Digital Commons Network^™

Sustainable Practices And Related Performance Measures At State Highway Agencies, Lenahan O’Connell

Kentucky Transportation Center Research Report

This report identifies seven ways in which an SHA can harm the environment: (1) excessive consumption of virgin materials; (2) unnecessary levels or amounts of storm water runoff; (3) release of environmental contaminants by SHA employees and contractors; (4) inadequate environmental training of employees and contractors; (5) wasteful use of energy by SHA employees and contractors; (6) the promotion of excessive driving by the public and concomitant release of green house gases; and (7) inadequate oversight mechanisms and procedures to prevent unsustainable practices. The report then identifies the sustainable practices and related performance measures SHAs can use to prevent or …

A Model Of The Information Seeking And Decision Making Of Online Coin Buyers, Donald O. Case

Information Science Faculty Publications

Introduction. The Everyday Life Information Seeking approach suggests that much information behaviour takes place in non-work settings, for example in the pursuit of leisure activities such as hobbies. This study focuses on a community of collectors to examine how they gather information to decide whether to purchase an item for their collection when the target item has an ambiguous or deficient description.

Method. Manual scanning of eBay and other online discussion board for coin buyers led to 187 postings indicating an attempt to reach a purchase decision, or to authenticate a purchased coin, through solicitation or posting of advice.

Analysis. …

Cell Lines Having Enhanced Cell Longevity And Protein Expression, Bruce Allen Webb, Jeremy Kroemer

Entomology Faculty Patents

It is the object of the current invention to provide methods and compositions relating to the expression of vankyrin proteins in cell lines to increase their viability, longevity and capacity for protein production. The inventors have discovered that the expression of P-ank-1 and I²-ank-3 proteins in cell culture has increased the cells' longevity and capacity for endogenous and/or heterologous target protein production. Specifically, the present invention relates to the enhanced expression of endogenous and/or heterologous target proteins/polypeptides in recombinant cells that are also expressing P-ank-1 and/or I²-ank-3 protein compared to expression host cells that are not …

Adar2-Dependent Rna Editing Of Glur2 Is Involved In Thiamine Deficiency-Induced Alteration Of Calcium Dynamics, Shuchen Lee, Guang Yang, Yue Yong, Ying Liu, Liyun Zhao, Jing Xu, Xiaomin Zhang, Yanjie Wan, Chun Feng, Zhiqin Fan, Yong Liu, Jia Luo, Zun-Ji Ke

Internal Medicine Faculty Publications

BACKGROUND: Thiamine (vitamin B1) deficiency (TD) causes mild impairment of oxidative metabolism and region-selective neuronal loss in the central nervous system (CNS). TD in animals has been used to model aging-associated neurodegeneration in the brain. The mechanisms of TD-induced neuron death are complex, and it is likely multiple mechanisms interplay and contribute to the action of TD. In this study, we demonstrated that TD significantly increased intracellular calcium concentrations [Ca2+]i in cultured cortical neurons.

RESULTS: TD drastically potentiated AMPA-triggered calcium influx and inhibited pre-mRNA editing of GluR2, a Ca2+-permeable subtype of AMPA receptors. The Ca2+ permeability of GluR2 is regulated …

Networks Of European Cities In Worlds Of Global Economic And Environmental Change, Stanley D. Brunn, Lomme Devriendt, Andrew Boulton, Ben Derudder, Frank Witlox

Geography Faculty Publications

Geographers have a long tradition of classifying cities using a number of criteria. Population size, industrial production, capital city functions, airline connections, sites of sporting events and major headquarters and banks are among them. While these studies are useful in looking at cities in an economy and population at a given point of time, they are less useful in assessing rapidly occurring changes within a regional or global system. Our research represents a new approach to classify cities and urban systems; we use the volume and networks/linkages or flows associated with electronic Information or “Knowledge worlds.” We argue that in …

T-Lymphocyte Responses To Intestinally Absorbed Antigens Can Contribute To Adipose Tissue Inflammation And Glucose Intolerance During High Fat Feeding, Yuehui Wang, Jianing Li, Lihua Tang, Yu Wang, Richard Charnigo, Willem De Villiers, Erik Eckhardt

Internal Medicine Faculty Publications

BACKGROUND: Obesity is associated with inflammation of visceral adipose tissues, which increases the risk for insulin resistance. Animal models suggest that T-lymphocyte infiltration is an important early step, although it is unclear why these cells are attracted. We have recently demonstrated that dietary triglycerides, major components of high fat diets, promote intestinal absorption of a protein antigen (ovalbumin, "OVA"). The antigen was partly transported on chylomicrons, which are prominently cleared in adipose tissues. We hypothesized that intestinally absorbed gut antigens may cause T-lymphocyte associated inflammation in adipose tissue.

