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At least 235 records · Page 13

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.

Non-NASA Center↗

Control of red blood cell mass during spaceflight

Data are reviewed from twenty-two astronauts from seven space missions in a study of red blood cell mass. The data show that decreased red cell mass in all astronauts exposed to space for more than nine days, although the actual dynamics of mass changes varies with flight duration. Possible mechanisms for these changes, including alterations in erythropoietin levels, are discussed.

STS Shuttle Project↗

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.

NASA Discipline Number 61-10↗

Food and nutrition in space: application to human health

The National Aeronautics and Space Administration begins the new millennium with the hope of expanding human space exploration beyond Earth's orbit. These extended-duration missions (3-5 years) require an in-depth assessment of the critical risks (referred to as "show stoppers") to humans when exposed to the remote environment and reduced gravity conditions for such long periods of time. Food, and the nutrition it provides, is paramount to crew health. For short-duration spaceflight (30 days), the nutrient requirements pertaining to physiological adaptations are likely to be satisfied without significant impact on crew performance or health. However, prolonged exposure to reduced gravity, or microgravity, and isolation may alter human nutrient requirements as well as increase the psychosocial role of food/meals in daily activities. An outline of critical questions and related research needs in the area of food and nutrition has been drafted (1) at NASA JSC with the help of the National Space Biomedical Research Institute (http://www.nsbri.org). The research areas outlined in this plan will directly impact the success of extended-duration human space missions. Findings from this research will have direct applications to human health issues faced here on Earth.

NASA Discipline Regulatory Physiology↗

The molecular response of bone to growth hormone during skeletal unloading: regional differences

Hind limb elevation of the growing rat provides a good model for the skeletal changes that occur during space flight. In this model the bones of the forelimbs (normally loaded) are used as an internal control for the changes that occur in the unloaded bones of the hind limbs. Previous studies have shown that skeletal unloading of the hind limbs results in a transient reduction of bone formation in the tibia and femur, with no change in the humerus. This fall in bone formation is accompanied by a fall in serum osteocalcin (bone Gla protein, BGP) and bone BGP messenger RNA (mRNA) levels, but a rise in bone insulin-like growth factor-I (IGF-I) protein and mRNA levels and resistance to the skeletal growth-promoting actions of IGF-I. To determine whether skeletal unloading also induced resistance to GH, we evaluated the response of the femur and humerus of sham and hypophysectomized rats, control and hind limb elevated, to GH (two doses), measuring mRNA levels of IGF-I, BGP, rat bone alkaline phosphatase (RAP), and alpha 1(1)-procollagen (coll). Hypophysectomy (HPX) decreased the mRNA levels of IGF-I, BGP, and coll in the femur, but was either less effective or had the opposite effect in the humerus. GH at the higher dose (500 micrograms/day) restored these mRNA levels to or above the sham control values in the femur, but generally had little or no effect on the humerus. RAP mRNA levels were increased by HPX, especially in the femur. The lower dose of GH (50 micrograms/day) inhibited this rise in RAP, whereas the higher dose raised the mRNA levels and resulted in the appearance of additional transcripts not seen in controls. As for the other mRNAs, RAP mRNA in the humerus was less affected by HPX or GH than that in the femur. Hind limb elevation led to an increase in IGF-I, coll, and RAP mRNAs and a reduction in BGP mRNA in the femur and either had no effect or potentiated the response of these mRNAs to GH. We conclude that GH stimulates a number of markers of bone formation by raising their mRNA levels, and that skeletal unloading does not block this response, but the response varies substantially from bone to bone.

Non-NASA Center↗

Immune responses in humans after 60 days of confinement

A confinement experiment in a normobaric diving chamber was undertaken to better understand the effect of confinement and isolation on human psychology and physiology. Pre- and postconfinement blood samples were obtained from four test subjects and control donors to analyze immune responses. No modification in the levels of CD2+, CD3+, CD4+, CD8+, CD19+, and CD56+ cells was observed after confinement. Mitogen-induced T-lymphocyte proliferation and interleukin-2 receptor expression were not altered significantly. Whole blood interferon-alpha and gamma-induction and plasma cortisol levels were also unchanged, as was natural killer cell activity. These data suggest that in humans, no specific components of the immune response are affected by a 2-month isolation and confinement of a small group.

