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640 records · Page 36

Electrotropism of maize roots. Role of the root cap and relationship to gravitropism

We examined the kinetics of electrotropic curvature in solutions of low electrolyte concentration using primary roots of maize (Zea mays L., variety Merit). When submerged in oxygenated solution across which an electric field was applied, the roots curved rapidly and strongly toward the positive electrode (anode). The strength of the electrotropic response increased and the latent period decreased with increasing field strength. At a field strength of 7.5 volts per centimeter the latent period was 6.6 minutes and curvature reached 60 degrees in about 1 hour. For electric fields greater than 10 volts per centimeter the latent period was less than 1 minute. There was no response to electric fields less than 2.8 volts per centimeter. Both electrotropism and growth were inhibited when indoleacetic acid (10 micromolar) was included in the medium. The auxin transport inhibitor pyrenoylbenzoic acid strongly inhibited electrotropism without inhibiting growth. Electrotropism was enhanced by treatments that interfere with gravitropism, e.g. decapping the roots or pretreating them with ethyleneglycol-bis-[beta-ethylether]-N,N,N',N' -tetraacetic acid. Similarly, roots of agravitropic pea (Pisum sativum, variety Ageotropum) seedlings were more responsive to electrotropic stimulation than roots of normal (variety Alaska) seedlings. The data indicate that the early steps of gravitropism and electrotropism occur by independent mechanisms. However, the motor mechanisms of the two responses may have features in common since auxin and auxin transport inhibitors reduced both gravitropism and electrotropism.

NASA Discipline Plant Biology↗

Ignition Characterization Test Results for the LO2/Ethanol Propellant Combination

A series of contracts were issued by the Marshall Space Flight Center (MSFC) of the National Aeronautics and Space Administration (NASA) un der the auspices of the Exploration Systems Mission Directorate to de velop and expand the maturity of candidate technologies considered to be important for future space exploration. One such technology was to determine the viability of incorporating non-toxic propellants for R eaction Control Subsystems (RCS). Contract NAS8-01109 was issued to A erojet to develop a dual thrust Reaction Control Engine (RCE) that ut ilized liquid oxygen and ethanol as the propellants. The dual thrust RCE incorporated a primary thrust level of 870 lbf, and a vernier thru st level of 10 - 30 lbf. The preferred RCS approach for the dual thru st RCE was to utilize pressure-fed liquid oxygen (LOX) and ethanol pr opellants; however, previous dual thrust feasibility testing incorporated GOX/Ethanol igniters as opposed to LOX/Ethanol igniters in the de sign. GOX/Ethanol was easier to ignite, but this combination had syst em design implications of providing GOX for the igniters. A LOX/Ethan ol igniter was desired; however, extensive LOX/Ethanol ignition data over the anticipated operating range for the dual thrust RCE did not e xist. Therefore, Aerojet designed and tested a workhorse LOX igniter to determine LOX/Ethanol ignition characteristics as part of a risk m itigation effort for the dual thrust RCE design. The objective of the ignition testing was to demonstrate successful ignition from GOX to LOX, encompassing potential two-phase flow conditions anticipated being present in real mission applications. A workhorse igniter was desig ned to accommodate the full LOX design flowrate, as well as a reduced GOX flowrate. It was reasoned that the initial LOX flow through the igniter would flash to GOX due to the latent heat stored in the hardwa re, causing a reduced oxygen flowrate because of a choked, or sonic, flow condition through the injection elements. As LOX flow continued, the hardware would chill-in, with the injected oxygen flow transitioning from cold GOX through two'phase flow to subcooled LOX. The Workh orse igniter was well instrumented: Pressure and temperature instrumentation permitted oxygen state points to be determined in the igniter oxidizer manifold, and gas-side igniter chamber thermocouples provide d chamber thermal profile characteristics. The cold flow chamber pres sure (Pc) for each test was determined and coupled with the igniter chamber diameter (De) to calculate the characteristic quench parameter (Pc x Dc), which was plotted as a function of core mixture ratio, MRc . Ignition limits were determined over a broad range of valve inlet conditions, and ignition was demonstrated with oxygen inlet conditions that ranged from subcooled 210 deg R LOX to 486 deg R GOX. Once ign ited at cold GOX conditions, combustion was continuous as the hardwar e chilled in and the core mixture ratio transitioned from values near 1.0 to over 12.5. Pulsing is required in typical RCS engines; therefore, the workhorse igniter was pulse tested to verify the ability to pr ovide the required ignition for a pulsing RCE. The minimum electrical pulse width (EPW) of the dual thrust RCE was 0.080 seconds. Igniter pulse tests were performed at three conditions: (1) an EPW of 0.080 se conds at 25% duty cycle for 400 pulses; (2) an EPW of 0.160 seconds a nd a 5% duty cycle for 124 pulses; (3) an EPW of 0.160 seconds and a 50% duty cycle for 380 pulses. Successful ignition of LOX/Ethanol was demonstrated over a broad range of valve inlet conditions, with the empirically determined LOX/Ethanol ignition limits extending the previous database established for GOX/Ethanol ignition limits. Although th e observed chill-in characteristics of the hardware varied significan tly with flowrate, ignition was readily achieved. Combustion was marg inal at extremely fuel-rich conditions, and it fluctuated as the oxygen passed rough the twophase flow regime during the period of hardware chill-in. Pulse testing showed good repeatability with 100 percent r e-ignition for all pulses. Certain pulse-to-pulse repeatability requirements for actual RCS operation may necessitate establishment of mini mum oxygen flow rates and engine thrust levels for satisfactory engin e performance.

