Motorized Regulation Systems for the SARAF Project

International audienceCEA is in charge of the tuning regulation systems for the SARAF-Linac project. These tuning systems will be used with LLRF to regulate the 3 Rebuncher cavities and the HWR cavities of the 4 cryomodules. These systems were already tested on the Rebuncher and Equipped Cavity Test stands to test respectively the warm and cold tunings. This paper describes the hardware and software architectures. Both tuning systems are based on Siemens PLC and EPICS-PLC communication. Ambiant temperature technology is based on SIEMENS motor controller solution whereas the cold one combines Phytron and PhyMOTION solutions

Saraf-Phase II: Test of the SRF Cavities with the First Cryomodule

International audienceCEA is committed to delivering a Medium Energy Beam Transfer line and a superconducting linac (SCL) for SARAF accelerator in order to accelerate 5 mA beam of either protons from 1.3 MeV to 35 MeV or deuterons from 2.6 MeV to 40 MeV. The SCL consists in four cryomodules. The first cryomodule hosts 6 half-wave resonator (HWR) low beta cavities (β = 0.09) at 176 MHz. The low-beta cavities were qualified in 2021, as well as the power couplers and frequency tuners. The Low-Level RF (LLRF) system was qualified in 2022 with a dedicated test stand. This contribution will present the results of the RF tests of the first SARAF cryomodule at Saclay

Status of the SARAF-Phase2 Control System

International audienceSNRC and CEA collaborate to the upgrade of the SARAF accelerator to 5 mA CW 40 Mev deuteron and proton beams and also closely to the control system. CEA is in charge of the Control System (including cabinets) design and implementation for the Injector (upgrade), MEBT and Super Conducting Linac made up of 4 cryomodules hosting HWR cavities and solenoid packages. This paper gives a detailed presentation of the control system architecture from hardware and EPICS software points of view. The hardware standardization relies on MTCA.4 that is used for LLRF, BPM, BLM and FC controls and on Siemens PLC 1500 series for vacuum, cryogenics and interlock. CEA IRFU EPICS Environment (IEE) platform is used for the whole accelerator. IEE is based on virtual machines and our MTCA.4 solutions and enables us to have homogenous EPICS modules. It also provides a development and production workflow. SNRC has integrated IEE into a new IT network based on advanced technology. The commissioning is planned to start late summer 2021

Distinct subsets of multi-lymphoid progenitors support ontogeny-related changes in human lymphopoiesis

International audienceChanges in lymphocyte production patterns occurring across human ontogeny remain poorly defined. In this study, we demonstrate that human lymphopoiesis is supported by three waves of embryonic, fetal, and postnatal multi-lymphoid progenitors (MLPs) differing in CD7 and CD10 expression and their output of CD127-/+ early lymphoid progenitors (ELPs). In addition, our results reveal that, like the fetal-to-adult switch in erythropoiesis, transition to postnatal life coincides with a shift from multilineage to B lineage-biased lymphopoiesis and an increase in production of CD127+ ELPs, which persists until puberty. A further developmental transition is observed in elderly individuals whereby B cell differentiation bypasses the CD127+ compartment and branches directly from CD10+ MLPs. Functional analyses indicate that these changes are determined at the level of hematopoietic stem cells. These findings provide insights for understanding identity and function of human MLPs and the establishment and maintenance of adaptative immunity

Novel Triazine JPC-2067-B Inhibits Toxoplasma gondii In Vitro and In Vivo

BACKGROUND AND METHODOLOGY Toxoplasma gondii causes substantial morbidity, mortality, and costs for healthcare in the developed and developing world. Current medicines are not well tolerated and cause hypersensitivity reactions. The dihydrotriazine JPC-2067-B (4, 6-diamino-1, 2-dihydro-2, 2-dimethyl-1-(3′(2-chloro-, 4-trifluoromethoxyphenoxy)propyloxy)-1, 3, 5-triazine), which inhibits dihydrofolate reductase (DHFR), is highly effective against Plasmodium falciparum, Plasmodium vivax, and apicomplexans related to T. gondii. JPC-2067-B is the primary metabolite of the orally active biguanide JPC-2056 1-(3′-(2-chloro-4-trifluoromethoxyphenyl​oxy)propyl oxy)- 5-isopropylbiguanide, which is being advanced to clinical trials for malaria. Efficacy of the prodrug JPC-2056 and the active metabolite JPC-2067-B against T. gondii and T. gondii DHFR as well as toxicity toward mammalian cells were tested. PRINCIPAL FINDINGS AND CONCLUSIONS Herein, we found that JPC-2067-B is highly effective against T. gondii. We demonstrate that JPC-2067-B inhibits T. gondii growth in culture (IC50 20 nM), inhibits the purified enzyme (IC50 6.5 nM), is more efficacious than pyrimethamine, and is cidal in vitro. JPC-2067-B administered parenterally and the orally administered pro-drug (JPC-2056) are also effective against T. gondii tachyzoites in vivo. A molecular model of T. gondii DHFR-TS complexed with JPC-2067-B was developed. We found that the three main parasite clonal types and isolates from South and Central America, the United States, Canada, China, and Sri Lanka have the same amino acid sequences preserving key binding sites for the triazine. SIGNIFICANCE JPC-2056/JPC-2067-B have potential to be more effective and possibly less toxic treatments for toxoplasmosis than currently available medicines