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

On Determining Smartphone Microphone Directivity with Application to Beamforming

An equiangular sampling scheme and accessory measurement set-up for determining the directivity gain pattern of a commercially available smartphone is presented. Determining this directivity gain pattern based on these measuremenents was not possible, because next to the impulse response of the microphone also the impulse response of the acoustic system. Different smartphone set-ups are tested and the directivity of a smartphone on a surface differs from a smartphone in mid-air. The determined directivity gain pattern is suitable for use by a beamforming algorithm, but it resulted in no improvement of the performance of the algorithm. Interpolation of the measured results was not considered, as the system for which the measurements are intended cannot measure accurate smartphone orientations. Other work has shown that the orientation of a modern smartphone is not yet known within 10 degrees margins, therefore interpolation of the measured results is not considered. This could be included in future work, along with to the determination of indoor position of a smartphone, a sampling scheme with fewer samples and a means to reverse the contribution of the acoustic system to the measurements.Multimedia computingTelecommunicationsElectrical Engineering, Mathematics and Computer Scienc

Component-Specific Usability Testing

This paper presents the results of a meta-analysis carried out on the results of six experiments to support the claim that component-specific usability measures are on average statistically more powerful than overall usability measures when comparing different versions of a part of a system. An increase in test effectiveness implies the need for fewer participants in usability tests that study different versions of a component. Three component-specific measures are presented and analyzed: an objective efficiency measure and two subjective measures, one about the ease-of-use and the other about the users’ satisfaction. Whereas the subjective measures are obtained with a questionnaire, the objective efficiency measure is based on the number of user messages received by a component. Besides describing the testing method, this paper also discusses the underlying principles such as layered interaction and multiple negative-feedback loops. The main contribution of the work described is the presentation of component-based usability testing as an alternative for traditional holistic-oriented usability tests. The former is more aligned with the component-based software engineering approach, helping engineers to select the most usable versions of a componentMediamaticsElectrical Engineering, Mathematics and Computer Scienc

The Effect Of 3D Audio And Other Audio Techniques On Virtual Reality Experience

Three studies were conducted to examine the effect of audio on people's experience in a virtual world. The first study showed that people could distinguish between mono, stereo, Dolby surround and 3D audio of a wasp. The second study found significant effects for audio techniques on people's self-reported anxiety, presence, and spatial perception. The third study found that adding sound to a visual virtual world had a significant effect on people's experience (including heart rate), while it found no difference in experience between stereo and 3D audio.Intelligent SystemsElectrical Engineering, Mathematics and Computer Scienc

On the Generic Utilization of Probabilistic Methods for Quantification of Uncertainty in Process-based Morhpodynamic Model Applications

A variety of uncertainty sources are inherent in process-based morphodynamic modelling applications. There is an increasing demand for the quantification of these uncertainties. This contribution introduces a probabilistic-morphodynamic (PM) modelling framework that enables this quantification. The PM modelling framework provides a systematic approach, while also lowering the required effort for inclusion of uncertainty quantification in morphodynamic model studies. Applicability and added value is shown using a pilot application to the Holland coast.Hydraulic EngineeringCivil Engineering and Geoscience

Ballistic supercurrent discretization and micrometer-long Josephson coupling in germanium

We fabricate Josephson field-effect transistors in germanium quantum wells contacted by superconducting aluminum and demonstrate supercurrents carried by holes that extend over junction lengths of several micrometers. In superconducting quantum point contacts we observe discretization of supercurrent, as well as Fabry-Pérot resonances, demonstrating ballistic transport. The magnetic field dependence of the supercurrent follows a clear Fraunhofer-like pattern, and Shapiro steps appear upon microwave irradiation. Multiple Andreev reflections give rise to conductance enhancement and evidence a transparent interface, confirmed by analyzing the excess current. These demonstrations of ballistic superconducting transport are promising for hybrid quantum technology in germanium.QCD/Veldhorst LabQuTechBusiness DevelopmentQCD/Scappucci La