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C-Abl And Arg Drive Cancer Chemoresistance Via Activation Of Multiple Signaling Pathways, Jonathan Thomas Sims

Theses and Dissertations--Pharmacology and Nutritional Sciences

Despite 35 years of clinical trials, there has been little improvement in one-year survival rates with any chemotherapeutic regimen for the treatment of metastatic melanoma due to resistance to all known agents. Regardless of advances in detection and prevention, diagnosis of metastatic disease remains a death sentence. Resistance mechanisms, including aberrant kinase signaling and drug transport pumps, indicate a need for identification of other therapeutic targets that impinge upon multiple signaling pathways. The Abl family of non-receptor tyrosine kinases (c-Abl, Arg) has been indicted as a causative force in leukemia for more than three decades; however, their role in solid …

Inflammatory Interactions And Secretion In Cardiac Remodeling, Fanmuyi Yang

Theses and Dissertations--Physiology

Heart failure contributes to nearly 60,000 deaths per year in the USA and is often caused by hypertension and preceded by the development of left ventricular hypertrophy (LVH). LVH is usually accompanied by intensive interstitial and perivascular fibrosis which may contribute to arrhythmogenic sudden cardiac death. Emerging evidence indicates that LV dysfunction in patients and animal models of cardiac hypertrophy is closely associated with perivascular inflammation.

To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of pressure-overload-induced LVH: transverse aortic constriction (TAC). Early perivascular inflammation …

Analysis Of Binary Data Via Spatial-Temporal Autologistic Regression Models, Zilong Wang

Theses and Dissertations--Statistics

Spatial-temporal autologistic models are useful models for binary data that are measured repeatedly over time on a spatial lattice. They can account for effects of potential covariates and spatial-temporal statistical dependence among the data. However, the traditional parametrization of spatial-temporal autologistic model presents difficulties in interpreting model parameters across varying levels of statistical dependence, where its non-negative autocovariates could bias the realizations toward 1. In order to achieve interpretable parameters, a centered spatial-temporal autologistic regression model has been developed. Two efficient statistical inference approaches, expectation-maximization pseudo-likelihood approach (EMPL) and Monte Carlo expectation-maximization likelihood approach (MCEML), have been proposed. Also, Bayesian …

The Relationship Of Social Stress, Economic Hardship, And Psychological Distress To Addiction Severity Among Kentucky Substance Abuse Treatment Participants, Elizabeth A. Wahler

Theses and Dissertations--Social Work

Stress is associated with poor mental health, specifically anxiety and depression, and stress and mental health problems are predictors of substance dependence and relapse. Social characteristics, such as racial/ethnic minority status, female gender, and low socioeconomic status, are often associated with increased psychological distress and substance use disorders. Pearlin’s social stress theory postulates that this association is due to increased exposure to stress and subsequent experiences of distress related to social disadvantage and decreased access to resources for coping with stress. This project uses a social stress theoretical perspective to examine predictors of substance use after treatment entry and follow-up …

Development Of Strategies To Minimize The Release Of Trace Elements From Coal Waste Sources, Mohammad Rezaee

Theses and Dissertations--Mining Engineering

To assess strategies aimed at minimizing the release of trace elements and the impact of disposal of coal waste materials on the environment, two long-term leaching experiments of up to five months duration were performed using waste materials from two plants cleaning high and low sulfur bituminous coal. The tests evaluated the mobility of major trace elements under different disposal scenarios: (i) a static leaching test designed to simulate the quiescent conditions encountered by coal waste material stored under water in a stable impoundment, and (ii) a dynamic test to simulate waste materials exposed to the atmosphere, either in variable …

Is Densified Biomass Fuel From Agro-Forestry Waste A Sustainable Energy Option?, William A. Linnig Iii

Theses and Dissertations--Mechanical and Aerospace Engineering

Raw biomass material is bulky, high in void fraction, and very low in transportation efficiency. Furthermore, biomass dissipates quickly in harsh environments of high heat furnaces because of its relatively low calorific value (BTU/lb) and has grinding or size degradation properties highly dissimilar from commonly-used fossil fuels like coal. Therefore, the development of transformational technologies are necessary to convert raw biomass into high-value and useful products of high hardness and calorific value without requiring excessive process energy.

