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Investigation Of Key Mechanisms Of Contact Dependent Growth Inhibition Systems In Burkholderia Cepacia Complex Species, Zaria K. Elery

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

Burkholderia cepacia complex is a group of closely related environmental bacteria that can exacerbate disease in immunocompromised individuals. B. cepacia bacteria are equipped with an arsenal of mechanisms to cooperate and compete for nutrients in various polymicrobial environments. Contact-dependent growth inhibition (CDI) systems are antagonistic mechanisms widespread among proteobacteria. CDI systems consist of Two Partner Secretion pathway proteins that function to deliver the toxic C-terminal portion of the large effector exoprotein (termed ‘BcpA’ in Burkholderia-type CDI systems) to the cytoplasm of a compatible recipient bacterial cell upon direct cell to cell contact. The translocation of BcpA out of the …

Factors Associated With Successful Military-To-Civilian Transition Among Special Forces Veterans, Edward Richter

Theses and Dissertations--Social Work

The purpose of this study was to explore the military-to-civilian transitional experience in a sample of Special Forces veterans. Acknowledging challenges in accessing the veteran population, most existing research on the military-to-civilian transition consolidates military occupations into a single sample. This method fails to address the intricacies that may exist within individual military occupations, especially that of U.S. Army Special Forces soldiers. Special Forces qualified soldiers represent the largest portion of all U.S. Military Special Operations Forces and are responsible for the majority of all Special Operations activities, yet their experience in transitioning out of the Army is largely unknown. …

When The Past Comes Knocking: An Alter-Centric Perspective On Network Mobilization In Prosocial Occupations, Jason Ross

Theses and Dissertations--Management

Networks are vital to our ability to access resources. However, scholars have often overlooked just how social networks are mobilized. Underexplored in the literature is how individuals think and feel about mobilizing networks with little attention directed towards the person (alter) being reached out to. In this dissertation, I use a basic, interpretive design to better understand how people think and feel about receiving requests for task-related help, paying particular attention to when those requests originate from people from one’s past. To do so, I conducted interviews with 40 animal rescuers given their passion for helping, but their inability to …

Home Is Where The Heart Is: Rural Residents, Deprivation, And The Impact Of Prd On Governmental Representation, Mary Rachael Blandau

Theses and Dissertations--Political Science

How does rural deprivation, defined here as the perception that rural residents are deprived of economic and social capital that comparatively disadvantages them more than their urban and suburban counterparts, impact their political attitudes? And how do these perceptions, termed perceived rural deprivation, impact their attitudes towards the government? While scholars have long studied rural behavior, interest in the topic was reinvigorated during the Trump presidency once it became clear that rural voters contributed to Donald Trump’s election in 2016 and became some of his strongest and most loyal supporters during his presidency.

Before we can answer the question of …

High Dimensional Data Analysis: Variable Screening And Inference, Lei Fang

Theses and Dissertations--Statistics

This dissertation focuses on the problem of high dimensional data analysis, which arises in many fields including genomics, finance, and social sciences. In such settings, the number of features or variables is much larger than the number of observations, posing significant challenges to traditional statistical methods.

To address these challenges, this dissertation proposes novel methods for variable screening and inference. The first part of the dissertation focuses on variable screening, which aims to identify a subset of important variables that are strongly associated with the response variable. Specifically, we propose a robust nonparametric screening method to effectively select the predictors …

Investigating The Use Of Mpges-1 Inhibitors For The Treatment Of Abdominal Aortic Aneurysms, Lauren M. Weaver

Theses and Dissertations--Pharmacy

The cardiovascular field is still searching for a treatment for abdominal aortic aneurysms (AAA). This inflammatory disease is a deadly, permanent ballooning of the aortic artery. It often goes undiagnosed until a late stage where associated rupture has a high mortality rate. Surgery is the only option available to patients, but it is risky. There are currently no FDA-approved pharmacological treatments for AAA available. Historically, drugs that have been examined in interventional clinical trials for treatment of AAA were repurposed therapeutics. Novel treatments have been unable to reach the clinic, stalling out in pre-clinical studies. Exceedingly few murine studies have …

Self-Assembled Ternary Polypeptide Nanoparticles With Improved Biostability For Drug Delivery In Cancer Therapy, Preye Mike Agbana

