A 3D finite-volume integral boundary layer method for icing applications

A three-dimensional integral boundary layer code was developed to allow fast computations of boundary layer flows for the purpose of ice accretion modelling. The model is derived in this paper. It is based on a surface Finite-Volume approach. The unsteady equations of momentum deficit and kinetic energy deficit are solved until convergence is reached, preventing from specifying explicitly the stagnation point or separation line. A validation of the code is also presented in the present article. First, the 3D solver is cross-checked against a 2D solver on test cases of self-similar flows and on a NACA0012 configuration. The modelling of the effects of three-dimensionality is also assessed on a self-similar flow test-case. Moreover, the use of unstructured grids is also validated. Finally, an example of the use of the code for the computation of ice accretion is presented

ZNF217 confers resistance to the pro-apoptotic signals of paclitaxel and aberrant expression of Aurora-A in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>ZNF217 is a candidate oncogene located at 20q13, a chromosomal region frequently amplified in breast cancers. The precise mechanisms involved in ZNF217 pro-survival function are currently unknown, and utmost importance is given to deciphering the role of ZNF217 in cancer therapy response.</p> <p>Results</p> <p>We provide evidence that stable overexpression of ZNF217 in MDA-MB-231 breast cancer cells conferred resistance to paclitaxel, stimulated cell proliferation <it>in vitro </it>associated with aberrant expression of several cyclins, and increased tumor growth in mouse xenograft models. Conversely, siRNA-mediated silencing of ZNF217 expression in MCF7 breast cancer cells, which possess high endogenous levels of ZNF217, led to decreased cell proliferation and increased sensitivity to paclitaxel. The paclitaxel resistance developed by ZNF217-overexpressing MDA-MB-231 cells was not mediated by the ABCB1/PgP transporter. However, ZNF217 was able to counteract the apoptotic signals mediated by paclitaxel as a consequence of alterations in the intrinsic apoptotic pathway through constitutive deregulation of the balance of Bcl-2 family proteins. Interestingly, ZNF217 expression levels were correlated with the oncogenic kinase Aurora-A expression levels, as ZNF217 overexpression led to increased expression of the Aurora-A protein, whereas ZNF217 silencing was associated with low Aurora-A expression levels. We showed that a potent Aurora-A kinase inhibitor was able to reverse paclitaxel resistance in the ZNF217-overexpressing cells.</p> <p>Conclusion</p> <p>Altogether, these data suggest that ZNF217 might play an important role in breast neoplastic progression and chemoresistance, and that Aurora-A might be involved in ZNF217-mediated effects.</p

NOXA-Induced Alterations in the Bax/Smac Axis Enhance Sensitivity of Ovarian Cancer Cells to Cisplatin

Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

Uncertainty quantification for characterization of high enthalpy facilities

The postflight analysis of a space mission requires accurate determination of the free-stream conditions for the trajectory. The Mach number, temperature, and pressure conditions can be rebuilt from the heat flux and pressure measured on the spacecraft by means of a Flush Air Data System (FADS). This instrumentation comprises a set of sensors flush mounted in the thermal protection system to measure the static pressure (pressure taps) and heat flux (calorimeters). Knowing that experimental data suffer from errors, this methodology needs to integrate quantification of uncertainties. Epistemic uncertainties on the models for chemistry in the bulk and at the wall (surface catalysis) should also be taken into account. To study this problem it is necessary to solve a stochastic backward problem. This paper focuses on a preliminary sensitivity analysis of the forward problem to understand which uncertainties need to be accounted for. In section 2, the uncertainty quantification methodologies used in this work are presented. Section 3 is dedicated to the one-dimensional (1D) simulations of the shock layer to identify which chemical reactions of the mechanism need to be accounted for in the Uncertainty Quantification (UQ). After this triage procedure, the two-dimensional (2D) axisymmetric flow around the blunt nose was simulated for two trajectory points of EXPERT (EXPErimental Reentry Test-bed) is simulated and the propagation of the uncertainties on the stagnation pressure and heat flux has been studied. To do this study, the open source software DAKOTA from Sandia National Laboratory [1] is coupled with two in-house codes: SHOCKING that simulates the evolution of the chemical relaxation in the shock layer [2], and COSMIC that simulates axisymmetric chemically reacting flows [3]