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BioSentinel: Mission Development of a Radiation Biosensor to Gauge DNA Damage and Repair Beyond Low Earth Orbit on a 6U Nanosatellite.

We are designing and developing a "6U" (10 x 22 x 34 cm; 14 kg) nanosatellite as a secondary payload to fly aboard NASA's Space Launch System (SLS) Exploration Mission (EM) 1, scheduled for launch in late 2017. For the first time in over forty years, direct experimental data from biological studies beyond low Earth orbit (LEO) will be obtained during BioSentinel's 12- to 18- month mission. BioSentinel will measure the damage and repair of DNA in a biological organism and allow us to compare that to information from onboard physical radiation sensors. In order to understand the relative contributions of the space environment's two dominant biological perturbations, reduced gravity and ionizing radiation, results from deep space will be directly compared to data obtained in LEO (on ISS) and on Earth. These data points will be available for validation of existing biological radiation damage and repair models, and for extrapolation to humans, to assist in mitigating risks during future long-term exploration missions beyond LEO. The BioSentinel Payload occupies 4U of the spacecraft and will utilize the monocellular eukaryotic organism Saccharomyces cerevisiae (yeast) to report DNA double-strand-break (DSB) events that result from ambient space radiation. DSB repair exhibits striking conservation of repair proteins from yeast to humans. Yeast was selected because of 1) its similarity to cells in higher organisms, 2) the well-established history of strains engineered to measure DSB repair, 3) its spaceflight heritage, and 4) the wealth of available ground and flight reference data. The S. cerevisiae flight strain will include engineered genetic defects to prevent growth and division until a radiation-induced DSB activates the yeast's DNA repair mechanisms. The triggered culture growth and metabolic activity directly indicate a DSB and its successful repair. The yeast will be carried in the dry state within the 1-atm P/L container in 18 separate fluidics cards with each card having 16 independent culture microwells, with integral microchannels and filters to supply nutrients and reagents, confine the yeast to the wells, and enable optical measurement. The measurement subsystem will monitor each subgroup of culture wells continuously for several weeks, optically tracking DSBtriggered cell growth and metabolism. BioSentinel will also include physical radiation sensors based on the TimePix sensor, as implemented by JSC's RadWorks group, which record individual radiation events including estimates of their linear-energytransfer (LET) values. Radiation-dose and LET data will be compared directly to the rate of DSB-and-repair events measured by the S. cerevisiae biosentinels. The spacecraft bus will operate in a deep space environment with functions that include command and data handling, communications, power generation (via deployable solar panels) and storage, and attitude determination-and-control system with micropropulsion. Development of the BioSentinel spacecraft will mature and prove multiple nanosatellite advances in order to function well beyond LEO: Communications from distances of ≥ 500,000 km; Autonomous attitude control, momentum management, and safe mode of nanosatellites in deep space; Shielding-, hardening-, design-, and software-derived radiation tolerance for electronics; Reliable functionality for 12 - 18 months of key subsystems for biofluidics, memory, communications, power, etc.; Close integration of living biological radiation event monitors with miniature physical radiation spectrometers; Biological measurement of solar particle events beyond Earth orbit In addition to providing the first biological results from beyond LEO in over 4 decades, BioSentinel will provide an adaptable small-satellite instrument platform to perform a range of human-exploration-relevant measurements that characterize the biological consequences of multiple outer space environments. BioSentinel is being developed under NASA's Advanced Exploration Systems program.

DNA damage↗

Chance of Necessity: Modeling Origins of Life

The fundamental nature of processes that led to the emergence of life has been a subject of long-standing debate. One view holds that the origin of life is an event governed by chance, and the result of so many random events is unpredictable. This view was eloquently expressed by Jacques Monod in his book Chance or Necessity. In an alternative view, the origin of life is considered a deterministic event. Its details need not be deterministic in every respect, but the overall behavior is predictable. A corollary to the deterministic view is that the emergence of life must have been determined primarily by universal chemistry and biochemistry rather than by subtle details of environmental conditions. In my lecture I will explore two different paradigms for the emergence of life and discuss their implications for predictability and universality of life-forming processes. The dominant approach is that the origin of life was guided by information stored in nucleic acids (the RNA World hypothesis). In this view, selection of improved combinations of nucleic acids obtained through random mutations drove evolution of biological systems from their conception. An alternative hypothesis states that the formation of protocellular metabolism was driven by non-genomic processes. Even though these processes were highly stochastic the outcome was largely deterministic, strongly constrained by laws of chemistry. I will argue that self-replication of macromolecules was not required at the early stages of evolution; the reproduction of cellular functions alone was sufficient for self-maintenance of protocells. In fact, the precise transfer of information between successive generations of the earliest protocells was unnecessary and could have impeded the discovery of cellular metabolism. I will also show that such concepts as speciation and fitness to the environment, developed in the context of genomic evolution also hold in the absence of a genome.

