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At least 919 records · Page 51

The Biological Effectiveness of Different Radiation Qualities for the Induction of Chromosome Damage in Human Lymphocytes

Chromosome aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to Si-28-ions with energies ranging from 90 to 600 MeV/u, Ti-48-ions with energies ranging from 240 to 1000 MeV/u, or to Fe-56-ions with energies ranging from 200 to 5,000 MeV/u. The LET of the various Si beams in this study ranged from 48 to 158 keV/ m, the LET of the Ti ions ranged from 107 to 240 keV/micron, and the LET of the Fe-ions ranged from 145 to 440 keV/ m. Doses delivered were in the 10- to 200-cGy range. Dose-response curves for chromosome exchanges in cells at first division after exposure, measured using fluorescence in situ hybridization (FISH) with whole-chromosome probes, were fitted with linear or linear-quadratic functions. 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 estimates of RBEmax values for total chromosome exchanges ranged from 4.4+/-0.4 to 31.5+/-2.6 for Fe ions, 21.4+/-1.7 to 28.3+/-2.4 for Ti ions, and 11.8+/-1.0 to 42.2+/-3.3 for Si ions. The highest RBEmax value for Fe ions was obtained with the 600 MeV/u beam, the highest RBEmax value for Ti ions was obtained 1000 MeV/u beam, and the highest RBEmax value for Si ions was obtained with the 170 MeV/u beam. For Si and Fe ions the RBEmax values increased with LET, reaching a maximum at about 180 keV/micron for Fe and about 100 keV/micron for Si, and decreasing with further increase in LET. Additional studies for low doses Si-28-ions down to 0.02 Gy will be discussed.

Hada, M.↗

Tracking Vector Magnetograms with the Magnetic Induction Equation

The differential affine velocity estimator (DAVE) that we developed in 2006 for estimating velocities from line-of-sight magnetograms is modified to directly incorporate horizontal magnetic fields to produce a differential affine velocity estimator for vector magnetograms (DAVE4VM). The DAVE4VM's performance is demonstrated on the synthetic data from the anelastic pseudospectral ANMHD simulations that were used in the recent comparison of velocity inversion techniques by Welsch and coworkers. The DAVE4VM predicts roughly 95% of the helicity rate and 75% of the power transmitted through the simulation slice. Intercomparison between DAVE4VM and DAVE and further analysis of the DAVE method demonstrates that line-of-sight tracking methods capture the shearing motion of magnetic footpoints but are insensitive to flux emergence - the velocities determined from line-of-sight methods are more consistent with horizontal plasma velocities than with flux transport velocities. These results suggest that previous studies that rely on velocities determined from line-of-sight methods such as the DAVE or local correlation tracking may substantially misrepresent the total helicity rates and power through the photosphere.

Schuck, P.↗

The Analysis of the Patterns of Radiation-Induced DNA Damage Foci by a Stochastic Monte Carlo Model of DNA Double Strand Breaks Induction by Heavy Ions and Image Segmentation Software

To create a generalized mechanistic model of DNA damage in human cells that will generate analytical and image data corresponding to experimentally observed DNA damage foci and will help to improve the experimental foci yields by simulating spatial foci patterns and resolving problems with quantitative image analysis. Material and Methods: The analysis of patterns of RIFs (radiation-induced foci) produced by low- and high-LET (linear energy transfer) radiation was conducted by using a Monte Carlo model that combines the heavy ion track structure with characteristics of the human genome on the level of chromosomes. The foci patterns were also simulated in the maximum projection plane for flat nuclei. Some data analysis was done with the help of image segmentation software that identifies individual classes of RIFs and colocolized RIFs, which is of importance to some experimental assays that assign DNA damage a dual phosphorescent signal. Results: The model predicts the spatial and genomic distributions of DNA DSBs (double strand breaks) and associated RIFs in a human cell nucleus for a particular dose of either low- or high-LET radiation. We used the model to do analyses for different irradiation scenarios. In the beam-parallel-to-the-disk-of-a-flattened-nucleus scenario we found that the foci appeared to be merged due to their high density, while, in the perpendicular-beam scenario, the foci appeared as one bright spot per hit. The statistics and spatial distribution of regions of densely arranged foci, termed DNA foci chains, were predicted numerically using this model. Another analysis was done to evaluate the number of ion hits per nucleus, which were visible from streaks of closely located foci. In another analysis, our image segmentaiton software determined foci yields directly from images with single-class or colocolized foci. Conclusions: We showed that DSB clustering needs to be taken into account to determine the true DNA damage foci yield, which helps to determine the DSB yield. Using the model analysis, a researcher can refine the DSB yield per nucleus per particle. We showed that purely geometric artifacts, present in the experimental images, can be analytically resolved with the model, and that the quantization of track hits and DSB yields can be provided to the experimentalists who use enumeration of radiation-induced foci in immunofluorescence experiments using proteins that detect DNA damage. An automated image segmentaiton software can prove useful in a faster and more precise object counting for colocolized foci images.

