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Single-Cell Massively Parallel Reporter Assays, Siqi Zhao
Single-Cell Massively Parallel Reporter Assays, Siqi Zhao
Arts & Sciences Graduate Student Theses and Dissertations
Our understanding of gene regulation needs to be generalizable as well as specific. A generalizable understanding enables us to transfer our knowledge of one gene to another, and the specificity allows us to understand the precise regulation of gene expression through development. One framework that confers generalizability and specificity is the hierarchical and modular model of gene regulation. To test whether gene regulation is hierarchical and modular requires methods to systematically analyze how different factors collectively control gene expression. This thesis describes the development of two functional genomics methods at single-cell resolution. These methods systematically examined how cellular contexts, chromatin …
A Structural Perspective On Neutralizing Antibodies To Flaviviruses And Coronaviruses, John Michael Errico
A Structural Perspective On Neutralizing Antibodies To Flaviviruses And Coronaviruses, John Michael Errico
Arts & Sciences Graduate Student Theses and Dissertations
The presence of neutralizing antibodies typically correlates strongly with protection from infection, particularly for RNA viruses; elicitation of neutralizing antibody responses is thus the primary goal of most vaccines, and monoclonal antibodies (mAbs) can be leveraged as potent therapeutics. Thus, understanding the properties of individual antibodies that comprise polyclonal antibody responses and their epitopes is essential for countermeasure design. In this dissertation, I explore the epitopes and functional properties of monoclonal antibodies targeting the structural proteins of two families of RNA viruses, flaviviruses and coronaviruses.Flaviviruses are globally distributed arthropod-borne positive-sense RNA viruses transmitted primarily by either mosquitos or ticks. Symptomatic …
The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland
The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland
Arts & Sciences Graduate Student Theses and Dissertations
The N-methyl-D-aspartate receptor (NMDAR) plays a variety of important roles in the development and function of primate central nervous systems. This thesis describes three nonhuman primate studies that, together, demonstrate that pharmacologically reducing NMDAR activity not only causes dramatic changes in neural activity in cortex, but also changes the relationship between that activity and a key signal often used as its proxy in human studies, the blood-oxygen-level-dependent (BOLD) signal. The first study reveals that NMDA antagonism is sufficient to induce powerful low-frequency modulation of spiking activity and extracellular local field potential (LFP) and discusses the implications of this finding for …
Truncated Realized Variations Of Lévy Models: Optimality, Debiasing, And Implementation Approaches, Yuchen Han
Truncated Realized Variations Of Lévy Models: Optimality, Debiasing, And Implementation Approaches, Yuchen Han
Arts & Sciences Graduate Student Theses and Dissertations
Statistical inference for stochastic processes under high-frequency observations has been an active research area in econometrics and financial statistics for over twenty years. In this thesis, we consider some aspects related to the estimation of the volatility of an Itô semimartingale in the presence of Lévy-type jumps, which is of fundamental importance in derivatives pricing evaluation, risk management and portfolio allocation. The main technique we use is the Truncated Realized Variation (TRV) that is both rate- and variance-efficient, in the Cramer-Rao lower bound sense, when jumps are of bounded variation.Motivated by recent results that state that the optimal threshold parameter, …
Understanding Individual Cells In Zebrafish Caudal Fin Regeneration (从单细胞视角理解斑马鱼尾鳍再生历程), Yiran Hou
Understanding Individual Cells In Zebrafish Caudal Fin Regeneration (从单细胞视角理解斑马鱼尾鳍再生历程), Yiran Hou
Arts & Sciences Graduate Student Theses and Dissertations
Humans are incapable of complex body structure regeneration. Understanding how other species retain the ability to regenerate can help us to find solutions for improving our regenerative capacities. The zebrafish is an organism that is capable of regenerating multiple organs in its body. Using zebrafish as a model organism, previous studies have identified key processes and illustrated the crucial cell types and genes for regeneration. In caudal fin specifically, blastema formation is a key predictor of successful regeneration. However, a comprehensive molecular understanding of cell type-specific contributions to this process is lacking. In this dissertation, I present our efforts toward …
