Digital Commons Network^™

Contribution Of Metabolic Cell Swelling On Microcirculatory Perfusion In Septic Shock, Charles E. Payne

Theses and Dissertations

Sepsis, a systemic immunological response that leads to organ-dysfunction, the development of septic shock, and death has mortality rate of 15-25%. A subset of sepsis, septic shock, has an in-hospital mortality rate of 30-50%. Sepsis and its treatment are the most expensive healthcare problem in the United States with the US Agency for Healthcare Research and Quality estimating annual costs over $20 billion. Hypoxia experienced in septic shock induces metabolic cell and tissue swelling leading to further microcirculatory dysfunction and poor tissue perfusion. Reversing metabolic cell swelling corrects these perfusion defects. Two models were used in rats to induce septic …

Dune Building Dynamics Impact Cross-Island Connectivity And Barrier Island Characteristics, Alexander Sabo

Theses and Dissertations

Located at the land-sea interface, barrier islands are important protective features that reduce wave energy and erosion from mainland areas. Further, barrier islands provide habitat for many different organisms and serve as popular areas for recreation and tourism. As sandy landforms, barrier islands are easily disturbed, but often recover after disturbance as a result of island plant communities, specifically dune building grasses. Disturbance on barrier islands is driven by storms, tides, and overwash events. After disturbance has occurred, dune grasses colonize the dunes allowing for dune building and habitat restoration. On the Virginia barrier islands, there are three dominant dune …

Pre-Clinical Trials With Precision-Medicine Based Therapeutics In Basal-Like Patient-Derived Xenografts, David C. Boyd

Theses and Dissertations

Breast cancer treatments have improved over time, but the diseases seeing the most benefit from these improvements have the estrogen receptor, progesterone receptor, or are positive for HER2. Basal-like breast cancer tends to not have these biomarkers, which necessitates their treatment to be traditional, untargeted therapeutics which are less effective and tend to have harsh adverse effect profiles – this is an important unmet need. These studies utilize a variety of techniques, including tissue culture, viability assays, high-throughput screening, in vivo drug treatments and imaging, pathway analyses, molecular techniques such as Western blot, antibody arrays, RNA sequencing, sc RNA sequencing, …

Intrinsic Efficacy As A Determinant Of Opioid Effectiveness In Treatment Of Pain-Depressed Behavior, Edna Santos

Theses and Dissertations

Pain is a major public health concern that is commonly associated with behavioral depression, and a major goal in pain treatment is alleviation of pain-related behavioral depression. High-efficacy mu opioid receptor (MOR) agonists (e.g. fentanyl, morphine, oxycodone) are effective to treat pain, but their use is limited by side effects that not only endanger the patient but may also obscure analgesic rescue of pain-depressed behavior. The ongoing epidemic of opioid abuse and overdose deaths has stimulated research to discover non-opioid alternative analgesics; however, this search neglects the clinical potential of safer intermediate-efficacy MOR agonists (e.g. buprenorphine). The objective of the …

X-Ray Crystallography: A Tool For Understanding Protein Function And Drug Discovery, Akua K. Donkor

Theses and Dissertations

Structural biology has become an indispensable tool for determining the 3D structures of proteins for a comprehensive understanding of their functions on molecular level, and for elucidating binding cavities that can be targeted for structure-based drug discovery. X-ray crystallography, the most widely used structural biology technique was utilized in addition to other techniques to: (1) understand the role of pyridoxal reductase (PDXI) in pyridoxal 5’-phosphate (PLP) homeostasis; (2) Determine whether the putative PLP binding protein, YggS, is involved in PLP homeostasis; (3) Elucidate the molecular basis underlying Agrobacterium receptor VirA pathogenesis; and (4) Elucidate the structural basis of aromatic aldehydes …

Unraveling The Consequence Of Adult Onset Sulfatide Depletion: Its Implications In Myelin And Axonal Heath In The Context Of Neurodegenerative Disease, Elizabeth Dustin

