Digital Commons Network^™

Investigations Of Interleukin-1 Alpha As A Novel Stroke Therapy In Experimental Ischemic Stroke, Kathleen Elizabeth Salmeron

Theses and Dissertations--Neuroscience

Stroke is a leading cause of death and disability worldwide. Although rapid recognition and prompt treatment have dropped mortality rates, most stroke survivors are left with permanent disability. Approximately 87% of all strokes result from the thromboembolic occlusion of the cerebrovasculature (ischemic strokes). Potential stroke therapeutics have included anti-inflammatory drugs, as well as many other targets with the goal of mitigating the acute and chronic inflammatory responses typically seen in an ischemic stroke. While these approaches have had great success in preclinical studies, their clinical translation has been less successful. Master inflammatory cytokines, such as IL-1, are of particular interest. …

“Listening With An Attitude”: The Role Of Attitude On Native And Non-Native Intergroup Communication, Aidah N. Aljuran

Theses and Dissertations--Linguistics

People tend to draw their own conclusions about similarities and differences between who they are and the “other.” Having perceptions of being similar to the in-group and being different from the out-group “satisfies psychological needs” (Robbins & Krueger, 2005). Based on this social perception, individuals show communication variations as a way of expressing their identities (Giles 1973). This study implements quantitative and qualitative methods in order to examine the attitude of native speakers (NSs), as well as the potential impact of these attitudes on their communication with non-native speakers (NNSs). The potential impact of NSs’ interactions on NNSs’ interactions was …

Myosin-Xva Is Key Molecule In Establishing The Architecture Of Mechanosensory Stereocilia Bundles Of The Inner Ear Hair Cells, Shadan Hadi

Theses and Dissertations--Medical Sciences

Development of hair cell stereocilia bundles involves three stages: elongation, thickening, and supernumerary stereocilia retraction. Although Myo-XVa is known to be essential for stereocilia elongation, its role in retraction/thickening remains unknown. We quantified stereocilia numbers/diameters in shaker-2 mice (Myo15^sh2) that have deficiencies in “long” and “short” isoforms of myosin-XVa, and in mice lacking only the “long” myosin-XVa isoform (Myo15^ΔN). Our data showed that myosin-XVa is largely not involved in the developmental retraction of supernumerary stereocilia. In normal development, the diameters of the first (tallest)/second row stereocilia within a bundle are equal and grow simultaneously. …

Increasing Inclusion: The Pursuit Of Racial Diversity In Three Historically White Universities In Kentucky, Michigan, And Ontario From 2000 To 2012, David J. Luke

Theses and Dissertations--Sociology

The University of Kentucky (UK) and University of Michigan (UM) present very different patterns in terms of black student enrollments and completions from 2000 to 2012 because of a structural explanation, a qualitative explanation, and a statistical explanation. Unfortunately, the patterns at the University of Western Ontario (UWO) are partial due to a lack of data.

First, the structural explanation is that UK, as a university in the state of Kentucky, was under a mandate from the U.S. Department of Education to desegregate because they were in violation of Title VI of the Civil Rights Act. The Kentucky Council on …

Understanding The Thermodynamics And Oral Absorption Potential Of Pharmaceutical Amorphous Solid Dispersions, Nico Setiawan

Theses and Dissertations--Pharmacy

Supersaturating drug delivery systems, such as amorphous solid dispersions (ASDs), have been used extensively to elevate the apparent solubility and oral bioavailability of poorly water-soluble drugs. However, despite the numerous examples of success in increasing solubility and oral bioavailability using ASDs, physical stability challenges remain as formulators seek to employ high drug loading for cost reduction and improved patient compliance. Therefore, stability in both the solid and solution state must be considered for ASDs to be successful. In the solid state, the drug must remain amorphous in the solid matrix throughout the shelf life of the product. Although excipients, such …

The Impact Of Bioactive Phytosterol, Stigmasterol, On Cholesterol Elimination Pathways In Mice, Hannah C. Lifsey

