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Complex adaptive system theory,agent-based modeling,and simulation in dominant technology formation
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作者 ZHANG Ruihan SUN Bing 《Journal of Systems Engineering and Electronics》 SCIE EI CSCD 2024年第1期130-153,共24页
Dominant technology formation is the key for the hightech industry to“cross the chasm”and gain an established foothold in the market(and hence disrupt the regime).Therefore,a stimulus-response model is proposed to i... Dominant technology formation is the key for the hightech industry to“cross the chasm”and gain an established foothold in the market(and hence disrupt the regime).Therefore,a stimulus-response model is proposed to investigate the dominant technology by exploring its formation process and mechanism.Specifically,based on complex adaptive system theory and the basic stimulus-response model,we use a combination of agent-based modeling and system dynamics modeling to capture the interactions between dominant technology and the socio-technical landscape.The results indicate the following:(i)The dynamic interaction is“stimulus-reaction-selection”,which promotes the dominant technology’s formation.(ii)The dominant technology’s formation can be described as a dynamic process in which the adaptation intensity of technology standards increases continuously until it becomes the leading technology under the dual action of internal and external mechanisms.(iii)The dominant technology’s formation in the high-tech industry is influenced by learning ability,the number of adopting users and adaptability.Therein,a“critical scale”of learning ability exists to promote the formation of leading technology:a large number of adopting users can promote the dominant technology’s formation by influencing the adaptive response of technology standards to the socio-technical landscape and the choice of technology standards by the socio-technical landscape.There is a minimum threshold and a maximum threshold for the role of adaptability in the dominant technology’s formation.(iv)The socio-technical landscape can promote the leading technology’s shaping in the high-tech industry,and different elements have different effects.This study promotes research on the formation mechanism of dominant technology in the high-tech industry,presents new perspectives and methods for researchers,and provides essential enlightenment for managers to formulate technology strategies. 展开更多
关键词 complex adaptive system theory agent-based modeling and simulation dominant technology socio-technical landscape adaptation-choice
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APPLICATION STUDY ON ADAPTIVE NEURAL FUZZY INFERENCE MODEL IN COMPLEX SOCIAL-TECHNICAL SYSTEM
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作者 冯绍红 李东 《Transactions of Nanjing University of Aeronautics and Astronautics》 EI 2011年第4期393-399,共7页
The adaptive neural fuzzy inference system (ANFIS) is used to make a ease study considering features of complex social-technical system with the target of increasing organizational efficiency of public scientific re... The adaptive neural fuzzy inference system (ANFIS) is used to make a ease study considering features of complex social-technical system with the target of increasing organizational efficiency of public scientific research institutions. An integrated ANFIS model is built and the effectiveness of the model is verified by means of investigation data and their processing results. The model merges the learning mechanism of neural network and the language inference ability of fuzzy system, and thereby remedies the defects of neural network and fuzzy logic system. Result of this case study shows that the model is suitable for complicated socio-technical systems and has bright application perspective to solve such problems of prediction, evaluation and policy-making in managerial fields. 展开更多
关键词 complex adaptive system adaptive neural fuzzy inference system (ANFIS) complex social-technical system organizational efficiency
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Model for cascading failures with adaptive defense in complex networks 被引量:2
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作者 胡柯 胡涛 唐翌 《Chinese Physics B》 SCIE EI CAS CSCD 2010年第8期65-71,共7页
