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Genetic models in applied physiology: selected contribution: effects of spaceflight on immunity in the C57BL/6 mouse. I. Immune population distributions

There are several aspects of the spaceflight environment that may lead to changes in immunity: mission-related psychological stress, radiation, and changes in gravity. On December 5, 2001, the space shuttle Endeavor launched for a 12-day mission to examine these effects on C57BL/6 mice for the first time. On their return, assays were performed on the spleen, blood, and bone marrow. In response to flight, there were no significant differences in the general circulating leukocyte proportions. In contrast, there was an increase in splenic lymphocyte percentages, with a corresponding decrease in granulocytes. There was an overall shift in splenic lymphocytes away from T cells toward B cells, and a decrease in the CD4-to-CD8 ratios due to a decrease in T helpers. In contrast, there were proportional increases in bone marrow T cells, with decreases in B cells. Although the blast percentage and count were decreased in flight mice, the CD34(+) population was increased. The data were more consistent with a shift in bone marrow populations rather than a response to changes in the periphery. Many of the results are similar to those using other models. Clearly, spaceflight can influence immune parameters ranging from hematopoiesis to mature leukocyte mechanisms.

Non-NASA Center↗

Proton production in relativistic heavy ion collisions; comparison with a thermodynamical model

Experimental results concerning proton production in nuclear collisions, obtained at Saturne with the Diogene 4 pi facility, are compared with the predictions of a thermodynamical model, using collective velocity distributions combined with a statistical thermodynamics in local rest frames. Experimental differential cross sections for alpha + nucleus and Neon + nucleus central collisions at incident energies between 200 and 800 MeV per nucleon are well reproduced by the model, for an angular range 30-110 degrees in the laboratory system. Extracted values of the temperatures are compared with those given by other authors.

NASA Program Biomedical Research↗

Improvements to the Ionizing Radiation Risk Assessment Program for NASA Astronauts

To perform dosimetry and risk assessment, NASA collects astronaut ionizing radiation exposure data from space flight, medical imaging and therapy, aviation training activities and prior occupational exposure histories. Career risk of exposure induced death (REID) from radiation is limited to 3 percent at a 95 percent confidence level. The Radiation Health Office at Johnson Space Center (JSC) is implementing a program to integrate the gathering, storage, analysis and reporting of astronaut ionizing radiation dose and risk data and records. This work has several motivations, including more efficient analyses and greater flexibility in testing and adopting new methods for evaluating risks. The foundation for these improvements is a set of software tools called the Astronaut Radiation Exposure Analysis System (AREAS). AREAS is a series of MATLAB(Registered TradeMark)-based dose and risk analysis modules that interface with an enterprise level SQL Server database by means of a secure web service. It communicates with other JSC medical and space weather databases to maintain data integrity and consistency across systems. AREAS is part of a larger NASA Space Medicine effort, the Mission Medical Integration Strategy, with the goal of collecting accurate, high-quality and detailed astronaut health data, and then securely, timely and reliably presenting it to medical support personnel. The modular approach to the AREAS design accommodates past, current, and future sources of data from active and passive detectors, space radiation transport algorithms, computational phantoms and cancer risk models. Revisions of the cancer risk model, new radiation detection equipment and improved anthropomorphic computational phantoms can be incorporated. Notable hardware updates include the Radiation Environment Monitor (which uses Medipix technology to report real-time, on-board dosimetry measurements), an updated Tissue-Equivalent Proportional Counter, and the Southwest Research Institute Radiation Assessment Detector. Also, the University of Florida hybrid phantoms, which are flexible in morphometry and positioning, are being explored as alternatives to the current NASA computational phantoms.

