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NASA NTRS2009

Biophysics Representation of the Two-Hit Model of Alzheimer's Disease for the Exploration of Late CNS Risks from Space Radiation

A concern for long-term space travel outside the Earth s magnetic field is the late effects to the central nervous system (CNS) from galactic cosmic ray (GCR) or solar particle events (SPE). Human epidemiology data is severely limited for making CNS risk estimates and it is not clear such effects occur following low LET exposures. We are developing systems biology models based on biological information on specific diseases, and experimental data for proton and heavy ion radiation. A two-hit model of Alzheimer s disease (AD) has been proposed by Zhu et al.(1), which is the framework of our model. Of importance is that over 50% of the US population over the age of 75-y have mild to severe forms of AD. Therefore we recommend that risk assessment for a potential AD risk from space radiation should focus on the projection of an earlier age of onset of AD and the prevention of this possible acceleration through countermeasures. In the two-hit model, oxidative stress and aberrant cell cycle-related abnormalities leading to amyloid-beta plaques and neurofibrillary tangles are necessary and invariant steps in AD. We have formulated a stochastic cell kinetics model of the two-hit AD model. In our model a population of neuronal cells is allowed to undergo renewal through neurogenesis and is susceptible to oxidative stress or cell cycle abnormalities with age-specific accumulation of damage. Baseline rates are fitted to AD population data for specific ages, gender, and for persons with an apolipoprotein 4 allele. We then explore how low LET or heavy ions may increase either of the two-hits or neurogenesis either through persistent oxidative stress, direct mutation, or through changes to the micro-environment, and suggest possible ways to develop accurate quantitative estimates of these processes for predicting AD risks following long-term space travel.

Cucinotta, Francis A.↗
NASA NTRS2009

Analytic Shielding Optimization to Reduce Crew Exposure to Ionizing Radiation Inside Space Vehicles

A sustainable lunar architecture provides capabilities for leveraging out-of-service components for alternate uses. Discarded architecture elements may be used to provide ionizing radiation shielding to the crew habitat in case of a Solar Particle Event. The specific location relative to the vehicle where the additional shielding mass is placed, as corroborated with particularities of the vehicle design, has a large influence on protection gain. This effect is caused by the exponential- like decrease of radiation exposure with shielding mass thickness, which in turn determines that the most benefit from a given amount of shielding mass is obtained by placing it so that it preferentially augments protection in under-shielded areas of the vehicle exposed to the radiation environment. A novel analytic technique to derive an optimal shielding configuration was developed by Lockheed Martin during Design Analysis Cycle 3 (DAC-3) of the Orion Crew Exploration Vehicle (CEV). [1] Based on a detailed Computer Aided Design (CAD) model of the vehicle including a specific crew positioning scenario, a set of under-shielded vehicle regions can be identified as candidates for placement of additional shielding. Analytic tools are available to allow capturing an idealized supplemental shielding distribution in the CAD environment, which in turn is used as a reference for deriving a realistic shielding configuration from available vehicle components. While the analysis referenced in this communication applies particularly to the Orion vehicle, the general method can be applied to a large range of space exploration vehicles, including but not limited to lunar and Mars architecture components. In addition, the method can be immediately applied for optimization of radiation shielding provided to sensitive electronic components.

Gaza, Razvan↗
NASA NTRS2009

A Cell Kinetic Model of Granulocytopoiesis Under Radiation Exposure: Extension from Murines to Canines and Humans

Space radiation poses significant challenges to space travel, and it is essential to understand the possible adverse effects from space radiation exposure to the radiosensitive organ systems that are important for immediate survival of human, e.g., the hematopoietic system. In this presentation a biomathematical model of granulocytopoiesis is described and used to analyze the blood granulocyte changes seen in the blood of mammalians under continuous and acute radiation exposure. This is one of a set of hematopoietic models that have been successfully utilized to simulate and interpret the experimental data of acute and chronic radiation on rodents. We discuss the underlying implicit regulation mechanism and the biological relevance of the kinetic parameters estimation method. Extension of the model to predictions in dogs and humans systems indicates that the modeling results are consistent with the cumulative experimental and empirical data from various sources. This implies the potential to integrate the models into one united system for monitoring the hematopoietic response of various species under irradiation. Based on the evidence of threshold responses of dogs to extended periods of low daily dose exposures, we discuss the potential health risks of the space traveler under chronic stress of low-dose irradiation and the possibly encountered Solar Particle Events.

