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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
NASA NTRS2013

Epidermal Homeostasis and Radiation Responses in a Multiscale Tissue Modeling Framework

The surface of skin is lined with several thin layers of epithelial cells that are maintained throughout life time by a small population of stem cells. High dose radiation exposures could injure and deplete the underlying proliferative cells and induce cutaneous radiation syndrome. In this work we propose a multiscale computational model for skin epidermal dynamics that links phenomena occurring at the subcellular, cellular, and tissue levels of organization, to simulate the experimental data of the radiation response of swine epidermis, which is closely similar to human epidermis. Incorporating experimentally measured histological and cell kinetic parameters, we obtain results of population kinetics and proliferation indexes comparable to observations in unirradiated and acutely irradiated swine experiments. At the sub-cellular level, several recently published Wnt signaling controlled cell-cycle models are applied and the roles of key components and parameters are analyzed. Based on our simulation results, we demonstrate that a moderate increase of proliferation rate for the survival proliferative cells is sufficient to fully repopulate the area denuded by high dose radiation, as long as the integrity of underlying basement membrane is maintained. Our work highlights the importance of considering proliferation kinetics as well as the spatial organization of tissues when conducting in vivo investigations of radiation responses. This integrated model allow us to test the validity of several basic biological rules at the cellular level and sub-cellular mechanisms by qualitatively comparing simulation results with published research, and enhance our understanding of the pathophysiological effects of ionizing radiation on skin.

Hu, Shaowen↗
NASA NTRS2000

Three-Dimensional Transgenic Cell Models to Quantify Space Genotoxic Effects

In this paper we describe a three-dimensional, multicellular tissue-equivalent model, produced in NASA-designed, rotating wall bioreactors using mammalian cells engineered for genomic containment of mUltiple copies of defined target genes for genotoxic assessment. The Rat 2(lambda) fibroblasts (Stratagene, Inc.) were genetically engineered to contain high-density target genes for mutagenesis. Stable three-dimensional, multicellular spheroids were formed when human mammary epithelial cells and Rat 2(lambda) fibroblasts were cocultured on Cytodex 3 Beads in a rotating wall bioreactor. The utility of this spheroidal model for genotoxic assessment was indicated by a linear dose response curve and by results of gene sequence analysis of mutant clones from 400micron diameter spheroids following low-dose, high-energy, neon radiation exposure

Gonda, S.↗
NASA NTRS2016

Weather and Climate Change Impacts on Human Mortality in Bangladesh

Weather and climate profoundly affect human health. Several studies have demonstrated a U-, V-, or J-shaped temperature-mortality relationship with increasing death rates at the lower and particularly upper end of the temperature distribution. The objectives of this study were (1) to analyze the relationship between temperature and mortality in Bangladesh for different subpopulations and (2) to project future heat-related mortality under climate change scenarios. We used (non-)parametric Generalized Additive Models adjusted for trend, season and day of the month to analyze the effect of temperature on daily mortality. We found a decrease in mortality with increasing temperature over a wide range of values; between the 90th and 95th percentile an abrupt increase in mortality was observed which was particularly pronounced for the elderly above the age of 65 years, for males, as well as in urban areas and in areas with a high socio-economic status. Daily historical and future temperature values were obtained from the NASA Earth Exchange Global Daily Downscaled Projections (NEX-GDDP) dataset. This dataset is comprised of downscaled climate scenarios for the globe that are derived from the General Circulation Model (GCM) runs conducted under the Coupled Model Intercomparison Project Phase 5 (CMIP5). The derived dose-response functions were used to estimate the number of heat-related deaths occurring during the 1990s (1980-2005), the 2020s (2011-2040) and the 2050s (2041-2070). We estimated that excess deaths due to heat will triple from the 1990s to the 2050s, with an annual number of 0.5 million excess deaths in 1990 to and expected number of 1.5 millions in 2050.

mortality↗
NASA NTRSDate not supplied

Statistical Engineering Toward Commercial Supersonic Flight: NASA's Quesst Mission

