44,964 research outputs found

    Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation.

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    Recent studies indicate that insulin stimulation of glucose transporter (GLUT)4 translocation requires at least two distinct insulin receptor-mediated signals: one leading to the activation of phosphatidylinositol 3 (PI-3) kinase and the other to the activation of the small GTP binding protein TC10. We now demonstrate that TC10 is processed through the secretory membrane trafficking system and localizes to caveolin-enriched lipid raft microdomains. Although insulin activated the wild-type TC10 protein and a TC10/H-Ras chimera that were targeted to lipid raft microdomains, it was unable to activate a TC10/K-Ras chimera that was directed to the nonlipid raft domains. Similarly, only the lipid raft-localized TC10/ H-Ras chimera inhibited GLUT4 translocation, whereas the TC10/K-Ras chimera showed no significant inhibitory activity. Furthermore, disruption of lipid raft microdomains by expression of a dominant-interfering caveolin 3 mutant (Cav3/DGV) inhibited the insulin stimulation of GLUT4 translocation and TC10 lipid raft localization and activation without affecting PI-3 kinase signaling. These data demonstrate that the insulin stimulation of GLUT4 translocation in adipocytes requires the spatial separation and distinct compartmentalization of the PI-3 kinase and TC10 signaling pathways

    Rank properties of exposed positive maps

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    Let \cK and \cH be finite dimensional Hilbert spaces and let \fP denote the cone of all positive linear maps acting from \fB(\cK) into \fB(\cH). We show that each map of the form ϕ(X)=AXA\phi(X)=AXA^* or ϕ(X)=AXTA\phi(X)=AX^TA^* is an exposed point of \fP. We also show that if a map ϕ\phi is an exposed point of \fP then either ϕ\phi is rank 1 non-increasing or \rank\phi(P)>1 for any one-dimensional projection P\in\fB(\cK).Comment: 6 pages, last section removed - it will be a part of another pape

    Erratum: The chemistry of transient molecular cloud cores

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    We assume that some, but not all, of the structure observed in molecular clouds is associated with transient features which are not bound by self-gravity. We investigate the chemistry of a transient density fluctuation, with properties similar to those of a core within a molecular cloud. We run a multipoint chemical code through a core's condensation from a diffuse medium to its eventual dispersion, over a period of ∼1 Myr. The dynamical description adopted for our study is based on an understanding of a particular mechanism, involving slow-mode wave excitation, for transient structure formation which so far has been studied in detail only with plane-parallel models in which self-gravity has not been included. We find a significant enhancement of the chemical composition of the core material on its return to diffuse conditions, whilst the expansion of the core as it disperses moves this material out to large distances from the core centre. This process transports molecular species formed in the high-density regions out into the diffuse medium. Chemical enrichment of the cloud as a whole also occurs, as other cores of various sizes, life-spans and separations evolve throughout. Enrichment is strongly affected by freeze-out on to dust grains, which takes place in high-density, high visual extinction regions. As the core disperses after reaching its peak density and the visual extinction drops below a critical value, grain mantles are evaporated back into the gas phase, initiating more chemistry. The influence of the sizes, masses and cycle periods of cores will be large both for the level of chemical enrichment of a dark cloud and ultimately for the low-mass star formation rate. The cores in which stars form are almost certainly bound by their self-gravity and are not transient in the sense that the cores on which most of our study is focused are transient. Obviously, enrichment of the chemistry of low-density material will not take place if self-gravity prevents the re-expansion of a core. We also consider the case of a self-gravitating core, by holding its peak density conditions for a further 0.4 Myr. We find that the differences near the peak densities between transient and gravitationally bound cores are generally small, and the resultant column densities for objects near the peak densities do not provide definitive criteria for discriminating between transient and bound cores. However, increases in fractional abundances due to reinjection of mantle-borne species may provide a criterion for detection of a non-bound core

    Toxoplasma effectors targeting host signaling and transcription

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    Early electron microscopy studies revealed the elaborate cellular features that define the unique adaptations of apicomplexan parasites. Among these were bulbous rhoptry (ROP) organelles and small, dense granules (GRAs), both of which are secreted during invasion of host cells. These early morphological studies were followed by the exploration of the cellular contents of these secretory organelles, revealing them to be comprised of highly divergent protein families with few conserved domains or predicted functions. In parallel, studies on host-pathogen interactions identified many host signaling pathways that were mysteriously altered by infection. It was only with the advent of forward and reverse genetic strategies that the connections between individual parasite effectors and the specific host pathways that they targeted finally became clear. The current repertoire of parasite effectors includes ROP kinases and pseudokinases that are secreted during invasion and that block host immune pathways. Similarly, many secretory GRA proteins alter host gene expression by activating host transcription factors, through modification of chromatin, or by inducing small noncoding RNAs. These effectors highlight novel mechanisms by whichhas learned to harness host signaling to favor intracellular survival and will guide future studies designed to uncover the additional complexity of this intricate host-pathogen interaction

