Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

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

Testing Challenges of Maritime Safety and Security Systems-of-Systems

Preprint of paper published in: TAIC PART 2008: Testing: Academic & Industrial Conference, Practice and Research Techniques, 29-31 August 2008; doi:10.1109/TAIC-PART.2008.14 Maritime Safety and Security systems represent a novel kind of large-scale distributed component-based systems in which the individual components are elaborate and complex systems in their own right. Two distinguishing characteristics are their ability to evolve during runtime, that is, joining and leaving of components, and the need for high reliability of the system. In this paper, we identify the challenges that will have to be addressed, given the current state of the art in component-based software engineering in order to build such system-of-systems. In particular, we highlight the specific difficulties regarding acceptance and testing. A first group of testing challenges is raised by the need of accepting the integration of such large systems, and the ability to reconfigure them at runtime. A second group of testing challenges comes from the fact that, generally, not all the sub-systems are designed along the same kind of architecture (e.g. client-server vs. publish-subscribe architecture). Devising an integration testing process for such hybrid architecture is inherently harder than for a homogeneous one.Software Computer TechnologyElectrical Engineering, Mathematics and Computer Scienc

RiTMO: A Method for Runtime Testability Measurement and Optimisation

Version: Accepted as short paper at QSIC 2009. Runtime testing is emerging as the solution for the integration and assessment of highly dynamic, high availability software systems where traditional development-time integration testing is too costly, or cannot be performed. However, in many situations, an extra cost will have to be invested in implementing appropriate measures to enable runtime tests to be performed without affecting the running system or its environment. This paper introduces a method for the improvement of the runtime testability of a system, which provides an optimal action plan considering the trade-off between testability and implementation cost. The computation of the action plan is driven by an estimation of runtime testability, and based on a model of the system. Runtime testability is estimated independently of the test cases and focused exclusively on the test-relevant features of the system. This method is used to direct integration- and testengineers in the implementation of improvement measures for the runtime testability during the integration of a system. Furthermore, it can also be applied earlier, on the design stage, providing a Design for Testability method for dynamic systems. By means of an example, we demonstrate how our method enables an optimal expenditure of resources towards runtime testability during the integration phase of a system.Computer Science & EngineeringElectrical Engineering, Mathematics and Computer Scienc

Reducing the Runtime Acceptance Costs of Large-Scale Distributed Component-Based Systems

Software Systems of Systems (SoS) are large-scale distributed component-based systems in which the individual components are elaborate and complex systems in their own right. Distinguishing characteristics are their short expected integration and deployment time, and the need to modify their architecture at runtime, while preserving the integrity of the system. Integration testing is a commonly used technique employed in the acceptance processes of software SoS. In this paper, we propose a scheme to test a complete SoS at every reconfiguration, re-exercising the test cases of every updated component. In practice, re-executing all the test cases, whenever a modification takes place in one of the components, would be very costly. This is the case, in particular, when the system has to keep running all the time. Our proposal, therefore, encompasses several methods to limit the amount of test cases to be executed. The basis of all these methods is to rely on as much information as possible extracted from previous runs of the test cases. We illustrate our findings with an example SoS coming from the maritime safety and security domain.Software Computer TechnologyElectrical Engineering, Mathematics and Computer Scienc

Effect of metallic waste addition on the electrical, thermophysical and microwave crack-healing properties of asphalt mixtures

This paper aims to evaluate the effect of metallic waste addition on the electrical, thermophysical and microwave crack-healing properties of asphalt mixtures. With this purpose, asphalt mixtures with two different types of metallic waste, steel wool fibres and steel shavings, added in four different contents, were tested. Electrical and thermophysical properties of asphalt mixture specimens with, and without, metallic waste were measured. The spatial distribution of the metallic waste inside the asphalt mixture samples was evaluated by using X-ray computed tomography. In addition, crack-healing properties of asphalt samples using microwave radiation heating were assessed at two different healing times, 30 s and 40 s. To quantify the efficiency of the healing process, five healing cycles were carried out for each asphalt sample. The main results showed that asphalt mixtures with shavings presented lower air void contents than mixtures with fibres. Moreover, fibres produced an increase in the electrical conductivity of the mixtures because long fibres in the mixtures form electrically conductive channels. In contrast, shavings did not have significant effect on the electrical properties of the mixtures. Likewise, it was proven that metallic waste reduced the thermal conductivity and the specific heat capacity of asphalt mixtures. Conversely, shavings decreased the thermal diffusivity of asphalt mixtures regardless of their content. Overall, it was found that the healing level reached by the asphalt mixtures tested by microwave radiation depends on the healing time and the type and content of metallic waste used. CT-scans results proved that the spatial distribution of metallic waste inside the asphalt mixture samples was not uniform and played an important role in the asphalt self-healing properties using microwave radiation heating.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

