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

Swaption Pricing Under Affine Interest Rate Models

In this thesis, we will analyze swaptions whose short term interest rates are assumed to follow some affine models with dimension of factors more than two, so called multiple-factor interest rate models. Considering there is generally no analytical swaption price, we attempt to approximate it, and our discussion will focus on one of these approximation method proposed by Collin-Dufresne and Goldstein. I implement and develop this method by providing an accurate measure of approximation errors. Besides, there are several of my innovation and research recommendations on my last chapter with respect to other methods to price swaptions.Applied mathematicsElectrical Engineering, Mathematics and Computer Scienc

Experimental tests and numerical simulation of delamination and fiber breakage in AP-PLY composite laminates

The behavior of delaminations and fiber breakage resulting from three-point bending test is a major concern in the study of composites. This research focused on analyzing fiber breakage and delaminations in advanced placed ply composite laminates through a series of tests. In order to compare simulation results with the experimental data, the cohesive zone model was implemented for analyzing the damage in the model. The results of the simulation were validated using experimental results. The predicted damage initiation load exhibited an approximate 20% deviation from the actual test loads and the discrepancy stems are analyzed.Aerospace Structures & Computational MechanicsGroup De Breuke

Where to Meet a Driver Privately: Recommending Pick-Up Locations for Ride-Hailing Services

Ride-Hailing Service (RHS) has motivated the rise of innovative transportation services. It enables riders to hail a cab or private vehicle at the roadside by sending a ride request to the Ride-Hailing Service Provider (RHSP). Such a request collects rider’s real-time locations, which incur serious privacy concerns for riders. While there are many location privacy-preserving mechanisms in the literature, few of them consider mobility patterns or location semantics in RHS. In this work, we propose a pick-up location recommendation scheme with location indistinguishability and semantic indistinguishability for RHS. Specifically, we give formal definitions of location indistinguishability and semantic indistinguishability. We model the rider mobility as a time-dependent first-order Markov chain and generates a rider’s mobility profile. Next, it calculates the geographic similarity between riders by using the Mallows distance and classifies them into different geographic groups. To comprehend the semantics of a location, it extracts such information through user-generated content from two popular social networks and obtains the semantic representations of locations. Cosine similarity and unified hypergraph are used to compute the semantic similarities between locations. Finally, it outputs a set of recommended pick-up locations. To evaluate the performance, we build our mobility model over the real-world dataset GeoLife, analyze the computational costs of a rider, show the utility, and implement it on an Android smartphone. The experimental results show that it costs less than 0.12 ms to recommend 10 pick-up locations within 500 m of walking distance.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.Cyber Securit

Investigating the Response of Vegetation to Flash Droughts by Using Cross-Spectral Analysis and an Evapotranspiration-Based Drought Index

Flash droughts tend to cause severe damage to agriculture due to their characteristics of sudden onset and rapid intensification. Early detection of the response of vegetation to flash droughts is of utmost importance in mitigating the effects of flash droughts, as it can provide a scientific basis for establishing an early warning system. The commonly used method of determining the response time of vegetation to flash drought, based on the response time index or the correlation between the precipitation anomaly and vegetation growth anomaly, leads to the late detection of irreversible drought effects on vegetation, which may not be sufficient for use in analyzing the response of vegetation to flash drought for early earning. The evapotranspiration-based (ET-based) drought indices are an effective indicator for identifying and monitoring flash drought. This study proposes a novel approach that applies cross-spectral analysis to an ET-based drought index, i.e., Evaporative Stress Anomaly Index (ESAI), as the forcing and a vegetation-based drought index, i.e., Normalized Vegetation Anomaly Index (NVAI), as the response, both from medium-resolution remote sensing data, to estimate the time lag of the response of vegetation vitality status to flash drought. An experiment on the novel method was carried out in North China during March–September for the period of 2001–2020 using remote sensing products at 1 km spatial resolution. The results show that the average time lag of the response of vegetation to water availability during flash droughts estimated by the cross-spectral analysis over North China in 2001–2020 was 5.9 days, which is shorter than the results measured by the widely used response time index (26.5 days). The main difference between the phase lag from the cross-spectral analysis method and the response time from the response time index method lies in the fundamental processes behind the definitions of the vegetation response in the two methods, i.e., a subtle and dynamic fluctuation signature in the response signal (vegetation-based drought index) that correlates with the fluctuation in the forcing signal (ET-based drought index) versus an irreversible impact indicated by a negative NDVI anomaly. The time lag of the response of vegetation to flash droughts varied with vegetation types and irrigation conditions. The average time lag for rainfed cropland, irrigated cropland, grassland, and forest in North China was 5.4, 5.8, 6.1, and 6.9 days, respectively. Forests have a longer response time to flash droughts than grasses and crops due to their deeper root systems, and irrigation can mitigate the impacts of flash droughts. Our method, based on cross-spectral analysis and the ET-based drought index, is innovative and can provide an earlier warning of impending drought impacts, rather than waiting for the irreversible impacts to occur. The information detected at an earlier stage of flash droughts can help decision makers in developing more effective and timely strategies to mitigate the impact of flash droughts on ecosystems.Optical and Laser Remote Sensin

