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Cell cycle progression can be studied with computational models that allow to describe and predict its perturbation by agents as ionizing radiation or drugs. Such models can then be integrated in tools for pre-clinical/clinical use, e.g. to optimize kinetically-based administration protocols of radiation therapy and chemotherapy.We present a deterministic compartmental model, specifically reproducing how cells that survive radiation exposure are distributed in the cell cycle as a function of dose and time after exposure. Model compartments represent the four cell-cycle phases, as a fuction of DNA content and time. A system of differential equations, whose parameters represent transition rates, division rate and DNA synthesis rate, describes the temporal evolution. Initial model inputs are data from unexposed cells in exponential growth. Perturbation is implemented as an alteration of model parameters that allows to best reproduce cell-cycle profiles post-irradiation. The model is validated with dedicated in vitro measurements on human lung fibroblasts (IMR90). Cells were irradiated with 2 and 5 Gy with a Varian 6 MV Clinac at IRCCS Maugeri. Flow cytometry analysis was performed at the RadBioPhys Laboratory (University of Pavia), obtaining cell percentages in each of the four phases in all studied conditions up to 72 hours post-irradiation.Cells show early G2-phase block (increasing in duration as dose increases) and later G1-phase accumulation. For each condition, we identified the best sets of model parameters that lead to a good agreement between model and experimental data, varying transition rates from G1- to S- and from G2- to M-phase.This work offers a proof-of-concept validation of the new computational tool, opening to its future development and, in perspective, to its integration in a wider framework for clinical use.Author summaryWe implemented a computational model able to describe how the progression in the cell cycle is perturbed when cells are exposed to ionizing radiation. It is known that radiation causes delays or arrest in cell cycle progression, and also that cells that are in different phases of the cycle at the time of exposure show different sensitivity to radiation. Chemotherapeutic drugs also affect cell cycle, and their action can be phase-specific. These findings can be exploited to find the optimal protocol of a combined radiotherapy/chemotherapy cancer treatment: to this aim, we need to know not only the effectiveness of an agent (dose/drug) in terms of cell killing, but also how surviving cells are distributed in the cell cycle. With the model we present, this information can be reproduced as a function of dose and time after radiation exposure. To test the model performance we measured distributions of cells in different phases of the cycle (using flow-cytometry) for human healthy fibroblast cells exposed to X-rays. The results of this work constitute a first step for further development of our model and its future integration in a tool for pre-clinical/clinical use.

The success of any research programme is dependent on a continuing influx of new expertise, and continuing education to ensure the newest technologies and methods are exploited. In the past decade, a strategic approach has been used to build up the research expertise in the area of radiation protection and risk estimation. The High Level Expert Group (HLEG, www.hleg.de) in their 2009 report on European low-dose research asserted that education and training were key components in the development and maintenance of expertise for research into the risks from low-levels of ionising radiation. Following their recommendations, a Euratom-funded Network of Excellence (DoReMi, www.doremi-noe.net) was setup to develop a platform of European research institutions to coordinate the research programme and develop expertise in the area. We present here the activities initiated by DoReMi and currently continued by CONCERT (www.concert-h2020.eu) in support of education and training in the scientific areas underpinning radiation protection research.

Track structure based simulations valuably complement experimental research on biological effects of ionizing radiation. They provide information at the highest level of detail on initial DNA damage induced by diverse types of radiation. Simulations with the biophysical Monte Carlo code PARTRAC have been used for testing working hypotheses on radiation action mechanisms, for benchmarking other damage codes and as input for modelling subsequent biological processes. To facilitate such applications and in particular to enable extending the simulations to mixed radiation field conditions, we present analytical formulas that capture PARTRAC simulation results on DNA single- and double-strand breaks and their clusters induced in cells irradiated by ions ranging from hydrogen to neon at energies from 0.5 GeV/u down to their stopping. These functions offer a means by which radiation transport codes at the macroscopic scale could easily be extended to predict biological effects, exploiting a large database of results from micro-/nanoscale simulations, without having to deal with the coupling of spatial scales and running full track-structure calculations.

The consideration of how a given technique affects results of experimental measurements is a must to achieve correct data interpretation. This might be challenging when it comes to measurements on biological systems, where it is unrealistic to have full control (e.g. through a software replica) of all steps in the measurement chain. In this work we address how the effectiveness of different radiation qualities in inducing biological damage can be assessed measuring DNA damage foci yields, only provided that artefacts related to the scoring technique are adequately considered. To this aim, we developed a unified stochastic modelling approach that, starting from radiation tracks, predicts both the induction, spatial distribution and complexity of DNA damage, and the experimental readout of foci when immunocytochemistry coupled to 2D fluorescence microscopy is used. The approach is used to interpret γ-H2AX data for photon and neutron exposures. When foci are reconstructed in the whole cell nucleus, we obtain information on damage characteristics “behind” experimental observations, as the average damage content of a focus. We reproduce how the detection technique affects experimental findings, e.g. contributing to the saturation of foci yields scored at 30 minutes after exposure with increasing dose and to the lack of dose dependence for yields at 24 hours.

An approach based on track-structure calculations has been developed to take account of artefacts occurring during γ-H2AX foci detection in 2D images of samples analyzed through immunocytochemistry. The need of this works stems from the observed saturation in foci yields measured after X-ray doses higher than few grays, hindering an unambiguous quantification of DNA damage and of radiation effectiveness. The proposed modelling approach allows to simulate the observer's point of view for foci scoring, mimicking the selection of a slice Δz of the cell nucleus due to the microscope depth of field, and applying a clustering algorithm to group together damages within a resolution parameter r. Calculation results were benchmarked with experimental measurements at an early time-point for mouse breast cancer cells, irradiated with X-ray doses in the range 0-5 Gy. The model is able to reproduce the saturation in experimental data.

