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All sourcesNASA NTRSDOE OSTI
NASA NTRS2010

Monte-Carlo Simulation of Radiation Track Structure and Calculation of Dose Deposition in Nanovolumes

INTRODUCTION: The radiation track structure is of crucial importance to understand radiation damage to molecules and subsequent biological effects. Of a particular importance in radiobiology is the induction of double-strand breaks (DSBs) by ionizing radiation, which are caused by clusters of lesions in DNA, and oxidative damage to cellular constituents leading to aberrant signaling cascades. DSB can be visualized within cell nuclei with gamma-H2AX experiments. MATERIAL AND METHODS: In DSB induction models, the DSB probability is usually calculated by the local dose obtained from a radial dose profile of HZE tracks. In this work, the local dose imparted by HZE ions is calculated directly from the 3D Monte-Carlo simulation code RITRACKS. A cubic volume of 5 micron edge (Figure 1) is irradiated by a (Fe26+)-56 ion of 1 GeV/amu (LET approx.150 keV/micron) and by a fluence of 450 H+ ions, 300 MeV/amu (LET approx. 0.3 keV/micron). In both cases, the dose deposited in the volume is approx.1 Gy. The dose is then calculated into each 3D pixels (voxels) of 20 nm edge and visualized in 3D. RESULTS AND DISCUSSION: The dose is deposited uniformly in the volume by the H+ ions. The voxels which receive a high dose (orange) corresponds to electron track ends. The dose is deposited differently by the 56Fe26+ ion. Very high dose (red) is deposited in voxels with direct ion traversal. Voxels with electron track ends (orange) are also found distributed around the path of the track. In both cases, the appearance of the dose distribution looks very similar to DSBs seen in gammaH2AX experiments, particularly when the visualization threshold is applied. CONCLUSION: The refinement of the dose calculation to the nanometer scale has revealed important differences in the energy deposition between high- and low-LET ions. Voxels of very high dose are only found in the path of high-LET ions. Interestingly, experiments have shown that DSB induced by high-LET radiation are more difficult to repair. Therefore, this new approach may be useful to understand the nature of DSB and oxidative damage induced by ionizing radiation.

Plante, I.↗
NASA NTRS2011

The Biological Effectiveness of Different Radiation Qualities for the Induction of Chromosome Damage in Human Lymphocytes

Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to Si-28-ions with energies ranging from 90 to 600 MeV/u, Ti-48-ions with energies ranging from 240 to 1000 MeV/u, or to Fe-56-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Si beams in this study ranged from 48 to 158 keV/ m, the LET of the Ti ions ranged from 107 to 240 keV/micron, and the LET of the Fe-ions ranged from 145 to 440 keV/ m. Doses delivered were in the 10- to 200-cGy range. Dose-response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose-response curve for chromosome damage with respect to gamma-rays. The estimates of RBEmax values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, 21.4+/-1.7 to 28.3+/-2.4 for Ti ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBEmax value for Fe ions was obtained with the 600 MeV/u beam, the highest RBEmax value for Ti ions was obtained 1000 MeV/u beam, and the highest RBEmax value for Si ions was obtained with the 170 MeV/u beam. For Si and Fe ions the RBEmax values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/micron for Si, and decreasing with further increase in LET. Additional studies for low doses Si-28-ions down to 0.02 Gy will be discussed.

Hada, M.↗
NASA NTRS2014

Radiation Quality Effects on Transcriptome Profiles in 3-d Cultures After Particle Irradiation

