Results for “CGI” — Page 7

NASA NTRS2011

Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

Hada, M.↗

NASA NTRS2012

Computational Ghost Imaging for Remote Sensing

This work relates to the generic problem of remote active imaging; that is, a source illuminates a target of interest and a receiver collects the scattered light off the target to obtain an image. Conventional imaging systems consist of an imaging lens and a high-resolution detector array [e.g., a CCD (charge coupled device) array] to register the image. However, conventional imaging systems for remote sensing require high-quality optics and need to support large detector arrays and associated electronics. This results in suboptimal size, weight, and power consumption. Computational ghost imaging (CGI) is a computational alternative to this traditional imaging concept that has a very simple receiver structure. In CGI, the transmitter illuminates the target with a modulated light source. A single-pixel (bucket) detector collects the scattered light. Then, via computation (i.e., postprocessing), the receiver can reconstruct the image using the knowledge of the modulation that was projected onto the target by the transmitter. This way, one can construct a very simple receiver that, in principle, requires no lens to image a target. Ghost imaging is a transverse imaging modality that has been receiving much attention owing to a rich interconnection of novel physical characteristics and novel signal processing algorithms suitable for active computational imaging. The original ghost imaging experiments consisted of two correlated optical beams traversing distinct paths and impinging on two spatially-separated photodetectors: one beam interacts with the target and then illuminates on a single-pixel (bucket) detector that provides no spatial resolution, whereas the other beam traverses an independent path and impinges on a high-resolution camera without any interaction with the target. The term ghost imaging was coined soon after the initial experiments were reported, to emphasize the fact that by cross-correlating two photocurrents, one generates an image of the target. In CGI, the measurement obtained from the reference arm (with the high-resolution detector) is replaced by a computational derivation of the measurement-plane intensity profile of the reference-arm beam. The algorithms applied to computational ghost imaging have diversified beyond simple correlation measurements, and now include modern reconstruction algorithms based on compressive sensing.

Erkmen, Baris I.↗

NASA NTRS2016

Phase Retrieval Implementation for the WFIRST Coronagraph Development Testbed

The Wide-Field Infrared Survey Telescope (WFIRST) is a 2.4m diameter space telescope NASA program. The payload will include two instruments, including a coronagraph instrument (CGI). The CGI will be the first active, high-contrast stellar coronagraph in space intended for imaging, discovery, and spectral characterization of exoplanets and debris discs. The CGI designs under development use deformable mirrors (DM) to create a point spread function (PSF) with a dark region around the obscured star object. Each DM consists of an array of actuators, and each actuator causes a local displacement to a thin, mirror-coated, glass face sheet. The actuator displacements are designed to create the PSF. Typically, phase retrieval is used to set the DM actuator displacements to their designed pattern, and then the actuators are further modified by an iterative control loop to correct for system non-idealities. To observe an exoplanet near the star object, the contrast in the annular region must be better than 10^8 (10^9 after post processing) relative to the unobstructed image of the star [1,2]. The coronagraph testbed at Jet Propulsion Laboratory is used to test coronagraph design and control algorithms. The optical system (Fig. 1) is maintained in a vacuum tank so that the PSF is stable for long integration times. Phase retrieval is an important tool for the testbed and serves several purposes, in addition to setting initial DM actuator displacements. Other uses include evaluation of systematic wavefront error introduced by system components, and alignment of the DMs and pupil masks. For example, the location of specific DM actuators relative to the Lyot mask can be determined by displacing the actuator, then measuring the location of the phase disturbance in the pupil plane with phase retrieval. In the next section we further describe the optical train of the testbed and the collection of source and pupil images available as inputs for phase retrieval, as well as one phase retrieval algorithm employed. Section 3 shows example phase retrieval results.

