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Statistical Methods For Modelling Structures In High-Dimensional Data From Genetics And Genomics, Chang Su Apr 2023

Statistical Methods For Modelling Structures In High-Dimensional Data From Genetics And Genomics, Chang Su

Yale Graduate School of Arts and Sciences Dissertations

With the advancements in genotyping arrays and high-throughput sequencing technologies, the field of genetics and genomics has witnessed a surge in the collection and analysis of high-dimensional data in recent decades. These data, collected from large cohorts of individuals or tissues with heterogeneous cell types, often encompass complex underlying structures. For instance, major variations in genetic variants capture the ancestry background of profiled individuals, and gene co-expression networks encode the biological functions and molecular mechanisms in tissues and cell types. However, the high-dimensionality and biological complexity of these data present challenges for statistical estimation and inference with traditional methods. To …

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The Total Synthesis Of Nenestatin A, Studies Towards The Total Synthesis Of Microansamycin A, And Exploration Of Aminoglycoside Anionic Glycosylation Applicability Using 4-Epi-Vancosamines, Madeline Chellel Frischling Apr 2023

The Total Synthesis Of Nenestatin A, Studies Towards The Total Synthesis Of Microansamycin A, And Exploration Of Aminoglycoside Anionic Glycosylation Applicability Using 4-Epi-Vancosamines, Madeline Chellel Frischling

Yale Graduate School of Arts and Sciences Dissertations

The thesis herein describes a series of synthetic endeavors encompassing different natural product scaffolds and chemical space. In chapter one, I outline the first total synthesis of nenestatin A (10), an isolate featuring the benzo[b]fluorene core found in other atypical angucyclines such as the lomaiviticins and kinamycins. The route development was highly inspired by the synthetic groundwork laid by our laboratory for the lomaiviticin A monomeric unit, utilizing key fragments cyclohexenone (19) and masked quinone (20). Additionally, an adopted radical mediated cyclization furnished the fused ring system following a stereocontrolled aldol addition (59→61). The oxidation state of target nenestatin A …

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The Formation And Evolution Of Planetesimals And Planetary Embryos, Zhongtian Zhang Apr 2023

The Formation And Evolution Of Planetesimals And Planetary Embryos, Zhongtian Zhang

Yale Graduate School of Arts and Sciences Dissertations

Planetesimals and planetary embryos are building blocks of Earth-sized planets. The formation and evolution of these objects are partly recorded by remnants of the early solar system in the form of (primarily) asteroids and our sampling of them through astronomical observations, meteorite collections and some in situ space-craft measurements. To decipher the information recorded in these remnants is critical for understanding planet formation and early solar system processes. In this thesis, I develop theoretical models for the interiors of planetesimals and planetary embryos at various stages of formation and evolution, and combine the model results with meteorite and asteroid observations …

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Visualization Of Infection And Therapies For Sars-Cov-2 Variants Of Concern In Murine Models Of Infection, Kelly Symmes Apr 2023

Visualization Of Infection And Therapies For Sars-Cov-2 Variants Of Concern In Murine Models Of Infection, Kelly Symmes

Yale Graduate School of Arts and Sciences Dissertations

The declaration of the COVID-19 pandemic compelled urgent research into better understanding the causative agent, SARS-CoV-2, and the race for a vaccine and therapeutics for the severely ill. Since its emergence in late 2019, several variants of concern have arisen, characterized in part by their mutations in the spike glycoprotein, that have altered ACE-2 binding efficiency, disease progression and pathogenesis, and viral kinetics. These mutations can also allow for immune evasion from antibodies, highlighting the need to better understand the immune response to infection and a rapid modality to characterize emerging variant pathogenesis and screen potential therapeutics. Here, we introduce …

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Stealth Dark Matter With Lattice Field Theory, Kimmy Kelly Cushman Apr 2023

Stealth Dark Matter With Lattice Field Theory, Kimmy Kelly Cushman

Yale Graduate School of Arts and Sciences Dissertations

This work presents non-perturbative lattice field theory calculations of the low-lying meson and baryon spectrum of the SU(4) gauge theory with fermion constituents in the funda-mental representation, known as stealth dark matter. This strongly coupled theory is an extension of the Standard Model, where the spin-zero baryon is the dark matter candidate. This work constitutes the first milestone in the research program to predict stealth dark matter self-interactions. The focus of this work is on reducing excited state contamination in the single baryon channel by applying the Laplacian Heaviside (LapH) method, as well as projecting the baryon operators into irreducible …

