Digital Commons Network^™

Near Wall Shear Stress Modification Using An Active Piezoelectric Nanowire Surface, Christopher R. Guskey

Theses and Dissertations--Mechanical and Aerospace Engineering

An experimental study was conducted to explore the possible application of dynamically actuated nanowires to effectively disturb the wall layer in fully developed, turbulent channel flow. Actuated nanowires have the potential to be used for the mixing and filtering of chemicals, enhancing convective heat transfer and reducing drag. The first experimental evidence is presented suggesting it is possible to manipulate and subsequently control turbulent flow structures with active nanowires. An array of rigid, ultra-long (40 μm) TiO₂ nanowires was fabricated and installed in the bounding wall of turbulent channel flow then oscillated using an attached piezoelectric actuator. Flow velocity …

Process-Induced Surface Integrity In Machining Of Niti Shape Memory Alloys, Yusuf Kaynak

Theses and Dissertations--Mechanical and Aerospace Engineering

NiTi alloys have been the focus of Shape Memory Alloys (SMA) research and applications due their excellent ductility and shape memory properties, and these alloys have been extensively used in automotive, aerospace, and in biomedical applications.

The effects of machining on the surface integrity and the corresponding material and mechanical properties of alloys can be best studied by utilizing NiTi alloys as workpiece material since their physical and mechanical properties are highly microstructure dependent. However, due to very poor machining performance of NiTi shape memory alloys, no comprehensive or systematic investigation on this topic has been conducted by researchers as …

Defining The Role Of Reactive Oxygen Species, Nitric Oxide, And Sphingolipid Signaling In Tumor Necrosis Factor - Induced Skeletal Muscle Weakness, Shawn Stasko

Theses and Dissertations--Physiology

In many chronic inflammatory diseases, patients suffer from skeletal muscle weakness, exacerbating their symptoms. Serum levels of tumor necrosis factor-alpha (TNF) and sphingomyelinase are increased, suggesting their possible role in the progression of this weakness. This dissertation focuses on the role that reactive oxygen species (ROS) and nitric oxide (NO) play in mediating TNF-induced skeletal muscle weakness and to what extent sphingolipid signaling mediates cellular response to TNF.

The first aim of this work was to identify which endogenous oxidant species stimulated by TNF contributes to skeletal muscle weakness. In C57BL/6 mice (n=38), intraperitoneal injection of TNF elicited a 25% …

Influence Of Coping Styles On Emotional State, Illness Perception, And Information Sources Of Men With Prostate Cancer, Gwendolyn M. Hooper

Theses and Dissertations--Nursing

Prostate cancer (PCa) has been the leading cause of cancer death in men since1930. While studies pertaining to PCa have primarily focused on the disease and the subsequent side effects of treatment, psychological distress in this group has yet to be adequately addressed. The purpose of this dissertation was to: 1) conceptualize health related quality of life (HRQL) and health seeking behavior of men by describing lifestyle, cultural and health risks associated with being male, 2) evaluate the psychometric properties of the SF-12 Health Survey (SF-12) combined with the urinary and sexual portions of the UCLA PCa Index (UCLA-PCI), 3) …

Diet-Induced Obesity: Dopaminergic And Behavioral Mechanisms As Outcomes And Predictors, Vidya Narayanaswami

Theses and Dissertations--Pharmacy

Obesity and drug abuse share common neural circuitries including the mesocoticolimbic and striatal dopamine reward system. In the current study, a rat model of diet-induced obesity (DIO) was used to determine striatal dopamine function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. For the outcome study, rats were randomly assigned a high-fat (HF) or a low-fat (LF) diet for 8 wk. Following the 8-wk HF-diet exposure, rats were segregated into obesity-prone and obesity-resistant groups based on maximum and minimum body weight gain, respectively, and neurobehavioral outcomes were evaluated. For the predictor study, neurobehavioral antecedents were evaluated prior to …

