The genomic and transcriptional landscape of primary central nervous system lymphoma

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations

Plasma-wall interaction studies within the EUROfusion consortium: Progress on plasma-facing components development and qualification

This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 under grant agreement No 633053. The views and opinions expressed herein do not necessarily reflect those of the European Commission.The provision of a particle and power exhaust solution which is compatible with first-wall components and edge-plasma conditions is a key area of present-day fusion research and mandatory for a successful operation of ITER and DEMO. The work package plasma-facing components (WP PFC) within the European fusion programme complements with laboratory experiments, i.e. in linear plasma devices, electron and ion beam loading facilities, the studies performed in toroidally confined magnetic devices, such as JET, ASDEX Upgrade, WEST etc. The connection of both groups is done via common physics and engineering studies, including the qualification and specification of plasma-facing components, and by modelling codes that simulate edge-plasma conditions and the plasma-material interaction as well as the study of fundamental processes. WP PFC addresses these critical points in order to ensure reliable and efficient use of conventional, solid PFCs in ITER (Be and W) and DEMO (W and steel) with respect to heat-load capabilities (transient and steady-state heat and particle loads), lifetime estimates (erosion, material mixing and surface morphology), and safety aspects (fuel retention, fuel removal, material migration and dust formation) particularly for quasi-steady-state conditions. Alternative scenarios and concepts (liquid Sn or Li as PFCs) for DEMO are developed and tested in the event that the conventional solution turns out to not be functional. Here, we present an overview of the activities with an emphasis on a few key results: (i) the observed synergistic effects in particle and heat loading of ITER-grade W with the available set of exposition devices on material properties such as roughness, ductility and microstructure; (ii) the progress in understanding of fuel retention, diffusion and outgassing in different W-based materials, including the impact of damage and impurities like N; and (iii), the preferential sputtering of Fe in EUROFER steel providing an in situ W surface and a potential first-wall solution for DEMO.European Commission; Consortium for Ocean Leadership 633053; Institute of Solid State Physics, University of Latvia as the Center of Excellence has received funding from the European Union’s Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART

Magnetically confined fusion plasmas with a radiating boundary and improved energy confinement

The concept of a cold radiating plasma boundary has been proposed as a solution of the problem of power exhaust in magnetically confined fusion plasmas. In the tokamak TEXTOR the injection of impurities (neon, silicon or argon) leads to the formation of a radiating plasma boundary where up to 90% of the input power can be distributed to large wall areas, thereby strongly reducing the convective heat flux density onto the plasma facing components. At high plasma densities the impurity seeding leads to a transition to an improved confinement state, termed the Radiative Improved Mode (RI-mode). This operational scenario combines high density and high confinement with power exhaust by radiation under quasi-stationary discharge conditions. The plasma density can be further increased by external gas fuelling, while the high confinement is maintained, if the gas is fuelled at a moderate rate. In contrast, strong gas fuelling leads to a confinement degradation back to the normal L-mode level. We have used plasma diagnostics based on optical methods to characterise particle, energy and neutral transport at the plasma boundary. When the radiated power is increased owing to the injected impurities, we observe a strong reduction of the plasma temperature at the plasma boundary. At the same time, the particle transport out of the confined volume decreases, accordingly the neutral flux back into the plasma decreases. In discharges, where the density is increased by strong gas fuelling and the energy confinement degrades, we observe a built-up of edge density and neutral pressure owing to a higher recycling coefficient. In contrast, with moderate gas fuelling the edge density and neutral pressure remain low. While the seeded impurities cause a substantial dilution at the plasma edge, the plasma core is much less affected, leading to hollow impurity concentration profiles. Operation at the highest densities is favourable with respect to the release of impurities at the edge as well as with respect to the resulting impurity content in the plasma bulk. The most prominent change of transport in the plasma core is a steepening of background density profile while the temperature in the core can be maintained or even slightly increased. The global energy confinement is strongly correlated with the density peaking. An analysis of the experimental plasma profiles with respect to stability against the ion temperature gradient driven mode (ITG mode) shows that the ITG mode is substantially reduced during the confinement improvement and that it reappears if the density is increased and a subsequent confinement roll-over occurs with too a strong gas fuelling. The dynamics of both the confinement improvement and of the degradation is initiated at the plasma edge. The resulting changes in the plasma core amplify the initial trigger. Consequently, we observe a non-linear interplay between edge and core which allows for a self-organisation of the plasma and a bifurcation between two rather different states. The transition and the changes of the plasma profiles can be described in agreement with the experimental findings by a transport model based on the ITC mode and the dissipative trapped electron (DTE-) mode, which is connected to a strong anomalous particle pinch. This inward pinch leads to the steepening of the density profile once the ITG mode growth is reduced by the impurities. During the confinement degradation with strong gas injection increased edge transport leads to a reduction of the impurity content in the core below the level needed for the ITC suppression