This paper investigates cascading failures in networks by considering interplay between the flow dynamic and the network topology, where the fluxes exchanged between a pair of nodes can be adaptively adjusted dependin... This paper investigates cascading failures in networks by considering interplay between the flow dynamic and the network topology, where the fluxes exchanged between a pair of nodes can be adaptively adjusted depending on the changes of the shortest path lengths between them. The simulations on both an artificially created scale-free network and the real network structure of the power grid reveal that the adaptive adjustment of the fluxes can drastically enhance the robustness of complex networks against cascading failures. Particularly, there exists an optimal region where the propagation of the cascade is significantly suppressed and the fluxes supported by the network are maximal. With this understanding, a costless strategy of defense for preventing cascade breakdown is proposed. It is shown to be more effective for suppressing the propagation of the cascade than the recent proposed strategy of defense based on the intentional removal of nodes. 展开更多
关键词 cascading failure adaptive defense complex network
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Understanding leukemic hematopoiesis as a complex adaptive system 被引量:1
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作者 Xavier Thomas 《World Journal of Stem Cells》 SCIE CAS 2015年第9期1145-1149,共5页
Normal and abnormal hematopoiesis is working as a complex adaptive system. From this perspective, the development and the behavior of hematopoietic cell lineages appear as a balance between normal and abnormal hematop... Normal and abnormal hematopoiesis is working as a complex adaptive system. From this perspective, the development and the behavior of hematopoietic cell lineages appear as a balance between normal and abnormal hematopoiesis in the setting of a functioning or malfunctioning microenvironment under the control of the immune system and the influence of hereditary and environmental events. 展开更多
关键词 ACUTE LEUKEMIA complex adaptive system STEM CELLS
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Patterns of Interactions of the Complex City System:Emotional Urban Objects as Triggering Agents-A Secondary Publication
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作者 O.A.Gonzalez Liliana Beatriz Sosa Compeán 《Journal of World Architecture》 2024年第1期45-53,共9页
This article presents an analysis of the patterns of interactions resulting from the positive and negative emotional events that occur in cities,considering them as complex systems.It explores,from the imaginaries,how... This article presents an analysis of the patterns of interactions resulting from the positive and negative emotional events that occur in cities,considering them as complex systems.It explores,from the imaginaries,how certain urban objects can act as emotional agents and how these events affect the urban system as a whole.An adaptive complex systems perspective is used to analyze these patterns.The results show patterns in the processes and dynamics that occur in cities based on the objects that affect the emotions of the people who live there.These patterns depend on the characteristics of the emotional charge of urban objects,but they can be generalized in the following process:(1)immediate reaction by some individuals;(2)emotions are generated at the individual level which begins to generalize,permuting to a collective emotion;(3)a process of reflection is detonated in some individuals from the reading of collective emotions;(4)integration/significance in the community both at the individual and collective level,on the concepts,roles and/or functions that give rise to the process in the system.Therefore,it is clear that emotions play a significant role in the development of cities and these aspects should be considered in the design strategies of all kinds of projects for the city.Future extensions of this work could include a deeper analysis of specific emotional events in urban environments,as well as possible implications for urban policy and decision making. 展开更多
关键词 Emotional events Urban objects complex adaptive systems adaptive complex systems City
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A Comment on Language Is a Complex Adaptive System: Position Paper
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作者 单妍 《海外英语》 2014年第8X期244-245,280,共3页
Language not only functions as a communication tool,it has fundamental functions.People’s social interaction and their past experience can affect people’s choice of language,as language is a complex,adaptive system.... Language not only functions as a communication tool,it has fundamental functions.People’s social interaction and their past experience can affect people’s choice of language,as language is a complex,adaptive system.The paper tries to comment on"A comment on Language Is a Complex Adaptive System:Position Paper"from several aspects to conclude that Language Is a Complex Adaptive System:Position Paper is a comprehensive,creative and influential academic paper which is characteristic of high originality,well-compact organization,detailed literature review. 展开更多
关键词 complex adaptive system(CAD) Usage-Based GRAMMAR S