Theses and Dissertations--Pharmacy

Cancer remains a real and present threat to global health. In the United States, according to cancer statistics, almost 40% of people will be diagnosed with cancer at some point in their lifetime. Conventional chemotherapy has become the mainstay for cancer treatment option. However, chemotherapeutic agents are plagued with problems such as poor aqueous solubility, chemical degradation, Bio instability, and off-site toxicity due to non-specificity. New drug modalities are needed to tackle the ever-growing burden on cancer. In recent times, the promise of nanotechnology has aided to develop drug delivery vehicles to facilitate the administration of potent chemotherapeutics. Nanoformulations such …

Investigation Of Folate-Poly(Glutamic Acid)/Polyethylenimine/Dna Complexes For In Vitro Gene Delivery, Caleb Akers

Theses and Dissertations--Pharmacy

Gene therapy is currently being studied as a treatment for a variety of indications, including cancer, infectious disease, and cardiovascular diseases, among others. While many of the early treatments in the field involved the use of viral delivery methods, various safety, ethical, and financial concerns limit the potential uses of this methodology. As such, more recent research has focused on developing non-viral delivery platforms to alleviate some of the issues inherent in viral delivery. Recently, the release of the COVID-19 vaccines from Pfizer and Moderna represents a promising use of non-viral delivery as both utilized a lipid-based delivery vector.

Despite …

Developing A Biocatalytic Toolbox To Aid In Understanding Nucleoside Antibiotics, Jasmine Brianna Woods

Theses and Dissertations--Pharmacy

Antibiotic resistance happens when bacteria develop the ability to survive medications that normally terminate them. Instead, these super germs are able to survive in the body and produce a community of antibiotic resistance germs which can cause human fatalities. It is important to discover and develop new compounds and molecules that will improve this clinical obstacle. This research focused on analyzing the biosynthesis that incorporates distinctive chemical characteristic of various nucleoside antibiotics, ß-hydroxy amino acids and α-methyl-amino acids. ß-hydroxy amino acids and α-methyl-amino acids are considered an important class of industrially useful compounds, particularly for pharmaceutical development, and are found …

Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis, or the organ damage that ensues after the body fails to properly contain a local infection, is the leading cause of in-patient hospitalization in the United States. Advances in critical care medicine over the last 20 years have enabled most sepsis patients to survive the life-threatening dysregulated immune response. However, a majority of survivors report chronic weakness and fatigue years after sepsis, and the cause of this weakness remains largely unknown. This dissertation work focused first on elucidating the major causes of post-sepsis muscle weakness (Aim 1). This aim involved a time-course study to determine when muscle weakness was …

Using Unconscious Thought To Improve Evaluations Of Complex Accounting Estimates, Blake Holman

Theses and Dissertations--Accountancy

Accounting practitioners and regulators have recently focused efforts toward increasing the efficiency of management review controls (MRCs), including the evaluation of complex accounting estimates. Although increasing cognitive effort (i.e., conscious deliberation) is an intuitively appealing strategy for improving decision quality, Unconscious Thought Theory (UTT) suggests that a period of unconscious thought is a more beneficial strategy in complex domains. Drawing on UTT, I predict and find across two studies that prompting accounting practitioners to engage in unconscious thought facilitates the recognition of patterns of bias within management provided estimates, resulting in higher quality assessments of fair value estimates. My findings …

Assessment Of Air Overpressure From Blasting Using Computational Fluid Dynamics, Cecilia Estefania Aramayo

Theses and Dissertations--Mining Engineering

Air overpressure is a shock wave that occurs when explosives detonate and travel through the air. This can cause damage and annoyance in mining blasts, making it a significant concern for the surroundings of the operation. Currently, the cube root scale distance is used to predict air overpressure, but this method has limitations. To accurately determine air overpressure behavior, a new method is needed. Computational fluid dynamics (CFD) is a reliable and advanced technique that can simulate and solve complex physical problems, including the behavior of air overpressure. In this thesis, two techniques, the bursting balloon, and total pressure boundary, …

Enhancing Dna-Damaging Therapy Through The Inhibition Of Dntp Synthesis Using A Synergistic Drug Combination To Treat Pancreatic Neuroendocrine Neoplasms, Jennifer Castle Md

