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Effects of Command and Control Vehicle (C2V) operational environment on soldier health and performance.

The purpose of this project was to use NASA technology to assist the US Army in the assessment of motion sickness incidences and effects on soldier performance and mood states within the Command and Control Vehicle (C2V). Specific objectives were (1) to determine if there was a significant difference between three internal configurations of the C2V and/or between seats within these vehicles; (2) to determine if there was a significant difference between the park, move, or short-halt field conditions; and (3) to validate a method of converging indicators developed by NASA to assess environmental impact of long duration spaceflight on crewmembers, using a large sample of subjects under ground-based operational conditions.

Adolescent↗

Regulatory coding of lymphoid lineage choice by hematopoietic transcription factors.

During lymphopoiesis, precursor cells negotiate a complex regulatory space, defined by the levels of several competing and cross-regulating transcription factors, before arriving at stable states of commitment to the B-, T- and NK-specific developmental programs. Recent perturbation experiments provide evidence that this space has three major axes, corresponding to the PU.1 versus GATA-1 balance, the intensity of Notch signaling through the CSL pathway, and the ratio of E-box transcription factors to their Id protein antagonists.

Animals↗

Is skeletal muscle ready for long-term spaceflight and return to gravity?

It is now clear that prevention of muscle debilitation during spaceflight will require a broader approach than simple exercise aimed at strengthening of the muscle fibers. The levels of several hormones and receptors are altered by unloading and must be returned to homeostasis. Pharmacotherapy and gene transfer strategies to raise the relative level of structural proteins may minimize the problems faced by astronauts in readapting to Earth-gravity. Up to now, we have only minimally exploited microgravity for advancing our understanding of muscle biology. A research laboratory in the space station with a centrifuge facility (gravity control) is essential for conducting basic research in this field. Microgravity has proven an excellent tool for noninvasively perturbing the synthesis of muscle proteins in the search for molecular signals and gene regulatory factors influencing differentiation, growth, maintenance and atrophy of muscle. Understanding the relation between blood flow and interstitial edema and between workload and subsequent structural failure are but two important problems that require serious attention. The roles of hormones and growth factors in regulating gene expression and their microgravity-induced altered production are other urgent issues to pursue. These types of studies will yield information that advances basic knowledge of muscle biology and offers insights into countermeasure design. This knowledge is likely to assist rehabilitation of diseased or injured muscles in humans on Earth, especially individuals in the more vulnerable aging population and persons participating in strenuous sports. Will the skeletal muscle system be prepared for the increased exposure to microgravity and the return to gravity loading without injury when space station is operational? The answer depends in large part on continued access to space and funding of ground-based models and flight experiments. The previous two decades of spaceflight research have described the effects of microgravity on multiple systems. The next generation of experiments promises to be even more exciting as we are challenged to define the cellular and molecular mechanisms of microgravity-induced changes.

Animals↗

Life sciences issues affecting space exploration.

The U.S. space program is undertaking a serious examination of new initiatives in human space exploration involving permanent colonies on the Moon and an outpost on Mars. Life scientists have major responsibilities to the crew, to assure their health, productivity, and safety throughout the mission and the postflight rehabilitation period; to the mission, to provide a productive working environment; and to the scientific community, to advance knowledge and understanding of human adaptation to the space environment. Critical areas essential to the support of human exploration include protection from the radiation hazards of the space environment, reduced gravity countermeasures, artificial gravity, medical care, life support systems, and behavior, performance, and human factors in an extraterrestrial environment. Developing solutions to these concerns is at the heart of the NASA Life Sciences ground-based and flight research programs. Facilities analogous to planetary outposts are being considered in Antarctica and other remote settings. Closed ecological life support systems will be tested on Earth and Space Station. For short-duration simulations and tests, the Space Shuttle and Spacelab will be used. Space Station Freedom will provide the essential scientific and technological research in areas that require long exposures to reduced gravity conditions. In preparation for Mars missions, research on the Moon will be vital. As the challenges of sustaining humans on space are resolved, advances in fundamental science, medicine and technology will follow.

