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All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Neuroimmune Responses to Space Radiation

One of the main health risks in human deep space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neurodegeneration and neuroinflammation associated with cognitive and behavioral dysfunction. The extent of CNS damage is partially mediated by the blood-brain barrier (BBB), which regulates the interaction between CNS and systemic responses to stressors in the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, neuroinflammation and oxidative stress. However, studies on BBB and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we developed a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments caused by deep space radiation. We investigated both immediate and delayed CNS responses to major GCR components: 600MeV/n 56Fe ions. We observed ionizing radiation-mediated dose-dependent increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by altered cytokine expression including interleukin-1 receptor alpha downregulation, and increased oxidative stress. In particular, 600MeV/n 56Fe particle irradiation selectively increased damage and blood-brain barrier permeability only in models that contained astrocytes in addition to endothelial cells, indicating astrocytes as a particularly radiosensitive component of the CNS that could therefore be a suitable a target for neuroprotection. Future studies will compare human and mouse CNS model responses to simulated GCRs and evaluate the induction of an anti-inflammatory phenotype in astrocytes as a potential countermeasure. Furthermore, in our lab we have been exploring the individual variability, genomic associations and secreted biomarkers of responses to space radiation, which could eventually be combined to address personalized CNS health risk and develop individual countermeasures. Ultimately, we aim to expand upon these results to uncover novel cellular and mechanistic targets for countermeasure development to mitigate human CNS damage in deep space exploration.

space radiation↗
NASA NTRSDate not supplied

Neuroimmune responses to space radiation

One of the main health risks in human deep space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neurodegeneration and neuroinflammation associated with cognitive and behavioral dysfunction. The extent of CNS damage is partially mediated by the blood-brain barrier (BBB), which regulates the interaction between CNS and systemic responses to stressors in the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, neuroinflammation and oxidative stress. However, studies on BBB and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we developed a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments caused by deep space radiation. We investigated both immediate and delayed CNS responses to major GCR components: 0.3-0.8Gy 600MeV/n 56Fe ions; as well as to 0.5-1Gy X-rays. We observed ionizing radiation-mediated increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by damage to endothelial cells and tight junctions, altered cytokine expression including TNFalpha upregulation, and increased oxidative stress. In particular, 600MeV/n 56Fe particle irradiation selectively induced astrocyte damage and increased blood-brain barrier permeability only in models that contained astrocytes in addition to endothelial cells, indicating astrocytes as a particularly radiosensitive component of the CNS that could therefore be a suitable a target for neuroprotection. Future studies will compare human and mouse CNS model responses to simulated GCRs and evaluate the induction of an anti-inflammatory phenotype in astrocytes as a potential countermeasure. Furthermore, in our lab we have been exploring the individual variability, genomic associations and secreted biomarkers of responses to space radiation, which could eventually be combined to address personalized CNS health risk and develop individual countermeasures. Ultimately, we aim to expand upon these results to uncover novel cellular and mechanistic targets for countermeasure development to mitigate human CNS damage in deep space exploration.

space radiation↗
NASA NTRS2014

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.↗
NASA NTRS1979

Theoretical models of interstellar shocks. I - Radiative transfer and UV precursors

Theoretical models of interstellar radiative shocks are constructed, with special attention to the transfer of ionizing radiation. These models are 'self-consistent' in the sense that the emergent ionizing radiation (the UV precursor) is coupled with the ionization state of H, He, and the metals in the preshock gas. For shock velocities of at least 110 km/s the shocks generate sufficient UV radiation for complete preionization of H and He, the latter to He(+). At lower velocities the preionization can be much smaller, with important consequences for the cooling function, the shock structure, and the emission. For models with shock velocities of 40 to 130 km/s the intensities of the strongest emission lines in the UV, optical, and infrared are tabulated, as well as postshock column densities of metal ions potentially observable by UV absorption spectroscopy. Possible applications to supernova remnants and high-velocity interstellar gas are assessed.

Shull, J. M.↗
NASA NTRS1996

Model calculations of the radiation dose and LET spectra on LDEF and comparisons with flight data

Ionizing radiation environment models, a 3-D spacecraft mass model, and radiation transport codes have been used to predict the radiation dose and linear energy transfer (LET) spectra measured at various locations on the LDEF satellite. The predictions are compared with thermoluminescent dosimeter measurements of the trapped proton and electron doses and with LET spectra measured by plastic nuclear track detectors. The predicted vs observed comparisons indicate some of the uncertainties of present ionizing radiation environment models for low Earth-orbit missions.