METHODOLOGY/PRINCIPAL FINDINGS: Triglyceride absorption promoted intestinal absorption of OVA into adipose tissue, …

Leishmania Major Survival In Selective Phlebotomus Papatasi Sand Fly Vector Requires A Specific Scg-Encoded Lipophosphoglycan Galactosylation Pattern, Deborah E. Dobson, Shaden Kamhawi, Phillip Lawyer, Salvatore J. Turco, Stephen M. Beverley, David L. Sacks

Molecular and Cellular Biochemistry Faculty Publications

Phlebotomine sand flies that transmit the protozoan parasite Leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. In "selective" sand flies, Leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (LPG), which exhibits species- and strain-specific modifications of the dominant phosphoglycan (PG) repeat units. For the "selective" fly Phlebotomus papatasi PpapJ, side chain galactosyl-modifications (scGal) of PG repeats play key roles in parasite binding. We probed the specificity and properties of this scGal-LPG PAMP (Pathogen Associated …

Intestinal Epithelial Serum Amyloid A Modulates Bacterial Growth In Vitro And Pro-Inflammatory Responses In Mouse Experimental Colitis, Erik R.M. Eckhardt, Jassir Witta, Jian Zhong, Razvan Arsenescu, Violeta Arsenescu, Yu Wang, Sarbani Ghoshal, Marcielle C. De Beer, Frederick C. De Beer, Willem J.S. De Villiers

Internal Medicine Faculty Publications

BACKGROUND: Serum Amyloid A (SAA) is a major acute phase protein of unknown function. SAA is mostly expressed in the liver, but also in other tissues including the intestinal epithelium. SAA reportedly has anti-bacterial effects, and because inflammatory bowel diseases (IBD) result from a breakdown in homeostatic interactions between intestinal epithelia and bacteria, we hypothesized that SAA is protective during experimental colitis.

METHODS: Intestinal SAA expression was measured in mouse and human samples. Dextran sodium sulfate (DSS) colitis was induced in SAA 1/2 double knockout (DKO) mice and in wildtype controls. Anti-bacterial effects of SAA1/2 were tested in intestinal epithelial …

Aminopeptidases Do Not Directly Degrade Tau Protein, K. Martin Chow, Hanjun Guan, Louis B. Hersh

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: Tau hyperphosphorylation and aggregation to form intracellular neurofibrillar tangles is prevalent in a number of tauopathies. Thus there is current interest in the mechanisms involved in Tau clearance. It was recently reported that Tau can be degraded by an aminopeptidase known as the puromycin sensitive aminopeptidase (PSA). Until now PSA has been reported to only cleave peptides, with the largest reported substrates having 30-50 amino acids. We have studied this unique PSA cleavage reaction using a number of different PSA preparations.

RESULTS: An N-terminally His tagged-PSA was expressed and purified from Sf9 insect cells. Although this PSA preparation cleaved …

The Endogenous Soluble Vegf Receptor-2 Isoform Suppresses Lymph Node Metastasis In A Mouse Immunocompetent Mammary Cancer Model, Masa-Aki Shibata, Jayakrishna Ambati, Eiko Shibata, Romulo J. C. Albuquerque, Junji Morimoto, Yuko Ito, Yoshinori Otsuki

Ophthalmology and Visual Science Faculty Publications

BACKGROUND: Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. A new splicing variant, endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2) that we recently identified is an endogenous selective inhibitor of lymphangiogenesis. To evaluate the antimetastatic potential of esVEGFR-2, gene therapy with vector expressing esVEGFR-2 (pesVEGFR-2) or endostatin (pEndo) as a positive control was conducted on murine metastatic mammary cancer.

METHODS: Syngeneic inoculated metastatic mammary cancers received direct intratumoral injection of pesVEGFR-2, pEndo or pVec as control, once a week for six weeks. In vivo gene electrotransfer was performed on the tumors after each …

Dysregulation Of The Mitogen Granulin In Human Cancer Through The Mir-15/107 Microrna Gene Group, Wang-Xia Wang, Natasha Kyprianou, Xiaowei Wang, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

Granulin (GRN) is a potent mitogen and growth factor implicated in many human cancers, but its regulation is poorly understood. Recent findings indicate that GRN is regulated strongly by the microRNA miR-107, which functionally overlaps with miR-15, miR-16, and miR-195 due to a common 5′ sequence critical for target specificity. In this study, we queried whether miR-107 and paralogs regulated GRN in human cancers. In cultured cells, anti-argonaute RNA coimmunoprecipitation with downstream microarray analyses indicates that GRN mRNA is directly targeted by numerous miR-15/107 miRNAs. We further tested this association in human tumors. MiR-15 and miR-16 are known to be …

