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Articles 391 - 420 of 612
Full-Text Articles in Laboratory and Basic Science Research
The Problem Of Too Many Statistical Tests: Subgroup Analyses In A Study Comparing The Effectiveness Of Online And Live Lectures, David M. Lane
The Problem Of Too Many Statistical Tests: Subgroup Analyses In A Study Comparing The Effectiveness Of Online And Live Lectures, David M. Lane
Numeracy
The more statistical analyses performed in the analysis of research data, the more likely it is that one or more of the conclusions will be in error. Multiple statistical analyses can occur when the sample contains several subgroups and the researchers perform separate analyses for each subgroup. For example, separate analyses may be done for different ethnic groups, different levels of education, and/or for both genders. Media reports of research frequently omit information on the number of subgroup analyses performed thus leaving the reader with insufficient information to assess the validity of the conclusions. This article discusses the problems with …
Enhancing Communication Between Scientists, Government Officials, And The Lay Public: Advancing Science And Protecting The Public's Welfare Through Better Multi-Stakeholder Interfacing, Clark J. Lee, Patrick P. Rose, Earl Stoddard Iii
Enhancing Communication Between Scientists, Government Officials, And The Lay Public: Advancing Science And Protecting The Public's Welfare Through Better Multi-Stakeholder Interfacing, Clark J. Lee, Patrick P. Rose, Earl Stoddard Iii
Homeland Security Publications
No abstract provided.
Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco
Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco
Graduate School of Biomedical Sciences Theses and Dissertations
Pathogenic Th17 cells drive progression of many autoimmune diseases. Th17 cells develop from naïve T cells in the immune system after antigen-driven stimulation in a specific cytokine environment. Normally, T cells act to fight off infection, but when not properly controlled, they can cause disease. The cytokine interleukin-23 (IL-23) plays an essential role in the expansion of pathogenic Th17 cells. IL-23 is a heterodimeric protein, composed of a p19 alpha chain and a p40 beta chain. The p40 is also part of IL-12 and binds to the IL-12 receptor beta 1 (IL-12Rβ1) subunit. Thus, it follows that the IL-23 receptor …
Humane Society International’S Global Campaign To End Animal Testing, Troy Seidle
Humane Society International’S Global Campaign To End Animal Testing, Troy Seidle
Experimentation Collection
The Research & Toxicology Department of Humane Society International (HSI) operates a multifaceted and science-driven global programme aimed at ending the use of animals in toxicity testing and research. The key strategic objectives include: a) ending cosmetics animal testing worldwide, via the multinational Be Cruelty-Free campaign; b) achieving near-term reductions in animal testing requirements through revision of product sector regulations; and c) advancing humane science by exposing failing animal models of human disease and shifting science funding toward human biology-based research and testing tools fit for the 21st century. HSI was instrumental in ensuring the implementation of the March 2013 …
A Vision Becoming Reality, Gill Langley
A Vision Becoming Reality, Gill Langley
Laboratory Experiments Collection
Non-animal science in toxicology and health research has been progressing for decades, but only now is it being seen widely as advanced science. The emergence of novel human biology-based tools and models, combined with legislative and regulatory change, a 21st century concept for toxicology, continuing failures in the drug pipeline, and systematic critiques of animal models, have created a pivotal moment of change. The leading edge is starting to become the norm. Humans and other animals are likely to benefit as a result.
