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

Narrative versus Style: Effect of Genre Typical Events versus Genre Typical Filmic Realizations on Film Viewers' Genre Recognition

This study investigated whether film viewers recognize four basic genres (comic, drama, action and nonfiction) on the basis of genre-typical event cues or of genretypical filmic realization cues of events. Event cues are similar to the narrative content of a film sequence, while filmic realization cues are similar to stylistic surface cues of a film sequence. It was predicted that genre recognition of short film fragments is cued more by filmic realization cues than by event cues. The results showed that: (a) filmic realization was the stronger cue in viewers’ genre recognition, except for drama recognition; (b) the influence of a genre-typical event on genre recognition decreased stepwise from drama to action to comic to nonfiction. The latter result is explained in terms of specific genre characteristics. The former result is consistent with a conception of memory for film that acknowledges the role of media-specific mental representations. It is suggested viewers possess a specific genre knowledge embodied in visual simulators that in most cases is dominant over genre knowledge embodied in event simulators, at least in a task requiring genre classification of film fragments lasting up to 24 seconds.Industrial DesignIndustrial Design Engineerin

Destillatieve scheiding van freon-11 en freon-12

DelftChemTechApplied Science

Viewer knowledge: Application of exposure-based layperson knowledge in genre-specific animation production

Laypeople are increasingly motivated to participate in design processes, but what knowledge do they actually possess that enables such participation? Some studies show that laypeople have gained detailed product knowledge from exposure. This knowledge can be applied to accurately recognize product categories, and to manage emotional expectations. In the experiment presented here, we test if laypeople can apply product category knowledge to production tasks using an animation production toolkit designed by the authors. In a betweensubjects experiment, participants with and without production training produced 3D animations for four distinct genres—comedy, drama, action, and non-fiction. Their task was to deliver versions of a basic animation film by adapting the motion of the film’s central figure by using an interactive test device. This device allowed participants to control four parameters of figure motion: velocity, efficiency, fluency, and deformation. As predicted, the animations produced by laypeople and experts were highly similar. We argue that in comparable cases it is important to not underestimate laypeople’s product knowledge, as toolkits could be designed to align to this implicit production knowledge in order to increase the motivation of laypeople to participate in the designIndustrial DesignIndustrial Design Engineerin

Innovative ICT solutions for monitoring and facilitating international trade

The use of information and communication technology (ICT) for international trade is increasingly impor- tant. The EU-funded projects ITAIDE and CASSANDRA propose further innovations to solve the trade con- trol and facilitation dilemma.Infrastructures, Systems and ServicesTechnology, Policy and Managemen

Multimodal data collection for social interaction analysis in-the-wild

The benefits of exploiting multi-modality in the analysis of human-human social behaviour has been demonstrated widely in the community. An important aspect of this problem is the collection of data-sets that provide a rich and realistic representation of how people actually socialize with each other in real life. These subtle coordination patterns are influenced by individual beliefs, goals, and, desires related to what an individual stands to lose or gain in the activities they perform in their every day life. These conditions cannot be easily replicated in a lab setting and require a radical re-thinking of both how and what to collect. This tutorial provides a guide on how to create such multi-modal multi-sensor data sets when holistically considering the entire experimental design and data collection process.Pattern Recognition and Bioinformatic

A separable cohesive element for modelling coupled failure in laminated composite materials

A three-dimensional separable cohesive element (SCE) is proposed to enable the modelling of interaction between matrix cracking and interfacial delamination in laminated fibre-reinforced composite materials. It is demonstrated that traditional cohesive elements are incapable of modelling the coupled failure mechanisms accurately if partitioning is not allowed. The SCE may be partitioned according to the configuration and geometry of matrix cracks in adjacent plies, thus maintaining appropriate connection between plies. Physically, the original interface is split and new interfaces are formed to bond the homologous cracked solids during fracturing process. The stress concentration induced by matrix cracks and the load transfer from cracked solid elements to interface cohesive element are effectively modelled. A comprehensive set of cases of multiple matrix crack configurations from plies of different fiber angles is considered. The proposed SCE is applied to model progressive failure in composite laminates and the results are found to agree with experiments.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.Aerospace Structures & Computational Mechanic

