215 research outputs found

    Experimental evaluation of temporal particle agglomeration and metal partitioning of urban rainfall-runoff

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    Rainfall-runoff quantity and quality control presents unique challenges due to the complexity and variability of hydrology and rainfall-runoff chemistry as well as the variable nature of constituent-producing processes in the environment. This study investigates two fundamental processes in rainfall-runoff: temporal particle agglomeration and metal partitioning between the solid and aqueous phase. A series of rainfall-runoff events were captured at an urban, Portland concrete cement (PCC) paved site in Baton Rouge, Louisiana and characterized with respect to particle gradation and metal phase fractions (dissolved and particulate) over time from a well-mixed, batch experimental system. Results indicate that equilibria and kinetics of natural particle agglomeration are inversely related to rainfall-runoff volume pH. Further, the average velocity gradient induced on a fully mixed system aids in particle agglomeration by entraining a larger fraction of the total particle gradation for particle-to-particle interaction. Following rainfall-runoff volume phase fractionation and ICP-MS analysis, metal partitioning was found to be in operational equilibrium at the naturally-occurring pH at the point of sample capture at the urban Baton Rouge site. Rainfall-runoff partitioning was compared between similar transportation land use sites in Baton Rouge, LA (544-m2 of PCC pavement) and Cincinnati, Ohio (300-m2 of asphalt pavement). Results suggest that the nature of the roadway material at Baton Rouge and elevated dissolved hardness cause both the state of equilibrium partitioning as well as a higher degree of particulate-bound partitioning. Partitioning is significantly particulate-bound for Cu, Zn, and Cd at the Baton Rouge site with arithmetic mean fp values of 0.72, 0.64, and 0.97, respectively as compared to fp values at the Cincinnati site of 0.04, 0.04, and 0.29 for these metals. While Pb was mostly particulate-bound for both the Baton Rouge and Cincinnati sites, the metal is significantly more particulate-bound at the Baton Rouge site with an fp value of 0.98 as compared to 0.68 for Cincinnati

    Draft genome of methanol-oxidizing Methylobacterium fujisawaense strain LAC1

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    We report the draft genome of Methylobacterium fujisawaense LAC1 isolated from an acidic aquifer in Indian Head, MD, USA. The genome contains 5,883,000 bp and has a GC content of 70% with 5,434 protein-encoding genes with functional assignments. This strain can grow on methanol with lanthanum, a rare earth element

    Reduction of CLABSIs at Riley NICU: It Takes a Village and a Continuous QI Process!

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    The NICU population is one of the most vulnerable for central line associated bloodstream infections (CLABSI) due to extended hospitalizations, necessary central line access, and prolonged catheter periods. Unfortunately, CLABSIs are associated with significant morbidity and mortality, as well as increased hospital costs. The objective set was to measure changes in the rate of CLABSI after implementation, ongoing education, and maintenance of our CLABSI bundle with the ultimate goal of achievement and sustainment of “ZERO CLABSI.

    Reconstruction of the metabolic network of Pseudomonas aeruginosa to interrogate virulence factor synthesis

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    Virulence-linked pathways in opportunistic pathogens are putative therapeutic targets that may be associated with less potential for resistance than targets in growth-essential pathways. However, efficacy of virulence-linked targets may be affected by the contribution of virulence-related genes to metabolism. We evaluate the complex interrelationships between growth and virulence-linked pathways using a genome-scale metabolic network reconstruction of Pseudomonas aeruginosa strain PA14 and an updated, expanded reconstruction of P. aeruginosa strain PAO1. The PA14 reconstruction accounts for the activity of 112 virulence-linked genes and virulence factor synthesis pathways that produce 17 unique compounds. We integrate eight published genome-scale mutant screens to validate gene essentiality predictions in rich media, contextualize intra-screen discrepancies and evaluate virulence-linked gene distribution across essentiality datasets. Computational screening further elucidates interconnectivity between inhibition of virulence factor synthesis and growth. Successful validation of selected gene perturbations using PA14 transposon mutants demonstrates the utility of model-driven screening of therapeutic targets

    Metabolic network analysis predicts efficacy of FDA-approved drugs targeting the causative agent of a neglected tropical disease

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    <p>Abstract</p> <p>Background</p> <p>Systems biology holds promise as a new approach to drug target identification and drug discovery against neglected tropical diseases. Genome-scale metabolic reconstructions, assembled from annotated genomes and a vast array of bioinformatics/biochemical resources, provide a framework for the interrogation of human pathogens and serve as a platform for generation of future experimental hypotheses. In this article, with the application of selection criteria for both <it>Leishmania major </it>targets (e.g. <it>in silico </it>gene lethality) and drugs (e.g. toxicity), a method (MetDP) to rationally focus on a subset of low-toxic Food and Drug Administration (FDA)-approved drugs is introduced.</p> <p>Results</p> <p>This metabolic network-driven approach identified 15 <it>L. major </it>genes as high-priority targets, 8 high-priority synthetic lethal targets, and 254 FDA-approved drugs. Results were compared to previous literature findings and existing high-throughput screens. Halofantrine, an antimalarial agent that was prioritized using MetDP, showed noticeable antileishmanial activity when experimentally evaluated <it>in vitro </it>against <it>L. major </it>promastigotes. Furthermore, synthetic lethality predictions also aided in the prediction of superadditive drug combinations. For proof-of-concept, double-drug combinations were evaluated <it>in vitro </it>against <it>L. major </it>and four combinations involving the drug disulfiram that showed superadditivity are presented.</p> <p>Conclusions</p> <p>A direct metabolic network-driven method that incorporates single gene essentiality and synthetic lethality predictions is proposed that generates a set of high-priority <it>L. major </it>targets, which are in turn associated with a select number of FDA-approved drugs that are candidate antileishmanials. Additionally, selection of high-priority double-drug combinations might provide for an attractive and alternative avenue for drug discovery against leishmaniasis.</p
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