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The 8×10 GHz Receiver Optical Subassembly Based on Silica Hybrid Integration Technology for Data Center Interconnection 被引量:3
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作者 Chao-Yi Li Jun-Ming An +8 位作者 Jiu-Qi Wang Liang-Liang Wang Jia-Shun Zhang Jian-Guang Li Yuan-Da Wu Yue Wang Xiao-Jie Yin Yong Li Fei Zhong 《Chinese Physics Letters》 SCIE CAS CSCD 2017年第10期39-43,共5页
An 8×10 GHz receiver optical sub-assembly (ROSA) consisting of an 8-channel arrayed waveguide grating (AWG) and an 8-channel PIN photodetector (PD) array is designed and fabricated based on silica hybrid in... An 8×10 GHz receiver optical sub-assembly (ROSA) consisting of an 8-channel arrayed waveguide grating (AWG) and an 8-channel PIN photodetector (PD) array is designed and fabricated based on silica hybrid integration technology. Multimode output waveguides in the silica AWG with 2% refractive index difference are used to obtain fiat-top spectra. The output waveguide facet is polished to 45° bevel to change the light propagation direction into the mesa-type PIN PD, which simplifies the packaging process. The experimentM results show that the single channel I dB bandwidth of AWG ranges from 2.12nm to 3.06nm, the ROSA responsivity ranges from 0.097 A/W to 0.158A/W, and the 3dB bandwidth is up to 11 GHz. It is promising to be applied in the eight-lane WDM transmission system in data center interconnection. 展开更多
关键词 AWG GHz Receiver Optical Subassembly based on Silica Hybrid integration Technology for Data Center Interconnection The 8 PD
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Discussion on Construction and Mechanism of Practice Bases for Professional Degree Postgraduates Based on the Integration of Production and Education in Local Universities
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作者 Dabing XIANG Yu FAN +5 位作者 Xueling YE Changying LIU Liangzhen JIANG Yan WAN Yuehua WANG Yanxia SUN 《Agricultural Biotechnology》 CAS 2023年第5期75-77,87,共4页
Under the background of emerging agricultural education,practice bases are an important place to train profession talented person that match social needs,so it is very important to build stable and long-term practice ... Under the background of emerging agricultural education,practice bases are an important place to train profession talented person that match social needs,so it is very important to build stable and long-term practice bases.At present,the main problems in the construction of practice bases for postgraduates in local colleges and universities are mainly focusing on construction and neglecting management,imperfect cooperation mechanism and lack of teaching management effectively.It is of great significance to build a long-term management mechanism to ensure the education quality of practice bases.Therefore,constructing the mode of"double integration and double promotion of production and education"with practice bases as the carrier and realizing the organic combination of industrial needs and postgraduate projects is an important idea for local colleges and universities to train professional degree postgraduates to"know agriculture,love agriculture,strengthen agriculture and promote agriculture",and it also provides a reference for the mechanism construction of postgraduate bases. 展开更多
关键词 Emerging Agricultural Education Professional master integration of science and education Practice base MECHANISM
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The Integration of Task-based Language Teaching and Information and Communication Technology into English Language Teaching in China
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作者 GAO Qiong-fang 《海外英语》 2013年第21期29-30,43,共3页
The purpose of this article is to explore how important that task-based language teaching(TBLT)interacts with Infor mation and Communication Technology(ICT)into English language teaching(ELT)in China.Many researchers ... The purpose of this article is to explore how important that task-based language teaching(TBLT)interacts with Infor mation and Communication Technology(ICT)into English language teaching(ELT)in China.Many researchers have already studied that ICT and TBLT innovate the traditional teaching methods and improve our teaching or learning.However,they sepa rated TBLT from ICT instead of integrating these two ways into ELT.Few researches studied on how importance task-based in teracts with integration ICT into ELT in China.Under this circumstance,this article reviews the literature related to the present situation,which includes the brief introduction in English language teaching problems,the general concepts of ICT in ELT,taskbased teaching methodology in ELT,some studies on task-based interacting with integration ICT into ELT,discussion and con clusion. 展开更多
关键词 ICT TASK-based integration ENGLISH LANGUAGE teachi
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A 330-500 GHz Zero-Biased Broadband Tripler Based on Terahertz Monolithic Integrated Circuits 被引量:3
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作者 任田昊 张勇 +4 位作者 延波 徐锐敏 杨成樾 周静涛 金智 《Chinese Physics Letters》 SCIE CAS CSCD 2015年第2期31-34,共4页
A 330-500 GHz zero-biased broadband monolithic integrated tripler is reported. The measured results show that the maximum efficiency and the maximum output power are 2% and 194μW at 348 GHz. The saturation characteri... A 330-500 GHz zero-biased broadband monolithic integrated tripler is reported. The measured results show that the maximum efficiency and the maximum output power are 2% and 194μW at 348 GHz. The saturation characteristic test shows that the output i dB compression point is about -8.5 dBm at 334 GHz and the maximum efficiency is obtained at the point, which is slightly below the 1 dB compression point. Compared with the conventional hybrid integrated circuit, a major advantage of the monolithic integrated circuit is the significant improvement of reliability and consistency. In this work, a terahertz monolithic frequency multiplier at this band is designed and fabricated. 展开更多