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Theory and model of water resources complex adaptive allocation system
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作者 ZHAO Jianshi,WANG Zhongjing,WENG Wenbin(Institute of Hydrology & Water Resou rces, Tsinghua University, Beijing 100084, China) 《Journal of Geographical Sciences》 SCIE CSCD 2003年第1期112-122,共11页
Complex adaptive sys tem theory is a new and important embranchment of system science, which prov ides a new thought to research water resources allocation system. Based on the a nalysis of complexity and complex adap... Complex adaptive sys tem theory is a new and important embranchment of system science, which prov ides a new thought to research water resources allocation system. Based on the a nalysis of complexity and complex adaptive mechanism of water resources allocat ion system, a fire-new analysis model is presented in this paper. With t he description of dynamical mechanism of system, behavior characters of agents and the evaluation method of system status, an integrity research system is built to analyse the evolvement rule of water resources allocation system. A nd a brief research for the impact of water resources allocation in benefi cial regions of the Water Transfer from South to North China Project is conducted. 展开更多
关键词 water resources allocation complex adaptive system comp lex giant system
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Lyapunov-Based Dynamic Neural Network for Adaptive Control of Complex Systems
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作者 Farouk Zouari Kamel Ben Saad Mohamed Benrejeb 《Journal of Software Engineering and Applications》 2012年第4期225-248,共24页
In this paper, an adaptive neuro-control structure for complex dynamic system is proposed. A recurrent Neural Network is trained-off-line to learn the inverse dynamics of the system from the observation of the input-o... In this paper, an adaptive neuro-control structure for complex dynamic system is proposed. A recurrent Neural Network is trained-off-line to learn the inverse dynamics of the system from the observation of the input-output data. The direct adaptive approach is performed after the training process is achieved. A lyapunov-Base training algorithm is proposed and used to adjust on-line the network weights so that the neural model output follows the desired one. The simulation results obtained verify the effectiveness of the proposed control method. 展开更多
关键词 complex DYNAMICAL systems LYAPUNOV Approach RECURRENT NEURAL Networks adaptive Control
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An exploratory study of the growth of the Accountable Care Organization and its impact on physician groups’ profit: a complex adaptive system approach
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作者 Mei Li S.M.Niaz Arifin +2 位作者 Sarv Devaraj Gregory R.Madey Alfredo Casetti 《Data Science and Management》 2021年第2期28-40,共13页
The emergence of Accountable Care Organizations(ACOs)in the landscape of the U.S.healthcare system marks a paradigm shift in healthcare operations.The potential impact of ACOs has been a topic of intense debate.Tradit... The emergence of Accountable Care Organizations(ACOs)in the landscape of the U.S.healthcare system marks a paradigm shift in healthcare operations.The potential impact of ACOs has been a topic of intense debate.Traditional analytical approaches do not lend themselves to examining the complex phenomenon of the emergence and growth of ACOs in the healthcare network.We adopt a complex adaptive system lens to examine the growth of ACOs among physician groups and explore factors that influence this growth.We also discuss the impact of ACOs on the profit of physician groups.An agent-based model was built to simulate physician groups'ACO entrance and exit based on a set of simple rules and their complex interactions with other agents.Based on the simulation results,we derive patterns of ACO expansion and contraction,following four stages of wait-and-see,rollercoaster,fast growth,and stabilizing.Findings suggest that the growth of ACOs is sensitive to the initial state of ACO membership.When the initial size of ACO membership increases,it helps to eliminate the rollercoaster stage.In addition,the growth of the ACO varies depending on the cost–quality tradeoff.When both cost and quality objectives can be met simultaneously,the growth of ACO membership follows wait-and-see and fast growth stages followed by a different stage that we term sticky state.The impact of ACOs on physician groups’cumulative profit varies by the service quality level of the physician group.Physician groups affiliated with insurance companies charging the lowest or the highest level of health insurance premiums are worse off with the ACO option.However,the ACO benefits physician groups affiliated with an insurance company charging a moderate level of premiums. 展开更多
