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Improving Genetic Diagnostics And Developing Gene Therapies In Rare Muscle Diseases, Kaiyue Ma

Yale Graduate School of Arts and Sciences Dissertations

The journey towards finding a cure for rare disease patients is hindered by two significant obstacles: the challenge of obtaining a definitive diagnosis and the difficulty in accessing effective treatment. This dissertation research aims to address both issues in rare muscle diseases. Firstly, a highly adaptable workflow called Saturation Mutagenesis-Reinforced Functional assays (SMuRF) was developed to enhance variant interpretation and aid in clinical decision-making. To validate its utility, SMuRF was applied to a group of rare diseases called dystroglycanopathies, which are caused by mutations in enzymes involved in alpha-dystroglycan glycosylation, including FKRP and LARGE1. Over 99.9% of all possible single …

Nuclear Spectroscopy Of Heavy Nuclei In The Shell Model Monte Carlo Method, Sohan Vartak

Yale Graduate School of Arts and Sciences Dissertations

As a strongly interacting finite-size quantum many-body system, the atomic nucleus provides a captivating arena for studying a multitude of phenomena. This thesis explores applications of the shell model Monte Carlo (SMMC) method, a powerful approach to investigate heavy nuclei ($A \sim 150$), where direct diagonalization is infeasible due to the rapid growth of the model space. The SMMC enables the use of standard Monte Carlo techniques to calculate ground state, statistical, and collective properties of nuclei. In this work, we refine a recently developed method for estimating low-lying excitation energies. This method is based on the imaginary time correlation …

A Multidisciplinary Approach With Dogs As The Model Organism To Identify Whole-Genome Breed-Specific Genotypes Potentially Relating To Human Complex Traits, Zicheng Li

Yale Graduate School of Arts and Sciences Dissertations

Background: Domestic dogs (Canis lupus familiaris) share more than 300 common diseases and similar spontaneous disease development characteristics with humans, making them an excellent animal model to study human heritable diseases. Besides, dogs as a model organism also have been favored for mapping complex traits that are hard to map in humans benefiting from drastically different phenotypes and limited genetic heterogeneity across breeds as results of intensive artificial selection. In light of previous studies that profiled breed-specific traits or used genome-wide association studies (GWAS) to refine loci associated with characteristic morphological features in dogs, the field has gained tremendous genetic …

Peripheral Immune Signatures Of Fibrotic Lung Diseases, Amy Zhao

Yale Graduate School of Arts and Sciences Dissertations

Fibrotic lung diseases constitute a heterogeneous group of disorders that cause scarring of the lung parenchyma, making breathing difficult for patients, and affect an estimated 300,000 people in the United States alone. These diseases may have either “intrinsic” or “extrinsic” immune etiologies. A subset of these fibrotic lung diseases, like Idiopathic Pulmonary Fibrosis (IPF; intrinsic) and Fibrotic Hypersensitivity Pneumonitis (FHP; extrinsic), can often be difficult to distinguish due to their similar symptoms, pulmonary function tests, and radiographic and histologic findings. However, their immune drivers, prognoses, and treatments are distinct; thus, accurate diagnosis of the fibrotic lung disease subtype is essential …

Manipulating And Measuring States Of A Superfluid Optomechanical Resonator In The Quantum Regime, Yiqi Wang

Yale Graduate School of Arts and Sciences Dissertations

Quantum optomechanics describes utilizing optics to precisely manipulate and read out the motional degrees of freedom of a mechanical oscillator. If the mechanical oscillator is very weakly coupled to its environment, then the optomechanical interaction can be used to control the state of the mechanical oscillator in a quantum way. Applying these systems to advanced sensing techniques has inaugurated experiments on dark matter searches, gravitational wave detection, quantum gravitational phenomena tests, and sensing beyond the standard quantum limit. I am motivated by asking: “What is the largest and most tangible object to reveal purely quantum phenomena?” In addition, I seek …

Investigating Stem Cell Chromatin Organization And Oncogenic Tissue Morphogenic Change Through Intravital Microscopy, Sangwon Yun

