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Exploring Function And Mechanism Through Intuitions, Explanations, & Learning, Amanda Mccarthy Apr 2024

Exploring Function And Mechanism Through Intuitions, Explanations, & Learning, Amanda Mccarthy

Yale Graduate School of Arts and Sciences Dissertations

Imagine learning about a car engine for the first time. You might expect that the person explaining to you how a car engine works would first explain the role that the car engine has within the car (functional information) before diving into how the camshaft, pistons, spark plugs, cylinders, and crankshaft all work together to make the car engine work (mechanistic information). Where might this intuition that functional information should come before mechanistic information come from? Is mechanistic information too convoluted to be understood without function as a cognitive scaffold? This thesis considers the strength of this intuition of explanatory …

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Identifying Mechanisms Of Pathogenicity In Familial Cardiomyopathy-Linked Alpha-Tropomyosin Mutations, Saiti Srabonti Halder Apr 2024

Identifying Mechanisms Of Pathogenicity In Familial Cardiomyopathy-Linked Alpha-Tropomyosin Mutations, Saiti Srabonti Halder

Yale Graduate School of Arts and Sciences Dissertations

Hypertrophic Cardiomyopathy (HCM) and Dilated Cardiomyopathy (DCM) are two very divergent diseases which often have poor prognosis and are major causes of sudden cardiac death. In HCM, the left ventricular wall stiffens and thickens, making it difficult for the heart to pump blood efficiently. In DCM, the left ventricular chamber becomes enlarged while the walls become thinner and weaker, being unable to pump blood. When HCM or DCM happens as a result of an inherited mutation, it is said to be familial and can be passed down from one generation to the next. Missense mutations in alpha-tropomyosin (TPM1), a regulatory …

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On Unperformable Plays And The Metaphysics Of The Stage: Hölderlin And Kleist, Netta Sovinsky Apr 2024

On Unperformable Plays And The Metaphysics Of The Stage: Hölderlin And Kleist, Netta Sovinsky

Yale Graduate School of Arts and Sciences Dissertations

This project reads through two German plays from around 1800 that were considered “unperformable” at their time: Hölderlin’s Der Tod des Empedokles and Kleist’s Penthesilea. My work thinks of theatrical “unperformability” as a rebellion against the epistemological and metaphysical frames that were dominating the theater of their time, as well as the public space that this theater was affirming and forming. The plays, I suggest, expose and in fact perform “on stage” the conditions of appearance of the Dramatic stage, which they do not obey – conditions that in Dramatic theater were supposed to be hidden. Those conditions characterize also …

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In Situ Characterization Of Electrochemically Intercalated Two-Dimensional Group Vi Transition Metal Dichalcogenides, Shiyu Xu Apr 2024

In Situ Characterization Of Electrochemically Intercalated Two-Dimensional Group Vi Transition Metal Dichalcogenides, Shiyu Xu

Yale Graduate School of Arts and Sciences Dissertations

Two-dimensional (2D) materials display various exotic structural and electronic phases, with layered transition metal dichalcogenides (TMDs) presenting multiple polymorphs featuring distinct physical and chemical properties. Intercalating alkali metal ions stands out as a highly effective method for inducing structural transformations and adjusting the optical and electrical characteristics of 2D group VI TMDs. The resulting novel metastable phases hold transformative potentials for applications in electronic memories, transport devices, hydrogen gas evolution catalysts, and biological sensors. Despite numerous studies on alkali metal intercalation into 2D VI TMDs, a comprehensive understanding of the mechanistic and microscopic aspects of intercalation-induced phase changes remains elusive. …

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Mechanical And Transcriptional Roles For Primary Cilia During Intracardiac Cushion Endomt, Kathryn Berg Apr 2024

Mechanical And Transcriptional Roles For Primary Cilia During Intracardiac Cushion Endomt, Kathryn Berg

Yale Graduate School of Arts and Sciences Dissertations

The first organ to develop in vertebrates is the heart, a necessary process for all other organ systems that follow. Proper development of the embryonic heart relies on the ability for intracardiac cells to sense and translate complex mechanical forces into transcriptional signals. Failure to do so results in numerous cardiac abnormalities, such as thinned compact myocardium, stunted trabeculations and atrioventricular canal defects. These structural abnormalities are a common occurrence in congenital heart disease (CHD), which affects more than 1% of all live births. Nonetheless, the mechanism by which mechanical forces are generated, sensed, and integrated into cardiac development remains …

