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At least 955 records · Page 53

Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

Background: Immunity, latent herpesvirus reactivation, physiological stress and circadian rhythms were assessed during six month spaceflight onboard ISS. Blood and saliva samples were collected early, mid and late in-flight and returned for immediate analysis. Mid-point study data (10 of 17 planned subjects) will be presented. Results: Some shifts in leukocyte distribution occurred during flight, including alterations in CD8+ T cell maturation. General T cell function was consistently reduced early in-flight. Levels CD8+/IFNg+ producing T cells were depressed early in-flight, and immediately upon landing. Persistent mitogen-dependant reductions were observed in IFNg, IL-17a, IL-10, TNFa and IL-6 production. Monocyte production of IL-10 was reduced, whereas IL-8 levels were increased. Levels of mRNA for the TNFa, IL-6 and IFNg were transiently elevated early in-flight, and the dynamics of TNF and IL-6 gene expression were somewhat antagonistic to their corresponding receptors during flight. The number of virus-specific CD8+ T-cells was measured using MHC tetramers, while their function was measured using intracellular cytokine analysis following peptide stimulation. Both the number and function of EBV-specific cells decreased during flight as compared to preflight levels. The number of CMV-specific T-cells generally increased as the mission progressed while their function was variable. Viral (EBV) load in blood was elevated postflight. Anti-EBV VCA antibodies were significantly elevated by R+0; anti-EA antibodies were not significantly elevated at landing; and anti-CMV antibodies were somewhat elevated during flight. Higher levels of salivary EBV DNA were found during flight. VZV DNA reactivation occurred in ~50 % of astronauts during flight, continuing for up to 30 days post-flight. CMV was shed in 35 % the in-flight and 30% of postflight urine samples of the crewmembers. There was generally a higher level of cortisol as measured in urine and saliva in the astronauts during flight, but plasma cortisol was relatively unchanged during flight. Circadian rhythm of salivary cortisol was altered during flight. Conclusion. Some alterations in immunity do not resolve during six month spaceflight, consequentially resulting in persistent herpesvirus reactivation. Ongoing immune dysregulation may represent specific clinical risks for exploration-class space missions.

Crucian, B. E.↗

Discovery and Identification of Dimethylsilanediol as a Contaminant in ISS Potable Water

In September of 2010, analysis of ISS potable water samples was undertaken to determine the contaminant responsible for a rise in total organic carbon (TOC). As analysis of the routine target list of organic compounds did not reveal the contaminant, efforts to look for unknown compounds was initiated, resulting in an unknown peak being discovered in the gas chromatography/mass spectrometry (GC/MS) analysis for glycols. A mass spectrum of the contaminant was then generated by concentrating one of the samples by evaporation and analyzing by GC/MS in full-scan mode. Although a computer match of the compound s identity could not be obtained with the instrument s database, a search with a more up to date mass spectral library yielded a good match with dimethylsilanediol (DMSD). Inductively Coupled Plasma/Mass Spectrometry (ICP/MS) analyses showed abnormally high silicon levels in the samples, confirming that the unknown contained silicon. DMSD was then synthesized to confirm the identification and provide a standard to develop a calibration curve. Further confirmation was provided by external Direct Analysis in Real Time (DART) GC/MS analysis. A preliminary GC/MS method was then developed and archived samples from various locations on ISS were analyzed to determine the extent of the contamination and provide data for troubleshooting. This paper describes these events in more detail as well as problems encountered in routine GC/MS analyses and the subsequent development of high performance liquid chromatography and LC/MS/MS methods for quantitation of DMSD.

