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Mechanisms Of Ppar-Alpha Targeted Therapy In Cholestasis: Translational Studies, Gina Gallucci

Open Access Dissertations

Cholestatic liver diseases, i.e. primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), result from a disruption of bile flow. While bile acids are crucial to maintain hemostasis, retention of bile acids becomes inherently cytotoxic and can lead to hepatocellular inflammation. Currently, the treatment options for these diseases are Ursodeoxycholic acid (Ursodiol) and Obeticholic acid. However, ~40% of patients do not respond to Ursodiol and pruritus is a limiting side effect of Obeticholic acid. Without proper treatment these diseases can progress to fibrosis, cirrhosis, and eventually liver failure. Recently, fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARa) agonist has become an …

Investigating The Mechanism And Expanding The Reactivity Of Cu(I)-Catalyzed [2+2] Photocycloaddition Reactions Of Olefins, Gethmini Kasunka Jayasekara

Open Access Dissertations

Light-matter interactions can change the physical and chemical properties of a substance. The energy of photons can be used to dissociate the chemical bonds as well as to generate new bonds. The work in this dissertation is an attempt to understand how photon energy governs the formation of new carbon bonds via alkene groups in the presence of copper catalyst.

Intermolecular and intramolecular [2+2] photocycloaddition reactions facilitate the generation of cyclobutane moieties which are otherwise difficult to synthesize. Transition metal-based salts are used as catalysts to promote photocycloaddition reactions. The structure and the ring strain of a substrate can affect …

Middle Children Of History: Male-Authored Post-1960s Fiction & The Nihilism Of White Male Protagonists, Emma C. Baughman

Open Access Dissertations

This dissertation addresses the phenomenon of the white male nihilist as a recurrent character in British and American fiction post-1960. The utilization of this archetype by predominantly white male authors during this time period is symptomatic of the social, political, and economic changes that fundamentally altered the perception of the white masculine mythos in much of the Western world after the end of World War II. Because the perception of whiteness and masculinity is a primary signifier of the period’s changing value, my project approaches fictional texts of white male nihilism as objects of socio-cultural analysis that constitute a genealogy …

The Global Dynamics Of Some Rational Difference Equations Exhibiting Neimark-Sacker Bifurcation, Connor O'Loughlin

Open Access Dissertations

This thesis is presented in manuscript format. The first chapter will introduce preliminary definitions and theorems that will be used in the succeeding chapters.

The second chapter will consider the dynamics of a second-order sigmoid Beverton-Holt equation

x_n+1 = x²_n / ax²_n + x²_n-1 + d

where the parameters a and d are positive numbers and the initial conditions are non-negative numbers. For this equation, we will begin by giving a description of the local dynamics of the equation, and then will also examine the global dynamics, including an investigation into the basins …

Nano/Bio Interactions For Synthetic And Natural Nanomaterials, Zachary Shepard

Open Access Dissertations

As the field of nanotechnology advances, it is becoming more important to understand nanomaterial interactions with microorganisms. New methods for examining bacterial response to and interaction with nanomaterials are presented in the studies included here. First, bacterial response to two-dimensional nanomaterials is evaluated using a high throughput approach. Next, a calibrated water jet is used to demonstrate the effect of ship speed on biofouling release. Finally, methods of purifying biogenic nanoparticles were reviewed and evaluated for potential application at large scale. Each of these studies utilizes novel techniques for examining bacterial responses or interactions with nanomaterials or nano-enabled surfaces.

The …

Investigations Into The Adaptive Potential Of Southern Ocean Phytoplankton, Ian W. Bishop

Open Access Dissertations

Southern Ocean (SO) phytoplankton are foundational to Antarctic marine food webs and global carbon and silica cycling. As polar ocean environments continue to rapidly evolve, it is important to assess the extent to which these communities can successfully respond. Adaptation to novel conditions will be particularly important here, as shifts in biogeography to track temperature preferences are unlikely where communities already inhabit the coldest surface waters in the Southern Hemisphere. This work employs high throughput physiological and genomic methods to better understand how three important attributes, thermal trait diversity, standing genetic diversity, and repetitive genomic elements, assessed at a multiple …

Biophysical Characterization Of Phlip And Phlip-Cargo Conjugates Developed For Imaging And Therapy, Hannah Visca

