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

Sequential ultrasonic spot welding of thermoplastic composites: An experimental study on the welding process and the mechanical behaviour of (multi-)spot welded joints

The popularity of thermoplastic composites (TPCs) has been growing steadily in the last decades in the aircraft industry. This is not only because of their excellent material properties, but also owing to their fast and cost-effective manufacturing process. Fusion bonding, or welding, is a typical joining method for TPCs due to the intrinsic properties of thermoplastic polymers. Among different welding technologies, ultrasonic welding has been regarded as one of the most promising techniques for the assembly of TPC components. Ultrasonic welding is by nature a spot welding technique. As it is known that a series of problems result from using mechanical fasteners for joining composite structures, e.g. breaking fibres during drilling and extensive labour work, ultrasonic spot welding can be considered as a promising alternative from the perspective of fast manufacturing cycle. However, fundamental understanding is still lacking to achieve application of ultrasonic spot welding in composite structures to be achieved:Structural Integrity & Composite

Ramp sinusoidal breakdown of epoxy resin under high voltage waveforms at different frequencies

In this study, the immediate time to breakdown for pure epoxy resin is measured by applying a ramp sinusoidal voltage signal at certain frequency (50Hz, 500Hz and 5000Hz) until breakdown occurs. The HV testing procedures, epoxy resin sample and experimental set-up preparation and Weibull analysis of obtained results are elaborated. The experiments were carried out on epoxy samples with the thickness between 0.1mm and 0.2mm and the thickness was divided into three groups for more accurate statistical analysis.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.High Voltage Technology Grou

Can I have a Mooc2Go, please? On The Viability of Mobile vs. Stationary Learning

The use of mobile technology has become a part of our dailylives and enabled us to perform tasks that once were possible only onstationary computers on-the-go anywhere and at any time. This shifthas also affected the way we learn. The use of mobile devices on-the-gorequires users to multitask and divide attention between several activi-ties. In the context of learning, it may lead to high cognitive load andpotential disruptions. While many MOOC platforms have provided thepossibility for learning on mobile devices, the learning situation and itseffect on learners’ while using mobile devices on-the-go has not been stud-ied in full. Contrary to the majority of available mobile learning studieswhich are conducted in lab conditions, we focus on real-life situationscommonly experienced by learners while learning on-the-go. We studythe differences in MOOC learners’ performance and interactions in twodifferent learning situations with mobile devices: stationary learning andlearning on-the-go on the edX platform.Web Information System

Experimental study of epoxy surface discharge under different frequencies

With widely use of power electronics in medium voltage level, there is increasing concern about behaviour of insulation material under arbitrary voltage stress. Solid-gas insulation is a general choice in medium voltage level. Therefore, it’s unavoidable to encounter surface discharge problem. In this paper, the surface discharge on epoxy-air interface is investigated, which is a commonly used insulation material. Point to plate electrode was used to test the surface flashover voltage and partial discharge (PD) behaviour at 50Hz, 500Hz, 1kHz, 2kHz and 5kHz. As the result, with increasing frequency, PDIV keeps roughly constant and flashover voltage first increases and then decrease, and the frequency obtaining highest flashover voltage is related to gap length.High Voltage Technology Grou

IntelliEye: Enhancing MOOC Learners' Video Watching Experience with Real-Time Attention Tracking

Massive Open Online Courses (MOOCs) have become an attractive opportunity for people around the world to gain knowledge and skills. Despite the initial enthusiasm of the first wave of MOOCs and the subsequent research efforts, MOOCs today suffer from retention issues: many MOOC learners start but do not finish. A main culprit is the lack of oversight and directions: learners need to be skilled in self-regulated learning to monitor themselves and their progress, keep their focus and plan their learning. Many learners lack such skills and as a consequence do not succeed in their chosen MOOC. Many of today's MOOCs are centered around video lectures, which provide ample opportunities for learners to become distracted and lose their attention without realizing it. If we were able to detect learners' loss of attention in real-time, we would be able to intervene and ideally return learners' attention to the video. This is the scenario we investigate: we designed a privacy-aware system (IntelliEye) that makes use of learners' Webcam feeds to determine---in real-time---when they no longer pay attention to the lecture videos. IntelliEye makes learners aware of their attention loss via visual and auditory cues. We deployed IntelliEye in a MOOC across a period of 74 days and explore to what extent MOOC learners accept it as part of their learning and to what extent it influences learners' behaviour. IntelliEye is open-sourced at https://github.com/Yue-ZHAO/IntelliEye.Web Information System