Food For Thought … Mechanistic Validation, Thomas Hartung, Sebastian Hoffman, Martin Stephens
Food For Thought … Mechanistic Validation, Thomas Hartung, Sebastian Hoffman, Martin Stephens
Experimentation Collection
Validation of new approaches in regulatory toxicology is commonly defined as the independent assessment of the reproducibility and relevance (the scientific basis and predictive capacity) of a test for a particular purpose. In large ring trials, the emphasis to date has been mainly on reproducibility and predictive capacity (comparison to the traditional test) with less attention given to the scientific or mechanistic basis. Assessing predictive capacity is difficult for novel approaches (which are based on mechanism), such as pathways of toxicity or the complex networks within the organism (systems toxicology). This is highly relevant for implementing Toxicology for the 21st …
History Of The 3rs In Toxicity Testing: From Russell And Burch To 21st Century Toxicology, Martin L. Stephens, Nina S. Mak
History Of The 3rs In Toxicity Testing: From Russell And Burch To 21st Century Toxicology, Martin L. Stephens, Nina S. Mak
Humane Science Movement Collection
Toxicity testing is a key part of the process of assessing the hazards, safety, or risk that chemicals and other substances pose to humans, animals, or the environment. Standardized methods for such testing, typically involving animals, began to emerge during the first half of the 20th century. In 1959, British scientists William Russell and Rex Burch proposed a framework for reducing, refining, or replacing animal use in toxicology and other forms of biomedical experimentation. This “3Rs” or “alternatives” approach emerged at a time of growing sensitivity to the use of animals in experimentation, and progress in its implementation has been …
The Effect Of Visual Wulst Lesions And Trigeminal Nerve Sectioning On The Discrimination Of Magnetic Inclination In The Homing Pigeon (Columba Livia), Merissa Acerbi
Honors Projects
The ability of homing pigeons to return to their loft from unknown places has fascinated scientists for centuries. It is well established that homing pigeons, like migratory birds, posses an innate magnetic inclination compass to determine direction by measuring the angle between the magnetic field vector and the Earth's surface. Recent work has indicated that the avian magnetic compass is light mediated and appears to mediate magnetic information to the brain. This occurs via a visual pathway with processing in the visual Wulst area of the forebrain. There is, however, also evidence from other avian species that magnetic direction may …
Diagnosis Of Schistosoma Mansoni Without The Stool: Comparison Of Three Diagnostic Tests To Detect Schiostosoma Mansoni Infection From Filtered Urine In Zambia, Nilanjan Lodh, James C. L. Mwansa, Mabel M. Mutengo, Clive J. Shiff
Diagnosis Of Schistosoma Mansoni Without The Stool: Comparison Of Three Diagnostic Tests To Detect Schiostosoma Mansoni Infection From Filtered Urine In Zambia, Nilanjan Lodh, James C. L. Mwansa, Mabel M. Mutengo, Clive J. Shiff
Clinical Lab Sciences Faculty Research and Publications
Diagnosis for intestinal Schistosoma mansoni lacks sensitivity and is arduous to conduct. The standard diagnostic tests, Kato-Katz (KK) and circulating cathodic antigen (CCA) both lack sensitivity and with KK, require obtaining, transporting, and examining fresh stool. We compared diagnostic efficacy of KK, CCA, and polymerase chain reaction (PCR) to detect S. mansoni infection (species-specific DNA) from 89 filtered urine samples collected in Zambia. The PCR was the strongest indicator of positive cases with sensitivity and specificity of 100% in comparison to CCA (67% and 60%) and KK (50% and 100%). High positive and negative predictive values (100%) were also indicative …
A Study Of Histone Deacetylase Inhibitors: Determination Of The Binding Energetics Of Suberoylanilide Hydroxamic Acid With Zinc And Cobalt And Preliminary Screening Of Nitric Oxide Donors, Erin Gallagher
College of Science and Health Theses and Dissertations
Inhibiting histone deacetylases (HDACs) can suppress tumor cell growth eventually leading to their death, makeing HDACs an important drug target. Therefore, understanding the mechanism behind inhibiting HDACs is imperative. To determine the thermodynamic parameters for the interaction of a known competitive HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), with zinc(II), the metal ion in the HDAC active site, and cobalt(II), isothermal titration calorimetry (ITC) was used. The results showed that SAHA binds to zinc(II) more strongly than it does to cobalt(II) as the equilibrium binding constants were 4.3 ± 0.5 x 102 M-1 and 2.0 ± 0.5 x 10 …
Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall
Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall
Dissertations and Theses (Open Access)
The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …
Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof
Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof
Dissertations and Theses (Open Access)
Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …
The Use Of Biomarkers Of Toxicity For Integrating In Vitro Hazard Estimates Into Risk Assessment For Humans, Bas Blaauboer, Kim Boekelheide, Harvey Clewell, Mardas Daneshian, Milou M.L. Dingemans, Alan M. Goldberg, Marjoke Heneweer, Joanna Jaworska, Nynke I. Kramer, Marcel Leist, Hasso Seibert, Emanuela Testai, Rob J. Vandebriel, James D. Yager, Joanne Zurlo
The Use Of Biomarkers Of Toxicity For Integrating In Vitro Hazard Estimates Into Risk Assessment For Humans, Bas Blaauboer, Kim Boekelheide, Harvey Clewell, Mardas Daneshian, Milou M.L. Dingemans, Alan M. Goldberg, Marjoke Heneweer, Joanna Jaworska, Nynke I. Kramer, Marcel Leist, Hasso Seibert, Emanuela Testai, Rob J. Vandebriel, James D. Yager, Joanne Zurlo
in Vitro Research Models Collection
The role that in vitro systems can play in toxicological risk assessment is determined by the appropriateness of the chosen methods, with respect to the way in which in vitro data can be extrapolated to the in vivo situation. This report presents the results of a workshop aimed at better defining the use of in vitro-derived biomarkers of toxicity (BoT) and determining the place these data can have in human risk assessment. As a result, a conceptual framework is presented for the incorporation of in vitro-derived toxicity data into the risk assessment process. The selection of BoT takes into account …
Role Of Poly [Adp-Ribose] Polymerase 1 In Retroviral Infection, Vanessa E. Rodriguez ^, Manuel Llano *
Role Of Poly [Adp-Ribose] Polymerase 1 In Retroviral Infection, Vanessa E. Rodriguez ^, Manuel Llano *
COURI Symposium Abstracts, Spring 2012
No abstract provided.