Robinson, Philip J.↗

Conditions of the Toll-Like Receptors System of the Human Innate Immunity Cells During the Long-Term Isolation

During long duration missions onboard the International Space Station (ISS), alterations in T cell function and plasma cytokine profiles have been observed. Recent studies involving pattern recognition receptors (PRRs) have established that adaptation of innate immunity to long duration space flight occurs through changes in signal PRRs, Toll-like receptors (TLRs). Despite the fact that fundamental research of PRR molecular biology is far from complete, there are an increasing number of arguments confirming the important role of this system in regulating the initial stages of the adaptive immune response, as well as in the formation of autoimmune and allergic diseases. Long duration isolation is widely used by NASA as an analog for space flight with previous missions including several Antarctic bases, an undersea research station (NEEMO), and other isolation chambers. ‘SIRIUS’ is a multi-compartment pressurized facility at the IMBP in Moscow, Russia, in which subjects will spend 8 months executing tasks similar to those performed by astronauts in space. Prolonged isolation studies like SIRIUS replicate many of the influences expected to occur during long duration spaceflight missions including isolation, stress, confinement, and living in remote conditions. The immune study to be performed on the upcoming SIRIUS mission is being led by Dr. Sergey Ponomarev at the Institute of Biomedical Problems in Moscow, Russia. The NASA JSC Immunology lab will provide analysis of immune cell function, serum cytokines and stress hormones, and salivary cortisol, cytokines, and viruses. This study will be conducted with SIRIUS subjects under the auspices of the parent program. The goal of the study is to evaluate the effect of the 8-month isolation mission on components of human innate immunity at the molecular and cellular level. Successful implementation and completion of this project will provide a unique assortment of new data, significantly expanding the current understanding of the molecular and cellular changes in TLRs during long-term isolation. We hypothesize that mission-like isolation in the Russian NEK facility, consisting of circadian misalignment, isolation, stress, and ‘station lifestyle’, will result in a pattern of immune dysregulation similar to that observed in astronauts onboard ISS. This pattern of alterations can be summarized as phenotypic changes (altered distribution of peripheral cytotoxic, central memory, CD8+ T cell subsets), reductions in T cell function, alterations in plasma cytokine profiles (increased inflammatory and certain chemokines), and reductions in mitogen stimulated cytokine profiles (spans Th1, Th2, Th17). We further hypothesize that these immune changes will correlate with the reactivation of latent herpesviruses (which persists during orbital flight), to be used as measurable adverse clinical manifestation or with other observed symptomology. The SIRIUS-21 mission began in November of 2021 and successfully concluded with the crew emerging in July of 2022. Currently, the logistics of shipping the samples from Russia to the United States is being organized.