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The Individual Environmental Niche: Drivers, Specialization, And Geometric Configuration, Ben S. Carlson Apr 2023

The Individual Environmental Niche: Drivers, Specialization, And Geometric Configuration, Ben S. Carlson

Yale Graduate School of Arts and Sciences Dissertations

The ecological niche is a central concept for understanding how species will respond to climate and land-use change. Although ecologists traditionally assess niches at the species level, emerging research shows that niche variation below the species level, for example, among individuals and populations, affects many ecological processes, such as population growth rates, community assembly, and ecosystem dynamics. Thus, niche variation may be integral to accurately forecasting biodiversity responses to global change. However, it is largely unknown whether individuals vary in their environmental niches (i.e., niches with axes for environmental conditions such as habitat or land cover) or whether this variation …

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Improving The Coherence Of Superconducting Quantum Circuits Through Loss Characterization And Design Optimization, Suhas Sham Ganjam Apr 2023

Improving The Coherence Of Superconducting Quantum Circuits Through Loss Characterization And Design Optimization, Suhas Sham Ganjam

Yale Graduate School of Arts and Sciences Dissertations

Realizing a practical quantum computer with superconducting qubits requires substantially higher gate fidelities, which necessitates further improvements in the coherence of superconducting quantum circuits. Steady improvements have been made over the past two decades, including substantial exploration into energy relaxation mechanisms in superconducting thin films. However, a comprehensive and quantitative understanding of the relative impact of these mechanisms does not yet exist. In this thesis, I utilize a multimode approach to systematically characterize microwave losses in the quantum regime, with the goals of understanding relaxation-limiting loss mechanisms and improving device coherence through materials, process, and circuit design optimization. Using this …

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Inclusive Hadron Yield Analysis In Small And Mid-Sized Collision Systems At Center-Of-Mass Collision Energy Of 200 Gev Per Nucleon At Star, Tong Liu Apr 2023

Inclusive Hadron Yield Analysis In Small And Mid-Sized Collision Systems At Center-Of-Mass Collision Energy Of 200 Gev Per Nucleon At Star, Tong Liu

Yale Graduate School of Arts and Sciences Dissertations

At extremely high temperature and energy density, the quarks and gluons that make up protons and neutrons become asymptotically deconfined and form a novel state of matter called the Quark-Gluon Plasma (QGP). This state of matter is experimentally created in relativistic heavy-ion collisions, where the high energy density carried by the incoming nuclei produce such a deconfined state.The QGP has been widely confirmed and studied in large collision systems like Au+Au and Pb+Pb, but whether the QGP exists in small systems like $p$+Au, and the dependence of QGP production on the collision system size are still open questions in the …

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Explicit Conformal Blocks, Alex Sandomirsky Apr 2023

Explicit Conformal Blocks, Alex Sandomirsky

Yale Graduate School of Arts and Sciences Dissertations

Conformal field theories (CFTs) are important in their application to critical phenomena,as fixed points in the renormalization group of QFTs, and with their role in the AdS-CFT correspondence. The conformal bootstrap has been a useful tool in carving out the space of allowed CFTs and relies on the computation of four point conformal blocks. Currently, a few specific examples for certain spin configurations are worked out in the literature; I set out to obtain general and explicit expressions for these blocks in three and four dimensions, for arbitrary spins. This is accomplished by working in the embedding space formalism of …

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Computational Investigations Of Solute And Solvent Transport In Nanoporous Desalination Membranes, Brian Andrew Shoemaker Apr 2023

Computational Investigations Of Solute And Solvent Transport In Nanoporous Desalination Membranes, Brian Andrew Shoemaker

Yale Graduate School of Arts and Sciences Dissertations

Solute and solvent transport through porous membranes is critical to important processes in biology and chemical separation. This is readily apparent in reverse osmosis desalination where nanoporous membranes with high permeability to water and excellent rejection of salt ions are utilized to procure clean, safe water from saline sources. Procuring sustainable worldwide access to an abundant supply of properly treated water is an immediate global concern for human health, economic development, and environmental preservation. Reverse osmosis desalination can play a central role in this pursuit by allowing access to the ample reserves of water in oceans and inland brackish sources, …

