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.]

Appraisal and mathematical properties of fragility analysis methods

Fragility analysis aims to compute the probabilities of a system exceeding certain damage conditions given different levels of hazard intensity. Fragility analysis is therefore a key process of performance-based earthquake engineering, with a number of approaches developed and widely recognized, including Incremental Dynamic Analysis (IDA), Multiple Stripe Analysis (MSA), and cloud analysis. Additionally, extended fragility analysis has recently been shown to possess important attributes of mathematical consistency and extensibility. This work provides a critical review of the different fragility methods by explaining the underlying probabilistic models and assumptions, as well as their connections to the extended fragility method. It is proven that IDA-based fragility curves provide an upper bound of the actual fragility, and cloud analysis manifests suboptimality issues arising from its underlying assumptions. MSA is identified to be a probit-linked Bernoulli regression model, similar to the one proposed by Shinozuka and coworkers. The latter, in turn, is shown to be a limiting subcase of the generalized linear model framework introduced within the extended fragility analysis. The paper first presents a simple case of one intensity measure and two damage condition states, and the discussion is subsequently extended to more general cases of multiple intensity measures and damage states. The discussed attributes are demonstrated in several numerical applications. Overall, this work aims to provide new insights on fragility methods, enabling efficient, accurate, and consistent estimations of structural performance, as well as promoting new research directions in earthquake engineering and other related fields.Structural Design & Mechanic

‘How Would you Score Yourself?’: The Effect of Self-assessment Strategy Through Robots on Children’s Motivation and Performance in Piano Practice

This research examines how to design social robots to support self-regulated learning skills for piano practice. More specifically, a social robot is used to provide feedback to children and initiate self-assessment. To assess the impact of this approach on children’s motivation and performance, we conducted an experiment in a music school where 50 children practiced with both a self-assessment and a non-evaluative robot. Results showed that when the children interacted with the self-assessment robot they had higher motivation and better performance than when they interacted with the non-evaluative robot. Furthermore, interaction effects were found between the robot conditions, the children’s learning stages, and their gender regarding their motivation and rhythm performance. Overall, the study demonstrates a positive influence of robot-initiated self-assessment on children’s musical instrument practice and provided insights for personalized child-robot interaction design.Human Information Communication Desig

New Development of China’s National Evaluation Standard for Green Building (ESGB-2014)

In 2006, China published the first National Evaluation Standard for Green Building (ESGB), which soon became the most widely spread evaluation system in the country. With the fast growth of urbanization, ESGB 2006 version no longer meets the current needs and requires an update. Based on the implementation outcomes of ESGB 2006 and expert opinions, the Ministry of Housing and Urban-rural Development published a new version of ESGB in 2014 (ESGB 2014). This research reviews the previous cases of buildings accredited with ESGB 2006 and collects the facts and data to explain the implementation results and identifies its weakness of the ESGB 2006. A comparative analysis of the ESGB 2014 with ESGB 2006 is based on an in-depth overview of both ESGB 2014 and ESGB 2006. The comparison results shows the improvement of the current ESGB 2014 in details, i.e., evaluated object, stage partition, weighted value, structure, indicators, etc. A case study is followed by choosing one building project to evaluate and calculate the green building accreditation according to both ESGB 2014 and ESGB 2006, and demonstrate the differences and development of ESGB 2014.OLD Housing Quality and Process Innovatio

Bioinformed Performative Composite Structures: From biological micro-structures to material composites and articulated assemblies

