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At least 919 records · Page 51
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Probing three-dimensional mesoscopic interfacial structures in a single view using multibeam X-ray coherent surface scattering and holography imaging

Abstract Visualizing surface-supported and buried planar mesoscale structures, such as nanoelectronics, ultrathin-film quantum dots, photovoltaics, and heterogeneous catalysts, often requires high-resolution X-ray imaging and scattering. Here, we discovered that multibeam scattering in grazing-incident reflection geometry is sensitive to three-dimensional (3D) structures in a single view, which is difficult in conventional scattering or imaging approaches. We developed a 3D finite-element-based multibeam-scattering analysis to decode the heterogeneous electric-field distribution and to faithfully reproduce the complex scattering and surface features. This approach further leads to the demonstration of hard-X-ray Lloyd’s mirror interference of scattering waves, resembling dark-field, high-contrast surface holography under the grazing-angle scattering conditions. A first-principles calculation of the single-view holographic images resolves the surface patterns’ 3D morphology with nanometer resolutions, which is critical for ultrafine nanocircuit metrology. The holographic method and simulations pave the way for single-shot structural characterization for visualizing irreversible and morphology-transforming physical and chemical processes in situ or operando .

47 OTHER INSTRUMENTATION↗
DOE OSTI2024

Assessing the sensitivity of aerosol mass budget and effective radiative forcing to horizontal grid spacing in E3SMv1 using a regional refinement approach

Abstract. Atmospheric aerosols have important impacts on air quality and the Earth–atmospheric energy balance. However, as computing power is limited, Earth system models generally use coarse spatial grids and parameterize finer-scale atmospheric processes. These parameterizations and the simulation of atmospheric aerosols are often sensitive to model horizontal resolutions. Understanding the sensitivities is necessary for the development of Earth system models at higher resolutions with the deployment of more powerful supercomputers. Using the Energy Exascale Earth System Model (E3SM) version 1, this study investigates the impact of horizontal grid spacing on the simulated aerosol mass budget, aerosol–cloud interactions, and the effective radiative forcing of anthropogenic aerosols (ERFaer) over the contiguous United States. We examine the resolution sensitivity by comparing the nudged simulation results for 2016 from the low-resolution model (LR) and the regional refinement model (RRM). As expected, the simulated emissions of natural dust, sea salt, and marine organic matter are substantially higher in the RRM than in the LR. In addition, RRM simulates stronger aqueous-phase production of sulfate through the enhanced oxidation of sulfur dioxide by hydrogen peroxide due to increased cloud liquid water content. In contrast, the gas-phase chemical production of sulfate is slightly suppressed. The RRM resolves more large-scale precipitation and produces less convective precipitation than the LR, leading to increased (decreased) aerosol wet scavenging by large-scale (convective) precipitation. Regarding aerosol effects on clouds, RRM produces larger temporal variabilities in the large-scale liquid cloud fractions than LR, resulting in increased microphysical cloud processing of aerosols (more interstitial aerosols are converted to cloud-borne aerosols via aerosol activation) in RRM. Water vapor condensation is also enhanced in RRM compared to LR. Consequently, the RRM simulation produces more cloud droplets, a larger cloud droplet radius, a higher liquid water path, and a larger cloud optical depth than the LR simulation. A comparison of the present-day and pre-industrial simulations indicates that, for this contiguous United States domain, the higher-resolution increases ERFaer at the top of the model by about 12 %, which is mainly attributed to the strengthened indirect effect associated with aerosol–cloud interactions.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRS1977

Unsteady linearized transonic flow analysis for slender bodies

An unsteady linearized formulation based on Oswatitsch-Keune's parabolic method is developed to analyze transonic flow past oscillating slender bodies. In contrast to the widely used integral transform method, it is shown that all solutions can be derived by a simpler method directly in the physical plane. By various expansion procedures, low-frequency solutions then are derived according to two clearly defined frequency ranges. Adams-Sears' iteration is employed to account for the second-order effects. Stability derivatives are compared with available theories and data. It is found that the derivatives depend more sensitively on thickness than on the reduced frequency. Finally, a critical assessment of the present method is given.

