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All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Global Variability in Sonic Boom Exposure due to Macroscopic Effects

Supersonic flight over land has been prohibited since 1973 due to the loudness of sonic booms. NASA is building the X-59 aircraft as part of its Quesst mission to demonstrate low-loudness shaped sonic booms, or “sonic thumps.” The Quesst mission will gather human perception data via a series of community noise surveys across the USA. The noise dose and perceptual response data will be provided to the International Civil Aviation Organization (ICAO) and the Federal Aviation Administration for use in determining potential future supersonic aircraft noise certification standards, effectively changing the prohibition from a speed limit to a noise limit. These noise regulations must be globally effective, as long travel distances see the largest benefit to supersonic flight. The state of the atmosphere through which a sonic boom travels affects the size of the region exposed to sound, the “carpet width” (CW), as well as the loudness. The focus of this dissertation is to understand and quantify the expected loudness and CW of sonic booms due to the macroscopic atmospheric effects around the world. A pair of large-scale propagation simulation studies were conducted using the NASA PCBoom code to compare predicted sonic boom loudness and CW statistics first across the USA and then across the world. For the USA study, near-field data of the X-59 in steady cruise was propagated at 4 cardinal headings at 138 locations through 5 years of Climate Forecast System Version 2 (CFSv2) atmospheric profiles. Results of a bootstrap forest predictor screening model indicated the importance of climate zone, latitude, ground elevation, season, and heading. It also noted the unimportance of time of day for predicting loudness and CW. The data is visualized in aggregate, and then broken out geographically, by season and heading, and by climate zone. Multiple linear regression models were fit to the data from the 138 locations so that estimates of the loudness and CW can be produced anywhere in the US. The results can aid in planning when and where to fly the X-59. For the global study, near-field data from three aircraft, the X-59 in a quiet and loud configuration, B-58, and Concorde, were propagated at four cardinal headings through data from three atmospheric models, the CFSv2, the Global Forecast System (GFS), and the ECMWF Reanalysis Version 5 (ERA5), at 100 global locations over 1 year. Results of a bootstrap forest predictor screening model indicated the importance of climate zone, ground elevation, season, and heading. Similar to the US study, the model indicated time of day was not an important predictor. The model also indicated that choice of weather model was not important, so the atmospheric model data are effectively interchangeable. The ERA5 model was chosen for use in an extension of the study to include 18 additional locations to ensure sampling of every climate zone. Loudness and CW results are shown in aggregate, and split geographically and by heading, season, and climate. Multiple linear regression models were fit to the data from the 118 locations so that estimates of loudness and CW can be produced around the world. N-waves and shaped booms did not have the same global variability. Koppen-Geiger climate zones were used as the climate zone definition for the global study. These are available as present-day and future climate projections. Making use of the multiple linear regression models, the future climate zones were input to estimate the effect of the changing climate on sonic boom loudness and CW. Results indicate that a changing climate would have little impact on the effectiveness of noise regulations.

X-59↗
NASA NTRS1998

An Adaptable Power System with Software Control Algorithm

A low cost, flexible and modular spacecraft power system design was developed in response to a call for an architecture that could accommodate multiple missions in the small to medium load range. Three upcoming satellites will use this design, with one launch date in 1999 and two in the year 2000. The design consists of modular hardware that can be scaled up or down, without additional cost, to suit missions in the 200 to 600 Watt orbital average load range. The design will be applied to satellite orbits that are circular, polar elliptical and a libration point orbit. Mission unique adaptations are accomplished in software and firmware. In designing this advanced, adaptable power system, the major goals were reduction in weight volume and cost. This power system design represents reductions in weight of 78 percent, volume of 86 percent and cost of 65 percent from previous comparable systems. The efforts to miniaturize the electronics without sacrificing performance has created streamlined power electronics with control functions residing in the system microprocessor. The power system design can handle any battery size up to 50 Amp-hour and any battery technology. The three current implementations will use both nickel cadmium and nickel hydrogen batteries ranging in size from 21 to 50 Amp-hours. Multiple batteries can be used by adding another battery module. Any solar cell technology can be used and various array layouts can be incorporated with no change in Power System Electronics (PSE) hardware. Other features of the design are the standardized interfaces between cards and subsystems and immunity to radiation effects up to 30 krad Total Ionizing Dose (TID) and 35 Mev/cm(exp 2)-kg for Single Event Effects (SEE). The control algorithm for the power system resides in a radiation-hardened microprocessor. A table driven software design allows for flexibility in mission specific requirements. By storing critical power system constants in memory, modifying the system code for other programs is simple. These constants can be altered also by ground command, or in response to an anomolous event. All critical power system functions have backup hardware functions to prevent a software or computer glitch from propagating. A number of battery charge control schemes can be implemented by selecting the proper control terms in the code. The architecture allows the design engineer to tune the system response to various system components and anticipated load profiles without costly alterations. A design trade was made with the size, weight and power dissipation of the electronics versus the performance of the power bus to load variations. Linear, fine control is maintained with a streamlined electronics design. This paper describes the hardware design as well as the software control algorithm. The challenges of closing the system control loop digitally is discussed. Control loop margin and power system performance is presented. Lab measurements are shown and compared to the system response of a hardware model running actual flight software.

