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Regulation Of Trio Gef1 Activity By The Spectrin Repeats And Cellular Factors, Josie Evelyn Bircher Apr 2022

Regulation Of Trio Gef1 Activity By The Spectrin Repeats And Cellular Factors, Josie Evelyn Bircher

Yale Graduate School of Arts and Sciences Dissertations

The Trio family of proteins consists of Trio, Kalirin, UNC-73 (in Caenorhabditis elegans) and dTrio (in Drosophila). Trio proteins are key regulators of cell morphogenesis and migration, tissue organization, and secretion and protein trafficking in many biological contexts. Recent discoveries have linked Trio and Kalirin to human disease, including neurological disorders and cancer. The genes for Trio family proteins encode a series of large multidomain proteins with up to three catalytic activities and multiple scaffolding and protein-protein interaction domains. As such, Trio family proteins engage a wide array of cell surface receptors, substrates, and interaction partners to coordinate changes in …

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Essays On Numerical Integration In Hamiltonian Monte Carlo, James Brofos Apr 2022

Essays On Numerical Integration In Hamiltonian Monte Carlo, James Brofos

Yale Graduate School of Arts and Sciences Dissertations

This thesis considers a variety of topics broadly unified under the theme of geometric integration for Riemannian manifold Hamiltonian Monte Carlo. In chapter 2, we review fundamental topics in numerical computing (section 2.1), classical mechanics (section 2.2), integration on manifolds (section 2.3), Riemannian geometry (section 2.5), stochastic differential equations (section 2.4), information geometry (section 2.6), and Markov chain Monte Carlo (section 2.7). The purpose of these sections is to present the topics discussed in the thesis within a broader context. The subsequent chapters are self-contained to an extent, but contain references back to this foundational material where appropriate. Chapter 3 …

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Leading From The Margins: The Wnba And The Emergence Of A New Model Of Sports Activism In The United States, Angele Delevoye Apr 2022

Leading From The Margins: The Wnba And The Emergence Of A New Model Of Sports Activism In The United States, Angele Delevoye

Yale Graduate School of Arts and Sciences Dissertations

After a first wave of activist athletes influenced the 1960s Civil Rights debates and faced negative professional and personal consequences, activist athletes largely disappeared from the American Politics landscape. The return of athlete activism in the last few years has been widely covered by journalists and scholars alike. In this dissertation, I argue that this trend is not a return to the activism of the past, but the emergence of a new model of sports activism. Building on recent developments in the persuasion literature, I show how in this new model, some leagues are in a unique and unprecedented position …

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Sick Time: Medicine, Management, And Slavery In Louisiana And Cuba, 1763-1868, Liana Demarco Apr 2022

Sick Time: Medicine, Management, And Slavery In Louisiana And Cuba, 1763-1868, Liana Demarco

Yale Graduate School of Arts and Sciences Dissertations

Modern, capitalist ideas of productivity became central to medicine under slavery. They shaped how physicians treated enslaved patients, crafted a scientific basis for medicine, and conceived of themselves as a profession. Between the late eighteenth century and the mid-nineteenth century, white male physicians in Louisiana and Cuba distinguished themselves from other healers: first, by aligning with Spanish colonialism, and then, by making themselves essential to a new form of plantation management that used clock-time discipline, hierarchical divisions of labor, and complex accounting systems. As these technologies became widespread in sugar and cotton production, they helped planters precisely interpret enslaved health …

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Philosophy, Psychology, And The Ethics Of Consent, Joanna Demaree-Cotton Apr 2022

Philosophy, Psychology, And The Ethics Of Consent, Joanna Demaree-Cotton

Yale Graduate School of Arts and Sciences Dissertations

Consent is morally transformative and suffuses our everyday moral and social lives. Valid consent makes the difference between permissible sex and rape; between a medical exam and assault; between entering a person’s home and trespass; between an economic transaction and theft; between contact sports and physical attacks; between the sharing of information and invasions of privacy. Moral philosophers writing on consent take themselves to capture and illuminate these ordinary practices, while claiming to do justice to commonsense claims about the circumstances under which consent is valid. Specifically, they purport to explain the way that ordinary consent can be morally transformative …

