Development of a computational aero/fluids analysis system

The Computational Aero/Fluids Analysis System (AFAS) provides the analytical capability to perform state-of-the-art computational analyses in two difficult fluid dynamics disciplines associated with the Space Shuttle program. This system provides the analysis tools and techniques for rapidly and efficiently accessing, analyzing, and reformulating the large and expanding external aerodynamic data base while also providing tools for complex fluid flow analyses of the SSME engine components. Both of these fluid flow disciplines, external aerodynamics and internal gasdynamics, required this capability to ensure that MSFC can respond in a timely manner as problems are encountered and operational changes are made in the Space Shuttle

Chronic-moderate ethanol exposure of L(tk-) cells expressing ? 4? 3? GABAA receptors reduces potency of allopregnanolone potentiation of GABA-evoked inward currents: Possible role of PKC

Aim: To investigate the effect of chronic-moderate ethanol (CME) treatment upon direct activation and allosteric modulation of GABAA receptors, and to assess the sensitivity of these parameters to PKC inhibition in control and ethanol-treated cells. Methods: L(tk-) cells were exposed to 20mM ethanol in culture media for 14 days prior to induction of stable expression of human recombinant ?4?3? receptors using dexamethasone. Concentration-response curves for GABA (1nM - 100µM), and allopregnanolone (ALLO; 1nM - 30µM) co-applied with 200nM GABA were obtained using whole-cell patch-clamp electrophysiology at a holding voltage of -60 mV. 400nM calphostin C (CphC) or vehicle (DMSO) was administered to cells via the pipette solution, which was prepared with 2mM Mg.ATP. SDS-PAGE and western blotting were used to compare levels of whole-cell expression, quantified relative to ?-actin, of ?4 and ? GABAA receptor subunits, and several isoforms of PKC (?, ?, ?, and ?), in control and CME-treated cells. Data was reported as Mean ± SEM and significance determined by either one-way ANOVA with Newman-Keuls multiple comparison tests, or two-way, unpaired t-tests. Results: Expression of ?4 subunits was reduced 35% (P0.05) and pEC50 (control: 6.18±0.04, n=13, CME: 6.17±0.04, n=4, P>0.05) of GABA were unchanged. CphC increased the GABA pEC50 relative to control (6.62±0.08, n=3, P<0.001) but had no effect upon responses at pEC20 GABA. Following CME, the potency of GABA was unaltered in the presence of CphC. The magnitude of ALLO-induced potentiation in control cells (7.34±0.6 fold, n=19) was unchanged by CME (ATP: 7.39±1.0 fold, n=9, P>0.05), and CphC had no significant effect in control or CME-treated cells. The ALLO pEC50 in control cells (6.23±0.05, n=19) was unaffected by CphC. Following CME, the potency of ALLO was reduced (5.68±0.06, n=9, P<0.001) but was enhanced in the presence of CphC, which restored potency almost back to control levels (5.94±0.09, n=5, P<0.05 relative to control). Expression of the ?, ?, ?, and ? isoforms of PKC was detected in whole-cell lysates of L(tk-) cells but only PKC? was significantly altered by CME treatment, exhibiting a nearly 4-fold increase (3.9±0.47 fold P<0.01) when compared with that in controls. Discussion: CME of un-induced L(tk-) cells was sufficient to alter sensitivity of ?4?3? receptor function to alterations of the balance of phosphorylation induced by CphC. The increased expression of PKC? after CME may have been directly related to the absence of effect of CphC upon GABA potency. As direct interaction of GABAA receptors with PKC? has not been determined, the effects observed for potency and efficacy of ALLO following CME may be indicative of changes to the phosphorylation of accessory proteins or other PKC isoforms by PKC?

Immunotherapy in hepatocellular carcinoma: the complex interface between inflammation, fibrosis, and the immune response.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and confers a poor prognosis. Beyond standard systemic therapy with multikinase inhibitors, recent studies demonstrate the potential for robust and durable responses from immune checkpoint inhibition in subsets of HCC patients across disease etiologies. The majority of HCC arises in the context of chronic inflammation and from within a fibrotic liver, with many cases associated with hepatitis virus infections, toxins, and fatty liver disease. Many patients also have concomitant cirrhosis which is associated with both local and systemic immune deficiency. Furthermore, the liver is an immunologic organ in itself, which may enhance or suppress the immune response to cancer arising within it. Here, we explore the immunobiology of the liver from its native state to chronic inflammation, fibrosis, cirrhosis and then to cancer, and summarize how this unique microenvironment may affect the response to immunotherapy

Computer program to predict spacecraft window deformations and compute window induced angular deviations of light rays

Computer program for predicting spacecraft window deformations and computing window induced angular deviations of light ray