Semones, E. J.↗

Evolution of telemedicine in the space program and earth applications

Remote monitoring of crew, spacecraft, and environmental health has always been an integral part of the National Aeronautics and Space Administration's (NASA's) operations. Crew safety and mission success face a number of challenges in outerspace, including physiological adaptations to microgravity, radiation exposure, extreme temperatures and vacuum, and psychosocial reactions to space flight. The NASA effort to monitor and maintain crew health, system performance, and environmental integrity in space flight is a sophisticated and coordinated program of telemedicine combining cutting-edge engineering with medical expertise. As missions have increased in complexity, NASA telemedicine capabilities have grown apace, underlying its role in the field. At the same time, the terrestrial validation of telemedicine technologies to bring healthcare to remote locations provides feedback, improvement, and enhancement of the space program. As NASA progresses in its space exploration program, astronauts will join missions lasting months, even years, that take them millions of miles from home. These long-duration missions necessitate further technological breakthroughs in tele-operations and autonomous technology. Earth-based monitoring will no longer be real-time, requiring telemedicine capabilities to advance with future explorers as they travel deeper into space. The International Space Station will serve as a testbed for the telemedicine technologies to enable future missions as well as improve the quality of healthcare delivery on Earth.

long duration↗

Space radiation health program plan

The Space Radiation Health Program intends to establish the scientific basis for the radiation protection of humans engaged in the exploration of space, with particular emphasis on the establishment of a firm knowledge base to support cancer risk assessment for future planetary exploration. This document sets forth the technical and management components involved in the implementation of the Space Radiation Health Program, which is a major part of the Life Sciences Division (LSD) effort in the Office of Space Science and Applications (OSSA) at the National Aeronautics and Space Administration (NASA). For the purpose of implementing this program, the Life Sciences Division supports scientific research into the fundamental mechanisms of radiation effects on living systems and the interaction of radiation with cells, tissues, and organs, and the development of instruments and processes for measuring radiation and its effects. The Life Sciences Division supports researchers at universities, NASA field centers, non-profit research institutes and national laboratories; establishes interagency agreements for cooperative use and development of facilities; and conducts a space-based research program using available and future spaceflight vehicles.

Source record↗

Spatial distribution and yield of DNA double-strand breaks induced by 3-7 MeV helium ions in human fibroblasts

Accelerated helium ions with mean energies at the target location of 3-7 MeV were used to simulate alpha-particle radiation from radon daughters. The experimental setup and calibration procedure allowed determination of the helium-ion energy distribution and dose in the nuclei of irradiated cells. Using this system, the induction of DNA double-strand breaks and their spatial distributions along DNA were studied in irradiated human fibroblasts. It was found that the apparent number of double-strand breaks as measured by a standard pulsed-field gel assay (FAR assay) decreased with increasing LET in the range 67-120 keV/microm (corresponding to the energy of 7-3 MeV). On the other hand, the generation of small and intermediate-size DNA fragments (0.1-100 kbp) increased with LET, indicating an increased intratrack long-range clustering of breaks. The fragment size distribution was measured in several size classes down to the smallest class of 0.1-2 kbp. When the clustering was taken into account, the actual number of DNA double-strand breaks (separated by at least 0.1 kbp) could be calculated and was found to be in the range 0.010-0.012 breaks/Mbp Gy(-1). This is two- to threefold higher than the apparent yield obtained by the FAR assay. The measured yield of double-strand breaks as a function of LET is compared with theoretical Monte Carlo calculations that simulate the track structure of energy depositions from helium ions as they interact with the 30-nm chromatin fiber. When the calculation is performed to include fragments larger than 0.1 kbp (to correspond to the experimental measurements), there is good agreement between experiment and theory.

