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外泌体递送CRISPR/Cas系统在靶细胞内可实现基因编辑
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作者 王白燕 杨树 +5 位作者 王弋鸣 吴梦晴 肖瑀 郭梓璇 张博艺 冯书营 《中国组织工程研究》 北大核心 2026年第7期1839-1849,共11页
背景:CRISPR/Cas基因编辑系统具有精准基因编辑、靶向设计简单、低成本以及高效率等特性,已被广泛应用于科学研究和相关临床治疗。然而,CRISPR/Cas系统如何更安全、更高效、更精准地递送到靶细胞内,仍是一个急需解决的难题。目的:从递送... 背景:CRISPR/Cas基因编辑系统具有精准基因编辑、靶向设计简单、低成本以及高效率等特性,已被广泛应用于科学研究和相关临床治疗。然而,CRISPR/Cas系统如何更安全、更高效、更精准地递送到靶细胞内,仍是一个急需解决的难题。目的:从递送CRISPR/Cas系统的外泌体来源及工程化策略、外泌体对CRISPR/Cas系统的装载方法、CRISPR/Cas系统的生物形式及其在细胞内的作用途径等方面进行全方面综述,为该领域的研究者提供更直观、更系统的视角。方法:以“exosome,drug delivery systems,delivery,CRISPR/Cas,gene editing,engineered exosomes,targeting”为英文检索词,以“外泌体,药物递送,CRISPR/Cas,工程化”为中文检索词,分别检索Pub Med数据库及中国知网,检索时限为2014-2024年。通过仔细阅读文献的标题和摘要进行初步筛选,排除研究内容相关性差及内容重复的文献,最终纳入了78篇文献进行归纳和探讨。结果与结论:(1)外泌体是一种直径30-150 nm的脂质囊泡,具有循环半衰期长、靶向组织的内在能力、良好的生物相容性以及较小的固有毒性等优势,显现出强大的靶向递送能力;(2)CRISPR/Cas系统虽是一种强大的基因编辑工具,然而现有的CRISPR/Cas系统递送载体各有利弊,无法完全满足需求;(3)递送CRISPR/Cas系统的外泌体主要来源于高产外泌体的细胞或组织,但研究者们依然需要根据研究所需进行选择或进一步工程化;(4)递送CRISPR/Cas系统的外泌体主要通过基因工程修饰、化学修饰、外泌体-脂质体杂交等策略实现工程化;(5)外泌体装载CRISPR/Cas系统的方法包括电穿孔、孵育、转染和主动装载途径等,选择合适的装载方法取决于CRISPR/Cas系统的理化性质;(6)外泌体递送CRISPR/Cas系统的生物形式包括质粒和核糖核蛋白复合体,两种形式各具特点,成功递送的CRISPR/Cas系统在靶细胞内实现基因编辑。 展开更多
关键词 外泌体 CRISPR/cas系统 基因编辑 药物负载 靶向递送 工程化
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Improving Performance of Computer Algebra Systems
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作者 Kostas Zotos Irena Atanassova 《Journal of Software Engineering and Applications》 2023年第10期521-529,共9页
Computer Algebra Systems have been extensively used in higher education. The reasons are many e.g., visualize mathematical problems, correlate real-world problems on a conceptual level, are flexible, simple to use, ac... Computer Algebra Systems have been extensively used in higher education. The reasons are many e.g., visualize mathematical problems, correlate real-world problems on a conceptual level, are flexible, simple to use, accessible from anywhere, etc. However, there is still room for improvement. Computer algebra system (CAS) optimization is the set of best practices and techniques to keep the CAS running optimally. Best practices are related to how to carry out a mathematical task or configure your system. In this paper, we are going to examine these techniques. The documentation sheets of CASs are the source of data that we used to compare them and examine their characteristics. The research results reveal that there are many tips that we can follow to accelerate performance. 展开更多
关键词 Mathematical Software computer algebra systems cas Improving Performance cas Performance cas Optimization MATLAB MAPLE MATHEMATICA
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基于CRISPR-Cas系统的多重耐药菌防治技术研究进展 被引量:1
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作者 周倩 唐梦君 +4 位作者 张小燕 陆俊贤 唐修君 杨星星 高玉时 《生物技术通报》 北大核心 2025年第5期42-51,共10页
动物源细菌耐药性影响动物养殖安全,同时对人类公共卫生和食品安全产生重要威胁。抗生素的滥用加剧了耐药细菌的传播,而新型抗菌药物研发日益困难,动物源细菌耐药污染已成为全球范围内的公共危机,一旦耐药菌从动物向人类扩散,将极大地... 动物源细菌耐药性影响动物养殖安全,同时对人类公共卫生和食品安全产生重要威胁。抗生素的滥用加剧了耐药细菌的传播,而新型抗菌药物研发日益困难,动物源细菌耐药污染已成为全球范围内的公共危机,一旦耐药菌从动物向人类扩散,将极大地威胁人类健康,亟须新的方法和策略应对细菌耐药。CRISPR-Cas(clustered regularly interspaced short palindromic repeats,CRISPR-associated)是第三代“基因组定点编辑技术”,该技术能够靶向剪切外源性核酸,保护微生物遗传物质遗传稳定性。与传统的多重耐药菌防治策略相比,CRISPR-Cas系统具备独特的DNA序列的靶向性和灵敏度,通过精准、简便和高效的基因编辑技术,与核酸扩增技术、比色技术等相结合,可以提高灵敏度和检测时效性等性能指标。本文介绍了CRISPR-Cas系统的由来、系统分类、基因编辑的作用机理,在此基础之上,聚焦于该系统在多重耐药菌防治领域的研究进展和应用,在耐药致病菌消除、耐药基因消除以及致病菌诊断检测方面给出案例分析以及目前存在的挑战。总的来说,基于CRISPR-Cas系统的序列特异性抗菌剂能够降低细菌多重耐药性,结合核酸扩增技术和实时监控设备提升检测的精准性和效率,为动物源细菌耐药防控和监测研究提供了新思路。 展开更多