Pohorille, Andrew↗

Vitamin D: Findings from Antarctic, Bed Rest, Houston, and ISS

Obtaining vitamin D is critical for space travelers because they lack ultraviolet light exposure and have an insufficient dietary supply of vitamin D. Despite the provision of 400 IU vitamin D supplements to International Space Station (ISS) early crewmembers, vitamin D status was consistently lower after flight than before flight, and in several crewmembers has decreased to levels considered clinically significant. Vitamin D has long been known to play a role in calcium metabolism, and more recently its non-calcitropic functions have been recognized. According to the results of several recent studies, functionally relevant measures indicate that the lower limit of serum 25-hydroxyvitamin D (a marker of vitamin D status) should be raised from the current 23 nmol/L to 80 nmol/L. The mean preflight serum 25-hydroxyvitamin D (25-OH vit D) for U.S. ISS crewmembers to date is 63 +/- 16 nmol/L, and after a 4- to 6-mo space flight it typically decreases 25-30% despite supplementation (400 IU/d). The sub-optimal pre- and postflight vitamin D status is an issue that needs to be addressed, to allow NASA to better define the appropriate amount of supplemental vitamin D to serve as a countermeasure against vitamin D deficiency in astronaut crews. A series of ground-based and flight studies in multiple models have been conducted, including Antarctica in winter months when UV-B radiation levels are essentially zero, bed rest where subjects are not exposed to UV-B radiation for 60-90 days, in free-living individuals in Houston, and in International Space Station crewmembers. In these studies, we looked at dose regimen and efficacy, compliance issues, as well as toxicity. Preliminary results from these studies will be presented. Together, the data from these studies will enable us to provide space crews with evidence-based recommendations for vitamin D supplementation. The findings also have implications for other persons with limited UV light exposure, including polar workers and the elderly.

Zwart, Sara R.↗

Payload Hardware and Experimental Protocol for Testing the Effect of Space Microgravity on the Resistance to Gentamicin of Stationary-Phase Uropathogenic Escherichia Coli and Its Sigma (sup S)-Deficient Mutant

Human immune response is compromised and bacteria can become more antibiotic resistant in space microgravity (MG). We report that under low-shear modeled microgravity (LSMMG) stationary-phase uropathogenic Escherichia coli (UPEC) become more resistant to gentamicin (Gm). UPEC causes urinary tract infections (UTIs), reported to afflict astronauts; Gm is a standard treatment, so these findings could impact astronaut health. Because LSMMG has been shown to differ from MG, we report here preparations to examine UPEC's Gm sensitivity during spaceflight using the E. coli Anti-Microbial Satellite (EcAMSat) on a free flying nanosatellite in low Earth orbit. Within EcAMSats payload, a 48-microwell fluidic card contains and supports study of bacterial cultures at constant temperature; optical absorbance changes in cell suspensions are made at three wavelengths for each microwell and a fluid-delivery system provides growth medium and predefined Gm concentrations. Performance characterization is reported for spaceflight prototypes of this payload system. Using conventional microtiter plates, we show that Alamar Blue (AB) absorbance changes due to cellular metabolism accurately reflect E. coli viability changes: measuring AB absorbance onboard EcAMSat will enable telemetry of spaceflight data to Earth. Laboratory results using payload prototypes are consistent with wellplate and flask findings of differential sensitivity of UPEC and its delta rpoS strain to Gm. Space MG studies using EcAMSat should clarify inconsistencies from previous space experiments on bacterial antibiotic sensitivity. Further, if sigma (sup s) plays the same role in space MG as in LSMMG and Earth gravity, EcAMSat results would facilitate utilizing our previously developed terrestrial UTI countermeasures in astronauts.

