Digital Commons Network^™

Factors Affecting Skeletal Muscle Protein Synthesis In The Horse, Ashley Leigh Wagner

Theses and Dissertations--Animal and Food Sciences

Skeletal muscle protein synthesis is regulated by the mammalian target of rapamycin (mTOR) signaling pathway. The first objective was to optimize the methodological procedures for assessing mTOR signaling in horses. The response of mTOR signaling (P-Akt Ser⁴⁷³, P-S6K1 Thr³⁸⁹, P-rpS6 Ser^{235/26 & 240/244}, and P-4EBP1 Thr^37/46 by Western blotting techniques) to meal consumption was determined at three gluteal muscle biopsy depths (6, 8, and 10 cm), and the repeatability of the contralateral side at 8 cm during 5 days of repeated biopsies. There was no effect (P > 0.05) of sampling side or biopsy …

Breast Cancer Trends Among Kentucky Women, 2004-2007, Kara Ann Hagan

Theses and Dissertations--Nutrition and Food Systems

The purpose of this study is to investigate the discrepancies of female breast cancer mortality between the Appalachian and Non-Appalachian regions of Kentucky using data from the Kentucky Cancer Registry. This study identified subtype, reproductive, and regional differences in women with breast cancer in Kentucky. Among women with breast cancer living in Kentucky from 2004 to 2007, one and three live births significantly increased a woman’s risk of breast cancer mortality by 91% and 58% respectively, compared to a woman with zero live births. Progesterone receptornegative tumor status significantly increased a woman’s risk of breast cancer mortality by 64% compared …

Selective Inguinal Lymphadenectomy In The Treatment Of Invasive Squamous Cell Carcinoma Of The Vulva, Christopher P. Desimone, Jeffrey Elder, John R. Van Nagell Jr.

Obstetrics and Gynecology Faculty Publications

En bloc radical vulvectomy with bilateral inguinofemoral lymphadenectomy has now been replaced by radical wide excision and selective inguinal lymphadenectomy based on the stage and location of invasive vulvar cancer. Early stage lateral cancers can be effectively treated by radical wide excision and ipsilateral superficial inguinal lymphadenectomy. Lymph node mapping using perilesional injection of radiocolloid and blue dye may identify sentinel lymph nodes which can be removed, thereby avoiding the morbidity of full inguinal lymphadenectomy in selected patients with early stage disease.

In Situ Generated Colloid Transport Of Cu And Zn In Reclaimed Mine Soil Profiles Associated With Biosolids Application, Jarrod O. Miller, Anastasios D. Karathanasis, Christopher J. Matocha

Plant and Soil Sciences Faculty Publications

Areas reclaimed for agricultural uses following coal mining often receive biosolids applications to increase organic matter and fertility. Transport of heavy metals within these soils may be enhanced by the additional presence of biosolids colloids. Intact monoliths from reclaimed and undisturbed soils in Virginia and Kentucky were leached to observe Cu and Zn mobility with and without biosolids application. Transport of Cu and Zn was observed in both solution and colloid associated phases in reclaimed and undisturbed forest soils, where the presence of unweathered spoil material and biosolids amendments contributed to higher metal release in solution fractions. Up to 81% …

Clinical And Functional Assessment Following Autologous Chondrocyte Implantation To The Knee: The Role Of Patient Reported Outcomes, Performance Based Assessment, And Response Shift, Jennifer Sebert Howard

Theses and Dissertations--Rehabilitation Sciences

Autologous chondrocyte implantation (ACI) is a cell based therapy for the treatment of articular cartilage defects. Numerous studies have reported outcomes following ACI using a variety of patient reported outcomes (PROs), but no clear recommendations exist regarding which PRO is the most responsive to changes following ACI. Few studies have documented changes in performance based assessments (PBAs) following ACI. Response shift theory proposes that residual changes in self-report measures occur over time. Failing to account for response shift may result in over or under reporting of outcomes from which clinical decisions are made. The purposes of this dissertation were 1) …

