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Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

Essays On Child Well-Being And The Social Safety Net, Cody N. Vaughn

Theses and Dissertations--Economics

This dissertation consists of three essays examining the role of two particular social safety net programs, the Temporary Assistance for Needy Families (TANF) program and the Supplemental Nutrition Assistance Program (SNAP), on the well-being of children from disadvantaged households. While the impact of these programs on the adults and parents of the household have been studied extensively, less is known about their effect on children. This is true for both their immediate impact on child well-being and any long-run impacts on children who grow up under these programs. Given the demonstrated importance of child well-being on later life adult outcomes, …

Unsupervised Learning In Phylogenomic Analysis Over The Space Of Phylogenetic Trees, Qiwen Kang

Theses and Dissertations--Statistics

A phylogenetic tree is a tree to represent an evolutionary history between species or other entities. Phylogenomics is a new field intersecting phylogenetics and genomics and it is well-known that we need statistical learning methods to handle and analyze a large amount of data which can be generated relatively cheaply with new technologies. Based on the existing Markov models, we introduce a new method, CURatio, to identify outliers in a given gene data set. This method, intrinsically an unsupervised method, can find outliers from thousands or even more genes. This ability to analyze large amounts of genes (even with missing …

Depressive Symptoms Among Farm Women Aged 50 And Older, Cheryl Dean Witt

Theses and Dissertations--Nursing

Alarming rates of suicide among production farmers have prompted researchers to investigate factors associated with depressive symptoms among this population. Aspects of farm life and farming can contribute to higher levels of depressive symptoms. Higher levels of depression can also increase an individual’s risk of injury and development of chronic disease, impacting overall quality of life. Despite the approximate 3.5 million farm women in the U.S., current research has focused on the male farmer.

Men and women have different responses to stressors, and women in general have a higher prevalence of depressive symptoms. Farm women can be further subjected to …

Neurochemical Factors Associated With The Initial Pathophysiological Reaction To Large Vessel Occlusion Stroke, Sarah R. Martha

Theses and Dissertations--Nursing

Ischemic stroke is the leading cause of disability world-wide and affects over 800,000 people per year in the United States. The majority of these strokes are ischemic due to a blockage of blood flow to the brain. Damage to the brain occurs at the onset of stroke, neuronal cell death is irreversible and therefore, quick treatment to remove blockage is critical factor in the recovery from stroke. Mechanical thrombectomy as a treatment for ischemic stroke provides an ideal opportunity to collect blood distal and proximal to the cerebral thrombus to examine neurochemical changes occurring during stroke.

The purpose of this …

Frailty In Patients Undergoing Left Ventricular Assist Device Implantation, Candice Falls

Theses and Dissertations--Nursing

Heart failure is a progressive condition that affects over 5.7 million Americans and costs associated with heart failure account for 2-3 % of the national health care budget. The high rates of morbidity and mortality along with increased costs from readmissions associated with advanced heart failure have led to the exploration of advanced treatments such as left ventricular assist devices (LVADs). LVADS have demonstrated morbidity and mortality benefit but cost remains extensive with costs per quality-adjusted years > $400,000. With this in mind, it is important to identify those who are most likely to benefit from an LVAD to avoid unfavorable …

The Impact Of Maternal Nutrition During Pregnancy On Inflammation And Birth Outcomes, Lori Ogden

Theses and Dissertations--Nursing

More than 85% of American adults do not consume recommended amounts of fruits or vegetables. Preterm birth and hypertensive disorders of pregnancy are common adverse conditions affecting pregnancy and are leading causes of maternal and fetal morbidity and mortality. Preterm birth affects nearly 10% of all births in the United States and is on the rise, as are hypertensive disorders, which have increased by 25% over the last two decades. Pregnancy is a state of controlled inflammation, and dysregulation has been linked to preterm birth and other adverse gestational outcomes. A healthy diet is recommended in pregnancy, but little is …

Actinomycin Familial Diversity Driven By Phenoxazinone-Core Reactivity, Matthew Richard Mcerlean

Theses and Dissertations--Pharmacy

Actinomycins are a class of compounds consisting of phenoxazinone-like core attached to two peptidolactone rings, denoted as α and β. A unique component of a few families—actinomycins G, Y, and Z—is a chlorinated β-ring threonine residue. Families G and Y also contained an actinomycin that possess a β-ring heterocycle (actinomycins G₅ and Y₅, respectively); prior to this work, no β-ring heterocycle-containing actinomycins were reported for the Z family. Unlike other actinomycin derivatives, Y₅’s cytotoxicity was abolished while still maintaining some antibacterial potency.

