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NASA NTRSDate not supplied

Effects of Low Dose Radiation and Radiation Countermeasures on Infection by Spaceflight Analogue Cultured Salmonella Using 3-D Biomimetic Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1.Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. We have completed infection studies of the 3-D biomimetic intestinal tissue models and are currently analyzing the data.

Jennifer Barrila↗

NASA NTRSDate not supplied

Effects of Low Dose Radiation and Radiation Countermeasures on Infection by Spaceflight Analogue Cultured Salmonella Using 3-D Biomimetic Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1. Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. This study has been initiated and data collection is beginning.

Jennifer Barrila↗

NASA NTRS2022

Si5345, SY88422L, LT3482, and MSK130 components Total Ionizing Dose Test Report

The purpose of this test was to characterize the SI-5345, SY88422L, LT3482 and MSK130 parameter degradation for total dose response. The components are associated with REAG ID #21-024. In the test, each device was exposed to high dose rate (HDR) irradiation using gamma radiation. Device parameters such as leakage currents, timing, and overall chip health were investigated. These devices were tested for an interstellar mission on a trajectory between 0.9 AU and 5.3 AU with a 2.5-year mission, yielding an expected overall dose of 29 krad(Si)behind 1 mm of aluminum shielding (at 95% confidence; environment and dose determined through SPENVIS). This test report gives an initial look at candidate parts. Extremely small sample sizes (only 1 or 2 devices tested) do not allow consideration of part-to-part variability. High dose rates were used despite LT3482 and MSK130 having potential enhanced low dose rate sensitivity (ELDRS). Care should be taken in interpreting results given these limitations.

Total Ionizing Dose (TID)↗

NASA NTRS1996

Quantitative assessment of the cataractogenic potential of very low doses of neutrons

We report on the prevalence and relative biological effectiveness (RBE) for various stages of lens opacification in rats induced by very low doses (2 to 250 mGy) of medium-energy (440 keV) neutrons, compared to those for X rays. Neutron doses were delivered either in a single fraction or in four separate fractions and the irradiated animals were followed for over 100 weeks. At the highest observed dose (250 mGy) and at early observation times, there was evidence of an inverse dose-rate effect; i.e., a fractionated exposure was more potent than a single exposure. Neutron RBEs relative to X rays were estimated using a non-parametric technique. The results were only weakly dependent on time postirradiation. At 30 weeks, for example, 80% confidence intervals for the RBE of acutely delivered neutrons relative to X rays were 8-16 at 250 mGy, 10-20 at 50 mGy, 50-100 at 10 mGy and 250-500 at 2 mGy. The results are consistent with the estimated neutron RBEs in Japanese A-bomb survivors, though broad confidence bounds are present in the Japanese results. Our findings are also consistent with data reported earlier for cataractogenesis induced by heavy ions in rats, mice, and rabbits. We conclude from these results that, at very low doses (<10 mGy), the RBE for neutron-induced cataractogenesis is considerably larger than the RBE of 20 commonly used, and use of a significantly larger value for calculating equivalent dose would be prudent.

NASA Discipline Radiation Health↗

NASA NTRS2004

Role of shielding in modulating the effects of solar particle events: Monte Carlo calculation of absorbed dose and DNA complex lesions in different organs

Distributions of absorbed dose and DNA clustered damage yields in various organs and tissues following the October 1989 solar particle event (SPE) were calculated by coupling the FLUKA Monte Carlo transport code with two anthropomorphic phantoms (a mathematical model and a voxel model), with the main aim of quantifying the role of the shielding features in modulating organ doses. The phantoms, which were assumed to be in deep space, were inserted into a shielding box of variable thickness and material and were irradiated with the proton spectra of the October 1989 event. Average numbers of DNA lesions per cell in different organs were calculated by adopting a technique already tested in previous works, consisting of integrating into "condensed-history" Monte Carlo transport codes--such as FLUKA--yields of radiobiological damage, either calculated with "event-by-event" track structure simulations, or taken from experimental works available in the literature. More specifically, the yields of "Complex Lesions" (or "CL", defined and calculated as a clustered DNA damage in a previous work) per unit dose and DNA mass (CL Gy-1 Da-1) due to the various beam components, including those derived from nuclear interactions with the shielding and the human body, were integrated in FLUKA. This provided spatial distributions of CL/cell yields in different organs, as well as distributions of absorbed doses. The contributions of primary protons and secondary hadrons were calculated separately, and the simulations were repeated for values of Al shielding thickness ranging between 1 and 20 g/cm2. Slight differences were found between the two phantom types. Skin and eye lenses were found to receive larger doses with respect to internal organs; however, shielding was more effective for skin and lenses. Secondary particles arising from nuclear interactions were found to have a minor role, although their relative contribution was found to be larger for the Complex Lesions than for the absorbed dose, due to their higher LET and thus higher biological effectiveness. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Non-NASA Center↗

