Clonal interference of signaling mutations worsens prognosis in core-binding factor acute myeloid leukemia

Mutations in receptor tyrosine kinase/RAS signaling pathway genes are frequent in core-binding factor (CBF) acute myeloid leukemias (AMLs), but their prognostic relevance is debated. A subset of CBF AML patients harbors several signaling gene mutations. Genotyping of colonies and of relapse samples indicates that these arise in independent clones, thus defining a process of clonal interference (or parallel evolution). Clonal interference is pervasive in cancers, but the mechanisms underlying this process remain unclear, and its prognostic impact remains unknown. We analyzed a cohort of 445 adult and pediatric patients with CBF AML treated with intensive chemotherapy and with deep sequencing of 6 signaling genes (, , , , , ). A total of 152 (34%), 167 (38%), and 126 (28%) patients harbored no, a single, and multiple signaling clones (clonal interference), respectively. Clonal interference of signaling mutations was associated with older age ( = .004) and inv(16) subtype ( = .025) but not with white blood cell count or mutations in chromatin or cohesin genes. The median allele frequency of signaling mutations was 31% in patients with a single clone or clonal interference ( = .14). The repertoire of , , and / variants differed between groups. Clonal interference did not affect complete remission rate or minimal residual disease after 1-2 courses, but it did convey inferior event-free survival ( < 10), whereas the presence of a single signaling clone did not ( = .44). This inferior outcome was independent of clinical parameters and of the presence of specific signaling clones. Our results suggest that specific clonal architectures can herald distinct prognoses in AML

Advance in the conceptual design of the European DEMO magnet system

The European DEMO, i.e. the demonstration fusion power plant designed in the framework of the Roadmap to Fusion Electricity by the EUROfusion Consortium, is approaching the end of the pre-conceptual design phase, to be accomplished with a Gate Review in 2020, in which all DEMO subsystems will be reviewed by panels of independent experts. The latest 2018 DEMO baseline has major and minor radius of 9.1 m and 2.9 m, plasma current 17.9 MA, toroidal field on the plasma axis 5.2 T, and the peak field in the toroidal-field (TF) conductor 12.0 T. The 900 ton heavy TF coil is prepared in four lowerature-superconductor (LTS) variants, some of them differing slightly, other significantly, from the ITER TF coil design. Two variants of the CS coils are investigated - a purely LTS one resembling the ITER CS, and a hybrid coil, in which the innermost layers made of HTS allow the designers either to increase the magnetic flux, and thus the duration of the fusion pulse, or to reduce the outer radius of the CS coil. An issue presently investigated by mechanical analyzes is the fatigue load. Two variants of the poloidal field coils are being investigated. The magnet and conductor design studies are accompanied by the experimental tests on both LTS and HTS prototype samples, covering a broad range of DC and AC tests. Testing of quench behavior of the 15 kA HTS cables, with size and layout relevant for the fusion magnets and cooled by forced flow helium, is in preparation.</p

Modelling of gob transfer in the delivery system on a glass bottle production machine

International audienc

SELFIE: ITER superconducting joint test facility

In the frame of a contract with ITER Organization (IO) on magnets assembly support, CEA designed and built a superconducting joint test facility called SELFIE (ITER SELf-FIEld joint test facility). This facility is installed at CEA Cadarache and started to operate in 2022. This project was initiated by IO for quality control of critical assembly activities. Indeed, the magnet superconducting joints assembly is a special process, for which the performance cannot be verified until the full Tokamak is at cryogenic temperature and obviously repair cannot be envisaged once the machine is assembled. Therefore, the quality control of these joints assembly relies on procedures and qualification of the workers in charge of their implementation. As the joints assemblies will span over three years of the ITER construction, the qualified workers will have to assemble periodically some Production Proof Samples (PPS) joints to train and keep their certification valid. The purpose of SELFIE is to test these PPS in a timely manner. The tests scope is the measurement of the PPS resistance (few nOhms). For that purpose, PPS integrated in ITER conductors length (∼200 kg weight and 3600 mm length) are tested in a liquid helium bath (4.2 K), at nominal current (up to 70 kA), in self-field. The current is provided by a superconducting transformer integrated in the same cryostat as the sample. CEA finalized the preliminary design in 2019, complying with the requirement to achieve a full test sequence within one week (controlled cool down, test and warm-up), with an optimised operation cost. The detailed design phase was started in April 2020 followed by the manufacturing phase up to mid 2021. SELFIE integration and installation were achieved in December 2021 and the cold commissioning done in January 2022. This paper presents the SELFIE test facility and the first results

Construction Status of the Superconducting Magnet System for JT-60SA

The construction of the JT-60SA tokamak is one of the three projects of the Broader Approach activities being undertaken jointly by Japan and Europe. The superconducting magnet system for JT-60SA consists of 18 toroidal field coils, a central solenoid with four modules, six equilibrium field coils, superconducting feeders, high-temperature-superconductor current leads, thermal shields, and the cryogenic system. This paper shows the latest construction activities of the superconducting magnet system

JT-60SA superconducting magnet system

International audienceThe JT-60SA experiment is one of the three projects to be undertaken in Japan as part of the Broader Approach Agreement, conducted jointly by Europe and Japan, and complementing the construction of ITER in Europe. The superconducting magnet system for JT-60SA consists of 18 Toroidal Field (TF) coils, a Central Solenoid (CS) and six Equilibrium Field (EF) coils. The TF magnet generates the field to confine charged particles in the plasma, the CS provides the inductive flux to ramp up plasma current and contribute to plasma shaping and the EF coils provide the position equilibrium of plasma current and the plasma vertical stability. The six EF coils are attached to the TF coil cases through supports with flexible plates allowing radial displacements. The CS assembly is supported from the bottom of the TF coils through its pre-load structure. The design status of the JT-60SA superconducting magnetic system is reviewed