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

A Cooperative Protocol for Vehicle Merging Using Bi-dimensional Artificial Potential Fields

In recent years, platooning solutions like cooperative adaptive cruise control (CACC) have been deeply studied. It is common in such platooning literature to assume that the vehicles drive on the same lane (longitudinal platooning). At the same time, lateral control during merging maneuvers is commonly addressed as a path planning problem, in which the ego vehicle changes the lane during merging without necessarily cooperating with its neighboring vehicles (i.e. without considering gap closing). The primary objective of this article is to develop a control strategy which involves both longitudinal and lateral vehicle dynamics, where the vehicles merge and form a platoon in a cooperative way without a priori path planning. Appropriately designed bi-dimensional artificial potential fields are used to achieve this goal and the proposed protocol is verified through simulations with CarSim.Accepted Author ManuscriptTeam Bart De Schutte

Adaptive strategies to platoon merging with vehicle engine uncertainty

While several synchronization-based protocols have been provided for formation-keeping of cooperative vehicles, the problem of synchronized merging is more challenging. Challenges associated to the merging scenario include the need for establishing bidirectional interaction (in place of unidirectional look-ahead interaction), and the need for considering different engine dynamics (in place of homogeneous engine dynamics). This work shows how such challenges can be tackled via a newly proposed strategy based on adaptive control with bidirectional error: the adaptive control framework autonomously adapts to different engine dynamics, while the bidirectional error seamlessly allows the vehicle that wants to merge to interact with both the front and the rear vehicles, in a similar way as humans do. Intelligent VehiclesTeam DeSchutte

Adaptive Integral Sliding Mode Control in the Presence of State-Dependent Uncertainty

Adaptive integral sliding mode control (AISMC) is an extension of adaptive sliding mode control which is a way to ensure sliding motion while handling system uncertainties. However, conventional AISMC formulations require to different extent a priori knowledge of the system uncertainty: either the upper bound of the uncertainty or of its time derivative are assumed to be bounded a priori, or the uncertainty is assumed to be parametrized by some structure-dependent factorization. This work proposes a variant of AISMC with reduced a priori knowledge of the system uncertainty: it is shown that Euler–Lagrange dynamics typical of sliding mode literature admit a structure-independent parametrization of the system uncertainty. This parametrization is not the result of structural knowledge, but it comes from basic properties of Euler–Lagrange dynamics, valid independently on the structure of the system. The AISMC control method arising from this parametrization is analyzed in the Lyapunov stability framework, and validated in systems with different structures: a surface vessel and an aerial vehicle.Accepted Author ManuscriptTeam DeSchutte

Establishing Platoons of Bidirectional Cooperative Vehicles with Engine Limits and Uncertain Dynamics

In adaptive platooning strategies proposed in literature to handle uncertain and nonidentical uncertain vehicle dynamics (uncertain heterogeneous platoons) two aspects requiring proper design are neglected: bidirectional interaction among vehicles which might lead to loss of string stability, and engine saturation constraints which might lead to loss of cohesiveness. This work proposes a novel adaptive platooning strategy handling these two crucial aspects. Specifically, bidirectional interaction is handled by designing bidirectional reference dynamics with proven string stability properties, to which the uncertain heterogeneous platoon should homogenize; engine constraints are handled via a proposed a mechanism that makes such reference dynamics 'not too demanding', by properly saturating their action. The saturation action will allow all vehicles in the platoon to not hit their engine limits, preserving cohesiveness. Simulations are conducted to validate the theoretical analysis and show the effectiveness of the method in retaining cohesiveness of the platoon. Accepted Author ManuscriptTeam DeSchutterIntelligent Vehicle

An Underactuated Control System Design for Adaptive Autopilot of Fixed-Wing Drones

Effective design of autopilots for fixed-wing unmanned aerial vehicles (UAVs) is still a great challenge, due to unmodeled effects and uncertainties that these vehicles exhibit during flight. Unmodeled effects and uncertainties comprise longitudinal/lateral cross-couplings, as well as poor knowledge of equilibrium points (trimming points) of the UAV dynamics. The main contribution of this article is a new adaptive autopilot design, based on uncertain Euler–Lagrange dynamics of the UAV and where the control can explicitly take into account under-actuation in the dynamics, reduced structural knowledge of cross-couplings and trimming points. This system uncertainty is handled via appropriately designed adaptive laws: stability of the controlled UAV is analyzed. Hardware-in-the-loop tests, comparisons with an Ardupilot autopilot and with a robustified autopilot validate the effectiveness of the control design, even in the presence of strong saturation of the UAV actuators.Accepted Author ManuscriptTeam DeSchutte

