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Genetic Background’S Influence On The Pathogenesis Of Spinocerebellar Ataxia Type 1 (Sca1), Victor Hipolito Olmos
Genetic Background’S Influence On The Pathogenesis Of Spinocerebellar Ataxia Type 1 (Sca1), Victor Hipolito Olmos
Yale Graduate School of Arts and Sciences Dissertations
Spinocerebellar ataxia type 1 (SCA1) is a rare, dominantly inherited monogenic neurodegenerative disease that primarily affects the Purkinje cells (PCs) of the cerebellum. Our lab utilizes SCA1 as a model to unravel the complexity that is neurodegeneration. Neurodegeneration has long been a challenge due to the interactions of multiple cell types, various disease-causing genes, and degeneration beyond a single brain region. We utilized the SCA1 82Q B05 transgenic model (B05) which expresses the disease-causing gene, ATAXIN-1 (ATXN1), only in the PCs of the cerebellum. This mouse model recapitulates the disease phenotypes seen in human patients and allows us to investigate …
Molecular Crosstalk Mechanisms: Small Molecules Involved In Host-Bacterial Interactions, Tayah Turocy
Molecular Crosstalk Mechanisms: Small Molecules Involved In Host-Bacterial Interactions, Tayah Turocy
Yale Graduate School of Arts and Sciences Dissertations
Human hosts receive signals from the body indicating their degree of health, especially during homeostatic disruption. However, these signals are received at the end of a long line of communication between host, host response, microbiome, and metabolites. Immune system response, inflammation, and disease can be triggered by complex crosstalk mechanisms. The microbiome, home to trillions of microorganisms, can interact with other microbial members, utilize surrounding synthetic machinery, or directly modulate host response. Metabolites produced by the microbiome or sourced from the diet can also partake in host, bacterial, and metabolic crosstalk. Further, each can be influenced by their environment, such …
Neutrophil Heterogeneity And Transmigration: Decoding Molecular Profiles Through Multi-Omic Analysis And In Vitro Mimicry Of The Venular Wall, Laura C. Morales
Neutrophil Heterogeneity And Transmigration: Decoding Molecular Profiles Through Multi-Omic Analysis And In Vitro Mimicry Of The Venular Wall, Laura C. Morales
Yale Graduate School of Arts and Sciences Dissertations
Neutrophils are crucial innate immune cells that comprise about 50-70% of the white blood cell population in the human peripheral circulation. These polymorphonuclear leukocytes play a pivotal role in the innate immune system, acting as the primary line of defense against pathogens and facilitating tissue repair. Neutrophils exhibit a diverse repertoire of cytotoxic mechanisms to eliminate offending pathogenic agents and promote the resolution of inflammation. These include phagocytosis, degranulation, generating reactive oxygen species, and forming neutrophil extracellular traps, underscoring their versatility in host defense. A critical aspect of neutrophil functionality is their capacity to infiltrate sites of injury or infection, …
Quasiparticles And Charge-Parity Switching In Transmon Qubits, Spencer Diamond
Quasiparticles And Charge-Parity Switching In Transmon Qubits, Spencer Diamond
Yale Graduate School of Arts and Sciences Dissertations
Nonequilibrium quasiparticle excitations (QPs) are a significant loss mechanism inherentto superconducting devices. There are two distinct mechanisms by which transmon qubits couple to QPs. First, when QPs tunnel across the Josephson junction (JJ) of a transmon, they couple to the phase difference across the junction and may cause decoherence of the quantum state. Second, when QPs are generated by a high‑energy photon absorbed at the JJ, this process likewise may cause a qubit transition. Both of these mechanisms result in a transfer of a single charge across the JJ, causing a switch in the charge parity of the qubit. While …
Histone Regulation Of The Maternal To Zygotic Transition: The Role Of Histone Modifications On Zygotic Genome Activation, Maria De Jesus Benitez Ortiz
Histone Regulation Of The Maternal To Zygotic Transition: The Role Of Histone Modifications On Zygotic Genome Activation, Maria De Jesus Benitez Ortiz
Yale Graduate School of Arts and Sciences Dissertations
Following fertilization, the zebrafish embryo experiences significant reprogramming events to erase the inherited program of the terminally differentiated gametes, paving the way for the establishment of the zygotic program, which will drive the early steps of embryonic development. An essential step within this process is zygotic genome activation (ZGA), which refers to the time of development when the zygotic genome goes from being largely transcriptionally inactive to a gradual onset of transcriptional activity. In zebrafish, this process coincides with the deposition of many histone modifications associated with the positive regulation of transcription. Here, to explore the function of these transcription-associated …