Chemical Evolution And Residence Time Of Groundwater In The Wilcox Aquifer Of The Northern Gulf Coastal Plain, Estifanos Haile

Theses and Dissertations--Earth and Environmental Sciences

This study aims to integrate groundwater geochemistry and mathematical modeling to determine the dominant geochemical processes and groundwater residence time within the Wilcox aquifer in the northern Gulf Coastal Plain. Groundwater samples were collected and analyzed for major ion chemistry, stable isotopes (¹⁸O, ²H, and ¹³C), and radioisotope ³⁶Cl content. Geochemical modeling enabled the identification of major sources and sinks of solutes in the aquifer. A two-dimensional, finite-difference, numerical model was used to determine the deep groundwater flow rate and transport of ³⁶Cl in the aquifer. Major ion chemistry shows a chromatographic pattern along …

Rotate And Hold And Scan (Rahas): Structured Light Illumination For Use In Remote Areas, Eli Ross Crane

University of Kentucky Master's Theses

As a critical step after the discovery of material culture in the field, archaeologists have a need to document these findings with a slew of different physical measurements and photographs from varying perspectives. 3-D imaging is becoming increasingly popular as the primary documenting method to replace the plethora of tests and measurements, but for remote areas 3-D becomes more cumbersome due to physical and environmental constraints. The difficulty of using a 3-D imaging system in such environments is drastically lessened while using the RAHAS technique, since it acquires scans untethered to a computer. The goal of this thesis is to …

World Production And Trade Of Pistachios: The Role Of The U.S. And Factors Affecting The Export Demand Of U.S. Pistachios, Zijuan Zheng

University of Kentucky Master's Theses

The primary purpose of this study is to evaluate the role of the US in the worldwide production and trade of pistachios, identify and estimate the major factors affecting export demand for US pistachios in 21 major markets, accounting for 78 percent of total US pistachio exports. The study estimated the impacts of US pistachio own price, cross price, importing markets’ GDP, real exchange rates and effect of food safety shocks. A panel data analysis was conducted using data from 1989 to 2009. A Houseman test indicated that the random effects estimator was the chosen estimator. Elasticity analysis indicated that …

Mathematical Modeling Of Clostridium Thermocellum’S Metabolic Responses To Environmental Perturbation, Bless Adotey

Theses and Dissertations--Biosystems and Agricultural Engineering

Clostridium thermocellum is a thermophilic anaerobe that is capable of producing ethanol directly from lignocellulosic compounds, however this organism suffers from low ethanol tolerance and low ethanol yields. In vivo mathematical modeling studies based on steady state traditional metabolic flux analysis, metabolic control analysis, transient and steady states’ flux spectrum analysis (FSA) were conducted on C. thermocellum’s central metabolism. The models were developed in Matrix Laboratory software ( MATLAB^® (The Language of Technical Computing), R2008b, Version 7.7.0.471)) based on known stoichiometry from C. thermocellum pathway and known physical constraints. Growth on cellobiose from Metabolic flux analysis (MFA) and Metabolic …

Moisture Control Methodology For Gas Phase Compost Biofilters, Lucas Dutra De Melo

Theses and Dissertations--Biosystems and Agricultural Engineering

Gas phase biofilters are used for controlling odors from animal facilities. Some characteristics can affect their performance and moisture content is one very important. A methodology for controlling and measuring moisture content is required to optimize these systems. An experiment was conducted to determine the appropriate placement of a set of soaker hoses 1.2 m in length for water application. It was found that the soaker hose installed in the lower region of the biofilter coupled with appropriate and timely application of water was able to minimize drying of the compost. Thermal conductance proved to be a reliable indicator for …

Nigrostriatal Dopamine-Neuron Function From Neurotrophic-Like Peptide Treatment And Neurotrophic Factor Depletion, Ofelia Meagan Littrell

