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2023

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Data-Driven Mapping Between Functional Connectomes Using Optimal Transport, Javid Dadashkarimi Oct 2023

Data-Driven Mapping Between Functional Connectomes Using Optimal Transport, Javid Dadashkarimi

Yale Graduate School of Arts and Sciences Dissertations

Open-source, publicly available neuroimaging datasets---whether from large-scale data collection efforts or pooled from multiple smaller studies---offer unprecedented sample sizes and promote generalization efforts. Releasing data can democratize science, increase the replicability of findings, and lead to discoveries. Due to patient privacy, computational, and data storage concerns, researchers typically release preprocessed data with the voxelwise time series parcellated into a map of predefined regions, known as an atlas. However, releasing preprocessed data also limits the choices available to the end-user. This is especially true for connectomics, as connectomes created from different atlases are not directly comparable. With the absence of gold …

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Religion And The Politics Of Gender, Radha Sarkar Oct 2023

Religion And The Politics Of Gender, Radha Sarkar

Yale Graduate School of Arts and Sciences Dissertations

This dissertation seeks to understand how religion shapes political outcomes related to women's participation. Much political science scholarship emphasizes the material or structural aspects of religion in shaping political commitments. In contrast, I highlight the importance of religious norms and beliefs, conveyed chiefly by clerical leaders. I delve into the Colombian case and compare the effects of Catholic and Pentecostal teachings about women's roles and attributes. With survey experimental data, text-as-data techniques, and interview-based fieldwork, I demonstrate that Catholic sermons tend to elicit benevolent sexism, a mindset that seeks to protect women who occupy traditional male roles in the public …

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Novel Methods For Identification And Inference In Public Health, Jinghao Sun Oct 2023

Novel Methods For Identification And Inference In Public Health, Jinghao Sun

Yale Graduate School of Arts and Sciences Dissertations

This dissertation consists of three essays, each one tackling issues related to "identification'' in the statistical methods used in public health research. In the context of statistics, ``identification'' refers to the process of learning the values of the parameters or characteristics of a model or system after obtaining an infinite number of observations from it. In these essays, I draw attention to the limitations of current methods, which often hinge on specifying a limited set of data generating processes (DGPs). However, these DGPs may fail to correspond accurately with the intricacies of actual situations or with the pre-existing knowledge within …

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'Force And Understanding' And Instability, Hugo William Havranek Oct 2023

'Force And Understanding' And Instability, Hugo William Havranek

Yale Graduate School of Arts and Sciences Dissertations

Critics agree that ‘Force and Understanding’ in Hegel’s Phenomenology of Spirit is of crucial importance for understanding Hegel’s considered position; but the interpretation of the content of the chapter remains highly controversial. In this dissertation, I adopt a reading of ‘Force and Understanding’ on which Hegel is introducing his idiosyncratic notions of atemporal change and identity-in-opposition. Readings that take this approach enjoy prima facie textual support, but have up to now suffered because the views they attribute to Hegel appear obviously philosophically confused. The purpose of the dissertation, therefore, is to argue that Hegel’s use of atemporal change and identity-in-opposition …

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Accelerator-Rich Computer Architectures For Brain-Computer Interfaces, Karthik Sriram Oct 2023

Accelerator-Rich Computer Architectures For Brain-Computer Interfaces, Karthik Sriram

Yale Graduate School of Arts and Sciences Dissertations

Brain-Computer Interfaces (BCIs) are our means of communicating directly with the brain. BCIs implanted on brain tissue offer the highest fidelity communication with the brain and can treat debilitating neurological disorders, control digital devices and improve our understanding of the brain. Unlocking their full potential requires devices capable of processing high data rates sensed from multiple brain regions. However, current BCIs are restricted to a single region, task/treatment, and process low data rates. This is because implantable BCIs must operate within milliwatts of power and respond in real-time within milliseconds to deliver safe treatment. These constraints run counter to the …

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The Role Of The Protection Of Telomeres 1b (Pot1b) Protein In The Protection Of Telomeric Overhangs And The Regulation Of Telomere Length, Taylor Nicholas Takasugi Oct 2023

