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Genetically Engineered Equine Influenza Virus And Uses Thereof, Peter Palese, Adolfo Garcia-Sastre, Thomas Chambers

Veterinary Science Faculty Patents

The present invention relates, in general, to attenuated equine influenza viruses having an impaired ability to antagonize the cellular interferon (IFN) response, and the use of such attenuated viruses in vaccine and pharmaceutical formulations. In particular, the invention relates to attenuated equine influenza viruses having modifications to an equine NS1 gene that diminish or eliminate the ability of the NS1 gene product to antagonize the cellular IFN response. These viruses replicate in vivo, but demonstrate decreased replication, virulence and increased attenuation, and therefore are well suited for use in live virus vaccines, and pharmaceutical formulations.

Modified Rubisco Large Subunit N-Methyltransferase Useful For Targeting Molecules To The Active-Site Vicinity Of Ribulose-1,5-Bisphosphate, Robert L. Houtz

Horticulture Faculty Patents

The present invention generally relates to a modified Rubisco large subunit ^εN-Methyltransferase (Rubisco LSMT, or RLSMT). The present invention also relates to a modified RLSMT-carbonic anhydrase (RLSMT-CA). This modified RLSMT-CA improves the efficiency of the reduction of CO₂ during photosynthesis, which may increase plant growth rates. The present invention also relates to nucleic acids encoding the modified RLSMT-CA or modified RLSMT. Also, the present invention relates to cells including the modified RLSMT-CA or modified RLSMT, plants containing the modified RLSMT-CA or modified RLSMT, and methods using compositions of the present invention. In addition, the present invention relates to …

Poster Session, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• Western Kentucky Deep Saline Reservoir CO₂ Storage Test: Shallow Groundwater Monitoring Results, E. Glynn Beck and others, Kentucky Geological Survey
• Baseline Soil Properties of a Central Kentucky Riparian Buffer, Amanda Gumbert and others, Dept of Plant and Soil Science, UK
• The Kentucky Water Well Driller’s Certification Program, Scotty E. Robertson and David A. Jackson, Kentucky Division of Water, Frankfort, KY
• Influences of Cladophora Bloom on the Diets of Amblema plicata and Elliptio dilatata in the Upper Green River, Kentucky, Jennifer M. Yates and others, Dept of Biology, Western Kentucky University
• Using Electrical Resistivity to Locate …

Session 2b, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• Agriculture Producer Responses to Government-Funded Conservation Programs to Address Water Quality, Wuyang Hu and others, Dept of Agricultural Economics, UK
• Abatement Costs for Agricultural Non-Point Source Polluters, Jack Schieffer and others, Dept of Agricultural Economics, UK
• Point Source Polluters in the Kentucky River Watershed and the Potential for Water Quality Trading, Ron Childress and others, Dept of Agricultural Economics, UK
• Point Source Abatement Costs and Preferences for Trading Market Mechanisms in the Kentucky River Watershed, Andrew McLaughlin and others, Dept of Agricultural Economics, UK

Session 2a, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• The Potential for Using a P Loss Model to Improve the Accuracy of the Kentucky Phosphorus Index, Carl H. Bolster, USDA-ARS, Bowling Green, KY
• Additive State Space Model – A Promising Approach to Water- Quality-Related Treatment Experiments in Heterogeneous Landscapes, Ole Wendroth, Dept of Plant and Soil Sciences, UK
• Development and Application of Numeric Interpretations of Kentucky’s Narrative Water Quality Standards for Nutrients, Lara Panayotoff, Kentucky Division of Water, Frankfort, KY
• Arsenic Removal in Reactor Systems, Aniruddha Dastidar and Y.T. Wang, Watershed Management Branch and Dept of Civil Engineering, UK
• Trends in Water Quality Issues for …

Session 1c, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• The Effects of Prescribed Fire on Amphibian and Reptile Diversity in an Oak-Grassland Restoration Area, Robert Knopp and Howard Whiteman, Dept Biological Sciences and Watershed Studies, Murray State University
• Results of a Data Evaluation to Establish Priority Remediation Areas for Dry Weather Fecal Contamination in a Karst Influenced Watershed, Steve Evans and others, Third Rock Consultants, Lexington, KY
• Development of In-House Methods for High-Throughput DNA Extraction, Kimberly L. Cook and LorraBelle Hill, USDA-ARS, Bowling Green, KY
• Validation of the Sanitary Category Value Model (SCV) for the Identification of Leaking Sewer Lines: A Study of the West Hickman …

