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NASA NTRS2002

A Plasma Rocket Demonstration on the International Space Station

The Advanced Space Propulsion Laboratory at the NASA Johnson Space Center has been engaged in the development of a magneto-plasma rocket for several years. This type of rocket could be used in the future to propel interplanetary spacecraft. One feature of this concept is the ability to vary its specific impulse so that it can be operated in a mode that maximizes propellant efficiency or a mode that maximizes thrust. For this reason the system is called the Variable Specific Impulse Magneto-plasma Rocket or VASIMR. This ability to vary specific impulse and thrust will allow for optimum low thrust interplanetary trajectories and results in shorter trip times than is possible with fixed specific impulse systems while preserving adequate payload margins. In the development of the VASIMR technology, a series of ground-based experiments and space demonstrations are envisioned. A ground-based experiment of a low-power VASIMR prototype rocket is currently underway at the Advanced Space Propulsion Laboratory. The next step is a proposal to build and fly a 25-kilowatt VASIMR rocket as an external payload on the International Space Station. This experiment will provide an opportunity to demonstrate the performance of the rocket in space and measure the induced environment. The experiment will also utilize the space station for its intended purpose as a laboratory with vacuum conditions that cannot be matched by any laboratory on Earth. The VASIMR experiment will also blaze the trail for the wider application of advanced electric propulsion on the space station. An electric propulsion system like VASIMR, if provided with sufficient electrical power, could provide continuous drag force compensation for the space station. Drag compensation would eliminate the need for reboosting the station, an operation that will consume about 60 metric tons of propellant in a ten-year period. In contrast, an electric propulsion system would require very little propellant. In fact, a system like VASIMR can use waste hydrogen from the station's life support system as its propellant. This waste hydrogen is otherwise dumped overboard. Continuous drag compensation would also improve the microgravity conditions on the station. So electric propulsion can reduce propellant delivery requirements and thereby increase available payload capacity and at the same time improve the conditions for scientific research.

Petro, Andrew J.↗

DOE OSTI2022

Modernization efforts for the R -Matrix code SAMMY [Abstract]

The R-Matrix code SAMMY is a widely used nuclear data evaluation code focused on the resolved range, which includes corrections for experimental effects. The code is still mostly written in Fortran 77, and uses a memory management system suitable for the time of its initial writing (1984). A modernization effort is under way to bring the code in-line with modern software development practices. A continuous-integration testing framework was added, automating the large existing set of test cases. It is run on every commit. The memory management was updated to current standard practices suitable for modern software analysis tools. The code can be obtained from https://code.ornl.gov/RNSD/SAMMY. The resonance parameters and covariance information are now stored in C++ objects shared by SAMMY and AMPX, the processing code that generates nuclear data libraries for SCALE. This allows for easier maintenance and access to the resonance parameters inside and outside of SAMMY. This feature is already used by accessing and changing parameters in memory in the Bayesian Monte Carlo Evaluation Framework for Cross Sections Nuclear Data and Integral Benchmark Experiments project, Further plans include the switch to the ENDF reading and writing routines in AMPX, as these routines are more robust, easier to maintain, and support more features. Of note here is support for the new GNDS format. Previously it wasn’t easy to share the full covariance matrix for evaluations containing more than one isotope due to limitations on the ENDF format; this is now supported in GNDS. The data are currently available in a binary SAMMY format and can be exported to GNDS to make them more widely available and sharable. The next step will be to use the same resonance processing code at 0K in AMPX and SAMMY as one of the available Reich-Moore R-Matrix formalism. The first step toward this goal is to isolate the reconstruction into a module that takes resonance parameters as its input and does not depend on SAMMY global parameters. This goal has been achieved and it should now be possible to more easily change the resonance formalism and add enhancements as the Phenomenological R-Matrix parameterization of direct, doorway, and compound nuclear reactions discussed elsewhere on this conference. This concerted modernization and enhancement effort provides multiple advantages to the nuclear data community. It will allow parameter optimization using enhanced formalisms, including experimental effects, that better match complex experimental data. Then those evaluated parameters can immediately be passed off to AMPX to be reconstructed with the exact same cross section model and be put into a data library for subsequent testing using SCALE and the Valid Benchmark suite or other suitable benchmark suites.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

