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At least 37 records · Page 2

Kinematics at the intersection of the Garlock and Death Valley fault zones, California: Integration of TM data and field studies

The Garlock and Death Valley fault zones in SE California are two active strike-slip faults coming together on the east side of the Avawatz Mtns. The kinematics of this intersection, and the possible continuation of either fault zone, are being investigated using a combination of field mapping, and processing and interpretation of remotely sensed image data. Regional and local relationships are derivable from Thematic Mapper data (30 m resolution), including discrimination and relative age dating of alluvial fans, bedrock mapping, and fault mapping. Aircraft data provide higher spatial resolution over more limited areas. Hypotheses being considered are: (1) the Garlock fault extends east of the intersection; (2) the Garlock fault terminates at the intersection and the Death Valley fault continues southeastward; and (3) the Garlock fault has been offset right laterally by the Death Valley fault which continues to the southeast. Preliminary work indicates that the first hypothesis is invalid. From kinematic considerations, image analysis, and field work the third hypothesis is favored. The projected continuation of the Death Valley zone defines the boundary between the Mojave crustal block and the Basin and Range block.

Abrams, Michael↗

Melatonin concentrations in the sudden infant death syndrome

To examine a possible relationship between pineal function and the sudden infant death syndrome (SIDS), samples of whole blood, ventricular cerebrospinal fluid (CSF) and/or vitreous humor (VH) were obtained at autopsy from 68 infants (45 male, 23 female) whose deaths were attributed to either SIDS (n = 32, 0.5-5.0 months of age; mean plus or minus S.E.M., 2.6 plus or minus 0.2 months) or other causes (non-SIDS, n = 36, 0.3-8.0 months of age 4.3 plus or minus 0.3 months). The melatonin concentrations were measured by radioimmunoassay. A significant correlation was observed for melatonin levels in different body fluids from the same individual. After adjusting for age differences, CSF melatonin levels were significantly lower among the SIDS infants (91 plus or minus 29 pmol/l; n = 32) than among those dying from other causes (180 plus or minus 27; n = 35, P less than 0.05). A similar, but non-significant trend was also noted in blood (97 plus or minus 23, n = 30 vs. 144 plus or minus 22 pmol/l, n = 33) and vitreous humor (68 plus or minus 21, n = 10 vs. 81 plus or minus 17 pmol/l, n = 15). These differences do not appear to be explainable in terms of the interval between death and autopsy, gender, premortem infection, or therapeutic measures instituted prior to death. Diminished melatonin production may be characteristic of SIDS and could represent an impairment in the maturation of physiologic circadian organization.

Sturner, W. Q.↗

Imaging Radar in the Mojave Desert-Death Valley Region

The Mojave Desert-Death Valley region has had a long history as a test bed for remote sensing techniques. Along with visible-near infrared and thermal IR sensors, imaging radars have flown and orbited over the area since the 1970's, yielding new insights into the geologic applications of these technologies. More recently, radar interferometry has been used to derive digital topographic maps of the area, supplementing the USGS 7.5' digital quadrangles currently available for nearly the entire area. As for their shorter-wavelength brethren, imaging radars were tested early in their civilian history in the Mojave Desert-Death Valley region because it contains a variety of surface types in a small area without the confounding effects of vegetation. The earliest imaging radars to be flown over the region included military tests of short-wavelength (3 cm) X-band sensors. Later, the Jet Propulsion Laboratory began its development of imaging radars with an airborne sensor, followed by the Seasat orbital radar in 1978. These systems were L-band (25 cm). Following Seasat, JPL embarked upon a series of Space Shuttle Imaging Radars: SIRA (1981), SIR-B (1984), and SIR-C (1994). The most recent in the series was the most capable radar sensor flown in space and acquired large numbers of data swaths in a variety of test areas around the world. The Mojave Desert-Death Valley region was one of those test areas, and was covered very well with 3 wavelengths, multiple polarizations, and at multiple angles. At the same time, the JPL aircraft radar program continued improving and collecting data over the Mojave Desert Death Valley region. Now called AIRSAR, the system includes 3 bands (P-band, 67 cm; L-band, 25 cm; C-band, 5 cm). Each band can collect all possible polarizations in a mode called polarimetry. In addition, AIRSAR can be operated in the TOPSAR mode wherein 2 antennas collect data interferometrically, yielding a digital elevation model (DEM). Both L-band and C-band can be operated in this way, with horizontal resolution of about 5 m and vertical errors less than 2 m. The findings and developments of these earlier investigations are discussed.