We constructed a model compound to probe the physical properties of the actinomycin …

Developing A Workflow To Evaluate Medications For Repurposing Using Health Claims Data: Application To Substance Use Disorders, Emily Ruth Hankosky

Theses and Dissertations--Pharmacy

Healthcare big data are a growing source of real-world data with which to identify and validate medications with repurposing potential. Previously, we developed a claims-based workflow to evaluate medications with potential to treat stimulant use disorders. In order to test the workflow, the framework was applied in the context of opioid use disorders (OUDs), for which there are medications with known efficacy. Using the Truven Marketscan Commercial Claims Database, a nested case-control analysis was conducted to determine the association between OUD medications (buprenorphine, naltrexone) and remission. Cases were defined as enrollees with a remission diagnosis and matched (1:4) to controls …

Phase Behavior Of Amorphous Solid Dispersions: Miscibility And Molecular Interactions, Kanika Sarpal

Theses and Dissertations--Pharmacy

Over the past few decades, amorphous solid dispersions (ASDs) have been of great interest to pharmaceutical scientists to address bioavailability issues associated with poorly water-soluble drugs. ASDs consist of an active pharmaceutical ingredient (API) that is typically dispersed in an inert polymeric matrix. Despite promising advantages, a major concern that has resulted in limited marketed formulations is the physical instability of these complex formulations. Physical instability is often manifested as phase heterogeneity, where the drug and carrier migrate and generate distinct phases, which can be a prelude to recrystallization. One important factor that dictates the physical stability of ASDs is …

Therapeutic Video Games And The Simulation Of Executive Function Deficits In Adhd, Markus Tiitto

Theses and Dissertations--Pharmacy

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by difficulty paying attention, impulsivity, and hyperactivity. Diagnosis of ADHD rose 42% from 2003–2004 to 2011–2012. In 2011, 3.5 million children were treated with drugs. Optimizing therapy can take a year, and may not be completely effective.

A clinical trial is currently being conducted of a device/drug combination using the computer game Minecraft, to determine how certain activities affect executive function, working memory, and restraint in patients diagnosed with ADHD. The human subjects’ responses are being modeled using artificial neural networks (ANNs), an artificial intelligence method that can be utilized …

Pharmacokinetic And Pharmacodynamic Evaluation Of Cocaine Hydrolases For The Treatment Of Cocaine Overdose And Cocaine Addiction Using Rodent Models, Xirong Zheng

Theses and Dissertations--Pharmacy

Overdose and addiction are two medical complications of cocaine abuse. To date, there is no FDA approved pharmacotherapy specific for cocaine abuse. Cocaine hydrolases (CocHs) have been extensively investigated for its potential in anti-cocaine therapy. Previous studies have demonstrated that CocHs efficiently hydrolyze cocaine to generate biologically inactive metabolites both in vivo and in vitro. However, it has not been studied whether there is gender difference in the therapy using CocHs. In addition, the effectiveness of CocHs is unknown for treating cocaine toxicity when alcohol is co-administered.

The main purpose of this dissertation is to characterize and evaluate efficient …

Mechanisms And Thermodynamics Of The Influence Of Solution-State Interactions Between Hpmc And Surfactants On Mixed Adsorption Onto Model Nanoparticles, Salin Gupta Patel

Theses and Dissertations--Pharmacy

Nanoparticulate drug delivery systems (NDDS) such as nanocrystals, nanosuspensions, solid-lipid nanoparticles often formulated for the bioavailability enhancement of poorly soluble drug candidates are stabilized by a mixture of excipients including surfactants and polymers. Most literature studies have focused on the interaction of excipients with the NDDS surfaces while ignoring the interaction of excipients in solution and the extent to which the solution-state interactions influence the affinity and capacity of adsorption. Mechanisms by which excipients stabilize NDDS and how this information can be utilized by formulators a priori to make a rational selection of excipients is not known.