Fructose Promotes The Growth Of Tumors Through Metabolite Exchange With Non-Malignant Tissues, Ronald Joseph Fowle-Grider
Fructose Promotes The Growth Of Tumors Through Metabolite Exchange With Non-Malignant Tissues, Ronald Joseph Fowle-Grider
Arts & Sciences Graduate Student Theses and Dissertations
The amount of dietary fructose consumed in the United States has increased considerably over the past five decades, largely due to the widespread use of high fructose corn syrup as a sweetener. The potential link between this elevated fructose intake and the development of cancer remains incompletely understood. Here we show that, even though cervical cancer cells themselves cannot directly utilize fructose carbon, diets high in fructose enhance the growth of cervical tumors by nearly threefold in mice. We demonstrate that efficient utilization of fructose carbon requires ketohexokinase-C, which was not expressed in ~100 cervical tumors that we examined from …
Behavioral, Neural, And Psychiatric Correlates Of Responses To Social Feedback, Brent Rappaport
Behavioral, Neural, And Psychiatric Correlates Of Responses To Social Feedback, Brent Rappaport
Arts & Sciences Graduate Student Theses and Dissertations
Problems responding to peer feedback and disrupted interpersonal relationships arise in numerous psychiatric disorders; yet heterogeneity and homogeneity across disorders suggests both common and unique mechanisms of impaired social function. Identifying brain correlates of these disruptions could help explain diagnostic comorbidities as well as unique pathways, thus informing more individualized treatments. However, studies seeking to understand the link between psychological and neural mechanisms often have to rely on reverse inference assumptions to match psychological processes to brain activity. One hypothesis is that social feedback is processed similar to other forms of feedback (e.g., monetary). Thus, we aimed to test such …
Testing Of A Novel Combined Eating-Disorder And Weight-Loss Online Guided-Self Help Intervention For Young Adults With A Binge-Type Eating Disorder And Overweight Or Obesity, Grace Elise Monterubio
Testing Of A Novel Combined Eating-Disorder And Weight-Loss Online Guided-Self Help Intervention For Young Adults With A Binge-Type Eating Disorder And Overweight Or Obesity, Grace Elise Monterubio
Arts & Sciences Graduate Student Theses and Dissertations
Binge-type eating disorders (EDs) and obesity-related health concerns are two serious medical issues, though study of their treatment has largely remained separate. This study implemented an online, guided self-help ED intervention that concurrently offered Cognitive Behavioral Therapy (CBT)-based tools to improve ED symptoms, while also teaching energy-density food principles of behavioral weight loss (BWL), for individuals with clinical/sub-clinical binge-type EDs with comorbid overweight/obesity. The study aimed to examine change in weight, change in ED symptoms, and program engagement between a combined intervention (CBT + BWL) and an ED-only intervention. Participants in the combined intervention group received weekly session content pertaining …
Canonical And Noncanonical Mechanisms Of Resistance To Arginine Starvation In Cancer, Leonard Christopher Rogers
Canonical And Noncanonical Mechanisms Of Resistance To Arginine Starvation In Cancer, Leonard Christopher Rogers
Arts & Sciences Graduate Student Theses and Dissertations
The enzyme argininosuccinate synthetase 1 (ASS1) catalyzes the condensation of citrulline and aspartate into argininosuccinate as part of the urea cycle and citrulline-nitric oxide cycle. This reaction is essential for mammals to synthesize the amino acid arginine, which is required for all cells. Nearly all human tissues express at least some ASS1, but they import most of their arginine from the extracellular space after it is produced and released by the kidneys. Most solid tumors lack a functional level of ASS1, including over 85% of sarcomas, which are cancers of connective tissues. Published evidence suggests that this provides a proliferation …
Essays In Microeconomics, Lintao Ye
Essays In Microeconomics, Lintao Ye
Arts & Sciences Graduate Student Theses and Dissertations
This dissertation has four chapters. The first chapter studies the testable implications of stable weighted (hedonic) coalitions. The second chapter explores an extension of Bayesian persuasion where the receiver can acquire additional information after receiving information from the sender. The third chapter studies observable implications when a decision-maker endogenously forms consideration sets. The last chapter examines weighted network formation where agents have social status concerns. Omitted proofs in each chapter are presented in the last section of each chapter.In the first chapter, we study the testable implications of a stable profile of weighted coalitions. We then apply our result to …