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Signaling Between Intraepithelial T Cells And Villous Enterocytes In Celiac Disease, Justin Johnson Apr 2023

Signaling Between Intraepithelial T Cells And Villous Enterocytes In Celiac Disease, Justin Johnson

Yale Graduate School of Arts and Sciences Dissertations

Celiac disease (CeD) is a common autoimmune disorder triggered by HLA-DQ2/DQ8-restricted CD4 T cells responding to gluten-derived peptides that have been deamidated by tissue transglutaminase 2 (TG2). These activated CD4 T cells then provide help to B cells that produce IgA antibodies to deamidated gluten peptides (DPG) and TG2. Histologically, the epithelial lining of the small intestinal villi is destroyed by infiltrating cytotoxic T cells (CTLs) that replace the normal resident T cell populations, resulting in villous flattening and absorptive dysfunction. The link between the response of CD4+ T cells to DPGs and the generation, recruitment, and activation of intraepithelial …

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Learning Brain Dynamics With Neural Operators, Antonio Henrique De Oliveira Fonseca Apr 2023

Learning Brain Dynamics With Neural Operators, Antonio Henrique De Oliveira Fonseca

Yale Graduate School of Arts and Sciences Dissertations

Understanding the intricate workings of the brain remains one of science's grand challenges. At its core, the brain operates as a dynamic system, with neural oscillations and coordinated activity patterns enabling integrated cognition. However, modeling these complex dynamics computationally has proven difficult. Traditional models often rely on restrictive assumptions about brain activity properties, limiting their utility. This thesis introduces innovative machine learning frameworks, utilizing neural operator techniques specifically designed for neural data, to model brain dynamics more effectively. Neural operators function as mappings between infinite-dimensional spaces, offering a flexible, data-driven approach to capture the complex spatiotemporal relationships in neural dynamics. …

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Dynamic And Individualized Small-Scale Brain Functional Organization, Wenjing Luo Apr 2023

Dynamic And Individualized Small-Scale Brain Functional Organization, Wenjing Luo

Yale Graduate School of Arts and Sciences Dissertations

Since functional MRI (fMRI) was first introduced as a non-invasive neuroimaging method for imaging brain function, it has been widely used for brain mapping wherein activities in various brain regions are associated with functions in both healthy and patient populations. To reduce noise in fMRI signals and ensure interpretability, the smallest spatial units in fMRI images, the voxels, tend to be grouped into nodes, and the nodes are grouped into networks, usually by applying an atlas defining the nodes. Despite that various parcellation methods have been proposed based on different imaging modalities and criteria, in almost all previous studies, a …

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Engineering Nanomaterials For Advanced, Aqueous−Based Applications: Exploring Physical And Chemical Dynamics With A Focus On Surface Chemistry, Junseok Lee Apr 2023

Engineering Nanomaterials For Advanced, Aqueous−Based Applications: Exploring Physical And Chemical Dynamics With A Focus On Surface Chemistry, Junseok Lee

Yale Graduate School of Arts and Sciences Dissertations

Despite recent advancements in water treatment processes, contaminants of emerging concerns (CECs), such as perfluorinated compounds, endocrine disruptors, pharmaceuticals and personal care products, and pesticides, among others, remain a challenge for conventional treatment processes. To address this, tailored, fit−for−purpose water treatment strategies are needed to meet specific raw water quality and end−user needs. Recently, advancements in engineered materials and processes at the nanoscale hold promise towards improving (or even reimagining) related environmental technologies. Nanoscale engineering and materials have been demonstrated to enable unique properties/processes, including high reactivity, allowing for enhanced adsorption, degradation, and filtration – and thus have significant potential …

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Defining The Function And Therapeutic Potential Of Mutant Ppm1d In High-Grade Glioma, Matthew A. Murray Apr 2023

Defining The Function And Therapeutic Potential Of Mutant Ppm1d In High-Grade Glioma, Matthew A. Murray