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Poetics Of The Letter: Translation And Correspondence In Augusto De Campos And Ana Cristina Cesar, Craig Osterbrock Apr 2024

Poetics Of The Letter: Translation And Correspondence In Augusto De Campos And Ana Cristina Cesar, Craig Osterbrock

Yale Graduate School of Arts and Sciences Dissertations

This dissertation examines the poetics of translation of Augusto de Campos (1931- ) and Ana Cristina Cesar (1952-1983), two of Brazil’s most important poet-translators of the second half of the twentieth century. I argue that their respective poetics of translation can be interpreted as a form of correspondence in which the translator corresponds with the author of the source text and with the potential reader of the target text. The focus of Augusto’s response to the demands of this double correspondence is the “letter” understood as the materiality of the source and target text. His response to the source text …

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Desert Places: Transnational Formations Of Race, Region, And Empire In The Nineteenth-Century Pampas And Prairies, Colin Allen Young Apr 2024

Desert Places: Transnational Formations Of Race, Region, And Empire In The Nineteenth-Century Pampas And Prairies, Colin Allen Young

Yale Graduate School of Arts and Sciences Dissertations

This dissertation asks why, in the long nineteenth century, the desert became a defining American region. As opposed to our modern climatological understanding of desert, nineteenth-century deserts were understood by their settler colonists to be cultural wastelands bereft of “civilization.” By juxtaposing the visual culture of the South American pampas and the North American prairies—two critical hemispheric desert places—I reveal that approaching these grasslands as a shared cultural, political, and artistic zone is essential to writing a more integrated art history of the Americas. Far from being “deserted,” the pampas and the prairies were home to Indigenous and Afro-descendant communities …

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A “Spicy” Molecular Mechanism Of Trpa1 Hyperactivation Conferred By A Disease Mutant And Insights Into C-Terminal Regulatory Components, Avnika Prasad Bali Apr 2024

A “Spicy” Molecular Mechanism Of Trpa1 Hyperactivation Conferred By A Disease Mutant And Insights Into C-Terminal Regulatory Components, Avnika Prasad Bali

Yale Graduate School of Arts and Sciences Dissertations

Roughly one third of Americans suffer from chronic pain and inflammation, yet so far little progress has been made to develop new pain remedies beyond non-steroidal anti-inflammatory agents and opioids, which often harbor deleterious side-effects. The identification and mechanistic analysis of pain-initiating receptors in peripheral nociceptor neurons is therefore an attractive approach to develop new analgesic and anti-inflammatory therapeutics. Transient receptor potential (TRP) ion channels are the largest group of receptors expressed in nociceptor neurons and are capable of transducing noxious thermal and chemical stimuli into cation influx that triggers pain signaling. My thesis work focuses on one such TRP …

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Reading Sonority: Heian Songbooks And The Japanese Poetic Tradition, James Scanlon Apr 2024

Reading Sonority: Heian Songbooks And The Japanese Poetic Tradition, James Scanlon

Yale Graduate School of Arts and Sciences Dissertations

This dissertation examines Heian period kayō “songs'' and their textual medium, fuhon, vernacular “songbooks.” Kayō and fuhon constitute a corpus of vernacular songs as well as a body of texts that inscribe popular banquet and ritual court songs produced at the height of vernacular literary production in the Heian period (ca. 9—13 c.). Historically, fuhon have been regarded as peripheral to the contemporaneous literary milieu, predominantly overlooked as reflections of aural performance. I argue that this view misconstrues fuhon as texts composed orally, instead of as oral texts. Drawing upon an analysis of extant manuscripts and commentaries, I show that …

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Nuclear Quantum Effects And Proton Transfer Mechanisms In Molecular And Solid- Liquid Interface Systems, Benjamin John Guy Rousseau Apr 2024

Nuclear Quantum Effects And Proton Transfer Mechanisms In Molecular And Solid- Liquid Interface Systems, Benjamin John Guy Rousseau