Theses and Dissertations

Multiple Sclerosis is an immune mediated disease of the CNS. MS is diagnosed through detection of demyelinated regions. However, recent studies demonstrate that Normal Appearing White Matter (NAWM) contains substantial pathology. One such pathology observed in the NAWM is the reduction of sulfatide. The proper stoichiometry of lipids in myelin acts to maintain rapid conduction velocity, provide trophic support to the neuron, and protect the axon from degeneration. We previously characterized a mouse lacking sulfatide’s synthesizing enzyme, CST through constitutive gene disruption and demonstrate that sulfide is required for proper stability of the myelin sheath. However, since MS is typically …

Development Of Tangible Code Blocks For The Blind And Visually Impaired, Hyun Woo Kim

Theses and Dissertations

The fields of Science, Technology, Engineering, and Mathematics (STEM) have been growing at an accelerating rate in recent times. Knowing how to program has become one key skill for entering all of these STEM fields. However, many students find programming difficult. The block based programming language, Scratch, was specifically designed to lower hurdles to learning how to program for sighted students. Unfortunately, although very effective and widely used in K12 classrooms, Scratch, similar to other block based languages, is inaccessible to students who are blind and visually impaired (BVI). This thesis is part of a larger project to make the …

Quantitative Changes In Hippocampal Ccr5+ Microglia With The Administration Of Maraviroc (Mvc): Does Sex Matter?, Ama S. Boakye-Agyei

Theses and Dissertations

Human immunodeficiency virus type-1 (HIV-1) has been greatly studied in recent decades. Combined anti-retroviral therapy (cART), the development of drug treatments such as maraviroc, and the wider availability of support for those in resource-rich environments have been instrumental in improving the prospects of people living with HIV (PLWH). It is well- documented that PLWH can suffer from a host of cognitive deficits collectively known as HIV- associated neurocognitive disorders (HAND). Moreover, the role of biological sex in the development of HAND and other cognitive deficits is still being studied. C-C chemokine receptor type 5 (CCR5) is one of the two …

Characterization Of Sphingosine-1-Phosphate Receptor Expression And Functionality In Niemann-Pick Type C Disease, Nathaniel-David I. Dizon

Theses and Dissertations

Niemann Pick Type C (NPC) is a recessively inherited lysosomal storage disorder for which there is currently no major treatment. It is widely acknowledged that the pathology of NPC is caused by a trafficking defect which leads to an accumulation of cholesterol in the late endosome/lysosome compartment (LE/L). In addition to cholesterol, multiple species of sphingolipids are observed to accumulate as well in the LE/L. Specifically, an accumulation of sphingosine is observed in NPC disease and is likely attributed to the decreased activity of an enzyme, sphingosine kinase 1 (SphK1), which is responsible for phosphorylating sphingosine into an important pro-survival …

Irene Cox, Lindsey Arturo

Theses and Dissertations

This document explores the question of “Who is Irene Cox?” as a jumping off point for creating an artwork which navigates online information landscapes and their logics circa 2023. By using thirteen unique but similar found paintings of the same floral still life by an artist named “Irene Cox” I create a visually meandering, absurd, haunting, and comical pathway for thinking through who exactly is Irene Cox via the internet. How such a question is even asked becomes the art in which a myriad of visual techniques are used to explore the nature of the question. Included in this paper …

The Hepatic Immunological Pattern Shaped By Dominant-Subdominant Cellular Interactions Creates A Collective Function Beyond The Function Of Each Cellular Constituent To Orchestrate Progression Of Hepatocellular Carcinoma, Nicholas J. Koelsch

Theses and Dissertations

Abundance of data on the role of inflammatory immune responses in the progression or inhibition of hepatocellular carcinoma (HCC) has failed to offer a curative immunotherapy for HCC. This is largely because of taking reductionist approaches and missing the collective function of the hepatic immune system by focusing on specific immune cell types. To this end, we propose that focusing on the dominant-subdominant patterns of the immune cells would allow understanding of the mechanism by which a collective immune function emerges. To identify the collective immune function through a systems immunology perspective, we performed high-throughput analysis of snRNAseq data collected …