The Role Of The Protection Of Telomeres 1b (Pot1b) Protein In The Protection Of Telomeric Overhangs And The Regulation Of Telomere Length, Taylor Nicholas Takasugi

Yale Graduate School of Arts and Sciences Dissertations

Malignant cancers must activate telomere maintenance mechanisms to achieve replicative immortality. Mutations in the human Protection of Telomeres 1 (POT1) gene are frequently detected in cancers with abnormally long telomeres, suggesting that the loss of POT1 function disrupts the regulation of telomere length homeostasis to promote telomere elongation. However, our understanding of the mechanisms leading to elongated telomeres remains incomplete. The mouse genome encodes two POT1 proteins, POT1a and POT1b possessing separation of hPOT1 functions. We performed serial transplantation of Pot1b-/- sarcomas to better understand the role of POT1b in regulating telomere length maintenance. While early-generation Pot1b-/- sarcomas initially possessed …

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Computational Methods For Single-Cell Data: From Decomposition, Integration, To Label Transfer, Yuge Wang Oct 2023

Computational Methods For Single-Cell Data: From Decomposition, Integration, To Label Transfer, Yuge Wang

Yale Graduate School of Arts and Sciences Dissertations

Over the past decade, significant advancements have been made in high-throughput single-cell sequencing technologies, revolutionizing our ability to investigate cellular heterogeneity across multiple molecular levels, including gene expression measured by scRNA-seq and chromatin accessibility measured by scATAC-seq. Unlike traditional bulk sequencing approaches, single-cell sequencing techniques enable the characterization of diverse cell types or states within a sample, shedding light on complex biological processes. However, the analysis of single-cell data presents several challenges, including high dimensionality, large-scale datasets, high sparsity, and batch effects arising from both intra- and inter-modalities. Failure to address these challenges can significantly impact downstream applications, such as …

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Exploring 3d Genomics And Its Regulation: Spatial Crispr Screening Reveals Regulators Of 3d Genome Architectures And Chromatin Tracing Unfolds X Chromosome Conformations In Human Pluripotent Stem Cells, Bing Yang Oct 2023

Exploring 3d Genomics And Its Regulation: Spatial Crispr Screening Reveals Regulators Of 3d Genome Architectures And Chromatin Tracing Unfolds X Chromosome Conformations In Human Pluripotent Stem Cells, Bing Yang

Yale Graduate School of Arts and Sciences Dissertations

3D genomics is a rapidly emerging field that seeks to understand the role of the three-dimensional organization of the genome in gene regulation, cellular function, and biological processes. Chromatin tracing has recently emerged as an image-based highly multiplexed fluorescent in-situ hybridization method to detect 3D genome architectures in various biological contexts. However, the regulation of 3D genomics remains less understood. Recent advances in CRISPR screening have enabled systematic identification of genetic perturbations critical to cellular phenotypes and diseases. Yet, the phenotype readouts provided by current CRISPR screens are limited to low content, posing challenges for detection of complex 3D genome …

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Investigation Of Variant Guanine Riboswitches And Other Nucleic Acid Motifs That Sense Metal Ions, Siddhartha Hamal Dhakal Oct 2023

Investigation Of Variant Guanine Riboswitches And Other Nucleic Acid Motifs That Sense Metal Ions, Siddhartha Hamal Dhakal

Yale Graduate School of Arts and Sciences Dissertations

Riboswitches are regulatory RNA elements commonly present in the 5′ untranslated regions (UTRs) of certain mRNA molecules. They carry a conserved aptamer region that binds to metabolites or elemental ions. The binding of ligand promotes distinct folding pathway in the RNA structure which is translated into a regulatory response that either activates or inhibits the expression of downstream genes. Over 55 different classes of riboswitches have been experimentally validated so far that govern various aspects of biology in bacteria, archaea, and select eukaryotes. These RNA elements are thought have played crucial roles in gene regulation during the RNA World era, …

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Determining The Role Of Beta-Tubulin 4b In Cilia And Development, Mycah Theair Sewell Oct 2023