We present predictions of neutron relative biological effectiveness (RBE) for cell irradiations with neutron beams at PTB-Braunschweig. A neutron RBE model is adopted to evaluate initial DNA damage induction given the neutron-induced charged particle field. RBE values are predicted for cell exposures to quasi-monoenergetic beams (0.56 MeV, 1.2 MeV) and to a broad energy distribution neutron field with dose-averaged energy of 5.75 MeV. Results are compared to what obtained with our RBE predictions for neutrons at similar energies, when a 30-cm sphere is irradiated in an isotropic neutron field. RBE values for experimental conditions are higher for the lowest neutron energies, because, as expected, target geometry determines the weight of the low-effectiveness photon component of the neutron dose. These results highlight the importance of characterizing neutron fields in terms of physical interactions, to fully understand neutron-induced biological effects, contributing to risk estimation and to the improvement of radiation protection standards.

The ANDANTE project began in January 2012 as a spin-off of results of an earlier Euratom project, ALLEGRO, designed to address the problems of medium- and long-term risks following radiotherapy. ANDANTE will investigate the relative risk of induction of cancer from exposure to neutrons compared to photons. The project will focus on three specific cancers that may be detected as second malignant neoplasms following paediatric radiotherapy: salivary gland, thyroid gland, and breast tissue. Stem cells from each of the types of tissue will be exposed to well characterised beams of both neutrons and photons. Biological markers of possible tumorigenesis will be used to develop RBE models for neutrons. The experimental beams will be measured in terms of fluence and energy spectra in order to provide date for a track structure model, which will be developed to simulate the exact experimental conditions and to explore the relationships between exposure parameters and response. The RBE model will be utilized in the assessment of follow-up data from paediatric photon radiotherapy patients. The out-of-beam mixed photon-neutron fields generated during proton therapy will be measured in phantoms, and an analytic algorithm will be developed for reconstructing the fields distant from the treatment site using data available from clinical records. One of the aims of the project is a critical analysis of the potential power of a multi-centre cohort of paediatric patients to give confidence in the neutron risk estimates in radiotherapy patients. This paper focuses on the challenges in the ANDANTE project posed by the need to know detailed neutron, photon, and charged particle fluences and energy spectra in order to determine the neutron RBE as a function of dose and energy.

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/ .

We present a design study for a wearable radiation-shielding spacesuit, designed to protect astronauts’ most radiosensitive organs. The suit could be used in an emergency, to perform necessary interventions outside a radiation shelter in the space habitat in case of a Solar Proton Event (SPE). A wearable shielding system of the kind we propose has the potential to prevent the onset of acute radiation effects in this scenario. In this work, selection of materials for the spacesuit elements is performed based on the results of dedicated GRAS/Geant4 1-dimensional Monte Carlo simulations, and after a trade-off analysis between shielding performance and availability of resources in the space habitat. Water is the first choice material, but also organic compounds compatible with a human space habitat are considered (such as fatty acids, gels and liquid organic wastes). Different designs and material combinations are proposed for the spacesuits. To quantify shielding performance we use GRAS/Geant4 simulations of an anthropomorphic phantom in an average SPE environment, with and without the spacesuit, and we compare results for the dose to Blood Forming Organs (BFO) in Gy-Eq, i.e. physical absorbed dose multiplied by the proton Relative Biological Effectiveness (RBE) for non-cancer effects. In case of SPE occurrence for Intra-Vehicular Activities (IVA) outside a radiation shelter, dose reductions to BFO in the range of 44–57% are demonstrated to be achievable with the spacesuit designs made only of water elements, or of multi-layer protection elements (with a thin layer of a high density material covering the water filled volume). Suit elements have a thickness in the range 2–6 cm and the total mass for the garment sums up to 35–43 kg depending on model and material combination. Dose reduction is converted into time gain, i.e. the increase of time interval between the occurrence of a SPE and the moment the dose limit to the BFO for acute effects is reached. Wearing a radiation shielding spacesuit of the kind we propose, the astronaut could have up to more than the double the time (e.g. almost 6 instead of 2.5 h) to perform necessary interventions outside a radiation shelter during a SPE, his/her exposure remaining within dose limits. An indicative mass saving thanks to the shielding provided by the suits is also derived, calculating the amount of mass needed in addition to the 1.5 cm thick Al module considered for the IVA scenario to provide the same additional shielding given by the spacesuit. For an average 50% dose reduction to BFO this is equal to about 2.5 tons of Al. Overall, our results offer a proof-of-principle validation of a complementary personal shielding strategy in emergency situations in case of a SPE event. Such results pave the way for the design and realization of a prototype of a water-filled garment to be tested on board the International Space Station for wearability. A successful outcome will possibly lead to the further refining of the design of radiation protection spacesuits and their possible adoption in future long-duration manned missions in deep space.

The understanding of the impact of radiation quality in early and late responses of biological targets to ionizing radiation exposure necessarily grounds on the results of mechanistic studies starting from physical interactions. This is particularly true when, already at the physical stage, the radiation field is mixed, as it is the case for neutron exposure. Neutron Relative Biological Effectiveness (RBE) is energy dependent, maximal for energies ~1 MeV, varying significantly among different experiments. The aim of this work is to shed light on neutron biological effectiveness as a function of field characteristics, with a comprehensive modeling approach: this brings together transport calculations of neutrons through matter (with the code PHITS) and the predictive power of the biophysical track structure code PARTRAC in terms of DNA damage evaluation. Two different energy dependent neutron RBE models are proposed: the first is phenomenological and based only on the characterization of linear energy transfer on a microscopic scale; the second is purely ab-initio and based on the induction of complex DNA damage. Results for the two models are compared and found in good qualitative agreement with current standards for radiation protection factors, which are agreed upon on the basis of RBE data.