The Role Of Human Capital And Institutions In Economic Growth, Alvaro Esteban Cox Lescano
The Role Of Human Capital And Institutions In Economic Growth, Alvaro Esteban Cox Lescano
Yale Graduate School of Arts and Sciences Dissertations
The role of human capital in development is a central topic of academic and policy discussions. The first two chapters of my dissertation are contributions to this topic. First, I use educational reform in Brazil to shed light on the impact of rising educational attainment on economic development. Second, I study the role of demand subsidies on access and increasing the quality of higher education. In Chapter 1, “From Classroom to Prosperity: Fostering Economic Development Through Higher Education,” I use both an empirical and theoretical approach to investigate the contribution of higher education to the development process, focusing on the …
(Private) Formal Methods For Rigorously Governable Systems, Samuel Judson
(Private) Formal Methods For Rigorously Governable Systems, Samuel Judson
Yale Graduate School of Arts and Sciences Dissertations
The increasing complexity of software systems presents a growing challenge to the societal and legal governance of modern technology. Understanding how algorithmic decisions are made and how private, proprietary, or otherwise legally-encumbered data is generated and consumed is essential to the design of robust and accountable computing. This dissertation contributes algorithmic techniques based on formal methods for program analysis and verification -- and at times combined with cryptographic constructions for privacy-preserving computation -- that are designed with the goal of supporting the principled and effective governance of software and cyberphysical systems. First, this dissertation investigates how Satisfiability Modulo Theories (SMT)-based …
Expressed Artificial Proteins That Induce Degradation Of The Platelet-Derived Growth Factor Beta Receptor, Emily Branham
Expressed Artificial Proteins That Induce Degradation Of The Platelet-Derived Growth Factor Beta Receptor, Emily Branham
Yale Graduate School of Arts and Sciences Dissertations
Targeted protein degradation (TPD) is a rapidly advancing field with diverse applications spanning from fundamental research to therapeutic interventions. With considerable opportunity for scientific creativity, emerging degradation strategies promise to expand the reach of this field to challenging targets that often elude conventional, small molecule-based degraders. Of particular interest in this report, transmembrane (TM) proteins represent more than half of all drug targets, yet their intrinsic properties present challenges for standard degradation approaches. Here, we describe a novel genetic approach to TPD, presenting the first example of expressible protein degraders: traptamer-based targeting chimeras (TRAPTACs). As their name implies, these innovative …
Essays On Digital Markets, Tan Gan
Essays On Digital Markets, Tan Gan
Yale Graduate School of Arts and Sciences Dissertations
The growing salience of digital markets calls for new models that analyze market behaviors in the presence of the massive collection of consumer data, market powers for consumer attention, and the ability to offer sophisticated mechanisms for digital service. My dissertation consists of three papers focusing on different aspects of digital markets. Chapter 1 studies the implication of having consumer data on the dynamic pricing policy of experience good such as streaming services and subscription services. Chapter 2 studies the social dimension of consumer data, where the data externality makes consumers dramatically under-evaluate the consequences of sharing their data. Chapter …
Investigations Of Bacteroides Thetaiotaomicron Population Dynamics, Anna P. Zagieboylo
Investigations Of Bacteroides Thetaiotaomicron Population Dynamics, Anna P. Zagieboylo
Yale Graduate School of Arts and Sciences Dissertations
The human intestine contains a large, complex, and dynamic community of microbes termed the microbiota, which is made up of hundreds of individual species populations. Certain community compositions are linked to health or disease in the human host, and substantial effort has been directed towards identifying methods of modulating the microbiota composition for therapeutic purposes. While many studies assess which species are present or fluctuate within the community, little is known about fluctuations within individual isogenic populations over time. These types of high-resolution changes could reasonably be expected to have profound impacts on a commensal’s ability to colonize the gut …