Open Access Dissertations

Acidity is considered an alternative biomarker for targeting diseased tissues, such as in the acute phase of inflammation or tumors with poor prognosis. The family of pH Low Insertion Peptides (pHLIPs) are known markers of tissue acidity which provide a useful method for the diagnosis and/or treatment of disease by extracellular or intracellular delivery of imaging agents or therapeutic molecules. In my research, I employ fluorescence and CD spectroscopic techniques to understand how pHLIP's pH-dependent interactions with and insertion into the lipid bilayer of the cell membrane are affected by its sequence and conjugation with cargo and how this correlates …

Strategies Towards The Synthesis And Analysis Of Materials With Potential Environmental Impacts, Justin Pantano

Open Access Dissertations

There are a number of environmental issues that are proving to have strong effects on local populations. Chief among them is the growing concentration of contaminants in seawater, of which there are limited ways to detect in a consumer-friendly way. Contaminants such as nitrite and phosphate have strong adverse effects on aquatic life, including algal blooms and observed hypoxia in fish. The main work presented in this dissertation discusses some ways to leverage organic chemistry to develop materials to help combat these contaminants. Chapter 2 discusses the design of a novel monomer and investigates its ability to polymerize under ring-opening …

Diagnostic Brains, Experiential Minds And Metamodernism: Mcewan, Self, And Mccarthy As Case Studies, Mohamed Anis Ferchichi

Open Access Dissertations

In the wake of critical stances encompassing both modernism and postmodernism, we witness a theoretical preoccupation with how recent literary innovations position today's British fiction within the legacy of the novel form. On the one hand, postmodernism disrupted modernism's experiential phenomenology of interiority, subject, and character (what I call an experiential inflexion in critical comprehension of the form). On the other hand, what was declared "the decade of the brain" shifted some narrativization to exteriority, syndromic specifics, and reductive somaticism (what I see as a diagnostic inflexion in critical comprehension of the form). In considering today's British fiction within the …

Evaluation Of The Toxicokinetic Mechanisms Of Perfluoroalkyl Substances: Accumulation, Distribution, And Elimination, Sangwoo Ryu

Open Access Dissertations

Per- and polyfluoroalkyl substances (PFAS) are a diverse class of anthropogenic chemicals associated with several adverse health outcomes in humans. The accumulation of these PFAS have been examined over several decades, however, the elucidation of the toxicokinetics of these chemicals are still in its infancy. The distribution and elimination mechanisms of specific PFAS, notably perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), have undergone comprehensive investigation, however, there are more than 10,000 currently detected PFAS in the environment that have not been examined. It is, therefore, imperative to not only address individual PFAS but also to encompass overarching trends and correlations …

13c Labeling For Cho Cell Metabolism Tracing And Ms Based Analysis For Advanced Upstream Culture Monitoring To Support Cqa Understanding, Xin Bush

Open Access Dissertations

Monoclonal antibodies (mAbs) make up a large part of biopharmaceutical sales due to their great success in treating cancer, autoimmune, and cardiovascular diseases. Due to an increasing number of mAbs using innovative approaches in drug development, combined with changes in the drug market, there is an increased need for optimizing process intensification and quality control. Thus, a profound understanding of cellular metabolism and how this impacts the protein product’s critical quality attributes (CQA) would be of great value. Among the quality attributes of mAbs, post-translational modifications such as N-linked glycosylation are of particular importance as they affect the activity, efficacy, …

The Influence Of Nutrient Regime On Diatom Diversity And Diatom Diazotroph Associations, Samantha Patricia Setta

Open Access Dissertations

Phytoplankton are important primary producers at the base of the marine food web. Diatoms are one of the most diverse groups of phytoplankton. Compared to other phytoplankton, diatoms have higher nutrient requirements due to their larger size, and as such, their distribution is limited by nutrients. Because of this, diatoms thrive in high-nutrient ocean regions, such as coastal and high-latitude waters, where the bulk of prior diatom research has occurred. However, diatoms are also found in low-nutrient oligotrophic waters, where they can form blooms and contribute up to 30% of total annual carbon sequestration. Many studies have documented the metabolic …

Advances In Deep-Sea Imaging And Soft Robotics, Russell Joseph Shomberg

Open Access Dissertations

This study contains three parts under the central theme of deep sea robotics for size, weight, power, and cost (SWAP-C) limited platforms.