The investigation of the bystander phenomena (i.e. the induction of damage in cells not directly traversed by radiation) is strictly related to the study of the mechanisms of intercellular communication and of the perturbative effects of radiation. A new possible way to try to solve the bystander puzzle is through a 'systems radiation biology' approach with the total integration of experimental and theoretical activities. In particular, this contribution will focus on: (1) 'ad hoc' experiments designed to quantify key parameters involved in intercellular signalling (focusing, as a pilot study, on release, decay and internalization of interleukine-6 molecules, their modulation by radiation, and possible differences between in vivo/in vitro behaviour); (2) the implementation and the development of two different modelling approaches: a stochastic model (based on a Monte Carlo code) that takes account of the local mechanisms of release and internalization of signalling molecules (e.g. cytokines) and an analytical model where signal molecules are treated as a population and their temporal behaviour is described by differential equations. This approach provided instruments to investigate the complex phenomena of signal transmission and the role of cell communication to guarantee (maintain) the robustness of the in vitro experimental systems against the effects of perturbations.

The PARTRAC code has been developed constantly in the last several years. It is a Monte Carlo code based on an event-by-event description of the interactions taking place between the ionising radiation and liquid water, and in the present version simulates the transport of photons, electrons, protons, helium and heavier ions. This is combined with an atom-by-atom representation of the biological target, i.e. the DNA target model of a diploid human fibroblast in its interphase (genome of 6 Gigabase pairs). DNA damage is produced by the events of energy depositions, either directly, if they occur in the volume occupied by the sugar-phosphate backbone, or indirectly, if this volume is reached by radiation-induced radicals. This requires the determination of the probabilities of occurrence of DNA damage. Experimental data are essential for this determination. However, after the adjustment of the relevant parameters through the comparison of the simulation data with the DNA fragmentation induced by photon irradiation, the code has been used without further parameter adjustments, and the comparison with the fragmentation induced by charged particle beams has validated the code. In this paper, the results obtained for the DNA fragmentation induced by gamma rays and by charged particle beams of various LET are shown, with a particular attention to the production of very small fragments that are not detected in experiments.

We studied the DNA fragmentation induced in human fibroblasts by iron-ion beams of two different energies: 115 MeV/nucleon and 414 MeV/nucleon. Experimental data were obtained in the fragment size range 1-5700 kbp; Monte Carlo simulations were performed with the PARTRAC code; data analysis was also performed through the Generalized Broken Stick (GBS) model. The comparison between experimental and simulated data for the number of fragments produced in two different size ranges, 1-23 kbp and 23-5700 kbp, gives a satisfactory agreement for both radiation qualities. The Monte Carlo simulations also allow the counting of fragments outside the experimental range: The number of fragments smaller than 1 kbp is large for both beams, although with a strong difference between the two cases. As a consequence, we can compute different RBEs depending on the size range considered for the fragment counting. The PARTRAC evaluation takes into account fragments of all sizes, while the evaluation from the experimental data considers only the fragments in the range of 1-5700 kbp. When the PARTRAC evaluation is restricted to this range, the agreement between experimental and computed RBE values is again good. When fragments smaller than 1 kbp are also considered, the RBE increases considerably, since gamma rays produce a small number of such fragments. The analysis performed with the GBS model proved to be quite sensitive to showing, with a phenomenological single parameter, variations in double-strand break (DSB) correlation.

Most accelerator-based space radiation experiments have been performed with single ion beams at fixed energies. However, the space radiation environment consists of a wide variety of ion species with a continuous range of energies. Due to recent developments in beam switching technology implemented at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), it is now possible to rapidly switch ion species and energies, allowing for the possibility to more realistically simulate the actual radiation environment found in space. The present paper discusses a variety of issues related to implementation of galactic cosmic ray (GCR) simulation at NSRL, especially for experiments in radiobiology. Advantages and disadvantages of different approaches to developing a GCR simulator are presented. In addition, issues common to both GCR simulation and single beam experiments are compared to issues unique to GCR simulation studies. A set of conclusions is presented as well as a discussion of the technical implementation of GCR simulation.

In this work we have compared the pattern of DNA fragmentation (in the size range 1–5700 kbp) induced in human fibroblasts by γ-rays with that induced by Fe ions with an energy of 115 MeV/u; Fe ions are considered of biological significance for radiation protection issues during long term astronauts’ travels. The study has taken into account the comparison of the experimental fragmentation spectra, their analysis performed through the implementation of a phenomenological model, and Monte Carlo simulations performed with the PARTRAC code. The phenomenological method characterizes in an approximate but simple way the nonrandom nature of the experimental fragment distribution caused by high LET radiation; it has the advantage to take into account in a detailed way the background fragmentation. The PARTRAC simulations, on the other hand, thanks to the accurate representation of the chromatin geometry and of the physical and physico-chemical processes associated with the energy deposition by radiation, offer the possibility to compute the spectra and to compare them with the experimental data. We found a satisfactory agreement between the experimental data and the results obtained with PARTRAC, recently upgraded with the implementation of ions heavier than alpha particles; this agreement represents a first validation of the code. A relevant result is represented by the very high number of fragments that, according to the Monte Carlo simulations, are produced by iron ions in the size range

The estimation of the risks from low doses of ionizing radiation – including heavy ions – is still a debated question. In particular, the action of heavy ions on biological targets needs further investigation. In this framework, we present a mechanistic model and a Monte Carlo simulation code for the induction of different types of chromosome aberrations. The model, previously validated for gamma rays and light ions, has recently started to be extended to heavy ions such as Iron and Carbon, which are of interest both for space radiation protection and for hadrontherapy. Preliminary results were found to be in agreement with experimental dose–response curves for aberration yields observed following heavy-ion irradiation of human lymphocytes treated with the Premature Chromosome Condensation technique. During the last 10 years, the “Linear No Threshold” hypothesis has been challenged by a large number of observations on the so-called “non-targeted effects” including bystander effect, which consists of the induction of cytogenetic damage in cells not directly traversed by radiation, most likely as a response to molecular messengers released by directly irradiated cells. Although it is now clear that cellular communication plays a fundamental role, our knowledge on the mechanisms underlying bystander effects is still poor, and would largely benefit from further investigations including theoretical models and simulation codes. In the present paper we will review different modelling approaches, including one that is being developed at the University of Pavia, focusing on the assumptions adopted by the various authors and on their implications in terms of low-dose radiation risk, as well as on the identification of “critical” parameters that can modulate the model outcomes.

