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 Vector Form Intrinsic Finite Element method and several other form-finding methods for general networks

Discrete networks is a kind of form-active structural system which actively change its shape under varying load conditions. And for this kind of structural system, form-finding is the initial and essential part in their design process. Before the computer age, people complete the form-finding process using physical models, while with the advances in computational techniques, the research has focused on the numerical form-finding methods since the 1960s. A brief discussion on several numerical formfinding methods is presented in this paper. Firstly, two relatively mature numerical method, Dynamic Relaxation method and Force Density method, are introduced conceptually. And then, a newly developed numerical method, the Vector Form Intrinsic Finite Element method, is presented in more detail. At last, with a replacement of the calculation of the internal force of the element which obeys the Hooke's Law by the product of the force density and the length of the element, two derived methods based on the above three methods are proposed in this paper. Moreover, several numerical examples of hanging networks are shown to illustrate the validity and characteristic of the VFIFE method and the two newly proposed derived methods.Structural Design & Mechanic

Simultaneous optimization of shape and topology of free-form shells based on uniform parameterization model

In current optimization methods for free-form shells, the shape and topology are usually optimized separately. These methods are based on the assumption that the shape and topology of a shell influence each other only slightly, but this is not always correct. Moreover, different parameterization models are used in the shape optimization and topology optimization of free-form shells, which brings difficulties to carry out the integrated optimization. To solve this problem, an integrated method is proposed for simultaneously optimizing shape and topology for free-form shells. A uniform parameterization model based on NURBS solids is established to parameterize the free-form shells. In this model, only a small number of variables are used to describe both the shape and topology of the shell. In this way, the integrated optimization problem can be simplified, thus decrease the computational complexity. The integrated optimization of shape and topology is a complicated and large-scale optimization problem. Solving this problem requires a suitable optimization method. In this paper, the Method of Moving Asymptotes (MMA) is adopted. Finally, numerical examples are presented to address the importance of the optimization sequences and show the effectiveness and application of the proposed method.Accepted Author ManuscriptApplied Mechanic

Form-finding of gridshells generated from hanging-chain models by using the Dynamic Relaxation method and the NURBS technique

Hanging models play an important role in shaping a structure since a very early age, and were favored by A. Gaudi, H. Isler, F. Otto and other architects or engineers. Nowadays, with the development of numerical analysis theory and computer technique, it is more accurate and convenient to simulate these physical models via numerical means. Based on the background, this paper presents a numerical form-finding method of gridshell structures generated from hanging-chain models by using Dynamic Relaxation method and the NURBS technique, which aims to obtain more complex structural forms with multiple control points.This method uses global NURBS surface interpolation to describe the initial cable-net model passing through the given target points, which serve as the fitting points of the NURBS surface. The cable elements of the cable-net are not allowed to elongate after form-finding, and clearly, this kind of cable-nets belongs to geometrically unstable system, whose form-finding process of it has a very strong nonlinearity. To solve this problem, it uses the Dynamic Relaxation method, which can complete the form-finding of geometrically unstable systems but with some special sets, to get the equilibrium form of the hanging cable-net under the gravity. However, this structural form may no longer pass through the given target points, and then it introduces the inverse iteration method to adjust the coordinates of the fitting points of the NURBS, which actually means to find the initial structural form which after form-finding can just right meet the target requirements. At last, some numerical examples are presented to demonstrate the validity of the proposed method in this paper.Structural Design & Mechanic

