Prediction of Helicopter Rotor Hover Performance using High Fidelity CFD Methods

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Protein kinase Cδ and c-Abl kinase are required for transforming growth factor β induction of endothelial-mesenchymal transition in vitro.

OBJECTIVE: The origin of the mesenchymal cells responsible for the intimal fibrosis in systemic sclerosis (SSc) has not been fully identified. The present study was undertaken to investigate whether subendothelial mesenchymal cells may emerge through transdifferentiation of endothelial cells (ECs) into myofibroblasts via endothelial-mesenchymal transition (EndoMT) in vitro and to explore the signaling pathways involved in this process. METHODS: Primary mouse pulmonary ECs isolated by immunomagnetic methods with sequential anti-CD34 and anti-CD102 antibody selection were cultured in monolayers. Cell morphology and diacetylated low-density lipoprotein uptake assays confirmed their EC characteristics. The induction of EndoMT was assessed by determination of α-smooth muscle actin (α-SMA), type I collagen, and VE-cadherin expression, and the expression of the transcriptional repressor Snail-1 was analyzed. The signaling pathways involved were examined using small-molecule kinase inhibitors and RNA interference. RESULTS: Transforming growth factor β1 (TGFβ1) induced α-SMA and type I collagen expression and inhibited VE-cadherin. These effects were mediated by a marked increase in Snail-1 expression and were abolished by treatment with either the c-Abl tyrosine kinase inhibitor imatinib mesylate or the protein kinase Cδ (PKCδ) inhibitor rottlerin. The inhibitory effects of imatinib mesylate and rottlerin were mediated by inhibition of phosphorylation of glycogen synthase kinase 3β at residue Ser(9). These observations were confirmed in experiments using small interfering RNA specific for c-Abl and PKCδ. CONCLUSION: These results indicate that c-Abl and PKCδ are crucial for TGFβ-induced EndoMT and that imatinib mesylate and rottlerin or similar kinase inhibitor molecules may be effective therapeutic agents for SSc and other fibroproliferative vasculopathies in which EndoMT plays a pathogenetic role

Using the X-ray Emission Lines of Seyfert 2 AGN to Measure Abundance Ratios

We measure the metal abundance ratios in the X-ray photoionized gas located near the narrow line region of a sample of Seyfert 2 AGN. The high-resolution X-ray spectra observed with the Chandra high- and low-energy transmission grating spectrometers are compared with models of the resonant scattering and recombination emission from a plasma in thermal balance, and with multiple temperature zones. The abundance ratios in the sample are close to the Solar values, with slight over-abundances of N in NGC 1068, and of Ne in NGC 4151. Our X-ray spectral models use fewer degrees of freedom than previous works.Comment: 2 pages, 1 figure, to appear in the proceedings of the conference "Multiwavelenth AGN Surveys", held in Cozumel, Mexico, December 200

Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of Systemic Sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality?

Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and multiple internal organs and severe functional and structural microvascular alterations. SSc is considered to be the prototypic systemic fibrotic disorder. Despite currently available therapeutic approaches SSc has a high mortality rate owing to the development of SSc-associated interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), complications that have emerged as the most frequent causes of disability and mortality in SSc. The pathogenesis of the fibrotic process in SSc is complex and despite extensive investigation the exact mechanisms have remained elusive. Myofibroblasts are the cells ultimately responsible for tissue fibrosis and fibroproliferative vasculopathy in SSc. Tissue myofibroblasts in SSc originate from several sources including expansion of quiescent tissue fibroblasts and tissue accumulation of CD34+ fibrocytes. Besides these sources, myofibroblasts in SSc may result from the phenotypic conversion of endothelial cells into activated myofibroblasts, a process known as endothelial to mesenchymal transition (EndoMT). Recently, it has been postulated that EndoMT may play a role in the development of SSc-associated ILD and PAH. However, although several studies have described the occurrence of EndoMT in experimentally induced cardiac, renal, and pulmonary fibrosis and in several human disorders, the contribution of EndoMT to SSc-associated ILD and PAH has not been generally accepted. Here, the experimental evidence supporting the concept that EndoMT plays a role in the pathogenesis of SSc-associated ILD and PAH will be reviewed

F stars, metallicity, and the ages of red galaxies at z > 1

We explore whether the rest-frame near-UV spectral region, observable in high-redshift galaxies via optical spectroscopy, contains sufficient information to allow the degeneracy between age and metallicity to be lifted. We do this by testing the ability of evolutionary synthesis models to reclaim the correct metallicity when fitted to the near-UV spectra of F stars of known (sub-solar and super-solar) metallicity. F stars are of particular interest because the rest-frame near-UV spectra of the oldest known elliptical galaxies at z > 1 appear to be dominated by F stars near to the main-sequence turnoff. We find that, in the case of the F stars, where the HST ultraviolet spectra have high signal:noise, model-fitting with metallicity allowed to vary as a free parameter is rather successful at deriving the correct metallicity. As a result, the estimated turnoff ages of these stars yielded by the model fitting are well constrained. Encouraged by this we have fitted these same variable- metallicity models to the deep, optical spectra of the z \simeq 1.5 mJy radio galaxies 53W091 and 53W069 obtained with the Keck telescope. While the age-metallicity degeneracy is not so easily lifted for these galaxies, we find that even when metallicity is allowed as a free parameter, the best estimates of their ages are still \geq 3 Gyr, with ages younger than 2 Gyr now strongly excluded. Furthermore, we find that a search of the entire parameter space of metallicity and star formation history using MOPED (Heavens et al., 2000) leads to the same conclusion. Our results therefore continue to argue strongly against an Einstein-de Sitter universe, and favour a lambda-dominated universe in which star formation in at least these particular elliptical galaxies was completed somewhere in the redshift range z = 3 - 5.Comment: 10 pages, LaTeX, uses MNRAS style file, incorporates 14 postscript figures, submitted to MNRAS. Changes include: inclusion of single stellar atmosphere model fits; more rigorous calculation of confidence regions; some re-structurin