331 research outputs found

    Biomechanics for Landing Instruction of a Box Horse Exercise

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    Generally, it seems that almost all children prefer physical education class in elementary school stage. For children it is said that physical exercise itself is play as well as training is essential to their normal growth and normal development. For example Jean Jacques Rousseau (1712-78), a French philosopher, wrote in his book Emile ou de I'Education (1762) that by returning to natural state, man is both good and happy, and that physical exercise has stimulating effect both in mind and body of children. Taking into consideration that physical education utilizes a basic physical exercise including such as working about, running around and jumping up and down, physical education class will have some function to provide a lot of opportunities meeting to satisfy their physical needs in instinct. A box horse exercise is one of the suitable exercises, which develops their organ and motor ability. And also, as one of educational materials in physical education class of elementary school, a box horse exercise makes up a challenging spirit to get over some obstacles. Especially in Japan, it is usual that a box horse exercise is compulsory for all children from elementary school to junior high school. In spite of the fact that children vault a box horse with joy, serious accidents have occured in landing phase as usual. However so far, little has been reported pertaining to scientific analysis of safety landing in a box horse exercise. Therefore scientific data of safety instruction, especially focused to landing skill for a box horse exercise are needed to be analyzed with biomechanical techniques in order to prevent children from getting some serious Injuries at a box horse exercise in physical education class of elementary school. The purpose of this study was to investigate the influence of instruction in a box horse exercise on landing impulse absorbing ability and landing motion for elementary school children attending physical education class

    Homogeneous bubble nucleation limit of mercury under the normal working conditions of the planned European Spallation Source

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    In spallation neutron sources, liquid mercury is the subject of big thermal and pressure shocks, upon adsorbing the proton beam. These changes can cause unstable bubbles in the liquid, which can damage the structural material. While there are methods to deal with the pressure shock, the local temperature shock cannot be avoided. In our paper we calculated the work of the critical cluster formation (i.e. for mercury micro-bubbles) together with the rate of their formation (nucleation rate). It is shown that the homogeneous nucleation rates are very low even after adsorbing several proton pulses, therefore the probability of temperature induced homogeneous bubble nucleation is negligible.Comment: 22 Pages, 11 figures, one of them is colour, we plan to publish it in Eur. Phys. J.

    Prognostic factors influencing clinical outcome of allogeneic hematopoietic stem cell transplantation following imatinib-based therapy in BCR–ABL-positive ALL

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    We investigated prognostic factors for the clinical outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) following imatinib-based therapy. Among 100 adult patients who were prospectively enrolled in the JALSG Ph+ALL202 study, 97 patients obtained complete remission (CR) by imatinib-combined chemotherapy, among whom 60 underwent allo-HSCT in their first CR. The probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years after HSCT were 64% (95% CI, 49–76) and 58% (95% CI, 43–70), respectively. Prognostic factor analysis revealed that the major BCR–ABL transcript was the only unfavorable predictor for OS and DFS after HSCT by both univariate (HR, 3.67 (95% CI 1.49–9.08); P=0.005 and HR, 6.25 (95% CI, 1.88–20.8); P=0.003, respectively) and multivariate analyses (HR, 3.20 (95% CI, 1.21–8.50); P=0.019 and HR, 6.92 (95% CI, 2.09–22.9); P=0.002, respectively). Minimal residual disease status at the time of HSCT had a significant influence on relapse rate (P=0.015). Further study of the BCR–ABL subtype for the clinical impact on outcome of allo-HSCT in Ph+ALL is warranted

    Evaluation of the Quasi‐Biennial Oscillation in global climate models for the SPARC QBO‐initiative

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    The Quasi‐Biennial Oscillation initiative (QBOi) is a model intercomparison programme that specifically targets simulation of the QBO in current global climate models. Eleven of the models or model versions that participated in a QBOi intercomparison study have upper boundaries in or above the mesosphere and therefore simulate the region where the stratopause semiannual oscillation (SAO) is the dominant mode of variability of zonal winds in the tropical upper stratosphere. Comparisons of the SAO simulations in these models are presented here. These show that the model simulations of the amplitudes and phases of the SAO in zonal‐mean zonal wind near the stratopause agree well with the information derived from available observations. However, most of the models simulate time‐average zonal winds that are more westward than determined from observations, in some cases by several tens of m·s1^{–1}. Validation of wave activity in the models is hampered by the limited observations of tropical waves in the upper stratosphere but suggests a deficit of eastward forcing either by large‐scale waves, such as Kelvin waves, or by gravity waves

    Teleconnections of the Quasi‐Biennial Oscillation in a multi‐model ensemble of QBO‐resolving models

