt, argues that although Coptic “died” out as a spoken language in the thirteenth century, Coptic intellectuals purposefully developed a way to teach Coptic as a classical language and thus set the course for its survival as a liturgical language until today.

The Arab conquest of Egypt in 642 CE conventionally marks the end of the period which Coptic studies covers. After the conquest, Arabic slowly superseded Coptic as a language of politics, administration, and finally (roughly by the end of the twelfth century) of everyday life. …

Investigating The Plasticity And Role Of Peripherally Derived Cd4 T Cells In The Brain At Homeostasis, Tomomi Marie Yoshida

Yale Graduate School of Arts and Sciences Dissertations

Specialized immune cells residing in tissues orchestrate diverse biological functions through communication with parenchymal cells. The contribution of the innate immune compartment in the meninges and central nervous system (CNS) is well-characterized, however, whether T cells as part of the adaptive immune system reside in the brain and are involved in homeostasis is poorly understood. Here, we identify that the subfornical organ (SFO) region of the brain is a nucleus for parenchymal T cells in the steady-state brain in both mice and humans. Using unbiased transcriptomics, we found that these extravascular T cells in the mouse brain are distinct from …

Host Defense Inside & Outside Of The Immune System: Modeling Antimicrobial Immunity By Gbps, Zhongyu Yuan

Yale Graduate School of Arts and Sciences Dissertations

Traditional views of host defense often focus on antibody-mediated neutralization, cytotoxic T-cell plus NK-cell-mediated killing, and phagocytic activities by cell populations originating in the bone marrow as part of the classical immune system. Additional effector activities, however, also operate in non-immune cells which compose the stroma or parenchyma of host tissues. These latter cell populations often mobilize antimicrobial activities in response to cytokines such as type II IFN (IFN-gamma; IFN-) against a wide variety of intracellular pathogens.

Among the most prominent IFN--stimulated genes are a family of immune dynamin-like GTPases termed the Guanylate Binding Proteins (GBPs). GBPs are widely expressed …

Distributional Considerations In Climate Economics, Simon Fridtjof Lang

Yale Graduate School of Arts and Sciences Dissertations

Climate change and climate policies have distributional consequences on a global scale. Climate impacts are unevenly distributed, responsibilities for emissions vary across countries, and capabilities to mitigate and adapt differ. These distributional aspects are at the heart of international climate policy discussions. In response, international climate finance—financial transfers from developed to developing countries for climate mitigation, adaptation, and damage compensation—has become a central topic in international climate negotiations. The three chapters of this dissertation explore distributional considerations in climate economics from different perspectives and assess how optimal climate policy may depend on these considerations.

The first paper examines how the …

Deep Learning Methods For Protein - Small Molecule Interactions With Applications To Early-Stage Drug Discovery, Gregory William Kyro

Yale Graduate School of Arts and Sciences Dissertations

Drug discovery is a challenging endeavor for multiple reasons including the complexity of protein-ligand interactions at the molecular-level, the vastness of chemical space, and safety constraints related to unintended biological effects. In this dissertation, I present a suite of novel deep learning approaches that address these challenges from multiple angles. I first introduce HAC-Net— a deep learning model that, at the time, was the state of the art for predicting protein-ligand binding affinity—which was used to identify a potential inhibitor of a G protein-coupled receptor whose overexpression leads to cancer, diabetes, and multiple sclerosis, as well as a potential antivirulence …

Spaced Learning Approaches To Attitude Change: Impressions Of Individuals, Outgroup Prejudice, And Policy Endorsement, Emily Grace Ritchie

Yale Graduate School of Arts and Sciences Dissertations

How does the schedule of information delivery influence attitude change? While decades of research highlights the cognitive benefits of spaced learning for memory, little is known about whether these same principles extend to the domain of persuasion— particularly for socially meaningful or politically charged attitudes. This dissertation bridges cognitive and social psychological approaches by investigating whether spacing persuasive content over time enhances its ability to revise attitudes. Across three empirical chapters, I test the effects of spaced versus massed presentation of new information on evaluative judgements in three distinct domains: person impressions, social group attitudes, and policy support. In Chapter …

Mumford Relations And The Cohomology Of Le Potier Moduli Spaces, Weite Pi

Yale Graduate School of Arts and Sciences Dissertations

The goal of this thesis is to study the cohomological aspect of Le Potier’s moduli space of 1-dimensional sheaves on the projective plane. Our main technical tools are Mumford-type geometric relations, formulated originally over moduli of bundles on curves and generalized to sheaves over del Pezzo surfaces in this thesis. We prove that these relations can be obtained effectively from certain primitive ones via the Virasoro operators. As applications, we prove a minimal generation result, a cohomological χ-dependence result, and fully compute the cohomology rings in low degrees. Finally, we propose a “Perverse = Chern” conjecture relating two filtrations …

Essays In Economic Theory, Ferdinand Manuel Pieroth

Yale Graduate School of Arts and Sciences Dissertations

My dissertation examines the role of information acquisition and other frictions in bargaining and contracting settings. Chapter 1 studies an informal common value auction where a seller controls buyers' access to costly information. It shows that allowing the winning bidder to acquire information after bidding, i.e., via due diligence, maximizes the seller’s worst-case payoff when stakes are sufficiently high. Chapter 2 analyzes competition between firms selling a homogeneous good to a rationally inattentive consumer. It identifies an attention effect, whereby competition increases trade engagement. As a result, firms’ aggregate profits are increasing in the number of active firms …

