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At least 163 records · Page 9

Radiation-induced gene expression in the nematode Caenorhabditis elegans

We used the nematode C. elegans to characterize the genotoxic and cytotoxic effects of ionizing radiation in a simple animal model emphasizing the unique effects of charged particle radiation. Here we demonstrate by RT-PCR differential display and whole genome microarray hybridization experiments that gamma rays, accelerated protons and iron ions at the same physical dose lead to unique transcription profiles. 599 of 17871 genes analyzed (3.4%) showed differential expression 3 hrs after exposure to 3 Gy of radiation. 193 were up-regulated, 406 were down-regulated and 90% were affected only by a single species of radiation. A novel statistical clustering technique identified the regulatory relationships between the radiation-modulated genes and showed that genes affected by each radiation species were associated with unique regulatory clusters. This suggests that independent homeostatic mechanisms are activated in response to radiation exposure as a function of track structure or ionization density.

Non-NASA Center↗

Space Radiation Induced Cytogenetic Damage in the Blood Lymphocytes of Astronauts

Cytogenetic analysis of astronauts blood lymphocytes provides a direct in vivo measurement of space radiation damage, which takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. We present our latest analyses of chromosome damage in astronauts blood lymphocytes assessed by fluorescence in situ hybridization (FISH) chromosome painting and collected at various times beginning directly after return from space to several years after flight. Dose was derived from frequencies of chromosome exchanges using preflight calibration curves, and the Relative Biological Effect (RBE) was estimated by comparison with individually measured physically absorbed doses. Values for average RBE were compared to the average quality factor (Q), from direct measurements of the lineal energy spectra using a tissue-equivalent proportional counter (TEPC) and radiation transport codes. Results prove that cytogenetic biodosimetry analyses on blood collected within a week or two of return from space provides a reliable estimate of equivalent radiation dose and risk after protracted exposure to space radiation of a few months or more. However, data collected several months or years after flight suggests that the yield of chromosome translocations may decline with time after the mission, indicating that retrospective doses may be more difficult to estimate. In addition, limited data on multiple flights show a lack of correlation between time in space and translocation yields. Data from one crewmember, who has participated in two separate long-duration space missions and has been followed up for over 10 years, provide limited information on the effect of repeat flights and show a possible adaptive response to space radiation exposure.

George, K.↗

Molecular dynamics simulations of ultrafast radiation induced melting at metal–semiconductor interfaces

Metal–semiconductor contacts in silicon carbide (SiC) diodes endure damages at the interface when exposed to harsh radiation environments. Due to the rapid rise in temperature and ultrafast cooling that follows the radiation impact, the structural properties of the materials can be altered through melting, recrystallization, and amorphization. A detailed understanding of the material failure modes at the interface is lacking, specifically at the nanoscale. We use molecular simulations to investigate the ultrafast melting at tungsten (W)–SiC interfaces following radiation damage and apply deep learning techniques to track the transient evolution of the local molecular structures. We show that W near the radiation track undergoes melting and, eventually, most of it recrystallizes with a noticeable degree of undercooling, while SiC is rendered permanently amorphous. The observation of local undercooling in W films is important as it can affect the device performance even before the bulk melting temperature of the material is reached. We also show that at high temperatures, the interface undergoes a fracture-like failure. The results presented here are significant in understating the different failure modes of SiC diode materials.

Ashwin Ravichandran↗

Differential Processing of Low and High LET Radiation Induced DNA Damage: Investigation of Switch from ATM to ATR Signaling

