1,809 research outputs found

    Some Relations on Paratopisms and An Intuitive Interpretation on the Adjugates of a Latin Square

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    This paper will present some intuitive interpretation of the adjugate transformations of arbitrary Latin square. With this trick, we can generate the adjugates of arbitrary Latin square directly from the original one without generating the orthogonal array. The relations of isotopisms and adjugate transformations in composition will also be shown. It will solve the problem that when F1*I1=I2*F2 how can we obtain I2 and F2 from I1 and F1, where I1 and I2 are isotopisms while F1 and F2 are adjugate transformations and * is the composition. These methods could distinctly simplify the computation on a computer for the issues related to main classes of Latin squares.Comment: Any comments and criticise are appreciate

    The intrinsic load-resisting capacity of kinesin

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    Conventional kinesin is a homodimeric motor protein that is capable of walking unidirectionally along a cytoskeletal filament. While previous experiments indicated unyielding unidirectionality against an opposing load up to the so-called stall force, recent experiments also observed limited processive backwalking under superstall loads. This theoretical study seeks to elucidate the molecular mechanical basis for kinesin's steps over the full range of external loads that can possibly be applied to the dimer. We found that kinesin's load-resisting capacity is largely determined by a synergic ratchet-and-pawl mechanism inherent in the dimer. Load susceptibility of this inner molecular mechanical mechanism underlies kinesin's response to various levels of external loads. Computational implementation of the mechanism enabled us to rationalize major trends observed experimentally in kinesin's stalemate and consecutive back steps. The study also predicts several distinct features of kinesin's load-affected motility, which are seemingly counterintuitive but readily verifiable by future experiment.Comment: 44 pages, 6 figure

    Recombinant human PDCD5 (rhPDCD5) protein is protective in a mouse model of multiple sclerosis.

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    BackgroundIn multiple sclerosis (MS) and its widely used animal model, experimental autoimmune encephalomyelitis (EAE), autoreactive T cells contribute importantly to central nervous system (CNS) tissue damage and disease progression. Promoting apoptosis of autoreactive T cells may help eliminate cells responsible for inflammation and may delay disease progression and decrease the frequency and severity of relapse. Programmed cell death 5 (PDCD5) is a protein known to accelerate apoptosis in response to various stimuli. However, the effects of recombinant human PDCD5 (rhPDCD5) on encephalitogenic T cell-mediated inflammation remain unknown.MethodsWe examined the effects of intraperitoneal injection of rhPDCD5 (10 mg/kg) on EAE both prophylactically (started on day 0 post-EAE induction) and therapeutically (started on the onset of EAE disease at day 8), with both of the treatment paradigms being given every other day until day 25. Repeated measures two-way analysis of variance was used for statistical analysis.ResultsWe showed that the anti-inflammatory effects of rhPDCD5 were due to a decrease in Th1/Th17 cell frequency, accompanied by a reduction of proinflammatory cytokines, including IFN-γ and IL-17A, and were observed in both prophylactic and therapeutic regimens of rhPDCD5 treatment in EAE mice. Moreover, rhPDCD5-induced apoptosis of myelin-reactive CD4+ T cells, along with the upregulation of Bax and downregulation of Bcl-2, and with activated caspase 3.ConclusionsOur data demonstrate that rhPDCD5 ameliorates the autoimmune CNS disease by inhibiting Th1/Th17 differentiation and inducing apoptosis of predominantly pathogenic T cells. This study provides a novel mechanism to explain the effects of rhPDCD5 on neural inflammation. The work represents a translational demonstration that rhPDCD5 has prophylactic and therapeutic properties in a model of multiple sclerosis

    The Complex Functions of the Receptor-Like Cytoplasmic Kinase BIK1 in Plant Immunity and Development