Yale Graduate School of Arts and Sciences Dissertations

Tissue architecture is predicated on actively maintained cellular equilibrium. Loss of homeostatic tissue organization is a hallmark of epithelial derived malignancy. In the following studies, we attempt to understand the principles governing cell behavior in a regenerative tissue, the skin epidermis, under homeostatic conditions and during oncogenic expression. Epidermal cells undergo continual proliferation and differentiation, navigating drastic changes in gene expression and chromatin architecture during identity transition from stem to differentiated. However, when and where genome reorganization occurs continues to be an arena of active investigation. We developed a high-throughput, quantitative pipeline that enabled us to longitudinally measure chromatin compaction …

Who Governs Schools?: Alienation And Participatory Democracy In New Haven Public Education, Alexander Kolokotronis

Yale Graduate School of Arts and Sciences Dissertations

Scholars, policymakers, and theoreticians have long debated the purpose of education and schooling. For all the articulations of what schools reproduce and what should be their purpose, political theorization rarely departs from what is endemic to schools and has long been reproduced by them: alienation. Whatever the stated or longed for purposes of schooling, these missions cannot be achieved if students, teachers, and other constituents of schools are alienated within the labor process of schooling. Thus, this dissertation asks: What form of political agency enables the redress of the entwined alienation of teachers and students in schools? What are its …

Learning And Decision Making Across Domains, Chelsea Yi Xu

Yale Graduate School of Arts and Sciences Dissertations

Rewards and punishments motivate human behavior and guide learning and decision-making processes. Rewarding or punishing feedback leads to updating of our expectations, or subjective values, associated with specific objects or experiences. The construction of subjective value is multi-faceted and can be influenced by various factors, including context, uncertainty, and timing. Many previous studies have predominantly focused on the domain of either rewards or punishments, leaving a significant gap in the literature. Furthermore, these studies have primarily been conducted in the realm of monetary decision making, failing to capture the diverse range of real-life decision outcomes that include diverse categories and …

Specters Of Degradation: Poverty And Uplift In Modern Political Thought, Chris Anthony Chambers

Yale Graduate School of Arts and Sciences Dissertations

This dissertation traces the imprint of Adam Smith on modern political theories of poverty and uplifting the poor to provide an original account of the surprising synergies between conservative, liberal, and radical perspectives on redressing poverty. Offering the first manuscript-length study of poverty and the poor in the history of political thought since the 2000s, it examines how claims about the degradation of the poor have paradoxically animated while limiting ideas of uplift and perfectibility. I show how, by focusing on the moral condition of the poor and effects of poverty, conservatives, liberals, and radicals alike reproduced hateful stereotypes about …

Semi-Inclusive Measurement Of The Shared Groomed Momentum Fraction Of Jets In Au+Au Collisions At Star, Daniel B. Nemes

Yale Graduate School of Arts and Sciences Dissertations

Jet quenching is one of the main signals used to investigate the properties of a quark-gluon plasma (QGP). Besides energy loss, jet quenching can also manifest itself in the modification of jet substructure. This thesis focuses on using STAR data to measure the substructure observable zg, a result of SoftDrop grooming, which probes the physics of the first hard splitting of a hard-scattered parton. As opposed to previous measurements, this thesis explores employing a semi-inclusive approach to measure zg, selecting candi- date jets found within the recoil region of a high transverse momentum trigger particle. Requiring a high transverse momentum …

Statistical Methods In High-Throughput Biomedical Data With Application To Precision Medicine, Yunqing Liu

Yale Graduate School of Arts and Sciences Dissertations

Precision medicine has emerged as a critical approach in healthcare due to its potential to revolutionize patient care. Traditional medical practices often adopt a one-size-fits-all approach, treating patients based on generalized guidelines. However, individuals exhibit significant variations in their genetic makeup, lifestyle factors, and environmental exposures. Precision medicine recognizes and leverages these differences to deliver personalized treatment plans tailored to each patient's unique characteristics. Recent technological advancements have facilitated the generation of high-throughput data, such as single-cell RNA sequencing (scRNA-seq) data, spatial transcriptomics (ST) data, locomotor activity assays measuring behavior, which offers the potential to the development of precision medicine. …

The Role Of Dietary Fats In Driving Atherosclerosis, Zenan Wang

Yale Graduate School of Arts and Sciences Dissertations

Cardiovascular diseases (CVDs) are the number one killer of people worldwide, of which coronary heart disease, which is mainly due to atherosclerosis, is the main contributor to death. Nonetheless, the etiology of atherosclerosis remains poorly understood. It is universally accepted that dietary fat influences atherosclerosis, however, the role of specific fats is not well-understood. Despite the widely-held perception that saturated fats drive atherosclerotic CVDs while monounsaturated fats are protective, there have been numerous studies from human and mice that do not fit with this prevailing narrative. Thus, despite the importance of dietary fats in CVDs, the exact effects remain controversial …