FLUKA is a Monte-Carlo code able to simulate interaction and transport of hadrons, heavy ions and electromagnetic particles from few keV (or thermal neutron) to cosmic ray energies in whichever material. The highest priority in the design and development of the code has always been the implementation and improvement of sound and modern physical models. A summary of the FLUKA physical models is given, while recent developments are described in detail: among the others, extensions of the intermediate energy hadronic interaction generator, refinements in photon cross sections and interaction models, analytical on-line evolution of radio-activation and remnant dose. In particular, new developments in the nucleus–nucleus interaction models are discussed. Comparisons with experimental data and examples of applications of relevance for space radiation are also provided.

UNLABELLED The usual method for estimating the risk from exposure to neutrons uses the concept of relative biological effectiveness (RBE) compared with the risk from photons, which is better known. RBE has been evaluated using cellular and animal models. But this causes difficulties in applying the concept to humans. The ANDANTE project takes a new approach using three different disciplines in parallel: Physics: a track structure model is used to contrast the patterns of damage to cellular macro-molecules from neutrons compared with photons. The simulations reproduce the same energy spectra as are used in the other two approaches. Stem cell radiobiology: stem cells from thyroid, salivary gland and breast tissue are given well characterised exposures to neutrons and photons. A number of endpoints are used to estimate the relative risk of damage from neutrons compared with photons. Irradiated cells will also be transplanted into mice to investigate the progression of the initial radiation effects in stem cells into tumours in a physiological environment. EPIDEMIOLOGY the relative incidence rates of second cancers of the thyroid, salivary gland and breast following paediatric radiotherapy (conventional radiotherapy for photons and proton therapy for neutrons) are investigated in a pilot single-institution study, exploring the possible design of a multi-institution prospective study comparing the long-term out-of-field and in-field effects of scanned and scattered protons. The results will be used to validate an RBE-based risk model developed by the project, and validate the corresponding RBE values.

Neutron relative biological effectiveness (RBE) is found to be energy dependent, being maximal for energies ∼1 MeV. This is reflected in the choice of radiation weighting factors wR for radiation protection purposes. In order to trace back the physical origin of this behaviour, a detailed study of energy deposition processes with their full dependences is necessary. In this work, the Monte Carlo transport code PHITS was used to characterise main secondary products responsible for energy deposition in a 'human-sized' soft tissue spherical phantom, irradiated by monoenergetic neutrons with energies around the maximal RBE/wR. Thereafter, results on the microdosimetric characterisation of secondary protons were used as an input to track structure calculations performed with PARTRAC, thus evaluating the corresponding DNA damage induction. Within the proposed simplified approach, evidence is suggested for a relevant role of secondary protons in inducing the maximal biological effectiveness for 1 MeV neutrons.

Human exposure to space radiation implies two kinds of risk, both stochastic and deterministic. Shielding optimisation therefore represents a crucial goal for long-term missions, especially in deep space. In this context, the use of radiation transport codes coupled with anthropomorphic phantoms allows to simulate typical radiation exposures for astronauts behind different shielding, and to calculate doses to different organs. In this work, the FLUKA Monte Carlo code and two phantoms, a mathematical model and a voxel model, were used, taking the Galactic Cosmic Rays (GCR) spectra from the model of Badhwar and O'Neill. The time integral spectral proton fluence of the August 1972 Solar Particle Event (SPE) was represented by an exponential function. For each aluminium shield thickness, besides total doses the contributions from primary and secondary particles for different organs and tissues were calculated separately. More specifically, organ-averaged absorbed doses, dose equivalents and a form of 'biological dose', defined on the basis of initial (clustered) DNA damage, were calculated. As expected, the SPE doses dramatically decreased with increasing shielding, and doses in internal organs were lower than in skin. The contribution of secondary particles to SPE doses was almost negligible; however it is of note that, at high shielding (10 g cm(-2)), most of the secondaries are neutrons. GCR organ doses remained roughly constant with increasing Al shielding. In contrast to SPE results, for the case of cosmic rays, secondary particles accounted for a significant fraction of the total dose.

Quantum Molecular Dynamics (QMD) models are considered viable tools to simulate the initial hot stages of heavy-ion collisions and investigate the properties of the nuclear matter equation of state. A new QMD model has been developed by scratch by our group during the last few years and recently coupled to the FLUKA fission/Fermi breakup/ evaporation module which describes the latest stage of the reactions, when slower processes leading nuclei to the equilibrium occur. Comparisons with experimental data collected both in symmetric and in asymmetric collisions are shown, covering a wide range of projectile and target masses. Reproduction of the experimental light particle (Z < 3) yields is one of the most difficult challenges to be met by QMD models, traditionally prone to underestimate a particle emission while dramatically overestimating proton and neutron emission. Our results seem to be quite satisfactory with respect to this issue, thanks to the form of the potential terms involved in the nucleon-nucleon interaction and to many refinements applied in the fragment definition scheme, based on the potential which each particle experiences because of its neighbors. Nucleon isospin is taken into account all over the simulation, as well as the experimental binding energy constraints on nuclear states. The introduction of further refinements to describe pre-equilibrium processes is under development.

