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DNA Damage Response to Low and High-LET in a Large Cohort of Mice and Humans and Latest Advancement in NASA Space Omics

This presentation will first focus on a thorough evaluation of the DNA damage response to both low and high-LET in a cohort of 76 mice primary skin fibroblast derived from 15 different strains or in human blood mononuclear cells derived from 550 healthy donors. In both the human and mice work, we have hypothesized that DNA repair capacity can be used as a marker to evaluate and differentiate individual radiation sensitivity. More specifically, this work is based on the concept that the combined time-dose dependence of radiation-induced foci (RIF) of p53-binding protein 1 (53BP1) following low-LET exposure contains sufficient information to infer sensitivity to any other LET. This work is one of the most extensive studies on the kinetics and possible genetic underpinnings of radiation-induced DNA damage and repair. Results on humans are still preliminary as we are still in the process of collecting and isolating primary blood mononuclear cells from 500 to 800 healthy subjects of European descent, 18-75 years of age, 50/50 male/female distribution. We have analyzed 53BP1+ RIF formation as well as oxidative stress and cell death in primary cells from 192 subjects in response to the same HZE particles as used in mice: 600 MeV/n Fe, 350 MeV/n Ar and 350 MeV/n Si, 1.1 and 3 particles/100m2, 4 and 24 hours after irradiation. The second part of the talk will focus on describing GeneLab: The NASA Systems Biology Platform for Space Omics Repository, Analysis and Visualization. NASA GeneLab is an open-access repository for omics datasets generated by biological experiments conducted in space or experiments relevant to spaceflight (e.g. simulated cosmic radiation, simulated microgravity, bed rest studies). Started as a repository designed to archive precious omics from space experiments, GeneLab has expanded its scope to maximize the intelligibility of the raw data (e.g. RNAseq, microarray, WGBS, metagenome), particularly for users with limited bioinformatics knowledge. As such GeneLab is now providing processed data derived from the raw data covering a large spectrum of omics (genome, epigenome, transcriptome, epitranscriptome, proteome, metabolome), to help users explore important questions: Which genes or proteins are expressed differently in space for various living organisms? What are the consequences arising from these changes? What specifics DNA mutations or epigenetic changes happen in space? What species or genetic features lead to better adaption to such a unique environment? In this presentation, we will report on the current and future objectives for GeneLab, and review recent published studies relating molecular changes observed in various animal models and tissue with microgravity, radiation, circadian rhythm, hydration and carbon dioxide conditions.

DNA repair kinetics↗

Solar Variability and the Near-Earth Environment: Mining Enhanced Low Dose Rate Sensitivity Data From the Microelectronics and Photonics Test Bed Space Experiment

This effort is a detailed analysis of existing microelectronics and photonics test bed satellite data from one experiment, the bipolar test board, looking to improve our understanding of the enhanced low dose rate sensitivity (ELDRS) phenomenon. Over the past several years, extensive total dose irradiations of bipolar devices have demonstrated that many of these devices exhibited ELDRS. In sensitive bipolar transistors, ELDRS produced enhanced degradation of base current, resulting in enhanced gain degradation at dose rates <0.1 rd(Si)/s compared to similar transistors irradiated at dose rates >1 rd(Si)/s. This Technical Publication provides updated information about the test devices, the in-flight experiment, and both flight-and ground-based observations. Flight data are presented for the past 5 yr of the mission. These data are compared to ground-based data taken on devices from the same date code lots. Information about temperature fluctuations, power shutdowns, and other variables encountered during the space flight are documented.

Turflinger, T.↗

Solar Irradiance and Thermospheric Airglow Rocket Experiments

This report describes work done in support of the Solar Irradiance and Thermospheric Air-glow Rocket Experiments at the University of Colorado for NASA grant NAG5-5021 under the direction of Dr. Stanley C. Solomon. (The overall rocket program is directed by Dr. Thomas N. Woods, formerly at the National Center for Atmospheric Research, and now also at the University of Colorado, for NASA grant NAG5-5141.) Grant NAG5-5021 provided assistance to the overall program through analysis of airglow and solar data, support of two graduate students, laboratory technical services, and field support. The general goals of the rocket program were to measure the solar extreme ultraviolet spectral irradiance, measure the terrestrial far-ultraviolet airglow, and analyze their relationship at various levels of solar activity, including near solar minimum. These have been met, as shown below. In addition, we have used the attenuation of solar radiation as the rocket descends through the thermosphere to measure density changes. This work demonstrates the maturity of the observational and modeling methods connecting energetic solar photon fluxes and airglow emissions through the processes of photoionization and photoelectron production and loss. Without a simultaneous photoelectron measurement, some aspects of this relationship remain obscure, and there are still questions pertaining to cascade contributions to molecular and atomic airglow emissions. However, by removing the solar irradiance as an "adjustable parameter" in the analysis, significant progress has been made toward understanding the relationship of far-ultraviolet airglow emissions to the solar and atmospheric conditions that control them.