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    The sessile plants have evolved a large number of receptor-like kinases (RLKs) and receptor-like cytoplasmic kinases (RLCKs) to modulate diverse biological processes, including plant innate immunity, growth and development. Phosphorylation of RLK/RLCK complex constitutes an essential step to initiate the immune signaling. Two Arabidopsis plasma membrane-resident RLKs FLS2 and BAK1 interact with RLCK BIK1 to initiate plant immune responses to bacterial flagellin. Classically defined as a serine/threonine kinase, BIK1 is shown here to possess tyrosine kinase activity with mass spectrometry, immunoblot and genetic analyses. BIK1 is auto-phosphorylated and trans-phosphorylated by BAK1 at multiple tyrosine (Y) residues in addition to serine/threonine residues. BIK1Y150 is likely catalytic important, whereas Y243 and Y250 are more specifically involved in tyrosine phosphorylation. Importantly, the BIK1 tyrosine phosphorylation plays a crucial role in BIK1-mediated plant innate immunity as the transgenic plants carrying BIK1Y150F, Y243F or Y250F (the mutation of tyrosine to phenylalanine) failed to complement the bik1 mutant deficiency in immunity. Together with previous finding of BAK1 as a tyrosine kinase, these results unveiled tyrosine phosphorylation as a common regulatory mechanism that controls membrane-resident receptor signaling in plants and metazoans. BAK1 complexes with the receptor kinase FLS2 in bacterial flagellin-triggered immunity and BRI1 in brassinosteroid (BR)-mediated growth. In contrast to its positive role in plant immunity, we report here that BIK1 acts as a negative regulator in BR signaling. The bik1 mutants display various BR hypersensitive phenotypes accompanied with increased accumulation of de-phosphorylated BES1 proteins and regulation of BZR1 and BES1 target genes. BIK1 associates with BRI1, and is released from BRI1 receptor upon BR treatment, which is reminiscent of FLS2-BIK1 complex dynamics in flagellin signaling. The ligand-induced release of BIK1 from receptor complexes is associated with BIK1 phosphorylation. However, in contrast to BAK1-dependent FLS2-BIK1 dissociation, BAK1 is dispensable for BRI1-BIK1 dissociation. Consequently, unlike FLS2 signaling which depends on BAK1 to phosphorylate BIK1, BRI1 directly phosphorylates BIK1 to transduce BR signaling. Rapid activation of two branches of Mitogen-activated protein kinase (MAPK) cascades consisting of MEKK1-MKK1/2-MPK4 and MEKK1/?-MKK4/5-MPK3/6 is associated with perception of flagellin. There is limited understanding of how the signal transmits from the FLS2-BAK1 receptor complex to MAPK cascades. I have performed a series of genetic studies on the mutants of bik1 and its related family members. Various combinations of higher order of mutants indicate that flagellin-mediated MAPK activation functions downstream of BIK1. I found that the mekk1/2/3 deletion mutant largely restored various growth defects of bik1, and further genetic assays revealed that the alleviated growth defects can mainly be attributed to the mekk1 mutation, but not mekk2. I also demonstrated that BIK1 likely associates with MEKK1 on the plasma membrane, indicating that BIK1 bridges PRR complexes and MAPK cascades to relay immune signaling

    Preparation of Polyfunctionalized Grignard Reagents and their Application in Aryne Chemistry

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    The preparation of polyfunctinalized arynes has been achieved by the controlled elimination of readily generated 2-magnesiated aryl arylsulfonates obtained by a low temperature halogen/Mg-exchange starting from the corresponding iodides. New types of Grignard reagents via the addition of magnesium aryl thiolates, amides and selenides to arynes and heteroarynes have been prepared. An easy access to highly functionalized arylmagnesium reagents prepared by direct magnesiation of carbocyclic aromatic rings with TMPMgClLiCl was developed

    Construction Safety Management Mode with BIM as Its Core

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    With rapid development of economy in China, the construction of the project has been increasing continuously. In the process of construction, accidents occurred every year, and loss of life and property are difficult to estimate. The tradi-tional model is unable to accurately report the real situation of real-time construction. Thus, it is necessary to have a more efficient, high-tech security integrated management approach to conduct a comprehensive, systematic and mod-ern management, which is BIM as the core security management model

    Simulation Of Auto-Inhibition Effect In Mev Ntail With Its Binding Partner XD

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