Theses and Dissertations--Neuroscience

Trophic factors have shown great promise in their potential to treat neurological disease. In particular, glial cell line-derived neurotrophic factor (GDNF) has been identified as a potent neurotrophic factor for midbrain dopamine (DA) neurons in the substantia nigra (SN), which lose function in Parkinson’s disease (PD). GDNF progressed to phase II clinical trials, which did not meet proposed endpoints. The large size and binding characteristics of GDNF have been suspected to contribute to some of the shortcomings of GDNF related to delivery to target brain regions. Smaller peptides derived from GDNF (Dopamine-Neuron Stimulating Peptides – DNSPs) have been recently investigated …

Lysophosphatidic Acid Production And Signaling In Platelets, Zachary Bennett Fulkerson

Theses and Dissertations--Physiology

Lysophosphatidic acid (LPA) belongs to a class of extracellular lipid signaling molecules. In the vasculature, LPA may regulate platelet activation and modulate endothelial and smooth muscle cell function. LPA has therefore been proposed as a mediator of cardiovascular disease.

The bulk of circulating LPA is produced from plasma lysophosphatidylcholine (LPC) by autotaxin (ATX), a secreted lysophospholipase D (lysoPLD). Early studies suggest that some of the production of circulating LPA is platelet-dependent. ATX possesses an N-terminal somatomedin B-like domain suggesting the hypothesis that ATX interacts with platelet integrins which may localize ATX to substrate in the membrane and/or alter the catalytic …

Mechanism And Kinetics Of Covalent Amide-Linked Adduct Formation In Solution And Solid Peptide Formulations, Michael Paul Dehart

Theses and Dissertations--Pharmacy

Peptides and proteins are prone to chemical and physical degradation in solutions and solids. One of the most common chemical degradation pathways involves deamidation of asparagine residues through a reactive succinimide intermediate resulting in the formation of aspartyl and isoaspartyl degradation products.

In this work, kinetic studies in aqueous solutions demonstrated that the succinimide intermediate is susceptible to attack by nucleophiles other than water. This may lead to a variety of alternative degradants. In solutions containing high concentrations of ammonia, the succinimide generated in the deamidation of the model peptides Phe-Asn-Gly and Phe-isoAsn-Gly underwent back-reaction with ammonia leading to peptide …

Viability Of A Controllable Chaotic Micromixer Through The Use Of Titanium-Nickel Shape Memory Alloy, David Ryan Lilly

Theses and Dissertations--Mechanical and Aerospace Engineering

Microfluidic devices have found applications in a number of areas, such as medical analysis, chemical synthesis, biological study, and drug delivery. Because of the small channel dimensions used in these systems, most microchannels exhibit laminar flow due to their low Reynold’s number, making mixing of fluids very challenging. Mixing at this size scale is diffusion-limited, so inducing chaotic flow patterns can increase the interface surface area between two fluids, thereby decreasing overall mixing time.

One method to create a chaotic flow within the channel is through the introduction of internal protrusions into the channel. In such an application protrusions that …

Target Validation Of Uk-101 And Functional Studies Of Β1i, Marie V. Wehenkel

Theses and Dissertations--Pharmacy

β1i is a major catalytic subunit of the immunoproteasome, an alternative form of the constitutive proteasome, and its upregulation has been demonstrated in a variety of disease states including cancer. Our lab has developed a small molecule inhibitor of β1i, dubbed UK-101. While UK-101 causes apoptosis in cancer cell lines, it was not clear whether this apoptotic effect was directly mediated by its irreversible inhibition of β1i. Since off-target effects are major roadblocks for the development of new and effective pharmaceuticals, target validation studies in this system would assist in the further progression of β1i inhibitors towards preclinical trials. Our …

Studies Of Solubilization Of Poorly Water-Soluble Drugs During In Vitro Lipolysis Of A Model Lipid-Based Drug Delivery System And In Mixed Micelles, Lin Song