Hu, Shaowen↗
NASA NTRS2009

Thermal Vacuum Test of Ice as a Phase Change Material Integrated with a Radiator

Water may be used as radiation shielding for Solar Particle Events (SPE) to protect crewmembers in the Lunar Electric Rover (LER). Because the water is already present for radiation protection, it could also provide a mass efficient solution to the vehicle's thermal control system. This water can be frozen by heat rejection from a radiator and used as a Phase Change Material (PCM) for thermal storage. Use of this water as a PCM can eliminate the need for a pumped fluid loop thermal control system as well as reduce the required size of the radiator. This paper describes the testing and analysis performed for the Rover Engineering Development Unit (REDU), a scaled-down version of a water PCM heat sink for the LER. The REDU was tested in a thermal-vacuum chamber at environmental temperatures similar to those of a horizontal radiator panel on the lunar surface. Testing included complete freeze and melt cycles along with scaled transient heat load profiles simulating a 24-hour day for the rover.

Lee, Steve↗
NASA NTRS2010

Molecular and Histopathological Changes in Mouse Intestinal Tissue After Proton Exposure

Radiation in space, including types from solar particle events (SPE's), poses serious health risks to astronauts and is especially dangerous for long duration missions. Protons are the most abundant particles in deep space and to date there is little known about the details of the negative consequences crew members will face upon exposure to them. This ongoing project involves a mouse model subjected to several minutes of proton radiation at an energy of 250 MeV and doses of 0 Gy, 0.1 Gy, 1 Gy, and 2 Gy. The gastrointestinal tract of each animal was dissected four hours post-irradiation and the small intestine was isolated and flash-frozen. Three specimens per dose were studied. Tissue was homogenized and RNA was isolated in order for cDNA synthesis and real-time PCR to be performed. Gene expression changes are currently being analyzed specific to mouse apoptosis. Immunohistochemistry will be used to confirm any significant changes found in the analyses. Immunohistochemistry is also being used to observe gamma H2AX staining to learn of any DNA damage that occurred as a result of proton exposure. We expect to see increased DNA damage due to proton exposure. Finally, histopathologic observation of the tissue will be completed using standard H&E staining methods to screen for morphologic changes. Increased apoptosis is expected to be seen in the tissues which is typical of radiation damage. Observations will be confirmed by a pathologist.

Purgason, A.↗
NASA NTRS2010

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

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

Kim, Myung-Hee Y.↗
NASA NTRS2010

Faster and More Accurate Transport Procedures for HZETRN

Several aspects of code verification are examined for HZETRN. First, a detailed derivation of the numerical marching algorithms is given. Next, a new numerical method for light particle transport is presented, and improvements to the heavy ion transport algorithm are discussed. A summary of various coding errors is also given, and the impact of these errors on exposure quantities is shown. Finally, a coupled convergence study is conducted. From this study, it is shown that past efforts in quantifying the numerical error in HZETRN were hindered by single precision calculations and computational resources. It is also determined that almost all of the discretization error in HZETRN is caused by charged target fragments below 50 AMeV. Total discretization errors are given for the old and new algorithms, and the improved accuracy of the new numerical methods is demonstrated. Run time comparisons are given for three applications in which HZETRN is commonly used. The new algorithms are found to be almost 100 times faster for solar particle event simulations and almost 10 times faster for galactic cosmic ray simulations.

Slaba, Tony C.↗
NASA NTRS2010

Thermal Vacuum Test of Ice as a Phase Change Material Integrated with a Radiator

Water may be used as radiation shielding for Solar Particle Events (SPE) to protect crewmembers in the Lunar Electric Rover (LER). Because the water is already present for radiation protection, it could also provide a mass efficient solution to the vehicle's thermal control system. This water can be frozen by heat rejection from a radiator and used as a Phase Change Material (PC1V1) for thermal storage. Use of this water as a PCM can eliminate the need for a pumped fluid loop thermal control system as well as reduce the required size of the radiator. This paper describes the testing and analysis performed for the Rover Engineering Development Unit (REDU), a scaled-down version of a water PCM heat sink for the LER. The REDU was tested in a thermal-vacuum chamber at environmental temperatures similar to those of a horizontal radiator panel on the lunar surface. Testing included complete freeze and melt cycles along with scaled transient heat load profiles simulating a 24-hour day for the rover.

