Digital Commons Network^™

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 …

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 …

Hegelianism As Anti-Authoritarianism, Tyler Van Wulven

Theses and Dissertations--Philosophy

My dissertation intervenes in two ongoing conversations about the nature of freedom. The first seeks to understand and combat the allure of authoritarianism. The second, rooted in 19^th and 20^th century philosophy, sheds light on this phenomenon by suggesting that the acknowledgment and endorsement of the social and historical origins of our normative commitments would awaken us to our radical freedom. My dissertation contributes to this conversation by suggesting that authoritarianism is rooted in a failure to comprehend ourselves, and that a proper investigation into human selfhood is needed to understand and actualize our powers of self-determination. Drawing …

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 …

Investigating A New Drug Target In Alzheimer’S Disease: Nox2, Tiffany Adams

Theses and Dissertations--Pharmacy

Introduction: Alzheimer’s disease (AD) is a neurodegenerative disease with neuropathological changes in the blood-brain barrier that offers possible therapeutic targets. Oxidative stress is one driving factor for AD. NADPH oxidase 2 (NOX2) in the capillary endothelium produces reactive oxygen species, leading to oxidative stress-mediated blood-brain barrier dysfunction. We hypothesized that using a specific NOX2 inhibitor, PhoxI2, has the potential to reduce reactive oxygen species and repair amyloid-β (Aβ)-driven blood-brain barrier leakage in an AD mouse model.

Methods: For this study, 5xFAD (Familiar Alzheimer Disease) mice were treated with vehicle or PhoxI2, a NOX2 inhibitor. Techniques utilized were Enzyme-Linked Immunosorbent Assay …

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 …

Sensitizing Keap1 Loss Non-Small Cell Lung Cancer To Artesunate Anti-Cancer Activity, Keng Hee Peh

Theses and Dissertations--Pharmacy

Lung cancer is the global leading cause of cancer related death. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer diagnoses conferring a significant disease burden. However, certain mutations in tumor suppressors such as Kelch-like ECH-associated protein 1 (KEAP1) confers resistance to standard of care therapy in NSCLC. KEAP1 is known to regulate multiple cellular processes such as oxidative stress response and anti-apoptotic pathways. Furthermore, KEAP1 loss of function in NSCLC is associated with poorer clinical outcomes and there are no currently approved therapies for KEAP1 loss NSCLC and represents an unmet clinical need. Artesunate (Art) demonstrated anti-cancer …

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 …

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 …

A Hyphenated Career: Sustainable Pathways For Dancers, Rebecca A. Ferrell

Theses and Dissertations--Arts Administration

Despite the rich cultural and artistic contributions of dancers, there exists a pressing need to comprehensively address the challenges and complexities surrounding the sustainability of careers in dance due to underemployment, underpayment, data undercounting and physical strain. This dissertation research aims to understand occupational trajectories that build a sustainable career for dancers. Through a historical examination of the professionalization of dance and an investigation of current career opportunities, this study investigates the growing support systems for dancers, the influence of occupational identity, and the workplace environments needed to sustain a dance career.

Occupational identity theory, motivation-hygiene theory, and transaction cost …

Music For The People: Comparing Public Funding Models For Popular Music In Atlanta, Glasgow, And Toronto, Heather Mcdonald

Theses and Dissertations--Arts Administration

This dissertation explores the complex landscape of public funding policies for popular music across three cities: Atlanta, Glasgow, and Toronto. Through comparative case studies and qualitative research methods, this work explores the varying approaches each city takes towards funding popular music, including the social, economic, and political environments in which these funding policies have developed.

Through document reviews and interviews with key stakeholders, the dissertation highlights the differences in how public funding for popular music is approached in Glasgow, Atlanta, and Toronto and the broader context of how these policies were created. Using Multiple Streams Approach, the Five Streams Confluence …

Orchestra Community Engagement: Factors Of Environmental Impact, Travis Newton

Theses and Dissertations--Arts Administration

The symphony orchestra industry in the United States was founded with the goal of serving the elite, but these orchestras are organized as not-for-profit organizations and are currently mandated to benefit the community more broadly. Professional symphony orchestras in the United States are beginning to address this disconnect between their elite-oriented origins and the more modern federal mandate of community-oriented service in a variety of ways, including through community engagement programming. There are a number of items that remain unknown, including the impact that environmental factors have on orchestras’ community-oriented work, and what “community engagement” means to orchestras.