High Dose Simvastatin As A Potential Anticancer Therapy In Leukemia Patients, Tamer Ahmed

Theses and Dissertations--Pharmacy

Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that is used for the treatment of hyperlipidemia. Simvastatin has recently been studied for its potential use in cancer therapy. In-vitro studies have shown that simvastatin displays anticancer activity, but at concentrations unlikely to be achieved in patients being receiving typical antihyperlipidemic treatment doses. Thus, several clinical trials were conducted to study the tolerability of high dose statins in cancer patients. The maximum tolerated dose of simvastatin was determined to be 15 mg/kg/day, 25-fold higher than a typical dose. However, it is not known if simvastatin plasma concentrations can reach those …

Towards Elucidation Of A Viral Dna Packaging Motor, Chad T. Schwartz

Theses and Dissertations--Pharmacy

Previously, gp16, the ATPase protein of phi29 DNA packaging motor, was an enigma due to its tendency to form multiple oligomeric states. Recently we employed new methodologies to decipher both its stoichiometry and also the mechanism in which the protein functions to hydrolyze ATP and provide the driving force for DNA packaging. The oligomeric states were determined by biochemical and biophysical approaches. Contrary to many reported intriguing models of viral DNA packaging, it was found that phi29 DNA packaging motor permits the translocation of DNA unidirectionally and driven cooperatively by three rings of defined shape. The mechanism for the generation …

Synthesis And Stability Studies Of Prodrugs And Codrugs Of Naltrexone And 6-Β-Naltrexol, Joshua A. Eldridge

Theses and Dissertations--Pharmacy

The present study was divided between two different drug delivery goals, each involving naltrexone (NTX) or its active metabolite, 6-β-naltrexol (NTXOL). First, amino acid esters of NTX and NTXOL were prepared in order to test their candidacy for microneedle-enhanced transdermal delivery. Second, a 3-O-(-)-cytisine-naltrexone (CYT-NTX) codrug was prepared for screening as a potential oral delivery form of NTX and (-)-cytisine (CYT). The amino acid prodrugs were intended for the treatment of alcohol abuse, while the codrug was designed as a single agent for the treatment of alcoholism and tobacco-dependency co-morbidities. One hypothesis of this work was that prodrugs …

Preclinical And Clinical Development Of The Lipophilic Camptothecin Analogue Ar-67, Eleftheria Tsakalozou

Theses and Dissertations--Pharmacy

AR-67 is a lipophilic third generation camptothecin analogue, currently under early stage clinical trials. It acts by targeting Topoisomerase 1 (Top1), a nuclear enzyme essential for DNA replication and transcription and is present in two forms, the pharmacologically active lipophilic lactone and the charged carboxylate. In oncology patients participating in a phase I clinical trial, AR-67 lactone was the predominant species in plasma. Similarly to other camptothecins, the identified dose-limiting toxicities for AR-67 were neutropenia, thrombocytopenia and fatigue. In addition, in vitro metabolism studies indicated AR-67 lactone as a substrate for CYP3A4/5 as well as the UGT1A7 and UGT1A8 enzymes …

The Critical Role Of Mechanism-Based Models For Understanding And Predicting Liposomal Drug Loading, Binding And Release Kinetics, Sweta Modi

Theses and Dissertations--Pharmacy

Liposomal delivery systems hold considerable promise for improvement of cancer therapy provided that critical formulation design criteria can be met. The main objective of the current project was to enable quality by design in the formulation of liposomal delivery systems by developing comprehensive, mechanism-based mathematical models of drug loading, binding and release kinetics that take into account not only the therapeutic requirement but the physicochemical properties of the drug, the bilayer membrane, and the intraliposomal microenvironment.

