357 research outputs found

    Evaluation of LLNL's Nuclear Accident Dosimeters at the CALIBAN Reactor September 2010

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    The Lawrence Livermore National Laboratory uses neutron activation elements in a Panasonic TLD holder as a personnel nuclear accident dosimeter (PNAD). The LLNL PNAD has periodically been tested using a Cf-252 neutron source, however until 2009, it was more than 25 years since the PNAD has been tested against a source of neutrons that arise from a reactor generated neutron spectrum that simulates a criticality. In October 2009, LLNL participated in an intercomparison of nuclear accident dosimeters at the CEA Valduc Silene reactor (Hickman, et.al. 2010). In September 2010, LLNL participated in a second intercomparison of nuclear accident dosimeters at CEA Valduc. The reactor generated neutron irradiations for the 2010 exercise were performed at the Caliban reactor. The Caliban results are described in this report. The procedure for measuring the nuclear accident dosimeters in the event of an accident has a solid foundation based on many experimental results and comparisons. The entire process, from receiving the activated NADs to collecting and storing them after counting was executed successfully in a field based operation. Under normal conditions at LLNL, detectors are ready and available 24/7 to perform the necessary measurement of nuclear accident components. Likewise LLNL maintains processing laboratories that are separated from the areas where measurements occur, but contained within the same facility for easy movement from processing area to measurement area. In the event of a loss of LLNL permanent facilities, the Caliban and previous Silene exercises have demonstrated that LLNL can establish field operations that will very good nuclear accident dosimetry results. There are still several aspects of LLNL's nuclear accident dosimetry program that have not been tested or confirmed. For instance, LLNL's method for using of biological samples (blood and hair) has not been verified since the method was first developed in the 1980's. Because LLNL and the other DOE participants were limited in what they were allowed to do at the Caliban and Silene exercises and testing of various elements of the nuclear accident dosimetry programs cannot always be performed as guests at other sites, it has become evident that DOE needs its own capability to test nuclear accident dosimeters. Angular dependence determination and correction factors for NADs desperately need testing as well as more evaluation regarding the correct determination of gamma doses. It will be critical to properly design any testing facility so that the necessary experiments can be performed by DOE laboratories as well as guest laboratories. Alternate methods of dose assessment such as using various metals commonly found in pockets and clothing have yet to be evaluated. The DOE is planning to utilize the Godiva or Flattop reactor for testing nuclear accident dosimeters. LLNL has been assigned the primary operational authority for such testing. Proper testing of nuclear accident dosimeters will require highly specific characterization of the pulse fields. Just as important as the characterization of the pulsed fields will be the design of facilities used to process the NADs. Appropriate facilities will be needed to allow for early access to dosimeters to test and develop quick sorting techniques. These facilities will need appropriate laboratory preparation space and an area for measurements. Finally, such a facility will allow greater numbers of LLNL and DOE laboratory personnel to train on the processing and interpretation of nuclear accident dosimeters and results. Until this facility is fully operational for test purposes, DOE laboratories may need to continue periodic testing as guests of other reactor facilities such as Silene and Caliban

    GDF-15 is abundantly expressed in plexiform lesions in patients with pulmonary arterial hypertension and affects proliferation and apoptosis of pulmonary endothelial cells