Marx, David↗

NASA NTRS2019

Exo-C: A Dedicated Probe-scale Space Mission for Coronagraphic Imaging and Spectroscopy of Exoplanetary Systems

"Exo-C", the Exoplanet Coronagraph, is a concept for a dedicated probe-scale (< $1B) space mission optimized for direct imaging of exoplanetary systems. It was the product of a detailed mission study carried in 2013-2015 under the sponsorship of the NASA Astrophysics Division. Exo-C was designed to be capable of spectrally characterizing 1-2 dozen nearby exoplanets in reflected visible light, discovering previously undetected planets, and imaging structure in hundreds of circumstellar disks. It would obtain unique science results on planets down to super-Earth size and serve as a technology pathfinder toward an eventual flagship-class mission to find and characterize habitable Earth-like exoplanets. Key design elements are an unobscured telescope aperture, an internal coronagraph with deformable mirrors for precise wavefront control, and an orbit and observatory design chosen for high thermal stability. ExoC’s telescope aperture, orbit, mission lifetime, and spacecraft bus are all comparable to those of the highly successful Kepler mission. Much of the needed technology development (precision pointing, wavefront sensing and correction, high contrast integral field spectroscopy, detector flight readiness) has been advanced by the WFIRST Coronagraph Instrument (CGI) project over the past several years. Mission performance, mass, power, and cost estimates have also benefited from detailed work by the WFIRST CGI team. A Cost and Technical Evaluation (CATE) was performed in 2015 by the Aerospace Corporation. Today Exo-C is a backup option to WFIRST CGI. It could nominally be implemented within seven years from project start. This white paper summarizes the study final report, with updates on performance and technical readiness as of spring 2019.

Karl R. Stapelfeldt↗

NASA NTRSDate not supplied

Artificial Neural Networks to Predict Cognitive Impairment of Rodents Subjected to Space Radiation

INTRODUCTION We use artificial neural networks (ANNs) as an example machine learning (ML) tool to predict the cognitive performance impairment of rats induced by irradiation. The experimental data in the analyses is attentional set-shifting (ATSET) test scores from a rodent model exposed to ≤15 cGy of individual galactic cosmic radiation (GCR) ions: 4He, 28Si, or 56Fe, expected for a Lunar or Mars mission [1]. This work investigates rats at a subject-based level and uses applied dose and performance scores taken before irradiation to predict whether a rat will be impaired when irradiated. The results of this study are significant to crewed space missions as they support the potential of predicting an astronaut’s impairment in a specific task before spaceflight through the implementation of appropriately trained ML tools. METHODS Data used in this work are scores from the ATSET, a multi-stage constrained cognitive flexibility test [2]. Our computational model utilizes the number of attempts to reach the criterion to pass a stage as a behavioral performance measure for rats. We use the post-irradiation scores, generate thresholds from cumulative distribution plots of non-irradiated rats, and calculate the percent of irradiated rats whose scores fall below the threshold to infer how each radiation type/dose affects a population. Rats scoring above the threshold are labeled impaired while the others are non-impaired. We then employ ANNs as a typical ML technique, and use each subject’s individual scores taken before radiation along with the applied dose, to predict their personal susceptibility to cognitive impairment due to space radiation exposure. RESULTS AND CONCLUSION A significant finding is the exhibition of a dose-dependent increasing probability of impairment for 1 to 10 cGy of 28Si or 56Fe in the simple discrimination (SD) stage of the ATSET, and for 1 to 10 cGy of 56Fe in the compound discrimination (CD) stage. On a subject-based level, implementing ML classifiers such as ANNs identifies rats that have a higher tendency for impairment after GCR exposure [1]. The receiver operating characteristic (ROC) and the precision-recall (PR) curves of the ML models show a better prediction of impairment when 56Fe is the ion in question in both SD (Figure 1) and CD stages. They, however, do not depict impairment due to 4He in SD (Figure 1) and 28Si in CD, suggesting no dose-dependent impairment response in these cases. In this work, “good” prediction pertains to “better-than-random-chance”, due to the limited sample size and the high inter- and intra-individual variabilities in response to brain stimulation paradigms, as applicable to both animals and humans. More behavioral tests and biomarkers should be investigated on the same subjects, to be fed to the ML models to capture the agents responsible for performance alterations of some individuals versus others.

machine learning↗

NASA NTRSDate not supplied

Machine Learning Models to Predict Cognitive Impairment of Rodents Subjected to Space Radiation