Liu, D. D.↗
NASA NTRS1987

The frequency of enhanced star formation in interacting and isolated galaxies

To probe the sensitivity of the star formation rate and extent in galaxies to gravitational encounters, ground based near and mid-infrared and IRAS far-infrared measurements of complete samples of isolated and interacting pairs of galaxies were obtained. The observed infrared properties of the isolated galaxies are used to gauge the magnitude of star formation in galaxies free from external influences, and to define the relationships between morphological type and infrared luminosity. These properties were contrasted with those of the interacting sample to examine the extent to which interactions can enhance or alter the nature of star formation. The mechanisms by which interactions influence activity such as star formation are investigated through correlations of the infrared characteristics with radio and optical measurements, and with morphological and physical parameters such as galaxy types, separations, encounter velocities and interaction types. Limits to the physical extent of the star formation are obtained by comparing the large aperture measurements of IRAS with the small aperture ground based photometry.

Cutri, Roc M.↗
NASA NTRS2011

Blur Clarified: A review and Synthesis of Blur Discrimination

Blur is an important attribute of human spatial vision, and sensitivity to blur has been the subject of considerable experimental research and theoretical modeling. Often these models have invoked specialized concepts or mechanisms, such as intrinsic blur, multiple channels, or blur estimation units. In this paper we review the several experimental studies of blur discrimination and find they are in broad empirical agreement. But contrary to previous modeling efforts, we find that the essential features of blur discrimination are fully accounted for by a visible contrast energy model (ViCE), in which two spatial patterns are distinguished when the integrated difference between their masked local contrast energy responses reaches a threshold value.

Watson, Andrew B.↗
NASA NTRS2022

Effects of Increasing the Category Resolution of the Sea Ice Thickness Distribution in a Coupled Climate Model on Arctic and Antarctic Sea Ice Mean State

Many modern sea ice models used in global climate models represent the subgrid-scale heterogeneity in sea ice thickness with an ice thickness distribution (ITD), which improves model realism by representing the significant impact of the high spatial heterogeneity of sea ice thickness on thermodynamic and dynamic processes. Most models default to five thickness categories. However, little has been done to explore the effects of the resolution of this distribution (number of categories) on sea-ice feedbacks in a coupled model framework and resulting representation of the sea ice mean state. Here, we explore this using sensitivity experiments in CESM2 with the standard 5 ice thickness categories and 15 ice thickness categories. Increasing the resolution of the ITD in a run with preindustrial climate forcing results in substantially thicker Arctic sea ice year-round. Analyses show that this is a result of the ITD influence on ice strength. With 15 ITD categories, weaker ice occurs for the same average thickness, resulting in a higher fraction of ridged sea ice. In contrast, the higher resolution of thin ice categories results in enhanced heat conduction and bottom growth and leads to only somewhat increased winter Antarctic sea ice volume. The spatial resolution of the ICESat-2 satellite mission provides a new opportunity to compare model outputs with observations of seasonal evolution of the ITD in the Arctic (ICESat-2; 2018–2021). Comparisons highlight significant differences from the ITD modeled with both runs over this period, likely pointing to underlying issues contributing to the representation of average thickness.