Lee, Steve A.↗
NASA NTRS2010

Recent Developments in Three Dimensional Radiation Transport Using the Green's Function Technique

In the future, astronauts will be sent into space for longer durations of time compared to previous missions. The increased risk of exposure to dangerous radiation, such as Galactic Cosmic Rays and Solar Particle Events, is of great concern. Consequently, steps must be taken to ensure astronaut safety by providing adequate shielding. In order to better determine and verify shielding requirements, an accurate and efficient radiation transport code based on a fully three dimensional radiation transport model using the Green's function technique is being developed

Rockell, Candice↗
NASA NTRS2010

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

The space radiation environment, particularly solar particle events (SPEs), poses the risk of acute radiation sickness (ARS) to humans; and organ doses from SPE exposure may reach critical levels during extra vehicular activities (EVAs) or within lightly shielded spacecraft. NASA has developed an organ dose projection model using the BRYNTRN with SUMDOSE computer codes, and a probabilistic model of Acute Radiation Risk (ARR). The codes BRYNTRN and SUMDOSE, written in FORTRAN, are a Baryon transport code and an output data processing code, respectively. The ARR code is written in C. The risk projection models of organ doses and ARR take the output from BRYNTRN as an input to their calculations. BRYNTRN code operation requires extensive input preparation. With a graphical user interface (GUI) to handle input and output for BRYNTRN, the response models can be connected easily and correctly to BRYNTRN in friendly way. A GUI for the Acute Radiation Risk and BRYNTRN Organ Dose (ARRBOD) projection code provides seamless integration of input and output manipulations, which are required for operations of the ARRBOD modules: BRYNTRN, SUMDOSE, and the ARR probabilistic response model. The ARRBOD GUI is intended for mission planners, radiation shield designers, space operations in the mission operations directorate (MOD), and space biophysics researchers. The ARRBOD GUI will serve as a proof-of-concept example for future integration of other human space applications risk projection models. The current version of the ARRBOD GUI is a new self-contained product and will have follow-on versions, as options are added: 1) human geometries of MAX/FAX in addition to CAM/CAF; 2) shielding distributions for spacecraft, Mars surface and atmosphere; 3) various space environmental and biophysical models; and 4) other response models to be connected to the BRYNTRN. The major components of the overall system, the subsystem interconnections, and external interfaces are described in this report; and the ARRBOD GUI product is explained step by step in order to serve as a tutorial.

Kim, Myung-Hee↗
NASA NTRS2010

Meeting Radiation Protection Requirements and Reducing Spacecraft Mass - A Multifunctional Materials Approach

Both crew and radio-sensitive systems, especially electronics must be protected from the effects of the space radiation environment. One method of mitigating this radiation exposure is to use passive-shielding materials. In previous vehicle designs such as the International Space Station (ISS), materials such as aluminum and polyethylene have been used as parasitic shielding to protect crew and electronics from exposure, but these designs add mass and decrease the amount of usable volume inside the vehicle. Thus, it is of interest to understand whether structural materials can also be designed to provide the radiation shielding capability needed for crew and electronics, while still providing weight savings and increased useable volume when compared against previous vehicle shielding designs. In this paper, we present calculations and analysis using the HZETRN (deterministic) and FLUKA (Monte Carlo) codes to investigate the radiation mitigation properties of these structural shielding materials, which includes graded-Z and composite materials. This work is also a follow-on to an earlier paper, that compared computational results for three radiation transport codes, HZETRN, HETC, and FLUKA, using the Feb. 1956 solar particle event (SPE) spectrum. In the following analysis, we consider the October 1989 Ground Level Enhanced (GLE) SPE as the input source term based on the Band function fitting method. Using HZETRN and FLUKA, parametric absorbed doses at the center of a hemispherical structure on the lunar surface are calculated for various thicknesses of graded-Z layups and an all-aluminum structure. HZETRN and FLUKA calculations are compared and are in reasonable (18% to 27%) agreement. Both codes are in agreement with respect to the predicted shielding material performance trends. The results from both HZETRN and FLUKA are analyzed and the radiation protection properties and potential weight savings of various materials and materials lay-ups are compared.

Atwell, William↗
NASA NTRS2000

A Shielding Model for an Inflatable Vehicle, TransHab, and the Associated Astronaut Space Radiation Risk Assessment

TransHab, a habitable inflatable structure, has been proposed as a possible module for the International Space Station that provides significant increase in the available volume compared with the US Hab module and fo r a human Mars mission . A study was undertaken to understand and provide design inputs for crew radiation exposures. The results show that the current design provides sufficient shielding to assure that the crew exposures are below the crew exposure limits currently adopted for the ISS. In addition, the shielding provides adequate protection from the largest solar particle events (SPEs) observed during the last 40 years.