INTRODUCTION We use artificial neural networks (ANNs) as an example machine learning (ML) tool to predict the cognitive performance impairment of rats induced by irradiation. The experimental data in the analyses is attentional set-shifting (ATSET) test scores from a rodent model exposed to ≤15 cGy of individual galactic cosmic radiation (GCR) ions: 4He, 28Si, or 56Fe, expected for a Lunar or Mars mission [1]. This work investigates rats at a subject-based level and uses applied dose and performance scores taken before irradiation to predict whether a rat will be impaired when irradiated. The results of this study are significant to crewed space missions as they support the potential of predicting an astronaut’s impairment in a specific task before spaceflight through the implementation of appropriately trained ML tools. METHODS Data used in this work are scores from the ATSET, a multi-stage constrained cognitive flexibility test [2]. Our computational model utilizes the number of attempts to reach the criterion to pass a stage as a behavioral performance measure for rats. We use the post-irradiation scores, generate thresholds from cumulative distribution plots of non-irradiated rats, and calculate the percent of irradiated rats whose scores fall below the threshold to infer how each radiation type/dose affects a population. Rats scoring above the threshold are labeled impaired while the others are non-impaired. We then employ ANNs as a typical ML technique, and use each subject’s individual scores taken before radiation along with the applied dose, to predict their personal susceptibility to cognitive impairment due to space radiation exposure. RESULTS AND CONCLUSION A significant finding is the exhibition of a dose-dependent increasing probability of impairment for 1 to 10 cGy of 28Si or 56Fe in the simple discrimination (SD) stage of the ATSET, and for 1 to 10 cGy of 56Fe in the compound discrimination (CD) stage. On a subject-based level, implementing ML classifiers such as ANNs identifies rats that have a higher tendency for impairment after GCR exposure [1]. The receiver operating characteristic (ROC) and the precision-recall (PR) curves of the ML models show a better prediction of impairment when 56Fe is the ion in question in both SD (Figure 1) and CD stages. They, however, do not depict impairment due to 4He in SD (Figure 1) and 28Si in CD, suggesting no dose-dependent impairment response in these cases. In this work, “good” prediction pertains to “better-than-random-chance”, due to the limited sample size and the high inter- and intra-individual variabilities in response to brain stimulation paradigms, as applicable to both animals and humans. More behavioral tests and biomarkers should be investigated on the same subjects, to be fed to the ML models to capture the agents responsible for performance alterations of some individuals versus others.

machine learning↗

NASA NTRS2017

Shaped pupil coronagraph design improvements for the WFIRST Coronagraph Instrument

NASA's WFIRST Coronagraph Instrument (CGI) is planned to image and characterize exoplanets at high contrast. The CGI operating modes are the hybrid Lyot coronagraph for planet detection and inner debris disk imaging, a shaped pupil coronagraph for planet characterization, and another shaped pupil for outer disk imaging. Early CGI designs focused on overcoming the di raction of the large pupil obscurations. Now that those designs have been proven to work in the lab, the design emphasis has been on achieving higher throughput and lower sensitivities to jitter and polarization aberrations. Here we present those improvements and the integration of science yield modeling into the spectrographic shaped pupil design process.

Riggs, A J Eldorado↗

NASA NTRS2021

Machine Learning Models to Predict Cognitive Impairment of Rodents Subjected to Space Radiation

This research uses machine-learned computational analyses to predict the cognitive performance impairment of rats induced by irradiation. The experimental data in the analyses is from a rodent model exposed to ≤ 15 cGy of individual Galactic Cosmic Radiation (GCR) ions: 4He, 16O, 28Si, 48Ti, or 56Fe, expected for a Lunar or Mars mission. This work investigates rats at a subject-based level and uses performance scores taken before irradiation to predict impairment in Attentional Set-shifting (ATSET) data post-irradiation. Here, the worst performing rats of the control group define the impairment thresholds based on population analyses via cumulative distribution functions, leading to the labeling of impairment for each subject. A significant finding is the exhibition of a dose-dependent increasing probability of impairment for 1 to 10 cGy of 28Si or 56Fe in the Simple Discrimination (SD) stage of the ATSET, and for 1 to 10 cGy of 56Fe in the Compound Discrimination (CD) stage. On a subject-based level, implementing Machine Learning (ML) classifiers such as the Gaussian Naïve Bayes, Support Vector Machine, and Artificial Neural Networks identifies rats that have a higher tendency for impairment after GCR exposure. The algorithms employ the experimental prescreenperformance scores as multidimensional input features to predict each rodent’s susceptibility to cognitive impairment due to space radiation exposure. The receiver operating characteristic and the precision-recall curves of the ML models show a better prediction of impairment when 56Feis the ion in question in both SD and CD stages. They, however, do not depict impairment due to 4Hein SD and 28Siin CD, suggesting no dose-dependent impairment response in these cases. One key finding of our study is that prescreen performance scores can be used to predict the ATSET performance impairments. This result is significant to crewed space missions as it supports the potential of predicting an astronaut’s impairment in a specific task before spaceflight through the implementation of appropriately trained ML tools. Future research can focus on constructing ML ensemble methods to integrate the findings from the methodologies implemented in this study for morerobust predictionsof cognitive decrements due to space radiation exposure.