Astronauts' exposure to the various components of the space radiation field is of great concern for long-term missions, especially for those in deep space such as a possible travel to Mars. Simulations based on radiation transport/interaction codes coupled with anthropomorphic model phantoms can be of great help in view of risk evaluation and shielding optimisation, which is therefore a crucial issue. The FLUKA Monte Carlo code can be coupled with two types of anthropomorphic phantom (a mathematical model and a ''voxel'' model) to calculate organ-averaged absorbed dose, dose equivalent and ''biological'' dose under different shielding conditions. Herein the ''biological dose'' is represented by the average number of ''Complex Lesions'' (CLs) per cell in a given organ. CLs are clustered DNA breaks previously calculated by means of event-by-event track structure simulations at the nm level and integrated on-line into FLUKA, which adopts a condensed-history approach; such lesions have been shown to play a fundamental role in chromosome aberration induction, which in turn can be correlated with carcinogenesis. Examples of calculation results will be presented relative to Galactic Cosmic Rays, as well as to the August 1972 Solar Particle Event. The contributions from primary ions and secondary particles will be shown separately, thus allowing quantification of the role played by nuclear reactions occurring in the shield and in the human body itself. As expected, the SPE doses decrease dramatically with increasing the Al shielding thickness; nuclear reaction products, essentially due to target fragmentation, are of minor importance. A 10 g/cm2 Al shelter resulted to be sufficient to respect the 30-day limits for deterministic effects recommended for missions in Low Earth Orbit. In contrast with the results obtained for SPEs, the calculated GCR doses are almost independent of the Al shield thickness, and the GCR doses to internal organs are not significantly lower than the skin doses. Furthermore, nuclear interactions play a much larger role for GCR than for SPE doses.

Astronauts’ exposure to space radiation is of high concern for long-term missions, especially for those in deep space such as possible travels to Mars. In these cases shielding optimization is a crucial issue, and simulations based on radiation transport codes and anthropomorphic model phantoms can be of great help. In this work the FLUKA Monte Carlo code was coupled with two anthropomorphic phantoms (a mathematical model and a “voxel” model) to calculate organ-averaged dose, dose equivalent and “biological dose” in the various tissues and organs following exposure to the August 1972 Solar Particle Event and to Galactic Cosmic Rays under different shielding conditions. The “biological dose” was characterized by the average number of induced “Complex Lesions” (CLs) per cell in a given organ or tissue, where CLs are clustered DNA breaks which can play an important role in chromosome aberration induction. Separate calculation of the contributions from secondary hadrons – in particular neutrons – with respect to primary particles allowed us to quantify the role played by nuclear interactions occurring in the shield and in the human body. Specifically for GCR, the contributions from the different components of the incident primary spectra were calculated separately as well. As expected, the SPE doses showed a dramatic decrease with increasing Al shielding. Furthermore, for SPEs internal organs received much lower doses with respect to skin, and nuclear interactions were found to be of minor importance. A 10 g/cm 2 Al storm shelter turned out to be sufficient to respect the NCRP limits for 30-days LEO missions in case of a SPE similar to the August 1972 event. In contrast with SPEs, GCR absorbed doses remained roughly constant with increasing Al shielding. The organ-averaged dose equivalent and biological dose showed a (slight) decrease starting from a shield thickness of 2 g/cm 2 , probably due the lower LET of projectile fragments.

To quantify the role played by radiation track structure and background fragments in modulating DNA fragmentation in human cells exposed to gamma-rays and light ions.Human fibroblasts were exposed in vitro to different doses (in the range from 40 - 200 Gy) of (60)Co gamma-rays and 0.84 MeV protons (Linear Energy Transfer, LET, in tissue 28.5 keV/microm). The resulting DNA fragments were scored under two electrophoretic conditions, in order to optimize separation in the size ranges 0.023 - 1.0 Mbp and 1.0 - 5.7 Mbp. In parallel, DNA fragmentation was simulated both with a phenomenological approach based on the "generalized broken-stick" model, and with a mechanistic approach based on the PARTRAC (acronym of PARticle TRACk) Monte Carlo code (1.32 MeV photons were used for the simulation of (60)Co gamma-rays).For both gamma-rays and protons, the experimental dose response in the range 0.023 - 5.7 Mbp could be approximated as a straight line, the slope of which provided a yield of (5.3 +/- 0.4) x 10(-9) Gy(-1) bp(-1) for gamma-rays and (7.1 +/- 0.6) x 10(-9) Gy(-1) bp(-1) for protons, leading to a Relative Biological Effectiveness (RBE) of 1.3 +/- 0.2. From both theoretical analyses it appeared that, while gamma-ray data were consistent with double-strand breaks (DSB) random induction, protons at low doses showed significant deviation from randomness, implying enhanced production of small fragments in the low molecular weight part of the experimental range. The theoretical analysis of fragment production was then extended to ranges where data were not available, i.e. to fragments larger than 5.7 Mbp and smaller than 23 kbp. The main outcome was that small fragments (23 kbp) are produced almost exclusively via non-random processes, since their number is considerably higher than that produced by a random insertion of DSB. Furthermore, for protons the number of these small fragments is a significant fraction (about 20%) of the total number of fragments; these fragments remain undetected in these experiments. Calculations for 3.3 MeV alpha particle irradiation (for which no experimental data were available) were performed to further investigate the role of fragments smaller than 23 kbp; in this case, besides the non-random character of their production, their number resulted to be at least as much as half of the total number of fragments.Comparison between experimental data and two different theoretical approaches provided further support to the hypothesis of an important role of track structure in modulating DNA damage. According to the theoretical approaches, non-randomness of fragment production was found for proton irradiation for the smaller fragments in the experimental size range and, in a significantly larger extent, for fragments of size less than 23 kbp, both for protons and alpha particles.

