3,851 research outputs found

    Lessons learned from the development and manufacture of ceramic reusable surface insulation materials for the space shuttle orbiters

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    Three ceramic, reusable surface insulation materials and two borosilicate glass coatings were used in the fabrication of tiles for the Space Shuttle orbiters. Approximately 77,000 tiles were made from these materials for the first three orbiters, Columbia, Challenger, and Discovery. Lessons learned in the development, scale up to production and manufacturing phases of these materials will benefit future production of ceramic reusable surface insulation materials. Processing of raw materials into tile blanks and coating slurries; programming and machining of tiles using numerical controlled milling machines; preparing and spraying tiles with the two coatings; and controlling material shrinkage during the high temperature (2100-2275 F) coating glazing cycles are among the topics discussed

    Toll-like receptor 4 in experimental kidney transplantation: early mediator of endogenous danger signals

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    The role of toll-like receptors (TLRs) has been described in the pathogenesis of renal ischemia/reperfusion injury, but data on the expression and function of TLR4 during renal allograft damage are still scarce. We analyzed the expression of TLR4 in an experimental rat model 6 and 28 days after allogeneic kidney transplantation in comparison to control rats and rats after syngeneic transplantation. On day 6, a significant induction in TLR4 expression - restricted to the glomerular compartment - was found in acute rejecting allografts only. TLR4 expression strongly correlated with renal function, and TLR4 induction was accompanied by a significant increase in CC chemokine expression within the graft as well as in urinary CC chemokine excretion. TLR4 induction may be caused by an influx of macrophages as well as TLR4-expressing intrinsic renal cells. Fibrinogen deposition in renal allografts correlated with renal TLR4 expression and may act as a potent stimulator of chemokine release via TLR4 activation. This study provides, for the first time, data about the precise intrarenal localization and TLR4 induction after experimental kidney transplantation. It supports the hypothesis that local TLR4 activation by endogenous ligands may be one pathological link from unspecific primary allograft damage to subsequent chemokine release, infiltration and activation of immune cells leading to deterioration of renal function and induction of renal fibrosis. Copyright (c) 2012 S. Karger AG, Base

    The upregulation of thiamine (vitamin B1) biosynthesis in Arabidopsis thaliana seedlings under salt and osmotic stress conditions is mediated by abscisic acid at the early stages of this stress response

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    <p>Abstract</p> <p>Background</p> <p>Recent reports suggest that vitamin B<sub>1 </sub>(thiamine) participates in the processes underlying plant adaptations to certain types of abiotic and biotic stress, mainly oxidative stress. Most of the genes coding for enzymes involved in thiamine biosynthesis in <it>Arabidopsis thaliana </it>have been identified. In our present study, we examined the expression of thiamine biosynthetic genes, of genes encoding thiamine diphosphate-dependent enzymes and the levels of thiamine compounds during the early (sensing) and late (adaptation) responses of Arabidopsis seedlings to oxidative, salinity and osmotic stress. The possible roles of plant hormones in the regulation of the thiamine contribution to stress responses were also explored.</p> <p>Results</p> <p>The expression of Arabidopsis genes involved in the thiamine diphosphate biosynthesis pathway, including that of <it>THI1</it>, <it>THIC</it>, <it>TH1 </it>and <it>TPK</it>, was analyzed for 48 h in seedlings subjected to NaCl or sorbitol treatment. These genes were found to be predominantly up-regulated in the early phase (2-6 h) of the stress response. The changes in these gene transcript levels were further found to correlate with increases in thiamine and its diphosphate ester content in seedlings, as well as with the enhancement of gene expression for enzymes which require thiamine diphosphate as a cofactor, mainly α-ketoglutarate dehydrogenase, pyruvate dehydrogenase and transketolase. In the case of the phytohormones including the salicylic, jasmonic and abscisic acids which are known to be involved in plant stress responses, only abscisic acid was found to significantly influence the expression of thiamine biosynthetic genes, the thiamine diphosphate levels, as well as the expression of genes coding for main thiamine diphosphate-dependent enzymes. Using Arabidopsis mutant plants defective in abscisic acid production, we demonstrate that this phytohormone is important in the regulation of <it>THI1 </it>and <it>THIC </it>gene expression during salt stress but that the regulatory mechanisms underlying the osmotic stress response are more complex.</p> <p>Conclusions</p> <p>On the basis of the obtained results and earlier reported data, a general model is proposed for the involvement of the biosynthesis of thiamine compounds and thiamine diphosphate-dependent enzymes in abiotic stress sensing and adaptation processes in plants. A possible regulatory role of abscisic acid in the stress sensing phase is also suggested by these data.</p

    Fitting Corrections to an RNA Force Field Using Experimental Data

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    Empirical force fields for biomolecular systems are usually derived from quantum chemistry calculations and validated against experimental data. We here show how it is possible to refine the full dihedral-angle potential of the Amber RNA force field by using solution NMR data as well as stability of known structural motifs. The procedure can be used to mix multiple systems and heterogeneous experimental information and crucially depends on a regularization term chosen with a cross-validation procedure. By fitting corrections to the dihedral angles on the order of less than 1 kJ/mol per angle, it is possible to increase the stability of difficult-to-fold RNA tetraloops by more than 1 order of magnitude

    Exogenously added GPI-anchored tissue inhibitor of matrix metal loproteinase-1 (TIMP-1) displays enhanced and novel biological activities