Castell, Karen↗
NASA NTRS2019

Predicting Cancer Risk from Ionizing Radiation

The ability to predict cancer risk associated with exposure to low doses of high-LET ionizing radiation (IR) remains a challenge. Epidemiological methods lack the sensitivity and power to provide detailed risk estimates for cancer and ignore individual variance in IR sensitivity. 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. Our hypothesis was tested in 15 different mouse strains as well as in primary human immune cells. We first approached individual ionizing radiation sensitivity in a mouse model by culturing primary skin fibroblasts extracted from 76 mice of 15 different genetic backgrounds and exposing them to HZE particles and X-rays. This work is one of the most extensive studies on the kinetics and possible genetic underpinnings of radiation-induced DNA damage and repair. Our results is in agreement with a DNA repair model we previously postulated, where nearby DNA double strand breaks (DSB) in the nucleus are brought together for more efficient repair, leading to RIF clustering. Such mechanism was evidenced by a specific dose and LET dependence of RIF numbers. Briefly, RIF quantification after low-LET X-ray exposure showed an asymptotic saturation for doses between 1 Gy and 4 Gy 4 hours post-irradiation across all 15 strains. The clustering of DSB across all strains also led to more RIF/Gy for lower LET (X-ray and 350 MeV/n Ar) than for higher LET (600 MeV/n Fe) 4 hours post-exposure. Considering the fact that the number of DSB/Gy should be independent of LET, our data suggest there are more DSB in individual RIF as the LET increases. RIF numbers for 24 and 48 hours post-exposure led to the inverse trend, with more remaining RIF/Gy for higher LET (by 600 MeV/n Fe). This result suggests cells have more difficulty resolving RIF from higher LET as they the number DSB/RIF increases. Note that for most conditions, the variance of RIF/Gy was small within individual animals of the same strain and large between strains, suggesting a strong genetics component. Furthermore, we present our preliminary data from an ongoing study on human genetic associations with IR sensitivity. To address the human variability in responses to HZE particle irradiation in a maximally comprehensive manner, we are in the process of collecting and isolating primary blood mononuclear cells from 768 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. We will next complete the quantification of HZE particle-induced DNA and cellular damage in the remaining subjects and compare it to their responses to low-LET irradiation. Finally, we will perform GWAS analysis to identify human genomic associations with IR sensitivity and potential targets for biomarker development.

High-LET radiation↗
NASA NTRSDate not supplied

An Open-Science Approach to Address Individual Response to Simulated GCR In Genetically Diverse Populations of Mice and Humans

