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At least 307 records · Page 17

The Biological Effectiveness of Four Energies of Neon Ions for the Induction of Chromosome Damage in Human Lymphocytes

Chromosomal aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to neon ions at energies of 64, 89, 142, or 267. The corresponding LET values for these energies of neon ranged from 38-103 keV/micrometers and doses delivered were in the 10 to 80 cGy range. Chromosome exchanges were assessed in metaphase and G2 phase cells at first division after exposure using fluorescence in situ hybridization (FISH) with whole chromosome probes and dose response curves were generated for different types of chromosomal exchanges. The yields of total chromosome exchanges were similar for the 64, 89, and 142 MeV exposures, whereas the 267 MeV/u neon with LET of 38 keV/micrometers produced about half as many exchanges per unit dose. The induction of complex type chromosome exchanges (exchanges involving three or more breaks and two or more chromosomes) showed a clear LET dependence for all energies. The ratio of simple to complex type exchanges increased with LET from 18 to 51%. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose response curve for chromosome damage with respect to gamma-rays. The RBE(sub max) values for total chromosome exchanges for the 64 MeV/u was around 30.

George, Kerry↗

Displacement Damage Induced Catastrophic Second Breakdown in Silicon Carbide Schottky Power Diodes

A novel catastrophic breakdown mode in reversed biased Silicon carbide diodes has been seen for low LET particles. These particles are too low in LET to induce SEB, however SEB was seen from particles of higher LET. The low LET mechanism correlates with second breakdown in diodes due to increase leakage and assisted charge injection from incident particles. Percolation theory was used to predict some basic responses of the devices, but the inherent reliability issue with silicon carbide have proven challenging.

breakdown↗

NASA Models of Space Radiation Induced Cancer, Circulatory Disease, and Central Nervous System Effects

The risks of late effects from galactic cosmic rays (GCR) and solar particle events (SPE) are potentially a limitation to long-term space travel. The late effects of highest concern have significant lethality including cancer, effects to the central nervous system (CNS), and circulatory diseases (CD). For cancer and CD the use of age and gender specific models with uncertainty assessments based on human epidemiology data for low LET radiation combined with relative biological effectiveness factors (RBEs) and dose- and dose-rate reduction effectiveness factors (DDREF) to extrapolate these results to space radiation exposures is considered the current "state-of-the-art". The revised NASA Space Risk Model (NSRM-2014) is based on recent radio-epidemiology data for cancer and CD, however a key feature of the NSRM-2014 is the formulation of particle fluence and track structure based radiation quality factors for solid cancer and leukemia risk estimates, which are distinct from the ICRP quality factors, and shown to lead to smaller uncertainties in risk estimates. Many persons exposed to radiation on earth as well as astronauts are life-time never-smokers, which is estimated to significantly modify radiation cancer and CD risk estimates. A key feature of the NASA radiation protection model is the classification of radiation workers by smoking history in setting dose limits. Possible qualitative differences between GCR and low LET radiation increase uncertainties and are not included in previous risk estimates. Two important qualitative differences are emerging from research studies. The first is the increased lethality of tumors observed in animal models compared to low LET radiation or background tumors. The second are Non- Targeted Effects (NTE), which include bystander effects and genomic instability, which has been observed in cell and animal models of cancer risks. NTE's could lead to significant changes in RBE and DDREF estimates for GCR particles, and the potential effectiveness of radiation mitigator's. The NSRM- 2014 approaches to model radiation quality dependent lethality and NTE's will be described. CNS effects include both early changes that may occur during long space missions and late effects such as Alzheimer's disease (AD). AD effects 50% of the population above age 80-yr, is a degenerative disease that worsens with time after initial onset leading to death, and has no known cure. AD is difficult to detect at early stages and the small number of low LET epidemiology studies undertaken have not identified an association with low dose radiation. However experimental studies in mice suggest GCR may lead to early onset AD. We discuss modeling approaches to consider mechanisms whereby radiation would lead to earlier onset of occurrence of AD. Biomarkers of AD include amyloid beta (A(Beta)) plaques, and neurofibrillary tangles (NFT) made up of aggregates of the hyperphosphorylated form of the micro-tubule associated, tau protein. Related markers include synaptic degeneration, dentritic spine loss, and neuronal cell loss through apoptosis. Radiation may affect these processes by causing oxidative stress, aberrant signaling following DNA damage, and chronic neuroinflammation. Cell types to be considered in multi-scale models are neurons, astrocytes, and microglia. We developed biochemical and cell kinetics models of DNA damage signaling related to glycogen synthase kinase-3(Beta) (GSK3(Beta)) and neuroinflammation, and considered multi-scale modeling approaches to develop computer simulations of cell interactions and their relationships to A(Beta) plaques and NFTs. Comparison of model results to experimental data for the age specific development of A(Beta) plaques in transgenic mice will be discussed.

