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

Introduction to Energy-Efficient Train Operation

Railway, as one of the most energy-efficient transport, plays an essential role in improving the world’s energy and environmental sustainability. Statistics about rail share of transport activities and the corresponding energy consumption will demonstrate the energy efficiency of railway and indicate the potential of developing railway transport. Therefore, this chapter will provide an overview of the railway's energy consumption and traffic volume shares. Statistics presented in this chapter show that railway energy consumption decreased in these decades while its transport volume kept stable, and the traffic volume share of the railway is extremely large in urban transport. To achieve the goal of carbon neutralization, the European Union and many countries have conducted research projects on railway energy conservation. The technologies developed in these projects include energy-efficient train driving, integrated timetabling, using regenerative braking energy, etc. A summary of these technologies is also given, along with their potential energy savings, which range from 1 to 25%. This book will analyse and illustrate the whole systems processes of train operation with optimisation solutions. The structure of the following chapters will be presented at the end.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

Study on vertical vibration and transmission characteristics of railway ballast using impact hammer test

The vertical vibration and transmission characteristics of ballast are key factors that affect the dynamic stability of railway track structures and control the settlement of ballasted beds. Therefore, the following study was conducted to explore this topic. Firstly, through an impact hammer test on a ballast sensor with embedding chip, the vertical vibration data of the ballast was accurately measured. Therefore, the vertical vibration characteristics of a single ballast can be studied. Then, the vertical vibration characteristics at different positions in the stack were obtained by embedding ballast sensors into a ballasted stack. Finally, combined with field tests, a discrete element numerical model was established, then the vibration transmission speed and diffusion angle in a ballasted stack were calculated. The results of this study show that the damping ratio of ballast particles is less than 0.1, and the natural frequency is above 1000 Hz. The damping ratio and natural frequency of ballasts are greatly affected by their shape. The damping ratio of a ballasted stack is greater than that of ballast particles, and its natural frequency is lower. This indicates that the ballasted stack has the attributes of a soft material. The vertical acceleration transmission rate of ballasts is lower at frequencies below 257.94 Hz. This shows that the vibration suppression ability of the ballasted bed is better in the lower frequency range. As the depth increases, the vertical vibration transmission speed of the ballast gradually decreases, as does the accumulated external force. In the impact hammer test of a ballasted box, the average vertical vibration transmission speed was calculated to be 0.88 mm/μs, and the ballast vibration was transmitted downward at a diffusion angle of 35.32°–54.51° from the direction of gravity.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.Railway Engineerin

Improve the long-term property of heat-cured mortars blended with fly ash by internal curing

Due to the satisfactory property and high productivity, heat-cured concretes have been widely used in engineering practice. However, heat curing process also brings some drawbacks that are detrimental to the long-term property of this material. To address this issue, lightweight fine aggregate (LWFA) was employed to provide internal curing (IC) for a heat-cured mortar (HCM) blended with fly ash (FA). The influences of LWFA on the interior relative humidity of HCM and the reaction environment and behavior of FA were measured. It was found that IC of LWFA could mitigate the drop of interior humidity and enhance the reaction degrees of cement and FA. This contributed significantly to the microstructure densification of HCM, higher compressive strength and better resistance to chloride ion. The results indicate that LWFA benefits to enhancing the efficiency of FA in a heat curing system and the combination of LWFA and FA contribute to improving the long-term property of HCM.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.Materials and Environmen

Benchmarking Robustness and Generalization in Multi-Agent Systems: A Case Study on Neural MMO

We present the results of the second Neural MMO challenge, hosted at IJCAI 2022, which received 1600+ submissions. This competition targets robustness and generalization in multi-agent systems: participants train teams of agents to complete a multi-task objective against opponents not seen during training. We summarize the competition design and results and suggest that, considering our work as a case study, competitions are an effective approach to solving hard problems and establishing a solid benchmark for algorithms. We will open-source our benchmark including the environment wrapper, baselines, a visualization tool, and selected policies for further research.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.Interactive Intelligenc

PBI mixed matrix hollow fiber membrane: Influence of ZIF-8 filler over H₂/CO₂ separation performance at high temperature and pressure

High performance and commercially attractive mixed-matrix membranes were developed for H2/CO2 separation via a scalable hollow fiber spinning process. Thin (~300 nm) and defect-free selective layers were successfully created with a uniform distribution of the nanosized (~60 nm) zeolitic-imidazole framework (ZIF-8) filler within the polymer (polybenzimidazole, PBI) matrix. These membranes were able to operate at high temperature (150 °C) and pressure (up to 30 bar) process conditions required in treatment of pre-combustion and syngas process gas streams. Compared with neat PBI hollow fibers, filler incorporation into the polymer matrix leads to a strong increase in H2 permeance from 65 GPU to 107 GPU at 150 °C and 7 bar, while the ideal H2/CO2 selectivity remained constant at 18. For mixed gas permeation, there is competition between H2 and CO2 transport inside ZIF-8 structure. Adsorption of CO2 in the nanocavities of the filler suppresses the transport of the faster permeating H2 and consequently decreases the H2 permeance with total feed pressure down to values equal to the pure PBI hollow fibers for the end pressure of 30 bar. Therefore, the improvement of fiber performance for gas separation with filler addition is compromised at high operating feed pressures, which emphasizes the importance of membrane evaluation under relevant process conditions.ChemE/Catalysis Engineerin

D-ribose in glycation and protein aggregation

Background: D-ribose is a naturally occurring pentose monosaccharide present in all living cells and their microenvironments and is a key component of numerous biomolecules involved in many important metabolic pathways. It also participates in the glycation of proteins producing advanced glycation end products (AGEs) that lead to cell dysfunction and death. As recent studies show, ribosylation, a rapid process, causes protein aggregation in vitro and in vivo