The goals of …

Development Of Mithramycin Analogues With Improved Efficacy And Reduced Toxicity For Treatment Of Ets-Dependent Tumors In Ewing Sarcoma And Prostate Cancer, Joseph Michael Eckenrode

Theses and Dissertations--Pharmacy

Introduction: Genetic rearrangements in Ewing sarcoma, prostate, and leukemia cells result in activation of oncogenic ETS transcription factor fusions. Mithramycin (MTM) has been identified as an inhibitor of EWS-FLI1 transcription factor, a gene fusion product responsible for oncogenesis in Ewing sarcoma. Despite preclinical success, a phase I/II clinical trial testing MTM therapy in refractory Ewing sarcoma was terminated. Liver and blood toxicities resulted in dose de-escalation and sub-therapeutic exposures. However, the promise of selectively targeting oncogenic ETS transcription factors like EWS-FLI1 prompted us to undertake the discovery of more selective, less toxic analogues of MTM. MTM is a potent inhibitor …

Computational Modeling Guided Discovery Of Novel Inhibitors Of Mpges-1 And Butyrylcholinesterase As Drug Candidates, Shuo Zhou

Theses and Dissertations--Pharmacy

Ever since the advent of computer-aided drug design (CADD), in silico simulation methods have greatly accelerated the drug discovery process and lead to the discovery of numerous drug candidates. With the exponential growth of computational power, we nowadays simulate biologic systems at a scale unimaginable a decade ago and thus provides perspectives for drug design. In this dissertation research, combining in silico simulation methods like molecular docking and molecular dynamics (MD) simulation with organic synthesis, in vitro/in vivo experiments and clinical data mining, we developed new drug discovery strategies. These strategies were applied in our drug discovery projects and led …

Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber

Theses and Dissertations--Pharmacy

Methyl group transfer from S-adenosyl-l-methionine (AdoMet) to various substrates including DNA, proteins, and natural products (NPs), is accomplished by methyltransferases (MTs). Analogs of AdoMet, bearing an alternative S-alkyl group can be exploited, in the context of an array of wild-type MT-catalyzed reactions, to differentially alkylate DNA, proteins, and NPs. This technology provides a means to elucidate MT targets by the MT-mediated installation of chemoselective handles from AdoMet analogs to biologically relevant molecules and affords researchers a fresh route to diversify NP scaffolds by permitting the differential alkylation of chemical sites vulnerable to NP MTs that are unreactive to …

Investigation Of Factors Influencing Protein Stability In Lyophilized Formulations Using Solid-State Nmr Spectroscopy, Ashley Lay-Fortenbery

Theses and Dissertations--Pharmacy

Many proteins are unstable in solution and must be formulated in the solid state. This has led to an increase in the use of lyophilized dosage forms. Lyophilization is a complicated processing method consisting of three major steps: freezing, primary drying, and secondary drying. This can lead to several formulation stability challenges including changes in ionization within the matrix, phase separation of the protein drug from added stabilizers, sufficient mobility within the system for movement of reactive species and protein side chains, and crystallization of excipients upon storage. Solid-State Nuclear Magnetic Resonance Spectroscopy (SSNMR) is used to characterize many important …

Transforming A Circular Economy Into A Helical Economy For Advancing Sustainable Manufacturing, Ryan T. Bradley

Theses and Dissertations--Mechanical and Aerospace Engineering

The U.N. projects the world population to reach nearly 10 billion people by 2050, which will cause demand for manufactured goods to reach unforeseen levels. In order for us to produce the goods to support an equitable future, the methods in which we manufacture those goods must radically change. The emerging Circular Economy (CE) concept for production systems has promised to drastically increase economic/business value by significantly reducing the world’s resource consumption and negative environmental impacts. However, CE is inherently limited because of its emphasis on recycling and reuse of materials. CE does not address the holistic changes needed across …

Quantification Of Papillary Muscle Motion And Mitral Regurgitation After Myocardial Infarction, Connor R. Ferguson