NASA’s Quesst Mission has dual goals of demonstrating low-noise supersonic technology in flight and surveying public reactions to low-noise supersonic overflight. For half a century, commercial aircraft have been required to fly slower than the speed of sound over land to prevent “creating an unacceptable situation” on the ground due to sonic booms. However, aircraft shaping techniques honed through decades of research have dramatically changed the way shockwaves from supersonic flight merge together as they travel to the ground. What used to sound like a boom on the ground will be transformed into a thump. NASA is now building a full-scale, piloted demonstration aircraft called the X-59 to demonstrate low-noise supersonic flight. In 2024, the X-59 aircraft will commence a national series of community overflight surveys to collect data on how people perceive “sonic thumps.” The results will be provided to national and international noise regulators as they consider creating new standards that allow commercial supersonic flight over land at acceptably low noise levels. In this presentation we provide historical context for the current prohibitions on supersonic commercial flight. Using data collected during earlier NASA tests, we demonstrate how generalized linear mixed models can be used to inform the functional dose-response curve. We also illustrate simulation experiments of the variability of sonic thump exposure across the United States. Finally, we discuss some of the challenges in designing the future community studies and generalizing them to a nationally-representative dose-response curve.

Quesst↗
NASA NTRS1996

The Implementation and Evaluation of the Emergency Response Dose Assessment System (ERDAS) at Cape Canaveral Air Station/Kennedy Space Center

The Emergency Response Dose Assessment System (ERDAS) is a system which combines the mesoscale meteorological prediction model RAMS with the diffusion models REEDM and HYPACT. Operators use a graphical user interface to run the models for emergency response and toxic hazard planning at CCAS/KCS. The Applied Meteorology Unit has been evaluating the ERDAS meteorological and diffusion models and obtained the following results: (1) RAMS adequately predicts the occurrence of the daily sea breeze during non-cloudy conditions for several cases. (2) RAMS shows a tendency to predict the sea breeze to occur slightly earlier and to move it further inland than observed. The sea breeze predictions could most likely be improved by better parameterizing the soil moisture and/or sea surface temperatures. (3) The HYPACT/REEDM/RAMS models accurately predict launch plume locations when RAMS winds are accurate and when the correct plume layer is modeled. (4) HYPACT does not adequately handle plume buoyancy for heated plumes since all plumes are presently treated as passive tracers. Enhancements should be incorporated into the ERDAS as it moves toward being a fully operational system and as computer workstations continue to increase in power and decrease in cost. These enhancements include the following: activate RAMS moisture physics; use finer RAMS grid resolution; add RAMS input parameters (e.g. soil moisture, radar, and/or satellite data); automate data quality control; implement four-dimensional data assimilation; modify HYPACT plume rise and deposition physics; and add cumulative dosage calculations in HYPACT.

Evans, Randolph J.↗
NASA NTRSDate not supplied

The Sufficient Component Cause Model Explaining Low-Dose Radiobiology through an Epidemiologic Lens

One of the major challenges in understanding space radiation-induced carcinogenesis is the uncertainty from translating radiobiological research in cellular and animal models to humans, especially at doses below 100 mSv. Biological studies have shown a host of potential outcomes at low doses in animal and cellular models. The existence of non-targeted effects as bystander and abscopal effects is well-documented from clinical research and basic science1,2,3. While some studies have shown increased effects at low doses, others have shown evidence of hormetic bystander effects, where radiation exposure may be beneficial4,5,6. Despite these varied and diverse findings, epidemiologic studies largely support the linear-no threshold (LNT) assumption used by radiation protection guidance7,8. Translational animal-to-human models have predominantly considered ratio values such as the relative biological effectiveness (RBE) and dose and dose-rate effectiveness factor (DDREF) that rely on the assumption of LNT rather than implementing specific dose-response shapes in the low-dose region, and translational cell-to-human models are uncommon. The sufficient component cause model presents an opportunity to examine biological findings at low doses from an epidemiological lens9. In this model, exposures “sufficient” to cause an outcome of interest are presented in pie charts, such that when all slices of a pie chart are fulfilled, the outcome will occur. Multiple pie charts may exist for a single outcome, illustrating individual differences9. In 1988,Greenland and Poole adapted the sufficient component cause model to incorporate interaction with other exposures (such as genetics or lifestyle factors)10. They show that a range of biological processes are possible in a population, but that an epidemiologic study will only reveal the mean outcome from the population at large10,11. Using this construct, the multiple outcomes presented in radiobiological models to date can be explained in the context of epidemiologic studies. This presentation aims to demonstrate a causal framework that can integrate radiobiological and epidemiological models to date. It is intended as a conversation starter to spur future research.

