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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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Mapping And Functional Characterization Of Hox Gene Expression Patterns In Human Normal Tissue And Solid Tumors, Vadim Kurbatov Apr 2024

Mapping And Functional Characterization Of Hox Gene Expression Patterns In Human Normal Tissue And Solid Tumors, Vadim Kurbatov

Yale Graduate School of Arts and Sciences Dissertations

HOX genes, fundamental in directing embryonic development, are implicated in the spatial organization and functional differentiation of tissues. Their influence, traditionally investigated during early developmental stages, has been noted in a wide variety of malignant processes, albeit at a single gene level in the context of individual cancer types. Given that the HOX genes represent a complex and interrelated network, a unified model evaluating the role of the entire set of HOX genes in cancer has not yet been achieved. Similarly, an overarching model that considers HOX gene patterns in multiple cancer types is absent. This study aims to discover …

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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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Deriving Cell And Gene Dynamics From Single-Cell Omics Data, Rihao Qu Apr 2024

Deriving Cell And Gene Dynamics From Single-Cell Omics Data, Rihao Qu

Yale Graduate School of Arts and Sciences Dissertations

Single-cell sequencing techniques have revolutionized our understanding of cellular diversity within tissues and organs. Typically, single-cell data is preprocessed into a feature-by-cell count matrix, where feature values represent gene expression, chromatin accessibility, protein levels, etc. In the realm of computational analysis, cells are conceptualized as points in a high-dimensional feature space. Under distinct conditions or due to experimental perturbations, specific cellular states may exhibit differential abundance. This can be detected by comparing cell density distributions within the feature space. In Chapter 1, we present a novel computational framework by employing a random-walk-based local two-sample test. This approach enables multiscale, cluster-free, …

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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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Neutrophil Heterogeneity And Transmigration: Decoding Molecular Profiles Through Multi-Omic Analysis And In Vitro Mimicry Of The Venular Wall, Laura C. Morales Apr 2024

Neutrophil Heterogeneity And Transmigration: Decoding Molecular Profiles Through Multi-Omic Analysis And In Vitro Mimicry Of The Venular Wall, Laura C. Morales

Yale Graduate School of Arts and Sciences Dissertations

Neutrophils are crucial innate immune cells that comprise about 50-70% of the white blood cell population in the human peripheral circulation. These polymorphonuclear leukocytes play a pivotal role in the innate immune system, acting as the primary line of defense against pathogens and facilitating tissue repair. Neutrophils exhibit a diverse repertoire of cytotoxic mechanisms to eliminate offending pathogenic agents and promote the resolution of inflammation. These include phagocytosis, degranulation, generating reactive oxygen species, and forming neutrophil extracellular traps, underscoring their versatility in host defense. A critical aspect of neutrophil functionality is their capacity to infiltrate sites of injury or infection, …

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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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Expressed Artificial Proteins That Induce Degradation Of The Platelet-Derived Growth Factor Beta Receptor, Emily Branham Apr 2024

Expressed Artificial Proteins That Induce Degradation Of The Platelet-Derived Growth Factor Beta Receptor, Emily Branham

Yale Graduate School of Arts and Sciences Dissertations

Targeted protein degradation (TPD) is a rapidly advancing field with diverse applications spanning from fundamental research to therapeutic interventions. With considerable opportunity for scientific creativity, emerging degradation strategies promise to expand the reach of this field to challenging targets that often elude conventional, small molecule-based degraders. Of particular interest in this report, transmembrane (TM) proteins represent more than half of all drug targets, yet their intrinsic properties present challenges for standard degradation approaches. Here, we describe a novel genetic approach to TPD, presenting the first example of expressible protein degraders: traptamer-based targeting chimeras (TRAPTACs). As their name implies, these innovative …

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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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Business Groups And Misallocation: Theory And Evidence From Chaebols, Jihoon Sung Apr 2024

Business Groups And Misallocation: Theory And Evidence From Chaebols, Jihoon Sung

Yale Graduate School of Arts and Sciences Dissertations

I study the role of business groups - collections of firms owned by a single family - in determining factor misallocation and aggregate productivity. One might expect that business groups improve allocative efficiency because profit-maximizing owners can allocate resources efficiently across their firms. Surprisingly, using evidence from Korea, an economy wherelarge business groups (chaebols) are prominent, I find the contrary: business groups appear to worsen misallocation. In the first chapter, I describe the history and institutional details of chaebols. In the second chapter, I present the empirical findings. I show, using firm-level data with business group ownership information, that factor …

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Engineering Polymeric Nanoparticles For Intra-Amniotic And Intravenous In Utero Delivery, Anna Lynn Apr 2024

Engineering Polymeric Nanoparticles For Intra-Amniotic And Intravenous In Utero Delivery, Anna Lynn