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“Everybody Is Locked Up”...Black Families With Incarcerated Loved Ones, Patrice Collins Apr 2022

“Everybody Is Locked Up”...Black Families With Incarcerated Loved Ones, Patrice Collins

Yale Graduate School of Arts and Sciences Dissertations

Increasing rates of parental incarceration in the U.S. are implications of a changing society for Black children and their families. Yet, very little is known ethnographically about the experiences of families with arrested and incarcerated parents. This study uses urban ethnographic methods to understand the contextual and social factors for families of the incarcerated, from the perspectives of poor Black families experiencing incarceration. I argue that the arrest of a parent initiates a powerful ripple effect that occurs within families, communities, and other social institutions. The arrest is often just the beginning of complicated interactions with the criminal system. This …

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Quantifying Membrane Topology At The Nanoscale, Zachary Ryan Connerty-Marin Apr 2022

Quantifying Membrane Topology At The Nanoscale, Zachary Ryan Connerty-Marin

Yale Graduate School of Arts and Sciences Dissertations

Changes in the shape of cellular membranes are linked with viral replication, Alzheimer's, heart disease and an abundance of other maladies. Some membranous organelles, such as the endoplasmic reticulum and the Golgi, are only 50 nm in diameter. As such, membrane shape changes are conventionally studied with electron microscopy (EM), which preserves cellular ultrastructure and achieves a resolution of 2 nm or better. However, immunolabeling in EM is challenging, and often destroys the cell, making it difficult to study interactions between membranes and other proteins. Additionally, cells must be fixed in EM imaging, making it impossible to study mechanisms of …

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Localization And Cantor Spectrum For Quasiperiodic Discrete Schrödinger Operators With Asymmetric, Smooth, Cosine-Like Sampling Functions, Yakir Moshe Forman Apr 2022

Localization And Cantor Spectrum For Quasiperiodic Discrete Schrödinger Operators With Asymmetric, Smooth, Cosine-Like Sampling Functions, Yakir Moshe Forman

Yale Graduate School of Arts and Sciences Dissertations

This dissertation addresses the question of Anderson localization for quasi-periodic discrete Schr\"odinger operators $H = \varepsilon\Delta + V$ with potential $V$ sampled with Diophantine frequency $\alpha$ from an asymmetric, smooth, cosine-like function $v \in C^2(\mathbb{T},[-1,1])$. After reviewing the known results in case $v$ is analytic or symmetric, we develop an inductive analysis on scales, whereby we show that locally the Rellich functions of Dirichlet restrictions of $H$ inherit the cosine-like structure of $v$ and are uniformly well-separated. We utilize this construction to prove almost-sure Anderson localization and Cantor spectrum in our case for sufficiently small interaction $\varepsilon \leq \varepsilon_0(v,\alpha)$.

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Essays In International Trade And Spatial Economics, Robert John Finlay Apr 2022

Essays In International Trade And Spatial Economics, Robert John Finlay

Yale Graduate School of Arts and Sciences Dissertations

The first chapter of this dissertation studies the relationship between credit constraints, exporting, and misallocation. When financial markets are imperfect, credit constraints hinder firm growth, distort the allocation of inputs, and lower aggregate productivity. Such constraints are particularly costly when they bind for the most productive firms. I focus on exporters, a group of firms that the international trade literature has identified as uniquely productive. Are exporters credit constrained? Do policies that target exporters — which are ubiquitous, particularly in developing countries — mitigate or worsen misallocation? I answer these questions by combining a natural experiment in India with a …

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An Abundance Of Quenching: Comparing Observations And Simulations Of Low Mass Galaxies, Claire Dickey Apr 2022

An Abundance Of Quenching: Comparing Observations And Simulations Of Low Mass Galaxies, Claire Dickey