Theses and Dissertations--Clinical and Translational Science

Despite clinical advances, pancreatic neuroendocrine neoplasms (pNEN) remain a difficult clinical entity to treat and can carry a poor prognosis. Systemic therapy is used to treat pNENs which are not amenable to surgical resection. Peptide receptor radionuclide therapy, a form of radiation therapy (RT) and cisplatin are two different forms of DNA-damaging therapy in current use to treat pNENs. However, their efficacy remains poor as single agents. This study aimed to increase the sensitivity of pNENs to the DNA-damaging agents, RT and cisplatin, by inhibiting deoxynucleotide triphosphate (dNTP) synthesis. Triapine, a ribonucleotide reductase inhibitor (RNRi), and ataxia telangiectasia and Rad3-related …

Role Of Autophagy In Aortic Aneurysms, Aida Javidan

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal Aortic Aneurysms (AAAs) are permanent dilations of the abdominal aorta with greater than 80% mortality after rupture. Currently, there are no proven non-surgical therapeutics to blunt expansion or rupture, which highlights the need to gain mechanistic insights into AAA formation. AAA formation involves a complex process of destruction of aortic media through activation of matrix metalloproteinases (MMPs), loss of smooth muscle cells, degradation of extracellular matrix proteins like elastin and collagen, and inflammation. Autophagy is a well-conserved cellular process whereby damaged cytoplasmic organelles and long-lived proteins are degraded. Cellular autophagic activity is usually low under normal conditions but can …

The Role Of High Mobility Group Box-1 Pathobiology In Angiotensin Ii-Induced Abdominal Aortic Aneurysms, Shayan Mohammadmoradi

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal aortic aneurysms (AAAs) are permanent luminal dilations of the vessel wall that can result in rupture and death. There is currently no evidence-based treatment to prevent or attenuate the development of this devastating condition. Although vascular inflammation is known to be one of the hallmarks of AAA, underlying mechanisms that initiate inflammatory pathways in the aorta are not clearly known. High-mobility group box 1 (HMGB1), a highly conserved nonhistone DNA-binding nuclear protein, may contribute to vascular diseases. Since whole-body genetic deletion of HMGB1 is embryonic lethal, pharmacological approaches have been used to manipulate HMGB1 in mice. However, it remains …

Exploring The Efficacy Of Mir-33 Antagonism In Promoting Regression Of Intracranial Atherosclerosis In A Nonhuman Primate Model, Peter Hecker

Theses and Dissertations--Pharmacology and Nutritional Sciences

Atherosclerosis, characterized by lipid accumulation and arterial inflammation, is a major contributor to global morbidity and mortality. Despite significant progress in understanding atherosclerosis in extracranial arteries, the study of intracranial atherosclerosis (ICAS) has been relatively neglected, despite its crucial role in stroke and vascular cognitive impairment. Challenges related to ICAS, including its location within the cranium and limited availability of suitable animal models, have hindered research progress in this area. Although nonhuman primates (NHPs) are commonly used for studying extracranial atherosclerosis, a comprehensive understanding of ICAS pathophysiology in these animals is lacking. By subjecting NHPs to a high-fat/cholesterol diet, we …

The Role Of Renal-Derived Human Soluble Prorenin Receptor In Blood Pressure Regulation And Kidney Function, Gertrude Arthur

Theses and Dissertations--Pharmacology and Nutritional Sciences

The soluble prorenin receptor (sPRR) is a cleaved form of the full-length prorenin receptor (PRR). It has been demonstrated to activate the renin-angiotensin system (RAS) independent of its full-length receptor and mediate similar physiological and pathophysiological processes, albeit via different mechanisms.

The sPRR hormone, a component of RAS, has been identified as a plasma biomarker for hypertension and cardiovascular diseases in humans. In mice, sPRR infusion has been shown to mediate blood pressure elevation through competitive AT1R binding and activation. However, the biological contribution of renal-derived human sPRR to blood pressure regulation and kidney function remains unknown. Therefore, this study …

Sex Dimorphisms Of Aldosterone And High Salt Induced Aortic Aneurysms In Mice, Xufang Mu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Aortic aneurysms, a permanent enlargement in the aorta, is a devastating disease with a high mortality rate after rupture. Aortic aneurysms exhibit strong sex dimorphisms: men are at higher risk than women while women experience worse outcomes if diagnosed. Currently, the only intervention is by open surgery or endovascular repair, and no drugs are approved for blunting the disease progression. This highlights the needs for mechanistic studies for sex-specific therapeutic targets.