LDEF Project↗
NASA NTRS2009

OLTARIS: On-Line Tool for the Assessment of Radiation in Space

The effects of ionizing radiation on humans in space is a major technical challenge for exploration to the moon and beyond. The radiation shielding team at NASA Langley Research Center has been working for over 30 years to develop techniques that can efficiently assist the engineer throughout the entire design process. OLTARIS: On-Line Tool for the Assessment of Radiation in Space is a new NASA website (http://oltaris.larc.nasa.gov) that allows engineers and physicists to access a variety of tools and models to study the effects of ionizing space radiation on humans and shielding materials. The site is intended to be an analysis and design tool for those working radiation issues for current and future manned missions, as well as a research tool for developing advanced material and shielding concepts. The site, along with the analysis tools and models within, have been developed using strict software practices to ensure reliable and reproducible results in a production environment. They have also been developed as a modular system so that models and algorithms can be easily added or updated.

Sandridge, Chris A.↗
NASA NTRS2004

High Altitude Radiations Relevant to the High Speed Civil Transport (HSCT)

The Langley Research Center (LaRC) performed atmospheric radiation studies under the SST development program in which important ionizing radiation components were measured and extended by calculations to develop the existing atmospheric ionizing radiation (AIR) model. In that program the measured neutron spectrum was limited to less than 10 MeV by the available 1960-1970 instrumentation. Extension of the neutron spectrum to high energies was made using the LaRC PROPER-3C monte carlo code. It was found that the atmospheric neutrons contributed about half of the dose equivalent and approximately half of the neutron contribution was from high energy neutrons above 10 MeV. Furthermore, monte carlo calculations of solar particle events showed that potential exposures as large as 10-100 mSv/hr may occur on important high latitude routes but acceptable levels of exposure could be obtained if timely descent to subsonic altitudes could be made. The principal concern was for pregnant occupants onboard the aircraft. As a result of these studies the FAA Advisory Committee on the Radiobiological Aspects of the SST recommended: 1. Crew members will have to be informed of their exposure levels 2. Maximum exposures on any flight to be limited to 5 mSv 3. Airborne radiation detection devices for total exposure and exposure rates 4. Satellite monitoring system to provide SST aircraft real-time information on atmospheric radiation levels for exposure mitigation 5. A solar forecasting system to warn flight operations of an impending solar event for flight scheduling and alert status. These recommendations are a reasonable starting point to requirements for the HSCT with some modification reflecting new standards of protection as a result of changing risk coefficients.

Wilson, J. W.↗
NASA NTRSDate not supplied

Neurovascular Outcomes of Space Radiation in Human Blood-Brain Barrier Models

One of the main health risks in human deep space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neurodegeneration and neuroinflammation associated with cognitive and behavioral dysfunction. The extent of CNS damage is partially mediated by the blood-brain barrier (BBB), which regulates the interaction between CNS and systemic responses to stressors in the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, neuroinflammation and oxidative stress. However, studies on BBB and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we developed a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments caused by deep space radiation. We investigated both immediate and delayed CNS responses to major GCR components: 0.15-0.5Gy 250MeV/n 4He and 0.3-0.8Gy 600MeV/n 56Fe; as well as to 0.5-1Gy X-rays. We observed ionizing radiation-mediated increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by damage to endothelial cells and tight junctions, altered cytokine expression including TNFalpha upregulation, and increased oxidative stress. In particular, 600MeV/n 56Fe particle irradiation selectively induced astrocyte damage and increased blood-brain barrier permeability only in models that contained astrocytes in addition to endothelial cells, indicating astrocytes as a particularly radiosensitive component of the CNS that could therefore be a suitable a target for neuroprotection. Future studies will compare human and mouse CNS model responses to simulated GCRs and evaluate the induction of an anti-inflammatory phenotype in astrocytes as a potential countermeasure. Ultimately, we aim to expand upon these results to uncover novel cellular and mechanistic targets for countermeasure development to mitigate human CNS damage in deep space exploration.

centrat nervous system↗
NASA NTRS2009

Total Dose Effects on Single Event Transients in Digital CMOS and Linear Bipolar Circuits

This presentation discusses the effects of ionizing radiation on single event transients (SETs) in circuits. The exposure of integrated circuits to ionizing radiation changes electrical parameters. The total ionizing dose effect is observed in both complementary metal-oxide-semiconductor (CMOS) and bipolar circuits. In bipolar circuits, transistors exhibit grain degradation, while in CMOS circuits, transistors exhibit threshold voltage shifts. Changes in electrical parameters can cause changes in single event upset(SEU)/SET rates. Depending on the effect, the rates may increase or decrease. Therefore, measures taken for SEU/SET mitigation might work at the beginning of a mission but not at the end following TID exposure. The effect of TID on SET rates should be considered if SETs cannot be tolerated.