This thesis investigates the sustainability of densified biomass fuels. In addition, a procedure that converts raw biomass from agro/forest industry waste into a …

Cryogenic Burnishing Of Co-Cr-Mo Biomedical Alloy For Enhanced Surface Integrity And Improved Wear Performance, Shu Yang

Theses and Dissertations--Mechanical and Aerospace Engineering

The functional performance of joint implants is largely determined by the surface layer properties in contact. Wear/debris-induced osteolysis and aseptic loosening has been identified as the major cause of failure of metal-on-metal joint implants. A crucial requirement for the long-term stability of the artificial joint is to minimize the release of debris particles.

Severe plastic deformation (SPD) processes have been used to modify the surface integrity properties by generating ultrafine, or even nano-sized grains and grain size gradients in the surface region of many materials. These fine grained materials often exhibit enhanced surface integrity properties and improved functional performance (wear …

Transport Phenomena Associated With Liquid Metal Flow Over Topographically Modified Surfaces, Wen Liu

Theses and Dissertations--Mechanical and Aerospace Engineering

Brazing and soldering, as advanced manufacturing processes, are of significant importance to industrial applications. It is widely accepted that joining by brazing or soldering is possible if a liquid metal wets the solids to be joined. Wetting, hence spreading and capillary action of liquid metal (often called filler) is of significant importance. Good wetting is required to distribute liquid metal over/between the substrate materials for a successful bonding.

Topographically altered surfaces have been used to exploit novel wetting phenomena and associated capillary actions, such as imbibitions (a penetration of a liquid front over/through a rough, patterned surface). Modification of surface …

Aerodynamics And Control Of A Deployable Wing Uav For Autonomous Flight, Michael Thamann

Theses and Dissertations--Mechanical and Aerospace Engineering

UAV development and usage has increased dramatically in the last 15 years. In this time frame the potential has been realized for deployable UAVs to the extent that a new class of UAV was defined for these systems. Inflatable wing UAVs provide a unique solution for deployable UAVs because they are highly packable (some collapsing to 5-10% of their deployed volume) and have the potential for the incorporation of wing shaping. In this thesis, aerodynamic coefficients and aileron effectiveness were derived from the equations of motion of aircraft as necessary parameters for autonomous flight. A wind tunnel experiment was performed …

From Celluloid Realities To Binary Dreamscapes: Cinema And Perceptual Experience In The Age Of Digital Immersion, Edwin Lloyd Mcguy Lohmeyer

Theses and Dissertations--Art and Visual Studies

Technologies in digital cinema are quickly changing the way contemporary filmmakers create films and how audiences currently perceive them. As we move onward into the digital turn, it becomes ever more apparent that the medium of film has been emancipated from its dependence on the photograph. Directors are no longer required to capture the objectively real as it sits before the photographic lens, but can essentially construct it via groundbreaking advancements in computer-generated imagery, motion capture technology, and digital 3D camera systems and display technologies. Since the origins of film, spectators and filmmakers have assumed an existing relationship between reality …

Applying Specific Arts Activities To Improve The Quality Of Life For Individuals With Alzheimer’S Disease And Dementia, Ann Christianson Tietyen

Theses and Dissertations--Art and Visual Studies

This study examined the effectiveness of a combination of seven different visual art activities, hat decoration, collage, embossing, painting, ceramics, photography, and printmaking, on quality of life for eight veterans with Alzheimer’s disease and dementia. The eight veterans were selected from the population of residents at the Thomson‐ Hood Veterans facility in Wilmore, Kentucky. These veterans were administered the seven art activities mentioned above, which ranged from less difficult to increasing difficulty. Three standard self‐reporting instruments, the Quality of Life‐AD, the Rosenberg Self‐Esteem Scale, and the Smiley‐Face Mood Assessment, as well as systematic observation and surveys were used to explore …

Medically Ill Smokers And Planning To Quit, Audrey Darville

Theses and Dissertations--Nursing

Cigarette smoking is the leading cause of preventable disease and is the cause of nearly 1 in 5 deaths in the United States. The prevalence of smoking has had a leveling off effect after many years of significant decline. Certain subgroups of the population, such as those with low income and certain illnesses, continue to smoke at disproportionately high rates. Reasons for these disparities in smoking rates are complex. Developing a better understanding of the issues related to persistent smoking particularly for those with medical illness and limited access to cessation resources can help focus interventions to help these high …

Discovery Of Gz-793a, A Novel Vmat2 Inhibitor And Potential Pharmacotherapy For Methamphetamine Abuse, David B. Horton