Membrane binding of the drug affects both drug loading and release from liposomes. The influence of bilayer composition and phase structure on the partitioning …

Amalgamation Of Nucleosides And Amino Acids In Antibiotic Biosynthesis, Sandra H. Barnard

Theses and Dissertations--Pharmacy

The rapid increase in antibiotic resistance demands the identification of novel antibiotics with novel targets. One potential antibacterial target is the biosynthesis of peptidoglycan cell wall, which is both ubiquitous and necessary for bacterial survival. Both the caprazamycin-related compounds A-90289 and muraminomicin, as well as the capuramycin-related compounds A-503083 and A-102395 are potent inhibitors of the translocase I enzyme, one of the key enzymes required for cell wall biosynthesis. The caprazamycin-related compounds contain a core nonproteinogen b-hydroxy-a-amino acid referred to as 5’-C-glycyluridine (GlyU). Residing within the biosynthetic gene clusters of the aforementioned compounds is a shared open reading …

The Pharmacokinetics Of Metal-Based Engineered Nanomaterials, Focusing On The Blood-Brain Barrier, Mo Dan

Theses and Dissertations--Pharmacy

Metal-based engineered nanomaterials (ENMs) have potential to revolutionize diagnosis, drug delivery and manufactured products, leading to greater human ENM exposure. It is crucial to understand ENM pharmacokinetics and their association with biological barriers such as the blood-brain barrier (BBB). Physicochemical parameters such as size and surface modification of ENMs play an important role in ENM fate, including their brain association. Multifunctional ENMs showed advantages across the highly regulated BBB. There are limited reports on ENM distribution among the blood in the brain vasculature, the BBB, and brain parenchyma.

In this study, ceria ENM was used to study the effect of …

Biosynthetic Pathway Of The Aminoribosyl Component Of Lipopeptidyl Nucleoside Antibiotics, Xiuling Chi

Theses and Dissertations--Pharmacy

Several lipopeptidyl nucleoside antibiotics that inhibit bacterial translocase I (MraY) involved in peptidoglycan cell wall biosynthesis contain an aminoribosyl moiety, an unusual sugar appendage in natural products. A-90289 and muraminomicin are the two representative antibiotics that belong to this family. Bioinformatic analysis of the biosynthetic A-90289 gene clusters revealed that five enzymes are likely involved in the assembly and attachment of the aminoribosyl unit. These enzymes of A-90289 are functionally assigned by in vitro characterization. The results reveal a unique ribosylation pathway that highlighted by uridine-5′-monophosphate as the source of the sugar, a phosphorylase strategy to generate a sugar-1-phosphate, and …

Microglia Activation In A Rodent Model Of An Alcohol Use Disorder: The Importance Of Phenotype, Initiation, And Duration Of Activation, Simon A. Marshall

Theses and Dissertations--Pharmacy

Chronic ethanol exposure results in neuroadaptations that drive the progression of an alcohol use disorder (AUD). One such driving force is alcohol-induced neurodegeneration. Neuroinflammation has been proposed as a mechanism underlying this damage. Although neuroinflammation is a physiological response to damage, overactivation of its pathways can lead to neurodegeneration. A hallmark indicator of neuroinflammation is microglial activation, but microglial activation is a heterogeneous continuum of phenotypes that can promote or inhibit neuroinflammation. Furthermore acute microglial activation is necessary to restore homeostasis, but prolonged activation can exacerbate damage. The diversity of microglia makes both the level and timecourse of activation vital …

Regulation Of 7-Dehydrocholesterol Reductase By Vitamin D3, Ling Zou

Theses and Dissertations--Pharmacy

7-Dehydrocholesterol (7-DHC) is the substrate of 7-dehydrocholesterol reductase (DHCR7) in the cholesterol synthesis pathway. Keratinocytes in human skin possess the enzymes necessary for cholesterol synthesis but are also responsible for vitamin D₃ synthesis from 7-DHC by exposure to UVB irradiation. It has been well established that DHCR7 is regulated by the SREBP pathway in the regulation of cholesterol synthesis, but little is known about the regulation of DHCR7 by the vitamin D pathway. In this study, the regulation of DHCR7 activity by vitamin D was explored. Treatment of adult human epidermal keratinocyte (HEKa) cells with vitamin D₃ resulted …