Yale Graduate School of Arts and Sciences Dissertations

This thesis focuses on low mass, quiescent galaxies in the local universe, with the goal of providing meaningful constraints on the feedback mechanisms that drive quenching in low mass galaxies. We present an in-depth exploration of what may be the lowest mass galaxies still able to self-quench on galaxy-wide scales, using Keck/ESI long-slit spectroscopy (Dickey et al. 2019). Despite their overall passive appearances, nearly all low-mass quiescent galaxies host AGN, in contrast to denser environments, where we observe significant numbers of quiescent galaxies lacking AGN signatures. These results suggest that the presence of hard ionizing radiation (AGN-like line ratios) is …

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The Role Of Γ-Secretase In Human Papillomavirus Infection, Mac Crite Apr 2022

The Role Of Γ-Secretase In Human Papillomavirus Infection, Mac Crite

Yale Graduate School of Arts and Sciences Dissertations

Human papillomaviruses (HPV) are important pathogens that cause 5% of all human cancers worldwide, including essentially all cases of cervical cancer. Prophylactic vaccines against HPV exist, however these are not widely utilized in all communities, cannot cure existing infection, and do not protect against all subtypes. Therefore, study of HPV infection may lead to important new therapeutics to reduce the spread of the virus and disease burden. In addition, thorough investigation of HPV infection is likely to provide new insights into many aspects of cell biology and biochemistry, as the study of viruses has in the past. HPV requires multiple …

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T Cell Regulation Of Antibody Responses To Infection And Immunization, Jennifer Shuen Chen Apr 2022

T Cell Regulation Of Antibody Responses To Infection And Immunization, Jennifer Shuen Chen

Yale Graduate School of Arts and Sciences Dissertations

T follicular helper (Tfh) cells are the conventional drivers of protective, germinal center (GC)-based antiviral antibody responses. However, loss of Tfh cells and GCs has been observed in patients with severe COVID-19. As T cell-B cell interactions and immunoglobulin class switching still occur in these patients, non-canonical pathways of antibody production may be operative during SARS-CoV-2 infection. We found that both Tfh-dependent and -independent antibodies were induced against SARS-CoV-2 infection, SARS-CoV-2 vaccination, and influenza A virus infection. Even though Tfh-independent antibodies to SARS-CoV-2 had evidence of reduced somatic hypermutation, they were still high-affinity, durable, and reactive against diverse spike-derived epitopes …

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Systematic Screen Of Histone H4 In Arabidopsis Thaliana, Emma Tung Corcoran Apr 2022

Systematic Screen Of Histone H4 In Arabidopsis Thaliana, Emma Tung Corcoran

Yale Graduate School of Arts and Sciences Dissertations

Histones regulate diverse processes in eukaryotes and consequently, can have widespread effects on organismal fitness and development. Histones are a dynamic target for a variety of post-translational modifications (PTMs) and the assessment of histone function has typically been accomplished by mutating enzymes that catalyze and/or recognize these PTMs (i.e., writers and readers, respectively). Although considerable information has been gained in the past several decades by using this strategy, multiple issues such as writer/reader redundancy, unidentified writers/readers of histone PTMs, and writers/readers with additional non-histone targets can preclude the identification of new roles for histones and complicate the assessment of mutant …

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The Melodramatic Unconscious: The Cinematic Afterlife Of Fin-De-Siècle Vienna, Maxfield Walker Fulton Apr 2022

The Melodramatic Unconscious: The Cinematic Afterlife Of Fin-De-Siècle Vienna, Maxfield Walker Fulton

Yale Graduate School of Arts and Sciences Dissertations

This dissertation centers on four auteurist films by Max Ophuls, Liliana Cavani, Nicolas Roeg, and Stanley Kubrick which turned to the artistic, intellectual, and cultural history of fin-de-siècle Vienna in order to adapt classical Hollywood melodrama for the art cinema genre. Drawing on art history, aesthetic philosophy, literary theory, and film studies, the dissertation intervenes in an ongoing discourse about the relationship between modernism and melodrama. Whereas scholars of European art cinema have tended to focus on how modernist provocateurs have appropriated Brechtian Verfremdungseffekte in order to undermine classical melodrama’s immersive emotionality and advance social critique, my project traces an …