Rutz, Jeffrey A.↗

The ESA-NASA CHOICE Study: Winterover at Concordia Station, Interior Antarctica, A Potential Analog for Spaceflight-Associated Immune Dysregulation

For ground-based space physiological research, the choice of terrestrial analog must carefully match the system of interest. Antarctica winter-over at the European Concordia Station is potentially a superior ground-analog for spaceflight-associated immune dysregulation (SAID). Concordia missions consist of prolonged durations in an extreme/dangerous environment, station-based habitation, isolation, disrupted circadian rhythms and international crews. The ESA-NASA CHOICE study assesses innate and adaptive immunity, viral reactivation and stress factors during Concordia winterover deployment. Initial data obtained from the first study deployment (2009 mission; 'n' of 6) will be presented, and logistical challenges regarding analog usage for biological studies will also be discussed. The total WBC increased, and alterations in some peripheral leukocyte populations were observed during winterover at Concordia Station. Percentages of lymphocytes and monocytes increased, and levels of senescent CD8+ T cells were increased during deployment. Transient increases in constitutively activated T cell subsets were observed, at mission time points associated with endemic disease outbreaks. T cell function (early blastogenesis response) was increased near the entry/exit deployment phases, and production of most measured cytokines increased during deployment. Salivary cortisol demonstrated high variability during winterover, but was generally increased. A 2-point circadian rhythm of cortisol measurement (morning/evening) was unaltered during winterover. Perceived stress was mildly elevated during winterover. Other measures, including in-vitro DTH assessment, viral specific T cell number/function and latent herpesvirus reactivation have not yet been completed for the 2009 winterover subjects. Based on the preliminary data, alterations in immune cell distribution and function appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Based on the initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune changes.

Crucian, B. E.↗

NASA N+3 Subsonic Fixed Wing Silent Efficient Low-Emissions Commercial Transport (SELECT) Vehicle Study

A conceptual commercial passenger transport study was performed to define a single vehicle for entry into service in the 2030 to 2035 timeframe, meeting customer demands as well as NASA goals for improved fuel economy, NOx emissions, noise, and operability into smaller airports. A study of future market and operational scenarios was used to guide the design of an advanced tube-and-wing configuration that utilized advanced material and structural concepts, an advanced three-shaft high-bypass turbofan engine, natural laminar flow technology, and a suite of other advanced technologies. This configuration was found to meet the goals for NOx emissions, noise, and field length. A 64 percent improvement in fuel economy compared to a current state-of-the-art airliner was achieved, which fell slightly short of the desired 70 percent goal. Technology maturation plans for the technologies used in the design were developed to help guide future research and development activities.

Bruner, Sam↗

Particular Characterisation of an In-Vitro-DTH Test to Monitor Cellular Immunity - Applications for Patient Care and Space Flight

Goal:i) Characterization of the role of the main immune reactive cell types contributing to the cellular immune response in the in-vitro DTH and ii) Validation of the in-vitro DTH under different clinical and field conditions. Methods:As positive control whole blood was incubated in the in-vitro DTH, supernatants were gathered after 12, 24 and 48h. Readout parameters of this test are cytokines in the assay's supernatant. To determine the role of T-cells, monocytes and natural killer (NK), these cell populations were depleted using magnetic beads prior to in-vitro-DTH incubation. Validation of the test has occurred under clinical (HIV-patients, ICU) and field-conditions (parabolic/space-flights, confinement). Results:T-cell depletion abandoned almost any IL-2 production and reduced IFN-gamma production irrespective of the type of antigen, whereas CD56 depleted cultures tended to lower IL-2 secretion and IFN-gamma and to parallel a IL-10-increase after viral challenge. This IL-10-increase was seen also in CD14-depleted setups. DTH read-out was significantly different under acute stress (parabolic flight) or chronic stress (ISS), respectively. Preliminary data of HIV infected patients demonstrate that this test can display the contemporary immune status during an antiviral therapy. Conclusion:The in-vitro DTH mirrors adaptive and innate immune activation and may serve as tool also for longitudinal follow up of Th1/Th2 weighed immune response under adverse life conditions on earth and in space. It is planned to implement the assay in the on the ISS (MoCISS).

Feurecker, M.↗

The ESA-NASA 'CHOICE' Study: Winterover at Concordia Station, Interior Antarctica, as an Analog for Spaceflight-Associated Immune Dysregu1ation

For ground-based space physiological research, the choice of analog must carefully match the system of interest. Antarctica winter-over at the European Concordia Station is potentially a ground-analog for spaceflight-associated immune dysregulation (SAID). Concordia missions consist of prolonged durations in an extreme/dangerous environment, station-based habitation, isolation, disrupted circadian rhythms and international crews. The ESA-NASA CHOICE study assess innate and adaptive immunity, viral reactivataion and stress factors during Concordia winter-over deployment. To date, not all samples have been analyzed. Here, only data will be preliminary presented for those parameters where sample/data analysis is completed (i.e., Leukocyte subsets, T cell function, and intracellular/secreted cytokine profiles.)