The members of the phosphatidylinositol kinase-like kinase family of proteins namely ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are directly responsible for the maintenance of genomic integrity by mounting DDR through signaling and facilitating the recruitment of repair factors at the sites of DNA damage along with coordinating the deployment of cell cycle checkpoints to permit repair by phosphorylating Checkpoint kinase Chk1, Chk2 and p53. High LET radiation from GCR (Galactic Cosmic Rays) consisting mainly of protons and high energy and charged (HZE) particles from SPE (Solar Particle Event) pose a major health risk for astronauts on their space flight missions. The determination of these risks and the design of potential safeguards require sound knowledge of the biological consequences of lesion induction and the capability of the cells to counter them. We here strive to determine the coordination of ATM and ATR kinases at the break sites directly affecting checkpoint signaling and DNA repair and whether differential processing of breaks induced by low and high LET radiation leads to possible augmentation of swap of these damage sensors at the sites of DNA damage. Exposure of cells to IR triggers rapid autophosphorylation of serine-1981 that causes dimer dissociation and initiates monomer formation of ATM. ATM kinase activity depends on the disruption of the dimer, which allows access and phosphorylation of downstream ATM substrates like Chk2. Evidence suggests that ATM is activated by the alterations in higher-order chromatin structure although direct binding of ATM to DSB ends may be a crucial step in its activation. On the other hand, in case of ATR, RPA (replication protein A)-coated ssDNA (single-stranded DNA) generated as a result of stalled DNA replication or during processing of chromosomal lesions is crucial for the localization of ATR to sites of DNA damage in association with ATR-interacting protein (ATRIP). Although the majority of RPA-coated ssDNA is generally present only during DNA replication, ATR activation in G1 and G2-phase might still require formation of RPA-coated ssDNA, probably initiated by the MRN-CtIP complex and then extended by the Exo1- or BLM-dependent mechanisms at the sites of DSBs. Evidence accumulates that activation of ATM and ATR are oppositely regulated by the length of single stranded overhangs generated at the break sites by processes mentioned above and these stretches of single stranded overhangs hold the clue for ATM to ATR switch at broken DNA ends. We irradiated 82-6hTERT human fibroblast cells with low LET gamma-rays and high LET Fe and Si particles. Preliminary results with cells exposed to 1Gy gamma-rays show that the kinetics of pChk2-pT68 foci formation is comparable to that of gamma-H2AX although they appear to recede quicker. The number and intensity of observed foci reaches a maximum at 30 min and 60 min post IR for Chk2-pT68 and gamma-H2AX foci respectively and all Chk2-pT68 foci colocalize with gamma-H2AX foci. The kinetics of Chk1-pS345 and ATRIP are being determined. Results of Chk2-pT68 foci kinetics was also corroborated by western blot experiments, although phosphorylation was detected as early as 10 min and started receding 30 min post IR with 2Gy of gamma-rays. On the other hand, level of ATR-pS428 reached its maximum between 60 and 120 min and was maintained until the last measured time point of 4 hours post IR as determined by western blotting. Experiments performed with high LET Fe and Si particles will be reported.

Saha, Janapriya↗

An Adverse Outcome Pathway for Potential Space Radiation Induced Neurological Diseases

Astronauts have begun to spend increasingly longer periods in space, putting themselves in foreign environments in order to explore the unknown. Space radiation is one of the largest health risks faced by astronauts on their missions. The space radiation environment has the ability to cause high levels of irreversible damage. Multiple sources of charged particle radiation exist in the space environment that may increase risk of carcinogenesis, degeneration of bodily tissue (e.g. gastrointestinal, cardiovascular, or pulmonary), acute radiation syndromes, and acute and late central nervous system (CNS) disorders. In order to help inform an understanding of the risk of degenerative CNS disease due to radiation exposure, an initial step is presented here to develop an adverse outcome pathway from radiation exposure focused on Alzheimer’s disease.

Mi, Kaitlyn↗

High-LET radiation-induced aberrations in prematurely condensed G2 chromosomes of human fibroblasts

PURPOSE: To determine the number of initial chromatid breaks induced by low- or high-LET irradiations, and to compare the kinetics of chromatid break rejoining for radiations of different quality. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290MeV/u), silicon (490MeV/u) and iron (200 and 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Chromatid breaks and exchanges in G2 cells were scored. PCC were collected after several post-irradiation incubation times, ranging from 5 to 600 min. RESULTS: The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components representing a rapid and a slow time constant. Chromatid breaks decreased rapidly during the first 10min after exposure, then continued to decrease at a slower rate. The rejoining kinetics were similar for exposure to each type of radiation. Chromatid exchanges were also formed quickly. Compared to low-LET radiation, isochromatid breaks were produced more frequently and the proportion of unrejoined breaks was higher for high-LET radiation. CONCLUSIONS: Compared with gamma-rays, isochromatid breaks were observed more frequently in high-LET irradiated samples, suggesting that an increase in isochromatid breaks is a signature of high-LET radiation exposure.

Non-NASA Center↗

Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

Zhang, Ye↗

Radiation-induced bystander effect and adaptive response in mammalian cells

Two conflicting phenomena, bystander effect and adaptive response, are important in determining the biological responses at low doses of radiation and have the potential to impact the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, we show here that non-irradiated cells acquire mutagenesis through direct contact with cells whose nuclei have been traversed with a single alpha particle each. Pretreatment of cells with a low dose of X-rays four hours before alpha particle irradiation significantly decreased this bystander mutagenic response. Results from the present study address some of the fundamental issues regarding both the actual target and radiation dose effect and can contribute to our current understanding in radiation risk assessment. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

NASA Discipline Radiation Health↗

Mitigating HZE Radiation-Induced Deficits in Marrow-Derived Mesenchymal Progenitor Cells and Skeletal Structure

Future long-duration space exploration beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure causes progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility.

cells↗

Radiation induced precursor flow field ahead of a Jovian entry body

The change in flow properties ahead of the bow shock of a Jovian entry body, resulting from absorption of radiation from the shock layer, is investigated. Ultraviolet radiation is absorbed by the free stream gases, causing dissociation, ionization, and an increase in enthalpy of flow ahead of the shock wave. As a result of increased fluid enthalpy, the entire flow field in the precursor region is perturbed. The variation in flow properties is determined by employing the small perturbation technique of classical aerodynamics as well as the thin layer approximation for the preheating zone. By employing physically realistic models of radiative transfer, solutions are obtained for velocity, pressure, density, temperature, and enthalpy variations. The results indicate that the precursor flow effects, in general, are greater at higher altitudes. Just ahead of the shock, however, the effects are larger at lower altitudes. Pre-heating of the gas significantly increases the static pressure and temperature ahead of the shock for velocities exceeding 36 km/sec.