The purpose …

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 …

The Relationship Between Sleep, Physical Activity, And Musculoskeletal Injury, In Us And Saudi College Students, Abdulaziz Hasan Alameer

Theses and Dissertations--Rehabilitation Sciences

According to the National Sleep Foundation, individuals should sleep 7-9 hours every night. Recently, insufficient or poor sleep has been linked to diabetes, cardiovascular illness, stroke, obesity, and Alzheimer's disease. Insufficient sleep for college students can negatively impact academic performance and mental health. In addition, especially for collegiate athletes, there is evidence that insufficient sleep is associated with an increased risk of musculoskeletal injury. However, it is uncertain if the link between sleep and injury varies between populations, types of individuals (athletes vs non-athletes), sports or types of exercise, or training volume. Despite the health risks of inadequate sleep, up …

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 …

The Delineation Of Platelet Pathology In Cardiometabolic Disease, Chi Peng

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity is a multifactorial disease with many comorbidities leading to multiorgan dysfunction. Current studies point towards dysregulation of platelet signaling as a driver for increased risk of cardiovascular disease and stroke. The exact mechanisms remain elusive due to the complex interplay of factors involved, warranting the need to further understand how platelets are affected. Our preliminary data evaluating changes in platelet and coagulation parameters from bariatric patients showed that obesity did not affect platelet count or clotting time as demonstrated in INR values. However, female patients had increased bleeding events before surgery that were decreased after surgery. Due to limitations …

Characterization Of Bowel Dysfunction After Spinal Cord Injury In Mice, Olivia Wireman

Theses and Dissertations--Physiology

Most individuals who suffer a spinal cord injury (SCI) will experience some form of bowel dysfunction. Trauma to the spinal cord can result in severe constipation and/or incontinence, otherwise known as neurogenic bowel. Constipation requires extensive bowel routines typically involving the help of another person. Still, many living with SCI are hospitalized due to bowel complications such as fecal impaction. While neurogenic bowel has been well characterized in the clinic, pre-clinical models of neurogenic bowel after SCI are still in development. Most pre-clinical studies in bowel dysfunction after SCI are published in rat models. Studies existing in mice, to our …

Indoor Pests And Human Health: Characterizing Contaminants And Improving Mitigation, Johnalyn Gordon

Theses and Dissertations--Entomology

Much of the United States population spends the majority of their time indoors and within the home. Not only are indoor arthropod pests an unsightly nuisance in our homes, but they can have serious impacts on human health, especially with chronic exposure. In addition to negative health impacts, costs associated with these medical impacts can be tremendous. For these reasons, it is critical to develop comprehensive strategies for pest reduction and mitigation of associated health impacts. The work outlined in this dissertation represent examination of the distribution of a hypothesized bed bug allergen within the indoor environment, identification of a …

Practical Challenges In Delivering Dsrna For Woody Plant Protection, Zachary Bragg

Theses and Dissertations--Entomology

Unprecedented weather events associated with climate change, coupled with extensive anthropogenic stresses, have reduced the effectiveness of traditional forest pest management approaches, which can no longer keep pace with invasive species overwhelming naïve landscapes and native pests experiencing eruptive and expansive outbreaks. Double-stranded RNA-(dsRNA) mediated gene silencing, a type of RNA interference (RNAi), has been coopted for use as a biopesticide against a multitude of agricultural and horticultural pests and could serve as a powerful tool for woody plant protection. While effective initiation of gene silencing and subsequent mortality have been demonstrated in multiple tree pests, effective and efficient methods …

Consequences Of Abiotic And Anthropogenic Stressors In The Antarctic Midge, Belgica Antarctica, Jack J. Devlin

Theses and Dissertations--Entomology

The ability to tolerate stress is key to maintaining fitness in extreme environments such as the polar regions. Subject to a myriad of extreme year-round abiotic conditions, invertebrates inhabiting the terrestrial ecosystems of Antarctica provide an excellent system to investigate adaptations to stress. Understanding the response of these species to abiotic and novel stressors is crucial in a world with rapidly occurring climate change and increasing anthropogenic activity. In this dissertation, I investigated physiological and molecular responses to naturally occurring and human-derived stresses in the midge Belgica antarctica, which is Antarctica’s only endemic insect.

