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Long-Period Ground Motions In The Upper Mississippi Embayment From Finite-Fault, Finite-Difference Simulations, Kenneth A. Macpherson

University of Kentucky Doctoral Dissertations

A 3D velocity model and 3D wave propagation code have been employed to simulate long-period ground motions in the upper Mississippi embayment. This region is exposed to seismic hazard in the form of large earthquakes in the New Madrid seismic zone and observational data are sparse, making simulation a valuable tool for predicting the effects of large events. These simulations were undertaken in order to estimate ground-motion characteristics and to investigate the influence of the 3D embayment structure and finite-fault mechanics. There are three primary fault zones in the New Madrid seismic zone, each of which was likely associated with …

Alterations Of Zinc Transporters In Alzheimer's Disease, Ganna Lyubartseva

University of Kentucky Doctoral Dissertations

Alzheimer’s disease (AD), one of the major causes of disability and mortality in Western societies, is a progressive age-related neurodegenerative disorder. Increasing evidence suggests the etiology of AD may involve disruptions of zinc (Zn) homeostasis. We hypothesize that disruption of Zn homeostasis leads to alterations of Zn transporter (ZnT) proteins, resulting in increased production of neurotoxic amyloid beta (Aβ) peptide in AD brain. To address this hypothesis we carried out the following studies.

1. We characterized alterations of ZnT-1, ZnT-4 and ZnT-6 in the brain of preclinical AD (PCAD) subjects, who show no overt clinical manifestations of AD but demonstrate …

Computational Design Of 3-Phosphoinositide Dependent Kinase-1 Inhibitors As Potential Anti-Cancer Agents, Mohamed Diwan Mohideen Abdulhameed

University of Kentucky Doctoral Dissertations

Computational drug design methods have great potential in drug discovery particularly in lead identification and lead optimization. 3-Phosphoinositide dependent kinase-1 (PDK1) is a protein kinase and a well validated anti-cancer target. Inhibitors of PDK1 have the potential to be developed as anti-cancer drugs. In this work, we have applied various novel computational drug design strategies to design and identify new PDK1 inhibitors with potential anti-cancer activity. We have pursued novel structure-based drug design strategies and identified a new binding mode for celecoxib and its derivatives binding with PDK1. This new binding mode provides a valuable basis for rational design of …

Roles Of Emx2 In Odorant Receptor Gene Expression And Olfactory Sensory Neuron Axon Growth, Jeremy Colin Mcintyre

University of Kentucky Doctoral Dissertations

The sense of smell relies upon the detection of odorants by neurons located in the nasal cavity. These neurons, referred to as olfactory sensory neurons (OSNs), line the olfactory epithelium and extend axons that make synaptic connections with mitral/tufted cells in the olfactory bulb. The mechanisms by which these synaptic connections form remain largely unknown. The development of these synaptic connections relies on the axons of immature OSNs innervating the olfactory bulb. The primary goal of this dissertation was to identify components of the mechanisms used by immature OSN axons to innervate the olfactory bulb. To accomplish this goal, a …

Role Of Aryl Hydrocarbon Receptor In Chronic Inflammatory Diseases, Violeta Arsenescu

University of Kentucky Doctoral Dissertations

Aryl Hydrocarbon Receptor (AhR) is a ligand-actviated receptor known as the dioxin receptor. Environmental pollutants called dioxin-like toxicants are found in food, cigarette smoke, automobile exhaust and air. Therefore, they could chronically amplify the pathology of numerous chronic inflammatory diseases. AhR is a well known target of these environmental chemicals that disrupt endocrine signaling. By the year 2020, the number of people older than 60 years is expected to top 1 billion. The burden of treating chronic disease is significant both in dollars spent and in lost productivity. The need to identify risk factors for chronic diseases must be evaluated …

The Distribution Of Unpaired During Drosophila Oogenesis, Travis Sexton

University of Kentucky Doctoral Dissertations

Janus Kinase (JAK) activity specifies the cell fates of the follicular epithelium during Drosophila oogenesis by establishing a gradient of JAK activity with highest levels at the A/P poles. Unpaired (Upd), a ligand for the pathway, is expressed and secreted exclusively from the polar cells potentially establishing the JAK activity gradient. This project proposed that Upd acts as a morphogen to directly establish the JAK activity gradient, specifying the fates of the follicular epithelium. The aims of this work were to investigate the extracellular distribution of Upd and, in addition, factors that may be involved. Furthermore, upd3, a gene …

