143 research outputs found

    Open-resorcinarenes, a new family of multivalent scaffolds

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    A new family of multivalent ligand platforms, the open-resorcinarenes, has been prepared in a straightforward two-step reaction. Modification of the core gives a range of topologically diverse scaffolds; functionalisation confirms the versatility of this approach, as shown through the formation of an octacalixarene array

    Discovery of Inhibitors of Leishmania β-1,2-Mannosyltransferases Using a Click-Chemistry-Derived Guanosine Monophosphate Library

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    Leishmania spp. are a medically important group of protozoan parasites that synthesize a novel intracellular carbohydrate reserve polymer termed mannogen. Mannogen is a soluble homopolymer of β-1,2-linked mannose residues that accumulates in the major pathogenic stages in the sandfly vector and mammalian host. While several steps in mannogen biosynthesis have been defined, none of the enzymes have been isolated or characterized. We report the development of a simple assay for the GDP-mannose–dependent β-1,2-mannosyltransferases involved in mannogen synthesis. This assay utilizes octyl α-d-mannopyranoside to prime the formation of short mannogen oligomers up to 5 mannose residues. This assay was used to screen a focussed library of 44 GMP-triazole adducts for inhibitors. Several compounds provided effective inhibition of mannogen β-1,2-mannosyltransferases in a cell-free membrane preparation. This assay and inhibitor compounds will be useful for dissecting the role of different mannosyltransferases in regulating de novo biosynthesis and elongation reactions in mannogen metabolism

    Research into the efficacy and cost-effectiveness of brief, free of charge and anonymous sex counselling to improve (mental) health in youth: Design of a randomised controlled trial

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    <p>Abstract</p> <p>Background</p> <p>The capacity to form romantic relationships and sexual health of adolescents in the Netherlands are compromised by several factors, including young age of first intercourse and adolescent depression. Several thresholds like own expenses, trust and embarrassment prevent adolescents to seek help for their sexual problems. To overcome these thresholds, brief sex counselling has been developed. It has been used since 2006 within the Rotterdam-Rijnmond Public Health Service, but there is lack of information about the (cost-) effectiveness. In the current study we will evaluate the (cost-) effectiveness of brief sex counselling for sexual problems in adolescents and young adults between 18 and 25 years of age.</p> <p>Methods</p> <p>In a randomised controlled trial we will compare (1) brief sex counselling with (2) intensive sexological treatment, and (3) delayed treatment (waiting list). Embedded in this RCT will be a trial-based economic evaluation, looking at the cost-effectiveness and cost-utility of brief sex counselling versus the two other interventions. Four hundred fifty adolescents (aged 18-25) with sexual problems will be recruited among the persons who visit the Public Health Service (PHS) and through various websites. After a screening procedure, eligible participants will be randomly allocated to one of the three intervention groups. Primary outcome measure of the clinical evaluation is the severity of sexual problems. Other outcomes include psychological distress, especially depression. The economic evaluation will be performed from a societal perspective. Costs will be assessed continuously by a retrospective questionnaire covering the last 3 month. All outcome assessments (including those for the economic evaluation) will take place via the internet at baseline, and at 3, 6, 9, and 12 months after baseline.</p> <p>Discussion</p> <p>The proposed research project will be the first study to provide preliminary data about the effect and cost-effectiveness of brief sex counselling in youth in comparison with intensive sexological treatment and delayed treatment. It is anticipated that positive results in (cost-) effectiveness of the proposed intervention will contribute to the improvement of sexual health care for adolescents and young adults.</p> <p>Trial registration</p> <p>The study has been registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre (NTR1952)</p

    A new type of fiber-optic-based interferometric ellipsometer for in situ and real-time measurements

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    International audienceIt is shown that it is possible to improve interferometric ellipsometers by using a Pockels cell or a Bragg cell hence avoiding the use of any moving components. Furthermore, these methods allow one to increase the beat frequency signal permitting a better insensitiveness to mechanical disturbances. It is also shown how to incorporate an optical fiber between the neutral beam splitter and the sample without losing any information concerning the ellipsometric angles of the sample. Several configurations are described and theoretically analyzed. The last ones do not contain any active component around the sample. They offer a new measurement technique for real-time and in situ measurements

    Critical dimension of biperiodic gratings determined by spectral ellipsometry and Mueller matrix polarimetry

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    We characterized two samples consisting of photoresist layers on silicon with square arrays of square holes by spectroscopic ellipsometry (SE) and Mueller matrix polarimetry (MMP). Hole lateral dimensions and depths were determined by fitting either SE data taken in conventional planar geometry or MMP data in general conical diffraction configurations. A method for objective determination of the optimal measurement conditions based on sensitivity and parameter correlations is presented. When applied to MMP, this approach showed that for one of the samples the optimal incidence angle was 45°, much below the widely used 70° value. The robustness of the dimensional characterisation based on MMP is demonstrated by the high stability of the results provided by separated fits of the data taken at different azimuthal angles
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