113 research outputs found

    A study in grid simulation and scheduling

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    Grid computing is emerging as an essential tool for large scale analysis and problem solving in scientific and business domains. Whilst the idea of stealing unused processor cycles is as old as the Internet, we are still far from reaching a position where many distributed resources can be seamlessly utilised on demand. One major issue preventing this vision is deciding how to effectively manage the remote resources and how to schedule the tasks amongst these resources. This thesis describes an investigation into Grid computing, specifically the problem of Grid scheduling. This complex problem has many unique features making it particularly difficult to solve and as a result many current Grid systems employ simplistic, inefficient solutions. This work describes the development of a simulation tool, G-Sim, which can be used to test the effectiveness of potential Grid scheduling algorithms under realistic operating conditions. This tool is used to analyse the effectiveness of a simple, novel scheduling technique in numerous scenarios. The results are positive and show that it could be applied to current procedures to enhance performance and decrease the negative effect of resource failure. Finally a conversion between the Grid scheduling problem and the classic computing problem SAT is provided. Such a conversion allows for the possibility of applying sophisticated SAT solving procedures to Grid scheduling providing potentially effective solutions

    Breast cancer cells adapt contractile forces to overcome steric hindrance

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    Cell migration through the extracellular matrix is governed by the interplay between cell-generated propulsion forces, adhesion forces, and resisting forces arising from the steric hindrance of the matrix. Steric hindrance in turn depends on matrix porosity, matrix deformability, cell size, and cell deformability. In this study, we investigate how cells respond to changes in steric hindrance that arise from altered cell mechanical properties. Specifically, we measure traction forces, cell morphology, and invasiveness of MDA-MB 231 breast cancer cells in three-dimensional collagen gels. To modulate cell mechanical properties, we either decrease nuclear deformability by twofold overexpression of the nuclear protein lamin A or we introduce into the cells stiff polystyrene beads with a diameter larger than the average matrix pore size. Despite this increase of steric hindrance, we find that cell invasion is only marginally inhibited, as measured by the fraction of motile cells and the mean invasion depth. To compensate for increased steric hindrance, cells employ two alternative strategies. Cells with higher nuclear stiffness increase their force polarity, whereas cells with large beads increase their net contractility. Under both conditions, the collagen matrix surrounding the cells stiffens dramatically and carries increased strain energy, suggesting that increased force polarity and increased net contractility are functionally equivalent strategies for overcoming an increased steric hindrance

    Measurement of Pion Enhancement at Low Transverse Momentum and of the Delta-Resonance Abundance in Si-Nucleus Collisions at AGS Energy

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    We present measurements of the pion transverse momentum (p_t) spectra in central Si-nucleus collisions in the rapidity range 2.0<y<5.0 for p_t down to and including p_t=0. The data exhibit an enhanced pion yield at low p_t compared to what is expected for a purely thermal spectral shape. This enhancement is used to determine the Delta-resonance abundance at freeze-out. The results are consistent with a direct measurement of the Delta-resonance yield by reconstruction of proton-pion pairs and imply a temperature of the system at freeze-out close to 140 MeV.Comment: 12 pages + 4 figures (uuencoded at end-of-file

    Phorbol Esters and SDF-1 Induce Rapid Endocytosis and Down Modulation of the Chemokine Receptor CXCR4

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    The chemokine receptor CXCR4 is required, together with CD4, for entry by some isolates of HIV-1, particularly those that emerge late in infection. The use of CXCR4 by these viruses likely has profound effects on viral host range and correlates with the evolution of immunodeficiency. Stromal cell-derived factor-1 (SDF-1), the ligand for CXCR4, can inhibit infection by CXCR4-dependent viruses. To understand the mechanism of this inhibition, we used a monoclonal antibody that is specific for CXCR4 to analyze the effects of phorbol esters and SDF-1 on surface expression of CXCR4. On human T cell lines SupT1 and BC7, CXCR4 undergoes slow constitutive internalization (1.0% of the cell surface pool/min). Addition of phorbol esters increased this endocytosis rate >6-fold and reduced cell surface CXCR4 expression by 60 to 90% over 120 min. CXCR4 was internalized through coated pits and coated vesicles and subsequently localized in endosomal compartments from where it could recycle to the cell surface after removal of the phorbol ester. SDF-1 also induced the rapid down modulation (half time ∌5 min) of CXCR4. Using mink lung epithelial cells expressing CXCR4 and a COOH-terminal deletion mutant of CXCR4, we found that an intact cytoplasmic COOH-terminal domain was required for both PMA and ligand-induced CXCR4 endocytosis. However, experiments using inhibitors of protein kinase C indicated that SDF-1 and phorbol esters trigger down modulation through different cellular mechanisms

    Human enteroids: Preclinical models of non-inflammatory diarrhea

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    Researchers need an available and easy-to-use model of the human intestine to better understand human intestinal physiology and pathophysiology of diseases, and to offer an enhanced platform for developing drug therapy. Our work employs human enteroids derived from each of the major intestinal sections to advance understanding of several diarrheal diseases, including those caused by cholera, rotavirus and enterohemorrhagic Escherichia coli. An enteroid bank is being established to facilitate comparison of segmental, developmental, and regulatory differences in transport proteins that can influence therapy efficacy. Basic characterization of major ion transport protein expression, localization and function in the human enteroid model sets the stage to study the effects of enteric infection at the transport level, as well as to monitor potential responses to pharmacological intervention

    Hadron yields and spectra in Au+Au collisions at the AGS

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    Inclusive double differential multiplicities and rapidity density distributions of hadrons are presented for 10.8 A GeV/c Au+Au collisions as measured at the AGS by the E877 collaboration. The results indicate that large amounts of stopping and collective transverse flow effects are present. The data are also compared to the results from the lighter Si+Al system.Comment: 12 pages, latex, 10 figures, submitted to Nuclear Physics A (Quark Matter 1996 Proceedings

    Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: A systematic review and meta-analysis

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    Background: Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemia is a concern with the use of mineralocorticoid receptor antagonists. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease. Methods: We conducted a meta-analysis investigating renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid receptor antagonists in chronic kidney disease. Trials were identified from MEDLINE (1966-2014), EMBASE (1947-2014) and the Cochrane Clinical Trials Database. Unpublished summary data were obtained from investigators. We included randomised controlled trials, and the first period of randomised cross over trials lasting ≄4 weeks in adults. Results: Nineteen trials (21 study groups, 1 646 patients) were included. In random effects meta-analysis, addition of mineralocorticoid receptor antagonists to renin angiotensin system inhibition resulted in a reduction from baseline in systolic blood pressure (-5.7 [-9.0, -2.3] mmHg), diastolic blood pressure (-1.7 [-3.4, -0.1] mmHg) and glomerular filtration rate (-3.2 [-5.4, -1.0] mL/min/1.73 m2). Mineralocorticoid receptor antagonism reduced weighted mean protein/albumin excretion by 38.7 % but with a threefold higher relative risk of withdrawing from the trial due to hyperkalaemia (3.21, [1.19, 8.71]). Death, cardiovascular events and hard renal end points were not reported in sufficient numbers to analyse. Conclusions: Mineralocorticoid receptor antagonism reduces blood pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes
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