Session 1b, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• University – Habitat for Humanity Green Infrastructure Demonstration Project, Nancy Givens and Terry Wilson, WKU Center for Environmental Education and Sustainability, Bowling Green, KY
• Effectiveness of Pollutant Removal in the McConnell Springs Stormwater Quality Wetland Pond and the Gainesway Pond Retrofit Project, Year Two, David J. Price and Susan L. Plueger, Lexington-Fayette Urban County Government
• Coca-Cola Stormwater Replenish Project, Eric Dawalt and Russ Turpin, Ridegewater, LLC and EcoGro, Lexington, KY
• ITEST and LFUCG Stormwater Professional Development, Brian Radcliffe and Carol D. Hanley, Tracy Farmer Institute for Sustainability and the Environment, UK

Session 1a, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

• A Regionally-Calibrated Critical Flow for Stream Channel Protection, Bob Hawley and others, Sustainable Streams LLC, Louisville, KY
• Monitoring Wetland Restoration Success at North Fork of Irish Creek, Brian C. Reeder, Center for Environmental Education and Institute for Regional Analysis and Public Policy, Morehead State University
• NC2D Open Channel Flow Model: Development and Applications for Stream Restoration Design in Kentucky, Brian J. Belcher, Beaver Creek Hydrology LLC, Lexington, KY
• Using Remote Sensing Tools to Target Stream Protection and Wastewater Treatment BMPs in Rural Kentucky, Catherine Carter and others, Tetra Tech, Research Triangle Park, NC
• Improving Water Quality …

Plenary Session: Water Research Needs In Kentucky, Alan E. Fryar, Peter T. Goodmann, Michael S. Griffin, James A. Kipp

Kentucky Water Resources Annual Symposium

Four panelists were invited to present their visions/predictions of current and future water research needs in Kentucky in an opening plenary session at the 2012 Kentucky Water Resources Annual Symposium. The requested overall general focus was ground water research needs.

Proceedings Of 2012 Kentucky Water Resources Annual Symposium, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

This symposium was planned and conducted as a part of the state water resources research institute annual program that is supported by Grant/Cooperative Agreement Number G11AP20081 from the United States Geological Survey. The contents of this proceedings document and the views and conclusions presented at the symposium are solely the responsibility of the individual authors and presenters and do not necessarily represent the official views of the USGS or of the symposium organizers and sponsors. This publication is produced with the understanding that the United States Government is authorized to reproduce and distribute reprints for government purposes.

Variable Effect Of Co-Infection On The Hiv Infectivity: Within-Host Dynamics And Epidemiological Significance, Diego F. Cuadros, Gisela García-Ramos

Biology Faculty Publications

BACKGROUND: Recent studies have implicated viral characteristics in accounting for the variation in the HIV set-point viral load (spVL) observed among individuals. These studies have suggested that the spVL might be a heritable factor. The spVL, however, is not in an absolute equilibrium state; it is frequently perturbed by immune activations generated by co-infections, resulting in a significant amplification of the HIV viral load (VL). Here, we postulated that if the HIV replication capacity were an important determinant of the spVL, it would also determine the effect of co-infection on the VL. Then, we hypothesized that viral factors contribute to …

Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers

Markey Cancer Center Faculty Publications

Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of …

Development And Functional Analysis Of Novel Genetic Promoters Using Dna Shuffling, Hybridization And A Combination Thereof, Rajiv Ranjan, Sunita Patro, Bhubaneswar Pradhan, Alok Kumar, Indu B. Maiti, Nrisingha Dey

Kentucky Tobacco Research and Development Center Faculty Publications

BACKGROUND: Development of novel synthetic promoters with enhanced regulatory activity is of great value for a diverse range of plant biotechnology applications.