Cody L Gutierrez↗

The intact capture of hypervelocity dust particles using underdense foams

The impact of a hypervelocity projectile (greater than 3 km/s) is a process that subjects both the impactor and the impacted material to a large transient pressure distribution. The resultant stresses cause a large degree of fragmentation, melting, vaporization, and ionization (for normal densities). The pressure regime magnitude, however, is directly related to the density relationship between the projectile and target materials. As a consequence, a high-density impactor on a low-density target will experience the lowest level of damage. Historically, there have been three different approaches toward achieving the lowest possible target density. The first employs a projectile impinging on a foil or film of moderate density, but whose thickness is much less than the particle diameter. This results in the particle experiencing a pressure transient with both a short duration and a greatly reduced destructive effect. A succession of these films, spaced to allow nondestructive energy dissipation between impacts, will reduce the impactor's kinetic energy without allowing its internal energy to rise to the point where destruction of the projectile mass will occur. An added advantage to this method is that it yields the possibility of regions within the captured particle where a minimum of thermal modification has taken place. Polymer foams have been employed as the primary method of capturing particles with minimum degradation. The manufacture of extremely low bulk density materials is usually achieved by the introduction of voids into the material base. It must be noted, however, that a foam structure only has a true bulk density of the mixture at sizes much larger than the cell size, since for impact processes this is of paramount importance. The scale at which the bulk density must still be close to that of the mixture is approximately equal to the impactor. When this density criterion is met, shock pressures during impact are minimized, which in turn maximizes the probability of survival for the impacting particle. The primary objectives of the experiment are to (1) Examine the morphology of primary and secondary hypervelocity impact craters. Primary attention will be paid to craters caused by ejecta during hypervelocity impacts of different substrates. (2) Determine the size distribution of ejecta by means of witness plates and collect fragments of ejecta from craters by means of momentum-sensitive mcropore foam. (3) Assess the directionality of the flux by means of penetration-hole alignment of thin films placed above the cells. (4) Capture intact the particles that perforated the thin film and entered the cell. Capture media consisted of both previously flight-tested micropore foams and aerogel. The foams had different latent heats of fusion and, accordingly, will capture particles over a range of momenta. Aerogel was incorporated into the cells to determine the minimum diameter than can be captured intact.

Maag, Carl R.↗

Convective Systems Over the South China Sea: Cloud-Resolving Model Simulations

The South China Sea Monsoon Experiment (SCSMEX) was conducted in May-June 1998. One of its major objectives is to better understand the key physical processes for the onset and evolution of the summer monsoon over Southeast Asia and southern China. Multiple observation platforms (e.g., upper-air soundings, Doppler radar, ships, wind profilers, radiometers, etc.) during SCSMEX provided a first attempt at investigating the detailed characteristics of convective storms and air pattern changes associated with monsoons over the South China Sea region. SCSMEX also provided rainfall estimates which allows for comparisons with those obtained from the Tropical Rainfall Measuring Mission (TRMM), a low earth orbit satellite designed to measure rainfall from space. The Goddard Cumulus Ensemble (GCE) model (with 1-km grid size) is used to understand and quantify the precipitation processes associated with the summer monsoon over the South China Sea. This is the first (loud-resolving model used to simulate precipitation processes in this particular region. The GCE-model results captured many of the observed precipitation characteristics because it used a fine grid size. For example, the temporal variation of the simulated rainfall compares quite well to the sounding-estimated rainfall variation. The time and domain-averaged temperature (heating/cooling) and water vapor (drying/ moistening) budgets are in good agreement with observations. The GCE-model-simulated rainfall amount also agrees well with TRMM rainfall data. The results show there is more evaporation from the ocean surface prior to the onset of the monsoon than after the on-~et of monsoon when rainfall increases. Forcing due to net radiation (solar heating minus longwave cooling) is responsible for about 25% of the precipitation in SCSMEX The transfer of heat from the ocean into the atmosphere does not contribute significantly to the rainfall in SCSMEX. Model sensitivity tests indicated that total rain production is reduced 17-18% in runs neglecting the ice phase. The SCSMEX results are compared to other GCE-model-simulated weather systems that developed during other field campaigns (i.e., west Pacific warm pool region, eastern Atlantic region and central USA). Large-scale forcing vie temperature and water vapor tendency, is the major energy source for net condensation in the tropical cases. The effects of large-scale cooling exceed that of large-scale moistening in the west pacific warm pool region and eastern Atlantic region. For SCSMEX, however, the effects of large-scale moistening predominate. Net radiation and sensible and latent hc,it fluxes play a much more important role in the central USA.