The Physics Of Associative Polymers And Applications To Biomolecular Condensates, Furqan Dar
The Physics Of Associative Polymers And Applications To Biomolecular Condensates, Furqan Dar
Arts & Sciences Graduate Student Theses and Dissertations
Biomolecular condensates represent a new and ubiquitous class of membraneless organelles (MLOs) that are essential for healthy cellular functioning. The constituent molecules of such condensates span a vast bio-macromolecular gamut from intrinsically disordered regions and proteins (IDPs/IDRs), to RNA and RNA-binding proteins (RNPs), to polymerases and DNA etc. Apart from being part of the regular healthy cell cycle, these condensates are also implicated in many diseases, most notably progressive neurodegenerative diseases like Amyotropic Lateral Sclerosis (ALS) and Huntingtin's Disease (HD). Since the constituent molecules of these condensates span a broad range of length scales and modes of interaction, uncovering a …
Local Spectroscopy Data Infrastructure: Solid State Nmr Crystallography With Experiment, First-Principal Analysis And Machine Learning, He Sun
Arts & Sciences Graduate Student Theses and Dissertations
Solid-state magnetic resonance (SSNMR) spectroscopy is a powerful tool for obtaining precise information about the local bonding and morphology of materials. The detailed local structure of crystalline materials cannot be easily solved by traditional experimental methods such as X-ray diffraction (XRD). SSNMR combined with first principal calculation methods such as density functional theory (DFT) can be of great use in this research area. The methodology that is called “NMR crystallography” today has been widely applied to the determination of a wide range of solid materials with an increasing amount of computationally simulated NMR spectra. The construction of a well-established computational …
The Role Of The Neurodevelopmental Disorder Gene Myt1l In Mammalian Brain Development, Jiayang Chen
The Role Of The Neurodevelopmental Disorder Gene Myt1l In Mammalian Brain Development, Jiayang Chen
Arts & Sciences Graduate Student Theses and Dissertations
Recent human genetic studies have associated mutations in a gene called Myelin Transcription Factor 1 Like (MYT1L) with neurodevelopmental disorders (NDDs). Patients with MYT1L loss of function (LoF) mutations (MYT1L Syndrome patients) demonstrate shared symptoms such as microcephaly, attention deficit and hyperactivity disorder (ADHD), and obesity. Despite prior studies showing MYT1L overexpression facilitates neuronal differentiation in vitro, its functions in vivo, especially in the mammalian brain, and how its mutation leads to human disease pathology remains poorly understood. Here, I established the first mouse model of MYT1L Syndrome mimicking a patient specific LoF mutation. I found mice with Myt1l heterozygous …
Toward Enhancing The Synthesis Of Renewable Polymers: Feedstock Conversions And Functionalizable Copolymers, Tedd Casey Wiessner
Toward Enhancing The Synthesis Of Renewable Polymers: Feedstock Conversions And Functionalizable Copolymers, Tedd Casey Wiessner
Arts & Sciences Graduate Student Theses and Dissertations
This thesis describes research under the rubric of the Center for Sustainable Polymers that is aimed at two separate goals. The goal of the first project (Chapters 1 and 2) was to develop a deeper mechanistic understanding of a method for the synthesis of linear α-olefins, while the second aimed at synthesizing statistical copolymers that incorporate olefin-containing monomers through ring-opening transesterification polymerization and showing that these copolymers could be functionalized. In Chapter 1, published methods for the conversion of fatty acids to linear α-olefins are reviewed to provide context for the mechanistic work we accomplished (Chapter 2). In Chapter 2 …
Tissue Resident Macrophages Drive Fibrosis During Pancreas Inflammatory Injury And Pancreatic Ductal Adenocarcinoma, John Baer
Arts & Sciences Graduate Student Theses and Dissertations
The immune system, and especially macrophages, are central in responding to infections, as well as providing a wide array of functions in other pathologies, especially in responding to inflammation. It is established that macrophages will accumulate within tissues during inflammation, many times secreting cytokines and chemokines central to the inflammatory response. This is particularly true during pancreatitis, or inflammation of the pancreas, where it has been shown that macrophages and monocytes accumulate in the pancreas to have various roles in further promoting inflammation. It is not well established, however, whether there are divergent roles for the distinct macrophage subsets that …