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    The family of tissue inhibitors of metalloproteinases (TIMPs) exhibits diverse physiological/biological functions including the inhibition of active matrix metalloproteinases, regulation of proMMP activation, cell growth, and the modulation of angiogenesis. TIMP-1 is a secreted protein that can be detected on the cell surface through its interaction with surface proteins. The diverse biological functions of TIMP-1 are thought to lie, in part, in the kinetics of TIMP-1/MMP/surface protein interactions. Proteins anchored by glycoinositol phospholipids (GPIs), when purified and added to cells in vitro, are incorporated into their surface membranes. A GPI anchor was fused to TIMP-1 to generate a reagent that could be added directly to cell membranes and thus focus defined concentrations of TIMP-1 protein on any cell surface independent of protein-protein interaction. Unlike native TIMP-1, exogenously added GPI-anchored TIMP-1 protein effectively blocked release of MMP-2 and MMP-9 from osteosarcoma cells. TIMP-1-GP1 was a more effective modulator of migration and proliferation than TIMP-1. While control hTIMP-1 protein did not significantly affect migration of primary microvascular endothelial cells at the concentrations tested, the GPI-anchored TIMP-1 protein showed a pronounced suppression of endothelial cell migration in response to bFGF. In addition, TIMP-1-GPI was more effective at inducing microvascular endothelial proliferation. In contrast, fibroblast proliferation was suppressed by the agent. Reagents based on this method should assist in the dissection of the protease cascades and activities involved in TIMP biology. Membrane-fixed TIMP-1 may represent a more effective version of the protein for use in therapeutic expression

    Telescopic hybrid fast solver for 3D elliptic problems with point singularities

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    This paper describes a telescopic solver for two dimensional h adaptive grids with point singularities. The input for the telescopic solver is an h refined two dimensional computational mesh with rectangular finite elements. The candidates for point singularities are first localized over the mesh by using a greedy algorithm. Having the candidates for point singularities, we execute either a direct solver, that performs multiple refinements towards selected point singularities and executes a parallel direct solver algorithm which has logarithmic cost with respect to refinement level. The direct solvers executed over each candidate for point singularity return local Schur complement matrices that can be merged together and submitted to iterative solver. In this paper we utilize a parallel multi-thread GALOIS solver as a direct solver. We use Incomplete LU Preconditioned Conjugated Gradients (ILUPCG) as an iterative solver. We also show that elimination of point singularities from the refined mesh reduces significantly the number of iterations to be performed by the ILUPCG iterative solver

    Dust in the bright supernova remnant N49 in the LMC

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    We investigate the dust associated with the supernova remnant (SNR) N49 in the Large Magellanic Cloud (LMC) as observed with the Herschel Space Observatory. N49 is unusually bright because of an interaction with a molecular cloud along its eastern edge. We have used PACS and SPIRE to measure the far IR flux densities of the entire SNR and of a bright region on the eastern edge of the SNR where the SNR shock is encountering the molecular cloud. Using these fluxes supplemented with archival data at shorter wavelengths, we estimate the dust mass associated with N49 to be about 10 Msun. The bulk of the dust in our simple two-component model has a temperature of 20-30 K, similar to that of nearby molecular clouds. Unfortunately, as a result of the limited angular resolution of Herschel at the wavelengths sampled with SPIRE, the uncertainties are fairly large. Assuming this estimate of the dust mass associated with the SNR is approximately correct, it is probable that most of the dust in the SNR arises from regions where the shock speed is too low to produce significant X-ray emission. The total amount of warm 50-60 K dust is ~0.1 or 0.4 Msun, depending on whether the dust is modeled in terms of carbonaceous or silicate grains. This provides a firm lower limit to the amount of shock heated dust in N49.Comment: accepted by the Astronomy & Astrophysics Lette

    Spectral Correlation in Incommensurate Multi-Walled Carbon Nanotubes

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    We investigate the energy spectra of clean incommensurate double-walled carbon nanotubes, and find that the overall spectral properties are described by the so-called critical statistics of Anderson metal-insulator transition. In the energy spectra, there exist three different regimes characterized by Wigner-Dyson, Poisson, and semi-Poisson distributions. This feature implies that the electron transport in incommensurate multi-walled nanotubes can be either diffusive, ballistic, or intermediate between them, depending on the position of the Fermi energy.Comment: final version to appear in Phys. Rev. Let

    Traditional and Nontraditional Cardiovascular Risk Factors and Estimated Risk for Coronary Artery Disease in Renal Transplant Recipients: A Single-Center Experience

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    Background/Aims: The prevalence of cardiovascular disease in renal transplant recipients is markedly higher than in the general population due to the high prevalence of traditional cardiovascular risk factors, renal transplant function impairment and treatment with immunosuppressive drugs that affect blood pressure, cholesterol and blood glucose levels. Methods: Cross-sectional analysis using our renal transplant clinic cohort investigating (1) the cardiovascular risk factors present in this cohort, and (2) estimating their impact on the risk of coronary artery disease (CAD) by using the Framingham algorithm. Results: Control of modifiable cardiovascular risk factors in 231 renal transplant recipients is suboptimal, i.e. 47.2% of patients are hypertensive, 10.3% actively smoke, 39.4% have serum cholesterol concentrations >200 mg/dl, and 19.7% have diabetes mellitus. Blood pressure, age, hyperlipidemia, smoking and diabetes modulate the estimated CAD risk in males and females. Furthermore, a short time period (less than 1 year) since transplantation and increased serum creatinine levels negatively influenced the CAD risk in this patient population. Conclusion: According to current guidelines, the control of modifiable cardiovascular risk factors in renal transplant recipients is suboptimal. The decreasing CAD risk over time after transplantation may be due to the reduction of immunosuppressive drugs with time and survival bias
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