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At least 289 records · Page 16

A Simple Model of Global Aerosol Indirect Effects

Most estimates of the global mean indirect effect of anthropogenic aerosol on the Earth's energy balance are from simulations by global models of the aerosol lifecycle coupled with global models of clouds and the hydrologic cycle. Extremely simple models have been developed for integrated assessment models, but lack the flexibility to distinguish between primary and secondary sources of aerosol. Here a simple but more physically based model expresses the aerosol indirect effect (AIE) using analytic representations of cloud and aerosol distributions and processes. Although the simple model is able to produce estimates of AIEs that are comparable to those from some global aerosol models using the same global mean aerosol properties, the estimates by the simple model are sensitive to preindustrial cloud condensation nuclei concentration, preindustrial accumulation mode radius, width of the accumulation mode, size of primary particles, cloud thickness, primary and secondary anthropogenic emissions, the fraction of the secondary anthropogenic emissions that accumulates on the coarse mode, the fraction of the secondary mass that forms new particles, and the sensitivity of liquid water path to droplet number concentration. Estimates of present-day AIEs as low as 5 W/sq m and as high as 0.3 W/sq m are obtained for plausible sets of parameter values. Estimates are surprisingly linear in emissions. The estimates depend on parameter values in ways that are consistent with results from detailed global aerosol-climate simulation models, which adds to understanding of the dependence on AIE uncertainty on uncertainty in parameter values.

Clouds↗

Discrete sensitivity derivatives of the Navier-Stokes equations with a parallel Krylov solver

This paper solves an 'incremental' form of the sensitivity equations derived by differentiating the discretized thin-layer Navier Stokes equations with respect to certain design variables of interest. The equations are solved with a parallel, preconditioned Generalized Minimal RESidual (GMRES) solver on a distributed-memory architecture. The 'serial' sensitivity analysis code is parallelized by using the Single Program Multiple Data (SPMD) programming model, domain decomposition techniques, and message-passing tools. Sensitivity derivatives are computed for low and high Reynolds number flows over a NACA 1406 airfoil on a 32-processor Intel Hypercube, and found to be identical to those computed on a single-processor Cray Y-MP. It is estimated that the parallel sensitivity analysis code has to be run on 40-50 processors of the Intel Hypercube in order to match the single-processor processing time of a Cray Y-MP.

Ajmani, Kumud↗

The design of low cost structures for extensive ground arrays

The development of conceptual designs of solar array support structures and their foundations including considerations of the use of concrete, steel, aluminum, or timber are reported. Some cost trends were examined by varying selected parameters to determine optimum configurations. Detailed civil/structural design criteria were developed. Using these criteria, eight detailed designs for support structures and foundations were developed and cost estimates were made. As a result of the study wind was identified as the major loading experienced by these low height structures, whose arrays are likely to extend over large tracts of land. Proper wind load estimating is considered essential to developing realistic structural designs and achieving minimum cost support structures. Wind tunnel testing of a conceptual array field was undertaken and some of the resulting wind design criteria are presented. The SPS rectenna system designs may be less sensitive to wind load estimates, but consistent design criteria remain important.

Franklin, H. A.↗

GRB 191016A: A Long Gamma-Ray Burst Detected by TESS

The Transiting Exoplanet Survey Satellite (TESS) exoplanet-hunting mission detected the rising and decaying optical afterglow of GRB 191016A, a long gamma-ray burst (GRB) detected by Swift-BAT but without prompt XRT or UVOT follow-up due to proximity to the Moon. The afterglow has a late peak at least 1000 s after the BAT trigger, with a brightest-detected TESS data point at 2589.7 s post-trigger. The burst was not detected by Fermi-LAT, but was detected by Fermi-GBM without triggering, possibly due to the gradual nature of the rising light curve. Using ground-based photometry, we estimate a photometric redshift of z(sub phot) = 3.29 ± 0.40. Combined with the high-energy emission and optical peak time derived from TESS, estimates of the bulk Lorentz factor Γ(sub BL) range from 90 to 133. The burst is relatively bright, with a peak optical magnitude in ground-based follow-up of R = 15.1 mag. Using published distributions of GRB afterglows and considering the TESS sensitivity and sampling, we estimate that TESS is likely to detect ∼1 GRB afterglow per year above its magnitude limit.

