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Blattnig, Steve R.

Publications and source records attributed to Blattnig, Steve R..

At least 19 records

Predicting Cell Death and Mutation Frequency for a Wide Spectrum of LET by Assuming DNA Break Clustering Inside Repair Domains

Cosmic radiation, which is composed of high charged and energy (HZE) particles, is responsible for cell death and mutation, which may be involved in cancer induction. Mutations are consequences of mis-repaired DNA breaks – especially double-strand breaks (DSBs) – that induce inter- and intra-chromosomal rearrangements (translocations, deletions, inversion). In this study, a computer simulation model is used to investigate the clustering of DSBs in repair domains, previously evidenced by our group in human breast cells [1]. This model is calibrated with experimental data measuring persistent 53BP1 radiation-induced foci (RIF) and is used to explain the high relative biological effectiveness (RBE) of HZE for both cell death and DNA mutation frequencies. We first validate our DSB cluster model using a new track structure model deployed on a simple geometrical configuration for repair domains in the nucleus; then we extend the scope from cell death to mutation induction. This work suggests that mechanism based on DSB repair process can explain several biological effects induced by HZE particles on different type of living cells

Plante, Ianik

Effects of the Serber First Step in 3DHZETRN-v2.1

3DHZETRN-v2 includes a detailed three dimensional (3D) treatment of neutron/light-ion transport based on a quasi-elastic/multiple-production assumption allowing improved agreement of the neutron/light-ion fluence compared with results of three Monte Carlo (MC) codes in the sense that the variance with respect to the individual MC results is less than the variance among the MC code results. The current numerical methods are no longer the main limitation to HZETRN code development and further changes in the nuclear model are required. In a prior study, an improved quasi-elastic spectrum based on a solution of the transport approximation to nuclear media effects showed promise, but the remaining multiple-production spectrum was based on a database derived from the Ranft model that used Bertini multiplicities. In the present paper, we will implement a more complete Serber first step into the 3DHZETRN-v2 code, but we retain the Bertini-Ranft branching ratios and evaporation multiplicities. It is shown that the new Serber model in the 3HZETRN-v2 code reduces the variance with individual MC codes, which are largely due to nuclear cross section model differences.

Wilson, John W.

Recent Developments in the Code RITRACKS (Relativistic Ion Tracks)

The code RITRACKS (Relativistic Ion Tracks) was developed to simulate detailed stochastic radiation track structures of ions of different types and energies. Many new capabilities were added to the code during the recent years. Several options were added to specify the times at which the tracks appear in the irradiated volume, allowing the simulation of dose-rate effects. The code has been used to simulate energy deposition in several targets: spherical, ellipsoidal and cylindrical. More recently, density changes as well as a spherical shell were implemented for spherical targets, in order to simulate energy deposition in walled tissue equivalent proportional counters. RITRACKS is used as a part of the new program BDSTracks (Biological Damage by Stochastic Tracks) to simulate several types of chromosome aberrations in various irradiation conditions. The simulation of damage to various DNA structures (linear and chromatin fiber) by direct and indirect effects has been improved and is ongoing. Many improvements were also made to the graphic user interface (GUI), including the addition of several labels allowing changes of units. A new GUI has been added to display the electron ejection vectors. The parallel calculation capabilities, notably the pre- and post-simulation processing on Windows and Linux machines have been reviewed to make them more portable between different systems. The calculation part is currently maintained in an Atlassian Stash® repository for code tracking and possibly future collaboration.

Plante, Ianik

Predicting Cell Death and Mutation Frequency for a Wide Spectrum of LET by Assuming DNA Break Clustering Inside Repair Domains

