4,503 research outputs found

    Excavations at the Bull-Jackson Farmstead, Orange County, New York

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    The Right of the State to Inflict Capital Punishment

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    Phage ϕC2 mediates transduction of Tn6215, encoding erythromycin resistance, between Clostridium difficile strains

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    UNLABELLED: In this work, we show that Clostridium difficile phage ϕC2 transduces erm(B), which confers erythromycin resistance, from a donor to a recipient strain at a frequency of 10(-6) per PFU. The transductants were lysogenic for ϕC2 and contained the erm(B) gene in a novel transposon, Tn6215. This element is 13,008 bp in length and contains 17 putative open reading frames (ORFs). It could also be transferred at a lower frequency by filter mating. IMPORTANCE: Clostridium difficile is a major human pathogen that causes diarrhea that can be persistent and difficult to resolve using antibiotics. C. difficile is potentially zoonotic and has been detected in animals, food, and environmental samples. C. difficile genomes contain large portions of horizontally acquired genetic elements. The conjugative elements have been reasonably well studied, but transduction has not yet been demonstrated. Here, we show for the first time transduction as a mechanism for the transfer of a novel genetic element in C. difficile. Transduction may also be a useful tool for the genetic manipulation of C. difficile.Peer reviewe

    Evolution by leaps : gene duplication in bacteria

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    © 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Biology Direct 4 (2009): 46, doi:10.1186/1745-6150-4-46.Sequence related families of genes and proteins are common in bacterial genomes. In Escherichia coli they constitute over half of the genome. The presence of families and superfamilies of proteins suggest a history of gene duplication and divergence during evolution. Genome encoded protein families, their size and functional composition, reflect metabolic potentials of the organisms they are found in. Comparing protein families of different organisms give insight into functional differences and similarities. Equivalent enzyme families with metabolic functions were selected from the genomes of four experimentally characterized bacteria belonging to separate genera. Both similarities and differences were detected in the protein family memberships, with more similarities being detected among the more closely related organisms. Protein family memberships reflected known metabolic characteristics of the organisms. Differences in divergence of functionally characterized enzyme family members accounted for characteristics of taxa known to differ in those biochemical properties and capabilities. While some members of the gene families will have been acquired by lateral exchange and other former family members will have been lost over time, duplication and divergence of genes and functions appear to have been a significant contributor to the functional diversity of today’s microbes. Protein families seem likely to have arisen during evolution by gene duplication and divergence where the gene copies that have been retained are the variants that have led to distinct bacterial physiologies and taxa. Thus divergence of the duplicate enzymes has been a major process in the generation of different kinds of bacteria.This research was supported by the Office of Science (BER), U.S. Department of Energy, Grant No. DE-FG02-08ER64511

    A Computer Model of the Quantity and Chemical Quality of Return Flow

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    A hybrid computer program is developed to predict the water and salt outflow from a river basin in which irrigation is the major water user. A chemical model which predicts the quality of water percolated through a soil profile is combined with a general hydrologic model into form the system simulation model. The chemical model considers the reactions that occur in the soil, including the exchange of calcium, magnesium, and sodium cations on the soil complex, and the dissolution and precipitation of gypsum and lime. The chemical composition of the outflow is a function of these chemical processes within the soil, plus bending of undiverted inflows, evaporations, transpirations, and the mixing of subsurface return flows with groundwater. The six common ions of western waters, namely calcium (Ca++), magnesium Mg ++), sodium (Na +), sulfate (SO 4=), chloride (Cl-), and bicarbonate (HCO3-), are considered in the study. Total dissolved solids (TDS) outflow is obtained by adding the individual ions. The overall model operates on monthly time increments. The model is tested on a portion of the Little Bear River Basin in northern Utah. The model successfully simulates measured outflows of water and each of the six ions for a 24-month period. Only sodium ions, which occurred in small concentrations comprising approximately 2 percent of the total salt outflow, exhibit significant discrepancies between predicted and observed values. All other ions agree within 10 percent on a weight basis for the two-year model period, with correlation coefficients ranging from .87 to .97. The usefulness of the model is demonstrated by a management study of the prototype system. For example, preliminary results indicated that the available water supply could be used to irrigate additional land without unduly increasing the salt outflow from the basin. With minor adjustments the model can be applied to other areas

    Emergence of negative viscosities and colored noise under current-driven Ehrenfest molecular dynamics