space radiation↗

NASA NTRS2022

Initial Laboratory Demonstration of Multi-Star Wavefront Control at the Occulting Mask Coronagraph Testbed

Online Abstract: A majority of Sun-like stars, such as the A and B components of Alpha Centauri, have at least one stellar companion that can introduce additional noise into the field of view of any high-contrast imaging instrument. Multi-Star Wavefront Control (MSWC) is a wavefront-control technique that removes stellar leakage from both stellar components, enabling direct imaging of planets in many binary star systems. We present the latest experimental and modeling results obtained with MSWC as part of the technology development effort focusing on demonstrations conducted on the Occulting Mask Coronagraph (OMC) testbed at JPL. OMC has a layout similar to the Roman Space Telescope coronagraph instrument (CGI), and we used a MSWC mask similar to the one that was contributed to the Roman CGI. Our results represent the first demonstrations of this technique on the OMC testbed, with the ultimate goal of demonstrating full MSWC with validated models at contrast levels relevant to Roman CGI. Technical Review Abstract: A majority of Sun-like stars have at least one stellar companion that can introduce additional noise into the field of view of any high-contrast imaging instrument, limiting the achievable contrast. These include high-quality target stars such as the A and B components of Alpha Centauri, our nearest stellar neighbor. Enabling direct imaging of binary stars has the potential to increase the scientific yield for coronagraphic instruments planned on NASA's future space missions including the Roman Space Telescope and the next IR/O/UV Flagship recommended by Astro2020. Multi-Star Wavefront Control (MSWC) is a wavefront-control technique that simultaneously removes the (mutually incoherent) stellar leakage from both stellar components, enabling direct imaging of planets in many binary star systems. MSWC is an algorithmic technique and can be used with existing wavefront control systems on coronagraphic instruments (as well as starshades if a deformable mirror is available in the optical path). We summarize the latest experimental and numerical results obtained with MSWC as part of the technology development effort to demonstrate compatibility with existing high-contrast imaging platforms for this technique. The Super-Nyquist regime of MSWC was tested in vacuum at JPL's High Contrast Imaging Testbed (HCIT) on the Decadal Survey Testbed (DST) reaching 8.6e-9 contrast in a 10% band. Recently, the Occulting Mask Coronagraph (OMC) testbed at JPL is being prepared for demonstrations of Multi-Star Wavefront Control. A shaped pupil mask similar to the contributed MSWC mask on the Roman Space Telescope's coronagraph instrument has been recently manufactured including matching Lyot and focal plane masks and being installed on the OMC testbed. The goal of this experiment is a demonstration of MSWC using validated models on a testbed configuration and at contrast levels relevant to the Roman coronagraphic instrument.

High-contrast imaging↗

NASA NTRSDate not supplied

Neurobehavioral Effects Of Five-Ion GCRSim Exposure In Male And Female Mice

Exposure to space galactic cosmic radiation is a principal consideration of spaceflight missions, and with upcoming missions to the Moon and Mars, it is increasingly imperative to elucidate the detrimental effects of space travel beyond the lower Earth orbit. Additionally, with the first female astronaut to soon travel to the Moon and beyond lower Earth orbit, there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Therefore, we investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy via Five-Ion Galactic Cosmic Ray Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. Both early (72hrs post exposure) and late (1-4 months post exposure) cognitive and behavioral deficits were investigated. In-cage behavior was analyzed as frequency/duration of digging, rearing, and grooming and nestlet building using a 5-stage Deacon score. Additionally, at NASA Ames, behavior tests included Catwalk (gait), Zero Maze (anxiety), Adhesive Removal (sensory motor), Novel Object Recognition and Barnes Maze (working memory). There were pronounced sex differences in both early and late time points. Females typically performed the tests better than males, specifically in nestlet building, gait and working memory, though males performed better at the sensory motor (adhesive removal) test. Dose effects were primarily observed at 50 cGy for both sexes, particularly with the Barnes Maze (working memory), where both males and females exposed to 50 cGy showed little to no improvement in test performance, though females again performed better than males. Currently, we are investigating the correlations between the observed behavior and cytokine levels in the plasma and brain. Future studies will continue to investigate cognitive consequences of galactic cosmic radiation in combination with other space-like environment stressors, including antigravity and social versus single housing.

