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

CAI 軟體編輯系統之管理系統研究

[[abstract]]目前我國正積極推展資訊教育，電腦輔助教學是電腦應用在教育上重要的一環，可改 善教育的環境與提高教學的品質，達成此效果的先決條件是需要好的課程軟體，現階 段我國尚未有實用編輯系統似供課程軟體的製作。因此，規畫中文CAI 編輯系統是有 需要的，俾對CAI 的發展有所助益，又現階段的CAI 大都有教學管理的功能，是促進 更有效率的主要因素，基於此，乃引起本研究的主要動機。 本研究之主要目的： 一、探討CAI 課程軟體的特性及表達方式，尋求教學流程安排的方式。 二、規劃教學管理系統架構，以支援編輯系統。 三設計發展以填表式來安排教學流程，具有簡單且容易使用的特性。 本研究之主要研究步驟為（１）擬定研究計劃；（２）相關文獻探討；（３）編輯系 統架構規劃；（４）管理系統架構規劃與設計；（５）歸納結論與建議。 綜合歸納研究過程，得到下列結論： 一、理想的CAI 教學系統，應配合一套多功能的教學管理系統，以增強其效率。 二、以CAI 卡和課程管理表配合的編輯方式，是發展課程軟體的可行方式。 三、以管理表方式所建立的教學流程控制，可節省課程軟體製作的時間。 四可製作不同內容的流向管理表，以適合不同的學習需要。 根據結論，提出下列建議，以供參考： 一、發展多功能的CMI 系統，以增強CAI 的效益。 二、發展智慧型CAI 系統，提升CAI 的境界。 三、運用CMI 的功能，加強CAI 與多媒體的配合應用。

Risk analysis of earth-rock dam breach based on dynamic Bayesian network

Despite the fact that the Bayesian network has great advantages in logical reasoning and calculation compared with the other traditional risk analysis methods, there are still obvious shortcomings in the study of dynamic risk. The risk factors of the earth-rock dam breach are complex, which vary with time during the operation period. Static risk analysis, limited to a specific period of time, cannot meet the needs of comprehensive assessment and early warning. By introducing time factors, a dynamic Bayesian network model was established to study the dynamic characteristics of dam-breach probability. Combined with the calculation of the conditional probability of nodes based on the Leaky Noisy-Or gate extended model, the reasoning results of Bayesian networks were modified by updating the data of different time nodes. Taking an earth-rock dam as an example, the results show that it has less possibility to breach and keep stable along the time axis. Moreover, the factors with vulnerability and instability were found effective, which could provide guidance for dam risk management.Safety and Security Scienc

Calculation of dam risk probability of cascade reservoirs considering risk transmission and superposition

Because of the risk transmission and superposition among dams in cascade reservoirs, the analysis and probability calculation of dam risk become more complex compared with a single reservoir. By analyzing the main risk sources and actionmechanisms, the disaster-causing factors, disaster-transmitting body and disaster-bearing body in the cascade reservoirs system were determined. By defining the influence coefficient (IC) to express the transmission and superposition degree of dam risk among cascade reservoirs, dam risk was divided into two parts: own risk (OR) and additional risk (AR). On this basis, the relevant concepts and equations for the calculation of the dam risk probability of cascade reservoirs were proposed. The numerical simulation was carried out to quantify the IC, and a Bayesian network analysis model was constructed to calculate the OR. Finally, taking five cascade reservoir dams in the Dadu River basin as examples, the value of their ORs, ARs and risk probabilities were calculated, and thereafter the weakest cascade, controlling cascade and general cascade in the system were divided. The proposed methodology realizes an effective connection with the dam risk calculation method of a single reservoir, which can provide a reference for the risk assessment and management of cascade reservoirs in the basin.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.Safety and Security Scienc

Risk consequence assessment of dam breach in cascade reservoirs considering risk transmission and superposition

Compared with a single reservoir, the risk in cascade reservoirs has the transmission and superposition effect, which increases the complexity of its risk consequence assessment. In view of this problem, the direct consequence (DC) and potential consequence (PC) were defined as two parts of the dam breach risk consequence of cascade reservoirs. The upstream dam-break flood inundation line and the downstream reservoir land acquisition line were taken as the upper and lower boundaries of the assessment space, which made the risk consequence assessment more intuitive and further improved its scientificity and practicability. Subsequently, the conditional probability of downstream dam breach under the upstream dam-break flood was determined to quantify the risk transmission and superposition. On this basis, the relevant concepts and formulas for calculating the dam breach risk consequence in cascade reservoirs were proposed. Taking five cascade reservoirs as examples, the risk consequences of each cascade dam breach were evaluated. The results show that the proposed method is effective in assessing the risk consequence of dam breach in cascade reservoirs and is more in line with the connotation of dam risk management, which can provide reference for the design and risk control of cascade reservoirs.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.Safety and Security Scienc