分支叉管對血液壓力波的影響與中藥活性之研究

[[abstract]]本文利用流體力學的觀點，設計簡單的物理模式（利用幫浦作為波動來源以模擬心臟 ，以塑膠管模擬血管，而以具有低頻共振特性的氣球模擬人體臟器），並佐以動物實 驗，探討血液在人體各臟器的分配原理，以了解人體血液循環系統的共振特性，進而 研究中藥對人體臟器的影響，結果發現： （一）主管與分支叉管間的couple oscillation，其表現與老鼠體內血管和各器管組 織間的共振特性現象相同。 （二）由心縮壓、心舒壓、分支叉管長度、氣球彈性都可以影響共振狀態，以了解中 藥對人體的可能作用是(a) 改變血管的物理特性(b) 改變臟器或分支動脈叢的物理特 性。 （三）三種不同溶劑（分別是酒精：水=1:1，乙酸乙酯，正己烷）的黃連萃取液皆可 降心火、肝火、補脾、胃，而以黃連正己烷萃取液的作用最強。黃連正己烷萃取液再 經管柱層析，發現極性較小的成份具有相同的作用，極性較大的成份則沒有這種作用 。 （四）經統計，老鼠死亡前都有一個共同特徵：脾(C )、胃(C )先衰，而後心火(C ) 上升，至肺脈(C )下降，膽脈(C )上升，大口呼吸時即已回天乏術了。

我國現階段高中美術科設計課程實施之調查研究

[[abstract]]本研究主要目的有：ぇ探討高中美術科中美術設計單元施教狀況。え探討高中美術科 中美術設計施教的背景條件。ぉ探討高中學生，在各不同背景下，接受美術設計教育 後，成果之差異。包括文化背景、地域背景、個人特質等因素下之差異。お探討高中 美術設計在精熟的訓練（美術實驗班）與普通之訓練（普通班級），成效差異之情形 。 研究者之對象為全省公私立高中教師，經問卷回收得１１６名現職教師，以及經抽樣 得全省２３所公私立高二學生１０５４名，三所美術實驗學生１２０名進行調查。 研究工具為研究者依理論研究自編的教師用之「高級中學美術設計課實施調查問卷， 暨學生用的「高級中學美術設計學習經驗調查問卷」。藉則者以得知教師實施美術科 設計單元時所產生的問題。以後者得知學生學習美前設計之反應成效。 本研究統計處理主要有四： （一）應用卡方考驗（Chi－Square test），了解教師在實施設計教學所遭遇問題反 應的情形。 （二）應用獨立樣本人數不等的單因子變異數分析，以比較高二學生（包括普通班與 美術實驗班），在美術設計學習成果三層面反應的差異情形，藉以瞭解其差異，進一 步探討實施之一般成效狀況。 根據有關文獻探討及問卷調查的發現，本研究可歸納以下之結論： （一）高級中學教師對現階段設計課程內容安排，尚稱滿意。但對「設計課程」的意 義，仍有美術教師予以誤解，造成設計教育在美術科中不易實施。 （二）對於設計教學的熱心與能力程度，仍以美術科系畢業者為優。部份學校以他科 教師或行政人員兼任美術教學，將殘害美術科教學的效果。 （三）公私立學校學生，學習設計課程級之應用方面比較，結果顯示私立學校學生優 於公立學校。 （四）高中美術實驗班學生學習美術設計成效優於一般高中學生，乃訓練名家，的問 題所致。

Size and Topology Optimization for Trusses with Discrete Design Variables by Improved Firefly Algorithm

Firefly Algorithm (FA, for short) is inspired by the social behavior of fireflies and their phenomenon of bioluminescent communication. Based on the fundamentals of FA, two improved strategies are proposed to conduct size and topology optimization for trusses with discrete design variables. Firstly, development of structural topology optimization method and the basic principle of standard FA are introduced in detail. Then, in order to apply the algorithm to optimization problems with discrete variables, the initial positions of fireflies and the position updating formula are discretized. By embedding the random-weight and enhancing the attractiveness, the performance of this algorithm is improved, and thus an Improved Firefly Algorithm (IFA, for short) is proposed. Furthermore, using size variables which are capable of including topology variables and size and topology optimization for trusses with discrete variables is formulated based on the Ground Structure Approach. The essential techniques of variable elastic modulus technology and geometric construction analysis are applied in the structural analysis process. Subsequently, an optimization method for the size and topological design of trusses based on the IFA is introduced. Finally, two numerical examples are shown to verify the feasibility and efficiency of the proposed method by comparing with different deterministic methods.Structural Design & Mechanic

