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

Wafer-level SLID bonding for MEMS encapsulation

Hermetic packaging is often an essential requirement to enable proper functionality throughout the device's lifetime and ensure the optimal performance of a micro electronic mechanical system (MEMS) device. Solid-liquid interdiffusion (SLID) bonding is a novel and attractive way to encapsulate MEMS devices at a wafer level. SLID bonding utilizes a low-melting-point metal to reduce the bonding process temperature; and metallic seal rings take out less of the valuable surface area and have a lower gas permeability compared to polymer or glass-based sealing materials. In addition, ductile metals can adopt mechanical and thermo-mechanical stresses during their service lifetime, which improves their reliability. In this study, the principles of Au-Sn and Cu-Sn SLID bonding are presented, which are meant to be used for wafer-level hermetic sealing of MEMS resonators. Seal rings in 15.24 cm silicon wafers were bonded at a width of 60 µm, electroplated, and used with Au-Sn and Cu-Sn layer structures. The wafer bonding temperature varied between 300 °C and 350 °C, and the bonding force was 3.5 kN under the ambient pressure, that is, it was less than 0.1 Pa. A shear test was used to compare the mechanical properties of the interconnections between both material systems. In addition, important factors pertaining to bond ring design are discussed according to their effects on the failure mechanisms. The results show that the design of metal structures can significantly affect the reliability of bond rings

The Expansion of the Pulmonary Rib Cage during Breath Stacking Is Influenced by Age in Obese Women

OBJECTIVE: To analyze in obese women the acute effects of the breath stacking technique on thoraco-abdominal expansion. DESIGN AND METHODS: Nineteen obese women (BMI ≥ 30 kg/m(2)) were evaluated by anthropometry, spirometry and maximal respiratory muscle pressures and successively analyzed by Opto-Electronic Plethysmography and a Wright respirometer during quiet breathing and breath stacking maneuvers and compared with a group of 15 normal-weighted healthy women. The acute effects of the maneuvers were assessed in terms of total and compartmental chest wall volumes at baseline, end of the breath stacking maneuver and after the maneuver. Obese subjects were successively classified into two groups, accordingly to the response during the maneuver, group 1 = prevalent rib cage or group 2 = abdominal expansion. RESULTS: Age was significantly lower in group 1 than group 2. When considering the two obese groups, FEV1 was lower and minute ventilation was higher only in group 2 compared to controls group. During breath stacking, inspiratory capacity was significant differences in obese subjects with a smaller expansion of the pulmonary rib cage and a greater expansion of the abdomen compared to controls and also between groups 1 and 2. A significant inverse linear relationship was found between age and inspiratory capacity of the pulmonary rib cage but not of the abdomen. CONCLUSIONS: In obese women the maximal expansion of the rib cage and abdomen is influenced by age and breath stacking maneuver could be a possible therapy for preventing respiratory complications