Solomon, Stanley C.↗

Chromosome Aberrations in Human Epithelial Cells Exposed Los Alamos High-Energy Secondary Neutrons: M-BAND Analysis

High-energy secondary neutrons, produced by the interaction of galactic cosmic rays (GCR) with the atmosphere, spacecraft structure and planetary surfaces, contribute a significant fraction to the dose equivalent radiation measurement in crew members and passengers of commercial aviation travel as well as astronauts in space missions. The Los Alamos Nuclear Science Center (LANSCE) neutron facility's 30L beam line (4FP30L-A/ICE House) is known to generate neutrons that simulate the secondary neutron spectrum of the Earth's atmosphere at high altitude. The neutron spectrum is also similar to that measured onboard spacecrafts like the MIR and the International Space Station (ISS). To evaluate the biological damage, we exposed human epithelial cells in vitro to the LANSCE neutron beams with an entrance dose rate of 2.5 cGy/hr, and studied the induction of chromosome aberrations that were identified with multicolor-banding in situ hybridization (mBAND) technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of inter-chromosomal aberrations (translocation to unpainted chromosomes) and intra-chromosomal aberrations (inversions and deletions within a single painted chromosome). Compared to our previous results with gamma-rays and 600 MeV/nucleon Fe ions of high dose rate at NSRL (NASA Space Radiation Laboratory at Brookhaven National Laboratory), the neutron data from the LANSCE experiments showed significantly higher frequency of chromosome aberrations. However, detailed analysis of the inversion type revealed that all of the three radiation types in the study induced a low incidence of simple inversions. Most of the inversions in gamma-ray irradiated samples were accompanied by other types of intrachromosomal aberrations but few inversions were accompanied by interchromosomal aberrations. In contrast, neutrons and Fe ions induced a significant fraction of inversions that involved complex rearrangements of both inter- and intrachromosome exchanges. The distribution of damage sites on chromosome 3 was also compared for different radiation types. The breakpoints were randomly localized on chromosome 3 with neutrons and Fe ions exposure, whereas non-random distribution with clustering breakpoints was observed with gamma-rays exposure. The specific fingerprint of neutron radiations on chromosomal aberrations will be discussed.

Hada, M.↗

Risk analysis: divergent models and convergent interpretations

Material presented at a NASA-sponsored workshop on risk models for exposure conditions relevant to prolonged space flight are described in this paper. Analyses used mortality data from experiments conducted at Argonne National Laboratory on the long-term effects of external whole-body irradiation on B6CF1 mice by 60Co gamma rays and fission neutrons delivered as a single exposure or protracted over either 24 or 60 once-weekly exposures. The maximum dose considered was restricted to 1 Gy for neutrons and 10 Gy for gamma rays. Proportional hazard models were used to investigate the shape of the dose response at these lower doses for deaths caused by solid-tissue tumors and tumors of either connective or epithelial tissue origin. For protracted exposures, a significant mortality effect was detected at a neutron dose of 14 cGy and a gamma-ray dose of 3 Gy. For single exposures, radiation-induced mortality for neutrons also occurred within the range of 10-20 cGy, but dropped to 86 cGy for gamma rays. Plots of risk relative to control estimated for each observed dose gave a visual impression of nonlinearity for both neutrons and gamma rays. At least for solid-tissue tumors, male and female mortality was nearly identical for gamma-ray exposures, but mortality risks for females were higher than for males for neutron exposures. As expected, protracting the gamma-ray dose reduced mortality risks. Although curvature consistent with that observed visually could be detected by a model parameterized to detect curvature, a relative risk term containing only a simple term for total dose was usually sufficient to describe the dose response. Although detectable mortality for the three pathology end points considered typically occurred at the same level of dose, the highest risks were almost always associated with deaths caused by tumors of epithelial tissue origin.