SmartRoads 2.0

ScenWise is an innovative company that specializes in data science revolving around traffic management. ScenWise strives to use the newest and best technologies and practices when it comes to web applications, data science and traffic management. The reason for this is that they provide tools to analyse and visualise a variety of situations that occur in traffic management. One such tool is SmartRoads 1.0, which allows users to analyse traffic data and situations via a web application. Unfortunately SmartRoads 1.0 does not perform as desired. Additionally, ScenWise itself has the problem of not being able to integrate previously made products by student groups into their own existing products. During the research aimed to resolve these problems another issue arose; the software development life cycle of ScenWise is very lacking. Research on the SmartRoads 1.0 performance problem showed that the bottleneck of its performance is due to the front-end. The outdated SmartRoads 1.0 front-end was thus replaced with a new and better SmartRoads 2.0 front-end. The integration problem and development life cycle problem are both addressed in the Longterm evolution (LTE) design found in appendix I. This LTE design contains the architecture migration plan. This plan will transform the current software architecture to a Service-oriented architecture (SOA) providing a solution for the current integration problems. A result of the first steps of this architecture migration plan is the Application Programming Interface (API) Gateway, which has been implemented in the aforementioned SmartRoads 2.0. Next to the migration plan, guidelines for ScenWise to improve their software development life cycle are elaborated in the LTE design. In this report the identified problems, their solutions and executions are explained, discussed and evaluated

Direct imaging of the circular chromosome in a live bacterium

Although the physical properties of chromosomes, including their morphology, mechanics, and dynamics are crucial for their biological function, many basic questions remain unresolved. Here we directly image the circular chromosome in live E. coli with a broadened cell shape. We find that it exhibits a torus topology with, on average, a lower-density origin of replication and an ultrathin flexible string of DNA at the terminus of replication. At the single-cell level, the torus is strikingly heterogeneous, with blob-like Mbp-size domains that undergo major dynamic rearrangements, splitting and merging at a minute timescale. Our data show a domain organization underlying the chromosome structure of E. coli, where MatP proteins induce site-specific persistent domain boundaries at Ori/Ter, while transcription regulators HU and Fis induce weaker transient domain boundaries throughout the genome. These findings provide an architectural basis for the understanding of the dynamic spatial organization of bacterial genomes in live cells.BN/Cees Dekker LabBN/Sander Tans LabBN/Technici en Analiste

Intracellular product recycling in high succinic acid producing yeast at low pH

Background: The metabolic engineering of Saccharomyces cerevisiae for the production of succinic acid has progressed dramatically, and a series of high-producing hosts are available. At low cultivation pH and high titers, the product transport can become bidirectional, i.e. the acid is reentering the cell and is again exported or even catabolized. Here, a quantitative approach for the identification of product recycling fluxes is developed. Results: The metabolic flux distributions at two time-points of the fermentation process were analyzed. 13C labeled succinic acid was added to the extracellular space and intracellular enrichments were measured and subsequently used for the estimation of metabolic fluxes. The labeling was introduced by a labeling switch experiment, leading to an immediate labeling of about 85% of the acid while keeping the total acid concentration constant. Within 100 s significant labeling enrichment of the TCA cycle intermediates fumarate, iso-citrate and α-ketoglutarate was observed, while no labeling was detected for malate and citrate. These findings suggest that succinic acid is rapidly exchanged over the cellular membrane and enters the oxidative TCA cycle. Remarkably, in the oxidative direction malate 13C enrichment was not detected, indicating that there is no flux going through this metabolite pool. Using flux modeling and thermodynamic assumptions on compartmentation it was concluded that malate must be predominantly cytosolic while fumarate and iso-citrate were more dominant in the mitochondria. Conclusions: Adding labeled product without changing the extracellular environment allowed to quantify intracellular metabolic fluxes under high producing conditions and identify product degradation cycles. In the specific case of succinic acid production, compartmentation was found to play a major role, i.e. the presence of metabolic activity in two different cellular compartments lead to intracellular product degradation reducing the yield. We also observed that the flux from glucose to succinic acid branches at two points in metabolism: (1) At the level of pyruvate, and (2) at cytosolic malate which was not expected.OLD BT/Cell Systems Engineerin

Chains of gold atoms with tailored electronic states

Applied Scienc

Strong spin-photon coupling in silicon

Long coherence times of single spins in silicon quantum dots make these systems highly attractive for quantum computation, but how to scale up spin qubit systems remains an open question. As a first step to address this issue, we demonstrate the strong coupling of a single electron spin and a single microwave photon. The electron spin is trapped in a silicon double quantum dot, and the microwave photon is stored in an on-chip high-impedance superconducting resonator. The electric field component of the cavity photon couples directly to the charge dipole of the electron in the double dot, and indirectly to the electron spin, through a strong local magnetic field gradient from a nearby micromagnet. Our results provide a route to realizing large networks of quantum dot–based spin qubit registers.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.QCD/Vandersypen LabQuTechBUS/GeneralBusiness DevelopmentQCD/Scappucci LabQN/Vandersypen La