Buchner, S.↗
NASA NTRS2007

Comparative MicroRNA Expression Patterns in Fibroblasts after Low and High Doses of Low-LET Radiation Exposure

Exposure to ionizing radiation causes DNA damage to cells, and provokes a plethora of cellular responses controlled by unique gene-directed signaling pathways. MicroRNAs (miRNAs) are small (~22-nucleotide), non-coding RNAs which functionally silence gene expression by either degrading the messages or inhibiting translation. Here we investigate radiation-dependent changes in these negative regulators by comparing the expression patterns of all 462 known human miRNAs in fibroblasts, after exposure to low (0.1 Gy) or high (2 Gy) doses of X-rays at 30 min, 2, 6 and 24 hrs post-treatment. The expression patterns of microRNAs after low and high doses of radiation show a similar qualitative down-regulation trend at early (0.5 hr) and late (24 hr) time points, with a quantitatively steeper slope following the 2 Gy exposures. Interestingly, an interruption of this downward trend is observed after the 2 Gy exposure, i.e. a significant up-regulation of microRNAs at 2 hrs, then reverting to the downward trend by 6 hrs; this interruption at the intermediate time point was not observed with the 0.1 Gy exposure. At the early time point (0.5 hr), candidate gene targets of selected down-regulated microRNAs, common to both 0.1 and 2 Gy exposures, were those functioning in chromatin remodeling. Candidate target genes of unique up-regulated microRNAs seen at a 2 hr intermediate time point, after the 2 Gy exposure only, are those involved in cell death signaling. Finally, putative target genes of down-regulated microRNAs seen at the late (24 hr) time point after either doses of radiation are those involved in the up-regulation of DNA repair, cell signaling and homeostasis. Thus we hypothesize that after radiation exposure, microRNAs acting as hub negative regulators for unique signaling pathways needed to be down-regulated so as to de-repress their target genes for the proper cellular responses, including DNA repair and cell maintenance. The unique microRNAs up-regulated at 2 hr after 2 Gy suggest the cellular response to functionally suppress the apoptotic death signaling reflex after exposure to high dose radiation. Further analyses with transcriptome and global proteomic profiling will validate the reciprocal expression of signature microRNAs selected in our radiation-exposed cells, and their candidate target gene families, and test our hypothesis that unique radiation-specific microRNAs are keys in governing signaling responses for damage control of this environmental hazard.

Maes, Olivier C.↗
NASA NTRSDate not supplied

NASA GeneLab Platform Utilized for Biological Response to Space Radiation in Animal Models

Ionizing radiation from Galactic Cosmic Rays (GCR) is one of the major risk factors that will impact the health of astronauts on extended missions outside the protective effects of Earth’s magnetic field. The NASA GeneLab project has detailed information on radiation exposure using animal models with curated dosimetry information for spaceflight experiments. We analyzed multiple GeneLab omics datasets associated with both ground-based and spaceflight radiation studies that included in vivo and in vitro approaches. A range of ions from protons to iron particles with doses from 0.1 Gy to 1.0 Gy for ground studies and samples flown in Low Earth Orbit (LEO) with total doses of 1.0 mGy to 30 mGy were utilized From this analysis we were able to identify distinct biological signatures associating specific ions with specific biological responses due to radiation exposure in space. For example, we discovered changes in mitochondrial function, ribosomal assembly, and immune pathways as a function of dose. We provided a summary of how the GeneLab’s rich database of omics experiments with animal models can be used to generate novel hypotheses to better understand human health risks from GCR exposures.

Afshin Beheshti↗
NASA NTRS2000

Reionization of the Universe and the Photoevaporation of Cosmological Minihalos

The first sources of ionizing radiation to condense out of the dark and neutral Intergalactic Medium (IGM) sent ionization fronts sweeping outward through their surroundings, overtaking other condensed objects and photoevaporating them. This feedback effect of universal reionization on cosmic structure formation is demonstrated here for the case of a cosmological minihalo of dark matter and baryons exposed to an external source of ionizing radiation with a quasar-like spectrum, just after the passage of the global ionization front created by the source. We model the pre-ionization minihalo as a truncated, nonsingular isothermal sphere in hydrostatic equilibrium following its collapse out of the expanding background universe and virialization. Results are presented of the first, gas dynamical simulations of this process, including radiative transfer. A sample of observational diagnostics is also presented, including the spatially-varying ionization levels of C, N, and O in the flow if a trace of heavy elements is present and the integrated column densities of H I, He I and He II, and C IV through the photoevaporating gas at different velocities, which would be measured in absorption against a background source like that responsible for the ionization.

