Experimental Investigation of the Shuttle Transportation System Composite Overwrapped Pressure Vessels for Stress Rupture Life

A viewgraph presentation describing stress rupture testing on Composite Overwrapped Pressure Vessels (COPV) is shown. The topics include: 1) Purpose for Testing; 2) NASA WSTF COPV Test Program; 3) NASA WSTF Test Facilities; 4) COPV Impact Study; 5) Fluids Compatibility Testing; 6) Stress Rupture Testing; and 7) COPV Lifting

Reovirus exerts potent oncolytic effects in head and neck cancer cell lines that are independent of signalling in the EGFR pathway

Background: reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas of the head and neck (SCCHN) over-express EGFR and SCCHN cell lines are sensitive to oncolytic reovirus, we conducted a detailed analysis of the effects of reovirus in 15 head and neck cancer cell lines. Both pre- and post-entry events were studied in an attempt to define biomarkers predictive of sensitivity/resistance to reovirus. In particular, we analysed the role of EGFR/Ras signalling in determining virus-mediated cytotoxicity in SCCHN. Methods: to test whether EGFR pathway activity was predictive of increased sensitivity to reovirus, correlative analyses between reoviral IC50 by MTT assay and EGFR levels by western blot and FACS were conducted. Inhibition or stimulation of EGFR signalling were analysed for their effect on reoviral oncolysis by MTT assay, and viral growth by TCID50 assay. We next analysed the effects of inhibiting signalling downstream of Ras, by specific inhibitors of p38MAPK, PI3-K or MEK, on reoviral killing examined by MTT assay. The role of PKR in reoviral killing was also determined by blockade of PKR using 2-aminopurine and assaying for cell survival by MTT assay. The apoptotic response of SCCHN to reovirus was examined by western blot analysis of caspase 3 cleavage. Results: correlative analyses between reoviral sensitivity and EGFR levels revealed no association. Intermediate sub-viral and core particles showed the same infectivity/cytotoxicity as intact reovirus. Therefore, sensitivity was not determined by cell entry. In 4 cell lines, oncolysis and viral growth were both unaffected by inhibition or stimulation of EGFR signalling. Inhibition of signalling downstream of Ras did not abrogate reoviral oncolysis and, in addition, modulation of PKR using 2-aminopurine did not alter reovirus sensitivity in resistant cell lines. Caspase 3 cleavage was not detected in infected cells and oncolysis was observed in pan-caspase inhibited cells. Conclusions: in summary, reovirus is potently oncolytic in a broad panel of SCCHN cell lines. Attempts to define sensitivity/resistance by analysis of the EGFR/Ras/MAPK pathway have failed to provide a clear predictive biomarker of response. Further analysis of material from in vitro and clinical studies is ongoing in an attempt to shed further light on this issue

Reliability of functional magnetic resonance imaging activation during working memory in a multi-site study: Analysis from the North American Prodrome Longitudinal Study

Multi-site neuroimaging studies offer an efficient means to study brain functioning in large samples of individuals with rare conditions; however, they present new challenges given that aggregating data across sites introduces additional variability into measures of interest. Assessing the reliability of brain activation across study sites and comparing statistical methods for pooling functional data is critical to ensuring the validity of aggregating data across sites. The current study used two samples of healthy individuals to assess the feasibility and reliability of aggregating multi-site functional magnetic resonance imaging (fMRI) data from a Sternberg-style verbal working memory task. Participants were recruited as part of the North American Prodrome Longitudinal Study (NAPLS), which comprises eight fMRI scanning sites across the United States and Canada. In the first study sample (n = 8), one participant from each home site traveled to each of the sites and was scanned while completing the task on two consecutive days. Reliability was examined using generalizability theory. Results indicated that blood oxygen level-dependent (BOLD) signal was reproducible across sites and was highly reliable, or generalizable, across scanning sites and testing days for core working memory ROIs (generalizability ICCs = 0.81 for left dorsolateral prefrontal cortex, 0.95 for left superior parietal cortex). In the second study sample (n = 154), two statistical methods for aggregating fMRI data across sites for all healthy individuals recruited as control participants in the NAPLS study were compared. Control participants were scanned on one occasion at the site from which they were recruited. Results from the image-based meta-analysis (IBMA) method and mixed effects model with site covariance method both showed robust activation in expected regions (i.e. dorsolateral prefrontal cortex, anterior cingulate cortex, supplementary motor cortex, superior parietal cortex, inferior temporal cortex, cerebellum, thalamus, basal ganglia). Quantification of the similarity of group maps from these methods confirmed a very high (96%) degree of spatial overlap in results. Thus, brain activation during working memory function was reliable across the NAPLS sites and both the IBMA and mixed effects model with site covariance methods appear to be valid approaches for aggregating data across sites. These findings indicate that multi-site functional neuroimaging can offer a reliable means to increase power and generalizability of results when investigating brain function in rare populations and support the multi-site investigation of working memory function in the NAPLS study, in particular