Our lab established the mouse model in which mineralocorticoid receptor (MR) agonist aldosterone induces aortic aneurysms in the presence of high salt in male mice age-dependently, mimicking the aging …

Clinical And Biological Factors Determine Spinal Cord Injury Outcomes: Liquor To Lipids, Ethan Glaser

Theses and Dissertations--Physiology

Spinal cord injuries (SCI) are debilitating and life altering events that can lead to permanent motor and sensory loss. SCI outcomes are impacted by both clinical factors such as blood alcohol content (BAC) at the time of injury as well as biological factors like the lipid-rich myelin debris that accumulates in the injury site. Both clinical and biological factors contribute to SCI recovery, impacting neuroinflammation, locomotor recovery, and histopathology. The purpose of the studies described here is to investigate the role of acute alcohol intoxication and intracellular lipid processing pathways on SCI outcomes in a rodent model.

An elevated BAC …

Exploring The Distinction Between Support And Enabling In Families With Substance Use Disorder, Krystal N. King

Theses and Dissertations--Family Sciences

Substance use disorders (SUD) are a pervasive public health problem facing families in the United States. Although families are frequently urged to support loved ones who have SUD and cautioned against enabling them, there is a dearth of literature that distinguishes between supporting and enabling. Through qualitative interviews, this phenomenological study examined the experiences of eight parents with adult children with SUD who were currently in recovery. Five themes emerged from the data including: (a) living in despair, (b) addiction and recovery knowledge, (c) support group philosophy, (d) coping with addiction, and (e) differentiation. The results from this study suggest …

Conceptualizing Asexual Identities, Miranda L. Bejda

Theses and Dissertations--Family Sciences

In current literature, there is little congruence on an inclusive definition of human asexuality. This study explored individuals’ self-identification with asexuality as well as their conceptualization of that identity via thematic analysis. Using a Qualtrics XM survey, 374 individuals (18+ years old) answer questions regarding their experience as a person identifying themselves as asexual. Identity label authenticity, perceived impact of compulsory heterosexuality and heteronormativity on participants' current identity within the asexual spectrum, and prescribed heteronormative ideals were correlated. Thematic analysis revealed themes such as confusion about identity membership, feeling abnormal, the burden of living in a heteronormative society, and identity …

Portrayals Of Family Resilience In Webcomics During The Covid-19 Pandemic: A Thematic Analysis, Claire Catherine Heaney

Theses and Dissertations--Family Sciences

Families and couples were challenged with stresses unlike any other as individuals faced adversities from lockdowns, as well as fears derived from the coronavirus. During the pandemic, trends of webcomics became more popular, particularly comics that depicted characters in romantic relationships dealing with “the new normal.” In this project, I suggest that social media webcomics incorporated topics of coping. The purpose of this study was to examine webcomics that documented daily life situations during lockdowns and stress-buffering skills found in couples’ interactions when dealing with concerns. Utilizing Braun and Clarke’s (2006) thematic analysis, 585 romantic relationship webcomics posted from March …

Mechanisms Of Rnai In Insects, Jin Mo Koo

Theses and Dissertations--Entomology

RNA interference (RNAi) mechanism is found in many eukaryotes and animal cells, with its endogenous functions as defense against transposable elements and viruses, as well as post transcriptional regulation of gene expression. Since its first discovery, RNAi has contributed enormously as a reverse genetic tool for functional genomic studies. In application, RNAi is used in therapeutics, as well as agricultural crop and livestock protection. Yet, for the wider application of RNAi, improvement of its potency and delivery technologies is needed. Deeper mechanistic understanding of every step of RNAi, from cellular uptake of RNAi trigger molecule to targeted mRNA degradation is …

Equine Fecal Microbiota Response To Short Term Antibiotic Administration, Jordan Lacey Parker

Theses and Dissertations--Veterinary Science

Though generally regarded as safe, research continues to demonstrate negative side effects of antibiotic administration on the gastrointestinal (GIT) microbiota across species. In horses, antibiotic associated diarrhea (AAD) is a life-threatening side effect linked to the GIT microbiota. This study tested the hypothesis that short term antibiotic administration to healthy horses would negatively impact the fecal microbiota as measured by their ability to digest nutrients and produce short chain fatty acids (SCFAs). Twenty-four horses were assigned to one of four treatments: control (CO); potassium penicillin/gentamicin sulfate (KPG); ceftiofur crystalline free acid (EX); trimethoprim/sulfamethoxazole (SMZ); and treated for 4 days. Fecal …