NASA Program Biomedical Research and Countermeasur↗

Spatial learning and memory deficits induced by exposure to iron-56-particle radiation

It has previously been shown that exposing rats to particles of high energy and charge (HZE) disrupts the functioning of the dopaminergic system and behaviors mediated by this system, such as motor performance and an amphetamine-induced conditioned taste aversion; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, spatial learning and memory were assessed in the Morris water maze 1 month after whole-body irradiation with 1.5 Gy of 1 GeV/nucleon high-energy (56)Fe particles, to test the cognitive behavioral consequences of radiation exposure. Irradiated rats demonstrated cognitive impairment compared to the control group as seen in their increased latencies to find the hidden platform, particularly on the reversal day when the platform was moved to the opposite quadrant. Also, the irradiated group used nonspatial strategies during the probe trials (swim with no platform), i.e. less time spent in the platform quadrant, fewer crossings of and less time spent in the previous platform location, and longer latencies to the previous platform location. These findings are similar to those seen in aged rats, suggesting that an increased release of reactive oxygen species may be responsible for the induction of radiation- and age-related cognitive deficits. If these decrements in behavior also occur in humans, they may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

NASA Program Biomedical Research and Countermeasur↗

Comparison of repair of DNA double-strand breaks in identical sequences in primary human fibroblast and immortal hamster-human hybrid cells harboring a single copy of human chromosome 11

We have optimized a pulsed-field gel electrophoresis assay that measures induction and repair of double-strand breaks (DSBs) in specific regions of the genome (Lobrich et al., Proc. Natl. Acad. Sci. USA 92, 12050-12054, 1995). The increased sensitivity resulting from these improvements makes it possible to analyze the size distribution of broken DNA molecules immediately after the introduction of DSBs and after repair incubation. This analysis shows that the distribution of broken DNA pieces after exposure to sparsely ionizing radiation is consistent with the distribution expected from randomly induced DSBs. It is apparent from the distribution of rejoined DNA pieces after repair incubation that DNA ends continue to rejoin between 3 and 24 h postirradiation and that some of these rejoining events are in fact misrejoining events, since novel restriction fragments both larger and smaller than the original fragment are generated after repair. This improved assay was also used to study the kinetics of DSB rejoining and the extent of misrejoining in identical DNA sequences in human GM38 cells and human-hamster hybrid A(L) cells containing a single human chromosome 11. Despite the numerous differences between these cells, which include species and tissue of origin, levels of TP53, expression of telomerase, and the presence or absence of a homologous chromosome for the restriction fragments examined, the kinetics of rejoining of radiation-induced DSBs and the extent of misrejoining were similar in the two cell lines when studied in the G(1) phase of the cell cycle. Furthermore, DSBs were removed from the single-copy human chromosome in the hamster A(L) cells with similar kinetics and misrejoining frequency as at a locus on this hybrid's CHO chromosomes.

NASA Program Biomedical Research and Countermeasur↗

Solar particle events observed at Mars: dosimetry measurements and model calculations

During the period from March 13, 2002 to mid-September, 2002, six solar particle events (SPE) were observed by the MARIE instrument onboard the Odyssey Spacecraft in Martian Orbit. These events were observed also by the GOES 8 satellite in Earth orbit, and thus represent the first time that the same SPE have been observed at these separate locations. The characteristics of these SPE are examined, given that the active regions of the solar disc from which the event originated can usually be identified. The dose rates at Martian orbit are calculated, both for the galactic and solar components of the ionizing particle radiation environment. The dose rates due to galactic cosmic rays (GCR) agree well with the HZETRN model calculations. Published by Elsevier Ltd on behalf of COSPAR.

Non-NASA Center↗

The effects of heavy particle irradiation on exploration and response to environmental change