Non-NASA Center↗

Post flight system analysis of FRECOPA (AO 138)

The unexpected duration for the flight of the Long Duration Exposure Facility (LDEF) conducted CNES to create a special investigation group in order to analyze all the materials and systems which compose the French Cooperative Payload (FRECOPA) except the experiments especially prepared for the flight. The FRECOPA tray was on the trailing face (V-) of the LDEF and protected from the atomic oxygen flux during all the flight. However, the solar irradiation was very important with solar flux quite perpendicular to the experiment once an orbit. There was also a good vacuum environment. The objectives are to test the effects of the combined space environment on materials and components like: structure, thermal control coatings and blankets, electronic unit, motors, and mechanical fixtures. When the LDEF returned to Kennedy Space Center, a visual inspection showed the very good behavior of the materials used and it was noted that the three mechanisms to open and close the experiment canisters worked completely. Many impacts of micrometeoroids or space debris on the structure and on the thermal protections were observed. After FRECOPA was brought back to Toulouse, many tests were performed and include: working order tests, mechanical tests (tension), optical and electronic microscopy (SEM), surface analysis (ESCA, SIMS, RBS, AUGER, etc.), thermal analysis, pressure measurements, and gas analysis (outgassing tests). The results of these experiments are discussed.

Durin, Christian↗

Studies of proton-irradiated SO2 at low temperatures Implications for Io

The infrared absorption spectrum from 3.3 to 27 microns of SO2 ice films has been measured at 20 and 88 K before and after 1-MeV proton irradiation. The radiation flux was chosen to simulate the estimated flux of Jovian magnetospheric 1-MeV protons incident on Io. After irradiation, SO3 is identified as the dominant molecule synthesized in the SO2 ice. This is also the case after irradiation of composite samples of SO2 with sulfur or disulfites. Darkening was observed in irradiated SO2 ice and in irradiated S8 pellets. Photometric and spectral measurements of the thermoluminescence of irradiated SO2 have been made during warming. The spectrum appears as a broad band with a maximum at 4450 A. Analysis of the luminescence data suggests that at Ionian temperatures irradiated SO2 ice would not be a dominant contributor to posteclipse brightening phenomena. After warming to room temperature, a form of SO3 remains along with a sulfate and S8. Based on these experiments, it is reasonable to propose that small amounts of SO3 may exist on the surface of Io as a result of irradiation synthesis in SO2 frosts.

Moore, M. H.↗

Lifetime prediction of materials exposed to the natural space environment

The goal of this study is to model the lifetime of different types of seal materials based on results obtained from accelerated experiments. A semi-mechanistic approach was taken. Thermal aging data were taken from the literature whereas experiments were conducted at Auburn under this contract for selected environments. The seal materials of interest are Silicone 383, Silicone 650, Viton 835, and Viton 747. The relevant conditions include thermal, oxygen, inert gas, vacuum, and gamma radiation. Compression set data available from NASA were used to examine the thermal effect. Experiments were conducted at Auburn University and at NASA to isolate the role of thermal, oxygen, inert gas, vacuum, gamma irradiation, and proton irradiation. A simple discrete stress relaxation method was developed to determine the relaxation response of the elastomers. Dynamic mechanical thermal analysis was also used to characterize the mechanical response of the specimens. These provide a more meaningful correlation between mechanisms and degradation.

Zee, Ralph↗

M-BAND Study of Radiation-Induced Chromosome Aberrations in Human Epithelial Cells: Radiation Quality and Dose Rate Effects

The advantage of the multicolor banding in situ hybridization (mBAND) technique is its ability to identify both inter- (translocation to unpainted chromosomes) and intra- (inversions and deletions within a single painted chromosome) chromosome aberrations simultaneously. To study the detailed rearrangement of low- and high-LET radiation induced chromosome aberrations in human epithelial cells (CH184B5F5/M10) in vitro, we performed a series of experiments with Cs-137 gamma rays of both low and high dose rates, neutrons of low dose rate and 600 MeV/u Fe ions of high dose rate, with chromosome 3 painted with multi-binding colors. We also compared the chromosome aberrations in both 2- and 3-dimensional cell cultures. Results of these experiments revealed the highest chromosome aberration frequencies after low dose rate neutron exposures. However, detailed analysis of the radiation induced inversions revealed that all three radiation types induced a low incidence of simple inversions. Most of the inversions in gamma-ray irradiated samples were accompanied by other types of intra-chromosomal aberrations but few inversions were accompanied by inter-chromosomal aberrations. In contrast, neutrons and Fe ions induced a significant fraction of inversions that involved complex rearrangements of both inter- and intrachromosomal exchanges. The location of the breaks involved in chromosome exchanges was analyzed along the painted chromosome. The breakpoint distribution was found to be randomly localized on chromosome 3 after neutron or Fe ion exposure, whereas non-random distribution with clustering breakpoints was observed after -ray exposure. Our comparison of chromosome aberration yields between 2- and 3-dimensional cell cultures indicated a significant difference for gamma exposures, but not for Fe ion exposures. These experimental results indicated that the track structure of the radiation and the cellular/chromosome structure can both affect radiation-induced chromosome aberrations.