Adaptation, Physiological↗

FRamework Assessing Notorious Contributing Influences for Error (FRANCIE).

FRamework Assessing Notorious Contributing Influences for Error (FRANCIE) is a framework and methodology for the systematic analysis, characterization, and prediction of human error. It was developed in a NASA Advanced Concepts Project by Idaho National Engineering and Environmental Laboratory, NASA Ames Research Center, Boeing, and America West Airlines, with input from United Airlines and Idaho State University. It was hypothesized that development of a comprehensive taxonomy of error-type and contributing-influences, in a framework and methodology addressing issues important for error analysis, would result in a useful tool for human error analysis. The development method included capturing expertise of human factors and domain experts in the framework, and ensuring that the approach addressed issues important for future human error analysis. This development resulted in creation of a FRANCIE taxonomy for airline maintenance, and a FRANCIE framework and approach that addresses important issues: proactive and reactive, comprehensive error-type and contributing-influences taxonomy, meaningful error reduction strategies, multilevel analyses, multiple user types, compatible with existing methods, applied in design phase or throughout system life cycle, capture of lessons learned, and ease of application. FRANCIE was designed to apply to any domain, given taxonomy refinement. This is demonstrated by its application for an aviation operations scenario for a new precision landing aid. Representative error-types and contributing-influences, two example analyses, and a case study are presented. In conclusion, FRANCIE is useful for analysis of human error, and the taxonomy is a starting point for development of taxonomies allowing application to other domains, such as spacecraft maintenance, operations, medicine, process control, and other transportation industries.

Aerospace Medicine↗

Cultural factors and the International Space Station.

The American and Russian/Soviet space programs independently uncovered psychosocial risks inherent in long-duration space missions. Now that these two countries are working together on the International Space Station (ISS), American-Russian cultural differences pose an additional set of risk factors. These may echo cultural differences that have been observed in the general population of the two countries and in space analogue settings, but little is known about how relevant these are to the select population of space program personnel. The evidence for the existence of mission-relevant cultural differences is reviewed and includes cultural values, emotional expressivity, personal space norms, and personality characteristics. The review is focused primarily on Russia and the United States, but also includes other ISS partner countries. Cultural differences among space program personnel may have a wide range of effects. Moreover, culture-related strains may increase the probability of distress and impairment. Such factors could affect the individual and interpersonal functioning of both crewmembers and mission control personnel, whose performance is also critical for mission safety and success. Examples from the anecdotal and empirical literature are given to illustrate these points. The use of existing assessment strategies runs the risk of overlooking important early warning signs of behavioral health difficulties. By paying more attention to cultural differences and how they might be manifested, we are more likely to detect problems early while they are still mild and resolvable.

Astronauts↗

Fluid flow releases fibroblast growth factor-2 from human aortic smooth muscle cells.

This study tested the hypothesis that fluid shear stress regulates the release of fibroblast growth factor (FGF)-2 from human aortic smooth muscle cells. FGF-2 is a potent mitogen that is involved in the response to vascular injury and is expressed in a wide variety of cell types. FGF-2 is found in the cytoplasm of cells and outside cells, where it associates with extracellular proteoglycans. To test the hypothesis that shear stress regulates FGF-2 release, cells were exposed to flow, and FGF-2 amounts were measured from the conditioned medium, pericellular fraction (extracted by heparin treatment), and cell lysate. Results from the present study show that after 15 minutes of shear stress at 25 dyne/cm(2) in a parallel-plate flow system, a small but significant fraction (17%) of the total FGF-2 was released from human aortic smooth muscle cells. FGF-2 levels in the circulating medium increased 10-fold over medium from static controls (P<0.01). A 50% increase in FGF-2 content versus control (P<0.01) was found in the pericellular fraction (extracted by heparin treatment). Furthermore, a significant decrease in FGF-2 was detected in the cell lysate, indicating that FGF-2 was released from inside the cell. Cell permeability studies with fluorescent dextran were performed to examine whether transient membrane disruption caused FGF-2 release. Flow cytometry detected a 50% increase in mean fluorescence of cells exposed to 25 dyne/cm(2) versus control cells. This indicates that the observed FGF-2 release from human aortic smooth muscle cells is likely due to transient membrane disruption on initiation of flow.

