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

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

Case Study of the Largest Concrete Earth Pressure Balance Pipe-Jacking Project in the World

Pipe jacking has been the dominant trenchless technology for constructing small (\2 m) to medium-diameter (\4 m) tunnels. Uncertainties and construction difficulties increase significantly when the diameter of the tunnel exceeds 4 m. This paper presents a case study of the largest concrete pipe-jacking tunnel project in the world, the sewerage tunnel along Jinshan Lake, Zhenjiang, China. In this project, an underwater tunnel with a diameter of 4.67 m was constructed by the earth pressure balance (EPB) pipe-jacking method. The case study reports project background, and geological and hydrogeology conditions. The key techniques such as the selection of pipe-jacking machine, jacking force estimation and control, design of intermediate jacking station, grouting process control, launching, and reception of the tunnel boring machine, trajectory control of pipe jacking, and ventilation and gas monitoring during the construction period were investigated and discussed. Furthermore, to overcome the technical difficulties associated with the oversized jacked tunnel, the corresponding countermeasures were adopted point by point, so that the safety of the whole project could be guaranteed. This study filled the knowledge gap of technical know-how for large-diameter (over 4.5 m) pipe-jacking tunnel and is expected to provide practical guide for future large-diameter pipe-jacking tunnels.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.Geo-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

Is the tropical cyclone surge in Shanghai more sensitive to landfall location or intensity change?

It has been shown that the proportion of intense tropical cyclones (TCs) has been increasing together with a poleward migration of TC track. However, their relative importance to TC surge at landfall remains unknown. Here we examine the sensitivity of TC surge in Shanghai to landfall location and intensity with a new dynamical modelling framework. We find a surge sensitivity of 0.8 m (°N)−1 to landfall location, and 0.1 m (m s−1)−1 to wind speed in Shanghai during landfall. The landfall location and intensity are comparably important to surge variation. However, based on a plausible range of reported trends of TC poleward migration and intensity, the potential surge hazard due to poleward migration is estimated to be about three times larger than that by intensity change. The long-term surge risk in Shanghai is therefore substantially more sensitive to changes of TC track and landfall location than intensity. This may also be true elsewhere and in the future.Coastal EngineeringHydraulic Structures and Flood Ris

Compound flood impact of water level and rainfall during tropical cyclone periods in a coastal city: the case of Shanghai

Compound flooding is generated when two or more flood drivers occur simultaneously or in close succession. Multiple drivers can amplify each other and lead to greater impacts than when they occur in isolation. A better understanding of the interdependence between flood drivers would facilitate a more accurate assessment of compound flood risk in coastal regions. This study employed the D-Flow Flexible Mesh model to simulate the historical peak coastal water level, consisting of the storm surge, astronomical tide, and relative sea level rise (RSLR), in Shanghai over the period 1961-2018. It then applies a copula-based methodology to calculate the joint probability of peak water level and rainfall during historical tropical cyclones (TCs) and to calculate the marginal contribution of each driver. The results indicate that the astronomical tide is the leading driver of peak water level, followed by the contribution of the storm surge. In the longer term, the RSLR has significantly amplified the peak water level. This study investigates the dependency of compound flood events in Shanghai on multiple drivers, which helps us to better understand compound floods and provides scientific references for flood risk management and for further studies. The framework developed in this study could be applied to other coastal cities that face the same constraint of unavailable water level records.Hydraulic Structures and Flood RiskCoastal Engineerin

Identification and degradation of structural extracellular polymeric substances in waste activated sludge via a polygalacturonate-degrading consortium