Investigation Of Sneathia Vaginalis And The Host Antibody Response To S. Vaginalis Pore-Forming Toxin, Cpta, In Vivo, Zion T. Mccoy

Theses and Dissertations

Sneathia vaginalis, formerly Sneathia amnii, is a gram-negative vaginal species that is associated with pregnancy complications including preterm birth. The only virulence factor of S. vaginalis that has been characterized is the cytopathogenic toxin, component A (CptA), a pore-forming toxin that lyses human red blood cells and human epithelial cells and plays a role in traversal of the bacteria through fetal membranes. The overarching goal of this work was to examine the host immune response to CptA. To investigate the immune response to CptA, levels of anti-CptA IgM, IgA, and IgG in human mid-vaginal swab samples obtained during …

A Tenth Of A Second, Natalia Andrea Mejía Murillo

Theses and Dissertations

A Tenth of a Second is an installation that explores modes of cartographic representation of the universe, specifically the moon, in dialogue with poetic language. The work is based on research and reflection on disciplines such as astronomy and archaeology and addresses issues such as the fragility of the reference and categorization systems we use to approach reality, tactility and the body as a standard of measurement.

Salinization Impacts On Heterotrophic Respiration, Ecosystem Respiration, And Plant Productivity In Tidal Freshwater Marshes, Kelsie J. Moses

Theses and Dissertations

Tidal freshwater marshes have preserved substantial stocks of soil carbon, which represents carbon dioxide that is no longer in the atmosphere. There is conflicting evidence in the literature about how disturbances such as sea level rise and associated wetland salinization impact the accumulation and long-term stability of this stored carbon. The goal of this experiment was to quantify how salinization impacts total ecosystem respiration and its component parts, autotrophic and heterotrophic respiration. This was a microcosm experiment using a C4 plant (Spartina cynosuroides) grown in soil derived from C3 plant matter and exposed to different salinities (0 to …

Role Of Histone Deacetylase (Hdac) In Epithelial To Mesenchymal Transition (Emt) In A Human Cholangiocyte Model Of Ischemic Cholangiopathy, Priyanshi Pragnesh Parikh

Theses and Dissertations

Organ transplants are a vital intervention for many diseases that result in end stage organ failure. Currently, the donation pool is not meeting the demands of the transplant list. Expanding this pool to include donation after cardiac death (DCD) is highly sought-after. However, the use of DCD livers can lead to increased odds of graft failure and ischemic cholangiopathy. The loss of epithelialization and fibrosis that occurs during ischemic cholangiopathy is characteristic of these cells undergoing epithelial-to-mesenchymal transition (EMT). The biological changes the cell experiences enhance migratory capacity, invasiveness, and increased resistance to apoptosis. Our earlier studies have shown differential …

Formal And Full Of Feeling, Kaitlyn Paston

Theses and Dissertations

Formal and Full of Feeling presents research and artistic work leading up to the thesis exhibition Come as you are, expanded in the Anderson Gallery May 2023. My research investigates the relationship between body and images. The research is presented as a journey guided by prompts, in pursuance of an aesthetic language to represent my experience of being a body. I discuss the animation process, research trajectories, installation of the exhibition and artworks that influenced the concepts.

Mechanisms Of Emulsion Destabilization: An Investigation Of Surfactant, Stabilizer, And Detergent Based Formulations Using Diffusing Wave Spectroscopy, Jordan N. Nowaczyk

Theses and Dissertations

Conventional approaches for studying emulsions, such as microscopy and macroscopic phase tracking, present challenges when it comes to establishing detailed mechanistic descriptions of the impact of emulsifier and stabilizer additives. Additionally, while a combination of sizing methods and macroscopic phase tracking can provide insights into droplet size changes and concentration, the use of multiple measurements can be cumbersome and error-prone. It is the focus of this work, to present a new method for studying water in oil (W/O) emulsions that involves using diffusing wave spectroscopy (DWS) to examine the impact of three different surface stabilizing additives at varying concentrations. By …

