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Investigations Across Biology And Education: Exploring The Gut Microbiome Of Freshwater Mussels And Understanding Undergraduate Biology Student Motivation, Mary Foley

Theses and Dissertations--Biology

A PhD aims to make a unique contribution to the current body of knowledge while developing as an independent researcher and critical thinker. This dissertation covers a wide range of topics, from microbiome analysis to biology education. Although there is no broad overarching research theme, all the chapters are connected by the process of scientific inquiry and by their contribution to the completion of a PhD.

Chapter One serves as a comprehensive literature review, delving into the standard methods of measuring the health of at-risk species. It describes direct measures of health (e.g., birth and death rates) crucial for predicting …

Estrogen Signaling Regulates The Sex Difference In Resynchronization To Abrupt Shifts Of The Light-Dark Cycle In A Mouse Model Of Jet Lag, Maria Venegas

Theses and Dissertations--Biology

The circadian system coordinates 24-hour cycles of internal biological processes with the environmental light-dark cycle. Abrupt shifts in the timing of the light-dark cycle misalign internal circadian clocks with the environment and cause jet lag until resynchronization occurs. The objective of this study was to investigate the mechanisms underlying sex differences in jet lag in mice. Female mice resynchronized faster than male mice to 6-hour advances and delays of the light-dark cycle, which mimicked eastward and westward travel, respectively. Circulating estradiol was necessary for rapid resynchronization in female mice since ovariectomized females resynchronized slower than mice treated with estradiol. We …

All Eyes On The Spiny Mouse: An Investigation Into Acomys Dimidiatus As A Model For Retinal Biology And Regeneration, Jessica D. Bills

Theses and Dissertations--Biology

The retina is a complex tissue with six types of neurons, supported by an intrinsic glia cell, that work in concert to input a visual stimulus and relay a visual message to the brain. Efficient communication between neurons is vital to this process and each neuron plays a significant role in vision. When retinal neurons degenerate, that visual signal is lost. Degenerative eye diseases affect the neurons of the retina in millions of people world-wide and can ultimately lead to blindness. While treatments are evolving, most are designed to prevent further damage; the field has yet to piece together how …

High Resolution Sedimentary Investigations Of Extant Lakes In North America, John Dilworth

Theses and Dissertations--Earth and Environmental Sciences

Investigation of past lake environments forms the discipline of paleolimnology. Paleolimnological studies seek to evaluate geophysical, geochemical, and ecological proxies and indicators contained within lake sediment archives. Using these potential stores of high-resolution environmental information, questions regarding climate, biological, and geochemical changes experienced by a lake and its watershed can be investigated. This dissertation research utilized lake sediment records from two lakes within North America to study different aspects of environmental change. This dissertation consists of three separate studies presented in three chapters.

Chapter Two presents a retrospective environmental assessment of Jackson Lake, Wyoming to investigate the impacts of dam …

A Geography Of Transgender Belonging In Louisville, Kentucky, Lj Mcallister

Theses and Dissertations--Geography

Louisville, Kentucky is home to a surprisingly robust – and complex – transgender community. This study uses qualitative data from interviews, collaborative maps, and archival research to analyze a geography of belonging for transgender residents in the city. It discusses how the twelve participants negotiate their relationships with the conservative, “red” state of Kentucky, as well as the geographical decision-making they use to navigate Louisville’s many neighborhoods. Ultimately, this thesis draws attention to the ways in which prejudice shapes the landscape of belonging for transgender life in Derby City.

Beyond The Hands: Exploring Intersectional Identities Of Black American Sign Language Users, Tatum Turner

Theses and Dissertations--Linguistics

There is a significant gap in research related to the impact of intersectionality on linguistic identity performance among individuals negotiating multiple marginalized identities. This gap is especially significant among deaf Black and African American individuals who use the American Sign Language (ASL) variety deemed Black American Sign Language (BASL) (Hairston & Smith, 1983). This research aims to identify and discuss the use of the eight distinguishing features of BASL (McCaskill et al. 2011) as indexes of intersectional identities.