Gamma-ray bursts↗

Further Studies on Oceanic Biogeochemistry and Carbon Cycling

This TM consists of two chapters. Chapter I describes the development of a coupled, one-dimensional biogeochemical model using turbulence closure mixed layer (TCMLM) dynamics. The model is applied to the Sargasso Sea at the BATS (Bermuda Atlantic Time Series) site and the results are compared with a previous model study in the same region described in NASNTP-2001-209991. The use of the TCMLM contributed to some improvements in the model simulation of chlorophyll, PAR, nitrate, phosphate, and oxygen, but most importantly, the current model achieved good agreement with the data with much more realistic background eddy diffusivity. However, off-line calculations of horizontal transport of biogeochemical properties revealed that one-dimensional dynamics can only provide a limited assessment of the nutrient and carbon balances at BATS. Future studies in the BATS region will require comprehensive three-dimensional field studies, combined with three-dimensional eddy resolving numerical experiments, to adequately quantify the impact of the local and remote forcing on ecosystem dynamics and carbon cycling. Chapter II addresses the sensitivity of global sea-air CO, flux estimates to wind speed, temperature, and salinity. Sensitivity analyses of sea-air CO, flux to wind speed climatologies, gas transfer algorithms, SSS and SST were conducted for the global oceans and regional domains. Large uncertainties in the global sea-air flux are identified, primarily due to the different gas transfer algorithms used. The sensitivity of the sea-air flux to SST and SSS is similar in magnitude to the effect of using different wind climatologies. Globally, the mean ocean uptake of CO, changes by 5 to 16%, depending upon the combination of SST and SSS used.

Signorini, S. R.↗

IMAGE-POLAR Concurrent Plasmapause Observations

Two critical issues that influence the quantitative scientific value of the IMAGE Ultraviolet Camera (EUV) are: (1) the accuracy with which EUV imaging can be used to determine the position/location of the plasmapause; and (2) the sensitivity threshold of the EUV instrument. These issues are addressed through analysis of concurrent observations of the plasmasphere/plasmapause made remotely using IMAGE EUV and in-situ with the Polar/TIDE/EFI instruments. Preliminary results are presented with regards to the validity of the extraction of the plasmapause using EUV and initial in-flight, in-situ estimates of the EUV sensitivity threshold.

Adrian, M. L.↗

Technology Benefit Estimator (T/BEST): User's Manual

The Technology Benefit Estimator (T/BEST) system is a formal method to assess advanced technologies and quantify the benefit contributions for prioritization. T/BEST may be used to provide guidelines to identify and prioritize high payoff research areas, help manage research and limited resources, show the link between advanced concepts and the bottom line, i.e., accrued benefit and value, and to communicate credibly the benefits of research. The T/BEST software computer program is specifically designed to estimating benefits, and benefit sensitivities, of introducing new technologies into existing propulsion systems. Key engine cycle, structural, fluid, mission and cost analysis modules are used to provide a framework for interfacing with advanced technologies. An open-ended, modular approach is used to allow for modification and addition of both key and advanced technology modules. T/BEST has a hierarchical framework that yields varying levels of benefit estimation accuracy that are dependent on the degree of input detail available. This hierarchical feature permits rapid estimation of technology benefits even when the technology is at the conceptual stage. As knowledge of the technology details increases the accuracy of the benefit analysis increases. Included in T/BEST's framework are correlations developed from a statistical data base that is relied upon if there is insufficient information given in a particular area, e.g., fuel capacity or aircraft landing weight. Statistical predictions are not required if these data are specified in the mission requirements. The engine cycle, structural fluid, cost, noise, and emissions analyses interact with the default or user material and component libraries to yield estimates of specific global benefits: range, speed, thrust, capacity, component life, noise, emissions, specific fuel consumption, component and engine weights, pre-certification test, mission performance engine cost, direct operating cost, life cycle cost, manufacturing cost, development cost, risk, and development time. Currently, T/BEST operates on stand-alone or networked workstations, and uses a UNIX shell or script to control the operation of interfaced FORTRAN based analyses. T/BEST's interface structure works equally well with non-FORTRAN or mixed software analysis. This interface structure is designed to maintain the integrity of the expert's analyses by interfacing with expert's existing input and output files. Parameter input and output data (e.g., number of blades, hub diameters, etc.) are passed via T/BEST's neutral file, while copious data (e.g., finite element models, profiles, etc.) are passed via file pointers that point to the expert's analyses output files. In order to make the communications between the T/BEST's neutral file and attached analyses codes simple, only two software commands, PUT and GET, are required. This simplicity permits easy access to all input and output variables contained within the neutral file. Both public domain and proprietary analyses codes may be attached with a minimal amount of effort, while maintaining full data and analysis integrity, and security. T/BESt's sotware framework, status, beginner-to-expert operation, interface architecture, analysis module addition, and key analysis modules are discussed. Representative examples of T/BEST benefit analyses are shown.

