8,124 research outputs found
Eurasian integration could offer a counterpoint to the EU and the United States, but only in close co-operation with states like India and China
Russia, Belarus and Kazakhstan have pursued integration with the aim of creating a Eurasian Union by 2015. David Lane writes on the economic and political background underpinning Eurasian integration and its potential to act as a counterpoint to the hegemony of the United States in the global system. He argues that while the economic weight of the three Eurasian Union states is fairly limited, pursuing close co-operation with ‘BRICS’ countries such as Brazil, India and China could offer the basis for a more pluralist and multi-polar world
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Health, demographic change and well-being: the European Union's Horizon 2020 Programme and System Dynamics
Analysis of the March 30, 2011 Hail Event at Shuttle Launch Pad 39A
The Kennedy Space Center (KSC) Hail Monitor System, a joint effort of the NASA KSC Physics Lab and the KSC Engineering Services Contract (ESC) Applied Technology Lab, was first deployed for operational testing in the fall of 2006. Volunteers from the Community Collaborative Rain, Hail, and Snow Network (CoCoRaHS) in conjunction with Colorado State University have been instrumental in validation testing using duplicate hail monitor systems at sites in the hail prone high plains of Colorado. The KSC Hail Monitor System (HMS), consisting of three stations positioned approximately 500 ft from the launch pad and forming an approximate equilateral triangle, as shown in Figure 1, was first deployed to Pad 39B for support of STS-115. Two months later, the HMS was deployed to Pad 39A for support of STS-116. During support of STS-117 in late February 2007, an unusually intense (for Florida standards) hail event occurred in the immediate vicinity of the exposed space shuttle and launch pad. Hail data of this event was collected by the HMS and analyzed. Support of STS-118 revealed another important application of the hail monitor system. Ground Instrumentation personnel check the hail monitors daily when a vehicle is on the launch pad, with special attention after any storm suspected of containing hail. If no hail is recorded by the HMS, the vehicle and pad inspection team has no need to conduct a thorough inspection of the vehicle immediately following a storm. On the afternoon of July 13, 2007, hail on the ground was reported by observers at the Vertical Assembly Building (VAB) and Launch Control Center (LCC), about three miles west of Pad 39A, as well as at several other locations at KSC. The HMS showed no impact detections, indicating that the shuttle had not been damaged by any of the numerous hail events which occurred on that day
Hail Disrometer Array for Launch Systems Support
Prior to launch, the space shuttle might be described as a very large thermos bottle containing substantial quantities of cryogenic fuels. Because thermal insulation is a critical design requirement, the external wall of the launch vehicle fuel tank is covered with an insulating foam layer. This foam is fragile and can be damaged by very minor impacts, such as that from small- to medium-size hail, which may go unnoticed. In May 1999, hail damage to the top of the External Tank (ET) of STS-96 required a rollback from the launch pad to the Vehicle Assembly Building (VAB) for repair of the insulating foam. Because of the potential for hail damage to the ET while exposed to the weather, a vigilant hail sentry system using impact transducers was developed as a hail damage warning system and to record and quantify hail events. The Kennedy Space Center (KSC) Hail Monitor System, a joint effort of the NASA and University Affiliated Spaceport Technology Development Contract (USTDC) Physics Labs, was first deployed for operational testing in the fall of 2006. Volunteers from the Community Collaborative Rain. Hail, and Snow Network (CoCoRaHS) in conjunction with Colorado State University were and continue to be active in testing duplicate hail monitor systems at sites in the hail prone high plains of Colorado. The KSC Hail Monitor System (HMS), consisting of three stations positioned approximately 500 ft from the launch pad and forming an approximate equilateral triangle (see Figure 1), was deployed to Pad 39B for support of STS-115. Two months later, the HMS was deployed to Pad 39A for support of STS-116. During support of STS-117 in late February 2007, an unusual hail event occurred in the immediate vicinity of the exposed space shuttle and launch pad. Hail data of this event was collected by the HMS and analyzed. Support of STS-118 revealed another important application of the hail monitor system. Ground Instrumentation personnel check the hail monitors daily when a vehicle is on the launch pad, with special attention after any storm suspected of containing hail. If no hail is recorded by the HMS, the vehicle and pad inspection team has no need to conduct a thorough inspection of the vehicle immediately following a storm. On the afternoon of July 13, 2007, hail on the ground was reported by observers at the VAB, about three miles west of Pad 39A, as well as at several other locations around Kennedy Space Center. The HMS showed no impact detections, indicating that the shuttle had not been damaged by any of the numerous hail events which occurred that day
