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Mechanisms Of Heart And Major Vessel Development: Nup107 And Cacna1g As Novel Regulators, Valentyna Kostiuk

Yale Graduate School of Arts and Sciences Dissertations

Congenital Heart Disease (CHD) is the most common congenital malformation and a leading cause of infant mortality. While advances in genomic sequencing technology have enabled a fast and inexpensive candidate gene identification, the molecular mechanisms of CHD remain mostly unknown. Both nup107 and cacna1g are novel CHD genes identified in CHD patients with no plausible mechanisms explaining their roles in cardiac development. Here, we show that nup107 plays a key role in early embryonic patterning and subsequent organ development. The loss of Nup107 has a direct impact on germ layer specification, Left-Right patterning and downstream cardiac looping. Specifically, Nup107 depletion …

Visual Circuits For Distance Estimation In Walking Drosophila, Joseph Shomar

Yale Graduate School of Arts and Sciences Dissertations

Animals must infer the three-dimensional structure of their environment from twodimensional retinal images. They use visual cues like motion parallax and binocular disparity to judge distances to objects, and studies across several animal models have foundand characterized neural signals that correlate with visual distance. However, the causal role of these neurons in distance estimation and the range of their possible neural properties remain poorly understood. Here we show that both directional and non-directional feature-selective neurons in the Drosophila visual system are involved in distance estimation during free locomotion. We used a high-throughput behavioral assay to perform a targeted silencing screen …

Quantum Error Detection And Correction Of Bosonic Codes In A Superconducting Cavity, Akshay Koottandavida

Yale Graduate School of Arts and Sciences Dissertations

Detecting and correcting decoherence errors is essential for the preser- vation of encoded information in quantum systems. Quantum error correction (QEC) based on bosonic codes where the information is stored in the multiple levels of harmonic oscillators has shown much promise recently. Bosonic codes, specifically those implemented in superconducting cavities, suffer from microwave photon losses which lead to increase in entropy of the system. How can we reduce this entropy, or in other words, can we detect and/or correct the errors associated with microwave photon loss of the cavity? This thesis work proposes and implements novel codes to address these …

Cosine-100 And Anais-112: Two Experiments, One Search For The Annual Modulation Of Dark Matter, Sophia J. Hollick

Yale Graduate School of Arts and Sciences Dissertations

Overwhelming evidence has been observed for the existence of dark matter; however, it has yet to be directly detected. Since 1997, the DAMA/LIBRA experiment has claimed to detect a dark matter signal, taking the form of an annual modulation consistent for over 20 yearly cycles. Though DAMA/LIBRA reports a 13.7 sigma significance, experiments utilizing different detector technologies have excluded their result by several orders of magnitude. To definitively test the validity of the claim, COSINE-100 and ANAIS-112 have mounted experiments with the same detector medium, NaI(Tl). Both experiments have reported results consistent with no modulation and are on the cusp …

Asymmetric Synthesis Of Bioactive Scaffolds Via Organocatalysis, Melody Guo

Yale Graduate School of Arts and Sciences Dissertations

Chiral catalysts allow chemists to access enantioenriched materials without the use of proportionate amounts of chiral reagents, while lowering the energy barrier of the original reaction. One way to form bioactive, heteroatom-containing scaffolds asymmetrically is through the use of chiral organocatalysts. This dissertation covers the development of stereoselective reaction methodology to access bioactive scaffolds and mechanistic investigations into intriguing features therein. Chapter 1 describes the development of the asymmetric synthesis of axially chiral quinazolinones. In this project, complementary applications for two different scaffold classes of chiral phosphoric acid (CPA) catalysts are found. We observe that while a C2-symmetric CPA catalyst …

The Role Of Local Factors In Shaping Microbial Communities And Biogeochemical Functions Across Scales, Alexander Polussa

Yale Graduate School of Arts and Sciences Dissertations

Microorganisms play a vital role in carbon cycling, driving the decomposition and transformation of organic matter (OM) in soils. This dissertation examines how both broad climatic and local factors shape microbial communities and influence organic matter decomposition. Through a combination of microcosm and field experiments, I demonstrate that local conditions like soil moisture, depth and plant identity impact microbial function, although these effects can be masked by broader climatic influences. I also investigate how the ericoid shrub, Kalmia latifolia, differentially affects fungal communities under arbuscular and ectomycorrhizal trees. Finally, integrating results from multiple forest sites in the eastern US, I …

Machine Learning In Finance: Applications To Understanding Investor Behavior And Asset Prices, Kangying Zhou

Yale Graduate School of Arts and Sciences Dissertations

This dissertation consists of three essays on machine learning in finance, focusing on its applications to understanding investor behavior and asset prices. The first essay is titled "Professional Investors and Media Narratives." I investigate the impact of media narratives on the portfolio strategies of active equity mutual funds. Using 1.5 million Wall Street Journal articles from 1984 to 2023, I use ChatGPT to distill media narratives into 59 distinct topics, and quantify each topic's time-varying share of news attention and sentiment. I then define a fund as having exposure to a topic if it overweights stocks expected to perform well …