Embedding Adaptive Features in the ArduPilot Control Architecture for Unmanned Aerial Vehicles

The operation of Unmanned Aerial Vehicles (UAVs) is often subject to state-dependent alterations and unstructured uncertainty factors, such as unmodelled dynamics, environmental weather disturbances, aerodynamics gradients, or changes in inertia and mass due to payloads. While a large number of autopilot solutions have been proposed to operate UAVs, none of these solutions is able to counteract the effects of state-dependent and unstructured uncertainties online by parameter estimation and adaptive control techniques. This work presents a systematic integration of adaptive control into ArduPilot, a popular open-source autopilot suite maintained by a large community of UAV developers. Adaptation features are embedded in the ArduPilot control structure without altering the original architecture, to allow users to use the autopilot suite as usual. Tests show that the proposed adaptive ArduPilot provides consistent improved performance in several uncertain flight conditions. The source code of the proposed adaptive ArduPilot is released at https://github.com/Friend-Peng/Adaptive-ArduPilot-Autopilot.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.Team Bart De Schutte

A Hybrid Recursive Implementation of Broad Learning With Incremental Features

The broad learning system (BLS) paradigm has recently emerged as a computationally efficient approach to supervised learning. Its efficiency arises from a learning mechanism based on the method of least-squares. However, the need for storing and inverting large matrices can put the efficiency of such mechanism at risk in big-data scenarios. In this work, we propose a new implementation of BLS in which the need for storing and inverting large matrices is avoided. The distinguishing features of the designed learning mechanism are as follows: 1) the training process can balance between efficient usage of memory and required iterations (hybrid recursive learning) and 2) retraining is avoided when the network is expanded (incremental learning). It is shown that, while the proposed framework is equivalent to the standard BLS in terms of trained network weights,much larger networks than the standard BLS can be smoothly trained by the proposed solution, projecting BLS toward the big-data frontier.Accepted Author ManuscriptTeam DeSchutte

An Adaptive Disturbance Decoupling Perspective to Longitudinal Platooning

Despite the progress in the field of longitudinal formations of automated vehicles, only recently an interpretation of longitudinal platooning has been given in the framework of disturbance decoupling, i.e. the problem of making a controlled output independent of a disturbance. The appealing feature of this interpretation is that the disturbance decoupling approach naturally yields a decentralized controller that guarantees stability and string stability. In this work, we further exploit the disturbance decoupling framework and we show that convergence to a stable, string stable and disturbance decoupled behavior can be achieved even in the presence of parametric uncertainty of the engine time constant. We refer to this framework as adaptive disturbance decoupling.Accepted Author ManuscriptTeam DeSchutte

Bio-safe drinking water with or without chlorine: a review

Drinking water biosafety has become an increasing concern for public health. Chlorination is widely used as the main disinfection strategy worldwide but has clear and well-known byproduct issues. The Netherlands has successfully demonstrated unchlorinated approach for almost 20 years but has not been widely adopted by other countries. To chlorine or not chlorine is becoming a critical question in front of all the water utilities. This review aims to provide a good overview of current biosafety management strategies, their disadvantages, as well as the latest developments and future trends. Firstly, the advantages and deficiencies of conventional disinfection and non-disinfection were discussed. Secondly, the commonly used and promising methods for biostability assessment are described. Finally, critical views on the strategy selection for ensuring drinking water biosafety were discussed. It is recommended to achieve both biological and chemical balance by removing pathogens while minimizing the organic matter and dosing a minimum level of disinfectants, which would represent the compromise choice between the current chlorine-based disinfection and chlorine-free strategy. It's worth noting that the complexity of ensuring biosafety lies in the variations among different regions, the selection of suitable methods should be tailored to specific situations on a case-by-case basis.Sanitary Engineerin