Generazio, Edward R.↗

Impact of Footprint Diameter and Off-Nadir Pointing on the Precision of Canopy Height Estimates from Spaceborne Lidar

A spaceborne lidar mission could serve multiple scientific purposes including remote sensing of ecosystem structure, carbon storage, terrestrial topography and ice sheet monitoring. The measurement requirements of these different goals will require compromises in sensor design. Footprint diameters that would be larger than optimal for vegetation studies have been proposed. Some spaceborne lidar mission designs include the possibility that a lidar sensor would share a platform with another sensor, which might require off-nadir pointing at angles of up to 16 . To resolve multiple mission goals and sensor requirements, detailed knowledge of the sensitivity of sensor performance to these aspects of mission design is required. This research used a radiative transfer model to investigate the sensitivity of forest height estimates to footprint diameter, off-nadir pointing and their interaction over a range of forest canopy properties. An individual-based forest model was used to simulate stands of mixed conifer forest in the Tahoe National Forest (Northern California, USA) and stands of deciduous forests in the Bartlett Experimental Forest (New Hampshire, USA). Waveforms were simulated for stands generated by a forest succession model using footprint diameters of 20 m to 70 m. Off-nadir angles of 0 to 16 were considered for a 25 m diameter footprint diameter. Footprint diameters in the range of 25 m to 30 m were optimal for estimates of maximum forest height (R(sup 2) of 0.95 and RMSE of 3 m). As expected, the contribution of vegetation height to the vertical extent of the waveform decreased with larger footprints, while the contribution of terrain slope increased. Precision of estimates decreased with an increasing off-nadir pointing angle, but off-nadir pointing had less impact on height estimates in deciduous forests than in coniferous forests. When pointing off-nadir, the decrease in precision was dependent on local incidence angle (the angle between the off-nadir beam and a line normal to the terrain surface) which is dependent on the off-nadir pointing angle, terrain slope, and the difference between the laser pointing azimuth and terrain aspect; the effect was larger when the sensor was aligned with the terrain azimuth but when aspect and azimuth are opposed, there was virtually no effect on R2 or RMSE. A second effect of off-nadir pointing is that the laser beam will intersect individual crowns and the canopy as a whole from a different angle which had a distinct effect on the precision of lidar estimates of height, decreasing R2 and increasing RMSE, although the effect was most pronounced for coniferous crowns.

Pang, Yong↗

A vehicle health monitoring system for the Space Shuttle Reaction Control System during reentry

A general two tier framework for vehicle health monitoring of Guidance Navigation and Control (GN&C) system actuators, effectors, and propulsion devices is presented. In this context, a top level monitor that estimates jet thrust is designed for the Space Shuttle Reaction Control System (RCS) during the reentry phase of flight. Issues of importance for the use of estimation technologies in vehicle health monitoring are investigated and quantified for the Shuttle RCS demonstration application. These issues include rate of convergence, robustness to unmodeled dynamics, sensor quality, sensor data rates, and information recording objectives. Closed loop simulations indicate that a Kalman filter design is sensitive to modeling error and robust estimators may reduce this sensitivity. Jet plume interaction with the aerodynamic flowfield is shown to be a significant effect adversely impacting the ability to accurately estimate thrust.

