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

Satellite-derived NO_x emissions over East Asia

Nitrogen oxides (NOx) are important air pollutants and play a crucial role in climate change. NOx emissions are important for chemical transport models to simulate and forecast air quality. Up-to-date emission information also helps policymakers to mitigate air pollution. In this thesis, we have focused on providing better NOx emission estimates with the DECSO (Daily Emission estimates Constrained by Satellite Observations) inversion algorithm applied to satellite observations. DECSO is a fast algorithm, which enables daily emissions estimates as soon as the satellite observations are available. Satellite-derived emissions reveal more specific information on the location and strength of sources than concentration observations. The monthly and yearly variability in emissions are well captured. This is demonstrated by our monitoring of the effect of air quality regulations on emissions during events like the 2014 Youth Olympic Games. Near the Chinese coast ship tracks, which are otherwise hidden under the outflow of air pollution from the mainland, are revealed in our NOx emissions derived with DECSO applied to OMI satellite observations. Trends of shipping emissions for a 10-year period (2007 to 2016) over Chinese seas are presented for the first time.Atmospheric Remote Sensin

Matrix-Pencil Approach-Based Interference Mitigation for FMCW Radar Systems

A novel matrix-pencil (MP)-based interference mitigation approach for frequency-modulated continuous-wave (FMCW) radars is proposed in this article. The interference-contaminated segment of the beat signal is first cut out, and then, the signal samples in the cutout region are reconstructed by modeling the beat signal as a sum of complex exponentials and using the MP method to estimate their parameters. The efficiency of the proposed approach for the interference with different parameters (i.e., interference duration, signal-to-noise ratio (SNR), and different target scenarios) is investigated by means of numerical simulations. The proposed interference mitigation approach is intensively verified on experimental data. Comparisons of the proposed approach with the zeroing and other beat-frequency interpolation techniques are presented. The results indicate the broad applicability and superiority of the proposed approach, especially in low SNR and long interference duration situations.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.Microwave Sensing, Signals & SystemsElectrical Engineering, Mathematics and Computer Scienc

Evaluation of modeling NO₂ concentrations driven by satellite-derived and bottom-up emission inventories using in situ measurements over China

Chemical transport models together with emission inventories are widely used to simulate NO2 concentrations over China, but validation of the simulations with in situ measurements has been extremely limited. Here we use ground measurements obtained from the air quality monitoring network recently developed by the Ministry of Environmental Protection of China to validate modeling surface NO2 concentrations from the CHIMERE regional chemical transport model driven by the satellite-derived DECSO and the bottom-up MIX emission inventories. We applied a correction factor to the observations to account for the interferences of other oxidized nitrogen compounds (NOz), based on the modeled ratio of NO2 to NOz. The model accurately reproduces the spatial variability in NO2 from in situ measurements, with a spatial correlation coefficient of over 0.7 for simulations based on both inventories. A negative and positive bias is found for the simulation with the DECSO (slope= 0.74 and 0.64 for the daily mean and daytime only) and the MIX (slope= 1.3 and 1.1) inventories, respectively, suggesting an underestimation and overestimation of NOx emissions from corresponding inventories. The bias between observed and modeled concentrations is reduced, with the slope dropping from 1.3 to 1.0 when the spatial distribution of NOx emissions in the DECSO inventory is applied as the spatial proxy for the MIX inventory, which suggests an improvement of the distribution of emissions between urban and suburban or rural areas in the DECSO inventory compared to that used in the bottom-up inventory. A rough estimate indicates that the observed concentrations, from sites predominantly placed in the populated urban areas, may be 10-40 % higher than the corresponding model grid cell mean. This reduces the estimate of the negative bias of the DECSO-based simulation to the range of -30 to 0 % on average and more firmly establishes that the MIX inventory is biased high over major cities. The performance of the model is comparable over seasons, with a slightly worse spatial correlation in summer due to the difficulties in resolving the more active NOx photochemistry and larger concentration gradients in summer by the model. In addition, the model well captures the daytime diurnal cycle but shows more significant disagreement between simulations and measurements during nighttime, which likely produces a positive model bias of about 15 % in the daily mean concentrations. This is most likely related to the uncertainty in vertical mixing in the model at night.Atmospheric Remote Sensin