Tao, Wei-Kuo↗

Reconstructing Quasar Spectra and Measuring the Lyα Forest with SpenderQ

Quasar spectra carry the imprint of foreground intergalactic medium (IGM) through absorption features. In particular, absorption caused by neutral hydrogen gas, the "Lyα forest," is a key spectroscopic tracer for cosmological analyses used to measure cosmic expansion and test physics beyond the standard model. Despite their importance, current methods for measuring Lyα absorption cannot directly derive the intrinsic quasar continuum and make strong assumptions on its shape, thus distorting the measured Lyα clustering. We present SpenderQ , a ML-based approach for directly reconstructing the intrinsic quasar spectra and measuring the Lyα forest from observations. SpenderQ uses the Spender spectrum autoencoder to learn a compact and redshift-invariant latent encoding of quasar spectra, combined with an iterative procedure to identify and mask absorption regions. To demonstrate its performance, we apply SpenderQ to 400,000 synthetic quasar spectra created to validate the Dark Energy Spectroscopic Instrument Year 1 Lyα cosmological analyses. SpenderQ accurately reconstructs the true intrinsic quasar spectra, including the broad Lyβ, Lyα, SiIV, CIV, and CIII emission lines. Redward of Lyα, SpenderQ provides percent-level reconstructions of the true quasar spectra. Blueward of Lyα, SpenderQ reconstructs the true spectra to < 5%. SpenderQ reproduces the shapes of individual quasar spectra more robustly than the current state-of-the-art. We, thus, expect it will significantly reduce biases in Lyα clustering measurements and enable studies of quasars and their physical properties. SpenderQ also provides informative latent variable encodings that can be used to, e.g., classify quasars with Broad Absorption Lines. Overall, SpenderQ provides a new data-driven approach for unbiased Lyα forest measurements in cosmological, quasar, and IGM studies.