NASA Discipline Number 18-10↗

Considerations in miniaturizing simplified agro-ecosystems for advanced life support

Miniaturizing the Earth's biogeochemical cycles to support human life during future space missions is the goal of the NASA research and engineering program in advanced life support. Mission requirements to reduce mass, volume, and power have focused efforts on (1) a maximally simplified agro-ecosystem of humans, food crops, and microbes; and, (2) a design for optimized productivity of food crops with high light levels over long days, with hydroponics, with elevated carbon dioxide and other controlled environmental factors, as well as with genetic selection for desirable crop properties. Mathematical modeling contributes to the goals by establishing trade-offs, by analyzing the growth and development of experimental crops, and by pointing to the possibilities of directed phasic control using modified field crop models to increase the harvest index.

Non-NASA Center↗

Postural tachycardia syndrome: time frequency mapping

Orthostatic tachycardia is common but its specificity remains uncertain. Our preliminary work suggested that using autonomic function testing in conjunction with time-frequency mapping (TFM), it might be possible to characterize a subset of the postural tachycardia syndrome (POTS), that is due to a restricted autonomic neuropathy. We describe 20 patients (17 women and 3 men, aged 14-43 years) with florid POTS and 20 controls (14 women and 6 men, aged 20-41 years). Autonomic failure was quantified by its distribution (cardiovagal, adrenergic and sudomotor) and severity, a symptom profile was generated, and spectral indices, based on modified Wigner distribution during rest and head-up tilt (80 degrees) were evaluated. During tilt-up POTS patients differed from controls by an excessive heart rate (> 130 bpm) (P < 0.001), and higher diastolic pressure (P < 0.01). During rest, cardiovagal oscillations (at respiratory frequencies [RF]) and slow rhythms at nonrespiratory frequencies (NONRF) (from 0.01 to 0.07 Hz) in R-R intervals (RRI) (P < 0.01) were reduced. Both RF and NONRF rhythms in RRI were further blunted with tilt-up (P < 0.001). Slow adrenergic vasomotor rhythms in blood pressure (BP) (approximately 0.07 Hz) surged with tilt-up and returned to normal levels afterwards. The index of sympatho-vagal balance (NONRF-Systolic BP (SBP)/RF-RRI) was dramatically increased in POTS (P < 0.001). Distal postganglionic sudomotor failure was observed, and impairment of the BP responses to the Valsalva maneuver (phase II) suggested peripheral adrenergic dysfunction. Persistent orthostatic dizziness, tiredness, gastrointestinal symptoms and palpitations were common in POTS patients. It is possible to identify a subset of POTS patients who have a length-dependent autonomic neuropathy, affecting the peripheral adrenergic and cardiovagal fibers, with relative preservation of cardiac adrenergic fibers.

NASA Discipline Number 14-10↗

Cytogenetic effects of space radiation in lymphocytes of MIR-18 crews

For assessing health risk, the measurement of physical dose received during a space mission, as well as the LETs, energies and charges of particles is important. It is also important to obtain quantitative information regarding the effectiveness of space radiation in causing damage to critical biological targets, e.g., chromosomes, since at present the estimated uncertainty of biological effects of space radiation is more than a factor of two. Such large uncertainty makes accurate health risk assessment very difficult. For this very reason, a study on cytogenetic effects of space radiation in human lymphocytes was proposed and done for MIR-18 mission. This study used FISH technique to score chromosomal translocations and C-banding method to determine dicentrics. Growth kinetics of cells and SCE were examined to ensure that chromosomal aberrations were scored in first mitosis and were induced not by chemical mutagens. Our results showed that chromosomal aberration frequency of post-flight samples was significantly higher than that of pre-flight ones and that SCE frequency was similar between pre- and post-flight samples. Based on a dose-response curve of preflight samples exposed to gamma rays, the absorbed dose received by crews during the mission was estimated to be about 14.5 cSv. Because the absorbed dose measured by physical dosimeters is 4.16 cGy for the entire mission, the RBE is about 3.5.