关键词 CRISPR-cas系统 基因编辑 多重耐药菌 耐药基因 防治技术
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基于CAS理论的公立医院财会监督体系运行机制模型探索
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作者 陈隽 向炎珍 +1 位作者 曹卉 胡金艳 《中国卫生经济》 北大核心 2025年第4期99-103,共5页
公立医院财会监督是1项复杂的系统性工程,目前缺乏全面、系统的指导,需要通过实践完善相关理论体系。文章在运用复杂适应系统(Complex Adaptive System,CAS)理论框架对公立医院财会监督体系进行分析的基础上,构建了CAS理论的公立医院财... 公立医院财会监督是1项复杂的系统性工程,目前缺乏全面、系统的指导,需要通过实践完善相关理论体系。文章在运用复杂适应系统(Complex Adaptive System,CAS)理论框架对公立医院财会监督体系进行分析的基础上,构建了CAS理论的公立医院财会监督体系运行机制模型。公立医院财会监督符合CAS理论的聚集性、非线性、要素流和多样性的特征,通过构建公立医院财会监督CAS模型,对于推动复杂治理环境下的公立医院财会监督体系建设具备可行性与推广性。 展开更多
关键词 公立医院 财会监督体系 复杂适应系统理论
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CONVERGENCE ANALYSIS OF RUNGE-KUTTA METHODS FOR A CLASS OF RETARDED DIFFERENTIAL ALGEBRAIC SYSTEMS 被引量:4
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作者 肖飞雁 张诚坚 《Acta Mathematica Scientia》 SCIE CSCD 2010年第1期65-74,共10页
This article deals with a class of numerical methods for retarded differential algebraic systems with time-variable delay. The methods can be viewed as a combination of Runge-Kutta methods and Lagrange interpolation. ... This article deals with a class of numerical methods for retarded differential algebraic systems with time-variable delay. The methods can be viewed as a combination of Runge-Kutta methods and Lagrange interpolation. A new convergence concept, called DA-convergence, is introduced. The DA-convergence result for the methods is derived. At the end, a numerical example is given to verify the computational effectiveness and the theoretical result. 展开更多
关键词 CONVERGENCE Runge-Kutta Methods Lagrange interpolation retarded dif-ferential algebraic systems
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2-D algebraic test for robust stability of time-delay systems with interval parameters 被引量:4
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作者 Xiao Yang 《Journal of Systems Engineering and Electronics》 SCIE EI CSCD 2006年第4期802-810,共9页
The robust stability test of time-delay systems with interval parameters can be concluded into the robust stability of the interval quasipolynomials. It has been revealed that the robust stability of the quasipolynomi... The robust stability test of time-delay systems with interval parameters can be concluded into the robust stability of the interval quasipolynomials. It has been revealed that the robust stability of the quasipolynomials depends on that of their edge polynomials. This paper transforms the interval quasipolynomials into two-dimensional (2-D) interval polynomials (2-D s-z hybrid polynomials), proves that the robust stability of interval 2-D polynomials are sufficient for the stability of given quasipolynomials. Thus, the stability test of interval quasipolynomials can be completed in 2-D s-z domain instead of classical 1-D s domain. The 2-D s-z hybrid polynomials should have different forms under the time delay properties of given quasipolynomials. The stability test proposed by the paper constructs an edge test set from Kharitonov vertex polynomials to reduce the number of testing edge polynomials. The 2-D algebraic tests are provided for the stability test of vertex 2-D polynomials and edge 2-D polynomials family. To verify the results of the paper to be correct and valid, the simulations based on proposed results and comparison with other presented results are given. 展开更多
关键词 automatic control theory time-delay systems robust stability 2-D algebraic test.