Madison M. Smith↗
NASA NTRS2018

Weak Hydrological Sensitivity to Temperature Change over Land, Independent of Climate Forcing

We present the global and regional hydrological sensitivity (HS) to surface temperature changes, for perturbations to CO2, CH4, sulfate and black carbon concentrations, and solar irradiance. Based on results from ten climate models, we show how modeled global mean precipitation increases by 2-3% per kelvin of global mean surface warming, independent of driver, when the effects of rapid adjustments are removed. Previously reported differences in response between drivers are therefore mainly ascribable to rapid atmospheric adjustment processes. All models show a sharp contrast in behavior over land and over ocean, with a strong surface temperature-driven (slow) ocean HS of 3-5%/K, while the slow land HS is only 0-2%/K. Separating the response into convective and large-scale cloud processes, we find larger inter-model differences, in particular over land regions. Large-scale precipitation changes are most relevant at high latitudes, while the equatorial HS is dominated by convective precipitation changes. Black carbon stands out as the driver with the largest inter-model slow HS variability, and also the strongest contrast between a weak land and strong sea response. We identify a particular need for model investigations and observational constraints on convective precipitation in the Arctic, and large-scale precipitation around the Equator.

Samset, B. H.↗
NASA NTRS2022

Direct Imaging and Spectroscopy of Exoplanetary Systems with the JWST Early Release Science Program

The direct characterization of exoplanetary systems with high contrast imaging is among the highest priorities for the broader exoplanet community. As large space missions will be necessary for detecting and characterizing exo-Earth twins, developing the techniques and technology for direct imaging of exoplanets is a driving focus for the community. For the first time, JWST will directly observe extrasolar planets at mid-infrared wavelengths beyond 5 μm, deliver detailed spectroscopy revealing much more precise chemical abundances and atmospheric conditions, and provide sensitivity to analogs of our solar system ice-giant planets at wide orbital separations, an entirely new class of exoplanet. However, in order to maximise the scientific output over the lifetime of the mission, an exquisite understanding of the instrumental performance of JWST is needed as early in the mission as possible. In this paper, we describe our 55-hour Early Release Science Program that will utilize all four JWST instruments to extend the characterisation of planetary mass companions to ∼15-20 μm as well as image a circumstellar disk in the mid-infrared with unprecedented sensitivity. Our program will also assess the performance of the observatory in the key modes expected to be commonly used for exoplanet direct imaging and spectroscopy, optimize data calibration and processing, and generate representative datasets that will enable a broad user base to effectively plan for general observing programs in future cycles.

Michael W McElwain↗
NASA NTRSDate not supplied

Exploring Radiation, Water and Energy Closure in Key Deep Tropical Regions Over the Last 3 Decades

The closure of global energy and water budgets at various time scales depends heavily upon the on the processes of water and energy exchange in the deep tropics. A key process observed is the change in convection regimes from disorganized convection to organized deep convection. During these periods an imbalance in key tropical regions is observed of water budget terms between observations and atmospheric reanalysis systems, implying that processes are not simulated well. For instance, periods of imbalance in the water budget may be at least partly attributed to precipitation estimates due to the transition between cloud and precipitation systems in which ice cloud affects microwave radar estimates (Lietmann-Niimi et al. 2024, submitted). A recent paper by Hsaio et al (2023, pre-published version) found that the transition process is characterized by wind shear and longwave cloud radiative feedback signatures as well. This is just one example how these processes also affect the radiative fluxes and thus the energy budget at the TOA. In this presentation, we assess the net radiative budget and components in the deep tropics by comparing multiple data products (GEWEX SRB Rel4IP, CERES EBAF/SYN1deg Ed4.2, ISSCP FH, etc.) and describing the temporal variability of energy balance terms across the deep tropics for the period from 1988 to near present in six key oceanic regions. These six key tropical oceanic regions are West Indian Ocean, the south Indian Ocean east, tropical western, central and eastern Pacific Ocean, and Tropical Atlantic Ocean. In these regions we assess the sensitivity of the fluxes as a function of fluctuations in cloud types in response to various larger scale atmospheric processes (e.g. El Niño, Indian Ocean Dipole). We assess this variability of the radiative flux anomalies (including the net TOA, surface and the atmospheric divergence fluxes) against water vapor divergence, cloud properties (include ISCCP “Weather States, Tselioudis et al. 2021) and larger scale wind shear to assess the uncertainties of energy closure in these regions. These are contrasted against the modeled radiative fluxes from ERA-5 and MERRA-2. Ocean buoy measurements of radiative fluxes are utilized to help assess data radiative flux uncertainty over the nearly 40 year period. In general, the variability for overlap periods of these various data products agrees well, but there are significant differences in the net fluxes that vary according to the rendering of surface, atmospheric, aerosol and cloud properties. These differences also affect closure terms and inferences on systematic uncertainties within the observational estimates. We conclude with recommendations for continuing work