Crucian, Brian E,↗

NASA 14 Day Undersea Missions: A Short-Duration Spaceflight Analog for Immune System Dysregulation?

This poster paper reviews the use of 14 day undersea missions as a possible analog for short duration spaceflight for the study of immune system dysregulation. Sixteen subjects from the the NASA Extreme Enviro nment Mission Operations (NEEMO) 12, 13 and 14 missions were studied for immune system dysregulation. The assays that are presented in this poster are the Virleukocyte subsets, the T Cell functions, and the intracellular/secreted cytokine profiles. Other assays were performed, but are not included in this presntation.

Crucian, B. E.↗

Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

This poster presentation reviews a study that is designed to address immune system dysregulation and the risk to crewmembers in long duration exploration class missions. This study will address these objectives: (1) Determine the status of adaptive immunity physiological stress, viral immunity, latent herpesvirus reactivation in astronauts during 6 month missions to the International Space Station; (2) determine the clinical risk related to immune dysregulation for exploration class spaceflight; and (3) determine an appropriate monitoring strategy for spaceflight-associated immune dysfunction that could be used for the evaluation of countermeasures. The study anticipates 17 subjects, and for this presentation, (midpoint study data) 10 subjects are reviewed.

Crucian, B. E.↗

Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

We have presented results of ultra-low dose rate irradiations (< or = 10 mrad(Si)/s) for a variety of radiation hardened and commercial linear bipolar devices. We observed low dose rate enhancement factors exceeding 1.5 in several parts. The worst case of dose rate enhancement resulted in functional failures, which occurred after 10 and 60 krad(Si), for devices irradiated at 0.5 and 10 mrad(Si)/s, respectively. Devices fabricated with radiation hardened processes and designs also displayed dose rate enhancement at below 10 mrad(Si)/s. Furthermore, the data indicated that these devices have not reached the damage saturation point. Therefore the degradation will likely continue to increase with increasing total dose, and the low dose rate enhancement will further magnify. The cases presented here, in addition to previous examples, illustrate the significance and pervasiveness of low dose rate enhancement at dose rates lower than 10 mrad(Si). These results present further challenges for radiation hardness assurance of bipolar linear circuits, and raise the question of whether the current standard test dose rate is conservative enough to bound degradations due to ELDRS.

Chen, Dakai↗

Icing Encounter Duration Sensitivity Study

This paper describes a study performed to investigate how aerodynamic performance degradation progresses with time throughout an exposure to icing conditions. It is one of the first documented studies of the effects of ice contamination on aerodynamic performance at various points in time throughout an icing encounter. Both a 1.5 and 6 ft chord, two-dimensional, NACA-23012 airfoils were subjected to icing conditions in the NASA Icing Research Tunnel for varying lengths of time. At the end of each run, lift, drag, and pitching moment measurements were made. Measurements with the 1.5 ft chord model showed that maximum lift and pitching moment degraded more rapidly early in the exposure and degraded more slowly as time progressed. Drag for the 1.5 ft chord model degraded more linearly with time, although drag for very short exposure durations was slightly higher than expected. Only drag measurements were made with the 6 ft chord airfoil. Here, drag for the long exposures was higher than expected. Novel comparison of drag measurements versus an icing scaling parameter, accumulation parameter times collection efficiency was used to compare the data from the two different size model. The comparisons provided a means of assessing the level of fidelity needed for accurate icing simulation.

