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

Reade: Connecting People - Users' Dynamics and its Architectural Representation

A rehabilitation Center building proposal in the center of Amsterdam. The design is derived from a research on the main user groups in a rehabilitation center and the dynamics among them, with an architectural result of the representation of these dynamics.Interiors, Buildings and CitiesArchitectureArchitecture and The Built Environmen

The Passive Display Case

Display cases around the world contain some of the most precious objects of our cultural heritage, from Leonardo Da Vinci’s La Gioconda to the Gutenberg Bible. We trust that these display cases will protect our objects of cultural heritage from vandalism, light, pollution and most importantly, moisture. Nevertheless, museums sometimes find that although their objects of art are in display cases, these are not providing the ideal protective microclimate. Hygroscopic materials can help restore this protective microclimate, but there are situations where the use of moisture-buffering materials is ineffective. This project aims to find when these situations occur. In order to do this, a computational and experimental model were developed, and the results are evaluated in this report.Building Engineering/Building Technology & PhysicsStructural EngineeringCivil Engineering and Geoscience

An efficient image-based telepresence system for videoconferencing

Electrical Engineering, Mathematics and Computer Scienc

Chemical fingerprinting of volatile organic compounds from asphalt binder for quantitative detection

Asphalt material is an irreplaceable material in road construction. However, it releases VOCs (Volatile Organic Compounds), which do cause pollution to the surrounding environment, during its full life cycle, especially in high-temperature paving stage and summer service time. Asphalt VOCs release mechanism and effective emission reduction technologies are therefore urgently needed. The chemical analysis of VOCs from asphalt binder always invariably excludes a vast number of compounds of unknown relevance, making the quantitative analysis lower data accuracy. In order to address this problem, fingerprint database was developed and introduced in this study, with the detected VOCs data from 104 kinds of asphalt binders. The analysis parameters, including fingerprint components and calibration curves were optimized through quantitative study. With the help of a self-developed fingerprint database, the calculation formulas of single VOC and total released VOCs were established for quantitative analysis of VOCs from asphalt binder. In addition, the influencing mechanism of heating temperature and asphalt types on VOCs volatilization characteristic were explored to achieve emission reduction in asphalt industry.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.Pavement Engineerin

A compact 0.135-mW/channel LNA array for piezoelectric ultrasound transducers

This paper presents a power- and area-efficient 9-channel LNA array for piezoelectric ultrasound transducers to enable real-time 3D imaging with miniature endoscopic and catheter-based probes. In view of the relatively low impedance of piezoelectric transducers, the LNA is implemented as a capacitive feedback voltage amplifier, rather than a trans-impedance amplifier, to achieve a better noise-power trade-off. The use of a current-efficient inverter-based OTA with optimized bias scheme and dual-rail regulation further improves the power efficiency of the LNA while keeping the area compact: 0.01 mm2 per channel. Electrical and acoustic measurement results show that the proposed LNA achieves a 0.6 mPa/√Hz input-referred noise at 4 MHz while consuming only 0.135 mW, which represents a noise efficiency 2.5 × better than the state-of-the-art.Electronic Instrumentatio

Direct gradient projection method with transformation of variables technique for structural topology optimization

This paper proposes an efficient and reliable topology optimization method that can obtain a black and white solution with a low objective function value within a few tens of iterations. First of all, a transformation of variables technique is adopted to eliminate the constraints on the design variables. After that, the optimization problem is considered as aiming at the minimum compliance in the space of design variables which is supposed to be solved by iterative method. Based on the idea of the original gradient projection method, the direct gradient projection method (DGP) is proposed. By projecting the negative gradient of objective function directly onto the hypersurface of the constraint, the most promising search direction from the current position is obtained in the vector space spanned by the gradients of objective and constraint functions. In order to get a balance between efficiency and reliability, the step size is constrained in a rational range via a scheme for step size modification. Moreover, a grey elements suppression technique is proposed to lead the optimization to a black and white solution at the end of the process. Finally, the performance of the proposed method is demonstrated by three numerical examples including both 2D and 3D problems in comparison with the typical SIMP method using the optimality criteria algorithm.Architectural Engineering +TechnologyArchitecture and The Built Environmen