METHODOLOGY: Using the Figwort mosaic virus full-length transcript promoter (F) and the sub-genomic transcript promoter (FS) sequences, we generated two single shuffled promoter libraries (LssF and LssFS), two multiple shuffled promoter libraries (LmsFS-F and LmsF-FS), two hybrid promoters (FuasFScp and FSuasFcp) and two hybrid-shuffled promoter libraries (LhsFuasFScp and LhsFSuasFcp). Transient expression activities of approximately 50 shuffled promoter clones from each of these libraries were assayed in tobacco (Nicotiana tabacum cv. Xanthi) protoplasts. It was observed that most …

Drug Dosage Individualization Based On A Random-Effects Linear Model, Francisco J. Diaz, Myladis R. Cogollo, Edoardo Spina, Vincenza Santoro, Diego M. Rendon, Jose De Leon

Psychiatry Faculty Publications

This article investigates drug dosage individualization when the patient population can be described with a random-effects linear model of a continuous pharmacokinetic or pharmacodynamic response. Specifically, we show through both decision-theoretic arguments and simulations that a published clinical algorithm may produce better individualized dosages than some traditional methods of therapeutic drug monitoring. Since empirical evidence suggests that the linear model may adequately describe drugs and patient populations, and linear models are easier to handle than the nonlinear models traditionally used in population pharmacokinetics, our results highlight the potential applicability of linear mixed models to dosage computations and personalized medicine.

Fibrinogen, Chronic Obstructive Pulmonary Disease (Copd) And Outcomes In Two United States Cohorts, Deepa Valvi, David M. Mannino, Hana Müllerova, Ruth Tal-Singer

Preventive Medicine and Environmental Health Faculty Publications

BACKGROUND: Fibrinogen is a marker of systemic inflammation and may be important in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD).

METHODS: We used baseline data from Atherosclerosis Risk in Communities and Cardiovascular Health Studies to determine the relation between fibrinogen levels and COPD and to examine how fibrinogen levels at baseline affected outcomes of death, development of COPD, lung function decline, and COPD-hospitalizations.

RESULTS: Our study sample included 20,192 subjects, of whom 2995 died during the follow-up period. The mean fibrinogen level was 307.6 mg/dL and 10% of the sample had levels >393.0 mg/dL. Subjects with Stage …

Inverse Relationship Between Psa And Il-8 In Prostate Cancer: An Insight Into A Nf-Κb-Mediated Mechanism, Yong Xu, Daret K. St. Clair, Fang Fang, William H. St. Clair

Toxicology and Cancer Biology Faculty Publications

Background: Prostate specific antigen (PSA) is traditionally used as an indicator for the presence of prostate cancer (PCa) and radiotherapy is generally used to treat inoperable and locally advanced PCa. However, how cellular PSA level is associated with sensitivity of PCa to radiotherapy is unknown. The previous finding that the RelB-based NF-κB alternative pathway differentially regulates PSA and interleukin-8 (IL-8) in aggressive PCa has directed our attention to the role of RelB in the response of PCa to radiotherapy.

Methodology/Principal Findings: RelB and its targets PSA and IL-8 in PCa cells were manipulated by ectopic expression in PCa …

The Bird Of Time: Cognition And The Avian Biological Clock, Vincent M. Cassone, David F. Westneat

Biology Faculty Publications

Avian behavior and physiology are embedded in time at many levels of biological organization. Biological clock function in birds is critical for sleep/wake cycles, but may also regulate the acquisition of place memory, learning of song from tutors, social integration, and time-compensated navigation. This relationship has two major implications. First, mechanisms of the circadian clock should be linked in some way to the mechanisms of all these behaviors. How is not yet clear, and evidence that the central clock has effects is piecemeal. Second, selection acting on characters that are linked to the circadian clock should influence aspects of the …

Alteration Of Tobacco Alkaloid Content Through Modification Of Specific Cytochrome P450 Genes, Ralph E. Dewey, Balaz Siminszky, Steven W. Bowen, Lily Gavilano

Plant and Soil Sciences Faculty Patents

Compositions and methods for reducing the level of nornicotine and N′-nitrosonornicotine (NNN) in Nicotiana plants and plant parts thereof are provided. The compositions comprise isolated polynucleotides and polypeptides for cytochrome P450s that are involved in the metabolic conversion of nicotine to nornicotine in these plants. Expression cassettes, vectors, plants, and plant parts thereof comprising inhibitory sequences that target expression or function of the disclosed cytochrome P450 polypeptides are also provided. Methods for the use of these novel sequences to inhibit expression or function of cytochrome P450 polypeptides involved in this metabolic conversion are also provided. The methods find use in …

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

Pharmaceutical Sciences Faculty Patents

To view this abstract, please download this patent.

