Track structure, radiation quality and initial radiobiological events: Considerations based on the PARTRAC code experience

Purpose: The role of track structures for understanding the biological effects of radiation has been the subject of research activities for decades. The physics that describes such processes is the core Monte Carlo codes, such as the biophysical PARTRAC (PARticle TRACks) code described in this review, which follow the mechanisms of radiation-matter interaction from the early stage. In this paper a review of the track structure theory (and of its possible extension concerning non-DNA targets) is presented. Materials and methods: The role of radiation quality and track structure is analyzed starting from the heavy ions results obtained with the biophysical Monte Carlo code PARTRAC (PARticles TRACks). PARTRAC calculates DNA damage in human cells based on the superposition of simulated track structures in liquid water to an ‘atom-by-atom’ model of human DNA. Results: Calculations for DNA fragmentation compared with experimental data for different radiation qualities are illustrated. As an example, the strong dependence of the complexity of DNA damage on radiation track structure, and the very large production of very small DNA fragments (lower than 1 kbp (kilo base pairs) usually not detected experimentally) after high LET (high-Linear Energy Transfer) irradiation is shown. Furthermore the possible importance of non-nuclear/non-DNA targets is discussed in the particular case of cellular membrane and mitochondria. Conclusions: The importance of the track structure is underlined, in particular the dependence of a given late cellular effect on the spatial distribution of DNA double-strand breaks (DSB) along the radiation track. These results show that the relative biological effectiveness (RBE) for DSB production can be significantly larger than 1. Moreover the cluster properties of high LET radiation may determine specific initial targets and damage evolution

Simulation of Radiation-Induced Damage Distribution to evaluate Models for Higher-Order Chromosome Organisation

The structure of chromatin at the level of the 30 nm fibre has been studied in considerable detail, but little is known about how this fibre is arranged within the interphase chromosome territory. Over the years, various polymer models were developed to simulate chromosome structure, for example the random-walk/giant-loop (RWGL) model, the multi-loop subcompartment (MLS) model, and the interconnected-fibre-loop model (Friedland et al., 1999). These models differ mainly in the size and arrangement of the chromatin loops and, correspondingly, in the predicted distribution of chromatin density within the nucleus. It occurred to us that densely ionising radiation can be used to probe the actual distribution of chromatin density in human interphase cells. In contrast to sparsely ionising radiation (e.g. X-rays), which induces DNA double-strand breaks (DSB) that are distributed randomly within the nucleus, irradiation with densely ionising accelerated ions leads to spatial clustering of DSB. This inhomogeneity in DSB localisation, together with an inhomogeneity of DNA density within the nucleus, causes an over-dispersion in the resulting distribution of DNA fragment sizes that can be detected by pulsed-field gel electrophoresis. Using the above-mentioned chromosome models, we performed computer simulations to predict the DNA fragment size distributions resulting from irradiation with accelerated ions, and compared the predicted distributions with those obtained experimentally. We found that simulations based on the MLS model, in which local variations in chromatin density are higher than in the other models, resulted in the best agreement between calculation and experiment

The COOLER Code:A Novel Analytical Approach to Calculate Subcellular Energy Deposition by Internal Electron Emitters

COmputation of Local Electron Release (COOLER), a software program designed for dosimetry assessment at the cellular/subcellular scale, with a given distribution of administered low-energy electron-emitting radionuclides in cellular compartments, which remains a critical step in risk/benefit analysis for advancements in internal radiotherapy. The software is intended to overcome the main limitations of the medical internal radiation dose (MIRD) formalism for calculations of cellular S-values (i.e., dose to a target region in the cell per decay in a given source region), namely, the use of the continuous slowing down approximation (CSDA) and the assumption of a spherical cell geometry. To this aim, we developed an analytical approach, entrusted to a MATLAB-based program, using as input simulated data for electron spatial energy deposition directly derived from full Monte Carlo track structure calculations with PARTRAC. Results from PARTRAC calculations on electron range, stopping power and residual energy versus traveled distance curves are presented and, when useful for implementation in COOLER, analytical fit functions are given. Example configurations for cells in different culture conditions (V79 cells in suspension or adherent culture) with realistic geometrical parameters are implemented for use in the tool. Finally, cellular S-value predictions by the newly developed code are presented for different cellular geometries and activity distributions (uniform activity in the nucleus, in the entire cell or on the cell surface), validated against full Monte Carlo calculations with PARTRAC, and compared to MIRD standards, as well as results based on different track structure calculations (Geant4-DNA). The largest discrepancies between COOLER and MIRD predictions were generally found for electrons between 25 and 30 keV, where the magnitude of disagreement in S-values can vary from 50 to 100%, depending on the activity distribution. In calculations for activity distribution on the cell surface, MIRD predictions appeared to fail the most. The proposed method is suitable for Auger-cascade electrons, but can be extended to any energy of interest and to beta spectra; as an example, the (3)H case is also discussed. COOLER is intended to be accessible to everyone (preclinical and clinical researchers included), and may provide important information for the selection of radionuclides, the interpretation of radiobiological or preclinical results, and the general establishment of doses in any scenario, e.g., with cultured cells in the laboratory or with therapeutic or diagnostic applications. The software will be made available for download from the DTU-Nutech website: http://www.nutech.dtu.dk/