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    <p>Abstract</p> <p>Background</p> <p>Growth-differentiation factor-15 (GDF-15) is a stress-responsive, transforming growth factor-β-related cytokine, which has recently been reported to be elevated in serum of patients with idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to examine the expression and biological roles of GDF-15 in the lung of patients with pulmonary arterial hypertension (PAH).</p> <p>Methods</p> <p>GDF-15 expression in normal lungs and lung specimens of PAH patients were studied by real-time RT-PCR and immunohistochemistry. Using laser-assisted micro-dissection, GDF-15 expression was further analyzed within vascular compartments of PAH lungs. To elucidate the role of GDF-15 on endothelial cells, human pulmonary microvascular endothelial cells (HPMEC) were exposed to hypoxia and laminar shear stress. The effects of GDF-15 on the proliferation and cell death of HPMEC were studied using recombinant GDF-15 protein.</p> <p>Results</p> <p>GDF-15 expression was found to be increased in lung specimens from PAH patients, com-pared to normal lungs. GDF-15 was abundantly expressed in pulmonary vascular endothelial cells with a strong signal in the core of plexiform lesions. HPMEC responded with marked upregulation of GDF-15 to hypoxia and laminar shear stress. Apoptotic cell death of HPMEC was diminished, whereas HPMEC proliferation was either increased or decreased depending of the concentration of recombinant GDF-15 protein.</p> <p>Conclusions</p> <p>GDF-15 expression is increased in PAH lungs and appears predominantly located in vascular endothelial cells. The expression pattern as well as the observed effects on proliferation and apoptosis of pulmonary endothelial cells suggest a role of GDF-15 in the homeostasis of endothelial cells in PAH patients.</p

    Distinguishing four components underlying physical activity: a new approach to using physical activity questionnaire data in old age

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    <p>Abstract</p> <p>Background</p> <p>It is evident that physical activity has many benefits, but it often remains unclear which types of activity are optimal for health and functioning in old age. The aim of this methodological study was to propose a method for distinguishing four components underlying self reported physical activity of older adults: intensity, muscle strength, turning actions and mechanical strain.</p> <p>Methods</p> <p>Physical activity was assessed by the validated LAPAQ questionnaire among 1699 older adults of the Longitudinal Aging Study Amsterdam. Based on expert consultation and literature review, the four component scores for several individual daily and sports activities were developed. Factor analysis was performed to confirm whether the developed components indeed measured different constructs of physical activity.</p> <p>Results</p> <p>Based on the factor analyses, three components were distinguished: 1. intensity and muscle strength loaded on the same factor, 2. mechanical strain and 3. turning actions. Analyses in gender, age and activity level subgroups consistently distinguished three factors.</p> <p>Conclusion</p> <p>Future research using these components may contribute to our understanding of how specific daily and sports activities may have a different influence on health and physical functioning in old age.</p

    Functional Phenotypic Rescue of Caenorhabditis elegans Neuroligin-Deficient Mutants by the Human and Rat NLGN1 Genes

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    Neuroligins are cell adhesion proteins that interact with neurexins at the synapse. This interaction may contribute to differentiation, plasticity and specificity of synapses. In humans, single mutations in neuroligin encoding genes lead to autism spectrum disorder and/or mental retardation. Caenorhabditis elegans mutants deficient in nlg-1, an orthologue of human neuroligin genes, have defects in different behaviors. Here we show that the expression of human NLGN1 or rat Nlgn1 cDNAs in C. elegans nlg-1 mutants rescues the fructose osmotic strength avoidance and gentle touch response phenotypes. Two specific point mutations in NLGN3 and NLGN4 genes, involved in autistic spectrum disorder, were further characterized in this experimental system. The R451C allele described in NLGN3, was analyzed with both human NLGN1 (R453C) and worm NLG-1 (R437C) proteins, and both were not functional in rescuing the osmotic avoidance behavior and the gentle touch response phenotype. The D396X allele described in NLGN4, which produces a truncated protein, was studied with human NLGN1 (D432X) and they did not rescue any of the behavioral phenotypes analyzed. In addition, RNAi feeding experiments measuring gentle touch response in wild type strain and worms expressing SID-1 in neurons (which increases the response to dsRNA), both fed with bacteria expressing dsRNA for nlg-1, provided evidence for a postsynaptic in vivo function of neuroligins both in muscle cells and neurons, equivalent to that proposed in mammals. This finding was further confirmed generating transgenic nlg-1 deficient mutants expressing NLG-1 under pan-neuronal (nrx-1) or pan-muscular (myo-3) specific promoters. All these results suggest that the nematode could be used as an in vivo model for studying particular synaptic mechanisms with proteins orthologues of humans involved in pervasive developmental disorders
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