The FLUKA Monte Carlo transport code is widely used for fundamental research, radioprotection and dosimetry, hybrid nuclear energy system and cosmic ray calculations. The validity of its physical models has been benchmarked against a variety of experimental data over a wide range of energies, ranging from accelerator data to cosmic ray showers in the earth atmosphere. The code is presently undergoing several developments in order to better fit the needs of space applications. The generation of particle spectra according to up-to-date cosmic ray data as well as the effect of the solar and geomagnetic modulation have been implemented and already successfully applied to a variety of problems. The implementation of suitable models for heavy ion nuclear interactions has reached an operational stage. At medium/high energy FLUKA is using the DPMJET model. The major task of incorporating heavy ion interactions from a few GeV/n down to the threshold for inelastic collisions is also progressing and promising results have been obtained using a modified version of the RQMD-2.4 code. This interim solution is now fully operational, while waiting for the development of new models based on the FLUKA hadron-nucleus interaction code, a newly developed QMD code, and the implementation of the Boltzmann master equation theory for low energy ion interactions. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Distributions of absorbed dose and DNA clustered damage yields in various organs and tissues following the October 1989 solar particle event (SPE) were calculated by coupling the FLUKA Monte Carlo transport code with two anthropomorphic phantoms (a mathematical model and a voxel model), with the main aim of quantifying the role of the shielding features in modulating organ doses. The phantoms, which were assumed to be in deep space, were inserted into a shielding box of variable thickness and material and were irradiated with the proton spectra of the October 1989 event. Average numbers of DNA lesions per cell in different organs were calculated by adopting a technique already tested in previous works, consisting of integrating into "condensed-history" Monte Carlo transport codes--such as FLUKA--yields of radiobiological damage, either calculated with "event-by-event" track structure simulations, or taken from experimental works available in the literature. More specifically, the yields of "Complex Lesions" (or "CL", defined and calculated as a clustered DNA damage in a previous work) per unit dose and DNA mass (CL Gy-1 Da-1) due to the various beam components, including those derived from nuclear interactions with the shielding and the human body, were integrated in FLUKA. This provided spatial distributions of CL/cell yields in different organs, as well as distributions of absorbed doses. The contributions of primary protons and secondary hadrons were calculated separately, and the simulations were repeated for values of Al shielding thickness ranging between 1 and 20 g/cm2. Slight differences were found between the two phantom types. Skin and eye lenses were found to receive larger doses with respect to internal organs; however, shielding was more effective for skin and lenses. Secondary particles arising from nuclear interactions were found to have a minor role, although their relative contribution was found to be larger for the Complex Lesions than for the absorbed dose, due to their higher LET and thus higher biological effectiveness. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

The Monte Carlo track structure code PARTRAC has been further improved by implementing electron scattering cross-sections for liquid water and by explicitly modelling the interaction of water radicals with DNA. The model of the genome inside a human cell nucleus in its interphase is based on the atomic coordinates of the DNA double helix with an additional volume for the water shell. The DNA helix is wound around histone complexes, and these nucleosomes are folded into chromatin fibres and further to fibre loops, which are interconnected to build chromosomes with a territorial organisation. Simulations have been performed for the irradiation of human fibroblast cells with carbon K and aluminium K ultrasoft x-rays, 220 kVp x-rays and 60Co gamma-rays. The ratio single-strand breaks to double-strand breaks (ssb/dsb) for both types of ultrasoft x-rays is lower than for gamma-rays by a factor of 2. The contributions of direct and indirect effects to strand break induction are almost independent of photon energy. Strand break patterns from indirect effects reflect differences in the susceptibility of the DNA helix to OH* attack inside the chromatin fibre. Distributions of small DNA fragments (3 kbp) are determined by the chromatin fibre structure irrespective of whether direct or indirect effects are causing the breaks. In the calculated fragment size distributions for larger DNA fragments (30 kbp), a substantial deviation from random breakage is found only for carbon K irradiation, and is attributed to its inhomogeneous dose distribution inside the cell nucleus. For the other radiation qualities, the results for larger fragments can be approximated by random breakage distributions calculated for a yield of dsb which is about 10% lower than the average for the whole genome. The excess of DNA fragments detected experimentally in the 8-300 kbp region after x-ray irradiation is not seen in our simulation results.

Many different orders of magnitude are involved in the development of radiation-induced biological damage, both at a spatial level (from atomic dimensions to cellular and organ dimensions) and at a temporal level (from the 10 −15 s of the physical interactions to the hours, and possibly years, of the biological processes). This chapter considers the very early events. The following aspects are treated: radiation interaction with matter; the Monte Carlo method; the track structure method, time evolution of the track, including the pre-chemical phase (radiolysis and radical production) and the chemical phase (diffusion and interaction with biological structures); the DNA damage; the microdosimetric approach; and the amorphous track approach. A final section is devoted to the criteria to integrate physical mechanistic investigations and approaches with a systems radiation biology approach.

A methodology is presented, based on proton nuclear activation (PNA), for the contemporary determination of two stable isotopes of ruthenium in biological samples. This technique can be successfully applied in studying the biokinetics of oligoelements, avoiding radiation hazards. On the basis of the possible proton-induced nuclear reactions and the decay characteristics of radioactive products, (p, n) reactions on 99 Ru and 101 Ru resulted to be the most convenient. The minimum detectable quantities resulted to be 15 and 3 ng/ml of plasma respectively. Ru fractional intestinal absorption in an experimental animal was determined, as a feasibility test for applications to humans. Following double tracer technique, one male rabbit was orally given 1 mg of 99 Ru and was injected 78 μg of 101 Ru. Eleven blood samples were drawn within 300 min after administration. Concentrations in plasma samples of intravenously and orally given Ru tracers are reported, as a function of time after administration. Fractional intestinal absorption was determined from concentrations of both isotopes, using the convolution integral technique. A Ru intestinal absorption of (5.5 ± 0.8)% within 300 min from the oral administration was obtained. The results show the effectiveness of this methodology and its applicability for future investigations in humans.

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.