Farr, Tom G.↗

Independent controls for neocortical neuron production and histogenetic cell death

We estimated the proportion of cells eliminated by histogenetic cell death during the first 2 postnatal weeks in areas 1, 3 and 40 of the mouse parietal neocortex. For each layer and for the subcortical white matter in each neocortical area, the number of dying cells per mm(2) was calculated and the proportionate cell death for each day of the 2-week interval was estimated. The data show that cell death proceeds essentially uniformly across the neocortical areas and layers and that it does not follow either the spatiotemporal gradient of cell cycle progression in the pseudostratified ventricular epithelium of the cerebral wall, the source of neocortical neurons, or the 'inside-out' neocortical neuronogenetic sequence. Therefore, we infer that the control mechanisms of neocortical histogenetic cell death are independent of mechanisms controlling neuronogenesis or neuronal migration but may be associated with the ingrowth, expansion and a system-wide matching of neuronal connectivity. Copyright 2000 S. Karger AG, Basel.

NASA Discipline Cell Biology↗

Predicting Cell Death and Mutation Frequency for a Wide Spectrum of LET by Assuming DNA Break Clustering Inside Repair Domains

The high relative biological effectiveness (RBE) of high charged and energy (HZE) particles for cell death, DNA mutations and cancer remain based on experimental data. In this work, we propose that the existence of DNA repair domains is sufficient to predict both cell death and mutation frequencies for any LET by only taking into account experimental data from low-LET, offering one mechanism for RBE across LET. We hypothesize that whenever multiple DNA double-strand breaks (DSBs) are generated within the same DNA repair domain, DSBs are actively regrouped for more efficient repair [1]. This hypothesis has been supported by the low-LET sublinear dose response observed at doses greater than ~1Gy for 53BP1 radiation-induced foci (RIF) reflecting increasing DSB/RIF with dose [2]. Previously, we modeled radiation-induced cell death of human breast cells by first inferring the size of these domains from the dose dependence of low-LET RIF, and by associating a lethality factor to the number of pairs of DSBs in each RIF [1]. In this work, we first integrate the new NASA computer models RITCARD (Relativistic Ion Tracks, Chromosome Aberrations, Repair, and Damage) [3] and BDSTracks (Biological Damage by Stochastic Tracks) for a more accurate microdosimetry and a better model of the nuclear organization to predict the location of DSBs. A large array of particles and energy are simulated, covering more than three orders of magnitude for LET (~1-1000 keV/µm). Next, we extend our previous model to predict mutation frequencies by assuming that clustered DSBs increase mutation probability, which is formalized by the mutation frequency being linearly dependent on both the number of DSBs and the number of pairs of DSBs inside individual RIF. Linear coefficients are estimated so that simulations predict accurately mutation frequencies observed in Chinese hamster cells exposed to low-LET. Keeping these coefficients unchanged, we then predict mutation frequencies induced by HZE by simulating DSBs and obtain RBEs for mutations and cell death following the expected experimental bell shape for LET dependence. We also observe an orientation effect that needs to be confirmed, showing different RBE depending on the angle of the HZE beam hitting the main axis of the cell.

Plante, Ianik↗

Intact archeological human bones and age at death studied with transmission x–ray diffraction and small angle x–ray scattering

In this work, high-energy, wide-angle x-ray scattering (WAXS, x-ray diffraction) and small-angle x-ray scattering (SAXS) were used to study intact human second metacarpal bones (mc2) from two UK archeological sites. A novel method correcting for irregular mass distribution was applied in these transmission geometry experiments done at beamline 1-ID of the Advanced Photon Source. The authors asked whether there were age-at-death-related changes in carbonated apatite (cAp) lattice parameters and whether SAXS could detect collagen D-period peaks in the archeological mc2. For each of the two sites, Ancaster and Wharram Percy in England, six female mc2s were studied; for each site, two were from each of three age-at-death cohorts (young, 18-29 years; middle, 30-49 years; old >= 50 years) along with a modern control mc2. The Rietveld method was applied to the WAXS patterns to provide precise lattice parameter values. The cAp lattice parameters did not correlate with age-at-death estimated from dental wear. From WAXS and the 00.2 diffraction peak widths, four archeological mc2s possessed coherently scattering domain lengths (crystallite c-axis sizes) that matched that of the modern mc2; SAXS revealed the same four archeological mc2 had D-period peak intensities equivalent to that of the modern mc2. The other eight archeological mc2s had significantly larger crystallite sizes (than the modern mc2) and weak or absent D-period peaks, differences attributed to diagenetic changes. Based on these data, the authors suggest that WAXS 00.2 peak width and SAXS D-period peak intensity can be used with intact bones to select those likely to retain largely unaltered tissue nanostructure, which might be required for other analyses. Taken as a whole, the results suggest detecting age-related deterioration in nanostructural features may be difficult in bone showing significant bioerosion.

