7,127 research outputs found

    Allosteric Modulation Balances Thermodynamic Stability and Restores Function of ΔF508 CFTR

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    Most cystic fibrosis is caused by a deletion of a single residue (F508) in CFTR that disrupts the folding and biosynthetic maturation of the ion channel protein. Progress towards understanding the underlying mechanisms and overcoming the defect remain incomplete. Here we show that the thermal instability of human ΔF508 CFTR channel activity evident in both cell-attached membrane patches and planar phospholipid bilayers is not observed in corresponding mutant CFTRs of several non-mammalian species. These more stable orthologs are distinguished from their mammalian counterparts by the substitution of proline residues at several key dynamic locations in the first nucleotide domain (NBD1), including the structurally diverse region (SDR), the gamma phosphate switch loop and the Regulatory Insertion (RI). Molecular Dynamic analyses revealed that addition of the prolines could reduce flexibility at these locations and increase the temperatures of unfolding transitions of ΔF508 NBD1 to that of the wild-type. Introduction of these prolines experimentally into full-length human ΔF508 CFTR together with the already recognized I539T suppressor mutation, also in the SDR, restored channel function and thermodynamic stability as well as its trafficking to and lifetime at the cell surface. Thus, while cellular manipulations that circumvent its culling by quality control systems leave ΔF508 CFTR dysfunctional at physiological temperature, restoration of the delicate balance between the dynamic protein’s inherent stability and channel activity returns a near-normal state

    History effects and pinning regimes in solid vortex matter

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    We propose a phenomenological model that accounts for the history effects observed in ac susceptibility measurements in YBa2Cu3O7 single crystals [Phys. Rev. Lett. 84, 4200 (2000) and Phys. Rev. Lett. 86, 504 (2001)]. Central to the model is the assumption that the penetrating ac magnetic field modifies the vortex lattice mobility, trapping different robust dynamical states in different regions of the sample. We discuss in detail on the response of the superconductor to an ac magnetic field when the vortex lattice mobility is not uniform inside the sample. We begin with an analytical description for a simple geometry (slab) and then we perform numerical calculations for a strip in a transverse magnetic field which include relaxation effects. In calculations, the vortex system is assumed to coexist in different pinning regimes. The vortex behavior in the regions where the induced current density j has been always below a given threshold (j_c^>) is described by an elastic Campbell-like regime (or a critical state regime with local high critical current density, j_c^>). When the VS is shaken by symmetrical (e.g. sinusoidal) ac fields, the critical current density is modified to j_c^) at regions where vortices have been forced to oscillate by a current density larger than j_c^>. Experimentally, an initial state with high critical current density (j_c^>) can be obtained by zero field cooling, field cooling (with no applied ac field) or by shaking the vortex lattice with an asymmetrical (e.g. sawtooth) field. We compare our calculations with experimental ac susceptibility results in YBa2Cu3O7 single crystals.Comment: 11 pages, 7 figures. To be published in PR

    Measurement of J/ψ production in association with a W ± boson with pp data at 8 TeV

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    A measurement of the production of a prompt J/ψ meson in association with a W± boson with W± → ΌΜ and J/ψ → ÎŒ+Ό− is presented for J/ψ transverse momenta in the range 8.5–150 GeV and rapidity |yJ/ψ| < 2.1 using ATLAS data recorded in 2012 at the LHC. The data were taken at a proton-proton centre-of-mass energy of s = 8 TeV and correspond to an integrated luminosity of 20.3 fb−1. The ratio of the prompt J/ψ plus W± cross-section to the inclusive W± cross-section is presented as a differential measurement as a function of J/ψ transverse momenta and compared with theoretical predictions using different double-parton-scattering cross-sections. [Figure not available: see fulltext.]
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