Digital Commons Network^™

Renal Humoral, Genetic And Genomic Mechanisms Underlying Spontaneous Hypertension, Jason A. Collett

Theses and Dissertations--Biology

In spite of significant progress in our knowledge of mechanisms that control blood pressure, our understanding of the pathogenesis of hypertension, its genetics, and population efforts to control blood pressure, hypertension remains the leading risk factor for mortality worldwide. It’s estimated that 1 out of every 3 adults has hypertension. Hypertension is a major risk factor for cardiovascular disease and stroke, and is considered a primary or contributing cause of death to more than 2.4 million US deaths each year. Although spontaneous hypertension has been the subject of substantial research, many critical questions remain unanswered.

To investigate mechanisms underlying spontaneous …

Knowing And Being Known: Sexual Delinquency, Stardom, And Adolescent Girlhood In Midcentury American Film, Michael Todd Hendricks

Theses and Dissertations--English

Sexual delinquency marked midcentury cinematic representations of adolescent girls in 1940s, 50, and early 60s. Drawing from the history of adolescence and the context of midcentury female juvenile delinquency, I argue that studios and teen girl stars struggled for decades with publicity, censorship, and social expectations regarding the sexual license of teenage girls. Until the late 1950s, exploitation films and B movies exploited teen sex and pregnancy while mainstream Hollywood ignored those issues, struggling to promote teen girl stars by tightly controlling their private lives but depriving fan magazines of the gossip and scandals that normally fueled the machinery of …

Subsistence And Biodiversity Conservation In The Sundarban Biosphere Reserve, West Bengal, India, Priyanka Ghosh

Theses and Dissertations--Geography

My dissertation research investigates the impacts of biodiversity conservation on the local population living in the Sundarban Biosphere Reserve (SBR). More specifically, the research examines the impacts of conservation on local fishing communities living on the edge of the Sundarban Reserve Forest. In addition, it examines the causes and characteristics of conflicts between the biosphere reserve managers and the local fishing communities over the resource use of the biosphere reserve. The research project also explores the impacts of ecotourism on the local population that lives on the edge of the Sundarban Tiger Reserve (STR). STR is one of the important …

Biomechanical Effects Of Trees And Soil Thickness In The Cumberland Plateau, Michael Shouse

Theses and Dissertations--Geography

Previous research in the Ouachita Mountains, Arkansas suggests that, on relatively thin soils overlying bedrock, individual trees locally thicken the regolith by root penetration into bedrock. However, that work was conducted mainly in areas of strongly dipping and contorted rock, where joints and bedding planes susceptible to root penetration are more common and accessible. This project extended this concept to the Cumberland Plateau, Kentucky, with flat, level-bedded sedimentary rocks. Spatial variability of soil thickness was quantified at three nested spatial scales, and statistical relationships with other potential influences of thickness were examined. In addition, soil depth beneath trees was compared …

Husserl's Dyadic Semantics, Jesse Delaney

Theses and Dissertations--Philosophy

Husserl’s Logical Investigations contain an apparent discrepancy in their account of meaning. They first present meanings, contra psychologism, as commonly available, reiterable, invariant, possibly valid, and independent of our “acts of meaning”. They then present meaning, almost psychologistically, as a kind of intentional experience on which all truths and other transcendent meanings depend. I offer a critical developmental study of this problem within Husserl’s semantics. I argue (1) that Husserl had reason to adopt his dyadic account of signification, (2) that this “two-sided” account shaped, and was reciprocally informed by, the two-step phenomenological method, and (3) that Husserl’s proposed resolution …

Truth And Falsehood In Plato's Sophist, Michael Oliver Wiitala

Theses and Dissertations--Philosophy

This dissertation is a study of the ontological foundations of true and false speech in Plato’s Sophist. Unlike most contemporary scholarship on the Sophist, my dissertation offers a wholistic account of the dialogue, demonstrating that the ontological theory of the “communing” of forms and the theory of true and false speech later in the dialogue entail one another.