Reassessing The History Of The Poverty Point Phenomenon: A Case Study From The Jaketown Site, Mississippi, Usa, Seth Bradley Grooms
Reassessing The History Of The Poverty Point Phenomenon: A Case Study From The Jaketown Site, Mississippi, Usa, Seth Bradley Grooms
Arts & Sciences Graduate Student Theses and Dissertations
Towards the end of the Late Archaic period (ca. 4800-3000 cal BP), between 3,600 and 3,300 years ago, Native Americans engineered a colossal earthwork complex that covers approximately 200 hectares in northeast Louisiana. Today, it is a UNESCO World Heritage site known as Poverty Point and the namesake for a material culture pattern documented to varying degrees at sites throughout the Lower Mississippi Valley (LMV). However, the nature of interactions between these sites and the type site is poorly understood. The people who constructed the Poverty Point site lived on wild food resources. They hunted, fished, and gathered food from …
Connections Between Mechanosensitive Ion Channel Msl10 And Er-Plasma Membrane Contact Sites, Jennette Marie Codjoe
Connections Between Mechanosensitive Ion Channel Msl10 And Er-Plasma Membrane Contact Sites, Jennette Marie Codjoe
Arts & Sciences Graduate Student Theses and Dissertations
Mechanosensitive (MS) ion channels are an evolutionarily conserved way for cells to sense mechanical forces and transduce them into ionic signals. A plasma membrane-localized MS channel from Arabidopsis thaliana, MscS-Like (MSL)10, senses cell swelling and initiates a signaling cascade that triggers programmed cell death. Whereas the channel properties of MSL10 have been well studied, how MSL10 signals remains largely unknown. I worked collaboratively to show that important lesions for cell death signaling in the cytosolic N- and C-terminal domains of MSL10 interact genetically. I also helped show that ionic flux through MSL10 is dispensable for signaling, which suggested that MSL10 …
Analyzing The Interconnectedness Of The Human Genome, Nicholas Jacobs
Analyzing The Interconnectedness Of The Human Genome, Nicholas Jacobs
Arts & Sciences Graduate Student Theses and Dissertations
The human genome is much more interconnected than many people realize. In this thesis, I will outline two efforts to portray this idea. First, I will seek to display that cell fitness is an omniphenotype. That is to say, cell fitness can be used to determine whether an unknown factor interacts with a known factor for any phenotype. The human genome is sufficiently interconnected that if two factors interact with one another then that can be reflected by a multiplicative change in cell fitness. This change in fitness can be used to determine if a new factor of interest is …
Cooperation And Conflict In The Social Amoeba Dictyostelium Discoideum And Its Paraburkholderia Endosymbionts, James Medina
Cooperation And Conflict In The Social Amoeba Dictyostelium Discoideum And Its Paraburkholderia Endosymbionts, James Medina
Arts & Sciences Graduate Student Theses and Dissertations
A big question in biology is how organisms compete in an environment of competitors for scarce resources. Part of the answer lies in distinguishing friend from foe and in forging cooperative bonds in the face of cheaters. The social amoeba – bacteria system I have studied here is an excellent place to explore these tensions. The first part of my thesis research involves a review of cooperation and conflict in the social amoeba Dictyostelium discoideum and a study of the limits on obligate social cheating in this species. The second part focuses on the benefits of associating with D. discoideum …
Inferring Adaptation In Social Microbes From Experimental Evolution Under Relaxed Selection, Tyler John Larsen
Inferring Adaptation In Social Microbes From Experimental Evolution Under Relaxed Selection, Tyler John Larsen
Arts & Sciences Graduate Student Theses and Dissertations
Microbes exist against a backdrop of other organisms, and the interactions between microbes have major consequences on their traits, their evolution, and their impact on the world. Microbial interactions and the adaptations that enable them are extremely diverse – they can unlock abilities beyond the reach of individual cells or lead to a population’s destruction, they can be temporary or permanent, they can be between genetically identical cells or different species entirely. The first chapter of this dissertation reviews microbial interactions and the related concept of the evolution of conflict and cooperation.To be certain a trait is an adaptation at …
