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

Seat Vibration Simulator for Ride Comfort Evaluation

Ride comfort is one of the aspects of vehicles that manufacturers are constantly trying to improve, and seat vibration is an important contributing factor to ride comfort. The present study developed a seat vibration simulator for investigating the human perception of seat vibration and its application on ride comfort evaluation. The simulator was delivered as a fully functional system. The design requirements of the simulator were defined based on the review of proving ground measurements and previous studies. It concluded that the operating frequency range was 10-80Hz with excitation applied in both longitudinal and vertical directions. A compact and cost-effective design was proposed featuring a modular floating vibration platform and compact electrodynamics actuators. The Time Waveform Replication (TWR) process was implemented as the control strategy of the simulator and yielded good accuracy for tracking the target stimuli within the frequency range of 6-80Hz. The second part of the present study discussed the application of the seat vibration simulator. An experimental measurement method was proposed and validated for measuring the difference threshold of human perception of seat vibration, including the spectrum baseline method for generating reference stimulus from proving ground measurements, the modified A-AFC protocol for reducing the experiment duration, and the software for the fully automated experiment. The proposal also included the potential application of the difference threshold as a new ride comfort indicator.Mechanical Engineering | Vehicle Engineering | Cognitive Robotic

Impact of Home-Based Learning Experience During COVID-19 on Future Intentions to Study Online: A Chinese University Perspective

As coronavirus disease 2019 (COVID-19) swept the world in early 2020, all the Chinese universities and colleges adopted online learning to fulfill the directive saying “classes suspended but learning continues.” Understanding the impact of this large-scale online learning experience on the future online learning intention of Chinese university students can help design better blended-learning activities. This study applies flow experience and theory of planned behavior (TPB) to construct a theoretical framework for assumption making and the assumptions made are validated by data gained from questionnaires. A total of 6,933 students from 54 institutions in China participated in the investigation, with 5,456 valid questionnaires returned. This study employs partial least squares (PLS) regression and confirmative factor analysis (CFA) to analyze and estimate the measurement model and the structural model. The results indicate that the experience of home-based learning significantly influenced the attitudes of Chinese university students, which in turn had a positive influence on their intention to continue online learning. The research findings provide a theoretical framework and practical guidelines on building a scientific online learning platform with appropriate online learning environments and tasks for a post-COVID-19 era blended-learning in Chinese universities.Design & Construction Managemen

Performance of one-way carsharing systems under combined strategy of pricing and relocations

A bilevel nonlinear mathematical programing model is formulated to determine the optimal pricing and operator-based relocations in a one-way station-based carsharing system in competition with private cars. In the upper level, the carsharing operator determines the vehicle fleet, prices, and relocation operations with the objective of maximizing profits, considering the potential reaction of travelers. In the lower level, travelers choose travel modes from a cost-minimization perspective. Travel utilities are calculated through a logit model. The Karush–Kuhn–Tucker conditions are used to transform the bilevel model into a single-level model and then a genetic algorithm is proposed to solve it. Computational tests in four different scenarios show the combined strategy is the best one. The four scenarios are base, relocations, dynamic pricing, and a combination of relocations and pricing separately. The combined strategy can make the best trade-offs between the operator’s profit and the travelers’ cost.Accepted author manuscriptTransport and Plannin

DEFEAT: Deep Hidden Feature Backdoor Attacks by Imperceptible Perturbation and Latent Representation Constraints

Backdoor attack is a type of serious security threat to deep learning models. An adversary can provide users with a model trained on poisoned data to manipulate prediction behavior in test stage using a backdoor. The backdoored models behave normally on clean images, yet can be activated and output incorrect prediction if the input is stamped with a specific trigger pattern. Most existing backdoor attacks focus on manually defining imperceptible triggers in input space without considering the abnormality of triggers' latent representations in the poisoned model. These attacks are susceptible to backdoor detection algorithms and even visual inspection. In this paper, We propose a novel and stealthy backdoor attack - DEFEAT. It poisons the clean data using adaptive imperceptible perturbation and restricts latent representation during training process to strengthen our attack's stealthiness and resistance to defense algorithms. We conduct extensive experiments on multiple image classifiers using real-world datasets to demonstrate that our attack can 1) hold against the state-of-the-art defenses, 2) deceive the victim model with high attack success without jeopardizing model utility, and 3) provide practical stealthiness on image data.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

A Novel Unspecific Peroxygenase from Galatian marginata for Biocatalytic Oxyfunctionalization Reactions

Unspecific peroxygenases (UPOs, EC 1.11.2.1) are promising oxyfunctionalization catalysts because of their unique stereoselectivity. However, so far only a few UPOs have been reported. In this study, gene mining was used to identify a gene from Galerina marginata that coded for a novel UPO (GmaUPO). GmaUPO was expressed in Pichia pastoris X-33 by scale-up fermentation (the UPO activity of the culture supernatant was 118 U/L). GmaUPO exhibited a molecular weight of 40 kDa and exhibited highest activity at 35°C and pH 9, respectively. Furthermore, GmaUPO was demonstrated to catalyze the epoxidation, sulfoxidation, and hydroxylation of common substrates, particularly fatty acids such as tridecanoic acid. The molecular basis for GmaUPO regioselectivity for fatty acid hydroxylation was explored by molecular modelling. The regioselectivity was mostly governed by the architecture of the enzyme's active site.BT/Biocatalysi