Determining The Role Of Beta-Tubulin 4b In Cilia And Development, Mycah Theair Sewell

Yale Graduate School of Arts and Sciences Dissertations

Microtubules (MTs) are a key component of the cytoskeleton and participate in multiple cellular functions and processes. MTs are made of α- and β-tubulin proteins that are encoded by multiple, individual isotype genes. Over the recent decades there has been mounting evidence that despite the high similarity among tubulin proteins, these various isotypes have unique functions rather than being functionally redundant. First, tubulins have different expression and localization patterns. Second, mutations in different tubulin genes result in a variety of disease phenotypes, some of which are exclusively tied to specific tubulins. Finally, multiple tubulin studies have shown that tubulin composition …

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Computational And Evolutionary Approaches For Translational Cancer Research, J Nic Fisk Oct 2023

Computational And Evolutionary Approaches For Translational Cancer Research, J Nic Fisk

Yale Graduate School of Arts and Sciences Dissertations

The progression of cancer, including the acquisition of therapeutic resistance and the mortality-inducing metastatic spread of therapy-resistant cell populations, is fundamentally an evolutionary process. To contribute to the development of effective treatments against this evolving scourge, this work leverages phylogenetics, statistics, and machine learning techniques to quantify the effects of genetic variants responsible for therapeutic resistance, resolve the timing of their occurrence, understand evolutionary trajectories, and profile the role of neoantigens in varied cancer systems. First, a bioinformatics pipeline for quantifying selection on neoantigens—tumor-specific antigens and potential targets of the immune systems—is detailed. Second, the evolutionary history of two patients …

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Gradient-Free Magnetic Resonance Imaging In A Nonuniform B0, With A Novel Low-Field Magnet System, Kartiga Selvaganesan Oct 2023

Gradient-Free Magnetic Resonance Imaging In A Nonuniform B0, With A Novel Low-Field Magnet System, Kartiga Selvaganesan

Yale Graduate School of Arts and Sciences Dissertations

Over the last 50 years Magnetic Resonance Imaging (MRI) has become a mainstay of modern medicine as a noninvasive diagnostic imaging tool. Most clinical and research MR scanners have trended towards higher field strengths as a means of improving spatial resolution while minimizing scan time. However, widespread availability of these systems is limited, with 90% of people worldwide still lacking access to MRI. Much of this discrepancy comes from the high cost and complexity associated with installing, operating, and maintaining conventional MR scanners. By relaxing the hardware requirements, moving to lower field-strengths, and creating more open-bore systems, MRI can become …

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Exitron Splicing Of Odor Receptors In Drosophila, Xueying Shang Oct 2023

Exitron Splicing Of Odor Receptors In Drosophila, Xueying Shang

Yale Graduate School of Arts and Sciences Dissertations

Odor receptors (Ors) are the major olfactory receptors in Drosophila. They signalthe presence of food, mates, and predators. Proper expression of Ors is critical for the function of olfactory receptor neurons (ORNs). In this study we discovered exitrons in five of the 39 Ors expressed in the adult antennae. Exitrons (exonic introns) are sequences that can be spliced from within a protein-coding exon, thereby altering the resulting protein. Exitrons have not been identified previously in Drosophila to our knowledge. We focused on Or88a, which encodes a pheromone receptor, and found that exitron splicing of Or88a is conserved across five Drosophila …

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Integrating Genetics And Brain Connectivity: Overcoming Statistical Challenges To Uncover The Neural Basis Of Psychiatric And Behavioral Disorders, Wei Dai Oct 2023

Integrating Genetics And Brain Connectivity: Overcoming Statistical Challenges To Uncover The Neural Basis Of Psychiatric And Behavioral Disorders, Wei Dai