Characterization And Investigation Of Cold Atmospheric Plasma And Its Effects On Cancer Cell Biology, Thomas M. Ritrosky

Theses and Dissertations

Modern cancer treatment uses radiation therapy in over 50% of patient cases. It is an e↵ective way of treating tumors because the mechanisms of cell killing are well known through the damage that ionizing radiation does to DNA. The amount of radiation can be tracked through measuring the dose of the clinical photon or electron beam used. However, there are limitations in the usage of radiation therapy, for example, a tumor can create hypoxic areas that become radioresistant leading to complete ine↵ectiveness of further radiation treatment. This project looks into the application of cold atmospheric plasma as an adjuvant therapy …

To, From: Of Time, Of Distance, Of Body And Mind, Fanxi Sun

Theses and Dissertations

This paper introduces the concepts, theories, and techniques associated with my thesis project “To, From.” The paper consists of three parts: Time as Structure, Distance as Premise, and Body and Mind. Each chapter is written in a mixture of personal narration and a general introduction to materials that are directly or implicatively relevant and important to the creation of my project. In this experimental narrative comprises film screening and live performance with multi-channel sound, I tell a story of non-story. Words and the exchange of words, movements and non- movements, objects that are being handled and subjects that are handling... …

一To二To三, Yameng Wang

Theses and Dissertations

This work relates to an animated film focusing on iteration, simulacrum, and artificial intelligence. It is based on the traditional Tao concept: “One life two, two beget three, three beget all things.”

Attitudes And Beliefs Of Cannabis Use During Pregnancy: Hashing Out The Impact Of Location And Legality, Anna Wiese

Theses and Dissertations

As more states authorize the use of cannabis for medical and recreational purposes, rates of prenatal cannabis use are on the rise. Yet research on perceptions of prenatal cannabis use has been limited, and the existing research lacks reliable, quantitative measures. In response, researchers in Denver developed the Perceptions of Prenatal Cannabis Use (PPCU) survey, a 16-item measure designed to assess perceived risks and benefits of prenatal cannabis use. The present study analyzed PPCU survey data administered at three different recruitment sites (Denver, CO; Pittsburgh, PA; and Richmond, VA). The present study examined women’s perceptions of the risks and benefits …

Frewayni's Garden: Preserving Tigrayan Culture During A Period Of Ethnocide, Gabrielle F. Tesfaye

Theses and Dissertations

The recent and ongoing genocidal war in Tigray, Ethiopia, has witnessed the destruction and looting of countless historical religious sites, ancient manuscripts, and artifacts, leaving Tigray’s remaining cultural heritage extremely vulnerable. Such cultural loss erases a shared understanding across generations, robbing them of their history and identity. My work contributes to the safeguarding of Tigray’s cultural heritage and collective memory, informed by literature on cultural preservation efforts in post-war societies, and a series of interviews with Tigrayans in the diaspora and in Ethiopia.

The outcome of this thesis is embodied in a series of distinct jebenas, traditional Tigrayan clay coffee …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

Face Anti-Spoofing And Deep Learning Based Unsupervised Image Recognition Systems, Enoch Solomon

Theses and Dissertations

One of the main problems of a supervised deep learning approach is that it requires large amounts of labeled training data, which are not always easily available. This PhD dissertation addresses the above-mentioned problem by using a novel unsupervised deep learning face verification system called UFace, that does not require labeled training data as it automatically, in an unsupervised way, generates training data from even a relatively small size of data. The method starts by selecting, in unsupervised way, k-most similar and k-most dissimilar images for a given face image. Moreover, this PhD dissertation proposes a new loss function to …

Genomic Comparison Of Dba/2j And C57bl/6j Strains Of Mus Musculus And Best Practice Of Genome Alignment For Bioinformatics Analyses, Dustin J. Zeliff

