67 research outputs found

    Discussion on a possible neutrino detector located in India

    Get PDF
    We have identified some important and worthwhile physics opportunitites with a possible neutrino detector located in India. Particular emphasis is placed on the geographical advantage with a stress on the complimentary aspects with respect to other neutrino detectors already in operation.Comment: 9 pages; arXiv copy of published proceedings contributio

    Transient Fcho1/2⋅Eps15/R⋅AP-2 Nanoclusters Prime the AP-2 Clathrin Adaptor for Cargo Binding.

    Get PDF
    Clathrin-coated vesicles form by rapid assembly of discrete coat constituents into a cargo-sorting lattice. How the sequential phases of coat construction are choreographed is unclear, but transient protein-protein interactions mediated by short interaction motifs are pivotal. We show that arrayed Asp-Pro-Phe (DPF) motifs within the early-arriving endocytic pioneers Eps15/R are differentially decoded by other endocytic pioneers Fcho1/2 and AP-2. The structure of an Eps15/R⋅Fcho1 μ-homology domain complex reveals a spacing-dependent DPF triad, bound in a mechanistically distinct way from the mode of single DPF binding to AP-2. Using cells lacking FCHO1/2 and with Eps15 sequestered from the plasma membrane, we establish that without these two endocytic pioneers, AP-2 assemblies are fleeting and endocytosis stalls. Thus, distinct DPF-based codes within the unstructured Eps15/R C terminus direct the assembly of temporary Fcho1/2⋅Eps15/R⋅AP-2 ternary complexes to facilitate conformational activation of AP-2 by the Fcho1/2 interdomain linker to promote AP-2 cargo engagement.Supported by NIH R01 GM106963 to L.M.T. and Wellcome Trust grants 090909/Z to D.J.O., 097040 to A.G.W., and 100140 to CIMR.This is the final version of the article. It first appeared from Cell Press / Elsevier via https://doi.org/10.1016/j.devcel.2016.05.00

    Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

    Get PDF
    Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

    Designing, modelling and optimising of an integrated reliability redundant system

    No full text
    The reliability of a system is generally treated as a function of cost; but in many real-life situations reliability will depend on a variety of factors. It is therefore interesting to probe the hidden impact of constraints apart from cost – such as weight, volume, and space. This paper attempts to study the impact of multiple constraints on system reliability. For the purposes of analysis, an integrated redundant reliability system is considered, modelled and solved by applying a Lagrangian multiplier that gives a real valued solution for the number of components, for its reliability at each stage, and for the system. The problem is further studied by using a heuristic algorithm and an integer programming method, and is validated by sensitivity analysis to present an integer solution.Die betroubaarheid van ‘n sisteem word normaalweg as ‘n funksie van koste beskou, alhoewel dit in baie gevalle afhang van ‘n verskeidenheid faktore. Dit is dus interessant om die verskuilde impak van randvoorwaardes soos massa, volume en ruimte te ondersoek. Hierdie artikel poog om die impak van meervoudige randvoorwaardes op sisteem-betroubaarheid te bestudeer. Vir die ontleding, word ‘n geïntegreerde betroubaarheid-sisteem met oortolligheid beskou, gemodelleer en opgelos aan die hand van ‘n Lagrange-vermenigvuldiger. Die problem word verder bestudeer deur gebruik te maak van ‘n heuristiese algoritme en heeltalprogrammering asook gevalideer by wyse van ‘n sensitiwiteitsanalise sodat ‘n heeltaloplossing voorgehou kan word.http://www.journals.co.za/ej/ejour_indeng.htm

    Wear, hardness and corrosion resistance characteristics of tungsten sulfide incorporated electroless Ni-P coatings

    No full text
    A novel composite coating containing WS2 in Ni-P matrix was obtained by electroless deposition route. The incorporation of tungsten sulfide particels enhanced the hardness and corrosion resistance of the Ni-P coatings. It was established that the electroless Ni-P-WS2 coating were able to sustain the low coefficients of friction under sever sliding condition in comparison with the Ni-P coatings. It is evident that the Ni-P_WS2 coatings have the option of being used as solid lubricants to the sliding parts of machinery in aerospace industries. The incorporation of WS2 and the existence of Ni3P in the matrix have been ascertained by XRD, SEM and AFM

