Drugs

Throughout history, intoxicants were an important part of the war experience. The First World War was by no means an exception in that respect: its main "war drugs" were alcohol (mostly beer, brandy, rum, schnapps, wine, and vodka), morphine, and cocaine. These were both "prescribed" by military authorities and "self-prescribed" by soldiers. As in the past, the reasons for using drugs varied: from purely medical (killing the pain, anesthetizing, and energizing) to performance enhancement, from raising the fighting spirit to alleviating combat trauma, from strengthening bonds between companions to mitigating the fear of battle. Simultaneously and paradoxically, in many states temperance ideas gained in popularity and prohibitionist regulations were adopted

Integrals of Motion in the Two Killing Vector Reduction of General Relativity

We apply the inverse scattering method to the midi-superspace models that are characterized by a two-parameter Abelian group of motions with two spacelike Killing vectors. We present a formulation that simplifies the construction of the soliton solutions of Belinski\v i and Zakharov. Furthermore, it enables us to obtain the zero curvature formulation for these models. Using this, and imposing periodic boundary conditions corresponding to the Gowdy models when the spatial topology is a three torus $T ^3$, we show that the equation of motion for the monodromy matrix is an evolution equation of the Heisenberg type. Consequently, the eigenvalues of the monodromy matrix are the generating functionals for the integrals of motion. Furthermore, we utilise a suitable formulation of the transition matrix to obtain explicit expressions for the integrals of motion. This involves recursion relations which arise in solving an equation of Riccati type. In the case when the two Killing vectors are hypersurface orthogonal the integrals of motion have a particularly simple form.Comment: 20 pages, plain TeX, SU-GP-93/7-8, UM-P-93/7

New science on the Open Science Grid

The Open Science Grid (OSG) includes work to enable new science, new scientists, and new modalities in support of computationally based research. There are frequently significant sociological and organizational changes required in transformation from the existing to the new. OSG leverages its deliverables to the large-scale physics experiment member communities to benefit new communities at all scales through activities in education, engagement, and the distributed facility. This paper gives both a brief general description and specific examples of new science enabled on the OSG. More information is available at the OSG web site: www.opensciencegrid.org

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Progress in Spacecraft Environment Interactions: International Space Station (ISS) Development and Operations

The set of spacecraft interactions with the space flight environment that have produced the largest impacts on the design, verification, and operation of the International Space Station (ISS) Program during the May 2000 to May 2007 time frame are the focus of this paper. In-flight data, flight crew observations, and the results of ground-based test and analysis directly supporting programmatic and operational decision-making are reported as are the analysis and simulation efforts that have led to new knowledge and capabilities supporting current and future space explorations programs. The specific spacecraft-environment interactions that have had the greatest impact on ISS Program activities during the first several years of flight are: 1) spacecraft charging, 2) micrometeoroids and orbital debris effects, 3) ionizing radiation (both total dose to materials and single event effects [SEE] on avionics), 4) hypergolic rocket engine plume impingement effects, 5) venting/dumping of liquids, 6) spacecraft contamination effects, 7) neutral atmosphere and atomic oxygen effects, 8) satellite drag effects, and 9) solar ultraviolet effects. Orbital inclination (51.6deg) and altitude (nominally between 350 km and 460 km) determine the set of natural environment factors affecting the performance and reliability of materials and systems on ISS. ISS operates in the F2 region of Earth s ionosphere in well-defined fluxes of atomic oxygen, other ionospheric plasma species, solar UV, VUV, and x-ray radiation as well as galactic cosmic rays, trapped radiation, and solar cosmic rays. The micrometeoroid and orbital debris environment is an important determinant of spacecraft design and operations in any orbital inclination. The induced environment results from ISS interactions with the natural environment as well as environmental factors produced by ISS itself and visiting vehicles. Examples include ram-wake effects, hypergolic thruster plume impingement, materials out-gassing, venting and dumping of fluids, and specific photovoltaic (PV) power system interactions with the ionospheric plasma. Vehicle size (L) and velocity (v), combined with the magnitude and direction of the geomagnetic field (B) produce operationally significant magnetic induction voltages (VxB.L) in ISS conducting structure during high latitude flight (>+/- 45deg) during each orbit. In addition, ISS is a large vehicle and produces a deep wake structure from which both ionospheric plasma and neutrals species are largely excluded. ISS must fly in a very limited number of approved flight attitudes, so that exposure of a particular material or system to environmental factors depends upon: 1) location on ISS, 2) ISS flight configuration, 3) ISS flight attitude, and 4) variation of solar exposure (Beta angle), and hence thermal environment, with time. Finally, an induced ionizing radiation environment is produced by trapped radiation and solar/cosmic ray interactions with the relatively massive ISS structural shielding