NASA NTRSDate not supplied

Orion Artemis I As Flown MMOD Analysis

Introduction The Lockheed Martin Orion spacecraft conducted the Artemis I flight around the Moon from November 16 through December 11, 2022. After the flight, an engineer from the NASA Johnson Space Center (JSC) Hypervelocity Impact Technology (HVIT) Group performed a Micrometeoroid and Orbital Debris MMOD analysis using the Bumper 3 risk assessment tool to predict the number of small impacts that would likely have occurred during the mission. Separately, a team from the same group inspected the Orion capsule for hypervelocity impact damage features. The results of the inspection were compared to those of the analysis to aid in improving the analysis, including the environment models. Scope of Work The spacecraft geometry model was created by Lockheed Martin during construction of the Artemis I Orion vehicle based on Computer Aided Design (CAD) models of the vehicle. New hypervelocity impact testing was performed to verify Ballistic Limit Equations (BLEs) used in the analysis to link impactor size and damage to the Thermal Protection System (TPS). The exact trajectory flown was recorded during the flight, including vehicle attitude. This data was used in conjunction with the ORDEM 3.2 and MEM 3 environment modeling tools to create models of particle flux impacting the spacecraft throughout the mission. Meteoroid shower forecast information was also included to account for additional particle flux associated with meteoroid showers. Inspection of the Orion capsule included the Backshell thermal tiles and the tape covering it, windows, fabric thermal materials, and small areas of other materials. Potential MMOD damage found was characterized using various techniques, including optical microscopy, computed tomography scanning, and X-ray spectroscopy. Findings The number of craters found in the Backshell tile, and their size distribution, matches well with the Bumper analysis prediction. Tape, window, and other material impacts recorded similarly align to Bumper analysis predictions. Conclusions and Recommendations This comparison of analysis with inspection of the hardware provides valuable insight into the MMOD environment and how accurately analysis tools assess the impact risk to spacecraft. As this was the first large, non-ablative returned surface from a lunar mission, this analysis extends the MMOD community’s insight beyond low Earth orbit into cis-lunar space.

MMOD↗

NASA NTRSDate not supplied

Orion Artemis I As Flown MMOD Analysis

MMOD↗

DOE OSTI2025

Auriga Streams – I: disrupting satellites surrounding Milky Way-mass haloes at multiple resolutions

In a hierarchically formed Universe, galaxies accrete smaller systems that tidally disrupt as they evolve in the host’s potential. We present a complete catalogue of disrupting galaxies accreted onto Milky Way-mass haloes from the Auriga suite of cosmological magnetohydrodynamic zoom-in simulations. We classify accretion events as intact satellites, stellar streams, or phase-mixed systems based on automated criteria calibrated to a visually classified sample, and match accretions to their counterparts in haloes re-simulated at higher resolution. Most satellites at the present day have lost substantial amounts of stellar mass – 67 per cent have $f_\text{bound} < 0.97$ (our threshold of lost stellar mass to no longer be considered intact), while 53 per cent satisfy a more stringent $f_\text{bound} < 0.8$. Streams typically outnumber intact systems, contribute a smaller fraction of overall accreted stars, and are substantial contributors at intermediate distances from the host centre ($\sim$0.1 to $\sim 0.7R_\text{200m}$, or $\sim$35 to $\sim$250 kpc for the Milky Way). We also identify accretion events that disrupt to form streams around massive intact satellites instead of the main host. Streams are more likely than intact or phase-mixed systems to have experienced pre-processing, suggesting this mechanism is important for setting disruption rates around Milky Way-mass haloes. All of these results are preserved across different simulation resolutions, though we do find some hints that satellites disrupt more readily at lower resolution. The Auriga haloes suggest that disrupting satellites surrounding Milky Way-mass galaxies are the norm and that a wealth of tidal features waits to be uncovered in upcoming surveys.