59 BASIC BIOLOGICAL SCIENCES↗

Effects of boundary hydraulics, dissolved oxygen, and dissolved organic carbon on growth and death dynamics of aerobic microbes in riverbed dune-induced hyporheic zones

Surface and groundwater interact in the hyporheic zone beneath and adjacent to rivers in the presence of a diverse microbial community. Heterotrophic bacteria mediate a range of environmentally important reactions, yet few studies have quantified bacterial growth and death dynamics in the hyporheic zone, and none have systematically analyzed their response to variations in hydraulic or chemical conditions. Here we used MODFLOW and SEAM3D to simulate hydraulics; dissolved oxygen (DO) and dissolved organic carbon (DOC) transport; and aerobic microbial metabolism, growth, and death in hyporheic zones induced by riverbed dunes. We ran simulations both with and without growth/death processes, and varied hydraulic parameters and DO/DOC boundary concentrations. Microbial biomass reached steady state (t = 3 days) in every simulation, at which time there was greater biomass and DOC biodegradation rates in the hyporheic flowcell (300% and 85% higher for the base case, respectively) when accounting for microbial growth dynamics. This occurred as microbial biomass tailored its spatial distribution to the availability of DO and DOC, demonstrating the importance of simulating growth/death processes. Biomass generally increased with hyporheic flow cell area as upwelling groundwater decreased. When varying surface water DO and DOC source concentrations relative to the base case, the greatest effect on biomass occurred when increasing DOC and decreasing DO. We determined minimum DO and DOC steady-state concentrations required for microbial growth, but the minimums were not absolute or related by stoichiometry. Increasing DOC created a smaller area of microbes with higher concentrations relative to the base case. Increasing DO slightly increased the area occupied by microbes while keeping the total biomass nearly constant. Overall, microbial growth and death dynamics depend on DO and DOC availability in the hyporheic zone, which is dependent on DOC/DO boundary concentrations and hyporheic flow paths, and in turn the hydraulic interaction between surface water and groundwater.

54 ENVIRONMENTAL SCIENCES↗

Congenital Malformations and Perinatal Deaths Among the Children of Atomic Bomb Survivors: A Reappraisal

From 1948 to 1954, the Atomic Bomb Casualty Commission conducted a study of pregnancy outcomes among births to atomic bomb survivors (Hiroshima and Nagasaki, Japan) who had received radiation doses ranging from 0 Gy to near-lethal levels. Past reports (1956, 1981, and 1990) on the cohort did not identify significant associations of radiation exposure with untoward pregnancy outcomes, such as major congenital malformations, stillbirths, or neonatal deaths, individually or in aggregate. We reexamined the risk of major congenital malformations and perinatal deaths in the children of atomic bomb survivors (n = 71,603) using fully reconstructed data to minimize the potential for bias, using refined estimates of the gonadal dose from Dosimetry System 2002 and refined analytical methods for characterizing dose-response relationships. The analyses showed that parental exposure to radiation was associated with increased risk of major congenital malformations and perinatal death, but the estimates were imprecise for direct radiation effects, and most were not statistically significant. Nonetheless, the uniformly positive estimates for untoward pregnancy outcomes among children of both maternal and paternal survivors are useful for risk assessment purposes, although extending them to populations other than the atomic bomb survivors comes with uncertainty as to generalizability.