Alternative Approaches For Medical Countermeasures To Biological And Chemical Terrorism And Warfare, Thomas Hartung, Joanne Zurlo
Alternative Approaches For Medical Countermeasures To Biological And Chemical Terrorism And Warfare, Thomas Hartung, Joanne Zurlo
Biomedical Research and Alternative Methods Collection
The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical trials normally crucial for drug development. Animal models have limited predictivity for drug efficacy, as is well known from many disappointments in clinical trials. Traditional in vitro and in silico approaches are not really game changers here, but the substantial investment into novel tools now underway might bring about a second generation of alternative approaches. The avenue pursued focuses primarily on the development of a Human on a Chip, i.e., the combination of different three-dimensional …
Accelerating The Development Of 21st-Century Toxicology: Outcome Of A Human Toxicology Project Consortium Workshop, Martin L. Stephens, Craig Barrow, Melvin E. Andersen, Kim Boekelheide, Paul L. Carmichael, Michael P. Holsapple, Mark Lafranconi
Accelerating The Development Of 21st-Century Toxicology: Outcome Of A Human Toxicology Project Consortium Workshop, Martin L. Stephens, Craig Barrow, Melvin E. Andersen, Kim Boekelheide, Paul L. Carmichael, Michael P. Holsapple, Mark Lafranconi
in Vitro Research Models Collection
The U.S. National Research Council (NRC) report on “Toxicity Testing in the 21st century” calls for a fundamental shift in the way that chemicals are tested for human health effects and evaluated in risk assessments. The new approach would move toward in vitro methods, typically using human cells in a high-throughput context. The in vitro methods would be designed to detect significant perturbations to “toxicity pathways,” i.e., key biological pathways that, when sufficiently perturbed, lead to adverse health outcomes. To explore progress on the report’s implementation, the Human Toxicology Project Consortium hosted a workshop on 9–10 November 2010 in Washington, …
It’S My Body: The Biomedical Ethics Of Cell And Organ Harvest, Christina Perri
It’S My Body: The Biomedical Ethics Of Cell And Organ Harvest, Christina Perri
Common Reading Essay Contest Winners
First Place
The Injustice Of Ignorance, Nicholas Tavares
The Injustice Of Ignorance, Nicholas Tavares
Common Reading Essay Contest Winners
Third Place (tie)
Pursuing Medawar’S Challenge For Full Replacement, Martin Stephens
Pursuing Medawar’S Challenge For Full Replacement, Martin Stephens
Experimentation Collection
In 1969, Nobel Prize-winning scientist Peter Medawar predicted that scientific innovation would someday fully replace the use of animals in biomedical research. Medawar correctly forecast the leveling off and subsequent decline in animal use in the last quarter of the 20th century – a period of remarkable innovation in the life sciences. A 2007 report by the U.S. National Academy of Sciences, Toxicity Testing in the 21st Century, proposed a strategy that is likely to replace all routine animal use in toxicology with innovative methods within one to two decades. Replacing animal use throughout biomedical research is more challenging given …
A Roadmap For The Development Of Alternative (Non-Animal) Methods For Systemic Toxicity Testing, David Basketter, Harvey Clewell, Ian Kimber, Annamaria Rossi, Bas Blaauboer, Robert Burrier, Mardas Daneshian, Chantra Eskes, Alan Goldberg, Nina Hasiwa, Sebastian Hoffmann, Joanna Jaworska, Thomas B. Knudsen, Robert Landsiedel, Marcel Leist, Paul Locke, Gavin Maxwell, James Mckim, Emily Mcvey, Gladys Ouédraogo, Grace Patlewicz, Olavi Pelkonen, Erwin Roggen, Costanza Rovida, Irmela Ruhdel, Michael Schwarz, Andreas Schepky, Greet Schoeters, Nigel Skinner, Kerstin Trentz, Marian Turner, Philippe Vanparys, James Yager, Joanne Zurlo, Thomas Hartung