Rosello, Anthony David↗

A real-time recursive filter for the attitude determination of the Spacelab instrument pointing subsystem

A real-time estimation filter which reduces sensitivity to system variations and reduces the amount of preflight computation is developed for the instrument pointing subsystem (IPS). The IPS is a three-axis stabilized platform developed to point various astronomical observation instruments aboard the shuttle. Currently, the IPS utilizes a linearized Kalman filter (LKF), with premission defined gains, to compensate for system drifts and accumulated attitude errors. Since the a priori gains are generated for an expected system, variations result in a suboptimal estimation process. This report compares the performance of three real-time estimation filters with the current LKF implementation. An extended Kalman filter and a second-order Kalman filter are developed to account for the system nonlinearities, while a linear Kalman filter implementation assumes that the nonlinearities are negligible. The performance of each of the four estimation filters are compared with respect to accuracy, stability, settling time, robustness, and computational requirements. It is shown, that for the current IPS pointing requirements, the linear Kalman filter provides improved robustness over the LKF with less computational requirements than the two real-time nonlinear estimation filters.

West, M. E.↗

Gaussian Process Regression Method for Costing SmallSat Bus Capabilities

NASA is responding to the growing interest in, andcapabilities of, small satellites for science applications with an increasingnumber and frequency of Announcements of Opportunityfor small satellite space missions. Estimating the probabilitythat these mission concepts will fit within the small cost capsof these opportunities is largely driven by the probability thatone of the burgeoning number of small satellite providers will beable to meet the payload’s accommodation requirements withinthe budget for the spacecraft. JPL has collected a databasecontaining technical specifications and cost of commerciallyavailable Smallsat buses across various vendors. The primarypurpose of the database is for use in JPL’s Team X architecturestudies to inform cost estimates of a spacecraft bus which fitsthe customer’s technical requirements for their payload andmission. Customer needs are often unique and don’t alignperfectly with an off-the-shelf commercial spacecraft bus, whichmotivates the need to develop a cost model across the continuoustechnical parameter space.Al’s Bus Cost Distribution Estimator (ABCDE) uses Gaussianprocess regression (GPR) to predict commercial Smallsat spacecraftbus cost based on a subset of a customer’s technicalrequirements (payload mass, payload power, delta V, pointingcontrol, and downlink rate). GPR is implemented in ABCDE asa Bayesian method which fits an implied multivariate regressionon the technical parameters and uses kriging to intentionally“overfit” the residuals. Overfitting the residuals allows costestimates to collapse in uncertainty closer to the data pointswhile maintaining larger uncertainty intervals in regions of parameterspace with fewer data records. The data used to fit thismodel is sensitive and represents cost estimates for off-the-shelfcommercial buses. GPR simultaneously protects the sensitivityof the database and uses the sparse nature of the database toaccount for uncertainty in cost in a useful way. For a givenset of customer technical requirements, the tool provides a costestimate distribution, the percentiles of which can be interpretedas a confidence level of finding a commercial bus under a specifiedcost cap. ABCDE dramatically pushes the boundaries ofspacecraft cost estimation models due to its Bayesian methodology(accounting for the maximum uncertainty in the underlyingregression), the mathematically advanced kriging methodology,and the novelty of its application in Team X architecture tradestudies.

Austin, Alex↗

Astrophysics to z approx. 10 with Gravitational Waves

The most useful characterization of a gravitational wave detector's performance is the accuracy with which astrophysical parameters of potential gravitational wave sources can be estimated. One of the most important source types for the Laser Interferometer Space Antenna (LISA) is inspiraling binaries of black holes. LISA can measure mass and spin to better than 1% for a wide range of masses, even out to high redshifts. The most difficult parameter to estimate accurately is almost always luminosity distance. Nonetheless, LISA can measure luminosity distance of intermediate-mass black hole binary systems (total mass approx.10(exp 4) solar mass) out to z approx.10 with distance accuracies approaching 25% in many cases. With this performance, LISA will be able to follow the merger history of black holes from the earliest mergers of proto-galaxies to the present. LISA's performance as a function of mass from 1 to 10(exp 7) solar mass and of redshift out to z approx. 30 will be described. The re-formulation of LISA's science requirements based on an instrument sensitivity model and parameter estimation will be described.

