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NASA NTRS1994

Parameter dimension of turbulence-induced phase errors and its effects on estimation in phase diversity

The method of phase diversity has been used in the context of incoherent imaging to estimate jointly an object that is being imaged and phase aberrations induced by atmospheric turbulence. The method requires a parametric model for the phase-aberration function. Typically, the parameters are coefficients to a finite set of basis functions. Care must be taken in selecting a parameterization that properly balances accuracy in the representation of the phase-aberration function with stability in the estimates. It is well known that over parameterization can result in unstable estimates. Thus a certain amount of model mismatch is often desirable. We derive expressions that quantify the bias and variance in object and aberration estimates as a function of parameter dimension.

Thelen, Brian J.↗

NASA NTRS1999

Radiation-Induced Cytogenetic Damage as a Predictor of Cancer Risk for Protons and Fe Ions

We have successfully completed the series of experiments planned for year 1 and the first part of year 2 measuring the induction of chromosome aberrations induced in multiple cell types by three model space radiations: Fe-ions, protons and photons. Most of these data have now been compiled and a significant part subjected to detailed data analyses, although continuing data analysis is an important part of our current and future efforts. These analyses are directed toward defining the patterns of chromosomal damage induction by the three radiations and the extent to which such patterns are dependent on the type of cell irradiated. Our studies show significant differences, both quantitatively and qualitatively, between response of different cell types to these radiations however there is an overall pattern that characterizes each type of radiation in most cell lines. Thus our data identifies general dose-response patterns for each radiation for induction of multiple types of chromosomal aberrations but also identifies significant differences in response between some cell types. Specifically, we observe significant resistance for induction of aberrations in rat mammary epithelial cells when they are irradiated in vivo and assayed in vitro. Further, we have observed some remarkable differences in susceptibility to certain radiation-induced aberrations in cells whose genome has been modulated for two cancer- relevant genes, TP53 and CDKNIA. This data, if confirmed, may represent the first evidence of gene-specific differences in cellular metabolism of damage induced by densely-ionizing radiation that confers substantial sensitivity to protons compared to photons.

Williams, Jerry R.↗

NASA NTRS2000

Overcoming Dynamic Disturbances in Imaging Systems

We develop and discuss a methodology with the potential to yield a significant reduction in complexity, cost, and risk of space-borne optical systems in the presence of dynamic disturbances. More robust systems almost certainly will be a result as well. Many future space-based and ground-based optical systems will employ optical control systems to enhance imaging performance. The goal of the optical control subsystem is to determine the wavefront aberrations and remove them. Ideally reducing an aberrated image of the object under investigation to a sufficiently clear (usually diffraction-limited) image. Control will likely be distributed over several elements. These elements may include telescope primary segments, telescope secondary, telescope tertiary, deformable mirror(s), fine steering mirror(s), etc. The last two elements, in particular, may have to provide dynamic control. These control subsystems may become elaborate indeed. But robust system performance will require evaluation of the image quality over a substantial range and in a dynamic environment. Candidate systems for improvement in the Earth Sciences Enterprise could include next generation Landsat systems or atmospheric sensors for dynamic imaging of individual, severe storms. The technology developed here could have a substantial impact on the development of new systems in the Space Science Enterprise; such as the Next Generation Space Telescope(NGST) and its follow-on the Next NGST. Large Interferometric Systems of non-zero field, such as Planet Finder and Submillimeter Probe of the Evolution of Cosmic Structure, could benefit. These systems most likely will contain large, flexible optomechanical structures subject to dynamic disturbance. Furthermore, large systems for high resolution imaging of planets or the sun from space may also benefit. Tactical and Strategic Defense systems will need to image very small targets as well and could benefit from the technology developed here. We discuss a novel speckle imaging technique with the potential to separate dynamic aberrations from static aberrations. Post-processing of a set of image data, using an algorithm based on this technique, should work for all but the lowest light levels and highest frequency dynamic environments. This technique may serve to reduce the complexity of the control system and provide for robust, fault-tolerant, reduced risk operation. For a given object, a short exposure image is "frozen" on the focal plane in the presence of the environmental disturbance (turbulence, jitter, etc.). A key factor is that this imaging data exhibits frame-to-frame linear shift invariance. Therefore, although the Point Spread Function is varying from frame to frame, the source is fixed; and each short exposure contains object spectrum data out to the diffraction limit of the imaging system. This novel speckle imaging technique uses the Knox-Thompson method. The magnitude of the complex object spectrum is straightforward to determine by well-established approaches. The phase of the complex object spectrum is decomposed into two parts. One is a single-valued function determined by the divergence of the optical phase gradient. The other is a multi-valued function determined by the circulation of the optical phase gradient-"hidden phase." Finite difference equations are developed for the phase. The novelty of this approach is captured in the inclusion of this "hidden phase." This technique allows the diffraction-limited reconstruction of the object from the ensemble of short exposure frames while simultaneously estimating the phase as a function of time from a set of exposures.