Theses and Dissertations--Pharmacy

Methamphetamine abuse is a serious public health concern affecting millions of people worldwide, and there are currently no viable pharmacotherapies to treat methamphetamine abuse. Methamphetamine increases extracellular dopamine (DA) concentrations through an interaction with the DA transporter (DAT) and the vesicular monoamine transporter-2 (VMAT2), leading to reward and abuse. While numerous studies have focused on DAT as a target for the discovery of pharmacotherapies to treat psychostimulant abuse, these efforts have been met with limited success. Taking into account the fact that methamphetamine interacts with VMAT2 to increase DA extracellular concentrations; the focus of the current work was to develop …

Molecular Mechanisms Of Thromboxane A2 Receptor-Mediated Invasion In Lung Cancer Cells, Xiuling Li

Theses and Dissertations--Pharmacy

Thromboxane A2 receptor (TP) has been shown to play important roles in multiple aspects of cancer development including regulation of tumor growth, survival and metastasis. Molecular mechanisms of TP mediated cancer cell invasion remain to be identified. TP agonist, I-BOP, significantly elevated several matrix metalloproteinases (MMPs) including MMP-1, MMP-3, MMP-9 and MMP-10 in A549 human lung adenocarcinoma cells overexpressing TPα (A549-TPα) or TPβ (A549-TPβ). Signaling pathways of I-BOP-induced MMP-1 expression were examined in further detail as a model system for MMPs induction. Signaling molecules involved in I-BOP-induced MMP-1 expression were identified by using specific inhibitors including small interfering (si)-RNAs of …

Localization And Functional Characterization Of Oatp4c1 Transporter In In Vitro Cell Systems And Human/Rat Tissues, Kuei-Ling Kuo

Theses and Dissertations--Pharmacy

The organic anion transporting polypeptide 4c1 (Oatp4c1) was previously identified as a novel uptake transporter predominantly expressed at the basolateral membrane in the rat kidney proximal tubules. Its functional role was suggested to be a vectorial transport partner of an apically-expressed efflux transporter for the efficient translocation of physiological substrates into urine, some of which were suggested to be uremic toxins. In vitro studies in polarized cell lines showed that upon transfection rat Oatp4c1 localizes at the apical membrane. The objectives of this project were to further validate the subcellular localization of Oatp4c1/OATP4C1 in rat and human tissues as well …

Influence Of Oncotype Dx® On Chemotherapy Prescribing In Early Stage Breast Cancer Patients: A Claims-Based Evaluation Of Utilization In The Real World, Kenneth Neil Kennedy

Theses and Dissertations--Pharmacy

The decision for adjuvant therapy in women with early stage breast cancer (ESBC) has historically been guided by the presence or absence of specific biological markers (hormone and HER2 receptors), age, and extent of nodal involvement. Oncotype DX® is a validated assay that quantifies protein expression that can predict the risk of cancer recurrence. This study evaluates if the use of Oncotype DX® impacts chemotherapy prescribing in ESBC. This retrospective, cohort study identified patients with ESBC from a large commercially insured population from January 2007 through June 2009. Patients were identified as having ESBC by utilizing procedure and diagnosis codes …

Nanocrystals Of Chemotherapeutic Agents For Cancer Theranostics: Development And In Vitro And In Vivo Evaluation, Christin P. Hollis

Theses and Dissertations--Pharmacy

The majority of pharmacologically active chemotherapeutics are poorly water soluble. Solubilization enhancement by the utilization of organic solvents often leads to adverse side effects. Nanoparticle-based cancer therapy, which is passively targeted to the tumor tissue via the enhanced permeation and retention effect, has been vastly developed in recent years. Nanocrystals, which exist as crystalline and carry nearly 100% drug loading, has been explored for delivering antineoplastic agents. Additionally, the hybrid nanocrystal concept offers a novel and simple way to integrate imaging agents into the drug crystals, enabling the achievement of theranostics. The overall objective of this dissertation is to formulate …

Role Of Cyclooxygenase-2 In Abdominal Aortic Aneurysms In Mice, Kamalika Mukherjee

Theses and Dissertations--Pharmacy

Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease with no available pharmacological treatment. AAA formation reduces the structural integrity of the vessel and increases the susceptibility to rupture. The inflammatory response within human aneurysmal tissue is characterized by increased expression of cyclooxygenase-2 (COX-2). Similarly, in a mouse model of the disease induced by chronic Angiotensin II (AngII) infusion, we have shown that COX-2 expression in the abdominal aortic smooth muscle layer increases early in the development of the disease. Furthermore, genetic or pharmacological inactivation of COX-2 prior to disease initiation reduces AAA incidence.