My data consists of videos sourced from YouTube, each chosen according to the following criteria: must have at least one self-identifying Black …

Advanced Mathematical Graph-Based Machine Learning And Deep Learning Models For Drug Design, Farjana Tasnim Mukta

Theses and Dissertations--Mathematics

Drug discovery is a highly complicated and time-consuming process. One of the main challenges in drug development is predicting whether a drug-like molecule will interact with a specific target protein. This prediction accelerates target validation and drug development. Recent research in biomolecular sciences has shown significant interest in algebraic graph-based models for representing molecular complexes and predicting drug-target binding affinity. In this thesis, we present algebraic graph-based molecular representations to create data-driven scoring functions (SF) using extended atom types to capture wide-range interactions between targets and drug candidates. Our model employs multiscale weighted colored subgraphs for the protein-ligand complex, colored …

Modulating The Mtor Pathway Using Inducible Retrogradely Transported Aavs As A Novel Approach To Improve Motor Recovery In Spinal Cord Injury, Christopher Bosse-Joseph

Theses and Dissertations--Medical Sciences

Spinal cord injury poses multiple regeneration barriers, including neuronal-intrinsic and extrinsic factors. Overcoming these barriers has stood as a longstanding challenge in neuroscience. A well-studied mechanism to promote spinal cord regeneration and locomotor recovery is activating the PI3K/mTOR pathway by knocking out phosphatase and tensin homolog protein (PTEN). PTEN knockout (PTEN-KO) studies have traditionally used adeno-associated virus (AAV) viral vectors to improve functional recovery. The use of traditional AAV serotypes to induce PTEN-KO has shown promise to improve functional recovery in rodent models; however, these approaches show significant limitations for translational utility. Firstly, the use of traditional AAV serotypes to …

The Effect Of Estrogen And A Mitochondrial Uncoupling Prodrug On Traumatic Brain Injury-Induced Dysfunction In Mice., Olivia J. Kalimon

Theses and Dissertations--Neuroscience

A large percent of both clinical and pre-clinical traumatic brain injury (TBI) studies report better outcomes females after severe injury compared to males. Mitochondrial dysfunction is a well-characterized driver of secondary injury and an attractive neurotherapeutic target; though, there is limited research available on mitochondrial dysfunction in females. However, a few studies have shown total mitochondria from the cortex of females appear protected from TBI-induced bioenergetic dysfunction. These results were replicated in these studies so further characterization was performed. Additionally, protein expression of some oxidative phosphorylation (OXPHOS) complexes were elevated in the uninjured cortex of females relative to uninjured males, …

Caenorhabditis Elegans Rapgef Promotes Synaptic Development Through A Small G Protein Signaling Cascade, Reagan Em Lamb

Theses and Dissertations--Neuroscience

Synaptic dysfunction is a major contributor toward the development of many neurological disorders. For proper development, synapses require a series of signaling pathways to guide them, but not all the mechanisms underlying these processes are understood. Here, we used the neuromuscular junction of Caenorhabditis elegans as a model circuitry for examining underlying pathways that mediate proper development of synapses. We hypothesized that the C. elegans RapGEF2 and RapGEF6 orthologue, PXF-1, contributed toward development of cholinergic synapses at the neuromuscular junction. Using behavioral assays and fluorescence microscopy, we found that pxf-1 mutant animals had decreased neuromuscular junction function and decreased synaptic …

Contributions Of The Replication Initiator Protein Dnaa To Physiology And Virulence Of The Lyme Disease Spirochete, Andrew Krusenstjerna

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Borrelia burgdorferi, the etiological agent of Lyme disease, is the most prevalent vector-borne disease in the United States. The spirochetal population is naturally maintained by consistently cycling between Ixodid ticks and small vertebrates. To survive within these diverse niches, B. burgdorferi has evolved a unique physiology and regulatory network to sense and respond to environmental fluxes. Replication is a hallmark of the Lyme spirochete’s enzootic life cycle, specifically at the nymphal tick-to-vertebrate interface. The mechanisms and regulatory schema for the basic cellular processes in B. burgdorferi, or indeed any member of the phylum spirochaetota, are largely unknown. The central hypothesis …

Enlarged Perivascular Spaces Are A Clinically Relevant Neuroimaging Biomarker Of Cerebral Small Vessel Disease, Timothy Justin Libecap

Theses and Dissertations--Neuroscience

Vascular contributions to cognitive impairment and dementia (VCID) represents the intersection between cerebrovascular disease and cognitive decline. Cerebral small vessel disease (cSVD) is an important risk factor that may precede the onset of VCID by years. cSVD is characterized by in-vivo neuroimaging biomarkers including enlarged perivascular spaces (ePVS). PVS are the site of interchange between interstitial fluid (ISF) and cerebrospinal fluid (CSF) which is believed to play a role in the removal of brain waste. Reduced clearance may lead to enlargement of the PVS and subsequent accumulation of toxic solutes characteristic of neurodegeneration. Given the presence of ePVS in brain …