Free radicals produced by exposure to heavy particles have been found to produce motor and cognitive behavioral toxicity effects in rats similar to those found during aging. The present research was designed to investigate the effects of exposure to 56Fe particles on the ability of male Sprague-Dawley rats to detect novel arrangements in a given environment. Using a test of spatial memory previously demonstrated to be sensitive to aging, open field activity and reaction to spatial and non-spatial changes were measured in a group that received a dose of 1.5 Gy (n=10) of 56Fe heavy particle radiation or in non-radiated controls (n=10). Animals irradiated with 1.5 Gy of 56Fe particles exhibited some age-like effects in rats tested, even though they were, for the most part, subtle. Animals took longer to enter, visited less and spent significantly less time in the middle and the center portions of the open field, independently of total frequency and duration of activity of both groups. Likewise, irradiated subjects spend significantly more time exploring novel objects placed in the open field than did controls. However, irradiated subjects did not vary from controls in their exploration patterns when objects in the open field were spatially rearranged. Thus, irradiation with a dose of 1.5 Gy of 56Fe high-energy particle radiation elicited age-like effects in general open field exploratory behavior, but did not elicit age-like effects during the spatial and non-spatial rearrangement tasks. Published by Elsevier Ltd on behalf of COSPAR.

NASA Program Biomedical Research and Countermeasur↗

Outcomes of a NASA Human Research Program’s (HRP) Space Radiation Element-sponsored Mini-Technical Interchange Meeting/workshop on Cardiovascular Disease Risk from Space Radiation

The NASA HRP’s Space Radiation Element funds research to characterize and mitigate adverse health outcomes from space radiation including cardiovascular risks to astronauts to enable deep space exploration and sustained human presence in space. Non-cancer effects such as damage to the cardiovascular system have been observed at clinically relevant high doses of ionizing radiation. However, an association between lower doses and risk of cardiovascular disease (CVD) remains somewhat controversial, especially in relation to the existence of low dose thresholds, radiation quality, and dose-rate effects, as well as gaps in characterizing the mechanisms and major pathways of disease. To facilitate, accelerate, and incubate new ideas to characterize and mitigate this risk, the Element is planning to organize a series of miniature technical interchange meetings (Tiny-TIMs) to provide a venue for HRP-funded investigators and thought leaders to present ongoing work and engage in open discussion on presented results, limitations of current approaches, incorporating better experimental strategies, model systems, etc. The initial Tiny-TIM held during the NASA HRP Investigators’ Workshop earlier this year – Upping the ante on characterizing and mitigating cardiovascular disease risk from space radiation exposure – aimed to stimulate discussion on the current state of scientific knowledge of CVD risk from space-like radiation exposure. The Tiny-TIM consisted of two 90-minute sessions; the first session concentrated on current knowledge of CVD risk from space radiation and the second session focused on innovative ideas, newer approaches, and techniques to accelerate research. The second session was followed by an open spirited discussion amongst peers on the current issues impeding the characterization of CVD risk from space radiation. The Element facilitated the discussion using a set of pressing open questions/gaps in knowledge that need to be addressed by the scientific community. The outcomes of the Tiny-TIM will be presented along with a plan of proposed future workshops and other initiatives of the Space Radiation Element.

Janapriya Saha↗

Overview of the Translational Radiation Research and Countermeasures (TRRaC) Project in Space Radiation

The Translational Radiation Research and Countermeasures (TRRaC) Project was initiated by the Space Radiation (SR) Element within NASA’s Human Research Program (HRP) to support the SR mission to understand and characterize the space radiation environment, understand and quantify radiation-associated risks, and mitigate the impacts of radiation-induced adverse health outcomes to enable human space exploration. TRRaC’s mission is to translate radiation research results from experimental studies and epidemiological data to humans and astronauts using bioinformatics and computational modeling. TRRaC will leverage existing datasets such as those available from NASA’s GeneLab repository and human medical radiation exposure registries, along with relevant data generated from ground-based research at molecular, cellular, tissue, and system levels, to: (1) refine the radiation dose rate effectiveness factor, (2) characterize radiation quality effects to improve estimates of the risk of exposure-induced death (REID) from space-relevant radiation exposures, and (3) identify pathways and biomarkers for cancer, cardiovascular disease, and central nervous system changes that are impacted by space radiation exposure.