关键词 Accountable Care Organization(ACO) ACO expansion and contraction Physician groups'profit complex adaptive system(cas)
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Linguistic Reflection on the Online Catchword of Appreciation —From the Perspective of Usage-based Language Model and Complex Adaptive System Theory
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作者 HE Xiang 《北京第二外国语学院学报》 2016年第5期139-139,共1页
Language is a special social phenomenon and is always on the changing process with the development of society. During the evolving process of language, new language varieties will continuously emerge due to the change... Language is a special social phenomenon and is always on the changing process with the development of society. During the evolving process of language, new language varieties will continuously emerge due to the changes of some social and cultural factors. Cyber language is universally accepted as one type of the social language varieties. Basically, cyber language can be treated as a complex adaptive system which is influenced by the interaction between users’ cognition, social culture and the surrounding environments. Thus it is safe to say that cyber language is always undergoing a dynamic evolving process. With the usage-based language model as the theoretical foundation, this paper proposes a Complex Adaptive System (CAS) approach to analyze the expression of Appreciation to explore the complex, dynamic and nonlinear development of cyber language from the angle of meaning construction, grammaticalization and functional adaption respectively. It is found that the expression of Appreciation is experiencing adaptively a semantic connotations development and a process of grammatical functions expansion as well. This paper suggests that the emergence and development of cyber language is a novel and trendy social language phenomenon. Network language can achieve its process and evolution under the huge impact of social changes and social promotions. When faced with the changing surroundings, cyber language itself enjoys a timely adaption and responsive development to keep up with the new environments, which reflects the basic principle of language development, namely, language changes with the development of society. 展开更多
关键词 Usage-based LANGUAGE Model complex adaptive system Theory the expression of APPRECIATION cyber LANGUAGE LANGUAGE var
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CAS理论视角下我国智慧社区公共体育服务多元治理 被引量:1
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作者 王祥全 涂娟 《上海体育大学学报》 CSSCI 北大核心 2024年第7期66-75,85,共11页
采用文献资料、案例分析等研究方法,结合嘉兴市“运动家”智慧体育社区治理实践,从复杂适应系统(CAS)理论视角分析智慧社区公共体育服务治理系统的结构、特征和运行机制。认为:智慧社区公共体育服务治理结构由服务供需主体、政策制度系... 采用文献资料、案例分析等研究方法,结合嘉兴市“运动家”智慧体育社区治理实践,从复杂适应系统(CAS)理论视角分析智慧社区公共体育服务治理系统的结构、特征和运行机制。认为:智慧社区公共体育服务治理结构由服务供需主体、政策制度系统、社区环境系统和社会环境系统等多元系统构成,具有聚集、多样性、“流”以及非线性特征,其运行机制包含以“刺激—反应”模型运行的内部自适应机制和以“回声”模型运行的外部交互机制。在此基础上,提出创新“积木块”组合方式、优化制度设计,拓宽资源“流”渠道、整合治理资源,建立创新引领新“标识”、聚合主体共识,重视主体间的“非线性”关系、营造协同治理环境等优化策略。 展开更多
关键词 智慧社区 公共体育服务 多元治理 复杂适应系统(cas)理论
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Decentralized Adaptive Strategies for Synchronization of Fractional-order Complex Networks 被引量:3
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作者 Quan Xu Shengxian Zhuang +1 位作者 Yingfeng Zeng Jian Xiao 《IEEE/CAA Journal of Automatica Sinica》 SCIE EI CSCD 2017年第3期543-550,共8页
This paper focuses on synchronization of fractionalorder complex dynamical networks with decentralized adaptive coupling.Based on local information among neighboring nodes,two fractional-order decentralized adaptive s... This paper focuses on synchronization of fractionalorder complex dynamical networks with decentralized adaptive coupling.Based on local information among neighboring nodes,two fractional-order decentralized adaptive strategies are designed to tune all or only a small fraction of the coupling gains respectively.By constructing quadratic Lyapunov functions and utilizing fractional inequality techniques,Mittag-Leffler function,and Laplace transform,two sufficient conditions are derived for reaching network synchronization by using the proposed adaptive laws.Finally,two numerical examples are given to verify the theoretical results. 展开更多
关键词 Decentralized adaptive control fractional-order complex networks quadratic Lyapunov functions SYNCHRONIZATION
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Adaptive generalized matrix projective lag synchronization between two different complex networks with non-identical nodes and different dimensions 被引量:3
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作者 戴浩 贾立新 张彦斌 《Chinese Physics B》 SCIE EI CAS CSCD 2012年第12期141-152,共12页