Yale Graduate School of Arts and Sciences Dissertations

There is growing evidence that mutations in the PPM1D gene are implicated in the development and malignancy of tumors, specifically for cancers like high-grade gliomas. These mutations enhance the activity of canonical PPM1D functions, causing the dysregulation of the DNA damage response and cell cycle progression. Recently, PPM1D mutations were reported to cause a synthetically lethal interaction to inhibitors targeting the enzyme, NAMPT, which is critical for NAD+ biogenesis. These mutations lead to global DNA hypermethylation, resulting in the epigenetic silencing of the enzyme NAPRT. Importantly, NAPRT loss was linked to NAMPT inhibitor (NAMPTi) sensitization, making it a biomarker for …

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Polymeric Antiscalants For Gypsum Scale Mitigation: Mechanisms And Implication For Membrane Desalination, Julianne Rolf Apr 2023

Polymeric Antiscalants For Gypsum Scale Mitigation: Mechanisms And Implication For Membrane Desalination, Julianne Rolf

Yale Graduate School of Arts and Sciences Dissertations

Water scarcity is one of the biggest threats to humanity, and the global problem is worsening due to population growth, water overuse, pollution, and climate change. Over half of the world’s population suffers from water scarcity at least one month of the year. The problem is further compounded in areas without electricity access. Cape Town’s 2018 “Day Zero” water crisis and Kenya’s 2017 severe drought are indicative of the future. Water conservation alone is not sufficient to meet water demand, especially when power generation is water dependent (e.g., hydropower and fossil fuels). As a result, alternative solutions such as water …

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Uncovering Novel Biological Regulators Of Ribosome Biogenesis, Carson J. Bryant Apr 2023

Uncovering Novel Biological Regulators Of Ribosome Biogenesis, Carson J. Bryant

Yale Graduate School of Arts and Sciences Dissertations

Ribosomes are the complex macromolecular machines which assemble proteins in all forms of life, and their production process is known as ribosome biogenesis (RB). In eukaryotes, RB begins in the nucleolus with the transcription of the pre-ribosomal (pre-r)RNA, which undergoes modification, processing, and assembly into mature ribosomes. Malfunctioning RB can cause severe human diseases including rare developmental disorders called ribosomopathies, as well as cancer. Therefore, better understanding of the human RB machinery and its regulation is imperative for pursuing more effective clinical diagnoses and therapies. In this dissertation, I present work which simultaneously advances the field of RB in the …

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Engineering The Emergent Properties Of Complex Communities, Chang-Yu Chang Apr 2023

Engineering The Emergent Properties Of Complex Communities, Chang-Yu Chang

Yale Graduate School of Arts and Sciences Dissertations

Microorganisms perform critical functions throughout the biosphere and in biotechnology: from the biogeochemical cycle to the production of sourdough. The overwhelming majority of these functions are usually emergent from the collective outcomes of a large number of microorganisms living in a diverse community. Controlling and manipulating the functions of complex microbial communities is a major aspiration in modern biology. However, we lack a quantitative understanding of how often these functions are emergent, and when it occurs, how we can engineer the emergent properties of microbial communities. In this dissertation, I combine computational approaches with experiments using microbial communities to explore …

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Investigating Factors That Influence Food Cue Reactivity In Humans, Emily Elizabeth Perszyk Apr 2023

Investigating Factors That Influence Food Cue Reactivity In Humans, Emily Elizabeth Perszyk

Yale Graduate School of Arts and Sciences Dissertations

The 21st century rise in obesity coincides with the increased prevalence of palatable, energy-dense foods and the ubiquitous cues signaling their availability. Food cue reactivity refers to the responses to these cues – such as increased salivation, brain activity, or the cognitive experience of craving – that become conditioned through prior consumption. Food cue reactivity is highly predictive of food intake and body weight; however, the mechanisms underlying risk are poorly understood. The overarching goal of this dissertation is to investigate factors that influence food cue reactivity in humans. Over three experiments, I examined factors related to the individual or …

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Investigation Of Hydrocarbyl Migration To Dinitrogen, Samuel Marsh Bhutto Apr 2023

