Factors in International Space Station Integration Feasibility Assessments

The International Space Station, ISS, is a growing vehicle. The ISS configuration changes internally and externally with each ISS flight. Each flight adds resources and capabilities such as docking/berthing ports, power, stowage volume, heat rejection, and data processing capability. The configuration, capabilities and performance characteristics of the vehicle will be in flux until assembly complete. At the same time the knowledge about what is required to support humans involved in long duration space flight is also being greatly expanded. In addition to the changes occurring on-orbit, the situation on the ground is also very dynamic. Proposals for new ISS elements, proposed deletions of elements, changes to the ISS requirements, and changes to the planned configuration are always under evaluation. Furthermore, budgetary issues have driven the need to explore alternative options for the ISS . This environment has made the role of the technical integrator in the ISS program unique in that the baseline against which proposals are evaluated is always changing. The nature of the International Space Station Program adds another dimension to the integrators task. ISS program activities are spread across several centers: KSC, MSFC, GRC, DFRC, ARC and JSc. There are six International Partners/participants each with their own unique organizations. The prime contractor is in Texas, California and Alabama. And, the Space Shuttle Program as the launch vehicle provider is another major interface. In spite of the fluidity of the technical baseline, projections and organizational complexity, in the course of evaluating proposals and producing feasibility assessments there are factors, which frequently emerge as significant. These factors tend to be the limiting conditions when they come into play. The finite resources, which tend to limit the options for ISS are: upmass, life support and crew rescue capability, crew time, utilities, exercise equipment, and docking/berthing ports. Upmass requirements need to be developed for each option proposed. Short term and long term impacts to upmass are the result of the implementation and long term operations. The upmass requirements need to be met by the existing launch vehicles and any change in flight rate will be a significant cost driver. In addition, when any item is brought to the ISS careful consideration must be given to the on-board stowage and crew time available to unpack, transfer, stow and use these items. If stowage is not available then something must be returned, use of non-standard stowage negotiated or the item in question stays on the ground. Additional crew time requirements will impact available utilization time or crew off-duty time. When the human element is affected, such as, by increasing the number of crew members or changing the duration of the crew stay (longer or shorter) there is an additional set of factors that come into play. The main considerations are: rescue capability, exercise requirements and availability of equipment, resupply, and life support capability

Mitogen-activated protein kinase (MAPK) pathways mediate embryonic responses to culture medium osmolarity by regulating Aquaporin 3 and 9 expression and localization, as well as embryonic apoptosis.

BACKGROUND: In order to advance the development of culture conditions and increase the potential for supporting normal preimplantation embryo development in vitro, it is critical to define the mechanisms that early embryos utilize to survive in culture. We investigated the mechanisms that embryos employ in response to culture medium osmolarity. We hypothesized that mitogen-activated protein kinase (MAPK) pathways mediate responses to hyperosmotic stress by regulating Aquaporin (AQP) 3 and 9 expression as well as embryonic apoptosis. METHODS: Real-time reverse transcription and polymerase chain reaction and whole-mount immunofluorescence were used to determine the relative mRNA levels and protein localization patterns of AQP 3 and 9 after hyperosmotic medium treatment. RESULTS: At 6 and 24 h, a significant increase in Aqp 3 and 9 mRNA was observed in the sucrose hyperosmotic treatment compared with standard medium and glycerol controls. Blockade of MAPK14/11 negated the increase in Aqp 3 and 9 mRNA levels, whereas culture in a MAPK8 blocker did not. Hyperosmotic sucrose treatment significantly increased embryonic apoptosis which was negated in the presence of MAPK8 blocker, but not MAPK14/11 blocker. CONCLUSIONS: MAPK14/11 activation is a component of the rapid adaptive stress response mechanism that includes the effects of AQP mRNA expression and protein localization, whereas the MAPK8 pathway is a regulator of apoptosis

The dynamics of HCV-specific antibody responses in HIV/HCV patients on long-term antiretroviral therapy

