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

Methodology to assess the effects of magnetohydrodynamic electromagnetic pulse (MHD-EMP) on power systems

This paper summarizes a method to evaluate the possible effects of magnetohydrodynamic-electromagnetic pulse (MHD-EMP) on power systems. This method is based on the approach adapted to study the impact of geomagnetic storms on power systems. The paper highlights the similarities and differences between the two phenomena. Also presented are areas of concern which are anticipated from MHD-EMP on the overall system operation. 12 refs., 1 fig

The use of polybutene for controlling the flow of liquids in centrifugal microfluidic systems

The field of centrifugal microfluidics has evolved over the last several decades to allow implementation of complex biological and chemical assays on Lab-on-Disc (LOD) platforms. Present study describes the use of polymer polybutene for tuning hydrophobic siphons and for liquid volume definition on a centrifugal microfluidic platform. Both the siphon tuning and the volume definition steps are carried out by generating negative pressure that results from the volume expansion caused by the transfer of polybutene from a dedicated chamber into a secondary reservoir via a connecting siphon. The hydrophobic valve of the chamber that holds polybutene bursts open at specific angular velocities that depend on the height and density of the liquid column. Thus, the parameters of siphon activation can be adjusted by tuning the burst angular velocity of the valve that is driven by filling the tuning reservoir with a specific volume of polybutene. The same disc construction can be utilized to provide volume definition functionality to transfer liquids from one reservoir to another reservoir in as many fractions as there are immiscible liquids of different densities in the tuning chamber. The presented work also demonstrates the use of polybutene in sealing fluidic chambers to improve heating efficiency and to minimize evaporation during thermal cycling required for applications such as PCR amplification. Finally, the use of polybutene as a stationary liquid phase in droplet production on a spinning disc is demonstrated.close0