This project addresses the challenge of understanding and predicting individual radiation sensitivity by integrating genetics, demographics and biomarker characteristics across species (mice and humans). We hypothesize that ex vivo DNA repair response to GCR components is a central determinant of cancer risk from space radiation and can serve as a biomarker of radiation risk in combination with genetics. Automated image quantification of 53BP1+ radiation-induced foci (RIF) during the first 4-48 h post-irradiation was performed as a function of dose and LET in non-immortalized primary skin fibroblasts derived from 76 mice across 15 strains (5 inbred reference strains and 10 collaborative-cross strains) exposed to X rays (0.1, 1 and 4 Gy), 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100sq. μm), as well as in peripheral blood mononuclear cells (PBMCs) from 768 healthy donors (matched ethnicity, 50/50 male/female, 18-70 years old) exposed to gamma rays (0.1 and 1 Gy), 350 MeV/n 28Si, 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100sq. μm). A genome-wide association study (GWAS) was performed on the mouse strains between DNA damage responses to space radiation and single nucleotide polymorphisms (SNPs). We found SNPs, which were significantly associated to the RIF phenotype, mapped to genes and pathways that are functionally linked to health hazards for deep space exploration (e.g. carcinogenesis, nervous system damage and immune dysfunction). Some of these SNPs were located within protein coding regions, potentially interfering with protein functions and providing promising genetic targets for countermeasures. We also found correlations between both spontaneous and radiation-induced DNA damage and SNPs mapped to pathways associated with cellular metabolism. GWAS is undergoing for the human data. All data have been made available via the NASA Space Biology Open-Science database (genelab.nasa.gov) and we will discuss how various genomic and transcriptomic datasets can be accessed for modeling and integrated using machine learning methods for discovering new radiation biology.

Sylvain V Costes↗
NASA NTRS1998

Effect of track structure and radioprotectors on the induction of oncogenic transformation in murine fibroblasts by heavy ions

The oncogenic potential of high-energy 56Fe particles (1 GeV/nucleon) accelerated with the Alternating Gradient Synchrotron at the Brookhaven National Laboratory was examined utilizing the mouse C3H 10T1/2 cell model. The dose-averaged LET for high-energy 56Fe is estimated to be 143 keV/micrometer with the exposure conditions used in this study. For 56Fe ions, the maximum relative biological effectiveness (RBEmax) values for cell survival and oncogenic transformation were 7.71 and 16.5 respectively. Compared to 150 keV/micrometer 4He nuclei, high-energy 56Fe nuclei were significantly less effective in cell killing and oncogenic induction. The prostaglandin E1 analog misoprostol, an effective oncoprotector of C3H 10T1/2 cells exposed to X rays, was evaluated for its potential as a radioprotector of oncogenic transformation with high-energy 56Fe. Exposure of cells to misoprostol did not alter 56Fe cytotoxicity or the rate of 56Fe-induced oncogenic transformation.

NASA Discipline Radiation Health↗
NASA NTRSDate not supplied

Multi-Omics Analysis of Mouse Retina Following Low Dose Radiation and/or Hindlimb Unloading

Rodent models have been used as analogs for studying the effects of spaceflight. NASA’s GeneLab provides access to omics datasets generated from spaceflight and ground-based experiments allowing for additional retrospective analysis. We used GeneLab’s GLDS-203, a dataset generated by researchers at Loma Linda University to study the impact of prolonged unloading and/or low-dose radiation on mouse retina. The purpose of this study was to understand the effect of gamma radiation and/or hindlimb unloading on mice retinas through a multi-omics analysis. In the experiment that generated the omics data, mice were irradiated with gamma-ray and/or subjected to hindlimb unloading for 21 days and multi-omics analysis was performed at 7 days, 1 month, or 4 months post exposure. In the current study, for each of the three timepoints, we compared epigenomic profiles for retinas from exposed mice against timepoint-matched controls. We identified a total of 5,271 differentially methylated loci (DML) and 321 differentially methylated regions (DMR; using a sliding window and step size of 500 bp) with methylation difference > 10% and q-value < 0.05 (sliding linear model corrected p-value) across the nine exposure groups. Highest correlation in methylation difference was seen for significant DMLs (q-value < 0.05) across different conditions at same post exposure timepoint (Figure 1).The location of DMLs and DMRs were characterized with respect to CpG islands and shores, putative promoters, gene body, and intergenic regions (Table 1). We analyzed RNA-seq counts and performed gene set enrichment analysis using differential expression results from comparing each exposure group to its timepoint-matched control group. Significant pathways (adjusted p-value <0.05) enriched in all three microgravity-only groups were related to morphogenesis of a branching epithelium, skeletal muscle cell differentiation, and response to fibroblast growth factor. Common processes across all timepoints in the radiation-only groups were retina homeostasis, synaptic vesicle exocytosis-endocytosis, and chemotaxis. In the combination groups, regulation of trans-synaptic signaling, and Rho protein signal transduction were enriched at all three timepoints. Processes related to purine nucleotide metabolism were enriched in all nine exposure groups, with activation at 1 month, and suppression at 7 days and 4 months. A total of 14 genes contained at least one DML and were differentially expressed at adjusted p-value < 0.05, including genes implicated in cataract development (Sipa1l3, Crybb3) and those involved in cytoskeletal organization (Plec, Flnb, Eef1a1). This analysis is part of a larger effort to understand the molecular mechanisms following spaceflight exposures that can help translate effects observed in animal models to human impacts.

