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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Waste Retrieval and Inspection Operations in Hanford Tank 241-AY-102 - 18234

In August 2012, a periodic annulus inspection of tank 241-AY-102 (AY-102) identified a leak from the primary tank into the secondary containment. A pumping plan was developed in 2013 to provide a path forward for recommended remediation actions to be implemented as part of the AY-102 Recovery Project. On March 21, 2014, the Washington State Department of Ecology issued an Administrative Order requiring Washington River Protection Solutions and the United States Department of Energy to conduct actions related to and including the removal of waste from AY-102. The parties agreed to resolve the appeal of the Administrative Order through a Settlement Agreement which addressed the remaining requirements and implemented enforceable milestone dates, including completion of waste removal operations, and performance of an inspection aimed at determining the cause of the leak. The AY-102 Recovery Project was developed to address the Settlement Agreement requirements. While retrieval of waste from Single-Shell Tanks has been performed at Hanford for decades, retrieval from Double-Shell Tank AY-102 required adaptation of the existing technologies to a new environment on a larger scale than previously encountered. Despite countless challenges and obstacles encountered throughout, the project successfully completed system design, fabrication, installation, testing, and retrieval operations within a highly compressed, aggressive schedule. Waste removal activities in AY-102 completed in February 2017. Subsequent inspection activities were completed as part of a multi-step process aimed at determining the likely cause of failure and assessing the feasibility of repair. A variety of input data were used in evaluating the likely failure mechanism, such as video examinations that revealed numerous through-floor penetrations and significant degradation across the visible surface area. Based on the operational history of the tank, corrosion testing and analysis, and the visual appearance of the confirmed leak sites, service-induced pitting corrosion due to the historic waste composition and operating conditions appears to be the primary degradation mechanism leading to failure of the tank. The inspection data has demonstrated that repairing and returning AY-102 to service would likely introduce substantial technical, logistical, and financial challenges due to the extent of bottom-plate damage. As a result, tank AY-102 will ultimately be closed. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
NASA NTRS1999

Initial Piloted Simulation Evaluation of the Reference-H High-Speed Civil Transport Design During Takeoff and Recovery From Limit Flight Conditions

An initial assessment of a proposed High-Speed Civil Transport (HSCT) was conducted in the fall of 1995 at the NASA Langley Research Center. This configuration, known as the Industry Reference-H (Ref.-H), was designed by the Boeing Aircraft Company as part of their work in the High Speed Research program. It included a conventional tail, a cranked-arrow wing, four mixed-flow turbofan engines, and capacity for transporting approximately 300 passengers. The purpose of this assessment was to evaluate and quantify operational aspects of the Reference-H configuration from a pilot's perspective with the additional goal of identifying design strengths as well as any potential configuration deficiencies. This study was aimed at evaluating the Ref.-H configuration at many points of the aircraft's envelope to determine the suitability of the vehicle to accomplish typical mission profiles as well as emergency or envelope-limit conditions. Pilot-provided Cooper-Harper ratings and comments constituted the primary vehicle evaluation metric. The analysis included simulated real-time piloted evaluations, performed in a 6 degree of freedom motion base NASA Langley Visual-Motion Simulator, combined with extensive bath analysis. The assessment was performed using the third major release of the simulation data base (known as Ref.-H cycle 2B).

Glaab, Louis J.↗
NASA NTRS2002

Vertical Field of View Reference Point Study for Flight Path Control and Hazard Avoidance

Researchers within the eXternal Visibility System (XVS) element of the High-Speed Research (HSR) program developed and evaluated display concepts that will provide the flight crew of the proposed High-Speed Civil Transport (HSCT) with integrated imagery and symbology to permit path control and hazard avoidance functions while maintaining required situation awareness. The challenge of the XVS program is to develop concepts that would permit a no-nose-droop configuration of an HSCT and expanded low visibility HSCT operational capabilities. This study was one of a series of experiments exploring the 'design space' restrictions for physical placement of an XVS display. The primary experimental issues here was 'conformality' of the forward display vertical position with respect to the side window in simulated flight. 'Conformality' refers to the case such that the horizon and objects appear in the same relative positions when viewed through the forward windows or display and the side windows. This study quantified the effects of visual conformality on pilot flight path control and hazard avoidance performance. Here, conformality related to the positioning and relationship of the artificial horizon line and associated symbology presented on the forward display and the horizon and associated ground, horizon, and sky textures as they would appear in the real view through a window presented in the side window display. No significant performance consequences were found for the non-conformal conditions.

