Simulation of cellular irradiation with the CENBG microbeam line using GEANT4

Light-ion microbeams provide a unique opportunity to irradiate biological samples at the cellular level and to investigate radiobiological effects at low doses of high LET ionising radiation. Since 1998 a single-ion irradiation facility has been developed on the focused horizontal microbeam line of the CENBG 3.5 MV Van de Graaff accelerator. This setup delivers in air single protons and alpha particles of a few MeV onto cultured cells, with a spatial resolution of a few microns, allowing subcellular targeting. In this paper, we present results from the use of the GEANT4 toolkit to simulate cellular irradiation with the CENBG microbeam line, from the entrance to the microprobe up to the cellular medium.Comment: 6 pages, 8 figures, presented at the 2003 IEEE-NSS conference, Portland, OR, USA, October 20-24, 200

Technical developments for computed tomography on the CENBG nanobeam line

The use of ion microbeams as probes for computedtomography has proven to be a powerful tool for the three-dimensional characterization of specimens a few tens of micrometers in size. Compared to other types of probes, the main advantage is that quantitative information about mass density and composition can be obtained directly, using specific reconstruction codes. At the Centre d’Etudes Nucléaires de Bordeaux Gradignan (CENBG), this technique was initially developed for applications in cellular biology. However, the observation of the cell ultrastructure requires a sub-micron resolution. The construction of the nanobeamline at the Applications Interdisciplinaires des Faisceaux d’Ions en Region Aquitaine (AIFIRA) irradiation facility has opened new perspectives for such applications. The implementation of computedtomography on the nanobeamline of CENBG has required a careful design of the analysis chamber, especially microscopes for precise sample visualization, and detectors for scanning transmission ion microscopy (STIM) and for particle induced X-ray emission (PIXE). The sample can be precisely positioned in the three directions X, Y, Z and a stepper motor coupled to a goniometer ensures the rotational motion. First images of 3D tomography were obtained on a reference sample containing microspheres of certified diameter, showing the good stability of the beam and the sample stage, and the precision of the motion

The Geant4-DNA project

The Geant4-DNA project proposes to develop an open-source simulation software based and fully included in the general-purpose Geant4 Monte Carlo simulation toolkit. The main objective of this software is to simulate biological damages induced by ionising radiation at the cellular and sub-cellular scale. This project was originally initiated by the European Space Agency for the prediction of deleterious effects of radiation that may affect astronauts during future long duration space exploration missions. In this paper, the Geant4-DNA collaboration presents an overview of the whole ongoing project, including its most recent developments already available in the last Geant4 public release (9.3 BETA), as well as an illustration example simulating the direct irradiation of a chromatin fibre. Expected extensions involving several research domains, such as particle physics, chemistry and cellular and molecular biology, within a fully interdiciplinary activity of the Geant4 collaboration are also discussed.Comment: presented by S. Incerti at the ASIA SIMULATION CONFERENCE 2009, October 7-9, 2009, Ritsumeikan University, Shiga, Japa

Allelic Variation of Wheat Flour Allergens in a Collection of Wheat Genotypes

Wheat is the most widely grown crop in the world and provides 20% of the daily protein and food calories for 4.5 billion people. Together with rice, it is the most important food crop in the developing world. In the last decades, various symptoms have been recorded across the population due to the consumption of wheat products, also summarized as "wheat allergy." Wheat allergy is usually reported as a food allergy but can also be a contact allergy as a result of exposure to wheat. Several important wheat allergens have been characterized in the last years through biochemical, immunological, and molecular biological techniques. In the present work, the identification of allelic variation of genes involved in wheat allergy was reported. A collection of wheat genotypes was screened in order to identify new alleles. A total of 14 new alleles were identified forprofilin, triosephosphate-isomerase, dehydrin, glyceraldehyde-3-phosphate-dehydrogenase,α/βgliadin, GluB3-23,andGlutathione transferaseallergen genes (located on chromosomes 1B, 3B, 6A, and homoelogous groups 5 and 7), potentially related to a minor allergenicity and useful in breeding programs

Probucol treatment is associated with an ABCA1-independent mechanism of cholesterol efflux to lipid poor apolipoproteins from foam cell macrophages