Benchmarking Robustness and Generalization in Multi-Agent Systems: A Case Study on Neural MMO

We present the results of the second Neural MMO challenge, hosted at IJCAI 2022, which received 1600+ submissions. This competition targets robustness and generalization in multi-agent systems: participants train teams of agents to complete a multi-task objective against opponents not seen during training. We summarize the competition design and results and suggest that, considering our work as a case study, competitions are an effective approach to solving hard problems and establishing a solid benchmark for algorithms. We will open-source our benchmark including the environment wrapper, baselines, a visualization tool, and selected policies for further research.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.Interactive Intelligenc

One-step controllable fabrication of 3D structured self-standing Al₃Ni₂/Ni electrode through molten salt electrolysis for efficient water splitting

Exploring more efficient and low-cost electrocatalysts to replace platinum (Pt) is highly desired to promote the practical hydrogen production through water splitting. Herein, a facile and effective strategy is proposed to fabricate self-standing Al3Ni2/Ni electrode with controlled phase composition and surface morphology, which is obtained by one-step electrochemical reduction of Al3+ on commercially available nickel in eutectic NaCl-KCl melt. Different from previously reported approaches, uniform Al3Ni2 monolith catalyst can directly grow onto Ni substrate. The deposit possesses unique three-dimensional (3D) cauliflower-like morphology comprising of nano- and microparticles due to the rapid nucleation rate during molten salt electrolysis. The as-fabricated Al3Ni2/Ni electrode can be directly used as the cathode to catalyze Hydrogen evolution reaction (HER). Impressively, it exhibits remarkable HER activity comparable to commercial Pt, including a low overpotential of 83.4 mV for a current density of 10 mA cm−2, a small Tafel slope of 40.7 mV dec-1, and excellent long-term stability over 36 h of continuous HER operation in 0.5 M H2SO4 solution. The intrinsic catalytic ability of Al3Ni2 with the unique hierarchical structure of nano/microsized grains can offer multiple effects, including massive exposed active sites, enhanced charge transfer and mass transport, and fast gas releasing that synergistically contribute to improving the electrocatalytic performance of HER. This work represents a highly promising approach to the design and one-step controllable fabrication of efficient and self-standing base metal electrode for electrocatalytic hydrogen production.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 Yongxiang Yan

Federated Learning With Heterogeneity-Aware Probabilistic Synchronous Parallel on Edge

With the massive amount of data generated from mobile devices and the increase of computing power of edge devices, the paradigm of Federated Learning has attracted great momentum. In federated learning, distributed and heterogeneous nodes collaborate to learn model parameters. However, while providing benefits such as privacy by design and reduced latency, the heterogeneous network present challenges to the synchronisation methods, or barrier control methods, used in training, regarding system progress and model convergence etc. The design of these barrier mechanisms is critical for the performance and scalability of federated learning systems. We propose a new barrier control technique called Probabilistic Synchronous Parallel (PSP). In contrast to existing mechanisms, it introduces a sampling primitive that composes with existing barrier control mechanisms to produce a family of mechanisms with improved convergence speed and scalability. Our proposal is supported with a convergence analysis of PSP-based SGD algorithm. In practice, we also propose heuristic techniques that further improve the efficiency of PSP. We evaluate the performance of proposed methods using the federated learning specific FEMNSIT dataset. The evaluation results show that PSP can effectively achieve good balance between system efficiency and model accuracy, mitigating the challenge of heterogeneity in federated learning.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.Distributed System

A Series of Ternary Metal Chloride Superionic Conductors for High-Performance All-Solid-State Lithium Batteries

Understanding the relationship between structure, ionic conductivity, and synthesis is the key to the development of superionic conductors. Here, a series of Li3-3xM1+xCl6 (−0.14 < x ≤ 0.5, M = Tb, Dy, Ho, Y, Er, Tm) solid electrolytes with orthorhombic and trigonal structures are reported. The orthorhombic phase of Li–M–Cl shows an approximately one order of magnitude increase in ionic conductivities when compared to their trigonal phase. Using the Li–Ho–Cl components as an example, their structures, phase transition, ionic conductivity, and electrochemical stability are studied. Molecular dynamics simulations reveal the facile diffusion in the z-direction in the orthorhombic structure, rationalizing the improved ionic conductivities. All-solid-state batteries of NMC811/Li2.73Ho1.09Cl6/In demonstrate excellent electrochemical performance at both 25 and −10 °C. As relevant to the vast number of isostructural halide electrolytes, the present structure control strategy guides the design of halide superionic conductors.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.RST/Storage of Electrochemical EnergyPhotovoltaic Materials and DevicesRID/TS/Instrumenten groe