The Open Science Grid Status and Architecture The Open Science Grid Executive Board on behalf of the OSG Consortium: Ruth Pordes, Don Petravick: Fermi National Accelerator Laboratory

Abstract. The Open Science Grid (OSG) provides a distributed facility where the Consortium members provide guaranteed and opportunistic access to shared computing and storage resources. The OSG project[1] is funded by the National Science Foundation and the Department of Energy Scientific Discovery through Advanced Computing program. The OSG project provides specific activities for the operation and evolution of the common infrastructure. The US ATLAS and US CMS collaborations contribute to and depend on OSG as the US infrastructure contributing to the World Wide LHC Computing Grid on which the LHC experiments distribute and analyze their data. Other stakeholders include the STAR RHIC experiment, the Laser Interferometer Gravitational-Wave Observatory (LIGO), the Dark Energy Survey (DES) and several Fermilab Tevatron experiments-CDF, D0, MiniBoone etc. The OSG implementation architecture brings a pragmatic approach to enabling vertically integrated community specific distributed systems over a common horizontal set of shared resources and services. More information can be found at the OSG web site: www.opensciencegrid.org

The Open Science Grid status and architecture

The Open Science Grid (OSG) provides a distributed facility where the Consortium members provide guaranteed and opportunistic access to shared computing and storage resources. The OSG project[1] is funded by the National Science Foundation and the Department of Energy Scientific Discovery through Advanced Computing program. The OSG project provides specific activities for the operation and evolution of the common infrastructure. The US ATLAS and US CMS collaborations contribute to and depend on OSG as the US infrastructure contributing to the World Wide LHC Computing Grid on which the LHC experiments distribute and analyze their data. Other stakeholders include the STAR RHIC experiment, the Laser Interferometer Gravitational-Wave Observatory (LIGO), the Dark Energy Survey (DES) and several Fermilab Tevatron experiments- CDF, D0, MiniBoone etc. The OSG implementation architecture brings a pragmatic approach to enabling vertically integrated community specific distributed systems over a common horizontal set of shared resources and services. More information can be found at the OSG web site: www.opensciencegrid.org

Modulation of SOCS protein expression influences the interferon responsiveness of human melanoma cells

<p>Abstract</p> <p>Background</p> <p>Endogenously produced interferons can regulate the growth of melanoma cells and are administered exogenously as therapeutic agents to patients with advanced cancer. We investigated the role of negative regulators of interferon signaling known as suppressors of cytokine signaling (SOCS) in mediating interferon-resistance in human melanoma cells.</p> <p>Methods</p> <p>Basal and interferon-alpha (IFN-α) or interferon-gamma (IFN-γ)-induced expression of SOCS1 and SOCS3 proteins was evaluated by immunoblot analysis in a panel of n = 10 metastatic human melanoma cell lines, in human embryonic melanocytes (HEM), and radial or vertical growth phase melanoma cells. Over-expression of SOCS1 and SOCS3 proteins in melanoma cells was achieved using the PINCO retroviral vector, while siRNA were used to inhibit SOCS1 and SOCS3 expression. Tyr⁷⁰¹-phosphorylated STAT1 (P-STAT1) was measured by intracellular flow cytometry and IFN-stimulated gene expression was measured by Real Time PCR.</p> <p>Results</p> <p>SOCS1 and SOCS3 proteins were expressed at basal levels in melanocytes and in all melanoma cell lines examined. Expression of the SOCS1 and SOCS3 proteins was also enhanced following stimulation of a subset of cell lines with IFN-α or IFN-γ. Over-expression of SOCS proteins in melanoma cell lines led to significant inhibition of Tyr⁷⁰¹-phosphorylated STAT1 (P-STAT1) and gene expression following stimulation with IFN-α (IFIT2, OAS-1, ISG-15) or IFN-γ (IRF1). Conversely, siRNA inhibition of SOCS1 and SOCS3 expression in melanoma cells enhanced their responsiveness to interferon stimulation.</p> <p>Conclusions</p> <p>These data demonstrate that SOCS proteins are expressed in human melanoma cell lines and their modulation can influence the responsiveness of melanoma cells to IFN-α and IFN-γ.</p