Rank classification method for cascade reservoirs considering scale, benefits, and risk consequences

Cascade reservoirs are essential in water resource utilization, flood control, and disaster mitigation. They have been built in several rivers worldwide. The rank classification for cascade reservoirs has significant practical implications for resource distribution decisions and risk management strategies and is also essential for ensuring the security of the basin. Internationally, reservoirs are typically classified based on project scale and dam failure consequences, whereas the risk transmission and superposition effect renders the classification method of reservoirs not directly applicable to cascade reservoirs. Therefore, to address this issue, this study proposed a rank classification method for cascade reservoirs. First, based on the scale, benefits, and risk consequences of dam failure, an index system for the rank classification of cascade reservoirs was established. Second, by constructing social risk criteria for cascade reservoirs and establishing a link among “project rank-reliability index-annual failure probability,” the allowable dam failure losses for different project ranks were determined. Thereafter, considering risk transmission and superposition, the rank classification standard and index quantification method for cascade reservoirs were proposed. Finally, five cascade reservoirs were selected for a feasibility study. The proposed method provides a supplement to the current rank classification standard of water conservancy projects in China and can also serve as a reference for risk assessment and classification management of cascade reservoirs in other countries.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.Safety and Security Scienc

Risk assessment methods of cascade reservoir dams: a review and reflection

Risk assessment of cascade reservoir dams is not only the key to ensure the safety of the basin, but also the objective requirement of dam risk management. Based on the development status of cascade reservoirs in China, the complexity of dam risk management of cascade reservoirs compared with a single reservoir was analyzed. By reviewing the advances on the studies of dam risk in cascade reservoirs, this paper summarized their limitations in terms of scientificity and practicability. Moreover, some concepts and methods were proposed on the risk assessment of cascade reservoirs: (1) The dam risk of a cascade reservoir was decomposed into own risk and additional risk, the consequence of its dam breach was decomposed into direct loss and potential loss, and an influence coefficient was defined to reflect the risk transmission and superposition degree among cascade reservoirs; (2) The related concepts and formulas for the calculation of dam risk probability and consequence of cascade reservoirs were proposed, which realized the transition of dam risk assessment method from a single reservoir to cascade reservoirs; (3) A project rank classification method for cascade reservoirs was proposed, which took into account not only the project scale and benefits in socioeconomic development, but also the successive dam breaches possibility and consequences. This study is of great significance to clarify the focus of future research and promote the practical application of dam risk management in cascade reservoirs.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.Safety and Security Scienc

Estimating loss of life caused by dam breaches based on the simulation of floods routing and evacuation potential of population at risk

Dam breaches often have catastrophic consequences in downstream areas. Hydrodynamic factors and the evacuation potential of the population at risk (PAR) have significant impacts on the loss of life (LOL) caused by dam breaches. However, the existing comprehensive evaluation models have not conducted in-depth research on the evacuation potential of populations. Thus, limited guidance is available for relevant departments to formulate emergency plans to reduce the potential LOL. Therefore, a new comprehensive evaluation model was proposed in this study. According to the relevant references and disaster theory, the main influencing factors and the process through which the LOL is caused by dam breaches were determined. The specific occurrence process was divided into six stages: a dam breach causes flood, the flood puts the PAR, the PAR complete the preparation work, the PAR evacuate, the un-evacuated population shelter themselves inside buildings, and flood causes the death of the exposed population. To calculate the LOL, the parameters relevant at each stage were defined. Furthermore, the Hydrologic Engineering Center's River Analysis System, Geographic Information System, and related materials were used to simulate the flood routing and evacuation potential of the PAR, quantifying the parameters in the model. The model was applied to 14 towns in the downstream areas of the Luhun Reservoir in Henan Province, China, and its accuracy was verified by comparing the results obtained from the two existing models. In addition, the specific suggestions for reducing the potential LOL were proposed based on the results of the simulation.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.Safety and Security Scienc

A planetary boundary for green water

Green water — terrestrial precipitation, evaporation and soil moisture — is fundamental to Earth system dynamics and is now extensively perturbed by human pressures at continental to planetary scales. However, green water lacks explicit consideration in the existing planetary boundaries framework that demarcates a global safe operating space for humanity. In this Perspective, we propose a green water planetary boundary and estimate its current status. The green water planetary boundary can be represented by the percentage of ice-free land area on which root-zone soil moisture deviates from Holocene variability for any month of the year. Provisional estimates of departures from Holocene-like conditions, alongside evidence of widespread deterioration in Earth system functioning, indicate that the green water planetary boundary is already transgressed. Moving forward, research needs to address and account for the role of root-zone soil moisture for Earth system resilience in view of ecohydrological, hydroclimatic and sociohydrological interactions.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.Water Resource