Hahn, ChangHoon [Arizona U., Astron. Dept. - Stewa↗

Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

Background: Immunity, latent herpesvirus reactivation, physiological stress and circadian rhythms were assessed during six month spaceflight onboard ISS. Blood and saliva samples were collected early, mid and late in-flight and returned for immediate analysis. Mid-point study data (10 of 17 planned subjects) will be presented. Results: Some shifts in leukocyte distribution occurred during flight, including alterations in CD8+ T cell maturation. General T cell function was consistently reduced early in-flight. Levels CD8+/IFNg+ producing T cells were depressed early in-flight, and immediately upon landing. Persistent mitogen-dependant reductions were observed in IFNg, IL-17a, IL-10, TNFa and IL-6 production. Monocyte production of IL-10 was reduced, whereas IL-8 levels were increased. Levels of mRNA for the TNFa, IL-6 and IFNg were transiently elevated early in-flight, and the dynamics of TNF and IL-6 gene expression were somewhat antagonistic to their corresponding receptors during flight. The number of virus-specific CD8+ T-cells was measured using MHC tetramers, while their function was measured using intracellular cytokine analysis following peptide stimulation. Both the number and function of EBV-specific cells decreased during flight as compared to preflight levels. The number of CMV-specific T-cells generally increased as the mission progressed while their function was variable. Viral (EBV) load in blood was elevated postflight. Anti-EBV VCA antibodies were significantly elevated by R+0; anti-EA antibodies were not significantly elevated at landing; and anti-CMV antibodies were somewhat elevated during flight. Higher levels of salivary EBV DNA were found during flight. VZV DNA reactivation occurred in ~50 % of astronauts during flight, continuing for up to 30 days post-flight. CMV was shed in 35 % the in-flight and 30% of postflight urine samples of the crewmembers. There was generally a higher level of cortisol as measured in urine and saliva in the astronauts during flight, but plasma cortisol was relatively unchanged during flight. Circadian rhythm of salivary cortisol was altered during flight. Conclusion. Some alterations in immunity do not resolve during six month spaceflight, consequentially resulting in persistent herpesvirus reactivation. Ongoing immune dysregulation may represent specific clinical risks for exploration-class space missions.

Crucian, B. E.↗

Influence of Vegetation Canopy Architecture on Dynamics of Spatiotemporal Light Distribution and its Effect on Land-Biosphere-Atmosphere Fluxes of Energy, Carbon, and Water

The dynamic spatiotemporal distribution of light and micro climatic variables (wind speed, atmospheric CO 2 concentration, humidity, pressure, and air temperature) within the plant canopy as determined by the canopy architecture play a critical role in land-biosphere-atmosphere (LBA) photosynthetic carbon uptake, transpiratory water loss and energy partitioning. Vegetation models that include effects of sun and shade flecks, leaf temperature and energy balance partitioning between sensible and latent heat fluxes, and reduced turbulent mixing in dense vegetation canopies can accurately predict canopy performance, particularly its shaded leaves, which can constitute 80% of leaf area and contribute up to 50% of carbon update and 65% of water loss. However, current vegetation models with their bulk characterization of shaded leaves poorly represent the complex three dimensional (3D) canopy architecture are insufficient to capture the spatiotemporal dynamics of shaded leaves. Here, we propose to employ an x-ray computed tomography (XCT) imaging technique in combination with an automated, high throughput, image processing pipeline (3DArch, to be developed) to obtain an explicit 3D triangulated surface mesh of a plant canopy (Fig 1). 3DArch would provide a much needed technological jump in 3D LBA modeling where computer generated artificial 3D models suffer from lack of high resolution detailed canopy architecture parameters. The 3D canopy surface mesh output from 3DArch is coupled with an explicit 3D forward ray tracing model (fastTracer) to obtain a high resolution representation of the dynamic spatiotemporal light environment within the canopy over the course of a day (Fig 1). The results from the light attenuation model are then coupled with a process based multi-scale bio-physical canopy and leaf model of photosynthesis (PlantGro) to get fluxes of carbon, water and energy at the leaf and canopy scale, in addition to estimating whole plant carbon uptake, and water loss. Our proposed model framework would be the first of its kind to provide a breakthrough capability in the field of process-based plant modeling that bridges the key technological gap in shaded leaf modeling through explicit representation of 3D canopy architecture. Computer generated artificial 3D model canopy simulations on grasses show that the canopy light distribution does not follow an exponential behavior as assumed in most 1D vegetation models, but rather exhibits a heterogeneous behavior, with a small but significant portion of interior canopy leaves experiencing peak light levels due to sun flecks while the rest of the canopy receives substantially lower light levels. These results indicate a bias in traditional models that overestimates shaded leaf contribution towards whole canopy photosynthesis by up to 15% and underestimate transpiration by up to 12% with an associated increase in sensible heat fluxes since photosynthesis, transpiration and energy partitioning are tightly coupled processes. However, these test results need to be validated using the 3D architecture obtained from a real plant imaged in 3D using 3DArch, rather than an artificial model plant. Our proposed model framework would allow us to identify inefficiencies in canopy light distribution and prescribe optimal canopy architectures (leaf optical properties, leaf area, leaf angles, row spacing, planting density, etc.) to traditional and genetic engineering based crop breeders, for maximizing target functions such as light use efficiency, water use efficiency, drought tolerance, crop yield, crop resilience etc., with important applications in biofuel crops such as sorghum, and switchgrass. Our model can also be applied for designing optimal canopy architecture that increase surface albedo as a mitigation strategy for global warming and projections of crop yield for future food and water security under climate change.