Young, Eric W.↗

NASA NTRS2000

Overcoming Dynamic Disturbances in Imaging Systems

We develop and discuss a methodology with the potential to yield a significant reduction in complexity, cost, and risk of space-borne optical systems in the presence of dynamic disturbances. More robust systems almost certainly will be a result as well. Many future space-based and ground-based optical systems will employ optical control systems to enhance imaging performance. The goal of the optical control subsystem is to determine the wavefront aberrations and remove them. Ideally reducing an aberrated image of the object under investigation to a sufficiently clear (usually diffraction-limited) image. Control will likely be distributed over several elements. These elements may include telescope primary segments, telescope secondary, telescope tertiary, deformable mirror(s), fine steering mirror(s), etc. The last two elements, in particular, may have to provide dynamic control. These control subsystems may become elaborate indeed. But robust system performance will require evaluation of the image quality over a substantial range and in a dynamic environment. Candidate systems for improvement in the Earth Sciences Enterprise could include next generation Landsat systems or atmospheric sensors for dynamic imaging of individual, severe storms. The technology developed here could have a substantial impact on the development of new systems in the Space Science Enterprise; such as the Next Generation Space Telescope(NGST) and its follow-on the Next NGST. Large Interferometric Systems of non-zero field, such as Planet Finder and Submillimeter Probe of the Evolution of Cosmic Structure, could benefit. These systems most likely will contain large, flexible optormechanical structures subject to dynamic disturbance. Furthermore, large systems for high resolution imaging of planets or the sun from space may also benefit. Tactical and Strategic Defense systems will need to image very small targets as well and could benefit from the technology developed here. We discuss a novel speckle imaging technique with the potential to separate dynamic aberrations from static aberrations. Post-processing of a set of image data, using an algorithm based on this technique, should work for all but the lowest light levels and highest frequency dynamic environments. This technique may serve to reduce the complexity of the control system and provide for robust, fault-tolerant, reduced risk operation. For a given object, a short exposure image is "frozen" on the focal plane in the presence of the environmental disturbance (turbulence, jitter, etc.). A key factor is that this imaging data exhibits frame-to-frame linear shift invariance. Therefore, although the Point Spread Function is varying from frame to frame, the source is fixed; and each short exposure contains object spectrum data out to the diffraction limit of the imaging system. This novel speckle imaging technique uses the Knox-Thompson method. The magnitude of the complex object spectrum is straightforward to determine by well-established approaches. The phase of the complex object spectrum is decomposed into two parts. One is a single-valued function determined by the divergence of the optical phase gradient. The other is a multi-valued function determined by, the circulation of the optical phase gradient-"hidden phase." Finite difference equations are developed for the phase. The novelty of this approach is captured in the inclusion of this "hidden phase." This technique allows the diffraction-limited reconstruction of the object from the ensemble of short exposure frames while simultaneously estimating the phase as a function of time from a set of exposures.