Parastou Eslami↗

Overview of NASA's space radiation research program

NASA is developing the knowledge required to accurately predict and to efficiently manage radiation risk in space. The strategy employed has three research components: (1) ground-based simulation of space radiation components to develop a science-based understanding of radiation risk; (2) space-based measurements of the radiation environment on planetary surfaces and interplanetary space, as well as use of space platforms to validate predictions; and, (3) implementation of countermeasures to mitigate risk. NASA intends to significantly expand its support of ground-based radiation research in line with completion of the Booster Applications Facility at Brookhaven National Laboratory, expected in summer of 2003. A joint research solicitation with the Department of Energy is under way and other interagency collaborations are being considered. In addition, a Space Radiation Initiative has been submitted by the Administration to Congress that would provide answers to most questions related to the International Space Station within the next 10 years.

NASA Discipline Radiation Health↗

The stopping of deuterons in lithium

The interaction of 52 MeV deuterons with lithium was investigated, in view of the optimization of a lithium target for an intense neutron source based on the d-Li stripping reaction. The experimental results are compared with theoretical calculations obtained from an updated version of the Bragg code. This code describes in detail the interaction of charged particles with matter. Within the experimental uncertainties the theoretical results are well reproduced by the experiments.

NASA Program Space Medicine↗

Physical and biological studies with protons and HZE particles in a NASA supported research center in radiation health

NASA has established and supports a specialized center for research and training (NSCORT) to specifically address the potential deleterious effects of HZE particles on human health. The NSCORT in radiation health is a joint effort between Lawrence Berkeley National Laboratory (LBNL) and Colorado State University (CSU). The overall scope of research encompasses a broad range of subjects from microdosimetric studies to cellular and tissue responses to initial damage produced by highly energetic protons and heavy charged particles of the type found in galactic cosmic rays (GCR) spectrum. The objectives of the microdosimetry studies are to determine the response of Tissue Equivalent Proportional Counter (TEPC) to cosmic rays using ground based accelerators. This includes evaluation of energy loss due to the escape of high-energy delta rays and increased energy deposition due to the enhanced delta ray production in the wall of the detector. In this report major results are presented for 56Fe at 1000, 740, 600 and 400 MeV/nucleon. An assessment of DNA repair and early development of related chromosomal changes is extremely important to our overall understanding of enhanced biological effectiveness of high LET particle radiation. Results are presented with respect to the fidelity of the rejoining of double strand breaks and the implications of misrejoining. The relationship between molecular and cytogenetic measurements is presented by studying damage processing in highly heterochromatic supernumerary (correction of sypernumerary) X chromosomes and the active X-chromosome. One of the important consequences of cell's inability to handle DNA damage can be evaluated through mutation studies. Part of our goal is the assessment of potential radioprotectors to reduce the mutation yield following HZE exposures, and some promising results are presented on one compound. A second goal is the integration of DNA repair and mutation studies. Results are presented on a direct comparison of initial double strand breaks induction, the time course and fidelity of double strand break rejoining, cell killing and mutation induction in the same human model system. In order to understand the carcinogenic potential of protons and HZE particles, the role of damaged microenvironment in this process must be understood. In this project it has been postulated that radiation affects the microenvironment, which then modifies cell interactions in a manner conducive to neoplastic progression. Both TGF-beta and FGF-2 are important components of microenvironment. A recent result on the assessment of the role of FGF-2 and its cross-talk with TGF-beta as a function of radiation quality is presented. Theoretical modeling has so far played a central role in analyzing and integrating experimental data on repair and mutation studies and predicting new phenomena. The integrated NSCORT program also provides a broad training experience for students and postdoctoral fellows in space radiation health.