In my first research chapter, I …

Acting On Routine Outcome Monitoring, Virginia Courtney

Theses and Dissertations--Family Sciences

This thesis explores the application of an Acceptance and Commitment Therapy (ACT) informed approach in achieving clients’ therapeutic objectives via systematically tracking client progress over the therapy process. The study utilized the Marriage and Family Therapy Practice Research Network (MFT-PRN), a specific tool that aids the tracking of therapy progress, to gather relevant client data. The data consisted of therapy progress for 27 individuals the author worked with, 1,001 individuals from the Individual Relational and Finance Therapy Clinic, and 4,424 individuals from the MFT-PRN-Network. Upon collecting this data, progress trajectories were generated using Microsoft Excel to compare the author’s clients’ …

Sex Differences In Pediatric Hypertension: Obesity, Stress, And The Renin-Angiotensin System, Allyson Dyar

Theses and Dissertations--Nutrition and Food Systems

Pediatric hypertension, linked to long-term cardiovascular risks, shows increasing prevalence and varying patterns between boys and girls. This study explores sex-based differences in hypertension among 251 children aged 6-18 from Kentucky Children’s Hospital. Using 24-hour ambulatory blood pressure monitoring (ABPM) and assessing plasma renin, aldosterone, and cortisol, we examined blood pressure severity by sex. Girls showed a higher incidence of severe hypertension and elevated cortisol levels, whereas boys had higher mean systolic blood pressure. Aldosterone was associated with night systolic blood pressure in girls, while night diastolic blood pressure was linked to aldosterone in both sexes and renin in girls. …

Assessing Endophyte Frequency Distributions And The Effect Of Epichloë Brachyelytri In The Chemotypic And Genotypic Diversity Of Brachyelytrum Erectum, Rachel Ann Sneed

Theses and Dissertations--Plant Pathology

Seed-transmissible epichloid fungal endophytes are best known for their roles as defensive mutualists in cool-season grasses. Historically, the discovery of fungal endophytes was driven by investigations of plant toxicity to livestock, followed by extensive study of their alkaloids and protection against insects and nematodes. Epichloae can produce four classes of alkaloids: ergot alkaloids, lolines (saturated aminopyrrolizidines), indole–diterpenes, and peramine. It is increasingly evident that these hereditary symbionts have much more diverse chemical profiles both in individual populations and between them. To this end, differences in chemotypic profiles of these symbionts may translate to different evolutionary and environmental advantages across plant …

Systemic Signaling In Plants: Role Of Cuticle, Salicylic Acid, Rna, And Vitamins, Huazhen Liu

Theses and Dissertations--Plant Pathology

Systemic acquired resistance (SAR) is a form of broad-spectrum resistance induced in response to local infection that protects uninfected parts against subsequent secondary infections. Several diverse chemical signals contributing to SAR have been isolated and characterized, including glycerol-3-phosphate (G3P) and pipecolic acid (Pip), both of which play an important role in human and plant disease physiologies. In addition to these, salicylic acid (SA) also regulates SAR and normal transport of SA and G3P is required for de novo biosynthesis of Pip in the distal leaves. Pip is catabolized via multiple pathways, and this in turn regulates vitamin homeostasis. A normal …

Current And New Perspectives On Equine Protozoal Myeloencephalitis Therapeutics, Izabela De Assis Rocha

Theses and Dissertations--Veterinary Science

Equine protozoal myeloencephalitis (EPM) is an important neurologic disease of horses in the Americas. It is caused by the apicomplexan parasite Sarcocystis neurona and less commonly by the related parasite Neospora hughesi. Current antiprotozoal treatment relies on the use of either folate inhibitors (sulfadiazine/pyrimethamine) or triazine drugs (diclazuril/ponazuril), with a success rate of 60-70% regardless of the drug of choice. Successful treatment is defined as the improvement of at least one ataxia grade following the modified Mayhew scale, which often is not enough for the horse to return to the previous level of performance. The goals of this dissertation …