IDEFIX: a versatile performance-portable Godunov code for astrophysical flows

Exascale super-computers now becoming available rely on hybrid energy-efficient architectures that involve an accelerator such as Graphics Processing Units (GPU). Leveraging the computational power of these machines often means a significant rewrite of the numerical tools each time a new architecture becomes available. To address these issues, we present Idefix, a new code for astrophysical flows that relies on the Kokkos meta-programming library to guarantee performance portability on a wide variety of architectures while keeping the code as simple as possible for the user. Idefix is based on a Godunov finite-volume method that solves the non-relativistic HD and MHD equations on various grid geometries. Idefix includes a wide choice of solvers and several additional modules (constrained transport, orbital advection, non-ideal MHD) allowing users to address complex astrophysical problems. Idefix has been successfully tested on Intel and AMD CPUs (up to 131 072 CPU cores on Irene-Rome at TGCC) as well as NVidia and AMD GPUs (up to 1024 GPUs on Adastra at CINES). Idefix achieves more than 1e8 cell/s in MHD on a single NVidia V100 GPU and 3e11 cell/s on 256 Adastra nodes (1024 GPUs) with 95% parallelization efficiency (compared to a single node). For the same problem, Idefix is up to 6 times more energy efficient on GPUs compared to Intel Cascade Lake CPUs. Idefix is now a mature exascale-ready open-source code that can be used on a large variety of astrophysical and fluid dynamics applications.Comment: 18 pages, 18 figures, 3 tables, accepted for publication in Astronomy & Astrophysic

Pre-clinical quantitative imaging and mouse-specific dosimetry for In-111-labelled radiotracers

Cancer Research UK and Engineering and Physical Sciences Research Council support to the Cancer Imaging Centre at The Institute of Cancer Research (ICR) and the Royal Marsden Hospital NHS Foundation Trust (RMH) in association with Medical Research Council and Department of Health C1060/A10334, C1060/A16464

Rapid identification of causal mutations in tomato EMS populations via mapping-by-sequencing

The tomato is the model species of choice for fleshy fruit development and for the Solanaceae family. Ethyl methanesulfonate (EMS) mutants of tomato have already proven their utility for analysis of gene function in plants, leading to improved breeding stocks and superior tomato varieties. However, until recently, the identification of causal mutations that underlie particular phenotypes has been a very lengthy task that many laboratories could not afford because of spatial and technical limitations. Here, we describe a simple protocol for identifying causal mutations in tomato using a mapping-by-sequencing strategy. Plants displaying phenotypes of interest are first isolated by screening an EMS mutant collection generated in the miniature cultivar Micro-Tom. A recombinant F2 population is then produced by crossing the mutant with a wild-type (WT; non-mutagenized) genotype, and F2 segregants displaying the same phenotype are subsequently pooled. Finally, whole-genome sequencing and analysis of allele distributions in the pools allow for the identification of the causal mutation. The whole process, from the isolation of the tomato mutant to the identification of the causal mutation, takes 6-12 months. This strategy overcomes many previous limitations, is simple to use and can be applied in most laboratories with limited facilities for plant culture and genotyping

Model-based versus specific dosimetry in diagnostic context: Comparison of three dosimetric approaches

International audienceThe dosimetric assessment of novel radiotracers represents a legal requirement in most countries. While the techniques for the computation of internal absorbed dose in a therapeutic context have made huge progresses in recent years, in a diagnostic scenario the absorbed dose is usually extracted from model-based lookup tables, most often derived from International Commission on Radiological Protection (ICRP) or Medical Internal Radiation Dose (MIRD) Committee models. The level of approximation introduced by these models may impact the resulting dosimetry. The aim of this work is to establish whether a more refined approach to dosimetry can be implemented in nuclear medicine diagnostics, by analyzing a specific case

Hybrid MicroPET Imaging for Dosimetric Applications in Mice: Improvement of Activity Quantification in Dynamic MicroPET Imaging for Accelerated Dosimetry Applied to 6-[ 18 F] Fluoro- L -DOPA and 2-[ 18 F]Fluoro- L -Tyrosine