Comstock, J. Raymond, Jr.↗
NASA NTRS2006

Functional brain imaging of a complex navigation task following one night of total sleep deprivation

Study Objectives: To assess the cerebral effects associated with sleep deprivation in a simulation of a complex, real-world, high-risk task. Design and Interventions: A two-week, repeated measures, cross-over experimental protocol, with counterbalanced orders of normal sleep (NS) and total sleep deprivation (TSD). Setting: Each subject underwent functional magnetic resonance imaging (fMRI) while performing a dual-joystick, 3D sensorimotor navigation task (simulated orbital docking). Scanning was performed twice per subject, once following a night of normal sleep (NS), and once following a single night of total sleep deprivation (TSD). Five runs (eight 24s docking trials each) were performed during each scanning session. Participants: Six healthy, young, right-handed volunteers (2 women; mean age 20) participated. Measurements and Results: Behavioral performance on multiple measures was comparable in the two sleep conditions. Neuroimaging results within sleep conditions revealed similar locations of peak activity for NS and TSD, including left sensorimotor cortex, left precuneus (BA 7), and right visual areas (BA 18/19). However, cerebral activation following TSD was substantially larger and exhibited higher amplitude modulations from baseline. When directly comparing NS and TSD, most regions exhibited TSD>NS activity, including multiple prefrontal cortical areas (BA 8/9,44/45,47), lateral parieto-occipital areas (BA 19/39, 40), superior temporal cortex (BA 22), and bilateral thalamus and amygdala. Only left parietal cortex (BA 7) demonstrated NS>TSD activity. Conclusions: The large network of cerebral differences between the two conditions, even with comparable behavioral performance, suggests the possibility of detecting TSD-induced stress via functional brain imaging techniques on complex tasks before stress-induced failures.

Strangman, Gary↗
NASA NTRS2016

Biomolecular Analysis Capability for Cellular and Omics Research on the International Space Station

International Space Station (ISS) assembly complete ushered a new era focused on utilization of this state-of-the-art orbiting laboratory to advance science and technology research in a wide array of disciplines, with benefits to Earth and space exploration. ISS enabling capability for research in cellular and molecular biology includes equipment for in situ, on-orbit analysis of biomolecules. Applications of this growing capability range from biomedicine and biotechnology to the emerging field of Omics. For example, Biomolecule Sequencer is a space-based miniature DNA sequencer that provides nucleotide sequence data for entire samples, which may be used for purposes such as microorganism identification and astrobiology. It complements the use of WetLab-2 SmartCycler"TradeMark", which extracts RNA and provides real-time quantitative gene expression data analysis from biospecimens sampled or cultured onboard the ISS, for downlink to ground investigators, with applications ranging from clinical tissue evaluation to multigenerational assessment of organismal alterations. And the Genes in Space-1 investigation, aimed at examining epigenetic changes, employs polymerase chain reaction to detect immune system alterations. In addition, an increasing assortment of tools to visualize the subcellular distribution of tagged macromolecules is becoming available onboard the ISS. For instance, the NASA LMM (Light Microscopy Module) is a flexible light microscopy imaging facility that enables imaging of physical and biological microscopic phenomena in microgravity. Another light microscopy system modified for use in space to image life sciences payloads is initially used by the Heart Cells investigation ("Effects of Microgravity on Stem Cell-Derived Cardiomyocytes for Human Cardiovascular Disease Modeling and Drug Discovery"). Also, the JAXA Microscope system can perform remotely controllable light, phase-contrast, and fluorescent observations. And upcoming confocal microscopy capability will allow for optical sectioning of biological tissues to determine microanatomical localization of biomarkers. Furthermore, NASA's geneLAB effort addresses integration of genomic, epigenomic, transcriptomic, proteomic and metabolomic datasets, by applying an innovative open source science platform for multi-investigator high throughput utilization of the ISS. In sum, the expanding ISS capability for analysis of biomolecules is enabling innovative research in a broad spectrum of areas such as cellular and molecular biology, biotechnology, tissue engineering, biomedicine, and Omics, providing manifold benefits for humanity.