Quantum Molecular Dynamics models (QMD) are Monte Carlo approaches targeted at the description of nucleon-ion and ion-ion collisions. We have developed a QMD code, which has been used for the simulation of the fast stage of ion-ion collisions, considering a wide range of system masses and system mass asymmetries. The slow stage of the collisions has been described by statistical methods. The combination of both stages leads to final distributions of particles and fragments, which have been compared to experimental data available in literature. A few results of these comparisons, concerning neutron double-differential production cross-sections for C, Ne and Ar ions impinging on C, Cu and Pb targets at 290 - 400 MeV/A bombarding energies and fragment isotopic distributions from Xe + Al at 790 MeV/A, are shown in this paper., Comment: 12 pages, 3 figures, submitted for publication in Adv. Space Res

Summary Background and purpose: Theoretical models and Monte Carlo simulations were developed, aimed to investigate the role played by the organisation of interphase DNA and the environmental scavenging capacity conditions in the induction of radiobiological damage. Methods: The induction of single- and double-strand breaks by gamma rays impinging on different DNA structures (e.g. linear DNA, SV40 minichromosome and cellular DNA) was simulated as a function of the environment scavenging capacity. Furthermore, yields of chromosome aberrations (CA) induced by gamma rays and light ions were simulated with a purposely developed MC code that explicitly takes into account the DNA higher-order organisation as chromosome territories. Results and Conclusions: Simulations performed with the PARTRAC code allowed quantification of the dependence of dsb and ssb both on the target structure, and on the scavenging capacity. The results relative to CA showed the importance of DNA damage complexity (nanometre scale) and interphase chromosome domains (micrometre scale) in the process of aberration formation. Very good agreement was found between the model predictions on ssb, dsb and CA and available experimental data.

FLUKA is a multipurpose Monte Carlo code which can transport a variety of particles over a wide energy range in complex geometries. The code is a joint project of INFN and CERN: part of its development is also supported by the University of Houston and NASA. FLUKA is successfully applied in several fields, including but not only, particle physics, cosmic ray physics, dosimetry, radioprotection, hadron therapy, space radiation, accelerator design and neutronics. The code is the standard tool used at CERN for dosimetry, radioprotection and beam-machine interaction studies. Here we give a glimpse into the code physics models with a particular emphasis to the hadronic and nuclear sector.

We present results concerning the study of reactions between light nuclei and quasi‐symmetric reactions between medium‐heavy nuclei at low energies, and relativistic quantum molecular‐dynamics calculations of heavy‐nucleus reactions at intermediate energies.

Tumor treatment with protons and Carbon ions can allow for a better optimization of Tumor Control Probability and Normal Tissue Complication Probability, especially for radio‐resistant tumors. Exposure to protons and heavier ions is also of concern for manned space missions such as future travels to the Moon and Mars. Nuclear reactions with the human body constituents, the beam line components (for hadrontherapy), and the spacecraft walls and shielding (for space radiation protection) can significantly modify the characteristics of the primary radiation field and thus the dose distributions in the various target tissues. In this context the FLUKA Monte Carlo transport code, integrated with radiobiological data and coupled with anthropomorphic phantoms, was applied to the characterization of therapeutic proton beams and the calculation of space radiation organ doses, with focus on the role of nuclear interactions. Besides absorbed and equivalent doses, distributions of “biological” dose (modeled as the ave...

The nuclear reaction models embedded in the FLUKA code cover hadron, ion, photon and neutrino induced nuclear interactions from energies as low as few tens of MeV up to several tens of TeV. A short description of the main physics ingredients in the FLUKA nuclear models is given, with emphasis on the intermediate energy range and on “exotic” reactions. The treatment of electromagnetic dissociation as recently implemented in FLUKA is described. Examples of performances are presented for illustrative situations covering some of the most typical FLUKA applications.

Simulating the space radiation environment with Monte Carlo codes, such as FLUKA, requires the ability to model the interactions of heavy ions as they penetrate spacecraft and crew member's bodies. Monte-Carlo-type transport codes use total interaction cross sections to determine when a particular type of interaction has occurred. Then, at that point, a distinct event generator is employed to determine separately the results of that interaction. The space radiation environment contains a full spectrum of radiation types, including relativistic nuclei, which are the most important component for the evaluation of crew doses. Interactions between incident protons with target nuclei in the spacecraft materials and crew member's bodies are well understood. However, the situation is substantially less comfortable for incident heavier nuclei (heavy ions). We have been engaged in developing several related heavy ion interaction models based on a quantum molecular dynamics-type approach for energies up through about 5 GeV per nucleon (GeV/A) as part of a NASA consortium that includes a parallel program of cross section measurements to guide and verify this code development

The modeling of ion transport and interactions in matter is a subject of growing interest, driven by the continuous increase of possible application fields. These include hadron therapy, dosimetry, and space missions, but there are also several issues involving fundamental research, accelerator physics, and cosmic ray physics, where a reliable description of heavy ion induced cascades is important. In the present work, the capabilities of the fluka code for ion beams will be briefly recalled and some recent developments presented. Applications of the code to the simulation of therapeutic carbon, nitrogen and oxygen ion beams, and of iron beams, which are of direct interest for space mission related experiments, will be also presented together with interesting consideration relative to the evaluation of dosimetric quantities. Both applications involve ion beams in the AGeV range.

Comprehensive analysis of heavy ion reactions at low and intermediate energies is made using the Boltzmann Master Equation theory and a Relativistic Quantum Molecular Dynamics model, respectively. As an example of the large variety of applications of such a study, a result concerning space radiation protection is presented.

Goal of the NASA funded FLEUR project is to develop a simulation tool to predict the impact of radiation environments, in particular to evaluate the effect of shielding in space applications. The heart of this tool is the FLUKA Monte Carlo transport code which is traditionally used in related areas of research such as radio‐protection and dosimetry, cosmic ray physics and modeling of biological effects of radiation on DNA (in connection with further external micro codes). An important aspect in this context are heavy ion nuclear interactions which at this point have been implemented in FLUKA for high and medium energies while work is proceeding to cover the low energy range. Further information is available at http://www.fluka.org and http://fleur.cern.ch

The space radiation environment is a mixed field consisting of different particles having different energies, including high charge and energy (HZE) ions. Conventional measurements of absorbed doses may not be sufficient to completely characterise the radiation field and perform reliable estimates of health risks. Biological dosimetry, based on the observation of specific radiation-induced endpoints (typically chromosome aberrations), can be a helpful approach in case of monitored exposure to space radiation or other mixed fields, as well as in case of accidental exposure. Furthermore, various ratios of aberrations (e.g. dicentric chromosomes to centric rings and complex exchanges to simple exchanges) have been suggested as possible fingerprints of radiation quality, although all of them have been subjected to some criticisms. In this context a mechanistic model and a Monte Carlo code for the simulation of chromosome aberration induction were developed. The model, able to provide dose-responses for different aberrations (e.g. dicentrics, rings, fragments, translocations, insertions and other complex exchanges), was further developed to assess the dependence of various ratios of aberrations on radiation quality. The predictions of the model were compared with available data, whose experimental conditions were faithfully reproduced. Particular attention was devoted to the scoring criteria adopted in different laboratories and to possible biases introduced by interphase death and mitotic delay. This latter aspect was investigated by taking into account both metaphase data and data obtained with Premature Chromosome Condensation (PCC).