Matin, A. C.↗

Design and Assembly of an Integrated Metabolic Heat Regenerated Temperature Swing Adsorption (MTSA) Subassembly Engineering Development Unit

Metabolic heat regenerated Temperature Swing Adsorption (MTSA) technology is being developed for thermal and carbon dioxide (CO2) control for a Portable Life Support System (PLSS), as well as water recycling. The core of the MTSA technology is a sorbent bed that removes CO2 from the PLSS ventilation loop gas via a temperature swing. A Condensing Icing Heat eXchanger (CIHX) is used to warm the sorbent while also removing water from the ventilation loop gas. A Sublimation Heat eXchanger (SHX) is used to cool the sorbent. Research was performed to explore an MTSA designed for both lunar and Martian operations. Previously the sorbent bed, CIHX, and SHX had been built and tested individually on a scale relevant to PLSS operations, but they had not been done so as an integrated subassembly. Design and analysis of an integrated subassembly was performed based on this prior experience and an updated transient system model. Focus was on optimizing the design for Martian operations, but the design can also be used in lunar operations. An Engineering Development Unit (EDU) of an integrated MTSA subassembly was assembled based on the design. Its fabrication is discussed. Some details on the differences between the as-assembled EDU and the future flight unit are considered.

Padilla, Sebastian A.↗

Ice Lens Formation and Frost Heave at the Phoenix Landing Site

Several lines of evidence indicate that the volume of shallow ground ice in the martian high latitudes exceeds the pore volume of the host regolith. Boynton et al. found an optimal fit to the Mars Odyssey Gamma Ray Spectrometer (GRS) data at the Phoenix landing site by modeling a buried layer of 50-75% ice by mass (up to 90% ice by volume). Thermal and optical observations of recent impact craters in the northern hemisphere have revealed nearly pure ice. Ice deposits containing only 1-2% soil by volume were excavated by Phoenix. The leading hypothesis for the origin of this excess ice is that it developed in situ by a mechanism analogous to the formation of terrestrial ice lenses and needle ice. Problematically, terrestrial soil-ice segregation is driven by freeze/thaw cycling and the movement of bulk water, neither of which are expected to have occurred in the geologically recent past on Mars. If however ice lens formation is possible at temperatures less than 273 K, there are possible implications for the habitability of Mars permafrost, since the same thin films of unfrozen water that lead to ice segregation are used by terrestrial psychrophiles to metabolize and grow down to temperatures of at least 258 K.

Zent, A. P.↗

Design and Assembly of an Integrated Metabolic Heat Regenerated Temperature Swing Adsorption (MTSA) Subassembly Engineering Development Unit

Metabolic heat regenerated Temperature Swing Adsorption (MTSA) technology is being developed for thermal and carbon dioxide (CO2) control for a Portable Life Support System (PLSS), as well as water recycling. The core of the MTSA technology is a sorbent bed that removes CO2 from the PLSS ventilation loop gas via a temperature swing. A Condensing Ice Heat eXchanger (CIHX) is used to warm the sorbent while also removing water from the ventilation loop gas. A Sublimation Heat eXchanger (SHX) is used to cool the sorbent. Research was performed to explore an MTSA designed for both lunar and Martian operations. Previously each the sorbent bed, CIHX, and SHX had been built and tested individually on a scale relevant to PLSS operations, but they had not been done so as an integrated subassembly. Design and analysis of an integrated subassembly was performed based on this prior experience and an updated transient system model. Focus was on optimizing the design for Martian operations, but the design can also be used in lunar operations. An Engineering Development Unit (EDU) of an integrated MTSA subassembly was assembled based on the design. Its fabrication is discussed. Some details on the differences between the as-assembled EDU to the future flight unit are considered.