Robust Locomotion Exploiting Multiple Balance Strategies: An Observer-Based Cascaded Model Predictive Control Approach

Robust locomotion is a challenging task for humanoid robots, especially when considering dynamic disturbances. This article proposes a disturbance observer-based cascaded model predictive control (MPC) approach for bipedal locomotion, with the capability of exploiting ankle, stepping, hip and height variation strategies. Specifically, based on the variable-height inverted pendulum model, a nonlinear MPC that is run at a low frequency is built for 3-D locomotion (i.e., with height variation) while accounting for the footstep modulation as well. Differing from previous works, the nonlinear MPC is formulated as a convex optimization problem by semidefinite relaxation. Subsequently, assuming a flywheel at the pelvis center, a linear MPC that is run at a high frequency is proposed to regulate angular momentum (e.g., through rotating the upper body), which is solved by convex quadratic programming. To run the cascaded MPC in a closed-loop manner, a high order sliding mode observer is designed to estimate system states and dynamic disturbances simultaneously. Simulation and hardware experiments demonstrate the walking robustness in real-world scenarios, including 3-D walking with varying speeds, walking across non-coplanar terrains and push recovery.Accepted Author ManuscriptLearning & Autonomous Contro

Robust Jumping with an Articulated Soft Quadruped via Trajectory Optimization and Iterative Learning

Quadrupeds deployed in real-world scenarios need to be robust to unmodelled dynamic effects. In this work, we aim to increase the robustness of quadrupedal periodic forward jumping (i.e., pronking) by unifying cutting-edge model-based trajectory optimization and iterative learning control. Using a reduced-order soft anchor model, the optimization-based motion planner generates the periodic reference trajectory. The controller then iteratively learns the feedforward control signal in a repetition process, without requiring an accurate full-body model. When enhanced by a continuous learning mechanism, the proposed controller can learn the control inputs without resetting the system at the end of each iteration. Simulations and experiments on a quadruped with parallel springs demonstrate that continuous jumping can be learned in a matter of minutes, with high robustness against various types of terrain.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.Learning & Autonomous Contro

NOx emission estimates during the 2014 Youth Olympic Games in Nanjing (discussion paper)

The Nanjing Government has taken temporary environmental regulations to guarantee good air quality during the Youth Olympic Games (YOG) in 2014. We study the effect of those regulations by applying the emission estimate algorithm DECSO (Daily Emission estimates Constrained by Satellite Observations) to measurements of the Ozone Monitoring Instrument (OMI). We improved DECSO by updating the chemical transport model CHIMERE from v2006 to v2013 and by adding an Observation minus Forecast (OmF) criterion to filter outlying satellite retrievals due to high aerosol concentrations. The comparison of model results with both ground and satellite observations indicates that CHIMERE v2013 is better performing than CHIMERE v2006. After filtering the satellite observations with high aerosol loads that were leading to large OmF values, unrealistic jumps in the emission estimates are removed. Despite the cloudy conditions during the YOG we could still see a decrease of tropospheric NO2 column concentrations of about 32% in the OMI observations as compared to the average NO2 concentrations from 2005 to 2012. The results of the improved DECSO algorithm for NOx emissions show a reduction of at least 25% during the YOG period. This indicates that air quality regulations taken by the local government were successful. The algorithm is also able to detect an emission reduction of 10% during the Chinese Spring Festival. This study demonstrates the capacity of the DECSO algorithm to capture the change of NOx emissions on a monthly scale. We also show that the observed concentrations and the derived emissions show different patterns that provide complimentary information. For example, the Nanjing smog episode in December 2013 led to a strong increase in NO2 concentrations without an increase in NOx emissions. Furthermore, DECSO gives us important information of the non-trivial seasonal relation between NOx emissions and NO2 concentrations on a local scale.Geoscience & Remote SensingCivil Engineering and Geoscience

Stable acetate production in extreme-thermophilic (70ºC) mixed culture fermentation by selective enrichment of hydrogenotrophic methanogens