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Molecular Profiling Of The Adult Corticospinal Tract Reveals Transcriptional, Anatomical, And Reactive Heterogeneity, Noa Golan Apr 2022

Molecular Profiling Of The Adult Corticospinal Tract Reveals Transcriptional, Anatomical, And Reactive Heterogeneity, Noa Golan

Yale Graduate School of Arts and Sciences Dissertations

The corticospinal tract (CST) is the major descending motor tract responsible for voluntary movement in all mammals. Corticospinal neurons (CSNs) have cell bodies in layer 5 of the primary motor cortex, with axons that descend through the internal capsule, decussate at the medullary pyramids, and innervate every spinal segment along the entire spinal neuro-axis. Injury, disease, and neurodegeneration within this pathway result in chronic, irreversible functional deficits in motor and sensory function due to inhibitory extrinsic substrates, including central nervous system (CNS) myelin and chondroitin sulfate proteoglycans (CSPGs) in the extracellular matrix, and poor intrinsic growth capacity. Current strategies for …

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Widespread Association Of The Argonaute Protein Ago2 With Meiotic Chromatin Suggests A Distinct Nuclear Function In Mammalian Male Reproduction, Kimberly Nicole Griffin Apr 2022

Widespread Association Of The Argonaute Protein Ago2 With Meiotic Chromatin Suggests A Distinct Nuclear Function In Mammalian Male Reproduction, Kimberly Nicole Griffin

Yale Graduate School of Arts and Sciences Dissertations

A variety of mechanisms in different compartments of the cell cooperate to regulate gene expression. Some mechanisms are specific to certain compartments, such as the regulation of transcription by changes in histone modifications in the nucleus or protein translation repression in the cytoplasm. Other mechanisms, such as gene regulation by Argonaute proteins, span multiple compartments. Argonaute 2 (AGO2) is the best characterized member of the Argonaute family. It is a ubiquitously expressed, key protein in the cytoplasmic regulation of RNA transcripts, vital to the development and homeostasis of organisms. Recent studies in lower organisms have implicated AGO2 function in the …

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Transmitters, Texts, And Traditions: The Zoroastrian Priesthood From The Sasanian To The Early Islamic Period, Kayla Dang Apr 2022

Transmitters, Texts, And Traditions: The Zoroastrian Priesthood From The Sasanian To The Early Islamic Period, Kayla Dang

Yale Graduate School of Arts and Sciences Dissertations

This dissertation examines the institutional framework of the Zoroastrian priesthood through its individual priests and their relationship with ruling authorities. Entitled “Transmitters, Texts, and Traditions: The Zoroastrian Priesthood from Late Antiquity to the Early Islamic Period,” it traces the survival and transformation of the priesthood across the divide of the Arab conquest of Iran, the period of transformation from Zoroastrianism as a state religion under the Sasanid kings to the gradual conversion of the population to Islam under Muslim rulers. Using primary sources in Arabic, Syriac, Armenian, and Greek alongside material culture and literary sources in Middle Persian, I study …

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Spatial And Prediction Models For Addressing Challenges In Pediatric Tuberculosis Control And Care, Kenneth Suranga Gunasekera Apr 2022

Spatial And Prediction Models For Addressing Challenges In Pediatric Tuberculosis Control And Care, Kenneth Suranga Gunasekera

