Space radiation dose analysis for solar flare of August 1989

Potential dose and dose rate levels to astronauts in deep space are predicted for the solar flare event which occurred during the week of August 13, 1989. The Geostationary Operational Environmental Satellite (GOES-7) monitored the temporal development and energy characteristics of the protons emitted during this event. From these data, differential fluence as a function of energy was obtained in order to analyze the flare using the Langley baryon transport code, BRYNTRN, which describes the interactions of incident protons in matter. Dose equivalent estimates for the skin, ocular lens, and vital organs for 0.5 to 20 g/sq cm of aluminum shielding were predicted. For relatively light shielding (less than 2 g/sq cm), the skin and ocular lens 30-day exposure limits are exceeded within several hours of flare onset. The vital organ (5 cm depth) dose equivalent is exceeded only for the thinnest shield (0.5 g/sq cm). Dose rates (rem/hr) for the skin, ocular lens, and vital organs are also computed

Advances in Thin Film Sensor Technologies for Engine Applications

Advanced thin film sensor techniques that can provide accurate surface strain and temperature measurements are being developed at NASA Lewis Research Center. These sensors are needed to provide minimally intrusive characterization of advanced materials (such as ceramics and composites) and structures (such as components for Space Shuttle Main Engine, High Speed Civil Transport, Advanced Subsonic Transports and General Aviation Aircraft) in hostile, high-temperature environments and for validation of design codes. This paper presents two advanced thin film sensor technologies: strain gauges and thermocouples. These sensors are sputter deposited directly onto the test articles and are only a few micrometers thick; the surface of the test article is not structurally altered and there is minimal disturbance of the gas flow over the surface. The strain gauges are palladium-13% chromium based and the thermocouples are platinum-13% rhodium vs. platinum. The fabrication techniques of these thin film sensors in a class 1000 cleanroom at the NASA Lewis Research Center are described. Their demonstration on a variety of engine materials, including superalloys, ceramics and advanced ceramic matrix composites, in several hostile, high-temperature test environments are discussed

Climate Change and San Francisco Bay-Delta Tidal Wetlands

Climate change will affect tidal wetlands with higher rates of sea-level rise and higher concentrations of salt in brackish and freshwater tidal systems, in addition to causing increases in atmospheric CO2 concentration, warmer temperatures, and shifts in precipitation. In the San Francisco Bay–Delta, the areas most likely to be affected—brackish and freshwater tidal wetlands—are also the sites with the majority of endemic plant species and the greater biodiversity and productivity. Effects on the San Francisco Bay– Delta estuary are complex and difficult to predict, but a few things are clear. Biodiversity of the tidal wetland system in the San Francisco Bay–Delta region will decline, with subsequent effects on ecosystem functioning and services. Altered plant production, physiological tolerances, and shifts in rates of mortality will modify wetland plant communities in ways not yet predictable. Lower ecosystem productivity from salinity increases will affect both primary and detrital-based food webs. Such changes will cascade via the food webs into invertebrate, bird, and pelagic systems. Tidal wetlands are especially sensitive to processes that climate change will alter. Several of these altered processes are exacerbated by water diversions from the Delta

Type I interferon receptor deficiency in dendritic cells facilitates systemic murine norovirus persistence despite enhanced adaptive immunity

In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs) play pleiotropic roles in the antiviral response, including through innate control of viral replication. Murine norovirus (MNoV) replicates in dendritic cells (DCs) and type I IFN signaling in DCs is important for early control of MNoV replication. We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN. Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses. Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1-/- recipients. Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN. These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance

Glacial controls on redox-sensitive trace element cycling in Arctic fjord sediments (Spitsbergen, Svalbard)

