1,023 research outputs found

    Noradrenaline inhibits exocytosis via the G protein βγ subunit and refilling of the readily releasable granule pool via the αi1/2 subunit.

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    The molecular mechanisms responsible for the ‘distal’ effect by which noradrenaline (NA) blocks exocytosis in the β-cell were examined by whole-cell and cell-attached patch clamp capacitance measurements in INS 832/13 β-cells. NA inhibited Ca2+-evoked exocytosis by reducing the number of exocytotic events, without modifying vesicle size. Fusion pore properties also were unaffected. NA-induced inhibition of exocytosis was abolished by a high level of Ca2+ influx, by intracellular application of antibodies against the G protein subunit Gβ and was mimicked by the myristoylated βγ-binding/activating peptide mSIRK. NA-induced inhibition was also abolished by treatment with BoNT/A, which cleaves the C-terminal nine amino acids of SNAP-25, and also by a SNAP-25 C-terminal-blocking peptide containing the BoNT/A cleavage site. These data indicate that inhibition of exocytosis by NA is downstream of increased [Ca2+]i and is mediated by an interaction between Gβγ and the C-terminus of SNAP-25, as is the case for inhibition of neurotransmitter release. Remarkably, in the course of this work, a novel effect of NA was discovered. NA induced a marked retardation of the rate of refilling of the readily releasable pool (RRP) of secretory granules. This retardation was specifically abolished by a Gαi1/2 blocking peptide demonstrating that the effect is mediated via activation of Gαi1 and/or Gαi2

    Evaluation of geometric tolerances using strain energy density

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    Traditionally, the geometric quality of assembled products has been evaluated by deviation from nominal values. However, the increased use mixed materials in especially automotive industry, in combination with an increased use of non-rigid simulation, open up for other evaluation criteria to complement the traditionally used deviation. The stiffness of a part or subassembly will, in combination with its deviation from nominal, give rise to different amounts of energy needed to join it to other parts. In this paper, the energy needed for joining is suggested as an evaluation criterion, complementary to geometric deviation, to judge the severity of the deviation

    Sexuality and Affection among Elderly German Men and Women in Long-Term Relationships: Results of a Prospective Population-Based Study

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    This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The study was funded by the German Federal Ministry for Families, Senior Citizens, Women and Youth (AZ 314-1722-102/16; AZ 301-1720-295/2), the Ministry for Science, Research and Art Baden-Württemberg, and the University of Rostock (FORUN 989020; 889048)

    Microstructural evolution in ODS-EUROFER steel caused by high-dose He ion implantations with systematic variation of implantation parameters

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    The paper presents a detailed analysis of helium (He) bubble development in ODS-EUROFER steel caused by helium ion implantation in different regimes, with a particular attention to the role of the oxide nanoparticles in promoting the growth of He bubbles, helium accumulation and gas-driven swelling. The Transmission Electron Microscopy (TEM) characterization of steel samples implanted applying systematic variation of experimental parameters has allowed clarifying the trends of the bubble microstructure evolution depending on the implantation dose, flux, and sample temperature. It was found that in all investigated implantation regimes He bubbles formed both in the grain bulk and on various structural defects (dislocations, grain boundaries, oxide particles and carbide precipitates), but the sizes and densities of bubbles in different bubble populations were sensitive to particular irradiation conditions. In the majority of cases the main traps for implanted helium and the main contributors to the estimated swelling were bubbles associated with grain boundaries, though in some cases (high implantation dose or lower temperature) the bubbles in the grain bulk were competitive with the grain boundary bubble population. Oxide particles in ODS-EUROFER were found to be excellent nucleation sites for He bubbles and practically each observed particle hosted a single relatively large bubble, sometimes as large as the particle itself. However, the contribution of oxide-associated bubbles to the estimated swelling and He inventory was found to be minor as compared to other bubble populations because of a relatively low number density of nano-oxides. Comparison of ODS-EUROFER and EUROFER 97 samples implanted with He ions in identical regimes has demonstrated lower efficiency of ODS-EUROFER for accumulating implanted helium in bubbles and noticeably higher share of helium atoms trapped in the vacancy defects invisible by TEM

    Pair Creation and an X-ray Free Electron Laser

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    Using a quantum kinetic equation coupled to Maxwell's equation we study the possibility that focused beams at proposed X-ray free electron laser facilities can generate electric field strengths large enough to cause spontaneous electron-positron pair production from the QED vacuum. Our approach yields the time and momentum dependence of the single particle distribution function. Under conditions reckoned achievable at planned facilities, repeated cycles of particle creation and annihilation take place in tune with the laser frequency. However, the peak particle number density is insensitive to this frequency and one can anticipate the production of a few hundred particle pairs per laser period. Field-current feedback and quantum statistical effects are small and can be neglected in this application of non-equilibrium quantum mean field theory.Comment: 4 pages, LaTeX2

    Evolution of microstructure in advanced ferritic-martensitic steels under irradiation : the origin of low temperature radiation embrittlement

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    Advanced reduced activation ferritic/martensitic steels and oxide dispersion-strengthened steels exhibit significant radiation embrittlement under low temperature neutron irradiation. In this study we focused on atom probe tomography (APT) of Eurofer97 and ODS Eurofer steels irradiated with neutrons and heavy ions at low temperatures. Previous TEM studies revealed dislocation loops in the neutron-irradiated f\m steels. At the same time, our APT showed early stages of solid solution decomposition. High density (1024^{24} m3^{-3}) of ∼3–5 nm clusters enriched in chromium, manganese, and silicon atoms were found in Eurofer 97 irradiated in BOR-60 reactor to 32 dpa at 332°C. In this steel irradiated with Fe ions up to the dose of 24 dpa, pair correlation functions calculated using APT data showed the presence of Cr-enriched pre-phases. APT study of ODS Eurofer found a significant change in the nanocluster composition after neutron irradiation to 32 dpa at 330 °C and an increase in cluster number density. APT of ODS steels irradiated with Fe ions at low temperatures revealed similar changes in nanoclusters. These results suggest that irradiation-induced nucleation and evolution of very small precipitates may be the origin of low temperature radiation embrittlement of f\m steels
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