By maintaining the cell integrity of waste activated sludge (WAS), structural extracellular polymeric substances (St-EPS) resist WAS anaerobic fermentation. This study investigates the occurrence of polygalacturonate in WAS St-EPS by combining chemical and metagenomic analyses that identify ∼22% of the bacteria, including Ferruginibacter and Zoogloea, that are associated with polygalacturonate production using the key enzyme EC 5.1.3.6. A highly active polygalacturonate-degrading consortium (GDC) was enriched and the potential of this GDC for degrading St-EPS and promoting methane production from WAS was investigated. The percentage of St-EPS degradation increased from 47.6% to 85.2% after inoculation with the GDC. Methane production was also increased by up to 2.3 times over a control group, with WAS destruction increasing from 11.5% to 28.4%. Zeta potential and rheological behavior confirmed the positive effect which GDC has on WAS fermentation. The major genus in the GDC was identified as Clostridium (17.1%). Extracellular pectate lyases (EC 4.2.2.2 and 4.2.2.9), excluding polygalacturonase (EC 3.2.1.15), were observed in the metagenome of the GDC and most likely play a core role in St-EPS hydrolysis. Dosing with GDC provides a good biological method for St-EPS degradation and thereby enhances the conversion of WAS to methane.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.BT/Environmental Biotechnolog

Enabling nanoscale flexoelectricity at extreme temperature by tuning cation diffusion

Any dielectric material under a strain gradient presents flexoelectricity. Here, we synthesized 0.75 sodium bismuth titanate −0.25 strontium titanate (NBT-25ST) core–shell nanoparticles via a solid-state chemical reaction directly inside a transmission electron microscope (TEM) and observed domain-like nanoregions (DLNRs) up to an extreme temperature of 800 °C. We attribute this abnormal phenomenon to a chemically induced lattice strain gradient present in the core–shell nanoparticle. The strain gradient was generated by controlling the diffusion of strontium cations. By combining electrical biasing and temperature-dependent in situ TEM with phase field simulations, we analyzed the resulting strain gradient and local polarization distribution within a single nanoparticle. The analysis confirms that a local symmetry breaking, occurring due to a strain gradient (i.e. flexoelectricity), accounts for switchable polarization beyond the conventional temperature range of existing polar materials. We demonstrate that polar nanomaterials can be obtained through flexoelectricity at extreme temperature by tuning the cation diffusion.QN/Zandbergen La

Executive Function Profile of Chinese Boys with Attention-Deficit Hyperactivity Disorder: Different Subtypes and Comorbidity

This study examined the executive function (EF) profile of Chinese boys with attention-deficit hyperactivity disorder (ADHD) using a large sample. Executive function performance within the ADHD subtypes and the effects of comorbidity were also investigated. Five hundred Chinese boys (375 with ADHD and 125 controls) aged 6-15 completed a battery of EF tests. Boys with all types of ADHD performed worse in all of the EF tests than age-and intelligence quotient-matched healthy controls. The boys with the inattention ADHD subtype and the combined subtype showed similar impairments across different EF tasks, whereas the boys with the hyperactive-impulsive ADHD subtype primarily displayed deficits in theory of mind and visual memory. Comorbid oppositional defiant disorder/conduct disorder had no additional influence on the EF characteristics of the boys with ADHD only, whereas comorbid learning disorder increased the severity of inhibition and shifting impairments

Comparative study of OROS-MPH and atomoxetine on executive function improvement in ADHD: a randomized controlled trial

This study aimed to compare the effects of osmotic release oral system-methylphenidate (OROS-MPH) and atomoxetine (ATX) on executive function in children and adolescents with attention deficit hyperactivity disorder (ADHD) by a randomized controlled trial. Subjects who met DSM-IV ADHD criteria were randomized to receive either OROS-MPH or ATX treatment. The doses were titrated to achieve optimal response and then maintained for 4-6 wk. A battery of executive function tests and the Behavior Rating Inventory of Executive Function (BRIEF) were administered to subjects who completed the dose titration (OROS-MPH, n = 85; ATX, n = 57) at the pre- and post-treatment periods. Forty-six children without ADHD were recruited as controls. Both OROS-MPH and ATX significantly improved scores in the Rey Complex Figure Test (RCFT), digit span, and Stroop color-word task. The scores in RCFT and the reverse digit span were not significantly different from the control group at post-treatment assessment (OROS-MPH = ATX = control, p > 0.05), whereas the word interference time of the Stroop test was still more than that of the control group (OROS-MPH = ATX > control, p > 0.05). OROS-MPH also significantly improved the total correct response in the verbal fluency test to normal level, and the shifting time in the trail-making test to subnormal level. The current findings suggest both OROS-MPH and ATX improved executive function generally in children and adolescents with ADHD, and could return working memory back to normative performance level