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Use Of Parthenolide Derivatives As Antileukemic And Cytotoxic Agents, Peter A. Crooks, Craig T. Jordan, Xiaochen Wei

Pharmaceutical Sciences Faculty Patents

Compounds of the formula having anti-tumor activity, wherein R₁ and R₂ are as described herein

Methods Of Delaying Development Of Cea-Associated Tumors Using Anti-Idiotype Antibody 3h1, Malaya Chatterjee, Kenneth A. Foon, Sunil K. Chatterjee

Pharmaceutical Sciences Faculty Patents

The present invention provides methods of delaying development of CEA-associated tumors using the anti-idiotype antibody 3H1, particularly in high-risk individuals.

Pre-Mrna Secondary Structures Influence Exon Recognition, Michael Hiller, Zhaiyi Zhang, Rolf Backofen, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

The secondary structure of a pre-mRNA influences a number of processing steps including alternative splicing. Since most splicing regulatory proteins bind to single-stranded RNA, the sequestration of RNA into double strands could prevent their binding. Here, we analyzed the secondary structure context of experimentally determined splicing enhancer and silencer motifs in their natural pre-mRNA context. We found that these splicing motifs are significantly more single-stranded than controls. These findings were validated by transfection experiments, where the effect of enhancer or silencer motifs on exon skipping was much more pronounced in single-stranded conformation. We also found that the structural context of …

Allelic Heterogeneity At The Equine Kit Locus In Dominant White (W) Horses, Bianca Haase, Samantha A. Brooks, Angela Schlumbaum, Pedro J. Azor, Ernest Bailey, Ferial Alaeddine, Meike Mevissen, Dominik Burger, Pierre-André Poncet, Stefan Rieder, Tosso Leeb

Veterinary Science Faculty Publications

White coat color has been a highly valued trait in horses for at least 2,000 years. Dominant white (W) is one of several known depigmentation phenotypes in horses. It shows considerable phenotypic variation, ranging from approximately 50% depigmented areas up to a completely white coat. In the horse, the four depigmentation phenotypes roan, sabino, tobiano, and dominant white were independently mapped to a chromosomal region on ECA 3 harboring the KIT gene. KIT plays an important role in melanoblast survival during embryonic development. We determined the sequence and genomic organization of the approximately 82 kb equine KIT gene. A mutation …

Transcriptional Control Of Vascular Smooth Muscle Cell Proliferation By Peroxisome Proliferator-Activated Receptor-Γ: Therapeutic Implications For Cardiovascular Diseases, Florence Gizard, Dennis Bruemmer

Internal Medicine Faculty Publications

Proliferation of vascular smooth muscle cells (SMCs) is a critical process for the development of atherosclerosis and complications of procedures used to treat atherosclerotic diseases, including postangioplasty restenosis, vein graft failure, and transplant vasculopathy. Peroxisome proliferator-activated receptor (PPAR) gamma is a member of the nuclear hormone receptor superfamily and the molecular target for the thiazolidinediones (TZD), used clinically to treat insulin resistance in patients with type 2 diabetes. In addition to their efficacy to improve insulin sensitivity, TZD exert a broad spectrum of pleiotropic beneficial effects on vascular gene expression programs. In SMCs, PPARgamma is prominently upregulated during neointima formation …

The Battle Over Implied Preemption: Products Liability And The Fda, Mary J. Davis

Law Faculty Scholarly Articles

A mere five years ago, the Food and Drug Administration (the "FDA") began, for the first time in its 100-year history, to take the position that its prescription drug labeling regulations defeated the ability of injured plaintiffs to pursue common law tort claims based on the adequacy of the labeling. This position, radical to many and rational to others, places federal preemption of prescription drug labeling actions directly in the center of the debate over the proper roles of federal regulation and state tort laws in promoting product safety. The U.S. Supreme Court has contributed to this debate with several …

A Non-Circadian Role For Clock-Genes In Sleep Homeostasis: A Strain Comparison, Paul Franken, Ryan Thomason, H. Craig Heller, Bruce F. O'Hara