Objective Probucol is a cholesterol-lowering agent whose ability to prevent atherosclerosis is currently under study. Herein, we investigate the putative mechanism of probucol by observation of changes in cellular cholesterol efflux and lipid droplet morphology in macrophages. Results The inhibitory activity of probucol was assessed in non-foam or foam cell macrophages expressing ABCA1 generated by treatment with fetal calf serum (FCS) alone or in combination with acetylated LDL, respectively. Probucol inhibited cholesterol efflux to apolipoprotein A-I (apoA-I) by 31.5±0.1% in THP-1 non-foam cells and by 18.5±0.2% in foam cells. In probucol-treated non-foam THP-1 cells, nascent high-density lipoprotein (nHDL) particles with a diameter < 7 nm were generated, while in probucol-treated THP-1 foam cells nHDL particles of > 7 nm in diameter containing cholesterol were produced. Foam cells also displayed a significant accumulation of free cholesterol at the plasma membrane, as measured by percent cholestenone formed. Intracellularly, there was a significant decrease in lipid droplet number and an increase in size in probucol-treated THP-1 foam cells when compared to non-treated cells. Conclusions We report for the first time that probucol is unable to completely inhibit cholesterol efflux in foam cells to the same extent as in non-foam cells. Indeed, functional nHDL is released from foam cells in the presence of probucol. This difference in inhibitory effect could potentially be explained by changes in the plasma membrane pool as well as intracellular cholesterol storage independently of ABCA1

Geant4 physics processes for microdosimetry simulation: design foundation and implementation of the first set of models

New physical processes specific for microdosimetry simulation are under development in the Geant4 Low Energy Electromagnetic package. The first set of models implemented for this purpose cover the interactions of electrons, protons and light ions in liquid water; they address a physics domain relevant to the simulation of radiation effects in biological systems, where water represents an important component. The design developed for effectively handling particle interactions down to a low energy scale and the physics models implemented in the first public release of the software are described

Models of biological effects of radiation in the Geant4 toolkit

A project, named Geant4-DNA, is in progress to extend the Geant4 simulation toolkit to model the effects of radiation with biological systems at cellular and DNA level. The first component implemented in the first development cycle of the project describes the fractional survival of a population of cells irradiated with photons or charged particles. The software system developed provides the user the option to choose among a small set of alternative models for the calculation of mammalian cell survival after irradiation. The flexible design adopted makes the system open to further extension to implement other cell survival models available in literature. The preliminary design of a prototype of the cell survival models implemented and preliminary results in some selected cell lines are described

First results obtained using the CENBG nanobeam line: performances and applications

A high resolution focused beam line has been recently installed on the AIFIRA (“Applications Interdisciplinaires des Faisceaux d’Ions en Région Aquitaine”) facility at CENBG. This nanobeam line, based on a doublet–triplet configuration of Oxford Microbeam Ltd. OM-50™ quadrupoles, offers the opportunity to focus protons, deuterons and alpha particles in the MeV energy range to a sub-micrometer beam spot. The beam optics design has been studied in detail and optimized using detailed ray-tracing simulations and the full mechanical design of the beam line was reported in the Debrecen ICNMTA conference in 2008. During the last two years, the lenses have been carefully aligned and the target chamber has been fully equipped with particle and X-ray detectors, microscopes and precise positioning stages. The beam line is now operational and has been used for its firstapplications to ion beam analysis. Interestingly, this set-up turned out to be a very versatile tool for a wide range of applications. Indeed, even if it was not intended during the design phase, the ion optics configuration offers the opportunity to work either with a high current microbeam (using the triplet only) or with a lower current beam presenting a sub-micrometer resolution (using the doublet–triplet configuration). The performances of the CENBGnanobeam line are presented for both configurations. Quantitative data concerning the beam lateral resolutions at different beam currents are provided. Finally, the firstresults obtained for different types of application are shown, including nuclear reaction analysis at the micrometer scale and the firstresults on biological sample

Le Digital Humanities per lo studio e la comunicazione di beni culturali architettonici: il caso dei mausolei di Teodorico e Galla Placidia in Ravenna

The paper presents a series of methodological reflections on the following themes: survey, restitution, analysis and communication. The objective of the research was the critical reading of two of the most famous monuments in Ravenna and UNESCO heritage sites: the Mausoleum of Theodoric (ca. 520 AD) and the Mausoleum of Galla Placidia (before 450 AD). From advanced and integrated survey data, 2D graphs and 3D models were elaborated for hypothesis testing and for the multimedia communication of the scientific contents identified during the work. This second topic of the paper is part of the experiments conducted by the research group on new modes of multimedia communication, interactive and not, based on virtual models as an edutainment tool for enjoying monuments and masterpieces of cultural importance