Stebbins, Robin↗

Retrieval Assimilation and Modeling of Atmospheric Water Vapor from Ground- and Space-Based GPS Networks: Investigation of the Global and Regional Hydrological Cycles

Uncertainty over the response of the atmospheric hydrological cycle (particularly the distribution of water vapor and cloudiness) to anthropogenic forcing is a primary source of doubt in current estimates of global climate sensitivity, which raises severe difficulties in evaluating its likely societal impact. Fortunately, a variety of advanced techniques and sensors are beginning to shed new light on the atmospheric hydrological cycle. One of the most promising makes use of the sensitivity of the Global Positioning System (GPS) to the thermodynamic state, and in particular the water vapor content, of the atmosphere through which the radio signals propagate. Our strategy to derive the maximum benefit for hydrological studies from the rapidly increasing GPS data stream will proceed in three stages: (1) systematically analyze and archive quality-controlled retrievals using state-of-the-art techniques; (2) employ both currently available and innovative assimilation procedures to incorporate these determinations into advanced regional and global atmospheric models and assess their effects; and (3) apply the results to investigate selected scientific issues of relevance to regional and global hydrological studies. An archive of GPS-based estimation of total zenith delay (TZD) data and water vapor where applicable has been established with expanded automated quality control. The accuracy of the GPS estimates is being monitored; the investigation of systematic errors is ongoing using comparisons with water vapor radiometers. Meteorological packages have been implemented. The accuracy and utilization of the TZD estimates has been improved by implementing a troposphere gradient model. GPS-based gradients have been validated as real atmospheric moisture gradients, establishing a link between the estimated gradients and the passage of weather fronts. We have developed a generalized ray tracing inversion scheme that can be used to analyze occultation data acquired from space- or land-based receivers. The National Center for Atmospheric Research mesoscale model (version MM5) has been adapted for Southern California, and assimilation studies are underway. Additional information is contained in the original.

Dickey, Jean O.↗

Simple Sensitivity Analysis for Orion GNC

The performance of Orion flight software, especially its GNC software, is being analyzed by running Monte Carlo simulations of Orion spacecraft flights. The simulated performance is analyzed for conformance with flight requirements, expressed as performance constraints. Flight requirements include guidance (e.g. touchdown distance from target) and control (e.g., control saturation) as well as performance (e.g., heat load constraints). The Monte Carlo simulations disperse hundreds of simulation input variables, for everything from mass properties to date of launch.We describe in this paper a sensitivity analysis tool (Critical Factors Tool or CFT) developed to find the input variables or pairs of variables which by themselves significantly influence satisfaction of requirements or significantly affect key performance metrics (e.g., touchdown distance from target). Knowing these factors can inform robustness analysis, can inform where engineering resources are most needed, and could even affect operations. The contributions of this paper include the introduction of novel sensitivity measures, such as estimating success probability, and a technique for determining whether pairs of factors are interacting dependently or independently. The tool found that input variables such as moments, mass, thrust dispersions, and date of launch were found to be significant factors for success of various requirements. Examples are shown in this paper as well as a summary and physics discussion of EFT-1 driving factors that the tool found.