galaxies: haloes↗

NASA NTRS1997

Effects of FU Orionis Outbursts on Protoplanetary Disks

In the early stages of work under this grant, we developed simulations to match the light curves of the three best studied systems: FU Ori, V1515 Cyg, & V1057 Cyg (Bell et al. 1995). We compared the details of model results to observations to test the validity of the thermal ionization instability model for outburst. In this paper, we were able to answer several of the key objections to the accretion disk outburst model for the FU Orionis phenomenon (eg. Herbig 1989). The declines in line width and reddening observed in V1057 Cyg following peak light had been used as arguments against the disk instability model. We showed these effects to be natural consequences of the slow outward progression and limited radial excursion of the ionization front during outburst. By the end of the grant period, we had begun combining the inner and outer disk models to derive the radiation expected in the planet forming region of the disk. A crucial step in this was the development of a radiative transfer model of the complete inner and outer disk system (Turner, Bodenheimer, & Bell 1997). In this work, wavelength dependent opacities were used to synthesize images and spectral energy distributions of FU Ori objects. New detailed opacities provided by Alexander (1995) allowed the resolution of coarse features such as silicate emission lines. Data for the fits were taken from the time dependent simulations in Bell et al. (1995) to which was added the effect of disk to disk or "self"-reprocessing which accounts for the illumination of the outer disk by the inner disk (Bell 1998). Through the course of work on this grant we have made considerable progress in computing detailed models of both the active outburst region of the disk and the outer quiescent disk. We have begun an investigation into the effects of a cocooning envelope. Direct comparisons with observations lend confidence that the basic underlying assumptions of the outburst model are reasonable. We are now ready to build upon these results to investigate the effects of outbursts on the central star and on the accumulation of small particles in the planet-forming regions.

Bodenheimer, Peter↗

NASA NTRS2018

More Efficient Precipitation Rate Data Acquisition with the STORM Swath-Based Analysis Tool

A multitude of locations exist for acquiring satellite-derived precipitation rate data. Because the volume of data exceeds what can reasonably be analyzed manually, online tools have been developed to help researchers make more informed data acquisition decisions. Some interfaces provide sample images generated from prioritized variables to enable efficient visual inspection, while others include the ability to subset geographically to reduce the volume of the data to the area of interest. Building upon such value-added services is the STORM (the NASA Precipitation Processing System (PPS) data product ordering system) Swath-Based Analysis Tool (https://storm.pps.eosdis.nasa.gov/storm/Analysis.jsp). With it, users can compare overflights of multiple precipitation satellites simultaneously and from this make determinations about which swaths will best serve their research. They can preview these overflights with two distinct visualization tools. Finally, they can then download geographically subset swaths that have precipitation rate characteristics matching their research needs. A user starts by making up to six selections. They then select their date range of interest going back to 1997. Finally, they select a geographical region either by inputting latitude-longitude corners of a rectangle or drawing that rectangle on an interactive map. The system processes each file, determining aggregate statistics about the precipitation rates within the selected region as observed by each instrument. These statistical values are added to a time series graph as a "time remaining" counter is continuously updated. The chart is fully interactive, with detailed values displayed upon mouseover, and numerous options available upon clicking each point. Since the user is likely to need the relevant files for their own research, they can generate an order from their request. All files are geographically subset to the region of interest, and the user can use the statistical values to limit which files are added to the order. This flexibility helps to ensure researchers are only downloading the files they need for their work, making for a more efficient process both from a time-consumption and a storage perspective. This paper will introduce the Swath-Based Analysis Tool and explore its numerous features. It will discuss several use cases for precipitation scientists.

remote sensing↗

DOE OSTI2026

Plutonium migration and phase evolution in irradiated U-Pu-Zr metallic fuels: An integrated EPMA-SEM-TEM study