Aorta↗

Changes in compensatory eye movements associated with simulated stimulus conditions of spaceflight.

Compensatory vertical eye movement gain (CVEMG) was recorded during pitch oscillation in darkness before, during and immediately after exposures to the stimulus rearrangement produced by the Preflight Adaptation Trainer (PAT) Tilt-Translation Device (TTD). The TTD is designed to elicit adaptive responses that are similar to those observed in microgravity-adapted astronauts. The data from Experiment 1 yielded a statistically significant CVEMG decrease following 15 min of exposure to a stimulus rearrangement condition where the phase angle between subject pitch tilt and visual scene translation was 270 degrees; statistically significant gain decreases were not observed following exposures either to a condition where the phase angle between subject pitch and scene translation was 90 degrees or to a no-stimulus-rearrangement condition. Experiment 2 replicated the 270 degrees-phase condition from Experiment 1 and extended the exposure duration from 30 to 45 min. Statistically significant additional changes in CVEMG associated with the increased exposure duration were not observed. The adaptation time constant estimated from the combined data from Experiments 1 and 2 was 29 min.

Adaptation, Physiological↗

Changes in the immune system during and after spaceflight.

The results of immunological analyses before, during and after spaceflight, have established the fact that spaceflight can result in a blunting of the immune mechanisms of human crew members and animal test species. There is some evidence that the immune function changes in short-term flights resemble those occurring after acute stress, while the changes during long-term flights resemble those caused by chronic stress. In addition, this blunting of the immune function occurs concomitant with a relative increase in potentially infectious microorganisms in the space cabin environment. This combination of events results in an increased probability of inflight infectious events. The realization of this probability has been shown to be partially negated by the judicious use of a preflight health stabilization program and other operational countermeasures. The continuation of these countermeasures, as well as microbial and immunological monitoring, are recommended for continued spaceflight safety.

Acute Disease↗

Immune changes during short-duration missions.

Spaceflight materially influences the immune mechanism of humans and animals. Effects resulting from missions of less than 1 month are examined. Effects from longer missions are discussed in the companion paper by Konstantinova et al. Most immunology studies have involved analyses of subjects and samples from subjects obtained after flight, with the data being compared with similar data obtained before flight. These studies have demonstrated that short-duration missions can result in a postflight depression in blast cell transformation, major changes in cytokine function, and alterations in the relative numbers of immune cell populations. In addition to these post- vs. preflight studies, some data have been produced in flight. However, these in vitro analyses have been less than satisfactory because of differences between in-flight and ground-control conditions. Recently, both the U.S. and Russian space programs have started collecting in-flight, in vivo, cell-mediated immunity data. These studies have confirmed that the human cell-mediated immune system is blunted during spaceflight.

Humans↗

The future of irradiation applications on Earth and in space.

What needs to be done to establish food irradiation on a truly commercial basis so that those living on planet Earth can fully realize the benefits of this versatile process? This question is answered in the first part of this paper. The second part covers the potential contributions of irradiated foods to feed humans in space.

Earth, Planet↗

The clinical chemistry and immunology of long-duration space missions.

Clinical laboratory diagnostic capabilities are needed to guide health and medical care of astronauts during long-duration space missions. Clinical laboratory diagnostics, as defined for medical care on Earth, offers a model for space capabilities. Interpretation of laboratory results for health and medical care of humans in space requires knowledge of specific physiological adaptations that occur, primarily because of the absence of gravity, and how these adaptations affect reference values. Limited data from American and Russian missions have indicated shifts of intra- and extracellular fluids and electrolytes, changes in hormone concentrations related to fluid shifts and stresses of the missions, reductions in bone and muscle mass, and a blunting of the cellular immune response. These changes could increase susceptibility to space-related illness or injury during a mission and after return to Earth. We review physiological adaptations and the risk of medical problems that occur during space missions. We describe the need for laboratory diagnostics as a part of health and medical care in space, and how this capability might be delivered.