Genetic And Metabolic Factors Shaping Functional And Systemic Recovery Post-Spinal Cord Injury: A Focus On Apoe, Chase Taylor

Theses and Dissertations--Neuroscience

There are currently approximately 300,000 individuals living with a spinal cord injury (SCI) in the United States with an additional 17,000 injuries occurring each year. Perhaps of equal importance the median age at which an SCI occurs within the population has steadily increased since the 1970s to the 2010s from 29 years to 43 years and is still on the rise. Women, historically underrepresented in biomedical research, have also seen a slight increase in SCI incidence. This increase in age of injury onset means that more people with an SCI will be impacted by genetic factors associated with Alzheimer’s disease …

Fathers’ Perspectives On The Role Of Spirituality In Substance Misuse Disorder Treatment And Engaging With Their Children, Kendra Michelle Eubank

Theses and Dissertations--Social Work

The father's role and the extent of involvement with his children have shifted over the past several decades. As a result, researchers have made considerable advances in understanding paternal influences on child development and families. However, one under-researched topic is how fathers' substance misuse, and the recovery process may influence father involvement and effective co-parenting, and specifically, how spirituality plays a role in that. In this qualitative study, fourteen participants participated in semi-structured interviews. The data revealed two main themes: 1) pillars of a spiritual awakening and 2) applying spirituality to healthy fatherhood engagement.

These findings led to four interpretations: …

A Praxis Towards Social Change Based On Foucault's Conceptualization Of Experience As Relational, Lila Maureen Wakeman

Theses and Dissertations--Philosophy

This project develops a praxis towards social change based on the works of Michel Foucault. It first establishes Foucault’s philosophical assumptions, methods, and political goal of countering “objectivizing” modern Western social forces. It then draws on sources from the three major phases of Foucault’s career to trace his development of a general conceptualization of experience as relational, or as non-exhaustively co-constituted by and through three indispensable kinds of social forces: knowledge, power, and ethics. It then evaluates implications of Foucauldian experience for efforts towards social change to conceptualize a general Foucauldian praxis towards social change. The praxis aims to affect …

On The Principles And Ends Of Education: A Thomistic Approach, Keith Parkinson

Theses and Dissertations--Philosophy

This dissertation develops an account of the nature of education from a Thomistic point of view. The thesis is that education is best understood as ‘human growth’—growth, because it is the natural development of potentialities inherent within the human person toward full actualization, and human, because it pertains in particular to those faculties of reason that are unique to human beings among all natural creatures, the intellect and will. The first three chapters provide an overview of Thomistic anthropology and virtue theory, from which I conclude that the final goal toward which all genuinely educational activity aims is the speculative …

Relationality In Rousseau's Philosophy Of Education, Thayne Cameron

Theses and Dissertations--Philosophy

Jean-Jacques Rousseau’s assertion of Emile that “Our true study is that of the human condition” serves as the foundation for this dissertation, which examines the significance of certain kinds of basic experiential relationships in Rousseau’s philosophy of education. By analyzing the relationships between the self and objects, the self and others, and the educator and the learner, this work elucidates how these interactions underpin Rousseau’s pedagogical views and their implications for fostering personal and social virtue.

The dissertation explores the self-object relationship through affectivity, embodiment, and purposeful activity, demonstrating how direct engagement with objects shapes perceptions and behaviors. It then …

Variable Selection For High-Dimensional Data With Interaction Effects: Methods, Applications, And Inferences, Leiyue Li

Theses and Dissertations--Statistics

For high-dimensional data where the number of variables greatly exceeds the number of observations, selecting important variables while maintaining the required heredity conditions can be challenging. This dissertation is structured into three interconnected parts. In the first part, we propose a variable selection method by implementing a well-known optimization technique, the Genetic Algorithm. An R package was developed to simplify the implementation and usage of the proposed method. We then propose another variable selection method by extending the study from the Genetic Algorithm to a different but related optimization technique, Simulated Annealing. We consider three different hierarchical structures in both …

Design Of Kappa Opioid Receptor Agonists For Potential Treatment Of Multiple Sclerosis, Lindsay Kornberger

