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Genetic Risk Factors For Neurodevelopmental Disorders: Insights From Hipsc-Cerebral Organoids, Michelle L. Wegscheid

Arts & Sciences Graduate Student Theses and Dissertations

Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder (NDD) characterized by remarkable phenotypic variability, where affected children manifest a spectrum of central nervous system (CNS) abnormalities, including brain tumors, impairments in attention, behavior, learning disabilities, and an increased incidence of autism spectrum disorder (ASD). A significant barrier to the implementation of precision medicine strategies for children with NF1 is a lack of prognostic risk factors to guide clinical management. However, emerging population-based genotype-phenotype association studies have suggested that the germline NF1 gene mutation may represent one clinically actionable risk factor for NF1-associated neurodevelopmental abnormalities. As a critical step in …

Surveillance And Dynamics Of Bacteria And Resistance Genes In Humans And Hospitals, Alaric Wences D'Souza

Arts & Sciences Graduate Student Theses and Dissertations

Bacteria live in, on, and around us. These bacteria affect human health through beneficial commensal interactions that promote normal development and through harmful infections or perturbations leading to disease. Understanding the prevalence, spread, and resilience of these bacteria in humans and human environments is critical to clinical medicine and epidemiology. I investigated environmental and human resident bacteria to understand dynamics in bacterial communities and how these dynamics may impact human health.Hospitals are one critical location of human-bacterial interactions. Bacteria can contaminate hospital surfaces from patients or environmental sources and subsequently transmit from surfaces to vulnerable patients. I analyzed bacteria from …

Racial/Ethnic Differences In The Relationship Between Wealth And Health, Sicong Sun

Brown School Graduate Student Theses and Dissertations

Racial wealth inequity is one of the most pressing social and economic issues in the United States, historically and contemporarily. Primarily due to unequal distribution of opportunity for economic advancement and mobility in addition to the accumulation of historic disadvantage endured by Black and Latinx Americans, U.S. racial wealth inequity leads to substantial racial health disparities. It is widely acknowledged that socioeconomic position (SEP) is a fundamental cause of disease and health disparities. Centering around three key constructs—race/ethnicity, wealth, and health—this dissertation had two overarching aims: (a) to investigate the relationship between wealth and health, delineating the effects of wealth …

The Potential Of Mental Health Policy Implementation: Methods And Applications, Meagan Renee Pilar

Arts & Sciences Graduate Student Theses and Dissertations

Mental illness affects roughly 20% of the world in some capacity and can be debilitating. Though a large emphasis has historically been placed on individual-level interventions (e.g., therapy or medication), mental health policies present an opportunity to intervene on a large scale, with the potential to enhance impact and equity. This dissertation contributes to the mental health policy research literature in three main ways—(1) exploring factors affecting policymakers’ overall support of mental health policies; (2) assessing the use and quality of quantitative and qualitative methods within this field; and (3) exploring implementation determinants and outcomes, as well as strategies used …

Acoustic Radiation Force And Its Application For Cell Manipulation And Ion Channels Activation, Xiangjun Peng

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sound is a stress wave that carries energy and momentum flux. Scattered sound waves can generate acoustic radiation force that can be used to manipulate particles or cells. This dissertation demonstrates the physics behind cell manipulation by ultrasound. The work begins with a detailed analysis of the mechanics of using standing surface acoustic waves to fabricate acoustic tweezers for contactless particle manipulation using acoustic radiation force. Models to design and analyze acoustic radiation force have traditionally relied on plane wave theories that cannot predict how standing surface acoustic waves can levitate cells in the direction perpendicular to the substrate. We …

Defining The Role Of Elastic Fibers In Tendon Mechanics, Jeremy D. Eekhoff

McKelvey School of Engineering Graduate Student Theses & Dissertations

Tendons serve as a linking component of the musculoskeletal system by transferring forces between muscle and bone. As such, the structural proteins of the tendon extracellular matrix are of vital importance for the tissue to function properly and maintain its mechanical integrity. Collagen is the principal constituent of tendon and makes up its aligned hierarchical organization. Other structural proteins, such as elastin, are in comparison understudied and not well understood in relation to tendon function. Elastin, the main component of elastic fibers, has unique mechanical properties including high extensibility, fatigue resistance, and elasticity; these properties are important for elastin-rich tissues …