Addy, Harold E., Jr.↗

Developing Flexible Discrete Event Simulation Models in an Uncertain Policy Environment

On February 1st, 2010 U.S. President Barack Obama submitted to Congress his proposed budget request for Fiscal Year 2011. This budget included significant changes to the National Aeronautics and Space Administration (NASA), including the proposed cancellation of the Constellation Program. This change proved to be controversial and Congressional approval of the program's official cancellation would take many months to complete. During this same period an end-to-end discrete event simulation (DES) model of Constellation operations was being built through the joint efforts of Productivity Apex Inc. (PAl) and Science Applications International Corporation (SAIC) teams under the guidance of NASA. The uncertainty in regards to the Constellation program presented a major challenge to the DES team, as to: continue the development of this program-of-record simulation, while at the same time remain prepared for possible changes to the program. This required the team to rethink how it would develop it's model and make it flexible enough to support possible future vehicles while at the same time be specific enough to support the program-of-record. This challenge was compounded by the fact that this model was being developed through the traditional DES process-orientation which lacked the flexibility of object-oriented approaches. The team met this challenge through significant pre-planning that led to the "modularization" of the model's structure by identifying what was generic, finding natural logic break points, and the standardization of interlogic numbering system. The outcome of this work resulted in a model that not only was ready to be easily modified to support any future rocket programs, but also a model that was extremely structured and organized in a way that facilitated rapid verification. This paper discusses in detail the process the team followed to build this model and the many advantages this method provides builders of traditional process-oriented discrete event simulations.

Miranda, David J.↗

Whole Blood Activation Results in Enhanced Detection of T Cell and Monocyte Cytokine Production by Flow Cytometry

An excellent monitor of the immune balance of peripheral circulating cells is to determine their cytokine production patterns in response to stimuli. Using flow cytometry a positive identification of cytokine producing cells in a mixed culture may be achieved. Recently, the ability to assess cytokine production following a wholeblood activation culture has been described. We compared whole blood culture to standard PBMC culture and determined the individual cytokine secretion patterns for both T cells and monocytes via flow cytometry. For T cells cytokine assessment following PMA +ionomycin activation: (1) a significantly greater percentages of T cells producing IFNgamma and IL-2 were observed following whole-blood culture; (2) altered T cell cytokine production kinetics were observed by varying whole blood culture times. In addition, a four-color cytometric analysis was used to allow accurate phenotyping and quantitation of cytokine producing lymphocyte populations. Using this technique we found IFNgamma production to be significantly elevated in the CD3+/CD8+ T cell population as compared to the CD3+/CD8- population following five hours of whole blood activation. Conversely, IL-2 and IL-10 production were significantly elevated in the CD3+/CD8- T cell population as compared to the CD3+/CD8+ population. Monocyte cytokine production was assessed in both culture systems following LPS activation for 24 hours. A three-color flow cytometric was used to assess two cytokines in conjunction with CD 14. The cytokine pairs used for analysis were IL-1a/IL-12, and IL-10ITNFa. Nearly all monocytes were stimulated to produce IL-1a, IL-12 and TNFalpha equally well in both culture systems. Monocyte production of IL-10 was significantly elevated following whole blood culture as compared to PBMC culture. IL-12 producing monocytes appeared to be a distinct subpopulation of the IL-1a producing set, whereas IL-10 and TNFa producing monocytes were largely mutually exclusive. IL-10 and TNFa producing monocytes may represent functionally different monocyte subsets with distinct functions. Whole blood culture eliminates the need to purify cell populations prior to culture and may have significant utility for the routine monitoring of the cytokine balances of the peripheral blood T cell and monocyte populations. In addition, there are distinct advantages to performing whole-blood (WB) activation as compared to PBMC activation. These advantages would include retaining all various cell-cell interactions as well as any soluble factors present in serum that influence cell activation. It is likely that the altered cytokine production observed following whole blood culture more accurately represents the in-vivo immune balance.

Sams, Clarence F.↗

Whole Blood Activation Results in Altered T Cell and Monocyte Cytokine Production Profiles by Flow Cytometry