Glacial meltwater is an important source of bioessential trace elements to high latitude oceans. Upon delivery to coastal waters, glacially sourced particulate trace elements are processed during early diagenesis in sediments and may be sequestered or recycled back to the water column depending on local biogeochemical conditions. In the glaciated fjords of Svalbard, large amounts of reactive Fe and Mn (oxyhydr)oxides are delivered to the sediment by glacial discharge, resulting in pronounced Fe and Mn cycling concurrent with microbial sulfate reduction. In order to investigate the diagenetic cycling of selected trace elements (As, Co, Cu, Mo, Ni, and U) in this system, we collected sediment cores from two Svalbard fjords, Van Keulenfjorden and Van Mijenfjorden, in a transect along the head-to-mouth fjord axis and analyzed aqueous and solid phase geochemistry with respect to trace elements, sulfur, and carbon along with sulfate reduction rates. We found that Co and Ni associate with Fe and Mn (oxyhydr)oxides and enter the pore water upon reductive metal oxide dissolution. Copper is enriched in the solid phase where sulfate reduction rates are high, likely due to reactions with H2S and the formation of sulfide minerals. Uranium accumulates in the solid phase likely following reduction by both Fe- and sulfate-reducing bacteria, while Mo adsorbs to Fe and Mn (oxyhydr)oxides in the surface sediment and is removed from the pore water at depth where sulfidization makes it particle-reactive. Arsenic is tightly coupled to Fe redox cycling and its partitioning between solid and dissolved phases is influenced by competition with FeS for adsorption sites on crystalline Fe oxides. Differences in trace element cycling between the two fjords suggest delivery of varying amount and composition of tidewater glacier (Van Keulenfjorden) and meltwater stream (Van Mijenfjorden) material, likely related to oxidative processes occurring in meltwater streams. This processing produces a partially weathered, more reactive sediment that is subject to stronger redox cycling of Fe, Mn, S, and associated trace elements upon delivery to Van Mijenfjorden. With climate warming, the patterns of trace element cycling observed in Van Mijenfjorden may also become more prevalent in other Svalbard fjords as tidewater glaciers retreat into meltwater stream valleys

Persistent enteric murine norovirus infection is associated with functionally suboptimal virus-specific CD8 T cell responses

Norovirus (NV) gastroenteritis is a major contributor to global morbidity and mortality, yet little is known about immune mechanisms leading to NV control. Previous studies using the murine norovirus (MNV) model have established a key role for T cells in MNV clearance. Despite these advances, important questions remain regarding the magnitude, location, and dynamics of the MNV-specific T cell response. To address these questions, we identified MNV-specific major histocompatibility complex (MHC) class I immunodominant epitopes using an overlapping peptide screen. One of these epitopes (amino acids 519 to 527 of open reading frame 2 [ORF2(519-527)]) was highly conserved among all NV genogroups. Using MHC class I peptide tetramers, we tracked MNV-specific CD8 T cells in lymphoid and mucosal sites during infection with two MNV strains with distinct biological behaviors, the acutely cleared strain CW3 and the persistent strain CR6. Here, we show that enteric MNV infection elicited robust T cell responses primarily in the intestinal mucosa and that MNV-specific CD8 T cells dynamically regulated the expression of surface molecules associated with activation, differentiation, and homing. Furthermore, compared to MNV-CW3 infection, chronic infection with MNV-CR6 resulted in fewer and less-functional CD8 T cells, and this difference was evident as early as day 8 postinfection. Finally, MNV-specific CD8 T cells were capable of reducing the viral load in persistently infected Rag1(−/−) mice, suggesting that these cells are a crucial component of NV immunity. Collectively, these data provide fundamental new insights into the adaptive immune response to two closely related NV strains with distinct biological behaviors and bring us closer to understanding the correlates of protective antiviral immunity in the intestine

The continuous performance test (rCPT) for mice: a novel operant touchscreen test of attentional function.