Theses and Dissertations--Pharmacy

Lipid-based drug delivery systems (LBDDSs) are becoming an increasingly popular approach to improve the oral absorption of poorly-water soluble drugs. Several possible mechanisms have been proposed to explain the means by which LBDDSs act in vivo to enhance absorption. The goal of the current dissertation is to provide a better understanding of one proposed mechanism; the capability of lipoidal components in LBDDS formulations to create and maintain a drug in a supersaturated state under simulated GI conditions. Moreover, molecular details of equilibrium solubilization of a drug in a series of model lipid assemblies were examined. The results of these studies …

Preclinical Evaluation Of Lobeline For The Treatment Of Adhd: Comparison With Psychostimulant Therapies, Yolanda D. Williams

Theses and Dissertations--Pharmacy

This dissertation work investigated the effect of acute and repeated in vivo administration of lobeline on dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) function. The effects of lobeline were then compared to the effects of acute and repeated in vivo administration of methylphenidate and amphetamine to determine if lobeline produced similar effects compared to these Attention Deficit Hyperactivity Disorder (ADHD) medications. These medications are considered the first line of pharmacotherapy for ADHD, although there is a growing concern associated with their potential for abuse and other side effects. This merits the need for novel ADHD treatments that have a …

Role Of The Sexual Cycle In Development Of Genotypic And Phenotypic Diversity In Gibberella Zeae, Sladana Bec

Theses and Dissertations--Plant Pathology

Gibberella zeae (anamorph Fusarium graminearum) is a homothallic ascomycete pathogen that is responsible for causing Fusarium head blight (FHB) of wheat and small grains. In addition to causing a reduction in yield, harvested grain is frequently contaminated with trichothecene mycotoxins that are harmful for human and animal health. Use of wheat varieties with resistance to FHB is an important strategy to lower its impact. In order to produce varieties with durable resistance, we must understand the origin and degree of genetic diversity present in the pathogen population. In my research, I focused my efforts on an investigation of the …

Status Of A Reintroduced Black Bear Population In The Big South Fork Area Of Kentucky, Sean Mccarthy Murphy

Theses and Dissertations--Forestry and Natural Resources

Large carnivores have been subjected to overexploitation and extensive habitat loss for centuries. Reintroduction has become an increasingly used tool for recovering and reestablishing large carnivore populations; however, most reintroductions have either failed or resulted in small populations that are vulnerable to deleterious demographic, environmental, and genetic effects that can lead to population loss or extinction. Longterm monitoring of small, reintroduced populations is critical to population persistence and viability. To evaluate long-term reintroduction success and current status of a recently reintroduced, small black bear (Ursus americanus) population in the Big South Fork area of Kentucky, I used non-invasive …

Genetic Immunization In The Horse: The Potential For Enhanced Immune Responses With Deacylated Polyethyleneimine (Pei) And Immunostimulatory Cytokines As Vaccine Adjuvants, Deborah Lee Even

Theses and Dissertations--Veterinary Science

DNA vaccines in larger animals, such as horses, are generally less effective and elicit significantly weaker immune responses, than in small animal model systems. To provide optimal protection against pathogenic microorganisms, the induction of both humoral and cellular immune responses from DNA vaccination may be necessary. One limitation to DNA immunization in the horse is the difficulty in generating high levels of antigen-specific antibody and CTL responses. Previous work in the laboratory has demonstrated that expression constructs containing native sequences encoding the surface unit (SU) envelope glycoprotein (pCiSU) of the Equine Infectious Anemia Virus (EIAV) are ineffective at stimulating immune …

Attention-Deficit/Hyperactivity Disorder In Childhood Is Associated With Cognitive Test Profiles In The Geriatric Population But Not With Mild Cognitive Impairment Or Alzheimer's Disease, N. Ivanchak, Erin L. Abner, S. A. Carr, S. J. Freeman, A. Seybert, John Ranseen, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