An excellent monitor of the immune balance of peripheral circulating cells is to determine their cytokine production patterns in response to stimuli. Using flow cytometry, a positive identification of cytokine producing cells in a mixed culture may be achieved. Recently, the ability to assess cytokine production following a whole-blood activation culture has been described. In this study, whole blood activation was compared to traditional PBMC activation and the individual cytokine secretion patterns for both T cells, T cell subsets and monocytes was determined by flow cytometry. RESULTS: For T cell cytokine assessment (IFNg/IL-10 and IL-21/L-4) following PMA +ionomycin activation: (1) a Significantly greater percentages of T cells producing IFNgamma and IL-2 were observed following whole-blood culture and (2) altered T cell cytokine production kinetics were observed by varying whole blood culture times. Four-color analysiS was used to allow assessment of cytokine production by specific T cell subsets. It was found that IFNgamma production was significantly elevated in the CD3+/CD8+ T cell population as compared to the CD3+/CD8- population following five hours of whole blood activation. Conversely, IL-2 and IL-10 production were Significantly elevated in the CD3+/CD8- T cell population as compared to the CD3+/CD8+ population. Monocyte cytokine production was assessed in both culture systems following LPS activation for 24 hours. A three-color flow cytometric was used to assess two cytokines (IL-1a/IL-12 and TNFa/IL-10) in conjunction with CD14. Nearly all monocytes were stimulated to produce IL-1a, IL-12 and TNFa. equally well in both culture systems, however monocyte production of IL-10 was significantly elevated in whole blood culture as compared to PBMC culture. IL-12 producing monocytes appeared to be a distinct subpopulation of the IL-1a producing set, whereas IL-10 and TNFa producing monocytes were largely mutually exclusive. IL-10 and TNFa producing monocytes may represent distinct monocyte subsets with unique functions. CONCLUSIONS: Whole blood culture eliminates the need to purify cell populations prior to culture and may have Significant utility for the routine monitoring of the cytokine balances of the peripheral blood T cell and monocyte populations. In addition, there are distinct advantages to performing whole-blood (WB) activation as compared to PBMC activation. These advantages would include retaining all various cell-cell interactions as well as any soluble factors present in serum that influence cell activation. In this study, alterations in cytokine production are demonstrated between whole blood and PBMC activation. It is likely that whole blood activation more accurately represents the in-vivo immune balance than PBMC activation.

Crucian, Brian E.↗

Desert Varnish - Preservation of Biofabrics/Implcations for Mars

Desert varnish is the orange to dark brown rind that accumulates on exposed rock surfaces in many arid environments. Samples from the Sonoran Desert of Arizona are composed predominantly of clays (illite, smectite) and Mn- and Fe- oxides (birnessite, hematite). Features that appear to be single organisms are found within the varnish and at the rock-varnish interface. Many of these features are embedded in films that strongly resemble the water-rich extracellular polysaccharides produced by diverse microorganisms. Most common are rod-shaped celllike objects, 0.5-2 microns in the longest dimension, located within the varnish coatings. Some of these objects are shown to contain amines by fluorescence microscopy. The rod-shaped objects are observed in various states of degradation, as indicated by C and S abundances. Rods with higher C and S abundances appear less degraded than those with lower concentrations of these two elements. Regions rich in apparent microbes are present, while other regions display Mn- and Fe-rich mineral fabrics with microbe-sized voids and no obvious cells. These textures are interpreted as biofabrics, preserved by the precipitation of Mn and Fe minerals. We are researching the preservation of biofabrics by desert varnish in Earth's geological record. Rock coatings may similarly preserve evidence of microbial life on the hyper-arid surface of Mars.

