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

The Durban Dig-Out Port, Project Durban

The Port of Durban is South Africa's premier port and hub of the region, especially for the Johannesburg (Gauteng Province) area. The current port will eventually not be sufficient to handle the capacity demand. The focus is on the development of a new port in the direct surroundings of Durban. A suitable new location is found at the old international airport. The Durban Dig-out Port is designed to cover a yearly container throughput of 10,000,000 TEU, a yearly liquid bulk throughput of 5,000,000 kL and 300,000 vehicles throughput per year. The governing vessel for the design is a 22,000 TEU container vessel with a length of 430 m, a width of 43.4 m and a draft of 16.3 m. The choice for the 22,000 TEU design vessel is reviewed. Based on global developments in ship manufacturing and a brief look at the developments in South Africa's container trade it is concluded that the 22,000 TEU vessel is recommended for the design of the port. In the proposed port layout the entrance channel is aligned such that it gives possibilities to bring the Isipingo estuary and its protected mangroves back to life. New land becomes available for an extension of the mangrove area and a new natural equilibrium between fresh and salt water inflow can be developed. The direction of the entrance channel also results in the central location of the turning circle and therefore the basins are relatively short. This makes manoeuvring for the vessels in the port convenient. A slight bend in the entrance channel is proposed to mitigate the wave action in the port. A straight entrance channel would lead to large downtime and has a direct impact on the port efficiency. The southern swell waves cannot enter the port due to the breakwaters and the eastern wind waves are either absorbed at the inside of the southern breakwater or at the safety beach at the end of the turning circle. The proposed sand bypass system makes sure that the coastal evolution is sustainable. In the proposed layout two configurations for the breakwaters are distinguished in terms of orientation and length. The proposed breakwaters are based on either a relatively high (10 kn) or low (6 kn) maximum vessel entrance speed. From research with a simplified wave model it is concluded that the shorter breakwaters cause downtime for the liquid bulk terminal during storm conditions from the south. During normal conditions it is however found that the liquid bulk terminal can be operational for more than 99% of the time. Next to that, it is found from the design of the breakwaters' cross sections that the breakwater dimensions become significantly larger at greater depths. However both breakwaters are found stable with numerical stability analysis and in combination with the result of the wave model it is concluded that the shorter configuration is preferred. This leads to significantly lower construction costs and the downtime of the liquid bulk terminal is limited.Civil Engineering and Geoscience

Improvements to the OMI O₂-O₂ operational cloud algorithm and comparisons with ground-based radar-lidar observations

The OMI (Ozone Monitoring Instrument on board NASA's Earth Observing System (EOS) Aura satellite) OMCLDO2 cloud product supports trace gas retrievals of for example ozone and nitrogen dioxide. The OMCLDO2 algorithm derives the effective cloud fraction and effective cloud pressure using a DOAS (differential optical absorption spectroscopy) fit of the O2-O2 absorption feature around 477m. A new version of the OMI OMCLDO2 cloud product is presented that contains several improvements, of which the introduction of a temperature correction on the O2-O2 slant columns and the updated look-up tables have the largest impact. Whereas the differences in the effective cloud fraction are on average limited to 0.01, the differences of the effective cloud pressure can be up to 200hPa, especially at cloud fractions below 0.3. As expected, the temperature correction depends on latitude and season. The updated look-up tables have a systematic effect on the cloud pressure at low cloud fractions. The improvements at low cloud fractions are very important for the retrieval of trace gases in the lower troposphere, for example for nitrogen dioxide and formaldehyde. The cloud pressure retrievals of the improved algorithm are compared with ground-based radar-lidar observations for three sites at mid-latitudes. For low clouds that have a limited vertical extent the comparison yields good agreement. For higher clouds, which are vertically extensive and often contain several layers, the satellite retrievals give a lower cloud height. For high clouds, mixed results are obtained.Atmospheric Remote Sensin

Minimizing aerosol effects on the OMI tropospheric NO₂ retrieval - An improved use of the 477nm O₂-O₂ band and an estimation of the aerosol correction uncertainty