Yale Graduate School of Arts and Sciences Dissertations

Fetal therapy is a rapidly expanding field that provides opportunities to treat or prevent congenital diseases early in the process of fetal development. Prior studies suggest that polymeric nanoparticles (NPs) are a safe, tunable, and effective vehicle for in utero delivery of therapeutic agents via administration into the amniotic fluid space. Previous work has focused on the feasibility of using poly(lactic-co-glycolic acid) (PLGA) NPs, as well as viral vectors and lipid NPs, for in utero delivery. Modifications to the core polymer and surface chemistry of NPs are known to be key in modulating the performance of NPs in various biological …

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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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Maternal And Paternal Migration And Children’S Human Capital, Siuyuat Wong Apr 2024

Maternal And Paternal Migration And Children’S Human Capital, Siuyuat Wong

Yale Graduate School of Arts and Sciences Dissertations

International migration opportunities improve earnings capacity, but can also create parental separation from children. The net effect of migration on children depends on the relative importance of money and parental presence in determining a child's human capital development, which parent migrates, and at what age they separate from the child. These considerations in turn affect whether, when, and who migrates. I estimate a dynamic model of migrant households with an embedded age-specific child education production function by conducting a panel survey of Filipino migrants and combining it with newly assembled administrative data from the Philippines Department of Education and the …

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Mechanisms And Functions Of Lipodystrophy In Dermal Fibrosis, Elizabeth Ann Caves Apr 2024

Mechanisms And Functions Of Lipodystrophy In Dermal Fibrosis, Elizabeth Ann Caves

Yale Graduate School of Arts and Sciences Dissertations

The skin is the largest organ in the human body and acts as a barrier between the inside and outside environments. A significant function of the skin is to maintain its structural integrity through extracellular matrix protein (ECM) homeostasis. Tissue fibrosis is characterized by a failure of ECM homeostasis, resulting in the accumulation of ECM proteins in healthy tissue. Systemic sclerosis is an autoimmune disease in which fibrosis develops throughout the body in organs such as the heart, lungs, and skin. Interestingly, during skin fibrosis, resident lipid-filled, mature adipocytes are depleted in humans and mice concomitant with ECM expansion. However, …

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Uncovering A Critical Role For Calmodulin In Calcium-Dependent Regulation Of The Nociceptor Trpa1, Justin Sanders Apr 2024

Uncovering A Critical Role For Calmodulin In Calcium-Dependent Regulation Of The Nociceptor Trpa1, Justin Sanders

Yale Graduate School of Arts and Sciences Dissertations

Transient receptor potential (TRP) channels are sensory receptors expressed throughout the peripheral nervous system that help shape how we respond to our environment. TRPA1 has been identified as a key component in the transition from acute to chronic pain and inflammation making it a prime target for development of novel analgesics. Calcium has been shown to regulate TRPA1 by rapidly potentiating channel activity followed by rapid desensitization. While the effects of calcium on TRPA1 activity have been well-described, the mechanisms governing these calcium effects have been difficult to elucidate. Work described within this thesis details the discovery of a novel …

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An Epigenetic Timer Regulates The Transition From Cell Division To Cell Expansion During Arabidopsis Petal Organogenesis, Ruirui Huang Apr 2024

An Epigenetic Timer Regulates The Transition From Cell Division To Cell Expansion During Arabidopsis Petal Organogenesis, Ruirui Huang

Yale Graduate School of Arts and Sciences Dissertations

Epigenetic changes, such as histone modifications or DNA methylation, can modify gene expression without affecting the genetic code. Such alterations can persist for many cell generations, and often are induced by various environmental inputs in both plants and animals. A number of studies have demonstrated that epigenetic factors regulate plant developmental timing in response to environmental changes. However, we still have an incomplete view of how epigenetic factors can regulate developmental events such as organogenesis, and the transition from cell division to cell expansion, in plants. The small number of cell types and the relatively simple developmental progression required to …

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Investor Relations And Esg, Tendai Masaya Apr 2024

Investor Relations And Esg, Tendai Masaya

Yale Graduate School of Arts and Sciences Dissertations

I investigate the relation between increased investor relations (IR) activities and four ESG outcomes: coverage by ESG rating agencies, ESG rating levels, the stock market response to bad ESG news, and the use of ESG-related terms in earnings conference calls. Firms with more IR activities—indicated by an IR Officer’s (IRO) presence on conference calls—could improve communication about ESG efforts with investors and ESG rating agencies, and feedback received might even increase the level of ESG efforts. I find that firms with IR prominence (1) are more likely to be covered by ESG raters; (2) experience an increase in overall, E, …

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Diverse Models Of Immunoediting: Exploring Tumor-T Cell Interactions In Developing Cancers, Julie F. Cheung Apr 2024