Constituent redistribution is a defining feature of irradiated U-Pu-Zr metallic fuels, yet its mechanisms and effects on fuel performance are not sufficiently resolved to guide model development. Although decades of irradiation testing have established broad trends, a true mechanistic understanding of constituent redistribution has not been achieved. Here, in this study, we use electron probe microanalysis (EPMA), scanning electron microscopy (SEM), and transmission electron microscopy-based (TEM) selective area electron diffraction (SAED) on a EBR-II irradiated U-19 wt.% Pu-6 wt.% Zr fuel pin cross-section to correlate the composition, porosity, and crystallographic phases formed after irradiation. Constituent redistribution is thought to consist of three distinct zones, in which uranium and zirconium migrate while plutonium remains relatively unchanged. Our EPMA results resolve eight distinct compositional regions, and more importantly, show that plutonium redistributes alongside zirconium, contrary to historical assumptions. The distribution of fission products was highly asymmetric with a few large lanthanide precipitates observed at isolated sites on the pin periphery instead of a uniform distribution of smaller precipitates around the periphery. Using thermodynamic data from TAF-ID and the measured EPMA compositions, matrix phase fractions were predicted across the fuel radius. Phase predictions based on composition did not match TEM/SAED results, which revealed a much higher fraction of α−U phase than would be expected if phases were retained from reactor temperatures. These findings highlight the need for expanded SAED phase identification to capture post-irradiation and storage effects, as well as rigorous uncertainty quantification in fuel performance and phase diagram modeling to better constrain predictions from compositional data.

11 - NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

DOE OSTI2020

Three-dimensional super line-localization in low signal-to-noise microscope images via prior-apprised unsupervised learning (PAUL)

Biological processes such as processive enzyme turnover and intracellular cargo tracking involve the dynamic motion of a small "article" along a curvilinear biopolymer track. To understand these processes that occur across multiple length and time scales, one must acquire both the trajectory of the particle and the position of the track along which it moves, possibly by combining high-resolution single-particle tracking with conventional microscopy. Yet, usually there is a significant resolution mismatch between these modalities: while the tracked particle is localized with a precision of 10 nm, the image of the surroundings is limited by optical difraction, with 200 nm lateral and 500 nm axial resolutions. Compared to the particle's trajectory, the surrounding curvilinear structure appears as a blurred and noisy image. This disparity in the spatial resolutions of the particle trajectory and the surrounding curvilinear structure image makes data reconstruction, as well as interpretation, particularly challenging. Analysis is further complicated when the curvilinear structures are oriented arbitrarily in 3D space. Here, we present a prior-apprised unsupervised learning (PAUL) approach to extract information from 3D images where the underlying features resemble a curved line such as a filament or microtubule. This three-stage framework starts with a Hessian-based feature enhancement, which is followed by feature registration, where local line segments are detected on repetitively sampled subimage tiles. In the final stage, statistical learning, segments are clustered based on their geometric relationships. Principal curves are then approximated from each segment group via statistical tools including principal component analysis, bootstrap and kernel transformation. This procedure is characterized on simulated images, where sub-voxel medium deviations from true curves have been achieved. The 3D PAUL approach has also been implemented for successful line localization in experimental 3D images of gold nanowires obtained using a multifocal microscope. Lastly, this work not only bridges the resolution gap between two microscopy modalities, but also allows us to conduct 3D super line-localization imaging experiments, without using super-resolution techniques.

42 ENGINEERING↗

NASA NTRSDate not supplied

An Approach for Practical Grid-Resolved Roughness Aerothermodynamic Simulations for Woven Heatshield Surfaces

An approach for simulating the aerothermal environment over a patterned roughness surface within an otherwise axisymmetric flow is developed. The patterned roughness is simplified into a sinusoidal shape that captures the basic features of a charred 3MDCP ablator. Two orientations of this pattern, which are equally flight relevant due to the forming process, enable periodic boundary conditions along the edges of a grid spanning a single roughness element. This simplified three-dimensional grid represents the minimum problem size for a patterned roughness simulation, which enables computationally efficient grid-resolved roughness simulations. This approach is validated by simulating the Langley Mach 6 measurements made on a similar sinusoidal surface, which results in convective heating within 5% of the experimental data. Applying this approach to Mars Sample Return (MSR) Earth Entry System (EES) flight cases, considering simulations with both 11 species air and 30 species air with ablation products, results in heating augmentation that is slightly lower than the widely-used Dahm correlation approach, with the difference being dependent on pattern orientation. This result provides the only insight into the behavior of the roughness augmentation at the high temperature reacting flow conditions present for EES flight cases, which are not captured by available ground test measurements. For shear augmentation, the simulations revealed that the surface-parallel pressure component is dominant. For arc-jet tests targeted to flight values for shear, the higher arc-jet pressures required to match flight values for shear result in up to a 400% increase in the rough wall shear value, which is not captured by the Dahm correlation. This indicates that, to avoid significant over-testing, grid-resolved roughness simulations are required to determine arc-jet conditions that produce flight shear levels in rough-wall scenarios.