Uneven primary healthcare supply of rural doctors and medical equipment in remote China: community impact and the moderating effect of policy intervention

Background: Unequal access to primary healthcare (PHC) has become a critical issue in global health inequalities, requiring governments to implement policies tailored to communities’ needs and abilities. However, the place-based facility dimension of PHCs is oversimplified in current healthcare literature, and formulating the equity-oriented PHC spatial planning remains challenging without understanding the multiple impacts of community socio-spatial dynamics, particularly in remote areas. This study aims to push the boundary of PHC studies one step further by presenting a nuanced and dynamic understanding of the impact of community environments on the uneven primary healthcare supply. Methods: Focusing on Shuicheng, a remote rural area in southwestern China, multiple data are included in this village-based study, i.e., the facility-level healthcare statistics data (2016–2019), the statistical yearbooks, WorldPop, and Chinese GDP’s spatial distribution data. We evaluate villages’ PHC service capacity using the number of doctors and essential equipment per capita, which are the major components of China’s PHC delivery. The indicators describing community environments are selected based on extant literature and China’s planning paradigms, including town- and village-level factors. Gini coefficients and local spatial autocorrelation analysis are used to present the divergences of PHC capacity, and multilevel regression model and (heterogeneous) difference in difference model are used to examine the driving role of community environments and the dynamics under the policy intervention. Results: Despite the general improvement, PHC inequalities remain significant in remote rural areas. The village’s location, aging, topography, ethnic autonomy, and economic conditions significantly influence village-level PHC capacity, while demographic characteristics and healthcare delivery at the town level are also important. Although it may improve the hardware setting in village clinics (coef. = 0.350), the recent equity-oriented policy attempts may accelerate the loss of rural doctors (coef. = − 0.517). Notably, the associations between PHC and community environments are affected inconsistently by this round of policy intervention. The town healthcare centers with higher inpatient service capacity (coef. = − 0.514) and more licensed doctors (coef. = − 0.587) and nurses (coef. = − 0.344) may indicate more detrimental policy effects that reduced the number of rural doctors, while the centers with more professional equipment (coef. = 0.504) and nurses (coef. = 0.184) are beneficial for the improvement of hardware setting in clinics. Conclusions: The findings suggest that the PHC inequalities are increasingly a result of joint social, economic, and institutional forces in recent years, underlining the increased complexity of the PHC resource allocation mechanism. Therefore, we claim the necessity to incorporate a broader understanding of community orientation in PHC delivery, particularly the interdisciplinary knowledge of the spatial lens of community, to support its sustainable development. Our findings also provide timely policy insights for ongoing primary healthcare reform in China.History, Form & Aesthetic

ж青中多环芳烃荧光特征及其浓度梯度下的 响应机制硏究

Polycyclic Aromatic Hydrocarbons (PAHs) in asphalt materials is a type of serious environmental hazard, and the main pollution resource in road engineering. Aiming at the requirement of PAHs rapid detection method in asphalt pavement construction for low environmental hazard, this research concentrated in experiments about PAHs content, fluorescence characteristics, solvent environment impact mechanism and correlation between fluorescence intensity and concentration in different asphalt materials, based on the fluorescence effect of PAHs from condensed ring structure. It is found that coal tar asphalt has a typical aggregation-caused quenching phenomenon and higher fluorescence quantum efficiency. Taking the three solvent environment parameters polarity, viscosity and pH value as the research objects, the optimal solvent environment for the fluorescence phenomenon of PAHs in asphalt materials was explored and established as dimethyl sulfoxide: tetrahydrofuran: deionized water: glycerol = 1 : 1 : 1 : 2. Under the optimal solvent environment, fluorescence intensity and concentration of the three asphalt materials all showed obvious linear relationship. Under the same concentration condition, fluorescence intensity of asphalt material showed positive correlation with the PAHs content. This study proves that the asphalt material has the linear relationship between fluorescence intensity and PAHs concentration, which will provide theoretical basis for the detection of PAHs content in asphalt materials, and support the development of low environmental hazard in construction technology for road engineering.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.Pavement Engineerin

