57 research outputs found
Characterization of the pressure fluctuations within a Controlled-Diffusion airfoil boundary layer at large Reynolds numbers
The present investigation targets the generation of airfoil trailing-edge broadband noise that arises from the interaction of turbulent boundary layer with the airfoil trailing edge. Large-eddy simulations, carried out using a massively parallel compressible solver CharLESX, are conducted for a Controlled-Diffusion (CD) airfoil with rounded trailing edge for seven configurations, characterized with a Reynolds number, angle of attack and Mach number. An analysis of the unsteady pressure signals in the boundary layer is proposed in regard to classical trailing edge noise modelling ingredients
Treatment of Fabry Disease: Outcome of a Comparative Trial with Agalsidase Alfa or Beta at a Dose of 0.2 mg/kg
Two different enzyme preparations, agalsidase alfa (Replagal(TM), Shire) and beta (Fabrazyme(TM), Genzyme), are registered for treatment of Fabry disease. We compared the efficacy of and tolerability towards the two agalsidase preparations administered at identical protein dose in a randomized controlled open label trial.Thirty-four Fabry disease patients were treated with either agalsidase alfa or agalsidase beta at equal dose of 0.2 mg/kg biweekly. Primary endpoint was reduction in left ventricular mass after 12 and 24 months of treatment. Other endpoints included occurrence of treatment failure (defined as progression of cardiac, renal or cerebral disease), glomerular filtration rate, pain, anti-agalsidase antibodies, and globotriaosylceramide levels in plasma and urine. After 12 and 24 months of treatment no reduction in left ventricular mass was seen, which was not different between the two treatment groups. Also, no differences in glomerular filtration rate, pain and decline in globotriaosylceramide levels were found. Antibodies developed only in males (4/8 in the agalsidase alfa group and 6/8 in the agalsidase beta group). Treatment failure within 24 months of therapy was seen in 8/34 patients: 6 male patients (3 in each treatment group) and 2 female patients (both agalsidase alfa). The occurrence of treatment failures did not differ between the two treatment groups; chi(2) = 0.38 p = 0.54.Our study revealed no difference in reduction of left ventricular mass or other disease parameters after 12 and 24 months of treatment with either agalsidase alfa or beta at a dose of 0.2 mg/kg biweekly. Treatment failure occurred frequently in both groups and seems related to age and severe pre-treatment disease.International Standard Randomized Clinical Trial ISRCTN45178534 [http://www.controlled-trials.com/ISRCTN45178534]
Type 2 Diabetes Susceptibility Gene Expression in Normal or Diabetic Sorted Human Alpha and Beta Cells: Correlations with Age or BMI of Islet Donors
BACKGROUND:
Genome-wide association studies have identified susceptibility genes for development of type 2 diabetes. We aimed to examine whether a subset of these (comprising FTO, IDE, KCNJ11, PPARG and TCF7L2) were transcriptionally restricted to or enriched in human beta cells by sorting islet cells into alpha and beta - specific fractions. We also aimed to correlate expression of these transcripts in both alpha and beta cell types with phenotypic traits of the islet donors and to compare diabetic and non-diabetic cells.
METHODOLOGY/PRINCIPAL FINDINGS:
Islet cells were sorted using a previously published method and RNA was extracted, reverse transcribed and used as the template for quantitative PCR. Sorted cells were also analysed for insulin and glucagon immunostaining and insulin secretion from the beta cells as well as insulin, glucagon and GLP-1 content. All five genes were expressed in both alpha and beta cells, with significant enrichment of KCNJ11 in the beta cells and of TCF7L2 in the alpha cells. The ratio of KCNJ11 in beta to alpha cells was negatively correlated with BMI, while KCNJ11 expression in alpha cells was negatively correlated with age but not associated with BMI. Beta cell expression of glucagon, TCF7L2 and IDE was increased in cells from islets that had spent more time in culture prior to cell sorting. In beta cells, KCNJ11, FTO and insulin were positively correlated with each other. Diabetic alpha and beta cells had decreased expression of insulin, glucagon and FTO.
CONCLUSIONS/SIGNIFICANCE:
This study has identified novel patterns of expression of type 2 diabetes susceptibility genes within sorted islet cells and suggested interactions of gene expression with age or BMI of the islet donors. However, expression of these genes in islets is less associated with BMI than has been found for other tissues
Numerical predictions of turbulence-cascade interaction noise using CAA with a stochastic model
Turbulent flow interactions with the outlet guide vanes are known to be mainly contributing to broadband noise emission of aeroengines at approach conditions. This paper presents a 3D CAA hybrid method aiming at simulating the aeroacoustic response of an annular cascade impacted by a prescribed homogeneous isotropic turbulent flow. It is based on a time-domain Euler solver coupled to a synthetic turbulence model implemented in the code by means of a suited inflow boundary condition proposed by Tam. The fluctuating pressure over the airfoil surface provided by CAA is used as an input to a FWH integral to calculate the radiated sound field. The method is first validated against an academic CAA benchmark in the case of a harmonic gust interacting with an annular flat plate cascade. Then, simulations are applied to turbulence-cascade interactions for annular configurations, in uniform and swirling mean flows, and numerical results in terms of sound power spectra in the outlet duct are compared to semi-analytical and numerical solutions, and to an available experimen
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