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At least 289 records · Page 16

Deep Space Radiation Affects Neurovascular Functions in Human Organ-on-a-Chip Models

A major health risk for human deep space exploration is central nervous system (CNS) damage by galactic cosmic ray radiation. Simulated galactic cosmic rays or their components, especially the high- linear energy transfer (LET) particles such as 56 Fe ions, cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates the interactions between CNS and the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal health and neuroinflammation. However, there have been few studies on BBB and astrocyte functions in regulating CNS responses, especially in human tissue/organ analogs. Therefore, we utilized a high-throughput human 3D organ-on-a-chip system, seeded with induced pluripotent stem cell-derived endothelial cells, astrocytes and neurons, to study human neurovascular responses to simulated deep space radiation. We investigated BBB permeability, oxidative stress, cellular and tissue damage, and secreted factors over the time period of 24 hours-1 week after irradiation with 0.25-0.5 Gy 5-ion simplified simulated galactic cosmic rays and 0.3-0.8 Gy high-LET 600MeV/n 56 Fe particles, and compared the outcomes to low-LET irradiation with 0.1-1 Gy doses of X-rays and gamma rays. Both high and low-LET radiation increased neurovascular permeability, caused oxidative stress, damaged endothelial cells and tight junctions, and altered expression of inflammatory cytokines. Ionizing radiation- induced neurovascular permeability and oxidative stress peaked at 3 days after irradiation and were further exacerbated by the presence of astrocytes. Furthermore, in response to particle irradiation, astrocytes stimulated interleukin-1 signaling by inhibiting the expression of interleukin-1 receptor antagonist. Thus, we also evaluated interleukin-1 receptor antagonist as a potential countermeasure against particle radiation. Ultimately, our results may help develop countermeasures to mitigate human CNS damage in deep space exploration.

Sonali D Verma↗

Quantifying radiation quality for space relevant radiation types: Fitting excess risk models to three combined HZE-irradiated mouse datasets

Radiation health risks are predominantly derived from low linear energy transfer (LET) terrestrial exposures; however, space radiation includes exposure to high-LET and high-charge, high-energy (HZE) particles. Accurately quantifying the differences in radiation quality between the space and terrestrial radiation environments is important for assessing and predicting health risks for astronauts. Weil et al. 2009 and 2014 used two different inbred mouse strains to study differences in hepatocellular carcinoma (HCC) tumorigenesis after exposures to low- and high- LET radiation[1-2]. More recently, Edmondson et al. 2020 provided valuable new tumor data in outbred mice that were exposed to low- and high-LET radiation[3]. The present study aims to rigorously investigate a relative biological effectiveness (RBE) factor by leveraging the HCC tumor data from the three datasets[1-3]. The three experiments were similarly designed, allowing the raw data to be combined into a pooled dataset to estimate excess relative risk (ERR) and excess absolute risk (EAR) models using Bayesian Poisson regression.

Lori J. Chappell↗

Effect of low Reynolds number turbulence amplification on the Galileo probe flowfield

The amplification of turbulence at low Reynolds numbers is analyzed as it affects the Jupiter-entry flowfield, surface-heating rate, and mass-loss rate of the 335-kg Galileo probe now being designed. The constant k(2) in the Clauser-Klebanoff outer law of the two-layer algebraic eddy-viscosity model of Cebeci (1970), as used in earlier models of the Galileo flowfield (Moss and Simmonds, 1982), is modified to increase at low Reynolds numbers, as found experimentally by Varner and Adams (1980). Calculations were performed for peak heating conditions (at 49.13 sec of entry), using a turbulent Prandtl number of 0.9 and turbulent Lewis numbers (LeT) of 0.8, 1.0, and 1.2. The low-Reynolds-number effect is found to produce mass-loss-ratio increases of from 4 to 50 percent, while an LeT of 1.2 produced an increase of from 4 to 10 percent as compared to an LeT of 1.0. While these findings are based on experimental data obtained under conditions somewhat different from those probably present on Jupiter, their importance for a conservative probe design is stressed.