The frequency of ADHD in the aging population and its relationship to late-life cognitive decline has not been studied previously. To address this gap in our understanding, the Wender-Utah ADHD Rating scale (WURS) was administered to 310 geriatric subjects with cognitive status ranging from normal cognition to mild cognitive impairment to overt dementia. The frequency of WURS-positive ADHD in this sample was 4.4%. WURS scores were not related to cognitive diagnoses, but did show nonlinear associations with tasks requiring sustained attention. The frequency of ADHD appears stable across generations and does not appear to be associated with MCI or dementia …

Evaluating Algal Growth At Different Temperatures, Keelin Owen Cassidy

Theses and Dissertations--Biosystems and Agricultural Engineering

In recent years, there has been a concern for the amount of carbon dioxide released into the atmosphere and how it will be captured. One way to capture carbon dioxide is with algae. In this study, algae's growth was measured at different temperatures. The first part of the study was to grow Scenedesmus and Chlorella with M8 or urea growth media at a temperature of 25, 30 or 35ºC. It was found that 30ºC had the best growth rates for both algae. The second part studied Scenedesmus growth with urea, more in-depth, and found the optimum growth temperature to be …

Direct Cloning Of Double-Stranded Rnas From Rnase Protection Analysis Reveals Processing Patterns Of C/D Box Snornas And Provides Evidence For Widespread Antisense Transcript Expression, Manli Shen, Eduardo Eyras, Jie Wu, Amit Khanna, Serene Josiah, Mathieu Rederstorff, Michael Q. Zhang, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

We describe a new method that allows cloning of double-stranded RNAs (dsRNAs) that are generated in RNase protection experiments. We demonstrate that the mouse C/D box snoRNA MBII-85 (SNORD116) is processed into at least five shorter RNAs using processing sites near known functional elements of C/D box snoRNAs. Surprisingly, the majority of cloned RNAs from RNase protection experiments were derived from endogenous cellular RNA, indicating widespread antisense expression. The cloned dsRNAs could be mapped to genome areas that show RNA expression on both DNA strands and partially overlapped with experimentally determined argonaute-binding sites. The data suggest a conserved processing pattern …

Cooperative And Antagonistic Roles For Heterochromatin Proteins In Transcriptional Regulation Of The Drosophila Sex Determination Masterswitch Gene, Hui Li

University of Kentucky Doctoral Dissertations

HOAP was originally identified as a component of an ORC-containing multi-protein complex of Heterochromatin Protein 1 (HP1) from early Drosophila embryos. HOAP immunostaining showed prominent association of it with telomeres, and mutants for HOAP (cav¹) showed it functions along with HP1 in forming a telomere capping complex that prevents telomeric fusions.

Weaker HOAP immunostaining is also observed in regions of pericentric heterochromatin and euchromatin. To examine the role of HOAP at these non-telomeric sites, we applied Affymetric Drosophila Genome Arrays to undertake a microarray expression profiling study of genes that are mis-expressed in cav¹ mutant larvae. The …

The Relationship Of Personality Preferences And Type To Health-Promoting Behaviors, Alcohol Use, And Cigarette Smoking, Billy Fredrick Martin

University of Kentucky Doctoral Dissertations

An individual’s personality traits and characteristics have been found to have an important relationship with health behaviors. However, there has been minimal research conducted with personality types. The purpose of the study was to examine the predictive relationship among MBTI® personality preferences and types and both selected health-promoting and selected risk-taking behaviors among residential college students. Furthermore, several potential mediating demographic variables were added to the study to determine their predictive relationship and if they should be entered into a model for the selected health behaviors.