Cucinotta, Francis A.↗

Cosmic Ray Exposure & Linear-Energy-Transfer Evaluations for the COBE Mission

Magnetospherically attenuated, orbit integrated, surface incident cosmic ray fluxes of galactic origin were determined for the COBE mission. All heavy ions up to Nickel (z=28) were considered in this, evaluation. In order to provide worst case approximations, estimates were based on solar minimum conditions. Transport and material shielding calculations were then performed for these vehicle encountered particles, for a simple spherical 3-D aluminum geometry, and the materially attenuated cosmic ray distributions emerging behind selected shield thicknesses were obtained. Finally, Linear-Energy-Transfer (LET) spectra were evaluated for the energy spectra of each ion specie and these were, in turn, integrated into the sum-total LET distribution contained in this report. The results are presented in tabular and graphical form for eight (8) different shield thicknesses from.01 to 10.0 gm/cm2 of aluminum. They show most conclusively, and not unexpectedly, that material shielding has virtually no 'effect on the final LET spectrum, at least not for aluminum shields. This was predictable. Please note that in the LET graphs, two curves were plotted. Of these, please ignore the one labeled "grazing" and use only the one labeled "normal". Again, it should be remembered that the end results contain contributions from all elements up to Nickel (z=28).

Stassinopoulos, E. G.↗

Monte Carlo Study of the Formation of Chromosome Aberrations by Direct Ion Traversal vs. Delta-Electrons

Space radiation constitutes a major risk for the safety of space travel. Galactic Cosmic Rays (GCRs) are made of high energy protons (87%), high energy helium ions (12%) and high-charge and energy (HZE) ions [1]. At a cellular scale, HZE ions display a characteristic pattern of energy deposition, known as the ion track, that correlates with the ion linear energy transfer (LET). These energy deposition events (ionizations/excitations) create DNA breaks that, if misrepaired, lead to the formation of chromosome aberrations (CAs). Compared to low-LET terrestrial radiations (X-rays and γ-rays), high LET ions are known to create complex, clustered DNA breaks that are particularly efficient at forming CAs. Indeed, ion tracks are usually described as a dense ionization core, where clustered breaks are formed, and a penumbra, made of low-LET δ-electrons that have sufficient energy to travel across many cells and induce breaks that are more homogeneously distributed. In this work, we investigated the formation of CAs, and separated them into two contributions (direct ion traversal of the nucleus vs.δ-electrons), to elucidate to which extent δ-electrons contribute to CA formation.

Floriane Poignant↗

Deep Space Radiation Affects Neurovascular Functions in Human Organ-on-a-Chip Models

A major health risk for human deep space exploration is central nervous system (CNS) damage by galactic cosmic ray radiation. Simulated galactic cosmic rays or their components, especially the high- linear energy transfer (LET) particles such as 56 Fe ions, cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates the interactions between CNS and the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal health and neuroinflammation. However, there have been few studies on BBB and astrocyte functions in regulating CNS responses, especially in human tissue/organ analogs. Therefore, we utilized a high-throughput human 3D organ-on-a-chip system, seeded with induced pluripotent stem cell-derived endothelial cells, astrocytes and neurons, to study human neurovascular responses to simulated deep space radiation. We investigated BBB permeability, oxidative stress, cellular and tissue damage, and secreted factors over the time period of 24 hours-1 week after irradiation with 0.25-0.5 Gy 5-ion simplified simulated galactic cosmic rays and 0.3-0.8 Gy high-LET 600MeV/n 56 Fe particles, and compared the outcomes to low-LET irradiation with 0.1-1 Gy doses of X-rays and gamma rays. Both high and low-LET radiation increased neurovascular permeability, caused oxidative stress, damaged endothelial cells and tight junctions, and altered expression of inflammatory cytokines. Ionizing radiation- induced neurovascular permeability and oxidative stress peaked at 3 days after irradiation and were further exacerbated by the presence of astrocytes. Furthermore, in response to particle irradiation, astrocytes stimulated interleukin-1 signaling by inhibiting the expression of interleukin-1 receptor antagonist. Thus, we also evaluated interleukin-1 receptor antagonist as a potential countermeasure against particle radiation. Ultimately, our results may help develop countermeasures to mitigate human CNS damage in deep space exploration.