Guinart-Ramirez, Y.↗
DOE OSTI2026

Do Flashing and Sealant Materials Need to be Exposed to Extreme Cycling?

In the U.S., over 50% of homes were built before 1980, when minimal building codes existed. The aging of building envelopes can significantly contribute to the air leakage, moisture intrusion, and durability of buildings leading to higher energy demands. Although the durability of building materials and envelope systems has been studied extensively, the durability of specific components like window-wall flashing and sealants remains underexplored. Current standards such as ASTM, NIST, and AAMA primarily focus on durability testing considering the high temperatures only and require sealant testing on anodized aluminum panels, leaving questions about performance in cold or fluctuating temperatures unanswered. Current ASTM and AAMA standards provide guidelines for durability testing but predominantly focus on exposure to higher temperature conditions. It remains unclear how exposure to cold temperatures, or cycles of both hot and cold conditions, affect the durability of these materials. Furthermore, AAMA standards mandate that flashing materials be tested on anodized aluminum panels, which may not reflect real-world applications. Therefore, this initial study aims to explore this concern through testing by constructing two window-wall interface prototypes and applying five different flashing and sealant materials to their joints. These samples were subjected to extreme temperatures, ranging from −34 ℃ (−30 °F) to 50 ℃ (122 °F), over a 28-day period (fourteen cycles of 24 hours), with daily visual inspections to document any signs of deterioration such as wrinkling, distortion, or warping. The study has two main objectives: (1) to determine whether flashing and sealant materials lose their durability and strength when exposed to varying climate conditions, specifically cold climates, and (2) to assess whether the interaction of these materials with different substrates (e.g., lumber, PVC, insulation) affects their durability and strength under varying climate conditions. The findings demonstrate how aging impacts the durability of window-wall systems interfaces, justifying future research that potentially could lead to the development of new testing protocols if significant defects are identified.

Palani, Hevar [ORNL] (ORCID:0000000220211994)↗
NASA NTRS1991

Aerodynamic performance of a drag reduction device on a full-scale tractor/trailer

The effectiveness of an aerodynamic boattail on a tractor/trailer road vehicle was measured in the NASA Ames Research Center 80- by 120-Foot Wind Tunnel. Results are examined for the tractor/trailer with and without the drag reduction device. Pressure measurements and flow visualization show that the aerodynamic boattail traps a vortex or eddy in the corner formed between the device and the rear corner of the trailer. This recirculating flow turns the flow inward as it separates from the edges of the base of the trailer. This modified flow behavior increases the pressure acting over the base area of the truck, thereby reducing the net aerodynamic drag of the vehicle. Drag measurements and pressure distributions in the region of the boattail device are presented for selected configurations. The optimum configuration reduces the overall drag of the tractor/trailer combination by about 10 percent at a zero yaw angle. Unsteady pressure measurements do not indicate strong vortex shedding, although the addition of the boattail plates increases high frequency content of the fluctuating pressure.

Lanser, Wendy R.↗
NASA NTRS1993

Fidelity assessment of a UH-60A simulation on the NASA Ames vertical motion simulator

Helicopter handling qualities research requires that a ground-based simulation be a high-fidelity representation of the actual helicopter, especially over the frequency range of the investigation. This experiment was performed to assess the current capability to simulate the UH-60A Black Hawk helicopter on the Vertical Motion Simulator (VMS) at NASA Ames, to develop a methodology for assessing the fidelity of a simulation, and to find the causes for lack of fidelity. The approach used was to compare the simulation to the flight vehicle for a series of tasks performed in flight and in the simulator. The results show that subjective handling qualities ratings from flight to simulator overlap, and the mathematical model matches the UH-60A helicopter very well over the range of frequencies critical to handling qualities evaluation. Pilot comments, however, indicate a need for improvement in the perceptual fidelity of the simulation in the areas of motion and visual cuing. The methodology used to make the fidelity assessment proved useful in showing differences in pilot work load and strategy, but additional work is needed to refine objective methods for determining causes of lack of fidelity.