The Impact Of Interactive Functionality On Learning Outcomes: An Application Of Outcome Interactivity Theory, James P. Gleason

University of Kentucky Doctoral Dissertations

Scholars have examined a variety of dimensions and models of interactivity in an attempt to articulate a comprehensive definition. Outcome Interactivity Theory (OIT) considers interactivity to be the result of a communication event involving the successful integration of three predictive dimensions: the presence of actual interactive technological features, the presence of similarly reactive content elements, and relevant user experiences that empower the user to employ these interactive elements within the communication event toward a desirable outcome.

This dissertation accomplishes three major objectives: clarify the literature relating to the interactivity construct; introduce Outcome Interactivity Theory as a new theory-based conceptualization …

Towards Elimination And Genetic Manipulation Of Ergot Alkaloid Production In Fungal Endophytes, Simona Florea

University of Kentucky Doctoral Dissertations

Clavicipitaceous fungal endophytes provide several ecological benefits to their hosts. Besides improving host’s growth characteristics, Neotyphodium coenophialum, the endophyte of tall fescue (Lolium arundinaceum), produces ergot alkaloids that have been proposed to be involved in fescue toxicosis. One approach to address the toxicosis problem is to genetically manipulate and modify N. coenophialum by knocking out a pair of homologous genes, (dmaW1 and dmaW2), encoding dimethylallyltryptophan synthase, the enzyme for the first and determinant step in ergot-alkaloid biosynthesis. In this study, disruption of dmaW2 was attempted using several disruption methods. Out of 1522 transformants screened, three …

Down-Regulation Of Ppargamma1 Suppresses Cell Growth And Induces Apoptosis In Mcf-7 Breast Cancer Cells, Yekaterina Y. Zaytseva, Xin Wang, R. Chase Southard, Natalie K. Wallis, Michael W. Kilgore

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily and is highly expressed in many human tumors including breast cancer. PPARgamma has been identified as a potential target for breast cancer therapy based on the fact that its activation by synthetic ligands affects the differentiation, proliferation, and apoptosis of cancer cells. However, the controversial nature of current studies and disappointing results from clinical trials raise questions about the contribution of PPARgamma signaling in breast cancer development in the absence of stimulation by exogenous ligands. Recent reports from both in vitro and in vivo studies …

Forage News [2008-12], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Improved Grass Varieties Benefit Farmers
• Alfalfa and the Environment
• Grass May Help Balance Hot Dairy Diets
• Ethanol Maker Files for Bankruptcy Relief
• Pricing Hay: Consider Plant Nutrient Value
• Performance and Physiology of Steers Grazing Toxic Tall Fescue as Influenced by Feeding Soybean Hulls and Steroidal Implants
• Upcoming Events

Aluminum Bioavailability From Tea Infusion, Robert A. Yokel, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

The objective was to estimate oral Al bioavailability from tea infusion in the rat, using the tracer ²⁶Al. ²⁶Al citrate was injected into tea leaves. An infusion was prepared from the dried leaves and given intra-gastrically to rats which received concurrent intravenous ²⁷Al infusion. Oral Al bioavailability (F) was calculated from the area under the ²⁶Al, compared to ²⁷Al, serum concentration × time curves. Bioavailability from tea averaged 0.37%; not significantly different from water (F = 0.3%), or basic sodium aluminum phosphate (SALP) in cheese (F = 0.1 to 0.3%), but greater than acidic SALP …

Manufactured Aluminum Oxide Nanoparticles Decrease Expression Of Tight Junction Proteins In Brain Vasculature, Lei Chen, Robert A. Yokel, Bernhard Hennig, Michal Toborek

Pharmaceutical Sciences Faculty Publications

Manufactured nanoparticles of aluminum oxide (nano-alumina) have been widely used in the environment; however, their potential toxicity provides a growing concern for human health. The present study focuses on the hypothesis that nano-alumina can affect the blood-brain barrier and induce endothelial toxicity. In the first series of experiments, human brain microvascular endothelial cells (HBMEC) were exposed to alumina and control nanoparticles in dose- and time-responsive manners. Treatment with nano-alumina markedly reduced HBMEC viability, altered mitochondrial potential, increased cellular oxidation, and decreased tight junction protein expression as compared to control nanoparticles. Alterations of tight junction protein levels were prevented by cellular …

