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

Ab initio structure determination using nano electron diffraction

This thesis is the summary of the development of electron diffraction into a mature method for ab initio structure determination. The progress is illustrated with the structure determination of some complicated unknown inorganic materials. The main step forwards is that it is now possible to apply electron crystallography method on solving the structure with a relatively large unit cell dimension along all directions and with both very heavy atoms and very light atoms. One main issue about structure determination using nano-electron diffraction discussed in the thesis is how to deal with all the difficulties caused by the dynamical effect of electron scattering. We have exemplified these with the structure determination of two compounds. One is monoclinic Eu2CaCu2O6 (a=6.08Å, b=6.14Å, c=15.34Å, ?=108.3°), and the other is cubic Mg10Ir19B16 (a=10.568Å). The success of solving these two complicated structures relies on three innovations comparing to the traditional structure analysis method (Exit wave reconstruction combined with Dynamical electron diffraction refinement) in our group. They are 1) the combined use of the chemical information of bond length in the step of constructing a reasonable initial structure model; 2) phase estimation of electron diffraction by Maximum Entropy method. 3) the combined use of first-principles calculation in the step of structure refinement to solve the possible local minimum problem of dynamical electron diffraction refinement. Based on the experiences of processing these problems evolved with structure determination using electron diffraction, a correlative structure analysis approach of combination all possible methods is proposed and discussed. So far, it is also introduced in the thesis an improved TEM sample preparation method for providing thin TEM sample for the consideredKavli Institute of Applied SciencesApplied Science

Risk analysis on real estate investment decision-making

Architectur

Electrochemistry of zirconium in molten chlorides

In this work, the electrochemical behavior of zirconium was studied on an inert molybdenum electrode at 550 °C in a LiCl-KCl-K2ZrF6 molten salt system, which is considered as an ideal electrolyte for the zirconium electrorefining process. Several transient electrochemical techniques were used such as cyclic voltammetry, chronopotentiometry, square wave voltammetry, and open circuit chronopotentiometry. The reduction of Zr (IV) was determined to follow a two-step mechanism of Zr (IV)/Zr (II) and Zr (II)/Zr. The diffusion coefficient of Zr (IV) was investigated with cyclic voltammetry and chronopotentiometry, and the results turned out to be in fair agreement from the both methods, as to be 4.26×10-5 and 4.98×10-5 cm2/s, respectively. The present study aims to provide a theoretical reference for the Zr electrorefining process.(OLD) MSE-

Alloy by design: A materials genome approach to advanced high strength stainless steels for low and high temperature applications

We report a computational 'alloy by design' approach which can significantly accelerate the design process and substantially reduce the development costs. This approach allows simultaneously optimization of alloy composition and heat treatment parameters based on the integration of thermodynamic, thermo-kinetics and a genetic algorithm optimization route. Novel steel compositions and associated key heat treatment parameters are identified so as to realize the target microstructure for applications either at the room temperature (ultra-high strength maraging stainless steel) or at high temperatures (creep resistant steels). Solid solution strengthening and precipitation hardening are the two strengthening mechanisms employed to improve the strength of designed steels. Either one of them or their combination is optimized in the four steel families considered. Each model is validated by analyzing the strengthening contributions in existing steels and by experimental characterization of prototype alloys. Very good agreement between experimental performance and model predictions is found. All newly designed alloys are predicted to outperform existing high end reference grades.Aerospace Structures & MaterialsAerospace Engineerin

Preliminary aeroelastic design of composite wings with distributed electric propulsion

In the development of electric aircraft, the use of distributed electric propulsion introduces a potential occurrence of propeller whirl flutter, which needs to be taken into account for wing structural design. To this end, this work extends an in-house aeroelastic optimization tool by means of including a post-processing procedure on whirl flutter analysis. In aeroelastic optimization, propellers are modeled as concentrated masses, and the wing mass is minimized by tailoring the lamination parameters and thickness of wing laminates subject to aerostructural design constraints. For the whirl flutter analysis of the optimized wing, a new aeroelastic model is built by coupling propeller motions and aerodynamic loads into wing aeroelastic model. The usefulness of the purposed approach is demonstrated using a numerical example, where the required inputs on propeller mounting properties are determined via a parametric study. The result indicates that flexibly mounting propellers on a flexible wing leads to the decrease of wing flutter speed, and it also confirms that the propeller mounting properties have a large influence on aeroelastic instability of the coupled propeller-wing system.Aerospace Structures & Computational Mechanic

Sodium ion ordering in NaxCoO2: Electron diffraction study

Applied Science

Method for removing a high definition nanostructure, a partly freestanding layer, a sensor comprising said layer and a method using said sensor

The present invention is in the field of a method for removing a high definition nanostructure in a partly free-standing layer, the layer, a sensor comprising said layer, a use of said sensor, and a method of detecting a species, and optional further characteristics thereof, using said sensor. The sensor and method are suited for detecting single ions, molecules, low concentrations thereof, and identifying sequences of base pairs, e.g. in a DNA-strand.QN/Quantum NanoscienceApplied Science

Unexpected origin of magnetism in monoclinic Nb12O29 from first-principles calculations

Nb12O29 is a 4d transition metal oxide that occurs in two forms with different symmetries, monoclinic (m) and orthorhombic (o). The monoclinic form has unusual magnetic properties; below a temperature of 12 K, it exhibits both metallic conductivity and antiferromagnetic ordering. Here, first-principles density-functional theory calculations are used to study the structure, relative stability and electronic properties of Nb12O29. The optimized crystal structures are in good agreement with experimental observations and total energy calculations show similar stability of the two phases, while a magnetic electronic state is slightly favoured for m-Nb12O29. The unusual magnetism of the monoclinic phase originates from a Stoner instability that can be attributed to the Nb atoms with valence states close to Nb5+, i.e., the atoms with an electronic configuration of [similar]d0. This is in clear contradiction to current models in which the magnetism is attributed to the presence of localized Nb4+ ions with a formal d1 configuration. Our study demonstrates that in complex structures, magnetic properties are best not inferred from ionic models, but require a full quantum mechanical calculation over the whole unit cell.Quantum NanoscienceApplied Science

Research on the Implementation of the New Accounting Standard on Assets Impairment: An Empirical Analysis of Its Effect on Earnings Management

本文利用2003~2010年我国A股主板上市公司的数据，对2007年开始，从而为新准则的实施效果提供了最新的经验证据。研究结果发现：新准则执行后，扭亏公司、连亏公司及微利公司利用减值转回进行盈余管理的行为显著减少，但重亏公司多提减值的“大清洗”行为则没有显著减少。此外，连亏公司和微利公司少提资产减值进行盈余管理的现象仍然存在。更细致的考察结果显示，上市公司的长期资产减值转回行为显著减少，而利用短期资产减值来进行盈余管理的行为虽有增多但不显著。Using a sample of A-share companies listed on the main board in China from 2003 to 2010, we examine the effect of ASBE No. 8 pertaining to asset impairment on earnings management activities. We find that following the accounting change in asset impairment standards, assets impairment reversals in companies with small current losses or continuing losses or small current profits are significantly reduced. However, we find that companies with substantial losses still engage in the “big bath” activities. In general, companies with small losses or small profits still engage in earnings management by reducing assets impairment provision. Further analysis shows that there is little evidence that listed companies use more short-term assets impairment than long-term assets impairment to manage earnings, even though short-term assets impairment is indeed used more often than long-term assets impairment. We conclude that the new assets impairment accounting standards restrict assets impairment reversals in listed companies. New assets impairment standards in general reduce earnings management activities, but there is no evidence that they enhance conservatism.作者单位：湘潭大学商学院会计