Radiation budget↗
DOE OSTI2024

Robust finite-temperature many-body scarring on a quantum computer

Mechanisms for suppressing thermalization in disorder-free many-body systems, such as Hilbert space fragmentation and quantum many-body scars, have recently attracted much interest in foundations of quantum statistical physics and potential quantum information processing applications. However, their sensitivity to realistic effects such as finite temperature remains largely unexplored. Here, we have utilized IBM's Kolkata quantum processor to demonstrate an unexpected robustness of quantum many-body scars at finite temperatures when the system is prepared in a thermal Gibbs ensemble. We identify such robustness in the PXP model, which describes quantum many-body scars in experimental systems of Rydberg atom arrays and ultracold atoms in tilted Bose-Hubbard optical lattices. By contrast, other theoretical models which host exact quantum many-body scars are found to lack such robustness and their scarring properties quickly decay with temperature. Our study sheds light on the important differences between scarred models in terms of their algebraic structures, which impacts their resilience to finite temperature. Published by the American Physical Society 2024

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2021

AlSb as a material for high index contrast nanophotonics

High contrast materials, i.e., materials with a high refractive index and low optical loss, are of wide interest for nanophotonics and metasurface designs at optical and near infrared wavelengths. We explore aluminum antimonide (AlSb) as a high contrast nanophotonic material, using the design of high contrast gratings (HCGs) for low loss dielectric mirrors as an example. The high index of refraction and low absorption coefficient of AlSb in the visible wavelength range enable designs of HCGs that can be effectively optimized to form mirrors with 93.5% reflectivity at red visible wavelengths. We detail a co-sputtering synthesis method for AlSb films, and achieve our target high index of refraction of 3.5 for 635 nm light. We also find that the high sensitivity of AlSb oxidation requires specific handling procedures in developing deposition processes to yield a near zero absorption coefficient.

Bauser, Haley C.↗
NASA NTRS1996

Ocean observations with EOS/MODIS: Algorithm development and post launch studies

An investigation of the influence of stratospheric aerosol on the performance of the atmospheric correction algorithm is nearly complete. The results indicate how the performance of the algorithm is degraded if the stratospheric aerosol is ignored. Use of the MODIS 1380 nm band to effect a correction for stratospheric aerosols was also studied. Simple algorithms such as subtracting the reflectance at 1380 nm from the visible and near infrared bands can significantly reduce the error; however, only if the diffuse transmittance of the aerosol layer is taken into account. The atmospheric correction code has been modified for use with absorbing aerosols. Tests of the code showed that, in contrast to non absorbing aerosols, the retrievals were strongly influenced by the vertical structure of the aerosol, even when the candidate aerosol set was restricted to a set appropriate to the absorbing aerosol. This will further complicate the problem of atmospheric correction in an atmosphere with strongly absorbing aerosols. Our whitecap radiometer system and solar aureole camera were both tested at sea and performed well. Investigation of a technique to remove the effects of residual instrument polarization sensitivity were initiated and applied to an instrument possessing (approx.) 3-4 times the polarization sensitivity expected for MODIS. Preliminary results suggest that for such an instrument, elimination of the polarization effect is possible at the required level of accuracy by estimating the polarization of the top-of-atmosphere radiance to be that expected for a pure Rayleigh scattering atmosphere. This may be of significance for design of a follow-on MODIS instrument. W.M. Balch participated on two month-long cruises to the Arabian sea, measuring coccolithophore abundance, production, and optical properties. A thorough understanding of the relationship between calcite abundance and light scatter, in situ, will provide the basis for a generic suspended calcite algorithm.