As I interpret it, the account of true and false speech in the Sophist is primarily concerned with true and false speech about the forms. As Plato sees it, we can only make true statements about spatio-temporal beings if it …

Effectiveness Of A Farm Field Trip, Bonnie S. Sigmon

Theses and Dissertations--Community & Leadership Development

The annual Sigmon Farm Tour was started in 1992 as an agricultural education program where students could experience being on a farm with the goal of increasing the agricultural literacy levels of the participants. Every year the entire 4th grade student population of Rockcastle County spends the day touring the farm and participating in experiential mini lessons given by the cooperating farm service and health agencies. The program has continued for 20+ years without an evaluation as to whether it is achieving its objectives. This evaluation will also exhibit the programs strengths and weakness so it can continue to improve. …

Evaluating Sampling Strategies For Rainfall Simulation Studies And Surface Transport Of Antibiotics From Swine Manure Applied To Fescue Plots, Holly K. Enlow

Theses and Dissertations--Biosystems and Agricultural Engineering

Antibiotics are commonly used in animal agriculture to treat and prevent diseases and promote growth. Unfortunately, large amounts of antibiotics are not metabolized, but instead are excreted in urine and feces. Rainfall simulation studies were used to investigate the transport of the antibiotic oxytetracycline and various constituents in runoff and the ability of alum to reduce pollutant transport. Runoff samples were collected at several points during the simulated storm event from each of four treatments: control (C), manure only (M), manure and antibiotics (MA), and manure, antibiotics and alum (MAA). Flow-weighted composite samples were created and compared to the flow …

Sequential Co-Culture Of Anaerobic Bacteria On Switchgrass In A Continuous Flow-Through Reactor For Biofuel Production, Noelia M. Elia

Theses and Dissertations--Biosystems and Agricultural Engineering

Solid substrate cultivation (SSC) using lignocellulosic non-food feedstock, such as switchgrass, is an alternative for advanced biofuel production. Acetone-Butanol-Ethanol (ABE) fermentation in two stages using a sequential culture of microorganisms from the class Clostridia is an approach proposed to increase the butanol production.

The goal was to test the efficacy of a sequential culture on high solid substrate cultivation in batch and continuous cultivation, and to evaluate conditions to optimize butanol production using switchgrass as substrate.

Initial batch experiments were used to determine particle size effect, choice of solvent producer and pretreatment evaluation: The effect of particle size on gas …

Storm Hydrograph Characteristics And Curve Numbers Of Loose-Dumped Spoil In Eastern Kentucky, Mary Katherine Weatherford

Theses and Dissertations--Biosystems and Agricultural Engineering

Traditional mine reclamation often results in highly compacted lands which prohibit tree growth and survival, reduce infiltration rates, and increase runoff. In 2005, six 0.4 ha plots were constructed on the Bent Mountain surface mine in eastern KY by the University of Kentucky in accordance with Forestry Reclamation Approach’s low compaction guidelines. The plots consisted of two replications each of (1) brown weathered sandstone (BROWN), (2) gray unweathered sandstone (GRAY), (3) and a combination of both sandstones and shales (MIXED). The goal of this project was to assess the hydrologic performance on a storm event basis (monitoring years 2012-2013) of …

Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh

Theses and Dissertations--Neuroscience

Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF-hand motif characteristic of the classical calpains, calpain 1 and 2, but retains catalytic and Ca²⁺ binding non EF domains. Tra-3, an ortholog of CAPN5, is involved in necrotic cell death in C.elegans; although specific role of CAPN5 has not been investigated in the mammalian CNS. I compared relative mRNA levels of calpains in rat CNS, which revealed that CAPN5 is the second most highly expressed calpain. We examined relative levels of CAPN5 from late embryonic day 18 to postnatal day 90 and …

Modulation Of Vaccine-Induced Responses By Anthelmintic Treatment In Ponies, Emily Rubinson

Theses and Dissertations--Medical Sciences

Vaccines and anthelmintics induce an inflammatory response in equids. Since they are commonly given concurrently, it is practical to study any interaction between them. This study evaluated whether IVM and PYR would modulate the acute phase inflammatory response, the systemic gene expression of pro-inflammatory cytokines, and vaccine-specific titers induced by WNV, EHV, and KLH vaccines. Naturally-infected, yearling ponies were sorted by gender, then fecal epgs. They were randomly assigned to three treatment groups: IVM, PYR, and control. All ponies received vaccinations intramuscularly on days 0 and 29. Whole blood, serum, and plasma samples were collected 1, 3, and 14 days …