Biology Faculty Publications

BACKGROUND: We have previously reported that the expression of circadian clock-genes increases in the cerebral cortex after sleep deprivation (SD) and that the sleep rebound following SD is attenuated in mice deficient for one or more clock-genes. We hypothesized that besides generating circadian rhythms, clock-genes also play a role in the homeostatic regulation of sleep. Here we follow the time course of the forebrain changes in the expression of the clock-genes period (per)-1, per2, and of the clock-controlled gene albumin D-binding protein (dbp) during a 6 h SD and subsequent recovery sleep in three inbred strains of mice for which …

Induction Of Insulin Secretion In Engineered Liver Cells By Nitric Oxide, Latha Muniappan, Sabire Özcan

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Type 1 Diabetes Mellitus results from an autoimmune destruction of the pancreatic beta cells, which produce insulin. The lack of insulin leads to chronic hyperglycemia and secondary complications, such as cardiovascular disease. The currently approved clinical treatments for diabetes mellitus often fail to achieve sustained and optimal glycemic control. Therefore, there is a great interest in the development of surrogate beta cells as a treatment for type 1 diabetes. Normally, pancreatic beta cells produce and secrete insulin only in response to increased blood glucose levels. However in many cases, insulin secretion from non-beta cells engineered to produce insulin occurs …

Chemotherapy And Survival For Patients With Multiple Myeloma: Findings From A Large Nationwide And Population-Based Cohort, Nidhi Rohatgi, Xianglin L. Du, Ann L. Coker, Lemuel L. Moye, Michael Wang, Shenying Fang

CRVAW Faculty Journal Articles

Objective: To assess the patterns of chemotherapy use for patients with multiple myeloma and to determine if chemotherapy is effective in prolonging survival outside the clinical trial settings.

Methods: We studied a nationwide and population-based retrospective cohort of 4902 patients ≥65 years of age with stage II or III multiple myeloma from 1992 to 1999, identified from the Surveillance, Epidemiology, and End-Results-Medicare data. Multivariate logistic regression was used to estimate the odds ratio of receiving chemotherapy and Cox proportional hazard model was used to estimate the hazard ratio of mortality associated with chemotherapy.

Results: Of 4902 patients with stage II …

Agricultural Situation And Outlook Fall 2007, Chuck Corby, Kenneth H. Burdine

Agricultural Situation and Outlook

No abstract provided.

A Comparison Of State Policies For Complying With The Endangered Species Act, Lenahan O'Connell, Ted Grossardt

Kentucky Transportation Center Research Report

In recent years the number of biological assessments (BAs) for the presence of endangered species conducted by KYTC has risen significantly. This was primarily due to new/additional restrictions imposed by the United States Fish and Wildlife Service (USFWS) in 2005. The most consequential restriction was the listing of the Indiana bat as potentially present in all Kentucky counties. Previously BAs for the Indiana bat were only conducted when a project occurred in a county in which the Indiana bat had been observed (a known occurrence). This study reviewed the policies of the states adjacent to Kentucky, as well as those …

A Simple Array Platform For Microrna Analysis And Its Application In Mouse Tissues, Xiaoqing Tang, Jozsef Gal, Xun Zhuang, Wang-Xia Wang, Haining Zhu, Guiliang Tang

Plant and Soil Sciences Faculty Publications

MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that regulate gene expression at the post-transcriptional level and play a critical role in many important biological processes. Most miRNAs are conserved between humans and mice, which makes it possible to analyze their expressions with a set of selected array probes. Here, we report a simple array platform that can detect 553 nonredundant miRNAs encompassing the entire set of miRNAs for humans and mice. The platform features carefully selected and designed probes with optimized hybridization parameters. Potential cross-reaction between mature miRNAs and their precursors was investigated. The array platform was …

Suppression Of Peroxisomal Enzyme Activities And Cytochrome P450 4a Isozyme Expression By Congeneric Polybrominated And Polychlorinated Biphenyls, Larry W. Robertson, Isabelle Berberian, Tim Borges, Li-Chuan Chen, Ching K. Chow, Howard P. Glauert, Johannes G. Filser, Helmut Thomas