Monte Carlo Simulation↗

Impacts of Marine Surface Pressure Observations From A Spaceborne Differential Absorption Radar Investigated With an Observing System Simulation Experiment

A new instrument has been proposed for measuring surface air pressure over the marine surface with a combined active/passive scanning multi-channel differential absorption radar (DAR) to provide an estimate of the total atmospheric column oxygen content. A demonstrator instrument, the Microwave Barometric Radar and Sounder (MBARS), has been funded by the National Aeronautics and Space Administration (NASA) for airborne test missions. Here, a proof-of-concept study to evaluate the potential impact of spaceborne surface pressure data on numerical weather prediction is performed using the Goddard Modeling and Assimilation Office global observing system simulation experiment (OSSE) framework. This OSSE framework employs the Goddard Earth Observing System model and the hybrid 4D ensemble variational Gridpoint Statistical Interpolation data assimilation system. Multiple flight and scanning configurations of potential spaceborne orbits are examined. Swath width and observation spacing for the surface pressure data are varied to explore a range of sampling strategies. For wider swaths, the addition of surface pressures reduces the root mean square surface pressure analysis error by as much as 20% over some ocean regions. The forecast sensitivity observation impact tool estimates impacts on the Pacific Ocean basin boundary layer 24-hour forecast temperatures for spaceborne surface pressures on par with rawinsondes and aircraft, and greater impacts than the current network of ships and buoys. The largest forecast impacts are found in the southern hemisphere extratropics.

N.C. Privé↗

NLR HPC Kestrel Jobs Data

Overview: Anonymized job-level records from the Kestrel HPC system at the National Laboratory of the Rockies (NLR). Each record represents a Slurm batch job with scheduling metadata, resource requests, utilization, energy estimates, and efficiency metrics. Sensitive fields (user, account, job name, submit line, working directory, submit script, and job type) are replaced with 7-character cryptographic hashes. System & Timeframe: Kestrel is located at the NLR campus. Standard compute nodes have 104 cores and 256 GB RAM; bigmem nodes have 2,000 GB. GPU nodes (gpu-h100 partition) use NVIDIA H100 GPUs. Data covers jobs submitted August 2023 through December 2025. Funding provided by the U.S. Department of Energy, EERE. Files: esif.hpc.kestrel.job-anon.zip — Anonymized job records (Hive-partitioned Parquet) datacard.md — Full dataset documentation ~11 million rows, 50 variables. Readable with PyArrow, pandas, DuckDB, Apache Spark, or any Parquet-compatible tool. Data Collection: Jobs collected via sacct with timezone-aware export (SLURM_TIME_FORMAT="%Y-%m-%dT%H:%M:%S%z"), loaded into PostgreSQL. Calculated columns updated via database triggers and batch functions. All timestamps use timestamptz and correctly handle DST transitions. Preprocessing: Anonymization of name, user, account, submit_line, work_dir, submit_script, and job_type via 7-char hex hashes Derived columns: queue_wait, cpu_eff, max/min/avg_mem_eff, energy estimates Simplified job state mapping (e.g., "CANCELLED by 132357" → "CANCELLED") Boolean flags: python_job, reframe_job Temporal decomposition: year, month, day, day_of_week, hour, minute from submit_time Shared node tracking: shared_job_count, nodes_shared, jobs_shared Key Variables: Scheduling: job_id, partition, state_simple, submit_time, start_time, end_time, queue_wait Resources: nodes_req/used, processors_req/used, memory_req, wallclock_req/used, gpus_requested Efficiency: cpu_eff, max/min/avg_mem_eff Energy: cpu_energy_tdp_estimated_max/used_watt_hours, consumed_energy_raw_joules, consumed_energy_raw_watt_hours Sharing: shared_job_count, nodes_shared, jobs_shared Partitions: short, standard, debug, gpu-h100 Job States: CANCELLED, COMPLETED, FAILED, PENDING, RUNNING QoS Levels: normal, high Important Notes: Timestamps include timezone offsets; DST transitions are handled correctly, though adding intervals across DST boundaries requires offset adjustment shared_job_count reflects physical node co-residency, not use of the shared partition Job step records and raw Slurm JSONB fields are excluded Do not attempt to re-identify individuals from hashed fields

97 MATHEMATICS AND COMPUTING↗

Large-Scale Features of Pliocene Climate: Results from the Pliocene Model Intercomparison Project