In this work, we evaluate the differential effects of low- and high-LET radiation on 3-D organotypic cultures in order to investigate radiation quality impacts on gene expression and cellular responses. Reducing uncertainties in current risk models requires new knowledge on the fundamental differences in biological responses (the so-called radiation quality effects) triggered by heavy ion particle radiation versus low-LET radiation associated with Earth-based exposures. We are utilizing novel 3-D organotypic human tissue models that provide a format for study of human cells within a realistic tissue framework, thereby bridging the gap between 2-D monolayer culture and animal models for risk extrapolation to humans. To identify biological pathway signatures unique to heavy ion particle exposure, functional gene set enrichment analysis (GSEA) was used with whole transcriptome profiling. GSEA has been used extensively as a method to garner biological information in a variety of model systems but has not been commonly used to analyze radiation effects. It is a powerful approach for assessing the functional significance of radiation quality-dependent changes from datasets where the changes are subtle but broad, and where single gene based analysis using rankings of fold-change may not reveal important biological information. We identified 45 statistically significant gene sets at 0.05 q-value cutoff, including 14 gene sets common to gamma and titanium irradiation, 19 gene sets specific to gamma irradiation, and 12 titanium-specific gene sets. Common gene sets largely align with DNA damage, cell cycle, early immune response, and inflammatory cytokine pathway activation. The top gene set enriched for the gamma- and titanium-irradiated samples involved KRAS pathway activation and genes activated in TNF-treated cells, respectively. Another difference noted for the high-LET samples was an apparent enrichment in gene sets involved in cycle cycle/mitotic control. It is plausible that the enrichment in these particular pathways results from the complex DNA damage resulting from high-LET exposure where repair processes are not completed during the same time scale as the less complex damage resulting from low-LET radiation.

Patel, Z. S.↗
NASA NTRS2017

Modeling Space Radiation with Radiomimetic Agent Bleomycin

Space radiation consists of proton and helium from solar particle events (SPE) and high energy heavy ions from galactic cosmic ray (GCR). This mixture of radiation with particles at different energy levels has different effects on biological systems. Currently, majority studies of radiation effects on human were based on single-source radiation due to the limitation of available method to model effects of space radiation on living organisms. While NASA Space Radiation Laboratory is working on advanced switches to make it possible to have a mixed field radiation with particles of different energies, the radiation source will be limited. Development of an easily available experimental model for studying effects of mixed field radiation could greatly speed up our progress in our understanding the molecular mechanisms of damage and responses from exposure to space radiation, and facilitate the discovery of protection and countermeasures against space radiation, which is critical for the mission to Mars. Bleomycin, a radiomimetic agent, has been widely used to study radiation induced DNA damage and cellular responses. Previously, bleomycin was often compared to low low Linear Energy Transfer (LET) gamma radiation without defined characteristics. Our recent work demonstrated that bleomycin could induce complex clustered DNA damage in human fibroblasts that is similar to DNA damage induced by high LET radiation. These type of DNA damage is difficult to repair and can be visualized by gamma-H2Ax staining weeks after the initial insult. The survival ratio between early and late plating of human fibroblasts after bleomycin treatment is between low LET and high LET radiation. Our results suggest that bleomycin induces DNA damage and other cellular stresses resembling those resulted from mixed field radiation with both low and high LET particles. We hypothesize that bleomycin could be used to mimic space radiation in biological systems. Potential advantages and limitations of using bleomycin to treat biological specimen as an easily available model to study effects of space radiation on biological systems and to develop countermeasures for space radiation associated risks will be discussed.

Lu, Tao↗
NASA NTRS2017

DNA Repair Domain Modeling Can Predict Cell Death and Mutation Frequency for Wide Range Spectrum of Radiation

Exploration missions to Mars and other destinations raise many questions about the health of astronauts. The continuous exposure of astronauts to galactic cosmic rays is one of the main concerns for long-term missions. Cosmic ionizing radiations are composed of different ions of various charges and energies notably, highly charged energy (HZE) particles. The HZE particles have been shown to be more carcinogenic than low-LET radiation, suggesting the severity of chromosomal aberrations induced by HZE particles is one possible explanation. However, most mathematical models predicting cell death and mutation frequency are based on directly fitting various HZE dose response and are in essence empirical approaches. In this work, we assume a simple biological mechanism to model DNA repair and use it to simultaneously explain the low- and high-LET response using the exact same fitting parameters. Our work shows that the geometrical position of DNA repair along tracks of heavy ions are sufficient to explain why high-LET particles can induce more death and mutations. Our model is based on assuming DNA double strand breaks (DSBs) are repaired within repair domain, and that any DSBs located within the same repair domain cluster into one repair unit, facilitating chromosomal rearrangements and increasing the probability of cell death. We introduced this model in 2014 using simplified microdosimetry profiles to predict cell death. In this work, we collaborated with NASA Johnson Space Center to generate more accurate microdosimetry profiles derived by Monte Carlo techniques, taking into account track structure of HZE particles and simulating DSBs in realistic cell geometry. We simulated 224 data points (D, A, Z, E) with the BDSTRACKS model, leading to a large coverage of LET from ~10 to 2,400 keV/μm. This model was used to generate theoretical RBE for various particles and energies for both cell death and mutation frequencies. The RBE LET dependence is in agreement with experimental data known in human and murine cells. It suggests that cell shape and its orientation with respect to the HZE particle beam can modify the biological response to radiation. Such discovery will be tested experimentally and, if proven accurate, will be another strong supporting evidence for DNA repair domains and their critical role in interpreting cosmic radiation sensitivity.