Gupta, R. N.↗

Late skin damage in rabbits and monkeys after exposure to particulate radiations

Preliminary results are reported of experiments on the late effects of exposure to particulate radiations on stem cell populations. Skin biopsies were taken from the ears of rabbits irradiated 2-5 years previously with 530 MeV/amu Ar ions (LET 90 keV/micron), or 365 MeV/amu Ne ions (LET 35 keV micron), and from the chests and inner thighs of rhesus monkeys irradiated 16-18 years previously with 32-MeV protons (LET about 1.2 keV/micron). Skin fibroblast cultures obtained from the biopsy samples in rabbits were observed to undergo dose-dependent decreases in in vitro life span, with estimated survival curves showing the effects of Ar-ion irradiation to be more severe than those of Ne-ion irradiation. In addition, the healing of the biopsy wound was observed to become slower as radiation dose increased. In the monkey, radiation reduced the average number of fibroblasts at the time of cessation of growth in culture. Results thus demonstrate the capacity of skin sampling to reveal stem cell destruction, and have important implications for astronauts and other persons at risk of particle exposure with regard to healing responses to trauma or surgery.

Bergtold, D. S.↗

Linear energy transfer spectrum measurement experiment (P0006)

The linear energy transfer (LET) is the energy deposited per unit path length of charged particle traversing matter. For estimating the rate of damage from single-hit phenomena, the quantity that best combines the radiation environment, orbital situation, and spacecraft shielding is the linear energy transfer (LET) spectrum at the device location. This experiment will measure the LET spectrum behind different shielding configurations for approximately 1 year. The shielding will be increased in increments of approximately 1 G/sq cm up to a maximum shieldng of 16 G/sq cm. In addition to providing critical information to future spacecraft designers, these measurements will also provide data that will be extremely valuable to other experiments on LDEF.

Benton, E. V.↗

Radiation measurements aboard Spacelab 1

The radiation environment inside Spacelab 1 was measured by a set of passive radiation detectors distributed throughout the volume inside the module, in the access tunnel, and outside on the pallet. Measurements of the low linear energy transfer (LET) component obtained from the thermoluminescence detectors ranged from 102 to 190 millirads, yielding an average low LET dose rate of 11.2 millirads/day inside the module, about twice the low LET dose rate measured on previous flights of the Space Shuttle. Because of the higher inclination of the orbit (57 versus 28.5 deg for previous Shuttle flights), substantial fluxes of highly ionizing high charge and energy galactic cosmic ray particles were observed, yielding an overall average mission dose-equivalent of about 150 millirems, more than three times higher than that measured on previous Shuttle missions.

Benton, E. V.↗

Cosmic ray simulation and testing program

Single event upset (SEU) and latchup vulnerabilities were determined for a number of parts of interest to NASA space programs. In cases where a threshold linear energy transfer (LET) for SEU could be measured, an upset rate in a low inclination Space Shuttle orbit was computed. The predicted upset rates are extremely low, except for the devices with LET thresholds below the geomagnetic cutoff for altitude and inclination of the Space Shuttle orbit. While some of the devices do exhibit latchup, the cross sections and threshold LETs are such that the risk associated with flying these devices in low, near equatorial orbits is small if not negligible.

Kolasinski, W. A.↗

Early and late mammalian responses to heavy charged particles

This overview summarizes murine results on acute lethality responses, inactivation of marrow CFU-S and intestinal microcolonies, testes weight loss, life span shortening, and posterior lens opacification in mice irradiated with heavy charged particles. RBE-LET relationships for these mammalian responses are compared with results from in vitro studies. The trend is that the maximum RBE for in vivo responses tends to be lower and occurs at a lower LET than for inactivation of V79 and T-1 cells in culture. Based on inactivation cross sections, the response of CFU-S in vivo conforms to expectations from earlier studies with prokaryotic systems and mammalian cells in culture. Effects of heavy ions are compared with fission spectrum neutrons, and the results are consistent with the interpretation that RBEs are lower than for fission neutrons at about the same LET, probably due to differences in track structure.

Ainsworth, E. J.↗

Fluence-related risk coefficients using the Harderian gland data as an example

A new concept is introduced for assessing the risk of radiation-induced cancer to space travelers: a fluence-related risk coefficient F (called the risk cross section), which is the risk of a cancer per unit particle fluence for a given particle type. Fs are functions of the LET of the particles in the radiation field and, when integrated over fluence-LET spectra and summed, yield the risk of the endpoint of interest. As an example, tumor prevalence data in mice are used to estimate the probability of the induction of mouse Harderian-gland tumor per year on an extramagnetospheric mission inside an idealized shielding configuration of a spherical 1 g/sq cm hick aluminum shell. Results indicate a yearly tumor prevalence of 0.06 at solar minimum conditions, with 60 percent of this arising from charge components with Z between 10 and 28, and two-thirds of the contribution arising from LET components between 10 and 200 keV/micron.