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    The Quasi-biennial Oscillation (QBO) dominates the interannual variability of the tropical stratosphere and influences other regions of the atmosphere. The high predictability of the QBO implies that its teleconnections could lead to increased skill of seasonal and decadal forecasts provided the relevant mechanisms are accurately represented in models. Here modelling and sampling uncertainties of QBO teleconnections are examined using a multi-model ensemble of QBO-resolving atmospheric general circulation models that have carried out a set of coordinated experiments as part of the Stratosphere-troposphere Processes And their Role in Climate (SPARC) QBO initiative (QBOi). During Northern Hemisphere winter, the stratospheric polar vortex in most of these models strengthens when the QBO near 50 hPa is westerly and weakens when it is easterly, consistent with, but weaker than, the observed response. These weak responses are likely due to model errors, such as systematically weak QBO amplitudes near 50 hPa, affecting the teleconnection. The teleconnection to the North Atlantic Oscillation is less well captured overall, but of similar strength to the observed signal in the few models that do show it. The models do not show clear evidence of a QBO teleconnection to the Northern Hemisphere Pacific-sector subtropical jet

    GPS-ARM: Computational Analysis of the APC/C Recognition Motif by Predicting D-Boxes and KEN-Boxes

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    Anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase incorporated with Cdh1 and/or Cdc20 recognizes and interacts with specific substrates, and faithfully orchestrates the proper cell cycle events by targeting proteins for proteasomal degradation. Experimental identification of APC/C substrates is largely dependent on the discovery of APC/C recognition motifs, e.g., the D-box and KEN-box. Although a number of either stringent or loosely defined motifs proposed, these motif patterns are only of limited use due to their insufficient powers of prediction. We report the development of a novel GPS-ARM software package which is useful for the prediction of D-boxes and KEN-boxes in proteins. Using experimentally identified D-boxes and KEN-boxes as the training data sets, a previously developed GPS (Group-based Prediction System) algorithm was adopted. By extensive evaluation and comparison, the GPS-ARM performance was found to be much better than the one using simple motifs. With this powerful tool, we predicted 4,841 potential D-boxes in 3,832 proteins and 1,632 potential KEN-boxes in 1,403 proteins from H. sapiens, while further statistical analysis suggested that both the D-box and KEN-box proteins are involved in a broad spectrum of biological processes beyond the cell cycle. In addition, with the co-localization information, we predicted hundreds of mitosis-specific APC/C substrates with high confidence. As the first computational tool for the prediction of APC/C-mediated degradation, GPS-ARM is a useful tool for information to be used in further experimental investigations. The GPS-ARM is freely accessible for academic researchers at: http://arm.biocuckoo.org

    Identification of amino acid residues responsible for von Willebrand factor binding to sulfatide by charged-to-alanine-scanning mutagenesis

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    von Willebrand factor (VWF) performs its hemostatic functions through binding to various proteins. The A1 domain of VWF contains binding sites of not only physiologically important ligands, but also exogenous modulators that induce VWF-platelet aggregation. Sulfatides, 3-sulfated galactosyl ceramides, that are expressed on oligodendrocytes, renal tubular cells, certain tumor cells and platelets, have been suggested to interact with VWF under some pathological conditions. The binding of VWF to sulfatide requires the A1 domain, but its binding sites have not been precisely identified. Here, we report that alanine mutations at Arg1392, Arg1395, Arg1399 and Lys1423 led to decreased VWF–sulfatide binding. These sites have been reported to be the binding sites for platelet membrane glycoprotein (GP) Ib and/or snake venom botrocetin, and, interestingly, are identical to the monoclonal antibody (mAb) NMC4 epitope previously reported to inhibit the VWF-GPIb interaction. We observed that NMC4 also inhibited VWF interaction with sulfatides in a dose-dependent manner. Thus, we conclude that VWF binding sites of sulfatide overlap those of platelet GPIb and botrocetin

    APCcdh1 Mediates Degradation of the Oncogenic Rho-GEF Ect2 after Mitosis

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    Background: Besides regulation of actin cytoskeleton-dependent functions, Rho GTPase pathways are essential to cell cycle progression and cell division. Rho, Rac and Cdc42 regulate G1 to S phase progression and are involved in cytokinesis. RhoA GDP/GTP cycling is required for normal cytokinesis and recent reports have shown that the exchange factor Ect2 and the GTPase activating protein MgcRacGAP regulate RhoA activity during mitosis. We previously showed that the transcription factors E2F1 and CUX1 regulate expression of MgcRacGAP and Ect2 as cells enter S-phase. Methodology/Principal Findings: We now report that Ect2 is subject to proteasomal degradation after mitosis, following ubiquitination by the APC/C complex and its co-activator Cdh1. A proper nuclear localization of Ect2 is necessary for its degradation. APC-Cdh1 assembles K11-linked poly-ubiquitin chains on Ect2, depending upon a stretch of,25 amino acid residues that contain a bi-partite NLS, a conventional D-box and two TEK-like boxes. Site-directed mutagenesis of target sequences generated stabilized Ect2 proteins. Furthermore, such degradation-resistant mutants of Ect2 were found to activate RhoA and subsequent signalling pathways and are able to transform NIH3T3 cells. Conclusions/Significance: Our results identify Ect2 as a bona fide cell cycle-regulated protein and suggest that its ubiquitination-dependent degradation may play an important role in RhoA regulation at the time of mitosis. Our findings raise the possibility that the overexpression of Ect2 that has been reported in some human tumors might result not only from deregulated transcription, but also from impaired degradation
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