Yale Graduate School of Arts and Sciences Dissertations

Tuberculosis (TB) is among the leading causes of global mortality among children <5 years. Each year, over 1 million TB cases occur among children <15 years worldwide, and nearly one quarter of those children die; approximately 80% of those deaths occur among children <5 years. Alleviating the burden of pediatric TB and mortality requires 1) enhanced efforts to prevent transmission to children and 2) treating more children for TB. Targeting resources to children with a known TB exposure has been a cornerstone of the public health response to prevent transmission and detect cases early. Infectious adults must be diagnosed and treated earlier to prevent transmission to their child contacts. Modeling studies suggest that targeting community-level active case-finding to areas with high local transmission intensity may demonstrate population-level reductions in TB incidence. However, obtaining conclusive evidence of concentrated transmission requires access to spatial and genomic data, which is often only available under research conditions in high TB-incidence settings. In chapter 1, I use Bayesian spatial modeling methods to probe routinely collected, age-disaggregated TB notification data to demonstrate that overrepresentation of young child cases co-locate with areas of high local transmission intensity, identified by molecular evidence of transmission from a prospective cohort study in the same setting. This finding suggests that the use of models that leverage widely available notification data should be explored as tools to target case-finding and treatment efforts in high-transmission locations to maximize the direct and indirect benefits of active screening approaches. In chapter 2, I leverage data from a large prevalence survey to investigate a poorly understood form of TB that may frustrate symptom-based active case-finding efforts. Given that modeling estimates suggest that 96% of global childhood mortality due to TB occurs among children not receiving antituberculosis treatment, identifying and treating more cases of pediatric TB provide an opportunity to reduce child mortality. Diagnostic tools for pediatric pulmonary TB are limited by paucibacillary disease in children as well by resource constraints in many high TB-incidence settings. This contributes to poorer treatment outcomes through missed diagnoses and treatment delays. In chapter 3, I describe the analysis of a cohort of children being evaluated for TB from Cape Town, South Africa to demonstrate that a majority of antituberculosis treatment-decisions could be made using clinical evidence alone, without the need for additional diagnostic testing. In chapter 4, I describe the assembly of a large cohort of pediatric TB diagnostic evaluation data sourced from multiple geographically diverse, high TB-incidence settings to develop a prediction model for TB and investigate its validity and generalizability. As part of this work, I describe efforts in partnership with the World Health Organization to operationalize the prediction model as a treatment-decision algorithm to guide the evaluation of children with presumptive pulmonary TB.

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Catalytic Stereoselective Construction Of Terphenyl And Imide Atropisomers By Brønsted Basic Guanidinylated Peptides, Omar Mustapha Beleh Apr 2022

Catalytic Stereoselective Construction Of Terphenyl And Imide Atropisomers By Brønsted Basic Guanidinylated Peptides, Omar Mustapha Beleh

Yale Graduate School of Arts and Sciences Dissertations

This dissertation describes our studies on the development of tetramethylguanidine (TMG)-based peptides as a new class of Brønsted basic catalysts and their application to challenging atroposelective reactions. The enhanced basicity of these peptides has enabled us to access novel reactivity to synthesize scaffolds of interest containing one or more stereogenic axes with high levels of catalyst control.Chapter 1 serves as an introduction to the concept of chirality, with a focus on its connection to the functional role of natural and synthetic molecules. An important subset of chirality is atropisomerism, which arises from restricted bond rotation most commonly between sp2–sp2 atoms. …

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Spectroscopic Probes Of Low-Barrier Proton-Transfer Dynamics, Lidor Foguel Apr 2022

Spectroscopic Probes Of Low-Barrier Proton-Transfer Dynamics, Lidor Foguel

Yale Graduate School of Arts and Sciences Dissertations

The diverse discipline of molecular spectroscopy, which has profited tremendously from the advent of tunable laser sources, has transformed the scientific community’s knowledge of the microscopic world, allowing the study of perplexing quantum-chemical phenomena. Classically-hindered proton transfer, a multidimensional process mediated by nuclear-quantum effects (e.g., potential-barrier tunneling), is a chemical transformation that forms the crux of all acid/base chemistry. Although extensive research efforts have aimed to establish the paradigms that govern this transformation, a full understanding has proven elusive with questions continuing to emerge.Exploring the proton-transfer reaction, and the related concept of hydrogen bonding, has benefitted greatly from investigations of …

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Essay In Social Coordination, Jacob Derechin Apr 2022