The current study utilized nonhyperlipidemic mice …

Glycerolipids And The Plant Cuticle Contribute To Plant Immunity, Qing-Ming Gao

Theses and Dissertations--Plant Pathology

The conserved metabolites, oleic acid (18:1), a major monounsaturated fatty acid (FA), and glycerol-3-phosphate (G3P) are obligatory precursors of glycerolipid biosynthesis in plants. In Arabidopsis, the SSI2-encoded SACPD is the major isoform that contributes to 18:1 biosynthesis. Signaling induced upon reduction in oleic acid (18:1) levels not only upregulates salicylic acid (SA)-mediated responses but also inhibits jasmonic acid (JA)- inducible defenses. I examined the transcription profile of ssi2 plants and identified two transcription factors, WRKY50 and WRKY51. Although the ssi2 wrky50 and ssi2 wrky51 plants were constitutively upregulated in SA-derived signaling, they were restored in JAdependent defense signaling. Not only …

Modeling Movement Behavior And Road Crossing In The Black Bear Of South Central Florida, Joseph Maddox Guthrie

Theses and Dissertations--Forestry and Natural Resources

We evaluated the influence of a landscape dominated by agriculture and an extensive road network on fine-scale movements of black bears (Ursus americanus) in south-central Florida. The objectives of this study were to (1) define landscape functionality including corridor use by the directionality and speed of bear movements, (2) to develop a model reflecting selected habitat characteristics during movements, (3) to identify habitat characteristics selected by bears at road-crossing locations, and (3) to develop and evaluate a predictive model for road-crossing locations based on habitat characteristics. We assessed models using GPS data from 20 adult black bears (9 …

Ingestion Of Endophyte-Infected Tall Fescue Seed Induces Peripheral Vasoconstriction But Does Not Affect Cyclicity In Non-Pregnant Mares, And A Population Of Biogenic Amine Receptors Relative To Vasoconstriction Is Identified, Daniel Andrew Hestad

Theses and Dissertations--Veterinary Science

Three experiments were conducted to explore the effect of fescue toxicosis on vasoconstriction and various parameters of the estrous cycle. In the experiment of Chapter 3, a 2x2 crossover experimental design with repeated measures was implemented to test whether the ingestion of endophyte-infected tall fescue seed would alter blood hormone concentrations of prolactin, progesterone, and estradiol, interovulatory intervals, and corpus luteum blood flow. Also, Doppler ultrasonography was used to assess whether palmar artery and palmar vein lumen diameter, area, circumference, and resistivity index could be altered by the ingestion of endophyte-infected tall fescue seed. Ingestion of endophyte-infected tall fescue seed …

The Transmission Dynamics Of Equine Herpesvirus Type 1 (Ehv-1) Infection In Outbreaks Characterized Predominately By Neurologic Or Respiratory Illness, Barry Jay Meade

Theses and Dissertations--Veterinary Science

Formalized epidemiological field investigations were conducted to compare and contrast the transmission dynamics of EHV-1 neurological disease among horses stabled at Churchill Downs Racetrack, Louisville, Kentucky and of EHV-1 respiratory illness among horses stabled in the student barn at Murray State University. Differences were assessed by means of statistical and mathematical modeling techniques applied to survey and biological data collected over the course of the respective disease events.

Regression methods applied to survey data enabled the construction of a statistical model to predict a date of onset of illness for horses within each equine cohort. Comparisons of the epidemic curves …

Breeding Induced Endometritis In The Mare: The Local Innate Immune Response, Elizabeth Moran Woodward

Theses and Dissertations--Veterinary Science

Uterine inflammation after breeding is considered necessary for the clearance of excess semen and debris from the uterus. A subpopulation of mares fails to clear the inflammation in a timely fashion, and develops a persistent breeding induced endometritis (PBIE). Experiments were preformed to evaluate correlations of PBIE to endometrial quality and age. Mares of advanced age and poor endometrial quality had a higher incidence of PBIE. In addition, mares fluctuated in susceptibility to PBIE from one season to the next. The uterine inflammatory gene expression in susceptible and resistant mares within the first 24 hours after breeding was investigated. The …

Development Of Molecular Diagnostic Assays For Equine Respiratory Viruses And Analysis Of The Role Of Equine Arteritis Virus Envelope Proteins In The Early Events Of Virus Entry, Zhengchun Lu

Theses and Dissertations--Veterinary Science

There is an urgent need for detection of viral respiratory pathogens to identify the causal agent(s) involved and to prevent the spread of related diseases. The first part of this dissertation focuses on development, optimization and validation of Real-time reverse transcription polymerase chain reaction (rRT-PCR) assays for the detection of several common equine viral pathogens: equine arteritis virus (EAV), equine influenza virus and equine rhinitis viruses A and B. Emphasis of the second part of this dissertation is on studying the role of EAV envelope proteins in virus attachment and entry. Using an infectious cDNA clone of EAV and reverse …