Atencio, Adolph, Jr.↗
DOE OSTI2019

The Role of Sensitivity Analysis in the Building Performance Analysis: A Critical Review

A building system is highly nonlinear and commonly includes a variety of parameters ranging from the architectural design to the building mechanical and energy system. Serving as a powerful tool to understand the complicated building system, sensitivity analysis (SA) has been receiving increasing attention in the recent decade. This review paper focused on the application of SA in the building performance analysis (BPA). First, the existing review papers on the application of SA for BPA were briefly reviewed and summarized. Then, a large amount of recent SA case studies in BPA were reviewed. The critical information regarding the implementation of a SA, such as the sampling method, the SA method, etc., were extracted and summarized. Next, an extensive analysis was performed to evaluate the role of the SA in the BPA. This includes: 1) The typical selection of the input and output parameters for the SA were visualized; 2) The uncertainty level and sampling strategies for the input parameters were investigated; 3) The principles, benefits, and drawbacks of the SA methods were analyzed and summarized; and 4) The various tools used in the SA, including the simulation software, sampling tools, and SA tools were introduced to facilitate the practitioners. Lastly, several conclusions were summarized on the role of the SA in the BPA. Suggestions were also provided to offer practical solutions to the current challenges.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2021

Carbohydrate-Containing Conjugated Polymers: Solvent-Resistant Materials for Greener Organic Electronics

Organic semiconducting polymers are exciting materials for electronic applications because of their good mechanical and optoelectronic properties. A major advantage of organic semiconductors is their solution processability. This allows access to a variety of simple and cost-effective device fabrication methods compared to the expensive, high-temperature processing methods required for silicon-based electronics. However, these materials often have low solubility, which limits their processing to toxic halogenated solvents. Also, their limited solubility often leads to interfacial mixing during device fabrication. Herein, this work explores the incorporation of environmentally friendly carbohydrate side chains in conjugated polymers to enhance processability in eco-friendly solvents. Moreover, a mild postprocessing treatment was designed to enable solvent resistance. Isoindigo-based polymers with varied ratios of acetyl-protected galactose side chains were synthesized to improve solubility in o-anisole in the protected state, while inducing solvent resistance through intramolecular hydrogen bonding in the deprotected state. Solvent resistance was confirmed both visually upon submersion in various solvents and using UV–visible spectroscopy. Importantly, the mild basic treatment to achieve solvent resistance has no negative impact on the electronic performance of these materials in organic field-effect transistors, even after subsequent submersion in various solvents, making them a valuable platform for the production of green processable multilayer electronics.

36 MATERIALS SCIENCE↗
DOE OSTI2016

Cerebral perfusion computed tomography deconvolution via structure tensor total variation regularization

Purpose: Cerebral perfusion computed tomography (PCT) imaging as an accurate and fast acute ischemic stroke examination has been widely used in clinic. Meanwhile, a major drawback of PCT imaging is the high radiation dose due to its dynamic scan protocol. The purpose of this work is to develop a robust perfusion deconvolution approach via structure tensor total variation (STV) regularization (PD-STV) for estimating an accurate residue function in PCT imaging with the low-milliampere-seconds (low-mAs) data acquisition. Methods: Besides modeling the spatio-temporal structure information of PCT data, the STV regularization of the present PD-STV approach can utilize the higher order derivatives of the residue function to enhance denoising performance. To minimize the objective function, the authors propose an effective iterative algorithm with a shrinkage/thresholding scheme. A simulation study on a digital brain perfusion phantom and a clinical study on an old infarction patient were conducted to validate and evaluate the performance of the present PD-STV approach. Results: In the digital phantom study, visual inspection and quantitative metrics (i.e., the normalized mean square error, the peak signal-to-noise ratio, and the universal quality index) assessments demonstrated that the PD-STV approach outperformed other existing approaches in terms of the performance of noise-induced artifacts reduction and accurate perfusion hemodynamic maps (PHM) estimation. In the patient data study, the present PD-STV approach could yield accurate PHM estimation with several noticeable gains over other existing approaches in terms of visual inspection and correlation analysis. Conclusions: This study demonstrated the feasibility and efficacy of the present PD-STV approach in utilizing STV regularization to improve the accuracy of residue function estimation of cerebral PCT imaging in the case of low-mAs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