The action of neutron fields on biological structures was investigated on the basis of chromosome aberration induction in human cells. Available experimental data on aberration induction by neutrons and their interaction products were reviewed. Present criteria adopted in neutron radiation protection were discussed. The linear coefficient alpha and the quadratic coefficient beta describing dose-response curves for dicentric chromosomes induced by neutrons of different energies were calculated via integration of experimental data on dicentric induction by photons and charged particles into the Monte Carlo transport code FLUKA. The predicted values of the linear coefficients for neutron beams of different energies showed good agreement with the corresponding experimental values, whereas the data themselves indicated that the neutron quadratic coefficient cannot be obtained by 'averaging' the beta values of recoil ions and other nuclear reaction products. This supports the hypothesis that neutron induced aberrations increase substantially linearly with dose, a question that has been object of debate for a long time and is still open.

Knowledge of radiation track structure and its interaction with biological targets is a fundamental starting point in understanding the mechanisms underlying the induction of biological damage. In this context Monte Carlo codes are a powerful tool of investigation, allowing one to simulate both track structure and the features of the target(s) of interest at different scales, from nanometres (linear dimensions of DNA) to micrometres (linear dimensions of human cell nuclei and interphase chromosome territories). In the light of recent experimental findings on nuclear architecture, different approaches in modelling chromosome structure and aberration induction are discussed. In particular, a model is presented in which chromosome territories were explicitly described as subnuclear regions and aberration induction was modelled by coupling the structure of the target with that of the radiation track. Comparisons between model predictions and experimental results from the literature are also reported.

The yield of DNA double-strand breaks (dsb) and DNA complex lesions induced by protons and alpha-particles of various energies was simulated using a Monte Carlo track structure code (MOCA15) and a simple model of the DNA molecule. DNA breaks of different complexity were analysed. The linear energy transfer (LET) and particle-type dependence of lesions of higher complexity seems to confirm the importance of clustered damage in DNA as a relevant step leading to biological endpoints such as cell inactivation. The detailed structure of proton and alpha-particle tracks was analysed to identify the main characteristics possibly responsible for such a dependence. The role of the primary ion and of its secondary electrons in inducing dsb and complex lesions is described, showing that the relative contribution of secondary electron tracks alone in inducing clustered lesions is almost negligible at high LET, but tends to dominate below = 10 keV/micron. This is consistent with the observed similar effectiveness of low-LET fast particle radiation and sparsely ionizing radiation such as x-rays. The dependence on LET and particle type is mainly due to energy deposition events of the primary ion together with short range electrons surrounding the ion track; the yield of complex lesions due to secondary electron tracks alone is substantially LET independent. The radial distributions of the energy contributing to the induction of complex lesions were analyzed and compared with the radial distributions of energy deposition of the full tracks. The results suggest that the stochastic behaviour (i.e. cluster properties) of the energy deposition pattern within a radius of a few nanometers around the ion track plays a relevant role in determining the biological radiation effectiveness.

The use of carbon ions for the treatment of certain tumour types, especially radioresistant tumours, is becoming more frequent due to the carbon- ion dose localization and high relative biological effectiveness (RBE) in the Bragg peak region. Human beings can also be exposed to heavy ions in space, since galactic cosmic rays are a mixed field consisting of not only high-energy protons and He ions, but also heavier ions including iron. Due to their high linear energy transfer (LET), heavy ions have peculiar track structures, characterized by a high level of energy deposition clustering. Furthermore, high-energy ions produce energetic secondary electrons ('delta rays') which can give rise to energy depositions several micrometres away from the core of the primary particle track. Also in view of hadron therapy and space radiation applications, it is therefore important to characterize heavy-ion tracks from a physical and biophysical point of view. In this framework, herein we will discuss the main physical features of heavy-ion track structure, as well as heavy-ion-induced DNA double-strand breaks, which are regarded as one of the most important initial radiobiological lesions and chromosome aberrations, which are correlated both with cell death and with cell conversion to malignancy.

Results which have been recently obtained with the Boltzmann master equation and the FLUKA code in the analysis of heavy ion interactions at relative energies ranging from Coulomb barrier up to a few GeV/n are discussed.

As reported in 2005 Aerospace Conference, the FLUKA Monte Carlo code is being modified as part of NASA's Space Radiation Shielding Program for use in simulating the space radiation environment, in order to evaluate the properties of spacecraft and habitat shielding. Since the last workshop, several notable enhancements have been made to the FLUKA code itself and the ancillary support software. These include improvements to the GUI-based packages for analysis of the results as well as GUI-based tools to ease the setup and running of the programs. Examples of these are presented. From the physics perspective, an accelerator run this July at the AGS was undertaken in collaboration with the groups from LBL and MSFC to measure the fragmentation, neutron and secondary charged particle spectra from Fe, Si and C beams at 3, 5 and 10 GeV/A on a variety of targets including C, Al, Fe, Cu and polyethylene. This energy range is the crossover point in event generator technique and the data help guide the evolution of the event generators in this crucial region. Preliminary results from this run is presented for the angular distribution of the secondary charged particles from scattering angles of 3-45 degrees along with normalized comparisons to RQMD and DPMJET, the event generators that are currently employed within FLUKA.