Mir Project↗

Using Virtual Reality and Motion Capture as tools for Human Factors Engineering at NASA Marshall Space Flight Center

NASA Marshall Space Flight Center (MSFC) Human Factors Engineering (HFE) Team is implementing virtual reality (VR) and motion capture (MoCap) into HFE analyses of various projects through its Virtual Environments Lab (VEL). VR allows for multiple analyses early in the design process and more opportunities to give design feedback. This tool can be used by engineers in most disciplines to compare design alternatives and is particularly valuable to HFE to give early input during these evaluations. These techniques are being implemented for concept development of Deep Space Habitats (DSH), and work is being done to implement VR for design aspects of the Space Launch System (SLS). VR utilization in the VEL will push the design to be better formulated before mockups are constructed, saving budget and time. The MSFC VEL will continue forward leaning implementation with VR technologies in these and other projects for better models earlier in the design process.

Andrews, Tanya↗

Thermoregulation and heat exchange in a nonuniform thermal environment during simulated extended EVA. Extravehicular activities

BACKGROUND: Nonuniform heating and cooling of the body, a possibility during extended duration extravehicular activities (EVA), was studied by means of a specially designed water circulating garment that independently heated or cooled the right and left sides of the body. The purpose was to assess whether there was a generalized reaction on the finger in extreme contradictory temperatures on the body surface, as a potential heat status controller. METHOD: Eight subjects, six men and two women, were studied while wearing a sagittally divided experimental garment with hands exposed in the following conditions: Stage 1 baseline--total body garment inlet water temperature at 33 degrees C; Stage 2--left side inlet water temperature heated to 45 degrees C; right side cooled to 8 degrees C; Stage 3--left side inlet water temperature cooled to 8 degrees C, right side heated to 45 degrees C. RESULTS: Temperatures on each side of the body surface as well as ear canal temperature (Tec) showed statistically significant Stage x Side interactions, demonstrating responsiveness to the thermal manipulations. Right and left finger temperatures (Tfing) were not significantly different across stages; their dynamic across time was similar. Rectal temperature (Tre) was not reactive to prevailing cold on the body surface, and therefore not informative. Subjective perception of heat and cold on the left and right sides of the body was consistent with actual temperature manipulations. CONCLUSIONS: Tec and Tre estimates of internal temperature do not provide accurate data for evaluating overall thermal status in nonuniform thermal conditions on the body surface. The use of Tfing has significant potential in providing more accurate information on thermal status and as a feedback method for more precise thermal regulation of the astronaut within the EVA space suit.

Non-NASA Center↗

Human life support for advanced space exploration

The requirements for a human life support system for long-duration space missions are reviewed. The system design of a controlled ecological life support system is briefly described, followed by a more detailed account of the study of the conceptual design of a Lunar Based CELSS. The latter is to provide a safe, reliable, recycling lunar base life support system based on a hybrid physicochemical/biological representative technology. The most important conclusion reached by this study is that implementation of a completely recycling CELSS approach for a lunar base is not only feasible, but eminently practical. On a cumulative launch mass basis, a 4-person Lunar Base CELSS would pay for itself in approximately 2.6 years relative to a physicochemical air/water recycling system with resupply of food from the Earth. For crew sizes of 30 and 100, the breakeven point would come even sooner, after 2.1 and 1.7 years, respectively, due to the increased mass savings that can be realized with the larger plant growth units. Two other conclusions are particularly important with regard to the orientation of future research and technology development. First, the mass estimates of the Lunar Base CELSS indicate that a primary design objective in implementing this kind of system must be to minimized the mass and power requirement of the food production plant growth units, which greatly surpass those of the other air and water recycling systems. Consequently, substantial research must be directed at identifying ways to produce food more efficiently. On the other hand, detailed studies to identify the best technology options for the other subsystems should not be expected to produce dramatic reductions in either mass or power requirement of a Lunar Base CELSS. The most crucial evaluation criterion must, therefore, be the capability for functional integration of these technologies into the ultimate design of the system. Secondly, this study illustrates that existing or near-term technologies are adequate to implement a Lunar Base CELSS. There are no apparent "show-stoppers" which require the development of new technologies. However, there are several areas in which new materials and technologies could be used for a more efficient implementation of the system, e.g., by decreasing mass or power requirement and increasing recycling efficiency. These areas must be further addressed through research and development. Finally, although this study focused on the development of a Lunar Base CELSS, the same technologies and a nearly identical design would be appropriate for a Mars base. Actually, except for the distance of transportation, the implementation of a CELSS on Mars would even be easier than it would be on the Moon. The presence of atmospheric CO2 on Mars, although in low concentration, coupled with the fact that the day/night cycle on Mars is very similar to that on Earth, makes the use of light-weight, greenhouse-like structures for growing food plants even more feasible than on the Moon. There are some environmental problems, which would have to be dealt with, like dust storms and the large amount of the ultraviolet radiation incident on the planet's surface. However, the materials and methods are largely available today to develop such a life support system for a Mars base.