60 APPLIED LIFE SCIENCES↗

The core autophagy machinery is not required for chloroplast singlet oxygen-mediated cell death in the Arabidopsis thaliana plastid ferrochelatase two mutant

Chloroplasts respond to stress and changes in the environment by producing reactive oxygen species (ROS) that have specific signaling abilities. The ROS singlet oxygen ( 1 O 2 ) is unique in that it can signal to initiate cellular degradation including the selective degradation of damaged chloroplasts. This chloroplast quality control pathway can be monitored in the Arabidopsis thaliana mutant plastid ferrochelatase two ( fc2 ) that conditionally accumulates chloroplast 1 O 2 under diurnal light cycling conditions leading to rapid chloroplast degradation and eventual cell death. The cellular machinery involved in such degradation, however, remains unknown. Recently, it was demonstrated that whole damaged chloroplasts can be transported to the central vacuole via a process requiring autophagosomes and core components of the autophagy machinery. The relationship between this process, referred to as chlorophagy, and the degradation of 1 O 2 -stressed chloroplasts and cells has remained unexplored. Results To further understand 1 O 2 -induced cellular degradation and determine what role autophagy may play, the expression of autophagy-related genes was monitored in 1 O 2 -stressed fc2 seedlings and found to be induced. Although autophagosomes were present in fc2 cells, they did not associate with chloroplasts during 1 O 2 stress. Mutations affecting the core autophagy machinery ( atg5 , atg7 , and atg10 ) were unable to suppress 1 O 2 -induced cell death or chloroplast protrusion into the central vacuole, suggesting autophagosome formation is dispensable for such 1 O 2 –mediated cellular degradation. However, both atg5 and atg7 led to specific defects in chloroplast ultrastructure and photosynthetic efficiencies, suggesting core autophagy machinery is involved in protecting chloroplasts from photo-oxidative damage. Finally, genes predicted to be involved in microautophagy were shown to be induced in stressed fc2 seedlings, indicating a possible role for an alternate form of autophagy in the dismantling of 1 O 2 -damaged chloroplasts. Conclusions Our results support the hypothesis that 1 O 2 -dependent cell death is independent from autophagosome formation, canonical autophagy, and chlorophagy. Furthermore, autophagosome-independent microautophagy may be involved in degrading 1 O 2 -damaged chloroplasts. At the same time, canonical autophagy may still play a role in protecting chloroplasts from 1 O 2 -induced photo-oxidative stress. Together, this suggests chloroplast function and degradation is a complex process utilizing multiple autophagy and degradation machineries, possibly depending on the type of stress or damage incurred.

59 BASIC BIOLOGICAL SCIENCES↗

Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis

Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death. We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice. We also performed mass spectrometry and fluorescence imaging to determine the localization of lipids and enzyme in islets. RNAi, apoptotic assay, and qPCR were performed to determine the role of a specific factor in lipid-mediated cytokine signaling. Across all three models, lipidomic analyses showed a consistent increase of lysophosphatidylcholine species and phosphatidylcholines with polyunsaturated fatty acids and a reduction of triacylglycerol species. Imaging assays showed that phosphatidylcholines with polyunsaturated fatty acids and their hydrolyzing enzyme phospholipase PLA2G6 are enriched in islets. In downstream signaling, omega-3 fatty acids reduce cytokine-induced β-cell death by improving the expression of ADP-ribosylhydrolase ARH3. The mechanism involves omega-3 fatty acid-mediated reduction of the histone methylation polycomb complex PRC2 component Suz12, upregulating the expression of Arh3, which in turn decreases cell apoptosis. Our data provide insights into the change of lipidomics landscape in β cells during insulitis and identify a protective mechanism by omega-3 fatty acids.

59 BASIC BIOLOGICAL SCIENCES↗

Circulating unmethylated CHTOP and INS DNA fragments provide evidence of possible islet cell death in youth with obesity and diabetes

Circulating unmethylated DNA fragments arising from the human INS gene have been proposed as biomarkers of islet beta-cell death and diabetes risk, but this gene alone does not yield sufficiently specific information to report ß-cell death. We employed an unbiased approach to identify the CHTOP gene as a new candidate biomarker whose CpGs show a greater frequency of unmethylation in human islets. Although both INS and CHTOP contained unmethylated CpG sites in several human tissues, they occurred in a non-overlapping pattern. Based on Naïve Bayes classifier analysis, the two genes used together, however, report 100% specificity for islet damage. Compared to healthy controls, differentially methylated CHTOP and INS levels were higher in youth with new onset type 1 diabetes (T1D) and, unexpectedly, in healthy autoantibody-negative youth who have first-degree relatives with T1D. When tested in youth at risk for type 2 diabetes (T2D), increased levels of unmethylated INS and CHTOP were observed in obese individuals. Our data suggest that concurrent measurement of circulating unmethylated INS and CHTOP detects islet death in youth at risk for both T1D and T2D, and support the use of multiple parameters to increase the confidence of detecting islet damage in at-risk individuals.