Differential Gene Expression Associated With Postnatal Equine Articular Cartilage Maturation, Michael J. Mienaltowski, Liping Huang, Arnold J. Stromberg, James N. Macleod

Veterinary Science Faculty Publications

BACKGROUND: Articular cartilage undergoes an important maturation process from neonate to adult that is reflected by alterations in matrix protein organization and increased heterogeneity of chondrocyte morphology. In the horse, these changes are influenced by exercise during the first five months of postnatal life. Transcriptional profiling was used to evaluate changes in articular chondrocyte gene expression during postnatal growth and development.

METHODS: Total RNA was isolated from the articular cartilage of neonatal (0-10 days) and adult (4-5 years) horses, subjected to one round of linear RNA amplification, and then applied to a 9,367-element equine-specific cDNA microarray. Comparisons were made with …

Forage News [2008-11], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• KFGC Awards
• Clayton Geralds Wins KFGC Forage Spokesman Contest
• 29th Alfalfa Conference Program Set
• Forages at KCA
• 9th Grazing Conference Proceedings
• Decision Aid Added to Website
• Enough Hay…
• Animal Grazing Habits
• Time to Focus On Switchgrass Economics
• Limiting Access Time to Hay Can Stretch the Roll
• Horse Gastric Ulcer Syndrome Can Be Controlled With Diet
• Upcoming Events

Childhood Lymphohematopoietic Cancer Incidence And Hazardous Air Pollutants In Southeast Texas, 1995–2004, Kristina W. Whitworth, Elaine Symanski, Ann L. Coker

CRVAW Faculty Journal Articles

BACKGROUND: Cancer is the second leading cause of death among U.S. children with few known risk factors. There is increasing interest in the role of air pollutants, including benzene and 1,3-butadiene, in the etiology of childhood cancers.

OBJECTIVE: Our goal was to assess whether census tracts with the highest benzene or 1,3-butadiene ambient air levels have increased childhood lymphohematopoietic cancer incidence.

METHODS: Our ecologic analysis included 977 cases of childhood lymphohematopoietic cancer diagnosed from 1995–2004. We obtained the U.S. Environmental Protection Agency’s 1999 modeled estimates of benzene and 1,3-butadiene for 886 census tracts surrounding Houston, Texas. We ran Poisson regression …

Stearoyl-Coenzyme A Desaturase 1 Gene Expression Increases After Pioglitazone Treatment And Is Associated With Peroxisomal Proliferator-Activated Receptor-Γ Responsiveness, Aiwei Yao-Borengasser, Negah Rassouli, Vijayalakshmi Varma, Angela M. Bodles, Neda Rasouli, Resat Unal, Bounleut Phanavanh, Gouri Ranganathan, Robert E. Mcgehee Jr., Philip A. Kern

Clinical and Translational Science Faculty Publications

Context and Objective: Stearoyl-coenzyme A desaturase (SCD1) is the rate-limiting enzyme that converts palmitoyl- and stearoyl-coenzyme A to palmitoleoyl- and oleoyl-cownzyme A, respectively. SCD-deficient mice are protected from obesity, and the ob/ob mouse has high levels of SCD. This study was designed to better characterize SCD1 gene and protein expression in humans with varying insulin sensitivity.

Design, Participants, and Setting: In a university hospital clinical research center setting, SCD1 gene expression was measured in sc adipose and vastus lateralis muscle of 86 nondiabetic subjects; 10 wk of pioglitazone (45 mg daily) and metformin (1000 mg twice daily) treatment were assessed …

Technical Variables In High-Throughput Mirna Expression Profiling: Much Work Remains To Be Done, Peter T. Nelson, Wang-Xia Wang, Bernard R. Wilfred, Guiliang Tang

Pathology and Laboratory Medicine Faculty Publications

MicroRNA (miRNA) gene expression profiling has provided important insights into plant and animal biology. However, there has not been ample published work about pitfalls associated with technical parameters in miRNA gene expression profiling. One source of pertinent information about technical variables in gene expression profiling is the separate and more well-established literature regarding mRNA expression profiling. However, many aspects of miRNA biochemistry are unique. For example, the cellular processing and compartmentation of miRNAs, the differential stability of specific miRNAs, and aspects of global miRNA expression regulation require specific consideration. Additional possible sources of systematic bias in miRNA expression studies include …