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An Algebraic Detection Approach for Control Systems under Multiple Stochastic Cyber-attacks 被引量:3
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作者 Yumei Li Holger Voos +1 位作者 Mohamed Darouach Changchun Hua 《IEEE/CAA Journal of Automatica Sinica》 SCIE EI 2015年第3期258-266,共9页
In order to compromise a target control system successfully, hackers possibly attempt to launch multiple cyberattacks aiming at multiple communication channels of the control system. However, the problem of detecting ... In order to compromise a target control system successfully, hackers possibly attempt to launch multiple cyberattacks aiming at multiple communication channels of the control system. However, the problem of detecting multiple cyber-attacks has been hardly investigated so far. Therefore, this paper deals with the detection of multiple stochastic cyber-attacks aiming at multiple communication channels of a control system. Our goal is to design a detector for the control system under multiple cyberattacks. Based on frequency-domain transformation technique and auxiliary detection tools, an algebraic detection approach is proposed. By applying the presented approach, residual information caused by different attacks is obtained respectively and anomalies in the control system are detected. Sufficient and necessary conditions guaranteeing the detectability of the multiple stochastic cyber-attacks are obtained. The presented detection approach is simple and straightforward. Finally, two simulation examples are provided, and the simulation results show that the detection approach is effective and feasible. © 2014 Chinese Association of Automation. 展开更多
关键词 algebra Communication channels (information theory) Control systems CRIME Frequency domain analysis Personal computing Stochastic systems
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The Relation between the Stabilization Problem for Discrete Event Systems Modeled with Timed Petri Nets via Lyapunov Methods and Max-Plus Algebra 被引量:2
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作者 Zvi Retchkiman Konigsberg 《Journal of Applied Mathematics and Physics》 2015年第7期839-845,共7页
A discrete event system is a dynamical system whose state evolves in time by the occurrence of events at possibly irregular time intervals. Timed Petri nets are a graphical and mathematical modeling tool applicable to... A discrete event system is a dynamical system whose state evolves in time by the occurrence of events at possibly irregular time intervals. Timed Petri nets are a graphical and mathematical modeling tool applicable to discrete event systems in order to represent its states evolution where the timing at which the state changes is taken into consideration. One of the most important performance issues to be considered in a discrete event system is its stability. Lyapunov theory provides the required tools needed to aboard the stability and stabilization problems for discrete event systems modeled with timed Petri nets whose mathematical model is given in terms of difference equations. By proving stability one guarantees a bound on the discrete event systems state dynamics. When the system is unstable, a sufficient condition to stabilize the system is given. It is shown that it is possible to restrict the discrete event systems state space in such a way that boundedness is achieved. However, the restriction is not numerically precisely known. This inconvenience is overcome by considering a specific recurrence equation, in the max-plus algebra, which is assigned to the timed Petri net graphical model. 展开更多
关键词 Discrete Event systems LYAPUNOV Methods Max-Plus algebra TIMED PETRI NETS
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On the Order of the Solutions of Systems of Complex Algebraic Differential Equations 被引量:1
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作者 SU Xian-feng GAO Ling-yun 《Chinese Quarterly Journal of Mathematics》 CSCD 2011年第2期196-199,共4页
This paper is concerned with the order of the solutions of systems of high-order complex algebraic differential equations.By means of Zalcman Lemma,the systems of equations of[1]is extended to more general form.