59 BASIC BIOLOGICAL SCIENCES↗

AVIRIS study of Death Valley evaporite deposits using least-squares band-fitting methods

Minerals found in playa evaporite deposits reflect the chemically diverse origins of ground waters in arid regions. Recently, it was discovered that many playa minerals exhibit diagnostic visible and near-infrared (0.4-2.5 micron) absorption bands that provide a remote sensing basis for observing important compositional details of desert ground water systems. The study of such systems is relevant to understanding solute acquisition, transport, and fractionation processes that are active in the subsurface. Observations of playa evaporites may also be useful for monitoring the hydrologic response of desert basins to changing climatic conditions on regional and global scales. Ongoing work using Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) data to map evaporite minerals in the Death Valley salt pan is described. The AVIRIS data point to differences in inflow water chemistry in different parts of the Death Valley playa system and have led to the discovery of at least two new North American mineral occurrences. Seven segments of AVIRIS data were acquired over Death Valley on 31 July 1990, and were calibrated to reflectance by using the spectrum of a uniform area of alluvium near the salt pan. The calibrated data were subsequently analyzed by using least-squares spectral band-fitting methods, first described by Clark and others. In the band-fitting procedure, AVIRIS spectra are fit compared over selected wavelength intervals to a series of library reference spectra. Output images showing the degree of fit, band depth, and fit times the band depth are generated for each reference spectrum. The reference spectra used in the study included laboratory data for 35 pure evaporite spectra extracted from the AVIRIS image cube. Additional details of the band-fitting technique are provided by Clark and others elsewhere in this volume.

Crowley, J. K.↗

Integration of AIRSAR and AVIRIS data for Trail Canyon alluvial fan, Death Valley, California

Combining quantitative geophysical information extracted from the optical and microwave wavelengths provides complementary information about both the surface mineralogy and morphology. This study combines inversion results from two remote sensing instruments, a polarimetric synthetic aperture radar, AIRSAR, and an imaging spectrometer, AVIRIS, for Trail Canyon alluvial fan in Death Valley, California. The NASA/JPL Airborne Synthetic Aperture Radar (AIRSAR) is a quad-polarization, three frequency instrument. AIRSAR collects data at C-band = 5.66 cm, L-band = 23.98 cm, and P-band = 68.13 cm. The data are processed to four-looks and have a spatial resolution of 10 m and a swath width of 12 km. The AIRSAR data used in this study were collected as part of the Geologic Remote Sensing Field Experiment (GRSFE) over Death Valley on 9/14/89. The Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) is a NASA/JPL instrument that flies in an ER-2 aircraft at an altitude of 20 km. AVIRIS uses four spectrometers to collect data in 224 spectral channels from 0.4 micrometer to 2.45 micrometer. The width of each spectral band is approximately 10 nm. AVIRIS collects data with a swath width of 11 km and a pixel size of 20 m. The AVIRIS data used in this study were collected over Death Valley on 5/31/92.

Kierein-Young, Kathryn S.↗

Monte Carlo Simulation of Sudden Death Bearing Testing

Monte Carlo simulations combined with sudden death testing were used to compare resultant bearing lives to the calculated hearing life and the cumulative test time and calendar time relative to sequential and censored sequential testing. A total of 30 960 virtual 50-mm bore deep-groove ball bearings were evaluated in 33 different sudden death test configurations comprising 36, 72, and 144 bearings each. Variations in both life and Weibull slope were a function of the number of bearings failed independent of the test method used and not the total number of bearings tested. Variation in L10 life as a function of number of bearings failed were similar to variations in lift obtained from sequentially failed real bearings and from Monte Carlo (virtual) testing of entire populations. Reductions up to 40 percent in bearing test time and calendar time can be achieved by testing to failure or the L(sub 50) life and terminating all testing when the last of the predetermined bearing failures has occurred. Sudden death testing is not a more efficient method to reduce bearing test time or calendar time when compared to censored sequential testing.

Vlcek, Brian L.↗

Cell birth, cell death, cell diversity and DNA breaks: how do they all fit together?