[[alternative]]A Case Study on Drop-out Counseling Strategies of Junior High School Students-One Junior High School in Changhua County as An Example

碩士教育研究所[[abstract]]中 文 摘 要 本研究之要旨，是研究者以實際服務學校中，中輟生輔導策略之個案研究。研究之目的最主要是在了解國中生中輟原因，進而擬定策略，確實實施，觀察實施結果，反省改進，幫助中輟生順利復學，以解決實際場域中所面臨的問題。本研究是以個案研究方法進行之，研究對象有4名中輟生，以質性研究方法的訪談、觀察和校內各種文件的分析為主要的資料蒐集方法。 玆歸納本研究之結果，做成結論如下： 壹、中輟原因－個人因素：因缺乏自信產生自我適應不良、生活作息不正常；家庭因素：家人溺愛或暴力管教、父母親離婚再婚致使家庭結構複雜；學校因素：對學校課業不感興趣、師生關係不佳、與同儕關係不良；社會因素：受已輟同學影響；其他因素；不明原因失蹤等。 貳、輔導策略－第一次輔導策略 擬定各種家庭、個人因素所造成難以適應國中生活、不滿校規或老師管教方式、學業困難、同儕相處問題之輔導策略。 第二次輔導策略 適時轉介到少年學園就讀；再一次請家長認真思考如何消除造成中輟的家庭因素，如改變家庭結構並確切實行；再努力找尋他們的重 要他人，請其幫忙鼓勵、督促其到校上課。 ?、實施結果 一、第一次輔導策略實施結果：4位研究對象實際上皆失敗。 二、第二次輔導策略實施結果：1位到少年學園就讀；1位成功復學；1位來一天修兩天，規避被報中輟；1位時輟時復。 根據以上研究的結果，研究者提供若干建議，供學校實際工作者、中輟生的家長及未來研究之參考。[[abstract]]A Case Study on Drop-out Counseling Strategies of Junior High School Students-One Junior High School in Changhua County as An Example Advisor : Tsong-Wen Chen, Ph.D. Author: Li-Yue Wu Abstract The study focused on a case study on drop-out counseling strategies in a junior high school which the researcher works for. By finding out the drop-out factors of junior high school students, making coping strategies, applying the strategies, examining the results and improving strategies, the study aimed to help dropouts return to schools successfully in order to solve the problems happening in the working field. The study adopted a case study method and a qualitative research method with the interviews, observations and all kinds of documents for data collection. Four dropouts joined the study. The conclusions are as following: First, the drop-out factors included personal, family, school, social and other factors. The personal factors were poor self-adaptation resulting from the lack of self-confidence and a disordered life. The family factors were doting parents, violent parents and complicated family structures arising from the remarriages of dropouts’ parents. The school factors were few interests in academic achievement, poor teacher-student relationship and poor peer relationship. The social factor was the influence of other dropouts. The other factor was missing dropouts. Second, counseling strategies included two stages . At the first stage of the counseling strategies, the researcher framed coping strategies according to family and personal factors that resulted in poor adaptation to campus life, dissatisfaction with campus rules or teachers’ instruction, poor academic achievement and poor peer relationship. At the second stage of the counseling strategies, the researcher timely referred dropouts to juvenile schools, asked the parents to think twice how to reduce the family factors resulting in dropouts, such as changing and applying family structures, tried to find out someone meaningful for dropouts and invited them to urge dropouts back to school. Third, the results of the study are as following. The first stage ended with the result that the strategies were not useful to four dropouts. The second stage got the result that one dropout went to juvenile school, another one successfully returned to school, another one went to school every two days so that he didn’t have to be notified as a dropout, and the other one sometimes returned to school. Finally, the researcher gave some suggestions to teachers, dropouts’ parents and future studies