Computed Tomography Image Analysis: Modeling Skeletal Injuries In Thoroughbred Racehorses, Grace Louise Camp

Theses and Dissertations--Veterinary Science

Musculoskeletal injuries account for the majority of career-ending health concerns in Thoroughbred racehorses. A small but very serious subset of these can be life-threatening and usually involve fractures of the bones in the lower limb that occur during high-speed exercise or racing competitions. Understanding the etiopathogenesis of lower forelimb bone fractures leading to catastrophic musculoskeletal injuries (CMI) is the highest safety and welfare priority in horse racing. This thesis conducted two studies utilizing computed tomography (CT) images of Thoroughbred lower limbs. The first examined bone lesion annotations in 134 horses (268 forelimbs) across 105 anatomical sites to assess the concordance …

Microalgae Immobilization With Filamentous Fungi: Process Development For Sustainable Food Systems, Suvro Talukdar

Theses and Dissertations--Biosystems and Agricultural Engineering

Demand for sustainable food sources has increased because of the rapid growth of the world's population.  In this study, microalgae cells of Haematococcus pluvialis were immobilized using the edible fungal strain Aspergillus awamori for potential food applications. The study investigated the impact of fungal loading, pellet geometry, and initial microalgae cell concentration on the immobilization performance and product characteristics. It was found that higher fungal loading and larger fungal pellets contributed to increased immobilization performance while increased initial microalgae concentration inhibited the process. Larger fungal pellets had decreased biomass density, which led to decreased surface concentration of immobilized microalgae but …

Improving Tax Compliance In Indonesia Through The 2022 Voluntary Disclosure Program, Farid Al Firdaus

MPA/MPP/MPFM Capstone Projects

Developed or developing countries have conducted Voluntary Disclosure Programs (VDP) to increase tax revenues and taxpayers' compliance. Non-compliant taxpayers prefer this way to regular law enforcement to be more compliant. This study focuses on supporting Indonesia, the lowest tax-to-Gross Domestic Product (GDP) ratio in Asia and the Pacific, in improving its taxpayers' long-term compliance through the 2022 VDP; this amnesty had fewer participants, shorter periods, and higher rates than the first one in 2016. Using descriptive analysis, it is concluded that the 2022 VDP could reveal taxpayers' wealth known and unknown by the tax authority, increase revenue as a fraction …

How The Increase In Remote Employees Due To Covid-19 Has Impacted Local Income Tax Revenues For U.S. Cities, Brian T. Pearson

MPA/MPP/MPFM Capstone Projects

This research paper will discuss COVID-19’s impact on remote work and its effect on local income taxes for cities across the United States. The paper specifically will be looking into how the increase in remote workers has affected revenue and policy changes for local income taxes since the pandemic. Before the pandemic, most US citizens with jobs had to be on-site, but COVID-19 seems to have changed how businesses are operating for the foreseeable future. A lot of businesses across the country have shifted to having more of their employees working fully remote or partially remote (hybrid) schedules. This has …

Public Health Access And Service For All, Austin Nugent

MPA/MPP/MPFM Capstone Projects

Collecting, analyzing, and reporting accurate, reliable data is necessary for achieving health equity. Although data alone will not lead to equitable health outcomes for all people, it helps health professionals, researchers, and policymakers understand health disparities and develop effective interventions, programs, and policies to reduce them. Necessary data includes disaggregated health information on diverse demographics, including people with disabilities. However, despite this need, disability data gaps exist. Fortunately, numerous solutions exist to address this issue, including implementing minimum data standards on disability and engaging all levels of health organizations in data practices. This capstone project investigated the current data practices …

The Financial Impact Of Undocumented Workers On Kentucky's Economy, Diana Gold

MPA/MPP/MPFM Capstone Projects

Undocumented immigrant workers have a significant presence and impact on the economy of the Commonwealth of Kentucky. However, it is difficult to fully understand their financial impact due to the scarcity of published statistics on this topic. In addition, undocumented immigrants try to live unnoticed due to the nature of their legal status and fear of deportation. Some nonprofit organizations and a few public institutions have been able to track data related to their tax contributions, population size, ages, work fields, spending habits, and public resources used. Gathering the available data will help better understand the financial impact of undocumented …