Investigation Of Hydrocarbyl Migration To Dinitrogen, Samuel Marsh Bhutto

Yale Graduate School of Arts and Sciences Dissertations

This thesis details the preparation, characterization, and reactivity of iron(I) hydrocarbyl complexes for the exploration of hydrocarbyl migration to N2 at formally iron(IV) centers. While the migratory insertion into CO is a well-established reaction step, the corresponding reaction with isoelectronic and isolobal N2 has not been reported. Chapter 1 describes the binding of N2 to transition metal centers. Methods of characterization and measurements of N–N bond weakening upon coordination are discussed. The most commonly observed binding modes of N2 and the corresponding effects on weakening of the N2 ligand are explained. Additionally, the various routes of N2 functionalization to form …

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Animation Before Anime, Jason Cody Douglass Apr 2023

Animation Before Anime, Jason Cody Douglass

Yale Graduate School of Arts and Sciences Dissertations

This dissertation asserts that animated media circulating into, within, and away from Japan during the mid-20th century stand to tell us much about how such texts shaped, and were shaped by, the cultural forces of class, gender, age, and race. The four chapters traverse intersecting, albeit disparate planes. Each uses a distinct critical lens to demonstrate how understudied archival materials can help to resolve some of the most pressing questions currently raised within animation studies. Chapter 1 focuses upon issues of socioeconomic class, forging a vital link between functional animation, such as television advertisements, and working-class animators who developed their …

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Uncovering The Function And Molecular Mechanism Of Mili In Mouse Germline Stem Cells, Yuqi Wang Apr 2023

Uncovering The Function And Molecular Mechanism Of Mili In Mouse Germline Stem Cells, Yuqi Wang

Yale Graduate School of Arts and Sciences Dissertations

Mouse germline stem cells (GSCs) play critical roles in spermatogenesis by self-renewal and differentiation into daughter spermatogonia. Like other stem cells, the proper functions of mouse GSCs are governed by a delicate regulatory network. PIWI proteins belong to the Argonaute protein family, and they act with piRNAs to control gene expression through transcriptional and post-transcriptional regulation. Extensive research has demonstrated the vital functions of PIWI proteins in germline development, stem cell maintenance, and transposon control. Despite this, the role of PIWI in mammalian GSCs remains largely unknown. MILI is one of three murine PIWI proteins. Recent study has discovered that …

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The Functional Effects Of Tree And Shrub Mycorrhizal Associations On Soil Organic Matter Dynamics In Forests, Elisabeth B. Ward Apr 2023

The Functional Effects Of Tree And Shrub Mycorrhizal Associations On Soil Organic Matter Dynamics In Forests, Elisabeth B. Ward

Yale Graduate School of Arts and Sciences Dissertations

Plant-fungal associations can strongly influence the composition, persistence, and turnover of soil organic matter in forests. The prevailing framework for understanding these relationships is through the relative abundance of tree mycorrhizal functional types, the vast majority of which associate with arbuscular (AM) and/or ectomycorrhizal (EcM) fungi. Differences in functional traits and ecosystem characteristics between AM and EcM trees have generated immense interest in assessing the ecosystem biogeochemical effects of tree mycorrhizal dominance within and among forest biomes to improve understanding of patterns in soil carbon and nitrogen pools and how they might respond to factors of global change. Yet, forests …

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Identifying The Role And Mechanism By Which Gdf15 And Fgf21 Regulate Glucose Homeostasis, Zongyu Li Apr 2023

Identifying The Role And Mechanism By Which Gdf15 And Fgf21 Regulate Glucose Homeostasis, Zongyu Li

Yale Graduate School of Arts and Sciences Dissertations

As a highly utilized substrate in most cells of the body, glucose homeostasis is strictly regulated by a variety of mechanisms. Under physiological conditions, blood glucose is sophisticatedly maintained by temporal coordination of whole-body glucose uptake, absorption from the digestive system, and endogenous glucose production from the liver and kidney. However, the factors and mechanisms by which plasma glucose is regulated under pathological conditions are not clearly understood. In this Ph.D. thesis, we interrogated the role of two cytokines, Growth Differentiation Factor 15 (GDF15) and fibroblast growth factor-21 (FGF-21), in regulating glucose output under extreme metabolic stress. By employing two …

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Price Experimentation And Plan Design For Digital Firms, Ian Nicholas Weaver Apr 2023

