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

Computation of Modal Radiation through an Engine Exhaust on Adaptively Refined Meshes

This paper outlines the method of a block-structured adaptive mesh refinement (AMR) and its application to the computation of noise radiation from a realistic engine exhaust geometry with flow. The computational model described allows acoustic waves, propagating inside the bypass duct of a generic aircraft engine, to be admitted into a computational domain that includes the aft duct section, the exit plane of the duct, and the jet flow immediately downstream. Other than working on a uniformly fine mesh, the computational mesh is adaptively refined as the propagation and radiation of acoustic waves with the aim of reducing the number of computational cells and improving the computational efficiency. The method is mainly consisted of three parts: an AMR framework to manage adaptively refined meshes; a range of $4^{th}$-order schemes to compute the near-field acoustic propagation and radiation; and an integral surface for predicting far-field directivity. Propagation inside the duct, diffraction at the lip of the duct and propagation into the near field is firstly modeled by the linearised Euler equations. Hydrodynamic instabilities are discovered in the exhaust mean flow and are leading to overwhelm the acoustic solutions. In order to suppress this kind of non-physical instabilities, the original linearised Euler equations are replaced with the acoustic perturbation equations, which have been extended in the cylindrical coordinates for this case. The effect and the accuracy of the acoustic perturbation equations are validated by comparing to solutions of the linearised Euler equations through a case study of the radiation of single spinning mode from a generic engine bypass duct. The quality of the proposed AMR method is also illustrated. For this case the computational efficiency of AMR is compared with that computed on a uniformly fine mesh. The results demonstrate the efficiency of the current adaptive mesh refinement algorithm

Qualitative analysis of certain nonlinear differential equations: Quadratic systems and delay equations

Electrical Engineering, Mathematics and Computer Scienc

Design for future DDL workplace

A physical work environment is essential for creating and supporting different activities in the workplace, not only for work performance but also for physical and mental wellbeing. Studies have been conducted on the influence of the working environment on work performance and people’s wellbeing since the 1950s. Most of these studies have been published in the domains of ergonomics and human factors or in historical papers on the office environment (Katja, 2019). In recent years, motivated by increasing demand for wellness-focused design, companies and organizations are putting more effort into investing in properties that improve employee’s performance while enhancing their wellbeing in the workplace (Zack, 2019), exploring opportunities of new emerging technologies. The same applies to universities where they always seek for new approaches. Students are more willing to adapt to changes and to participate in experimental setups. Delft Design Labs offers multiple opportunities for student participation and master thesis project is one of them. Working on a graduation project is a challenging time and a graduation lab workplace should be an environment that can help. This project is focused on designing for the future Delft Design Labs workplace, which is being used by students who are working on their graduation projects for Delft Design Labs. The final design is a product system called "Hexabond" which encourages meaningful interactions between students, without disturbing everyone. It gives the user an opportunity to connect and interact with others, which can be a start point for students to get to know each other. The Hexabond is simple to set up and does not require a precious time investment. The aesthetic of the products is simple and minimalistic and makes it fit into any workplace. For validation of the Hexabond, some prototypes were created for user tests. The results of the test showed that the final design met the design goals well. The resulting product fulfills the need for encouraging students to offer and ask for help in the workplace, creating connections between students and making students feel a sense of belonging. However, there is still room for improvement for maintaining the connections between students. The biggest limitation during the project is the unfortunate pandemic. Making it impossible to do user tests in the DDL workplace or in general. The current design is still rather hypothetical and is not fully validated with the right usage. The product is rather a user-centered design that needs input and feedback from the user group. If it was possible to actually test the product in a shared workplace with the students, it would have yielded insightful feedback for iterations. Integrated Product Desig

High Tc Ceramic Superconductors in Chemical Devices

Applied Science

Magnetic HUB: prototype to shorten the distance between Cd Juarez and El Paso

The aim of my project would be using the complex building as the activators for the cities to improve the urban decentralization around the border area.Architecture and The Built EnvironmentArchitectur

Ultra-Low-Power Event-Driven Radio Design

The emerging field of internet of things promises mankind an enhanced life quality, produc-tivity and security. One critical technology enabler is ubiquitous and unobtrusive wireless connectivity activated by ambient events and operated with little human intervention for con-figuration and maintenance. Commercial off-the-shelf radio devices cannot achieve the desired performance, reliability and ultra-low power consumption around 100µW at the same time. In this work, research is carried out on the design and implementation of an ultra-low-power radio for generic wireless event-driven applications including healthcare, information and enter-tainment, industrial and home automation, as well as environment monitoring. To fulfill the stringent power budget, the envelope detection and the direct-modulation are the architectures of choice for receiver and transmitter front-ends, respectively. However, such radios suffer from poor sensitivity and frequency selectivity, and thus are unable to op-erate reliably across the desired link distance or in the presence of interference. This work investigated the root causes of insufficient sensitivity and selectivity in envelope detection receivers, and proposed design guidelines to optimize their performance. Furthermore, two novel envelope detection schemes have been proposed. The synchronized-switching technique improves the sensitivity by suppressing DC offset and 1/f noise in the receiver, while the 2-tone signaling technique enables in-band interference rejection which was not possible in prior arts. Prototype circuits have been built to verify the proposed techniques. On a 90nm CMOS technology, a transmitter and a receiver front-end are designed to benchmark the performance of 2-tone envelope detection in practice. The digital-IF, direct-modulation transmitter carries out the 2-tone IF-PSK modulation with -6dBm output power while consuming 893µW. The 2-tone envelope detection receiver realized up to 282 times improvement in interference re-jection while dissipating between 63.5µW and 121µW. A link budget of over 80dB is realized by this transceiver pair, which translates to a link span up to 30 meters in indoor environments and 100 meters outdoors. By following a systematic approach, devising innovative architectures, and optimizing circuit performance, this work has confirmed the feasibility of ultra-low-power, autonomous and robust event-driven radios in low-cost and commercially available CMOS technologies.Microelectronics & Computer EngineeringElectrical Engineering, Mathematics and Computer Scienc