Atwell, William↗
NASA NTRS2002

Uncertainties in Estimates of the Risks of Late Effects from Space Radiation

The health risks faced by astronauts from space radiation include cancer, cataracts, hereditary effects, and non-cancer morbidity and mortality risks related to the diseases of the old age. Methods used to project risks in low-Earth orbit are of questionable merit for exploration missions because of the limited radiobiology data and knowledge of galactic cosmic ray (GCR) heavy ions, which causes estimates of the risk of late effects to be highly uncertain. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. Within the linear-additivity model, we use Monte-Carlo sampling from subjective uncertainty distributions in each factor to obtain a Maximum Likelihood estimate of the overall uncertainty in risk projections. The resulting methodology is applied to several human space exploration mission scenarios including ISS, lunar station, deep space outpost, and Mar's missions of duration of 360, 660, and 1000 days. The major results are the quantification of the uncertainties in current risk estimates, the identification of factors that dominate risk projection uncertainties, and the development of a method to quantify candidate approaches to reduce uncertainties or mitigate risks. The large uncertainties in GCR risk projections lead to probability distributions of risk that mask any potential risk reduction using the "optimization" of shielding materials or configurations. In contrast, the design of shielding optimization approaches for solar particle events and trapped protons can be made at this time, and promising technologies can be shown to have merit using our approach. The methods used also make it possible to express risk management objectives in terms of quantitative objective's, i.e., the number of days in space without exceeding a given risk level within well defined confidence limits.

Cucinotta, F. A.↗
NASA NTRS2011

A Review of the Experimental and Modeling Development of a Water Phase Change Heat Exchanger for Future Exploration Support Vehicles

Water affords manifold benefits for human space exploration. Its properties make it useful for the storage of thermal energy as a Phase Change Material (PCM) in thermal control systems, in radiation shielding against Solar Particle Events (SPE) for the protection of crew members, and it is indisputably necessary for human life support. This paper envisions a single application for water which addresses these benefits for future exploration support vehicles and it describes recent experimental and modeling work that has been performed in order to arrive at a description of the thermal behavior of such a system. Experimental units have been developed and tested which permit the evaluation of the many parameters of design for such a system with emphasis on the latent energy content, temperature rise, mass, and interstitial material geometry. The experimental results are used to develop a robust and well correlated model which is intended to guide future design efforts toward the multi-purposed water PCM heat exchanger envisioned.

Cognata, Thomas↗
NASA NTRS2010

A Comparison of Molecular and Histopathological Changes in Mouse Intestinal Tissue Following Whole-Body Proton- or Gamma-Irradiation

There are many consequences following exposure to the space radiation environment which can adversely affect the health of a crew member. Acute radiation syndrome (ARS) involving nausea and vomiting, damage to radio-sensitive tissue such as the blood forming organs and gastrointestinal tract, and cancer are some of these negative effects. The space radiation environment is ample with protons and contains gamma rays as well. Little knowledge exists to this point, however, regarding the effects of protons on mammalian systems; conversely several studies have been performed observing the effects of gamma rays on different animal models. For the research presented here, we wish to compare our previous work looking at whole-body exposure to protons using a mouse model to our studies of mice experiencing whole-body exposure to gamma rays as part of the radio-adaptive response. Radio-adaptation is a well-documented phenomenon in which cells exposed to a priming low dose of radiation prior to a higher dose display a reduction in endpoints like chromosomal aberrations, cell death, micronucleus formation, and more when compared to their counterparts receiving high dose-irradiation only. Our group has recently completed a radio-adaptive experiment with C57BL/6 mice. For both this study and the preceding proton research, the gastrointestinal tract of each animal was dissected four hours post-irradiation and the isolated small intestinal tissue was fixed in formalin for histopathological examination or snap-frozen in liquid nitrogen for RNA isolation. Histopathologic observation of the tissue using standard H&E staining methods to screen for morphologic changes showed an increase in apoptotic lesions for even the lowest doses of 0.1 Gy of protons and 0.05 Gy of gamma rays, and the percentage of apoptotic cells increased with increasing dose. A smaller percentage of crypts showed 3 or more apoptotic lesions in animals that received 6 Gy of gamma-irradiation compared to mice receiving only 2 Gy of protons. Tissue of the gastrointestinal tract was also homogenized and RNA was isolated for cDNA synthesis and real-time PCR analysis. Inspecting apoptotic lesions of the duodenum of the small intestine as an endpoint of damage did not reveal a radio-adaptive response in C57BL/6 mice at the four hour time point. Results of gene expression changes showed consistent up or down regulation of a number of genes for all of the exposure doses that may play a role in proton-induced apoptosis. Preliminary results of gene expression alterations as a result of gamma-irradiation revealed a wealth of genes involved in oxidative stress and antioxidant defense processes being up- or down-regulated only at the highest exposure dose of 6 Gy and the combined dose of 5 cGy with 6 Gy. Those animals undergoing only 5 cGy of gamma-irradiation showed very little modification of gene expression. Taken together these results lead us to conclude that protons cause more severe morphologic damage to the duodenum of the small intestine at a dose of 2 Gy than a higher dose of 6 Gy of gamma rays to the same organ. Both protons and gamma rays lead to significant variation in gene expression at high doses in the small intestine and these changes may provide insight into the mechanism of injury seen in the gastrointestinal tract following radiation exposure. Astronauts experiencing prolonged exposure to protons in the low Earth orbit and in deep space, and experiencing acute exposure to protons from solar particle events, may face biological consequences that will impact a mission s success. We will continue this work by studying, quantifying, and comparing damage due to protons and gamma rays in the small intestine as well as other organs in a time-dependent manner.