Toxicology and Cancer Biology Faculty Publications

The purpose of this study was to determine the effects of PCBs and PBBs on peroxisome proliferator-activated receptor-alpha-(PPARalpha-) associated enzyme activities or protein levels. Male Sprague-Dawley rats were administered a single IP injection (150 mu mol/kg) of either 3,3',4,4'-tetrabromobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, 3,3',5,5'-tetrabromobiphenyl, 2',3,3',4,5-pentachlorobiphenyl, 3,3',4,4',5-pentachlorobiphenyl, 2,2',3,3',5,5'-hexachlorobiphenyl, or 3,3',4,4',5,5'-hexabromobiphenyl in corn oil (10 ml/kg). One week later, the activities of catalase, peroxisomal fatty acyl-CoA oxidase, and peroxisomal beta-oxidation as well as cytochrome P450 4A (CYP4A) protein content were determined in subcellular liver fractions. None of the peroxisomal enzyme activities were significantly increased by any of the halogenated biphenyl congeners tested. Except for minor …

Evaluation Of Us 119 Pine Mountain Safety Improvements (Final Report), Jerry G. Pigman, Kenneth R. Agent

Kentucky Transportation Center Research Report

The Transportation Center at the University of Kentucky was requested to perform an evaluation of the safety improvement project over a 7.1-mile section of US 119 on the Whitesburg side of Pine Mountain in Letcher County to determine whether the types of improvements undertaken affected the overall safety of the roadway. Specific attention was given to the effects of a ban on truck traffic that was implemented in March 2001. In addition, there was a need to determine if the use of flexible design was successful after removal of the truck restriction by permitting trucks with dimensions up to the …

Rapid Phase Adjustment Of Melatonin And Core Body Temperature Rhythms Following A 6-H Advance Of The Light/Dark Cycle In The Horse, Barbara A. Murphy, Jeffrey A. Elliott, Dawn R. Sessions, Mandi M. Vick, Erin L. Kennedy, Barry P. Fitzgerald

Veterinary Science Faculty Publications

BACKGROUND: Rapid displacement across multiple time zones results in a conflict between the new cycle of light and dark and the previously entrained program of the internal circadian clock, a phenomenon known as jet lag. In humans, jet lag is often characterized by malaise, appetite loss, fatigue, disturbed sleep and performance deficit, the consequences of which are of particular concern to athletes hoping to perform optimally at an international destination. As a species renowned for its capacity for athletic performance, the consequences of jet lag are also relevant for the horse. However, the duration and severity of jet lag related …

Mutants And Assay System To Identify Usp/Rxr Ligands, Grace Jones, Davy Jones

Biology Faculty Patents

The invention relates to mutant nuclear hormone receptors that encode mutant nuclear hormone receptors, in which particular amino acid residues are substituted with respect to wild type, so as to be able to detect ligand binding to the mutant receptor by either a change in a physical property of the mutant receptor and/or an transcriptional induction of a nuclear hormone receptor construct. The invention also relates to a nuclear hormone receptor response element denoted by the formula YDRXZ comprising a direct repeat (DR) comprising two half sites separated by X nucleic acid bases; wherein Z indicates the presence of at …

Nucleic Acids Encoding Sarcocystis Neurona Antigen And Uses Thereof, Daniel K. Howe

Veterinary Science Faculty Patents

The present invention provides novel isolated nucleic acids encoding antigenic proteins derived from Sarcocystis neurona, or unique fragments thereof. In particular, the invention provides novel isolated nucleic acids encoding membrane-associated polypeptides SnSAG2, SnSAG3, and SnSAG4. Also provided are purified antigenic polypeptide fragments encoded by the novel nucleic acid sequences set forth herein that encode for SnSAG2, SnSAG3, and SnSAG4. Also provided are isolated nucleic acids capable of selectively hybridizing with the nucleic acid from Sarcocystis neurona. The invention also provides vectors comprising the nucleic acids of the invention encoding an antigenic protein derived from Sarcocystis neurona or a …

Defective Dna Base Excision Repair In Brain From Individuals With Alzheimer's Disease And Amnestic Mild Cognitive Impairment, Lior Weissman, Dong-Gyu Jo, Martin M. Sørensen, Nadja C. De Souza-Pinto, William R. Markesbery, Mark P. Mattson, Vilhelm A. Bohr

Pathology and Laboratory Medicine Faculty Publications

Oxidative stress is thought to play a role in the pathogenesis of Alzheimer's disease (AD) and increased oxidative DNA damage has been observed in brain tissue from AD patients. Base excision repair (BER) is the primary DNA repair pathway for small base modifications such as alkylation, deamination and oxidation. In this study, we have investigated alterations in the BER capacity in brains of AD patients. We employed a set of functional assays to measure BER activities in brain tissue from short post-mortem interval autopsies of 10 sporadic AD patients and 10 age-matched controls. BER activities were also measured in brain …

