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

Cross Culture Analysis to Reconstruct the Dimensions of Long-term Orientation and Uncertainty Avoidance

The cross cultural analysis has increasingly become an important research field. One of its merit is to facilitate understanding how the people from different cultural background make decisions differently. The most famous work is done by Hofstede, who introduce a powerful cultural model with 6 cultural dimensions. However, two of these dimensions, Uncertainty Avoidance (UA) and Long-term Orientation (LTO) is not as convincing as others, both theoretically and practically. The paper aims to figure out whether better alternative dimensions can be found to give clarifications.Multi Actor SystemsTechnology, Policy and Managemen

Behavior of Orthotropic Steel-UHPC Composite Bridge Deck under Cyclic Loading

In recent years, ultra-high performance concrete (UHPC) has been introduced in the design of orthotropic steel decks (OSD) to reduce the risk of fatigue cracking. To investigate the fatigue behaviour and fatigue damage process of the orthotropic steel-UHPC composite bridge deck, a fullscale specimen was designed and tested under cyclic loading. Test results show that the fatigue resistance of orthotropic steel-UHPC composite bridge deck satisfies the requirements of the designed vehicle load up to 2 million cycles with no cracks occurred in this phase. Rib-to-crossbeam weld and U-rib butt-welded connection are the two most vulnerable details to crack in OSD under cyclic loading. The fatigue resistance of U-rib bolted connection was investigated, and it is concluded that it performs better than that of U-rib butt-welded connection. The short-headed studs fractured under excessive cyclic loading and 5 types of the fatigue failure modes are identified. And the UHPC layer above the crossbeam exhibited limited number of cracks with the maximum crack width less than 0.05mm at the end of the cyclic, much beyond the requirements.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.Steel & Composite Structure

Risk analysis on cascade breaching of the Tangjiashan landslide dam and two smaller downstream landslide dams

The 2008 Mw 7.9 Wenchuan earthquake triggered at least 257 landslide dams, most of which formed in series along rivers. The failure of an upstream dam could cause the failure of dams downstream one after another. The cascade dam breaching may result in sharp increase of flood and more serious damage downstream. This paper aims to analyze the risks on cascade breaching of the Tangjiashan landslide dam and two smaller downstream landslide dams, which were triggered by the Wenchuan earthquake. The paper first simulates the cascade breaching of these three landslide dams. A modified DABA model is applied for this purpose, in which the water-soil interactions are simulated with erosion and shallow water flow theory. A human risk analysis model, named HURAM, is applied to analyze the cascade breach risks of these three dams. Two scenarios, namely, the simulated real case and the case with the highest flood with overlapping effect, will be considered to show the characteristics of the cascade dam breaching risks. It is found that cascading dam breaching is very likely to form multiple-peak floods which may cause multi-round impact to the people downstream. The overlapping effect of cascading dam breaching would amplify the breach flood risk to the people downstream

Influence of liquid-binder ratio on the performance of alkali-activated slag mortar with superabsorbent polymer

The influences of liquid-binder ratio and mixing sequence on the performance of superabsorbent polymer (SAP)-containing alkali-activated slag (AAS) mortar are investigated in this study. It is found that the SAP absorbs much less liquid in upper supernatant of AAS than in water. Mixing SAP with liquid first induces a larger absorption capacity of the SAP than mixing it with solid first. Increasing the liquid-binder ratio improves the flowability but reduces the strength of AAS mortar with SAP. Nonetheless, the strength of internally cured mixtures is higher than that of the reference even with an extra liquid-binder ratio of 0.09. The reason behind lies in the refinement of capillary and gel porosity by internal curing, despite the presence of large voids originated from SAP. The autogenous shrinkage of AAS paste is reduced significantly by the incorporation of SAP but the further mitigating effect of increased liquid-binder ratio is limited.Materials and Environmen

Behavior of short-headed stud connectors in orthotropic steel-UHPC composite bridge deck under fatigue loading