Interpretable Machine Learning And Causal Inference In Medicine And Public Health, Colleen Elise Chan
Interpretable Machine Learning And Causal Inference In Medicine And Public Health, Colleen Elise Chan
Yale Graduate School of Arts and Sciences Dissertations
Machine learning (ML) methods have seen rapidly increasing prevalence and adoption across many industries due to their ability to learn complex patterns from large amounts of data with high accuracy. However, these models often lack transparency, operating as opaque ``black boxes’’, which is especially concerning in high-stakes domains. Two key avenues to improve transparency and user trust are 1) developing interpretable ML models that explain their reasoning to users and 2) developing causal methods to estimate the effects of interventions from observational data when randomized controlled trials are infeasible. This dissertation addresses challenges and advances methods in interpretable ML and …
Labor Supply And Life-Cycle Risk, William Daniel Felipe Giraldo Paez
Labor Supply And Life-Cycle Risk, William Daniel Felipe Giraldo Paez
Yale Graduate School of Arts and Sciences Dissertations
Technological and social changes in recent decades have affected the economic riskspeople face over their lives and their ability to work to earn money and insure against such risks. This dissertation examines two such shifts: the increasing age-friendliness of work and women’s increasing attachment to the labor force. The first chapter examines the labor force participation of older Americans, which has been increasing since the 1990s. I measure the contribution of the changing nature of American work to the increase in older labor force participation, its impacts on the distribution of welfare at older ages, and implications for Social Security …
Public Vs. Private: The Industrial Organization Of Education And Other Regulated Markets, Fernando Pereira Cordeiro
Public Vs. Private: The Industrial Organization Of Education And Other Regulated Markets, Fernando Pereira Cordeiro
Yale Graduate School of Arts and Sciences Dissertations
This dissertation studies two distinct but equally essential industries: higher education and water utilities. In the context of higher education, I investigate the impact of subsidies on equilibrium prices and quality levels. For water utilities, I explore the differences between public and private providers in terms of productivity and investment. A theme that emerges from these seemingly disparate analyses is how public provision or subsidies affect and contrast with private firms' behavior. Throughout this process, I use the lens and methods of Industrial Organization to conduct my analysis, a choice motivated by the inherent nature of imperfect competition that characterizes …
Business Groups And Misallocation: Theory And Evidence From Chaebols, Jihoon Sung
Business Groups And Misallocation: Theory And Evidence From Chaebols, Jihoon Sung
Yale Graduate School of Arts and Sciences Dissertations
I study the role of business groups - collections of firms owned by a single family - in determining factor misallocation and aggregate productivity. One might expect that business groups improve allocative efficiency because profit-maximizing owners can allocate resources efficiently across their firms. Surprisingly, using evidence from Korea, an economy wherelarge business groups (chaebols) are prominent, I find the contrary: business groups appear to worsen misallocation. In the first chapter, I describe the history and institutional details of chaebols. In the second chapter, I present the empirical findings. I show, using firm-level data with business group ownership information, that factor …
Essays On Firms And Workers In An Informal Economy, Pedro Miguel Casavilca Silva
Essays On Firms And Workers In An Informal Economy, Pedro Miguel Casavilca Silva
Yale Graduate School of Arts and Sciences Dissertations
Informal employment does not comply with labor regulations, leaving workers unprotected against unemployment or health risks. Despite this, informal employment is prevalent, accounting for over 30% of the labor force in many developing countries. To address this issue, governments have implemented labor market policies aimed at (i) promoting formal job creation and (ii) preventing formal job destruction. Among the first group of policies, countries have introduced fixed-term or temporary contracts, a flexible device for firms to adjust labor. Among the second group, governments have imposed employment protection policies such as severance pay upon firing. These policies have led to the …