NASA NTRS1993

Comparison of Gavage, Water Bottle, and a High-Moisture Diet Bolus as Dosing Methods for Quantitative D-xylose Administration to B6D2F1 (Mus musculus) Mice

Gavage, water bottle, and diet incorporation are 3 dosing methods used orally to administer test compounds to rodents. These 3 methods were compared in mice to determine which represented the most quantitative delivery system. For dietary incorporation, a high-moisture bolus form of NIH-31 rodent meal was developed using hydroxypropyl methylcellulose as an autoclave-stable binding agent. A high-moisture bolus were selected to increase the acceptability of the dosed diet and to promote quantitative consumption through reduced wastage. The test compound used was D-xylose, a pentose sugar that may be quantitatively detected, colorimetrically, in urine following oral dosing. Six male and 6 female B6D2FI mice were placed in metabolism cages and dosed with a known quantity of D-xylose by each of the 3 methods. Urine was collected before and after each method of administration and analysed for total D-xylose; the per cent recovery was based upon the amount of D-xylose consumed. Quantitative consumption was apparently greatest for water bottle dosing with an average recovery of 56.0% of the original D-xylose dose. High-moisture bolus incorporation ranked second with 50.0% D-xylose recovery, and gavage was third with 41.0% D-xylose recovery.

Zimmer, J. Paul↗

NASA NTRS1999

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.↗

NASA NTRS1999

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.↗

NASA NTRS2002

Shuttle radiation dose measurements in the International Space Station orbits

The International Space Station (ISS) is now a reality with the start of a permanent human presence on board. Radiation presents a serious risk to the health and safety of the astronauts, and there is a clear requirement for estimating their exposures prior to and after flights. Predictions of the dose rate at times other than solar minimum or solar maximum have not been possible, because there has been no method to calculate the trapped-particle spectrum at intermediate times. Over the last few years, a tissue-equivalent proportional counter (TEPC) has been flown at a fixed mid-deck location on board the Space Shuttle in 51.65 degrees inclination flights. These flights have provided data that cover the expected changes in the dose rates due to changes in altitude and changes in solar activity from the solar minimum to the solar maximum of the current 23rd solar cycle. Based on these data, a simple function of the solar deceleration potential has been derived that can be used to predict the galactic cosmic radiation (GCR) dose rates to within +/-10%. For altitudes to be covered by the ISS, the dose rate due to the trapped particles is found to be a power-law function, rho(-2/3), of the atmospheric density, rho. This relationship can be used to predict trapped dose rates inside these spacecraft to +/-10% throughout the solar cycle. Thus, given the shielding distribution for a location inside the Space Shuttle or inside an ISS module, this approach can be used to predict the combined GCR + trapped dose rate to better than +/-15% for quiet solar conditions.

NASA Discipline Radiation Health↗

NASA NTRS1996

Measurement of LET distribution and dose equivalent on board the space shuttle STS-65