Antibody responses have not been fully characterised in chronically HIV/HCV patients receiving antiretroviral therapy (ART). Seventeen HIV/HCV patients receiving ART were followed for a median (range) interval of 597 (186–766) weeks. Prior to ART, HIV/HCV patients had lower levels of antibodies reactive with HCV core and JFH-1, and lower genotype cross-reactive neutralising antibodies (nAb) titres, than HCV patients. Levels of JFH-1 reactive antibody increased on ART, irrespective of CD4+ T-cell counts or changes in serum ALT levels. The appearance of nAb coincided with control of HCV viral replication in five HIV/HCV patients. In other patients, HCV viral loads remained elevated despite nAb responses. Sustained virological responses following HCV therapy were associated with reduced antibody responses to JFH-1 and core but elevated responses to non-structural proteins. We conclude that nAb responses alone may fail to clear HCV, but contribute to control of viral replication in some HIV/HCV patients responding to ART

Mechanosensitivity in the model sea anemone Nematostella vectensis

Abstract Tentacles of the sea anemone, Nematostella vectensis, are covered with hair bundles. Hair bundles were deXected by water jets to test whether they are mechanoreceptors. Electrophysiological recordings conWrm that deXections of hair bundles induce transients in membrane current. In a diVerent species of anemone, hair bundle mechanoreceptors are known to change shape and responsiveness according to the activity of chemoreceptors that bind prey-derived compounds including N-acetylated sugars. In Nematostella, hair bundles signiWcantly elongate upon exposure to NANA, an N-acetylated sugar. Based on a bioassay in which discharged nematocysts are counted in gelatin-coated test probes touched to tentacles, we Wnd that NANA shifts vibration dependent discharge of basitrich nematocysts to lower frequencies overlapping those produced during swimming by known prey including planktonic crustaceans. Furthermore, we Wnd for the Wrst time that vibration detection extends at least 2.5 cm beyond the tentacle tips. Thus, Nematostella likely employs its hair bundles to detect swimming movements of nearby prey

Quantitative changes in intracellular calcium and extracellular-regulated kinase activation measured in parallel in CHO cells stably expressing serotonin (5-HT) 5-HT2A or 5-HT2C receptors

<p>Abstract</p> <p>Background</p> <p>The serotonin (5-HT) 2A and 2C receptors (5-HT_2AR and 5-HT_2CR) are involved in a wide range of physiological and behavioral processes in the mammalian central and peripheral nervous systems. These receptors share a high degree of homology, have overlapping pharmacological profiles, and utilize many of the same and richly diverse second messenger signaling systems. We have developed quantitative assays for cells stably expressing these two receptors involving minimal cell sample manipulations that dramatically improve parallel assessments of two signaling responses: intracellular calcium (<it>Ca_i</it>⁺⁺) changes and activation (phosphorylation) of downstream kinases. Such profiles are needed to begin to understand the simultaneous contributions from the multiplicity of signaling cascades likely to be initiated by serotonergic ligands.</p> <p>Results</p> <p>We optimized the <it>Ca_i</it>⁺⁺assay for stable cell lines expressing either 5-HT_2AR or 5-HT_2CR (including dye use and measurement parameters; cell density and serum requirements). We adapted a quantitative 96-well plate immunoassay for pERK in the same cell lines. Similar cell density optima and time courses were observed for 5-HT_2AR- and 5-HT_2CR-expressing cells in generating both types of signaling. Both cell lines also require serum-free preincubation for maximal agonist responses in the pERK assay. However, 5-HT_2AR-expressing cells showed significant release of <it>Ca_i</it>⁺⁺in response to 5-HT stimulation even when preincubated in serum-replete medium, while the response was completely eliminated by serum in 5-HT_2CR-expressing cells. Response to another serotonergic ligand (DOI) was eliminated by serum-replete preincubation in both cells lines.</p> <p>Conclusions</p> <p>These data expand our knowledge of differences in ligand-stimulated signaling cascades between 5-HT_2AR and 5-HT_2CR. Our parallel assays can be applied to other cell and receptor systems for monitoring and dissecting concurrent signaling responses.</p

Multivariate models from RNA-Seq SNVs yield candidate molecular targets for biomarker discovery: SNV-DA