Listeria Monocytogenes Can Utilize Both M Cell Transcytosis And Inla-Mediated Uptake To Cross The Epithelial Barrier Of The Intestine During An Oral Infection Model Of Listeriosis, Hilary Denney

Theses and Dissertations--Medical Sciences

The invasive pathways, InlA- and InB-mediated uptake and M cell transcytosis, that Listeria monocytogenes uses to invade the intestine have mainly been studied using infection models that do not truly replicate what occurs during a natural infection. Recently, our lab has developed an oral infection model that is more physiolocally relevant to what occurs during food borne listeriosis. We have sought to evaluate the relative roles of the previously defined invasive pathways, in our oral model of infection. We have done this by utilizing an InlAmCG Lm strain that is able to bind murine E-cadherin, knockout Lm strains, ΔinlA Lm …

Dopamine And Glutamate Dysfunction In A Rodent Model Of Attention-Deficit/Hyperactivity Disorder: Implications For Future Neuropharmacology, Erin M. Miller

Theses and Dissertations--Neuroscience

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common disorders of childhood. It is theorized to be caused by catecholamine dysfunction in the striatum (Str) and frontal cortex (FC). The spontaneously hypertensive rat (SHR) has been used as a model for ADHD because of its attention deficits, impulsiveness, and hyperactivity. Prior studies of dopamine (DA) in the Str and FC have revealed conflicting results in the SHR compared to control, indicative of a need for a better understanding of DA dynamics in this model. In addition to the DA hypothesis, studies have begun implicating glutamate in the etiology of ADHD. …

Immunotherapy In Combination With Behavioral Enrichment In A Canine Model Of Aging, Paulina R. Davis

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is characterized by cognitive decline and hallmark neuropathology, including β-amyloid (Aβ). Therapeutic strategies for AD are focusing on reducing Aβ. Canines develop Aβ neuropathology and cognitive decline with age similar to AD patients. In previous studies, immunization with Aβ1-42 (VAC) in aged canines decreased brain Aβ but did not improve cognition. Behavioral enrichment (ENR) improved cognition without reducing brain Aβ. We hypothesized that VAC combined with ENR would provide cognitive benefits and reduce Aβ neuropathology, as compared individual VAC and ENR treatments. Aged beagles were placed into groups: control, VAC with fibrillar Aβ1-42, ENR, and combination treatment …

A Brief Elevation Of Serum Amyloid A Is Sufficient To Increase Atherosclerosis, Joel C. Thompson

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease is now the leading cause of death worldwide. Serum amyloid A (SAA), a positive acute phase reactant, along with C-reactive protein is used clinically as a marker of cardiovascular disease risk. However, recent data has shed light on a possible causal role of SAA in the development of atherosclerosis, the most pervasive form of cardiovascular disease. Several inflammatory diseases such as diabetes and obesity are known to confer increased risk of developing cardiovascular disease. Individuals with these diseases all have modest but persistent elevation of SAA. To determine if SAA caused the development of atherosclerosis, apoe^-/-chow …

Immobilizing Mutation In An Unconventional Myosin15a Affects Not Only The Structure Of Mechanosensory Stereocilia In The Inner Ear Hair Cells But Also Their Ionic Conductances, Diana Syam

Theses and Dissertations--Medical Sciences

In the inner and outer hair cells (OHCs) of the inner ear, an unconventional myosin 15a localizes at the tips of mechanosensory stereocilia and plays an important role in forming and maintaining their normal structure. A missense mutation makes the motor domain of myosin 15a dysfunctional and is responsible for the congenital deafness DFNB3 in humans and deafness and vestibular defects in Shaker-2 (Sh2) mouse model. All hair cells of homozygous Shaker-2 mice (Myo15^sh2/sh2) have abnormally short stereocilia, but, only stereocilia of Myo15^sh2/sh2OHCs start to degenerate after the first few days of postnatal development …

Natural Phenomena As Potential Influence On Social And Political Behavior: The Earth’S Magnetic Field, Jackie R. East

