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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 …

Crisis, Genre, And The Informatic Infrastructure Of The Critical Path Aids Project In Philadelphia's Early Epidemic, Sid Feinberg

Theses and Dissertations--Geography

The Critical Path AIDS Project was a grassroots information network that distributed AIDS-related information related to biomedicine, social services, and politics. I explore the ways the project made sense of the shattering social service and care landscapes they emerged within and responded to. I situate Critical Path’s work within Philadelphia’s splintering care infrastructures and the experience of crisis Lauren Berlant argues structures perception of neoliberal life. I focus on the ways that Critical Path’s articulation of crisis and spatial re-orientation pull on the modernist design work of Buckminster Fuller. Fuller’s design work formed a framework through which the project constructed …

Beauty And The Anthropocene: On The Emancipatory Potential Of Experiences Of Beautiful Places In The Natural World, Matthew John

Theses and Dissertations--Geography

This dissertation investigates the proposition that beauty—specifically, experiences of beautiful places in the natural world—can contribute to the emancipation of modern persons (and thereby developed societies) from instrumental rationality, which is theorized as a major driver of contemporary socioecological crises of the Anthropocene. Buber’s concept of the I–Thou relation provides a framework for conceptualizing ideal non-instrumental relations. The project’s methodology, rooted in post-phenomenology, consisted of semi-structured remote interviews and four follow-up focus groups with 35 then current and recently former residents of Juneau, Alaska. Taken together, data confirm that experiences of beautiful places in the natural world can and do …

"Many Fabulous Stories And Idle Tales": The Intersection Of Elizabethan Political Gambits And Indigenous Erasure In The Early American Republic, Daniel Ryan Lewis

Theses and Dissertations--History

Welsh Indian Theory, originating in Elizabethan England, stated that a group of Welsh explorers settled in the Americas in the late 12^th century and intermarried with the Indigenous tribes, thereby explaining “advanced cultures” ranging from the Mississippians to the Aztec Empire. This act of erasure became rooted in Kentucky and the surrounding area in the 18^th and 19^th centuries; a series of prominent individuals from Kentucky in turn contributed to a growing body of false historical narratives that denied Indigenous Americans their cultural identities and connection their ancestral lands in the United States. With a 460-year trail …

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 Role Of Intracellular Growth During The Systemic Spread Of Listeria Monocytogenes, Jamila S. Tucker

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

Listeria monocytogenes is a facultative intracellular pathogen transmitted through the consumption of contaminated food products. Typically, infections range from mild, self-limiting gastroenteritis to life-threatening systemic infections; however, the events that occur in the gut to allow for this spread are unclear.

The focus of my thesis aims to determine how L. monocytogenes escape the mesenteric lymph nodes (MLN), the final barrier to systemic spread for both commensal and pathogenic bacteria in the gut. I have shown that intracellular replication of L. monocytogenes in an as-yet-unidentified cell type is essential for the colonization and dissemination of the bacteria from the MLN. …

Effects Of Pancreatic Amylin On The Peripheral And Cns Immune Response In A Model Of Type-2 Diabetic Brain Injury, Edric Da'shon Winford

Theses and Dissertations--Neuroscience

Type-2 diabetes (T2D) is a metabolic disorder that increases the risk for cerebrovascular disease and dementia and is associated with the progression of Alzheimer's Disease; however, the mechanisms responsible for T2D-associated dementia are still poorly understood. T2D leads to alterations of the innate and adaptive immune response that contribute to its progression, but how these cells contribute to cognitive decline during T2D is unknown. As there are no approved therapeutics for T2D that modulate the immune response, it is important that we investigate how peripheral immune cells contribute to cognitive decline during T2D. Amylin is an amyloidogenic hormone synthesized and …

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 …

Characterizing Age-Associated Cd19+ B Cells After Stroke In Aged Male And Female Mice Reveals Sex-Dependent Functional Recovery, Katie Colson

Theses and Dissertations--Neuroscience

Age-Associated B cells (ABCs) are atypical memory B cells commonly expressing CD11b, CD11c, and T-bet. We hypothesized that aged female mice would have worse functional outcomes after stroke due to higher brain-localized ABCs. We identified 6 ABC subsets expressed in the brain, with higher levels in uninjured animals versus 3 weeks after stroke. Contradictory to my hypothesis, aged uninjured males with higher numbers of Classical ABCs (CD11bhighCXCR5+/CXCR5-) in the brain exhibited better motor function, though with limited differences by injury or sex for other classical ABC subsets. Rare CD11b+CXCR5+ populations from uninjured mice secreted more IFN-γ when exposed to TLR7/9 …

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 …