59 BASIC BIOLOGICAL SCIENCES↗

Global Precipitation Measurement (GPM) Mission: Overview and Status

The Global Precipitation Measurement (GPM) Mission is an international satellite mission specifically designed to unify and advance precipitation measurements from a constellation of research and operational microwave sensors. NASA and JAXA will deploy a Core Observatory in 2014 to serve as a reference satellite to unify precipitation measurements from the constellation of sensors. The GPM Core Observatory will carry a Ku/Ka-band Dual-frequency Precipitation Radar (DPR) and a conical-scanning multi-channel (10-183 GHz) GPM Microwave Radiometer (GMI). The DPR will be the first dual-frequency radar in space to provide not only measurements of 3-D precipitation structures but also quantitative information on microphysical properties of precipitating particles. The DPR and GMI measurements will together provide a database that relates vertical hydrometeor profiles to multi-frequency microwave radiances over a variety of environmental conditions across the globe. This combined database will be used as a common transfer standard for improving the accuracy and consistency of precipitation retrievals from all constellation radiometers. For global coverage, GPM relies on existing satellite programs and new mission opportunities from a consortium of partners through bilateral agreements with either NASA or JAXA. Each constellation member may have its unique scientific or operational objectives but contributes microwave observations to GPM for the generation and dissemination of unified global precipitation data products. In addition to the DPR and GMI on the Core Observatory, the baseline GPM constellation consists of the following sensors: (1) Special Sensor Microwave Imager/Sounder (SSMIS) instruments on the U.S. Defense Meteorological Satellite Program (DMSP) satellites, (2) the Advanced Microwave Scanning Radiometer-2 (AMSR-2) on the GCOM-W1 satellite of JAXA, (3) the Multi-Frequency Microwave Scanning Radiometer (MADRAS) and the multi-channel microwave humidity sounder (SAPHIR) on the French-Indian MeghaTropiques satellite, (4) the Microwave Humidity Sounder (MHS) on the National Oceanic and Atmospheric Administration (NOAA)-19, (5) MHS instruments on MetOp satellites launched by the European Organization for the Exploitation of Meteorological Satellites (EUMETSAT), (6) the Advanced Technology Microwave Sounder (ATMS) on the National Polar-orbiting Operational Environmental Satellite System (NPOESS) Preparatory Project (NPP), and (7) ATMS instruments on the NOAA-NASA Joint Polar Satellite System (JPSS) satellites. Data from Chinese and Russian microwave radiometers may also become available through international collaboration under the auspices of the Committee on Earth Observation Satellites (CEOS) and Group on Earth Observations (GEO). The current generation of global rainfall products combines observations from a network of uncoordinated satellite missions using a variety of merging techniques. GPM will provide "next-generation" precipitation products characterized by: (1) more accurate instantaneous precipitation estimate (especially for light rain and cold-season solid precipitation), (2) intercalibrated microwave brightness temperatures from constellation radiometers within a consistent framework, and (3) unified precipitation retrievals from constellation radiometers using a common a priori hydrometeor database constrained by combined radar/radiometer measurements provided by the GPM Core Observatory. GPM is a science mission with integrated applications goals. GPM will provide a key measurement to improve understanding of global water cycle variability and freshwater availability in a changing climate. The DPR and GMI measurements will offer insights into 3-dimensional structures of hurricanes and midlatitude storms, microphysical properties of precipitating particles, and latent heat associated with precipitation processes. The GPM mission will also make data available in near realtime (within 3 hours of observations) forocietal applications ranging from position fixes of storm centers, numerical weather prediction, flood forecasting, freshwater management, landslide warning, crop prediction, to tracking of water-borne diseases. An overview of the GPM mission design, retrieval strategy, ground validation activities, and international science collaboration will be presented.