Theses and Dissertations--Mechanical and Aerospace Engineering

Change in papillary muscle motion as a result of left ventricular (LV) remodeling after posterolateral myocardial infarction is thought to contribute to ischemic mitral regurgitation. A finite element (FE) model of the LV was created from magnetic resonance images acquired immediately before myocardial infarction and 8 weeks later in a cohort of 12 sheep. Severity of mitral regurgitation was rated by two-dimensional echocardiography and regurgitant volume was estimated using MRI. Of the cohort, 6 animals (DC) received hydrogel injection therapy shown to limit ventricular remodeling after myocardial infarction while the control group (MI) received a similar pattern of saline injections. …

A Computational Study Of Patch Implantation And Mitral Valve Mechanics, Dara Singh

Theses and Dissertations--Mechanical and Aerospace Engineering

Myocardial infarction (i.e., a heart attack) is the most common heart disease in the United States. Mitral valve regurgitation, or the backflow of blood into the atrium from the left ventricle, is one of the complications associated with myocardial infarction. In this dissertation, a validated model of a sheep heart that has suffered myocardial infarction has been employed to study mitral valve regurgitation. The model was rebuilt with the knowledge of geometrical changes captured with MRI technique and is assigned with anisotropic, inhomogeneous, nearly incompressible and highly non-linear material properties. Patch augmentation was performed on its anterior leaflet, using a …

The Effects Of System Characteristics, Reference Command, And Command-Following Objectives On Human-In-The-Loop Control Behavior, Seyyedalireza Seyyedmousavi

Theses and Dissertations--Mechanical and Aerospace Engineering

Humans learn to interact with many complex physical systems. For example, humans learn to fly aircraft, operate drones, and drive automobiles. We present results from human-in-the-loop (HITL) experiments, where human subjects interact with dynamic systems while performing command-following tasks multiple times over a one-week period. We use a new subsystem identification (SSID) algorithm to estimate the control strategies (feedforward, feedforward delay, feedback, and feedback delay) that human subjects use during their trials. We use experimental and SSID results to examine the effects of system characteristics (e.g., system zeros, relative degree, system order, phase lag, time delay), reference command, and command-following …

Single-Degree-Of-Freedom Experiments Demonstrating Electromagnetic Formation Flying For Small Satellite Swarms Using Piecewise-Sinusoidal Controls, Ajin Sunny

Theses and Dissertations--Mechanical and Aerospace Engineering

This thesis presents a decentralized electromagnetic formation flying (EMFF) control method using frequency-multiplexed sinusoidal control signals. We demonstrate the EMFF control approach in open-loop and closed-loop control experiments using a single-degree-of-freedom testbed with an electromagnetic actuation system (EAS). The EAS sense the relative position and velocity between satellites and implement a frequency-multiplexed sinusoidal control signal. We use a laser-rangefinder device to capture the relative position and an ARM-based microcontroller to implement the closed-loop control algorithm. We custom-design and build the EAS that implements the formation control in one dimension. The experimental results in this thesis demonstrate the feasibility of the …

Design Process For The Containment And Manipulation Of Liquids In Microgravity, Chris Meek

Theses and Dissertations--Mechanical and Aerospace Engineering

In order to enhance accessibility to microgravity research, the design process for experiments on the ISS must be streamlined and accessible to all scientific disciplines, not just aerospace engineers. Thus, a general design and analysis toolbox with accompanying best practices manual for microgravity liquid containment is proposed. The work presented in this thesis improves the design process by introducing a modular liquid tank design which can be filled, drained, or act as a passive liquid-gas separation device. It can also be pressurized, and used for aerosol spray. This tank can be modified to meet the design requirements of various experimental …

Photography, Visual Culture, And The (Re)Definition/Queering Of The Male Gaze, David Nicholas Martin

Theses and Dissertations--Art and Visual Studies

The traditional notion of the Male Gaze, first conceptualized by feminist film critic Laura Mulvey in 1975, focused on the objectification of women through depictions structured to gratify a male heterosexual perspective. In this chapter we will revisit this concept and investigate how that gaze may have shifted away from a primarily heterosexual perspective to a socially dominant male perspective (maleness here referring to dominance rather than specific gender, just as “whiteness” might refer to privilege rather than race). With gender roles in an increasingly global and mobile society becoming more fluid and complex, opening up visibility to LGBTQ communities, …

Changes In Muscle Size, Quality And Power Are Related To Physical Function In Patients With Critical Illness, Kirby Mayer