Tiwari, S.↗

Radiation induced precursor flow field ahead of a Jovian entry body

The change in flow properties ahead of the bow shock of a Jovian entry body, resulting from absorption of radiation from the shock layer, is investigated. Ultraviolet radiation is absorbed by the free stream gases, causing dissociation, ionization, and an increase in enthalpy of flow ahead of the shock wave. As a result of increased fluid enthalpy, the entire flow field in the precursor region is perturbed. The variation in flow properties is determined by employing the small perturbation technique of classical aerodynamics as well as the thin layer approximation for the preheating zone. By employing physically realistic models for radiative transfer, solutions are obtained for velocity, pressure, density, temperature, and enthalpy variations. The results indicate that the precursor effects, in general, are greater for lower altitudes and higher entry velocities. At higher altitudes precursor effects are felt farther in the free-stream. Just ahead of the shock the effects are larger at lower altitudes.

Tiwari, S. N.↗

The radiation-induced rotation of cosmic dust particles: A feasibility study

A crossed beam, horizontal optical trap, used to achieve laser levitation of particles in an effort to determine how solar radiation produces high spin rate in interplanetary dust particles, is described. It is suggested that random variations in albedo and geometry give rise to a nonzero effective torque when the influence of a unidrectional source of radiaton (due to the Sun) over the surface of a interplanetary dust particle is averaged. This resultant nonzero torque is characterized by an asymmetry factor which is the ratio of the effective moment arm to the maximum linear dimension of the body and is estimated to be 5 X 10 to the minus four power. It is hoped that this symmetry factor, which stabilizes the nonstatistical response of the particle, can be measured in a future Spacelab experiment.

Misconi, N. Y.↗

On the Utilization of In-flight Radiation-induced Performance Data and Anomaly Resolution of Commercial Off the Shelf (COTS) Electronics

This viewgraph presentation presents an overview of the use of in-flight science data to review the radiation effects on commercial off the shelf (COTS) electronics used in recent spacecraft missions. The authors review the hazards that the space radiation environment pose for spacecraft electronics. They specifically discuss long term effects such as total ionizing dose (TID) and short term effects like single particle events (SEE). The advantages of using COTS electronics despite not being radiation hardened are mentioned. The reasons cite for tracking in-flight performance of COTS electronics include: anomaly resolution, validate ground tests and environmental predictions and provide lessons for future designers. Sample radiation impacts of science data from the following missions are analyzed: SOHO/LASCO 3 Coronograph, Microwave Anisotrophy Probe, Hubble Space Telescope and Chandra X-Ray Observatory.

Kenneth A. LeBel↗

Intraseasonal Variations in Tropical Deep Convection, Tropospheric Mean Temperature and Cloud-Induced Radiative Fluxes

Intraseasonal variability of deep convection represents a fundamental mode of variability in the organization of tropical convection. While most studies of intraseasonal oscillations (ISOs) have focused on the spatial propagation and dynamics of convectively coupled circulations, we examine the projection of ISOs on the tropically-averaged temperature and energy budget. The area of interest is the global oceans between 20oN/S. Our analysis then focuses on these questions: (i) How is tropospheric temperature related to tropical deep convection and the associated ice cloud fractional amount (ICF) and ice water path (IWP)? (ii) What is the source of moisture sustaining the convection and what role does deep convection play in mediating the PBL - free atmospheric temperature equilibration? (iii) What affect do convectively generated upper-tropospheric clouds have on the TOA radiation budget? Our methodology is similar to that of Spencer et al., (2007) with some modifications and some additional diagnostics of both clouds and boundary layer thermodynamics. A composite ISO time series of cloud, precipitation and radiation quantities built from nearly 40 events during a six-year period is referenced to the atmospheric temperature signal. The increase of convective precipitation cannot be sustained by evaporation within the domain, implying strong moisture transports into the tropical ocean area. While there is a decrease in net TOA radiation that develops after the peak in deep convective rainfall, there seems little evidence that an "Infrared Iris"- like mechanism is dominant. Rather, the cloud-induced OLR increase seems largely produced by weakened convection with warmer cloud tops. Tropical ISO events offer an accessible target for studying ISOs not just in terms of propagation mechanisms, but on their global signals of heat, moisture and radiative flux feedback processes.