The Effects Of Molecular Chaperone Modulation On Protein Folding, Prion Formation, And Prion Propagation In Saccharomyces Cerevisiae, Leeran Blythe Dublin Ryan

Arts & Sciences Graduate Student Theses and Dissertations

Proper and efficient protein folding is vital for cell survival. Many factors affect protein folding fidelity and prion formation, including molecular chaperone availability and activity. Research has shown that modulating chaperone availability and function can affect protein misfolding and aggregation, as well as de novo prion formation and propagation. However, the factors involved and underlying mechanisms influencing prion formation and protein folding are largely unknown. The following work aims to elucidate these areas. The Nascent Polypeptide-Associated Complex (NAC) is the first point of chaperone contact for nascent polypeptides. Previous work has shown that disruption of the NAC leads to improved …

Human Plcg2 Haploinsufficiency Results In A Novel Immunodeficiency, Joshua Brandon Alinger

Arts & Sciences Graduate Student Theses and Dissertations

NK cells are critical for the recognition and lysis of herpesvirus-infected cells. Patients with NK cell immunodeficiency may suffer from unusually severe and/or recurrent herpesvirus infections; however, the genetic cause is frequently unknown. PLCG2 encodes a signaling protein in NK cell and B cell receptor signaling, in which dominant-negative or gain-of-function mutations may cause cold urticaria, antibody deficiency, or autoinflammation. However, loss-of-function mutations and PLCG2 haploinsufficiency have never been reported in human disease. We examined 2 families with autosomal dominant NK cell immunodeficiency with dual high-dimensional techniques, mass cytometry and whole-exome sequencing, to identify the cause of disease. We identified …

Examining Individual Differences In Forgetting From Long-Term Memory, Christopher Lee Zerr

Arts & Sciences Graduate Student Theses and Dissertations

Forgetting reflects the decreased likelihood of memory retrieval over time. With a few exceptions, although the mean likelihood of retrieval (or retention) across experimental conditions may differ markedly, rates of forgetting across those conditions do not differ. Similarly, although groups (e.g., young and old adults) may differ in the amount retained at a given point in time, the rates of forgetting tend not to differ across groups. In contrast, recent work suggests that individual differences in rates of forgetting may emerge when more sensitive statistical analyses are used on person-level performance. Some person-level variables purported to influence forgetting rate include …

Influence Of Focal Activity On Macroscale Brain Dynamics In Health And Disease, Zachary Pollack Rosenthal

Arts & Sciences Graduate Student Theses and Dissertations

Macroscopic recordings of brain activity (e.g. fMRI, EEG) are a sensitive biomarker of the neural networks supporting neurocognitive function. However, it remains largely unclear what mechanisms mediate changes in macroscale networks after focal brain injuries like stroke, seizure, and TBI. Recently, optical neuroimaging in animal models has emerged as a powerful tool to begin addressing these questions. Using widefield imaging of cortical calcium dynamics in mice, this dissertation investigates the mechanisms by which focal disruptions in activity alter brain-wide functional dynamics. In two chapters, I demonstrate 1) that focal sensory stimulation elicits state-dependent, global slow waves propagating from primary somatosensory …

Photoacoustic Imaging Of Colorectal Cancer And Ovarian Cancer, Xiandong Leng

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic (PA) imaging is an emerging hybrid imaging technology that uses a short-pulsed laser to excite tissue. The resulting photoacoustic waves are used to image the optical absorption distribution of the tissue, which is directly related to micro-vessel networks and thus to tumor angiogenesis, a key process in tumor growth and metastasis. In this thesis, the acoustic-resolution photoacoustic microscopy (AR-PAM) was first investigated on its role in human colorectal tissue imaging, and the optical-resolution photoacoustic microscopy (OR-PAM) was investigated on its role in human ovarian tissue imaging.Colorectal cancer is the second leading cause of cancer death in the United States. …

Numerical Investigations Of Logic Gates And Transistors In Quantum And Classical Information Processing, Anthony Corbin