Yale Graduate School of Arts and Sciences Dissertations

Due to their small mass, protons often exhibit non-classical behavior that can dramatically affect chemical processes. For molecular systems, nuclear quantum effects (NQEs) can be accurately described by electronic structure theory within the nuclear electronic orbital (NEO) framework, wherein select nuclei of interest are treated on the same level of ES theory as the electrons. Within the NEO framework, an affordable and systematically improvable method was developed that produces proton affinities and proton densities of the same quality as a highly accurate and expensive method. In addition to affecting ground state properties of molecules, nuclear quantum effects can also dramatically …

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Essays On Positive And Normative Aspects Of Environmental Policy, Mirco Dinelli Apr 2024

Essays On Positive And Normative Aspects Of Environmental Policy, Mirco Dinelli

Yale Graduate School of Arts and Sciences Dissertations

Climate change is one of the main global challenges we face today. It is significant not only because of the size of the impact that a changing climate can potentially have on our lives, but also because of how challenging it is to solve. Economists are often concerned with externalities: when an individual's or group's actions have a positive or negative effect on others, but there is no incentive for the acting group to take the damage or benefit into account. Climate change, unfortunately, has a host of externalities tied to it: At the individual level, I have an incentive …

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Matching Missions To Means: Targeted Resource Allocation In The Non-Profit Sector, Akshaya Suresh Apr 2024

Matching Missions To Means: Targeted Resource Allocation In The Non-Profit Sector, Akshaya Suresh

Yale Graduate School of Arts and Sciences Dissertations

This dissertation addresses the challenge of optimizing resource allocation in the non-profit sector. Non-profit organizations have to make real-time decisions that are not only efficient but also equitable. In many cases, new analytic approaches could allow for better informed, data-driven decision-making. Yet, despite their critical role, these organizations often lack the capacity to tap into these tools to increase their impact. This research attempts to bridge this gap through two applications: the identification of students with reading disabilities and the matching of volunteers to organizations. Chapter 2 critiques the current process for diagnosing reading disabilities among students, highlighting the inefficiencies …

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Single-Cell Perturbation Of Human Accelerated Regions In Neural Stem Cells, Mark Alan Noble Apr 2024

Single-Cell Perturbation Of Human Accelerated Regions In Neural Stem Cells, Mark Alan Noble

Yale Graduate School of Arts and Sciences Dissertations

The evolutionary emergence of the uniquely large and complex human brain isunderpinned by the alteration and expansion of the neural stem and progenitor cell (NSC) pool during development. These modifications are the manifestation of numerous regulatory and genetic changes, many of which have yet to be described. One salient set of candidates consists of ~1500 Human Accelerated Regions (HARs), which are noncoding regions of the genome that have been highly constrained throughout evolution until the human lineage, where a significant number of substitutions occur, indicating divergent functions. I designed a direct-capture Perturb-seq screen repressing 180 HARs with evidence of neurodevelopmental …

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Bodipy As A Chromophore And An Anchor To Metal Oxides For Solar Fuel Applications, Josephine Anne Jayworth Apr 2024

Bodipy As A Chromophore And An Anchor To Metal Oxides For Solar Fuel Applications, Josephine Anne Jayworth

Yale Graduate School of Arts and Sciences Dissertations

To meet current goals for carbon neutral economies it is important to transition to renewable energy sources and storage solutions. Solar radiation is a cheap and abundant source of renewable energy, but it suffers in grid scale applications due to being intermittent and diffuse. Similar to how plants use sunlight to store energy in the form of sugar via photosynthesis, artificial systems can store solar energy in the form of chemical bonds as solar fuels. One such type of artificial system is a water splitting dye sensitized photoelectrochemical cell (WS-DSPEC), which will be discussed throughout this thesis. WS-DSPECs are introduced …

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Characterizations Of Replica-Symmetry In Mean-Field Spin Glasses, Lai Heng Timothy Wee Apr 2024

Characterizations Of Replica-Symmetry In Mean-Field Spin Glasses, Lai Heng Timothy Wee

Yale Graduate School of Arts and Sciences Dissertations

This thesis studies structural properties of mean-field spin glasses in the replica-symmetric phase and establishes their equivalences in a general framework. We give a random projections result that characterizes the distribution of low-dimensional projections of random vectors exhibiting replica-symmetric properties of thin-shell and overlap concentration as approximately random Gaussians. A converse is provided, showing that asymptotically random Gaussian projections imply these hypotheses. This extends and unites several existing results in geometric functional analysis and spin glasses. We then present a new approach to local independence in spin glasses, i.e.~the phenomenon that any fixed subset of coordinates is asymptotically independent in …