    Linear LL-positive sets and their polar subspaces

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    In this paper, we define a Banach SNL space to be a Banach space with a certain kind of linear map from it into its dual, and we develop the theory of linear LL-positive subsets of Banach SNL spaces with Banach SNL dual spaces. We use this theory to give simplified proofs of some recent results of Bauschke, Borwein, Wang and Yao, and also of the classical Brezis-Browder theorem.Comment: 11 pages. Notational changes since version

    Aspects of Discrete Breathers and New Directions

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    We describe results concerning the existence proofs of Discrete Breathers (DBs) in the two classes of dynamical systems with optical linear phonons and with acoustic linear phonons. A standard approach is by continuation of DBs from an anticontinuous limit. A new approach, which is purely variational, is presented. We also review some numerical results on intraband DBs in random nonlinear systems. Some non-conventional physical applications of DBs are suggested. One of them is understanding slow relaxation properties of glassy materials. Another one concerns energy focusing and transport in biomolecules by targeted energy transfer of DBs. A similar theory could be used for describing targeted charge transfer of nonlinear electrons (polarons) and, more generally, for targeted transfer of several excitations (e.g. Davydov soliton).Comment: to appear in the Proceedings of NATO Advanced Research Workshop "Nonlinearity and Disorder: Theory and Applications", Tashkent,Uzbekistan,October 1-6, 200

    Cascading Effects and Escalations in Wide Area Power Failures: A Summary for Emergency Planners

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    This special report is the result of a collaboration between academics and practitioners. It aims to provide a synthetic overview of the cascading effects caused by wide-area power failures, and to define the recurrent impacts and sources of escalation. It provides a reference for the training and the situational awareness of decision makers and emergency operators. The format uses bullet points and examples to facilitate reading in conditions of limited availability of time. The following topics have been developed:- ⚫ A definition of cascading effects. ⚫ An introduction for of wide area power failures (PF) policies and practices. ⚫ Illustrative examples. ⚫ A table listing cascading effects and escalations caused by wide area PF. ⚫ Resources for training and essential references for further reading

    Dissipation of parallel and oblique Alfvén-cyclotron waves - implications for heating of alpha particles in the solar wind

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    We perform 2.5D hybrid simulations with massless fluid electrons and kinetic particle-in-cell ions to study the temporal evolution of ion temperatures, temperature anisotropies, and velocity distribution functions in relation to the dissipation and turbulent evolution of a broadband spectrum of parallel and obliquely propagating Alfvén-cyclotron waves. The purpose of this paper is to study the relative role of parallel versus oblique Alfvén-cyclotron waves in the observed heating and acceleration of alpha particles in the fast solar wind. We consider collisionless homogeneous multi-species plasma, consisting of isothermal electrons, isotropic protons, and a minor component of drifting α particles in a finite-β fast stream near the Earth. The kinetic ions are modeled by initially isotropic Maxwellian velocity distribution functions, which develop nonthermal features and temperature anisotropies when a broadband spectrum of low-frequency nonresonant, ω ≤ 0.34 Ωp, Alfvén-cyclotron waves is imposed at the beginning of the simulations. The initial plasma parameter values, such as ion density, temperatures, and relative drift speeds, are supplied by fast solar wind observations made by the Wind spacecraft at 1 AU. The imposed broadband wave spectra are left-hand polarized and resemble Wind measurements of Alfvénic turbulence in the solar wind. The imposed magnetic field fluctuations for all cases are within the inertial range of the solar wind turbulence and have a Kraichnan-type spectral slope α = −3/2. We vary the propagation angle from θ = 0° to θ = 30° and θ = 60°, and find that the heating of alpha particles is most efficient for the highly oblique waves propagating at 60°, whereas the protons exhibit perpendicular cooling at all propagation angles

    Increased insolation threshold for runaway greenhouse processes on Earth like planets

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    Because the solar luminosity increases over geological timescales, Earth climate is expected to warm, increasing water evaporation which, in turn, enhances the atmospheric greenhouse effect. Above a certain critical insolation, this destabilizing greenhouse feedback can "runaway" until all the oceans are evaporated. Through increases in stratospheric humidity, warming may also cause oceans to escape to space before the runaway greenhouse occurs. The critical insolation thresholds for these processes, however, remain uncertain because they have so far been evaluated with unidimensional models that cannot account for the dynamical and cloud feedback effects that are key stabilizing features of Earth's climate. Here we use a 3D global climate model to show that the threshold for the runaway greenhouse is about 375 W/m2^2, significantly higher than previously thought. Our model is specifically developed to quantify the climate response of Earth-like planets to increased insolation in hot and extremely moist atmospheres. In contrast with previous studies, we find that clouds have a destabilizing feedback on the long term warming. However, subsident, unsaturated regions created by the Hadley circulation have a stabilizing effect that is strong enough to defer the runaway greenhouse limit to higher insolation than inferred from 1D models. Furthermore, because of wavelength-dependent radiative effects, the stratosphere remains cold and dry enough to hamper atmospheric water escape, even at large fluxes. This has strong implications for Venus early water history and extends the size of the habitable zone around other stars.Comment: Published in Nature. Online publication date: December 12, 2013. Accepted version before journal editing and with Supplementary Informatio
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