Focus On Rna Isolation: Obtaining Rna For Microrna (Mirna) Expression Profiling Analyses Of Neural Tissue, Wang-Xia Wang, Bernard R. Wilfred, Donald A. Baldwin, R. Benjamin Isett, Na Ren, Arnold J. Stromberg, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are present in all known plant and animal tissues and appear to be somewhat concentrated in the mammalian nervous system. Many different miRNA expression profiling platforms have been described. However, relatively little research has been published to establish the importance of 'upstream' variables in RNA isolation for neural miRNA expression profiling. We tested whether apparent changes in miRNA expression profiles may be associated with tissue processing, RNA isolation techniques, or different cell types in the sample. RNA isolation was performed on a single brain sample using eight different RNA isolation methods, and results were correlated using a conventional …

Sequiterpene Synthase Gene And Protein, Joe Chappell, Bryan T. Greenhagen

Pharmaceutical Sciences Faculty Patents

The invention relates to sesquiterpene synthases and methods for their production and use. Particularly, the invention provides nucleic acids comprising the nucleotide sequence of citrus valencene synthase (CVS) which codes for at least one CVS. The invention further provides nucleic acids comprising the nucleotide sequence coding for amino acid residues forming the tier 1 and tier 2 domains of CVS. The invention also provides for methods of making and using the nucleic acids and amino acids of the current invention.

Supplementing Cattle On Pasture: When, What And How Much?, Roy Burris

Kentucky Grazing Conference

The biggest advantage of maintaining cattle in the southeast is our ability to grow forages. It is generally an economic advantage to make maximum use of our forage and then supplement only when needed to meet our production goals. Judicious use of extra nutrition to grazing cattle can allow us to meet an objective which was best stated by Hoveland in 1986:

“Our objective is to maintain pasture at the highest quality that the environment will allow and efficiently convert as much of the pasture as possible into saleable animal product.”

Fencing And Watering Systems: Simpler Is Better, Ralph Quillin

Kentucky Grazing Conference

Sustainability and Grazing Management have taken on a new importance in the Americana farm community. The key components of the sustainable approach, profitability, agronomic, social and ecological responsibility and quality of life are becoming obtainable goals for this and future farming generations.

Practical Grazing Management And Feed Strategies To Alleviate Fescue Toxicosis, Glen Aiken

Kentucky Grazing Conference

Tall fescue grown in Kentucky is productive and persistent and that is why the state has 5 million acres of the stuff! Fescue has tolerances to drought, low fertility, and overgrazing that are attributed to a fungal endophyte which infects most tall fescue plants. Unfortunately, these advantages of tall fescue that livestock producers appreciate are offset by reduced calving percentages and calf weight gains caused by consumption of ergot alkaloids produced by the endophyte. Ergot alkaloids affect the physiology of cattle to cause elevation in body temperature, reduced sweating, retention of winter hair coats and uncontrollable growth of summer hair …

Herbicide Options For Pasture Weed Control, Jonathan D. Green

Kentucky Grazing Conference

Weeds have become more evident and problematic in grazed pastures as forage and livestock production systems have intensified. As animals consume the more desirable and palatable plant species in pastures, weedy plants become more abundant. In particular, animals tend to avoid grazing plants which contain thorns, prickly spines, or are unpalatable making some pastures less productive. In fact, many of the more problematic plants observed in Kentucky’s grazed pastures possess these characteristics including thistles, spiny amaranth (spiny pigweed), horsenettle, common cocklebur, tall ironweed, and buttercups.

