144 research outputs found

    Implementation and Initial Validation of a 100-Kilowatt Class Nested-Channel Hall Thruster

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    The X3 is a 100-kilowatt class nested-channel Hall thruster developed by the Plasmadynamics and Electric Propulsion Laboratory at the University of Michigan in collaboration with the Air Force Research Laboratory and NASA. The cathode, magnetic circuit, boron nitride channel rings, and anodes all required specific design considerations during thruster development, and thermal modeling was used to properly account for thermal growth in material selection and component design. A number of facility upgrades were required at the University of Michigan to facilitate operation of the X3. These upgrades included a re-worked propellant feed system, a completely redesigned power and telemetry break-out box, and numerous updates to thruster handling equipment. The X3 was tested on xenon propellant at two current densities, 37% and 73% of the nominal design value. It was operated to a maximum steady-state discharge power of 60.8 kilowatts. The tests presented here served as an initial validation of thruster operation. Thruster behavior was monitored with telemetry, photography and high-speed current probes. The photography showed a uniform plume throughout testing. At constant current density, reductions in mass flow rate of 18% and 26% were observed in the three-channel operating configuration as compared to the superposition of each channel running individually. The high-speed current probes showed that the thruster was stable at all operating points and that the channels influence each other when more than one is operating simultaneously. Additionally, the ratio of peak-to-peak AC-coupled discharge current oscillations to mean discharge current did not exceed 51% for any operating points reported here, and did not exceed 17% at the higher current density

    Ion Collection in Hall Thruster Plumes

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77342/1/AIAA-11953-462.pd

    Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic

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    Background: There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ART coverage has increased for reasons which remain unclear. Methods: We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Results: HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990–1997, 0.45/100 py 1998–2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006–2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections. Conclusion: A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections

    RESCUE OF HIPPO CO-ACTIVATOR YAP1 TRIGGERS DNA DAMAGE-INDUCED APOPTOSIS IN HEMATOLOGICAL CANCERS

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    Oncogene–induced DNA damage elicits genomic instability in epithelial cancer cells, but apoptosis is blocked through inactivation of the tumor suppressor p53. In hematological cancers, the relevance of ongoing DNA damage and mechanisms by which apoptosis is suppressed are largely unknown. We found pervasive DNA damage in hematologic malignancies including multiple myeloma, lymphoma and leukemia, which leads to activation of a p53–independent, pro-apoptotic network centered on nuclear relocalization of ABL1 kinase. Although nuclear ABL1 triggers cell death through its interaction with the Hippo pathway co–activator YAP1 in normal cells, we show that low YAP1 levels prevent nuclear ABL1–induced apoptosis in these hematologic malignancies. YAP1 is under the control of a serine–threonine kinase, STK4. Importantly, genetic inactivation of STK4 restores YAP1 levels, triggering cell death in vitro and in vivo. Our data therefore identify a novel synthetic–lethal strategy to selectively target cancer cells presenting with endogenous DNA damage and low YAP1 levels

    The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

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    The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

    A Cis-Regulatory Map of the Drosophila Genome

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    Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide1, 2 has successfully identified specific subtypes of regulatory elements3. In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements4, chromatin states5, transcription factor binding sites6, 7, 8, 9, RNA polymerase II regulation8 and insulator elements10; however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and validated a subset of predictions for promoters, enhancers and insulators in vivo. We identified also nearly 2,000 genomic regions of dense transcription factor binding associated with chromatin activity and accessibility. We discovered hundreds of new transcription factor co-binding relationships and defined a transcription factor network with over 800 potential regulatory relationships

    Internet & human rights in foreign policy: comparing narratives in the US and EU internet governance agenda

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    The intricate relationship between Internet, on the one hand, and Human Rights, on the other, is increasingly becoming relevant in foreign policy. Discussions are animated by different actors, providing contributions from multiple perspectives, yet the debate on Internet and Human Rights is still fragmented and has not evolved into a unified agenda. This paper explores this on-going debate over competing perspectives, and frames the current discussion on Internet and Human Rights in foreign policy by providing an overview of the key governmental conferences addressing the Internet and Human rights over the first 3 years (2010-2012) since the beginning of the debate. It then proceeds to analyze key narratives, stakeholders and agendas within these conferences, as well as questions of power and legitimacy. Finally, it argues that the conferences draw from a common discourse and language, but are also representing divergent agendas between stakeholders and states

    Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

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