Young, Eric W.↗

NASA NTRSDate not supplied

Exoplanet Yield Sensitivity for the Hybrid Lyot Coronagraph from end-to-end modeling for LUVOIR-A

NASA's future direct imaging flagship mission will require telescope mirror segmentation to survey a statistically significant population of nearby stellar systems by increasing aperture size beyond that achieved by traditional space-borne monolithic apertures thus far. Segmentation is a path for the size expansion, but it entails a challenge due to the introduction of temporal pupil discontinuities in terms of both phase and amplitude. Modeling of the integrated performance of the coronagraph with the expected dynamical profile of the telescope is an important step toward realistic estimates of the mission's science yields. We present results of a study using the hybrid Lyot coronagraph with a 15-m on-axis, segmented optical telescope assembly (OTA), akin to that of the Large UV / Optical /Infrared (LUVOIR) mission. We have developed a high-fidelity, end-to-end model as part of the Segmented Coronagraph Design and Analysis (SCDA) study that includes diffractive optical propagations at the 1e-10 contrast level across the optical train including the OTA and intermediate re-imaging optics inside the coronagraph instrument. We perform a sensitivity analysis to assess the contrast sensitivity to wavefront perturbations for a set of key telescope terms including segment-level low-order and mid-spatial frequency aberrations and evaluate expected exoplanet yields obtained in the presence of these sets of aberrations. Industry-provided segment-level wavefront aberration datasets involving the following mechanisms are input to the end-to-end model: (1) thermal gradients and accelerations, and (2) telescope dynamics including line-of-sight and segment jitter. Dynamically averaged PSFs in the presence of aberrations are fed into AYO (Altruistic Yield Optimization), a mission design reference simulator, that then assesses the scientific yield sensitivities.

high-contrast imaging↗

NASA NTRSDate not supplied

The PIAA-Vortex Coronagraph: A New Coronagraph Technology to Maximize Exo-Earth Yields in the Astro2020 Era

Detecting and characterizing the atmospheres of terrestrial exoplanets is a main goal of the IR/O/UV flagship mission recommended by the Astro2020 Report. Achieving this goal depends critically on developing coronagraph technology that maximizes the potential number of terrestrial exoplanets we predict we can characterize, i.e. the exoEarth yield. Stringent constraints on low-order aberration sensitivity, inner working angle, and throughput as a function of telescope pupil complexity have been one of the main limiting factors affecting the yield of coronagraphs, and is a driving factor for telescope design considerations such as whether to use an off-axis or on-axis architecture. We present a hybrid PIAA-Vortex coronagraph concept that relaxes many of these constraints, and makes on-axis telescopes with centrally obstructed pupils a viable region of the design trade-space for the IR/O/UV flagship. Using the LUVOIR-A pupil as a baseline to design around, we present a coronagraph architecture with a small, ~2.5 lambda/D working angle that is insensitive to tip/tilt aberrations and stellar angular diameters on the order of 0.1 lambda/D. Pupil-plane apodization is achieved with PIAA-style mirror apodizations we obtain using a formalism we have developed to simultaneously optimize the contrast and low-order aberration sensitivity of coronagraphs designed for arbitrary telescope pupils and dark-hole geometries. By using PIAA to apodize in the pupil plane, the PIAA-Vortex coronagraph mitigates the trade-off between planet throughput, IWA, and aberration sensitivity, resulting in significantly higher yields for coronagraphs on obstructed pupils and new opportunities to maximize our ability to detect biomarkers in the Astro2020 era.

Kevin Fogarty↗

NASA NTRS2024

Comparison of Geant4-DNA and RITRACKS/RITCARD: Microdosimetry, Nanodosimetry and DNA Damage Predictions for Low to High LET Ions