Stephanie Puukila↗

NASA NTRSDate not supplied

Early And Late Neurobehavioral Effects Of Male And Female Mice Exposed To Five-Ion GCRSim

With upcoming missions to the Moon and beyond to Mars, it is increasingly imperative to elucidate the detrimental effects of space travel beyond the lower Earth orbit, particularly to galactic cosmic radiation. Additionally, with the first female astronaut to soon travel to the Moon there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Here, we investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy via Five-Ion Galactic Cosmic Ray Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. Both early (72hrs post exposure) and late (1-4 months post exposure) cognitive and behavioral deficits were investigated. Early analysis was performed by observing in-cage behavior including frequency/duration of digging, rearing, and grooming and nestlet building. Additionally, late effects were analyzed at NASA Ames via in-cage behavior as well as Catwalk (gait), Zero Maze (anxiety), Adhesive Removal (sensory motor), Novel Object Recognition and Barnes Maze (working memory). There were pronounced sex differences in both early and late time points. Females scored better than males in nestlet building, gait and working memory while males scored better at the sensory motor (adhesive removal) test. Dose effects were primarily observed at 50 cGy for both sexes, particularly with the Barnes Maze (working memory), where both males and females exposed to 50 cGy showed little to no improvement in test performance, though females again performed better than males. Currently, we are investigating the correlations between the observed behavior and cytokine levels in the plasma and brain. Future studies will continue to investigate cognitive consequences of galactic cosmic radiation in combination with other space-like environment stressors, including antigravity and social versus single housing.

S Puukila↗

NASA NTRSDate not supplied

Neurobehavioral Effects Of Five-Ion GCRSim Exposure In Male And Female Mice

Exposure to space galactic cosmic radiation is a principal consideration of spaceflight missions, and with upcoming missions to the Moon and Mars, it is increasingly imperative to elucidate the detrimental effects of space travel beyond the lower Earth orbit. Additionally, with the first female astronaut to soon travel to the Moon and beyond lower Earth orbit, there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Therefore, we investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy via Five-Ion Galactic Cosmic Ray Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. Both early (72hrs post exposure) and late (1-4 months post exposure) cognitive and behavioral deficits were investigated. In-cage behavior was analyzed as frequency/duration of digging, rearing, and grooming and nestlet building using a 5-stage Deacon score. Additionally, at NASA Ames, behavior tests included Catwalk (gait), Zero Maze (anxiety), Adhesive Removal (sensory motor), Novel Object Recognition and Barnes Maze (working memory). There were pronounced sex differences in both early and late time points. Females typically performed the tests better than males, specifically in nestlet building, gait and working memory, though males performed better at the sensory motor (adhesive removal) test. Dose effects were primarily observed at 50 cGy for both sexes, particularly with the Barnes Maze (working memory), where both males and females exposed to 50 cGy showed little to no improvement in test performance, though females again performed better than males. Currently, we are investigating the correlations between the observed behavior and cytokine levels in the plasma and brain. Future studies will continue to investigate cognitive consequences of galactic cosmic radiation in combination with other space-like environment stressors, including antigravity and social versus single housing.

