1,655 research outputs found

    Comparison of NASA and contractor results from aeroacoustic tests of QCSEE OTW engine

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    The aerodynamics and acoustics of the over-the-wing (OTW) Quiet, Clean, Short Haul Experimental Engine (QCSEE) were tested. A boilerplate (nonflight weight), high-throat Mach number, acoustically treated inlet and a D-shaped OTW exhaust nozzle with variable position side doors were used. Some acoustic directivity results for the type "D" nozzle and acoustic effects of variations in the nozzle side door positions are included. It was found that the results are in agreement with those previously obtained

    Mechanisms of toxic action and structure-activity relationships for organochlorine and synthetic pyrethroid insecticides.

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    The mechanisms and sites of action of organochlorine (DDT-types and chlorinated alicyclics) and synthetic pyrethroid insecticides are presented with discussion of symptoms, physiological effects, and selectivity. The structural requirements for toxicity are assessed, and structure-activity relationships are considered for each subclass. Lipophilicity is important for all the groups because it facilitates delivery of these neurotoxicants to the site of action in the nerve. Steric factors including molecular volume, shape, and isomeric configuration greatly influence toxicity. Electronic parameters also have been demonstrated to affect biological activity in some of the groups of insecticides, e.g., Hammett's sigma and Taft's sigma * as indicators of electronegativity. New synthetic pyrethroids continue to be developed, with varied structures and different physicochemical and biological properties

    Influence of the disorder on tracer dispersion in a flow channel

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    Tracer dispersion is studied experimentally in periodic or disordered arrays of beads in a capillary tube. Dispersion is measured from light absorption variations near the outlet following a steplike injection of dye at the inlet. Visualizations using dye and pure glycerol are also performed in similar geometries. Taylor dispersion is dominant both in an empty tube and for a periodic array of beads: the dispersivity l_dl\_d increases with the P\'eclet number PePe respectively as PePe and Pe0.82Pe^{0.82} and is larger by a factor of 8 in the second case. In a disordered packing of smaller beads (1/3 of the tube diameter) geometrical dispersion associated to the disorder of the flow field is dominant with a constant value of l_dl\_d reached at high P\'eclet numbers. The minimum dispersivity is slightly higher than in homogeneous nonconsolidated packings of small grains, likely due heterogeneities resulting from wall effects. In a disordered packing with the same beads as in the periodic configuration, l_dl\_d is up to 20 times lower than in the latter and varies as PeαPe^\alpha with α=0.5\alpha = 0.5 or =0.69= 0.69 (depending on the fluid viscosity). A simple model accounting for this latter result is suggested.Comment: available online at http://www.edpsciences.org/journal/index.cfm?edpsname=epjap&niv1=contents&niv2=archive

    Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

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    BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction

    Role of serum N-terminal pro-brain natriuretic peptide measurement in diagnosis of cardiac involvement in patients with anderson-fabry disease

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    Enzyme replacement therapy has the potential to delay or reverse adverse cardiac remodeling in Anderson-Fabry disease (AFD); however, the current indications for enzyme replacement therapy rely on detecting relatively advanced features of the disease. We aimed to determine the relation between the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and cardiac abnormalities in patients with AFD. We hypothesized that it might help to detect early disease. NT-proBNP was measured under at rest conditions in 117 patients with AFD (age 48 ± 15 years, 46.2% men). All patients underwent clinical evaluation with electrocardiography and echocardiography. The median NT-proBNP concentration was 24 pmol/L (range <5 to 6,059). Of the 117 patients, 67 (57%) had elevated, age-corrected, NT-proBNP levels. In the 56 patients (48%) with normal echocardiographic findings, the NT-proBNP levels were greater than the age-predicted cutoffs in 10 of 25 patients with abnormal electrocardiographic findings and 3 of 31 patients with normal electrocardiographic findings (p <0.05). On multiple regression analysis, age, creatinine, left atrial volume index, E/Ea, and the presence of abnormal electrocardiographic findings were independently associated with log NT-proBNP (R(2) = 0.67, p <0.05). In conclusion, NT-proBNP concentrations were elevated in patients with AFD and early cardiac involvement, suggesting its measurement could assist in decisions regarding the timing of enzyme replacement therapy

    Transport in rough self-affine fractures

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    Transport properties of three-dimensional self-affine rough fractures are studied by means of an effective-medium analysis and numerical simulations using the Lattice-Boltzmann method. The numerical results show that the effective-medium approximation predicts the right scaling behavior of the permeability and of the velocity fluctuations, in terms of the aperture of the fracture, the roughness exponent and the characteristic length of the fracture surfaces, in the limit of small separation between surfaces. The permeability of the fractures is also investigated as a function of the normal and lateral relative displacements between surfaces, and is shown that it can be bounded by the permeability of two-dimensional fractures. The development of channel-like structures in the velocity field is also numerically investigated for different relative displacements between surfaces. Finally, the dispersion of tracer particles in the velocity field of the fractures is investigated by analytic and numerical methods. The asymptotic dominant role of the geometric dispersion, due to velocity fluctuations and their spatial correlations, is shown in the limit of very small separation between fracture surfaces.Comment: submitted to PR

    The embryonic transcription cofactor LBH is a direct target of the Wnt signaling pathway in epithelial development and in aggressive basal subtype breast cancers

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    Limb-bud and heart (LBH) is a novel key transcriptional regulator of vertebrate development. However, the molecular mechanisms upstream of LBH and its role in adult development are unknown. Here we show that in epithelial development, LBH expression is tightly controlled by Wnt signaling. LBH is transcriptionally induced by the canonical Wnt pathway, as evident by the presence of conserved functional T-cell factor (TCF)/lymphoid enhancer-binding factor (LEF) binding sites in the LBH locus and rapid β-catenin-dependent upregulation of endogenous LBH by Wnt3a. In contrast, LBH induction by Wnt/β-catenin signaling is inhibited by Wnt7a, which in limb development signals through a noncanonical pathway involving Lmx1b. Furthermore, we show that LBH is aberrantly overexpressed in mammary tumors of mouse mammary tumor virus (MMTV)-Wnt1-transgenic mice and in aggressive basal subtype human breast cancers that display Wnt/β-catenin hyperactivation. Deregulation of LBH in human basal breast cancer appears to be Wnt/β-catenin dependent, as DKK1 and Wnt7a inhibit LBH expression in breast tumor cells. Overexpression studies indicate that LBH suppresses mammary epithelial cell differentiation, an effect that could contribute to Wnt-induced tumorigenesis. Taken together, our findings link LBH for the first time to the Wnt signaling pathway in both development and cancer and highlight LBH as a potential new marker for therapeutically challenging basal-like breast cancers
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