Breast: up and downstream SNVs model. (CSV 22.1 kb

Fatal COVID-19 infection in a patient with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: A case report

Long-chain fatty-acyl CoA dehydrogenase deficiency (LCHADD) is an inborn error of long chain fatty acid oxidation with various features including hypoketotic hypoglycemia, recurrent rhabdomyolysis, pigmentary retinopathy, peripheral neuropathy, cardiomyopathy, and arrhythmias. Various stresses trigger metabolic decompensation. Coronavirus disease 2019 (COVID-19) is a pandemic caused by the RNA virus SARS-CoV-2 with diverse presentations ranging from respiratory symptoms to myocarditis. We report a case of a patient with LCHADD who initially presented with typical metabolic decompensation symptoms including nausea, vomiting, and rhabdomyolysis in addition to mild cough, and was found to have COVID-19. She developed acute respiratory failure and refractory hypotension from severe cardiomyopathy which progressed to multiple organ failure and death. Our case illustrates the need for close monitoring of cardiac function in patients with a long-chain fatty acid oxidation disorder

Detection of human telomerase reverse transcriptase mRNA in cells obtained by lavage of the pleura is not associated with worse outcome in patients with stage I/II non–small cell lung cancer: Results from Cancer and Leukemia Group B 159902

ObjectivePrevious studies suggest that cytologic analysis of cells obtained by lavage of the pleural surfaces at the time of resection of non–small cell lung cancer can identify patients at risk for recurrence. Because telomerase gene expression has been associated with worse outcome in non–small cell lung cancer, we hypothesized that identification of cells obtained from pleural lavage that express telomerase would identify patients at risk for recurrent disease.MethodsPatients with presumed non–small cell lung cancer underwent thoracotomy with curative intent. Cells obtained by lavage of the pleural surfaces were analyzed for telomerase catalytic subunit human telomerase reverse transcriptase mRNA expression using reverse transcriptase polymerase chain reaction.ResultsA total of 194 patients with stage I/II non–small cell lung cancer had adequate samples, and median follow-up was 60 months (17-91 months). By using Cox models, no statistical differences were found between human telomerase reverse transcriptase–negative and positive patients in disease-free survival (hazard ratio, 1.28; 95% confidence interval, 0.85-1.94; log-rank test, P = .2349) or overall survival (hazard ratio, 1.13; 95% confidence interval, 0.72-1.79; log-rank test, P = .5912)ConclusionsDetection of human telomerase reverse transcriptase in cells obtained from pleural lavage of patients with stage I/II non–small cell lung cancer does not identify patients at risk for recurrent disease

Confidence does not mediate a relationship between owner experience and likelihood of using weight management approaches for native ponies

Funding: This study was funded by Mars Petcare and is part of a PhD studentship funded by the Scottish Funding Council Research Excellence Grant (REG). Authors WR and MN receive salary support from the Rural and Environment Science and Analytical Services Division (RESAS). With the exception of PH (employed by the funding organization), the funding organization did not have any additional role in the conceptualization, methodology, investigation, data curation, formal analysis, decision to publish, or preparation of the manuscript. PH was involved in study design, data interpretation, and manuscript preparation.Peer reviewedPublisher PD

The GOBLET training portal: a global repository of bioinformatics training materials, courses and trainers

Summary: Rapid technological advances have led to an explosion of biomedical data in recent years. The pace of change has inspired new collaborative approaches for sharing materials and resources to help train life scientists both in the use of cutting-edge bioinformatics tools and databases and in how to analyse and interpret large datasets. A prototype platform for sharing such training resources was recently created by the Bioinformatics Training Network (BTN). Building on this work, we have created a centralized portal for sharing training materials and courses, including a catalogue of trainers and course organizers, and an announcement service for training events. For course organizers, the portal provides opportunities to promote their training events; for trainers, the portal offers an environment for sharing materials, for gaining visibility for their work and promoting their skills; for trainees, it offers a convenient one-stop shop for finding suitable training resources and identifying relevant training events and activities locally and worldwide. Availability and implementation: http://mygoblet.org/training-portal Contact: [email protected]