The adaptive generalized matrix projective lag synchronization between two different complex networks with non-identical nodes and different dimensions is investigated in this paper. Based on Lyapunov stability theory... The adaptive generalized matrix projective lag synchronization between two different complex networks with non-identical nodes and different dimensions is investigated in this paper. Based on Lyapunov stability theory and Barbalat's lemma, generalized matrix projective lag synchronization criteria are derived by using the adaptive control method. Furthermore, each network can be undirected or directed, connected or disconnected, and nodes in either network may have identical or different dynamics. The proposed strategy is applicable to almost all kinds of complex networks. In addition, numerical simulation results are presented to illustrate the effectiveness of this method, showing that the synchronization speed is sensitively influenced by the adaptive law strength, the network size, and the network topological structure. 展开更多
关键词 complex networks generalized matrix projective lag synchronization adaptive control Lyapunov stability theory
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Robust adaptive synchronization of uncertain and delayed dynamical complex networks with faulty network 被引量:1
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作者 金小峥 杨光红 《Chinese Physics B》 SCIE EI CAS CSCD 2010年第8期184-190,共7页
This paper presents a new robust adaptive synchronization method for a class of uncertain dynamical complex networks with network failures and coupling time-varying delays. Adaptive schemes are proposed to adjust cont... This paper presents a new robust adaptive synchronization method for a class of uncertain dynamical complex networks with network failures and coupling time-varying delays. Adaptive schemes are proposed to adjust controller parameters for the faulty network compensations, as well as to estimate the upper and lower bounds of delayed state errors and perturbations to compensate the effects of delay and perturbation on-line without assuming symmetry or irreducibility of networks. It is shown that, through Lyapunov stability theory, distributed adaptive controllers con- structed by the adaptive schemes are successful in ensuring the achievement of asymptotic synchronization of networks in the present of faulty and delayed networks, and perturbation inputs. A Chua's circuit network example is finally given to show the effectiveness of the proposed synchronization criteria. 展开更多
关键词 dynamical complex networks SYNCHRONIZATION robust adaptive control faulty network time-varying delays
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Adaptive function projective synchronization of uncertain complex dynamical networks with disturbance 被引量:1
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作者 王树国 郑松 《Chinese Physics B》 SCIE EI CAS CSCD 2013年第7期84-88,共5页
We investigate the problem of function projective synchronization (FPS) in drive–response dynamical networks with non-identical nodes. An adaptive controller is proposed for the FPS of complex dynamical networks wi... We investigate the problem of function projective synchronization (FPS) in drive–response dynamical networks with non-identical nodes. An adaptive controller is proposed for the FPS of complex dynamical networks with uncertain parameters and disturbance. Not only are the unknown parameters of the networks estimated by the adaptive laws obtained from the Lyapunov stability theory and Taylor expansions, but the unknown bounded disturbances are also simultaneously conquered by the proposed control. Finally, a numerical simulation is provided to illustrate the feasibility and effectiveness of the obtained result. 展开更多
关键词 complex networks function projective synchronization disturbance adaptive control
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A Novel Evolutionary-Fuzzy Control Algorithm for Complex Systems 被引量:1
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作者 王攀 徐承志 +1 位作者 冯珊 徐爱华 《Journal of Systems Engineering and Electronics》 SCIE EI CSCD 2002年第3期52-60,共9页
This paper presents an adaptive fuzzy control scheme based on modified genetic algorithm. In the control scheme, genetic algorithm is used to optimze the nonlinear quantization functions of the controller and some key... This paper presents an adaptive fuzzy control scheme based on modified genetic algorithm. In the control scheme, genetic algorithm is used to optimze the nonlinear quantization functions of the controller and some key parameters of the adaptive control algorithm. Simulation results show that this control scheme has satisfactory performance in MIMO systems, chaotic systems and delay systems. 展开更多
关键词 Modified genetic algorithm Nonlinear quantization factor adaptive fuzzy controller ITAE index complex systems.