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    Molecules in molecular junctions are subject to current-induced forces that can break chemical bonds, induce reactions, destabilize molecular geometry, and halt the operation of the junction. Theories behind current-driven molecular dynamics simulations rely on a perturbative time-scale separation within the system with subsequent use of nonequilibrium Green's functions (NEGF) to compute conservative, non-conservative, and stochastic forces exerted by electrons on nuclear degrees of freedom. We analyze the effectiveness of this approximation, paying particular attention to the phenomenon of negative viscosities. The perturbative approximation is directly compared to the nonequilibrium Ehrenfest approach. We introduce a novel time-stepping approach to calculate the forces present in the Ehrenfest method via exact integration of the equations of motion for the nonequilibrium Green's functions, which does not necessitate a time-scale separation within the system and provides an exact description for the corresponding classical dynamics. We observe that negative viscosities are not artifacts of a perturbative treatment but also emerge in Ehrenfest dynamics. However, the effects of negative viscosity have the possibility of being overwhelmed by the predominantly positive dissipation due to the higher-order forces unaccounted for by the perturbative approach. Additionally, we assess the validity of the white-noise approximation for the stochastic forces, finding that it is justifiable in the presence of a clear time-scale separation and is more applicable when the current-carrying molecular orbital is moved outside of the voltage window. Finally, we demonstrate the method for molecular junction models consisting of one and two classical degrees of freedom

    Identification of Trypanocidal Activity for Known Clinical Compounds Using a New <i>Trypanosoma cruzi</i> Hit-Discovery Screening Cascade

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    <div><p>Chagas disease is a significant health problem in Latin America and the available treatments have significant issues in terms of toxicity and efficacy. There is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities. A key first step is the identification of compounds with anti-<i>Trypanosoma cruzi</i> activity from compound libraries. Here we describe a hit discovery screening cascade designed to specifically identify hits that have the appropriate anti-parasitic properties to warrant further development. The cascade consists of a primary imaging-based assay followed by newly developed and appropriately scaled secondary assays to predict the cidality and rate-of-kill of the compounds. Finally, we incorporated a cytochrome P450 CYP51 biochemical assay to remove compounds that owe their phenotypic response to inhibition of this enzyme. We report the use of the cascade in profiling two small libraries containing clinically tested compounds and identify Clemastine, Azelastine, Ifenprodil, Ziprasidone and Clofibrate as molecules having appropriate profiles. Analysis of clinical derived pharmacokinetic and toxicity data indicates that none of these are appropriate for repurposing but they may represent suitable start points for further optimisation for the treatment of Chagas disease.</p></div

    Energy Impacts of Water Based Recreation

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    The overall objective of the study reported here was to determine to what extent energy accounting could supplement and/or complement economic benfit/cost analyses of water management projects and to specifically examine the energy impacts of water based recreation. The energy accounting literature was carefully reviewed and an energy accounting methodology applicable to water management was devised. Data pertaining to receation at five reservoirs in Utah were assembled from visitation recoreds and on-site surveys. Energy requirements for site construction, travel to and from the recreation site, and recreation at the site were estimated. It was determined that energy devoted to water based recreation is not inconsequential. As much energy is devoted to recreation at Lake Powell alone as is required for all of production agriculture in Utah. It is suggested that while the models developed in this study could be used with confidence in the preparation of energy impact statements the authors are not persuaded energy accounting provides additional information to water use planners beyong that obtainable from traditional economic analysis

    Inhibition of Tendon Cell Proliferation and Matrix Glycosaminoglycan Synthesis by Non-Steroidal Anti-Inflammatory Drugs in vitro

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    The purpose of this study was to investigate the effects of some commonly used non-steroidal anti-inflammatory drugs (NSAIDs) on human tendon. Explants of human digital flexor and patella tendons were cultured in medium containing pharmacological concentrations of NSAIDs. Cell proliferation was measured by incorporation of 3H-thymidine and glycosaminoglycan synthesis was measured by incorporation of 35S-Sulphate. Diclofenac and aceclofenac had no significant effect either on tendon cell proliferation or glycosaminoglycan synthesis. Indomethacin and naproxen inhibited cell proliferation in patella tendons and inhibited glycosaminoglycan synthesis in both digital flexor and patella tendons. If applicable to the in vivo situation, these NSAIDs should be used with caution in the treatment of pain after tendon injury and surgery
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