Probst, Luke W.↗

NASA's Soil Moisture Active and Passive (SMAP) Mission

The Soil Moisture Active-Passive (SMAP) Mission is one of the first Earth observation satellites being formulated by NASA in response to the 2007 National Research Council s Decadal Survey. SMAP will make global measurements of soil moisture at the Earth's land surface and its freeze-thaw state. These measurements will allow significantly improved estimates of water, energy and carbon transfers between the land and atmosphere. Soil moisture measurements are also of great importance in assessing flooding and monitoring drought. Knowledge gained from SMAP observations can help mitigate these natural hazards, resulting in potentially great economic and social benefits. SMAP observations of soil moisture and freeze/thaw timing over the boreal latitudes will also reduce a major uncertainty in quantifying the global carbon balance and help to resolve an apparent missing carbon sink over land. The SMAP mission concept will utilize an L-band radar and radiometer sharing a rotating 6-meter mesh reflector antenna flying in a 680 km polar orbit with an 8-day exact ground track repeat aboard a 3-axis stabilized spacecraft to provide high-resolution and high-accuracy global maps of soil moisture and freeze/thaw state every two to three days. In addition, the SMAP project will use these surface observations with advanced modeling and data assimilation to provide estimates of deeper root-zone soil moisture and net ecosystem exchange of carbon. SMAP recently completed its Phase A Mission Concept Study Phase for NASA and transitioned into Phase B (Formulation and Detailed Design). A number of significant accomplishments occurred during this initial phase of mission development. The SMAP project held several open meetings to solicit community feedback on possible science algorithms, prepared preliminary draft Algorithm Theoretical Basis Documents (ATBDs) for each mission science product, and established a prototype algorithm testbed to enable testing and evaluation of the performance of candidate algorithms. SMAP conducted an Applications Workshop in September 2009 to coordinate with potential application users interested in the mission data. A draft Applications Plan describing the Project s planned outreach to potential applications users has been prepared and will be updated during Phase B. SMAP made a significant evaluation of the potential terrestrial radio frequency interference (RFI) source environment and established radiometer and radar flight hardware and ground processing mitigation approaches. SMAP finalized its science orbit and orbit injection approach to optimize launch mass and prepared launch and commissioning scenarios and timeline. A science data communications approach was developed to maximize available science data volume to improve science margins while maintaining moderately short data product latencies to support many potential applications using existing ground assets and with minimum impact to the flight system. SMAP developed rigid multi-body and flexible body dynamics and control models and system designs for the 6-meter rotating instrument reflector-boom assembly (RBA) and flight system to confirm pointing and control performance, and devised strategies to efficiently implement on-orbit balancing if needed. Industry partners were selected for the spin mechanism assembly (SMA) and RBA. Preliminary designs for the radar and radiometer were initiated, including constructing breadboards of key assemblies.

Kellogg, Kent↗

Spectroelectrochemical Instrument Measures TOC

A spectroelectrochemical instrument has been developed for measuring the total organic carbon (TOC) content of an aqueous solution. Measurements of TOC are frequently performed in environmental, clinical, and industrial settings. Until now, techniques for performing such measurements have included, various ly, the use of hazardous reagents, ultraviolet light, or ovens, to promote reactions in which the carbon contents are oxidized. The instrument now being developed is intended to be a safer, more economical means of oxidizing organic carbon and determining the TOC levels of aqueous solutions and for providing a low power/mass unit for use in planetary missions.

Kounaves, Sam↗

Coaxial Cables for Martian Extreme Temperature Environments

Work was conducted to validate the use of the rover external flexible coaxial cabling for space under the extreme environments to be encountered during the Mars Science Laboratory (MSL) mission. The antennas must survive all ground operations plus the nominal 670-Martian-day mission that includes summer and winter seasons of the Mars environment. Successful development of processes established coaxial cable hardware fatigue limits, which were well beyond the expected in-flight exposures. In keeping with traditional qualification philosophy, this was accomplished by subjecting flight-representative coaxial cables to temperature cycling of the same depth as expected in-flight, but for three times the expected number of in-flight thermal cycles. Insertion loss and return loss tests were performed on the coaxial cables during the thermal chamber breaks. A vector network analyzer was calibrated and operated over the operational frequency range 7.145 to 8.450 GHz. Even though some of the exposed cables function only at UHF frequencies (approximately 400 MHz), the testing was more sensitive, and extending the test range down to 400 MHz would have cost frequency resolution. The Gore flexible coaxial cables, which were the subject of these tests, proved to be robust and displayed no sign of degradation due to the 3X exposure to the punishing Mars surface operations cycles.

Ramesham, Rajeshuni↗

The Limits of Coding with Joint Constraints on Detected and Undetected Error Rates

We develop a remarkably tight upper bound on the performance of a parameterized family of bounded angle maximum-likelihood (BA-ML) incomplete decoders. The new bound for this class of incomplete decoders is calculated from the code's weight enumerator, and is an extension of Poltyrev-type bounds developed for complete ML decoders. This bound can also be applied to bound the average performance of random code ensembles in terms of an ensemble average weight enumerator. We also formulate conditions defining a parameterized family of optimal incomplete decoders, defined to minimize both the total codeword error probability and the undetected error probability for any fixed capability of the decoder to detect errors. We illustrate the gap between optimal and BA-ML incomplete decoding via simulation of a small code.

Undetected Error Rate↗