A Late Role for bmp2b in the Morphogenesis of Semicircular Canal Ducts in the Zebrafish Inner Ear

BACKGROUND:The Bone Morphogenetic Protein (BMP) genes bmp2 and bmp4 are expressed in highly conserved patterns in the developing vertebrate inner ear. It has, however, proved difficult to elucidate the function of BMPs during ear development as mutations in these genes cause early embryonic lethality. Previous studies using conditional approaches in mouse and chicken have shown that Bmp4 has a role in semicircular canal and crista development, but there is currently no direct evidence for the role of Bmp2 in the developing inner ear. METHODOLOGY/PRINCIPAL FINDINGS:We have used an RNA rescue strategy to test the role of bmp2b in the zebrafish inner ear directly. Injection of bmp2b or smad5 mRNA into homozygous mutant swirl (bmp2b(-/-)) embryos rescues the early patterning defects in these mutants and the fish survive to adulthood. As injected RNA will only last, at most, for the first few days of embryogenesis, all later development occurs in the absence of bmp2b function. Although rescued swirl adult fish are viable, they have balance defects suggestive of vestibular dysfunction. Analysis of the inner ears of these fish reveals a total absence of semicircular canal ducts, structures involved in the detection of angular motion. All other regions of the ear, including the ampullae and cristae, are present and appear normal. Early stages of otic development in rescued swirl embryos are also normal. CONCLUSIONS/SIGNIFICANCE:Our findings demonstrate a critical late role for bmp2b in the morphogenesis of semicircular canals in the zebrafish inner ear. This is the first demonstration of a developmental role for any gene during post-embryonic stages of otic morphogenesis in the zebrafish. Despite differences in the early stages of semicircular canal formation between zebrafish and amniotes, the role of Bmp2 in semicircular canal duct outgrowth is likely to be conserved between different vertebrate species

Clear and independent associations of several HLA-DRB1 alleles with differential antibody responses to hepatitis B vaccination in youth

To confirm and refine associations of human leukocyte antigen (HLA) genotypes with variable antibody (Ab) responses to hepatitis B vaccination, we have analyzed 255 HIV-1 seropositive (HIV+) youth and 80 HIV-1 seronegatives (HIV−) enrolled into prospective studies. In univariate analyses that focused on HLA-DRB1, -DQA1, and -DQB1 alleles and haplotypes, the DRB1*03 allele group and DRB1*0701 were negatively associated with the responder phenotype (serum Ab concentration ≥ 10 mIU/mL) (P = 0.026 and 0.043, respectively). Collectively, DRB1*03 and DRB1*0701 were found in 42 (53.8%) out of 78 non-responders (serum Ab <10 mIU/mL), 65 (40.6%) out of 160 medium responders (serum Ab 10–1,000 mIU/mL), and 27 (27.8%) out of 97 high responders (serum Ab >1,000 mIU/mL) (P < 0.001 for trend). Meanwhile, DRB1*08 was positively associated with the responder phenotype (P = 0.010), mostly due to DRB1*0804 (P = 0.008). These immunogenetic relationships were all independent of non-genetic factors, including HIV-1 infection status and immunodeficiency. Alternative analyses confined to HIV+ youth or Hispanic youth led to similar findings. In contrast, analyses of more than 80 non-coding, single nucleotide polymorphisms within and beyond the three HLA class II genes revealed no clear associations. Overall, several HLA-DRB1 alleles were major predictors of differential Ab responses to hepatitis B vaccination in youth, suggesting that T-helper cell-dependent pathways mediated through HLA class II antigen presentation are critical to effective immune response to recombinant vaccines