Methylphenidate And Atomoxetine Treatment During Adolescence In The Spontaneously Hypertensive Rat: Mechanisms Underlying High Cocaine Abuse Liability In Attention Deficit/Hyperactivity Disorder, Sucharita S. Somkuwar

Theses and Dissertations--Pharmacy

Effects of pharmacotherapies for Attention Deficit/Hyperactivity Disorder (ADHD) on cocaine abuse liability in ADHD are not understood. Spontaneously Hypertensive Rats (SHR), an ADHD model, exhibited greater cocaine self-administration than control Wistar-Kyoto and Wistar rats. Methylphenidate, but not atomoxetine during adolescence enhanced cocaine self-administration in adult SHRs compared to controls. The mesocortical dopaminergic system, including medial prefrontal (mPFC) and orbitofrontal (OFC) cortices, is important for ADHD and cocaine addiction. Dopamine and norepinephrine transporter (DAT and NET) are molecular targets for methylphenidate, atomoxetine and cocaine action.

In the current studies, SHR, Wistar-Kyoto and Wistar were administered methylphenidate (1.5 mg/kg/day, p.o.), atomoxetine (0.3 …

Post Use Analysis Of Firefighter Turnout Gear- Phase Iii, Meredith Laine Cinnamon

Theses and Dissertations--Retailing and Tourism Management

The purpose of this research was to perform a post-use evaluation of retired firefighter turnout gear. Garments were categorized as 10-12 years old, 13-17 years old and 18-21 years old. Inspection and test procedures required by National Fire Protection Association (NFPA) 1851 and NFPA 1971 were followed to determine if the current recommended 10 year wear life (retirement age) is appropriate. Testing included a visual inspection (closure system functionality, light evaluation, leakage evaluation and flashlight test) and performance properties (Thermal Protective Performance (TPP), flammability, breaking strength, tear strength, seam strength and water penetration) completed on 108 garments. Ten-year retirement, care, …

Cellular And Molecular Aspects Of The Interaction Betwen Maize And The Anthracnose Pathogen Colletotrichum Graminicola, Maria F. Torres

Theses and Dissertations--Plant Pathology

Maize anthracnose, caused by the fungus Colletotrichum graminicola, is an economically important species contributing to major yield losses. C. graminicola is a hemibiotroph; initially it invades its host while it is alive, and then it switches to destructive necrotrophic growth and the host is killed. Establishment of compatible interactions by biotrophic pathogens is usually associated with suppression of host defenses and cell death, while necrotrophic pathogens typically secrete phytotoxic compounds and induce cell death. To understand the relationship of hemibiotrophy in C. graminicola to biotrophy and necrotrophy, I compared a compatible and an incompatible interaction, utilizing a non-pathogenic …

Overexpression/Silencing Of Selected Soybean Genes Alters Resistance To Pathogens, Mohamed H. El-Habbak

Theses and Dissertations--Plant Pathology

Plant diseases remain a major obstruction to meeting the world’s increased demand for soybean oil and protein. Reducing the losses caused by diseases in order to improve crop production is a high priority for agricultural research. The need for novel strategies for plant disease control cannot be overstated. In the present study, selected defense-related genes were silenced and/or overexpressed in soybean using a virus-based vector and the resultant plants were tested for their responses to pathogens. The first part of the study focused on Rps1k (Resistance to Phytophthora sojae) gene. The two conserved domains encoding ‘P-Loop NTPase’ and ‘PLN03210’ …

Effects Of Streamside Management Zone Timber Harvest On Salamander Communities In Robinson Forest, Thomas Maigret