The high relative biological effectiveness (RBE) of high charged and energy (HZE) particles for cell death, DNA mutations and cancer remain based on experimental data. In this work, we propose that the existence of DNA repair domains is sufficient to predict both cell death and mutation frequencies for any LET by only taking into account experimental data from low-LET, offering one mechanism for RBE across LET. We hypothesize that whenever multiple DNA double-strand breaks (DSBs) are generated within the same DNA repair domain, DSBs are actively regrouped for more efficient repair [1]. This hypothesis has been supported by the low-LET sublinear dose response observed at doses greater than ~1Gy for 53BP1 radiation-induced foci (RIF) reflecting increasing DSB/RIF with dose [2]. Previously, we modeled radiation-induced cell death of human breast cells by first inferring the size of these domains from the dose dependence of low-LET RIF, and by associating a lethality factor to the number of pairs of DSBs in each RIF [1]. In this work, we first integrate the new NASA computer models RITCARD (Relativistic Ion Tracks, Chromosome Aberrations, Repair, and Damage) [3] and BDSTracks (Biological Damage by Stochastic Tracks) for a more accurate microdosimetry and a better model of the nuclear organization to predict the location of DSBs. A large array of particles and energy are simulated, covering more than three orders of magnitude for LET (~1-1000 keV/µm). Next, we extend our previous model to predict mutation frequencies by assuming that clustered DSBs increase mutation probability, which is formalized by the mutation frequency being linearly dependent on both the number of DSBs and the number of pairs of DSBs inside individual RIF. Linear coefficients are estimated so that simulations predict accurately mutation frequencies observed in Chinese hamster cells exposed to low-LET. Keeping these coefficients unchanged, we then predict mutation frequencies induced by HZE by simulating DSBs and obtain RBEs for mutations and cell death following the expected experimental bell shape for LET dependence. We also observe an orientation effect that needs to be confirmed, showing different RBE depending on the angle of the HZE beam hitting the main axis of the cell.

Plante, Ianik

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

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

Viger, Louise

Application of Interval Predictor Models to Space Radiation Shielding

This paper develops techniques for predicting the uncertainty range of an output variable given input-output data. These models are called Interval Predictor Models (IPM) because they yield an interval valued function of the input. This paper develops IPMs having a radial basis structure. This structure enables the formal description of (i) the uncertainty in the models parameters, (ii) the predicted output interval, and (iii) the probability that a future observation would fall in such an interval. In contrast to other metamodeling techniques, this probabilistic certi cate of correctness does not require making any assumptions on the structure of the mechanism from which data are drawn. Optimization-based strategies for calculating IPMs having minimal spread while containing all the data are developed. Constraints for bounding the minimum interval spread over the continuum of inputs, regulating the IPMs variation/oscillation, and centering its spread about a target point, are used to prevent data over tting. Furthermore, we develop an approach for using expert opinion during extrapolation. This metamodeling technique is illustrated using a radiation shielding application for space exploration. In this application, we use IPMs to describe the error incurred in predicting the ux of particles resulting from the interaction between a high-energy incident beam and a target.

Crespo, Luis G.

GCR Simulator Reference Field and a Spectral Approach for Laboratory Simulation

The galactic cosmic ray (GCR) simulator at the NASA Space Radiation Laboratory (NSRL) is intended to deliver the broad spectrum of particles and energies encountered in deep space to biological targets in a controlled laboratory setting. In this work, certain aspects of simulating the GCR environment in the laboratory are discussed. Reference field specification and beam selection strategies at NSRL are the main focus, but the analysis presented herein may be modified for other facilities. First, comparisons are made between direct simulation of the external, free space GCR field and simulation of the induced tissue field behind shielding. It is found that upper energy constraints at NSRL limit the ability to simulate the external, free space field directly (i.e. shielding placed in the beam line in front of a biological target and exposed to a free space spectrum). Second, variation in the induced tissue field associated with shielding configuration and solar activity is addressed. It is found that the observed variation is likely within the uncertainty associated with representing any GCR reference field with discrete ion beams in the laboratory, given current facility constraints. A single reference field for deep space missions is subsequently identified. Third, an approach for selecting beams at NSRL to simulate the designated reference field is presented. Drawbacks of the proposed methodology are discussed and weighed against alternative simulation strategies. The neutron component and track structure characteristics of the simulated field are discussed in this context.

Slaba, Tony C.

NASA Space Radiation Risk Project: Overview and Recent Results

The NASA Space Radiation Risk project is responsible for integrating new experimental and computational results into models to predict risk of cancer and acute radiation syndrome (ARS) for use in mission planning and systems design, as well as current space operations. The project has several parallel efforts focused on proving NASA's radiation risk projection capability in both the near and long term. This presentation will give an overview, with select results from these efforts including the following topics: verification, validation, and streamlining the transition of models to use in decision making; relative biological effectiveness and dose rate effect estimation using a combination of stochastic track structure simulations, DNA damage model calculations and experimental data; ARS model improvements; pathway analysis from gene expression data sets; solar particle event probabilistic exposure calculation including correlated uncertainties for use in design optimization.