Padilla, Sebastian A.↗

Impact of Track Structure Effects on Shielding and Dosimetry

Galactic cosmic rays (GCR) consisting of nuclei of all the known elements with kinetic energies extending from tens to millions of MeV pose a significant health hazard to future deep space operations. Even half of the radiation exposures expected in ISS will result from GCR components. The biological actions of these radiations are known to depend on the details of the energy deposition (not just linear energy transfer, LET, but the lateral dispersion of energy deposition about the particle track). Energy deposits in tissues are dominated by the transfer of tens to hundreds of eV to the tissue's atomic electrons. In the case of low LET radiations, the collisions are separated by large dimensions compared to the size of important biomolecular structures. If such events are also separated in time, then the radiation adds little to the background of radicals occurring from ordinary metabolic processes and causes little or no biological injury. Hence, dose rate is a strong determinant of the action of low LET exposures. The GCR exposures are dominated by ions of high charge and energy (HZE) characterized by many collisions with atomic electrons over biomolecular dimensions, resulting in high radical- density events associated with a few isolated ion paths through the cell and minimal dose rate dependence at ordinary exposure levels. The HZE energy deposit declines quickly laterally and merges with the background radical density in the track periphery for which the exact lateral distribution of the energy deposit is the determinant of the biological injury. Although little data exists on human exposures from HZE radiations, limited studies in mice and mammalian cell cultures allow evaluation of the effects of track structure on shield attenuation properties and evaluation of implications for dosimetry. The most complete mammalian cell HZE exposure data sets have been modeled including the C3H10T1/2 survival and transformation data of Yang et al., the V79 survival and mutation data of various groups, and the Harderian gland tumor data of Alpen et al. Model results for the Harderian gland tumor data in comparison with data from Alpen et al. The Harderian target cell initiation cross section compares closely with the transformation cross section found for the C3H10T1/2 cell transformation data of Yang et al. The most notable feature of the cross sections are the multivalued cross sections for a given LET which implies the corresponding relative biological effectiveness (RBE) is dependent not only on the LET but also the ion type. This fact is at variance with the latest ICRP recommended quality factor which is a defined function of only the LET.

Wilson, J. W.↗

Computational Model of Heat Transfer on the ISS

SCRAM Lite (SCRAM signifies Station Compact Radiator Analysis Model) is a computer program for analyzing convective and radiative heat-transfer and heat-rejection performance of coolant loops and radiators, respectively, in the active thermal-control systems of the International Space Station (ISS). SCRAM Lite is a derivative of prior versions of SCRAM but is more robust. SCRAM Lite computes thermal operating characteristics of active heat-transport and heat-rejection subsystems for the major ISS configurations from Flight 5A through completion of assembly. The program performs integrated analysis of both internal and external coolant loops of the various ISS modules and of an external active thermal control system, which includes radiators and the coolant loops that transfer heat to the radiators. The SCRAM Lite run time is of the order of one minute per day of mission time. The overall objective of the SCRAM Lite simulation is to process input profiles of equipment-rack, crew-metabolic, and other heat loads to determine flow rates, coolant supply temperatures, and available radiator heat-rejection capabilities. Analyses are performed for timelines of activities, orbital parameters, and attitudes for mission times ranging from a few hours to several months.

Torian, John G.↗

Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

Halloran, B.↗

Design of Test Support Hardware for Advanced Space Suits

As a member of the Space Suit Assembly Development Engineering Team, I designed and built test equipment systems to support the development of the next generation of advanced space suits. During space suit testing it is critical to supply the subject with two functions: (1) cooling to remove metabolic heat, and (2) breathing air to pressurize the space suit. The objective of my first project was to design, build, and certify an improved Space Suit Cooling System for manned testing in a 1‐G environment. This design had to be portable and supply a minimum cooling rate of 2500 BTU/hr. The Space Suit Cooling System is a robust, portable system that supports very high metabolic rates. It has a highly adjustable cool rate and is equipped with digital instrumentation to monitor the flowrate and critical temperatures. It can supply a variable water temperature down to 34 deg., and it can generate a maximum water flowrate of 2.5 LPM. My next project was to design and build a Breathing Air System that was capable of supply facility air to subjects wearing the Z‐2 space suit. The system intakes 150 PSIG breathing air and regulates it to two operating pressures: 4.3 and 8.3 PSIG. It can also provide structural capabilities at 1.5x operating pressure: 6.6 and 13.2 PSIG, respectively. It has instrumentation to monitor flowrate, as well as inlet and outlet pressures. The system has a series of relief valves to fully protect itself in case of regulator failure. Both projects followed a similar design methodology. The first task was to perform research on existing concepts to develop a sufficient background knowledge. Then mathematical models were developed to size components and simulate system performance. Next, mechanical and electrical schematics were generated and presented at Design Reviews. After the systems were approved by the suit team, all the hardware components were specified and procured. The systems were then packaged, fabricated, and thoroughly tested. The next step was to certify the equipment for manned used, which included generating a Hazard Analysis and giving a presentation to the Test Readiness Review Board. Both of these test support systems will perform critical roles in the development of next‐generation space suits. They will used on a regular basis to test the NASA's new Z‐2 Space Suit. The Space Suit Cooling System is now the primary cooling system for all advanced suit tests.