Quantum Control Of An Oscillator With A Kerr-Cat Qubit, Andy Zhenghao Ding

Yale Graduate School of Arts and Sciences Dissertations

Noise presents a major obstacle to scaling up quantum computers, causing logical errors and preventing the reliable execution of quantum algorithms. Quantum error correction provides a path toward fault-tolerance, but this typically comes at the cost of significant resource overhead. Bosonic codes offer a hardware-efficient strategy for quantum error correction by redundantly encoding quantum information in the large Hilbert space of a harmonic oscillator. These codes have been employed to achieve landmark experimental demonstrations. However, these demonstrations are limited by transmon ancilla errors propagating to the encoded logical qubit during syndrome measurements. The Kerr-cat qubit has been proposed as a …

Characterizing And Improving The Readout Of Superconducting Qubits, Wei Dai

Yale Graduate School of Arts and Sciences Dissertations

The development of fault-tolerant quantum computers relies critically on fast and accurate readout of qubit states. In state-of-the-art superconducting quantum processors, the readout operations exhibit higher error rates and longer execution times compared to single- and two-qubit gates, bottlenecking their performance. How can we realize faster readout with lower error rates in superconducting circuits? In this dissertation, we answer this question through addressing two pressing limitations in the dispersive readout scheme: readout-induced state transitions and Purcell decay of the qubit. We introduce the "readout channel benchmarking" technique for the faithful benchmarking of readout performance accounting for the readout-induced state transitions. …

The Linc Complex Component Kms1 And Cenp-B Protein Cbp1 Cooperate To Enforce Faithful Homology-Directed Dna Repair At The Nuclear Periphery, Alyssa Laffitte

Yale Graduate School of Arts and Sciences Dissertations

DNA double-stranded breaks (DSBs) represent a danger to genome stability. Cells repair DSBs mainly through one of two pathways: canonical non-homologous end-joining (cNHEJ), which requires the direct ligation of the two DSB ends, or homologous recombination (HR), which involves the use of a homologous template to create a faithful repair product. While HR is often considered to be an error-free mechanism, the ultimate fidelity of this pathway depends on the ability of the cell to identify and engage with the correct homologous template. This is particularly challenging during repair of repetitive regions of the genome for which non-allelic sequences can …

Resource Efficiency At The Network Edge And Deep Learning Methods, Akrit Mudvari

Yale Graduate School of Arts and Sciences Dissertations

Next-generation networks, especially wireless and cellular networks, will feature massive IoT and embedded device deployments alongside various novel services, most of which may be constrained by energy and computational capabilities. As a result, these networks must address challenges such as device limitations, scalability, resource management, and energy efficiency for both computation and communication. The rise of deep learning has unlocked significant potential for various new AI-driven applications, meaning next-generation communication networks could benefit tremendously from these approaches, particularly for efficient resource allocation. Simultaneously, the growing prevalence of AI-driven applications on intelligent devices at the network edge implies that numerous applications, …

Computational Study Of Redox-Active Protein Residues And Biological Proton-Coupled Electron Transfer, Qiwen Zhu

Yale Graduate School of Arts and Sciences Dissertations

Proton-coupled electron transfer (PCET) reactions are essential processes in biological systems, fundamental to various enzymatic functions and redox biology. Key to these reactions are redox-active residues, such as tyrosine and tryptophan, which enhance the efficiency and specificity of electron transfer events. This thesis investigates the thermodynamics, kinetics, and conformational influences of PCET in proteins involving these residues through three projects, each offering significant insights into the mechanisms and broader implications for biological function. The studies have focused on two protein systems: a simple de novo protein system, α3X, and ribonucleotide reductase, an enzyme critical to DNA synthesis. Combining a wide …

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 …

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 …

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 …

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 …

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 …

Impact Of Maternal Chronic Diseases In Pregnancy On Duration Of Infant Intake Of Breastmilk In The Postpartum Period, Danielle Nicole Lodge

Public Health Theses

Background: Chronic disease in pregnancy, including hypertensive disease, diabetes, and mental health disorders, is associated with adverse mother and infant health outcomes. Breastfeeding offers well-documented benefits, but currently, little evidence exists on how maternal chronic disease impacts the duration of breastfeeding postpartum, especially multiple chronic disease diagnoses. Objectives: To examine associations between maternal chronic disease and (1) duration of any breastmilk feeding through six months postpartum, (2) in-hospital infant feeding patterns, and (3) the impact of in-hospital breastmilk exposure on postpartum duration of breastmilk feeding among women with a chronic disease. Methods: This retrospective cohort study analyzed 1,294 maternal-infant records …

Glp-1 Receptor Agonist Use And Patient-Reported Well-Being Among Individuals With Diabetes And Obesity: Evidence From The All Of Us Research Program, Tinsae Gashachew Admassu