Ponomarev, Artem↗

Induction of a Radio-Adaptive Response by Low-dose Gamma Irradiation in Mouse Cardiomyocytes

One of the most significant occupational hazards to an astronaut is the frequent exposure to radiation. Commonly associated with increased risk for cancer related morbidity and mortality, radiation is also known to increase the risk for cardiovascular related disorders including: pericarditis, hypertension, and heart failure. It is believed that these radiation-induced disorders are a result of abnormal tissue remodeling. It is unknown whether radiation exposure promotes remodeling through fibrotic changes alone or in combination with programmed cell death. Furthermore, it is not known whether it is possible to mitigate the hazardous effects of radiation exposure. As such, we assessed the expression and mechanisms of radiation-induced tissue remodeling and potential radio-adaptive responses of p53-mediated apoptosis and fibrosis pathways along with markers for oxidative stress and inflammation in mice myocardium. 7 week old, male, C57Bl/6 mice were exposed to 6Gy (H) or 5cGy followed 24hr later with 6Gy (LH) 137Cs gamma radiation. Mice were sacrificed and their hearts extirpated 4, 24, or 72hr after final irradiation. Real Time - Polymerase Chain Reaction was used to evaluate target genes. Apoptotic genes Bad and Bax, pro-cell survival genes Bcl2 and Bcl2l2, fibrosis gene Vegfa, and oxidative stress genes Sod2 and GPx4 showed a reduced fold regulation change (Bad,-6.18; Bax,-6.94; Bcl2,-5.09; Bcl2l2,-4.03; Vegfa, -11.84; Sod2,-5.97; GPx4*,-28.72; * = Bonferroni adjusted p-value < or = 0.003) 4hr after H, but not after 4hr LH compared to control. Other p53-mediated apoptosis genes Casp3, Casp9, Trp53, and Myc exhibited down-regulation but did not achieve a notable level of significance 4hr after H. 24hr after H, genetic down-regulation was no longer present compared to 24hr control. These data suggest a general reduction in genetic expression 4hrs after a high dose of gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio-adaptive response that mitigates the reduction in genetic expression associated with single high-dose gamma radiation exposure. This radio-adaptive response may serve as a potential countermeasure to radiation-induced myocardial remodeling and preserve the cardiovascular health of astronauts; thus, reducing the risks of human space exploration.

Westby, Christian M.↗

Flux-Based Deadbeat Control of Induction-Motor Torque

An improved method and prior methods of deadbeat direct torque control involve the use of pulse-width modulation (PWM) of applied voltages. The prior methods are based on the use of stator flux and stator current as state variables, leading to mathematical solutions of control equations in forms that do not lend themselves to clear visualization of solution spaces. In contrast, the use of rotor and stator fluxes as the state variables in the present improved method lends itself to graphical representations that aid in understanding possible solutions under various operating conditions. In addition, the present improved method incorporates the superposition of high-frequency carrier signals for use in a motor-self-sensing technique for estimating the rotor shaft angle at any speed (including low or even zero speed) without need for additional shaft-angle-measuring sensors.

Kenny, Barbara H.↗

Induction of Cell Death through Alteration of Oxidants and Antioxidants in Epithelial Cells Exposed to High Energy Protons

Radiation affects several cellular and molecular processes including double strand breakage, modifications of sugar moieties and bases. In outer space, protons are the primary radiation source which poses a range of potential health risks to astronauts. On the other hand, the use of proton radiation for tumor radiation therapy is increasing as it largely spares healthy tissues while killing tumor tissues. Although radiation related research has been conducted extensively, the molecular toxicology and cellular mechanisms affected by proton radiation remain poorly understood. Therefore, in the present study, we irradiated rat epithelial cells (LE) with different doses of protons and investigated their effects on cell proliferation and cell death. Our data showed an inhibition of cell proliferation in proton irradiated cells with a significant dose dependent activation and repression of reactive oxygen species (ROS) and antioxidants, glutathione and superoxide dismutase respectively as compared to control cells. In addition, apoptotic related genes such as caspase-3 and -8 activities were induced in a dose dependent manner with corresponding increased levels of DNA fragmentation in proton irradiated cells than control cells. Together, our results show that proton radiation alters oxidant and antioxidant levels in the cells to activate apoptotic pathway for cell death.