Impacts Of T-Phylloplanin Gene Knockdown And Of Helianthus And Datura Phylloplanins On Peronospora Tabacina Spore Germination And Disease Potential, Antoaneta B. Kroumova, Ryan W. Shepherd, George J. Wagner

Plant and Soil Sciences Faculty Publications

T-phylloplanin proteins secreted to aerial surfaces of tobacco (Nicotiana tabacum) by short procumbent trichomes inhibit spore germination and blue mold disease caused by the oomycete pathogen Peronospora tabacina. Many other plants were found to contain water-washed leaf surface proteins (phylloplanins), but the functions and properties of these are not known. Here we extend earlier evidence for the antifungal activity of T-phylloplanins using a reverse genetics approach. RNA interference of the T-phylloplanin gene in tobacco ‘T.I. 1068’ resulted in loss of T-phylloplanin mRNA and protein, loss of in vitro spore germination inhibition activity, and leaf infection …

Optical Monitoring System With Molecular Filters, Robert A. Lodder, John Carberry

Pharmaceutical Sciences Faculty Patents

An optical monitoring system for determining the constituents of a sample or specimen. An absorption spectrum is obtained from a sample and is passed through one or more filters having a specified absorption spectrum defined by a single atom or a compound. If the filter's absorption spectrum is included in the sample's absorption spectrum, then the sample contains that atom or compound. The apparatus includes a switching assembly that sequentially places one or more filters into the light path to determine if the subject atom or compound is contained in the sample.

Chronic Administration Of R-Flurbiprofen Attenuates Learning Impairments In Transgenic Amyloid Precursor Protein Mice, Thomas Kukar, Sonya Prescott, Jason L. Eriksen, Vallie Holloway, M. Paul Murphy, Edward H. Koo, Todd E. Golde, Michelle M. Nicolle

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Abeta42 in cell culture and animal models, and that the effect of NSAIDs on Abeta42 is independent of the inhibition of cyclooxygenase by these compounds. Since Abeta42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Abeta42 selectively may be associated with their protective effect. We have previously identified R-flurbiprofen (tarenflurbil) as a selective Abeta42 lowering agent with greatly reduced cyclooxygenase activity that …

Post Hoc Pattern Matching: Assigning Significance To Statistically Defined Expression Patterns In Single Channel Microarray Data, Randall Hulshizer, Eric M. Blalock

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Researchers using RNA expression microarrays in experimental designs with more than two treatment groups often identify statistically significant genes with ANOVA approaches. However, the ANOVA test does not discriminate which of the multiple treatment groups differ from one another. Thus, post hoc tests, such as linear contrasts, template correlations, and pairwise comparisons are used. Linear contrasts and template correlations work extremely well, especially when the researcher has a priori information pointing to a particular pattern/template among the different treatment groups. Further, all pairwise comparisons can be used to identify particular, treatment group-dependent patterns of gene expression. However, these approaches …

Transitions Into And Out Of The Wic Program: A Cause For Concern?, Alison Jacknowitz, Laura Tiehen

University of Kentucky Center for Poverty Research Discussion Paper Series

Despite the health benefits of participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), many eligible households do not participate in WIC during pregnancy and others exit WIC after a child turns one year old. This research uses the first two waves of the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B) to advance our understanding of these transitions into and out of WIC. Findings suggest that those who exhibit better economic health across a variety of dimensions are more likely to delay entry into the program or exit after a child turns one year of age.

Energizing Mirna Research: A Review Of The Role Of Mirnas In Lipid Metabolism, With A Prediction That Mir-103/107 Regulates Human Metabolic Pathways, Bernard R. Wilfred, Wang-Xia Wang, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are powerful regulators of gene expression. Although first discovered in worm larvae, miRNAs play fundamental biological roles-including in humans-well beyond development. MiRNAs participate in the regulation of metabolism (including lipid metabolism) for all animal species studied. A review of the fascinating and fast-growing literature on miRNA regulation of metabolism can be parsed into three main categories: (1) adipocyte biochemistry and cell fate determination; (2) regulation of metabolic biochemistry in invertebrates; and (3) regulation of metabolic biochemistry in mammals. Most research into the 'function' of a given miRNA in metabolic pathways has concentrated on a given miRNA acting upon …

Compounds Of Use In The Treatment Of Epilepsy, Seizure, And Electroconvulsive Disorders, Peter A. Crooks, Aimee K. Bence, David Robert Worthern

Pharmaceutical Sciences Faculty Patents

The present invention provides pharmaceutical preparations and the uses thereof for preventing and/or treating seizures and other electroconvulsive disorders by administering a pharmaceutically effective amount of a therapeutic compound . . .