Sonali D Verma↗

Quantifying radiation quality for space relevant radiation types: Fitting excess risk models to three combined HZE-irradiated mouse datasets

Radiation health risks are predominantly derived from low linear energy transfer (LET) terrestrial exposures; however, space radiation includes exposure to high-LET and high-charge, high-energy (HZE) particles. Accurately quantifying the differences in radiation quality between the space and terrestrial radiation environments is important for assessing and predicting health risks for astronauts. Weil et al. 2009 and 2014 used two different inbred mouse strains to study differences in hepatocellular carcinoma (HCC) tumorigenesis after exposures to low- and high- LET radiation[1-2]. More recently, Edmondson et al. 2020 provided valuable new tumor data in outbred mice that were exposed to low- and high-LET radiation[3]. The present study aims to rigorously investigate a relative biological effectiveness (RBE) factor by leveraging the HCC tumor data from the three datasets[1-3]. The three experiments were similarly designed, allowing the raw data to be combined into a pooled dataset to estimate excess relative risk (ERR) and excess absolute risk (EAR) models using Bayesian Poisson regression.

Lori J. Chappell↗

Modeling Radiation-Induced Epithelial Cell Injury in Murine Three-Dimensional Esophageal Organoids

Esophageal squamous cell carcinoma (ESCC) is a deadly consequence of radiation exposure to the esophagus. ESCC arises from esophageal epithelial cells that undergo malignant transformation and features a perturbed squamous cell differentiation program. Understanding the dose- and radiation quality-dependence of the esophageal epithelium response to radiation may provide insights into the ability of radiation to promote ESCC. We have explored factors that may play a role in esophageal epithelial radiosensitivity and their potential relationship to ESCC risk. We have utilized a murine three-dimensional (3D) organoid model that recapitulates the morphology and functions of the stratified squamous epithelium of the esophagus to study persistent dose- and radiation quality-dependent changes. Interestingly, although high-linear energy transfer (LET) Fe ion exposure induced a more intense and persistent alteration of squamous differentiation and 53BP1 DNA damage foci levels as compared to Cs, the MAPK/SAPK stress pathway signaling showed similar altered levels for most phospho-proteins with both radiation qualities. In addition, the lower dose of high-LET exposure also revealed nearly the same degree of morphological changes, even though only ~36% of the cells were predicted to be hit at the lower 0.1 Gy dose, suggesting that a bystander effect may be induced. Although p38 and ERK/MAPK revealed the highest levels following high-LET exposure, the findings reveal that even a low dose (0.1 Gy) of both radiation qualities can elicit a persistent stress signaling response that may critically impact the differentiation gradient of the esophageal epithelium, providing novel insights into the pathogenesis of radiation-induced esophageal injury and early stage esophageal carcinogenesis.