Theses and Dissertations--Pharmacy

Despite advances in healthcare, cardiovascular disease (CVD) remains the leading cause of death in the United States. Elevated levels of plasma cholesterol are highly predictive of CVD and stroke and are the principal driver of atherosclerosis. Unfortunately, current cholesterol lowering agents, such as statins, are not known to reverse atherosclerotic disease once it has been established. In preclinical models, agonists of nuclear receptor, LXR, have been shown to reduce and reverse atherosclerosis. Phytosterols are bioactive non-cholesterol sterols that act as LXR agonists and regulate cholesterol metabolism and transport. We hypothesize that stigmasterol would act as an LXR agonist and alter …

Discovery Of Novel Muraymycin Antibiotics And Insight Into The Biosynthetic Pathway, Zheng Cui

Theses and Dissertations--Pharmacy

New antibiotics with novel targets or mechanisms of action are needed to counter the steady emergence of bacterial pathogens that are resistant to antibiotics used in the clinic. MraY, a promising novel target for antibiotic development, initiates the lipid cycle for the biosynthesis of peptidoglycan cell wall, which is essential for the survival of most, if-not-all, bacteria. MraY is an enzyme that catalyzes the transfer and attachment of phospho-MurNAc-pentapeptide to a lipid carrier, undecaprenylphosphate. Muraymycins are recently discovered lipopeptidyl nucleoside antibiotics that exhibit remarkable antibiotic activity against Gram-positive as well as Gram-negative bacteria by inhibiting MraY. We conducted a thorough …

Discovery Of New Antimicrobial Options And Evaluation Of Aminoglycoside Resistance Enzyme-Associated Resistance Epidemic, Selina Y. L. Holbrook

Theses and Dissertations--Pharmacy

The extensive and sometimes incorrect and noncompliant use of various types of antimicrobial agents has accelerated the development of antimicrobial resistance (AMR). In fact, AMR has become one of the greatest global threat to human health in this era. The broad-spectrum antibiotics aminoglycosides (AGs) display excellent potency against most Gram-negative bacteria, mycobacteria, and some Gram-positive bacteria, such as Staphylococcus aureus. The AG antibiotics amikacin, gentamicin, kanamycin, and tobramycin are still commonly prescribed in the U.S.A. for the treatment of serious infections. Unfortunately, bacteria evolve to acquire resistance to AGs via four different mechanisms: i) changing in membrane permeability to …

Synthesis And Biological Evaluation Of Novel Drug Candidates To Address Drug Resistance In Tuberculosis And Fungal Diseases, Huy Ngo

Theses and Dissertations--Pharmacy

Tuberculosis (TB) and fungal infections are two of the most lethal infectious diseases worldwide due to the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) and fungal strains that can resist the most potent antimicrobial drugs currently employed. Due to the rise of these drug resistant strains, effective treatment options for these two infections are limited. This dissertation aims at exploring novel drug scaffolds to help combat drug resistance in TB and fungal infections.

TB caused by the pathogenic Mtb is, alongside with human immunodeficiency virus acquired immunodeficiency virus (HIV), the deadliest infectious disease worldwide with approximately 2-3 billion people …

Conceptualizing The Prevention Of Human Trafficking: Survivors Perspectives, Jessica James Donohue-Dioh

Theses and Dissertations--Social Work

The following study seeks to conceptualize the prevention of human trafficking from the perspective of survivors. The study design was informed through a Public Health Framework and the application of Postmodernism, Social Constructionist Theory, Ecological Perspective and Empowerment Perspective. An integrative mixed-method, participatory research design was applied, namely Concept Mapping. Data was collected over approximately two-months, and included 35 survivors of human trafficking from 4 different states. Data collected from survivors resulted in a statement set (N = 108) and a 10-Cluster Final solution depicting the ways in which survivors conceptualized prevention. Additional outputs provide insight as to survivors’ perspectives …

Thermo-Mechanical Coupling For Ablation, Rui Fu

Theses and Dissertations--Mechanical and Aerospace Engineering

In order to investigate the thermal stress and expansion as well as the associated strain effect on material properties caused by high temperature and large temperature gradient, a two-way thermo-mechanical coupling solver is developed. This solver integrates a new structural response module to the Kentucky Aerothermodynamics and Thermal response System (KATS) framework. The structural solver uses a finite volume approach to solve either hyperbolic equations for transient solid mechanics, or elliptic equations for static solid mechanics. Then, based on the same framework, a quasi-static approach is used to couple the structural response and thermal response to estimate the thermal expansion …