Watters, Jeffrey A.↗

Noninvasive, near infrared spectroscopic-measured muscle pH and PO2 indicate tissue perfusion for cardiac surgical patients undergoing cardiopulmonary bypass

OBJECTIVE: To determine whether near infrared spectroscopic measurement of tissue pH and Po2 has sufficient accuracy to assess variation in tissue perfusion resulting from changes in blood pressure and metabolic demand during cardiopulmonary bypass. DESIGN: Prospective clinical study. SETTING: Academic medical center. SUBJECTS: Eighteen elective cardiac surgical patients. INTERVENTION: Cardiac surgery under cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: A near infrared spectroscopic fiber optic probe was placed over the hypothenar eminence. Reference Po2 and pH sensors were inserted in the abductor digiti minimi (V). Data were collected every 30 secs during surgery and for 6 hrs following cardiopulmonary bypass. Calibration equations developed from one third of the data were used with the remaining data to investigate sensitivity of the near infrared spectroscopic measurement to physiologic changes resulting from cardiopulmonary bypass. Near infrared spectroscopic and reference pH and Po2 measurements were compared for each subject using standard error of prediction. Near infrared spectroscopic pH and Po2 at baseline were compared with values during cardiopulmonary bypass just before rewarming commenced (hypotensive, hypothermic), after rewarming (hypotensive, normothermic) just before discontinuation of cardiopulmonary bypass, and at 6 hrs following cardiopulmonary bypass (normotensive, normothermic) using mixed-model analysis of variance. Near infrared spectroscopic pH and Po2 were well correlated with the invasive measurement of pH (R2 =.84) and Po2 (R 2 =.66) with an average standard error of prediction of 0.022 +/- 0.008 pH units and 6 +/- 3 mm Hg, respectively. The average difference between the invasive and near infrared spectroscopic measurement was near zero for both the pH and Po2 measurements. Near infrared spectroscopic Po2 significantly decreased 50% on initiation of cardiopulmonary bypass and remained depressed throughout the bypass and monitored intensive care period. Near infrared spectroscopic pH decreased significantly during cardiopulmonary bypass, decreased significantly during rewarming, and remained depressed 6 hrs after cardiopulmonary bypass. Diabetic patients responded differently than nondiabetic subjects to cardiopulmonary bypass, with lower muscle pH values (p =.02). CONCLUSIONS: Near infrared spectroscopic-measured muscle pH and Po2 are sensitive to changes in tissue perfusion during cardiopulmonary bypass.

Non-NASA Center↗

Sabatier Carbon Dioxide Reduction Assembly Development for Closed Loop Water Recovery

The Sabatier Carbon Dioxide Reduction System (CRA) offers water recovery on a long duration space mission to reduce water resupply. Currently, NASA Johnson Space Center (JSC), NASA Marshall Space Flight Center (MSFC), Hamilton Sundstrand Space Systems International, Inc. (HSSSI), and Southwest Research Institute (SWRI) are working together to develop a Sabatier CRA for the International Space Station (ISS). This effort is being funded by the Office of Biological and Physical Research (Code U)/Advanced Life Support program which is administered by NASA JSC. The Sabatier CRA is the next step in closing the oxygen life support loop on future space missions. The Sabatier reaction combines the waste carbon dioxide (recovered from crew metabolism) with waste hydrogen (a byproduct of electrolysis to produce oxygen) to produce water and methane (CH4). On ISS, the methane would be vented overboard, however the methane can be utilized for propulsion during a planetary exploration mission. Based on a crew size of 7-equivalent people, the Sabatier CRA can produce as much a 2000 lb/year water. Use of the Sabatier CRA will significantly reduce the amount of water that needs to be resupplied to the ISS on a yearly basis, at a tremendous cost saving to the program. Additionally, by recycling this additional water, the Sabatier CRA enables additional launch capacity for science experiments to be brought up to the ISS. The NASA/Industry team noted above has been working to reduce technical risks associated with the Sabatier CRA system. To date the technical risks have been considerably reduced, bringing the Technology Readiness Level (TRL) from TRL 4 to TRL 5/6. In doing so, the team has developed the system schematic, system models, control scheme, produced engineering development unit (EDU) hardware, performed limited integration testing of the EDU's and verified system modeling through testing. Additionally, the system schematic has been evaluated for failure modes and hazards and had a successful technical review by the NASA Safety Board. The current focus is now related to development of the water/methane phase separator, liquid sensor and CO2 compressor piston seal life. The overall goal of the current effort is to bring the system up to a TRL6 by the end of GFY04. Although the Sabatier CRA is not currently baselined for use on the ISS, its benefits are significant enough such that volume within the Oxygen Generation System rack has been reserved for future installation. The value of the water the CRA recover will allow NASA the additional crew time and payload needed to pursue its mission of scientific research.

