Methods of space radiation dose analysis with applications to manned space systems

The full potential of state-of-the-art space radiation dose analysis for manned missions has not been exploited. Point doses have been overemphasized, and the critical dose to the bone marrow has been only crudely approximated, despite the existence of detailed man models and computer codes for dose integration in complex geometries. The method presented makes it practical to account for the geometrical detail of the astronaut as well as the vehicle. Discussed are the major assumptions involved and the concept of applying the results of detailed proton dose analysis to the real-time interpretation of on-board dosimetric measurements

Processing Solar Probe Tracking Data /sunblazer/

Tracking data processing from Sunblazer solar prob

Underground nuclear power plant siting

This study is part of a larger evaluation of the problems associated with siting nuclear power plants in the next few decades. This evaluation is being undertaken by the Environmental Quality Laboratory of the California Institute of Technology in conjunction with The Aerospace Corporation and several other organizations. Current efforts are directed toward novel approaches to siting plants within the State of California. This report contains the results of efforts performed by The Aerospace Corporation to provide input information to the larger evaluation relative to underground siting of large central station nuclear power plants. Projections of electric power demand in California and the country as a whole suggest that a major increase in generating capacity will be required. The problem is complicated beyond that of a large but straightforward extension of capital investment by increased emphasis on environmental factors combined with the early stage of commercial application and regulation of nuclear power sources. Hydroelectric power generation is limited by the availability of suitable sites, and fossil fueled plants are constrained by the availability of high quality fuels and the adverse environmental and/or economic impact from the use of more plentiful fuels. A substantial increase in the number of nuclear power plants is now under way. This source of power is expected to provide the maj or portion of increased capacity. Other power sources such as geothermal and nuclear fusion are unlikely to satisfy the national needs due to technical problems and the lack of a comprehensive development program. There are several problems associated with meeting the projected power demand. Chief among these is the location of acceptable and economic plant sites. Indeed a sufficient number of sites may not be found unless changes occur in the procedures for selecting sites, the criteria for accepting sites, or the type of site required. Placement of a nuclear plant underground has been suggested as an alternative to present siting practices. It is postulated that the advantages of underground siting in some situations may more than compensate for added costs so that such facilities could be preferred even where surface sites are available. By virtue of greater safety, reduced surface area requirements, and improved aesthetics, underground sites might also be found where acceptable surface sites are not available. Four small European reactors have been constructed partially underground but plans for large size commercial plants have not progressed. Consequently, the features of underground power plant siting are not well understood. Gross physical features such as depth of burial, number and size of excavated galleries, equipment layout, and access or exit shafts/tunnels must be specified. Structural design features of the gallery liners, containment structure, foundations, and gallery interconnections must also be identified. Identification of the nuclear, electrical, and support equipment appropriate to underground operation is needed. Operational features must be defined for normal operations, refueling, and construction. Several magazine articles have been published addressing underground concepts. but adequate engineering data is not available to support an evaluation of the underground concept. There also remain several unresolved questions relative to the advantages of underground siting as well as the costs and other possible penalties associated with this novel approach to siting. These include the degree of increased safety through improved containment; the extent and value of isolation from falling objects, e. g. aircraft; the value of isolation from surface storms and tidal waves; the value of protection from vandalism or sabotage; the extent by which siting constraints are relieved through reduced population-distance requirements or aggravated by underground construction requirements; and the value to be placed upon the aesthetic differences of a less visible facility. The study described in this report has been directed toward some of these questions and uncertainties. Within the study an effort has been made to identify viable configurations and structural liners for typical light water reactor nuclear power plants. Three configurations are summarized in Section 3. A discussion of the underground gallery liner design and associated structural analyses is presented in Section 4. Also addressed in the study and discussed in Section 5 are some aspects of containment for underground plants. There it is suggested that the need for large separations between the plant and population centers may be significantly reduced, or perhaps eliminated. Section 6 contains a brief discussion of operational considerations for underground plants. The costs associated with excavation and lining of the underground galleries have been estimated in Section 7. These estimates include an assessment of variations implied by different seismic loading assumptions and differences in geologic media. It is shown that these costs are a small percentage of the total cost of comparable surface plants. Finally, the parameters characterizing an acceptable underground site are discussed in Section 8. Material is also included in the appendices pertaining to foreign underground plants, span limits of underground excavations, potential siting areas for underground plants in the State of California, pertinent data from the Underground Nuclear Test Program, and other supporting technical discussions

T-cell modulation for the treatment of chronic plaque psoriasis with efalizumab (Raptiva (TM)): Mechanisms of action