McKelvey School of Engineering Graduate Student Theses & Dissertations

The development of numerical analysis techniques for electromagnetics and quantum mechanics problems has dramatically increased the rate of new discoveries. Propelled by the exponential growth of computers over the past decades, numerical software has brought the ability to reliably experiment with new ideas and predict new phenomena, even before the physical realizations of these ideas in the labs. This work will demonstrate the application of this capability by applying numerical analysis techniques to design and analyze new devices. First, a system of optical logic gates using a nonlinear metallodielectric grating is completely designed and simulated using numerical analysis. Second, the …

Deep Learning For Automatic Microscopy Image Analysis, Shenghua He

McKelvey School of Engineering Graduate Student Theses & Dissertations

Microscopy imaging techniques allow for the creation of detailed images of cells (or nuclei) and have been widely employed for cell studies in biological research and disease diagnosis in clinic practices.Microscopy image analysis (MIA), with tasks of cell detection, cell classification, and cell counting, etc., can assist with the quantitative analysis of cells and provide useful information for a cellular-level understanding of biological activities and pathology. Manual MIA is tedious, time-consuming, prone to subject errors, and are not feasible for the high-throughput cell analysis process. Thus, automatic MIA methods can facilitate all kinds of biological studies and clinical tasks. Conventional …

Paleo-Environmental Pollution Of The Bronze Production During The Shang Period At Anyang, Henan Province, China, Yi-Ling Lin

Arts & Sciences Graduate Student Theses and Dissertations

Paleo-environmental pollution is invested in both identifying anthropogenic activities and evaluating the environmental condition and its impact on humans to understand human-environment relationships and the human experience of the past. This project first investigates the environmental and health consequences of bronze production during the Shang period at Anyang. As a contribution to the growing scholarship in paleo-environmental and archaeological studies, this dissertation uses Shang bronze production in Anyang as a case study into how paleo- environmental pollution study can inform us about the on environmental and health conditions of lives in the Bronze Age China. Through geochemical analysis (ICP-MS, ICP-OES) …

Developments In Proteomics, Trans-Splicing Technology And Endogenous Transcript Manipulation, Justin Alexander Melendez

Arts & Sciences Graduate Student Theses and Dissertations

Technological innovation drives scientific discovery, unlocks new avenues of research, and allows us to ask questions in ways that were previously unavailable. With each technological advance, our ability to perturb and explore biological systems has grown in ways previously unimagined. The theme of my thesis is the development of new technologies in biology. To this end, I have worked on three technologies that contribute to the areas of protein sequencing, RNA barcoding for trans-splicing and single-cell applications, and a new method for transcriptional knockdown. In my first project, digital analysis of proteins by end sequencing (DAPES), we set out to …

The Role Of Neuronal Atp-Sensitive Potassium Channels In Learning And Memory, Shaul Vladimir Yahil

Arts & Sciences Graduate Student Theses and Dissertations

ATP-sensitive potassium (KATP) channels link cellular metabolism and membrane excitability in many tissues, including brain and pancreas. Gain-of-function (GOF) mutations to KATP channels cause neonatal diabetes, with some patients exhibiting developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. Diabetic symptoms have been attributed to loss of membrane excitability and insulin secretion in pancreatic β-cells, though the origin of neurological deficits and the effects of neuronal KATP-GOF mutations more generally remain elusive. In this dissertation, I will present evidence that mice expressing KATP-GOF mutations pan-neuronally (nKATP-GOF) demonstrated sensorimotor and cognitive deficits, whereas hippocampus-specific hKATP-GOF mice exhibited predominantly learning and memory deficits. …

Deep Multi-Omics Investigations Elucidate Novel Oncogenesis Paradigms, Therapeutic Targets, And Mechanisms Of Treatment Resistance In Cancer, Daniel Cui Zhou

Arts & Sciences Graduate Student Theses and Dissertations

No abstract provided.