Hada, Megumi↗

Analysis of photographic X-ray images

Some techniques used to extract quantitative data from the information contained in photographic images produced by grazing incidence soft X-ray optical systems are described. The discussion is focussed on the analysis of the data returned by the S-054 X-Ray Spectrographic Telescope Experiment on Skylab. The parameters of the instrument and the procedures used for its calibration are described. The technique used to convert photographic density to focal plane X-ray irradiance is outlined. The deconvolution of the telescope point response function from the image data is discussed. Methods of estimating the temperature, pressure, and number density of coronal plasmas are outlined.

Krieger, A. S.↗

Induction of a bystander mutagenic effect of alpha particles in mammalian cells

Ever since the discovery of X-rays was made by Rontgen more than a hundred years ago, it has always been accepted that the deleterious effects of ionizing radiation such as mutation and carcinogenesis are attributable mainly to direct damage to DNA. Although evidence based on microdosimetric estimation in support of a bystander effect appears to be consistent, direct proof of such extranuclear/extracellular effects are limited. Using a precision charged particle microbeam, we show here that irradiation of 20% of randomly selected A(L) cells with 20 alpha particles each results in a mutant fraction that is 3-fold higher than expected, assuming no bystander modulation effect. Furthermore, analysis by multiplex PCR shows that the types of mutants induced are significantly different from those of spontaneous origin. Pretreatment of cells with the radical scavenger DMSO had no effect on the mutagenic incidence. In contrast, cells pretreated with a 40 microM dose of lindane, which inhibits cell-cell communication, significantly decreased the mutant yield. The doses of DMSO and lindane used in these experiments are nontoxic and nonmutagenic. We further examined the mutagenic yield when 5-10% of randomly selected cells were irradiated with 20 alpha particles each. Results showed, likewise, a higher mutant yield than expected assuming no bystander effects. Our studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by alpha particles and that cell-cell communication process play a critical role in mediating the bystander phenomenon.

Non-NASA Center↗

Whole-rock uranium analysis by fission track activation

We report a whole-rock uranium method in which the polished sample and track detector are separated in a vacuum chamber. Irradiation with thermal neutrons induces uranium fission in the sample, and the detector records the integrated fission track density. Detection efficiency and geometric factors are calculated and compared with calibration experiments.

Weiss, J. R.↗

Analyzing the Chemical and Spectral Effects of Pulsed Laser Irradiation to Simulate Space Weathering of a Carbonaceous Chondrite

Space weathering processes alter the chemical composition, microstructure, and spectral characteristics of material on the surfaces of airless bodies. The mechanisms driving space weathering include solar wind irradiation and the melting, vaporization and recondensation effects associated with micrometeorite impacts e.g., [1]. While much work has been done to understand space weathering of lunar and ordinary chondritic materials, the effects of these processes on hydrated carbonaceous chondrites is poorly understood. Analysis of space weathering of carbonaceous materials will be critical for understanding the nature of samples returned by upcoming missions targeting primitive, organic-rich bodies (e.g., OSIRIS-REx and Hayabusa 2). Recent experiments have shown the spectral properties of carbonaceous materials and associated minerals are altered by simulated weathering events e.g., [2-5]. However, the resulting type of alteration i.e., reddening vs. bluing of the reflectance spectrum, is not consistent across all experiments [2-5]. In addition, the microstructural and crystal chemical effects of many of these experiments have not been well characterized, making it difficult to attribute spectral changes to specific mineralogical or chemical changes in the samples. Here we report results of a pulsed laser irradiation experiment on a chip of the Murchison CM2 carbonaceous chondrite to simulate micrometeorite impact processing.