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Complex Systems Theory: Some Considerations for Sociology 被引量:1
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作者 Rosalia Condorelli 《Open Journal of Applied Sciences》 2016年第7期422-448,共28页
This essay presents a reflection on the main implications of Complexity Theory for science in general, redefining and dispelling myths of traditional science, and Sociology in particular, suggesting a redefinition of ... This essay presents a reflection on the main implications of Complexity Theory for science in general, redefining and dispelling myths of traditional science, and Sociology in particular, suggesting a redefinition of Parsons’ classic concept of Social System, articulated around the property of self-maintenance of order rather than on its possible discontinuity and instability. It argues that Complexity Theory has established the limits of Classic Science, leading to a more realistic awareness of working and evolution mechanisms of Natural and Social Systems and showing the limits of our capacity to predict and control events. Dissipative structures have shown the creative role of time. Instability, emergence, surprise, unpredictability are the rule rather than the exception when systems move away from equilibrium (entropy), even if these processes are generated from a system’s deterministic working mechanisms. Therefore, we have come to realize how constructive the contribution of Complexity is, in regards to the long lasting problem of the relationship between order and disorder. Today, the terms of this relationship have been re-specified in its new configuration of inter-relationship link, according to a unicum which finds its synthesis in self-organization and deterministic chaos concepts. From this perspective, as Prigogine suggested, studies on Complex Systems are heading toward a historical, biological conception of Physics, and a new alliance between natural systems and living, social systems. Non-linearity, far from equilibrium self-organization, emergence and surprise meet at all levels, as this paper attempts to highlight. In Sociology, insights of Complexity Theory have contributed to a new way of thinking about social systems, by re-addressing some fundamental issues starting to social system, emergence and change concepts. The current social system conception as complex dynamical systems is supported by a profitable use of non-liner models (in particular, the Logistic map) in the study of social processes. 展开更多
关键词 complexity Theory complex adaptive and Autopoietic systems SELF-ORGANIZATION EMERGENCE SURPRISE complex Social systems complexity Theory in Sociology
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CA Investment Casting Process of Complex Castings
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作者 WU Jian-tao, FENG Di, XIE Yun-peng, LI Jun-tao, KONG Sheng-guo (Superalloy Institute of Central Iron & Steel Institute, Beijing 100081, China) 《厦门大学学报(自然科学版)》 CAS CSCD 北大核心 2002年第S1期17-18,共2页
CA (Computer aided) investment casting technique used in superalloy castings of aerospace engine parts was presented. CA investment casting integrated computer application, RP (Rapid Prototyping) process, solidificati... CA (Computer aided) investment casting technique used in superalloy castings of aerospace engine parts was presented. CA investment casting integrated computer application, RP (Rapid Prototyping) process, solidification simulation and investment casting process. It broke the bottle neck of making metal die. Solid model of complex parts were produced by UGII or other software, then translated into STL(Stereolithography) file, after RP process of SLS(Selective Laser Sintering), wax pattern used in investment casting can be acquired without metal die in short time. These can reduce period and cost greatly of complex superalloy parts development of engine. The key processes of CA investment casting were discussed. The accuracy of model translation should match that of RP system. Choice of RP material, surface polishing, sintering parameter plays important role in RP process. Other processes, like solidification simulating and optimization of gate system were introduced. The conclusion was that complex parts can be produced by CA investment casting with lots of advantages. The accuracy of castings can reach CT5~7,and the smoothness can get Ra3~13 mm. These parts of engines worked well. 展开更多