Yale Graduate School of Arts and Sciences Dissertations

The exploration of the associations between genetic variants or single nucleotide polymor- phisms (SNPs), brain connectivity, and mental disorders is crucial for comprehending the biological origins of psychiatric and behavioral conditions. Biomedical technologies, such as magnetic resonance imaging (MRI) and next-generation sequencing (NGS), can help elu- cidate the underlying biological processes. Resting state functional MRI (rsfMRI) studies have demonstrated altered functional connectivity in numerous psychiatric and behavioral disorders, which is moderately heritable and can be linked to genetic variants. Diffusion tensor imaging (DTI) can be employed to investigate the structural foundation of func- tional networks. However, challenges remain in analyzing …

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On The Evolution Of Crassulacean Acid Metabolism: Diversity, Anatomy, And Genetic Components, Ian Spencer Gilman Oct 2023

On The Evolution Of Crassulacean Acid Metabolism: Diversity, Anatomy, And Genetic Components, Ian Spencer Gilman

Yale Graduate School of Arts and Sciences Dissertations

Crassulacean acid metabolism (CAM) is an adaption to water- and CO2-limitation that has evolved independently in dozens of vascular plant lineages. The study of CAM began with 18th and 19th botanists, who noted curious changes in plant sap acidity and dark-period gas exchange in succulent plants, and continues into the genomics age with goals of engineering CAM into crops in light of global climate change. The major enzymes, metabolites, and day-night rhythms of CAM have long been established, but many fundamental questions remain, and modern molecular and computational tools allow us to ask new questions about the evolution and genetic …

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Deciphering Immune Interactions In The Tumor Microenvironment, Orr-El Weizman Oct 2023

Deciphering Immune Interactions In The Tumor Microenvironment, Orr-El Weizman

Yale Graduate School of Arts and Sciences Dissertations

Deciphering the Tumor Immune Interactome Cancerous transformations are initiated in normal healthy cells by oncogenic hits. Subsequent acquisition of somatic mutations over time results in the transformation of aberrant cells to cancerous outgrowth to eventual metastatic dissemination. Since the multistep process of oncogenesis does not exist in a vacuum, as these cells arise within the context of a tissue, how does host defenses interact with aberrant transformed cancerous cells? As early as 1909, Paul Ehrlich offered the first hypothesis of immune interaction with tumor cells, arguing that the immune cells can recognize and protect against cancer cells. Further developed by …

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Identifying Cellular And Molecular Mechanisms Contributing Towards Neuronal Vulnerability In Spinocerebellar Ataxia Type 1, Kimberly Petra Luttik Oct 2023

Identifying Cellular And Molecular Mechanisms Contributing Towards Neuronal Vulnerability In Spinocerebellar Ataxia Type 1, Kimberly Petra Luttik

Yale Graduate School of Arts and Sciences Dissertations

Neurodegenerative disorders are highly complex, progressive disorders often involving interactions of multiple cell types, disease-causing genes and pathways, and brain regions. For the majority of neurodegenerative disorders, no effective therapeutics are currently available to slow disease onset or progression, and the mechanisms underlying the degeneration of specific cellular populations remain largely unknown. Here, we use spinocerebellar ataxia type 1 (SCA1) as a model to investigate the impact of the disease-causing gene, ATAXIN-1 (ATXN1), in diverse cell types and brain regions. We identify region-specific differences in disease signatures, and investigate the mechanistic contribution of glia, specifically astrocytes, towards SCA1 pathology and …

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Uncovering A Novel Role For Lsr2 In Mycobacterial Mutagenesis And Deciphering The Determinants Of Lsr2 Transcriptional Regulation, Wei Lynn Ng Oct 2023

Uncovering A Novel Role For Lsr2 In Mycobacterial Mutagenesis And Deciphering The Determinants Of Lsr2 Transcriptional Regulation, Wei Lynn Ng

Yale Graduate School of Arts and Sciences Dissertations

Chromosomal mutations drive the evolution of antibiotic resistance in M. tuberculosis. Unlike many other pathogens, M. tuberculosis has no demonstrated ability for horizontal gene transfer, a major mechanism for developing antibiotic resistance. The error-prone translesion polymerase complex DnaE2/ImuA’/ImuB is one of the primary mediators of mutagenesis and antibiotic resistance in vitro and possibly in vivo. To catalyze error-prone DNA synthesis, DnaE2/ImuA’/ImuB must be able to access the DNA by binding the β2-sliding clamp of the replisome, and potentially compete with other polymerases, including the high-fidelity replicative polymerase DnaE1. However, the mechanisms that govern polymerase switching are not well understood, especially …