A Phospho-SIM in the Antiviral Protein PML is Required for Its Recruitment to HSV-1 Genomes
Herpes simplex virus type 1 (HSV-1) is a significant human pathogen that infects a large portion of the human population. Cells deploy a variety of defenses to limit the extent to which the virus can replicate. One such factor is the promyelocytic leukemia (PML) protein, the nucleating and organizing factor of nuclear domain 10 (ND10). PML responds to a number of stimuli and is implicated in intrinsic and innate cellular antiviral defenses against HSV-1. While the role of PML in a number of cellular pathways is controlled by post-translational modifications, the effects of phosphorylation on its antiviral activity toward HSV-1 have been largely unexplored. Consequently, we mapped phosphorylation sites on PML, mutated these and other known phosphorylation sites on PML isoform I (PML-I), and examined their effects on a number of PML’s activities. Our results show that phosphorylation at most sites on PML-I is dispensable for the formation of ND10s and colocalization between PML-I and the HSV-1 regulatory protein, ICP0, which antagonizes PML-I function. However, inhibiting phosphorylation at sites near the SUMO-interaction motif (SIM) of PML-I impairs its ability to respond to HSV-1 infection. Overall, our data suggest that PML phosphorylation regulates its antiviral activity against HSV-1
Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer: A nested case-control study
Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer
Forum: On the limited utility of KAP-style survey data in the practical epidemiology of AIDS
This issue of Forum presents a debate on Herbert L. Smith’s, ‘On the limited utility of KAP-style survey data in the practical epidemiology of AIDS, with reference to the AIDS epidemic in Chile’, Health Transition Review 3,1,1993. His response to issues raised in this debate will appear in Health Transition Review 4,1,1994
Enantioselective Decarboxylative Arylation of α-Amino Acids via the Merger of Photoredox and Nickel Catalysis
An asymmetric decarboxylative C_(sp)^3–C_(sp)^2 cross-coupling has been achieved via the synergistic merger of photoredox and nickel catalysis. This mild, operationally simple protocol transforms a wide variety of naturally abundant α-amino acids and readily available aryl halides into valuable chiral benzylic amines in high enantiomeric excess, thereby producing motifs found in pharmacologically active agents
The value of source data verification in a cancer clinical trial
Background
Source data verification (SDV) is a resource intensive method of quality assurance frequently used in clinical trials. There is no empirical evidence to suggest that SDV would impact on comparative treatment effect results from a clinical trial.
Methods
Data discrepancies and comparative treatment effects obtained following 100% SDV were compared to those based on data without SDV. Overall survival (OS) and Progression-free survival (PFS) were compared using Kaplan-Meier curves, log-rank tests and Cox models. Tumour response classifications and comparative treatment Odds Ratios (ORs) for the outcome objective response rate, and number of Serious Adverse Events (SAEs) were compared. OS estimates based on SDV data were compared against estimates obtained from centrally monitored data.
Findings
Data discrepancies were identified between different monitoring procedures for the majority of variables examined, with some variation in discrepancy rates. There were no systematic patterns to discrepancies and their impact was negligible on OS, the primary outcome of the trial (HR (95% CI): 1.18(0.99 to 1.41), p = 0.064 with 100% SDV; 1.18(0.99 to 1.42), p = 0.068 without SDV; 1.18(0.99 to 1.40), p = 0.073 with central monitoring). Results were similar for PFS. More extreme discrepancies were found for the subjective outcome overall objective response (OR (95% CI): 1.67(1.04 to 2.68), p = 0.03 with 100% SDV; 2.45(1.49 to 4.04), p = 0.0003 without any SDV) which was mostly due to differing CT scans.
Interpretation
Quality assurance methods used in clinical trials should be informed by empirical evidence. In this empirical comparison, SDV was expensive and identified random errors that made little impact on results and clinical conclusions of the trial. Central monitoring using an external data source was a more efficient approach for the primary outcome of OS. For the subjective outcome objective response, an independent blinded review committee and tracking system to monitor missing scan data could be more efficient than SDV
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