NASA Discipline Radiation Health↗

Overview of NASARTI (NASA Radiation Track Image) Program: Highlights of the Model Improvement and the New Results

This presentation summarizes several years of research done by the co-authors developing the NASARTI (NASA Radiation Track Image) program and supporting it with scientific data. The goal of the program is to support NASA mission to achieve a safe space travel for humans despite the perils of space radiation. The program focuses on selected topics in radiation biology that were deemed important throughout this period of time, both for the NASA human space flight program and to academic radiation research. Besides scientific support to develop strategies protecting humans against an exposure to deep space radiation during space missions, and understanding health effects from space radiation on astronauts, other important ramifications of the ionizing radiation were studied with the applicability to greater human needs: understanding the origins of cancer, the impact on human genome, and the application of computer technology to biological research addressing the health of general population. The models under NASARTI project include: the general properties of ionizing radiation, such as particular track structure, the effects of radiation on human DNA, visualization and the statistical properties of DSBs (DNA double-strand breaks), DNA damage and repair pathways models and cell phenotypes, chromosomal aberrations, microscopy data analysis and the application to human tissue damage and cancer models. The development of the GUI and the interactive website, as deliverables to NASA operations teams and tools for a broader research community, is discussed. Most recent findings in the area of chromosomal aberrations and the application of the stochastic track structure are also presented.

Ponomarev, Artem L.↗

Genetic models in applied physiology: selected contribution: effects of spaceflight on immunity in the C57BL/6 mouse. II. Activation, cytokines, erythrocytes, and platelets

This portion of the study quantified the effects of a 12-day space shuttle mission (Space Transport System-108/UF-1) on body and lymphoid organ masses, activation marker expression, cytokine secretion, and erythrocyte and thrombocyte characteristics in C57BL/6 mice. Animals in flight (Flt group) had 10-12% lower body mass compared with ground controls housed either in animal enclosure modules or under standard vivarium conditions (P < 0.001) and the smallest thymus and spleen masses. Percentages of CD25(+) lymphocytes, CD3(+)/CD25(+) T cells, and NK1.1(+)/CD25(+) natural killer cells from Flt mice were higher compared with both controls (P < 0.05). In contrast, CD71 expression was depressed in the Flt and animal enclosure module control mice compared with vivarium control animals (P < 0.001). Secretion of interferon-gamma, IL-2, and IL-4, but not tumor necrosis factor-alpha and IL-5, by splenocytes from Flt mice was decreased relative to either one or both ground controls (P < 0.05). Flt mice also had high red blood cell and thrombocyte counts compared with both sets of controls; low red blood cell volume and distribution width, percentage of reticulocytes, and platelet volume were also noted (P < 0.05) and were consistent with dehydration. These data indicate that relatively short exposure to the spaceflight environment can induce profound changes that may become significant during long-term space missions.

Flight Experiment↗

2013 Space Radiation Standing Review Panel Status Review for: The Risk of Acute and Late Central Nervous System Effects from Radiation Exposure, The Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs), The Risk Of Degenerative Tissue Or Other Health Effects From Radiation Exposure, and The Risk of Radiation Carcinogenesis

The Space Radiation Standing Review Panel (from here on referred to as the SRP) was impressed with the strong research program presented by the scientists and staff associated with NASA's Space Radiation Program Element and National Space Biomedical Research Institute (NSBRI). The presentations given on-site and the reports of ongoing research that were provided in advance indicated the potential Risk of Acute and Late Central Nervous System Effects from Radiation Exposure (CNS) and were extensively discussed by the SRP. This new data leads the SRP to recommend that a higher priority should be placed on research designed to identify and understand these risks at the mechanistic level. To support this effort the SRP feels that a shift of emphasis from Acute Radiation Syndromes (ARS) and carcinogenesis to CNS-related endpoints is justified at this point. However, these research efforts need to focus on mechanisms, should follow pace with advances in the field of CNS in general and should consider the specific comments and suggestions made by the SRP as outlined below. The SRP further recommends that the Space Radiation Program Element continue with its efforts to fill the vacant positions (Element Scientist, CNS Risk Discipline Lead) as soon as possible. The SRP also strongly recommends that NASA should continue the NASA Space Radiation Summer School. In addition to these broad recommendations, there are specific comments/recommendations noted for each risk, described in detail below.

Source record↗