Curtis, S. B.↗

A study of the generation of linear energy transfer spectra for space radiations

The conversion of particle-energy spectra into a linear energy transfer (LET) distribution is a guide in assessing biologically significant components. The mapping of LET to energy is triple valued and can be defined only on open subintervals. A well-defined numerical procedure is found to allow generation of LET spectra on the open subintervals that are integrable in spite of their singular nature.

Wilson, John W.↗

Semiempirical fragmentation models on galactic cosmic ray transport calculations with hydrogen target

Nuclear fragmentation cross sections of Silberberg and Tsao that are more accurate for a hydrogen target were implemented in the data base to replace those of Rudstam for a galactic cosmic ray transport code (HZETRN). Sample calculations were made for the transported galactic cosmic ray flux through a liquid hydrogen shield at solar minimum condition to determine the effect of such a change. The transported flux based on the Silberberg-Tsao semiempirical formalism contains fewer high-LET (linear energy transfer) components but more low-LET components than the results based on Rudstam's formalism: and this disparity deepens as the shield thickness increases. A comparison of the results obtained from using both energy-dependent and energy-independent cross sections of Silberberg and Tsao indicates that the energy-independent assumption results in an underestimation of high-LET flux above 100 keV/micron by approximately 40 percent for a 15-g/cm(sup 2) thickness of liquid hydrogen. Similar results were obtained in a previous study when both energy-dependent and energy-independent cross sections of Rudstam were considered. Nonetheless, the present study found that an energy-independent calculation would be best accomplished by using Rudstam's cross sections as done in the past for various engineering applications.

Shinn, Judy L.↗

Mutagenic effects of heavy ion radiation in plants

Genetic and developmental effects of heavy ions in maize and rice were investigated. Heavy particles with various charges and energies were accelerated at the BEVALAC. The frequency of occurrence of white-yellow stripes on leaves of plants developed from irradiated maize seeds increased linearly with dose, and high Linear Energy Transfer (LET) heavy charged particles, e.g., neon, argon, and iron, were 2-12 times as effective as gamma rays in inducing this type of mutation. The effectiveness of high-LET heavy ion in (1) inhibiting rice seedling growth, (2) reducing plant fertility, (3) inducing chromosome aberration and micronuclei in root tip cells and pollen mother cells of the first generation plants developed from exposed seeds, and (4) inducing mutation in the second generation, were greater than that of low-LET gamma rays. All effects observed were dose-dependent; however, there appeared to be an optimal range of doses for inducing certain types of mutation, for example, for argon ions (400 MeV/u) at 90-100 Gy, several valuable mutant lines with favorable characters, such as semidwarf, early maturity and high yield ability, were obtained. Experimental results suggest that the potential application of heavy ions in crop improvement is promising. Restriction-fragment-length-polymorphism (RFLP) analysis of two semidwarf mutants induced by argon particles revealed that large DNA alterations might be involved in these mutants.

Mei, M.↗

A study of the radiation environment on board the space shuttle flight STS-57

A joint NASA-Russian study of the radiation environment inside a SPACEHAB 2 locker on space shuttle flight STS-57 was conducted. The shuttle flew in a nearly circular orbit of 28.5 deg inclination and 462 km altitude. The locker carried a charged particle spectrometer, a tissue equivalent proportional counter (TEPC), and two area passive detectors consisting of combined NASA plastic nuclear track detectors (PNTD's) and thermoluminescent detectors (TLD's), and Russian nuclear emulsions, PNTD's, and TLD's. All the detector systems were shielded by the same shuttle mass distribution. This makes possible a direct comparison of the various dose measurement techniques. In addition, measurements of the neutron energy spectrum were made using the proton recoil technique. The results show good agreement between the integral LET spectrum of the combined galactic and trapped particles using the tissue equivalent proportional counter and track detectors between about 15 keV/micron and 200 keV/micron. The LET spectrum determined from nuclear emulsions was systematically lower by about 50%, possibly due to emulsion fading. The results show that the TEPC measured an absorbed dose 20% higher than TLD's, due primarily to an increased TEPC response to neutrons and a low sensitivity of TLD's to high LET particles under normal processing techniques. There is a significant flux of high energy neutrons that is currently not taken into consideration in dose equivalent calculations. The results of the analysis of the spectrometer data will be reported separately.