Theses and Dissertations

Alcohol use disorder is known to have significant genetic components that contribute to an individual’s susceptibility to the disease. Mouse models are commonly used to study the mechanisms underlying alcohol use disorder, with C57BL/6J (B6) and DBA/2J (D2) being two of the more prominently used inbred strains. Research in the Miles Laboratory has used these two strains, and genetic panels of mice derived from them, to identify potential genes associated with variance in ethanol-related behaviors using quantitative trait loci (QTL) analysis. For example, Ninein (Nin) was identified as a potential candidate gene for the anxiolytic effects of ethanol, discovered because …

Mechanistic Insight Into Traumatic Brain Injury Induced Neuronal Membrane Disruption: Cathepsin B Relocalization And A Neun Negative Cortical Neuron Subpopulation, Martina L. Hernandez

Theses and Dissertations

Traumatic brain injury (TBI) is a mechanical insult to the head that leads to brain damage and, in turn, causes long-term sensory, motor, cognitive, and affective dysfunction. Diffuse pathologies seen following such injury are associated with these life-altering outcomes that impact the daily lives of TBI survivors. The diffuse pathology that this body of work focuses on is neuronal membrane disruption; it is characterized by increased permeability of the neuron’s plasma membrane. Moreover, our lab had previously found that membrane disruption is exacerbated with intracranial pressure (ICP) elevation. We set out to measure the duration of membrane disruption following injury …

Fascism In Sci-Fi: "Mobilizing Passions" In Robert A. Heinlein's Starship Troopers, Alton C. Ayers

Theses and Dissertations

This thesis responds to criticism of Robert A. Heinlein’s Starship Troopers (1959) as a “fascist” novel by further investigating the claim through a close reading of the novel that applies political theory scholarship on fascism. Chapters I and II introduce the novel along with its general reception and controversy. These chapters consider the accusations of “fascism” given to the novel while at the same time understanding that a clear, exact definition of “fascism” has long been grappled with by scholars since the rise of the regimes in Nazi Germany and Fascist Italy. Chapters III and IV apply political theory to …

"Always A Rocky And Rippling Stream": The Penobscot River And War, 1604-1869, Mary Moody Mclean

Theses and Dissertations

This paper broadly examines how rivers can be used as a pawn in war and, more specifically, how the Penobscot River, located in Penobscot County, Maine, influenced significant battles in America and the fabric of the developing nation due to its geographical location and geological development. This analysis focuses on one critical aspect of the Penobscot River that motivated attacks: the fur, fish and lumber trades, all of which were established due to the proximity of the coast and how the land developed during the Holocene era.

My thesis illustrates how North Americans, British and French used the Penobscot River …

Characterizing 3-O-Sulfation-Induced Novel Compact Topologies In Heparan Sulfate And Their Interactions With Proteins, Samuel Holmes

Theses and Dissertations

Heparan sulfate (HS) is highly-charged, linear polysaccharide that interacts with numerous proteins in humans as consituents of proteoglycans. The action of sulfotransferase enzymes during the biosynthesis of HS can generate a combinatorially massive library of differentially sulfated sequences. Furthermore, the number and position of these sulfate groups are key to their biological activity, modulating their selectivities for certain proteins at the cell surface or ECM. The installation of a sulfate on the C3 hydroxyl of a glucosamine residue in HS represents the rarest of the sulfations, despite the HS 3-O-sulfotransferase (3OST) family being the most diverse of the other sulfotransferases. …

Tgif1 Physiological Levels Limit Β-Cell Distress And Neonatal Diabetes, Creighton J. Friend

Theses and Dissertations

TGIF1 belongs to the superfamily of homeodomain proteins, which regulate a wide variety of biological functions, including cell stemness and specification of cell fate during early development. Perhaps surprisingly, we found that enforced expression in pancreatic progenitor cells during embryogenesis resulted in severe diabetes, hinting at the possibility that TGIF1 might regulate pancreas development. Subsequent genetic experiments targeting β-cells showed that TGIF1 affected β-cell function and homeostasis. Transcriptomic analysis revealed that TGIF1 expression inhibits the expression of essential components of UPR signaling, underscoring a potential mechanism in which TGIF1 disrupts protein folding and secretion. Congruently, TGIF1 expression led to a …