Low linear energy transfer (LET) ionizing radiations induce homogeneously distributed DNA damage at the cellular scale, while high LET ionizing radiations are well known to create complex biological damage including clustered double strand breaks (DSB). Clustered DSB are critical events that are difficult to repair, leading to increased biological outcomes compared to low LET radiation exposure. Recent studies have shown that DNA compaction, which can be actively modified by the cell to allow DNA repair, influences the yield of DSB [1]. The goal of this work is to determine the impact of DNA compaction on chromosome aberration formation, a biomarker of radiation-induced cancer risk. The RITRACKS track structure code [2], together with the RITCARD code [3], allow one to simulate the transport of high LET ions, calculate DNA damage and repair, and chromosome aberration formation, but does not include detailed geometrical models of DNA. The Geant4-DNA toolkit provides such detailed models with different levels of DNA compaction [1,4], but does not model chromosome aberration formation. In this work, these highly detailed DNA geometries are used to compute DNA breaks with Geant4-DNA and combine the results with the RITCARD tool to compute chromosome aberrations. As a first step, we compared the transport models used in RITRACKS and Geant4-DNA and newly released heavy ion model transport (G4DNARuddIonisationExtendedModel Geant4 v11.2) to ensure consistency between the physical stage of the two radiation transport codes. We compared energy deposition at the micrometric and nanometric scales for different ions (H 250 MeV, H 150 Me, He 250 MeV/n, C 290 MeV/n, O 350 MeV/n, O 55 MeV/n, Si 170MeV/n, Ti 300 MeV/n, Ti 300 MeV/n, Fe 600 MeV/n, Fe 450 MeV/n and Fe 300 MeV/n) with LET ranging from ~0.4 keV/μm up to 235 keV/μm. Excellent agreement is found for both microdosimetric and nanodosimetric spectra for all ion types and energies. The calculation of DNA breaks and their complexity with the Geant4-DNA is an ongoing work, and comparison with RITCARD will be presented based on result availability at the time of the conference. [1] Tang et al. (2019). Med. Phys., 46(3), 1501-1511. [2] Plante et al. (2008). NJP, 10(12), 125020. [3] Plante et al. (2019). Rad. Res., 192(3), 282-298. [4] Incerti et al. (2018). Med. Phys., 45(8), e722-e739.

Floriane Poignant↗

DOE OSTI2021

Cytogenetic follow-up studies on humans with internal and external exposure to ionizing radiation

Cells exposed to ionizing radiation have a wide spectrum of DNA lesions that include DNA single-strand breaks, DNA double-strand breaks (DSBs), oxidative base damage and DNA-protein crosslinks. Among them, DSB is the most critical lesion, which when mis-repaired leads to unstable and stable chromosome aberrations. Currently, chromosome aberration analysis is the preferred method for biological monitoring of radiation-exposed humans. Here, stable chromosome aberrations, such as inversions and balanced translocations, persist in the peripheral blood lymphocytes of radiation-exposed humans for several years and, therefore, are potentially useful tools to prognosticate the health risks of radiation exposure, particularly in the hematopoietic system. In this review, we summarize the cytogenetic follow-up studies performed by REAC/TS (Radiation Emergency Assistance Center/Training site, Oak Ridge, USA) on humans exposed to internal and external radiation. In the light of our observations as well as the data existing in the literature, this review attempts to highlight the importance of follow-up studies for predicting the extent of genomic instability and its impact on delayed health risks in radiation-exposed victims.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2023

Multi-element metasurface system for imaging in the near-infrared

Metasurfaces are optically thin 2D arrays of subwavelength scatterers that modify scalar and vector properties of incident electromagnetic fields. Metasurface lenses are of particular interest for imaging applications for their flat form factor, compatibility with CMOS fabrication processes, and potential for correcting aberrations with a small number of elements. Here, we advance this capability by realizing a millimeter-diameter, polarization-independent metalens triplet system with chromatic aberration correction over the wavelength range of 1.30–1.60 μm and monochromatic aberration correction enabling a field of view of 50°.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

NASA NTRS2003

Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage Measured in Metaphase and Interphase Human Lymphocytes

Chromosome aberrations were investigated in human lymphocytes after in vitro exposure to 1H-, 3He-, 12C-, 40Ar-, 28Si-, 56Fe-, or 197Au-ion beams, with LET ranging from approximately 0.4-1393 keV/microm in the dose range of 0.075-3 Gy. Dose-response curves for chromosome exchanges, measured at the first mitosis postirradiation 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 chromosomal damage with respect to low- or high-dose-rate gamma rays. Estimates of RBEmax values for mitotic spreads, which ranged from near 0.7 to 11.1 for total exchanges, increased with LET, reaching a maximum at about 150 keV/microm, and decreased with further increase in LET. RBEs for complex aberrations are undefined due to the lack of an initial slope for gamma rays. Additionally, the effect of mitotic delay on RBE values was investigated by measuring chromosome aberrations in interphase after chemically induced premature chromosome condensation (PCC), and values were up to threefold higher than for metaphase analysis.