Cyanidin-3-Glucoside Inhibits Ethanol-Induced Invasion Of Breast Cancer Cells Overexpressing Erbb2, Mei Xu, Kimberly A. Bower, Siying Wang, Jacqueline A. Frank, Gang Chen, Min Ding, Shiow Wang, Xianglin Shi, Zunji Ke, Jia Luo

Internal Medicine Faculty Publications

BACKGROUND: Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This …

Endothelial Cell Capture Of Heparin-Binding Growth Factors Under Flow, Bing Zhao, Changjiang Zhang, Kimberly Forsten-Williams, Jun Zhang, Michael Fannon

Ophthalmology and Visual Science Faculty Publications

Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated …

Retention And Loss Of Rna Interference Pathways In Trypanosomatid Protozoans, Lon-Fye Lye, Katherine Owens, Huafang Shi, Silvane M. F. Murta, Ana Carolina Vieira, Salvatore J. Turco, Christian Tschudi, Elisabetta Ullu, Stephen M. Beverley

Molecular and Cellular Biochemistry Faculty Publications

RNA interference (RNAi) pathways are widespread in metaozoans but the genes required show variable occurrence or activity in eukaryotic microbes, including many pathogens. While some Leishmania lack RNAi activity and Argonaute or Dicer genes, we show that Leishmania braziliensis and other species within the Leishmania subgenus Viannia elaborate active RNAi machinery. Strong attenuation of expression from a variety of reporter and endogenous genes was seen. As expected, RNAi knockdowns of the sole Argonaute gene implicated this protein in RNAi. The potential for functional genetics was established by testing RNAi knockdown lines lacking the paraflagellar rod, a key component of the …

Plant Phenolics: Extraction, Analysis And Their Antioxidant And Anticancer Properties, Jin Dai, Russell J. Mumper

Pharmaceutical Sciences Faculty Publications

Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro …

Complement Factor H-Related Proteins Cfhr2 And Cfhr5 Represent Novel Ligands For The Infection-Associated Crasp Proteins Of Borrelia Burgdorferi, Corinna Siegel, Teresia Hallström, Christine Skerka, Hannes Eberhardt, Barbara Uzonyi, Tobias Beckhaus, Michael Karas, Reinhard Wallich, Brian Stevenson, Peter F. Zipfel, Peter Kraiczy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: One virulence property of Borrelia burgdorferi is its resistance to innate immunity, in particular to complement-mediated killing. Serum-resistant B. burgdorferi express up to five distinct complement regulator-acquiring surface proteins (CRASP) which interact with complement regulator factor H (CFH) and factor H-like protein 1 (FHL1) or factor H-related protein 1 (CFHR1). In the present study we elucidate the role of the infection-associated CRASP-3 and CRASP-5 protein to serve as ligands for additional complement regulatory proteins as well as for complement resistance of B. burgdorferi.

METHODOLOGY/PRINCIPAL FINDINGS: To elucidate whether CRASP-5 and CRASP-3 interact with various human proteins, both borrelial proteins …

Agmatine And Agmatine Analogs In The Treatment Of Epilepsy, Seizure, And Electroconvulsive Disorders, Peter A. Crooks, Aimee K. Bence, David R. Worthen

Pharmaceutical Sciences Faculty Patents

Pharmaceutical preparations containing of agmatine, congeners, analogs or derivatives thereof for use in preventing or treating epilepsy, seizures and other electroconvulsive disorders are provided. Embodiments include administering an effective amount of agmatine, an agmatine analog or a pharmaceutically acceptable salt thereof to a human subject in need of treatment or prevention of epilepsy, seizure or other electroconvulsive disorder to treat, reduce, or prevent the disorder in the subject.

Compositions And Methods For Inhibiting Drusen Complement Components C3a And C5a For The Treatment Of Age-Related Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Activated C3 (C3a) and its receptor (C3aR) and activated C5 (C5a) and its receptor (C5aR) have been shown to induce vascular endothelial growth factor (VEGF) expression in vitro and in vivo. Compositions and methods for inhibiting C3a, C3aR, C5a and C5aR for the treatment and/or prevention of neovascular disease are provided. Also provided are Novel therapeutic targets and diagnostic markers for choroidal neovascularization.

Composition And Methods For Treating Yersinia Pestis Infection, Susan C. Straley, Brian S. Murphy, Stanislav Forman, Christine R. Wulff, Robert D. Perry, Tanya Myers-Morales

Microbiology, Immunology and Molecular Genetics Faculty Patents

Compositions and methods for treating a Yersinia pestis (Y. pestis) infection are provided. Compositions and methods of for inducing an immune response in a subject are provided. Composition can include a YadC polypeptide.