Theses and Dissertations--Pharmacy

Multiple Sclerosis (MS) is a neurodegenerative disease of the central nervous system characterized by demyelination and neuroinflammation. There is currently no cure for MS. There is a critically unmet need for the development of pharmacotherapies that can induce remyelination promoting both repair and recovery. The kappa opioid receptor (KOR) has been identified as a potential target for the development of remyelinating pharmacotherapies. KOR activation has been shown to promote functional recovery and remyelination preclinically. However, typical KOR agonists like U50,488 have limitations such as sedation and dysphoria limiting their use. This necessitates further development of new KOR agonists that maintain …

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …

Transfer Learning-Enhanced Transformer For Virtual Sensing Applications In Resistance Spot Welding, Ethan York

Theses and Dissertations--Mechanical and Aerospace Engineering

Resistance spot welding is a crucial manufacturing process used across a wide range of industries for permanently joining metal components. Characterized by its applications in the automotive industry, resistance spot welding is valued for its speed, efficiency, and relatively low cost to set up and maintain. The process involves running a pulse of electrical current through two metal sheets to liquify the material and create a permanent bond. The process complexity necessitates precise control over various parameters to ensure acceptable results, emphasizing the importance of quality control. Because there are no low-cost and non-invasive techniques to inspect welds, strategies utilizing …

Multiscale Fiber Remodeling In The Heart Using A Finite Element Framework, Mohammad Mehri

Theses and Dissertations--Mechanical and Aerospace Engineering

The organization of myofibers and extra cellular matrix within the myocardium plays a significant role in defining cardiac function. When pathological events occur, such as myocardial infarction (MI) or hypertrophic cardiomyopathy (HCM), this organization can become disrupted, leading to alteration in pumping performance. The current study proposes a multiscale finite element (FE) framework to determine realistic fiber distributions in the left ventricle (LV). This is achieved by implementing a stress-based fiber reorientation law, which seeks to align the fibers with local traction vectors, such that contractile force and load bearing capabilities are maximized. By utilizing the total stress (passive and …

Characterization Of Heterogeneous Material Architectures Through X-Ray Computed Micro-Tomography, Cameron Brewer

Theses and Dissertations--Mechanical and Aerospace Engineering

Low-density carbon-phenolic composites, such as phenolic impregnated carbon ablator (PICA), possess meso-, micro-, and nano-pores making the structure of the resin difficult to characterize. X-ray Computed Tomography (XRCT) is a widely ac- cepted method for characterizing the carbon fiber preform, yet this technique is often insufficient for visualizing the resin because of its minimal attenuation of the incident x-ray beam. Phase Contrast Retrieval (PCR) reconstruction considers not only the linear attenuation coefficient, but also the refractive indices of the constituent materials. This research leverages phase contrast tomography to characterize the meso- and micro-structure of the porous resin phase with a …

Repolarizing Tumor-Associated Macrophages In Ovarian Cancer: A Novel Immunotherapeutic Approach, David Schweer

Theses and Dissertations--Clinical and Translational Science

Ovarian cancer, recognized for its high lethality and resistance to conventional immunotherapies, mandates innovative strategies to confront its intricate challenges. The tumor microenvironment (TME), orchestrated by tumor-associated macrophages (TAMs), assumes a pivotal role in disease progression, rendering TAMs an appealing therapeutic target. This study endeavors to explore the prospect of repolarizing TAMs from a protumor M2 phenotype to an antitumor M1 state, employing M1 macrophage-derived vesicles (MEVs) as a groundbreaking immunotherapeutic approach.

The primary objective is to investigate the capacity of M1 MEVs to repolarize M2 macrophages in vitro towards an anti-tumor M1-like phenotype. By inducing human macrophages to adopt …

Developing Radiosensitizers To Enhance Radiotherapy In Treating Gastroenteropancreatic Neuroendocrine Tumor, Zeta Chow

Theses and Dissertations--Clinical and Translational Science

Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) is a heterogeneous group of malignancies arising from multipotent neuroendocrine stem cells in the gastrointestinal tract. The incidence of GEP-NET continues to rise, possibly due to the advancement of imaging and biomarkers available for diagnosis. However, even though the majority of patients are diagnosed with low-grade and localized disease, a significant percentage of patients present with advanced-stage metastatic disease with poor prognosis in months to a few years. These advanced-stage GEP-NET patients can also present with a variety of debilitating symptoms that significantly impact their quality of life. The role of palliative-intent surgery is limited, and …