Many-Body Physics With A Ultracold Uniform Fermi Gas, Yunpeng Ji

Yale Graduate School of Arts and Sciences Dissertations

Ultracold atomic gases, traditionally produced in harmonic traps, have been a successful platform in studying many-body problems. In recent years, the realization of homogeneous quantum gases in optical box potentials has opened up new opportunities to study complex problems without the complications arising from the density inhomogeneity, and allows for more direct comparisons with theories. In this thesis, we present the production and the study of a homogeneous Fermi gas consisting of Lithium-6 atoms. We begin by examining the experimental setup for cooling and trapping atoms, with a particular emphasis on how the box trapping potential is implemented. We then …

Computational Study Of The Mechanism Of Attention In Cortical Information Coding, Xiang Wang

Yale Graduate School of Arts and Sciences Dissertations

The animals’ visual perception of natural scenes is influenced by both the external condi-tions of the environment and the internal states. External conditions include the contrast of the stimulus, the crowding of distractors and the complexity of visual features. Internal states include the level of arousal, the deployment of attention, and the goal of behavior. An important and extensively studied internal state is selective attention, which is thought to be critical in solving visual perception problems by increasing the saliency of the attended ob-jects against the background. Electrophysiological studies have indicated attentional modu-lation of single neurons along the hierarchy of …

A New View Of Galaxy Morphology, Timothy Blake Miller

Yale Graduate School of Arts and Sciences Dissertations

A galaxy’s morphology provides crucial constraints on its formation history. Most studies rely on forward modeling procedure utilizing the S\ersic profile to measure morphological parameters and focus on the half-light radius of galaxies measured at optical wavelength. In this P.hD I investigated how common assumptions made when measuring galaxy structure bias the interpretation. First I consider the size-mass distribution using the radii that contain 20% and 80% of the light, as opposed to the traditional half-light radius. We find qualitatively different relations and suggest that the 20% radius is related to the star-formation history of galaxies while the 80% radius …

Multi-Scale Gene Regulation Analysis With Chip-Seq And Beyond, Jiahao Gao

Yale Graduate School of Arts and Sciences Dissertations

Regulation of gene expression is one of the most important and fundamental aspects of biological systems. The intricate regulation could be observed in different aspects, including the variations in individual genes, dynamic interactions between multiple genes, and complicated regulatory relationships between expression and other properties such as methylation level. Therefore, studying gene regulation at all these multiple scales is crucial. Transcription factors (TFs) are a special group of proteins that recognize specific DNA sequences and control gene expression by DNA binding. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) had been developed to identify genome-wide protein–DNA interactions. It has become the standard …

Probing Diverse Biological Systems And Their Hydration Shells By Modeling Chiral Sum Frequency Generation Spectroscopy, Daniel Konstantinovsky

Yale Graduate School of Arts and Sciences Dissertations

All biological processes occur in aqueous solution. Water dictates biomolecular structure, is responsible for a large portion of the free energy of ligand binding, and participates structurally in protein-protein interactions. However, few experimental techniques can probe the biomolecular hydration shell and its diverse environments. Chirality-sensitive vibrational sum frequency generation spectroscopy (chiral SFG) is a powerful technique that probes hydration shell water. The work presented here clarifies the conditions required for a chiral SFG signal to emerge, identifies the water immediately neighboring a biomolecule as the source of the aqueous chiral SFG signal, and investigates the interaction between biomolecules and their …

Exploiting Dna Repair Deficiencies In Cancer To Develop And Characterize Novel Therapeutics, Sateja Paradkar

Yale Graduate School of Arts and Sciences Dissertations

Genomic instability is one of the hallmarks of cancer, which underlies cancer development and progression. This DNA repair vulnerability presents cancer researchers with a therapeutic opportunity. Targeted therapies designed to overwhelm DNA repair pathways in cancer have proven largely effective as anti-cancer treatments. However, there are currently three major issues with their widespread use in cancer. Firstly, for cancers such as glioblastomas (GBMs), there have been no targeted therapies approved for decades. Secondly, for most targeted therapies there is an incomplete understanding of their precise mechanism of action, which limits their clinical utility. Thirdly, cancers develop resistance to most targeted …