Badhwar, G. D.↗

HZE reactions and data-base development

The primary cosmic rays are dispersed over a large range of linear energy transfer (LET) values and their distribution over LET is a determinant of biological response. This LET distribution is modified by radiation shielding thickness and shield material composition. The current uncertainties in nuclear cross sections will not allow the composition of the shield material to be distinguished in order to minimize biological risk. An overview of the development of quantum mechanical models of heavy ion reactions will be given and computational results compared with experiments. A second approach is the development of phenomenological models from semi-classical considerations. These models provide the current data base in high charge and energy (HZE) shielding studies. They will be compared with available experimental data. The background material for this lecture will be available as a review document of over 30 years of research at Langley but will include new results obtained over the last year.

Townsend, Lawrence W.↗

An Examination of Environment Perturbation Effects on Single Event Upset Rates

This paper presents an analysis of the sensitivity of single event upset (SEU) rate predictions to changes in the direct ionization-inducing environment. An examination based on the nature of the SEU rate equation is presented for the case in which the perturbation is constant across varying particle linear energy transfer (LET). It is shown that the relative variation in SEU rate is equal to the relative perturbation in flux. Results are also presented for the case in which the environment perturbations exist in small LET bins. Through this analysis it is shown that the relative variation in expected SEU rate is equal to that in flux only for the LET regime in which the product of the cross section and differential flux is maximum.

Gates, Michele M.↗

Relative Efficiency of TLD-100 to High Linear Energy Transfer Radiation: Correction to Astronaut Absorbed Dose

Response of thermoluminescent detectors (TLD-100) to high linear energy transfer (LET) particles has been studied using helium, carbon, silicon, and iron ions from the Heavy Ion Medical Accelerator at Chiba (Japan), iron ions from the Brookhaven National Laboratory (NY) Alternate Gradient Synchrotron, and 53, 134, 185, and 232 MeV protons from the Loma Linda accelerator. Using the measured relative (to 137Cs) dose efficiency, and measured LET spectra from a tissue equivalent proportional counter (TEPC) on 20 Space Shuttle flights, and 7 Mir flights, the underestimation of absorbed dose by these detectors has been evaluated. The dose underestimation is between 15-20% depending upon the flight inclination and shielding location. This has been confirmed by direct correlation of measured dose by TEPC and TLD-100 at a low shielded location in the Shuttle mid-deck. A comparison of efficiency- LET data with a compilation of similar data from TLD-700, shows that shapes of the two curves are nearly identical, but that the TLD-100 curve is systematically lower by about 13%, and is the major cause of dose underestimation. These results strongly suggest that TLDs used for crew dose estimation be regularly calibrated using heavy ions.

Badhwar, G. D.↗

Relative Efficiency of TLD-100 to Linear Energy Transfer Radiation: Correction to Astronaut Absorbed Dose

Response of thermoluminescent detectors (TLD-100) to high linear energy transfer (LET) particles has been studied using helium, carbon, silicon, and iron ions from the Heavy Ion Medical Accelerator at Chiba (Japan), iron ions from the Brookhaven National Laboratory (NY) Alternate Gradient Synchrotron, and 53, 134, 185, and 232 MeV protons from the Loma Linda accelerator. Using the measured relative (to (137)Cs dose efficiency, and measured LET spectra from a tissue equivalent proportional counter (TEPC) on 20 Space Shuttle flights, and 7 Mir flights, the underestimation of absorbed dose by these detectors has been evaluated. The dose underestimation is between 15-20% depending upon the flight inclination and shielding location. This has been confirmed by direct correlation of measured dose by TEPC and TLD-100 at a low shielded location in the Shuttle mid-deck. A comparison of efficiency- LET data with a compilation of similar data from TLD-700, shows that shapes of the two curves are nearly identical, but that the TLD-100 curve is systematically lower by about 13%, and is the major cause of dose underestimation. These results strongly suggest that TLDs used for crew dose estimation be regularly calibrated using heavy ions.

Badhwar, Gautam D.↗

A Nuclear Interaction Model for Understanding Results of Single Event Testing with High Energy Protons

An internuclear cascade and evaporation model has been adapted to estimate the LET spectrum generated during testing with 200 MeV protons. The model-generated heavy ion LET spectrum is compared to the heavy ion LET spectrum seen on orbit. This comparison is the basis for predicting single event failure rates from heavy ions using results from a single proton test. Of equal importance, this spectra comparison also establishes an estimate of the risk of encountering a failure mode on orbit that was not detected during proton testing. Verification of the general results of the model is presented based on experiments, individual part test results, and flight data. Acceptance of this model and its estimate of remaining risk opens the hardware verification philosophy to the consideration of radiation testing with high energy protons at the board and box level instead of the more standard method of individual part testing with low energy heavy ions.

Culpepper, William X.↗