Pre-dismantling THM modelling

FEBEX (Full-scale Engineered Barrier Experiment in Crystalline Host Rock) is a research and demonstration project that was initiated by ENRESA (Spain). The aim of the project is to study the behaviour of near-field components in a repository for high-level radioactive waste in granite formations. The main objectives of the project may be grouped in two areas: demonstration of the feasibility of constructing the engineered barrier system in a horizontal configuration according to the Spanish concept for deep geological storage (AGP-abbreviation in Spanish), and analysis of the technical problems to be solved for this type of disposal method to develop a better understanding of the thermo-hydro-mechanical (THM) and thermo-hydrogeochemical (THG) processes in the near-field, and development and validation of the modelling tools required for interpretation and prediction of the evolution of such processes. The project consists of two large-scale tests (see Fig. 1-1) – "in situ" and "mock-up" (the latter is managed by CIEMAT in Spain) –, a series of laboratory tests, and THM and THG modelling tasks. The full-scale heating test ("in-situ" test), to which this document refers, was performed at the Grimsel underground laboratory in Switzerland, also known as Grimsel Test Site (GTS) or Felslabor Grimsel (FLG in German). A complete description of the FEBEX project objectives and test program may be found in the "FEBEX Full-scale Engineered Barriers Experiment in Crystalline Host Rock

In vitro proteasome processing of neo-splicetopes does not predict their presentation in vivo

Proteasome catalyzed peptide splicing (PCPS) of cancer-driving antigens could generate attractive neoepitopes to be targeted by TCR-based adoptive T cell therapy. Based on a spliced peptide prediction algorithm TCRs were generated against putative KRAS(G12V) and RAC2(P29L) derived neo-splicetopes with high HLA-A*02:01 binding affinity. TCRs generated in mice with a diverse human TCR repertoire specifically recognized the respective target peptides with high efficacy. However, we failed to detect any neo-splicetope specific T cell response when testing the in vivo neo-splicetope generation and obtained no experimental evidence that the putative KRAS(G12V)- and RAC2(P29L)-derived neo-splicetopes were naturally processed and presented. Furthermore, only the putative RAC2(P29L)-derived neo-splicetopes was generated by in vitro PCPS. The experiments pose severe questions on the notion that available algorithms or the in vitro PCPS reaction reliably simulate in vivo splicing and argue against the general applicability of an algorithm-driven 'reverse immunology' pipeline for the identification of cancer-specific neo-splicetopes

A Cell-Centred CVD-MPFA Finite Volume Method for Two-Phase Fluid Flow Problems with Capillary Heterogeneity and Discontinuity

A novel finite-volume method is presented for porous media flow simulation that is applicable to discontinuous capillary pressure fields. The method crucially retains the optimal single of freedom per control-volume being developed within the flux-continuous control-volume distributed multi-point flux approximation (CVD-MPFA) framework (Edwards and Rogers in Comput Geosci 02(04):259–290, 1998; Friis et al. in SIAM J Sci Comput 31(02):1192–1220, 2008) . The new methods enable critical subsurface flow processes involving oil and gas trapping to be correctly resolved on structured and unstructured grids. The results demonstrate the ability of the method to resolve flow with oil/gas trapping in the presence of a discontinuous capillary pressure field for diagonal and full-tensor permeability fields. In addition to an upwind approximation for the saturation equation flux, the importance of upwinding on capillary pressure flux via a novel hybrid formulation is demonstrated