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At least 235 records · Page 13

Simulation of DNA Damage in Human Cells from Space Radiation Using a Physical Model of Stochastic Particle Tracks and Chromosomes

The formation of double-strand breaks (DSBs) and chromosomal aberrations (CAs) is of great importance in radiation research and, specifically, in space applications. We are presenting a recently developed model, in which chromosomes simulated by NASARTI (NASA Radiation Tracks Image) is combined with nanoscopic dose calculations performed with the Monte-Carlo simulation by RITRACKS (Relativistic Ion Tracks) in a voxelized space. The model produces the number of DSBs, as a function of dose for high-energy iron, oxygen, and carbon ions, and He ions. The combined model calculates yields of radiation-induced CAs and unrejoined chromosome breaks in normal and repair deficient cells. The merged computational model is calibrated using the relative frequencies and distributions of chromosomal aberrations reported in the literature. The model considers fractionated deposition of energy to approximate dose rates of the space flight environment. The merged model also predicts of the yields and sizes of translocations, dicentrics, rings, and more complex-type aberrations formed in the G0/G1 cell cycle phase during the first cell division after irradiation.

Ponomarev, Artem↗

Design and Modeling of the Off-Axis Parabolic Deformable (OPD) Mirror Laboratory

Coronagraph-equipped direct imaging missions need an active wavefront control system to cancel out the optical aberrations that degrade the performance of the coronagraphs. A fast steering mirror is used to control Line-of-Sight (LoS) pointing error caused by the telescope jitter. In addition to controlling other low-order aberrations such as astigmatism and coma, high stroke, high actuator density deformable mirrors (DMs) are also used to control the electric field at the required high spatial frequencies. We are designing a testbed to verify a different deformable architecture, where the powered optic in the optical train are controllable and have lower actuator count compared to the existing DMs with flat nominal surfaces. This simplifies the packaging issue for space missions and reduces both cost and risk of having the entire coronagraph instrument's performance depending on one or two high-actuator count DMs. The testbed would also be capable of testing different low-order wavefront sensing algorithms, which focuses in the near-term on a new adaptive Kalman filtering and gradient decent method to estimate the harmonic LoS errors that affect space telescopes. In long run, we would test different machine learning techniques to estimate low-order aberrations and non-linear algorithms for digging the region of high contrast called the dark holes (DH).

Subedi, Hari↗

Design and Modeling of the Off-Axis Parabolic Deformable Mirror Laboratory

Coronagraph-equipped direct imaging missions need an active wavefront control system to cancel out the optical aberrations that degrade the performance of the coronagraphs. A fast steering mirror is used to control Line-of-Sight (LoS) pointing error caused by the telescope jitter. In addition to controlling other low-order aberrations such as astigmatism and coma, high stroke, high actuator density deformable mirrors (DMs) are also used to control the electric field at the required high spatial frequencies. We are designing a testbed to verify a different deformable architecture, where the powered optic in the optical train are controllable and have lower actuator count compared to the existing DMs with flat nominal surfaces. This simplifies the packaging issue for space missions and reduces both cost and risk of having the entire coronagraph instrument's performance depending on one or two high-actuator count DMs. The testbed would also be capable of testing different low-order wavefront sensing algorithms, which focuses in the near-term on a new adaptive Kalman filtering and gradient decent method to estimate the harmonic LoS errors that affect space telescopes. In long run, we would test different machine learning techniques to estimate low-order aberrations and non-linear algorithms for digging the region of high contrast called the dark holes (DH).

Communication↗

Star Tracker Accuracy Improvement and Optimization for Attitude Measurement in Three-Axis

High precision attitude measurement systems obviate the need for the beacon from the receiver making it possible for the spacecraft to beam a laser communications signal to a ground station without the ground station advertising its location. The research presented targets new detection and estimation methods to improve the accuracy in locating stars on a focal plane detector, and an understanding of the effects of changes in the optics design parameters and aberration, including defocus, on the navigation solution itself. This understanding can lead to an optimization of the attitude solution with respect to those optics realm parameter changes. The methodology discussed includes the development of a model of a current star tracker system. Using this model, multiple algorithms are implemented, including a multi-hypothesis method (MHT), to detect and estimate the position of the stars on the focal plane detector. It will be shown that using the MHT for detection and estimation, a greater accuracy can be found for each star estimation from more traditional detection and estimation algorithms. The approach then uses the model to develop statistics of the star tracker and the attitude estimation outputs to understand the accuracy, or variance, of the system's attitude solution. This solution is repeated for a range of defocus aberration, and a lower limit to the variance of the attitude solution is shown. A Cramer Rao lower bound solution is derived for the star tracker system and the results are compared to the Monte Carlo analysis from the model and shown to correlate very well. The approach uses a star image not as a Gaussian spot on the focal plane as done in previous work, and use of an image that includes the effects of aberrations of the optic system, and the effects of under-sampling and noise from the focal plane detector as well. Analysis includes exploring a star tracker's accuracy improvement through the combination of focus error and under-sampling effects alone, possibly contradicting conventional wisdom and approaches.

