275 research outputs found

    A regional ocean circulation model for the mid-Cretaceous North Atlantic Basin: implications for black shale formation

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    High concentrations of organic matter accumulated in marine sediments during Oceanic Anoxic Events (OAEs) in the Cretaceous. Model studies examining these events invariably make use of global ocean circulation models. In this study, a regional model for the North Atlantic Basin during OAE2 at the Cenomanian-Turonian boundary has been developed. A first order check of the results has been performed by comparison with the results of a recent global Cenomanian CCSM3 run, from which boundary and initial conditions were obtained. The regional model is able to maintain tracer patterns and to produce velocity patterns similar to the global model. The sensitivity of the basin tracer and circulation patterns to changes in the geometry of the connections with the global ocean is examined with three experiments with different bathymetries near the sponges. Different geometries turn out to have little effect on tracer distribution, but do affect circulation and upwelling patterns. The regional model is also used to test the hypothesis that ocean circulation may have been behind the deposition of black shales during OAEs. Three scenarios are tested which are thought to represent pre-OAE, OAE and post-OAE situations. Model results confirm that Pacific intermediate inflow together with coastal upwelling could have enhanced primary production during OAE2. A low sea level in the pre-OAE scenario could have inhibited large scale black shale formation, as could have the opening of the Equatorial Atlantic Seaway in the post-OAE scenario

    Zeniplatin in patients with advanced ovarian cancer, a phase II study with a third generation platinum complex

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    25 patients with residual or recurrent ovarian cancer were treated with the new platinum complex zeniplatin (CL 286,558) and 23 patients were evaluable for response. Responses were achieved in 4 patients, 1 complete and 3 partial remissions (16%). 7 patients had stable disease and 12 patients had tumour progression. At a median follow-up of 12 months, the median progression-free survival in responding patients was 11 months and overall survival 81%. The median overall survival of progressive patients amounted to 9 months, indicating the advanced stage of disease in most patients. Renal function was monitored by isotope clearance studies. There was no significant change in effective renal plasma flow (ERPF) or glomerular filtration rate (GFR) in 10 patients who completed six cycles of treatment. 1 patient with a marginal creatinine clearance at baseline suffered from sudden and severe renal failure during the first cycle. Zeniplatin may be active in relapsing, platinum-pretreated patients, and has no direct effects on renal function as measured by isotope clearance. Despite these findings, occasional nephrotoxicity may occur in patients with compromised kidney function, even with prophylactic hydration, and thus limit the application of this new analogue

    Time-dependent failure in load-bearing polymers: a potential hazard in structural applications of polylactides

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    With their excellent biocompatibility and relatively high mechanical strength, polylactides are attractive candidates for application in load-bearing, resorbable implants. Pre-clinical studies provided a proof of principle for polylactide cages as temporary constructs to facilitate spinal fusion, and several cages already made it to the market. However, also failures have been reported: clinical studies reported considerable amounts of subsidence with lumbar spinal fusion cages, and in an in vivo goat study, polylactide spinal cages failed after only three months of implantation, although mechanical testing had predicted sufficient strength for at least eight months. The failures appear to be related to the long-term performance of polylactides under static loading conditions, a phenomenon which is common to all glassy polymers and finds its origin in stress-activated molecular mobility leading to plastic flow. This paper reviews the mechanical properties and deformation kinetics of amorphous polylactides. Compression tests were performed with various strain rates, and static stress experiments were done to determine time-to failure. Pure PLLA appeared to have a higher yield strength than its co-polymers with d-lactide, but the kinetic behaviour of the polymers was the same: an excellent short-term strength at higher loading rates, but lifetime under static stress is rather poor. As spinal implants need to maintain mechanical integrity for a period of at least six months, this has serious implications for the clinical application of amorphous polylactides in load bearing situations. It is recommended that standards for mechanical testing of implants made of polymers be revised in order to consider this typical time-dependent behaviour

    A High-Throughput Screen for Tuberculosis Progression

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    One-third of the world population is infected with Mycobacterium tuberculosis and multi-drug resistant strains are rapidly evolving. The noticeable absence of a whole organism high-throughput screening system for studying the progression of tuberculosis is fast becoming the bottleneck in tuberculosis research. We successfully developed such a system using the zebrafish Mycobacterium marinum infection model, which is a well-characterized model for tuberculosis progression with biomedical significance, mimicking hallmarks of human tuberculosis pathology. Importantly, we demonstrate the suitability of our system to directly study M. tuberculosis, showing for the first time that the human pathogen can propagate in this vertebrate model, resulting in similar early disease symptoms to those observed upon M. marinum infection. Our system is capable of screening for disease progression via robotic yolk injection of early embryos and visual flow screening of late-stage larvae. We also show that this system can reliably recapitulate the standard caudal vein injection method with a throughput level of 2,000 embryos per hour. We additionally demonstrate the possibility of studying signal transduction leading to disease progression using reverse genetics at high-throughput levels. Importantly, we use reference compounds to validate our system in the testing of molecules that prevent tuberculosis progression, making it highly suited for investigating novel anti-tuberculosis compounds in vivo

    Search for the standard model Higgs boson decaying to a bb pair in events with one charged lepton and large missing transverse energy using the full CDF data set

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    We present a search for the standard model Higgs boson produced in association with a W boson in sqrt(s) = 1.96 TeV p-pbar collision data collected with the CDF II detector at the Tevatron corresponding to an integrated luminosity of 9.45 fb-1. In events consistent with the decay of the Higgs boson to a bottom-quark pair and the W boson to an electron or muon and a neutrino, we set 95% credibility level upper limits on the WH production cross section times the H->bb branching ratio as a function of Higgs boson mass. At a Higgs boson mass of 125 GeV/c2 we observe (expect) a limit of 4.9 (2.8) times the standard model value.Comment: Submitted to Phys. Rev. Lett (v2 contains clarifications suggested by PRL

    Search for the standard model Higgs boson decaying to a bbˉb\bar{b} pair in events with no charged leptons and large missing transverse energy using the full CDF data set

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    We report on a search for the standard model Higgs boson produced in association with a vector boson in the full data set of proton-antiproton collisions at s=1.96\sqrt{s} = 1.96 TeV recorded by the CDF II detector at the Tevatron, corresponding to an integrated luminosity of 9.45 fb1^{-1}. We consider events having no identified charged lepton, a transverse energy imbalance, and two or three jets, of which at least one is consistent with originating from the decay of a bb quark. We place 95% credibility level upper limits on the production cross section times standard model branching fraction for several mass hypotheses between 90 and 150GeV/c2150 \mathrm{GeV}/c^2. For a Higgs boson mass of 125GeV/c2125 \mathrm{GeV}/c^2, the observed (expected) limit is 6.7 (3.6) times the standard model prediction.Comment: Accepted by Phys. Rev. Let
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