Light Enhanced Electrochemical And Photochemical Co2 Reduction, Bo Shang

Yale Graduate School of Arts and Sciences Dissertations

The anthropogenic increase in atmospheric CO2 levels has driven a global push toward sustainable energy solutions that mitigate climate change while enabling carbon-neutral fuel production. The photocatalytic and photoelectrochemical reduction of CO2 into value-added fuels such as carbon monoxide (CO) and methanol offers a promising approach to harness solar energy for clean fuel generation. However, achieving efficient, selective, and stable CO2 reduction on a semiconductor surface remains a formidable challenge due to sluggish reaction kinetics, poor charge separation, and competing hydrogen evolution reactions. Recent advancements in molecular catalysts and semiconductor-integrated systems have demonstrated remarkable progress in overcoming these limitations, paving …

Stage-Specific Disruption Of Cancer Cell Metabolism By Pfas: Connecting “Forever Chemicals” To The Growing Public Health Challenge Of Colorectal Cancer, Hannah O'Halloran

Public Health Theses

Per and polyfluoroalkyl substances (PFAS), termed “forever chemicals” for their persistence in the environment, are under investigation for their carcinogenic effects, but their specific impacts on colorectal cancer (CRC) progression remain largely unexplored. This study uses untargeted metabolomics to examine the effects of PFAS exposure on cells of CRC stages 2, 3, and 4, and identify state-specific alterations in important metabolic pathways. Later stage cells exhibit a greater response than early stage cells, suggesting increased susceptibility to PFAS effects in cells of more advanced cancer. PFOS had a greater effect on the metabolism of the cell lines compared to PFOA, …

Evaluating Saliva Based Glucose Testing For Accessible Diabetes Care In Tanzania, Shannon Dhindsa

Public Health Theses

Background: In Tanzania, limited healthcare infrastructure and reliance on invasive diagnostic methods significantly hinder effective diabetes screening and management. Individuals with diabetes often go undetected and have lower immune systems that make them prone to further infectious complications. Thus, properly managing this chronic condition can prevent additional infectious diseases. Salivary glucose testing offers a non-invasive, innovative alternative with the potential to transform the early detection and management of diabetes, especially in resource-constrained settings.

Design: This cross-sectional study, conducted at Muhimbili National Hospital's Diabetes Clinic in Dar es Salaam, evaluates the feasibility of salivary glucose testing using a colorimetric glucose-oxidase-peroxidase point-of-care …

Secondhand Smoke Exposure And The Risk Of Tuberculosis In Children: A Systematic Review And Meta-Analysis, Cenyun Guan

Public Health Theses

ABSTRACT

Introduction: Tuberculosis (TB) remains one of the leading causes of death globally, with children and young adolescents having a significant burden of the disease. Smoking is a well-established risk factor for TB, but the association between secondhand smoke (SHS) exposure and TB remains inconclusive. Pediatric populations are commonly exposed to SHS due to living with smokers in their households. Inconsistencies in the findings of previous systematic reviews on the associations between SHS exposure and TB status (infection and disease) highlight the need for an updated systematic review to better establish these associations and provide evidence-based guidance for reducing the …

Present Tense Love: How To Stay Close Amidst A Changing Mind, Brit Fleck

Public Health Theses

This thesis examines how long-term partners sustain intimacy when one partner lives with dementia. Through an Appreciative Inquiry (AI) workshop with four couples from the Empowering Partnership Network—a joint initiative of the Yale Social Gerontology Lab and the Livewell Institute—this research explores how relationships adapt and endure amidst cognitive change. Drawing on Irene Smith’s Touch Awareness methodology and theories of relational autonomy, the study challenges dominant deficit-based narratives by highlighting the enduring capacity for meaningful connection. Participants described intimacy as grounded in embodied practices, daily rituals, and what they called the “third body”—a shared relational space that transforms rather than …

Empowering Mothers In New Haven: Evaluating The Impact Of A Maternal Health Program For New And Expecting Black And Brown Mothers, Ethelia Holt

Public Health Theses

The U.S. maternal mortality rate has surpassed that of other high-income countries, with mental health conditions now among the leading causes of perinatal death. These challenges disproportionately affect Black and Brown women, who are less likely to receive adequate follow-up care. The Maternal Health Program for New & Expectant Black and Brown Mothers aimed to improve maternal mental health through psychoeducation, skill-building, financial literacy, and connection to local resources.

A mixed-methods evaluation was conducted using pre- and post-program survey data (N = 7) to assess changes in mental health symptoms, knowledge, self-care, and financial habits. Descriptive statistics were the primary …

The Evolution And Effectiveness Of Sterile Insect Technique For Vector Control: A Historical And Modern Analysis, Katerina Karaiskos

Public Health Theses

Sterile Insect Technique (SIT) has emerged as an important tool in the control of vector-borne diseases, providing an alternative to traditional chemical insecticides. Initially based on the irradiation of insects to induce sterility, SIT has proven effective in eradication campaigns, including the cases of the screwworm and tsetse fly. SIT’s primary strengths lie in its species specificity, environmental safety, and the avoidance of pesticide resistance. However, “classic” irradiating SIT is limited by high operational costs, reduced mating competitiveness of sterilized males, and difficulties in addressing high-density vector populations. Recent advancements in genetic-based SIT methods, such as the Release of Insects …

Assessing The Cross-Species Vaccine Potential Of Pfripr Using Transgenic Chimeric Plasmodium Knowlesi Models, Peiqi Li

Public Health Theses

Malaria remains a major global health burden, with an estimated 263 million cases and597,000 deaths reported in 83 countries in 2023 (1). While P. falciparum is responsible for the most severe cases, non-falciparum species such as P. vivax, P. ovale curtisi, P. ovale wallikeri, P. malariae, and P. knowlesi also pose significant public health risks, particularly in co-endemic regions. Current malaria vaccine efforts mainly focus on P. falciparum which is reasonable because over 90% of the global malaria-related morbidity and mortality are caused by P. falciparum (2). However, laying emphasis on targeting P. falciparum leaves a critical gap in cross- …