Horse Pasture Monitoring Program: Results After Three Years, Tom Keene, S. Ray Smith

Kentucky Grazing Conference

Since 2001-2002 and the outbreak of Mare Reproductive Loss Syndrome (MLRS) the University of Kentucky has been developing stronger ties with the state’s equine industry. Approximately 30% of the foal crop was lost in the Central Bluegrass region during this period with a devastating impact on the industry. Traditionally, many Thoroughbred farms have functioned as independent entities, but MLRS helped them to realize that the University of Kentucky had tremendous amount of expertise that they could provide in the areas of animal health, forage management, and other areas. Initially, there were many theories as to the cause of MLRS with …

Forage Legumes Vs. Fertilizer Nitrogen, Garry D. Lacefield

Kentucky Grazing Conference

A few weeks after I started to work as a Forage Extension Specialist at the University of Kentucky, I heard my mentor and forage idol, Mr. Warren Thompson, speak on forage legumes. Warren, along with Dr’s. Tim Taylor and W.C. Templeton had pioneered the “Pasture Renovation Program” in Kentucky. In addition, Mr. Ed Smith had joined the team and collectively they developed the “Power-til Pasture Renovator.” Warren began his presentation by talking about Kentucky Forages pointing out we were so fortunate to have a good grass base and the opportunity to grow lots of legumes. He also talked about all …

Growth Of Grasses And Legumes: Impact On Grazing, S. Ray Smith

Kentucky Grazing Conference

The primary, cool season, perennial pasture grasses used in Kentucky are orchardgrass, bluegrass, and tall fescue. When not grazed or harvested, each of these passes through successive stages of growth in the spring: 1) leafy vegetative; 2) boot with seed heads enclosed in leaf sheath; 3) heading when the seed heads begin to show and, 4) bloom when pollination has occurred ( Figure 2). Since fiber and lignin contents increase steadily beyond the vegetative stage, while percent protein and digestibility decrease, a major goal in grazing management is to maintain these grasses in the leafy, vegetative stage at all times. …

Focal Cerebral Ischemia In The Tnfalpha-Transgenic Rat, L. Creed Pettigrew, Mark S. Kindy, Stephen W. Scheff, Joe E. Springer, Richard J. Kryscio, Yizhao Li, David S. Grass

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: To determine if chronic elevation of the inflammatory cytokine, tumor necrosis factor-alpha (TNFalpha), will affect infarct volume or cortical perfusion after focal cerebral ischemia.

METHODS: Transgenic (TNFalpha-Tg) rats overexpressing the murine TNFalpha gene in brain were prepared by injection of mouse DNA into rat oocytes. Brain levels of TNFalpha mRNA and protein were measured and compared between TNFalpha-Tg and non-transgenic (non-Tg) littermates. Mean infarct volume was calculated 24 hours or 7 days after one hour of reversible middle cerebral artery occlusion (MCAO). Cortical perfusion was monitored by laser-Doppler flowmetry (LDF) during MCAO. Cortical vascular density was quantified by stereology. …

System And Technique For Retrieving Depth Information About A Surface By Projecting A Composite Image Of Modulated Light Patterns, Laurence G. Hassebrook, Daniel L. Lau, Chun Guan

Electrical and Computer Engineering Faculty Patents

A technique, associated system and program code, for retrieving depth information about at least one surface of an object. Core features include: projecting a composite image comprising a plurality of modulated structured light patterns, at the object; capturing an image reflected from the surface; and recovering pattern information from the reflected image, for each of the modulated structured light patterns. Pattern information is preferably recovered for each modulated structured light pattern used to create the composite, by performing a demodulation of the reflected image. Reconstruction of the surface can be accomplished by using depth information from the recovered patterns to …

High-Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis And Method Of Generating The Same, Chang-Guo Zhan, Hoon Cho, Hsin-Hsiung Tai

Pharmaceutical Sciences Faculty Patents

A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, …

Transcriptional Response Of Mexican Axolotls To Ambystoma Tigrinum Virus (Atv) Infection, Jennifer D. Cotter, Andrew Storfer, Robert B. Page, Christopher K. Beachy, S. Randal Voss

Biology Faculty Publications

BACKGROUND: Very little is known about the immunological responses of amphibians to pathogens that are causing global population declines. We used a custom microarray gene chip to characterize gene expression responses of axolotls (Ambystoma mexicanum) to an emerging viral pathogen, Ambystoma tigrinum virus (ATV).

RESULT: At 0, 24, 72, and 144 hours post-infection, spleen and lung samples were removed for estimation of host mRNA abundance and viral load. A total of 158 up-regulated and 105 down-regulated genes were identified across all time points using statistical and fold level criteria. The presumptive functions of these genes suggest a robust innate immune …