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Utilizing Meta-Analytical And Causal Inference Methods To Evaluate The Impacts Of Environmental Risk Factors On Non-Hodgkin Lymphoma, Xiaoting Shi Apr 2024

Utilizing Meta-Analytical And Causal Inference Methods To Evaluate The Impacts Of Environmental Risk Factors On Non-Hodgkin Lymphoma, Xiaoting Shi

Yale Graduate School of Arts and Sciences Dissertations

Non-Hodgkin lymphoma (NHL) is one of the most common hematologic malignancies in the world. Despite substantial efforts to identify causes and risk factors for NHL over the past few decades, the etiology of NHL is largely unclear. The overarching goal of this three-part dissertation is to use different meta-analytical and causal inference methods to identify and evaluate potential environmental risk factors for NHL. For the first project of this dissertation, we conducted an umbrella review to summarize the range, strength, and consistency of all associations between environmental risk factors and NHL reported in published meta-analyses. We identified 85 meta-analyses of …

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Error Mitigation And Detection In Circuit Quantum Electrodynamics Powered By Qnd Measurements, Jacob Charles Curtis Apr 2024

Error Mitigation And Detection In Circuit Quantum Electrodynamics Powered By Qnd Measurements, Jacob Charles Curtis

Yale Graduate School of Arts and Sciences Dissertations

Superconducting cavities coupled to transmon ancillae are a promising platform for fault-tolerant quantum computation. This pairing produces universal control over a long-lived bosonic mode, in whose many levels we encode a logical qubit or physical quantum system, such as the vibrational modes of a molecule. However, unwanted static interactions and spurious couplings to the environment limit the accuracy of computations. In this dissertation, we tackle each of these error sources in turn. Our solutions exploit the ability of the transmon to perform high-fidelity measurements of the cavity mode without disturbing its stored information. First, we present our efforts to reduce …

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Aristotle's Privations, Benjamin Koons Apr 2024

Aristotle's Privations, Benjamin Koons

Yale Graduate School of Arts and Sciences Dissertations

Aristotle’s hylomorphism—his analysis of material substances into form and matter—has seen a resurgence in contemporary metaphysics. Yet Aristotle himself appealed to a third principle of material substances—privation. This is surprising, since substances are supposed to be the paradigmatic beings in Aristotle’s ontology, and yet privations—what a substance should have but does not—seem to be a kind of non-being. Equally surprising, Aristotle also ascribes efficient causality to privations: a privation like the absence of a pilot from the ship can cause a shipwreck. What do privations have to be like to play these kinds of roles in Aristotle’s philosophy? Such roles …

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Structural Insights Into Group Ii Intron Splicing And Retrotransposition, Kevin Chung Apr 2024

Structural Insights Into Group Ii Intron Splicing And Retrotransposition, Kevin Chung

Yale Graduate School of Arts and Sciences Dissertations

Pre-mRNA processing is a critical metabolic step in eukaryotes. RNA transcripts must be spliced, polyadenylated, and capped, among other modifications, to ensure their proper function. Group II introns are an archetypal splicing system that can catalyze their self-excision and retroelements that invade DNA. They provide a window into understanding the evolution of splicing and have played an important role in shaping the eukaryotic genome as the ancestors of spliceosomal introns, telomerases, and non-LTR retrotransposons. Group II introns consist of a well-folded, large-structured RNA that forms a ribonucleoprotein complex with their encoded maturases to carry out splicing and intron integration functions. …

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Quantum Control And Error Correction Of Grid States In A Superconducting Oscillator, Alec William Eickbusch Apr 2024

Quantum Control And Error Correction Of Grid States In A Superconducting Oscillator, Alec William Eickbusch

Yale Graduate School of Arts and Sciences Dissertations

The potential of quantum systems for computation is challenged by decoherence, a process in which the system interacts with its noisy, uncontrolled environment. However, with quantum error correction (QEC), robust quantum computation in the presence of noise is possible. In a QEC encoding, information is stored as non-local correlations in an engineered multi-state, quantum many-body system. One promising encoding is the Gottesman-Kitaev-Preskill (GKP) code, in which logical states are encoded as oscillator grid states. However, ever since the code was envisioned in 2001, its experimental realization had remained out of reach. The most important barrier for realization was the code …