The control of metabolite production is difficult in mixed culture fermentation. This is particularly related to hydrogen inhibition. In this work, hydrogenotrophic methanogens were selectively enriched to reduce the hydrogen partial pressure and to realize efficient acetate production in extreme-thermophilic (706C) mixed culture fermentation. The continuous stirred tank reactor (CSTR) was stable operated during 100 days, in which acetate accounted for more than 90% of metabolites in liquid solutions. The yields of acetate, methane and biomass in CSTR were 1.5 ± 0.06, 1.0 ± 0.13 and 0.4 ± 0.05 mol/mol glucose, respectively, close to the theoretical expected values. The CSTR effluent was stable and no further conversion occurred when incubated for 14 days in a batch reactor. In fed-batch experiments, acetate could be produced up to 34.4 g/L, significantly higher than observed in common hydrogen producing fermentations. Acetate also accounted for more than 90% of soluble products formed in these fed-batch fermentations. The microbial community analysis revealed hydrogenotrophic methanogens (mainly Methanothermobacter thermautotrophicus and Methanobacterium thermoaggregans) as 98% of Archaea, confirming that high temperature will select hydrogenotrophic methanogens over aceticlastic methanogens effectively. This work demonstrated a potential application to effectively produce acetate as a value chemical and methane as an energy gas together via mixed culture fermentation.BT/BiotechnologyApplied Science

NOx emission estimates during the 2014 Youth Olympic Games in Nanjing

The Nanjing Government applied temporary environmental regulations to guarantee good air quality during the Youth Olympic Games (YOG) in 2014. We study the effect of those regulations by applying the emission estimate algorithm DECSO (Daily Emission estimates Constrained by Satellite Observations) to measurements of the Ozone Monitoring Instrument (OMI). We improved DECSO by updating the chemical transport model CHIMERE from v2006 to v2013 and by adding an Observation minus Forecast (OmF) criterion to filter outlying satellite retrievals due to high aerosol concentrations. The comparison of model results with both ground and satellite observations indicates that CHIMERE v2013 is better performing than CHIMERE v2006. After filtering the satellite observations with high aerosol loads that were leading to large OmF values, unrealistic jumps in the emission estimates are removed. Despite the cloudy conditions during the YOG we could still see a decrease of tropospheric NO2 column concentrations of about 32 % in the OMI observations when compared to the average NO2 columns from 2005 to 2012. The results of the improved DECSO algorithm for NOx emissions show a reduction of at least 25 % during the YOG period and afterwards. This indicates that air quality regulations taken by the local government have an effect in reducing NOx emissions. The algorithm is also able to detect an emission reduction of 10 % during the Chinese Spring Festival. This study demonstrates the capacity of the DECSO algorithm to capture the change of NOx emissions on a monthly scale. We also show that the observed NO2 columns and the derived emissions show different patterns that provide complimentary information. For example, the Nanjing smog episode in December 2013 led to a strong increase in NO2 concentrations without an increase in NOx emissions. Furthermore, DECSO gives us important information on the non-trivial seasonal relation between NOx emissions and NO2 concentrations on a local scale.Geoscience & Remote SensingCivil Engineering and Geoscience

NOx Emissions Reduction and Rebound in China Due to the COVID-19 Crisis

During the COVID-19 lockdown (24 January–20 March) in China low air pollution levels were reported in the media as a consequence of reduced economic and social activities. Quantification of the pollution reduction is not straightforward due to effects of transport, meteorology, and chemistry. We have analyzed the NOx emission reductions calculated with an inverse algorithm applied to daily NO2 observations from TROPOMI onboard the Copernicus Sentinel-5P satellite. This method allows the quantification of emission reductions per city and the analysis of emissions of maritime transport and of the energy sector separately. The reductions we found are 20–50% for cities, about 40% for power plants, and 15–40% for maritime transport depending on the region. The reduction in both emissions and concentrations shows a similar timeline consisting of a sharp reduction (34–50%) around the Spring festival and a slow recovery from mid-February to mid-March.Atmospheric Remote Sensin