Diverse Models Of Immunoediting: Exploring Tumor-T Cell Interactions In Developing Cancers, Julie F. Cheung

Yale Graduate School of Arts and Sciences Dissertations

Cancer's complexity is characterized by its genetic diversity, adaptability to environmental changes, and the extent of immunoediting that results from interactions with the immune system. T cells, tasked with eliminating mutated cells, have entered the cancer research spotlight due to their therapeutic potential to restore the natural host immune response against established tumors. However, their effectiveness is limited to a subset of cancers, and their inability to eradicate all tumors from the outset has perplexed researchers. Consequently, immunoediting, which encapsulates the interplay between T cells and developing tumor cells within their specific microenvironment, is a linchpin in determining cancer fate. …

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Developing Metabolism-Targeting Adjuvants To Immunotherapy In Murine Melanoma, Xinyi Zhang Apr 2024

Developing Metabolism-Targeting Adjuvants To Immunotherapy In Murine Melanoma, Xinyi Zhang

Yale Graduate School of Arts and Sciences Dissertations

Melanoma is the deadliest skin cancer type, causing 8000 deaths per year in the United States. The development of immunotherapy significantly prolongs the survival of cancer patients, including patients with melanoma. By impairing the inhibitory signaling pathway, immunotherapy, for example anti-PD-1 monoclonal antibody, reinforces the anti-tumor effector function of T cells that recognize cancer cells and therefore suppresses tumor progression. However, the problem of low responsiveness and development of resistance significantly prevents a large proportion of patients from benefiting from immunotherapy. Therefore, it is of great importance to develop adjuvants to increase the efficacy of immunotherapy. Metabolic alterations have long …

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Insights On The Functional Importance Of Molecular Motions In Phosphatases, Erik Zavala Apr 2024

Insights On The Functional Importance Of Molecular Motions In Phosphatases, Erik Zavala

Yale Graduate School of Arts and Sciences Dissertations

Enzymes are biomolecules that catalyze biological reactions, and as such, demand thorough investigation so that manipulation of their associated biological processes can be achieved. Biological processes are made up of complex pathways where enzymes play a key role in regulating pathway flux. Enzymes are a diverse subset of biomolecules and different classes of enzymes regulate pathway activity in different ways. For example, phosphatases and kinases are the enzymes responsible for regulating the phosphorylation levels of proteins. Phosphatases remove phosphates by catalyzing the hydrolysis of phosphate groups and kinases attach phosphate groups by catalyzing the transfer of phosphates from adenosine triphosphate …

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Deep Learning For Multi-Modal Tomography Imaging: Radiation Dose, Image Artifacts, And Acquisition Time Reductions, Bo Zhou Apr 2024

Deep Learning For Multi-Modal Tomography Imaging: Radiation Dose, Image Artifacts, And Acquisition Time Reductions, Bo Zhou

Yale Graduate School of Arts and Sciences Dissertations

PET-CT/MRI is the most used multi-modal tomography imaging exam which can provide both functional and anatomical information from a single exam and aid clinical decision-making. The CT/MRI component focuses on visualizing the anatomical structures, and the PET component focuses on visualizing molecular-level functional activities in tissues. Millions of PET-CT/MRI scans were performed each year worldwide with wide applications in oncology, cardiology, neurology, and biomedical research. While being an indispensable multi-modal tomography imaging tool in medicine, PET-CT/MRI has several key issues limiting its broader impacts on patients, including 1) the potential hazard caused by radiation dose from the PET and CT, …

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Decoding Novel Metabolic Functions And Binding Products Of Human Aldo-Keto Reductase 1c3, Natavan Dudkina Apr 2024

Decoding Novel Metabolic Functions And Binding Products Of Human Aldo-Keto Reductase 1c3, Natavan Dudkina

Yale Graduate School of Arts and Sciences Dissertations

The increased incidents of many chronic diseases such as asthma, allergies, diabetes, heart disease, and mental disorders cannot be fully explained by genetic factors. The exposure to environment, diet, and behavioral changes is equally or sometimes even more greatly associated with disease progression. Such non-genetic factors could be reflected in chemical fingerprints that cellular processes leave behind. Metabolite profiling provides biochemical information that is not available at the gene or protein level. The emerging technological advances such as sensitive metabolomic approaches have allowed to assess these metabolic changes in a way that was not possible before. As a consequence, in …

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Coding Sequence Dependent Mrna Decay Regulation, Damir Musaev Apr 2024