Theses and Dissertations--Political Science

Researchers use natural phenomena in a number of disciplines to help explain human behavioral outcomes. Research regarding the potential effects of magnetic fields on animal and human behavior indicates that fields could influence outcomes of interest to social scientists. Tests so far have been limited in scope. This work is a preliminary evaluation of whether the earth’s magnetic field influences human behavior it examines the baseline relationship exhibited between geomagnetic readings and a host of social and political outcomes. The emphasis on breadth of topical coverage in these statistical trials, rather than on depth of development for any one model, …

Beyond Peroxisome: Abcd2 Modifies Pparα Signaling And Identifies A Subclass Of Peroxisomes In Mouse Adipose Tissue, Xiaoxi Liu

Theses and Dissertations--Pharmacy

ABCD2 (D2) has been proposed as a peroxisomal long-chain acyl-CoA transporter that is essential for very long chain fatty acid metabolism. In the livers of mice, D2 is highly induced by fenofibrate, a PPARα ligand that has been widely used as a lipid lowering agent in the treatment of hypertriglyceridemia. To determine if D2 is a modifier of fibrate responses, wild-type and D2 deficient mice were treated with fenofibrate for 14 days. The absence of D2 altered expression of gene clusters associated with lipid metabolism, including PPARα signaling. Using 3T3-L1 adipocytes, which express high levels of D2, we confirmed that …

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

Synthesis And Biological Evaluation Of Novel Resveratrol And Combretastatin A4 Derivatives As Potent Anti-Cancer Agents, Nikhil Reddy Madadi

Theses and Dissertations--Pharmacy

Resveratrol has been reported as a potential anticancer agent but cannot be used as an antitumor drug due to its chemical and metabolic instability. We have designed and synthesized 184 novel compounds related to resveratrol in an attempt to produce more potent and drug-like molecules. We have identified a tetrazole analog of resveratrol, ST-145(a) as a lead anticancer agent from the resveratrol analog series of compounds with a GI₅₀ value of less than 10nM against almost all the human cancer cell lines in the National Cancer Institute’s screening panel.

In a separate study, we tested the hypothesis that the …

Human Butyrylcholinesterase Mutants For Cocaine Detoxification, Shurong Hou

Theses and Dissertations--Pharmacy

Cocaine is one of the most reinforcing drugs of abuse and has caused serious medical and social problems. There is no FDA-approved medication specific for cocaine. It is of a high priority to develop an effective therapeutic treatment for cocaine abuse. Human butyrylcholinesterase (BChE) has been recognized as a promising candidate of enzyme therapy to metabolize cocaine into biologically inactive metabolites and prevent it from reaching central nervous system (CNS). However, the catalytic activity of wide-type human BChE against cocaine is not sufficiently high for treatment of cocaine abuse. Dr. Zhan’s lab has successfully designed and discovered a series of …

Lobelane Analogs With Various Methylene Linker Lengths And Acyclic Lobelane Analogs As Potential Pharmacotherapies To Treat Methamphetamine Abuse, Zheng Cao

Theses and Dissertations--Pharmacy

Methamphetamine interacts with vesicular monoamine transporter-2 (VMAT2) to inhibit dopamine (DA) uptake and promotes DA release from presynaptic vesicles, increasing cytosolic DA available for methamphetamine-induced reverse transport by DA transporters. By inhibiting VMAT2, lobelane, a defunctionalized, saturated lobeline analog, decreases methamphetamine-evoked DA release and methamphetamine self-administration in rats. In this dissertation structure-activity relationships around the lobelane structure were investigated on racemic lobelane analogs with varying methylene linker lengths at central piperidine ring. Affinity for dihydrotetrabenazine (DTBZ) sites on VMAT2 and for inhibition of VMAT2 function was determined to be 0.88-63 and 0.024-4.6 µM, respectively, and positively correlated. The most potent …

Mechanisms Of Cyclooxygenase-2-Dependent Human Aortic Smooth Muscle Cell Phenotypic Modulation, Oreoluwa O. Adedoyin