道路沥青挥发性有机化合物减排材料的研究进展

Due to the complex organic properties of asphalt materials, the heating process during asphalt pavement construction will lead to the release of asphalt VOCs‧ Asphalt VOCs volatilization will cause irreversible harm to both the environment and health of construction workers‧ Researchers in the field of road construction have carried out extensive research on various emission reduction materials and technologies based on release mechanism of asphalt VOCs‧ There are no comprehensive research and intuitive comparison on emission reduction materials due to the differences between quantitative standards for emission reduction effects‧ This paper summarizes the current research status of asphalt VOCs emission reduction, including the development history of emission reduction technology and reduction mechanism of various asphalt VOCs emission reduction materials mainly based on inhibitors, warm mixing agents and flame retardants‧ In addition, the emission reduction effects of different emission reduction materials are compared and the improvement trend research direction of new and efficient asphalt VOCs reduction technology and materials are proposed to achieve green and low-emission construction‧ Finally, around the environmental protection theme of VOCs emission reduction, this study also put forward the prospect of full life cycle emission mechanism and feasibility of efficient composite materials design to support the urgent need for green transport.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.Pavement Engineerin

Effects of temperature on autogenous deformation and early-age stress evolution in cement pastes with low water to cement ratio

This paper investigates the influence of temperature on autogenous deformation and early-age stress (EAS) evolution in ordinary Portland cement paste using a recently developed Mini Temperature Stress Testing Machine (Mini-TSTM) and Mini Autogenous Deformation Testing Machine (Mini-ADTM). In the Mini-TSTM/ ADTM, CEM I 42.5 N paste with a water-cement ratio of 0.30 was tested under a curing temperature of 10, 15, 20, 25, 30, and 40 °C. X-Ray diffraction (XRD) tests were conducted to measure the amount of ettringite and calcium hydroxide, which reveals the micro-scale mechanisms of autogenous expansion. The applicability of the Maturity Concept (MC) for the prediction of autogenous deformation and relaxation modulus under different temperatures was also examined by the experimental data and the viscoelastic model. This paper leads to the following findings: 1) The autogenous deformation of ordinary Portland cement paste is a four-stage process comprising the initial shrinkage, autogenous expansion, plateau, and autogenous shrinkage; 2) Higher temperature leads to higher early-age cracking (EAC) risk because it accelerates the transitions through the first three stages and causes the autogenous shrinkage stage to start earlier. Moreover, higher temperatures also result in increased rates of autogenous shrinkage and EAS in the autogenous shrinkage stage; 3) Autogenous expansion and plateau are attributed to the crystallization pressure induced by CH. Temperature-dependent CH formation rates determine the duration of the plateau stage; 4) Low-temperature curing can delay but not completely prevent the EAC induced by autogenous deformation; 5) The MC cannot predict the autogenous deformation at different temperatures but can be used to calculate the relaxation modulus, which in turn aids in EAS prediction based on autogenous deformation data.Materials and Environmen

An Area-Efficient Ultra-Low-Power Time-Domain Feature Extractor for Edge Keyword Spotting

Keyword spotting (KWS) is an important task on edge low-power audio devices. A typical edge KWS system consists of a front-end feature extractor which outputs mel-scale frequency cepstral coefficients (MFCC) features followed by a back-end neural network classifier. KWS edge designs aim for the best power-performance-area metrics. This work proposes an area-efficient ultra-low-power time-domain infinite impulse response (IIR) filter-based feature extractor for a KWS system. It uses a serial architecture, and the architecture is further optimized for a low-cost computing structure and mixed-precision bit selection of the IIR coefficients while maintaining good KWS accuracy. Using a 65 nm process technology and a back-end neural network classifier, this simulated feature extractor has an area of 0.02 mm2 and achieves 3.3 μW @ 1.2 V, and achieves 92.5% accuracy on a 10-keyword, 12-class KWS task using the GSCD dataset.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.Electronic