S. Puukila↗

NASA NTRSDate not supplied

Neurobiological Outcomes of Mice Exposed to Combined Spaceflight Stressors

As NASA plans for exploration beyond Low-Earth Orbit, it is imperative to understand how deep spaceflight stressors impact human physiology. Deep space exposes crew members to multiple NASA-defined risks, including altered gravity, ionizing radiation, and social isolation. While the effects of individual stressors have been studied, there are still gaps in our understanding of their combined effects. In this study, we utilized the simulated five-ion galactic cosmic radiation (GCR) and isolation to assess the combinatorial effects of space stressors on the central nervous system (CNS) in mice. Our study captures sexually dimorphic responses by quantifying CNS outcomes in crewage-matched male and female mice. We assessed CNS responses in mice exposed to four days of isolation, followed by three different dosage of acute radiation exposure (5 cGy, 15 cGy, and 50 cGy 5-ion GCRsim). Comprehensive hippocampal cytokine biomarker analyses were conducted in both males and females at two weeks post-irradiation (intermediate cohort) and 124 days post-irradiation (delayed cohort). Proteomics on hippocampal lysates were conducted in the delayed cohort. Our results provide evidence for sex-specific differentially regulated hippocampal cytokines and proteomic profiles. Immunohistochemical analysis of the mice brain from intermediate and delayed cohorts is currently underway for multiple protein markers, including microglial activation, astrocytes, and dopaminergic neuronal population, among others. This project closely aligns with NASA’s efforts to characterize sex-specific risks associated with deep space exploration. We anticipate the results from this project will aid in our understanding of spaceflight stressors to ensure crew health and performance.

spaceflight↗

DOE OSTI2024

Non-DNA radiosensitive targets that initiate persistent behavioral deficits in rats exposed to space radiation

Predicting future CNS risks for astronauts during deep-space missions will rely substantially on ground-based rodent data with space-relevant ions and behaviors. For rats, the accumulated evidence indicates that less densely ionizing radiation, such as 4 He and 12 C ions, induce behavior deficits at lower doses than densely ionizing ions, such as 48 Ti and 56 Fe. However, this observation conflicts with standard somatic radiobiology, in which densely ionizing ions are generally more effective than less densely ionizing ions, and where the DNA/nucleus is the accepted target for radiation-induced tumorigenesis, cytogenetic aberrations, genetic mutations, and reproductive cell death. To gain deeper insight into the subcellular nature of the radiation targets for behavior risks, we compared the effects of dose, fluence, and linear energy transfer (LET) of 4 He and 56 Fe particles using existing datasets for four distinct behavioral outcomes in rats: elevated plus maze (EPM-anxiety), novel object recognition (NOR-memory), operant responding (OR-response to environmental stimuli), and attentional set-shifting (ATSET-cognitive flexibility). We confirmed that less densely ionizing particles (except protons) showed ~100-fold lower threshold doses than densely ionizing particles for behavioral deficits (0.1–1 cGy for 4 He vs. 15–100 cGy for 56 Fe). However, when analyzed by fluence the behavioral responses converged, indicating that 4 He and 56 Fe were equally effective on a per-track basis. When analyzed by LET, there were ~100-fold differences in the LET for maximum effectiveness for behavioral deficits and DNA endpoints (~1 vs ~100 keV/μm, respectively). These unique features of radiation-induced behavioral deficits (high sensitivity to particles in the 1-keV/μm range, insensitivity to protons in the 0.2 keV/μm range, and isofluence dependence for particles with LET>1 keV/μm) provide evidence in support of a new hypothesis of sub-micron sized radiosensitive targets for behavioral effects consistent with the thickness of plasma membranes and/or small subcellular structures, smaller than a whole synapse. Like our behavior findings, mouse immature oocyte killing which is known to have a plasma membrane target was also better explained by fluence, rather than dose. In contrast, fluence analyses for DNA/nuclear endpoints in somatic cells (e.g., tumor induction, chromosome aberrations) showed opposite results, suggesting that behavior targets are not DNA. Our findings raise questions regarding the identity of subcellular targets and the multi-cellular functional unit for behavior risks, low-dose susceptibility, and generalizability from rat to other species and astronauts.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

DOE OSTI2021

Evaluation of Histone Deacetylase Inhibitors as Radiosensitizers for Proton and Light Ion Radiotherapy

