TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association wit

Overview of the TCV tokamak experimental programme

The tokamak a configuration variable (TCV) continues to leverage its unique shaping capabilities, flexible heating systems and modern control system to address critical issues in preparation for ITER and a fusion power plant. For the 2019-20 campaign its configurational flexibility has been enhanced with the installation of removable divertor gas baffles, its diagnostic capabilities with an extensive set of upgrades and its heating systems with new dual frequency gyrotrons. The gas baffles reduce coupling between the divertor and the main chamber and allow for detailed investigations on the role of fuelling in general and, together with upgraded boundary diagnostics, test divertor and edge models in particular. The increased heating capabilities broaden the operational regime to include T (e)/T (i) similar to 1 and have stimulated refocussing studies from L-mode to H-mode across a range of research topics. ITER baseline parameters were reached in type-I ELMy H-modes and alternative regimes with \u27small\u27 (or no) ELMs explored. Most prominently, negative triangularity was investigated in detail and confirmed as an attractive scenario with H-mode level core confinement but an L-mode edge. Emphasis was also placed on control, where an increased number of observers, actuators and control solutions became available and are now integrated into a generic control framework as will be needed in future devices. The quantity and quality of results of the 2019-20 TCV campaign are a testament to its successful integration within the European research effort alongside a vibrant domestic programme and international collaborations

Physics research on the TCV tokamak facility: from conventional to alternative scenarios and beyond

The research program of the TCV tokamak ranges from conventional to advanced-tokamak scenarios and alternative divertor configurations, to exploratory plasmas driven by theoretical insight, exploiting the device’s unique shaping capabilities. Disruption avoidance by real-time locked mode prevention or unlocking with electron-cyclotron resonance heating (ECRH) was thoroughly documented, using magnetic and radiation triggers. Runaway generation with high-Z noble-gas injection and runaway dissipation by subsequent Ne or Ar injection were studied for model validation. The new 1 MW neutral beam injector has expanded the parameter range, now encompassing ELMy H-modes in an ITER-like shape and nearly non-inductive H-mode discharges sustained by electron cyclotron and neutral beam current drive. In the H-mode, the pedestal pressure increases modestly with nitrogen seeding while fueling moves the density pedestal outwards, but the plasma stored energy is largely uncorrelated to either seeding or fueling. High fueling at high triangularity is key to accessing the attractive small edge-localized mode (type-II) regime. Turbulence is reduced in the core at negative triangularity, consistent with increased confinement and in accord with global gyrokinetic simulations. The geodesic acoustic mode, possibly coupled with avalanche events, has been linked with particle flow to the wall in diverted plasmas. Detachment, scrape-off layer transport, and turbulence were studied in L- and H-modes in both standard and alternative configurations (snowflake, super-X, and beyond). The detachment process is caused by power ‘starvation’ reducing the ionization source, with volume recombination playing only a minor role. Partial detachment in the H-mode is obtained with impurity seeding and has shown little dependence on flux expansion in standard single-null geometry. In the attached L-mode phase, increasing the outer connection length reduces the in–out heat-flow asymmetry. A doublet plasma, featuring an internal X-point, was achieved successfully, and a transport barrier was observed in the mantle just outside the internal separatrix. In the near future variable-configuration baffles and possibly divertor pumping will be introduced to investigate the effect of divertor closure on exhaust and performance, and 3.5 MW ECRH and 1 MW neutral beam injection heating will be added

Observation of the bulk ion density peaking in a discharge with an impurity hole in the LHD

Radial profiles of bulk ion and impurity ions density are simultaneously measured and quantified using charge exchange spectroscopy and peaking parameter, Cv. The peaking parameter is positive for inward and negative for outward convection in a plasma with an impurity hole in the Large Helical Device. Following the formation of an impurity hole associated with the transition from L-mode to ion ITB plasma, the bulk ion becomes peaked by the inward convection (Cv>0), while impurities (helium and carbon) become hollow due to the outward convection (Cv0), where the bulk ion density profile remains flat (Cv∼0). Understanding of the impurity behavior in the ion ITB plasma could lead to a self cleaning plasma reactor concept, with an efficient impurity exhaust

Observation of the bulk ion density peaking in a discharge with an impurity hole in the LHD

\u3cp\u3eRadial profiles of bulk ion and impurity ions density are simultaneously measured and quantified using charge exchange spectroscopy and peaking parameter, C\u3csub\u3ev\u3c/sub\u3e. The peaking parameter is positive for inward and negative for outward convection in a plasma with an impurity hole in the Large Helical Device. Following the formation of an impurity hole associated with the transition from L-mode to ion ITB plasma, the bulk ion becomes peaked by the inward convection (C\u3csub\u3ev\u3c/sub\u3e&gt;0), while impurities (helium and carbon) become hollow due to the outward convection (C\u3csub\u3ev\u3c/sub\u3e&lt;0). In contrast to the ion ITB plasma, in the L-mode plasma the impurity profiles are peaked (C\u3csub\u3ev\u3c/sub\u3e&gt;0), where the bulk ion density profile remains flat (C\u3csub\u3ev\u3c/sub\u3e∼0). Understanding of the impurity behavior in the ion ITB plasma could lead to a self cleaning plasma reactor concept, with an efficient impurity exhaust.\u3c/p\u3