Theses and Dissertations--Rehabilitation Sciences

Patients admitted to intensive care unit (ICU) are known to develop significant impairments in physical function. Patients with critical illness suffer up to 30% reductions in muscle size within the first ten days of admission to the ICU. Muscle strength testing, Medical Research Council-sum score, is current gold-standard to diagnosis ICU-acquired weakness and predicts risk of mortality and long-term physical function. Muscle power different from muscle strength in that it accounts for velocity of movement, is potentially a better independent predictor of function that has not been studied in this population. In addition, we hypothesize that muscle size and quality …

Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, Nika Larian

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death among critically ill patients that results in metabolic alterations including hypercatabolism, lipoatrophy, and muscle wasting, contributing to the development of cachexia. Septic cachexia is associated with loss of body weight, fat mass, and lean mass and dysregulated immune function. There are currently no efficacious treatment strategies for septic cachexia, and nutritional interventions have limited success in preventing hypercatabolic wasting. Pyocyanin is a virulence factor produced by sepsis-causing Pseudomonas aeruginosa that has been shown to activate the aryl hydrocarbon receptor (AhR), increase inflammation, and produce reactive oxygen species. Thus, pyocyanin represents a novel mechanistic …

The Role Of Endoplasmic Reticulum Stress In Ethanol-Induced Neurodegeneration, Yongchao Wang

Theses and Dissertations--Pharmacology and Nutritional Sciences

Heavy ethanol use causes neurodegeneration manifested by neuronal loss and dysfunction. It is becoming imperative to delineate the underlying mechanism to promote the treatment of ethanol-induced neurodegeneration. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases. This study aims to investigate the role of ER stress in ethanol-induced neurodegeneration. In experimental design, adult mice were exposed to binge ethanol drinking by daily gavage for 1, 5, or 10 days and the response of ER stress was examined. We found the induction of ER stress appeared at 5 days and remained at 10 days. Moreover, …

Effects Of A Systemic High Urea Concentration On The Endometrial And Embryonic Transcriptomes Of The Mare, Yatta Linhares Boakari

Theses and Dissertations--Veterinary Science

Pregnancy loss remains a major source of economic cost to the equine industry. Frequently, the exact causes of pregnancy loss remain unknown. It has been shown, in other species, that increased dietary protein leading to elevated blood urea nitrogen concentrations (BUN) can be a factor in decreased survival of the early embryo. Our studies provided novel information regarding the effects of elevated BUN on endometrium and embryos from mares as well as insights on changes in their gene expression. Our first objective was to develop an experimental model to elevate BUN during diestrus using intravenous urea infusion. We analyzed the …

Spatial And Temporal Patterns Of Invasive Exotic Plant Species In Response To Timber Harvesting In A Mixed Mesophytic Forest Of Eastern Kentucky, Benjamin Christopher Rasp

Theses and Dissertations--Forestry and Natural Resources

Invasive exotic species (IES) responses to silvicultural treatments eight years after timber harvesting were examined and compared to one-year post-harvest IES survey in University of Kentucky’s Robinson Forest. The temporal effects of harvesting were further compared between harvested and non-harvested watersheds. Analyses were performed to identify IES spatial distribution and determine the relationships between IES presence and disturbance effects, biological, and environmental characteristics. IES prevalence was higher in the harvested watersheds and was influenced by canopy cover, shrub cover and disturbance proximity. Ailanthus altissima and Microstegium vimineum presence in the study area has decreased over time. Comparing to the 1-yr …

A Gis Model For Apiary Site Selection Based On Proximity To Nectar Sources Utilized In Varietal Honey Production On Former Mine Sites In Appalachia, Douglass W. Potter

Theses and Dissertations--Forestry and Natural Resources

Beekeepers in Appalachia market varietal honeys derived from particular species of deciduous trees; however, finding places in a mountainous landscape to locate new beeyards is difficult. Site selection is hindered by the high up-front costs of negotiating access to remote areas with limited knowledge of the available forage. Remotely sensed data and species distribution modeling (SDM) of trees important to beekeepers could aid in locating apiary sites at the landscape scale. The objectives of this study are i) using publicly available forest inventory data, to model the spatial distribution of three native tree species that are important to honey producers …