Christopher O Johnston↗

NASA NTRS2024

Harnessing Collaborative Learning Automata to Guide Multi-objective Optimization based Inverse Analysis for Structural Damage Identification

Structural damage identification based on physical models is often transformed into an optimization problem that minimizes the difference between measurement information of structure being monitored and the model prediction in the parametric space. However, the objective function in this context often exhibits multimodality, involving high-dimensional variables due to the reliance on finite element models for damage identification. These features pose challenges to optimization algorithms, where entrapment in local solutions can lead to false positives and false negatives in damage identification. In this research, we propose a reinforcement learning based multi-swarm optimizer to tackle such challenges in pursuit of a small yet diverse solution set that can capture the true damage scenario as one of the solutions. The proposed method leverages the flexibility of the particle swarm optimizer and incorporates novel strategies of metaheuristics to realize targeted improvement. To enable the particle swarm to adaptively select the appropriate search strategy based on the current environment, we adopt the learning automata technique, which sidesteps the need for reward strategy selection that is usually ad hoc at each step of the search. The integration harnesses the automatic learning and self-adaptation capabilities of learning automata, enabling the particles to navigate based on environmental signals. This leads to accumulated probabilities tied to advantageous movements, fostering an adaptive exploration of particles in the search space. The proposed approach is first validated through implementing into benchmark test cases with comparisons. It is then applied to structural damage identification with piezoelectric admittance experimental signals. `The results highlight the capability of the algorithm to identify a small solution set with high accuracy to match the actual damage scenario.

Yang Zhang↗

NASA NTRS2014

The Nustar Spectrum of Mrk 335: Extreme Relativistic Effects Within Two Gravitational Radii of the Event Horizon?

We present 3-50 keV NuSTAR observations of the active galactic nuclei Mrk 335 in a very low flux state. The spectrum is dominated by very strong features at the energies of the iron line at 5-7 keV and Compton hump from 10-30 keV. The source is variable during the observation, with the variability concentrated at low energies, which suggesting either a relativistic reflection or a variable absorption scenario. In this work, we focus on the reflection interpretation, making use of new relativistic reflection models that self consistently calculate the reflection fraction, relativistic blurring and angle-dependent reflection spectrum for different coronal heights to model the spectra. We find that the spectra can be well fitted with relativistic reflection, and that the lowest flux state spectrum is described by reflection alone, suggesting the effects of extreme light-bending occurring within approx. 2 gravitational radii (RG) of the event horizon. The reflection fraction decreases sharply with increasing flux, consistent with a point source moving up to above 10 RG as the source brightens. We constrain the spin parameter to greater than 0.9 at the 3(sigma) confidence level. By adding a spin-dependent upper limit on the reflection fraction to our models, we demonstrate that this can be a powerful way of constraining the spin parameter, particularly in reflection dominated states. We also calculate a detailed emissivity profile for the iron line, and find that it closely matches theoretical predictions for a compact source within a few RG of the black hole.

galaxies: active aEuro" galaxies: individual: Mrk ↗

DOE OSTI2021

A data-driven approach to modeling cancer cell mechanics during microcirculatory transport