Space radiation dosimetry measurements have been made on board the Space Shuttle STS-65 in the Second International Microgravity Laboratory (IML-2). In these measurements, three kinds of detectors were used; one is a newly developed active detector telescope called "Real-time Radiation Monitoring Device (RRMD)" utilizing silicon semi-conductor detectors and others are conventional detectors of thermoluminescence dosimeters (TLDs) and CR-39 plastic track detectors. Using the RRMD detector, the first attempt of real-time monitoring of space radiation has been achieved successfully for a continuous period of 251.3 h, giving the temporal variations of LET distribution, particle count rates, and rates of absorbed dose and dose equivalent. The RRMD results indicate that a clear enhancement of the number of trapped particles is seen at the South Atlantic Anomaly (SAA) without clear enhancement of dose equivalent, while some daily periodic enhancements of dose equivalent due to high LET particles are seen at the lower geomagnetic cutoff regions for galactic cosmic ray particles (GCRs). Therefore, the main contribution to dose equivalent is seen to be due to GCRs in this low altitude mission (300 km). Also, the dose equivalent rates obtained by TLDs and CR-39 ranged from 146.9 to 165.2 microSv/day and the average quality factors from 1.45 to 1.57 depending on the locations and directions of detectors inside the Space-lab at this highly protected orbit for space radiation with a small inclination (28.5 degrees) and a low altitude (300 km). The LET distributions obtained by two different detectors, RRMD and CR-39, are in good agreement in the region of 15-200 keV/mm and difference of these distributions in the regions of LET < 15 keV/mm and LET > 200 keV/mm can be explained by considering characteristics of CR-39 etched track formation especially for the low LET tracks.

manned↗

NASA NTRS1996

The calculation of radial dose from heavy ions: predictions of biological action cross sections

The track structure model of heavy ion cross sections was developed by Katz and co-workers in the 1960s. In this model the action cross section is evaluated by mapping the dose-response of a detector to gamma rays (modeled from biological target theory) onto the radial dose distribution from delta rays about the path of the ion. This is taken to yield the radial distribution of probability for a "hit" (an interaction leading to an observable end-point). Radial integration of the probability yields the cross section. When different response from ions of different Z having the same stopping power is observed this model may be indicated. Since the 1960s there have been several developments in the computation of the radial dose distribution, in the measurement of these distributions, and in new radiobiological data against which to test the model. The earliest model, by Butts and Katz made use of simplified delta ray distribution functions, of simplified electron range-energy relations, and neglected angular distributions. Nevertheless it made possible the calculation of cross sections for the inactivation of enzymes and viruses, and allowed extension to tracks in nuclear emulsions and other detectors and to biological cells. It set the pattern for models of observable effects in the matter through which the ion passed. Here we outline subsequent calculations of radial dose which make use of improved knowledge of the electron emission spectrum, the electron range-energy relation, the angular distribution, and some considerations of molecular excitation, of particular interest both close to the path of the ion and the outer limits of electron penetration. These are applied to the modeling of action cross sections for the inactivation of several strains of E-coli and B. subtilis spores where extensive measurements in the "thin-down" region have been made with heavy ion beams. Such calculations serve to test the radial dose calculations at the outer limit of electron penetration. We lack data from which to test these calculations in regions close to the path of the ion aside from our earliest work on latent tracks in plastics, though it appears that the criterion then suggested for the threshold of track formation, of a minimal dose at a minimal distance (of about 20 angstroms, in plastics), remains valid.

NASA Discipline Radiation Health↗

NASA NTRS2010

Overview of Graphical User Interface for ARRBOD (Acute Radiation Risk and BRYNTRN Organ Dose Projection)

Solar particle events (SPEs) pose the risk of acute radiation sickness (ARS) to astronauts, because organ doses from large SPEs may reach critical levels during extra vehicular activities (EVAs) or lightly shielded spacecraft. NASA has developed an organ dose projection model of Baryon transport code (BRYNTRN) with an output data processing module of SUMDOSE, and a probabilistic model of acute radiation risk (ARR). BRYNTRN code operation requires extensive input preparation, and the risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. With a graphical user interface (GUI) to handle input and output for BRYNTRN, these response models can be connected easily and correctly to BRYNTRN in a user friendly way. The GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. Assessment of astronauts organ doses and ARS from the exposure to historically large SPEs is in support of mission design and operation planning to avoid ARS and stay within the current NASA short-term dose limits. The ARRBOD GUI will serve as a proof-of-concept for future integration of other risk projection models for human space applications. We present an overview of the ARRBOD GUI product, which is a new self-contained product, for the major components of the overall system, subsystem interconnections, and external interfaces.