Functionalized Plasmonic Nanostructures For Ultrasensitive Single Cell Analysis, Priya Rathi
Functionalized Plasmonic Nanostructures For Ultrasensitive Single Cell Analysis, Priya Rathi
Arts & Sciences Graduate Student Theses and Dissertations
Ultrasensitive detection and quantification of soluble, secreted and cell surface-bound proteins is critical for advancing our understanding of cellular systems, enabling effective drug development, novel therapies, and bio-diagnostics. However, exiting technologies are largely limited by their sensitivity, making the detection and quantification of low-abundant proteins extremely challenging. This forms a major barrier in various fields of biology and biomedical sciences. In this work, we introduce novel cellular analysis methodologies based on plasmon-enhanced fluorescence for analyzing cell structure and probing surface and secreted proteins from cells. In the first part, we introduce plasmon-enhanced expansion microscopy and demonstrate the effectiveness of employing …
The Effect Of Ionization Density In Applications Of Radiation Detection, Dosimetry, And Therapy, Daniel Mulrow
The Effect Of Ionization Density In Applications Of Radiation Detection, Dosimetry, And Therapy, Daniel Mulrow
Arts & Sciences Graduate Student Theses and Dissertations
This dissertation covers a wide range of topics but is linked by the common theme of radiation interacting with materials and studying the result of those interactions. The introduction describes the fundamentals of how radiation interacts with material and how we are able to detect that radiation and the application of how we use those interactions in radiation oncology. The thesis starts with a chapter detailing the temperature dependence of the photophysics in two organic scintillators. This chapter is the foundation for a future study that will look the degree to which these scintillators can distinguish between gammas and neutrons …
Essays On Macroeconomics And Finance, Matias Nicolas Marzani
Essays On Macroeconomics And Finance, Matias Nicolas Marzani
Arts & Sciences Graduate Student Theses and Dissertations
This dissertation investigates the relationship between risk and finance at the level of firms. In the first chapter, a model is developed in which optimal debt maturity is determined by a balance between the higher rollover risk of short-term debt and the higher risk-taking incentives of long-term debt. Evidence is provided using firm-level data on sales growth volatility and resource allocation to business lines. The second chapter explores the role of financial innovation in securities issuance, finding that the introduction of new financial products improves a firm's ability to raise funds. A model of the allocation of financial products among …
The Enemy Within: An Investigation Of The Intracellular Bacteria In Urinary Tract Infections, Jennie Elizabeth Hazen
The Enemy Within: An Investigation Of The Intracellular Bacteria In Urinary Tract Infections, Jennie Elizabeth Hazen
Arts & Sciences Graduate Student Theses and Dissertations
Urinary tract infections (UTIs) are common diseases that are associated with significant morbidities. Multiple studies have indicated that multiple species of uropathogenesis bacteria invade and persist within bladder epithelial cells as a necessary step of uropathogenesis. Interestingly, many of these species are not canonically associated with intracellular infections. Although the first study describing bacteria within the urothelium was published two decades ago, this critical step of uropathogenesis remains relatively understudied.I established a murine model of community-acquired A. baumannii UTI, a previously unstudied manifestation of the disease. While immunocompetent mice resolved their infections quickly, immunocompromised mice displayed high bacterial burdens throughout …
A Universal Mechanism Of G Protein Inhibition, Tyson Daniel Todd
A Universal Mechanism Of G Protein Inhibition, Tyson Daniel Todd
Arts & Sciences Graduate Student Theses and Dissertations
G protein coupled receptors transduce a truly staggering number of diverse extracellular signals including chemical messengers, physical force, and even photons into specific cellular responses through their coupling to heterotrimeric G proteins. G proteins amplify the originating signal through their binding to downstream effectors, activating a complex network of overlapping responses that allow the cell to respond perfectly to that specific stimulus. It is critical to the cell that this process is carried out faithfully in order to respond to the myriad environmental cues and avoid injury, exhaustion, and death for the individual cell or the development of pathology if …
Modernism As Public Art: Reawakening The Social Agency Of Abstract Public Sculpture, 1950–1980, Tola Porter