C M Milder↗
NASA NTRSDate not supplied

The Potential Outcome Model: Explaining Low-Dose Radiobiology through an Epidemiologic Lens

One of the major challenges in understanding space radiation-induced carcinogenesis is the uncertainty from translating radiobiological research in cellular and animal models to humans, especially at doses below 100 mSv. Biological studies have shown a host of potential outcomes at lowdoses in animal and cellular models. The existence of non-targeted effects as bystander and abscopal effects is well-documented from clinical research and basic science1,2,3. While some studies have shown increased effects at low doses, others have shown evidence of hormetic bystander effects, where radiation exposure may be beneficial4,5,6. Despite these varied and diverse findings, epidemiologic studies largely support the linear-no threshold (LNT) assumption used by radiation protection guidance7,8. Translational animal-to-human models have predominantly considered ratio values such as the relative biological effectiveness (RBE) and dose and dose-rate effectiveness factor (DDREF) that rely on the assumption of LNT rather than implementing specific dose-response shapes in the low-dose region, and translational cell-to-human models are uncommon. The sufficient component cause model presents an opportunity to examine biological findings at low doses from an epidemiological lens9. In this model, exposures “sufficient” to cause an outcome of interest are presented in pie charts, such that when all slices of a pie chart are fulfilled, the outcome will occur. Multiple pie charts may exist for a single outcome, illustrating individual differences9. In 1988,Greenland and Poole adapted the sufficient component cause model to incorporate interaction with other exposures (such as genetics or lifestyle factors)10. They show that a range of biological processes are possible in a population, but that an epidemiologic study will only reveal the mean outcome from the population at large10,11. Using this construct, the multiple outcomes presented in radiobiological models to date can be explained in the context of epidemiologic studies. This presentation aims to demonstrate a causal framework that can integrate radiobiological and epidemiological models to date. It is intended as a conversation starter to spur future research.

C M Milder↗
NASA NTRS2000

Analysis of MIR-18 results for physical and biological dosimetry: radiation shielding effectiveness in LEO

We compare models of radiation transport and biological response to physical and biological dosimetry results from astronauts on the Mir space station. Transport models are shown to be in good agreement with physical measurements and indicate that the ratio of equivalent dose from the Galactic Cosmic Rays (GCR) to protons is about 3/2:1 and that this ratio will increase for exposures to internal organs. Two biological response models are used to compare to the Mir biodosimetry for chromosome aberration in lymphocyte cells; a track-structure model and the linear-quadratic model with linear energy transfer (LET) dependent weighting coefficients. These models are fit to in vitro data for aberration formation in human lymphocytes by photons and charged particles. Both models are found to be in reasonable agreement with data for aberrations in lymphocytes of Mir crew members: however there are differences between the use of LET dependent weighting factors and track structure models for assigning radiation quality factors. The major difference in the models is the increased effectiveness predicted by the track model for low charge and energy ions with LET near 10 keV/micrometers. The results of our calculations indicate that aluminum shielding, although providing important mitigation of the effects of trapped radiation, provides no protective effect from the galactic cosmic rays (GCR) in low-earth orbit (LEO) using either equivalent dose or the number of chromosome aberrations as a measure until about 100 g/cm 2 of material is used.