Hou, Arthur Y.↗

BLOOD-BASED MULTI-SCALE MODEL FOR CANCER RISK FROM GCR IN GENETICALLY DIVERSE POPULATIONS

OBJECTIVES AND METHODS This project addresses the challenge of understanding and predicting individual radiation sensitivity by integrating genetics, demographics and biomarker characteristics across species (mice and humans). We hypothesize that ex vivo DNA repair response to GCR components is a central determinant of cancer risk from space radiation and can serve as a biomarker of radiation risk in combination with genetics. Automated image quantification of 53BP1+ radiation-induced foci (RIF) during the first 4-48 h post-irradiation was performed as a function of dose and LET in non-immortalized primary skin fibroblasts derived from 76 mice across 15 strains (5 inbred reference strains and 10 collaborative-cross strains) exposed to X rays (0.1, 1 and 4 Gy), 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100μm2), as well as in peripheral blood mononuclear cells (PBMCs) from 768 healthy donors (matched ethnicity, 50/50 male/female, 18-70 years old) exposed to gamma rays (0.1 and 1 Gy), 350 MeV/n 28Si, 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100μm2). QUANTIFICATION OF 53BP1+ FOCI IN VITRO AND ASSOCIATIONS TO IN VIVO RADIATION SUSCEPTIBILITY IN 15 MOUSE STRAINS We reported in vitro repair kinetic and repairable fractions of RIF for the 15 mouse strains and introduced a mathematical model for RIF as a function of time, dose and LET. We noted that the metabolic activity of cells modulates the RIF response, and we introduced the open access tool terRIFic (Tool for Enhanced Results of RIF In Cells, https://radbiolab.shinyapps.io/terrific/) to correct for such bias using confluence level. Notably, at 4h post-irradiation, RIF/Gy decreased with dose or LET: as the dose or LET increases, so does the proximity of DNA double-strand-breaks (DSB) and our data suggest that proximal DSBs are brought together inside isolated RIF for repair. The RIF/Gy trend was inverted at 24h, suggesting RIF with high DSB content are more difficult to repair. We showed that in vitro metrics correlate with in vivo measurements in the same 15 mouse strains, such as survival levels of immune cells or spontaneous cancer incidence, suggesting a relationship between the efficiency of DSB repair and cancer risk or radiation toxicity. In addition to the efficiency of repair and persistent RIF, the amount of spontaneous foci before irradiation was also found to be strain dependent. Finally, we performed genome-wide association study in the same 15 mouse strains using all RIF phenotypes measured in vitro, identifying genes of interest and validating RIF as an ideal biomarker for individual radiation sensitivity. BASELINE 53BP1+ FOCI PREDICTS INDIVIDUAL HUMAN RESPONSE TO GCR COMPONENTS Based on the analysis of radiation responses of 576 donor PBMCs (using quantification of 53BP1+ foci, oxidative stress and cell death), we observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing with LET, though oxidative stress being notably reduced by high-LET irradiation, potentially due to a switch between hydrogen peroxide and oxygen radical-based mechanisms. We identified a relationship between few spontaneous DNA foci at baseline and increased DNA repair after irradiation, accompanied by an alteration in immunoregulatory cytokine secretion, which might be adapted as biomarkers to predict ionizing radiation sensitivity. Among demographic variables, only latent cytomegalovirus infection and age were predictive of high baseline foci formation. Finally, we have performed low-throughput whole genome sequencing of all samples and are currently in the process of identifying the genes and pathways associated with low and high-LET ionizing radiation sensitivity in humans.

53BP1↗