Review, Tutorial↗

Application of high-performance computing to numerical simulation of human movement

We have examined the feasibility of using massively-parallel and vector-processing supercomputers to solve large-scale optimization problems for human movement. Specifically, we compared the computational expense of determining the optimal controls for the single support phase of gait using a conventional serial machine (SGI Iris 4D25), a MIMD parallel machine (Intel iPSC/860), and a parallel-vector-processing machine (Cray Y-MP 8/864). With the human body modeled as a 14 degree-of-freedom linkage actuated by 46 musculotendinous units, computation of the optimal controls for gait could take up to 3 months of CPU time on the Iris. Both the Cray and the Intel are able to reduce this time to practical levels. The optimal solution for gait can be found with about 77 hours of CPU on the Cray and with about 88 hours of CPU on the Intel. Although the overall speeds of the Cray and the Intel were found to be similar, the unique capabilities of each machine are better suited to different portions of the computational algorithm used. The Intel was best suited to computing the derivatives of the performance criterion and the constraints whereas the Cray was best suited to parameter optimization of the controls. These results suggest that the ideal computer architecture for solving very large-scale optimal control problems is a hybrid system in which a vector-processing machine is integrated into the communication network of a MIMD parallel machine.

NASA Discipline Musculoskeletal↗

Uncertainties in estimates of the risks of late effects from space radiation

Methods used to project risks in low-Earth orbit are of questionable merit for exploration missions because of the limited radiobiology data and knowledge of galactic cosmic ray (GCR) heavy ions, which causes estimates of the risk of late effects to be highly uncertain. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. Using the linear-additivity model for radiation risks, we use Monte-Carlo sampling from subjective uncertainty distributions in each factor to obtain an estimate of the overall uncertainty in risk projections. The resulting methodology is applied to several human space exploration mission scenarios including a deep space outpost and Mars missions of duration of 360, 660, and 1000 days. The major results are the quantification of the uncertainties in current risk estimates, the identification of factors that dominate risk projection uncertainties, and the development of a method to quantify candidate approaches to reduce uncertainties or mitigate risks. The large uncertainties in GCR risk projections lead to probability distributions of risk that mask any potential risk reduction using the "optimization" of shielding materials or configurations. In contrast, the design of shielding optimization approaches for solar particle events and trapped protons can be made at this time and promising technologies can be shown to have merit using our approach. The methods used also make it possible to express risk management objectives in terms of quantitative metrics, e.g., the number of days in space without exceeding a given risk level within well-defined confidence limits. Published by Elsevier Ltd on behalf of COSPAR.

Non-NASA Center↗

Postspaceflight orthostatic hypotension occurs mostly in women and is predicted by low vascular resistance

About 20% of astronauts suffer postspaceflight presyncope. We studied pre- to postflight (5- to 16-day missions) cardiovascular responses to standing in 35 astronauts to determine differences between 1) men and women and 2) presyncopal and nonpresyncopal groups. The groups were presyncopal women, presyncopal men, and nonpresyncopal men based on their ability to stand for 10 min postflight. Preflight, women and presyncopal men had low vascular resistance, with the women having the lowest. Postflight, women experienced higher rates of presyncope (100 vs. 20%; P = 0.001) and greater losses of plasma volume (20 vs. 7%; P < 0.05) than men. Also, presyncopal subjects had lower standing mean arterial pressure (P < or = 0.001) and vascular resistance (P < 0.05), smaller increases in norepinephrine (P < or = 0.058) and greater increases in epinephrine (P < or = 0.058) than nonpresyncopal subjects. Presyncopal subjects had a strong dependence on plasma volume to maintain standing stroke volume. These findings suggest that postflight presyncope is greatest in women, and this can be ascribed to a combination of inherently low-resistance responses, a strong dependence on volume status, and relative hypoadrenergic responses. Conversely, high vascular resistance and postflight hyperadrenergic responses prevent presyncope.