Flight Experiment↗
NASA NTRS2003

Stereology techniques in radiation biology

Clinicians involved in conventional radiation therapy are very concerned about the dose-response relationships of normal tissues. Before proceeding to new clinical protocols, radiation biologists involved with conformal proton therapy believe it is necessary to quantify the dose response and tolerance of the organs and tissues that will be irradiated. An important focus is on the vasculature. This presentation reviews the methodology and format of using confocal microscopy and stereological methods to quantify tissue parameters, cell number, tissue volume and surface area, and vessel length using the microvasculature as a model tissue. Stereological methods and their concepts are illustrated using an ongoing study of the dose response of the microvessels in proton-irradiated hemibrain. Methods for estimating the volume of the brain and the brain cortex, the total number of endothelial cells in cortical microvessels, the length of cortical microvessels, and the total surface area of cortical microvessel walls are presented step by step in a way understandable for readers with little mathematical background. It is shown that stereological techniques, based on a sound theoretical basis, are powerful and reliable and have been used successfully.

Non-NASA Center↗
NASA NTRS2003

A constitutively activated mutant of human soluble guanylyl cyclase (sGC): implication for the mechanism of sGC activation

Heterodimeric alphabeta soluble guanylyl cyclase (sGC) is a recognized receptor for nitric oxide (NO) and mediates many of its physiological functions. Although it has been clear that the heme moiety coordinated by His-105 of the beta subunit is crucial for mediating the activation of the enzyme by NO, it is not understood whether the heme moiety plays any role in the function of the enzyme in the absence of NO. Here we analyze the effects of biochemical and genetic removal of heme and its reconstitution on the activity of the enzyme. Detergent-induced loss of heme from the wild-type alphabeta enzyme resulted in several-fold activation of the enzyme. This activation was inhibited after hemin reconstitution. A heme-deficient mutant alphabetaCys-105 with Cys substituted for His-105 was constitutively active with specific activity approaching the activity of the wild-type enzyme activated by NO. However, reconstitution of mutant enzyme with heme and/or DTT treatment significantly inhibited the enzyme. Mutant enzyme reconstituted with ferrous heme was activated by NO and CO alone and showed additive effects between gaseous effectors and the allosteric activator 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrim idin-4-ylamine. We propose that the heme moiety through its coordination with His-105 of the beta subunit acts as an endogenous inhibitor of sGC. Disruption of the heme-coordinating bond induced by binding of NO releases the restrictions imposed by this bond and allows the formation of an optimally organized catalytic center in the heterodimer.

Non-NASA Center↗
NASA NTRS2009

Development of a GCR Event-based Risk Model

A goal at NASA is to develop event-based systems biology models of space radiation risks that will replace the current dose-based empirical models. Complex and varied biochemical signaling processes transmit the initial DNA and oxidative damage from space radiation into cellular and tissue responses. Mis-repaired damage or aberrant signals can lead to genomic instability, persistent oxidative stress or inflammation, which are causative of cancer and CNS risks. Protective signaling through adaptive responses or cell repopulation is also possible. We are developing a computational simulation approach to galactic cosmic ray (GCR) effects that is based on biological events rather than average quantities such as dose, fluence, or dose equivalent. The goal of the GCR Event-based Risk Model (GERMcode) is to provide a simulation tool to describe and integrate physical and biological events into stochastic models of space radiation risks. We used the quantum multiple scattering model of heavy ion fragmentation (QMSFRG) and well known energy loss processes to develop a stochastic Monte-Carlo based model of GCR transport in spacecraft shielding and tissue. We validated the accuracy of the model by comparing to physical data from the NASA Space Radiation Laboratory (NSRL). Our simulation approach allows us to time-tag each GCR proton or heavy ion interaction in tissue including correlated secondary ions often of high multiplicity. Conventional space radiation risk assessment employs average quantities, and assumes linearity and additivity of responses over the complete range of GCR charge and energies. To investigate possible deviations from these assumptions, we studied several biological response pathway models of varying induction and relaxation times including the ATM, TGF -Smad, and WNT signaling pathways. We then considered small volumes of interacting cells and the time-dependent biophysical events that the GCR would produce within these tissue volumes to estimate how GCR event rates mapped to biological signaling induction and relaxation times. We considered several hypotheses related to signaling and cancer risk, and then performed simulations for conditions where aberrant or adaptive signaling would occur on long-duration space mission. Our results do not support the conventional assumptions of dose, linearity and additivity. A discussion on how event-based systems biology models, which focus on biological signaling as the mechanism to propagate damage or adaptation, can be further developed for cancer and CNS space radiation risk projections is given.