Engineering Polymeric Nanoparticles For Intra-Amniotic And Intravenous In Utero Delivery, Anna Lynn
Engineering Polymeric Nanoparticles For Intra-Amniotic And Intravenous In Utero Delivery, Anna Lynn
Yale Graduate School of Arts and Sciences Dissertations
Fetal therapy is a rapidly expanding field that provides opportunities to treat or prevent congenital diseases early in the process of fetal development. Prior studies suggest that polymeric nanoparticles (NPs) are a safe, tunable, and effective vehicle for in utero delivery of therapeutic agents via administration into the amniotic fluid space. Previous work has focused on the feasibility of using poly(lactic-co-glycolic acid) (PLGA) NPs, as well as viral vectors and lipid NPs, for in utero delivery. Modifications to the core polymer and surface chemistry of NPs are known to be key in modulating the performance of NPs in various biological …
From Efficacy To Implementation: Translating Lifestyle Behavior Interventions Into Routine Breast Oncology Care, Leah Silverman Puklin
From Efficacy To Implementation: Translating Lifestyle Behavior Interventions Into Routine Breast Oncology Care, Leah Silverman Puklin
Yale Graduate School of Arts and Sciences Dissertations
Background: Obesity, poor diet quality, and low levels of physical activity (PA) are increasingly prevalent public health challenges with important implications for breast cancer treatment adherence and survival. The field of energy balance and breast cancer survivorship has made significant advancements in recognizing the importance of integrating programs that promote positive lifestyle behavior change in oncology care. However, there remain significant gaps in translating research findings into routine clinical practice. These gaps include conflicting evidence surrounding who experiences weight change post breast cancer diagnosis and how post-diagnosis weight patterns impact survival; what aspects need to be addressed when designing and …
Maternal And Paternal Migration And Children’S Human Capital, Siuyuat Wong
Maternal And Paternal Migration And Children’S Human Capital, Siuyuat Wong
Yale Graduate School of Arts and Sciences Dissertations
International migration opportunities improve earnings capacity, but can also create parental separation from children. The net effect of migration on children depends on the relative importance of money and parental presence in determining a child's human capital development, which parent migrates, and at what age they separate from the child. These considerations in turn affect whether, when, and who migrates. I estimate a dynamic model of migrant households with an embedded age-specific child education production function by conducting a panel survey of Filipino migrants and combining it with newly assembled administrative data from the Philippines Department of Education and the …
On Schrödinger Equations With Non-Perturbative Potentials, Adam Black
On Schrödinger Equations With Non-Perturbative Potentials, Adam Black
Yale Graduate School of Arts and Sciences Dissertations
This thesis consists of four parts, each studying a different class of Schrödinger equations. Though the setting and relevant questions vary between chapters, a theme that runs through all of them is the study of a Hamiltonian with a potential that is not small enough to be treated perturbatively. Indeed, in all of the Schrödinger equations below, the potential is, in some sense, large enough that it may affect the asymptotic behavior of the system.In Chapters 2 and 3, we investigate the scattering theory of Schrödinger operators with potentials that have anisotropic decay. More specifically, we assume that the potential …
Mechanisms And Functions Of Lipodystrophy In Dermal Fibrosis, Elizabeth Ann Caves
Mechanisms And Functions Of Lipodystrophy In Dermal Fibrosis, Elizabeth Ann Caves
Yale Graduate School of Arts and Sciences Dissertations
The skin is the largest organ in the human body and acts as a barrier between the inside and outside environments. A significant function of the skin is to maintain its structural integrity through extracellular matrix protein (ECM) homeostasis. Tissue fibrosis is characterized by a failure of ECM homeostasis, resulting in the accumulation of ECM proteins in healthy tissue. Systemic sclerosis is an autoimmune disease in which fibrosis develops throughout the body in organs such as the heart, lungs, and skin. Interestingly, during skin fibrosis, resident lipid-filled, mature adipocytes are depleted in humans and mice concomitant with ECM expansion. However, …
