125 research outputs found

    Physics of intense, high energy radiation effects.

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    This document summarizes the work done in our three-year LDRD project titled 'Physics of Intense, High Energy Radiation Effects.' This LDRD is focused on electrical effects of ionizing radiation at high dose-rates. One major thrust throughout the project has been the radiation-induced conductivity (RIC) produced by the ionizing radiation. Another important consideration has been the electrical effect of dose-enhanced radiation. This transient effect can produce an electromagnetic pulse (EMP). The unifying theme of the project has been the dielectric function. This quantity contains much of the physics covered in this project. For example, the work on transient electrical effects in radiation-induced conductivity (RIC) has been a key focus for the work on the EMP effects. This physics in contained in the dielectric function, which can also be expressed as a conductivity. The transient defects created during a radiation event are also contained, in principle. The energy loss lead the hot electrons and holes is given by the stopping power of ionizing radiation. This information is given by the inverse dielectric function. Finally, the short time atomistic phenomena caused by ionizing radiation can also be considered to be contained within the dielectric function. During the LDRD, meetings about the work were held every week. These discussions involved theorists, experimentalists and engineers. These discussions branched out into the work done in other projects. For example, the work on EMP effects had influence on another project focused on such phenomena in gases. Furthermore, the physics of radiation detectors and radiation dosimeters was often discussed, and these discussions had impact on related projects. Some LDRD-related documents are now stored on a sharepoint site (https://sharepoint.sandia.gov/sites/LDRD-REMS/default.aspx). In the remainder of this document the work is described in catergories but there is much overlap between the atomistic calculations, the continuum calculations and the experiments

    Dosimetry experiments at the MEDUSA Facility (Little Mountain).

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    A series of experiments on the MEDUSA linear accelerator radiation test facility were performed to evaluate the difference in dose measured using different methods. Significant differences in dosimeter-measured radiation dose were observed for the different dosimeter types for the same radiation environments, and the results are compared and discussed in this report

    Measurements of prompt radiation induced conductivity in Teflon (PTFE).

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    We performed measurements of the prompt radiation induced conductivity (RIC) in thin samples of Teflon (PTFE) at the Little Mountain Medusa LINAC facility in Ogden, UT. Three mil (76.2 microns) samples were irradiated with a 0.5 %CE%BCs pulse of 20 MeV electrons, yielding dose rates of 1E9 to 1E11 rad/s. We applied variable potentials up to 2 kV across the samples and measured the prompt conduction current. Details of the experimental apparatus and analysis are reported in this report on prompt RIC in Teflon

    Analysis of System Training Impact for Major Defense Acquisition Programs (MDAPs): Training Systems Acquisition

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    This work was conducted by the Institute for Defense Analyses (IDA) under contract W91WAW-09-C-0003, Task BE-2-3376, “Analysis of Systems Training Impact for Major Defense Acquisition Programs,” for the Director, Training Readiness and Strategy, in the Office of the Under Secretary of Defense for Personnel and Readiness.W91WAW-09-C-0003, Task BE-2-337

    Involvement of Bruton's Tyrosine Kinase in FcεRI-dependent Mast Cell Degranulation and Cytokine Production

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    We investigated the role of Bruton's tyrosine kinase (Btk) in FcεRI-dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these mice exhibited significant abnormalities in FcεRI-dependent function. xid mice primed with anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early-phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast cells derived from the bone marrow cells of xid or btk null mice exhibited mild impairments in degranulation, and more profound defects in the production of several cytokines, upon FcεRI cross-linking. Moreover, the transcriptional activities of these cytokine genes were severely reduced in FcεRI-stimulated btk mutant mast cells. The specificity of these effects of btk mutations was confirmed by the improvement in the ability of btk mutant mast cells to degranulate and to secrete cytokines after the retroviral transfer of wild-type btk cDNA, but not of vector or kinase-dead btk cDNA. Retroviral transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the ability of btk mutant mast cells to secrete mediators. Taken together, these results demonstrate an important role for Btk in the full expression of FcεRI signal transduction in mast cells

    Swift X-Ray Observations of Classical Novae. II. The Super Soft Source sample

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    The Swift GRB satellite is an excellent facility for studying novae. Its rapid response time and sensitive X-ray detector provides an unparalleled opportunity to investigate the previously poorly sampled evolution of novae in the X-ray regime. This paper presents Swift observations of 52 Galactic/Magellanic Cloud novae. We included the XRT (0.3-10 keV) X-ray instrument count rates and the UVOT (1700-8000 Angstroms) filter photometry. Also included in the analysis are the publicly available pointed observations of 10 additional novae the X-ray archives. This is the largest X-ray sample of Galactic/Magellanic Cloud novae yet assembled and consists of 26 novae with super soft X-ray emission, 19 from Swift observations. The data set shows that the faster novae have an early hard X-ray phase that is usually missing in slower novae. The Super Soft X-ray phase occurs earlier and does not last as long in fast novae compared to slower novae. All the Swift novae with sufficient observations show that novae are highly variable with rapid variability and different periodicities. In the majority of cases, nuclear burning ceases less than 3 years after the outburst begins. Previous relationships, such as the nuclear burning duration vs. t_2 or the expansion velocity of the eject and nuclear burning duration vs. the orbital period, are shown to be poorly correlated with the full sample indicating that additional factors beyond the white dwarf mass and binary separation play important roles in the evolution of a nova outburst. Finally, we confirm two optical phenomena that are correlated with strong, soft X-ray emission which can be used to further increase the efficiency of X-ray campaigns.Comment: Accepted to ApJ Supplements. Full data for Table 2 and Figure 17 available in the electronic edition. New version of the previously posted paper since the earlier version was all set in landscape mod

    Identification by Virtual Screening and In Vitro Testing of Human DOPA Decarboxylase Inhibitors

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    Dopa decarboxylase (DDC), a pyridoxal 5′-phosphate (PLP) enzyme responsible for the biosynthesis of dopamine and serotonin, is involved in Parkinson's disease (PD). PD is a neurodegenerative disease mainly due to a progressive loss of dopamine-producing cells in the midbrain. Co-administration of L-Dopa with peripheral DDC inhibitors (carbidopa or benserazide) is the most effective symptomatic treatment for PD. Although carbidopa and trihydroxybenzylhydrazine (the in vivo hydrolysis product of benserazide) are both powerful irreversible DDC inhibitors, they are not selective because they irreversibly bind to free PLP and PLP-enzymes, thus inducing diverse side effects. Therefore, the main goals of this study were (a) to use virtual screening to identify potential human DDC inhibitors and (b) to evaluate the reliability of our virtual-screening (VS) protocol by experimentally testing the “in vitro” activity of selected molecules. Starting from the crystal structure of the DDC-carbidopa complex, a new VS protocol, integrating pharmacophore searches and molecular docking, was developed. Analysis of 15 selected compounds, obtained by filtering the public ZINC database, yielded two molecules that bind to the active site of human DDC and behave as competitive inhibitors with Ki values ≥10 µM. By performing in silico similarity search on the latter compounds followed by a substructure search using the core of the most active compound we identified several competitive inhibitors of human DDC with Ki values in the low micromolar range, unable to bind free PLP, and predicted to not cross the blood-brain barrier. The most potent inhibitor with a Ki value of 500 nM represents a new lead compound, targeting human DDC, that may be the basis for lead optimization in the development of new DDC inhibitors. To our knowledge, a similar approach has not been reported yet in the field of DDC inhibitors discovery
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