Price Experimentation And Plan Design For Digital Firms, Ian Nicholas Weaver

Yale Graduate School of Arts and Sciences Dissertations

This thesis provides insights for firms on how to price and design product plans by combining experimentation and machine learning methods. In Chapter 1, we use multi-armed bandits from reinforcement learning to better inform firms on how to price experiment when faced with an unknown demand curve. Chapters 2 and 3 focus on plan design for a subscription based firm. In Chapter 2, we run a field experiment to determine the optimal amount of free offered by a firm, while in Chapter 3 we perform a content-level analysis using machine learning, which helps a firm choose a more appropriate plan …

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Messages, Secrets, And Catalysts In Population Protocols With Probabilistic Scheduling, Talley Amir Apr 2023

Messages, Secrets, And Catalysts In Population Protocols With Probabilistic Scheduling, Talley Amir

Yale Graduate School of Arts and Sciences Dissertations

The population protocol model introduced by Angluin et al. in 2006 offers a theoretical framework for designing and analyzing distributed algorithms among limited-resource mobile agents. The original model elegantly abstracts computation in complex systems of simple devices. However, some of these simplifications detract from the pragmatism of the theory in properly modeling real-world systems. In this work, we study various adaptations of the original population protocol model that are inspired by the networks that these algorithms aim to simulate. We focus on three such modifications to the model. First, we consider the separation of agent memory into two components: an …

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Apoptosis Recognition Receptors Regulate Skin Tissue Repair In Mice, Olivia Justynski Apr 2023

Apoptosis Recognition Receptors Regulate Skin Tissue Repair In Mice, Olivia Justynski

Yale Graduate School of Arts and Sciences Dissertations

The skin is an essential barrier against the outside world, and must withstand constant exposure to damage from the environment. When this barrier is broken, it must be repaired quickly and effectively in order to prevent infection and restore function. The skin’s ability to heal wounds is vital for human health, and insufficient wound treatment is a major clinical problem, contributing to decreased quality of life and increased healthcare costs for many patients due to chronic or non-healing wounds. The complex process of wound healing involves the coordination of many cell types and signals, which were here investigated using single-cell …

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Peptide Nucleic Acids And Crispr-Cas9: Mechanisms And Rational Applications For Gene Editing Systems, Nicholas George Economos Apr 2023

Peptide Nucleic Acids And Crispr-Cas9: Mechanisms And Rational Applications For Gene Editing Systems, Nicholas George Economos

Yale Graduate School of Arts and Sciences Dissertations

In the past decade, gene editing technology development has exploded across life sciences fields with promise to advance research, agriculture, industry, and the development of curative human therapeutics. Initially lead by CRISPR-associated nucleases and their ability to induce targeted DNA double-strand breaks (DSBs), the gene editing toolbox continues to grow as new technologies emerge and improve. While the goal of these tools is to precisely manipulate DNA sequences in living cells, not all modifications are created equal. Small or large deletions and insertions, precise nucleotide changes, and combination approaches each entail different challenges and require cooperation with endogenous repair pathways …

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"Topographies Of Memory": Understanding State Violence Through Memorialization Practices, Morgan Faye Galloway Apr 2023

"Topographies Of Memory": Understanding State Violence Through Memorialization Practices, Morgan Faye Galloway

Yale Graduate School of Arts and Sciences Dissertations

How do the politics of participation in memorialization processes vary across different forms of memory sites, and what do these processes reveal about participants’ understandings of state violence? Drawing on ethnographic and archival methods to study processes to memorialize victims of two cases of state violence in the U.S., I show that memorialization has political implications for the communities involved. First, I analyze the politics of participation of the Bainbridge Island Japanese American Exclusion Memorial (BIJAEM), a permanent, site-specific memorial to the first victims of forced removal and exclusion of Americans of Japanese descent during World War II. Second, I …

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Essays On Labor Economics, Lucas Finamor Apr 2023

Essays On Labor Economics, Lucas Finamor

Yale Graduate School of Arts and Sciences Dissertations

Labor earnings account for almost the totality of household earnings for most families. In the United States in 2019, salaries and wages correspond to 68.3% of the total income reported to the Internal Revenue Service. Labor market choices are dynamic decisions often chosen in an environment with substantial uncertainty. Various risks are associated with and influence labor market choices. Business cycle fluctuations can have long-lasting effects, particularly when hitting individuals in key stages of their professional careers. During their time in the labor market, individuals are exposed to considerable employment, productivity, and health shocks. Even after retirement, individuals continue to …

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