Glycoinositolphospholipids From Leishmania Braziliensis And L. Infantum: Modulation Of Innate Immune System And Variations In Carbohydrate Structure, Rafael Ramiro Assis, Izabela Coimbra Ibraim, Fátima Soares Noronha, Salvatore J. Turco, Rodrigo Pedro Soares

Molecular and Cellular Biochemistry Faculty Publications

The essential role of the lipophosphoglycan (LPG) of Leishmania in innate immune response has been extensively reported. However, information about the role of the LPG-related glycoinositolphospholipids (GIPLs) is limited, especially with respect to the New World species of Leishmania. GIPLs are low molecular weight molecules covering the parasite surface and are similar to LPG in sharing a common lipid backbone and a glycan motif containing up to 7 sugars. Critical aspects of their structure and functions are still obscure in the interaction with the vertebrate host. In this study, we evaluated the role of those molecules in two medically important …

A Special Issue On Dna Damage Response And Genome Stability, Guo-Min Li

Markey Cancer Center Faculty Publications

No abstract provided.

Krüppel-Like Factor 4 Regulates Intestinal Epithelial Cell Morphology And Polarity, Tianxin Yu, Xi Chen, Wen Zhang, Juan Li, Ren Xu, Timothy C Wang, Walden Ai, Chunming Liu

Markey Cancer Center Faculty Publications

Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays a vital role in regulating cell lineage differentiation during development and maintaining epithelial homeostasis in the intestine. In normal intestine, KLF4 is predominantly expressed in the differentiated epithelial cells. It has been identified as a tumor suppressor in colorectal cancer. KLF4 knockout mice demonstrated a decrease in number of goblet cells in the colon, and conditional ablation of KLF4 from the intestinal epithelium led to altered epithelial homeostasis. However, the role of KLF4 in differentiated intestinal cells and colon cancer cells, as well as the mechanism by which …

Active Site Mutations Change The Cleavage Specificity Of Neprilysin., Travis Sexton, Lisa J. Hitchcook, David W. Rodgers, Luke H. Bradley, Louis B. Hersh

Molecular and Cellular Biochemistry Faculty Publications

Neprilysin (NEP), a member of the M13 subgroup of the zinc-dependent endopeptidase family is a membrane bound peptidase capable of cleaving a variety of physiological peptides. We have generated a series of neprilysin variants containing mutations at either one of two active site residues, Phe⁵⁶³ and Ser⁵⁴⁶. Among the mutants studied in detail we observed changes in their activity towards leucine⁵-enkephalin, insulin B chain, and amyloid β_1-40. For example, NEP^F563I displayed an increase in preference towards cleaving leucine⁵-enkephalin relative to insulin B chain, while mutant NEP^S546E was less discriminating …

Aluminum In Food – The Nature And Contribution Of Food Additives, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

No abstract provided.

Division Of Undergraduate Education Proposal To The University Of Kentucky Faculty Senate Council: Establishing Policy And Guidelines For University Of Kentucky Dual Credit Partnerships With Secondary Schools, Randolph Hollingsworth

Undergraduate Education White Papers

This proposal was presented via handouts and accompanying slides to the University of Kentucky Faculty Senate Council on February 20, 2012. The proposal hinges on two main purposes:

1. an alternative for Kentucky's high school students that choose to accelerate their time to degree by completing a challenging course at UK; and,
2. a strategic improvement to existing enrollments at UK by high school students that would lead to more long-term relationships and shorten time to a college degree from UK.