Global mapping of satellite tropospheric NO2 vertical column density (VCD), a key gas in air quality monitoring, requires accurate retrievals over complex urban and industrialized areas and under any atmospheric conditions. The high abundance of aerosol particles in regions dominated by anthropogenic fossil fuel combustion, e.g. megacities, and/or biomass-burning episodes, affects the space-borne spectral measurement. Minimizing the tropospheric NO2 VCD biases caused by aerosol scattering and absorption effects is one of the main retrieval challenges from air quality satellite instruments. In this study, the reference Ozone Monitoring Instrument (OMI) DOMINO-v2 product was reprocessed over cloud-free scenes, by applying new aerosol correction parameters retrieved from the 477 nm O2-O2 band, over eastern China and South America for 2 years (2006 2007). These new parameters are based on two different and separate algorithms developed during the last 2 years in view of an improved use of the OMI 477 nm O2-O2 band: 1. the updated OMCLDO2 algorithm, which derives improved effective cloud parameters, 2. the aerosol neural network (NN), which retrieves explicit aerosol parameters by assuming a more physical aerosol model. The OMI aerosol NN is a step ahead of OMCLDO2 because it primarily estimates an explicit aerosol layer height (ALH), and secondly an aerosol optical thickness τ for cloud-free observations. Overall, it was found that all the considered aerosol correction parameters reduce the biases identified in DOMINO-v2 over scenes in China with high aerosol abundance dominated by fine scattering and weakly absorbing particles, e.g. from [-20% V -40%] to [0% V 20%] in summertime. The use of the retrieved OMI aerosol parameters leads in general to a more explicit aerosol correction and higher tropospheric NO2 VCD values, in the range of [0% V 40%], than from the implicit correction with the updated OMCLDO2. This number overall represents an estimation of the aerosol correction strategy uncertainty nowadays for tropospheric NO2 VCD retrieval from space-borne visible measurements. The explicit aerosol correction theoretically includes a more realistic consideration of aerosol multiple scattering and absorption effects, especially over scenes dominated by strongly absorbing particles, where the correction based on OMCLDO2 seems to remain insufficient. However, the use of ALH and τ from the OMI NN aerosol algorithm is not a straightforward operation and future studies are required to identify the optimal methodology. For that purpose, several elements are recommended in this paper. Overall, we demonstrate the possibility of applying a more explicit aerosol correction by considering aerosol parameters directly derived from the 477 nm O2-O2 spectral band, measured by the same satellite instrument. Such an approach can, in theory, easily be transposed to the new-generation of space-borne instruments (e.g. TROPOMI on board Sentinel- 5 Precursor), enabling a fast reprocessing of tropospheric NO2 data over cloud-free scenes (cloudy pixels need to be filtered out), as well as for other trace gas retrievals (e.g. SO2, HCHO).Atmospheric Remote Sensin

Semantic Crowds: Reusable Population for Virtual Worlds

Recent advances in crowd simulation techniques have led to realistic agent and group behavior through elaborate behavioral models, complex motion planning algorithms and impressive physics systems. As many crowd simulation solutions typically target only specific types of environment and scenario, a variety of special-purpose methods and systems has emerged that are hard to re-configure and re-use in other contexts. Solving this situation demands a higher-level approach that takes re-use and configuration of crowds as a priority, for adequate application in a broad variety of scenarios, virtual environments and inter- action with the entities present in that environment. In this article we propose semantic crowds, a novel approach that allows one to re-use the same crowds for virtually any environment, and have them use the objects available in it in a meaningful manner, without any modification. To have the agents autonomously interact within any virtual world, we minimize in them the information relative to what objects do and how to use them. Instead, that information is stored in the objects themselves, which the agents can then query, based on what they plausibly want to achieve. To facilitate creating such crowds, we devel- oped an interactive crowd editor that provides high-level editing parameters for defining crowd templates. We illustrate the flexibility of semantic crowds by means of two cases, in which we let the same crowd populate quite differently configured airport terminal environments. These examples also highlight that this modular approach easily combines with your custom implementations of agent behavior model and/or motion planner.Intelligent SystemsElectrical Engineering, Mathematics and Computer Scienc

Woningmarkt- en leefbaarheidsonderzoek aardbevingsgebied Groningen

OLD Housing SystemsOLD Geo-information and Land DevelopmentOLD Support RE

Prospects of modelling societal transitions: Position paper of an emerging community

Policy AnalysisEnergy & Industr

An exploratory study on the aerosol height retrieval from OMI measurements of the 477 nmO₂ O₂ spectral band using a neural network approach