A Roadmap For The Development Of Alternative (Non-Animal) Methods For Systemic Toxicity Testing, David Basketter, Harvey Clewell, Ian Kimber, Annamaria Rossi, Bas Blaauboer, Robert Burrier, Mardas Daneshian, Chantra Eskes, Alan Goldberg, Nina Hasiwa, Sebastian Hoffmann, Joanna Jaworska, Thomas B. Knudsen, Robert Landsiedel, Marcel Leist, Paul Locke, Gavin Maxwell, James Mckim, Emily Mcvey, Gladys Ouédraogo, Grace Patlewicz, Olavi Pelkonen, Erwin Roggen, Costanza Rovida, Irmela Ruhdel, Michael Schwarz, Andreas Schepky, Greet Schoeters, Nigel Skinner, Kerstin Trentz, Marian Turner, Philippe Vanparys, James Yager, Joanne Zurlo, Thomas Hartung
Biomedical Research and Alternative Methods Collection
Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity. Based on a major analysis of the status of alternative methods (Adler et …
Why Do We Collect?, Allison Marsh
Why Do We Collect?, Allison Marsh
Section 2: Imaging the Microscopic
No abstract provided.
Spotlight On Usc: A.C. Moore Herbarium, Allison Marsh
Spotlight On Usc: A.C. Moore Herbarium, Allison Marsh
Section 2: Imaging the Microscopic
No abstract provided.
Imaging And Aesthetics, Allison Marsh
Imaging And Aesthetics, Allison Marsh
Section 2: Imaging the Microscopic
No abstract provided.
Harnessing Opportunities In Non-Animal Asthma Research For A 21st-Century Science, Gemma L. Buckland
Harnessing Opportunities In Non-Animal Asthma Research For A 21st-Century Science, Gemma L. Buckland
Experimentation Collection
The incidence of asthma is on the increase and calls for research are growing, yet asthma is a disease that scientists are still trying to come to grips with. Asthma research has relied heavily on animal use; however, in light of increasingly robust in vitro and computational models and the need to more fully incorporate the ‘Three Rs’ principles of Replacement, Reduction and Refinement, is it time to reassess the asthma research paradigm? Progress in non-animal research techniques is reaching a level where commitment and integration are necessary. Many scientists believe that progress in this field rests on linking disciplines …
The Role Of The Androgen Receptor Cofactor P44/Wdr77 In Astrocyte Activation, Bryce H. Vincent
The Role Of The Androgen Receptor Cofactor P44/Wdr77 In Astrocyte Activation, Bryce H. Vincent
Dissertations and Theses (Open Access)
Astrogliosis is induced by neuronal damage and is also a pathological feature of the major aging-related neurodegenerative disorders. The mechanisms that control the cascade of astrogliosis have not been well established. In a previous study, we identified a novel androgen receptor (AR)-interacting protein (p44/WDR77) and found that it plays a critical role in the control of proliferation and differentiation of prostate epithelial cells. In the present study, we found that deletion of the p44 gene in the mouse brain caused accelerated aging with dramatic astrogliosis. The p44/WDR77 is expressed in astrocytes and loss of p44/WDR77 expression in astrocytes leads to …
Post-Exercise Hypotension In Brief Exercise, Jeremiah G. Bush
Post-Exercise Hypotension In Brief Exercise, Jeremiah G. Bush
Masters Theses & Specialist Projects
The purpose of this investigation was to examine whether a single 10 minute bout of exercise, performed at multiple intervals throughout the day to equal 30 minutes, can effectively elicit post-exercise hypotension (PEH). Secondly, it is important to explore whether a light (40% VO2R) or moderate (70% VO2R) intensity is required to elicit PEH within 10 minutes. Subjects (N=11) completed a VO2max test utilizing the Bruce Treadmill protocol. Each subject returned within 3 – 5 days to complete two separate exercising trials. A counter balanced system was employed so that each subject did not perform the same intensity rotation (Counter …