Flight Experiment↗

Peripheral leukocyte subpopulations and catecholamine levels in astronauts as a function of mission duration

OBJECTIVE: The objective of this study was to determine the effects of spaceflight duration on immune cells and their relationship to catecholamine levels. METHODS: Eleven astronauts who flew aboard five different US Space Shuttle flights ranging in duration from 4 to 16 days were studied before launch and after landing. RESULTS: Consistent with prior studies, spaceflight was associated with a significant increase in the number of circulating white blood cells (p <.01), including neutrophils (p <.01), monocytes (p <.05), CD3+CD4+ T-helper cells (p <.05), and CD19+ B cells (p <.01). In contrast, the number of CD3-CD16+56+ natural killer cells was decreased (p <.01). Plasma norepinephrine levels were increased at landing (p <.01) and were significantly correlated with the number of white blood cells (p <.01), neutrophils (p <.01), monocytes (p <.01), and B cells (p <.01). Astronauts who were in space for approximately 1 week showed a significantly larger increase on landing in plasma norepinephrine (p =.02) and epinephrine (p =.03) levels, as well as number of circulating CD3+CD4+ T-helper cells (p <.05) and CD3+CD8+ T-cytotoxic cells (p <.05) as compared with astronauts in space for approximately 2 weeks. CONCLUSIONS: The data suggest that the stress of spaceflight and landing may lead to a sympathetic nervous system-mediated redistribution of circulating leukocytes, an effect potentially attenuated after longer missions.

Flight Experiment↗

Sleep, performance, circadian rhythms, and light-dark cycles during two space shuttle flights

Sleep, circadian rhythm, and neurobehavioral performance measures were obtained in five astronauts before, during, and after 16-day or 10-day space missions. In space, scheduled rest-activity cycles were 20-35 min shorter than 24 h. Light-dark cycles were highly variable on the flight deck, and daytime illuminances in other compartments of the spacecraft were very low (5.0-79.4 lx). In space, the amplitude of the body temperature rhythm was reduced and the circadian rhythm of urinary cortisol appeared misaligned relative to the imposed non-24-h sleep-wake schedule. Neurobehavioral performance decrements were observed. Sleep duration, assessed by questionnaires and actigraphy, was only approximately 6.5 h/day. Subjective sleep quality diminished. Polysomnography revealed more wakefulness and less slow-wave sleep during the final third of sleep episodes. Administration of melatonin (0.3 mg) on alternate nights did not improve sleep. After return to earth, rapid eye movement (REM) sleep was markedly increased. Crewmembers on these flights experienced circadian rhythm disturbances, sleep loss, decrements in neurobehavioral performance, and postflight changes in REM sleep.

Non-NASA Center↗

Evaluation of muscle injury using magnetic resonance imaging

The objective of this study was to investigate spin echo T2 relaxation time changes in thigh muscles after intense eccentric exercise in healthy men. Spin echo and calculated T2 relaxation time images of the thighs were obtained on several occasions after exercise of one limb; the contralateral limb served as control. Muscle damage was verified by elevated levels of serum creatine kinase (CK). Thirty percent of the time no exercise effect was discernible on the magnetic resonance (MR) images. In all positive MR images (70%) the semitendinosus muscle was positive, while the biceps femoris, short head, and gracilis muscles were also positive in 50% and 25% of the total cases, respectively. The peak T2 relaxation time and serum CK were correlated (r = 0.94, p<0.01); temporal changes in muscle T2 relaxation time and serum CK were similar, although T2 relaxation time remained positive after serum CK returned to background levels. We conclude that magnetic resonance imaging can serve as a useful tool in the evaluation of eccentric exercise muscle damage by providing a quantitative indicator of damage and its resolution as well as the specific areas and muscles.

NASA Discipline Number 26-10↗