Institute for Radiation Protection and Nuclear Safety (IRSN)
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Ionizing radiation has negligible effects on the age, telomere length and corticosterone levels of Chornobyl tree frogs
No full textInternational audienceThe accident that occurred at the Chornobyl nuclear power plant (Ukraine, 1986) contaminated a large extension of territory after the deposition of radioactive material. It is still under debate whether the chronic exposure to the radiation levels currently present in the area has long-term effects on organisms, such as decreases in longevity. Here, we investigate whether current levels of radiation in Chornobyl negatively impact the age of the Eastern tree frog Hyla orientalis. We also explore whether radiation induces changes in an ageing marker, telomere length or the stress hormone corticosterone. We found no effect of total individual absorbed radiation (including both external and internal exposure) on frog age (n = 197 individuals sampled in 3 consecutive years). We also did not find any relationship between individual absorbed radiation and telomere length, nor between individual absorbed radiation and corticosterone levels. Our results suggest that radiation levels currently experienced by Chornobyl tree frogs may not be high enough to cause severe chronic damage to semi-aquatic vertebrates such as this species. This is the first study addressing age and stress hormones in Chornobyl wildlife, and thus future research will confirm if these results can be extended to other taxa
Non-homogenous intratumor ionizing radiation doses synergize with PD1 and CXCR2 blockade
No full textInternational audienceThe efficacy and side effects of radiotherapy (RT) depend on parameters like dose and the volume of irradiated tissue. RT induces modulations of the tumor immune microenvironment (TIME) that are dependent on the dose. Low dose RT (LDRT, i.e., single doses of 0.5-2 Gy) has been shown to promote immune infiltration into the tumor. Here we hypothesize that partial tumor irradiation combining the immunostimulatory/non-lethal properties of LDRT with cell killing/shrinkage properties of high dose RT (HDRT) within the same tumor mass could enhance anti-tumor responses when combined with immunomodulators. In models of colorectal and breast cancer in immunocompetent female mice, partial irradiation (PI) with millimetric precision to deliver LDRT (2 Gy) and HDRT (16 Gy) within the same tumor induces substantial tumor control when combined with anti-PD1. Using flow cytometry, cytokine profiling and single-cell RNA sequencing, we identify a crosstalk between the TIME of the differentially irradiated tumor volumes. PI reshapes tumor-infiltrating CD8 + T cells into more cytotoxic and interferon-activated phenotypes but also increases the infiltration of pro-tumor neutrophils driven by CXCR2. The combination of the CXCR2 antagonist SB225002 with PD1 blockade and PI improves tumor control and mouse survival. Our results suggest a strategy to reduce RT toxicity and improve the therapeutic index of RT and immune checkpoint combinations
Protein expression patterns and activities of two metabolic enzymes (CS and LDH) highlight a disturbance in the metabolic pathways of tree frogs living in the Chernobyl Exclusion Zone
No full textInternational audienceWhile wildlife is chronically exposed to various sources and levels of ionizing radiation in the environment, studies regarding the long-term impact of long-lived radio-contaminant released in case of accident (137Cs, 90Sr, Pu), are still scarce, patchy, and sometimes contradictory1. Among the species relevant to understand and quantify the effects of radiological exposure on wildlife, amphibians such as the tree frog are sentinel organisms of choice2; they (i) have a highly permeable skin to pollutants, (ii) are exposed to pollutants via diversified habitats (aquatic and terrestrial), (iii) have a limited migration capacity, (iv) are among the reference animals listed by the International Commission on Radiological Protection (ICRP) to assess the toxic risk of ionizing radiation3. In radiocontaminated areas immediately after the Chernobyl (nuclear power plant) and Kychtym (Maïak, reprocessing plant) accidents, the effects described on brown frogs (Rana arvalis) were a reduction in male fertility, egg size and egg laying3. Beyond this acute short term results, in more recent IRSN studies on the tree frog Hyla orientalis living in the Chornobyl Exclusion Zone (CEZ) for ~15 generations, analyses of genetic diversity and transcriptomics studies showed a high rate of mitochondrial mutations, a modulation of genes relative to energy metabolism, and, a small population size with a higher affiliation rate for those living in the most radio-contaminated areas4,5. This raises questions on the ability of populations to maintain themselves and on their health status. In that way, to go further, proteomic analyses of frog muscles of the same individuals were performed after protein extraction and digestion, peptide separation and analysis via nanoHPLC (Ultimate 3000RSLC) and mass spectrometry (Orbitrap Fusion Lumos Tribrid - Thermo Fisher Scientific). In addition, the activity of two enzymes involved in the energetic metabolism, i.e. citrate synthase6 (aerobic metabolism) and lactate dehydrogenase7 (anaerobic metabolism), was measured. All results were analyzed in relation to individual dose rates.Regarding proteomics, the full detected protein set was around 3600 proteins, whereas for