Blattnig, Steve R.

A Reference Field for GCR Simulation and an LET-Based Implementation at NSRL

Exposure to galactic cosmic rays (GCR) on long duration deep space missions presents a serious health risk to astronauts, with large uncertainties connected to the biological response. In order to reduce the uncertainties and gain understanding about the basic mechanisms through which space radiation initiates cancer and other endpoints, radiobiology experiments are performed. Some of the accelerator facilities supporting such experiments have matured to a point where simulating the broad range of particles and energies characteristic of the GCR environment in a single experiment is feasible from a technology, usage, and cost perspective. In this work, several aspects of simulating the GCR environment in the laboratory are discussed. First, comparisons are made between direct simulation of the external, free space GCR field and simulation of the induced tissue field behind shielding. It is found that upper energy constraints at the NASA Space Radiation Laboratory (NSRL) limit the ability to simulate the external, free space field directly (i.e. shielding placed in the beam line in front of a biological target and exposed to a free space spectrum). Second, variation in the induced tissue field associated with shielding configuration and solar activity is addressed. It is found that the observed variation is within physical uncertainties, allowing a single reference field for deep space missions to be defined. Third, an approach for simulating the reference field at NSRL is presented. The approach allows for the linear energy transfer (LET) spectrum of the reference field to be approximately represented with discrete ion and energy beams and implicitly maintains a reasonably accurate charge spectrum (or, average quality factor). Drawbacks of the proposed methodology are discussed and weighed against alternative simulation strategies. The neutron component and track structure characteristics of the proposed strategy are discussed in this context.

Slaba, Tony C.

GCR Environmental Models I: Sensitivity Analysis for GCR Environments

Accurate galactic cosmic ray (GCR) models are required to assess crew exposure during long-duration missions to the Moon or Mars. Many of these models have been developed and compared to available measurements, with uncertainty estimates usually stated to be less than 15%. However, when the models are evaluated over a common epoch and propagated through to effective dose, relative differences exceeding 50% are observed. This indicates that the metrics used to communicate GCR model uncertainty can be better tied to exposure quantities of interest for shielding applications. This is the first of three papers focused on addressing this need. In this work, the focus is on quantifying the extent to which each GCR ion and energy group, prior to entering any shielding material or body tissue, contributes to effective dose behind shielding. Results can be used to more accurately calibrate model-free parameters and provide a mechanism for refocusing validation efforts on measurements taken over important energy regions. Results can also be used as references to guide future nuclear cross-section measurements and radiobiology experiments. It is found that GCR with Z>2 and boundary energies below 500 MeV/n induce less than 5% of the total effective dose behind shielding. This finding is important given that most of the GCR models are developed and validated against Advanced Composition Explorer/Cosmic Ray Isotope Spectrometer (ACE/CRIS) measurements taken below 500 MeV/n. It is therefore possible for two models to very accurately reproduce the ACE/CRIS data while inducing very different effective dose values behind shielding.

Slaba, Tony C.

GCR Environmental Models III: GCR Model Validation and Propagated Uncertainties in Effective Dose

This is the last of three papers focused on quantifying the uncertainty associated with galactic cosmic rays (GCR) models used for space radiation shielding applications. In the first paper, it was found that GCR ions with Z>2 and boundary energy below 500 MeV/nucleon induce less than 5% of the total effective dose behind shielding. This is an important finding since GCR model development and validation have been heavily biased toward Advanced Composition Explorer/Cosmic Ray Isotope Spectrometer measurements below 500 MeV/nucleon. Weights were also developed that quantify the relative contribution of defined GCR energy and charge groups to effective dose behind shielding. In the second paper, it was shown that these weights could be used to efficiently propagate GCR model uncertainties into effective dose behind shielding. In this work, uncertainties are quantified for a few commonly used GCR models. A validation metric is developed that accounts for measurements uncertainty, and the metric is coupled to the fast uncertainty propagation method. For this work, the Badhwar-O'Neill (BON) 2010 and 2011 and the Matthia GCR models are compared to an extensive measurement database. It is shown that BON2011 systematically overestimates heavy ion fluxes in the range 0.5-4 GeV/nucleon. The BON2010 and BON2011 also show moderate and large errors in reproducing past solar activity near the 2000 solar maximum and 2010 solar minimum. It is found that all three models induce relative errors in effective dose in the interval [-20%, 20%] at a 68% confidence level. The BON2010 and Matthia models are found to have similar overall uncertainty estimates and are preferred for space radiation shielding applications.