Reachability analysis to design zero-wait entry guidance

This paper presents a novel reentry guidance architecture that aims to improve cur- rent mission safety by enabling zero-wait orbital aborts. To do so, an on-board trajectory planner based on Adaptive Multivariate Pseudospectral Interpolation (AMPI) is devel- oped. This planner generates mathematical approximations of the reference trajectory to be tracked by comparing the vehicle-state information at the entry point against a pre-computed trajectory database that is stored on-board. Such a trajectory database is populated by systematically solving a number of optimal-control problems, which ulti- mately generate a set of reference angle-of-attack and bank-angle profiles that feed a Linear Quadratic Regulator trajectory tracker. The architecture proposed in this paper is tested using a scaled-down version of the X-38, SPHYNX, a small lifting-body reentry vehicle developed by the European Space Agency. The proposed on-board trajectory planner is able to generate reference commands in the order of a few milliseconds, thus proving the ability to run the system in current ight-hardware. Furthermore, a Monte Carlo test campaign showed that the trajectory database can be compressed with a loss-less process without having a detrimental impact on the landing dispersions and constraint compliance, achieving database sizes as low as 18 MB. Finally, the presented architecture allows for easy targeting of any landing site, as long as reference guidance commands are stored in the database.Astrodynamics & Space Mission

Runtime Testability in Dynamic Highly-Availability Component-based Systems

Runtime testing is emerging as the solution for the integration and assessment of highly dynamic, high availability software systems where traditional development-time integration testing cannot be performed. A prerequisite for runtime testing is the knowledge about to which extent the system can be tested safely while it is operational, i.e., the system’s runtime testability. This article evaluates RTM, a cost-based metric for estimating runtime testability. It is used to assist system engineers in directing the implementation of remedial measures, by providing an action plan which considers the trade-off between testability and cost. Two testability case studies are performed on two different component-based systems, assessing RTM’s ability to identify runtime testability problems Preprint accepted for publication in Valid 2010 2nd International Conference on Advances in System Testing and Validation Lifecycle, Nice (France), 22-27 Augus, 2010Software TechnologyElectrical Engineering, Mathematics and Computer Scienc

Statistical Evaluation of SCADA data for Wind Turbine Condition Monitoring and Farm Assessment

Operational data from wind farms is crucial for wind turbine condition monitoring and performance assessment. In this paper, we analyse three wind farms with the aim to monitor environmental and operational conditions that might result in underperformance or failures. The assessment includes a simple wind speed characterisation and wake analysis. The evolution of statistical parameters is used to identify anomalous turbine behaviour. In total, 88 turbines and 12 failures are analysed, covering different component failures. Notwithstanding the short period of data available, several operational parameters are found to deviate from the farm trend in some turbines affected by failures. As a result, some parameters show better monitoring capabilities than others, for the detection of certain failures. However, the limitations of SCADA statistics are also shown as not all failures showed anomalies in the observed parameters.Wind Energ

Evaluation of an in vivo heterotopic model of osteogenic differentiation of equine bone marrow and muscle mesenchymal stem cells in fibrin glue scaffold

Autologous mesenchymal stem cells (MSCs) have been used as a potential cell-based therapy in various animal and human diseases. Their differentiation capacity makes them useful as a novel strategy in the treatment of tissue injury in which the healing process is compromised or delayed. In horses, bone healing is slow, taking a minimum of 6–12 months. The osteogenic capacity of equine bone marrow and muscle MSCs mixed with fibrin glue or phosphate-buffered saline (PBS) as a scaffold is assessed. Bone production by the following groups was compared: Group 1, bone marrow (BM) MSCs in fibrin glue; Group 2, muscle (M) MSCs in fibrin glue; Group 3, BM MSCs in PBS; Group 4, M MSCs in PBS and as a control; Group 5, fibrin glue without cells. BM and M MSCs underwent osteogenic stimulation for 48 h prior to being injected intramuscularly into nude mice. After 4 weeks, the mice were killed and muscle samples were collected and evaluated for bone formation and mineralization by using radiology, histochemistry and immunohistochemistry. Positive bone formation and mineralization were confirmed in Group 1 in nude mice based on calcium deposition and the presence of osteocalcin and collagen type I; in addition, a radiopaque area was observed on radiographs. However, no evidence of mineralization or bone formation was observed in Groups 2–5. In this animal model, equine BM MSCs mixed with fibrin glue showed better osteogenic differentiation capacity compared with BM MSCs in PBS and M MSCs in either carrier