3D organoid culture↗

Designing and prototyping extensions to the Message Passing Interface in MPICH

As HPC system architectures and the applications running on them continue to evolve, the MPI standard itself must evolve. The trend in current and future HPC systems toward powerful nodes with multiple CPU cores and multiple GPU accelerators makes efficient support for hybrid programming critical for applications to achieve high performance. However, the support for hybrid programming in the MPI standard has not kept up with recent trends. The MPICH implementation of MPI provides a platform for implementing and experimenting with new proposals and extensions to fill this gap and to gain valuable experience and feedback before the MPI Forum can consider them for standardization. Here, in this work, we detail six extensions implemented in MPICH to increase MPI interoperability with other runtimes, with a specific focus on heterogeneous architectures. First, the extension to MPI generalized requests lets applications integrate asynchronous tasks into MPI’s progress engine. Second, the iovec extension to datatypes lets applications use MPI datatypes as a general-purpose data layout API beyond just MPI communications. Third, a new MPI object, MPIX_Stream, can be used by applications to identify execution contexts beyond MPI processes, including threads and GPU streams. MPIX stream communicators can be created to make existing MPI functions thread-aware and GPU-aware, thus providing applications with explicit ways to achieve higher performance. Fourth, MPIX Streams are extended to support the enqueue semantics for offloading MPI communications onto a GPU stream context. Fifth, thread communicators allow MPI communicators to be constructed with individual threads, thus providing a new level of interoperability between MPI and on-node runtimes such as OpenMP. Lastly, we present an extension to invoke MPI progress, which lets users spawn progress threads with fine-grained control to adapt the communication performance to their application designs. We describe the design and implementation of these extensions, provide usage examples, and highlight their expected benefits with performance results.

97 MATHEMATICS AND COMPUTING↗

Effect of low Reynolds number turbulence amplification on the Galileo probe flowfield

The amplification of turbulence at low Reynolds numbers is analyzed as it affects the Jupiter-entry flowfield, surface-heating rate, and mass-loss rate of the 335-kg Galileo probe now being designed. The constant k(2) in the Clauser-Klebanoff outer law of the two-layer algebraic eddy-viscosity model of Cebeci (1970), as used in earlier models of the Galileo flowfield (Moss and Simmonds, 1982), is modified to increase at low Reynolds numbers, as found experimentally by Varner and Adams (1980). Calculations were performed for peak heating conditions (at 49.13 sec of entry), using a turbulent Prandtl number of 0.9 and turbulent Lewis numbers (LeT) of 0.8, 1.0, and 1.2. The low-Reynolds-number effect is found to produce mass-loss-ratio increases of from 4 to 50 percent, while an LeT of 1.2 produced an increase of from 4 to 10 percent as compared to an LeT of 1.0. While these findings are based on experimental data obtained under conditions somewhat different from those probably present on Jupiter, their importance for a conservative probe design is stressed.

Gupta, R. N.↗

Late skin damage in rabbits and monkeys after exposure to particulate radiations

Preliminary results are reported of experiments on the late effects of exposure to particulate radiations on stem cell populations. Skin biopsies were taken from the ears of rabbits irradiated 2-5 years previously with 530 MeV/amu Ar ions (LET 90 keV/micron), or 365 MeV/amu Ne ions (LET 35 keV micron), and from the chests and inner thighs of rhesus monkeys irradiated 16-18 years previously with 32-MeV protons (LET about 1.2 keV/micron). Skin fibroblast cultures obtained from the biopsy samples in rabbits were observed to undergo dose-dependent decreases in in vitro life span, with estimated survival curves showing the effects of Ar-ion irradiation to be more severe than those of Ne-ion irradiation. In addition, the healing of the biopsy wound was observed to become slower as radiation dose increased. In the monkey, radiation reduced the average number of fibroblasts at the time of cessation of growth in culture. Results thus demonstrate the capacity of skin sampling to reveal stem cell destruction, and have important implications for astronauts and other persons at risk of particle exposure with regard to healing responses to trauma or surgery.

Bergtold, D. S.↗

Linear energy transfer spectrum measurement experiment (P0006)

The linear energy transfer (LET) is the energy deposited per unit path length of charged particle traversing matter. For estimating the rate of damage from single-hit phenomena, the quantity that best combines the radiation environment, orbital situation, and spacecraft shielding is the linear energy transfer (LET) spectrum at the device location. This experiment will measure the LET spectrum behind different shielding configurations for approximately 1 year. The shielding will be increased in increments of approximately 1 G/sq cm up to a maximum shieldng of 16 G/sq cm. In addition to providing critical information to future spacecraft designers, these measurements will also provide data that will be extremely valuable to other experiments on LDEF.

Benton, E. V.↗

Radiation measurements aboard Spacelab 1

The radiation environment inside Spacelab 1 was measured by a set of passive radiation detectors distributed throughout the volume inside the module, in the access tunnel, and outside on the pallet. Measurements of the low linear energy transfer (LET) component obtained from the thermoluminescence detectors ranged from 102 to 190 millirads, yielding an average low LET dose rate of 11.2 millirads/day inside the module, about twice the low LET dose rate measured on previous flights of the Space Shuttle. Because of the higher inclination of the orbit (57 versus 28.5 deg for previous Shuttle flights), substantial fluxes of highly ionizing high charge and energy galactic cosmic ray particles were observed, yielding an overall average mission dose-equivalent of about 150 millirems, more than three times higher than that measured on previous Shuttle missions.