In order to understand the effect of cellular level features on the transport of circulating cancer cells in the microcirculation, there has been an increasing reliance on high-resolution in silico models. Accurate simulation of cancer cells flowing with blood cells requires resolving cellular-scale interactions in 3D, which is a significant computational undertaking warranting a cancer cell model that is both computationally efficient yet sufficiently complex to capture relevant behavior. Given that the characteristics of metastatic spread are known to depend on cancer type, it is crucial to account for mechanistic behavior representative of a specific cancer’s cells. To address this gap, in the present work we develop and validate a means by which an efficient and popular membrane model-based approach can be used to simulate deformable cancer cells and reproduce experimental data from specific cell lines. Here, cells are modeled using the immersed boundary method (IBM) within a lattice Boltzmann method (LBM) fluid solver, and the finite element method (FEM) is used to model cell membrane resistance to deformation. Through detailed comparisons with experiments, we (i) validate this model to represent cancer cells undergoing large deformation, (ii) outline a systematic approach to parameterize different cell lines to optimally fit experimental data over a range of deformations, and (iii) provide new insight into nucleated vs. non-nucleated cell models and their ability to match experiments. While many works have used the membrane-model based method employed here to model generic cancer cells, no quantitative comparisons with experiments exist in the literature for specific cell lines undergoing large deformation. Here, we describe a phenomenological, data-driven approach that can not only yield good agreement for large deformations, but explicitly detail how it can be used to represent different cancer cell lines. This model is readily incorporated into cell-resolved hemodynamic transport simulations, and thus offers significant potential to complement experiments towards providing new insights into various aspects of cancer progression.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRSDate not supplied

rHealth One Demonstration Aboard ISS: A Microfluidic Bioanalyzer Based on Sheath/Hydrodynamic Focusing Flow Cytometry

The Exploration Medical Capability (ExMC) element aims to provide astronauts with the means for their own health monitoring, diagnosis, and treatment during exploration missions. As space flight ventures further from earth, the need for autonomous medical care increases under greater constraints on size, mass, and resources. One pillar for diagnosis that crew would be separated from is laboratory analysis. Even now on ISS, blood samples must be collected and returned to earth for testing. In response, ExMC is assessing how assays for hematology, bone health, radiation exposure etc. could be addressed through commercial-off-the-shelf (COTS) and Small Business Innovation Research (SBIR) funded bioanalyzers that are miniaturizing lab technology. Since missions will reach distances where there are no timely replacements, validation on the International Space Station (ISS) is a necessary part of that assessment. In partnership with NASA Johnson Space Center (JSC) Immunology Lab and the Research Operations and Integration (ROI) element, ExMC conducted a technology demonstration on ISS of the rHEALTH ONE, a flow cytometry based bioanalyzer, to assess future devices based on this design. In flow cytometry, there are predominantly three ways to focus the cells (or particles) into a single file stream: hydrodynamic focusing, microcapillary, and acoustic focusing. The rHEALTH ONE utilizes the commercial standard, sheath-based hydrodynamic focusing. rHEALTH itself represents both a company and a suite of medical tools NASA has funded through SBIR grants towards the development of a promising diagnosis instrument for exploration missions. rHEALTH ONE is the interim version of the technology, functional as a benchtop analyzer and test bed for the next generation of rHEALTH in development. Several modifications were made to the rHEALTH ONE analyzer for operation in microgravity. For function, fluid management was key. A sheath-based analyzer uses sheath fluid to flow the sample, cleaning fluid to prevent biological contamination, and a reservoir to collect the liquid waste. The rHEALTH ONE analyzer uses bottles dependent on gravity to separate the air and liquid pathways and keep the liquids contained. It uses only 1 psig of air pressure to directly push the liquid through the device, requiring little-to-no resistance at inlet and outlet. A microtubing assembly with self-sealing luer connectors was designed – featuring 0.014 mm thick durable medical balloons to hold water inside the supply bottles – to create safe containment and easy access for the crew while maintaining the analyzer’s function. For safety, copper tape was added to the interior of the plastic housing to reduce electromagnetic interference, fluid and electrical connections were secured against vibration and leaks, and gaps were further sealed to ensure containment of the optical block and lasers. Water as the sheath and cleaning fluid and TOX 0 samples were used to reduce the biohazard risk to the crew. In May 2022, European Space Agency astronaut Samantha Cristoforetti demonstrated the rHEALTH ONE aboard ISS for its sample loading, flow cytometry, and data collection capability in microgravity. The JSC Immunology Lab provided flow cytometry expertise, designed the sample test protocol, and manufactured and benchmarked the flight samples on a ‘gold-standard’ flow cytometer. The analyzer was primed with water, purged of air, and four calibration solutions of polystyrene microparticles were tested to characterize its performance. Tightly controlled procedures and excellent execution prevented air bubble interference during air/water separation, fluid transfer, sample mixing and loading. Data showed a slight increase in signal noise on 3 of 5 channels and an anomaly of fluorophores migrating in one sample (confirmed by JSC post-flight). Flight results correctly detected the change in sample, matched the analyzer’s ground performance, and were consistent with the gold-standard’s ground results. Although areas were noted for improvement, these outcomes signified complete mission success.