Prachi Kothiyal↗
NASA NTRS2000

Alterations in dose and lineal energy spectra under different shieldings in the Los Alamos high-energy neutron field

Nuclear interactions of space radiation with shielding materials result in alterations in dose and lineal energy spectra that depend on the specific elemental composition, density and thickness of the material. The shielding characteristics of materials have been studied using charged-particle beams and radiation transport models by examining the risk reduction using the conventional dose-equivalent approach. Secondary neutrons contribute a significant fraction of the total radiation exposure in space. An experiment to study the changes in dose and lineal energy spectra by shielding materials was carried out at the Los Alamos Nuclear Science Center neutron facility. In the energy range of about 2 to 200 MeV, this neutron spectrum is similar in shape within a factor of about 2 to the spectrum expected in the International Space Station habitable modules. It is shown that with a shielding thickness of about 5 g cm(-2), the conventional radiation risk increases, in some cases by as much as a factor of 2, but decreases with thicknesses of about of 20 g cm(-2). This suggests that care must be taken in evaluating the shielding effectiveness of a given material by including both the charged-particle and neutron components of space radiation.

NASA Discipline Radiation Health↗
NASA NTRS1999

GCR Transport in the Brain: Assessment of Self-Shielding, Columnar Damage, and Nuclear Reactions on Cell Inactivation Rates

Radiation shield design is driven by the need to limit radiation risks while optimizing risk reduction with launch mass/expense penalties. Both limitation and optimization objectives require the development of accurate and complete means for evaluating the effectiveness of various shield materials and body-self shielding. For galactic cosmic rays (GCR), biophysical response models indicate that track structure effects lead to substantially different assessments of shielding effectiveness relative to assessments based on LET-dependent quality factors. Methods for assessing risk to the central nervous system (CNS) from heavy ions are poorly understood at this time. High-energy and charge (HZE) ion can produce tissue events resulting in damage to clusters of cells in a columnar fashion, especially for stopping heavy ions. Grahn (1973) and Todd (1986) have discussed a microlesion concept or model of stochastic tissue events in analyzing damage from HZE's. Some tissues, including the CNS, maybe sensitive to microlesion's or stochastic tissue events in a manner not illuminated by either conventional dosimetry or fluence-based risk factors. HZE ions may also produce important lateral damage to adjacent cells. Fluences of high-energy proton and alpha particles in the GCR are many times higher than HZE ions. Behind spacecraft and body self-shielding the ratio of protons, alpha particles, and neutrons to HZE ions increases several-fold from free-space values. Models of GCR damage behind shielding have placed large concern on the role of target fragments produced from tissue atoms. The self-shielding of the brain reduces the number of heavy ions reaching the interior regions by a large amount and the remaining light particle environment (protons, neutrons, deuterons. and alpha particles) may be the greatest concern. Tracks of high-energy proton produce nuclear reactions in tissue, which can deposit doses of more than 1 Gv within 5 - 10 cell layers. Information on rates of cell killing from GCR, including patterns of cell killing from single particle tracks. can provide useful information on expected differences between proton and HZE tracks and clinical experiences with photon irradiation. To model effects on cells in the brain, it is important that transport models accurately describe changes in the GCR due to interactions in the cranium and proximate tissues. We describe calculations of the attenuated GCR particle fluxes at three dose-points in the brain and associated patterns of cell killing using biophysical models. The effects of the brain self-shielding and bone-tissue interface of the skull in modulating the GCR environment are considered. For each brain dose-point, the mass distribution in the surrounding 4(pi) solid angle is characterized using the CAM model to trace 512 rays. The CAM model describes the self-shielding by converting the tissue distribution to mass-equivalent aluminum, and nominal values of spacecraft shielding is considered. Particle transport is performed with the proton, neutron, and heavy-ion transport code HZETRN with the nuclear fragmentation model QMSFRG. The distribution of cells killed along the path of individual GCR ions is modeled using in vitro cell inactivation data for cells with varying sensitivity. Monte Carlo simulations of arrays of inactivated cells are considered for protons and heavy ions and used to describe the absolute number of cell killing events of various magnitude in the brain from the GCR. Included are simulations of positions of inactivated cells from stopping heavy ions and nuclear stars produced by high-energy ions most importantly, protons and neutrons.

