12,741 research outputs found

    Regulation of the formation and water permeability of endosomes from toad bladder granular cells.

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    Osmotic water permeability (Pf) in toad bladder is regulated by the vasopressin (VP)-dependent movement of vesicles containing water channels between the cytoplasm and apical membrane of granular cells. Apical endosomes formed in the presence of serosal VP have the highest Pf of any biological or artificial membrane (Shi and Verkman. 1989. J. Gen. Physiol. 94:1101-1115). We examine here: (a) the influence of protein kinase A and C effectors on transepithelial Pf (Pfte) in intact bladders and on the number and Pf of labeled endosomes, and (b) whether endosome Pf can be modified physically or biochemically. In paired hemibladder studies, Pfte induced by maximal serosal VP (50 mU/ml, 0.03 cm/s) was not different than that induced by 8-Br-cAMP (1 mM), forskolin (50 microM), VP + 8-Br-cAMP, or VP + forskolin. Pf was measured in endosomes labeled in intact bladders with carboxyfluorescein by a stopped-flow, fluorescence-quenching assay using an isolated microsomal suspension; the number and Pf (0.08-0.11 cm/s, 18 degrees C) of labeled endosomes was not different in bladders treated with VP, forskolin, and 8-Br-cAMP. Protein kinase C activation by 1 microM mucosal phorbol myristate acetate (PMA) induced submaximal bladder Pfte (0.015 cm/s) and endosome Pf (0.022 cm/s) in the absence of VP, but had little effect on maximal Pfte and endosome Pf induced by VP. However, PMA increased by threefold the number of apical endosomes with high Pf formed in response to serosal VP. Pf of endosomes containing the VP-sensitive water channel decreased fourfold by increasing membrane fluidity with hexanol or chloroform (0-75 mM); Pf of phosphatidylcholine liposomes (0.002 cm/s) increased 2.5-fold under the same conditions. Endosome Pf was mildly pH dependent, strongly inhibited by HgCl2, but not significantly altered by GTP gamma S, Ca, ATP + protein kinase A, and phosphatase action. We conclude that: (a) water channels cycled in endocytic vesicles are functional and not subject to physiological regulation, (b) VP and forskolin do not have cAMP-independent cellular actions, (c) activation of protein kinase C stimulates trafficking of water channels, but does not increase the number of apical membrane water channels induced by maximal VP, and (d) water channel function is sensitive to membrane fluidity. By using VP and PMA together, large quantities of endosomes containing the VP-sensitive water channel are labeled with fluid-phase endocytic markers

    An Improved Differential Evolution Algorithm for Maritime Collision Avoidance Route Planning

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    High accuracy navigation and surveillance systems are pivotal to ensure efficient ship route planning and marine safety. Based on existing ship navigation and maritime collision prevention rules, an improved approach for collision avoidance route planning using a differential evolution algorithm was developed. Simulation results show that the algorithm is capable of significantly enhancing the optimized route over current methods. It has the potential to be used as a tool to generate optimal vessel routing in the presence of conflicts

    Organizing the innovation process : complementarities in innovation networking

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    This paper contributes to the developing literature on complementarities in organizational design. We test for the existence of complementarities in the use of external networking between stages of the innovation process in a sample of UK and German manufacturing plants. Our evidence suggests some differences between the UK and Germany in terms of the optimal combination of innovation activities in which to implement external networking. Broadly, there is more evidence of complementarities in the case of Germany, with the exception of the product engineering stage. By contrast, the UK exhibits generally strong evidence of substitutability in external networking in different stages, except between the identification of new products and product design and development stages. These findings suggest that previous studies indicating strong complementarity between internal and external knowledge sources have provided only part of the picture of the strategic dilemmas facing firms

    The interferon-stimulated gene IFITM3 restricts West Nile virus infection and pathogenesis