Multi-messenger Observations of a Binary Neutron Star Merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ∼ 1.7 {{s}} with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of {40}-8+8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 {M}⊙ . An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ∼ 40 {{Mpc}}) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient's position ∼ 9 and ∼ 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.The AST3 project is supported by the National Basic Research Program (973 Program) of China (Grant Nos. 2013CB834901, 2013CB834900, 2013CB834903), and the Chinese Polar Environment Comprehensive Investigation & Assessment Program (grant No. CHINARE2016-02-03-05). The construction of the AST3 telescopes has received fundings from Tsinghua University, Nanjing University, Beijing Normal University, University of New South Wales, and Texas A&M University, the Australian Antarctic Division, and the National Collaborative Research Infrastructure Strategy (NCRIS) of Australia. It has also received funding from Chinese Academy of Sciences through the Center for Astronomical Mega-Science and National Astronomical Observatory of China (NAOC).The collaboration between LIGO/Virgo and EVN/e-MERLIN is part of a project that has received funding from the European Unions Horizon 2020 research and innovation programme under grant agreement No. 653477.B.C., V.C., A.G., and W.S.P. gratefully acknowledge NASA funding through contract NNM13AA43C. M.S.B., R.H., P.J., C.A.M., S.P., R.D.P., M.S., and P.V. gratefully acknowledge NASA funding from cooperative agreement NNM11AA01A. E.B. is supported by an appointment to the NASA Postdoctoral Program at the Goddard Space Flight Center, administered by Universities Space Research Association under contract with NASA. D.K., C.A.W.H., C.M. H., and J.R. gratefully acknowledge NASA funding through the Fermi-GBM project. Support for the German contribution to GBM was provided by the Bundesministerium für Bildung und Forschung (BMBF) via the Deutsches Zentrum für Luft und Raumfahrt (DLR) under contract number 50 QV 0301. A. v.K. was supported by the Bundesministeriums für Wirtschaft und Technologie (BMWi) through DLR grant 50 OG 1101. S. M.B. acknowledges support from Science Foundation Ireland under grant 12/IP/1288.Part of the funding for GROND was generously granted from the Leibniz-Prize to Prof. G. Hasinger (DFG grant HA 1850/28-1). “We acknowledge the excellent help in obtaining GROND data from Angela Hempel, Markus Rabus and Régis Lachaume on La Silla.

Statelessness and environmental-induced displacement: future scenarios of deterritorialisation, rescue and recovery examined

This article examines the prospect of environmental displacement and the creation of stateless populations in the context of low lying islands in Melanesia (Carteret Islands and Vanuatu), Micronesia (Kiribati) and Polynesia (Tuvalu), and the Maldives. It reviews the literature on environmental displacement and statelessness before evaluating pre-emptive attempts at ‘national rescue’. This article concludes with a reconsideration of the ideas of deterritorialisation and ‘national moorings’ in light of the obligations on receiving states to respect the human rights of stateless people

Decision Maker Preferences for International Legal Cooperation

Why do some decision makers prefer big multilateral agreements while others prefer cooperation in small clubs? Does enforcement encourage or deter institutional cooperation? We use experiments drawn from behavioral economics and cognitive psychology - along with a substantive survey focused on international trade - to illustrate how two behavioral traits (patience and strategic reasoning) of individuals who play key roles in negotiating and ratifying an international treaty shape their preferences for how treaties are designed and whether they are ratified. Patient subjects were more likely to prefer treaties with larger numbers of countries (and larger long-term benefits), as were subjects with the skill to anticipate how others will respond over multiple iterations of strategic games. The presence of an enforcement mechanism increased subjects' willingness to ratify treaties; however, strategic reasoning had double the effect of adding enforcement to a trade agreement: more strategic subjects were particularly likely to favor ratifying the agreement. We report these results for a sample of 509 university students and also show how similar patterns are revealed in a unique sample of ninety-two actual US policy elites. Under some conditions certain types of university student convenience samples can be useful for revealing elite-dominated policy preferences - different types of people in the same situation may prefer to approach decision-making tasks and reason through trade-offs in materially different ways

First image revisited: human nature, original sin and international relations

In Waltz’s famous classification, human nature’s propensity to evil is catalogued as a first-image causal explanation of war. Ever since, human nature explanations of conflict have been attacked for resting on metaphysical assumptions and a priori pessimism. This paper argues that modern conceptions about the inherent wickedness of human nature or, equally, reductionist sociobiological explanations about its hard-wired conflict-proneness are impoverished secularised versions of Christian anthropological assumptions grounded in the doctrine of original sin. Itself a widely contested dogma, in its Augustinian formulation it was closely connected with a soteriological perspective, that is, a defence of its status as a corollary of the doctrine that all human beings are equally in need of salvation in Jesus Christ. However, its use was never entirely disconnected from the purposes of theodicy and Christian apologetics striving to reconcile the existence of a benevolent and omnipotent God with the reality of evil and suffering in the world. It is this latter legacy – associated with the explanation of suffering and evil in the world but stripped of its salvific eschatological content – that is picked up by secularist theorisations of human nature which tend to reduce the paradox of original sin to the parody of man’s evil nature