The proposal includes definitions of terms commonly used, a few examples from UK benchmark institutions and an example lifecycle for the …

Bmi-1 Absence Causes Premature Brain Degeneration, Guangliang Cao, Minxia Gu, Min Zhu, Junying Gao, Ying Yin, Charles Marshall, Ming Xiao, Jiong Ding, Dengshun Miao

Physical Therapy Faculty Publications

Bmi-1, a polycomb transcriptional repressor, is implicated in cell cycle regulation and cell senescence. Its absence results in generalized astrogliosis and epilepsy during the postnatal development, but the underlying mechanisms are poorly understood. Here, we demonstrate the occurrence of oxidative stress in the brain of four-week-old Bmi-1 null mice. The mice showed various hallmarks of neurodegeneration including synaptic loss, axonal demyelination, reactive gliosis and brain mitochondrial damage. Moreover, astroglial glutamate transporters and glutamine synthetase decreased in the Bmi-1 null hippocampus, which might contribute to the sporadic epileptic-like seizures in these mice. These results indicate that Bmi-1 is required for maintaining …

Ipla2Β Overexpression In Smooth Muscle Exacerbates Angiotensin Ii-Induced Hypertension And Vascular Remodeling, Lindsay E Calderon, Shu Liu, Wen Su, Zhongwen Xie, Zhenheng Guo, Wanda Eberhard, Ming C. Gong

Physiology Faculty Publications

OBJECTIVES: Calcium independent group VIA phospholipase A₂ (iPLA₂β) is up-regulated in vascular smooth muscle cells in some diseases, but whether the up-regulated iPLA₂β affects vascular morphology and blood pressure is unknown. The current study addresses this question by evaluating the basal- and angiotensin II infusion-induced vascular remodeling and hypertension in smooth muscle specific iPLA₂β transgenic (iPLA₂β-Tg) mice.

METHOD AND RESULTS: Blood pressure was monitored by radiotelemetry and vascular remodeling was assessed by morphologic analysis. We found that the angiotensin II-induced increase in diastolic pressure was significantly higher in iPLA₂β-Tg …

A Placebo-Controlled, Double-Blind, Dose-Escalation Study To Assess The Safety, Tolerability And Pharmacokinetics/Pharmacodynamics Of Single And Multiple Intravenous Infusions Of Azd9773 In Patients With Severe Sepsis And Septic Shock, Peter E. Morris, Brian Zeno, Andrew C. Bernard, Xiangning Huang, Shampa Das, Timi Edeki, Steven G. Simonson, Gordon R. Bernard

Surgery Faculty Publications

INTRODUCTION: Tumor necrosis factor-alpha (TNF-α), an early mediator in the systemic inflammatory response to infection, is a potential therapeutic target in sepsis. The primary objective of this study was to determine the safety and tolerability of AZD9773, an ovine, polyclonal, anti-human TNF-α Fab preparation, in patients with severe sepsis. Secondary outcomes related to pharmacokinetic (PK) and pharmacodynamic (PD) parameters.

METHODS: In this double-blind, placebo-controlled, multicenter Phase IIa study, patients were sequentially enrolled into five escalating-dose cohorts (single doses of 50 or 250 units/kg; multiple doses of 250 units/kg loading and 50 units/kg maintenance, 500 units/kg loading and 100 units/kg maintenance, …

Gene Expression Modulation System For Use In Plants And Method For Modulating Gene Expression In Plants, Subba Reddy Palli, Ajay Kumar Singh

Entomology Faculty Patents

An EcR-based gene expression modulation system for use in plants includes an EcR gene expression cassette, a modified RXR gene expression cassette, and a gene-of-interest expression cassette, which can be expressed in a host plant cell.

Lithium Treatment Of Appswdi/Nos2−/− Mice Leads To Reduced Hyperphosphorylated Tau, Increased Amyloid Deposition And Altered Inflammatory Phenotype, Tiffany L. Sudduth, Joan G. Wilson, Angela Everhart, Carol A. Colton, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Lithium is an anti-psychotic that has been shown to prevent the hyperphosphorylation of tau protein through the inhibition of glycogen-synthase kinase 3-beta (GSK3β). We recently developed a mouse model that progresses from amyloid pathology to tau pathology and neurodegeneration due to the genetic deletion of NOS2 in an APP transgenic mouse; the APPSwDI/NOS2-/- mouse. Because this mouse develops tau pathology, amyloid pathology and neuronal loss we were interested in the effect anti-tau therapy would have on amyloid pathology, learning and memory. We administered lithium in the diets of APPSwDI/NOS2-/- mice for a period of eight months, followed by water maze …