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

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Microstructure of polymer cement concrete

Civil Engineering and Geoscience

Maintenance optimization for railway infrastructure networks

Maintenance is crucial for the proper functioning and lifetime extension of a railway infrastructure network, which is composed of various infrastructures with different functions. In this thesis we develop robust and tractable model-based approaches for maintenance optimization of railway infrastructure networks. In addition, we develop a compact formulation for a variant of the multiple Traveling Salesman Problem (TSP), that can be applied to optimal scheduling of maintenance crews for a railway network, and a systematic numerical solution method for reverse Stackelberg game with incomplete information, which can be viewed as the framework for optimal maintenance contract design.Hybrid, Adaptive and Nonlinea

Whole failure process analysis for jointed rock masses based on coupling method of DDA and FEM

The elastic-plastic mechanical behaviour is a typical characteristic of rock mass. The load action will bring on the local destruction, large deformation, even whole failure of rock mass with the discontinuous mediums (e.g. joint, crack and fault). It is a coupling process of the continuous deformation and the discontinuous deformation. The discontinuous deformation analysis (DDA) and finite element method (FEM) are combined to build the elastic-plastic mechanical model. The rock block is divided into the finite element meshes. FEM is used to solve the displacement field and the stress field inside the block. The contacts between the deformable blocks are simulated DDA method. The parametric variational principle is derived to analyze the elastic-plastic problem with above coupling model. The theoretical calculating formulae are obtained from the variational principle. The governing equations of mechanical model are established. The proposed method coupling DDA and FEM is used to implement the simulation and analysis for the deformation process of jointed rock masses around one underground cavern. It is easy to simulate the whole process from plastic to elastic yielding failure, and to the large deformation under the condition of plastic flow or instability

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

Grid Integration of Offshore Wind Power: Standards, Control, Power Quality and Transmission

Offshore wind is expected to be a major player in the global efforts toward decarbonization, leading to exceptional changes in modern power systems. Understanding the impacts and capabilities of the relatively new and uniquely positioned assets in grids with high integration levels of inverter-based resources, however, is lacking, raising concerns about grid reliability, stability, power quality, and resilience, with the absence of updated grid codes to guide the massive deployment of offshore wind. To help fill the gap, this paper presents an overview of the state-of-the-art technologies of offshore wind power grid integration. First, the paper investigates the most current grid requirements for wind power plant integration, based on a harmonized European Network of Transmission System Operators (ENTSO-E) framework and notable international standards, and it illuminates future directions. The paper discusses the wind turbine and wind power plant control strategies, and new control approaches, such as grid-forming control, are presented in detail. The paper reviews recent research on the ancillary services that offshore wind power plants can potentially provide, which, when harmonized, will not only comply with regulations but also improve the value of the asset. The paper explores topics of wind power plant harmonics, reviewing the latest standards in detail and outlining mitigation methods. The paper also presents stability analysis methods for wind power plants, with discussions centered on validity and computational efficiency. Finally, the paper discusses wind power plant transmission solutions, with a focus on high-voltage direct-current topologies and controls.DC systems, Energy conversion & Storag

Effects of climate variability on evaporation in Dongping Lake, China, during 2003–2010

Based on two long-term, hourly (10:30–11:30 and 13:10–14:10) meteorological over-lake observations and data from Shenxian meteorological station, nearby Dongping Lake, the Penman-Monteith equation and reference evaporation ratio algorithm were used to calculate lake evaporation in Dongping Lake, China, from 2003 to 2010. The variation trend of evaporation of Dongping Lake was analyzed, and the influences that caused changes in lake evaporation were also discussed. The results show that (1) the total annual evaporation in Dongping Lake increased at 18.24 mm/a during 2003–2010.The major climatic factors accounting for this increase are the rising net radiation and the rising air temperature; (2) the total annual evaporation in a particular hour (13:10–14:10) in Dongping Lake increased at 4.55 mm/a during 2003–2010—the major climate factors that accounted for this increase are rising net radiation, followed by air temperature, wind velocity, and air humidity; (3) against the background of global warming, the climate of Dongping Lake tended to be dry during 2003–2010; the largest contribution to this comes from air temperature, followed by wind velocity and relative humidity; and (4) the monthly evaporation in Dongping Lake has seasonal variability.Water ManagementCivil Engineering and Geoscience

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

Uniaxial tensile response and tensile constitutive model of ultra-high performance concrete containing coarse aggregate (CA-UHPC)

To establish the tensile constitutive model of ultra-high performance concrete containing coarse aggregate (CA-UHPC), monotonic and cyclic uniaxial tensile tests for CA-UHPC with fiber volume fractions of 2.5% and 2.0% were conducted. Test results showed that CA-UHPC exhibits approximately linear stress-strain relation up to the tensile strength, and tensile softening response composed of the smeared- and localized-cracking stages, regardless of the tested fiber contents. Based on the monotonic test data, the tensile stress-crack opening model of CA-UHPC was established, and the model was further simplified into tri-linear relation. Based on the cyclic test results, tensile damage evolution laws according to the strain equivalence principle and the energy equivalence principle were developed, respectively. Finally, the proposed tensile constitutive model and the calibrated tensile damage evolution laws were demonstrated to effectively predict the mechanical response of CA-UHPC members under both monotonic tension and cyclic tension through numerical simulations.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