Pressure-Driven Stabilization Of Capacitive Deionization, Landon S. Caudill

Theses and Dissertations--Mechanical and Aerospace Engineering

The effects of system pressure on the performance stability of flow-through capacitive deionization (CDI) cells was investigated. Initial data showed that the highly porous carbon electrodes possessed air/oxygen in the micropores, and the increased system pressure boosts the gases solubility in saline solution and carries them out of the cell in the effluent. Upon applying a potential difference to the electrodes, capacitive-based ion adsorption occurs in competition with faradaic reactions that consume oxygen. Through the addition of backpressure, the rate of degradation decreases, allowing the cell to maintain its salt adsorption capacity (SAC) longer. The removal of oxygen from the …

Scale Models Of Acoustic Scattering Problems Including Barriers And Sound Absorption, Nan Zhang

Theses and Dissertations--Mechanical and Aerospace Engineering

Scale modeling has been commonly used for architectural acoustics but use in other noise control areas is nominal. Acoustic scale modeling theory is first reviewed and then feasibility for small-scale applications, such as is common in the electronics industry, is investigated. Three application cases are used to examine the viability. In the first example, a scale model is used to determine the insertion loss of a rectangular barrier. In the second example, the transmission loss through parallel tubes drilled through a cylinder is measured and results are compared to a 2.85 times scale model with good agreement. The third example …

Verification And Validation Studies For The Kats Aerothermodynamics And Material Response Solver, Olivia Schroeder

Theses and Dissertations--Mechanical and Aerospace Engineering

Modeling the atmospheric entry of spacecraft is challenging because of the large number of physical phenomena that occur during the process. In order to study thermal protection systems, engineers rely on high fidelity solvers to provide accurate predictions of both the thermochemical environment surrounding the heat shield, and its material response. Therefore, it is necessary to guarantee that the numerical models are correctly implemented and thoroughly validated. In recent years, a high-fidelity modeling tool has been developed at the University of Kentucky for the purpose of studying atmospheric entry. The objective of this work is to verify and validate this …

Multiphase Interaction In Low Density Volumetric Charring Ablators, Ali D. Omidy

Theses and Dissertations--Mechanical and Aerospace Engineering

The present thesis provides a description of historical and current modeling methods with recent discoveries within the ablation community. Several historical assumptions are challenged, namely the presence of water in Thermal Protection System (TPS) materials, presence of coking in TPS materials, non-uniform elemental production during pyrolysis reactions, and boundary layer gases, more specifically oxygen, interactions with the charred carbon interface.

The first topic assess the potential effect that water has when present within the ablator by examining the temperature prole histories of the recent flight case Mars Science Laboratory. The next topic uses experimental data to consider the instantaneous gas …

Vitamin D Works Through The Lipid Droplet Protein Plin2 To Augment Mitochondrial Function In Skeletal Muscle, David M. Schnell

Theses and Dissertations--Pharmacology and Nutritional Sciences

Vitamin D has been connected with increased intramyocellular lipid (IMCL) mitochondrial function in skeletal muscle. It is also shown to prevent lipotoxicity in several tissues, but this has not yet been examined in skeletal muscle. Perilipin 2 (PLIN2), a lipid droplet protein upregulated with vitamin D treatment, is integral to managing IMCL capacity and lipid oxidation in skeletal muscle. Increased lipid storage and oxidation is associated with increased tolerance to a hyperlipidic environment and resistance to lipotoxicity. Therefore, I hypothesized that vitamin D increases β-oxidation and lipid turnover though a PLIN2 mediated mechanism, thereby preventing lipotoxicity.

This hypothesis was divided …

Pcb Disruption Of Gut And Host Health: Implications Of Prebiotic Nutritional Intervention, Jessie Baldwin Hoffman

Theses and Dissertations--Pharmacology and Nutritional Sciences

Exposure to environmental pollutants poses numerous risk factors for human health, including increasing incidence of cardiovascular disease and diabetes. Persistent organic pollutants, such as polychlorinated biphenyls (PCBs) have been strongly linked to the development of these chronic inflammatory diseases and the primary route of exposure is through consumption of contaminated food products. Thus, the gastrointestinal tract is susceptible to the greatest levels of these pollutants and is an important facet to study.