Essay In Social Coordination, Jacob Derechin

Yale Graduate School of Arts and Sciences Dissertations

Social Coordination is an essential feature of any social system. Coordination is a precondition for certain kinds of cooperation, as cooperation implies agents working together for a common cause, while coordination only implies agents synchronizing their behavior. For example, social contagion suggests a mechanism for groups to socially coordinate without necessarily cooperating. When behaviors spread across social ties the people may not be actively intending to spread the behavior, so they are not always cooperating. The necessity of coordination does not imply that it is easy to achieve. In Chapter 1, I survey two theoretical frameworks for operationalizing the challenges …

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Two Projects Informed By Work On Glucosepane, Robert Donald Hale Apr 2022

Two Projects Informed By Work On Glucosepane, Robert Donald Hale

Yale Graduate School of Arts and Sciences Dissertations

Part 1: Having developed a reaction to synthesize the protein-sugar crosslink glucosepane, we sought to apply our lessons to the synthesis of structurally similar molecules. Marine alkaloids containing a diaminoimidazole-derived core possess intriguing chemical structures and have displayed promising antimicrobial activity in preliminary screens. However, these compounds generally contain densely functionalized multicyclic cores and relatively large numbers of nitrogen atoms. For these reasons, they have proven difficult to synthesize. In this work, we report a novel total synthesis of the marine alkaloid (±)-dibromoagelaspongin. Our key intermediate is a 2,5-diaminoisoimidazole accessed in one step from a suitably protected guanylhydrazine and an …

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Automated Approaches For Program Verification And Repair, William Triest Hallahan Apr 2022

Automated Approaches For Program Verification And Repair, William Triest Hallahan

Yale Graduate School of Arts and Sciences Dissertations

Formal methods techniques, such as verification, analysis, and synthesis,allow programmers to prove properties of their programs, or automatically derive programs from specifications. Making such techniques usable requires care: they must provide useful debugging information, be scalable, and enable automation. This dissertation presents automated analysis and synthesis techniques to ease the debugging of modular verification systems and allow easy access to constraint solvers from functional code. Further, it introduces machine learning based techniques to improve the scalability of off-the-shelf syntax-guided synthesis solvers and techniques to reduce the burden of network administrators writing and analyzing firewalls. We describe the design and implementationof …

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Processor Microarchitecture Security, Shuwen Deng Apr 2022

Processor Microarchitecture Security, Shuwen Deng

Yale Graduate School of Arts and Sciences Dissertations

As computer systems grow more and more complicated, various optimizations can unintentionally introduce security vulnerabilities in these systems. The vulnerabilities can lead to user information and data being compromised or stolen. In particular, the ending of both Moore's law and Dennard scaling motivate the design of more exotic microarchitectural optimizations to extract more performance -- further exacerbating the security vulnerabilities. The performance optimizations often focus on sharing or re-using of hardware components within a processor, between different users or programs. Because of the sharing of the hardware, unintentional information leakage channels, through the shared components, can be created. Microarchitectural attacks, …

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Inflammatory Stress Disrupts Endothelial Cell Cholesterol Homeostasis And Increases Srebp2-Dependent Gene Expression To Amplify The Acute Inflammatory Response, Joseph Wayne Montano Fowler Apr 2022

Inflammatory Stress Disrupts Endothelial Cell Cholesterol Homeostasis And Increases Srebp2-Dependent Gene Expression To Amplify The Acute Inflammatory Response, Joseph Wayne Montano Fowler

Yale Graduate School of Arts and Sciences Dissertations

Immunometabolism is a growing field that centers on a core paradigm:perturbations in metabolism alter a cell’s biological response in immunity and, likewise, inflammatory signals, such as cytokines and pathogens, can directly influence cellular metabolism. Although the carbons within cholesterol cannot be used for catabolic energy production, there is a growing appreciation that a similar relationship exists between cholesterol homeostasis and immunity. The majority of this literature is focused on cholesterol dynamics in the context of leukocyte immunobiology. However, the endothelium also plays an important role during the acute inflammatory response. Endothelial cells (ECs) rapidly respond to extrinsic signals, such as …

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Collared Men: Ethnographic Essays On Navigating Race And Status In Everyday Live, Craig Holloway Apr 2022

Collared Men: Ethnographic Essays On Navigating Race And Status In Everyday Live, Craig Holloway