Afrekete’S Touch: Black Queer Feminist Errantry And Global African Art, Alexandra Monet Thomas
Afrekete’S Touch: Black Queer Feminist Errantry And Global African Art, Alexandra Monet Thomas
Yale Graduate School of Arts and Sciences Dissertations
The dissertation proposes that black queer feminist conceptual tools are advantageous to interpreting modern and contemporary art. Utilizing visual analysis and interdisciplinary black feminist criticism to analyze artwork by Mildred Thompson, Simone Leigh, Wangechi Mutu, Zanele Muholi, Senzeni Marasela, and others, becomes a way through which to build the concept of black queer feminist errantry. Defined as a political, aesthetic, and intellectual mode through which artists enact practices of wandering, refusal, fabulation, and waywardness, black queer feminist errantry was developed with the work of several scholars in mind, such as Sarah Jane Cervenak, Tavia Nyong’o, and Saidiya Hartman. The preface, …
Three Essays In Financial Economics, Joseph Leland Bybee
Three Essays In Financial Economics, Joseph Leland Bybee
Yale Graduate School of Arts and Sciences Dissertations
This dissertation consists of three chapters. The first is titled ``The Ghost in the Machine: Generating Beliefs with Large Language Models''.I introduce a methodology to generate economic expectations by applying large language models to historical news. Leveraging this methodology, I make three key contributions. (1) I show generated expectations closely match existing survey measures and capture many of the same deviations from full-information rational expectations. (2) I use my method to generate 120 years of economic expectations from which I construct a measure of economic sentiment capturing systematic errors in generated expectations. (3) I then employ this measure to investigate …
Deep Learning Methods Of Attenuation Correction, Reconstruction, Registration, And Denoising For Multi-Modal Cardiac Spect, Xiongchao Chen
Deep Learning Methods Of Attenuation Correction, Reconstruction, Registration, And Denoising For Multi-Modal Cardiac Spect, Xiongchao Chen
Yale Graduate School of Arts and Sciences Dissertations
Single-Photon Emission Computed Tomography (SPECT) is a non-invasive nuclear medicine imaging technique that visualizes the radiotracer distribution within the patient body through the detection of the emitted gamma-ray photons. Myocardial perfusion imaging (MPI) using SPECT is the most widely performed nuclear medicine exam that allows sensitive detection, localization, and risk stratification of ischemic heart diseases. Cardiac SPECT imaging presents a range of challenges and topics that are worth investigation, including attenuation correction (AC), limited-view (LV) reconstruction, cross-modality registration, low-dose denoising, etc. AC is essential for performing accurate quantitative or semi-quantitative analysis in cardiac SPECT. Currently, CT transmission scanning is typically …
Essays On Housing, Inequality, And Spatial Mobility, Anthony Elias Tokman
Essays On Housing, Inequality, And Spatial Mobility, Anthony Elias Tokman
Yale Graduate School of Arts and Sciences Dissertations
The first chapter of this dissertation uses parcel-level tax assessment and sales transaction data to estimate the stringency of housing unit density restrictions at the census tract level for 35 metropolitan areas in the United States, focusing on the period between 2000 and 2020. I do this by inferring the marginal regulatory "cost" of building an additional housing unit, conditioning on a parcel's total acreage and developed floor space. Regression on variables from the Wharton land use survey offers basic validation of this measure. I show that the inferred unit regulatory costs vary drastically across cities and neighborhoods; they tend …
Great Powers, Regional Powers, And The Balance Of Power In Conflict, John Dana Stuster-Kim
Great Powers, Regional Powers, And The Balance Of Power In Conflict, John Dana Stuster-Kim
Yale Graduate School of Arts and Sciences Dissertations
When do great powers cooperate with regional powers and when do they fight? This dissertation considers how the distribution of power at the systemic level and at the regional level conditions relations between great powers and regional powers and incentivizes conflict, hedging, or cooperation. I propose a general theory of great power-regional power relations. The theory contends that great powers are responsive to competition with other great powers, while regional powers have more limited interests and respond primarily to competition with regional rivals. When states engage in peer competition, they are incentivized to cooperate with other states and look for …