Kim, Myung-Hee Y.↗

NASA NTRS2010

Calculation of Dose Deposition in Nanovolumes and Simulation of gamma-H2AX Experiments

Monte-Carlo track structure simulations can accurately simulate experimental data: a) Frequency of target hits. b) Dose per event. c) Dose per ion. d) Radial dose. The dose is uniform in micrometers sized voxels; at the nanometer scale, the difference in energy deposition between high and low-LET radiations appears. The calculated 3D distribution of dose voxels, combined with chromosomes simulated by random walk is very similar to the distribution of DSB observed with gamma-H2AX experiments. This is further evidenced by applying a visualization threshold on dose.

Plante, Ianik↗

NASA NTRSDate not supplied

Madidrop for Passive Silver Dosing

Madidrop is a rectangular ceramic tablet originally designed to dose a 10-20-liter volume of water with silver to act as a biocide for remote communities with unreliable water sources. Silver as a biocide is a proposed method to control bacteria on the International Space Station or future Artemis missions. This would replace iodine currently used due to issues with a dual biocide system in place between Russian and US segments and the extra cost of iodine removal required before consumption. NASA has been reviewing this Madidrop technology and its potential application with a water reclamation system on orbit to dose silver after purifying the water. While there are a couple alternative methods to dosing silver on station, this method is like the existing passive dosing method used currently to dose iodine. Tests conducted characterize the manufacturer’s original intent to leave the tablet in a tank for a specified amount of time before removing and testing alternative passive flow-through methods. Passive flow testing involved two options: keeping the tablet intact or crushing the tablet into smaller particle sizes to increase the surface area while varying particle sizes. The results of these tests revealed a large amount of silver output at first that quickly reduced to a constant lower output within a reasonable dosing concentration range. The initial high concentration peaks after a couple days of quiescence and could be useful for shocking the initial tank water contents. Madidrop used as a passive particle doser could act as a stand-in replacement for iodine in future spaceflight water reclamation systems.

Ryan Ogilvie↗

NASA NTRS2024

Madidrop for Passive Silver Dosing

Ryan Ogilvie↗

NASA NTRS1987

Enhancement of phototropic response to a range of light doses in Triticum aestivum coleoptiles in clinostat-simulated microgravity

The phototropic dose-response relationship has been determined for Triticum aestivum cv. Broom coleoptiles growing on a purpose-built clinostat apparatus providing gravity compensation by rotation about a horizontal axis at 2 rev min-1. These data are compared with data sets obtained with the clinostat axis vertical and stationary, as a 1 g control, and rotating vertically to examine clinostat effects other than gravity compensation. Triticum at 1 g follows the well-established pattern of other cereal coleoptiles with a first positive curvature at low doses, followed by an indifferent response region, and a second positive response at progressively increasing doses. However, these response regions lie at higher dose levels than reported for Avena. There is no significant difference between the responses observed with the clinostat axis vertical in the rotating and stationary modes, but gravity compensation by horizontal rotation increases the magnitude of first and second positive curvatures some threefold at 100 min after stimulation. The indifferent response is replaced by a significant curvature towards the light source, but remains apparent as a reduced curvature response at these dose levels.

Non-NASA Center↗

NASA NTRS2011

Dose Rate Effects in Linear Bipolar Transistors

Dose rate effects are examined in linear bipolar transistors at high and low dose rates. At high dose rates, approximately 50% of the damage anneals at room temperature, even though these devices exhibit enhanced damage at low dose rate. The unexpected recovery of a significant fraction of the damage after tests at high dose rate requires changes in existing test standards. Tests at low temperature with a one-second radiation pulse width show that damage continues to increase for more than 3000 seconds afterward, consistent with predictions of the CTRW model for oxides with a thickness of 700 nm.

linear integrated circuit↗

NASA NTRS1972

Methods of space radiation dose analysis with applications to manned space systems

The full potential of state-of-the-art space radiation dose analysis for manned missions has not been exploited. Point doses have been overemphasized, and the critical dose to the bone marrow has been only crudely approximated, despite the existence of detailed man models and computer codes for dose integration in complex geometries. The method presented makes it practical to account for the geometrical detail of the astronaut as well as the vehicle. Discussed are the major assumptions involved and the concept of applying the results of detailed proton dose analysis to the real-time interpretation of on-board dosimetric measurements.

Langley, R. W.↗