Lichter, Michael J.↗

Science Yield Estimates and Sensitivities With the AstroPIC Integrated Photonic Coronagraph for the Habitable Worlds Observatory

The Habitable Worlds Observatory (HWO) flagship has a goal to survey ~100 of the nearest stellar systems and their habitable zones in order to detector and spectroscopically characterize ~25 potentially “Earth-like planets” (or “Exoearths”). The HWO telescope will feature a >6-m diameter aperture and a coronagraph that will suppress starlight by ten orders of magnitude to enable the detection and characterization of Earth analogues in the habitable zone. Three Exploratory Analytic Cases (EACs) are currently considering different aperture configurations for HWO including on-axis and off-axis apertures and both different hexagonal and keystone segmentation configurations. Photonic Integrated Circuits (PICs) offer a path to miniaturize traditional, bulk optics coronagraph functionality reducing risk margins and increasing mission science exoearth yields for the HWO mission. We have developed a simulation pipeline that enables evaluation of the AstroPIC photonic integrated coronagraph through to estimates mission yields. We present sensitivities to aberrations for different types of segmentation and low-order aberrations for HWO EACs demonstrating that AstroPIC is suitable for both on-axis and off-axis configurations. We perform a parametric sweep of the exoearth science yield sensitivities in terms of key coronagraph parameters including coronagraphic end-to-end throughput, inner working angle, robustness to aberrations, and bandwidth. We consider both a hybrid and a pure photonic architecture; a pure integrated photonic architecture provides the greatest potential in science yield improvements, although a hybrid PIC limited in its numbers of modes can provide complementary science to a traditional, bulk-optic coronagraph and increasing the estimated science yield when operated jointly.

Photonics↗

Radiation-induced genomic instability: radiation quality and dose response

Genomic instability is a term used to describe a phenomenon that results in the accumulation of multiple changes required to convert a stable genome of a normal cell to an unstable genome characteristic of a tumor. There has been considerable recent debate concerning the importance of genomic instability in human cancer and its temporal occurrence in the carcinogenic process. Radiation is capable of inducing genomic instability in mammalian cells and instability is thought to be the driving force responsible for radiation carcinogenesis. Genomic instability is characterized by a large collection of diverse endpoints that include large-scale chromosomal rearrangements and aberrations, amplification of genetic material, aneuploidy, micronucleus formation, microsatellite instability, and gene mutation. The capacity of radiation to induce genomic instability depends to a large extent on radiation quality or linear energy transfer (LET) and dose. There appears to be a low dose threshold effect with low LET, beyond which no additional genomic instability is induced. Low doses of both high and low LET radiation are capable of inducing this phenomenon. This report reviews data concerning dose rate effects of high and low LET radiation and their capacity to induce genomic instability assayed by chromosomal aberrations, delayed lethal mutations, micronuclei and apoptosis.

Review↗

Estimate of true incomplete exchanges using fluorescence in situ hybridization with telomere probes

PURPOSE: To study the frequency of true incomplete exchanges in radiation-induced chromosome aberrations. MATERIALS AND METHODS: Human lymphocytes were exposed to 2 Gy and 5 Gy of gamma-rays. Chromosome aberrations were studied using the fluorescence in situ hybridization (FISH) technique with whole chromosome-specific probes, together with human telomere probes. Chromosomes 2 and 4 were chosen in the present study. RESULTS: The percentage of incomplete exchanges was 27% when telomere signals were not considered. After excluding false incomplete exchanges identified by the telomere signals, the percentage of incomplete exchanges decreased to 11%. Since telomere signals appear on about 82% of the telomeres, the percentage of true incomplete exchanges should be even lower and was estimated to be 3%. This percentage was similar for chromosomes 2 and 4 and for doses of both 2 Gy and 5 Gy. CONCLUSIONS: The percentage of true incomplete exchanges is significantly lower in gamma-irradiated human lymphocytes than the frequencies reported in the literature.