This ongoing investigation aims to learn from nature novel material organizations and structural systems in order to develop innovative architectural system. We developed a multidisciplinary approach, using scientific analysis and design research and prototyping. We focus on the study of a \u93living fossil\u94 fish, whose armor system is so efficient it has remained almost unchanged for millions of years. We investigate its morphological characteristics, its structural properties, the assembly mechanisms and the underlying material properties in order to derive new principles to design new enhanced structural systems. We use micro computerized tomography and scanning electron microscopy to observe microstructures, parametric design to reconstruct the data into digital models and then several 3D printing technologies to prototype systems with high flexibility and adaptive capabilities, proposing new gradual material interfaces and transitions to embed performative capabilities and multifunctional potentials

iTOP: Inferring the topology of omics data

Motivation In biology, we are often faced with multiple datasets recorded on the same set of objects, such as multi-omics and phenotypic data of the same tumors. These datasets are typically not independent from each other. For example, methylation may influence gene expression, which may, in turn, influence drug response. Such relationships can strongly affect analyses performed on the data, as we have previously shown for the identification of biomarkers of drug response. Therefore, it is important to be able to chart the relationships between datasets. Results We present iTOP, a methodology to infer a topology of relationships between datasets. We base this methodology on the RV coefficient, a measure of matrix correlation, which can be used to determine how much information is shared between two datasets. We extended the RV coefficient for partial matrix correlations, which allows the use of graph reconstruction algorithms, such as the PC algorithm, to infer the topologies. In addition, since multi-omics data often contain binary data (e.g. mutations), we also extended the RV coefficient for binary data. Applying iTOP to pharmacogenomics data, we found that gene expression acts as a mediator between most other datasets and drug response: only proteomics clearly shares information with drug response that is not present in gene expression. Based on this result, we used TANDEM, a method for drug response prediction, to identify which variables predictive of drug response were distinct to either gene expression or proteomics. Availability and implementation An implementation of our methodology is available in the R package iTOP on CRAN. Additionally, an R Markdown document with code to reproduce all figures is provided as Supplementary Material. Supplementary information Supplementary data are available at Bioinformatics online.Pattern Recognition and Bioinformatic

Encoding and controlling of two droplet trains in a microfluidic network with the loop-like structure

A theoretical model is derived mathematically for the encoding and controlling of the navigating of two droplet trains in a microfluidic network with a loop-like structure. The model reveals the relationship between the new outlet droplet train's arrangement information (output signals) and the parameters including the two droplet trains' input signals (droplet intervals), tuning flow rates, etc. The theoretical results are compared with the experimental results and they agree with each other. We find that every tuning flow rate corresponds to a certain output signal and a new droplet train can be obtained accurately. The generation orders of the successive droplets of the new droplet train remain unchanged within a certain range of the tuning flow rates. This work can be a useful reference for traffic controlling of two or more droplet trains in many microfluidic networks including the loop structure; the output signal of this work can be the input one for the next level which makes the multilevel studies possible. In addition, this study can help to promote the effective fusion of droplets and further the biological and chemical applications on droplet microfluidics

Anisotropic, gradient and metal-like mechanical behaviors of teeth and their implications on tooth functions

The anisotropy and gradient of the elastic modulus and the hardness of teeth were investigated by means of instrumented indentation method. Such properties are attributed to the unique microstructures of teeth based on scanning electron microscopic analysis. By comparing the relationship between the ratio of hardness to the reduced elastic modulus and the ratio of elastic unloading work to the total work of teeth in course of indentation to those of other materials, we found that the material behaviors of teeth display metal-like characteristics rather than ceramics as considered traditionally. These material behaviors and relevant functions are discussed briefly

Experimental study on the microstructure and nanomechanical properties of the wing membrane of dragonfly

Detailed investigations on the microstructure and the mechanical properties of the wing membrane of the dragonfly are carried out. It is found that in the direction of the thickness the membrane was divided into three layers rather than a single entity as traditionally considered, and on the surfaces the membrane displays a random distribution rough microstructure that is composed of numerous nanometer scale columns coated by the cuticle wax secreted. The characteristics of the surface structure are measured and described. The mechanical properties of the membranes taken separately from the wings of live and dead dragonflies are investigated by the nanoindentation technique. The Young's moduli obtained here are approximately two times greater than the previous result, and the reasons that yield the difference are discussed