Defining The Role Of Egfr Acetylation In Cellular Processes: Clinical Implications, Hui Song
Defining The Role Of Egfr Acetylation In Cellular Processes: Clinical Implications, Hui Song
Dissertations and Theses (Open Access)
Epidermal growth factor receptor (EGFR) is a cell membrane tyrosine kinase receptor and plays a pivotal role in regulating cell growth, differentiation, cell cycle, and tumorigenesis. Deregulation of EGFR causes many diseases including cancers. Intensive investigation of EGFR alteration in human cancers has led to profound progress in developing drugs to target EGFR-mediated cancers. While exploring possible synergistic enhancement of therapeutic efficacy by combining EGFR tyrosine kinase inhibitors (TKI) with other anti-cancer agents, we observed that suberoylanilide hydroxamic acid (SAHA, a deacetylase inhibitor) enhanced TKI-induced cancer cell death, which further led us to question whether SAHA-mediated sensitization to TKI was …
Role Of Vascular Endothelial Growth Factor, Placental Growth Factor And Cytokines On Outer Blood Retinal Barrier Breakdown., Sangeetha Sukumaran
Role Of Vascular Endothelial Growth Factor, Placental Growth Factor And Cytokines On Outer Blood Retinal Barrier Breakdown., Sangeetha Sukumaran
Masters
The aim of this thesis was to investigate the effect of the VEGF family of growth factors and
cytokines TNF- α and IL-1β on oBRB function. The human RPE line ARPE-19 was
employed as an in vitro model of the oBRB. Two-Dimensional gel electrophoresis was
employed to study the effect of growth factors on the RPE proteome. The barrier properties of
the oBRB were evaluated by expression of the TJ proteins occludin or Zo-1, or claudins-1, 2,
3 and 4, determined by western blotting analysis. Claudins 2, 3 and 4 were found to be
significantly up-regulated by TNF-α, while interleukin …
Neuroprotective Effects Of A Nicotinic Acetylcholine Receptor Agonist And Modulator In The Rodent Retina, Kazuhiro Iwamoto
Neuroprotective Effects Of A Nicotinic Acetylcholine Receptor Agonist And Modulator In The Rodent Retina, Kazuhiro Iwamoto
Dissertations
The purpose of this dissertation is to assess the potential neuroprotective effect of an alpha7 nAChR agonist, PNU-282987, and modulator, PNU-120596, in an in vitro model of excitotoxicity and an in vivo model of acute glaucoma. In in vitro studies, retinas obtained from Long Evans rats were cultured using various concentrations of the PNU compounds to analyze neuroprotection against glutamate-induced excitotoxicity. After 3 days in culture, RGCs were identified using an antibody against Thy 1.1, visualized using a fluorescent dye and quantified. In culture, glutamate significantly decreased the number of RGCs. However, if either PNU compound was introduced before the …
Caffeine Supplementation And Moderate Intensity Exercise Modulates The Cytotoxic Lymphocyte Subset (Cd+8) In Naive And Tolerant Individuals, Elizabeth Ann Fedor
Caffeine Supplementation And Moderate Intensity Exercise Modulates The Cytotoxic Lymphocyte Subset (Cd+8) In Naive And Tolerant Individuals, Elizabeth Ann Fedor
Masters Theses & Specialist Projects
The purpose of this investigation was to determine the effects of caffeine supplementation on caffeine tolerant and caffeine naïve individual’s lymphocyte counts, apoptosis and migration levels. In addition, effects of exercise on post-caffeine ingestion lymphocyte counts, apoptosis and migration levels were determined. It was hypothesized that caffeine would alter the immune system cell counts, but that exercise would be able to restore the immune system to homeostasis. Seventeen Western Kentucky University students were tested (males n=7, females n=10; n=7: caffeine tolerant= 200mg or more per day group, n=9: caffeine naïve= 50mg or less per day group). In this double-blind investigation, …