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

Mechanical attachement of the conductor ends in the ITER polodial field coils

The ITER poloidal field (PF) coils are wound from a large cable-in-conduit-conductor, with a stainless steel (SS) jacket. Tapered bonded tails, consisting of shaped steel profiles welded to the conductor ends, are used in these PF coils to mecha

Qualification of a 40 Ka Nb3sn Superconducting Conductor for Net/Iter Coils

A 40 kA Nb3Sn conductor, designed to operate with forced helium flow at 4.5 K was tested in the SULTAN III facility, (I(max) = 50kA, B(max) (background) = 11T). The test sample and the operating conditions of the test facility are described. Two measurement procedures were used to investigate the conductor behaviour near the critical value : Sample current or temperature are increased up to the quench with background field and temperature or current reciprocally kept at steady state. The critical current of the conductor could be measured with the same criterion as for the basic strand (0.1muV/cm). The obtained results are discussed and compared with the basic strand performances. In addition some results on the thermohydraulic behaviour of the CIC conductor are presented

Tests and Analyses of Two TF Conductor Prototypes for JT-60SA

In the framework of the JT-60SA project, included inside the Broader Approach agreement, EU is expected to provide to JA the totality of the toroidal field (TF) magnet system. It consists in 18 coils, evenly shared for in-kind procurement between France and Italy while the TF conductor providing is under the responsibility of Fusion for Energy. The conductor is a rectangular-shaped, NbTi-based, cable-in-conduit (CICC) and will be wound in double-pancake inside the TF casing