NASA Discipline Radiation Health↗

Biodosimetry results from space flight Mir-18

Astronauts are classified as radiation workers due to the presence of ionizing radiation in space. For the assessment of health risks, physical dosimetry has been indispensable. However, the change of the location of dosimeters on the crew members, the variation in dose rate with location inside the spacecraft and the unknown biological effects of microgravity can introduce significant uncertainties in estimating exposure. To circumvent such uncertainty, a study on the cytogenetic effects of space radiation in human lymphocytes was proposed and conducted for Mir-18, a 115-day mission. This study used fluorescence in situ hybridization (FISH) with whole-chromosome painting probes to score chromosomal exchanges and the Giemsa staining method to determine the frequency of dicentrics. The growth kinetics of cells and sister chromatid exchanges (SCEs) were examined to ensure that chromosomal aberrations were scored in the first mitosis and were induced primarily by space radiation. Our results showed that the frequency of chromosomal aberrations increased significantly in postflight samples compared to samples drawn prior to flight, and that the frequency of SCEs was similar for both pre- and postflight samples. Based on a dose-response curve for preflight samples exposed to gamma rays, the absorbed dose received by crew members during the mission was estimated to be about 14.75 cSv. Because the absorbed dose measured by physical dosimeters is 5.2 cGy for the entire mission, the RBE is about 2.8.

NASA Discipline Radiation Health↗

Centric rings, acentric rings and excess acentric fragments based on a random-walk interphase chromosome model

Excess acentric fragments, consisting of acentric rings and acentric linear fragments, are among the most frequent kinds of chromosome-type aberrations produced by radiation. The frequency of acentric rings cannot be obtained directly by experiment but is estimated here from the ratio of acentric to centric rings, evaluated using a random-walk model for the organization of chromatin during interphase and an assumption that the probability of an exchange formation is proportional to the rate of collision between two DSB. This ratio is calculated to be 2.5 in low-LET irradiated human fibroblasts, significantly greater than the ratio if proximity effects are not considered. The calculated frequency of acentric rings is insufficient to account for all the observed excess acentric fragments. Assuming that the rest of the excess acentric fragments are due to incomplete exchanges, all possible recombinations between two DSB that result in acentric rings and acentric linear fragments have been identified. From the chromosome aberration data, the incompleteness parameter has been estimated. Intra-arm chromosome exchanges, either complete or incomplete, were estimated to account for more than 50% of the excess acentric fragments in human fibroblasts.

NASA Center JSC↗

Cytogenetic effects of space radiation in lymphocytes of MIR-18 crews

For assessing health risk, the measurement of physical dose received during a space mission, as well as the LETs, energies and charges of particles is important. It is also important to obtain quantitative information regarding the effectiveness of space radiation in causing damage to critical biological targets, e.g., chromosomes, since at present the estimated uncertainty of biological effects of space radiation is more than a factor of two. Such large uncertainty makes accurate health risk assessment very difficult. For this very reason, a study on cytogenetic effects of space radiation in human lymphocytes was proposed and done for MIR-18 mission. This study used FISH technique to score chromosomal translocations and C-banding method to determine dicentrics. Growth kinetics of cells and SCE were examined to ensure that chromosomal aberrations were scored in first mitosis and were induced not by chemical mutagens. Our results showed that chromosomal aberration frequency of post-flight samples was significantly higher than that of pre-flight ones and that SCE frequency was similar between pre- and post-flight samples. Based on a dose-response curve of preflight samples exposed to gamma rays, the absorbed dose received by crews during the mission was estimated to be about 14.5 cSv. Because the absorbed dose measured by physical dosimeters is 4.16 cGy for the entire mission, the RBE is about 3.5.

Mir Project↗

Rejoining and misrejoining of radiation-induced chromatin breaks. II. Biophysical Model

A biophysical model for the kinetics of the formation of radiation-induced chromosome aberrations is developed to account for the recent experimental results obtained with a combination of the premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) techniques. In this model, we consider the broken ends of DNA double-strand breaks (DSBs) to be reactant and make use of the interaction distance hypothesis. The repair/misrepair process between broken ends is suggested to consist of two steps; the first step represents the two break ends approaching each other, and the second step represents the enzymatic processes leading to DNA end-to-end rejoining. Only the second step is reflected in the kinetics observed in experiments using PCC. The model appears to be able to fit existing data for human cells. It is shown that the kinetics of the formation of chromosome aberrations can be explained by a single rate that characterizes both rejoining and misrejoining of DSBs, suggesting that repair and misrepair share the same mechanism. Fast repair (completed in minutes) in a subset of DSBs is suggested as an explanation of the complete exchanges observed with PCC in human lymphocytes immediately after irradiation. The fast repair component seems to be absent in human fibroblasts.