关键词 normal family order systems of complex algebraic differential equations
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Algebraic structure and Poisson's theory of mechanico-electrical systems 被引量:3
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作者 刘鸿基 唐贻发 傅景礼 《Chinese Physics B》 SCIE EI CAS CSCD 2006年第8期1653-1661,共9页
The algebraic structure and Poisson's integral theory of mechanico-electrical systems are studied. The Hamilton canonical equations and generalized Hamilton canonical equations and their the contravariant algebraic f... The algebraic structure and Poisson's integral theory of mechanico-electrical systems are studied. The Hamilton canonical equations and generalized Hamilton canonical equations and their the contravariant algebraic forms for mechanico-electrical systems are obtained. The Lie algebraic structure and the Poisson's integral theory of Lagrange mechanico-electrical systems are derived. The Lie algebraic structure admitted and Poisson's integral theory of the Lagrange-Maxwell mechanico-electrical systems are presented. Two examples are presented to illustrate these results. 展开更多
关键词 algebraic structure Poisson integral method mechanico-electrical system
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CAS协同理论框架下产教融合共同体的复杂度分析与构建策略
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作者 韩莉莉 安建业 +1 位作者 王文佳 胡梦涵 《北京城市学院学报》 2025年第4期33-39,共7页
产教融合共同体在国家职业教育革新与人才强国战略中扮演着至关重要的角色。文章依托复杂适应系统(CAS)理论,深入剖析了产教融合共同体的复杂性,如参与主体的多样性与非线性交织、利益链条的复杂性与差异化并存、合作模式的多元化发展... 产教融合共同体在国家职业教育革新与人才强国战略中扮演着至关重要的角色。文章依托复杂适应系统(CAS)理论,深入剖析了产教融合共同体的复杂性,如参与主体的多样性与非线性交织、利益链条的复杂性与差异化并存、合作模式的多元化发展与挑战共生,发展环境的开放性与不确定性同在等难题。在此基础上,结合融合协同理论,文章提出了构建产教融合共同体的三大策略。 展开更多
关键词 cas协同理论 产教融合共同体 时代境遇 复杂度分析 构建策略
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CRISPR-Cas系统的小型化研究进展 被引量:1
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作者 董颖 马孟丹 黄卫人 《合成生物学》 北大核心 2025年第1期105-117,共13页
CRISPR-Cas基因编辑技术由于其简便性和高效性,已被广泛应用于生物学、医学、农学等领域的基础与应用研究。目前广泛使用的Cas核酸酶均具有较大的分子量(通常大于1000个氨基酸),而广泛应用于基因治疗中的腺相关病毒(AAV)载体的承载容量... CRISPR-Cas基因编辑技术由于其简便性和高效性,已被广泛应用于生物学、医学、农学等领域的基础与应用研究。目前广泛使用的Cas核酸酶均具有较大的分子量(通常大于1000个氨基酸),而广泛应用于基因治疗中的腺相关病毒(AAV)载体的承载容量却十分有限,在容纳CRISPR核酸酶与gRNA的编码序列之余往往难以承载更多其他功能元件,如碱基编辑、转录调控、多基因编辑等相应元件,这严重限制了其在基因治疗等领域的应用。使用紧凑型Cas蛋白变体的CRISPR-Cas系统可能有助于用AAV产生和传递基因组编辑和调节工具到人类细胞。因此,小型化的CRISPR-Cas系统开发是解决这一技术难题的重要途径,本文主要概括了基于Cas9、Cas12和Cas13蛋白系统在小型化方面的研究进展,包括筛选新型Cas蛋白、缩减蛋白结构域以及引导RNA的改造等,旨在为开发微型精准基因编辑和调控工具提供新思路。目前小型化的CRISPR-Cas系统的局限性主要体现在蛋白分子量的大小和基因编辑的效率、特异性不可兼得上,在未来的研究中若能解决这一问题,获得更小型化的结构域,相信不仅能够优化该系统在体内的传递,更有望为临床带来高效率且低损害的治疗方法。 展开更多
关键词 CRISPR-cas系统 小型化cas蛋白 cas蛋白工程化改造 紧凑型cas蛋白 基因调控工具
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Meshing analysis of toroidal drive by computer algebra system 被引量:1
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作者 张春丽 徐晓俊 《Journal of Harbin Institute of Technology(New Series)》 EI CAS 2000年第1期82-85,共4页
Presents the meshing analysis based on the Computer Algebra System to make it easier to deduce complex formulas while the expression of more complicated surface equations are visualized, by which, the contact line, me... Presents the meshing analysis based on the Computer Algebra System to make it easier to deduce complex formulas while the expression of more complicated surface equations are visualized, by which, the contact line, meshing bordlines and undercut bordlines of toroidal drive are deduced, and the results obtained are consistent with the results discussed in literature [1] , and concludes that the absolute value of the induced normal curvature is usually smaller (less than 0.12, for example), and it increases as parameters φ 2, V and R increase, decreases as parameter r increases, and hardly varies with W 2, and the variation with a, i 21  is not definite. 展开更多
关键词 MESHING THEORY TOROIDAL DRIVE computer algebra System.