ORNL Campus Sustainability and Decarbonization using Waste Heat Recovery from the Oak Ridge Leadership Computing Facility’s High-Performance Computing Data Center

Heat pumps are a clean and efficient technology that can be powered by renewable electricity to transfer heat using a refrigerant from one place to another by different heat sources, making buildings clean and environmentally friendly. With the support of the ORNL Laboratory Modernization Division, this project explored and evaluated an innovative solution that uses water-water cost-effective midtemperature heat pump (MTHP) technology to leverage the low-grade waste heat from ORNL Frontier and the data center to deliver 85°C hot water, which replaces hot steam generated using natural gas combustion boilers for water heating or space heating in the buildings of ORNL campus. Two scenarios were studied. In the first scenario, which considered the 5600-5700-5800 complex only, Carrier’s commercial 1,000 kW MTHP technology achieves more than 6,640 MWh/year energy savings, an emission reduction of 858 TCO2e/year CO2, and a payback time of 4.85 years. In the second scenario, which considered the 5600-5700-5800 complex and Buildings 5100, 5200, and 5300, the CO2 emission reduction is 1,483 TCO2e/year, the operating cost savings are $0.21 million annually, and the payback time is 3.74 years. Additionally, a comprehensive HP ShowCase Tool was developed for evaluating the optimal solution to improve sustainability and decarbonization of the buildings on the ORNL campus. The tool is an Excel-based tool integrated with VBA (Visual Basic for Applications) coding. The tool includes collected ORNL campus building information and an MTHP library, which comprises collected commercial and ORNL-defined MTHPs. The tool was used to evaluate the sustainability and decarbonization of the ORNL campus. The tool can be widely used or referenced for heat pump solutions and building decarbonization renovation strategies to modernize ORNL facilities and energy use–intensive equipment to enable efficient, sustainable, and resilient operations in the future.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
NASA NTRS1992

Mixing in straight shear layers

Planar laser-induced fluorescence measurements were performed in a liquid plane mixing layer to extract the probability density function (pdf) of the mixture fraction of a passive scalar across the layer. Three Reynolds number (Re) cases were studied, 10,000, 33,000 and 90,000, with Re based on velocity difference and visual thickness. The results show that a non-marching pdf (central hump invariant from edge to edge of the layer) exists for Re = 10,000 but that a marching type pdf characterizes the Re = 33,000 and Re = 90,000 cases. For all cases, a broad range of mixture fraction values is found at each location across the layer. Streamwise and spanwise ramps across the layer, and structure-to-structure variation were observed and are believed to be responsible for the above behavior of the composition field. Tripping the boundary layer on the high-speed side of the splitter plate for each of the above three cases resulted in increased three-dimensionality and a change in the composition field. Average and average mixed fluid compositions are reported for all cases.