Substantial death of migrating and differentiating neurons occurs within the developing CNS of mice that are deficient in genes required for repair of double-stranded DNA breaks. These findings suggest that large-scale, yet previously unrecognized, double-stranded DNA breaks occur normally in early postmitotic and differentiating neurons. Moreover, they imply that cell death occurs if the breaks are not repaired. The cause and natural function of such breaks remains a mystery; however, their occurrence has significant implications. They might be detected by histological methods that are sensitive to DNA fragmentation and mistakenly interpreted to indicate cell death when no relationship exists. In a broader context, there is now renewed speculation that DNA recombination might be occurring during neuronal development, similar to DNA recombination in developing lymphocytes. If this is true, the target gene(s) of recombination and their significance remain to be determined.

NASA Discipline Cell Biology↗

Predicting Cell Death and Mutation Frequency for a Wide Spectrum of LET by Assuming DNA Break Clustering Inside Repair Domains

Cosmic radiation, which is composed of high charged and energy (HZE) particles, is responsible for cell death and mutation, which may be involved in cancer induction. Mutations are consequences of mis-repaired DNA breaks – especially double-strand breaks (DSBs) – that induce inter- and intra-chromosomal rearrangements (translocations, deletions, inversion). In this study, a computer simulation model is used to investigate the clustering of DSBs in repair domains, previously evidenced by our group in human breast cells [1]. This model is calibrated with experimental data measuring persistent 53BP1 radiation-induced foci (RIF) and is used to explain the high relative biological effectiveness (RBE) of HZE for both cell death and DNA mutation frequencies. We first validate our DSB cluster model using a new track structure model deployed on a simple geometrical configuration for repair domains in the nucleus; then we extend the scope from cell death to mutation induction. This work suggests that mechanism based on DSB repair process can explain several biological effects induced by HZE particles on different type of living cells

Plante, Ianik↗

Predicting cell death and mutation frequency for a wide spectrum of LET and across cell lines from DNA break clustering inside repair domains

Cosmic radiation, which is composed of high charged and energy (HZE) particles, is responsible for cell death and mutation, which may be involved in cancer induction. Mutations are consequences of mis-repaired DNA breaks – especially double-strand breaks (DSBs) – that induce inter- and intra-chromosomal rearrangements (translocations, deletions, inversion). In this study, a computer simulation model is used to investigate the clustering of DSBs in repair domains, previously evidenced by our group in human breast cells. This model is calibrated with experimental data measuring persistent 53BP1 radiation-induced foci (RIF) and is used to explain the high relative biological effectiveness (RBE) of HZE for both cell death and DNA mutation frequencies. We first validate our DSB cluster model using a new track structure model deployed on a simple geometrical configuration for repair domains in the nucleus; then we extend the scope from cell death to mutation induction. This work suggests that mechanism based on DSB repair process can explain several biological effects induced by HZE particles on different type of living cells.

Ianik Plante↗

DNA Break Clustering as a Predictor of Cell Death across Various Radiation Qualities: Influence of Cell Size, Cell Asymmetry, and Beam Orientation

Cosmic radiation, composed of high charge and energy (HZE) particles, causes cellular DNA damage that can result in cell death or mutation that can evolve into cancer. In this work, a cell death model is applied to several cell lines exposed to HZE ions spanning a broad range of linear energy transfer (LET) values. We hypothesize that chromatin movement leads to the clustering of multiple double strand breaks (DSB) within one radiation-induced foci (RIF). The survival probability of a cell population is determined by averaging the survival probabilities of individual cells, which is function of the number of pairwise DSB interactions within RIF. The simulation code RITCARD was used to compute DSB. Two clustering approaches were applied to determine the number of RIF per cell. RITCARD outputs were combined with experimental data from four normal human cell lines to derive the model parameters and expand its predictions in response to ions with LET ranging from ∼0.2keV/μmto∼3000keV/μm. Spherical and ellipsoidal nuclear shapes and two ion beam orientations were modeled to assess the impact of geometrical properties on cell death. The calculated average number of RIF per cell reproduces the saturation trend for high doses and high-LET values that is usually experimentally observed. The cell survival model generates the recognizable bell shape of LET dependence for the relative biological effectiveness (RBE). At low LET, smaller nuclei have lower survival due to increased DNA density and DSB clustering. At high LET, nuclei with a smaller irradiation area either because of a smaller size or a change in beam orientation have a higher survival rate due to a change in the distribution of DSB/RIF per cell. If confirmed experimentally, the geometric characteristics of cells would become a significant factor in predicting radiation-induced biological effects.

cell survival↗