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Lie symmetry algebra of one-dimensional nonconservative dynamical systems 被引量:1
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作者 刘翠梅 吴润衡 傅景礼 《Chinese Physics B》 SCIE EI CAS CSCD 2007年第9期2665-2670,共6页
Lie symmetry algebra of linear nonconservative dynamical systems is studied in this paper. By using 1-1 mapping, the Lie point and Lie contact symmetry algebras are obtained from two independent solutions of the one-d... Lie symmetry algebra of linear nonconservative dynamical systems is studied in this paper. By using 1-1 mapping, the Lie point and Lie contact symmetry algebras are obtained from two independent solutions of the one-dimensional linear equations of motion. 展开更多
关键词 Lie algebra symmetry infinitesimal transformation nonconserved dynamical system
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ALGEBRAIC STRUCTURES AND POISSON INTEGRALS OF RELATIVISTIC DYNAMICAL EQUATIONS FOR ROTATIONALSYSTEMS
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作者 傅景礼 陈向炜 罗绍凯 《Applied Mathematics and Mechanics(English Edition)》 SCIE EI 1999年第11期1266-1274,共9页
The algebraic structures of the dynamical equations for the rotational relativistic systems are studied. It is found that the dynamical equations of holonomic conservative rotational relativistic systems and the speci... The algebraic structures of the dynamical equations for the rotational relativistic systems are studied. It is found that the dynamical equations of holonomic conservative rotational relativistic systems and the special nonholonomic rotational relativistic systems have Lie's algebraic structure, and the dynamical equations of the general holonomic rotational relativistic systems and the general nonholonomic rotational relativistic systems have Lie admitted algebraic structure. At last the Poisson integrals of the dynamical equations for the rotational relativistic systems are given. 展开更多
关键词 rotational systems RELATIVITY analytic mechanics equation of motion algebraic structure Poisson integral
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Deformed oscillator algebra for quantum superintegrable systems in two-dimensional Euclidean space and on a complex two-sphere
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作者 H.Panahi Z.Alizadeh 《Chinese Physics B》 SCIE EI CAS CSCD 2013年第6期175-180,共6页
In this work, we study superintegrable quantum systems in two-dimensional Euclidean space and on a complex twosphere with second-order constants of motion. We show that these constants of motion satisfy the deformed o... In this work, we study superintegrable quantum systems in two-dimensional Euclidean space and on a complex twosphere with second-order constants of motion. We show that these constants of motion satisfy the deformed oscillator algebra. Then, we easily calculate the energy eigenvalues in an algebraic way by solving of a system of two equations satisfied by its structure function. The results are in agreement to the ones obtained from the solution of the relevant Schroedinger equation. 展开更多
关键词 superintegrable systems constants of motion deformed oscillator algebra structure function
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Computation Method for the Real-Time Control Problems in Differential-Algebraic Systems
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作者 Fei, Jinggao 《Journal of Systems Engineering and Electronics》 SCIE EI CSCD 1999年第2期20-28,共9页
In this paper, a real-time computation method for the control problems in differential-algebraic systems is presented. The errors of the method are estimated, and the relation between the sampling stepsize and the con... In this paper, a real-time computation method for the control problems in differential-algebraic systems is presented. The errors of the method are estimated, and the relation between the sampling stepsize and the controlled errors is analyzed. The stability analysis is done for a model problem, and the stability region is ploted which gives the range of the sampling stepsizes with which the stability of control process is guaranteed. 展开更多