R. S. Miller↗

DOE OSTI2026

Identification of drug repurposing candidates for amyotrophic lateral sclerosis using electronic health records: a retrospective cohort study

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a life expectancy of only 3–5 years and few approved treatments. To identify drug repurposing candidates for the treatment of ALS, we analysed the electronic health records (EHRs) of a large cohort of military veterans with ALS. We analysed the EHRs of individuals in the US Veterans Health Administration (VHA) database who were diagnosed with ALS between Jan 1, 2009 and Dec 31, 2019 to assess medication effects. Individuals without recorded prescriptions after the date of diagnosis were excluded. Two sets of criteria were applied to ascertain exposure. Exposure criteria A were met if the dispense date or the end date of the medication was within 12 months of ALS diagnosis and the end date was at least 6 months after the dispense date. Exposure criteria B were met if there were at least two dispenses within 6 months before diagnosis and 12 months after diagnosis. Propensity score-matched control groups were generated on the basis of confounders included in the EHR, with methodology of potential outcomes used to infer treatment effects. The primary outcome was death. A standard Cox proportional hazards analysis was done to assess association with survival. Survival was defined as the time from diagnosis date recorded in the EHR to death reported in the Department for Veterans Affairs Vital Status File. Follow-up survival time was censored on Dec 31, 2020, for those alive on this date. Downstream protein targets of drugs with clinically significant effects were analysed using the protein–protein interaction networks-based algorithm PathFX. The EHRs of 11 003 individuals with ALS in the VHA database were appropriate for analysis. 162 medications with treatment groups of 30 or more individuals were identified. Among these 162 medications, 27 were associated with statistically significant changes (≥0·1) in the hazard ratio (HR) for death. 18 of the medications were associated with a reduced HR for death (prolonged survival), and nine were associated with an increased HR for death (reduced survival). Drugs associated with reduced HR included HMG-CoA reductase inhibitors (simvastatin, pravastatin, lovastatin, and atorvastatin), PDE5 inhibitors (vardenafil and sildenafil), and α-adrenergic antagonists (tamsulosin and terazosin). The medications associated with an increased HR were drugs used either in the management of clinical features of ALS associated with poor outcomes or in end-of-life care. PathFx analysis identified a complex of proteins interacting with several of the identified drugs. To our knowledge, this analysis is the largest EHR-based study for identifying drug repurposing candidates for ALS. We identified several drugs that warrant further assessment as therapeutic options in ALS, as well as a protein network complex that might serve as a therapeutic target for ALS.

Reimer, Richard J. [Stanford Univ., CA (United Sta↗

NASA NTRSDate not supplied

Oxidative Stress and the Neuroconsequences of Spaceflight Environment - Immune Dysregulation and Antioxidant Dietary Countermeasure Efficacy

In this project, we will test the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. Specific Aims for this project are: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. The project relies on established and highly translatable ground-based mouse models and assays with IR exposures to be performed at the NASA Space Radiation Laboratory (NSRL). The experimental approach will provide definitive data on the timing and mechanisms involved in the oxidative stress response, immune and brain changes, and ensuing functional (behavioral/cognitive) impairments expected during human transit to Mars. This project will identify potential biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. The project will address NASA’s efforts to rapidly advance the characterization of risks and identify appropriate countermeasures in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Further, despite historically low numbers of female astronauts, the two most recent NASA Astronaut Corps class selections, comprised of ~50% women as compared to men, signal the need to understand how sex differences affect physiological adaptation and health in the space environment. Here, we will determine how key features of the deep space environment may interact to increase risk to crewmembers by negatively impacting health and performance, and identify and develop strategies to characterize and mitigate the potential risks via countermeasures. Supported by the NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18-18FLAG_2-0028.