Characterizing Operations Preserving Separability Measures via Linear Preserver Problems

We use classical results from the theory of linear preserver problems to characterize operators that send the set of pure states with Schmidt rank no greater than k back into itself, extending known results characterizing operators that send separable pure states to separable pure states. We also provide a new proof of an analogous statement in the multipartite setting. We use these results to develop a bipartite version of a classical result about the structure of maps that preserve rank-1 operators and then characterize the isometries for two families of norms that have recently been studied in quantum information theory. We see in particular that for k at least 2 the operator norms induced by states with Schmidt rank k are invariant only under local unitaries, the swap operator and the transpose map. However, in the k = 1 case there is an additional isometry: the partial transpose map.Comment: 16 pages, typos corrected, references added, proof of Theorem 4.3 simplified and clarifie

Reconciling end-to-end and population concepts for marine ecosystems

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Journal of Marine Systems 83 (2010): 99-103, doi:10.1016/j.jmarsys.2010.06.006.The inherent complexities in the structure and dynamics of marine food webs have led to two major simplifying concepts, a species-centric approach focused on physical processes driving the population dynamics of single species and a trophic-centric approach emphasizing energy flows through broad functional groups from nutrient input to fish production. Here we review the two approaches and discuss their advantages and limitations. We suggest that these concepts are complementary: their applications involve different time scales and distinct aspects of population and community resilience, but their integration is necessary for ecosystem-based managementWe acknowledge NOAA-CICOR award NA17RJ1233 (J.H. Steele) and NSF award OCE0217399 (D.J. Gifford)

Pathways between Primary Production and Fisheries Yields of Large Marine Ecosystems

The shift in marine resource management from a compartmentalized approach of dealing with resources on a species basis to an approach based on management of spatially defined ecosystems requires an accurate accounting of energy flow. The flow of energy from primary production through the food web will ultimately limit upper trophic-level fishery yields. In this work, we examine the relationship between yield and several metrics including net primary production, chlorophyll concentration, particle-export ratio, and the ratio of secondary to primary production. We also evaluate the relationship between yield and two additional rate measures that describe the export of energy from the pelagic food web, particle export flux and mesozooplankton productivity. We found primary production is a poor predictor of global fishery yields for a sample of 52 large marine ecosystems. However, chlorophyll concentration, particle-export ratio, and the ratio of secondary to primary production were positively associated with yields. The latter two measures provide greater mechanistic insight into factors controlling fishery production than chlorophyll concentration alone. Particle export flux and mesozooplankton productivity were also significantly related to yield on a global basis. Collectively, our analyses suggest that factors related to the export of energy from pelagic food webs are critical to defining patterns of fishery yields. Such trophic patterns are associated with temperature and latitude and hence greater yields are associated with colder, high latitude ecosystems

Search for new phenomena in monophoton final states in proton-proton collisions at root s=8 TeV

Peer reviewe

Track structure and DNA damage simulation for light ion energies around the bragg peak

Radiation damage induced by low-energy ions significantly contributes to the high relative biological efficiency (RBE) of ion beams around Bragg peak regions. Further, slow light ions released through nuclear interactions of neutrons are responsible for the wide energy dependence of neutrons’ RBE. In the PARTRAC family of biophysical Monte Carlo codes for simulating track structures, DNA damage and its repair [1], cross sections for ions heavier than helium were scaled from proton data [2] by the effective charge according to Barkas [3]. This procedure, however, is applicable only for specific energies above about 1 MeV/u; it leads to an underestimation of the stopping power at lower energies. To solve this issue, the scaling procedure has been modified so that it reproduces in principle the slowing- down behaviour of protons/hydrogen atoms. Charge changing processes (stripping and subsequent electron pick-up) are considered as ionizations with electron emission with the ion’s velocity. The resulting range and linear energy transfer (LET) values for C, N, O, P and Ca ions agree with ICRU data [4] and SRIM calculations [5]. For the determination of DNA damage yields per unit dose due to carbon ion irradiation, the dose inhomogeneity within the cell nucleus has been taken into account for energies around the Bragg peak. The almost constant yield of strand breaks due to direct effects decreases below about 5 MeV/u. The total induction of DSB has a maximum at the highest LET-values at about 0.5 MeV/u. However, if local clusters of DSB with <20 bp distance are scored as one DSB, the highest yield is found at about 4 MeV/u. Further calculations are underway and results will be presented at the meeting. This work has been supported by the FP7-EURATOM project DoReMi (INITIUM)