Public Health Theses

Abstract Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes and obesity, with growing interest in their potential effects on mental health and functional outcomes. However, clinical trials often exclude individuals with psychiatric comorbidities, limiting generalizability. Objective: To examine the association between GLP-1 RA use and self-reported mental health and functional outcomes in individuals with diabetes and obesity using real-world data from the All of Us Research Program. Methods: This cross-sectional study analyzed 53,127 adults with type 2 diabetes and 35,430 adults with obesity who had both EHR and survey data. GLP-1 RA users were …

Subsidized And Forgotten: The Quiet Erosion Of The Supplemental Security Income Program In American Social Policy, Johntrell Bowles

Public Health Theses

The Supplemental Security Income (SSI) program was created to guarantee a basic level of income security for the nation's most economically vulnerable populations: low-income elderly adults, people who are blind, and individuals with disabilities. Despite this foundational mission, SSI has stagnated over the past fifty years, becoming increasingly inadequate in addressing the economic and social realities of those it was designed to support.

This thesis examines how congressional neglect, enduring stigma toward welfare recipients, and outdated policy structures have eroded SSI’s ability to fulfill its original promise. Grounded in a critical social policy framework and informed by the author's professional …

Statistical Methods For Investigating Cell-Type Specificity And Genetic Regulation Of Dna Methylation In Complex Traits, Youshu Cheng

Yale Graduate School of Arts and Sciences Dissertations

DNA methylation is one of the most widely studied epigenetic modifications that capture the cumulative effects of environmental exposures and inheritable effects and regulates gene expression. DNA methylation occurs at CpG sites, where the cytosine and guanine bases are connected by a phosphate group. Over the past decades, DNA methylation have been useful resources to understand the etiology and mechanisms of complex diseases. Multiple studies have linked DNA methylation with diseases to identify differentially methylated CpGs that associated with complex traits. In addition, another research direction is to focus on the single nucleotide polymorphisms (SNPs) associated with DNA methylation levels, …

Tau-Connectome Predictive Modeling And Subtyping In Preclinical Alzheimer's Disease, Hamid Abuwarda

Yale Graduate School of Arts and Sciences Dissertations

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-? and tau, yet clinical progression varies widely across individuals. The central aim of this dissertation was to evaluate whether functional brain connectivity derived from resting-state fMRI can serve as a clinically meaningful predictive tool in the asymptomatic phase of the disease, preclinical AD. In Chapter 2, I develop connectome-based predictive models linking whole-brain functional connectivity to regional tau positron emission tomography (PET) signal in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study. These models predicted tau burden, particularly in regions vulnerable to tau deposition in Braak stages IV/V. In …

Genetic Variants Linked To Neurodevelopmental Disorders Within The Beta3-Beta4 Loop Of The Trio Ph 2 Domain Release Autoinhibition Of The Trio Gef2 Activity, Melissa Carrizales

Yale Graduate School of Arts and Sciences Dissertations

The TRIO family of proteins, which includes Trio, Kalirin, UNC-73 (in Caenorhabditis elegans), and dTrio (in Drosophila), are key regulators of cell morphogenesis, migration, tissue organization, and neuronal development through their regulation of Rho GTPases. These proteins feature multiple catalytic and scaffolding domains that mediate GTPase activation and cellular localization. TRIO proteins are essential for processes like actin dynamics, cell migration, and synaptic function, and disruptions in their activity have been linked to neurodevelopmental and neuropsychiatric disorders. This study focuses on Trio, specifically its regulatory mechanisms and how disease-related mutations disrupt its catalytic activity, contributing to various human diseases.

In …

Disability, Cure, And (Anti)Normativity In Modern And Contemporary Spanish Literature, Martha Engvall

Yale Graduate School of Arts and Sciences Dissertations

In my dissertation, I examine the role of disability, diagnosis, and cure in modern and contemporary Spanish novels. In the first three chapters, I show how authors of the late 19th and early 20th century used disability’s relationship to race, gender, and social class to question exclusionary social norms. I analyze critiques of industrialization in Galdós’s Marianela (1878) and Blasco Ibáñez’s Del vivir (1904); examine portrayals of leprosy in Galdós’s Misericordia (1897), Pardo Bazán’s La prueba (1890), Miró’s Del vivir (1904) and El obispo leproso (1926), and Hoyos y Vinent’s El monstruo (1915); and explore connections between disability, sexuality, and …

Interpretable And Data-Driven Machine Learning Models For Analyzing High-Dimensional Biological Data, Junchen Yang

Yale Graduate School of Arts and Sciences Dissertations

High-dimensional biological data, including single-cell omics, are prevalent in modern biology for characterizing a wide range of biological processes and phenomena. Although our capacity to generate such data has expanded at an unprecedented pace, significant challenges remain in extracting the informative features and the underlying biological signals. In particular, these datasets not only exhibit high dimensionality but also suffer from issues including inherent noise, low signal-to-noise ratio, and intrinsic heterogeneity. While machine learning models hold great promise for analyzing such data, their complexity and sensitivity to data characteristics often impede biological interpretability. To address these interconnected challenges, this thesis develops …