Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Photogrammetric Solution for Analysis of Out-Of-Plane Movements of a Masonry Structure in a Large-Scale Laboratory Experiment

This paper proposes a photogrammetric procedure able to determine out-of-plane movements experienced by a masonry structure subjected to a quasi-static cyclic test. The method tracks the movement of circular targets by means of a coarse-to-fine strategy. These targets were captured by means of a photogrammetric network, made up of four cameras optimized following the precepts of a zero-, first-, and second-order design. The centroid of each circular target was accurately detected for each image using the Hough transform, a sub-pixel edge detector based on the partial area effect, and a non-linear square optimization strategy. The three-dimensional (3D) coordinates of these targets were then computed through a photogrammetric bundle adjustment considering a self-calibration model of the camera. To validate the photogrammetric method, measurements were carried out in parallel to an ongoing test on a full-scale two-story unreinforced masonry structure (5.4 × 5.2 × 5.4-m) monitored with more than 200 contact sensors. The results provided by the contact sensors during one of the load phases were compared with those obtained by the proposed approach. According to this accuracy assessment, the method was able to determine the out-of-plane displacement during the quasi-static cyclic test with a sub-pixel accuracy of 0.58.Optical and Laser Remote SensingApplied Mechanic

Results of the AVATAR project for the validation of 2D aerodynamic models with experimental data of the DU95W180 airfoil with unsteady flap

The FP7 AdVanced Aerodynamic Tools for lArge Rotors - Avatar project aims to develop and validate advanced aerodynamic models, to be used in integral design codes for the next generation of large scale wind turbines (10-20MW). One of the approaches towards reaching rotors for 10-20MW size is the application of flow control devices, such as flaps. In Task 3.2: Development of aerodynamic codes for modelling of flow devices on aerofoils and, rotors of the Avatar project, aerodynamic codes are benchmarked and validated against the experimental data of a DU95W180 airfoil in steady and unsteady flow, for different angle of attack and flap settings, including unsteady oscillatory trailing-edge-flap motion, carried out within the framework of WP3: Models for Flow Devices and Flow Control, Task 3.1: CFD and Experimental Database. The aerodynamics codes are: AdaptFoil2D, Foil2W, FLOWer, MaPFlow, OpenFOAM, Q3UIC, ATEFlap. The codes include unsteady Eulerian CFD simulations with grid deformation, panel models and indicial engineering models. The validation cases correspond to 18 steady flow cases, and 42 unsteady flow cases, for varying angle of attack, flap deflection and reduced frequency, with free and forced transition. The validation of the models show varying degrees of agreement, varying between models and flow cases.Wind EnergyAerodynamic