Theses and Dissertations--Forestry and Natural Resources

Salamanders are critical components of forest ecosystems, in terms of total biomass, as well as for their value as indicators of ecosystem stress. Considering the worldwide decline in amphibian populations, the known effects of timber harvest on salamander populations, and the importance of the forest products industry in Kentucky and elsewhere, the impacts of silvicultural operations on salamander communities cannot be overlooked. The objective was to investigate the effects of three different silvicultural treatments, each involving different streamside management zone (SMZ) characteristics, on salamander communities in ephemeral streams. Data were collected by regular checks of pitfall traps, coverboards, and transect …

Chondrodysplasia-Like Dwarfism In The Miniature Horse, John E. Eberth

Theses and Dissertations--Veterinary Science

Dwarfism is considered one of the most recognized congenital defects of animals and humans and can be hereditary or sporadic in cause and expression. There are two general morphologic categories within this vastly diverse disease. These categories are disproportionate and proportionate dwarfism and within each of these there are numerous phenotypes which have been extensively described in humans, and to a lesser extent in dogs, cattle, mice, chickens, and other domestic species. Ponies and Miniature horses largely differ from full size horses only by their stature. Ponies are often defined as those whose height is not greater than 14.2 hands; …

Forest Harvest Equipment Movement And Sediment Delivery To Streams, Daniel Whiteside Bowker

Theses and Dissertations--Forestry and Natural Resources

Streamside management zones (SMZs) have become important management techniques to prevent the introduction of sediment to stream networks. This study examined the current Kentucky best management practice (BMP) guidelines for SMZs by outfitting mobile forest harvest equipment with global positioning system (GPS) receivers, enabling modeling of equipment traffic and spatial analysis of stream sediment delivery. Three SMZ configurations were implemented during commercial timber harvest, along with four different techniques of crossing ephemeral channels, in order to determine where and why sediment was introduced to the stream network. Results indicate that increasing the SMZ buffer width leads to decreased sediment delivery, …

Equine Serum Antibody Responses To Streptococcus Equi And Streptococcus Zooepidemicus, Rafaela De Negri

Theses and Dissertations--Veterinary Science

Streptococcus zooepidemicus (Sz) and Streptococcus equi (Se) share 98% DNA sequence homology, but display different pathogenic properties. Infection by one organism does not cross-protect against the other. To better understand pathogenic differences between these organisms and gain information about which proteins are expressed in horses infected experimentally with Se, intrauterine Sz or naturally with respiratory Sz we compared antibody specificities of convalescent sera using ELISA. These comparisons were based on sets of 8 and 14 immunoreactive recombinant proteins of Se strain CF32 and Sz strain NC78, respectively. Sera from donkeys that were previously naturally affected with strangles and later developed …

Carbon Life-Cycle And Economic Analysis Of Forest Carbon Sequestration And Woody Bioenergy Production, Prativa Shrestha

Theses and Dissertations--Forestry and Natural Resources

Sequestering carbon in standing biomass, using woody bioenergy, and using woody products are the three potential ways to utilize forests in reducing greenhouse gases (GHGs) and mitigating climate change. These forestry related strategies are, however, greatly influenced by the existing markets and market based policies. This study focuses on the first two forest strategies. It investigates the combined impact of carbon and woody bioenergy markets on two different types of forests in the US – oak dominated mixed hardwood forests in the Central Hardwood Forests Region and loblolly pine forests in the southeastern US. A modification of the Harman model …

Development Of A New Allelic Discrimination Real-Time Pcr Assay For The Diagnosis Of Equine Herpesvirus-1 And Characterization Of The Virulence Determinants Of The Virus, Kathryn L. Smith

Theses and Dissertations--Veterinary Science

Equine herpesvirus-1 (EHV-1) can cause acute upper respiratory tract disease, abortion, neonatal death and neurological disease in horses. Rapid, accurate and timely diagnosis of EHV-1 infection in horses is important to curtail the spread of this pathogen. It has been reported that the neuropathogenic phenotype of EHV-1 can result from a single non-synonymous nucleotide substitution at position 2254 (A→G₂₂₅₄) in open reading frame 30 (ORF30). This was the basis for the development of an allelic discrimination, real-time PCR assay to distinguish between potential neuropathogenic and non-neuropathogenic EHV-1 strains. However, PCR analysis of a panel of EHV-1 abortion isolates …

