116 research outputs found

    A genuinely multi-dimensional relaxation scheme for hyperbolic conservation laws

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    A novel genuinely multi-dimensional relaxation scheme is proposed. Based on a new discrete velocity Boltzmann equation, which is an improvement over previously introduced relaxation systems in terms of isotropic coverage of the multi-dimensional domain by the foot of the characteristic, a finite volume method is developed in which the fluxes at the cell interfaces are evaluated in a genuinely multi-dimensional way, in contrast to the traditional dimension-by-dimension treatment. This algorithm is tested on some bench-mark test problems for hyperbolic conservation laws

    Comment on “Structural Determinants of Drug Partitioning in Surrogates of Phosphatidylcholine Bilayer Strata”

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    This article gives comment to a previous article published in 'Molecular Pharmaceuticals' titled, "Structural Determinants of Drug Partitioning in Surrogates of Phosphatidylcholine Bilayer Strata.

    Towards third generation matrix metalloproteinase inhibitors for cancer therapy

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    The failure of matrix metalloproteinase (MMP) inhibitor drug clinical trials in cancer was partly due to the inadvertent inhibition of MMP antitargets that counterbalanced the benefits of MMP target inhibition. We explore how MMP inhibitor drugs might be developed to achieve potent selectivity for validated MMP targets yet therapeutically spare MMP antitargets that are critical in host protection

    Horizontally acquired glycosyltransferase operons drive salmonellae lipopolysaccharide diversity.

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    The immunodominant lipopolysaccharide is a key antigenic factor for Gram-negative pathogens such as salmonellae where it plays key roles in host adaptation, virulence, immune evasion, and persistence. Variation in the lipopolysaccharide is also the major differentiating factor that is used to classify Salmonella into over 2600 serovars as part of the Kaufmann-White scheme. While lipopolysaccharide diversity is generally associated with sequence variation in the lipopolysaccharide biosynthesis operon, extraneous genetic factors such as those encoded by the glucosyltransferase (gtr) operons provide further structural heterogeneity by adding additional sugars onto the O-antigen component of the lipopolysaccharide. Here we identify and examine the O-antigen modifying glucosyltransferase genes from the genomes of Salmonella enterica and Salmonella bongori serovars. We show that Salmonella generally carries between 1 and 4 gtr operons that we have classified into 10 families on the basis of gtrC sequence with apparent O-antigen modification detected for five of these families. The gtr operons localize to bacteriophage-associated genomic regions and exhibit a dynamic evolutionary history driven by recombination and gene shuffling events leading to new gene combinations. Furthermore, evidence of Dam- and OxyR-dependent phase variation of gtr gene expression was identified within eight gtr families. Thus, as O-antigen modification generates significant intra- and inter-strain phenotypic diversity, gtr-mediated modification is fundamental in assessing Salmonella strain variability. This will inform appropriate vaccine and diagnostic approaches, in addition to contributing to our understanding of host-pathogen interactions

    Vascular Disruption and the Role of Angiogenic Proteins After Spinal Cord Injury

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