21 research outputs found

    Soliciting feedback for a British Standard Code of Practice for using IT in delivering assessments

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    The British Standards Institution has set up a panel, IST/43/-/1, to draw at a new British Standard Code of Practice for the use of IT in delivering assessments (BS 7988). This paper describes the work in progress and plans for creating this standard

    Genetic_AND_metric_distance_per_cluster

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    Pairwise Genetic and Matrix distances among localities within each genetic groups (EUR,ASI, ME) to test for IB

    Functional and Structural Analysis of Phenazine <i>O</i>‑Methyltransferase LaPhzM from <i>Lysobacter antibioticus</i> OH13 and One-Pot Enzymatic Synthesis of the Antibiotic Myxin

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    Myxin is a well-known antibiotic that had been used for decades. It belongs to the phenazine natural products that exhibit various biological activities, which are often dictated by the decorating groups on the heteroaromatic three-ring system. The three rings of myxin carry a number of decorations, including an unusual aromatic <i>N</i>5,<i>N</i>10-dioxide. We previously showed that phenazine 1,6-dicarboxylic acid (PDC) is the direct precursor of myxin, and two redox enzymes (LaPhzS and LaPhzNO1) catalyze the decarboxylative hydroxylation and aromatic <i>N</i>-oxidations of PDC to produce iodinin (1.6-dihydroxy-<i>N</i>5,<i>N</i>10-dioxide phenazine). In this work, we identified the <i>LaPhzM</i> gene from <i>Lysobacter antibioticus</i> OH13 and demonstrated that <i>LaPhzM</i> encodes a SAM-dependent <i>O</i>-methyltransferase converting iodinin to myxin. The results further showed that LaPhzM is responsible for both monomethoxy and dimethoxy formation in all phenazine compounds isolated from strain OH13. LaPhzM exhibits relaxed substrate selectivity, catalyzing <i>O</i>-methylation of phenazines with non-, mono-, or di-<i>N</i>-oxide. In addition, we demonstrated a one-pot biosynthesis of myxin by <i>in vitro</i> reconstitution of the three phenazine-ring decorating enzymes. Finally, we determined the X-ray crystal structure of LaPhzM with a bound cofactor at 1.4 Ă… resolution. The structure provided molecular insights into the activity and selectivity of the first characterized phenazine <i>O</i>-methyltransferase. These results will facilitate future exploitation of the thousands of phenazines as new antibiotics through metabolic engineering and chemoenzymatic syntheses

    Final GBS vcf dataset 4274 SNPs

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    Final GBS dataset used for population genetic inferences (.vcf) and its associated information for each sample used (X/Y, Country, cluster assignation, ID)

    Heterocyclic Aromatic <i>N</i>‑Oxidation in the Biosynthesis of Phenazine Antibiotics from Lysobacter antibioticus

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    Heterocyclic aromatic <i>N</i>-oxides often have potent biological activities, but the mechanism for aromatic <i>N</i>-oxidation is unclear. Six phenazine antibiotics were isolated from Lysobacter antibioticus OH13. A 10 gene cluster was identified for phenazine biosynthesis. Mutation of <i>LaPhzNO1</i> abolished all <i>N</i>-oxides, while non-oxides markedly increased. LaPhzNO1 is homologous to Baeyer–Villiger flavoproteins but was shown to catazlye phenazine <i>N</i>-oxidation. LaPhzNO1 and LaPhzS together converted phenazine 1,6-dicarboxylic acid to 1,6-dihydroxyphenazine <i>N</i>5,<i>N</i>10-dioxide. LaPhzNO1 also catalyzed <i>N</i>-oxidation of 8-hydroxyquinoline

    Antiretroviral agents available for first-line ART, ART anchor agent, reported reason for major modification and selected switched-to ART regimen by country income grouping.

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    *<p>Individual ARV agents with each class where less than 5 people initiated where excluded from the total count.</p><p>N(t)RTI = <u>N</u>ucleos<u>(t)</u>ide <u>R</u>everse <u>T</u>ranscriptase <u>I</u>nhibitor, NNRTI = <u>N</u>on-<u>N</u>ucleoside <u>R</u>everse <u>T</u>ranscriptase <u>I</u>nhibitor, PI = <u>P</u>rotease <u>I</u>nhibitors, II = <u>I</u>ntegrase <u>I</u>nhibitor.</p

    Predictors of major first-line modification by income grouping.

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    <p>Hazard ratios calculated from multivariable model including adjustment for site resourcing.</p>*<p>Closest record to ART initiation within a window of 6 month prior to ART and 1 week following ART initiation.</p
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