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Steve R Blattnig

Publications and source records attributed to Steve R Blattnig.

At least 19 records

DNA Break Clustering as a Predictor of Cell Death across Various Radiation Qualities: Influence of Cell Size, Cell Asymmetry, and Beam Orientation

Cosmic radiation, composed of high charge and energy (HZE) particles, causes cellular DNA damage that can result in cell death or mutation that can evolve into cancer. In this work, a cell death model is applied to several cell lines exposed to HZE ions spanning a broad range of linear energy transfer (LET) values. We hypothesize that chromatin movement leads to the clustering of multiple double strand breaks (DSB) within one radiation-induced foci (RIF). The survival probability of a cell population is determined by averaging the survival probabilities of individual cells, which is function of the number of pairwise DSB interactions within RIF. The simulation code RITCARD was used to compute DSB. Two clustering approaches were applied to determine the number of RIF per cell. RITCARD outputs were combined with experimental data from four normal human cell lines to derive the model parameters and expand its predictions in response to ions with LET ranging from ∼0.2keV/μmto∼3000keV/μm. Spherical and ellipsoidal nuclear shapes and two ion beam orientations were modeled to assess the impact of geometrical properties on cell death. The calculated average number of RIF per cell reproduces the saturation trend for high doses and high-LET values that is usually experimentally observed. The cell survival model generates the recognizable bell shape of LET dependence for the relative biological effectiveness (RBE). At low LET, smaller nuclei have lower survival due to increased DNA density and DSB clustering. At high LET, nuclei with a smaller irradiation area either because of a smaller size or a change in beam orientation have a higher survival rate due to a change in the distribution of DSB/RIF per cell. If confirmed experimentally, the geometric characteristics of cells would become a significant factor in predicting radiation-induced biological effects.

cell survival↗

Advances in Space Radiation Physics and Transport

The space radiation environment is a complex mixture of particle types and energies originating from sources inside and outside of the galaxy. These environments may be modified by the heliospheric and geomagnetic conditions as well as planetary bodies and vehicle or habitat mass shielding. In low Earth orbit (LEO), the geomagnetic field deflects a portion of the galactic cosmic rays (GCR) and all but the most intense solar particle events (SPE). There are also dynamic belts of trapped electrons and protons with low to medium energy and intense particle count rates. In deep space, the GCR exposure is more severe than in LEO and varies inversely with solar activity. Unpredictable solar storms also present an acute risk to astronauts if adequate shielding is not provided. Near planetary surfaces such as the Earth, moon or Mars, secondary particles are produced when the ambient deep space radiation environment interacts with these surfaces and/or atmospheres. These secondary particles further complicate the local radiation environment and modify the associated health risks. Characterizing the radiation fields in this vast array of scenarios and environments is a challenging task and is currently accomplished with a combination of computational models and dosimetry. The computational tools include models for the ambient space radiation environment, mass shielding geometry, and atomic and nuclear interaction parameters. These models are then coupled to a radiation transport code to describe the radiation field at the location of interest within a vehicle or habitat. Many new advances in these models have been made in the last decade, and the present review article focuses on the progress and contributions made by workers and collaborators at NASA in the same time frame. Although great progress has been made, and models continue to improve, significant gaps remain and are discussed in the context of planned future missions. Of particular interest is the juxtaposition of various review committee findings regarding the accuracy and gaps of combined space radiation environment, physics, and transport models with the progress achieved over the past decade. While current models are now fully capable of characterizing radiation environments in the broad range of forecasted mission scenarios, it should be remembered that uncertainties still remain and need to be addressed.

Space radiation↗

HZETRN Radiation Transport Validation Using Balloon-Based Experimental Data

The deterministic radiation transport code HZETRN (High charge (Z) and Energy TRaNsport) was developed by NASA to study the effects of cosmic radiation on astronauts and instrumentation shielded by various materials. This work presents an analysis of computed differential flux from HZETRN compared with measurement data from three balloon-based experiments over a range of atmospheric depths, particle types, and energies. Model uncertainties were quantified using an interval-based validation metric that takes into account measurement uncertainty both in the flux and the energy at which it was measured. Average uncertainty metrics were computed for the entire dataset as well as subsets of the measurements (by experiment, particle type, energy, etc.) to reveal any specific trends of systematic over- or under-prediction by HZETRN. The distribution of individual model uncertainties was also investigated to study the range and dispersion of errors beyond just single scalar and interval metrics. The differential fluxes from HZETRN were generally well-correlated with balloon-based measurements; the median relative model difference across the entire dataset was determined to be 30%. The distribution of model uncertainties, however, revealed that the range of errors was relatively broad, with approximately 30% of the uncertainties exceeding ± 40%. The distribution also indicated that HZETRN systematically under-predicts the measurement dataset as a whole, with approximately 80% of the relative uncertainties having negative values. Instances of systematic bias for subsets of the data were also observed, including a significant underestimation of alpha particles and protons for energies below 2.5 GeV/u. Muons were found to be systematically over-predicted at atmospheric depths deeper than 50 g/cm(sup 2) but under-predicted for shallower depths. Furthermore, a systematic under-prediction of alpha particles and protons was observed below the geomagnetic cutoff, suggesting that improvements to the light ion production cross sections in HZETRN should be investigated.

James E Warner↗

Predicting cell death and mutation frequency for a wide spectrum of LET and across cell lines from 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. 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.

Ianik Plante↗

Planned Investigations to Address Acute Central Nervous System Effects of Space Radiation Exposure with Human Performance Data

This work intends to generate evidence of acute, incremental human performance decrement similar to that due to space radiation andits impacts on the brain, to accompany ongoing human performance modeling work. The planned work will explore the boundaries of human behavioral and performance decrement after exposure to stress, which may be expected based in part on rodent responses found afterexposure to ionizing radiation. The collection of evidence via simulation studies can characterize real human errors toward determining what stress levels lead to significantly-low levels of performance (below permissible outcome limits) which would imperilmission accomplishment. If mission-relevant animal-study-linked tasks are used, human and animal performance levels may be aligned to enable quantitative assignment of permissible exposure limits based on animal exposure studies. Ultimately, a transfer function between the performances of exposed rodents and humans under stress can be developed using shared impairment mechanisms.

human performance↗

Utility of Terrestrial Cardiovascular Disease Data in Astronaut Radiation Risk Assessment – A Case Study Showing Increased Risk with Clonal Hematopoiesis of Indeterminate Potential

Cardiovascular disease (CVD) is associated with high doses of radiation and is are cognized health risk for astronauts on multiple or long duration exploration missions to the Moon or Mars. Currently, radiation risk assessment is based on background population disease rates and does not consider individual risk factors that may modify analysis, especially at lower radiation doses.

Zarana S Patel↗

Integration of the Cardiovascular Clinical Risk Prediction Model Astro-CHARM Into the NASA Radiation Risk Model

Space radiation poses an increased risk for cardiovascular diseases (CVD) during and after spaceflight, that should be quantified to plan future space missions such as the flight to Mars. The radiation-induced CVD risk is evaluated using a linear no-threshold dose response excess relative risk (ERR) model, so that the risk is function of the radiation dose and of the background (i.e., non-exposed) incidence rate. The background CVD risk can be evaluated using clinical prediction models (CPMs). The first CPMs developed in the 1960’s have identified CVD risk factors such as blood pressure, diabetes, cholesterol, and smoking. In this work, the steps used to integrate the CVD risk provided by a CPM into the NASA Radiation Risk Model are described. Simulation results calculated using available data for relevant mission scenarios are also shown, and the challenges in CVD risk predictions are discussed.

I Plante↗