To view the rest of this abstract, please download this patent.

Efficacy Of The De Novo-Derived Antimicrobial Peptide Wlbu2 Against Oral Bacteria, Karen F. Novak, William J. Diamond, Sreenatha S. Kirakodu, Rebecca Peyyala, Kimberly W. Anderson, Ronald C. Montelaro, Timothy A. Mietzner

Center for Oral Health Research Faculty Publications

The efficacy of a novel synthetic antimicrobial peptide (WLBU2) was evaluated against three oral microorganisms (grown planktonically): Streptococcus gordonii, Fusobacterium nucleatum, and Porphyromonas gingivalis. WLBU2 killed all three species, with F. nucleatum being the most susceptible. WLBU2 also reduced the bacterial burden of S. gordonii and F. nucleatum biofilms.

Trans-Excision-Splicing Ribozyme And Methods Of Use, Stephen M. Testa, Michael A. Bell

Chemistry Faculty Patents

A group I intron-derived ribozyme which binds RNA in trans, excises an internal segment from within the RNA, and splices the remaining 5′ and 3′ ends of the RNA back together (the trans-excision-splicing reaction) is disclosed. The excised segment can be as long as 28 nucleotides, or more, and as little as one nucleotide. The ribozymes of the invention are easily modified to alter their sequence specificity. Such ribozymes represent a new and potentially powerful class of generally adaptable genetic therapeutics.

Corn Stover Availability And Collection Efficiency Using Typical Hay Equipment, Robert M. Prewitt, Michael D. Montross, Scott A. Shearer, Timothy S. Stombaugh, Stephen F. Higgins, Samuel G. Mcneill, Shahab Sokhansanj

Biosystems and Agricultural Engineering Faculty Publications

Corn stover has been identified as a potential feedstock for the production of fermentable sugars and thermochemical processes. The availability and efficiency of typical hay equipment for collecting corn stover has not been well quantified. Corn stover was collected for two years on a central Kentucky farm near Louisville. Six different harvesting treatments, using traditional hay equipment, were used to harvest corn stover. A rotary mower, rotary scythe (flail-type mower with windrow-forming shields), parallel bar rake, and a round baler were utilized. The average stover moisture content prior to grain harvest was above 40%, and field drying was required before …

Soil Microbial Community Response To Hexavalent Chromium In Planted And Unplanted Soil, Ioannis Ipsilantis, Mark S. Coyne

Plant and Soil Sciences Faculty Publications

Theories suggest that rapid microbial growth rates lead to quicker development of metal resistance. We tested these theories by adding hexavalent chromium [Cr(VI)] to soil, sowing Indian mustard (Brassica juncea), and comparing rhizosphere and bulk soil microbial community responses. Four weeks after the initial Cr(VI) application we measured Cr concentration, microbial biomass by fumigation extraction and soil extract ATP, tolerance to Cr and growth rates with tritiated thymidine incorporation, and performed community substrate use analysis with BIOLOG GN plates. Exchangeable Cr(VI) levels were very low, and therefore we assumed the Cr(VI) impact was transient. Microbial biomass was reduced …

Expansion Of The Calcium Hypothesis Of Brain Aging And Alzheimer's Disease: Minding The Store, Olivier Thibault, John C. Gant, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Publications

Evidence accumulated over more than two decades has implicated Ca2+ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca2+ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have revealed aging-related increases in the slow afterhyperpolarization, Ca2+ spikes and currents, Ca2+transients, and L-type voltage-gated Ca2+ channel (L-VGCC) activity. Several of these changes have been associated with age-related deficits in learning or memory. Consequently, one version of the Ca2+ hypothesis has been that increased L-VGCC activity drives many of the other Ca2+-related biomarkers of hippocampal aging. …