Smith, Frederick↗

Cyclic Adenosine Monophosphate Accumulation and beta-Adrenergic Binding in Unweighted and Denervated Rat Soleus Muscle

Unweighting, but not denervation, of muscle reportedly "spares" insulin receptors, increasing insulin sensitivity. Unweighting also increases beta-adrenergic responses of carbohydrate metabolism. These differential characteristics were studied further by comparing cyclic adenosine monophosphate (cAMP) accumulation and beta-adrenergic binding in normal and 3-day unweighted or denervated soleus muscle. Submaximal amounts of isoproterenol, a p-agonist, increased cAMP accumulation in vitro and in vivo (by intramuscular (IM) injection) to a greater degree (P less than .05) in unweighted muscles. Forskolin or maximal isoproterenol had similar in vitro effects in all muscles, suggesting increased beta-adrenergic sensitivity following unweighting. Increased sensitivity was confirmed by a greater receptor density (B(sub max)) for iodo-125(-)-pindolol in particulate preparations of unweighted (420 x 10(exp -18) mol/mg muscle) than of control or denervated muscles (285 x 10(exp-18) mol/mg muscle). The three dissociation constant (Kd) values were similar (20.3 to 25.8 pmol/L). Total binding capacity (11.4 fmol/muscle) did not change during 3 days of unweighting, but diminished by 30% with denervation. This result illustrates the "sparing" and loss of receptors, respectively, in these two atrophy models. In diabetic animals, IM injection of insulin diminished CAMP accumulation in the presence of theophylline in unweighted muscle (-66% +/- 2%) more than in controls (-42% +'- 6%, P less than .001). These results show that insulin affects CAMP formation in muscle, and support a greater in vivo insulin response following unweighting atrophy. These various data support a role for lysosomal proteolysis in denervation, but not in unweighting, atrophy.

Kirby, Christopher R.↗

Work capacity and metabolic and morphologic characteristics of the human quadriceps muscle in response to unloading

The response of skeletal muscle to unweighting was studied in six healthy males who were subjected to four weeks of lowerlimb suspension. They performed three bouts of 30 consecutive maximal concentric knee extensions, before unloading and the day after (POST 1), 4 days after (POST 2) and 7 weeks after (REC) resumed weight-bearing. Peak torque of each contraction was recorded and work was calculated as the mean of the average peak torque for the three bouts and fatigability was measured as the decline in average peak torque over bouts. Needle biopsies were obtained from m. vastus lateralis of each limb before and at POST 1. Muscle fibre type composition and area, capillarity and the enzyme activities of citrate synthase (CS) and phosphofructokinase (PFK) were subsequently analysed. Mean average peak torque for the three bouts at POST1, POST2 and REC was reduced (P < 0.05) by 17, 13 and 7%, respectively. Fatigability was greater (P < 0.05) at POST2 than before unloading. Type I, IIA and IIB percentage, Type I and II area and capillaries per fibre of Type I and II did not change (P > 0.05) in response to unloading. The activity of CS, but not PFK, decreased (P < 0.05) after unloading. The weight-bearing limb showed no changes in the variables measured. The results of this study suggest that this human lowerlimb suspension model produces substantial impairments of work and oxidative capacity of skeletal muscle. The performance decrements are most likely induced by lack of weight-bearing.

NASA Center KSC↗

Acquisition of a Gas Chromatograph/Mass Spectrometer System for Laboratory Study of Prebiotic Organic Geochemical Processes on the Early Earth, Mars, and Meteorites