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Learning Latent Representations For Biological Molecules, Tianxiao Li Oct 2023

Learning Latent Representations For Biological Molecules, Tianxiao Li

Yale Graduate School of Arts and Sciences Dissertations

Recent progresses in machine learning have achieved phenomenal successes in the prediction of properties of biological molecules from large biological data. However, how much the models really “understand” the nature of the data remains an important question. Representation learning aims at extracting information-rich, low dimensional vector representations from complex high dimensional data. Such representations not only facilitate visualization and interpretation of the data, but also flexibly and efficiently generalized to other downstream tasks without having to re-learn universal patterns in every application. Furthermore, in generative modelling, the latent representations can be directly manipulated to direct the generation towards desired properties. …

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Disruption Of Trio Gef Function And Regulation In Neurodevelopmental Disorders, Ellen Elizabeth Corcoran Oct 2023

Disruption Of Trio Gef Function And Regulation In Neurodevelopmental Disorders, Ellen Elizabeth Corcoran

Yale Graduate School of Arts and Sciences Dissertations

There is a critical need to elucidate the biochemical events that control dendrite and synapse function to develop better targeted therapeutic strategies for neurodevelopmental disorders. Functionally damaging mutations in TRIO are enriched in individuals with neurodevelopmental disorders. TRIO encodes a synaptic regulatory protein with three catalytic domains (Hence the name, TRIO) - two guanine nucleotide exchange factor domains, GEF1 (Rac1 and RhoG) and GEF2 (RhoA), and a putative kinase domain. Broadly speaking, Trio serves as a signaling hub to integrate signals from cell surface receptors and coordinate cytoskeletal rearrangements by activating small GTPases. However, the mechanistic details of how Trio …

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Autoregulation Mechanism Of Lim Domain Kinases, Gabriela Casanova Sepulveda Oct 2023

Autoregulation Mechanism Of Lim Domain Kinases, Gabriela Casanova Sepulveda

Yale Graduate School of Arts and Sciences Dissertations

LIM kinases 1 (LIMK1) and 2 (LIMK2) are major regulators of cytoskeletal dynamics in the cell. LIMK regulates actin dynamics by phosphorylating the actin-depolymerizing factor (ADF)/cofilin family of actin-binding proteins. Cofilin proteins bind preferentially and cooperatively to ADP-bound subunits in F-actin. This binding event changes the helical rotation of actin filaments, promoting actin filament severing. LIMKs promote actin filament stabilization by inactivating cofilin through phosphorylation of Ser3. Phosphorylation of cofilin at Ser3 deactivates cofilin severing activity by inhibition of cofilin binding to actin filaments. This cycling between actin depolymerization and polymerization impacts higher-order cellular processes, including motility, differentiation, and metastasis. …

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A Multidisciplinary Approach With Dogs As The Model Organism To Identify Whole-Genome Breed-Specific Genotypes Potentially Relating To Human Complex Traits, Zicheng Li Oct 2023

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 …

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Peripheral Immune Signatures Of Fibrotic Lung Diseases, Amy Zhao Oct 2023

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 …

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The Maladaptive And Adaptive Effects Of Trust And Distrust On Externalizing Behavior, Shou-An Ariel Chang Oct 2023

The Maladaptive And Adaptive Effects Of Trust And Distrust On Externalizing Behavior, Shou-An Ariel Chang

Yale Graduate School of Arts and Sciences Dissertations

A wide range of behaviors, from hostility and defiance to more severe forms ofnorm violations, such as theft and violence, comprise the spectrum of externalizing behaviors. The psychological, physical, and social consequences associated with externalizing behaviors place a significant burden on the individual, their families, and society. Research has made substantial advances in identifying environmental-level and individual-level risk factors for externalizing behavior. However, despite work indicating that both externalizing behaviors themselves and several risk factors associated with externalizing behaviors are related to disruptions in trust and distrust, limited work has considered interactions between environmental- and individual-level risk factors and levels …