Viger, Louise↗
NASA NTRS1979

The condition of a finite Markov chain and perturbation bounds for the limiting probabilities

The inequalities bounding the relative error the norm of w- w squiggly/the norm of w are exhibited by a very simple function of E and A. Let T denote the transition matrix of an ergodic chain, C, and let A = I - T. Let E be a perturbation matrix such that T squiggly = T - E is also the transition matrix of an ergodic chain, C squiggly. Let w and w squiggly denote the limiting probability (row) vectors for C and C squiggly. The inequality is the best one possible. This bound can be significant in the numerical determination of the limiting probabilities for an ergodic chain. In addition to presenting a sharp bound for the norm of w-w squiggly/the norm of w an explicit expression for w squiggly will be derived in which w squiggly is given as a function of E, A, w and some other related terms.

Meyer, C. D., Jr.↗
NASA NTRS1984

A summary of JPL single event upset test data from May 1982, through January 1984

A summary of single event upset data for 42 device types (including RAMs, 4-bit slices, microprocessors, 4-bit counters, and flip-flops) studied at 11 different accelerator tests (performed chiefly with the Berkeley 88-inch cyclotron and the Cal Tech Van de Graaff) is presented. All bipolar and NMOS RAMs were found to be SEU sensitive, some with very low LET thresholds. Some CMOS or CMOS/SOS RAMs were hard; and the CMOS microprocessors were hard, but the bipolar and NMOS microprocessors were soft. Several devices were found to exhibit a cross section that depends strongly on LET, even when the LET is well above the LET threshold. A ranking of hardness is presented for the logic devices tested.

Nichols, D. K.↗
NASA NTRS1987

Isotropic probability measures in infinite dimensional spaces: Inverse problems/prior information/stochastic inversion

Let R be the real numbers, R(n) the linear space of all real n-tuples, and R(infinity) the linear space of all infinite real sequences x = (x sub 1, x sub 2,...). Let P sub n :R(infinity) approaches R(n) be the projection operator with P sub n (x) = (x sub 1,...,x sub n). Let p(infinity) be a probability measure on the smallest sigma-ring of subsets of R(infinity) which includes all of the cylinder sets P sub n(-1) (B sub n), where B sub n is an arbitrary Borel subset of R(n). Let p sub n be the marginal distribution of p(infinity) on R(n), so p sub n(B sub n) = p(infinity)(P sub n to the -1(B sub n)) for each B sub n. A measure on R(n) is isotropic if it is invariant under all orthogonal transformations of R(n). All members of the set of all isotropic probability distributions on R(n) are described. The result calls into question both stochastic inversion and Bayesian inference, as currently used in many geophysical inverse problems.

Backus, George↗
NASA NTRS1987

Isotropic probability measures in infinite-dimensional spaces

Let R be the real numbers, R(n) the linear space of all real n-tuples, and R(infinity) the linear space of all infinite real sequences x = (x sub 1, x sub 2,...). Let P sub in :R(infinity) approaches R(n) be the projection operator with P sub n (x) = (x sub 1,...,x sub n). Let p(infinity) be a probability measure on the smallest sigma-ring of subsets of R(infinity) which includes all of the cylinder sets P sub n(-1) (B sub n), where B sub n is an arbitrary Borel subset of R(n). Let p sub n be the marginal distribution of p(infinity) on R(n), so p sub n(B sub n) = p(infinity) (P sub n to the -1 (B sub n)) for each B sub n. A measure on R(n) is isotropic if it is invariant under all orthogonal transformations of R(n). All members of the set of all isotropic probability distributions on R(n) are described. The result calls into question both stochastic inversion and Bayesian inference, as currently used in many geophysical inverse problems.