Modernism As Public Art: Reawakening The Social Agency Of Abstract Public Sculpture, 1950–1980, Tola Porter
Arts & Sciences Graduate Student Theses and Dissertations
This dissertation presents a critical reassessment of postwar modern public sculpture and offers a framework for both the reevaluation and reawakening of these significant, inherited public images. Between 1950 and 1980, as a result of new national policies, the United Kingdom and the United States experienced a boom in public sculpture. That phenomenon was augmented by architectural modernism, whose stark buildings called for the addition of sculpture. The growing prestige of abstract art made it a popular choice for architects and commissioners, who sought to leverage the cachet of contemporary artists. For both private sector architects and public sector patrons, …
Genetic And Transcriptomic Aspects Of Major Depressive Disorder: In Vivo Functional Assays Of Risk-Associated Variation, Candidate Disease Cell Types, And Their Pharmacologic And Sex Interactions, Bernard Mulvey
Arts & Sciences Graduate Student Theses and Dissertations
Major depressive disorder (MDD) is a debilitating illness that affects hundreds of millions globally, with substantial personal, medical, economic, and societal consequences. While depression occurs more commonly in females, the biology of the brain and sex underlying this skewed prevalence remains unclarified. This body of work explores two aspects of how biological sex may influence the brain at the level of gene expression: through intrinsic sex differences and through sex-mediated effects of depression risk genetics.The monoamine hypothesis of depression suggests that modulatory neurotransmitters including serotonin and norepinephrine constitute a key axis in development of MDD. Large-scale studies of MDD treatment …
Tracking Reducing Equivalents Between Cellular Compartments To Understand The Metabolic Demands Of Proliferation, Yahui Wang
Arts & Sciences Graduate Student Theses and Dissertations
Proliferating cancer cells compartmentalize metabolic reactions, many of which require reducing equivalents. This compartmentalization is functionally important, but it is challenging to study with current technologies. As a consequence, our understanding of proliferating metabolism has been limited. Here, I developed an approach to track reducing equivalents between cellular compartments. By applying this method to a panel of different cell lines under various conditions, I investigated a dysregulated metabolic phenotype in proliferating cells known as “aerobic glycolysis”. Aerobic glycolysis is characterized by an elevated rate of glucose fermentation to lactate irrespective of oxygen availability. Using the NCI-60 cell lines, I first …
Mechanisms For High Light Tolerance In A Fast-Growing Cyanobacterium, Patricia Walker
Mechanisms For High Light Tolerance In A Fast-Growing Cyanobacterium, Patricia Walker
Arts & Sciences Graduate Student Theses and Dissertations
Through oxygenic photosynthesis, cyanobacteria, algae, and plants convert light into chemical energy. However, highly energetic light often damages the photosynthetic apparatus, which can lead to the decline of photosynthetic activity (photoinhibition), and prolonged photoinhibition can lead to cell death. Cyanobacteria enact various protective mechanisms to mitigate photodamage, many of which have been conserved in plants. Repair of PSII reaction centers, decreased light absorption, quenching of excess absorbed energy, and biosynthesis of antioxidants all work to mitigate damage during high light. Due to the adjustments to photosynthesis, acclimation to high light requires remodeling of cellular metabolism and physiology. Therefore, phototrophs have …
Roles Of Behavioral Novelty And Organismal Energetics In The Evolution Of Extreme Encephalization, Erika Laurie Schumacher
Roles Of Behavioral Novelty And Organismal Energetics In The Evolution Of Extreme Encephalization, Erika Laurie Schumacher
Arts & Sciences Graduate Student Theses and Dissertations
Brains and their component brain regions vary widely in size and structure across vertebrates. However, extreme increases in total brain size relative to body size (extreme encephalization) and increases in specific major brain region sizes independent of other brain regions (mosaic brain evolution) are relatively rare. There are several hypotheses as to why, but the energetic cost of increased brain tissue and the regional interconnectedness in both brain development and function likely constrain how brains are able to change in response to selection. In this dissertation, I sought to address both how behavioral novelty relates to evolutionary changes in brain …