Benton, E. V.↗

Cosmic ray simulation and testing program

Single event upset (SEU) and latchup vulnerabilities were determined for a number of parts of interest to NASA space programs. In cases where a threshold linear energy transfer (LET) for SEU could be measured, an upset rate in a low inclination Space Shuttle orbit was computed. The predicted upset rates are extremely low, except for the devices with LET thresholds below the geomagnetic cutoff for altitude and inclination of the Space Shuttle orbit. While some of the devices do exhibit latchup, the cross sections and threshold LETs are such that the risk associated with flying these devices in low, near equatorial orbits is small if not negligible.

Kolasinski, W. A.↗

Early and late mammalian responses to heavy charged particles

This overview summarizes murine results on acute lethality responses, inactivation of marrow CFU-S and intestinal microcolonies, testes weight loss, life span shortening, and posterior lens opacification in mice irradiated with heavy charged particles. RBE-LET relationships for these mammalian responses are compared with results from in vitro studies. The trend is that the maximum RBE for in vivo responses tends to be lower and occurs at a lower LET than for inactivation of V79 and T-1 cells in culture. Based on inactivation cross sections, the response of CFU-S in vivo conforms to expectations from earlier studies with prokaryotic systems and mammalian cells in culture. Effects of heavy ions are compared with fission spectrum neutrons, and the results are consistent with the interpretation that RBEs are lower than for fission neutrons at about the same LET, probably due to differences in track structure.

Ainsworth, E. J.↗

Fluence-related risk coefficients using the Harderian gland data as an example

A new concept is introduced for assessing the risk of radiation-induced cancer to space travelers: a fluence-related risk coefficient F (called the risk cross section), which is the risk of a cancer per unit particle fluence for a given particle type. Fs are functions of the LET of the particles in the radiation field and, when integrated over fluence-LET spectra and summed, yield the risk of the endpoint of interest. As an example, tumor prevalence data in mice are used to estimate the probability of the induction of mouse Harderian-gland tumor per year on an extramagnetospheric mission inside an idealized shielding configuration of a spherical 1 g/sq cm hick aluminum shell. Results indicate a yearly tumor prevalence of 0.06 at solar minimum conditions, with 60 percent of this arising from charge components with Z between 10 and 28, and two-thirds of the contribution arising from LET components between 10 and 200 keV/micron.

Curtis, S. B.↗

A study of the generation of linear energy transfer spectra for space radiations

The conversion of particle-energy spectra into a linear energy transfer (LET) distribution is a guide in assessing biologically significant components. The mapping of LET to energy is triple valued and can be defined only on open subintervals. A well-defined numerical procedure is found to allow generation of LET spectra on the open subintervals that are integrable in spite of their singular nature.

Wilson, John W.↗

Semiempirical fragmentation models on galactic cosmic ray transport calculations with hydrogen target

Nuclear fragmentation cross sections of Silberberg and Tsao that are more accurate for a hydrogen target were implemented in the data base to replace those of Rudstam for a galactic cosmic ray transport code (HZETRN). Sample calculations were made for the transported galactic cosmic ray flux through a liquid hydrogen shield at solar minimum condition to determine the effect of such a change. The transported flux based on the Silberberg-Tsao semiempirical formalism contains fewer high-LET (linear energy transfer) components but more low-LET components than the results based on Rudstam's formalism: and this disparity deepens as the shield thickness increases. A comparison of the results obtained from using both energy-dependent and energy-independent cross sections of Silberberg and Tsao indicates that the energy-independent assumption results in an underestimation of high-LET flux above 100 keV/micron by approximately 40 percent for a 15-g/cm(sup 2) thickness of liquid hydrogen. Similar results were obtained in a previous study when both energy-dependent and energy-independent cross sections of Rudstam were considered. Nonetheless, the present study found that an energy-independent calculation would be best accomplished by using Rudstam's cross sections as done in the past for various engineering applications.

Shinn, Judy L.↗