关键词 algebra Computational complexity computer control systems Error analysis Mathematical models Process engineering Production engineering Real time systems Sampling System stability
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Symbolic generation of the kinematics of multibody systems in EasyDyn: From MuPAD to Xcas/Giac
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作者 Olivier Verlinden Lassaad Ben Fkih Georges Kouroussis 《Theoretical & Applied Mechanics Letters》 CAS 2013年第1期89-94,共6页
In the EasyDyn multibody open source project, computer algebra has been used from the beginning to generate the expressions of velocities and accelerations of the bodies, by symbolic differentiation of their position.... In the EasyDyn multibody open source project, computer algebra has been used from the beginning to generate the expressions of velocities and accelerations of the bodies, by symbolic differentiation of their position. Originally, the MuPAD computer algebra system had been retained because it was freely available for non commercial purposes and showed very good technical features.Unfortunately, MuPAD is nowadays only available through commercial channels and needs to be replaced to keep EasyDyn publicly available. This paper presents why Xcas/Giac is finally selected,among other long-term promising projects like Axiom, Maxima, Sage or Yacas. Among the choice criteria, the accessibility, the portability, the ease of use, the automatic export to C language, and the similarity with the -MuPAD language are all considered. The performances of the MuPAD and Xcas/Giac implementations are also compared on some examples.C 2013 The Chinese Society of Theoretical and Applied Mechanics. [doi:10.1063/2.13013012] 展开更多
关键词 symbolic multibody systems KINEMATICS computer algebra system open source
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Anti-CRISPRs: The natural inhibitors for CRISPR-Cas systems 被引量:1
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作者 Fei Zhang Guoxu Song Yong Tian 《Animal Models and Experimental Medicine》 CSCD 2019年第2期69-75,共7页
CRISPR (clustered regularly interspaced short palindromic repeats)‐Cas (CRISPR associated protein) systems serve as the adaptive immune system by which prokaryotes defend themselves against phages. It has also been d... CRISPR (clustered regularly interspaced short palindromic repeats)‐Cas (CRISPR associated protein) systems serve as the adaptive immune system by which prokaryotes defend themselves against phages. It has also been developed into a series of powerful gene‐editing tools. As the natural inhibitors of CRISPR‐Cas systems, anti‐CRISPRs (Acrs) can be used as the “off‐switch” for CRISPR‐Cas systems to limit the off‐target effects caused by Cas9. Since the discovery of CRISPR‐Cas systems, much research has focused on the identification, mechanisms and applications of Acrs. In light of the rapid development and scientific significance of this field, this review summarizes the history and research status of Acrs, and considers future applications. 展开更多
关键词 anti‐CRISPRs cas9 CRISPR‐cas system
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靶向RNA的CRISPR/Cas系统及衍生技术 被引量:1
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作者 周迅 周世杰 +1 位作者 刘捷 王宇祥 《遗传》 北大核心 2025年第8期842-860,共19页
RNA编辑是表观遗传学领域重要的研究方向之一。随着研究的深入,科学家们发现CRISPR/Cas系统不仅可以靶向DNA,也可以靶向RNA,从而实现转录水平的基因精准编辑;同时,使用CRISPR/Cas系统进行RNA编辑也可以避免对基因组的破坏。目前,基于靶... RNA编辑是表观遗传学领域重要的研究方向之一。随着研究的深入,科学家们发现CRISPR/Cas系统不仅可以靶向DNA,也可以靶向RNA,从而实现转录水平的基因精准编辑;同时,使用CRISPR/Cas系统进行RNA编辑也可以避免对基因组的破坏。目前,基于靶向RNA的CRISPR系统已开发出多种衍生技术,如RNA敲低和编辑、核酸检测和成像、RNA示踪等。这些衍生技术的出现,为生物遗传机制解析和疾病治疗提供了有利工具。本文归纳总结了靶向RNA的CRISPR/Cas系统的结构、功能、机制以及开发的衍生技术,以期丰富人们对CRISPR/Cas系统编辑RNA的认知。 展开更多
关键词 基因编辑 CRISPR/cas系统 RNA 功能及应用
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