Aerospace Medicine↗

Applications of telemedicine in the United States space program.

Since the beginning of human space flight, NASA has been placing humans in extreme and remote environments. There are many challenges in maintaining humans in outer space, including the provision of life-support systems, radiation shielding, and countermeasures for minimizing the effect of microgravity. Because astronauts are selected for their health, among other factors, disease and illness are minimized. However, it is still of great importance to have appropriate medical care systems in place to address illness and injury should they occur. With the exception of the Apollo program, exploration of space has been limited to missions that are within several hundred miles of the surface of the Earth. At the drawn of the 21st century and the new millennium, human exploration will be focused on operation of the International Space Station (ISS) and preparation for human missions to Mars. These missions will present inherent risks to human health, and, therefore, appropriate plans must be established to address these challenges and risks. Crews of long-duration missions must become more independent from ground controllers. New systems, protocols, and procedures are currently being perfected. Application of emerging technologies in information systems and telecommunications will be critical to inflight medical care. Application of these technologies through telemedicine will provide crew members access to information, noninvasive procedures for assessing health status, and guidance through the integration of sensors, holography, decision-support systems, and virtual environments. These technologies will also serve as a basis to enhance training and medical education. The design of medical care for space flight should lead to a redesign of the practice of medicine on Earth.

Computer Communication Networks↗

The effects of spaceflight on open-loop and closed-loop postural control mechanisms: human neurovestibular studies on SLS-2.

Stabilogram-diffusion analysis was used to examine how prolonged periods in microgravity affect the open-loop and closed-loop postural control mechanisms. It was hypothesized that following spaceflight: (1) the effective stochastic activity of the open-loop postural control schemes in astronauts is increased; (2) the effective stochastic activity and uncorrelated behavior, respectively, of the closed-loop postural control mechanisms in astronauts are increased; and (3) astronauts utilized open-loop postural controls schemes for shorter time intervals and smaller displacements. Four crew members and two alternates from the 14-day Spacelab Life Sciences 2 Mission were included in the study. Each subject was tested under eyes-open, quiet-standing conditions on multiple preflight and postflight days. The subjects' center-of-pressure trajectories were measured with a force platform and analyzed according to stabilogram-diffusion analysis. It was found that the effective stochastic activity of the open-loop postural control schemes in three of the four crew members was increased following spaceflight. This result is interpreted as an indication that there may be in-flight adaptations to higher-level descending postural control pathways, e.g., a postflight increase in the tonic activation of postural muscles. This change may also be the consequence of a compensatory (e.g., "stiffening") postural control strategy that is adopted by astronauts to account for general feeling of postflight unsteadiness. The crew members, as a group, did not exhibit any consistent preflight/postflight differences in the steady-state behavior of their closed-loop postural control mechanisms or in the functional interaction of their open-loop and closed-loop postural control mechanisms. These results are interpreted as indications that although there may be in-flight adaptations to the vestibular system and/or proprioceptive system, input from the visual system can compensate for such changes during undisturbed stance.

Humans↗

Migration of lymphocytes on fibronectin-coated surfaces: temporal evolution of migratory parameters.

Lymphocytes typically interact with implanted biomaterials through adsorbed exogenous proteins. To provide a more complete characterization of these interactions, analysis of lymphocyte migration on adsorbed extracellular matrix proteins must accompany the commonly performed adhesion studies. We report here a comparison of the migratory and adhesion behavior of Jurkat cells (a T lymphoblastoid cell line) on tissue culture treated and untreated polystyrene surfaces coated with various concentrations of fibronectin. The average speed of cell locomotion showed a biphasic response to substrate adhesiveness for cells migrating on untreated polystyrene and a monotonic decrease for cells migrating on tissue culture-treated polystyrene. A modified approach to the persistent random walk model was implemented to determine the time dependence of cell migration parameters. The random motility coefficient showed significant increases with time when cells migrated on tissue culture-treated polystyrene surfaces, while it remained relatively constant for experiments with untreated polystyrene plates. Finally, a cell migration computer model was developed to verify our modified persistent random walk analysis. Simulation results suggest that our experimental data were consistent with temporally increasing random motility coefficients.