Shavers, M. R.↗
NASA NTRSDate not supplied

Quantifying Leak Rates and Vacuum Impact on Granular Soil Column Pneumatic Seal

Introduction: All In-Situ Resource Utilization (ISRU) regolith reactor systems that aim to extract gases or vapors must maintain a seal along the flow path of the regolith from the inlet hopper to where extracted gases or vapors are generated. Using a column of regolith at the inlet has been proposed as an alternative to systems using series of mechanical valves to reduce mass and complexity. Preliminary investigations into the use of regolith itself as a barrier to escaping fluids have been conducted, which this research seeks to expand upon. Different vertical regolith simulant plug diameters and heights were tested under vacuum with dry nitrogen to observe leak rates and approximate steady state pressure gradient equilibria. The effect of absolute ambient pressure was also studied by repeating tests at incremental pressures ranging from 10e-5 Torr up to 1 atm to corroborate ambient bench tests from previous work. The impact of regolith dynamics was addressed to emulate continuous-feed regolith reaction processes by measuring leak rates through continuously draining simulant columns. OB-1 lunar highlands regolith simulant was used. Experimental Setup: Regolith simulant columns were constructed using a motorized butterfly valve separating upper acrylic tubes of various diameters from a larger, lower aluminum pipe plenum (See Figure 1). The butterfly valve was cracked open such that gas could freely pass through whereas regolith would bridge and stay suspended as a cohesive plug above in the acrylic portion. These assemblies were loaded into a vacuum chamber, and a compressed dry nitrogen line was routed into the lower plenum. Pressure transducers measured the absolute pressure of the lower plenum, which was compared to absolute chamber pressure to monitor the pressure gradient across the regolith simulant. A precision mass flow controller enabled fine control of plenum pressure. The plenum pressure was quasi-statically increased to set points informed by previous work [1] before shutting off the gas supply to allow the now pressurized gas volume to dissipate through the simulant into the chamber in what was referred to as a ‘leak test.’ In a separate set of tests, the pressure was allowed to quasi-statically build until visual disturbances in the soil were observed via remote camera feeds. Initial leak rate tests were repeated on the disturbed soil to observe changes in leak rates between initial as-poured and post-bubbling soil conditions. This test schedule was applied to simulant columns of three different diameters (approximately 2, 4, and 6 inches) as well as two different heights (around 8 and 16 inches) and was repeated at least three times for each configuration. Plenums were also pressurized while the butterfly valves were opened slightly further to facilitate slow, controlled, constant flowrate draining of the simulant to observe the impact that continuous-feed systems might have on leak rate through the regolith column. Finally, the regolith columns were reset and refilled and static leak rate tests were repeated approximately every decade in ambient pressure from 10e-5 Torr up to ambient conditions to observe the impact of transitioning out of the molecular flow regime on regolith column seal performance. Analysis: Trends with respect to each factor examined were constructed and reported alongside commentary on the most likely responsible physical phenomena. Confidence intervals were applied to the predictive findings of the data by quantifying instrumentation error and accounting for probabilistic impacts of curve fitting the generic exponential function onto pressure decay data. The leak rate is assumed directly proportional to the exponential term coefficient, while the steady-state static pressure gradient is assumed to be the asymptotic limit of each curve fit. Finally, a generic model developed by Ogino et al. [2] and later tuned for ambient testing was re-tuned using vacuum data to estimate leak rates on the lunar surface. Results: Pressure decay rates decreased up to 27-fold under vacuum when compared to ambient pressure, as shown in Figure 2. Simulant column diameter was found to exponentially correlate to both regolith column leak rate and steady-state equilibrium pressure delta. Height was found to be linearly related to leak rate –doubling the regolith column height consistently yielded around a 40% reduction in leak rate. Dynamic regolith draining was found to slightly increase leak rate, although to a lower degree than expected. Conclusion: Because of the transition into molecular gas flow through regolith, vacuum testing is required to properly estimate performance. Regolith columns should be designed as narrow as possible to avoid bridging and minimize leak rate, and as tall as is feasible to both further reduce leak rate and to help prevent bubbling, which has been shown to degrade the quality of the regolith seal. Disrupted soil was found to exhibit higher leak rates than pristine, as-poured soil, indicating the need to consider the impact of recovery from depressurization events. Regolith columns appear equally feasible for both dosed and continuous-feed reactors.