This was a major equipment grant that provided funds ($72K) for purchase of a benchtop gas chromatograph-mass spectrometer (GC-MS) for use in experimental studies of prebiotic organic compounds. An Agilent model 689015973 GC-MS was purchased and installed in the PI's lab in August of 2003. The instrument is now being used for a variety of research projects. The primary use of the instrument is to analyze and quantify organic products of laboratory experiments conducted by the PI. One example is shown, which shows organic products (predominantly n-alkanes) formed during Fischer-Tropsch-type abiotic synthesis under hydrothermal conditions. The analytical capabilities of the GC- MS allowed identification of the numerous organic products of this as well as other laboratory experiments. A key use of the instrument in this research is that the mass spectrometer capabilities allow use of isotopically labeled reactants to trace the progress of reactions and evaluate background contaminants. collaborative projects with other scientists involved in exobiology & astrobiology research (e.g., Mitch Schulte, NASA Ames; Katrina Edwards, Woods Hole Oceanographic Institution). For instance, an analysis of membrane lipids of an lithoautotrophic iron-oxidizing bacteria being grown on basalt as a source of metabolic energy, a project where the instrument is being used to evaluate possible biomarker compounds from these organisms is shown. These iron oxidizers are thought to be similar to those living within the ocean crust, and are being investigated as possible analog organisms to those on the early Earth or crust of Mars. The instrument has also been used by an outside investigator (graduate student Brandon Canfeld, Arizona State University) for identification and isotopic characterization of experimental products of abiotic organic synthesis experiments he is conducting with Dr. John Holloway. analysis of quality control samples for other NASA-funded projects. For instance, an analysis of residual hydrocarbon contaminants on the internal surface of the shell of an atmospheric sounding rocket is shown. This analysis was used to help determine the source of the contaminating compounds. In the future, the instrument will continue to be used for quality control analysis in clean rooms and instrument construction facilities within the Laboratory for Atmospheric and Space Physics, where the GC-MS is housed.

McCollom, Thomas↗

The action of a dietary retinoid on gene expression and cancer induction in electron-irradiated rat skin

Current models of radiation carcinogenesis generally assume that the DNA is damaged in a variety of ways by the radiation and that subsequent cell divisions contribute to the conversion of the damage to heritable mutations. Cancer may seem complex and intractable, but its complexity provides multiple opportunities for preventive interventions. Mitotic inhibitors are among the strongest cancer preventive agents, not only slowing the growth rate of preneoplasias but also increasing the fidelity of DNA repair processes. Ionizing radiation, including electrons, is a strong inducer of cancer in rat skin, and dietary retinoids have shown potent cancer preventive activity in the same system. A non-toxic dietary dose of retinyl acetate altered gene expression levels 24 hours after electron irradiation of rat skin. Of the 8740 genes on an Affymetrix rat expression array, the radiation significantly (5 fold or higher) altered 188, while the retinoid altered 231, including 16 radiation-altered genes that were reversely altered. While radiation strongly affected the expression of stress response, immune/inflammation and nucleic acid metabolism genes, the retinoid most strongly affected proliferation-related genes, including some significant reversals, such as, keratin 14, retinol binding protein, and calcium binding proteins. These results point to reversal of proliferation-relevant genes as a likely basis for the anti-radiogenic effects of dietary retinyl acetate.

Non-NASA Center↗

Development of Carbon Dioxide Removal Systems for Advanced Exploration Systems

"NASA's Advanced Exploration Systems (AES) program is pioneering new approaches for rapidly developing prototype systems, demonstrating key capabilities, and validating operational concepts for future human missions beyond Earth orbit" (NASA 2012). These forays beyond the confines of earth's gravity will place unprecedented demands on launch systems. They must not only blast out of earth's gravity well as during the Apollo moon missions, but also launch the supplies needed to sustain a crew over longer periods for exploration missions beyond earth's moon. Thus all spacecraft systems, including those for the separation of metabolic carbon dioxide and water from a crewed vehicle, must be minimized with respect to mass, power, and volume. Emphasis is also placed on system robustness both to minimize replacement parts and ensure crew safety when a quick return to earth is not possible. Current efforts are focused on improving the current state-of-the-art systems utilizing fixed beds of sorbent pellets by seeking more robust pelletized sorbents, evaluating structured sorbents, and examining alternate bed configurations to improve system efficiency and reliability. These development efforts combine testing of sub-scale systems and multi-physics computer simulations to evaluate candidate approaches, select the best performing options, and optimize the configuration of the selected approach, which is then implemented in a full-scale integrated atmosphere revitalization test. This paper describes the carbon dioxide (CO2) removal hardware design and sorbent screening and characterization effort in support of the Atmosphere Resource Recovery and Environmental Monitoring (ARREM) project within the AES program. A companion paper discusses development of atmosphere revitalization models and simulations for this project.

Knox, James C.↗