Ramey, Holly S.↗

Relationships Between Tropical Deep Convection, Tropospheric Mean Temperature and Cloud-Induced Radiative Fluxes on Intraseasonal Time Scales

Intraseasonal variability of deep convection represents a fundamental mode of variability in the organization of tropical convection. While most studies of intraseasonal oscillations (ISOs) have focused on the spatial propagation and dynamics of convectively coupled circulations, we examine the projection of ISOs on the tropically-averaged temperature and energy budget. The area of interest is the global oceans between 20oN/S. Our analysis then focuses on these questions: (i) How is tropospheric temperature related to tropical deep convection and the associated ice cloud fractional amount (ICF) and ice water path (IWP)? (ii) What is the source of moisture sustaining the convection and what role does deep convection play in mediating the PBL - free atmospheric temperature equilibration? (iii) What affect do convectively generated upper-tropospheric clouds have on the TOA radiation budget? Our methodology is similar to that of Spencer et al., (2007) with some modifications and some additional diagnostics of both clouds and boundary layer thermodynamics. A composite ISO time series of cloud, precipitation and radiation quantities built from nearly 40 events during a six-year period is referenced to the atmospheric temperature signal. The increase of convective precipitation cannot be sustained by evaporation within the domain, implying strong moisture transports into the tropical ocean area. While there is a decrease in net TOA radiation that develops after the peak in deep convective rainfall, there seems little evidence that an "Infrared Iris"- like mechanism is dominant. Rather, the cloud-induced OLR increase seems largely produced by weakened convection with warmer cloud tops. Tropical ISO events offer an accessible target for studying ISOs not just in terms of propagation mechanisms, but on their global signals of heat, moisture and radiative flux feedback processes.

Ramey, Holly S.↗

Relationships Between Tropical Deep Convection, Tropospheric Mean Temperature and Cloud-Induced Radiative Fluxes on Intraseasonal Time Scales

Intraseasonal variability of deep convection represents a fundamental mode of variability in the organization of tropical convection. While most studies of intraseasonal oscillations (ISOs) have focused on the spatial propagation and dynamics of convectively coupled circulations, we examine the projection of ISOs on the tropically-averaged temperature and energy budget. The area of interest is the global oceans between 20degN/S. Our analysis then focuses on these questions: (i) How is tropospheric temperature related to tropical deep convection and the associated ice cloud fractional amount (ICF) and ice water path (IWP)? (ii) What is the source of moisture sustaining the convection and what role does deep convection play in mediating the PBL - free atmospheric temperature equilibration? (iii) What affect do convectively generated upper-tropospheric clouds have on the TOA radiation budget? Our methodology is similar to that of Spencer et al., (2007) with some modifications and some additional diagnostics of both clouds and boundary layer thermodynamics. A composite ISO time series of cloud, precipitation and radiation quantities built from nearly 40 events during a six-year period is referenced to the atmospheric temperature signal. The increase of convective precipitation cannot be sustained by evaporation within the domain, implying strong moisture transports into the tropical ocean area. While there is a decrease in net TOA radiation that develops after the peak in deep convective rainfall, there seems little evidence that an "Infrared Iris"- like mechanism is dominant. Rather, the cloud-induced OLR increase seems largely produced by weakened convection with warmer cloud tops. Tropical ISO events offer an accessible target for studying ISOs not just in terms of propagation mechanisms, but on their global signals of heat, moisture and radiative flux feedback processes.

Ramey, Holly S.↗

Modeling Space Radiation Induced Bone Changes in Rat Femurs through Finite Element Analysis

As the duration of manned missions outside of the Earth’s protective shielding increase, astronauts are at risk for exposure to space radiation. Various organ systems may be damaged due to exposure. This study investigates the bonestrength changes using finite element modeling of Long Evans rats (n=85) subjected to graded, head-only proton (0, 10, 25, and 100 cGy, 150 MeV/n) and 28silicon (0, 10, 25, and 50 cGy, 300 MeV/n) radiation. The strength of the femoral neck will be examined due its clinical relevance to hip fractures. It has been shown in previous studies that bone mineral density was not reduced at the site of fracture. These findings question whether measurements of bone mineral density may be used to assess risk of hip fracture. The mechanisms leading to the irregular relationship between bone density and strength are still uncertain within literature and investigated to greater extent in clinical applications. Finite element analysis within this study simulated physiological loading of the femoral neck. No significant changes in femoral neck strength were found across doses of proton or 28silicon head-only radiation. Future work includes performing mechanical testing of the bone samples. Moving from mouse to larger animal models may also provide the increased lifespan for assessing the long-term outcomes of radiation exposure.

Dale Johnson↗