Gordon, Howard R.↗
NASA NTRS1997

1,25 (OH)2D3 enhances PTH-induced Ca2+ transients in preosteoblasts by activating L-type Ca2+ channels

We previously demonstrated electrophysiologically that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] shifts the activation threshold of L-type Ca2+ channels in osteoblasts toward the resting potential and prolongs mean open time. Presently, we used single-cell Ca2+ imaging to study the combined effects of 1,25(OH)2D3 and parathyroid hormone (PTH) during generation of Ca2+ transients in fura 2-loaded MC3T3-E1 cells. Pretreatment with 1,25(OH)2D3 concentrations, which alone did not produce Ca2+ transients, consistently enhanced Ca2+ responses to PTH. Enhancement was dose dependent over the range of 1 to 10 nM and was blocked by pretreatment with 5 microM nitrendipine during pretreatment. A 1,25(OH)2D3 analog that activates L-type channels and shifts their activation threshold also enhanced PTH responses. In contrast, an analog devoid of membrane Ca2+ effects did not enhance PTH-induced Ca2+ transients. The PTH-induced Ca2+ transient involved activation of a dihydropyridine-insensitive cation channel that was inhibited by Gd3+. Together, these data suggest that 1,25(OH)2D3 increases osteoblast responsiveness to PTH through rapid modification of L-type Ca2+ channel gating properties, whose activation enhances Ca2+ entry through other channels such as the PTH-responsive, Gd(3+)-sensitive cation channel.

Non-NASA Center↗
DOE OSTI2023

From Layered Antiferromagnet to 3D Ferromagnet: LiMnBi-to-MnBi Magneto-Structural Transformation

Here, the intermetallic compound LiMnBi was synthesized by the two-step solid-state reaction from the elements. The synthesis temperature of 850 K was selected based on in-situ high-temperature powder X-ray diffraction data. LiMnBi crystalizes in the layered-like PbClF structure type (a = 4.3131(7) Å, c = 7.096(1) Å at 100 K, P4/nmm space group, Z = 2). LiMnBi structure is built of the alternating [MnBi] and Li layers, as determined from single-crystal X-ray diffraction data. Magnetic properties measurements and solid-state 7 Li Nuclear Magnetic Resonance data collected for polycrystalline LiMnBi samples indicate the long-range antiferromagnetic ordering of Mn sublattice at ~340 K, with no superconductivity down to 5 K detected. LiMnBi is air- and water-sensitive. In aerobic conditions, Li can be extracted from LiMnBi structure to form Li 2 O/LiOH and MnBi (NiAs structure type, P6 3 /mmc). The obtained MnBi polymorph was previously reported to be one of the strongest rare-earth-free ferromagnets, yet its bulk synthesis in powder form is cumbersome. The proposed magneto-structural transformation from ternary LiMnBi to ferromagnetic MnBi involves condensation of the MnBi4 tetrahedra upon Li deintercalation and is exclusive to LiMnBi. In contrast, ferromagnetic MnBi cannot be obtained from either isostructural NaMnBi and KMnBi, or from the structurally related CaMn 2 Bi 2 . Such a distinctive transformation in the case of LiMnBi is presumed to be due to its fitting reactivity to yield MnBi and favorable interlayer distance between [MnBi] layers, while the interlayer distance in NaMnBi and KMnBi structural analogs is unfavorably long. The studies of delithiation from the layered-like LiMnBi under different chemical environments indicate that the yield of the MnBi depends on the type of solvent used and the kinetics of the reaction. A slow rate and mild reaction media lead to a high fraction of the MnBi product. The saturation magnetization of the “as-prepared” MnBi is ~50 % of the expected value of 81.3 emu/g. Overall, this study adds a missing member to the family of ternary pnictides and illustrates how soft-chemistry methods can be used to obtain “difficult-to-synthesize” compounds.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Deconvoluting Structures of Component Plant Biopolymers Using Deuterium Labeled Brassica oleracea Stems