Yale Graduate School of Arts and Sciences Dissertations

The demands of the American society are changing as it develops into a more plural anddiverse society that is characterized by an increasingly specialized economy. Many are willing to say that we are in both a post-industrial and post-racial society that renders equal opportunity for all people. Yet, black men continue to be in relatively peculiar circumstances as people from varied statuses. Status is fluid. And their narrations of their everyday lives and the lives of their counterparts through their own status can at times be strikingly different from mainstream society. These men navigate the demands of race, family and …

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Quantitative Methods For Improving Medical Decision-Making, Margret Erlendsdottir Apr 2022

Quantitative Methods For Improving Medical Decision-Making, Margret Erlendsdottir

Yale Graduate School of Arts and Sciences Dissertations

Innovation in causal inference and implementation of electronic health record systems are rapidly transforming medical care. In this dissertation, we present three examples in which use of methods in causal inference and large electronic health record data address existign challenges in medical decision-making. First, we use principles of causal inference to examine the structure of randomized trials of biomarker targets, which have produced divergent results and controversial clinical guidelines for management of hypertension and other chronic diseases. We discuss four key threats to the validity of trials of this design. Second, we use methods in causal inference for adjustment of …

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Essays In The Industrial Organization Of Regulatory Policy, Jonathan Thomas Hawkins-Pierot Apr 2022

Essays In The Industrial Organization Of Regulatory Policy, Jonathan Thomas Hawkins-Pierot

Yale Graduate School of Arts and Sciences Dissertations

Governments use a wide variety of policy instruments to achieve their goals, including price signals, constraints on firms’ behavior, and direct action. The consequences of such policies depend on how they interact with the underlying economic system. Measuring the impact of an intervention can be difficult, especially when the policy was not designed or implemented with evaluation in mind. Moreover, it is often ex ante prediction of a policy’s costs and benefits, rather than ex post evaluation, which is relevant for decision making. This dissertation examines issues related to both evaluating and predicting the effects of regulations in two important …

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The Parkinson’S Gene Vps13c Encodes An Er-Lysosome Lipid Transfer Protein Linking Lysosomal Lipid Homeostasis And Cgas/Sting-Mediated Innate Immunity, William Franklin Hancock-Cerutti Apr 2022

The Parkinson’S Gene Vps13c Encodes An Er-Lysosome Lipid Transfer Protein Linking Lysosomal Lipid Homeostasis And Cgas/Sting-Mediated Innate Immunity, William Franklin Hancock-Cerutti

Yale Graduate School of Arts and Sciences Dissertations

Biallelic loss-of-function mutations in VPS13C cause early-onset Parkinson’s Disease (PD), and the VPS13C locus is a GWAS hit for sporadic PD risk. VPS13C is a member of the VPS13 family, which in humans contains three other proteins, VPS13A, VPS13B, and VPS13D, all with ties to neurological diseases. Mutations in VPS13A cause chorea-acanthocytosis a Huntington’s like syndrome with dysmorphic erythrocytes, mutations in VPS13B cause the neurodevelopmental disorder Cohen syndrome, and mutations in VPS13D cause spastic ataxia with varying presentation. The molecular function of these proteins, why their loss cause neurological diseases, and why they are each associated with distinct diseases despite …

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Learning Non-Parametric And High-Dimensional Distributions Via Information-Theoretic Methods, Soham Jana Apr 2022

Learning Non-Parametric And High-Dimensional Distributions Via Information-Theoretic Methods, Soham Jana

Yale Graduate School of Arts and Sciences Dissertations

Learning distributions that govern generation of data and estimation of related functionals are the foundations of many classical statistical problems. In the following dissertation we intend to investigate such topics when either the hypothesized model is non-parametric or the number of free parameters in the model grows along with the sample size. Especially, we study the above scenarios for the following class of problems with the goal of obtaining minimax rate-optimal methods for learning the target distributions when the sample size is finite. Our techniques are based on information-theoretic divergences and related mutual-information based methods. (i) Estimation in compound decision …

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