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

Combined 3D Scanning PIV and Scanning LIF for flow and phase transfer measurements around a melting particle

Interfacial flow and phase transfer around a melting solid particle were investigated with combined 3D Scanning PIV and Scanning LIF technique. Experiments were carried out with a spherical ice-particle, which was initially shock-frozen from water saturated with fluorescent dye. Flow in a water tank seeded with small tracer particles was investigated, when the ice-particle was released at the water surface in the center of the tank and the melting process began. A scanning light-sheet was generated with a polygonal mirror and flow was recorded with two high-speed cameras with a beam splitter plate. The cameras were equipped with different color filter such that cam#1 recorded only the clean water while cam#2 recorded the molten fluid generated by the heat transfer of the frozen fluorescent ice-particle. This allowed us to record the 3D flow and 3D concentration field simultaneous. The results showed the complexity of induced flow process by the heat/phase transfer and buoyancy interacting with the base flow in the water tank. A small swirl in the tank was enforced by buoyancy-induced vortex stretching and resulted in increasing particle rotation. This self-enforcing process generated a columnar vortex in the wake below the particle which underwent vortex breakdown. Fluid originating from the phase transfer process was accumulated in the vortex

4D analysis of flow around a Tumbling Ring-Type Particle using Scanning PIV and 3D Least Squares Matching

This work describes the flow around a sphere with a longitudinal hole inside. Such ring-type particles are useful in many applications like chemical reactors as catalysts (seed particles) to increase the reacting surface in the multi-phase flow. Both heat transfer and the flow structure in and around those catalysts are of interest for fixed bed reactors as well as floating bed systems with solid particles. The focus of this work is the analysis of the 3D flow structure in the borehole and the outer flow around the particle and its influence on particle motion and rotation as well as the change of heat transfer involved herein. Since internal and external flow may induce Lift- and Magnus-forces we expect a complex interaction of particle motion and flow field which is tested in a special flow tank. Refractive index matching is used in combination with Light-Sheet Scanning and 3D Least Squares Matching to obtain the flow field around a silicone sphere with a longitudinal hole. The results show that the flow through the hole imposes pressure forces that lead to particle rotation and drift in a non-trivial way. Thereby, drag and lift-forces as well as torque are changed by an order of magnitude and cannot be represented by semi-empirical equations of the global body shape anymore

Relationships between achievement in high school, college and occupation;

"Cooperative research project no.542 ... supported through ... Office of Education."Includes bibliography.Mode of access: Internet

Study of phenylxylylethane (PXE) as scintillator for low energy neutrino experiments

We report on the study of a new liquid scintillator target for neutrino interactions in the framework of the research and development program of the Borexino solar neutrino experiment. The scintillator consists of 1,2-dimethyl-4-(1-phenylethyl)-benzene (phenyl-o-xylylethane, PXE) as solvent and 1,4-diphenylbenzene (para-Terphenyl, p-Tp) as primary and 1,4-bis(2-methylstyryl)benzene (bis-MSB) as secondary solute. The density close to that of water and the high flash point makes it an attractive option for large scintillation detectors in general. The study focused on optical properties, radioactive trace impurities and novel purification techniques of the scintillator. Attenuation lengths of the scintillator mixture of 12 in at 430 nm were achieved after purification with an alumina column. A radiocarbon isotopic ratio of C-14/C-11 = 9.1 x 10(-18) has been measured in the scintillator. Initial trace impurities, e.g. U-238 at 3.2 x 10(-14) g/g could be purified to levels below 1 x 10(-17) g/g by silica gel solid column purification