Backus, George↗
NASA NTRS1991

Prediction of error rates in dose-imprinted memories on board CRRES by two different methods

An analysis of the expected space radiation effects on the single event upset (SEU) properties of CMOS/bulk memories onboard the Combined Release and Radiation Effects Satellite (CRRES) is presented. Dose-imprint data from ground test irradiations of identical devices are applied to the predictions of cosmic-ray-induced space upset rates in the memories onboard the spacecraft. The calculations take into account the effect of total dose on the SEU sensitivity of the devices as the dose accumulates in orbit. Estimates of error rates, which involved an arbitrary selection of a single pair of threshold linear energy transfer (LET) and asymptotic cross-section values, were compared to the results of an integration over the cross-section curves versus LET. The integration gave lower upset rates than the use of the selected values of the SEU parameters. Since the integration approach is more accurate and eliminates the need for an arbitrary definition of threshold LET and asymptotic cross section, it is recommended for all error rate predictions where experimental sigma-versus-LET curves are available.

Brucker, G. J.↗
NASA NTRS1993

Potential health effects of space radiation

Crewmembers on missions to the Moon or Mars will be exposed to radiation belts, galactic cosmic rays, and possibly solar particle events. The potential health hazards due to these space radiations must be considered carefully to ensure the success of space exploration. Because there is no human radioepidemiological data for acute and late effects of high-LET (Linear-Energy-Transfer) radiation, the biological risks of energetic charged particles have to be estimated from experimental results on animals and cultured cells. Experimental data obtained to date indicate that charged particle radiation can be much more effective than photons in causing chromosome aberrations, cell killing, mutation, and tumor induction. The relative biological effectiveness (RBE) varies with biological endpoints and depends on the LET of heavy ions. Most lesions induced by low-LET radiation can be repaired in mammalian cells. Energetic heavy ions, however, can produce large complex DNA damages, which may lead to large deletions and are irreparable. For high-LET radiation, therefore, there are less or no dose rate effects. Physical shielding may not be effective in minimizing the biological effects on energetic heavy ions, since fragments of the primary particles can be effective in causing biological effects. At present the uncertainty of biological effects of heavy particles is still very large. With further understanding of the biological effects of space radiation, the career doses can be kept at acceptable levels so that the space radiation environment need not be a barrier to the exploitation of the promise of space.

Yang, Chui-Hsu↗
NASA NTRS1995

Dosimetry on STS-42 with the RME APD

Beginning with the STS-42 mission, this laboratory began participating in instrument comparison studies in which space radiation was measured contiguously by passive and active methods. The active instrument was the RME-3 microdosimeter. This instrument measures four-channel LET spectra and employs a tissue-equivalent proportional counter. It is sensitive to the full LET range of ionizing radiation present. Our area passive dosimeter, the RME APD, contained arrays of plastic nuclear track detectors (PNTD's) and thermoluminescent detectors (TLD's). The PNTD's measure LET spectra, while the TLD's measure total absorbed dose. The object of this experiment is to compare the active and passive measurements on the basis of LET spectra, total absorbed dose, and dose equivalent. The STS-42 mission was launched on January 22, 1992, with a flight duration of 8.052 days. The orbit had an inclination of 57 deg and an altitude of 302 km. The shuttle in this orbit is expected to encounter radiation levels dominated by galactic cosmic rays (GCR's) with a lesser contribution from trapped protons in the lower region of the South Atlantic Anomaly (SAA).