关键词 CA investment casting RP solidification simulation complex parts of engine
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Recent Progress in Reinforcement Learning and Adaptive Dynamic Programming for Advanced Control Applications 被引量:4
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作者 Ding Wang Ning Gao +2 位作者 Derong Liu Jinna Li Frank L.Lewis 《IEEE/CAA Journal of Automatica Sinica》 SCIE EI CSCD 2024年第1期18-36,共19页
Reinforcement learning(RL) has roots in dynamic programming and it is called adaptive/approximate dynamic programming(ADP) within the control community. This paper reviews recent developments in ADP along with RL and ... Reinforcement learning(RL) has roots in dynamic programming and it is called adaptive/approximate dynamic programming(ADP) within the control community. This paper reviews recent developments in ADP along with RL and its applications to various advanced control fields. First, the background of the development of ADP is described, emphasizing the significance of regulation and tracking control problems. Some effective offline and online algorithms for ADP/adaptive critic control are displayed, where the main results towards discrete-time systems and continuous-time systems are surveyed, respectively.Then, the research progress on adaptive critic control based on the event-triggered framework and under uncertain environment is discussed, respectively, where event-based design, robust stabilization, and game design are reviewed. Moreover, the extensions of ADP for addressing control problems under complex environment attract enormous attention. The ADP architecture is revisited under the perspective of data-driven and RL frameworks,showing how they promote ADP formulation significantly.Finally, several typical control applications with respect to RL and ADP are summarized, particularly in the fields of wastewater treatment processes and power systems, followed by some general prospects for future research. Overall, the comprehensive survey on ADP and RL for advanced control applications has d emonstrated its remarkable potential within the artificial intelligence era. In addition, it also plays a vital role in promoting environmental protection and industrial intelligence. 展开更多
关键词 adaptive dynamic programming(ADP) advanced control complex environment data-driven control event-triggered design intelligent control neural networks nonlinear systems optimal control reinforcement learning(RL)
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基于小型化Cas蛋白的CRISPR/Gal4BD-Cas供体适配基因编辑系统研究
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作者 杨森 马宝霞 +7 位作者 钱泓润 崔婕妤 张潇筠 李利达 魏泽辉 张智英 王建刚 徐坤 《遗传》 CAS CSCD 北大核心 2024年第9期716-726,共11页
在哺乳动物细胞中,利用同源引导修复(homology-directed repair,HDR)机制的基因编辑策略能够实现精准的点编辑和敲入,但是HDR的低效性严重制约了该策略在精准医疗和分子设计育种中的应用。鉴于HDR机制所需的供体DNA模板不能自主募集到... 在哺乳动物细胞中,利用同源引导修复(homology-directed repair,HDR)机制的基因编辑策略能够实现精准的点编辑和敲入,但是HDR的低效性严重制约了该策略在精准医疗和分子设计育种中的应用。鉴于HDR机制所需的供体DNA模板不能自主募集到基因组双链断裂(double-stranded break,DSB)处,本课题组提出了供体适配系统(donor adapting system,DAS)的概念并开发出CRISPR/SpCas9-Gal4BD供体适配基因编辑系统。由于SpCas9蛋白分子较大,与Gal4BD适配器结合不利于表达、病毒载体包装及活体递送等过程,因此本研究进一步采用两种小型化Cas蛋白——路邓葡萄球菌(Staphylococcus lugdunensis)源SlugCas9变体SlugCas9-HF与氨基酸球菌(Acidaminococcus sp.)源AsCas12a,开发了新型的CRISPR/Gal4BD-SlugCas9和CRISPR/Gal4BD-AsCas12a供体适配基因编辑系统。通过SSA活性报告实验初步证明了Gal4BD与SlugCas9、AsCas12a N-端融合对其打靶活性影响较小。通过HDR效率报告实验进行功能验证并优化供体设计方案,结果表明:对于CRISPR/Gal4BD-AsCas12a DAS,适配器结合序列(binding sequence,BS)与供体5′-端融合(BS-dsDNA)效果较好;对于CRISPR/Gal4BD-SlugCas9 DAS,则BS与供体3′-端融合(dsDNA-BS)较佳。最终,利用CRISPR/Gal4BD-SlugCas9 DAS对HEK293T细胞中的EMX1、NUDT5、AAVS1三个基因位点分别实现了24%、37%、31%的精准编辑,相比对照组得到了显著提高。本研究为供体适配基因编辑系统的进一步优化提供了参考和借鉴,为后续动物分子设计育种应用研究提供了新的基因编辑工具。 展开更多
关键词 基因编辑 同源引导修复 供体适配 小型化cas蛋白 适配器
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