Karasso, P. S.↗
NASA NTRS2014

NASA Tech Briefs, June 2014

Topics include: Real-Time Minimization of Tracking Error for Aircraft Systems; Detecting an Extreme Minority Class in Hyperspectral Data Using Machine Learning; KSC Spaceport Weather Data Archive; Visualizing Acquisition, Processing, and Network Statistics Through Database Queries; Simulating Data Flow via Multiple Secure Connections; Systems and Services for Near-Real-Time Web Access to NPP Data; CCSDS Telemetry Decoder VHDL Core; Thermal Response of a High-Power Switch to Short Pulses; Solar Panel and System Design to Reduce Heating and Optimize Corridors for Lower-Risk Planetary Aerobraking; Low-Cost, Very Large Diamond-Turned Metal Mirror; Very-High-Load-Capacity Air Bearing Spindle for Large Diamond Turning Machines; Elevated-Temperature, Highly Emissive Coating for Energy Dissipation of Large Surfaces; Catalyst for Treatment and Control of Post-Combustion Emissions; Thermally Activated Crack Healing Mechanism for Metallic Materials; Subsurface Imaging of Nanocomposites; Self-Healing Glass Sealants for Solid Oxide Fuel Cells and Electrolyzer Cells; Micromachined Thermopile Arrays with Novel Thermo - electric Materials; Low-Cost, High-Performance MMOD Shielding; Head-Mounted Display Latency Measurement Rig; Workspace-Safe Operation of a Force- or Impedance-Controlled Robot; Cryogenic Mixing Pump with No Moving Parts; Seal Design Feature for Redundancy Verification; Dexterous Humanoid Robot; Tethered Vehicle Control and Tracking System; Lunar Organic Waste Reformer; Digital Laser Frequency Stabilization via Cavity Locking Employing Low-Frequency Direct Modulation; Deep UV Discharge Lamps in Capillary Quartz Tubes with Light Output Coupled to an Optical Fiber; Speech Acquisition and Automatic Speech Recognition for Integrated Spacesuit Audio Systems, Version II; Advanced Sensor Technology for Algal Biotechnology; High-Speed Spectral Mapper; "Ascent - Commemorating Shuttle" - A NASA Film and Multimedia Project DVD; High-Pressure, Reduced-Kinetics Mechanism for N-Hexadecane Oxidation; Method of Error Floor Mitigation in Low-Density Parity-Check Codes; X-Ray Flaw Size Parameter for POD Studies; Large Eddy Simulation Composition Equations for Two-Phase Fully Multicomponent Turbulent Flows; Scheduling Targeted and Mapping Observations with State, Resource, and Timing Constraints;

Source record↗
DOE OSTI2022

Optimizing Magnetic Force Microscopy Resolution and Sensitivity to Visualize Nanoscale Magnetic Domains

Magnetic force microscopy (MFM) enables mapping local magnetic fields across a sample surface with nanoscale resolution. To perform MFM, an atomic force microscopy (AFM) probe whose tip has been magnetized vertically (i.e., perpendicular to the probe cantilever) is oscillated at a fixed height above the sample surface. The resultant shifts in the oscillation phase or frequency, which are proportional to the magnitude and sign of the vertical magnetic force gradient at each pixel location, are then tracked and mapped. Although the spatial resolution and sensitivity of the technique increases with decreasing lift height above the surface, this seemingly straightforward path to improved MFM images is complicated by considerations such as minimizing topographical artifacts due to shorter range van der Waals forces, increasing the oscillation amplitude to further improve sensitivity, and the presence of surface contaminants (in particular water due to humidity under ambient conditions). In addition, due to the orientation of the probe's magnetic dipole moment, MFM is intrinsically more sensitive to samples with an out-of-plane magnetization vector. Here, high-resolution topographical and magnetic phase images of single and bicomponent nanomagnet artificial spin-ice (ASI) arrays obtained in an inert (argon) atmosphere glovebox with <0.1 ppm O 2 and H 2 O are reported. Further, optimization of lift height and drive amplitude for high resolution and sensitivity while simultaneously avoiding the introduction of topographical artifacts is discussed, and detection of the stray magnetic fields emanating from either end of the nanoscale bar magnets (~250 nm long and <100 nm wide) aligned in the plane of the ASI sample surface is shown. Likewise, using the example of a Ni-Mn-Ga magnetic shape memory alloy (MSMA), MFM is demonstrated in an inert atmosphere with magnetic phase sensitivity capable of resolving a series of adjacent magnetic domains each ~200 nm wide.