1) We developed and deployed a rapid action pressure compensated deep sea hydraulic engine for Flexible Elastomeric Actuators (FEAs) and other soft robotic actuators. The engine draws low electric power and has a compact form factor, making it suitable for use on remote deep sea platforms such as science class Remote Operated Vehicles (ROVs) and other Unmanned Underwater Vehicles (UUVs). The design can be scaled and optimized for different use cases. The design principles, performance models, prototypes, and …

Biochemical And Genetic Mechanisms Underpinning Escherichia Coli Cell Cycle And Growth Transitions, Josiah Morrison

Open Access Dissertations

Bacterial cell division and the decision to divide is a process that requires a wide variety of factors. In bacterial cells, such as the widely studied Escherichia coli, a large protein complex, termed the Z-ring, assembles at midcell to enable division. The Z-ring is subject to many regulators which govern the spatiotemporal positioning of the ring. The Z-ring is made up of the eukaryotic tubulin homolog FtsZ, which polymerizes to recruit division proteins to the midcell. FtsZ polymers are tethered to the cytoplasmic membrane by the actin homolog FtsA. Together, FtsZ and FtsA act as the first step in …

Groundwater Dynamics In An Unconfined Coastal Aquifer: Geophysical Investigations And Modeling, Jeeban Panthi

Open Access Dissertations

Coastal groundwater plays a vital role in the sustainability of coastal ecosystems and the freshwater supply for over one billion people worldwide. Understanding the movement and interaction of saltwater and freshwater in coastal aquifers is crucial for effective water resource management. The interface between these density-contrast waters is highly dynamic and sensitive to natural drivers, such as sea level rise, storm surges, and drought, as well as anthropogenic factors, including groundwater over-pumping. In recent years, the drivers of coastal groundwater dynamics have been increasingly well understood and quantified. However, there is a need for data-model fusion, including integrating different forms …

Utilization Of Large-Scale Genomic Data And Phylogenetic Methods In Studying Evolutionary Radiations, Eren Ada

Open Access Dissertations

The remarkable biodiversity of the Earth fascinated natural scientists for centuries. Studying this biodiversity has been a major occupation of the life sciences because deciphering the underlying biological mechanisms of diversification provides fundamental knowledge for biological evolution. A significant body of evidence shows that today’s biodiversity originated from successive adaptive diversification periods (i.e.: evolutionary radiations) which are generally characterized by the rapid multiplication of lineages with a variety of adaptations and ecological roles. Some of the most well-known examples of evolutionary radiations include the striking wing pattern diversity of Heliconius butterflies, the great body form variety of Caribbean anole lizards, …

Defining The Essential Genome Of Haemophilus Parainfluenzae And Conditionally Essential Genes Required For Its Survival In Biofilms And Serum Complement, Thaís Harder De Palma

Open Access Dissertations

Haemophilus parainfluenzae (Hp), a Gram-negative bacterium is found in different niches of the mouth, and it is very abundant in the supragingival plaque. While considered a commensal in the mouth, Hp is also a HACEK microorganism associated with endocarditis and considered an opportunistic pathogenic species. However, Hp remains a subject of limited investigation. Specifically, the genes necessary for Hp's survival and those that are conditionally essential for thriving under various environmental conditions are yet to be identified. This research addresses those questions using transposon sequencing (TnSeq) to identify the essential genome and the core essential genome in …

Cell Stress, Protein Quality Control, And Activation Of Toxin Antitoxin Systems In Escherichia Coli, Benjamin Piraino

Open Access Dissertations

Responding to environmental stress is critical for all organismal survival, including in bacteria. One of the key bacterial responses to stress is protection of proteins within the cell, which helps to maintain proteins in a functional state. Protection of the proteome is done through a collaborative network of proteins and systems, all functioning to protect the cell. Within Escherichia coli (E. coli), three main proteomic protection systems are chaperones, proteases, and toxin-antitoxin (TA) systems. They work together, with overlapping functions, to regulate stress responses. Chaperones, such as DnaK(Hsp70) and SecB, are major regulators of protein folding within the cell, …

Associations Between Stress, Intuitive Eating, And Adiposity In A Cohort Of Midlife Women, Bridget A. Owens

