689 research outputs found

    Functional analysis of the interface between the tandem C2 domains of synaptotagmin-1.

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    C2 domains are widespread motifs that often serve as Ca(2+)-binding modules; some proteins have more than one copy. An open issue is whether these domains, when duplicated within the same parent protein, interact with one another to regulate function. In the present study, we address the functional significance of interfacial residues between the tandem C2 domains of synaptotagmin (syt)-1, a Ca(2+) sensor for neuronal exocytosis. Substitution of four residues, YHRD, at the domain interface, disrupted the interaction between the tandem C2 domains, altered the intrinsic affinity of syt-1 for Ca(2+), and shifted the Ca(2+) dependency for binding to membranes and driving membrane fusion in vitro. When expressed in syt-1 knockout neurons, the YHRD mutant yielded reductions in synaptic transmission, as compared with the wild-type protein. These results indicate that physical interactions between the tandem C2 domains of syt-1 contribute to excitation-secretion coupling.This study was supported by a grant from the NIH (MH061876). C.S.E. was supported by a PhRMA Foundation predoctoral fellowship and by a UW–Madison Molecular and Cellular Pharmacology Training Grant (5T32-GM008688). R.B.S. was supported by an NIH grant (AR063634). P.J. and J.M.E. were funded by Kidney Research UK, and J.M.E. was funded by the Biotechnology and Biological Sciences Research Council (Grant BB/J018236/1). E.R.C. is an investigator of the Howard Hughes Medical Institute.This is the final version of the article. It first appeared from the American Society for Cell Biology via http://dx.doi.org/10.1091/mbc.E15-07-050

    A three arm cluster randomised controlled trial to test the effectiveness and cost-effectiveness of the SMART work & life intervention for reducing daily sitting time in office workers : study protocol

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    Background:Office-based workers typically spend 70-85% of working hours, and a large proportion of leisure time, sitting. High levels of sitting have been linked to poor health. There is a need for fully powered randomised controlled trials (RCTs) with long-term follow-up to test the effectiveness of interventions to reduce sitting. This paper describes the methodology of a three-arm cluster RCT designed to determine the effectiveness and cost-effectiveness of the SMART Work & Life intervention, delivered with and without a height-adjustable desk, for reducing daily sitting. Methods/Design:A three-arm cluster RCT of 33 clusters (660 council workers) will be conducted in three areas in England (Leicester; Manchester; Liverpool). Office groups (clusters) will be randomised to the SMART Work & Life intervention delivered with (group 1) or without (group 2) a height-adjustable desk or a control group (group 3). SMART Work & Life includes organisational (e.g., management buy-in, provision/support for standing meetings), environmental (e.g., relocating waste bins, printers), and group/individual (education, action planning, goal setting, addressing barriers, coaching, self-monitoring, social support) level behaviour change strategies, with strategies driven by workplace champions. Baseline, 3, 12 and 24 month measures will be taken. Objectively measured daily sitting time (activPAL3). objectively measured sitting, standing, stepping, prolonged sitting and moderate-to-vigorous physical activity time and number of steps at work and daily; objectively measured sleep (wrist accelerometry). Adiposity, blood pressure, fasting glucose, glycated haemoglobin, cholesterol (total, HDL, LDL) and triglycerides will be assessed from capillary blood samples. Questionnaires will examine dietary intake, fatigue, musculoskeletal issues, job performance and satisfaction, work engagement, occupational and general fatigue, stress, presenteeism, anxiety and depression and sickness absence (organisational records). Quality of life and resources used (e.g. GP visits, outpatient attendances) will also be assessed. We will conduct a full process evaluation and cost-effectiveness analysis. Discussion:The results of this RCT will 1) help to understand how effective an important simple, yet relatively expensive environmental change is for reducing sitting, 2) provide evidence on changing behaviour across all waking hours, and 3) provide evidence for policy guidelines around population and workplace health and well-being. Trial registration: ISRCTN11618007 . Registered on 21 January 2018