Putting Theory Into Practice: Predicting The Invasion And Stability Of Wolbachia Using Simulation Models And Empirical Studies, Philip R. Crain

Theses and Dissertations--Entomology

A new strategy to fight mosquito-borne disease is based on infections of the maternally-transmitted, intracellular bacterium Wolbachia pipientis. Estimates predict that Wolbachia infects nearly half of all insect species, as well as other arthropods and some nematodes. Wolbachia manipulates the reproduction of its host to promote infection, most commonly causing a form of conditional sterility known as cytoplasmic incompatibility. Generally, Wolbachia infections are benign and do not inflict significant costs upon its host. However, studies demonstrate that some infections are associated with substantial costs to its host. These same infections can also induce pathogen interference and decrease vector competency …

Selective Utilization Of Microhabitats By Web-Building Spiders, Kelton D. Welch

Theses and Dissertations--Entomology

Natural enemies are members of complex ecological communities, and their ability to contribute to the biological control of pest organisms is strongly influenced by a convoluted network of ecological interactions with many other organisms within these communities. Researchers must develop an understanding of the mechanisms that shape trophic webs to predict and promote top-down effects of predators. The behavior of predators can have a strong influence on their potential as biological control agents.

Web-building spiders are a useful example organism for the study of natural enemy behavior because of the experimentally tractable nature of their foraging behavior. Specifically, patterns in …

An Assessment Of The Invasive Poison Hemlock And Its Insect Associates In Kentucky, Christine D. Allen

Theses and Dissertations--Entomology

Poison hemlock, Conium maculatum (Apiaceae), is an invasive plant in North America with a unique toxic chemistry. Previous research on this plant has focused on identifying herbivores as potential biological control agents or describing the toxic plant alkaloids. However, none have examined the role of higher trophic levels in the food web surrounding poison hemlock. Generalist predators and food web interactions are an important component of studies investigating invasion effects, as plant or animal introductions can alter ecosystem functioning. In this study, predators in poison hemlock were sampled at the foliar and epigeal levels, resulting in 956 Carabidae and 321 …

Positive Affect, Hemispheric Lateralization, And Relational Problem Solving: A Mixed-Methods Exploration Of Parent-Adolescent Communication, Nichole L. Huff

Theses and Dissertations--Family Sciences

Using quantitative and qualitative data analytic techniques, the present study explores the parent-adolescent relationship from a pilot study of 15 triads (overall N = 45). First, the statistical relationship between positive relational affect and electrical brain activity was assessed during parent-adolescent conflict communication (N = 30). Specifically, using electroencephalography (EEG) technology, electrical brain activity was recorded during family problem-solving discussions between a mother, father, and adolescent child. Observational coding was used to determine participant and triad positive affect ratios (PARs). Principles of positive-to-negative affect were incorporated into an affective neuroscience framework and used as the theoretical basis …

Enhancing Beneficial Insect Biodiversity And Biological Control In Turf: Mowing Height, Naturalized Roughs, And Operation Pollinator, Emily Dobbs

Theses and Dissertations--Entomology

The goal of this study was to evaluate several sustainable turf maintenance techniques for their potential to increase beneficial insect populations, which could then provide ecosystem services including pest suppression and pollination. The three techniques in question were 1) raising mowing height in commercial and residential lawns, 2) establishing naturalized roughs on golf courses, and 3) creating pollinator refuges on golf courses through the program Operation Pollinator. We found that raising mowing heights did increase populations of some predators such as spiders and staphylinids, but did not increase predation, which was ubiquitously high because ant populations were unaffected by mowing …