NASA Center JSC↗

Application of Monte Carlo techniques to optimization of high-energy beam transport in a stochastic environment

An algorithm employing a modified sequential random perturbation, or creeping random search, was applied to the problem of optimizing the parameters of a high-energy beam transport system. The stochastic solution of the mathematical model for first-order magnetic-field expansion allows the inclusion of state-variable constraints, and the inclusion of parameter constraints allowed by the method of algorithm application eliminates the possibility of infeasible solutions. The mathematical model and the algorithm were programmed for a real-time simulation facility; thus, two important features are provided to the beam designer: (1) a strong degree of man-machine communication (even to the extent of bypassing the algorithm and applying analog-matching techniques), and (2) extensive graphics for displaying information concerning both algorithm operation and transport-system behavior. Chromatic aberration was also included in the mathematical model and in the optimization process. Results presented show this method as yielding better solutions (in terms of resolutions) to the particular problem than those of a standard analog program as well as demonstrating flexibility, in terms of elements, constraints, and chromatic aberration, allowed by user interaction with both the algorithm and the stochastic model. Example of slit usage and a limited comparison of predicted results and actual results obtained with a 600 MeV cyclotron are given.

Parrish, R. V.↗

A general purpose wideband optical spatial frequency spectrum analyzer

The light scattered at various angles by a transparent media is studied. An example of these applications is the optical Fourier spectrum measurement resulting from various spatial frequencies which were recorded on a photographic emulsion. A method for obtaining these measurements consists of illuminating the test object with parallel monochromatic light. A stationary lens, placed in the resulting wavefield at a distance of one focal length from the object, will focus parallel waves emanating from the test object at a point lying in the focal plane of the lens. A light detector with a small filtering aperture is then used to measure the intensity variation of the light in the focal or transform plane of the lens. Such measurements require the use of a lens which is highly corrected for all of the common aberrations except chromatic aberration.

Ballard, G. S.↗

In-situ measurement of objective lens data of a high-resolution electron microscope.

Bragg-reflex images of small individual crystallites in the size range of 20-100 A diameter with known crystallographic orientation were used in a transmission electron microscope to determine in-situ: (a) the relationship between objective lens current (or accelerating voltage) changes in discrete steps and corresponding defocus, (b) the spherical aberration coefficient, and (c) the axial chromatic aberration coefficient of the objective lens. The accuracy of the described method is better than 5%. The same specimen can advantageously be used to properly aline the illuminating beam with respect to the optical axis.

Heinemann, K.↗

Anastigmatic three-mirror telescope

A three-mirror telescope arrangement that can be corrected for four aberrations (coma, spherical aberration, field curvature, and astigmatism) is described. Geometric spot size is less than 0.1 sec of arc, in an easily accessible flat field of 1.5 deg. The primary-secondary configuration is Cassegrain-like, with the real image formed closely behind the primary. This secondary image is re-imaged by a tertiary mirror at roughly unit magnification. A small, flat mirror at the exit pupil, located between primary and tertiary, folds the light rectangularly away from the telescope axis. The shape of the large image area is helpful in space applications where several instruments may share the focal plane.

Korsch, D.↗

Performance analysis of grazing incidence imaging systems

An exact expression relating the coordinates of a point on the incident ray, a point of reflection from an arbitrary surface, and a point on the reflected ray is derived. The exact relation is then specialized for the case of grazing incidence, and first order and third order systematic analyses are carried out for a single reflective surface and then for a combination of two surfaces. The third order treatment yields a complete set of primary aberrations for single element and two element systems. The importance of a judicious choice for a coordinate system in showing field curvature to clearly be the predominant aberration for a two element system is discussed. The validity of the theory is verified through comparisons with the exact ray trace results for the case of the telescope.

Winkler, C. E.↗

Effect of ultrasonic irradiation on mammalian cells and chromosomes in vitro

Human peripheral blood and HeLa cells were irradiated in vitro at the ultrasonic frequency of 65 kHz. The whole blood and HeLa cell suspensions were exposed to continuous and pulsed ultrasonic power levels of 0.12, 0.16, 0.72, 1.12 and 2.24 W for a period of one minute. The method of ultrasonic irradiation was carried out with the whole blood or HeLa cell suspensions coupled directly to a cylindrical transducer while heating of the cell suspensions in excess of 41 C was avoided. Irradiated and unirradiated peripheral blood lymphocyte chromosome cultures were prepared and scored for selected numerical and morphological aberrations. There was no significant difference in the frequency of chromosomal aberrations between irradiated and unirradiated cells.

Roseboro, J. A.↗

A high resolution holographic particle sizing system

This paper will review briefly the requirements of holography with respect to particle sizing techniques. A holographic construction system and the appropriate reconstruction system will be discussed regarding their characteristics and performance (i.e. system resolution, magnification, system aberration and correction of aberrations, and maximum total test volume). The capabilities of a commercial particle sizing system used to obtain particle sizes and distribution information from reconstructed holograms will be described and characterized. It will be shown that by using the methods described, high resolution throughout large test volumes can be achieved.

Witherow, W. K.↗