Vitamin D Binding Protein-Macrophage Activating Factor Directly Inhibits Proliferation, Migration, And Upar Expression Of Prostate Cancer Cells, Kalvin J. Gregory, Bing Zhao, Diane R. Bielenberg, Sami Dridi, Jason Wu, Weihua Jiang, Bin Huang, Steven Pirie-Shepherd, Michael Fannon

Ophthalmology and Visual Science Faculty Publications

BACKGROUND: Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors.

METHODS AND FINDINGS: In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry …

The Us Preventive Service Taskforce And The Guide To Clinical Preventive Services., F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Route Of Administration For Illicit Prescription Opioids: A Comparison Of Rural And Urban Drug Users, April M. Young, Jennifer R. Havens, Carl G. Leukefeld

Behavioral Science Faculty Publications

BACKGROUND: Nonmedical prescription opioid use has emerged as a major public health concern in recent years, particularly in rural Appalachia. Little is known about the routes of administration (ROA) involved in nonmedical prescription opioid use among rural and urban drug users. The purpose of this study was to describe rural-urban differences in ROA for nonmedical prescription opioid use.

METHODS: A purposive sample of 212 prescription drug users was recruited from a rural Appalachian county (n = 101) and a major metropolitan area (n = 111) in Kentucky. Consenting participants were given an interviewer-administered questionnaire examining sociodemographics, psychiatric disorders, and self-reported …

High-Intensity Mechanical Therapy For Loss Of Knee Extension For Worker's Compensation And Non-Compensation Patients, Amanda L. Dempsey, Thomas P. Branch, Timothy Mills, Robert M. Karsch

Orthopaedic Surgery and Sports Medicine Faculty Publications

BACKGROUND: Knee flexion contractures have been associated with increased pain and a reduced ability to perform activities of daily living. Contractures can be treated either surgically or conservatively, but these treatment options may not be as successful with worker's compensation patients. The purposes of retrospective review were to 1) determine the efficacy of using adjunctive high-intensity stretch (HIS) mechanical therapy to treat flexion contractures, and 2) compare the results between groups of worker's compensation and non-compensation patients.

METHODS: Fifty-six patients (19 women, 37 men, age = 51.5 ± 17.0 years) with flexion contractures were treated with HIS mechanical therapy as …

Community Health Assesments, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Insulin Degrading Enzyme Assays For Treatment Of Alzheimer's Disease, Louis B. Hersh

Molecular and Cellular Biochemistry Faculty Patents

Estrogen has been shown to increase the expression and activity of amyloid peptide inactivating enzymes in the brain. Peptides have been shown to increase the activity of an amyloid peptide inactivating enzyme. Methods of identifying compounds for, and methods of treating patients with, Alzheimer's Disease is disclosed.

Public Health Services And Systems Research: Data For Research, F. Douglas Scutchfield Md

Preventive Medicine and Environmental Health Presentations

No abstract provided.

Global Ky (Fall 2010), University Of Kentucky International Center

Global Kentucky

No abstract provided.

Mapsplice: Accurate Mapping Of Rna-Seq Reads For Splice Junction Discovery, Kai Wang, Darshan Singh, Zheng Zeng, Stephen J. Coleman, Yan Huang, Gleb L. Savich, Xiaping He, Piotr Mieczkowski, Sara A. Grimm, Charles M. Perou, James N. Macleod, Derek Y. Chiang, Jan F. Prins, Jinze Liu

Computer Science Faculty Publications

The accurate mapping of reads that span splice junctions is a critical component of all analytic techniques that work with RNA-seq data. We introduce a second generation splice detection algorithm, MapSplice, whose focus is high sensitivity and specificity in the detection of splices as well as CPU and memory efficiency. MapSplice can be applied to both short (<75 bp) and long reads (≥75 bp). MapSplice is not dependent on splice site features or intron length, consequently it can detect novel canonical as well as non-canonical splices. MapSplice leverages the quality and diversity of read alignments of a given splice to increase accuracy. We demonstrate that MapSplice achieves higher sensitivity and specificity than TopHat and SpliceMap on a set of simulated RNA-seq data. Experimental studies also support the accuracy of the algorithm. Splice junctions derived from eight breast cancer RNA-seq datasets recapitulated the extensiveness of alternative splicing on a global level as well as the differences between molecular subtypes of breast cancer. These combined results indicate that MapSplice is a highly accurate algorithm for the alignment of RNA-seq reads to splice junctions. Software download URL: http://www.netlab.uky.edu/p/bioinfo/MapSplice.

Factors Impacting Burley Outlook, Department Of Agricultural Economics, University Of Kentucky

Agricultural Economics Presentations

No abstract provided.

Agricultural Situation And Outlook Fall 2010, Sara Williamson, Kenneth H. Burdine

Agricultural Situation and Outlook

No abstract provided.