data treatment the data sets used were either of 2370 proteins (i.e. 70% proteins with quantitative values for each site), or of 1700 proteins (i.e. 100% proteins with quantitative values, no missing data). Differential analysis between extrema conditions (lower vs higher dose rates) highlighted ~150 proteins oppositely modulated, that could correspond to a protein signature of radio-contamination present in the CEZ. highlighted differential signature and abundancy depending on the area of sampling (highly contaminated in the Chernobyl Exclusion Zone (CEZ) vs control area). Study of underlying biological pathways is in process and will be presented. Parallelly, dose-response modelling of proteomic data has been proceeded using DRomics8 on the full quantitative data set. Results showed 364 significant proteins successfully modelled over the dose gradient. GO enrichment highlighted four significant enriched pathways (FDR 5%) i.e. ‘Carboxylic acid metabolic process’, ‘Cellular lipid catabolic process’, ‘Fatty acid beta-oxidation’ and ‘Small molecule catabolic process’. Regarding enzyme activities, preliminary results showed a tendency to modify the ratio between anaerobic and aerobic metabolisms.All these results seem to confirm by two further approaches a disturbance in the metabolic pathways, notably the ones linked to fatty acids (β-oxidation, catabolism). Investigations will be carried on deciphering the biological pathways involved in long term effects of radiocontamination and conclude on CEZ tree frog health status.Acknowledgements to G. Orizaola (Oviedo University, Spain), P. Burraco (Doñana Biological Station, Spain) for sampling campaign help; S. Gashack and Y. Gulyaichenko (Chornobyl Center for Nuclear Safety, Radioactive Waste and Radioecology, Ukraine) for sampling campaign help and sample radioactive activity measurements.1 Beresford, N. A., N. Horemans, et al. (2020). Journal of Environmental Radioactivity 211.2 Helbing, C. C. (2012). Frontiers in Genetics 3(MAR).3 ICRP (2008). ICRP Publication 108. : 206.4 Car, C., A. Gilles, et al. (2022). Evolutionary Applications 15(2): 203-219.5 Car, C., A. Gilles, et al. (2023). BMC Biology 21(1).6 Alp, P., Newsholme, E. et al. (1976) Biochem. J. 154, 689-7007 Crabtree, B. and Newsholme, E. (1972) Biochem. J. 126, 49-588 Larras, F., E. Billoir, et al. (2018). Environmental Science and Technology 52(24): 14461-14468
On the progress made in safety assessment and severe accident management as part of the french Fukushima post-accident research programme
No full textInternational audienceThe Fukushima-Daiichi accidents in 2011 underlined the importance of severe accident management (SAM), including external events, in nuclear power plants (NPP) and the need of deepen safety research implementing efficient mitigation strategies. For these reasons, the French General Commissariat for Investment has released significant additional resources to strengthen research in this area. Within this framework, several projects have been launched on the highest priority issues, in order to fill the knowledge gap and reduce the uncertainties still hanging over the main phenomena governing severe accidents and their management. Among them, the PERFROI, DENOPI, ICE, MITHYGENE and MIRE projects, led by IRSN, addressed remaining issues related respectively to fuel degradation and reflooding, spent fuel loss of cooling, fuelcoolant interaction, hydrogen risk and source term mitigation. For each of the projects mentioned, experimental and analytical activities were carried out to help understand possible accident scenarios and related phenomena, and to contribute to improving the safety of existing and future reactors. This article gives an overview of the main results of these projects. The achievements in terms of modelling severe accidents and improving severe accident management are presented and their applicability to innovative reactors, including SMRs, is discussed
Database for the Fault Displacement Hazard Initiative Project
No full textInternational audienceNew predictive models for fault displacement and surface rupture hazard analysis developed through the Fault Displacement Hazard Initiative (FDHI) research program require a high-quality empirical database to apply advanced statistical methods and improve hazard estimates. This article discusses the development and contents of the FDHI Project database. We systematically collected, reviewed, and organized fault displacement measurements, surface rupture maps, and supporting information from the scientific literature. A framework was developed and implemented to classify principal and distributed faulting. Best-estimate net displacement amplitudes were calculated from slip component measurements and quality codes were assigned to all net displacement values. The database contains 75 historical, surface-rupturing crustal earthquakes ranging from M 4.9 to 8.0. Thirty-five earthquakes have a strike-slip faulting mechanism, while 25 and 15 events are reverse/reverse-oblique and normal/normal-oblique, respectively. Although most of the earthquakes are from Western North America, Japan, and other active tectonic regions, there are nine reverse faulting events from the stable continental region of Australia. The database contains over 40,000 individual fault displacement measurements for various slip components from roughly 28,000 observation sites. Geographic coordinates are included for all data, and event-specific coordinate systems are provided for each earthquake that transform data into an along-strike dimension. Our new database provides a standardized collection of surface rupture and fault displacement data and metadata that is the result of a comprehensive effort to create a reliable and stable product for the FDHI model development teams and the geoscience community