This paper presents an exploratory study on the aerosol layer height (ALH) retrieval from the OMI 477nm O2 O2 spectral band. We have developed algorithms based on the multilayer perceptron (MLP) neural network (NN) approach and applied them to 3-year (2005-2007) OMI cloud-free scenes over north-east Asia, collocated with MODIS Aqua aerosol product. In addition to the importance of aerosol altitude for climate and air quality objectives, our long-term motivation is to evaluate the possibility of retrieving ALH for potential future improvements of trace gas retrievals (e.g. NO2, HCHO, SO2) from UV-visible air quality satellite measurements over scenes including high aerosol concentrations. This study presents a first step of this long-term objective and evaluates, from a statistic point of view, an ensemble of OMI ALH retrievals over a long time period of 3 years covering a large industrialized continental region. This ALH retrieval relies on the analysis of the O2 O2 slant column density (SCD) and requires an accurate knowledge of the aerosol optical thickness,. Using MODIS Aqua(550nm) as a prior information, absolute seasonal differences between the LIdar climatology of vertical Aerosol Structure for space-based lidar simulation (LIVAS) and average OMI ALH, over scenes with MODIS(550nm) ≥ 1. 0, are in the range of 260-800m (assuming single scattering albedo 0 Combining double low line 0. 95) and 180-310m (assuming 0 Combining double low line 0. 9). OMI ALH retrievals depend on the assumed aerosol single scattering albedo (sensitivity up to 660 m) and the chosen surface albedo (variation less than 200 m between OMLER and MODIS black-sky albedo). Scenes with ≤ 0. 5 are expected to show too large biases due to the little impact of particles on the O2 O2 SCD changes. In addition, NN algorithms also enable aerosol optical thickness retrieval by exploring the OMI reflectance in the continuum. Comparisons with collocated MODIS Aqua show agreements between 0. 02 ± 0. 45 and 0. 18 ± g 0. 24, depending on the season. Improvements may be obtained from a better knowledge of the surface albedo and higher accuracy of the aerosol model. Following the previous work over ocean of Park et al.(2016), our study shows the first encouraging aerosol layer height retrieval results over land from satellite observations of the 477 nm O2 gO2 absorption spectral band.Atmospheric Remote Sensin

Prospects of modelling societal transitions: Position paper of an emerging community

Societal transitions involve multiple actors, changes in institutions, values and technologies, and interactions across multiple sectors and scales. Given this complexity, this paper takes on the view that the societal transitions research field would benefit from the further maturation and broader uptake of modelling approaches. This paper shows how modelling can enhance the understanding of and support stakeholders to steer societal transitions. It discusses the benefits modelling provides for studying large societal systems and elaborates on different ways models can be used for transitions studies. Two model applications are presented in some detail to illustrate the benefits. Then, limitations of modelling societal transitions are discussed, which leads to an agenda for future activities: (1) better cooperation in the development of dynamic models, (2) stronger interaction with other transition scholars and stakeholders, and (3) use of additional modelling approaches that we think are relevant to and largely unexplored in transitions studies.Multi Actor SystemsTechnology, Policy and Managemen

Error sources in the retrieval of aerosol information over bright surfaces from satellite measurements in the oxygen A band

Retrieving aerosol optical thickness and aerosol layer height over a bright surface from measured top-of-atmosphere reflectance spectrum in the oxygen A band is known to be challenging, often resulting in large errors. In certain atmospheric conditions and viewing geometries, a loss of sensitivity to aerosol optical thickness has been reported in the literature. This loss of sensitivity has been attributed to a phenomenon known as critical surface albedo regime, which is a range of surface albedos for which the top-of-atmosphere reflectance has minimal sensitivity to aerosol optical thickness. This paper extends the concept of critical surface albedo for aerosol layer height retrievals in the oxygen A band, and discusses its implications. The underlying physics are introduced by analysing the top-of-atmosphere reflectance spectrum as a sum of atmospheric path contribution and surface contribution, obtained using a radiative transfer model. Furthermore, error analysis of an aerosol layer height retrieval algorithm is conducted over dark and bright surfaces to show the dependence on surface reflectance. The analysis shows that the derivative with respect to aerosol layer height of the atmospheric path contribution to the top-of-atmosphere reflectance is opposite in sign to that of the surface contribution - an increase in surface brightness results in a decrease in information content. In the case of aerosol optical thickness, these derivatives are anti-correlated, leading to large retrieval errors in high surface albedo regimes. The consequence of this anti-correlation is demonstrated with measured spectra in the oxygen A band from the GOME-2 instrument on board the Metop-A satellite over the 2010 Russian wildfires incident.Atmospheric Remote Sensin