NASA Discipline Radiation Health↗

NASA NTRS2001

Relative effectiveness of HZE iron-56 particles for the induction of cytogenetic damage in vivo

One of the risks of prolonged manned space flight is the exposure of astronauts to radiation from galactic cosmic rays, which contain heavy ions such as (56)Fe. To study the effects of such exposures, experiments were conducted at the Brookhaven National Laboratory by exposing Wistar rats to high-mass, high-Z, high-energy (HZE) particles using the Alternating Gradient Synchrotron (AGS). The biological effectiveness of (56)Fe ions (1000 MeV/nucleon) relative to low-LET gamma rays and high-LET alpha particles for the induction of chromosome damage and micronuclei was determined. The mitotic index and the frequency of chromosome aberrations were evaluated in bone marrow cells, and the frequency of micronuclei was measured in cells isolated from the trachea and the deep lung. A marked delay in the entry of cells into mitosis was induced in the bone marrow cells that decreased as a function of time after the exposure. The frequencies of chromatid aberrations and micronuclei increased as linear functions of dose. The frequency of chromosome aberrations induced by HZE particles was about 3.2 times higher than that observed after exposure to (60)Co gamma rays. The frequency of micronuclei in rat lung fibroblasts, lung epithelial cells, and tracheal epithelial cells increased linearly, with slopes of 7 x 10(-4), 12 x 10(-4), and 11 x 10(-4) micronuclei/binucleated cell cGy(-1), respectively. When genetic damage induced by radiation from (56)Fe ions was compared to that from exposure to (60)Co gamma rays, (56)Fe-ion radiation was between 0.9 and 3.3 times more effective than (60)Co gamma rays. However, the HZE-particle exposures were only 10-20% as effective as radon in producing micronuclei in either deep lung or tracheal epithelial cells. Using microdosimetric techniques, we estimated that 32 cells were hit by delta rays for each cell that was traversed by the primary HZE (56)Fe particle. These calculations and the observed low relative effectiveness of the exposure to HZE particles suggest that at least part of the cytogenetic damage measured was caused by the delta rays. Much of the energy deposited by the primary HZE particles may result in cell killing and may therefore be "wasted" as far as production of detectable micronuclei is concerned. The role of wasted energy in studies of cancer induction may be important in risk estimates for exposure to HZE particles.

Non-NASA Center↗

NASA NTRS1998

Rejoining and misrejoining of radiation-induced chromatin breaks. IV. Charged particles

We have recently reported the kinetics of chromosome rejoining and exchange formation in human lymphocytes exposed to gamma rays using the techniques of fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC). In this paper, we have extended previous measurements to cells exposed to charged particles. Our goal was to determine differences in chromatin break rejoining and misrejoining after exposure to low- and high-linear energy transfer (LET) radiation. Cells were irradiated with hydrogen, neon, carbon or iron ions in the LET range 0.3-140 keV/microm and were incubated at 37 degrees C for various times after exposure. Little difference was observed in the yield of early prematurely condensed chromosome breaks for the different ions. The kinetics of break rejoining was exponential for all ions and had similar time constants, but the residual level of unrejoined breaks after prolonged incubation was higher for high-LET radiation. The kinetics of exchange formation was also similar for the different ions, but the yield of chromosome interchanges measured soon after exposure was higher for high-LET particles, suggesting that a higher fraction of DNA breaks are misrejoined quickly. On the other hand, the rate of formation of complete exchanges was slightly lower for densely ionizing radiation. The ratios between the yields of different types of aberrations observed at 10 h postirradiation in prematurely condensed chromosome preparations were dependent on LET. We found significant differences between the yields of aberrations measured in interphase (after repair) and metaphase for densely ionizing radiation. This difference might be caused by prolonged mitotic delay and/or interphase death. Overall, the results point out significant differences between low- and high-LET radiation for the formation of chromosome aberrations.