A Scaling-upMethod for Assessing the Impacts of ITS on Traffic Efficiency

Human beings today have to face a series of problems brought by transport development — severe urban congestion, increasing number of injuries and fatalities as well as global warming caused by excessive emissions. Intelligent Transport Systems (ITS), as effective tools to solve these problems, thus have drawn much attention. In the future, it is expected that more and more ITS would be developed and applied in real practice. Before adopting ITS measures, it is necessary for policy makers to know the impacts of the ITS measure on on a large scale (e.g. national/European level). In many cases, the impacts of ITS are evaluated on a much smaller scale, for example from a microscopic traf- fic simulation or a field experiment. These effects need to be scaled up to the larger scale. There are two known scaling-up methods. The modelling method can accurately represent the large scale scenario, but requires considerable effort and a large amount of data which may not be available. Furthermore, it requires a macroscopic model of the ITS, which may be a challenge to derive. The statistical method describes the local scenarios via situational variables (like road types, vehicle types and traffic situations), classifies the local scenar- ios into categories and calculates the impacts on large scale as the weighted average of the local impacts. This method is easier and faster than the modelling method. However, the statistical method is only applicable for cases which only consider categorical situational variables, because the classification of the local scenarios into categories is not feasible when numerical situational variables are used. As a result, the statistical method is only suitable for ITS whose impacts are on the microscopic mechanisms (e.g speed and headway) and thus mainly affected by categorical situational variables (e.g road type and vehicle type). A scaling-up method to assess the impacts of ITS on traffic efficiency which is generally suitable for all ITS is still missing. To start filling this gap, this study develops a new scaling-up method for ITS that have direct network-wide influences to assess their large-scale impacts on traffic efficiency. The framework of the new scaling-up method is shown in Figure 2.2 and the graphical and mathematical interpretations are presented in Figure 2.3 and Figure 2.4. In brief, the new scaling-up method firstly chooses the suitable indicator of the impacts and situational vari- ables, then collects needed data and builds deterministic relationships between the indi- cator and the numerical situational variables, at last uses scaling sideways to calculate all local impacts and aggregates the local impacts to large scale. From the theoretical perspec- tive, the designed method is considered to be able to evaluate the impacts of ITS measures with direct network-wide influence on traffic efficiency in a large-scale scenario. To provide an evidence of the quality of the new scaling-up method, this study applies it to a specific ITS measure, that is the on-trip dynamic navigation system. Although the final large-scale impacts of the on-trip dynamic navigation system is not calculated due to the limitation of data source, it is proved that the new method is able to accurately assessthe large-scale impacts of the on-trip dynamic navigation system with enough available data. Other findings from the case study are also valuable. For example, the choice of the indicator and the situational variables, and the built deterministic relationship can be directly adopted in other projects that study the impacts of the on-trip dynamic navigation system, which indicates the practical contribution of this study. From a methodological perspective, the new scaling-up method is a great improvement of the current scaling-up approaches. The new scaling-up method expands the applica- tion area of scaling-up methods to ITS that have network-wide influences. Compared to the current methods, the new scaling-up method also improves the accuracy of scaling up and leads to more reliable assessments. Apart from the merits, there are also some dis- advantages of the new scaling-up method, such as the possibility of more time cost and data needed, as well as the possible difficulty to explain the deterministic relationships in a sensible way. The new scaling-up method is regarded to be with significant political value. The out- puts can provide useful information to support policy making. On one hand, according to the political economy model designed by Beuthe, the impacts of ITS play an important role in making policy decisions. The impacts of ITS can directly reflect the perceived effectiveness and the perceived distribution of benefits and costs. On the other hand, based on the outputs of the new scaling-up method, there are also other policy advices that could be made. For instance, the built deterministic relationship(s) can suggest the to-be-set value of the related parameters when adopting a certain ITS measure. For future researches, the attention could be focusing on applying the new method to more ITS measures and investigating the applicability of the new method on assessing the impacts on safety and environment. Specifically regarding the study of the on-trip dynamic navigation system, if the needed data is available, it would be beneficial to conduct a com- plete assessment of the large-scale impacts in a specific scenario in the future. In addition, the influences of other situational variables besides the considered situational variables could also be taken into account. Furthermore, a more specific classification of network structure is expected in future researches.Transport, Infrastructure and LogisticsTransport & PlanningCivil Engineering and Geoscience

Credit Portfolio Losses

Applied ScienceElectrical Engineering, Mathematics and Computer Scienc