The short-headed stud connectors play a critical role on the interaction of the orthotropic steel deck (OSD) and the ultra-high performance concrete (UHPC) layer in orthotropic steel-UHPC composite bridge deck. In this paper, the fatigue behavior of these short-headed stud connectors was experimentally investigated in a beam test. The failure modes of the short-headed stud connectors were identified and classified into 5 types. The fatigue test results were analyzed by linear regression analysis neglecting run-outs and treating run-outs as failure respectively. On the other hand, the maximum likelihood estimation (MLE) approach was used to shape the S-N curve by considering the influence of run-outs. Additionally, the push-out and beam fatigue test data were compared, and the push-out test presented a relatively conservative result. Last, the applicability of existing specifications on design guidelines regarding the short-headed stud connectors design in orthotropic steel–UHPC composite bridge deck is discussed, and a design S-N curve with 95% survival probability is proposed.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.Steel & Composite Structure

Effective contact texture region aware pavement skid resistance prediction via convolutional neural network

The surface texture of asphalt pavement has a significant effect on skid resistance performance. However, its contribution to the performance of skid resistance is non-homogeneous and subjects to local validity. There are also a few deep learning models that take into account the effective contact texture region. This paper proposes a convolutional neural network model based on the effective contact texture region, containing macro- and micro-scale awareness sub-modules. In this study, the asphalt mixture with varying gradations was designed to accurately obtain the effective contact texture region. Then, the textures were disentangled into macro- and micro-texture scales by applying the fast Fourier transform and fed into the model for training. Finally, the area of effective contact texture region was calculated, and the effective contact ratio parameter was then proposed using the triangulation algorithm. The results showed that the effective contact texture area of pavement varies by the asphalt mixture type. The effective contact ratio parameter exhibited a significant positive correlation (Pearson correlation coefficient is 0.901, R2= 0.8129) with skid resistance performance and was also influenced by key sieve aggregate content from 2.36 to 4.75 mm. The data of effective contact texture region following disentanglement significantly released the model performance (the relative error dropped to 1.81%). The model exhibited improved precision and performance, which can be utilized as an efficient, non-contact alternative method for skid resistance 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.Transport and Plannin

Effect of superabsorbent polymer introduction on properties of alkali-activated slag mortar

Internal curing by superabsorbent polymer (SAP) has been applied in alkali-activated slag (AAS) systems by a few previous studies with the purpose to mitigate the autogenous shrinkage. However, the effects of SAP on other properties of AAS have been rarely studied. In this paper, the workability, strength, permeability, and frost resistance of AAS mortar with synthesized SAP are investigated besides the autogenous shrinkage. Two SAP introducing ways (dry mixing and wet mixing) are considered. It is found that the flowability of AAS mortar decreases with the increase of SAP dosage regardless of the introducing way. The strength and permeability increase with the SAP dosage when it is below a certain amount depending on the mixing way. The autogenous shrinkage can be mitigated significantly by the incorporation of SAP and the mitigating effect is more pronounced by wet mixing. The frost resistance becomes better when more SAP is introduced in either way. The mechanisms behind these phenomena are explained based on the characterization results on the reaction kinetics, reaction products and pore structure of the mixtures with SAP.Materials and Environmen

Thermal annealing of C ion irradiation defects in nuclear graphite studied by positron annihilation

In order to investigate the thermal behaviour of radiation induced point defects in nuclear graphite, ETU10 graphite was implanted with 350 keV C+ ion to doses of 1015 and 1016 cm-2. The point defects introduced by the implantation were characterized by Positron Annihilation Doppler Broadening (PADB) and their thermal behaviour was studied during "in situ" annealing at Delft Variable Energy Positron beam (VEP). The annealing was performed for 5 minutes at temperatures ranging from 300 K (as implanted) to 1500 K in steps of 100 K. For both doses, an annealing stage at around 450 K is observed followed by a second stage around 700 K. For the high dose implantation vacancy complexes are found which are stable up to a temperature around 1400K.RST/Neutron and Positron Methods in Material