522 research outputs found

    Life extending control for rocket engines

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    The concept of life extending control is defined. A brief discussion of current fatigue life prediction methods is given and the need for an alternative life prediction model based on a continuous functional relationship is established. Two approaches to life extending control are considered: (1) the implicit approach which uses cyclic fatigue life prediction as a basis for control design; and (2) the continuous life prediction approach which requires a continuous damage law. Progress on an initial formulation of a continuous (in time) fatigue model is presented. Finally, nonlinear programming is used to develop initial results for life extension for a simplified rocket engine (model)

    H3 histamine receptor-mediated activation of protein kinase calpha inhibits the growth of cholangiocarcinoma in vitro and in vivo

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    Histamine regulates functions via four receptors (HRH1, HRH2, HRH3, and HRH4). The D-myo-inositol 1,4,5-trisphosphate (IP(3))/Ca(2+)/protein kinase C (PKC)/mitogen-activated protein kinase pathway regulates cholangiocarcinoma growth. We evaluated the role of HRH3 in the regulation of cholangiocarcinoma growth. Expression of HRH3 in intrahepatic and extrahepatic cell lines, normal cholangiocytes, and human tissue arrays was measured. In Mz-ChA-1 cells stimulated with (R)-(alpha)-(-)-methylhistamine dihydrobromide (RAMH), we measured (a) cell growth, (b) IP(3) and cyclic AMP levels, and (c) phosphorylation of PKC and mitogen-activated protein kinase isoforms. Localization of PKC alpha was visualized by immunofluorescence in cell smears and immunoblotting for PKC alpha in cytosol and membrane fractions. Following knockdown of PKC alpha, Mz-ChA-1 cells were stimulated with RAMH before evaluating cell growth and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation. In vivo experiments were done in BALB/c nude mice. Mice were treated with saline or RAMH for 44 days and tumor volume was measured. Tumors were excised and evaluated for proliferation, apoptosis, and expression of PKC alpha, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF receptor 2, and VEGF receptor 3. HRH3 expression was found in all cells. RAMH inhibited the growth of cholangiocarcinoma cells. RAMH increased IP(3) levels and PKC alpha phosphorylation and decreased ERK1/2 phosphorylation. RAMH induced a shift in the localization of PKC alpha expression from the cytosolic domain into the membrane region of Mz-ChA-1 cells. Silencing of PKC alpha prevented RAMH inhibition of Mz-ChA-1 cell growth and ablated RAMH effects on ERK1/2 phosphorylation. In vivo, RAMH decreased tumor growth and expression of VEGF and its receptors; PKC alpha expression was increased. RAMH inhibits cholangiocarcinoma growth by PKC alpha-dependent ERK1/2 dephosphorylation. Modulation of PKC alpha by histamine receptors may be important in regulating cholangiocarcinoma growth. (Mol Cancer Res 2009;7(10):1704-13

    Time-of-flight mass measurements of neutron-rich chromium isotopes up to N = 40 and implications for the accreted neutron star crust

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    We present the mass excesses of 59-64Cr, obtained from recent time-of-flight nuclear mass measurements at the National Superconducting Cyclotron Laboratory at Michigan State University. The mass of 64Cr is determined for the first time, with an atomic mass excess of -33.48(44) MeV. We find a significantly different two-neutron separation energy S2n trend for neutron-rich isotopes of chromium, removing the previously observed enhancement in binding at N=38. Additionally, we extend the S2n trend for chromium to N=40, revealing behavior consistent with the previously identified island of inversion in this region. We compare our results to state-of-the-art shell-model calculations performed with a modified Lenzi-Nowacki-Poves-Sieja interaction in the fp shell, including the g9/2 and d5/2 orbits for the neutron valence space. We employ our result for the mass of 64Cr in accreted neutron star crust network calculations and find a reduction in the strength and depth of electron-capture heating from the A=64 isobaric chain, resulting in a cooler than expected accreted neutron star crust. This reduced heating is found to be due to the >1-MeV reduction in binding for 64Cr with respect to values from commonly used global mass models.Comment: Accepted to Physical Review

    CoRoT light curves of RR Lyrae stars. CoRoT 101128793: long-term changes in the Blazhko effect and excitation of additional modes