Several Brassica species are cultivated globally for the production of seed oils as food, lubricants, and increasingly biofuels. The stem and leaf residues of these herbaceous dicotyledonous crops constitute another feedstock for biofuels and other products. Plant cell walls are complex, multipolymeric structures that consist primarily of polysaccharides and lignin. Cellulose chains coalesce to form crystalline microfibrils while the amorphous biopolymers, hemicellulose, and lignin form a network structure and fill the interstitial space. Neutron scattering has been used for the structural study of the assembly and deconstruction of the plant cell walls. However, similar neutron sensitivity of the different amorphous biopolymers has made structural association to individual component biopolymers nontrivial and ambiguous. To improve the association of structural features to specific biopolymer components, partial deuteration of the plant cell wall can be employed to increase the difference in the neutron scattering length density between amorphous carbohydrate and lignin plant polymers. Vegetative stems from partially deuterated Brassica oleracea acephala (kale) plants were obtained commercially, and the plant cell wall structures were studied by contrast-variation small-angle neutron scattering (CV-SANS) and Fourier-transform infrared spectroscopy (FTIR). FTIR results indicated that deuterium substitution for hydrogen in the carbohydrates was higher than that in lignin. By combining CV-SANS and FTIR results, the neutron scattering length density (nSLD) of the polysaccharides and lignin was determined to match nSLD of 65%:35% and 48%:52% D 2 O/H 2 O solvent mixtures, respectively. These nSLD values were higher than the nSLD values of polysaccharides and lignin for H 2 O grown biopolymers. The nSLD increase correlates to replacing about 42.5% of hydrogens present as both C–H and O–H groups in cellulose with deuterium atoms, while only 21% for lignin. In conclusion, this study lays the foundation to use partially deuterated plants to deconvolute structural features of the different component biopolymers, especially cellulose, hemicellulose, and lignin, of the plant cell wall without introducing unintended structural modifications due to the pretreatment extraction processes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Long-term warming in a Mediterranean-type grassland affects soil bacterial functional potential but not bacterial taxonomic composition

Abstract Climate warming is known to impact ecosystem composition and functioning. However, it remains largely unclear how soil microbial communities respond to long-term, moderate warming. In this study, we used Illumina sequencing and microarrays (GeoChip 5.0) to analyze taxonomic and functional gene compositions of the soil microbial community after 14 years of warming (at 0.8–1.0 °C for 10 years and then 1.5–2.0 °C for 4 years) in a Californian grassland. Long-term warming had no detectable effect on the taxonomic composition of soil bacterial community, nor on any plant or abiotic soil variables. In contrast, functional gene compositions differed between warming and control for bacterial, archaeal, and fungal communities. Functional genes associated with labile carbon (C) degradation increased in relative abundance in the warming treatment, whereas those associated with recalcitrant C degradation decreased. A number of functional genes associated with nitrogen (N) cycling (e.g., denitrifying genes encoding nitrate-, nitrite-, and nitrous oxidereductases) decreased, whereas nifH gene encoding nitrogenase increased in the warming treatment. These results suggest that microbial functional potentials are more sensitive to long-term moderate warming than the taxonomic composition of microbial community.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1999

Detection of endogenous alkaline phosphatase activity in intact cells by flow cytometry using the fluorogenic ELF-97 phosphatase substrate