radiation↗

DOE OSTI2021

An unstructured C-grid type variational formulation for the sea ice dynamics

Historically, B-grid formulations of sea ice dynamics have been dominant because they have matched the grid type used by ocean models. The reason for the grid match is simple – it facilitates penetration of the curl of ice-ocean stress into the deep ocean with minimal numerical diffusivity because sea ice and ocean velocity are co-located. In recent years, as ocean models have increasingly progressed to C-grids, sea ice models have followed suit on quadrilateral meshes, but the implementation of an unstructured C-grid sea ice models is new. We present an unstructured C-grid discretization of the Elastic Viscous Plastic (EVP) rheology, where the velocity unknowns are discretized at the edges of the mesh cells with n-sides, where typically n is greater than or equal to four, rather than at the vertices, as in the B-grid. Our framework of choice is the Model for Prediction Across Scales (MPAS) within E3SM, the climate model of the U.S. Department of Energy, although our approach is general and could be applied to other models as well. While MPAS-Seaice is currently defined on a B-grid, MPAS-Ocean runs on a C-grid, hence interpolation operators are heavily used when coupled simulations are performed. In this work, we describe a mathematical formulation to transition the dynamics of MPAS-Seaice to a C-grid, in order to ultimately facilitate the coupling with MPAS-Ocean and reduce numerical errors associated with this communication. Numerical results are reported to highlight the features of the method.

58 GEOSCIENCES↗

DOE OSTI2020

Fine structure of the isovector giant dipole resonance in Nd 142 – 150 and Sm 152

Inelastic proton scattering at energies of a few hundred MeV and very-forward scattering angles including 0° has been established as a tool for the study of electric-dipole strength distributions in nuclei. The present work reports a systematic investigation of the chain of stable even-mass Nd isotopes representing a transition from spherical to quadrupole-deformed nuclei. Extraction of the equivalent photo-absorption cross sections and analysis of their fine structure in the energy region of the isovector giant dipole resonance (IVGDR). Method: Proton inelastic scattering reactions of 200 MeV protons were measured at the iThemba Laboratory for Accelerator Based Sciences in Cape Town, South Africa. The scattering products were momentum-analyzed by the K600 magnetic spectrometer positioned at θ Lab = 0°. Using dispersion-matching techniques, energy resolutions of ΔE ≈ 40–50 keV (full width at half maximum) were obtained. After subtraction of background and contributions from other multipoles, the spectra were converted to photoabsorption cross sections using the equivalent virtual-photon method. Wavelet-analysis techniques are used to extract characteristic energy scales of the fine structure of the IVGDR from the experimental data. Fine structure of the IVGDR is observed even for the most deformed nuclei studied. Comparisons between the extracted experimental energy scales and those energy scales obtained from the quasiparticle-phonon model (QPM) and Skyrme separable random phase approximation (SSRPA) predictions provide insight into the role of different giant-resonance damping mechanisms. It can be seen that the scales in the spherical and most likely also in the deformed nuclei mainly result from the fragmentation of the one-particle-one-hole (1p1h) strength into several dominant transitions serving as doorway states. In cases where calculations beyond the 1p1h level are available, some impact of the spreading due to coupling of the two-particle-two-hole (2p2h) states to the 1p1h doorway states is observed. New virtual-photon absorption data for the chain of stable Nd isotopes and 152 Sm are presented, with a focus on the phenomenon of nonstatistical cross-section fluctuations, referred to as fine structure, in the energy region of the IVGDR. The wavelet-analysis techniques used allowed for the features of the fine structure to be quantified in the form of characteristic scales. Finally, comparisons between experimental results and model predictions indicate that Landau damping seems to be the main source of the fine structure in both the spherical and deformed nuclei, but calculations including 2p2h degrees of freedom would be beneficial to confirm this for the deformed cases.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