On-Orbit Maintenance Operations Strategy for the International Space Station - Concept and Implementation

The International Space Station (ISS) has an operational mission and profile that makes it a Logistics and Maintenance (L&M) support challenge different from previous programs. It is permanently manned, assembled on orbit, and multi-national. With this technical and operational challenge, a unique approach is needed to support the hardware and crew. The key is the integration of on-orbit and ground analysis, supply, maintenance, and crew training into a coherent functional process that supports ISS goals and objectives. To integrate all the necessary aspects of hardware and personnel to support on-orbit maintenance, a myriad of products and processes must be created and coordinated, such that the right resources are in the right place at the right time to ensure continued ISS functionality. This paper will familiarize the audience with ISS On-Orbit Maintenance (OOM) concepts and capabilities for different maintenance tasks and discuss some of the logic behind their selection. It will also identify the operational maintenance support responsibility split between the U.S. and the various International Partners (IPs)

Cooler winters as a possible cause of mass extinctions at the eocene/oligocene boundary

The Eocene/Oligocene boundary, at about 33.7 Myr ago, marks one of the largest extinctions of marine invertebrates in the Cenozoic period(1). For example, turnover of mollusc species in the US Gulf coastal plain was over 90% at this time(2,3). A temperature change across this boundary-from warm Eocene climates to cooler conditions in the Oligocene-has been suggested as a cause of this extinction event(4), but climate reconstructions have not provided support for this hypothesis. Here we report stable oxygen isotope measurements of aragonite in fish otoliths-ear stones-collected across the Eocene/Oligocene boundary. Palaeotemperatures reconstructed from mean otolith oxygen isotope values show little change through this interval, in agreement with previous studies(5,6). From incremental microsampling of otoliths, however, we can resolve the seasonal variation in temperature, recorded as the otoliths continue to accrete new material over the life of the fish. These seasonal data suggest that winters became about 4 degrees C colder across the Eocene/Oligocene boundary. We suggest that temperature variability, rather than change in mean annual temperature, helped to cause faunal turnover during this transition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62707/1/407887a0.pd

Block of death-receptor apoptosis protects mouse cytomegalovirus from macrophages and is a determinant of virulence in immunodeficient hosts.

The inhibition of death-receptor apoptosis is a conserved viral function. The murine cytomegalovirus (MCMV) gene M36 is a sequence and functional homologue of the human cytomegalovirus gene UL36, and it encodes an inhibitor of apoptosis that binds to caspase-8, blocks downstream signaling and thus contributes to viral fitness in macrophages and in vivo. Here we show a direct link between the inability of mutants lacking the M36 gene (ΔM36) to inhibit apoptosis, poor viral growth in macrophage cell cultures and viral in vivo fitness and virulence. ΔM36 grew poorly in RAG1 knockout mice and in RAG/IL-2-receptor common gamma chain double knockout mice (RAGγC(-/-)), but the depletion of macrophages in either mouse strain rescued the growth of ΔM36 to almost wild-type levels. This was consistent with the observation that activated macrophages were sufficient to impair ΔM36 growth in vitro. Namely, spiking fibroblast cell cultures with activated macrophages had a suppressive effect on ΔM36 growth, which could be reverted by z-VAD-fmk, a chemical apoptosis inhibitor. TNFα from activated macrophages synergized with IFNγ in target cells to inhibit ΔM36 growth. Hence, our data show that poor ΔM36 growth in macrophages does not reflect a defect in tropism, but rather a defect in the suppression of antiviral mediators secreted by macrophages. To the best of our knowledge, this shows for the first time an immune evasion mechanism that protects MCMV selectively from the antiviral activity of macrophages, and thus critically contributes to viral pathogenicity in the immunocompromised host devoid of the adaptive immune system

Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial

Objective To determine whether cognitive therapy is effective in preventing the worsening of emerging psychotic symptoms experienced by help seeking young people deemed to be at risk for serious conditions such as schizophrenia

Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1

Background: Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD. Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked. Conclusions/Significance: These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications

Lunar Surface Systems Supportability Technology Development Roadmap

The Lunar Surface Systems Supportability Technology Development Roadmap is a guide for developing the technologies needed to enable the supportable, sustainable, and affordable exploration of the Moon and other destinations beyond Earth. Supportability is defined in terms of space maintenance, repair, and related logistics. This report considers the supportability lessons learned from NASA and the Department of Defense. Lunar Outpost supportability needs are summarized, and a supportability technology strategy is established to make the transition from high logistics dependence to logistics independence. This strategy will enable flight crews to act effectively to respond to problems and exploit opportunities in an environment of extreme resource scarcity and isolation. The supportability roadmap defines the general technology selection criteria. Technologies are organized into three categories: diagnostics, test, and verification; maintenance and repair; and scavenge and recycle. Furthermore, "embedded technologies" and "process technologies" are used to designate distinct technology types with different development cycles. The roadmap examines the current technology readiness level and lays out a four-phase incremental development schedule with selection decision gates. The supportability technology roadmap is intended to develop technologies with the widest possible capability and utility while minimizing the impact on crew time and training and remaining within the time and cost constraints of the program

Temporal trends in serum concentrations of polychlorinated dioxins, furans, and PCBs among adult women living in Chapaevsk, Russia: a longitudinal study from 2000 to 2009

<p>Abstract</p> <p>Background</p> <p>The present study assessed the temporal trend in serum concentrations of polychlorinated dibenzo-<it>p</it>-dioxins, dibenzofurans, and biphenyls (PCBs) among residents of a Russian town where levels of these chemicals are elevated due to prior industrial activity.</p> <p>Methods</p> <p>Two serum samples were collected from eight adult women (in 2000 and 2009), and analyzed with gas chromatography-high-resolution mass spectrometry.</p> <p>Results</p> <p>The average total toxic equivalency (TEQ) decreased by 30% (from 36 to 25 pg/g lipid), and the average sum of PCB congeners decreased by 19% (from 291 to 211 ng/g lipid). Total TEQs decreased for seven of the eight women, and the sum of PCBs decreased for six of eight women. During this nine year period, larger decreases in serum TEQs and PCBs were found in women with greater increases in body mass index.</p> <p>Conclusions</p> <p>This study provides suggestive evidence that average serum concentrations of dioxins, furans, and PCBs are decreasing over time among residents of this town.</p

The Role of Maternal Depression on Treatment Outcome for Children with Externalizing Behavior Problems

Studies have shown that, on average, Parent Management Training combined with cognitive-behavioral therapy decreases children’s externalizing behavior, but some children do not improve through treatment. The current study aimed to examine the role of maternal depression in understanding this variability in treatment outcome. Children with externalizing behavioral problems and their parents were recruited from combined Parent Management Training and Cognitive-Behavioral programs in “real-world” clinical settings. At pre- and post treatment, maternal depression and children’s externalizing behavior were assessed. Results showed that treatment was less effective for children of depressed mothers compared to non-depressed mothers and that improvements in maternal depression were associated with improvements in children’s externalizing behavior. These findings suggest that treatment programs for children with externalizing problems may be able to improve outcomes if maternal depression is a target of intervention

Perceived parental control, restructuring ability, and leisure motivation: A cross-cultural comparison

Leisure is viewedworldwide as an important developmental context for adolescents. As leisure research and programs are shared across nations, it is crucial to examine the cultural equivalence of leisure-related constructs and how they are related. Grounded in self-determination theory, this study explored the influence of perceived parental control and leisure restructuring ability on leisure motivation (amotivation and autonomous motivation) using samples of eighth grade adolescents in the United States and South Africa. Results of multiple-group structural equation modeling showed that the measurement model of the constructs was equivalent across the two samples, but the determinants of leisure motivation differed between the two samples. The findings provide implications for future cross-cultural research in leisure and offer insights on design and adaptation of leisure-based intervention and education programs in different cultural contexts.IS