Coding Sequence Dependent Mrna Decay Regulation, Damir Musaev

Yale Graduate School of Arts and Sciences Dissertations

Post-transcriptional mRNA regulation shapes gene expression, yet the full extent of cis-regulatory sequences and how translation shapes the regulation of these elements is poorly understood. To identify conserved cis-regulatory elements shaping mRNA stability, I analyzed the features associated with differential mRNA decay in two vertebrate systems: steady-state HEK293 cells and developing zebrafish embryos. I found that strength of translation initiation (Kozak score), uORF content, codon optimality, AU-rich elements, microRNA binding sites, and ORF length function combinatorially to regulate mRNA stability. Surprisingly, machine learning analysis identified ORF length as the most important conserved feature regulating mRNA decay. I found that mRNAs …

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Advances In Multi-Agent Learning And Private Statistical Estimation, John Lazarsfeld Apr 2024

Advances In Multi-Agent Learning And Private Statistical Estimation, John Lazarsfeld

Yale Graduate School of Arts and Sciences Dissertations

Modern machine learning systems and other data science settings are increasingly subject to various reliability constraints: these systems may be decentralized and involve multiple agents acting without coordination, may be limited in memory and other computational resources, or may be subject to societal constraints like differential privacy. This dissertation presents algorithmic advances for several learning and data analysis tasks under such constraints. In the first chapter, we present new families of algorithms for the multi-agent cooperative bandit problem in the randomized gossip communication model. Our algorithms are fully decentralized and require only constant local memory per agent, and we highlight …

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Transcriptional Regulation Of Fate Specification In Human Megakaryocytic-Erythroid Progenitors, Nayoung Kwon Apr 2024

Transcriptional Regulation Of Fate Specification In Human Megakaryocytic-Erythroid Progenitors, Nayoung Kwon

Yale Graduate School of Arts and Sciences Dissertations

Megakaryocytic-erythroid progenitors (MEP) are a population of bipotent hematopoietic progenitors that give rise to the megakaryocytic (Mk) or erythroid (E) lineages. The Mk lineage produces platelets, and the E lineage produces RBCs, that govern coagulation and oxygen transport, respectively. Both are critical components of the blood system, and maintaining an adequate and balanced pool of platelets and red blood cells is essential for life. As MEP stand as a final branchpoint before committing to Mk or E lineages, understanding the fate specification mechanism of MEP may provide insight into treating conditions that involve platelets and/or red blood cells.This thesis focuses …

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Impacts Of Altitude On Plant Green Leaf, Fresh Litter, And Soil Stoichiometry In Subtropical Forests, Dehuang Zhu, Yan Zhou, Suhong Peng, Weiping Hua, Bin Luo, Dafeng Hui Apr 2024

Impacts Of Altitude On Plant Green Leaf, Fresh Litter, And Soil Stoichiometry In Subtropical Forests, Dehuang Zhu, Yan Zhou, Suhong Peng, Weiping Hua, Bin Luo, Dafeng Hui

Biology Faculty Research

BackgroundEcological stoichiometric characteristics of carbon (C), nitrogen (N), phosphorus (P), and potassium (K) serve as crucial indicators of nutrient cycling and limitation in terrestrial ecosystems. However, our current understanding of stoichiometric characteristics in subtropical forests and their response to different climate conditions is still limited.MethodsWe selected six altitudes ranging from 700 m to 1,200 m to simulate different climate conditions of an evergreen broadleaf forest in Wuyi Mountain, Fujian Province, China. We investigated C, N, P, and K stoichiometry and homeostasis in the green leaves, newly senesced leaf litter (fresh litter), and soil of this forest.ResultsLeaf P and K levels …

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Shall We Place More Advanced Students In A Separate Class?, Shahnaz Shahbazova, Olga Kosheleva, Vladik Kreinovich Apr 2024

Shall We Place More Advanced Students In A Separate Class?, Shahnaz Shahbazova, Olga Kosheleva, Vladik Kreinovich

Departmental Technical Reports (CS)

In every class, we have students who are more advanced and students who are more behind. From this viewpoint, it seems reasonable to place more advanced students in a separate class. This should help advanced students progress faster, and it should help other students as well, since the teachers in the remaining class can better attend to their needs. However, empirically, this does not work: when we form a separate class, the overall amount of gained knowledge decreases. In this paper, we provide a possible explanation for this seemingly counterintuitive phenomenon.

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The Magazine, Spring 2024, Morehead State University. Office Of Communications & Marketing. Apr 2024

The Magazine, Spring 2024, Morehead State University. Office Of Communications & Marketing.

Morehead State Alumni Association Publications

The Magazine of Morehead State University from spring of 2024.

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The Medium And Message Of Salvation: Canonical Theism And Marshall Mcluhan, Sam Klein Apr 2024

The Medium And Message Of Salvation: Canonical Theism And Marshall Mcluhan, Sam Klein

Harding School of Theology Dissertations and Theses

No abstract provided.

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