Superconducting Surface Impedance under Radiofrequency Field

Based on BCS theory with moving Cooper pairs, the electron states distribution at 0K and the probability of electron occupation with finite temperature have been derived and applied to anomalous skin effect theory to obtain the surface impedance of a superconductor under radiofrequency (RF) field. We present the numerical results for Nb and compare these with representative RF field-dependent effective surface resistance measurements from a 1.5 GHz resonant structure

Qualitative Criterion for Interception in a Pursuit/Evasion Game

A qualitative account is given of a differential pursuit/evasion game. A criterion for the existence of an intercept solution is obtained using future cones that contain all attainable trajectories of target or interceptor originating from an initial position. A sufficient and necessary conditon that an opportunity to intercept always exist is that, after some initial time, the future cone of the target be contained within the future cone of the interceptor. The sufficient condition may be regarded as a kind of Nash equillibrium.Comment: 8 pages; revsions and corrigend

Organic geochemistry of the crater-fill sediments from Boltysh impact crater, Ukraine

The Boltysh impact crater, is a complex structure formed on the basement rocks of the Ukrainian shield which has been dated at 65.17±0.64 Ma [1]. The Boltysh crater has been know for several decades and was originally drilled in the 1960s-1980s in a study of economic oil shale deposits. Unfortunately, the cores were not curated and have been lost. However we have recently re-drilled the impact crater and have recovered a near continuous record of ~400 m of organic rich sediments deposited in a deep isolated lake which overlie the basement rocks spanning a period ~10 Ma. At 24km diameter, Boltysh will not have contributed substantially to the worldwide devastation at the end of the Cretaceous. However, the precise age of the Boltysh impact relative to the Chicxulub impact and its location on a stable low lying coastal plain which allowed formation of the postimpact crater lake make it a particularly important locality. After the impact, the crater quickly filled with water in a short marine phase but returned to fresh water which persisted for >10Ma [2]. These strata contain a valuable record of Paleogene environmental change in central Europe, and one of very few terrestrial records of the KT event. This pre-eminent record of the Paleogene can help us to answer several related scientific questions including the relative age of Boltysh compared with Chicxulub, recovery from the impact, and later climate signals. The organic geochemistry and playnology indicate main inputs to be algal and higher plant within most of the core although there are some marked changes in inputs in some sections. A number of carbon isotope excursions are also present within the core which are currently being further investigated

New ⁴⁰Ar/³⁹Ar dating of the Grande Ronde lavas, Columbia River Basalts, USA: Implications for duration of flood basalt eruption episodes

Grande Ronde Basalt (GRB) lavas represent the most voluminous eruptive pulse of the Columbia River-Snake River-Yellowstone hotspot volcanism. With an estimated eruptive volume of 150,000 km3, GRB lavas form at least 66% of the total volume of the Columbia River Basalt Group. New 40Ar/39Ar dates for GRB lavas reveal they were emplaced within a maximum period of 0.42 ± 0.18 My. A well-documented stratigraphy indicates at least 110 GRB flow fields (or individual eruptions), and on this basis suggests an average inter-eruption hiatus of less than 4,000 years. Isotopic age-dating cannot resolve time gaps between GRB eruptions, and it is difficult to otherwise form a picture of the durations of eruptions because of non-uniform weathering in the top of flow fields and a general paucity of sediments between GR lavas. Where sediment has formed on top of the GRB, it varies in thickness from zero to 20-30 cm of silty to fine-sandy material, with occasional diatomaceous sediment. Individual GRB eruptions varied considerably in volume but many were greater than 1000 km3 in size. Most probably eruptive events were not equally spaced in time; some eruptions may have followed short periods of volcanic repose (perhaps 102 to 103 of yrs), whilst others could have been considerably longer (many 1000 s to > 104 yrs). Recent improvements in age-dating for other continental flood basalt (CFB) lava sequences have yielded estimates of total eruptive durations of less than 1 My for high-volume pulses of lava production. The GRB appears to be a similar example, where the main pulse occupied a brief period. Even allowing for moderate to long-duration pahoehoe flow field production, the amount of time the system spends in active lava-producing mode is small – less than c. 2.6% (based on eruption durations of approximately 10,000 yrs, as compared to the duration of the entire eruptive pulse of c. 420,000 yrs). A review of available 40Ar/39Ar data for the major voluminous phases of the Columbia River Basalt Group suggests that activity of the Steens Basalt-Imnaha Basalt-GRB may have, at times, been simultaneous, with obvious implications for climatic effects. Resolving intervals between successive eruptions during CFB province construction, and durations of main eruptive pulses, remains vital to determining the environmental impact of these huge eruptions