Open Access Dissertations

Stress and eating behaviors can influence the health of midlife women, a population at risk for weight gain and redistribution of fat to the abdominal area related to shifts in reproductive hormones and aging. Higher stress is associated with negative health outcomes such as increased abdominal adiposity, depression, and chronic diseases such as cardiovascular disease. Women report higher stress and more emotional and physical side effects from stress than men and are more likely than men to engage in emotional eating in response to stress. Further, the desire to lose weight and the prevalence of body dissatisfaction is high among …

Stunned And Stranded: Characterizing Hypothermic Threats To Sea Turtles In The Northwest Atlantic And Enhancing Conservation By Fostering Community Engagement, Felicia M. Page

Open Access Dissertations

Over 40 years of conservation efforts have led to increases in sea turtle populations, but all species found in U.S. waters are still at risk of extinction. While the contributions of such programs like the Sea Turtle Stranding and Salvage Network and bi-national Kemp’s Ridley Sea Turtle Restoration and Enhancement Program have rescued and rehabilitated stranded sea turtles, and protected sea turtles and their nests, there are still substantial knowledge gaps that could significantly enhance current conservation programs protecting the most imperiled sea turtle species - Kemp’s ridleys (Lepidochelys kempii).

Manuscript 1 is an overview of the efforts …

Heterogeneous Ribosomes And Bs21: An Investigation Of Impacts And Mechanisms Of Altered Translation In Francisella Tularensis, Hannah Trautmann

Open Access Dissertations

Francisella tularensis is a pathogenic bacterium that requires coordinated regulation of gene expression to cause disease. In this dissertation, I explore a novel area of translation-level gene regulation in F. tularensis: heterogeneous ribosomes that preferentially translate specific mRNAs. Through mass spectrometry and immunoblotting, I find that wild-type F. tularensis ribosomes are heterogeneous with respect to the small ribosomal protein bS21 and all three bS21 homologs are able to be incorporated into ribosomes. Comparing proteomics and transcriptomics data, I determine that cells lacking one homolog, bS21-2, have genome-wide changes in protein abundance that are not explained by changes in transcript …

Associations Between Oyster Consumption And Iron, Zinc, And Cadmium Concentrations In Ghanaian Women, Alyssa Abreu

Open Access Dissertations

Background: Oysters are an excellent source of iron and zinc but may be contaminated by heavy metals such as cadmium. The micronutrient and metal content of smoked, dried oysters as well as the impact of oyster consumption on iron, zinc, and cadmium concentrations in Ghana is unknown.

Objectives: Our objectives were to 1) determine the micronutrient and metal content and health risk of dried, smoked oysters, 2) determine the associations between dietary iron intake with hemoglobin or ferritin concentrations and anemia, 3) determine the associations between oyster consumption and iron, zinc and cadmium concentrations in Ghanaian women living near the …

Improving Quality: Exploring Ceramic Water Filters In Developing Communities, Hem Kumar Pokharel

Open Access Dissertations

The main objectives of this dissertation were to determine the underlying factors involved in the ceramic water filter (CWF) manufacturing and assist in quality control of the CWFs using peer reviewed articles, empirical models, and statistical procedures. First, the progress, bias and gaps in the ceramic filter research were identified based on the peer reviewed articles published after 2011. Second, flow rate (FR) and nominal pore diameter (NPD) values as parameters were used to predict the microbial removal of CWFs. Two empirical models (flow rate model, FRM, and nominal pore diameter model, NPDM) were developed based on the log removal …

Signature Of Energetic Materials Under Pyrolysis And Ambient Conditions, Athina Kominia

Open Access Dissertations

Law enforcement and military personnel must be prepared to deal with explosives, unidentified chemicals, and even chemical warfare agents. This is a vast problem space. The included studies examine issues with characterization, mitigation, and disposal of energetic materials.

Among oxidizers those containing the ammonium cation have the potential of self-oxidization, making them of special hazard. We have examined ammonium nitrite and ammonium chlorate, two ionic compounds with well-known hazard potential, and compare their explosive performance with related materials. A novel protocol for assessment of explosivity on the gram-scale was employed.