Effectiveness Of Elevated Skid Trail Headwater Stream Crossings In The Cumberland Plateau, Christopher D. Reeves

Theses and Dissertations--Forestry and Natural Resources

One of the primary concerns associated with timber harvesting is the production of sediments from stream crossings. While research has shown that using improved haul road crossings can mitigate sediment production in perennial streams compared to the use of unimproved crossings little research has been undertaken on temporary skidder crossings of headwater streams, a situation common to a significant percentage of ground skidding operations. This experiment consisted of a controlled replicated testing of the effectiveness of four types of temporary skidder stream crossings (unimproved ford, corrugated culvert, wood panel skidder bridge, and PVC pipe bundle) relative to bedload and suspended …

Rhodococcus Equi Infection And Interferon-Gamma Regulation In Foals, Lingshuang Sun

Theses and Dissertations--Veterinary Science

Rhodococcus equi (R. equi) is one of the most serious causes of pneumonia in young foals. The clinical disease is of great concern to breeding farms worldwide due to the impact of mortality on economic losses. While adult horses are resistant to R. equi, foals exhibit a distinct age-associated susceptibility. The mechanism underlying this susceptibility in foals is not well understood. Interferon-gamma (IFNg) plays an important role in the clearance of R. equi, but its expression is impaired in neonatal foals. Moreover, the regulation of this age-related IFNg expression in foals remains unknown. In humans, IFNg …

A Comparison Of Noninvasive Survey Methods For Monitoring Mesocarnivore Populations In Kentucky, Bryan Matthew Tom

Theses and Dissertations--Forestry and Natural Resources

Harvest data are typically used to evaluate mesocarnivore population dynamics in many states, including Kentucky. While relatively easy to collect, these data are subject to reporting biases, and inferences about population trends can often only be made at coarse spatial scales. Gray fox (Urocyon cinereoargenteus), bobcat (Lynx rufus), and coyote (Canis latrans) populations in Kentucky are managed primarily through harvest data used to establish future harvest quotas. Increasingly, noninvasive survey methods have been used to characterize a number of population parameters for a variety of species; however, successful use of these methods is often …

Control And Passive Treatment Of Runoff From Horse Muck Storage Structures Using Rain Gardens, Hillary K. Otte

Theses and Dissertations--Forestry and Natural Resources

Runoff from livestock operations may contain a variety of pathogens and high levels of nutrients and other harmful contaminants, and is of particular concern in central Kentucky as watersheds are threatened by waste generated from a high concentration of equine activity. Rain gardens are a type of stormwater management tool used to capture and passively treat runoff. This project aimed to incorporate rain gardens into the horse muck storage structures at a thoroughbred facility in the Canr Run watershed in Lexington, Kentucky. Water quality data from soil water within two rain garden muck pads and two control pads, and grab …

Glycerol-3-Phosphate Is A Novel Regulator Of Basal And Induced Defense Signaling In Plants, Bidisha Chanda

Theses and Dissertations--Plant Pathology

Plants use several strategies to defend themselves against microbial pathogens. These include basal resistance, which is induced in response to pathogen encoded effector proteins, and resistance (R) protein-mediated resistance that is activated upon direct or indirect recognition of pathogen encoded avirulence protein(s). The activation of Rmediated signaling is often associated with generation of a signal, which, upon its translocation to the distal uninfected parts, confers broad-spectrum immunity against related or unrelated pathogens. This phenomenon known as systemic acquired resistance (SAR) is one of the well-established forms of induced defense response. However, the molecular mechanism underlying SAR remains largely unknown. Induction …

Effects Of Methoprene On The Survivorship Of Adult Aedes Mosquitoes: A Strategy Or Inactivating Released Mosquitoes, Peter J. Brabant Iii

Theses and Dissertations--Entomology

Methoprene is a Juvenile Hormone (JH) analogue commonly used for the control of mosquito larvae. When applied to a mosquito breeding site, methoprene enters the haemolymph, where it mimics the function of JH and interferes with normal metamorphosis, resulting in larval mortality. Methoprene is commonly used for the control of larvae and has not been used as an adulticide, due to an absence of acute effects. This study evaluated possible chronic effects caused by the exposure of adult Aedes mosquitoes to methoprene. Methoprene was applied, in both technical grade and the commercially available Altosid®, topically to adults through droplet application …