ISRU↗
NASA NTRS1994

Charged-particle mutagenesis II. Mutagenic effects of high energy charged particles in normal human fibroblasts

The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 micrometer2 and 0.09 to 5.56 x 10(-3) micrometer2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(-5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

NASA Center JSC↗
NASA NTRS2002

Response of thyroid follicular cells to gamma irradiation compared to proton irradiation: II. The role of connexin 32

The objective of this study was to determine whether connexin 32-type gap junctions contribute to the "contact effect" in follicular thyrocytes and whether the response is influenced by radiation quality. Our previous studies demonstrated that early-passage follicular cultures of Fischer rat thyroid cells express functional connexin 32 gap junctions, with later-passage cultures expressing a truncated nonfunctional form of the protein. This model allowed us to assess the role of connexin 32 in radiation responsiveness without relying solely on chemical manipulation of gap junctions. The survival curves generated after gamma irradiation revealed that early-passage follicular cultures had significantly lower values of alpha (0.04 Gy(-1)) than later-passage cultures (0.11 Gy(-1)) (P < 0.0001, n = 12). As an additional way to determine whether connexin 32 was contributing to the difference in survival, cultures were treated with heptanol, resulting in higher alpha values, with early-passage cultures (0.10 Gy(-1)) nearly equivalent to untreated late-passage cultures (0.11 Gy(-1)) (P > 0.1, n = 9). This strongly suggests that the presence of functional connexin 32-type gap junctions was contributing to radiation resistance in gamma-irradiated thyroid follicles. Survival curves from proton-irradiated cultures had alpha values that were not significantly different whether cells expressed functional connexin 32 (0.10 Gy(-1)), did not express connexin 32 (0.09 Gy(-1)), or were down-regulated (early-passage plus heptanol, 0.09 Gy(-1); late-passage plus heptanol, 0.12 Gy(-1)) (P > 0.1, n = 19). Thus, for proton irradiation, the presence of connexin 32-type gap junctional channels did not influence their radiosensitivity. Collectively, the data support the following conclusions. (1) The lower alpha values from the gamma-ray survival curves of the early-passage cultures suggest greater repair efficiency and/or enhanced resistance to radiation-induced damage, coincident with the expression of connexin 32-type gap junctions. (2) The increased sensitivity of FRTL-5 cells to proton irradiation was independent of their ability to communicate through connexin 32 gap junctions. (3) The fact that the beta components of the survival curves from both gamma rays and proton beams were similar (average 0.022 +/- 0.008 Gy(-2), P > 0.1, n = 39) suggests that at higher doses the loss of viability occurs at a relatively constant rate and is independent of radiation quality and the presence of functional gap junctions.

Non-NASA Center↗
NASA NTRS2019

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↗
NASA NTRS2002

Oxygen control of ethylene biosynthesis during seed development in Arabidopsis thaliana (L.) Heynh