Cucinotta, Francis A.↗
NASA NTRS1999

Applications of amorphous track models in radiation biology

The average or amorphous track model uses the response of a system to gamma-rays and the radial distribution of dose about an ion's path to describe survival and other cellular endpoints from proton, heavy ion, and neutron irradiation. This model has been used for over 30 years to successfully fit many radiobiology data sets. We review several extensions of this approach that address objections to the original model, and consider applications of interest in radiobiology and space radiation risk assessment. In the light of present views of important cellular targets, the role of target size as manifested through the relative contributions from ion-kill (intra-track) and gamma-kill (inter-track) remains a critical question in understanding the success of the amorphous track model. Several variations of the amorphous model are discussed, including ones that consider the radial distribution of event-sizes rather than average electron dose, damage clusters rather than multiple targets, and a role for repair or damage processing.

NASA Discipline Radiation Health↗
NASA NTRS2018

Coalescence of DNA Double Strand Breaks Induced by Galactic Cosmic Radiation is Modulated by Genetics in 15 Inbred Strains of Mice

In this manuscript we address the challenges associated with the ability to predict radiation sensitivity associated with exposure to either cosmic radiation or X-rays in a population study, by monitoring DNA damage sensing protein 53BP1 forming small nuclear radiation-induced foci (RIF) as a surrogate biomarker of DNA double strand breaks (DSB). 76 primary skin fibroblasts were isolated from 10 collaborative cross strains and five reference inbred mice (C57Bl/6, BALB/CByJ, B6C3, C3H and CBA/CaJ) and exposed to three different charged nuclei of increasing LET (350 MeV/n Si, 350 MeV/n Ar and 600 MeV/n Fe) and X-ray. Our data brings strong evidence against the classic "contact-first" model where DSBs are assumed to be immobile and repaired at the lesion site. In contrast, our model suggests nearby DSBs move into single repair unit characterized by large RIF before the repair machinery kicks in. Such model has the advantage of being much more efficient molecularly but is poorly suited to deal with cosmic radiation, where energy is concentrated along the particle trajectory, inducing a large density of DSBs along each particle track. In accordance with this model, RIF quantification after X-ray exposition showed a saturated dose response for early time points post-irradiation for all strains. Similarly, the high-LET response showed that RIF number matched the number of track per cell, not the number of expected DSB per cell (1). At the temporal level, we noted that the percentage of unrepaired high-LET tracks over a 48 hour time-course increased with LET, confirming that the DNA repair process becomes more difficult as more DSB coalesce into single RIF. There was also good agreement between persistent RIF levels measured in-vitro in the primary skin cultures and survival levels of T-cells and B-cells collected in blood samples from 10 CC strains 24 hours after 0.1 Gy whole-body dose of X-ray. This suggests that persistent RIF 24 hour post-IR is a good surrogate in-vitro biomarker for in-vivo radiation toxicity. Finally, at the genomic level, large differences in repair rates between strains for high-LET allowed us to identify suggestive genetic loci associated with radiation sensitivity. Interestingly, the two highest LETs provided the most strain variation with a common locus on Chromosome 10 highly enriched for DNA repair associated genes we discussed in detail.

Radiation-Induced Foci↗
NASA NTRS1998

Depth dependence of absorbed dose, dose equivalent and linear energy transfer spectra of galactic and trapped particles in polyethylene and comparison with calculations of models