Shapiro, Paul R.↗
NASA NTRS1991

Asymmetric soft-error resistant memory

A memory system is provided, of the type that includes an error-correcting circuit that detects and corrects, that more efficiently utilizes the capacity of a memory formed of groups of binary cells whose states can be inadvertently switched by ionizing radiation. Each memory cell has an asymmetric geometry, so that ionizing radiation causes a significantly greater probability of errors in one state than in the opposite state (e.g., an erroneous switch from '1' to '0' is far more likely than a switch from '0' to'1'. An asymmetric error correcting coding circuit can be used with the asymmetric memory cells, which requires fewer bits than an efficient symmetric error correcting code.

Buehler, Martin G.↗
NASA NTRS2003

A Biodosimeter for Multiparametric Determination of Radiation Dose, Radiation Quality, and Radiation Risk

Predicting risk of human cancer following exposure of an individual or a population to ionizing radiation is challenging. To an approximation, this is because uncertainties of uniform absorption of dose and the uniform processing of dose-related damage at the cellular level within a complex set of biological variables degrade the confidence of predicting the delayed expression of cancer as a relatively rare event. Cellular biodosimeters that simultaneously report: 1) the quantity of absorbed dose after exposure to ionizing radiation, 2) the quality of radiation delivering that dose, and 3) the risk of developing cancer by the cells absorbing that dose would therefore be useful. An approach to such a multiparametric biodosimeter will be reported. This is the demonstration of a dose responsive field effect of enhanced expression of keratin 18 (K18) in cultures of human mammary epithelial cells irradiated with cesium-1 37 gamma-rays. Dose response of enhanced K18 expression was experimentally extended over a range of 30 to 90 cGy for cells evaluated at mid-log phase. K18 has been reported to be a marker for tumor staging and for apoptosis, and thereby serves as an example of a potential marker for cancer risk, where the reality of such predictive value would require additional experimental development. Since observed radiogenic increase in expression of K18 is a field effect, ie., chronically present in all cells of the irradiated population, it may be hypothesized that K18 expression in specific cells absorbing particulate irradiation, such as the high-LET-producing atomic nuclei of space radiation, will report on both the single-cell distributions of those particles amongst cells within the exposed population, and that the relatively high dose per cell delivered by densely ionizing tracks of those intersecting particles will lead to cell-specific high-expression levels of K18, thereby providing analytical end points that may be used to resolve both the quantity and the quality of the radiation dose absorbed by individual cells. The principal value of this reported potential multiparametric cellular biodosimeter is suggested to be that it justifies a search for similar but more robust radiogenic assays. That is, K18 is only one radiation dose-sensitive expressed protein, whereas analytical techniques of genomics and proteomics can be used to simultaneously analyze multiple gene and protein expressions resulting from radiation-dose absorption. The potential usefulness of multiparametric cellular biodosimeters will be best realized from quantitatively profiling these multiple markers using these modern techniques.

Richmond, Robert↗
NASA NTRS1972

Low-mass protogalaxies and absorption lines in quasi-stellar objects.

The possibility is explored that the many weak unidentified absorption lines in high-redshift QSO spectra are L-alpha lines of hydrogen. The likely existence of a metagalactic flux of ionizing radiation indicates that hydrogen clouds at high redshifts must be thoroughly ionized. Observations of PHL 957 show that the suggested clouds may be low-mass protogalaxies. A simple model for the clouds' collapse and for the flux of ionizing radiation is used to compute the distribution of expected L-alpha lines in the spectrum of a QSO as a function of wavelength and H I column density. The computed distribution is in accord with observations of the two most distant QSOs, PHL 957 and 4C 05.34. Crudities in the theory and stronger tests of its validity are also discussed.

Arons, J.↗
NASA NTRS1982

The ionization equilibrium of astrophysically abundant elements

The paper presents new calculations of ionization equilibrium fractions of 11 abundant elements (C, N, O, Ne, Mg, Si, S, Ar, Ca, Fe, Ni) as functions of temperature. Convenient coefficients for fitting the rates of collisional ionization, radiative recombination, and dielectronic recombination are also tabulated. Many of the ionization rates are based on recent experimental measurements of cross sections for collisional ionization and autoionization following inner-shell excitation. These rates are used elsewhere in computations of nonequilibrium ionization, radiative cooling, radiative shock models, and plasma emission diagnostics.

Shull, J. M.↗