An unforeseen side-effect on plant growth in reduced oxygen is the loss of seed production at concentrations around 25% atmospheric (50 mmol mol-1 O2). In this study, the model plant Arabidopsis thaliana (L.) Heynh. cv. 'Columbia' was used to investigate the effect of low oxygen on ethylene biosynthesis during seed development. Plants were grown in a range of oxygen concentrations (210 [equal to ambient], 160, 100, 50 and 25 mmol mol-1) with 0.35 mmol mol-1 CO2 in N2. Ethylene in full-sized siliques was sampled using gas chromatography, and viable seed production was determined at maturity. Molecular analysis of ethylene biosynthesis was accomplished using cDNAs encoding 1-aminocyclopropane-1-carboxylic acid (ACC) synthase and ACC oxidase in ribonuclease protection assays and in situ hybridizations. No ethylene was detected in siliques from plants grown at 50 and 25 mmol mol-1 O2. At the same time, silique ACC oxidase mRNA increased three-fold comparing plants grown under the lowest oxygen with ambient controls, whereas ACC synthase mRNA was unaffected. As O2 decreased, tissue-specific patterning of ACC oxidase and ACC synthase gene expression shifted from the embryo to the silique wall. These data demonstrate how low O2 modulates the activity and expression of the ethylene biosynthetic pathway during seed development in Arabidopsis.

NASA Discipline Plant Biology↗
NASA NTRS2003

Impact of low-temperature plasmas on Deinococcus radiodurans and biomolecules

The effects of cold plasma on Deinococcus radiodurans, plasmid DNA, and model proteins were assessed using microbiological, spectrometric, and biochemical techniques. In low power O(2) plasma (approximately 25 W, approximately 45 mTorr, 90 min), D. radiodurans, a radiation-resistant bacterium, showed a 99.999% reduction in bioburden. In higher power O(2) plasma (100 W and 500 mTorr), the reduction rate increased about 10-fold and observation by atomic force microscopy showed significant damage to the cell. Damage to cellular lipids, proteins, and chromosome was indicated by losses of infrared spectroscopic peaks at 2930, 1651, 1538, and 1245 cm(-1), respectively. In vitro experiments show that O(2) plasmas induce DNA strand scissions and cross-linking as well as reduction of enzyme activity. The observed degradation and removal of biomolecules was power-dependent. Exposures to 200 W at 500 mTorr removed biomolecules to below detection limits in 60 s. Emission spectroscopy indicated that D. radiodurans cells were volatilized into CO(2), CO, N(2), and H(2)O, confirming that these plasmas were removing complex biological matter from surfaces. A CO(2) plasma was not as effective as the O(2) plasma, indicating the importance of plasma composition and the dominant role of chemical degradation. Together, these findings have implications for NASA planetary protection schemes and for the contamination of Mars.