Purpose: Dynamic microPET imaging has advantages over traditional organ harvesting, but is pronetoquantificationerrorsinsmallvolumes.Hybridimaging,wheremicroPETactivitiesarecross- calibrated using post scan harvested organs, can improve quantification. Organ harvesting, dynamic imaging and hybrid imaging were applied to determine the human and mouse radiation dosimetry of 6-[18 F]fluoro-L-DOPA and 2-[18 F]fluoro-L-tyrosine and compared. Procedures: Two-hour dynamic microPET imaging was performed with both tracers in four separate mice for 18 F-FDOPA and three mice for 18 F-FTYR. Organ harvesting was performed at 2, 5, 10, 30, 60 and 120 min post tracer injection with n=5 at each time point for 18 F-FDOPA and n=3 at each time point for 18 F-FTYR. Human radiation dosimetry projected from animal data was calculated for the three different approaches for each tracer using OLINDA/EXM. S- factors for the MOBY phantom were used to calculate the animal dosimetry. Results: Correlations between dose estimates based on organ harvesting and imaging was improved from r=0.997 to r=0.999 for 18 F-FDOPA and from r=0.985 to r=0.996 (p<0.0001 for all) for 18 F-FTYR by using hybrid imaging. Conclusion: Hybrid imaging yields comparable results to traditional organ harvesting while partially overcoming the limitations of pure imaging. It is an advantageous technique in terms of number of animals needed and labour involved

Phosphorylation state of a Tob/BTG protein, FOG-3, regulates initiation and maintenance of the Caenorhabditis elegans sperm fate program

FOG-3, the single Caenorhabditis elegans Tob/BTG protein, directs germ cells to adopt the sperm fate at the expense of oogenesis. Importantly, FOG-3 activity must be maintained for the continued production of sperm that is typical of the male sex. Vertebrate Tob proteins have antiproliferative activity and ERK phosphorylation of Tob proteins has been proposed to abrogate “antiproliferative” activity. Here we investigate FOG-3 phosphorylation and its effect on sperm fate specification. We found both phosphorylated and unphosphorylated forms of FOG-3 in nematodes. We then interrogated the role of FOG-3 phosphorylation in sperm fate specification. Specifically, we assayed FOG-3 transgenes for rescue of a fog-3 null mutant. Wild-type FOG-3 rescued both initiation and maintenance of sperm fate specification. A FOG-3 mutant with its four consensus ERK phosphorylation sites substituted to alanines, called FOG-3(4A), rescued partially: sperm were made transiently but not continuously in both sexes. A different FOG-3 mutant with its sites substituted to glutamates, called FOG-3(4E), had no rescuing activity on its own, but together with FOG-3(4A) rescue was complete. Thus, when FOG-3(4A) and FOG-3(4E) were both introduced into the same animals, sperm fate specification was not only initiated but also maintained, resulting in continuous spermatogenesis in males. Our findings suggest that unphosphorylated FOG-3 initiates the sperm fate program and that phosphorylated FOG-3 maintains that program for continued sperm production typical of males. We discuss implications of our results for Tob/BTG proteins in vertebrates

A review of the use and potential of the GATE Monte Carlo simulation code for radiation therapy and dosimetry applications

International audienceIn this paper, the authors' review the applicability of the open-source GATE Monte Carlo simulation platform based on the GEANT4 toolkit for radiation therapy and dosimetry applications. The many applications of GATE for state-of-the-art radiotherapy simulations are described including external beam radiotherapy, brachytherapy, intraoperative radiotherapy, hadrontherapy, molecular radiotherapy, and in vivo dose monitoring. Investigations that have been performed using GEANT4 only are also mentioned to illustrate the potential of GATE. The very practical feature of GATE making it easy to model both a treatment and an imaging acquisition within the same frameworkis emphasized. The computational times associated with several applications are provided to illustrate the practical feasibility of the simulations using current computing facilities

Validated MAGIC and GWAS populations mapping reveal the link between vitamin E contents and natural variation in chorismate metabolism in tomato

Tocochromanols constitute the different forms of vitamin E (VTE), essential for the human diet and display a high membrane protectant activity. By combining interval mapping and genome-wide association studies (GWAS) we unveiled the genetic determinants of tocochromanol accumulation in tomato fruits. To enhance the nutritional value of this highly consumed vegetable, we dissected the natural intraspecific variability of tocochromanols in tomato fruits and genetically engineered their biosynthetic pathway. These analyses allowed the identification of a total of 25 QTL interspersed across the genome pinpointing the chorismate-tyrosine pathway as a regulatory hub controlling the supply of the aromatic head group for tocochromanol biosynthesis. To validate the link between the chorismate-tyrosine pathway and VTE, we engineered tomato plants to bypass the pathway at the arogenate branchpoint. Transgenic tomatoes showed moderate increments in tocopherols (up to ~ 20%) and a massive accumulation of tocotrienols (up to ~ 3,400%). Gene expression analyses of these plants reveal a trade-off between VTE and natural variation in chorismate metabolism explained by transcriptional reprogramming of specific structural genes of the pathway. By restoring the accumulation of α-t3 (alfa tocotrienols) in fruits, the plants produced here are of high pharmacological and nutritional interest