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Motion Correction Strategies In Dynamic Pet, Xueqi Guo Apr 2024

Motion Correction Strategies In Dynamic Pet, Xueqi Guo

Yale Graduate School of Arts and Sciences Dissertations

Dynamic positron emission tomography (PET) is more desirable in oncologic and cardiovascular measurements with tracer dynamics compared with static PET. Parametric imaging can extract more informative physiological parameters from whole-body dynamic PET images using compartmental kinetic modeling. Absolute myocardial blood flow (MBF) estimation from cardiac dynamic PET provides incremental information on heart function that cannot be determined from conventional relative myocardial perfusion imaging. However, during the relatively long time period of dynamic PET scanning, the inevitable subject motion in dynamic PET introduces inter-frame mismatch, seriously impacting parametric imaging and MBF quantification. Additionally, the tracer distribution change across the dynamic frames …

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Quantum Geometry And Topology In Graphene Moiré Superlattices, Chao Ma Apr 2024

Quantum Geometry And Topology In Graphene Moiré Superlattices, Chao Ma

Yale Graduate School of Arts and Sciences Dissertations

Geometry, an old yet vibrant field in mathematics whose name originates from Ancient Greek, signifying “land measurement,” holds profound and expansive applications across a spectrum of disciplines including art, architecture, science, and engineering. Fundamental concepts within geometry, such as vector bundles and connections, curvature and metric, symmetry and topology, serve as indispensable tools for comprehending the physical universe: from the standard model of elementary particles to Einstein’s general theory of relativity, and electromagnetic waves and matter at various scales. Quantum geometry emerges as a set of geometrical principles crucial for understanding the natural world when quantum mechanics dominates the underlying …

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Essays In Gender Economics, Helena Laneuville Teixeira Garcia Apr 2024

Essays In Gender Economics, Helena Laneuville Teixeira Garcia

Yale Graduate School of Arts and Sciences Dissertations

In the first chapter, I identify a gender promotion gap among judges in the state of São Paulo, Brazil, and characterize its labor-demand and labor-supply-related drivers. To do so, I construct a novel dataset that measures characteristics, skills, and observable performance on the job and the process of career advancement. Women take significantly longer to be promoted within the Trial Court and, consequently, acquire less experience with larger court districts. At the end of their career, they are four times less likely than men to reach the Appeals Court. On the labor supply side, women are 14% less likely to …

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Integrated Multiscale Mechano-Biological Study Of Lung And Liver Tissues, Hugh Xiao Apr 2024

Integrated Multiscale Mechano-Biological Study Of Lung And Liver Tissues, Hugh Xiao

Yale Graduate School of Arts and Sciences Dissertations

Tissues and bodily fluids undergo continuous changes as a natural life cycle process. Extracellular matrices (ECMs), which provide structural and biochemical support for the cells, and extracellular fluids (ECFs), which transport nutrients, oxygen, and waste products, exhibit several mechanical properties that can impact cell behaviors. These properties include, for example, fibrillar alignment, density, and stiffness of ECMs, and osmolarity and viscosity of ECFs. These mechano-biological cues can impact cell behaviors and change tissue landscapes. Fibrosis is known for thickened extracellular matrix, which involves many changes in mechanical properties of extracellular environment. There is much to be explored as to how …

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Genetic Background’S Influence On The Pathogenesis Of Spinocerebellar Ataxia Type 1 (Sca1), Victor Hipolito Olmos Apr 2024

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 …

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Quasiparticles And Charge-Parity Switching In Transmon Qubits, Spencer Diamond Apr 2024

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 …

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Histone Regulation Of The Maternal To Zygotic Transition: The Role Of Histone Modifications On Zygotic Genome Activation, Maria De Jesus Benitez Ortiz Apr 2024

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 …

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Interpretable Machine Learning And Causal Inference In Medicine And Public Health, Colleen Elise Chan Apr 2024

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 …

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Labor Supply And Life-Cycle Risk, William Daniel Felipe Giraldo Paez Apr 2024

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 …

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From Efficacy To Implementation: Translating Lifestyle Behavior Interventions Into Routine Breast Oncology Care, Leah Silverman Puklin Apr 2024

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 …

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