Adsorption↗

The evolution of transcriptional regulation in eukaryotes.

Gene expression is central to the genotype-phenotype relationship in all organisms, and it is an important component of the genetic basis for evolutionary change in diverse aspects of phenotype. However, the evolution of transcriptional regulation remains understudied and poorly understood. Here we review the evolutionary dynamics of promoter, or cis-regulatory, sequences and the evolutionary mechanisms that shape them. Existing evidence indicates that populations harbor extensive genetic variation in promoter sequences, that a substantial fraction of this variation has consequences for both biochemical and organismal phenotype, and that some of this functional variation is sorted by selection. As with protein-coding sequences, rates and patterns of promoter sequence evolution differ considerably among loci and among clades for reasons that are not well understood. Studying the evolution of transcriptional regulation poses empirical and conceptual challenges beyond those typically encountered in analyses of coding sequence evolution: promoter organization is much less regular than that of coding sequences, and sequences required for the transcription of each locus reside at multiple other loci in the genome. Because of the strong context-dependence of transcriptional regulation, sequence inspection alone provides limited information about promoter function. Understanding the functional consequences of sequence differences among promoters generally requires biochemical and in vivo functional assays. Despite these challenges, important insights have already been gained into the evolution of transcriptional regulation, and the pace of discovery is accelerating.

Animals↗

Phylogenetic relationships of the Fox (Forkhead) gene family in the Bilateria.

The Forkhead or Fox gene family encodes putative transcription factors. There are at least four Fox genes in yeast, 16 in Drosophila melanogaster (Dm) and 42 in humans. Recently, vertebrate Fox genes have been classified into 17 groups named FoxA to FoxQ. Here, we extend this analysis to invertebrates, using available sequences from D. melanogaster, Anopheles gambiae (Ag), Caenorhabditis elegans (Ce), the sea squirt Ciona intestinalis (Ci) and amphioxus Branchiostoma floridae (Bf), from which we also cloned several Fox genes. Phylogenetic analyses lend support to the previous overall subclassification of vertebrate genes, but suggest that four subclasses (FoxJ, L, N and Q) could be further subdivided to reflect their relationships to invertebrate genes. We were unable to identify orthologs of Fox subclasses E, H, I, J, M and Q1 in D. melanogaster, A. gambiae or C. elegans, suggesting either considerable loss in ecdysozoans or the evolution of these subclasses in the deuterostome lineage. Our analyses suggest that the common ancestor of protostomes and deuterostomes had a minimum complement of 14 Fox genes.

Animals↗

The role of bioregenerative life-support systems in a manned future in space.

Thus far in the manned space program, human life support has depended on storage of air, water, food, and energy. There are no refrigerators on Shuttle, and fresh foods are limited to what can be stowed in lockers for the first 3 days of a mission, when spoilage becomes a factor. Oxygen is stored, CO2 is scrubbed, and water is stored and treated. As we approach the Space Station era, life support will be a combination of storage and resupply. Duty cycles will be 90 days, and physico-chemical (P/C) systems will be important for recycling oxygen and water. Nutritionists seek a capability for refrigerated storage of fresh food on Station. However, most food still will be thermostabilized, rehydratables that can be stored at room temperature. Present Shuttle food is not much more sophisticated than repackaged camp food, and tends to be high in salt content. Hopefully, menus will be healthier on Station, where dietary countermeasures against biomedical responses to chronic microgravity might be implemented, and certainly need to be studied.

Biomass↗