Slaba, Tony C.

Radiation Shielding Optimization on Mars

Future space missions to Mars will require radiation shielding to be optimized for deep space transit and an extended stay on the surface. In deep space, increased shielding levels and material optimization will reduce the exposure from most solar particle events (SPE) but are less effective at shielding against galactic cosmic rays (GCR). On the surface, the shielding provided by the Martian atmosphere greatly reduces the exposure from most SPE, and long-term GCR exposure is a primary concern. Previous work has shown that in deep space, additional shielding of common materials such as aluminum or polyethylene does not significantly reduce the GCR exposure. In this work, it is shown that on the Martian surface, almost any amount of aluminum shielding increases exposure levels for humans. The increased exposure levels are attributed to neutron production in the shield and Martian regolith as well as the electromagnetic cascade induced in the Martian atmosphere. This result is significant for optimization of vehicle and shield designs intended for the surface of Mars.

Slaba, Tony C.

Correlated Uncertainties in Radiation Shielding Effectiveness

The space radiation environment is composed of energetic particles which can deliver harmful doses of radiation that may lead to acute radiation sickness, cancer, and even death for insufficiently shielded crew members. Spacecraft shielding must provide structural integrity and minimize the risk associated with radiation exposure. The risk of radiation exposure induced death (REID) is a measure of the risk of dying from cancer induced by radiation exposure. Uncertainties in the risk projection model, quality factor, and spectral fluence are folded into the calculation of the REID by sampling from probability distribution functions. Consequently, determining optimal shielding materials that reduce the REID in a statistically significant manner has been found to be difficult. In this work, the difference of the REID distributions for different materials is used to study the effect of composition on shielding effectiveness. It is shown that the use of correlated uncertainties allows for the determination of statistically significant differences between materials despite the large uncertainties in the quality factor. This is in contrast to previous methods where uncertainties have been generally treated as uncorrelated. It is concluded that the use of correlated quality factor uncertainties greatly reduces the uncertainty in the assessment of shielding effectiveness for the mitigation of radiation exposure.

Werneth, Charles M.

NASA Standard for Models and Simulations: Philosophy and Requirements Overview

Following the Columbia Accident Investigation Board report, the NASA Administrator chartered an executive team (known as the Diaz Team) to identify those CAIB report elements with NASA-wide applicability and to develop corrective measures to address each element. One such measure was the development of a standard for the development, documentation, and operation of models and simulations. This report describes the philosophy and requirements overview of the resulting NASA Standard for Models and Simulations.

Blattnig, Steve R.

Review of Nuclear Physics Experiments for Space Radiation

Human space flight requires protecting astronauts from the harmful effects of space radiation. The availability of measured nuclear cross section data needed for these studies is reviewed in the present paper. The energy range of interest for radiation protection is approximately 100 MeV/n to 10 GeV/n. The majority of data are for projectile fragmentation partial and total cross sections, including both charge changing and isotopic cross sections. The cross section data are organized into categories which include charge changing, elemental, isotopic for total, single and double differential with respect to momentum, energy and angle. Gaps in the data relevant to space radiation protection are discussed and recommendations for future experiments are made.

Norbury, John W.