Theses and Dissertations--Pharmacy

Abdominal aortic aneurysm (AAA) is a disease of the aorta characterized by pathological remodeling and progressive weakening of the vessel resulting in the increased risk of rupture and sudden death. In a mouse model of the disease induced by chronic Angiotensin II (AngII) infusion, progression of AAAs is associated with reduced differentiation of smooth muscle cells (SMCs) at the site of lesion development. In the mouse model, the effectiveness of cyclooxygenase-2 (COX-2) inhibition for attenuating AAA progression is associated with maintenance of a differentiated SMC phenotype. However, the safety of COX-2 inhibitors is currently in question due to the increased …

Flavonoids With Novel Nicotinic Activity As Potential Pharmacotherapies To Treat Ethanol-Induced Neurotoxicity, Joseph A. Lutz

Theses and Dissertations--Pharmacy

Ethanol causes neurotoxicity via several mechanisms at different points in the cycle of dependence, including neuroinflammation and oxidative stress during ethanol exposure as well as excitotoxicity during ethanol withdrawal. The primary therapeutic implication is that ethanol-induced neurotoxicity requires multifunctional pharmacotherapies which reduce all mechanisms. Using an innovative pharmacological high throughput screening method on a large plant extract library we discovered flavonoids with alpha7 nicotinic acetylcholine receptor (nAChR) activity. In addition to their well-known anti-inflammatory and antioxidant properties, this novel activity means they can potentially reduce excitotoxicity and therefore makes them ideal for inhibition of ethanol-induced neurotoxicity. Rhamnetin, the candidate compound, …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

Development Of Industry Oriented Cfd Code For Analysis / Design Of Face Ventilation Systems, Todor P. Petrov

Theses and Dissertations--Mining Engineering

Two of the main safety and health issues recognized during deep cut coal mining are methane and dust hazards. Advances in continuous miner technology have improved safety and productivity. However, these advances have created some environmental problems, notably more dust and methane being generated at the face during coal extraction.

Results of studies performed in the last three decades concerning the face ventilation for deep cut mining showed very complicated airflow behavior. The specifics of flow patterns developed by the face ventilation systems presents significant challenge for analytical description even for equipment-free entry. Fortunately, there are methods, such as numerical …

Computational Investigation Of Injectable Treatment Strategies For Myocardial Infarction, Hua Wang

Theses and Dissertations--Mechanical and Aerospace Engineering

Heart failure is an important medical disease and impacts millions of people throughout the world. In order to treat this problem, biomaterial injectable treatment injected into the myocardium of the failing LV are currently being developed. Through this treatment, the biomaterial material injections can reduce wall stresses during the cardiac remodeling process. By using computational techniques to analyze the effects of a treatment involving the injection of biomaterial material into the LV after MI, the material parameters of the hydrogel injections can be optimized. The results shows that the hydrogel injections could reduce the global average fiber stress and the …

Finite Element Modeling And Fabrication Of An Sma-Smp Shape Memory Composite Actuator, Mohammad Souri

Theses and Dissertations--Mechanical and Aerospace Engineering

Shape memory alloys and polymers have been extensively researched recently because of their unique ability to recover large deformations. Shape memory polymers (SMPs) are able to recover large deformations compared to shape memory alloys (SMAs), although SMAs have higher strength and are able to generate more stress during recovery.

This project focuses on procedure for fabrication and Finite Element Modeling (FEM) of a shape memory composite actuator. First, SMP was characterized to reveal its mechanical properties. Specifically, glass transition temperature, the effects of temperature and strain rate on compressive response and recovery properties of shape memory polymer were studied. Then, …

Estimating Passive Material Properties And Fiber Orientation In A Myocardial Infarction Through An Optimization Scheme Using Mri And Fe Simulation, Dimitri Mojsejenko

Theses and Dissertations--Mechanical and Aerospace Engineering

Myocardial infarctions induce a maladaptive ventricular remodeling process that independently contributes to heart failure. In order to develop effective treatments, it is necessary to understand the way and extent to which the heart undergoes remodeling over the course of healing. There have been few studies to produce any data on the in-vivo material properties of infarcts, and much less on the properties over the time course of healing. In this paper, the in-vivo passive material properties of an infarcted porcine model were estimated through a combined use of magnetic resonance imaging, catheterization, finite element modeling, and a genetic algorithm optimization …