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    The interferon-induced transmembrane protein (IFITM) family of proteins inhibit infection of several different enveloped viruses in cell culture by virtue of their ability to restrict entry and fusion from late endosomes. As few studies have evaluated the importance of Ifitm3 in vivo in restricting viral pathogenesis, we investigated its significance as an antiviral gene against West Nile virus (WNV), an encephalitic flavivirus, in cells and mice. Ifitm3(−/−) mice were more vulnerable to lethal WNV infection, and this was associated with greater virus accumulation in peripheral organs and central nervous system tissues. As no difference in viral burden in the brain or spinal cord was observed after direct intracranial inoculation, Ifitm3 likely functions as an antiviral protein in nonneuronal cells. Consistent with this, Ifitm3(−/−) fibroblasts but not dendritic cells resulted in higher yields of WNV in multistep growth analyses. Moreover, transcomplementation experiments showed that Ifitm3 inhibited WNV infection independently of Ifitm1, Ifitm2, Ifitm5, and Ifitm6. Beyond a direct effect on viral infection in cells, analysis of the immune response in WNV-infected Ifitm3(−/−) mice showed decreases in the total number of B cells, CD4(+) T cells, and antigen-specific CD8(+) T cells. Finally, bone marrow chimera experiments demonstrated that Ifitm3 functioned in both radioresistant and radiosensitive cells, as higher levels of WNV were observed in the brain only when Ifitm3 was absent from both compartments. Our analyses suggest that Ifitm3 restricts WNV pathogenesis likely through multiple mechanisms, including the direct control of infection in subsets of cells. IMPORTANCE As part of the mammalian host response to viral infections, hundreds of interferon-stimulated genes (ISGs) are induced. The inhibitory activity of individual ISGs varies depending on the specific cell type and viral pathogen. Among ISGs, the genes encoding interferon-induced transmembrane protein (IFITM) have been reported to inhibit multiple families of viruses in cell culture. However, few reports have evaluated the impact of IFITM genes on viral pathogenesis in vivo. In this study, we characterized the antiviral activity of Ifitm3 against West Nile virus (WNV), an encephalitic flavivirus, using mice with a targeted gene deletion of Ifitm3. Based on extensive virological and immunological analyses, we determined that Ifitm3 protects mice from WNV-induced mortality by restricting virus accumulation in peripheral organs and, subsequently, in central nervous system tissues. Our data suggest that Ifitm3 restricts WNV pathogenesis by multiple mechanisms and functions in part by controlling infection in different cell types

    Novel Z2 Topological Metals and Semimetals

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    © 2016 American Physical Society.We report two theoretical discoveries for Z2 topological metals and semimetals. It is shown first that any dimensional Z2 Fermi surface is topologically equivalent to a Fermi point. Then the famous conventional no-go theorem, which was merely proven before for Z Fermi points in a periodic system without any discrete symmetry, is generalized so that the total topological charge is zero for all cases. Most remarkably, we find and prove an unconventional strong no-go theorem: all Z2 Fermi points have the same topological charge νZ2=1 or 0 for periodic systems. Moreover, we also establish all six topological types of Z2 models for realistic physical dimensions.postprin

    Modelling of sediment nutrient fluxes for a pulsed organic load

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    A sediment model has been developed to simulate the Sediment Oxygen Demand (SOD) and sediment nutrient fluxes after a sudden input of Particulate Organic Matter (POM). Compared with previous sediment models, the main advances are the use of a continuous function to represent the kinetics of POM diagenesis and inclusion of the biomass content in POM diagenesis. Laboratory experiments were also carried out to investigate the SOD dynamics and sediment nutrient fluxes after an input of fish food pellets into the sediment. The simulation results of SOD and nutrient fluxes compared fairly well with the experimental measurements. Copyright © 2011 Inderscience Enterprises Ltd.postprin

    Modified and Trefftz unsymmetric finite element models

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    The unsymmetric finite element method employs compatible test functions but incompatible trial functions. The pertinent 8-node quadrilateral and 20-node hexahedron unsymmetric elements possess exceptional immunity to mesh distortion. It was noted later that they are not invariant and the proposed remedy is to formulate the element stiffness matrix in a local frame and then transform the matrix back to the global frame. In this paper, a more efficient approach will be proposed to secure the invariance. To our best knowledge, unsymmetric 4-node quadrilateral and 8-node hexahedron do not exist. They will be devised by using the Trefftz functions as the trial function. Numerical examples show that the two elements also possess exceptional immunity to mesh distortion with respect to other advanced elements of the same nodal configurations.postprin

    A robust statistics based adaptive lattice-ladder filter in impulsive noise

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    In this paper, a new robust adaptive lattice-ladder filter for impulsive noise suppression is proposed. The filter is obtained by applying the non-linear filtering technique in [l] and the robust statistic approach to the gradient adaptive lattice filter. A systematic method is also developed to determine the corresponding threshold parameters for impulse suppression. Simulation results showed that the performance of the proposed algorithm is better than the conventional RLS, N-RLS, the gradient adaptive lattice normalised-LMS (GAL-NLMS), RMN and ATNA algorithms when the input and desired signals are corrupted by individual and consecutive impulses. The initial convergence, steady-state error, computational complexity and tracking capability of the proposed algorithm are also comparable to the conventional GAL-NLMS algorithm.published_or_final_versio

    Simultaneous stabilization via static output feedback and state feedback

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    In this paper, the simultaneous stabilization problem is considered using the matrix inequality approach. Some necessary and sufficient conditions for simultaneous stabilizability of r strictly proper multi-input/multi-output (MIMO) plants via static output feedback and state feedback are obtained in the form of coupled ARI's. It is shown that any such stabilizing feedback gain is the solution of some coupled linear quadratic control problems where every cost functional has a suitable cross term. A heuristic iterative algorithm based on the linear matrix inequality (LMI) technique is presented to solve the coupled matrix inequalities. The effectiveness of the approach is illustrated by numerical example.published_or_final_versio
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