    Removal of Toluidine blue in water using green synthesized nanomaterials

    No full text
    Green synthesis is a simple, eco-friendly, and emerging approach to synthesizing nanoparticles and is currently attracting the scientific community worldwide. The objective of the present study was to synthesize green titanium dioxide NPs and evaluate their performance for the photocatalytic treatment of textile wastewater after the secondary treatment process. TiO2 NPs were synthesized using leaf extracts of asausage tree (Kigelia Africana) in asingle step. The green synthesized TiO2 NPs were characterized by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray spectroscopy (EDX), X-Ray Diffraction (XRD), Fourier-Transform Infrared spectroscopy (FT-IR), Diffuse Light Scattering spectroscopy (DLS), Transmission Electron Microscopy (TEM). The findings validated the synthesis of the spherical-shaped TiO2 NPs and their anatase phase. The green-produced TiO2 NPs were used for the treatment of textile effluent. During the photocatalytic treatment of aself-designed dye solution, 99.59% removal of Toluidine blue(TB) dye was achieved within 60 minupon the treatment of green synthesized TiO2 NPs studied by a UV–Visible spectrophotometer. Therefore, the green TiO2NPs that were developed have been examined for the treatment of wastewater, and the catalyst has reusability make it more efficient and affordable, and it might be used to remove organic dyes from textile industrie

    Stability indicating Rp-UPLC method development and validation for the simultaneous estimation of fosnetupitant and palonosetron in bulk and injection dosage form

    No full text
    A stability indicating UPLC method has been developed and validated for the simultaneous determination of fosnetupitant and palonosetron in bulk and in injection dosage form. This combination is used for the prevention of acute and delayed nausea and vomiting associated with initial and repeated courses of highly emetogenic chemotherapy for cancer. The chromatographic analysis was performed on an HSS, RP C18 column (2.1 x 100 mm, 1.8 µm) with an isocratic mobile phase composed of 0.25 M potassium dihydrogen orthophosphate buffer (pH 6.5), pH adjusted with dilute sodium hydroxide:acetonitrile (55:45 v/v), at a flow rate of 0.5 mL/min, and the eluents were monitored at an isosbestic point of 286 nm. The developed method was validated according to the ICH guidelines pertaining to specificity, precision, accuracy, linearity and robustness, and the stability indicating nature of the method was established by forced degradation studies. The retention times of fosnetupitant and palonosetron were observed at 1.390 and 2.404 min, respectively. The developed method proved to be accurate and precise. Linearity was established between 4.70 and 14.10 µg/mL for fosnetupitant and between 0.05 and 0.15 µg/mL for palonosetron. The LOD and LOQ were 0.115 and 0.385 µg/mL, respectively, for fosnetupitant, and 0.005 and 0.016 µg/mL, respectively, for palonosetron. Therefore, the proposed UPLC method was reliable, reproducible, precise and sensitive for the quantification of fosnetupitant and palonosetron

    Kinetic and Mechanistic Parameters of Laccase Catalyzed Direct Electrochemical Oxygen Reduction Reaction

    No full text
    This article presents the kinetic studies of oxygen reduction by one of the most important multicopper oxidases (fungal laccase) using the classic tool of electrochemistry: rotating ring-disk electrode (RRDE). Laccase was immobilized on a multiwalled carbon nanotube (MWNT) modified inert disk electrode using 1-pyrenebutanoic acid succinimidyl ester (PBSE), as a tethering agent. The conditions for laccase immobilization on MWNT were optimized to prepare a highly active composite electro-catalyst for O<sub>2</sub> reduction. The mechanistic as well as kinetic parameters such as Tafel slopes, number of electrons transferred, electrochemical rate constants (for heterogeneous charge transfer) and electron transfer rate constant were calculated from the RRDE experiment results. The Tafel slope obtained was close to the value of that of ideal four-electron reduction of O<sub>2</sub> to water indicating a highly active laccase in the tethered composite. The RRDE results also suggested the presence of intermediate steps in the oxygen reduction reaction. A model pathway for O<sub>2</sub> reduction reaction at the laccase composite modified electrode was postulated, and rate constants for individual reactions in the pathway were calculated. The rate constant for four-electron O<sub>2</sub> reduction was determined to be 1.46 × 10<sup>–3</sup> mol s<sup>–1</sup>, indicating excellent electro-catalytic activity of the laccase-MWNT composite catalyst
    corecore