Thompson, M. S.↗

Studies Relative to the Radiosensitivity of Man: Based on Retrospective Evaluations of Therapeutic and Accidental Total-Body Irradiation

The radiobiologic studies carried out with joint (AEC) ERDA and NASA support during the years 1964 to 1974 at the Medical Division of Oak Ridge Associated Universities are presented. The physiologic data generated were similar in many ways to those previously observed in other medical radiobiologic experiences. They differed, however, in the methods of data acquisition and analysis. Instead of more conventional analytical methods, pulmonary impedance was recorded and quantitated as a measure of radiation-induced gastrointestinal distress and fatiguability. While refinements in dose response related to gastrointestinal distress were accomplished, it was also found that through the use of Fourier analysis of pulmonary impedance waveform GI distress could easily be recognized and quantified even when the initial stages of nausea were below the subjects subjective level of recognition. The results demonstrate that change in pulmonary impedance waveform closely parallel well-defined stages of GI distress, i.e., initial nausea, a progressive increase in nausea, and finally vomiting episodes.

Ricks, R. C.↗

Mechanical and SEM analysis of artificial comet nucleus samples

Since 1987 experiments dealing with comet nucleus phenomena have been carried out in the DFVLR space simulation chambers. The main objective of these experiments is a better understanding of thermal behavior, surface phenomena and especially the gas dust interaction. As a function of different sample compositions and exposure to solar irradiation (xenon-bulbs) crusts of different hardness and thickness were measured. The measuring device consists of a motor driven pressure foot (5 mm diameter), which is pressed into the sample. The applied compressive force is electronically monitored. The microstructure of the crust and dust residuals is investigated by scanning electron microscopy (SEM) techniques. Stress-depth profiles of an unirradiated and an irradiated model comet are given.

Thiel, K.↗

Development of response models for the Earth Radiation Budget Experiment (ERBE) sensors. Part 4: Preliminary nonscanner models and count conversion algorithms

Two count conversion algorithms and the associated dynamic sensor model for the M/WFOV nonscanner radiometers are defined. The sensor model provides and updates the constants necessary for the conversion algorithms, though the frequency with which these updates were needed was uncertain. This analysis therefore develops mathematical models for the conversion of irradiance at the sensor field of view (FOV) limiter into data counts, derives from this model two algorithms for the conversion of data counts to irradiance at the sensor FOV aperture and develops measurement models which account for a specific target source together with a sensor. The resulting algorithms are of the gain/offset and Kalman filter types. The gain/offset algorithm was chosen since it provided sufficient accuracy using simpler computations.

Halyo, Nesim↗

Total solar irradiance measurements by ERB/Nimbus-7 - A review of nine years

The total solar irradiance measurements made by the cavity sensor of the Earth Radiation Budget experiment on the Nimbus-7 spacecraft have detected the sunspot-blocking effect, established the downward trend of the declining solar cycle, and appear to be confirming an upturn in irradiance at the outset of the new cycle. Studies of the measurements' frequency spectra have advanced the interest in helioseismology or mode analysis, and studies of photospheric activity have advanced through the modeling of the sunspot blocking and photospheric brightening vs measured irradiance.

Hickey, John R.↗

Multi-Scale Analysis of an Ilmenite Microcrater in Lunar Sample 71055

Micrometeorite impacts are a key space weathering process on the lunar surface, generating a variety of physical and chemical changes in the lunar regolith. Several experiments using nanosecond pulsed lasers to simulate micrometeorite impact have been published in the past two decades, providing a wealth of knowledge, including how minerals vary in their response to laser irradiation. Although these experiments have produced many features analogous to those observed in natural samples, none could be attributed to the passage of a shock wave, resulting instead from hot ablation. Recent femtosecond laser irradiation of olivine and enstatite have more accurately reproduced the shock textures observed in lunar samples, improving our ability to coordinate experimental and lunar sample data. Both pulsed laser experiments and studies of lunar impact craters have focused on silicates, as they comprise the bulk of the regolith. Ilmenite (FeTiO 3 ) is the most abundant opaque mineral in lunar rocks and an important sink of solar wind implanted helium. Ilmenite is known to vary in its response to radiation processing relative to the silicates, but its response to micrometeorite impact has not yet been studied in natural samples nor in the laboratory. In this investigation, we characterize an ilmenite microcrater using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to learn how ilmenite responds to impact and if there are implications for helium cycling in the regolith.

B A Cymes↗