NASA Center JSC↗

DOE OSTI2026

Control Algorithms for Dual-wavefront Sensor Single-conjugate Adaptive Optics

High-contrast imaging systems using active control with adaptive optics (AO) are often limited by non-common path (NCP) aberrations that are seen only at the final science image. AO systems employing focal-plane wavefront sensors (FP-WFSs) are able to simultaneously correct NCP aberrations and measure science images, but they typically require a second stage of control that adds system cost and complexity. We present control algorithms to augment AO systems with FP-WFSs within their existing control setup. We demonstrate inter-arm NCP aberration transfer can be mitigated through temporal filtering, present frequency- and time-domain validation of controller stability and performance, and discuss the optimality of the chosen controllers. This work will enable the development, testing, and installation of FP-WFS technologies for direct imaging of exoplanets.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2021

A transmission hologram for slitless spectrophotometry on a convergent telescope beam. 1. Focus and resolution

We report in this paper the test of a plane holographic optical element to be used as an aberration-corrected grating for a slitless spectrograph, inserted in a convergent telescope beam. Our long-term objective is the optimization of a specific hologram to switch the auxiliary telescope imager of the Vera Rubin Observatory into an accurate slitless spectrograph, dedicated to the atmospheric transmission measurement. We present and discuss here the promising results of tests performed with prototype holograms at the CTIO $0.9\,$m telescope during a run of 17 nights in 2017 May–June. After their on-sky geometrical characterization, the performances of the holograms as aberration-balanced dispersive optical elements have been established by analysing spectra obtained from spectrophotometric standard stars and narrow-band emitter planetary nebulae. Thanks to their additional optical function, our holographic disperser prototypes allow us to produce significantly better focused spectra within the full visible wavelength domain $[370,1050]\,$nm than a regular grating, which suffers from strong defocusing and aberrations when used in similar conditions. We show that the resolution of our slitless on-axis spectrograph equipped with the hologram approaches its theoretical performance. While estimating the benefits of a hologram for the spectrum resolution, the roadmap to produce a competitive holographic element for the Vera Rubin Observatory auxiliary telescope has been established.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2024

Binary pseudo-random array standards for calibration of 3D optical surface profilers used for metrology with significantly curved x-ray optics

High-accuracy metrology is vitally important in manufacturing ultra-high-quality free-form mirrors designed to manipulate X-ray light with nanometer-scale wavelengths. The current capabilities and possibility for improvements in X-ray mirror manufacturing are limited by inherent imperfections of the integrated metrology tools. In the case of Fizeau interferometry, metrology tools are currently calibrated with super-polished flat test-standard/reference mirrors. This is acceptable for measuring slightly curved X-ray optics. However, for even moderately curved aspherical X-ray mirrors the flat-reference calibration is not sufficiently accurate and stitching Fizeau interferometer-based surface metrology is used to mitigate the problem. But still, the retrace and aberration errors, as well as the limited spatial resolution, described with the instrument transfer function (ITF), can be transferred into the optical surface topography of X-ray mirrors obtained in stitching metrology. For ITF calibration, we have developed an original technique, based on test standards structured as two-dimensional (2D) highly-randomized (HR) binary pseudo-random arrays (BPRAs). The technique employs the unique properties of the HR BPRA patterns in the spatial frequency domain., i.e. the inherent 2D power spectral density of the HR BPRA pattern has a deterministic white-noise-like character that allows direct determination of the ITF with uniform sensitivity over the entire spatial frequency range and field-of-view of an instrument. Here, we explore technological, metrological, and analytical aspects essential for calibration of the retrace and aberration errors of Fizeau interferometers using different types of tilted test samples, including a super-polished reference mirror for the re-trace calibration and the uniformly redundant array (URA) BPRA standards for the geometrical distortion (aberration) calibration. While the first method was previously demonstrated by researchers at DIAMOND Light Source, a method based on the URA BPRA is described and demonstrated here for the first time. We outline the design and fabrication process used in fabrication of URA BPRA test standards, and present the results of application of the URA BPRA standards demonstrating the high efficacy of our approach to geometrical distortion calibration of Fizeau interferometers. We also discuss the possible sources of unexpected peculiarities of the systematic errors, including an astigmatic character of the retrace error, observed with Fizeau interferometers at the Advanced Light Source X-Ray Optics Laboratory.