Purgason, Ashley↗
NASA NTRS2000

Radiation Transport Modeling and Assessment to Better Predict Radiation Exposure, Dose, and Toxicological Effects to Human Organs on Long Duration Space Flights

NASA's long-range plans include possible human exploratory missions to the moon and Mars within the next quarter century. Such missions beyond low Earth orbit will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and the missions long, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. The focus of this study is radiation exposure to the blood-forming organs of the NASA astronauts. NASA/JSC developed the Phantom Torso Experiment for Organ Dose Measurements which housed active and passive dosimeters that would monitor and record absorbed radiation levels at vital organ locations. This experiment was conducted during the STS-9 I mission in May '98 and provided the necessary space radiation data for correlation to results obtained from the current analytical models used to predict exposure to the blood-forming organs. Numerous models (i.e., BRYNTRN and HZETRN) have been developed and used to predict radiation exposure. However, new models are continually being developed and evaluated. The Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronomy, is to be used and evaluated as a part of the research activity. It is the intent of this research effort to compare the modeled data to the findings from the STS-9 I mission; assess the accuracy and efficiency of this model; and to determine its usefulness for predicting radiation exposure and developing better guidelines for shielding requirements for long duration manned missions.

Denkins, Pamela↗
NASA NTRS2011

Biological Based Risk Assessment for Space Exploration

Exposures from galactic cosmic rays (GCR) - made up of high-energy protons and high-energy and charge (HZE) nuclei, and solar particle events (SPEs) - comprised largely of low- to medium-energy protons are the primary health concern for astronauts for long-term space missions. Experimental studies have shown that HZE nuclei produce both qualitative and quantitative differences in biological effects compared to terrestrial radiation, making risk assessments for cancer and degenerative risks, such as central nervous system effects and heart disease, highly uncertain. The goal for space radiation protection at NASA is to be able to reduce the uncertainties in risk assessments for Mars exploration to be small enough to ensure acceptable levels of risks are not exceeded and to adequately assess the efficacy of mitigation measures such as shielding or biological countermeasures. We review the recent BEIR VII and UNSCEAR-2006 models of cancer risks and their uncertainties. These models are shown to have an inherent 2-fold uncertainty as defined by ratio of the 95% percent confidence level to the mean projection, even before radiation quality is considered. In order to overcome the uncertainties in these models, new approaches to risk assessment are warranted. We consider new computational biology approaches to modeling cancer risks. A basic program of research that includes stochastic descriptions of the physics and chemistry of radiation tracks and biochemistry of metabolic pathways, to emerging biological understanding of cellular and tissue modifications leading to cancer is described.

Cucinotta, Francis A.↗
NASA NTRS2011

Full Mission Astronaut Radiation Exposure Assessments for Long Duration Lunar Surface Missions

Risk to astronauts due to ionizing radiation exposure is a primary concern for missions beyond Low Earth Orbit (LEO) and will drive mission architecture requirements, mission timelines, and operational practices. For short missions, radiation risk is dominated by the possibility of a large Solar Particle Event (SPE). Longer duration missions have both SPE and Galactic Cosmic Ray (GCR) risks. SPE exposure can contribute significantly toward cancer induction in combination with GCR. As mission duration increases, mitigation strategies must address the combined risks from SPE and GCR exposure. In this paper, full mission exposure assessments were performed for the proposed long duration lunar surface mission scenarios. In order to accomplish these assessments, previously developed radiation shielding models for a proposed lunar habitat and rover were utilized. End-to-End mission exposure assessments were performed by first calculating exposure rates for locations in the habitat, rover, and during Extra-Vehicular Activities (EVA). Subsequently, total mission exposures were evaluated for the proposed timelines. Mission exposure results, assessed in terms of effective dose, are presented for the proposed timelines and recommendations are made for improved astronaut shielding and safer operational practices.

Adamczyk, Anne↗