Climate and environments of the mid-Pliocene warm period (3.264 to 3.025 Ma) have been extensively studied.Whilst numerical models have shed light on the nature of climate at the time, uncertainties in their predictions have not been systematically examined. The Pliocene Model Intercomparison Project quantifies uncertainties in model outputs through a coordinated multi-model and multi-mode data intercomparison. Whilst commonalities in model outputs for the Pliocene are clearly evident, we show substantial variation in the sensitivity of models to the implementation of Pliocene boundary conditions. Models appear able to reproduce many regional changes in temperature reconstructed from geological proxies. However, data model comparison highlights that models potentially underestimate polar amplification. To assert this conclusion with greater confidence, limitations in the time-averaged proxy data currently available must be addressed. Furthermore, sensitivity tests exploring the known unknowns in modelling Pliocene climate specifically relevant to the high latitudes are essential (e.g. palaeogeography, gateways, orbital forcing and trace gasses). Estimates of longer-term sensitivity to CO2 (also known as Earth System Sensitivity; ESS), support previous work suggesting that ESS is greater than Climate Sensitivity (CS), and suggest that the ratio of ESS to CS is between 1 and 2, with a "best" estimate of 1.5.

mathematical models↗

Predicting Cancer Risk from Ionizing Radiation

The ability to predict cancer risk associated with exposure to low doses of high-LET ionizing radiation (IR) remains a challenge. Epidemiological methods lack the sensitivity and power to provide detailed risk estimates for cancer and ignore individual variance in IR sensitivity. We have hypothesized that DNA repair capacity can be used as a marker to evaluate and differentiate individual radiation sensitivity. More specifically, this work is based on the concept that the combined time-dose dependence of radiation-induced foci (RIF) of p53-binding protein 1 (53BP1) following low-LET exposure contains sufficient information to infer sensitivity to any other LET. Our hypothesis was tested in 15 different mouse strains as well as in primary human immune cells. We first approached individual ionizing radiation sensitivity in a mouse model by culturing primary skin fibroblasts extracted from 76 mice of 15 different genetic backgrounds and exposing them to HZE particles and X-rays. This work is one of the most extensive studies on the kinetics and possible genetic underpinnings of radiation-induced DNA damage and repair. Our results is in agreement with a DNA repair model we previously postulated, where nearby DNA double strand breaks (DSB) in the nucleus are brought together for more efficient repair, leading to RIF clustering. Such mechanism was evidenced by a specific dose and LET dependence of RIF numbers. Briefly, RIF quantification after low-LET X-ray exposure showed an asymptotic saturation for doses between 1 Gy and 4 Gy 4 hours post-irradiation across all 15 strains. The clustering of DSB across all strains also led to more RIF/Gy for lower LET (X-ray and 350 MeV/n Ar) than for higher LET (600 MeV/n Fe) 4 hours post-exposure. Considering the fact that the number of DSB/Gy should be independent of LET, our data suggest there are more DSB in individual RIF as the LET increases. RIF numbers for 24 and 48 hours post-exposure led to the inverse trend, with more remaining RIF/Gy for higher LET (by 600 MeV/n Fe). This result suggests cells have more difficulty resolving RIF from higher LET as they the number DSB/RIF increases. Note that for most conditions, the variance of RIF/Gy was small within individual animals of the same strain and large between strains, suggesting a strong genetics component. Furthermore, we present our preliminary data from an ongoing study on human genetic associations with IR sensitivity. To address the human variability in responses to HZE particle irradiation in a maximally comprehensive manner, we are in the process of collecting and isolating primary blood mononuclear cells from 768 healthy subjects of European descent, 18-75 years of age, 50/50 male/female distribution. We have analyzed 53BP1+ RIF formation as well as oxidative stress and cell death in primary cells from 192 subjects in response to the same HZE particles as used in mice: 600 MeV/n Fe, 350 MeV/n Ar and 350 MeV/n Si, 1.1 and 3 particles/100m2, 4 and 24 hours after irradiation. We will next complete the quantification of HZE particle-induced DNA and cellular damage in the remaining subjects and compare it to their responses to low-LET irradiation. Finally, we will perform GWAS analysis to identify human genomic associations with IR sensitivity and potential targets for biomarker development.

High-LET radiation↗