47 OTHER INSTRUMENTATION↗
DOE OSTI2018

Dynamic Data Repartitioning for Load-Balanced Parallel Particle Tracing

We present a novel dynamic load-balancing algorithm based on data repartitioning for parallel particle tracing in flow visualization. Instead of static data assignment, we dynamically repartition the data into blocks and reassign the blocks to processes to balance the workload distribution among the processes. Block repartitioning is performed based on a dynamic workload estimation method that predicts the workload in the flow field on the fly as the input. In our approach, we allow data duplication in the repartitioning, enabling the same data blocks to be assigned to multiple processes. Load balance is achieved by regularly exchanging the blocks (together with the particles in the blocks) among processes according to the output of the data repartitioning. Compared with other load-balancing algorithms, our approach does not need any preprocessing on the raw data and does not require any dedicated process for work scheduling, while it has the capability to balance uneven workload efficiently. Results show improved load balance and high efficiency of our method on tracing particles in both steady and unsteady flow.

data repartitioning↗
NASA NTRS2011

Space Radiation Effects on Human Cells: Modeling DNA Breakage, DNA Damage Foci Distribution, Chromosomal Aberrations and Tissue Effects

Future long-tem space travel will face challenges from radiation concerns as the space environment poses health risk to humans in space from radiations with high biological efficiency and adverse post-flight long-term effects. Solar particles events may dramatically affect the crew performance, while Galactic Cosmic Rays will induce a chronic exposure to high-linear-energy-transfer (LET) particles. These types of radiation, not present on the ground level, can increase the probability of a fatal cancer later in astronaut life. No feasible shielding is possible from radiation in space, especially for the heavy ion component, as suggested solutions will require a dramatic increase in the mass of the mission. Our research group focuses on fundamental research and strategic analysis leading to better shielding design and to better understanding of the biological mechanisms of radiation damage. We present our recent effort to model DNA damage and tissue damage using computational models based on the physics of heavy ion radiation, DNA structure and DNA damage and repair in human cells. Our particular area of expertise include the clustered DNA damage from high-LET radiation, the visualization of DSBs (DNA double strand breaks) via DNA damage foci, image analysis and the statistics of the foci for different experimental situations, chromosomal aberration formation through DSB misrepair, the kinetics of DSB repair leading to a model-derived spectrum of chromosomal aberrations, and, finally, the simulation of human tissue and the pattern of apoptotic cell damage. This compendium of theoretical and experimental data sheds light on the complex nature of radiation interacting with human DNA, cells and tissues, which can lead to mutagenesis and carcinogenesis later in human life after the space mission.

Ponomarev, A. L.↗
DOE OSTI2019

Imaging doxorubicin and polymer-drug conjugates of doxorubicin-induced cardiotoxicity with bispecific anti-myosin-anti-DTPA antibody and Tc-99m-labeled polymers

Background: Radiolabeled anti-myosin imaging is well-established for imaging doxorubicin-induced cardiotoxicity. However, to enable imaging of drug-induced cardiotoxicity in small experimental animals, pretargeting with bispecific anti-myosin-anti-DTPA-Fab-Fab’ and targeting with high-specific radioactivity Tc-99m-DTPA-succinylated-polylysine (DSPL) was developed. Methods: Mice were injected biweekly with 10 mg/kg Dox or its equivalent as D-Dox-PGA. Tc-99m-DSPL myocardial activity after pretargeting with bsAb-Fab-Fab’ was determined after gamma imaging performed at day 7 for Dox-treated mice and day 39 for all others. Results: Mice treated with 10 mg/kg Dox lost 10% total body weight in 1 week and 20% after a second dose. Pretargeted mice treated with 30 mg/kg cumulative D-Dox-PGA dose showed no loss of body weight for the duration of the study. Cardiotoxicity was confirmed by gamma imaging and scintillation counting (1.9 ± 0.25 [mean% ID/g ± SD]) after 1 dose of Dox. Mice injected with 3 × 10 mg/kg Dox equivalent as D-Dox-PGA (0.4 ± 0.04, P < .01) and untreated 2 control groups (0.20 ± 0.05 and 0.19 ± 0.04, P < .01) showed significantly lower myocardial anti-myosin radioactivity relative to the 10 mg/kg Dox group. Conclusion: Pretargeting with bsAb-Fab-Fab’ and targeting with Tc-99m labeled high-specific activity polymers enabled early visualization of doxorubicin induce cardiotoxicity in mice. Tolerated dose of D-Dox-PGA was greater than to 30 mg/kg Dox-equivalent dose with minimal cardiotoxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