On the progress made in source terms evaluation and possible open issues relative to advanced technologies
No full textInternational audienceSince 2000's, many progresses have been made on the knowledge regarding the source term through different R&D programmes. The outside releases in severe accident (SA) conditions result from different phenomena: releases from degraded fuel, transport and chemistry in the RCS and aerosol physics and chemistry in the containment. Each phenomenon has been studied experimentally to provide the knowledge and data for developing and validating models. The physical models gained were implemented, for IRSN side, in ASTEC software dedicated to SA scenario simulations for nuclear power plants providing an understanding of the main phenomena involved and finally a more accurate prediction of source term. The source term assessment contributes to enhance the prevention and mitigation of severe accident consequences by evaluating the effectiveness of mitigation systems and the Severe Accident Management Guidelines (SAMGs) effect. In addition, source term evaluations enable informed decision-making during crisis situations by helping to prepare emergency plans. This paper gives an overview of the progress made over the last decade on ST issues, with new impacting phenomena, as well as a special focus on ongoing IRSN activities, mainly relative to chemical speciation of main fission products in the primary circuit under LOCA or Severe Accident conditions, and chemical reactivity of iodine in the containment. Impact of new models dedicated to iodine behaviour in the containment coming from last R&D data, is presented using the results of ASTEC calculation of a LOCA scenario for French PWR 1300 MWe. Finally, some possible open issues linked to new situations (LTO) and/or the development of a set of advanced technologies like Accident Tolerant Fuels (ATF) and Small Modular Reactors (SMR) will be discussed
Vers l’application clinique de la radiothérapie à ultra-haut débit de dose et l’effet FLASH : défis et situation actuelle
No full textInternational audienceUltra-high dose rate external beam radiotherapy (UHDR-RT) uses dose rates of several tens to thousands of Gy/s, compared with the dose rate of the order of a few Gy/min for conventional radiotherapy techniques, currently used in clinical practice. The use of such dose rate is likely to improve the therapeutic index by obtaining a radiobiological effect, known as the “FLASH” effect. This would maintain tumor control while enhancing tissues protection. To date, this effect has been achieved using beams of electrons, photons, protons, and heavy ions. However, the conditions required to achieve this “FLASH” effect are not well defined, and raise several questions, particularly with regard to the definition of the prescription, including dose fractionation, irradiated volume and the temporal structure of the pulsed beam. In addition, the dose delivered over a very short period induces technical challenges, particularly in terms of detectors, which must be mastered to guarantee safe clinical implementation. IRSN has carried out an in-depth literature review of the UHDR-RT technique, covering various aspects relating to patient radiation protection: the radiobiological mechanisms associated with the FLASH effect, the used temporal structure of the UHDR beams, accelerators and dose control, the properties of detectors to be used with UHDR beams, planning, clinical implementation, and clinical studies already carried out or in progress.La radiothérapie externe d’ultra-haut débit de dose utilise des débits de dose de plusieurs dizaines à plusieurs milliers de Gy/s, comparé au débit de dose de l’ordre de quelques Gy/min pour les techniques classiques de radiothérapie actuellement utilisées en clinique. L’utilisation d’un tel débit de dose est susceptible d’améliorer l’indice thérapeutique par l’obtention d’un effet radiobiologique, appelé effet « FLASH ». Ce dernier permettrait de maintenir le contrôle tumoral tout en améliorant la protection des tissus. À ce jour, cet effet a été obtenu en utilisant des faisceaux d’électrons, de photons, de protons et d’ions lourds. Néanmoins, les conditions nécessaires pour l’obtention de cet effet « FLASH » ne sont pas bien déterminées et soulèvent un grand nombre de questions vis-à-vis de la définition de la prescription, notamment le fractionnement de la dose, le volume irradié ou encore la structure temporelle du faisceau pulsé. Par ailleurs, la dose délivrée sur un temps très court induit des défis techniques, notamment pour les détecteurs, qui doivent être maîtrisés pour garantir une mise en œuvre clinique sûre. L’Institut de radioprotection et de sûreté nucléaire (IRSN) a réalisé une étude bibliographique approfondie sur la technique de la radiothérapie externe d’ultra-haut débit de dose portant sur différents aspects en lien avec la radioprotection des patients1 : les mécanismes radiobiologiques associés à l’effet FLASH, la structure temporelle des faisceaux de radiothérapie externe d’ultra-haut débit de dose utilisés, le contrôle des accélérateurs et de la dose, les propriétés des détecteurs pour un usage avec des faisceaux UHDD, la planification et la mise en œuvre en clinique ainsi que les études cliniques déjà menées ou en cours