    Molecular dynamics simulation of the order-disorder phase transition in solid NaNO2_2

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    We present molecular dynamics simulations of solid NaNO2_2 using pair potentials with the rigid-ion model. The crystal potential surface is calculated by using an \emph{a priori} method which integrates the \emph{ab initio} calculations with the Gordon-Kim electron gas theory. This approach is carefully examined by using different population analysis methods and comparing the intermolecular interactions resulting from this approach with those from the \emph{ab initio} Hartree-Fock calculations. Our numerics shows that the ferroelectric-paraelectric phase transition in solid NaNO2_2 is triggered by rotation of the nitrite ions around the crystallographical c axis, in agreement with recent X-ray experiments [Gohda \textit{et al.}, Phys. Rev. B \textbf{63}, 14101 (2000)]. The crystal-field effects on the nitrite ion are also addressed. Remarkable internal charge-transfer effect is found.Comment: RevTeX 4.0, 11 figure

    Reverse analysis of scan strategies for controlled 3D laser forming of sheet metal

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    Laser forming is an advanced manufacturing technique for the shaping and adjustment of metallic and non-metallic components by controlled laser induced thermal stress. Important advantages of laser forming include the absence of external mechanical tooling, flexibility and potential for automatic control. A large number of relevant two-dimensional laser forming studies have been completed to date. However, for the production of complex 3D shapes, such as ship hull components, airplane fuselages and automotive bodies, two-dimensional laser forming is limited. Therefore, in order to advance process for realistic applications, the investigation of the 3D scanning strategies becomes essential. This includes both in plane shortening and out-of-plane bending. In order to determining the scanning patterns and process parameters for forming any arbitrary 3D shape, numerical simulation is a strong tool to analyse the required stress and strain distribution and related processing parameters. In the presented investigation, the object is to develop optimal irradiation patterns and parameters to form a S275 steel square thin plate to a given generic ship hull shape through finite element simulation and experiment verification. A novel approach was used for the development of scan strategies for controlled 3D laser forming of sheet metal components based on a reverse analysis. A patched modular virtual press tool was employed in a commercial FE package COMSOL Multiphysics to extract the required strain-displacement map to achieve a given shape from a starting condition. The laser processing conditions have then been extracted from the magnitude of strain and displacement of each patch. A closed loop control iterative approach has then been used to ensure part accuracy during experimental verification

    Optimization of process parameters for high efficiency laser forming of advanced high strength steels within metallurgical constraints

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    Laser forming (LF) has been shown to be a viable alternative to form automotive grade advanced high strength steels (AHSS). Due to their high strength, heat sensitivity and low conventional formability show early fractures, larger spring-back, batch-to-batch inconsistency and high tool wear. In this paper, optimisation of the LF process parameters has been conducted to further understand the impact of a surface heat treatment on DP1000. A FE numerical simulation has been developed to analyse the dynamic thermo-mechanical effects. This has been verified against empirical data. The goal of the optimisation has been to develop a usable process window for the LF of AHSS within strict metallurgical constraints. Results indicate it is possible to LF this material, however a complex relationship has been found between the generation and maintenance of hardness values in the heated zone. A laser surface hardening effect has been observed that could be beneficial to the efficiency of the process

    Natural occurrence of Cucumber mosaic virus infecting water mint (Mentha aquatica) in Antalya and Konya, Turkey

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    A virus causing a disease in mint (the aromatic and culinary plant) has recently become a problem in the Taurus Mountains, a mountain range in the Mediterranean region of Turkey. To detect the virus and investigate its distribution in the region, mint leaf samples were collected from the vicinity of spring areas in the plateaus of Antalya and Konya in 2009. It was found that Cucumber mosaic virus (CMV) was detected in 27.08% of symptomatic samples tested by DAS-ELISA. To the best of our knowledge, this is the first report of CMV on mint plants in this region of Turkey
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