Error Detection In Bosonic Circuit Quantum Electrodynamics, James David Teoh

Yale Graduate School of Arts and Sciences Dissertations

Any useful quantum computer must be robust to errors on the individual qubits. This means a quantum algorithm can still reliably give the correct answer despite the qubits suffering from decoherence. Quantum error correction provides a means for achieving this, by encoding logical qubits redundantly in many additional physical qubits and/or additional energy levels. In the presence of errors the logical information is still preserved, but this remains a monumentally difficult task to achieve in practice. But what can we do with quantum error detection? Rather than trying to recover from a quantum error we instead reset qubits that are …

Yale Medicine Magazine Autumn 2023, Issue 171, Yale University. School Of Medicine

Yale Medicine Magazine - alumni bulletin and magazine

This is the Autumn 2023 issue of Yale Medicine Magazine, issue 171. Prepared in cooperation with the alumni and development offices at the School of Medicine. Earlier volumes are called Yale School of Medicine alumni bulletins, dating from v.1 (1953) through v.13 (1965) and Yale Medicine: alumni bulletin of the School of Medicine, v.1 (1965) through v. 52, no.1. (Autumn 2017).

Commercial Bank Examination Manual: Section 3300.1, Federal Reserve System: Board Of Governors

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No abstract provided.

Programme Timeline For Cyprus, European Stability Mechanism

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No abstract provided.

Material Loss Review Of Silicon Valley Bank, United States: Deparment Of The Treasury: Office Of Inspector General, United States: Consumer Financial Protection Bureau

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No abstract provided.

Lessons For The Discount Window From The March 2023 Bank Failures, Susan Mclaughlin

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No abstract provided.

Report Of The Expert Group On Banking Stability 2023: The Need For Reform After The Demise Of Credit Suisse, Switzerland: Federal Department Of Finance

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No abstract provided.

Lessons Learned: Raghuram Rajan, Matthew A. Lieber

Journal of Financial Crises

Raghuram Rajan, a University of Chicago professor of economics and finance, served as director of research at the International Monetary Fund (IMF) from 2003 to 2006. In 2005, Rajan warned very publicly of the risks of a financial crisis. Following his tenure at the IMF, Rajan served as chief economic adviser to India’s Finance Ministry and governor of the Reserve Bank of India. An expert on financial institutions and their effects on economic growth and development across countries, Rajan was recognized as a fellow of the American Academy of Arts and Sciences in 2009. He is co-author of Saving Capitalism …

2021 Special Drawing Rights Allocation—Ex-Post Assessment Report, International Monetary Fund

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No abstract provided.

Differences In Predicted Risk Of Mortality After Coronary Artery Bypass Graft Between Black And White Patients With Identical Clinical Profiles Using The Society Of Thoracic Surgeons Calculator: An In-Silico Cohort Study, Kiara Marmolejos

Yale School of Medicine Physician Associate Program Theses

Abstract/Summary:

Background: “The Society of Thoracic Surgeons mortality risk calculator”, which includes a race variable, is recommended for estimating Short- term (30 day) predicted risk of mortality after isolated coronary artery bypass graft, with a risk estimate of 3-4% stratifying patients into intermediate risk, a risk estimate above 5% stratifying patients into high risk for surgery and a risk estimate above 8% stratifying patients into the very high-risk category. We compared differences between Black and White individuals in Society of Thoracic Surgeons-predicted risk of mortality across various plausible risk factor combinations with the aim of evaluating if using the predictive …

Narrative Therapy And Quality Of Life In Functional Neurological Disorder, Amber Wilder

Yale School of Medicine Physician Associate Program Theses

Functional Neurological Disorder is a severely disabling and stigmatized condition in which motor or sensory neurological symptoms cannot be attributed to a known neurological condition and are considered to be psychological in nature. Cognitive behavioral therapy improves depression and neurological symptoms for some patients, but many do not respond to therapy, and treatment adherence is extremely low. Narrative therapy is a psychotherapeutic model based in reframing one’s life story, and it is associated with decreased self-stigma and improved treatment adherence and engagement, but it has not been studied in Functional Neurological Disorder. In this randomized controlled trial, we will compare …

Frequently Asked Questions (Faq) Credit Suisse, Switzerland: Federal Department Of Finance

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No abstract provided.