On The Evolution Of Spinoza's Metaphysics: Humility, The Origins Of Power, And The Nature Of Causation, Josefine Klingspor
On The Evolution Of Spinoza's Metaphysics: Humility, The Origins Of Power, And The Nature Of Causation, Josefine Klingspor
Yale Graduate School of Arts and Sciences Dissertations
This dissertation aims to understand key aspects of Spinoza’s early metaphysics and the reasons for and the significance of its evolution. Focusing on Spinoza’s first and final works on metaphysics, the Short Treatise and the Ethics, it demonstrates the individual significance and deep interconnectedness of three shifts in particular, namely Spinoza’s re-thinking of humility, the power and finite things and its relationship to divine power, and the nature of causation in general. Uncovering the layers of the evolution of Spinoza’s thought, it shows that Spinoza’s re-thinking of humility is a consequence of his re-thinking of power, and that his re-thinking …
Uncovering A Critical Role For Calmodulin In Calcium-Dependent Regulation Of The Nociceptor Trpa1, Justin Sanders
Uncovering A Critical Role For Calmodulin In Calcium-Dependent Regulation Of The Nociceptor Trpa1, Justin Sanders
Yale Graduate School of Arts and Sciences Dissertations
Transient receptor potential (TRP) channels are sensory receptors expressed throughout the peripheral nervous system that help shape how we respond to our environment. TRPA1 has been identified as a key component in the transition from acute to chronic pain and inflammation making it a prime target for development of novel analgesics. Calcium has been shown to regulate TRPA1 by rapidly potentiating channel activity followed by rapid desensitization. While the effects of calcium on TRPA1 activity have been well-described, the mechanisms governing these calcium effects have been difficult to elucidate. Work described within this thesis details the discovery of a novel …
An Epigenetic Timer Regulates The Transition From Cell Division To Cell Expansion During Arabidopsis Petal Organogenesis, Ruirui Huang
An Epigenetic Timer Regulates The Transition From Cell Division To Cell Expansion During Arabidopsis Petal Organogenesis, Ruirui Huang
Yale Graduate School of Arts and Sciences Dissertations
Epigenetic changes, such as histone modifications or DNA methylation, can modify gene expression without affecting the genetic code. Such alterations can persist for many cell generations, and often are induced by various environmental inputs in both plants and animals. A number of studies have demonstrated that epigenetic factors regulate plant developmental timing in response to environmental changes. However, we still have an incomplete view of how epigenetic factors can regulate developmental events such as organogenesis, and the transition from cell division to cell expansion, in plants. The small number of cell types and the relatively simple developmental progression required to …
Essays On Economic Growth, International Trade, And Environment, Wei Xiang
Essays On Economic Growth, International Trade, And Environment, Wei Xiang
Yale Graduate School of Arts and Sciences Dissertations
n my dissertation, I study how globalization affects economic growth, environment, and welfare. Local environmental regulations can stimulate homegrown clean technology innovation, thereby contributing to the reduction of global emissions over the long term. However, in the short term, these regulations may lead to the displacement of polluting activities to other regions, undermining their initial efficacy. In Chapter 1, I construct a structural model that incorporates both clean innovation and production relocation and use the model to assess the short- and long-term effects of environmental policies. Using a comprehensive firm-level dataset, I begin by documenting that more stringent local environmental …
Investor Relations And Esg, Tendai Masaya
Investor Relations And Esg, Tendai Masaya
Yale Graduate School of Arts and Sciences Dissertations
I investigate the relation between increased investor relations (IR) activities and four ESG outcomes: coverage by ESG rating agencies, ESG rating levels, the stock market response to bad ESG news, and the use of ESG-related terms in earnings conference calls. Firms with more IR activities—indicated by an IR Officer’s (IRO) presence on conference calls—could improve communication about ESG efforts with investors and ESG rating agencies, and feedback received might even increase the level of ESG efforts. I find that firms with IR prominence (1) are more likely to be covered by ESG raters; (2) experience an increase in overall, E, …