Significant opportunities remain for pharmacologically enhancing the clinical effectiveness of proton and carbon ion-based radiotherapies to achieve both tumor cell radiosensitization and normal tissue radioprotection. We investigated whether pretreatment with the hydroxamate-based histone deacetylase inhibitors (HDACi) SAHA (vorinostat), M344, and PTACH impacts radiation-induced DNA double-strand break (DSB) induction and repair, cell killing, and transformation (acquisition of anchorage-independent growth in soft agar) in human normal and tumor cell lines following gamma ray and light ion irradiation. Treatment of normal NFF28 primary fibroblasts and U2OS osteosarcoma, A549 lung carcinoma, and U87MG glioma cells with 5–10 µM HDACi concentrations 18 h prior to cesium-137 gamma irradiation resulted in radiosensitization measured by clonogenic survival assays and increased levels of colocalized gamma-H2AX/53BP1 foci induction. We similarly tested these HDACi following irradiation with 200 MeV protons, 290 MeV/n carbon ions, and 350 MeV/n oxygen ions delivered in the Bragg plateau region. Unlike uniform gamma ray radiosensitization, effects of HDACi pretreatment were unexpectedly cell type and ion species-dependent with C-12 and O-16 ion irradiations showing enhanced G0/G1-phase fibroblast survival (radioprotection) and in some cases reduced or absent tumor cell radiosensitization. DSB-associated foci levels were similar for proton-irradiated DMSO control and SAHA-treated fibroblast cultures, while lower levels of induced foci were observed in SAHA-pretreated C-12 ion-irradiated fibroblasts. Fibroblast transformation frequencies measured for all radiation types were generally LET-dependent and lowest following proton irradiation; however, both gamma and proton exposures showed hyperlinear transformation induction at low doses (≤25 cGy). HDACi pretreatments led to overall lower transformation frequencies at low doses for all radiation types except O-16 ions but generally led to higher transformation frequencies at higher doses (>50 cGy). The results of these in vitro studies cast doubt on the clinical efficacy of using HDACi as radiosensitizers for light ion-based hadron radiotherapy given the mixed results on their radiosensitization effectiveness and related possibility of increased second cancer induction.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Development of a Machine-Learned Cruise Guide Indicator for Rotorcraft

This paper presents a machine-learned virtual cruise guide indicator (vCGI) for Chinook helicopters. Two temporal neural networks were trained and evaluated on measured data from 55 flight tests, one for the fore rotor and another for the aft rotor, to predict a vCGI value, which protects 23 components from fatigue damage during steady-state conditions. Three different classes of machine learning architectures were evaluated for prediction of the vCGI from time sequences: a temporal convolutional neural network with 1D dilated causal convolutions, a long short-term memory recurrent neural network, and an attention-based transformer architecture. The final average model accuracy on unseen flight data is currently greater than 93% for CGI values which could result in fatigue damage and 90% for normal operation CGI values. Model accuracy was improved through a series of advancements in:(1) selection of optimal training data using temporal collective variables and unsupervised learning, (2) dataset augmentation with maximum-entropy temporal collective variables, and (3) implementation of a mixture-of-experts classification- regression approach using an adversarial classification approach to assign maneuver labels. The results are presented for each advancement in model development along with lessons learned in training machine learning models on real- world, time-dependent rotorcraft data.

Boyer, Mathew↗

NASA NTRS1980

Time delays in flight simulator visual displays

It is pointed out that the effects of delays of less than 100 msec in visual displays on pilot dynamic response and system performance are of particular interest at this time because improvements in the latest computer-generated imagery (CGI) systems are expected to reduce CGI displays delays to this range. Attention is given to data which quantify the effects of display delays in the range of 0-100 msec on system stability and performance, and pilot dynamic response for a particular choice of aircraft dynamics, display, controller, and task. The conventional control system design methods are reviewed, the pilot response data presented, and data for long delays, all suggest lead filter compensation of display delay. Pilot-aircraft system crossover frequency information guides compensation filter specification.

Crane, D. F.↗

NASA NTRS1985

Piloted simulation of one-on-one helicopter air combat at NOE flight levels

A piloted simulation designed to examine the effects of terrain proximity and control system design on helicopter performance during one-on-one air combat maneuvering (ACM) is discussed. The NASA Ames vertical motion simulator (VMS) and the computer generated imagery (CGI) systems were modified to allow two aircraft to be independently piloted on a single CGI data base. Engagements were begun with the blue aircraft already in a tail-chase position behind the red, and also with the two aircraft originating from positions unknown to each other. Maneuvering was very aggressive and safety requirements for minimum altitude, separation, and maximum bank angles typical of flight test were not used. Results indicate that the presence of terrain features adds an order of complexiaty to the task performed over clear air ACM and that mix of attitude and rate command-type stability and control augmentation system (SCAS) design may be desirable. The simulation system design, the flight paths flown, and the tactics used were compared favorably by the evaluation pilots to actual flight test experiments.

Lewis, M. S.↗