Psoriasis is a chronic, incurable, auto-immune disorder with cutaneous manifestations. New evidence on the central role of the immune system in the pathogenesis of psoriasis increasingly provides insight into pathogenic steps that can be modulated to provide disease control. Numerous biological therapies are in various stages of clinical development, with expectation of providing enhanced safety and efficacy over currently available psoriasis therapies. Efalizumab, a recombinant humanized monoclonal IgG1 antibody, is a novel targeted T-cell modulator that inhibits multiple steps in the immune cascade that result in the production and maintenance of psoriatic plaques, including initial T-cell activation and T-cell trafficking into sites of inflammation, including psoriatic skin, with subsequent reactivation in these sites. This article reviews the pharmacodynamic, pharmacokinetic and clinical effects observed during phase I, II and III efalizumab trials in patients with moderate to severe chronic plaque psoriasis. Copyright (C) 2004 S. Karger AG, Basel

Portable headset microphone checker

Simple and reliable test system gives go/no-go indication of output level of headset microphones. Portable system has its own internal battery power supply and can be used in field or in laboratory with wide variety of headset types

Contributions from DMS and ship emissions to CCN observed over the summertime North Pacific

Measurements of cloud condensation nuclei (CCN) made over the North Pacific Ocean in July 2002 are analysed with concurrent measurements of aerosol number, mass and composition. Overall the CCN are controlled by the sulphate, including one case that suggests particle nucleation and growth resulting from dimethyl sulphide oxidation that enhanced CCN concentrations. Hourly CCN concentrations are correlated with concentrations of sulphate plus methanesulphonic acid (MSA) over the entire study period (<i>r</i><sup>2</sup>=0.43 and 0.52 for supersaturations of 0.34% and 0.19%, respectively), and are not well correlated with other organics (<i>r</i><sup>2</sup><0.2). One case study reveals elevated mass and number concentrations of ultrafine and fine organic particles due to regional ship emissions, identified through quadrupole aerosol mass spectrometer (Q-AMS) measurements, during which organic mass concentrations are correlated with CCN values (<i>r</i><sup>2</sup>=0.39 and 0.46 for supersaturations of 0.19% and 0.34%, respectively). The evolution of the time series and mass distributions of organics, sulphate and MSA over this timeframe indicate that the regional distribution of small, diffuse ship-sourced organic particles act as condensation sites for sulphur species, resulting in a subsequent increase in number concentrations of CCN. We conclude that, where present, direct emissions of anthropogenic organic particles may exert a strong control on marine CCN concentrations once diffused into the marine atmosphere, by acting as condensation sites for biogenic and anthropogenic sulphur species

Derivatives of meromorphic functions of finite order

A result is proved concerning meromorphic functions of finite order in the plane such that all but finitely many zeros of the second derivative are zeros of the first derivative

Mechanistic Characterization and Molecular Modeling of Hepatitis B Virus Polymerase Resistance to Entecavir

BACKGROUND: Entecavir (ETV) is a deoxyguanosine analog competitive inhibitor of hepatitis B virus (HBV) polymerase that exhibits delayed chain termination of HBV DNA. A high barrier to entecavir-resistance (ETVr) is observed clinically, likely due to its potency and a requirement for multiple resistance changes to overcome suppression. Changes in the HBV polymerase reverse-transcriptase (RT) domain involve lamivudine-resistance (LVDr) substitutions in the conserved YMDD motif (M204V/I +/- L180M), plus an additional ETV-specific change at residues T184, S202 or M250. These substitutions surround the putative dNTP binding site or primer grip regions of the HBV RT. METHODS/PRINCIPAL FINDINGS: To determine the mechanistic basis for ETVr, wildtype, lamivudine-resistant (M204V, L180M) and ETVr HBVs were studied using in vitro RT enzyme and cell culture assays, as well as molecular modeling. Resistance substitutions significantly reduced ETV incorporation and chain termination in HBV DNA and increased the ETV-TP inhibition constant (K(i)) for HBV RT. Resistant HBVs exhibited impaired replication in culture and reduced enzyme activity (k(cat)) in vitro. Molecular modeling of the HBV RT suggested that ETVr residue T184 was adjacent to and stabilized S202 within the LVDr YMDD loop. ETVr arose through steric changes at T184 or S202 or by disruption of hydrogen-bonding between the two, both of which repositioned the loop and reduced the ETV-triphosphate (ETV-TP) binding pocket. In contrast to T184 and S202 changes, ETVr at primer grip residue M250 was observed during RNA-directed DNA synthesis only. Experimentally, M250 changes also impacted the dNTP-binding site. Modeling suggested a novel mechanism for M250 resistance, whereby repositioning of the primer-template component of the dNTP-binding site shifted the ETV-TP binding pocket. No structural data are available to confirm the HBV RT modeling, however, results were consistent with phenotypic analysis of comprehensive substitutions of each ETVr position. CONCLUSIONS: Altogether, ETVr occurred through exclusion of ETV-TP from the dNTP-binding site, through different, novel mechanisms that involved lamivudine-resistance, ETV-specific substitutions, and the primer-template