Munechika, Keiko↗

DOE OSTI2020

Cellular Response to Proton Irradiation: A Simulation Study with TOPAS-nBio

The cellular response to ionizing radiation continues to be of significant research interest in cancer radiotherapy, and DNA is recognized as the critical target for most of the biologic effects of radiation. Incident particles can cause initial DNA damages through physical and chemical interactions within a short time scale. Initial DNA damages can undergo repair via different pathways available at different stages of the cell cycle. The misrepair of DNA damage results in genomic rearrangement and causes mutations and chromosome aberrations, which are drivers of cell death. This work presents an integrated study of simulating cell response after proton irradiation with energies of 0.5–500 MeV (LET of 60–0.2 keV/µm). A model of a whole nucleus with fractal DNA geometry was implemented in TOPAS-nBio for initial DNA damage simulations. The default physics and chemistry models in TOPAS-nBio were used to describe interactions of primary particles, secondary particles, and radiolysis products within the nucleus. The initial DNA double-strand break (DSB) yield was found to increase from 6.5 DSB/Gy/Gbp at low-linear energy transfer (LET) of 0.2 keV/µm to 21.2 DSB/Gy/Gbp at high LET of 60 keV/µm. A mechanistic repair model was applied to predict the characteristics of DNA damage repair and dose response of chromosome aberrations. It was found that more than 95% of the DSBs are repaired within the first 24 h and the misrepaired DSB fraction increases rapidly with LET and reaches 15.8% at 60 keV/µm with an estimated chromosome aberration detection threshold of 3 Mbp. The dicentric and acentric fragment yields and the dose response of micronuclei formation after proton irradiation were calculated and compared with experimental results.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2021

The progeria research foundation 10 th international scientific workshop; researching possibilities, ExTENding lives – webinar version scientific summary

Progeria is an ultra-rare (prevalence 1 in 20 million), fatal, pediatric autosomal dominant premature aging disease caused by a mutation in the LMNA gene. This mutation results in accumulation of a high level of an aberrant form of the nuclear membrane protein, Lamin A. This aberrant protein, termed progerin, accumulates in many tissues and is responsible for the diverse array of disease phenotypes. Children die predominantly from premature atherosclerotic cardiovascular disease. The Progeria Research Foundation’s 10th International Scientific Workshop took place via webinar on November 2 and 3, 2020. Participants from 30 countries joined in this new, virtual meeting format. Patient family presentations led the program, followed by updates on Progeria’s first-ever application for FDA drug approval as well as initial results from the only current Progeria clinical trial. This was followed by presentations of unpublished preclinical data on drugs in development targeting the disease-causing DNA mutation, the aberrant mRNA, progerin protein, and its downstream effector proteins. Tying bench to bedside, clinicians presented new discoveries on the natural history of disease to inform future clinical trial development and new Progeria aortic valve replacement procedures. The program engaged the Progeria research community as a single unit with a common goal – to treat and cure children with Progeria worldwide.

60 APPLIED LIFE SCIENCES↗

NASA NTRS1971

Improvements in Ross type astrometric objectives

It is shown that aspheric deformations of the first and fourth elements of the four element Ross objective can be introduced to permit one to obtain improved color corrections for astrometric purposes. The usual monochromatic aberrations are as well corrected as for the standard Ross lens. In addition, one can eliminate or reduce additional aberrations, such as secondary spectrum, chromatic spherical aberration, chromatic coma and chromatic distortion. The resulting objectives are suitable for use as intermediate and long focus astrometric objectives covering large angle fields.

Baker, J.↗