12,610 research outputs found

    β-cell dysfunctional ERAD/ubiquitin/proteasome system in type 2 diabetes mediated by islet amyloid polypeptide-induced UCH-L1 deficiency.

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    ObjectiveThe islet in type 2 diabetes is characterized by β-cell apoptosis, β-cell endoplasmic reticulum stress, and islet amyloid deposits derived from islet amyloid polypeptide (IAPP). Toxic oligomers of IAPP form intracellularly in β-cells in humans with type 2 diabetes, suggesting impaired clearance of misfolded proteins. In this study, we investigated whether human-IAPP (h-IAPP) disrupts the endoplasmic reticulum-associated degradation/ubiquitin/proteasome system.Research design and methodsWe used pancreatic tissue from humans with and without type 2 diabetes, isolated islets from h-IAPP transgenic rats, isolated human islets, and INS 832/13 cells transduced with adenoviruses expressing either h-IAPP or a comparable expression of rodent-IAPP. Immunofluorescence and Western blotting were used to detect polyubiquitinated proteins and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) protein levels. Proteasome activity was measured in isolated rat and human islets. UCH-L1 was knocked down by small-interfering RNA in INS 832/13 cells and apoptosis was evaluated.ResultsWe report accumulation of polyubiquinated proteins and UCH-L1 deficiency in β-cells of humans with type 2 diabetes. These findings were reproduced by expression of oligomeric h-IAPP but not soluble rat-IAPP. Downregulation of UCH-L1 expression and activity to reproduce that caused by h-IAPP in β-cells induced endoplasmic reticulum stress leading to apoptosis.ConclusionsOur results indicate that defective protein degradation in β-cells in type 2 diabetes can, at least in part, be attributed to misfolded h-IAPP leading to UCH-L1 deficiency, which in turn further compromises β-cell viability

    Diffusion rates of Cu adatoms on Cu(111) in the presence of an adisland nucleated at FCC or HCP sites

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    The surface diffusion of Cu adatoms in the presence of an adisland at FCC or HCP sites on Cu(111) is studied using the EAM potential derived by Mishin {\it et al.} [Phys. Rev. B {\bf 63} 224106 (2001)]. The diffusion rates along straight (with close-packed edges) steps with (100) and (111)-type microfacets (resp. step A and step B) are first investigated using the transition state theory in the harmonic approximation. It is found that the classical limit beyond which the diffusion rates follow an Arrhenius law is reached above the Debye temperature. The Vineyard attempt frequencies and the (static) energy barriers are reported. Then a comparison is made with the results of more realistic classical molecular dynamic simulations which also exhibit an Arrhenius-like behavior. It is concluded that the corresponding energy barriers are completely consistent with the static ones within the statistical errors and that the diffusion barrier along step B is significantly larger than along step A. In contrast the prefactors are very different from the Vineyard frequencies. They increase with the static energy barrier in agreement with the Meyer-Neldel compensation rule and this increase is well approximated by the law proposed by Boisvert {\it et al.} [Phys. Rev. Lett. {\bf 75} 469 (1995)]. As a consequence, the remaining part of this work is devoted to the determination of static energy barriers for a large number of diffusion events that can occur in the presence of an adisland. In particular, it is found that the corner crossing diffusion process for triangular adislands is markedly different for the two types of borders (A or B). From this set of results the diffusion rates of the most important atomic displacements can be predicted and used as input in Kinetic Monte-Carlo simulations

    Quantum electrodynamics of relativistic bound states with cutoffs

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    We consider an Hamiltonian with ultraviolet and infrared cutoffs, describing the interaction of relativistic electrons and positrons in the Coulomb potential with photons in Coulomb gauge. The interaction includes both interaction of the current density with transversal photons and the Coulomb interaction of charge density with itself. We prove that the Hamiltonian is self-adjoint and has a ground state for sufficiently small coupling constants.Comment: To appear in "Journal of Hyperbolic Differential Equation

    Spin-dependent electron dynamics and recombination in GaAs(1-x)N(x) alloys at room temperature

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    We report on both experimental and theoretical study of conduction-electron spin polarization dynamics achieved by pulsed optical pumping at room temperature in GaAs(1-x)N(x) alloys with a small nitrogen content (x = 2.1, 2.7, 3.4%). It is found that the photoluminescence circular polarization determined by the mean spin of free electrons reaches 40-45% and this giant value persists within 2 ns. Simultaneously, the total free-electron spin decays rapidly with the characteristic time ~150 ps. The results are explained by spin-dependent capture of free conduction electrons on deep paramagnetic centers resulting in dynamical polarization of bound electrons. We have developed a nonlinear theory of spin dynamics in the coupled system of spin-polarized free and localized carriers which describes the experimental dependencies, in particular, electron spin quantum beats observed in a transverse magnetic field.Comment: 5 pages, 4 figures, Submitted to JETP Letter

    Les effets de l'adoption obligatoire des normes IFRS sur les incorporels : le cas de la France.

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    International audienceCet article examine les effets de l'adoption obligatoire des IFRS sur les incorporels, dans le contexte français. Utilisant un échantillon de 83 entreprises issues du SBF 120, nous recherchons une typologie des pratiques comptables liées aux incorporels à la période de transition aux IFRS. Les résultats font ressortir trois classes d'entreprises affectées différemment par le passage aux normes internationales. La première classe est caractérisée par un changement important avec une forte augmentation du goodwill liée au retraitement d'immobilisations incorporelles comme les parts de marché. Elle permet d'illustrer la spécificité de la réglementation française. La deuxième classe se caractérise par une stabilité s'expliquant par le poids prédominant du goodwill sous référentiel français. Enfin la troisième classe ne subit pas non plus de changement compte tenu de la présence de marques en normes françaises. Le phénomène d'inertie décrit par Nobes (2006) selon lequel les traitements comptables pré-IFRS pourraient perdurer sous IFRS est vérifié

    Revealing exciton masses and dielectric properties of monolayer semiconductors with high magnetic fields

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    In semiconductor physics, many essential optoelectronic material parameters can be experimentally revealed via optical spectroscopy in sufficiently large magnetic fields. For monolayer transition-metal dichalcogenide semiconductors, this field scale is substantial --tens of teslas or more-- due to heavy carrier masses and huge exciton binding energies. Here we report absorption spectroscopy of monolayer MoS2_2, MoSe2_2, MoTe2_2, and WS2_2 in very high magnetic fields to 91~T. We follow the diamagnetic shifts and valley Zeeman splittings of not only the exciton's 1s1s ground state but also its excited 2s2s, 3s3s, ..., nsns Rydberg states. This provides a direct experimental measure of the effective (reduced) exciton masses and dielectric properties. Exciton binding energies, exciton radii, and free-particle bandgaps are also determined. The measured exciton masses are heavier than theoretically predicted, especially for Mo-based monolayers. These results provide essential and quantitative parameters for the rational design of opto-electronic van der Waals heterostructures incorporating 2D semiconductors.Comment: updated; now also including data on MoTe2. Accepted & in press, Nature Commu
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