The study used a cross-sectional design with two self-report instruments and demographic questionnaire. The …

High Performance Piezoelectric Materials And Devices For Multilayer Low Temperature Co-Fired Ceramic Based Microfluidic Systems, Wenli Zhang

University of Kentucky Doctoral Dissertations

The incorporation of active piezoelectric elements and fluidic components into micro-electromechanical systems (MEMS) is of great interest for the development of sensors, actuators, and integrated systems used in microfluidics. Low temperature cofired ceramics (LTCC), widely used as electronic packaging materials, offer the possibility of manufacturing highly integrated microfluidic systems with complex 3-D features and various co-firable functional materials in a multilayer module. It would be desirable to integrate high performance lead zirconate titanate (PZT) based ceramics into LTCC-based MEMS using modern thick film and 3-D packaging technologies. The challenges for fabricating functional LTCC/PZT devices are: 1) formulating piezoelectric compositions which …

Fabrication And Characterization Of Mesoscale Protein Patterns Using Atomic Force Microscopy (Afm), Pei Gao

University of Kentucky Doctoral Dissertations

A versatile AFM local oxidation lithography was developed for fabricating clean protein patterns ranging from nanometer to sub-millimeter scale on octadecyltrichlorosilane (OTS) layer of Si (100) wafer. This protein patterning method can generate bio-active protein pattern with a clean background without the need of the anti-fouling the surface or repetitive rinsing.

As a model system, lysozyme protein patterns were investigated through their binding reactions with antibodies and aptamers by AFM. Polyclonal anti-lysozyme antibodies and anti-lysozyme aptamer are found to preferentially bind to the lysozyme molecules on the edge of a protein pattern before their binding to the interior ones. It …

Role Of Lipids In Tombusvirus Replication, Monika Sharma

University of Kentucky Doctoral Dissertations

Positive-strand RNA virus group are the most abundant among viruses affecting plants and animals. To successfully achieve replication, these viruses usurp or co-opt host proteins. To facilitate the discovery of host factors involved in Tomato bushy stunt virus (TBSV), yeast has been developed as a surrogate model host. Genome-wide approaches covering 95% of yeast genes, has revealed approximately hundred factors that could affect virus replication. Among the identified host factors, there are fourteen yeast genes, which affect/regulate lipid metabolism of the host.

One of the identified host gene is ERG25, which is an important factor for sterol biosynthesis pathway, affecting …

Characterization Of G10h Promoter And Isolation Of Wrky Transcription Factors Involved In Catharanthus Terpenoid Indole Alkaloid Biosynthesis Pathway, Nitima Suttpanta

University of Kentucky Doctoral Dissertations

Catharanthus roseus produces a large array of terpenoid indole alkaloids (TIAs) that are an important source of natural or semi-synthetic anticancer drugs. Biosynthesis of TIAs is tissue-specific and induced by certain phytohormones and fungal elicitors, indicating the involvement of a complex transcriptional control network. However, the transcriptional regulation of the TIA pathway is poorly understood. This study reports the isolation and characterization of the G10H promoter and two WRKY transcription factors regulating TIA biosynthesis.

Geraniol 10-hydroxylase (G10H) controls the first committed step in the biosynthesis of terpenoid indole alkaloids (TIA). The C. roseus G10H promoter sequence was isolated by a …

Development And Characterization Of Novel Monoclonal Antibodies For Studying Prion Pathogenesis, Chu-Chun Weng

University of Kentucky Master's Theses

Monoclonal antibodies (mAbs) recognizing different regions of PrP are potential tools in the study of prion diseases and immunotherapy. We used shuffled recombinant prion protein containing elk and mouse PrP as antigen to produce monoclonal antibodies in mice. We found that mAb 5C6 mapped to a discontinuous epitope comprised of amino acid 132 and 158 (mouse numbering). Monoclonal anibody 9E9 which maps to a unique N-terminal epitope at amino acid preferentially recognized cervid PrP. In contrast, the epitope of mAb 9H9 is located in the C-terminus and only reacted with mouse and hamster. The epitope for mAb 7H11 appears to …