Source record↗
NASA NTRS1995

ACTS aeronautical terminal experiment: System description and link analysis

During the summer of 1994, the performance of an experimental mobile satellite communication system was demonstrated to the industry and government representatives by the NASA Lewis Research Center (LeRC) and the Jet Propulsion Laboratory (JPL). The system was based on the Advanced Communications Technology Satellite (ACTS) and consisted of an K-/Ka-band active MMIC phased array antenna system, ACTS Mobile Terminal (AMT) and Link Evaluation Terminal (LET). A LeRC research aircraft, Learjet Model 25, was outfitted with the active MMIC phased array antenna system and AMT and served as the experimental 20/30 Ghz aeronautical terminal. The LET at LeRC in Cleveland, OH was interfaced with portions of fixed-AMT equipment and together provided the gateway station functions including ACTS satellite interface and Public Service Telephone Network (PSTN) interface. The ACTS was operated in its Microwave Switch Matrix (MSM) mode with a spot beam for the Learjet and another spot beam dedicated to the LET. The Learjet was flown over several major cities across the US and demonstrated the feasibility of full-duplex compressed voice link for an aeronautical terminal through the 20/30 Ghz ACTS satellite channel. This paper will present a technical description of the system including the MMIC phased array antenna system, AMT, Learjet, LET and ACTS satellite. The array antenna system consists of a 30 Ghz transmit array (LeRC/Texas Instruments) and two 20 Ghz receive arrays (USAF Rome Lab/Boeing and Martin Marietta), each one very small with sufficient performance for satellite voice link. The AMT consists of 2.4/4.8/9.6 Kbps voice coder/decoder, modem, PSTN interface and RF/IF converters. Link analysis will be presented and compared to the actual performance data collected during the demonstration flights.

Sohn, Philip↗
NASA NTRS1996

ACTS Aeronautical Terminal Experiment System Description and Link Analysis

During the summer of 1994, the performance of an experimental mobile satellite communication system was demonstrated to industry and government representatives by the NASA Lewis Research Center (LeRC) and the Jet Propulsion Laboratory (JPL). The system was based on the advanced communications technology satellite (ACTS) and consisted of a K-/Ka-band active monolithic microwave integrated circuit (MMIC) phased array antenna system, ACTS mobile terminal (AMT) and link evaluation terminal (LET). A LeRC research aircraft, Learjet model 25, was outfitted with the active MMIC phased array antenna system and AMT and served as the experimental 20/30 Ghz aeronautical terminal. The LET at LeRC in Cleveland, OH, was interfaced with portions of fixed-AMT equipment and together provided the gateway station functions including ACTS interface and public service telephone network (PSTN) interface. The ACTS was operated in its microwave switch matrix (MSM) mode with a spot beam for the Learjet and another spot beam dedicated to the LET. The Learjet was flown over several major cities across the US and demonstrated the feasibility of a full-duplex compressed voice links for an aeronautical terminal through the 20/30 Ghz ACTS channel. This paper presents a technical description of the system including the MMIC phased array antenna system, AMT, Learjet, LET, and ACTS. The array antenna system consists of a 30 Ghz transmit array (LeRc/Texas Instruments) and two 20 Ghz receive arrays (USAF Rome Lab., Boeing, and Martin Marietta), each one very small with sufficient performance for a satellite voice link. The AMT consists of 2.4/4.8/9.6 Kbps voice coder/decoder, modem, PSTN interface and RF/IF converters. Link analysis is presented and compared to the actual performance data collected during the demonstration flights.

Sohn, Philip↗
NASA NTRS1998

Track Structure Model for Radial Distributions of Electron Spectra and Event Spectra from High-Energy Ions

An analytic method is described for evaluating the average radial electron spectrum and the radial and total frequency-event spectrum for high-energy ions. For high-energy ions, indirect events make important contributions to frequency-event spectra. The method used for evaluating indirect events is to fold the radial electron spectrum with measured frequency-event spectrum for photons or electrons. The contribution from direct events is treated using a spatially restricted linear energy transfer (LET). We find that high-energy heavy ions have a significantly reduced frequency-averaged final energy (yF) compared to LET, while relativistic protons have a significantly increased yF and dose-averaged lineal energy (yD) for typical site sizes used in tissue equivalent proportional counters. Such differences represent important factors in evaluating event spectra with laboratory beams, in space- flight, or in atmospheric radiation studies and in validation of radiation transport codes. The inadequacy of LET as descriptor because of deviations in values of physical quantities, such as track width, secondary electron spectrum, and yD for ions of identical LET is also discussed.