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Manipulating And Measuring States Of A Superfluid Optomechanical Resonator In The Quantum Regime, Yiqi Wang Oct 2023

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 …

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Investigating Stem Cell Chromatin Organization And Oncogenic Tissue Morphogenic Change Through Intravital Microscopy, Sangwon Yun Oct 2023

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 …

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Consequences Of Childhood Maltreatment And Exposure To Community Violence: A Single-Moment And Longitudinal Trajectory Examination, Suzanne Charlotte Estrada Oct 2023

Consequences Of Childhood Maltreatment And Exposure To Community Violence: A Single-Moment And Longitudinal Trajectory Examination, Suzanne Charlotte Estrada

Yale Graduate School of Arts and Sciences Dissertations

Childhood adversity is one of the strongest predictors of long-term psychological,social, and physical negative life outcomes. Two subtypes of adversity, one perpetrated by someone in the home environment (i.e., childhood maltreatment, parental harshness) and the other perpetrated by someone in the community (i.e., exposure to community violence), are especially salient predictors of poor mental health and increased antisocial behavior. Research aimed at describing the occurrence of adversity often examines these subtypes separately. As a result, our understanding of the ways individuals experience adversity in the home and community and the long-term impact of co-occurring adversity is limited. Additionally, perhaps following …

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Investigating The Synaptic Plasticity Mechanisms Underlying A Learned Behavioral Preference In C. Elegans, Joon Ha Lee Oct 2023

Investigating The Synaptic Plasticity Mechanisms Underlying A Learned Behavioral Preference In C. Elegans, Joon Ha Lee

Yale Graduate School of Arts and Sciences Dissertations

A fundamental goal in neuroscience is to elucidate the cellular and molecular mechanisms that regulate learned behavioral preferences, or memories. While modulation of synaptic connections has been well-established as a component of memory formation, there remains a critical lack in understanding of how specific molecular changes that alter synaptic physiology result in learned behaviors. In this thesis, I utilize the paradigm of learned thermal preferences and the connection between a sensory neuron (AFD) and its postsynaptic partner (AIY) in Caenorhabditis elegans to bridge this gap at the single-synapse level. I first characterize the neurotransmission requirements of this synapse and find …

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Learning Data-Driven Representations For Biomolecular Analysis, Optimization, And Design, Egbert Castro Oct 2023

Learning Data-Driven Representations For Biomolecular Analysis, Optimization, And Design, Egbert Castro

Yale Graduate School of Arts and Sciences Dissertations

Recently, the study of biomolecules has undergone a shift toward high-throughput experimentation, leveraging advancements across various fields to produce datasets of unprecedented scale. Within these datasets, there are undiscovered truths that carry major implications for our understanding of biology and our ability to treat disease. However, innovative approaches are needed to distill signals from noise and enable the next generation of discoveries. Deep learning methods have excelled in their ability to learn from complex and large datasets in many domains, but their potential for biomolecular data has yet to be fully realized. To do so requires the ability to integrate …

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Tenascin-C: A Regulator Of Venous Remodeling Following Aortocaval Fistula Creation, Luis Gonzalez Oct 2023

Tenascin-C: A Regulator Of Venous Remodeling Following Aortocaval Fistula Creation, Luis Gonzalez

Yale Graduate School of Arts and Sciences Dissertations

End-stage kidney disease (ESKD) represents a growing medical problem globally with a high burden to patients. In the United States alone more than 740,000 individuals have ESKD and are primarily dependent on hemodialysis for treatment. For patients who require hemodialysis, arteriovenous fistulae (AVF) are the preferred mode of vascular access due to their superior patency rates and reduced infection rates when compared to grafts or catheters. However, the lifespan of an AVF is limited by several complications, which includes neointimal hyperplasia (NIH) and thrombosis. Loss of AVF patency at 1-year ranges ~40-50%. Successful AVF maturation is characterized by venous wall …

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