The first two hypotheses of this dissertation tested that exposure to PCBs disrupts gut microbiota directly (in vitro) and within a whole body system. PCB exposure …

The Prebiotic Inulin Beneficially Modulates The Gut-Brain Axis By Enhancing Metabolism In An Apoe4 Mouse Model, Jared D. Hoffman

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is the most common form of dementia and a growing disease burden that has seen pharmacological interventions primarily fail. Instead, it has been suggested that preventative measures such as a healthy diet may be the best way in preventing AD. Prebiotics are one such potential measure and are fermented into metabolites by the gut microbiota and acting as gut-brain axis components, beneficially impact the brain. However, the impact of prebiotics in AD prevention is unknown. Here we show that the prebiotic inulin increased multiple gut-brain axis components such as scyllo-inositol and short chain fatty acids in the …

Role Of Sex Chromosomes In Sexual Dimorphism Of Angii-Induced Abdominal Aortic Aneurysms, Yasir Alsiraj

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal aortic aneurysms (AAAs), a permanent dilation in the abdominal region of the aorta, is a highly sexually dimorphic disease. AAAs prevalence is ranging from 4-10 fold higher in males than females. Defining the mechanistic basis for reduced (in females) or increased (in males) AAA formation and progression may uncover potential therapeutic targets. The majority of studies examining sexual dimorphism focus on the role of sex hormones. However, genes residing on sex chromosomes, in addition to sex hormones, may contribute to sexual dimorphism of AAAs. For example, the X chromosome contains about 5% of the whole genome, but the role …

Effects Of Endophyte-Infected Tall Fescue Seed And Bromocriptine On Endocrine And Immune Function In Horses, Jessica Marie Hanneman

Theses and Dissertations--Veterinary Science

Consumption of endophyte-infected (E+) grasses has long been associated with health problems in animals. In cattle E+ tall fescue consumption leads to fescue toxicosis, and in horses it leads reproductive problems. The health-related issues associated with endophyte consumption have been attributed to the effects caused by the ergot alkaloids produced by the fungus. These ergot alkaloids are considered D2-like receptor agonists, and 5-HT2 serotonin and α-adrenergic receptor partial agonists. Many studies in humans, swine, cattle, and horses have identified that ergopeptines cause a decrease in prolactin production due to their dopaminergic activities. Additionally, these molecules have been found to cause …

Diet Composition Explains Reductions In Stream Salamander Occupancy And Abundance Along A Conductivity Gradient, Jacob Matthew Hutton

Theses and Dissertations--Forestry and Natural Resources

Changes in land use such as mountaintop removal mining with valley fills (MTR/VF) affect chemical, physical, and hydrological properties of headwater streams. Although numerous stream taxa have experienced significant declines from MTR/VF, stream salamanders appear to be particularly sensitive. Yet, the specific mechanism(s) responsible for the population declines has eluded researchers. We sampled salamander assemblages across a continuous specific conductivity (SC) gradient in southeastern Kentucky and estimated occupancy rates and abundance estimates along this gradient. We also examined the diet of larval and adult salamanders to determine if autochthony (A/T prey), total prey volume, and body condition is influenced by …

Efficacy Of Herbivore Exclusion On Planted Tree Seedling Vitality On A Reclaimed Surface Mine In Eastern Kentucky, Zachary J. Hackworth

Theses and Dissertations--Forestry and Natural Resources

Conventional Appalachian surface-mine reclamation techniques repress natural forest regeneration, and tree plantings are often necessary for reforestation. Reclaimed Appalachian surface mines harbor a suite of mammal herbivores that forage on recently planted seedlings. Anecdotal reports across Appalachia have implicated herbivory in the hindrance and failure of reforestation efforts, yet empirical evaluation of herbivory impacts on planted seedling vitality in this region remains relatively uninitiated. First growing-season survival, height growth, and mammal herbivory damage of black locust (Robinia pseudoacacia L.), shortleaf pine (Pinus echinata Mill.), and white oak (Quercus alba L.) are presented in response to varying intensities …