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    The CoRoT (Convection, Rotation and planetary Transits) space mission provides a valuable opportunity to monitor stars with uninterrupted time sampling for up to 150 days at a time. The study of RR Lyrae stars, performed in the framework of the Additional Programmes belonging to the exoplanetary field, will particularly benefit from such dense, long-duration monitoring. The Blazhko effect in RR Lyrae stars is a long-standing, unsolved problem of stellar astrophysics. We used the CoRoT data of the new RR Lyrae variable CoRoT 101128793 (f0=2.119 c/d, P=0.4719296 d) to provide us with more detailed observational facts to understand the physical process behind the phenomenon. The CoRoT data were corrected for one jump and the long-term drift. We applied different period-finding techniques to the corrected timeseries to investigate amplitude and phase modulation. We detected 79 frequencies in the light curve of CoRoT 101128793. They have been identified as the main frequency f0, and its harmonics, two independent terms, the terms related to the Blazhko frequency, and several combination terms. A Blazhko frequency fB=0.056 c/d and a triplet structure around the fundamental radial mode and harmonics were detected, as well as a long-term variability of the Blazhko modulation. Indeed, the amplitude of the main oscillation is decreasing along the CoRoT survey. The Blazhko modulation is one of the smallest observed in RR Lyrae stars. Moreover, the additional modes f1=3.630 and f2=3.159 c/d are detected. Taking its ratio with the fundamental radial mode into account, the term f1 could be the identified as the second radial overtone. Detecting of these modes in horizontal branch stars is a new result obtained by CoRoT.Comment: 13 pages, 2 figures, 2 long tables. Accepted for publication in A&

    Ground-based astrometry calibrated by Gaia DR1: new perspectives in asteroid orbit determination

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    Context. The Gaia Data Release 1 (GDR1) is a first, important step on the path of evolution of astrometric accuracy towards a much improved situation. Although asteroids are not present in GDR1, this intermediate release already impacts asteroid astrometry. Aims. Our goal is to investigate how the GDR1 can change the approach to a few typical problems, including the determination of orbits from short-arc astrometry, the exploitation of stellar occultations, and the impact risk assessment. Methods.We employ optimised asteroid orbit determination tools, and study the resulting orbit accuracy and post-fit residuals. For this goal, we use selected ground-based asteroid astrometry, and occultation events observed in the past. All measurements are calibrated by using GDR1 stars. Results. We show that, by adopting GDR1, very short measurement arcs can already provide interesting orbital solutions, capable of correctly identifying near-Earth asteroids (NEAs) and providing a much more accurate risk rating. We also demonstrate that occultations, previously used to derive asteroid size and shapes, now reach a new level of accuracy at which they can be fruitfully used to obtain astrometry at the level of accuracy of Gaia star positions

    Activation of Fas/FasL pathway and the role of c-FLIP in primary culture of human cholangiocarcinoma cells

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    Intrahepatic cholangiocarcinoma (iCCA) represents a heterogeneous group of malignancies emerging from the biliary tree, often in the context of chronic bile ducts inflammation. The immunological features of iCCA cells and their capability to control the lymphocytes response have not yet been investigated. The aims of the present study were to evaluate the interaction between iCCA cells and human peripheral blood mononuclear cells (PBMCs) and the role of Fas/FasL in modulating T-cells and NK-cells response after direct co-culture. iCCA cells express high levels of Fas and FasL that increase after co-culture with PBMCs inducing apoptosis in CD4(+), CD8(+) T-cells and in CD56(+) NK-cells. In vitro, c-FLIP is expressed in iCCA cells and the co-culture with PBMCs induces an increase of c-FLIP in both iCCA cells and biliary tree stem cells. This c-FLIP increase does not trigger the caspase cascade, thus hindering apoptotis of iCCA cells which, instead, underwent proliferation. The increased expression of Fas, FasL and c-FLIP is confirmed in situ, in human CCA and in primary sclerosing cholangitis. In conclusion our data indicated that iCCA cells have immune-modulatory properties by which they induce apoptosis of T and NK cells, via Fas/FasL pathway, and escape inflammatory response by up-regulating c-FLIP system

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
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