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

A general RDE-based simulator for statistical timing analysis

Accurate timing analysis of digital integrated circuits is becoming harder to achieve with current and future CMOS technologies. The shrinking feature sizes lead to increasingly important local process variations (PV), making existing methods like corner-based static timing analysis (STA) yield overly pessimistic results. While industry faces the uncertainty introduced by PV with time-consuming Monte Carlo (MC) simulations, this thesis presents a general purpose statistical circuit simulator for accurate timing analysis. This simulator uses a statistical simplified transistor model (SSTM) as its main building block, which allows the accurate modeling of both combinational and sequential circuits, and it is able to perform a fast statistical timing analysis of any input circuit by solving a system of random differential equations (RDE). Different experiments, ranging from simple cells to complex combinational circuits, were conducted to validate the simulator accuracy and performance for the 45nm CMOS technology. The obtained results show accurate results for both deterministic and statistical analysis of the circuit signals while effectively reducing the runtime when compared to MC simulations.MSc EE MicroelectronicsMicroelectronics & Computer EngineeringElectrical Engineering, Mathematics and Computer Scienc

Surface velocity contour analysis in the airborne dust generation due to open storage piles

In the framework of the Research Project CTM2005-00187/TECNO, \u93Prediction models and prevention systems in the particle atmospheric contamination in an industrial environment\u94 of the Spanish National R+D Plan of the Ministry of Education and Science, 2004-2007 period, there have been developed several CFD models to simulate particulated material emission from mineral stockpiles. US EPA regulation determines the influence of the wind in the pile surface through tables and figures obtained from several tests done in atmospheric wind tunnels, depending on two typical shapes of stockpiles: a cone and a flat top pile. In order to create a computer based system that obtains the particulated material emission factor, CFD was selected as the way to simulate the effect of wind gusts in the pile surface. Several models were developed using the commercial code Ansys CFX 10.0, starting from several 3-D meshes of different resolutions generated using ICEM CFD 10.0. There were selected medium complexity turbulence models in order to obtain affordable resolution times in single processor machines, as well as following advices contained in related bibliography. These models were: k-epsilon (with and without surface roughness) and k-w based Shear-Stress-Transport (SST), combined with different logarithmic and plain wind profiles. Results were compared against the experimental data included within EPA and the best fit was obtained with a roughness k-epsilon model using a logarithmic wind profile

Gaining insight into unfamiliar contexts: A design toolbox as input for using role-play techniques

This paper presents a design toolbox developed for Philips Design in commission of Philips Medical Systems that provides insight into the healthcare context of rural India. Creating products for this context requires an understanding of the needs of the people within it. This paper discusses contextual design through the combination of different descriptive and experiential tools, used to introduce designers into a context they are not familiar with. The toolbox has been evaluated using different performance techniques with design students. The use of role-play techniques has proven increasing relevance in many aspects: increasing the understanding and experience of participants about the context, creating an embodied and common understanding of the ideas being developed and communicating the concepts in their context.Industrial Design Engineerin

Modelling of capillary water absorption in sound and cracked concrete using a dual-lattice approach: Computational aspects

Lattice models have been used to simulate mass transport to predict durability of cementitious materials. In particular, the use of dual lattice meshes allows for the coupling of fracture and transport processes, which commonly occur at the same time in these materials. Literature has shown good agreement between simulations and experimental results. Nevertheless, work regarding relevant computational aspects of the numerical model are scarce. In this study, a Voronoi-discretized lattice model is used to simulate unsaturated moisture transport in cement-base materials through the Richards equation. First, investigations regarding the choice of elemental volume approximation, time-stepping procedure and quadrature are evaluated. After validation of the approximations, simulated moisture transport in sound concrete was compared to experiments and mesh and time step sensitivity were discussed. A new approach to model capillary absorption of water in cracked concrete was also proposed and its advantages with respect to existing approaches are discussed by comparing to experimental measurements. The results confirm that the model can accurately predict the transport processes for the earlier stage of capillary absorption. Furthermore, moisture ingress in cracked concrete is simulated for different crack configurations and the use of different approaches is suggested accordingly. Finally, guidelines regarding the approximations used for optimization of the computations are presented.Applied MechanicsMaterials and EnvironmentMaterials- Mechanics- Management & Desig

Optimisation d’une desserte ferroviaire tenant compte des flux de voyageurs et de la qualité de service

Transport and Plannin

Design and evaluation of a Flight Envelope Protection haptic feedback system

This paper describes the design and evaluation of a shared control, haptic feedback system to communicate Flight Envelope Protection System intent. The concept uses a combination of stiffness feedback and vibration to communicate proximity of the aircraft state to flight envelope boundaries. In addition, a stick center shift can be applied by the envelope protection system to cooperatively perform corrective actions in case of severe excursions of the envelope margins. Results from the evaluation experiment show improved performance with haptic feedback in both scenarios. Workload ratings were unaffected. Pilot opinion was unanimously positive, especially with regard to the combination of stiffness feedback and vibration cues.Control & OperationsControl & Simulatio

Optimization of a passenger railway transportation plan considering mobility flows and service quality

This research focuses on designing transportation plan for SNCF Transilien (French rail-way operator for the Parisian suburban mass transit). The objective is to develop methods and decision support tools to propose a timetable adapted to the passenger demand in the Parisian mass transit system, including comfort and reliability criterias.This paper aims to present the first step of this research. We propose a graph theoretic ILP formulation for the Line Planning Problem, minimizing both travelers travel time and operating cost. We furthermore develop a multi-objective method to solve this problem. This method offers a pool of solutions in order to let the final designer choose the solution. We report computational results on real world instances provided from SNCF Transilien.Power Point PresentationTransport and Plannin