Evaluation Studies↗
NASA NTRS2015

2015 Space Radiation Standing Review Panel

The 2015 Space Radiation Standing Review Panel (from here on referred to as the SRP) met for a site visit in Houston, TX on December 8 - 9, 2015. The SRP met with representatives from the Space Radiation Element and members of the Human Research Program (HRP) to review the updated research plan for the Risk of Radiation Carcinogenesis Cancer Risk. The SRP also reviewed the newly revised Evidence Reports for the Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs) (Acute Risk), the Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure (CNS Risk), and the Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation (Degen Risk), as well as a status update on these Risks. The SRP would like to commend Dr. Simonsen, Dr. Huff, Dr. Nelson, and Dr. Patel for their detailed presentations. The Space Radiation Element did a great job presenting a very large volume of material. The SRP considers it to be a strong program that is well-organized, well-coordinated and generates valuable data. The SRP commended the tissue sharing protocols, working groups, systems biology analysis, and standardization of models. In several of the discussed areas the SRP suggested improvements of the research plans in the future. These include the following: It is important that the team has expanded efforts examining immunology and inflammation as important components of the space radiation biological response. This is an overarching and important focus that is likely to apply to all aspects of the program including acute, CVD, CNS, cancer and others. Given that the area of immunology/inflammation is highly complex (and especially so as it relates to radiation), it warrants the expansion of investigators expertise in immunology and inflammation to work with the individual research projects and also the NASA Specialized Center of Research (NSCORs). Historical data on radiation injury to be entered into the Watson “big data” study must be used with caution. The general scientific issues of reproducibility, details of experimental methods and data analysis from preclinical and basic research laboratories have been raised broadly over the last few years (not specific to this work) and indicate that caution must be applied in the ways these data are used. This pertains to preclinical data and also to phase 3 clinical trials in radiation oncology and medical oncology. Of course, appropriate use and analysis of these “big-data” sets also offer the potential of pinpointing limitations and extracting remaining useful information. Emphasis should be placed on the latter possibility. A key target is risk reduction from radiation exposure. Progress of the entire space program, now moving towards the Mars mission, requires timely answers to key components of human risk, which are known to be complex. Periodic review of progress should be conducted with additional resources directed into achieving critical milestones. Turning the long red bars to yellow and green (or for some risks such as CNS possibly to grey) must be high priority. That such progress will require new science and not engineering means that it should be viewed in a knowledge-based light. The technology-based aspects of engineering issues are certainly as important, however, science and knowledge-based problems are solved in a different way than engineering. Timelines for engineering are more predictable, while for science, progress can be methodical with occasional major incremental findings that can rapidly change the rate of progress. As opportunities for rapid incremental changes arise, periodic enhancement of investment is strongly recommended to enable such new knowledge to be quickly and efficiently exploited. Collaborations and linkages with National Institute of Allergy and Infectious Diseases (NIAID), the Biomedical Advanced Research and Development Authority (BARDA) and the Department of Defense (DoD) are in place and more are encouraged, where possible, with the radiation injury and medical countermeasure studies. This could include utilizing some of their animal model testing contracts to facilitate obtaining results using common platforms. Such approach will facilitate the comparison of results among laboratories, and will facilitate and accelerate the development of medical countermeasures. It is particularly noteworthy that the NASA Space Radiation Element is reaching out to the Multidisciplinary European Low Dose Initiative (MELODI) platform coordinating low dose radiation risk research, and to other international agencies that are studying low dose radiation effects in an effort to fill the void generated by the cancelation of the Department of Energy (DOE) low dose radiation program. While NASA is working actively with NIAID and BARDA to integrate their relevant findings of radiation mitigator investigations to NASA programs, the committee notes its disappointment that the United States currently lacks a dedicated low dose radiation program with clear mechanistic orientation and aimed at the quantification and mitigation of human radiation risk on Earth. This void gives to the NASA Space Radiation Program Element special societal value, but also makes its overall design more challenging.

Steinberg, Susan↗
NASA NTRS2001

Modulation of lens cell adhesion molecules by particle beams

Cell adhesion molecules (CAMs) are proteins which anchor cells to each other and to the extracellular matrix (ECM), but whose functions also include signal transduction, differentiation, and apoptosis. We are testing a hypothesis that particle radiations modulate CAM expression and this contributes to radiation-induced lens opacification. We observed dose-dependent changes in the expression of beta 1-integrin and ICAM-1 in exponentially-growing and confluent cells of a differentiating human lens epithelial cell model after exposure to particle beams. Human lens epithelial (HLE) cells, less than 10 passages after their initial culture from fetal tissue, were grown on bovine corneal endothelial cell-derived ECM in medium containing 15% fetal bovine serum and supplemented with 5 ng/ml basic fibroblast growth factor (FGF-2). Multiple cell populations at three different stages of differentiation were prepared for experiment: cells in exponential growth, and cells at 5 and 10 days post-confluence. The differentiation status of cells was characterized morphologically by digital image analysis, and biochemically by Western blotting using lens epithelial and fiber cell-specific markers. Cultures were irradiated with single doses (4, 8 or 12 Gy) of 55 MeV protons and, along with unirradiated control samples, were fixed using -20 degrees C methanol at 6 hours after exposure. Replicate experiments and similar experiments with helium ions are in progress. The intracellular localization of beta 1-integrin and ICAM-1 was detected by immunofluorescence using monoclonal antibodies specific for each CAM. Cells known to express each CAM were also processed as positive controls. Both exponentially-growing and confluent, differentiating cells demonstrated a dramatic proton-dose-dependent modulation (upregulation for exponential cells, downregulation for confluent cells) and a change in the intracellular distribution of the beta 1-integrin, compared to unirradiated controls. In contrast, there was a dose-dependent increase in ICAM-1 immunofluorescence in confluent, but not exponentially-growing cells. These results suggest that proton irradiation downregulates beta 1-integrin and upregulates ICAM-1, potentially contributing to cell death or to aberrant differentiation via modulation of anchorage and/or signal transduction functions. Quantification of the expression levels of the CAMs by Western analysis is in progress.

NASA Discipline Radiation Health↗