A 3D separable cohesive element for modelling the coupled failure in laminated composite materials

The interaction between matrix cracks and interface delamination is a major failure mechanism in composite laminates and has been a subject of active research in recent years. Although coupled failure behaviour of composite laminates between matrix cracks and delamination has been observed in experiments, accurate modelling of this phenomenon for application in composite structures remains challenging. In this work, a three-dimensional separable cohesive element (SCE) is proposed to enable the modelling of interaction between matrix cracking and interfacial delamination in laminated fibre-reinforced composite materials. It is demonstrated that traditional cohesive elements are incapable of modelling the coupled failure mechanisms accurately if partitioning is not allowed. The SCE may be partitioned according to the configuration and geometry of matrix cracks in adjacent plies, thus maintaining appropriate connection between plies. Physically, the original interface is split and new interfaces are formed to bond the homologous cracked solids during fracturing process. The stress concentration induced by matrix cracks and the load transfer from cracked solid elements to interface cohesive element are effectively modelled. The proposed SCE is applied to model progressive failure in composite laminates and the results are found to agree with experiments.Aerospace Structures & Computational Mechanic

A Framework for Understanding Circular Economy Monitoring: Insights from the Automotive Industry

The United Nations’ Sustainable Development Goals (SDGs) have paved the way toward a more sustainable future. The 2019 EU Green Deal and the 2020 EU Circular Economy Action Plan [1] introduce laws and regulations to facilitate and encourage the transition towards sustainability and a circular economy (CE). For the implementation of these regulatory measures, public authorities face the challenge to gain access to relevant business data for compliance monitoring. Digital infrastructures and access to business data (sources) such as the material composition of products are useful for compliance monitoring, however CE-relevant data is spread across multiple platforms of the supply chain partners and across multiple supply chains. Therefore, digital infrastructures and information-sharing arrangements need to be developed to create visibility and traceability for monitoring the circular economy flows. In this paper, we use a conceptual framework with four dimensions (context, actors, public value, and digital infrastructures) to analyze key actors and potential data of value they hold in their digital infrastructures to explore options for data-sharing solutions.By focusing predominantly on the actor dimension, we analyze a case study in the automotive industry, taking the perspective of two focal Dutch governmental actors: Customs and the Ministry of Infrastructure and Water Management. In our analysis, we also show how this actor dimension is linked to the other dimensions: context, public value, and digital infrastructures. These dimensionsplay an instrumental role in navigating through the complex actornetwork in a systematic way toward identifying pathways for the development of digital infrastructures and data-sharing solutions for circular economy monitoring.Research Support & InnovationInnovation AffairsInformation and Communication Technolog

Adaptive floating node method for modelling cohesive fracture of composite materials

The cohesive element has been widely employed to model delamination and matrix cracking in composite materials. However, an extremely fine mesh along the potential crack path is required to achieve accurate predictions of stresses within the cohesive zone. A sufficient number of cohesive elements must be present within the cohesive zone ahead of the crack tip, resulting in very high computational cost and time for application to practical composite structures. To mitigate this problem, an adaptive floating node method (A-FNM) with potential to reduce model size and computational effort is proposed. An element with adaptive partitioning capabilities is designed such that it can be formulated as a master element, a refined element and a coarsened element, depending on the damage state in the progressive damage process. A relatively coarse overall mesh may be used initially, and by transforming the element configurations adaptively, the local refinement and coarsening schemes are applied in the analysis. The localized stress gradient ahead of the crack front within the refinement zone is captured by the refined elements. The refinement and coarsening operations are performed at the elemental level with fixed nodal connectivity, so that global successive remeshing in adaptive mesh refinement (AMR) techniques is avoided; this is the key difference between AMR and A-FNM. It is demonstrated that, without loss of accuracy, the present method simplifies the modelling procedure and reduces computational cost.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.Aerospace Structures & Computational Mechanic