Evaluation Of The Cellular And Physiologic Impact Of Mitomycin C On Colon Cancer, Hannah Mcdonald

Theses and Dissertations--Clinical and Translational Science

Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) with Mitomycin C (MMC) has more than doubled the overall and disease-free survival in patients with peritoneal metastases (PM) due to colorectal cancer (CRC) over the past two decades. Although MMC is the most used HIPEC drug for PM due to CRC, dosing protocols vary dramatically between and within institutions across the world. Additionally, little is known about the impact of hyperthermia and MMC on intracellular pathways for CRC. The aim of this work is to determine the optimal dosing strategy in the clinical application of MMC and hyperthermia for treatment of …

Abl1/2 And Ddr1 Cooperate To Stabilize Braf/Craf To Drive Erk1/2 Reactivation And Promote Mek Inhibitor Resistance In Nras-Mutant Melanomas, Anastasia Lyon

Theses and Dissertations--Pharmacology and Nutritional Sciences

This study addresses the escalating incidence of NRAS-mutant melanomas, a type of skin cancer lacking FDA-approved targeted therapies. Despite ongoing research targeting the RAF/MEK/ERK pathway, existing drugs fail to enhance progression-free survival due to acquired resistance. This project identifies a novel role for ABL1/2 and DDR1 kinases in driving drug resistance and proliferation of NRAS-mutant melanoma cells. ABL1/2 and DDR1 cooperate to promote RAF homodimerization and protein stability in order to reactivate MEK/ERK signaling to drive MEK1/2 inhibitor (MEKi) resistance and promote survival of resistant cells. By targeting ABL1/2 and DDR1 with nilotinib, a FDA-approved anti-leukemic inhibitor, we …

Exenatide As Chronopharmacotherapy For T2dm Associated Complications: Targeting Nondipping Blood Pressure And Sleep Insufficiency, Aaron Chacon

Theses and Dissertations--Pharmacology and Nutritional Sciences

Although largely impacted by age, race and ethnicity, and socioeconomic factors, Type 2 Diabetes Mellitus (T2DM) is primarily driven by obesity, currently affecting ~30 million in the U.S and ~463 million globally. T2DM carries numerous complications, including high prevalence of hypertension and nondipping blood pressure (BP), sleep insufficiency and fragmentation. Nondipping BP is an inadequate drop in BP (≤ 10%) during sleeping hours compared with waking hours. Lending to this, sleep disturbance acts as both precursor and consequence of metabolic dysregulation, greatly impacting circadian rhythmicity. To model these conditions, we utilized diabetic (db/db) mice. These mice carry a point mutation …

Mitigating Risks For Dementia In Apoe4 Mice: Efficacy Of Prebiotic Inulin, Probiotics, And Fecal Microbiota Transplants, Ya-Hsuan Chang

Theses and Dissertations--Pharmacology and Nutritional Sciences

Apolipoprotein E4 allele (APOE4) carriers show early metabolic changes, heightening the genetic risk of late-onset Alzheimer's Disease (AD), characterized by amyloid-β and tau tangle plaques and neurodegeneration. Its development is influenced by age, environment, and genetics, with Mild Cognitive Impairment (MCI) often preceding AD, providing a crucial window for early intervention. Factors in AD progression include sex differences and gut microbiome imbalances, with women disproportionately affected and APOE4 carriers showing early metabolic and cognitive changes. This study explores the potential of prebiotic inulin, probiotic Bifidobacterium animalis, and fecal microbiota transplants (FMT) from healthy donors to mitigate AD …

Cell-Based Cardiac Repair And The Natural Cardiac Healing In Regenerative Adult Mammal, Hsuan Peng

Theses and Dissertations--Pharmacology and Nutritional Sciences

Heart failure (HF) following myocardial infarction (MI) remains a significant global health concern, with the initial ischemic injury often leading to microvascular damage and infarct expansion, exacerbating the overall cardiac impairment. Despite extensive research, there are currently no effective therapies to limit myocardial damage post-MI, resulting in a substantial number of patients progressing to HF. Stem cell therapy has emerged as a promising approach to modulate cardiac injury and promote healing. However, clinical trials have shown only modest success, underscoring the need for improved strategies to enhance efficacy. Additionally, the lack of significant ventricular regeneration highlights the necessity of targeting …