Cucinotta, F. A.↗
NASA NTRS2000

Physiologic Responses Produced by Active and Passive Personal Cooling Vests

Personal thermoregulatory systems which provide chest cooling are used in the industrial and aerospace environments to alleviate thermal stress. However, little information is available regarding the physiologic and circulatory changes produced by routine operation of these systems. The objectives of this study were to document and compare the subjects' response to three cooling vests in their recommended configurations. The Life Enhancement Tech (LET) lightweight active cooling vest with cap, the MicroClimate Systems Change of Phase garment (MCS), and the Steele Vest were each used to cool the chest regions of 12 male and 8 female Healthy subjects (21 to 69 yr.) in this study. The subjects, seated in an upright position at normal room temperature (approx. 22 C), were tested for 60 min. with one of the cooling garments. The LET active garment had an initial coolant fluid inlet temperature of 60 F, and was ramped down to 50 F. Oral, right and left ear canal temperatures were logged manually every 5 min. Arm, leg, chest and rectal temperatures; heart rate; and respiration were recorded continuously on a U.F.I., Inc. Biolog ambulatory monitor. For men, all three vests had similar, significant cooling effects. Decreases in the average rectal temperature, oral temperature, and ear canal temperatures were approximately 0.2 C, 0.2 C and 0.1 C, respectively. In contrast to the men, the female subjects wearing the MCS and Steel vests had similar cooling responses in which the core temperature remained elevated and oral and ear canal temperatures did not drop. The LET active garment cooled most of the female subjects in this study; rectal, oral and ear temperature decreased about 0.2 C, 0.3 C and 0.3 C, respectively. These results show that the garment configurations tested do not elicit a similar thermal response in all subjects. A gender difference is evident. The LET active garment configuration was most effective in decreasing temperatures of the female subjects; the MCS vest was least effective. For male subjects, the three vests appear to be more nearly equivalent. The active garment system under study included a cooling cap, which may account for some of the difference in response.

Ku, Yu-Tsuan E.↗
NASA NTRS2003

TEPC Response Functions

The tissue equivalent proportional counter had the purpose of providing the energy absorbed from a radiation field and an estimate of the corresponding linear energy transfer (LET) for evaluation of radiation quality to convert to dose equivalent. It was the recognition of the limitations in estimating LET which lead to a new approach to dosimetry, microdosimetry, and the corresponding emphasis on energy deposit in a small tissue volume as the driver of biological response with the defined quantity of lineal energy. In many circumstances, the average of the lineal energy and LET are closely related and has provided a basis for estimating dose equivalent. Still in many cases the lineal is poorly related to LET and brings into question the usefulness as a general purpose device. These relationships are examined in this paper.

Shinn, J. L.↗
NASA NTRS2003

Radiation-induced genomic instability: radiation quality and dose response

Genomic instability is a term used to describe a phenomenon that results in the accumulation of multiple changes required to convert a stable genome of a normal cell to an unstable genome characteristic of a tumor. There has been considerable recent debate concerning the importance of genomic instability in human cancer and its temporal occurrence in the carcinogenic process. Radiation is capable of inducing genomic instability in mammalian cells and instability is thought to be the driving force responsible for radiation carcinogenesis. Genomic instability is characterized by a large collection of diverse endpoints that include large-scale chromosomal rearrangements and aberrations, amplification of genetic material, aneuploidy, micronucleus formation, microsatellite instability, and gene mutation. The capacity of radiation to induce genomic instability depends to a large extent on radiation quality or linear energy transfer (LET) and dose. There appears to be a low dose threshold effect with low LET, beyond which no additional genomic instability is induced. Low doses of both high and low LET radiation are capable of inducing this phenomenon. This report reviews data concerning dose rate effects of high and low LET radiation and their capacity to induce genomic instability assayed by chromosomal aberrations, delayed lethal mutations, micronuclei and apoptosis.

Review↗