Comparative analysis of in-plane and out-of-plane mechanical behaviour of spot-welded and mechaincally fastened joints in thermoplastic composites

Ultrasonic welding is a promising assembly technique for thermoplastic composites and it is well-suited for spot welding. In this paper, the in-plane and out-of-plane mechanical behaviour of ultrasonically spot-welded and mechanically fastened joints are investigated by double-lap shear and pull-through tests, respectively. Special attention was paid to the comparison of onset failure load and joint stiffness of both types of joints in either type of test. Fractography was utilized to analyse the teste specimens. Failure of welded specimens was found limited in the joints but catastrophic damage was introduced into composite substrates of mechanically fastened specimens. The possibility of the substitution for mechanically fastened joints by spot-welded joints is discussed.Structural Integrity & CompositesAerospace Structures & Material

Towards high-quality multi-spot-welded joints in thermoplastic composite structures

Ultrasonic welding is a promising assembly technique for thermoplastic composites and it is well-suited for spot welding. In this study, two typical welding process control strategies, i.e. displacement-controlled and energy-controlled welding, were selected to manufacture spot-welded joints. The influence of different boundary conditions, provided by different welding jigs, on the welding process and the performance of thus-created welded joints were investigated. The optimum input energy was found dependent on the welding jigs, while the optimum displacement was consistent for achieving the maximum weld strength in both welding jigs. Therefore, displacement-controlled welding showed more potential in producing consistent welds in sequential multi-spot welding.Structural Integrity & CompositesAerospace Structures & Material

Impact of Home-Based Learning Experience During COVID-19 on Future Intentions to Study Online: A Chinese University Perspective

As coronavirus disease 2019 (COVID-19) swept the world in early 2020, all the Chinese universities and colleges adopted online learning to fulfill the directive saying “classes suspended but learning continues.” Understanding the impact of this large-scale online learning experience on the future online learning intention of Chinese university students can help design better blended-learning activities. This study applies flow experience and theory of planned behavior (TPB) to construct a theoretical framework for assumption making and the assumptions made are validated by data gained from questionnaires. A total of 6,933 students from 54 institutions in China participated in the investigation, with 5,456 valid questionnaires returned. This study employs partial least squares (PLS) regression and confirmative factor analysis (CFA) to analyze and estimate the measurement model and the structural model. The results indicate that the experience of home-based learning significantly influenced the attitudes of Chinese university students, which in turn had a positive influence on their intention to continue online learning. The research findings provide a theoretical framework and practical guidelines on building a scientific online learning platform with appropriate online learning environments and tasks for a post-COVID-19 era blended-learning in Chinese universities.Design & Construction Managemen

Towards robust sequential ultrasonic spot welding of thermoplastic composites: Welding process control strategy for consistent weld quality

The research in this paper is an essential part of a bigger effort on developing robust sequential ultrasonic welding of multi-spot welded joints in thermoplastic composites. It mainly focused on assessing the impact of the changes in boundary conditions on the welding process and whether it could be circumvented by using an appropriate process control strategy. A two-step approach was followed by investigating: (1) the effect of boundary conditions on displacement- and energy-controlled single-spot welded joints and (2) displacement- and energy-controlled sequential ultrasonic welding of double-spot welded joints. The results showed that previous spots indeed affect the energy required to obtain an optimum new welded spot, which challenges the use of energy-controlled welding for this application. Contrarily, displacement-controlled welding was shown to provide consistent-quality welds with a constant set of welding parameters and it was hence identified as the most promising welding strategy for sequential ultrasonic welding of thermoplastic composites.Structural Integrity & CompositesEducation AEAerospace Structures & Material