Petrology, Geochemistry, And Experimental Studies Of Mafic Enclaves And Amphibole At Shiveluch Volcano, Kamchatka, Andrea Elizabeth Goltz

Arts & Sciences Graduate Student Theses and Dissertations

This thesis connects mineralogical, chemical, and physical observables in quenched mafic inclusions from Shiveluch Volcano in Kamchatka and high pressure and temperature experiments to elucidate the water content of primitive magmas at Shiveluch, the timing of magmatic recharge events relative to eruption, and the petrogenetic history of andesites erupted at Shiveluch. Using the petrology of basaltic andesite mafic inclusions erupted from Shiveluch, in Chapter 2, the water content of primitive magmas at Shiveluch is found to be 8-10 wt%, which is two to three times higher than the global average determined by other methods, and the temperature of primitive magmas …

Addressing Pragmatic Challenges In Utilizing Ai For Security Of Industrial Iot, Maede Zolanvari

McKelvey School of Engineering Graduate Student Theses & Dissertations

Industrial control systems (ICSs) are an essential part of every nation's critical infrastructure and have been utilized for a long time to supervise industrial machines and processes. Today’s ICSs are substantially different from the information technology (IT) devices a decade ago. The integration of internet of things (IoT) technology has made them more efficient and optimized, improved automation, and increased quality and compliance. Now, they are a sub (and arguably the most critical) part of IoT's domain, called industrial IoT (IIoT).

In the past, to secure ICSs from malicious outside attack, these systems were isolated from the outside world. However, …

A Case Study On Hls Portability From Intel To Xilinx Fpgas, Zhili Xiao

McKelvey School of Engineering Graduate Student Theses & Dissertations

Field-programmable gate arrays (FPGAs) are a hardware accelerator option that is growing in popularity. However, FPGAs are notoriously hard to program. To this end, high-level synthesis (HLS) tools have been developed to allow programmers to design hardware accelerators with FPGAs using familiar software languages. The two largest FPGA vendors, Intel and Xilinx, support both C/C++ and OpenCL C to construct kernels. However, little is known about the portability of designs between these two platforms. In this work, we evaluate the portability and performance of Intel and Xilinx kernels. We conduct a case study, porting the Needleman-Wunsch application from the Rodinia …

Advancements In Pressurized Oxy-Combustion Process: Pollutant Control And Process Development, Piyush Kumar Verma

McKelvey School of Engineering Graduate Student Theses & Dissertations

The emission of carbon dioxide from the power industry is one of the major causes of climate change. However, it is well established that the development of human societies across the globe depends on reliable and dispatchable power, which are generally the source of these emissions. There has been a recent growth in the integration of intermittent sources such as wind and solar which are carbon free. But these intermittent sources have significant temporal changes in power production and thus lack reliability and dispatchablity. This is a complicated problem to solve. However, flexible power plants with carbon capture and storage, …

“Africa Of The Heart”: The African Experience In Derek Walcott's Omeros, Hussein Kadhum Challab

Alustath Journal for Human and Social Sciences

Derek Walcott's book-length poem Omeros won critical acclaim soon after its publication in 1990. In this poem, the world of the Caribbean is linked with that of Homer by recalling the dramas of Homer’s Iliad and Odyssey in a Caribbean setting. Africa is heavily featured in Omeros as most of the major characters of the poem who in one way or another go through the African experience. 'Return to Africa' is a recurrent theme in Derek Walcott's works. However, this kind of return is not for the sole purpose of finding their old lost homeland, but rather for establishing roots …

The Scars Of Capitalism In Virginia Woolf’S Mrs. Dalloway And ‘Kew Gardens’, Median Mashkoor Hussein

Alustath Journal for Human and Social Sciences

This paper discusses the scars of capitalism in Virginia Woolf’s Mrs. Dalloway and ‘Kew Gardens’. Following one day of the character’s life, the discussion will investigate how the novel and the short story introduce the capitalist ideology that dictates the character’s everyday life and how the characters, in different ways and to certain extents, react to it. In Mrs. Dalloway, Woolf depicts capitalism as an oppressive system that can be very rewarding to those who submit to its ideals and, at the same time, very catastrophic to those who try to confront it or question its validity. In ‘Kew …

Quantitative Characterization Of Microbial Ecologies In Dysbiosis And Infection, Eric Keen

Arts & Sciences Graduate Student Theses and Dissertations

In 1973, Theodosius Dobzhansky famously wrote that nothing in biology makes sense except in the light of evolution. Today, nearly 50 years later, little in microbiology – or in biology, for that matter – makes sense except in the light of genomics. Microbial genomics populates the field with innumerable testable hypotheses for evaluation in vitro and in vivo, allows us to monitor microbial populations in real time and at a massive scale, and underpins our approach to entire domains of microbiology, including microbial evolution. In this Thesis, I present three studies from my graduate research united by their common theme …