Enhanced energy, conversion efficiency and collimation of protons driven by high-contrast and ultrashort laser pulses
No full textInternational audienceProgress in laser-driven proton acceleration requires increasing the proton maximum energy and laser-to-proton conversion efficiency while reducing the divergence of the proton beam. However, achieving all these qualities simultaneously has proven challenging experimentally, with the increase in beam energy often coming at the cost of beam quality. Numerical simulations suggest that coupling multi-PW laser pulses with ultrathin foils could offer a route for such simultaneous improvement. Yet, experimental investigations have been limited by the scarcity of such lasers and the need for very stringent temporal contrast conditions to prevent premature target expansion before the pulse maximum. Here, combining the newly commissioned Apollon laser facility that delivers high-power ultrashort (∼24 fs) pulses with a double plasma mirror scheme to enhance its temporal contrast, we demonstrate the generation of up to 35 MeV protons with only 5 J of laser energy. This approach also achieves improved laser-to-proton energy conversion efficiency, reduced beam divergence, and optimized spatial beam profile. Therefore, despite the laser energy losses induced by the plasma mirror, the proton beams produced by this method are enhanced on all accounts compared to those obtained under standard conditions. Particle-in-cell simulations reveal that this improvement mainly results from a better space-time synchronization of the maximum of the accelerating charge-separation field with the proton bunch
Understanding and phenomenological modeling of the pinching effect of the load–deflection curve of reinforced concrete beams subjected to bending
No full textInternational audienceThe reliable prediction of the seismic response of reinforced concrete (RC) structures hinges on accurate modeling of the cyclic behavior of their constituent elements. The load-deflection curve in RC beams exhibits a pinched hysteresis pattern corresponding to energy dissipations. This pinching effect, often observed under seismic loading conditions, reflects a reduction in stiffness and energy dissipation capacity at certain loading stages. Despite its significance, the detailed mechanisms underlying this phenomenon remain underexplored in existing literature. This paper aims to address this gap by presenting simplified models that directly represents the pinching effect at the crack scale. The model is grounded in a comprehensive analysis of shear stress interactions and crack closure dynamics, hypothesized as primary contributors to the pinching phenomenon. Our approach involves a meticulous examination of the hysteresis loops' area and shape, facilitating the estimation of an equivalent viscous damping ratio to represent energy dissipation in seismic simulations, irrespective of changes in the structure's damage or ductility levels. The paper unfolds in three key sections: The first section underscores the significance of a nuanced understanding of the pinching effect in seismic analysis. The second section presents an extensive literature review, consolidating crucial insights into the nature of the pinching phenomenon. The third section details the development and application of the proposed mesoscopic model, highlighting the impact of various geometrical and material parameters on the pinching effect
Investigation into the mercury intrusion porosimetry (MIP) and micro-computed tomography (μCT) methods for determining the pore size distribution of MX80 bentonite pellet
No full textInternational audienceThe pore size distribution (PSD) plays an important role in the hydro-mechanical behaviour of porous materials. In this study, the PSD of MX80 bentonite pellets under various imposed suctions from 262 to 1.5 MPa was determined by both mercury intrusion porosimetry (MIP) and micro-computed tomography (μCT). The void ratios e18–344 in the overlapping pore range (18–344 μm) identified by MIP and μCT were compared to clarify the difference between the two techniques. Results showed that the MIP-detection e18–344 nearly overlapped with the μCT-detection one at suction s ≥ 57 MPa, indicating the reliability of MIP and μCT results for pellets at s ≥ 57 MPa. However, the μCT-detection e18–344 became larger than the MIP-detection one at 9 MPa ≤ s ≤ 38 MPa, while the changes of MIP-detection and μCT-detection e18–344 with suctions were opposite at s ≤ 4.2 MPa. As the difficulty of interpreting the variation in μCT attenuation coefficient at low suctions undermined the reliability of μCT thresholding, the segmentation of μCT images was suggested to be determined by making the μCT-detection e18–344 equal to the MIP-detection one. Because the reliability of MIP results at s ≤ 4.2 MPa was reduced by the difficulty of keeping the integrity of freeze-dried samples, the MIP-detection e18–344 determined in a previous study without the sample integrity problem was chosen as reference for the μCT thresholding at 1.5 MPa ≤ s ≤ 4.2 MPa. The corrected μCT-detection e18–344 calculated by the new thresholds matched well with the MIP-detection e18–344, completing the μCT-detection at suctions smaller than 57 MPa. Since the MIP-detection PSD only covers the pores smaller than 344 µm, the μCT-detection PSD with pores larger than 344 µm was then integrated into the MIP-detection PSD, enlarging the MIP-detection to millimetric pores