A Deterministic Electron, Photon, Proton and Heavy Ion Radiation Transport Suite for the Study of the Jovian System

A deterministic suite of radiation transport codes, developed at NASA Langley Research Center (LaRC), which describe the transport of electrons, photons, protons, and heavy ions in condensed media is used to simulate exposures from spectral distributions typical of electrons, protons and carbon-oxygen-sulfur (C-O-S) trapped heavy ions in the Jovian radiation environment. The particle transport suite consists of a coupled electron and photon deterministic transport algorithm (CEPTRN) and a coupled light particle and heavy ion deterministic transport algorithm (HZETRN). The primary purpose for the development of the transport suite is to provide a means for the spacecraft design community to rapidly perform numerous repetitive calculations essential for electron, proton and heavy ion radiation exposure assessments in complex space structures. In this paper, the radiation environment of the Galilean satellite Europa is used as a representative boundary condition to show the capabilities of the transport suite. While the transport suite can directly access the output electron spectra of the Jovian environment as generated by the Jet Propulsion Laboratory (JPL) Galileo Interim Radiation Electron (GIRE) model of 2003; for the sake of relevance to the upcoming Europa Jupiter System Mission (EJSM), the 105 days at Europa mission fluence energy spectra provided by JPL is used to produce the corresponding dose-depth curve in silicon behind an aluminum shield of 100 mils ( 0.7 g/sq cm). The transport suite can also accept ray-traced thickness files from a computer-aided design (CAD) package and calculate the total ionizing dose (TID) at a specific target point. In that regard, using a low-fidelity CAD model of the Galileo probe, the transport suite was verified by comparing with Monte Carlo (MC) simulations for orbits JOI--J35 of the Galileo extended mission (1996-2001). For the upcoming EJSM mission with a potential launch date of 2020, the transport suite is used to compute the traditional aluminum-silicon dose-depth calculation as a standard shield-target combination output, as well as the shielding response of high charge (Z) shields such as tantalum (Ta). Finally, a shield optimization algorithm is used to guide the instrument designer with the choice of graded-Z shield analysis.

Norman, Ryan B.

On-Line Tool for the Assessment of Radiation in Space - Deep Space Mission Enhancements

The On-Line Tool for the Assessment of Radiation in Space (OLTARIS, https://oltaris.nasa.gov) is a web-based set of tools and models that allows engineers and scientists to assess the effects of space radiation on spacecraft, habitats, rovers, and spacesuits. The site is intended to be a design tool for those studying the effects of space radiation for current and future missions as well as a research tool for those developing advanced material and shielding concepts. The tools and models are built around the HZETRN radiation transport code and are primarily focused on human- and electronic-related responses. The focus of this paper is to highlight new capabilities that have been added to support deep space (outside Low Earth Orbit) missions. Specifically, the electron, proton, and heavy ion design environments for the Europa mission have been incorporated along with an efficient coupled electron-photon transport capability to enable the analysis of complicated geometries and slabs exposed to these environments. In addition, a neutron albedo lunar surface environment was also added, that will be of value for the analysis of surface habitats. These updates will be discussed in terms of their implementation and on how OLTARIS can be used by instrument vendors, mission designers, and researchers to analyze their specific requirements.12

Sandridge, Chris a.

Investigating Material Approximations in Spacecraft Radiation Analysis

During the design process, the configuration of space vehicles and habitats changes frequently and the merits of design changes must be evaluated. Methods for rapidly assessing astronaut exposure are therefore required. Typically, approximations are made to simplify the geometry and speed up the evaluation of each design. In this work, the error associated with two common approximations used to simplify space radiation vehicle analyses, scaling into equivalent materials and material reordering, are investigated. Over thirty materials commonly found in spacesuits, vehicles, and human bodies are considered. Each material is placed in a material group (aluminum, polyethylene, or tissue), and the error associated with scaling and reordering was quantified for each material. Of the scaling methods investigated, range scaling is shown to be the superior method, especially for shields less than 30 g/cm2 exposed to a solar particle event. More complicated, realistic slabs are examined to quantify the separate and combined effects of using equivalent materials and reordering. The error associated with material reordering is shown to be at least comparable to, if not greater than, the error associated with range scaling. In general, scaling and reordering errors were found to grow with the difference between the average nuclear charge of the actual material and average nuclear charge of the equivalent material. Based on this result, a different set of equivalent materials (titanium, aluminum, and tissue) are substituted for the commonly used aluminum, polyethylene, and tissue. The realistic cases are scaled and reordered using the new equivalent materials, and the reduced error is shown.

Walker, Steven A.