RATIONALE: Continuous performance tests (CPTs) are widely used to assess attentional processes in a variety of disorders including Alzheimer's disease and schizophrenia. Common human CPTs require discrimination of sequentially presented, visually patterned 'target' and 'non-target' stimuli at a single location. OBJECTIVES: The aims of this study were to evaluate the performance of three popular mouse strains on a novel rodent touchscreen test (rCPT) designed to be analogous to common human CPT variants and to investigate the effects of donepezil, a cholinesterase inhibitor and putative cognitive enhancer. METHODS: C57BL/6J, DBA/2J and CD1 mice (n = 15-16/strain) were trained to baseline performance using four rCPT training stages. Then, probe tests assessed the effects of parameter changes on task performance: stimulus size, duration, contrast, probability, inter-trial interval or inclusion of flanker distractors. rCPT performance was also evaluated following acute administration of donepezil (0-3 mg/kg, i.p.). RESULTS: C57BL/6J and DBA/2J mice showed similar acquisition rates and final baseline performance following rCPT training. On probe tests, rCPT performance of both strains was sensitive to alteration of visual and/or attentional demands (stimulus size, duration, contrast, rate, flanker distraction). Relative to C57BL/6J, DBA/2J mice exhibited (1) decreasing sensitivity (d') across the 45-min session, (2) reduced performance on probes where the appearance of stimuli or adjacent areas were changed (size, contrast, flanking distractors) and (3) larger dose- and stimulus duration-dependent changes in performance following donepezil administration. In contrast, CD1 mice failed to acquire rCPT (stage 3) and pairwise visual discrimination tasks. CONCLUSIONS: rCPT is a potentially useful translational tool for assessing attention in mice and for detecting the effects of nootropic drugs.Funding for this research was provided by Professor Mark Johnson, Imperial College London. CHK received funding from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI11C1183). MHE, SRON, TWR, LMS, TJB and ACM received funding from the Innovative Medicine Initiative Joint Undertaking under grant agreement no 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). LMS and TJB were funded by Medical Research Council/Wellcome Trust grant 089703/Z/09/Z.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00213-015-4081-

IRF-3, IRF-5, and IRF-7 coordinately regulate the type I IFN response in myeloid dendritic cells downstream of MAVS signaling

Although the transcription factors IRF-3 and IRF-7 are considered master regulators of type I interferon (IFN) induction and IFN stimulated gene (ISG) expression, Irf3(-/-)×Irf7(-/-) double knockout (DKO) myeloid dendritic cells (mDC) produce relatively normal levels of IFN-β after viral infection. We generated Irf3(-/-)×Irf5(-/-)×Irf7(-/-) triple knockout (TKO) mice to test whether IRF-5 was the source of the residual induction of IFN-β and ISGs in mDCs. In pathogenesis studies with two unrelated positive-sense RNA viruses (West Nile virus (WNV) and murine norovirus), TKO mice succumbed at rates greater than DKO mice and equal to or approaching those of mice lacking the type I IFN receptor (Ifnar(-/-)). In ex vivo studies, after WNV infection or exposure to Toll-like receptor agonists, TKO mDCs failed to produce IFN-β or express ISGs. In contrast, this response was sustained in TKO macrophages following WNV infection. To define IRF-regulated gene signatures, we performed microarray analysis on WNV-infected mDC from wild type (WT), DKO, TKO, or Ifnar(-/-) mice, as well as from mice lacking the RIG-I like receptor adaptor protein MAVS. Whereas the gene induction pattern in DKO mDC was similar to WT cells, remarkably, almost no ISG induction was detected in TKO or Mavs(-/-) mDC. The relative equivalence of TKO and Mavs(-/-) responses suggested that MAVS dominantly regulates ISG induction in mDC. Moreover, we showed that MAVS-dependent induction of ISGs can occur through an IRF-5-dependent yet IRF-3 and IRF-7-independent pathway. Our results establish IRF-3, -5, and -7 as the key transcription factors responsible for mediating the type I IFN and ISG response in mDC during WNV infection and suggest a novel signaling link between MAVS and IRF-5

Allergen Micro-Bead Array for IgE Detection: A Feasibility Study Using Allergenic Molecules Tested on a Flexible Multiplex Flow Cytometric Immunoassay

Background: Allergies represent the most prevalent non infective diseases worldwide. Approaching IgE-mediated sensitizations improved much by adopting allergenic molecules instead of extracts, and by using the micro-technology for multiplex testing. Objective and Methods: To provide a proof-of-concept that a flow cytometric bead array is a feasible mean for the detection of specific IgE reactivity to allergenic molecules in a multiplex-like way. A flow cytometry Allergenic Moleculebased micro-bead Array system (ABA) was set by coupling allergenic molecules with commercially available micro-beads. Allergen specific polyclonal and monoclonal antibodies, as well as samples from 167 allergic patients, characterized by means of the ISAC microarray system, were used as means to show the feasibility of the ABA. Three hundred and thirty-six sera were tested for 1 or more of the 16 selected allergens, for a total number of 1,519 tests on each of the two systems. Results: Successful coupling was initially verified by detecting the binding of rabbit polyclonal IgG, mouse monoclonal, and pooled human IgE toward three allergens, namely nDer s 1, nPen m 1, and nPru p 3. The ABA assay showed to detect IgE t