Law enforcement and military personnel must deal with scenarios where …

Underlying Mechanisms Of Ubiquitin Specific Peptidase 2 Isoforms Regulation In Hepatocellular Carcinoma By The Farnesoid X Receptor Signaling Pathway, Winifer M. Ali

Open Access Dissertations

Hepatocellular carcinoma (HCC), or liver cancer, is the sixth most common cancer worldwide, and the third leading cause of cancer-related deaths. In 2023, an estimated 41,210 new HCC cases and 29,380 deaths have been reported in the United States with an overall 5-year relative survival rate of 20.8%. It has been predicted that by 2025, there will be more than one million cases of HCC globally. Unfortunately, there are limited effective treatments and current treatment options available are invasive and burdensome. HCC patients are usually diagnosed at the late stages of liver cancer when the only viable treatment options are …

Femtosecond Time-Resolved Coherent Raman Spectroscopy Of Equilibrium Phonons In Cubic Perovskites, Jeremy Sylvester

Open Access Dissertations

Essential to green energy technologies are new materials for high-power electronics, especially wide-bandgap semiconductors such as Barium Stannate (BSO) and Strontium Titanate (STO) which promise outstanding performance in high power transistor applications. Design and performance of these materials relies on detailed knowledge of basic physical parameters, including charge-carrier mobility. The mobility values can be as high as 500 cm2/Vs for electron concentrations >1x10¹⁹ /cm³ provided that the effect of impurity scattering is reduced using special doping techniques. In this case, the inelastic carrier-phonon scattering is the only mechanism that strongly affects the mobility as the polar optical (LO) …

Dynamics Of Non-Autonomous Discrete Systems With Applications To Evolutionary Dynamics, Susan Trolle

Open Access Dissertations

This dissertation focuses on difference equations that are of a certain type, non-autonomous competitive and cooperative systems. Previously, systems of this nature were investigated for the single species model. Here, this investigation extends to the case of two species or more, corresponding to a two dimensional system all the way to an n dimensional system. The purpose is to establish global attractivity results for these systems through a method using difference inequalities along with Northeast and Southeast partial ordering for competitive and cooperative systems, respectively. The non-autonomous case of some systems, established and well-known, are discussed for purpose of comparing …

Detection Of Coastal Phytoplankton Taxonomy, Morphology And Optical Signals With Machine Learning And Time Series Analysis, Virginie Sonnet

Open Access Dissertations

Phytoplankton are microscopic organisms crucial in the food web, primary production, and carbon export. Their abundance and diversity changes also influence the evolution of marine ecosystems and global biogeochemical cycles. In addition to extensive taxonomic diversity, phytoplankton can harbor different sets of photosynthetic pigments and display a wide range of size, morphologies, and functional traits. These particularities have led phytoplankton monitoring and phytoplankton dynamics studies to develop in many forms. Satellite remote sensing, light microscopy, and more recently particle imaging, are among those. However, they not only have widely different sampling resolution and taxonomic precision, but also target different properties …

Development Of Localized Drug Delivery Strategies For The Treatment Of Cancers And Infectious Diseases, Weizhou Yue

Open Access Dissertations

Difficult-to-treat human diseases and disorders such as brain cancer and posterior segment eye diseases greatly threaten human health and quality of life. However, the presence of physiological barriers such as the blood-brain barrier (BBB), cornea, and the blood-retinal barrier, renders these organs highly impervious to most therapeutics. As a result, most therapeutics administered systemically have low therapeutic efficacy even with high doses and are often associated with systemic side effects and/or toxicity. Localized drug delivery strategies such as injectables/implants, or locally-acting dosage forms, can circumvent physiological barriers and directly introduce therapeutics to the site of action to improve bioavailability, and …

Home Health Care Nurses’ Experiences And Perceptions Of Providing Care To Older Adults During The Covid-19 Pandemic: A Qualitative Descriptive Study, Joan R. Dugas

Open Access Dissertations

Home health care nurses were essential front line healthcare providers during the COVID-19 pandemic in the United States. Research in this area has primarily focused on the experiences of nurses in the acute and long-term care settings. This study aims to: (1) gain an understanding of the subjective experiences and perceptions of home health care nurses providing care to OAs during the COVID-19 pandemic and (2) elucidate aspects affecting the care provided to OAs during the COVID-19 pandemic.

Twenty nurses were interviewed between July 2022 and September 2022. The interviews were semi-structured and were analyzed using reflexive thematic analysis. Four …