A matched set of five tissue-equivalent proportional counters (TEPCs), embedded at the centers of 0 (bare), 3, 5, 8 and 12-inch-diameter polyethylene spheres, were flown on the Shuttle flight STS-81 (inclination 51.65 degrees, altitude approximately 400 km). The data obtained were separated into contributions from trapped protons and galactic cosmic radiation (GCR). From the measured linear energy transfer (LET) spectra, the absorbed dose and dose-equivalent rates were calculated. The results were compared to calculations made with the radiation transport model HZETRN/NUCFRG2, using the GCR free-space spectra, orbit-averaged geomagnetic transmission function and Shuttle shielding distributions. The comparison shows that the model fits the dose rates to a root mean square (rms) error of 5%, and dose-equivalent rates to an rms error of 10%. Fairly good agreement between the LET spectra was found; however, differences are seen at both low and high LET. These differences can be understood as due to the combined effects of chord-length variation and detector response function. These results rule out a number of radiation transport/nuclear fragmentation models. Similar comparisons of trapped-proton dose rates were made between calculations made with the proton transport model BRYNTRN using the AP-8 MIN trapped-proton model and Shuttle shielding distributions. The predictions of absorbed dose and dose-equivalent rates are fairly good. However, the prediction of the LET spectra below approximately 30 keV/microm shows the need to improve the AP-8 model. These results have strong implications for shielding requirements for an interplanetary manned mission.

Flight Experiment↗
NASA NTRS1994

Kinetics model for initiation and promotion for describing tumor prevalence from HZE radiation

A kinetics model for cellular repair and misrepair for multiple radiation-induced lesions (mutation-inactivation) is coupled to a two-mutation model of initiation and promotion in tissue to provide a parametric description of tumor prevalence in the Harderian gland in a mouse. Dose-response curves are described for gamma-rays and relativistic ions. The effects of nuclear fragmentation are also considered for high-energy proton and alpha particle exposures The model described provides a parametric description of age-dependent cancer induction for a wide range of radiation fields. We also consider the two hypotheses that radiation acts either solely as an initiator or as both initiator and promoter and make model calculations for fractionation exposures from gamma-rays and relativistic Fe ions. For fractionated Fe exposures, an inverse dose-rate effect is provided by a promotion hypothesis using a mutation rate for promotion typical of single-gene mutations.

Cucinotta, Francis A.↗
NASA NTRS2009

A New View of Radiation-Induced Cancer: Integrating Short-and Long-Term Processes. Part I: Approach

Mathematical models of radiation carcinogenesis are important for understanding mechanisms and for interpreting or extrapolating risk. There are two classes of such models: (1) long-term formalisms that track premalignant cell numbers throughout an entire lifetime but treat initial radiation dose-response simplistically and (2) short-term formalisms that provide a detailed initial dose-response even for complicated radiation protocols, but address its modulation during the subsequent cancer latency period only indirectly. We argue that integrating short- and long-term models is needed. As an example of this novel approach, we integrate a stochastic short-term initiation/ inactivation/repopulation model with a deterministic two-stage long-term model. Within this new formalism, the following assumptions are implemented: radiation initiates, promotes, or kills pre-malignant cells; a pre-malignant cell generates a clone, which, if it survives, quickly reaches a size limitation; the clone subsequently grows more slowly and can eventually generate a malignant cell; the carcinogenic potential of pre-malignant cells decreases with age.

Shuryak, Igor↗
NASA NTRS1992

Commentary 2 to Cox and Little: radiation-induced oncogenic transformation: the interplay between dose, dose protraction, and radiation quality

There is now a substantial body of evidence for end points such as oncogenic transformation in vitro, and carcinogenesis and life shortening in vivo, suggesting that dose protraction leads to an increase in effectiveness relative to a single, acute exposure--at least for radiations of medium linear energy transfer (LET) such as neutrons. Table I contains a summary of the pertinent data from studies in which the effect is seen. [table: see text] This phenomenon has come to be known as the "inverse dose rate effect," because it is in marked contrast to the situation at low LET, where protraction in delivery of a dose of radiation, either by fractionation or low dose rate, results in a decreased biological effect; additionally, at medium and high LET, for radiobiological end points such as clonogenic survival, the biological effectiveness is independent of protraction. The quantity and quality of the published reports on the "inverse dose rate effect" leaves little doubt that the effect is real, but the available evidence indicates that the magnitude of the effect is due to a complex interplay between dose, dose rate, and radiation quality. Here, we first summarize the available data on the inverse dose rate effect and suggest that it follows a consistent pattern in regard to dose, dose rate, and radiation quality; second, we describe a model that predicts these features; and, finally, we describe the significance of the effect for radiation protection.

Review, Tutorial↗