BACKGROUND: The alkaline phosphatase (AP) substrate 2-(5'-chloro-2'-phosphoryloxyphenyl)-6-chloro-4-(3H)-quinazolinone (ELF((R))-97 for enzyme-labeled fluorescence) has been found useful for the histochemical detection of endogenous AP activity and AP-tagged proteins and oligonucleotide probes. In this study, we evaluated its effectiveness at detecting endogenous AP activity by flow cytometry. METHODS: The ELF-97 phosphatase substrate was used to detect endogenous AP activity in UMR-106 rat osteosarcoma cells and primary cultures of chick chondrocytes. Cells were labeled with the ELF-97 reagent and analyzed by flow cytometry using an argon ultraviolet (UV) laser. For comparison purposes, cells were also assayed for AP using a Fast Red Violet LB azo dye assay previously described for use in detecting AP activity by flow cytometry. RESULTS: The ELF-97 phosphatase substrate effectively detected endogenous AP activity in UMR-106 cells, with over 95% of the resulting fluorescent signal resulting from AP-specific activity (as determined by levamisole inhibition of AP activity). In contrast, less than 70% of the fluorescent signal from the Fast Red Violet LB (FRV) assay was AP-dependent, reflecting the high intrinsic fluorescence of the unreacted components. The ELF-97 phosphatase assay was also able to detect very low AP activity in chick chondrocytes that was undetectable by the azo dye method. CONCLUSIONS: The ELF-97 phosphatase assay was able to detect endogenous AP activity in fixed mammalian and avian cells by flow cytometry with superior sensitivity to previously described assays. This work also shows the applicability of ELF-97 to flow cytometry, supplementing its previously demonstrated histochemical applications. Copyright 1999 Wiley-Liss, Inc.

Non-NASA Center↗
NASA NTRS2018

Coalescence of DNA Double Strand Breaks Induced by Galactic Cosmic Radiation is Modulated by Genetics in 15 Inbred Strains of Mice

In this manuscript we address the challenges associated with the ability to predict radiation sensitivity associated with exposure to either cosmic radiation or X-rays in a population study, by monitoring DNA damage sensing protein 53BP1 forming small nuclear radiation-induced foci (RIF) as a surrogate biomarker of DNA double strand breaks (DSB). 76 primary skin fibroblasts were isolated from 10 collaborative cross strains and five reference inbred mice (C57Bl/6, BALB/CByJ, B6C3, C3H and CBA/CaJ) and exposed to three different charged nuclei of increasing LET (350 MeV/n Si, 350 MeV/n Ar and 600 MeV/n Fe) and X-ray. Our data brings strong evidence against the classic "contact-first" model where DSBs are assumed to be immobile and repaired at the lesion site. In contrast, our model suggests nearby DSBs move into single repair unit characterized by large RIF before the repair machinery kicks in. Such model has the advantage of being much more efficient molecularly but is poorly suited to deal with cosmic radiation, where energy is concentrated along the particle trajectory, inducing a large density of DSBs along each particle track. In accordance with this model, RIF quantification after X-ray exposition showed a saturated dose response for early time points post-irradiation for all strains. Similarly, the high-LET response showed that RIF number matched the number of track per cell, not the number of expected DSB per cell (1). At the temporal level, we noted that the percentage of unrepaired high-LET tracks over a 48 hour time-course increased with LET, confirming that the DNA repair process becomes more difficult as more DSB coalesce into single RIF. There was also good agreement between persistent RIF levels measured in-vitro in the primary skin cultures and survival levels of T-cells and B-cells collected in blood samples from 10 CC strains 24 hours after 0.1 Gy whole-body dose of X-ray. This suggests that persistent RIF 24 hour post-IR is a good surrogate in-vitro biomarker for in-vivo radiation toxicity. Finally, at the genomic level, large differences in repair rates between strains for high-LET allowed us to identify suggestive genetic loci associated with radiation sensitivity. Interestingly, the two highest LETs provided the most strain variation with a common locus on Chromosome 10 highly enriched for DNA repair associated genes we discussed in detail.

Radiation-Induced Foci↗