Ramesh, Govindarajan↗

Single and Multi-Pulse Low-Energy Conical Theta Pinch Inductive Pulsed Plasma Thruster Performance

Fabricated and tested CTP IPPTs at cone angles of 20deg, 38deg, and 60deg, and performed direct single-pulse impulse bit measurements with continuous gas flow. Single pulse performance highest for 38deg angle with impulse bit of approx.1 mN-s for both argon and xenon. Estimated efficiencies low, but not unexpectedly so based on historical data trends and the direction of the force vector in the CTP. Capacitor charging system assembled to provide rapid recharging of capacitor bank, permitting repetition-rate operation. IPPT operated at repetition-rate of 5 Hz, at maximum average power of 2.5 kW, representing to our knowledge the highest average power for a repetitively-pulsed thruster. Average thrust in repetition-rate mode (at 5 kV, 75 sccm argon) was greater than simply multiplying the single-pulse impulse bit and the repetition rate.

Hallock, Ashley K.↗

Induction of Chromosomal Aberrations at Fluences of Less Than One HZE Particle per Cell Nucleus

The assumption of a linear dose response used to describe the biological effects of high LET radiation is fundamental in radiation protection methodologies. We investigated the dose response for chromosomal aberrations for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) nuclei. Human fibroblast and lymphocyte cells where irradiated with several low doses of <0.1 Gy, and several higher doses of up to 1 Gy with O (77 keV/ (long-s)m), Si (99 keV/ (long-s)m), Fe (175 keV/ (long-s)m), Fe (195 keV/ (long-s)m) or Fe (240 keV/ (long-s)m) particles. Chromosomal aberrations at first mitosis were scored using fluorescence in situ hybridization (FISH) with chromosome specific paints for chromosomes 1, 2 and 4 and DAPI staining of background chromosomes. Non-linear regression models were used to evaluate possible linear and non-linear dose response models based on these data. Dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Best fits for the dose response data for human lymphocytes irradiated in blood tubes were a NTE model for O and a linear response model fit best for Si and Fe particles. Additional evidence for NTE were found in low dose experiments measuring gamma-H2AX foci, a marker of double strand breaks (DSB), and split-dose experiments with human fibroblasts. Our results suggest that simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. The current and prior experimental studies provide important evidence against the linear dose response assumption used in radiation protection for HZE particles and other high LET radiation at the relevant range of low doses.

Hada, Megumi↗

Induction of Oxidation in Living Cells by Time-Varying Electromagnetic Fields

We are studying how biological systems can harness quantum effects of time varying electromagnetic (EM) waves as the time-setting basis for universal biochemical organization via the redox cycle. The effects of extremely weak EM field on the biochemical redox cycle can be monitored through real-time detection of oxidation-induced light emissions of reporter molecules in living cells. It has been shown that EM fields can also induce changes in fluid transport rates through capillaries (approximately 300 microns inner diameter) by generating annular proton gradients. This effect may be relevant to understanding cardiovascular dis-function in spaceflight, beyond the ionosphere. Importantly, we show that these EM effects can be attenuated using an active EM field cancellation device. Central for NASA's Human Research Program is the fact that the absence of ambient EM field in spaceflight can also have a detrimental influence, namely via increased oxidative damage, on DNA replication, which controls heredity.

oxidation↗

Predicting Global Ground Geoelectric Field With Coupled Geospace and Three-Dimensional Geomagnetic Induction Models

We forecast the global effects of space weather on the geoelectric and geomagnetic fields using a novel combination of methods. We use a realistic three-dimensional (3-D) model of Earth's electrical conductivity and a realistic representation of magnetospheric and ionospheric current systems. Our scheme involves the following steps: (1) We run a global magnetohydrodynamic model of the magnetosphere coupled to an electrostatic model of the ionosphere. (2) We calculate a global time series of the ground magnetic field resulting from the ionospheric, field-aligned, and magnetospheric currents of the global magnetohydrodynamic model. (3) We approximate this external field by an equivalent source current flowing in a thin shell above Earth. (4) We calculate a global time series of geoelectric and geomagnetic fields from the equivalent current and a 3-D conductivity model of Earth that also takes into account the coast effect due to large horizontal conductivity gradient. We verify our implementation by comparing the results against known analytic and numeric solutions, and then apply our scheme to the geomagnetic storm of 14 and 15 December 2006. In particular, we show that accounting for 3-D structure of Earth's conductivity results in significantly enhanced geoelectric field at large lateral gradients of conductivity, especially in coastal regions, both at middle and high latitudes. In the studied geomagnetic storm the largest values of 3-D geoelectric field are detected at high latitudes reaching 2.5 volts per kilometer and the 3-D effect extends inland by a few hundred kilometers.

Honkonen, I.↗