Satirizing Empire: Comparing Ancient China And Rome, Di Wang

Arts & Sciences Graduate Student Theses and Dissertations

Comparative scholars of the ancient Mediterranean and East Asian worlds have recently taken a serious interest in the unprecedented and simultaneous emergence of two classical empires: Rome and China. The trend, invigorated by the contemporary geopolitical development of China’s rise as a world empire challenging the post-World War II Western hegemony, has yielded new insights into the many divergences and convergences of the world’s two most enduring political and cultural systems. However, preoccupied with describing the political, cultural institutions and grand narratives of empire, scholarship has largely ignored the detractors of empire, whose ingenious expressions are as enduring as these …

Causal Function And Bias Correlation Of The Orbitofrontal Cortex In Economic Choices, Shi Weikang

Arts & Sciences Graduate Student Theses and Dissertations

Economic choices entail two mental processes, value calculation and value comparison (Niehans, 1990). Studies in the last twenty years have shown that neurons in the orbitofrontal cortex (OFC) could support both processes. Namely, in the studies in which monkeys chose between two juice options with various amounts, three functional cell groups had been found in the OFC: offer value cells encode the value of individual juices, chosen juice cells encode the choice in a binary way and chosen value cells encode the value of the chosen juice (Padoa-Schioppa and Assad, 2006). These results suggest a decision circuit within OFC with …

Probing New Physics Beyond The Standard Model Via New Neutrino Interactions, Garv Chauhan

Arts & Sciences Graduate Student Theses and Dissertations

The Standard Model (SM) of Particle Physics provides a self-consistent quantum field theoretic framework to explain three of the four known fundamental forces (electromagnetic, weak, strong) along with classifying all known elementary particles. Since its conception in the 1960s, the SM has been one of the most tested theories of physics and has withstood all experimental batterings. In spite of these successes, there are compelling indications, both experimental and theoretical, that require us to expand our understanding of the nature beyond the SM (BSM). Arguably the most glaring indication of BSM physics is the observation of neutrino oscillations, which implies …

Slo2.1 Channels: A New Molecular Mechanism To Regulate Uterine Excitability, Juan Jose Ferreira

Arts & Sciences Graduate Student Theses and Dissertations

At the end of pregnancy, the uterus transitions from a non-contractile state to a highly contractile state. Two processes primarily drive this transition. First, from the 28th week of pregnancy until labor, the resting membrane potential of uterine (myometrial) smooth muscle cells (MSMCs) gradually becomes more positive (depolarizes) (Parkington et al. 1999). Second, at the end of pregnancy, MSMCs express more oxytocin receptors and become more sensitive to oxytocin (Kimura et al. 1996). However, the detailed mechanisms by which these processes occur have not been determined. My central hypothesis was that the Na+-activated K+ channel SLO2.1 plays a key role …

On Arousal And The Internal Regulation Of Brain Function: Theory And Evidence Across Modalities And Species, Ryan Raut

Arts & Sciences Graduate Student Theses and Dissertations

The brain is an organ. It is subject to the same physiological regulatory processes that engage the rest of the body’s organs, sculpted over hundreds of millions of years to sustain life so effectively. The central message of this thesis is that the holistic functioning of the brain, rather than operating at some level above or independent from these systemic regulatory processes, is deeply related to them. In short, as our limited attention spans might suggest: brain function is internally regulated. I propose that this internal regulation is a primary function of intrinsic brain activity. Chapter 2 provides a theoretical …

Quantifying Components Of Protein Translation And Metabolite Heterogeneity In Isogenic Microbial Populations, Alexander Schmitz

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cell-to-cell variation in gene expression and metabolite levels have a significant impact on ensemble productivity of microbial bioproduction. New metabolic engineering tools and approaches are needed that consider cell cultures as an amalgam of uniquely behaving individuals to improve the slow commercialization of metabolically engineered systems. Stochastic cellular process including gene expression, metabolism, and growth lead to phenotypic variation between genetically identical cells. Understanding and the ability to control microbial phenotypic variation is key to improving microbial bioproduction metrics. During protein translation, codon usage strongly influences ensemble gene expression but the effect on the variation of gene expression was not …