关键词 InP InGaAs A 330-500 GHz Zero-Biased Broadband Tripler based on Terahertz Monolithic integrated Circuits dBm SBD
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Structured Illumination Chip Based on Integrated Optics 被引量:1
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作者 刘勇 王辰 +3 位作者 Anastasia Nemkova 胡诗铭 李智勇 俞育德 《Chinese Physics Letters》 SCIE CAS CSCD 2016年第5期46-49,共4页
A compact structured illumination chip based on integrated optics is proposed and fabricated on a silicon-on- insulator platform. Based on the simulation of Caussian beam interference, we adopt a chirped diffraction g... A compact structured illumination chip based on integrated optics is proposed and fabricated on a silicon-on- insulator platform. Based on the simulation of Caussian beam interference, we adopt a chirped diffraction grating to achieve a specific interference pattern. The experimental results match well with the simulations. The portability and flexibility of the structured illumination chip can be increased greatly through horizontal encapsulation. High levels of integration, compared with the conventional structured illumination approach, make this chip very compact, with a footprint of only around 1 mm2. The chip has no optical lenses and can be easily combined with a microfluidic system. These properties would make the chip very suitable for portable 3D scanner and compact super-resolution microscopy applications. 展开更多
关键词 of for Structured Illumination Chip based on integrated Optics IS on SOI into been
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Integration and Development of Traditional Artistic Accomplishments in the Construction of Practice Teaching Bases of Universities and Colleges 被引量:1
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作者 SUN Jingsong 《Journal of Landscape Research》 2015年第6期21-22,共2页
Learning, inheritance and development of undergraduates' traditional artistic accomplishments is of realistic signifi cance in the modern society, integration of traditional artistic accomplishments in practice te... Learning, inheritance and development of undergraduates' traditional artistic accomplishments is of realistic signifi cance in the modern society, integration of traditional artistic accomplishments in practice teaching will broaden the channels of modern undergraduates acquiring traditional artistic accomplishments. Learning traditional artistic accomplishments should be the colorful and vivid practice class on and off campus, moreover, students' recognition of traditional artistic accomplishments should be strengthened, and their understanding about traditional arts should be deepened. Full utilization of social resources of traditional arts helps learn the connotations of traditional artistic accomplishments, so that traditional artistic accomplishments will realize its theoretical and practical signifi cance in the rapidly-developing modern society. 展开更多
关键词 Traditional artistic accomplishments Practice base integration DEVELOPMENT
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Integrating a flipped classroom and problem-based learning into ophthalmology education 被引量:2
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作者 Jingyi Luo Tao Lin +4 位作者 Nan Wang Yuxian Zou Xing Liu Chengguo Zuo Yimin Zhong 《Eye Science》 CAS 2017年第1期25-32,共8页
Background: Ophthalmology is an important medical science subject, but it is given with insufficient attention in undergraduate medical education. Flipped classroom(FC) and problem-based learning(PBL) are well-known e... Background: Ophthalmology is an important medical science subject, but it is given with insufficient attention in undergraduate medical education. Flipped classroom(FC) and problem-based learning(PBL) are well-known education methods that can be integrated into ophthalmology education to improve students' competence level and promote active learning. Methods: We used a mixed teaching methodology that integrated a FC and PBL into a 1-week ophthalmology clerkship for 72 fourth-year medical students. The course includes two major sessions: FC session and PBL session, relying on clinical and real-patient cases. Written examinations were set up to assess students' academic performance and questionnaires were designed to evaluate their perceptions. Results: The post-course examination results were higher than the pre-course results, and many students gained ophthalmic knowledge and learning skills to varying levels. Comparison of pre-and post-course questionnaires indicated that interests in ophthalmology increased and more students expressed desires to be eye doctors. Most students were satisfied with the new method, while some suggested the process should be slower and the communication with their teacher needed to strengthen.Conclusions: FC and PBL are complementary methodologies. Utilizing the mixed teaching meth of FC and PBL was successful in enhancing academic performance, student satisfactions and promoting active learning. 展开更多
关键词 Flipped classroom(FC) integrated ophthalmology education problem-based learning(FBL) UNDERGRADUATE
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Integrating Color and Spatial Feature for Content-Based Image Retrieval 被引量:1
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作者 Cao Kui Feng Yu-cai 《Wuhan University Journal of Natural Sciences》 EI CAS 2002年第3期290-296,共7页
In this paper, we present a novel and efficient scheme for extracting, indexing and retrieving color images. Our motivation was to reduce the space overhead of partition-based approaches taking advantage of the fact t... In this paper, we present a novel and efficient scheme for extracting, indexing and retrieving color images. Our motivation was to reduce the space overhead of partition-based approaches taking advantage of the fact that only a relatively low number of distinct values of a particular visual feature is present in most images. To extract color feature and build indices into our image database we take into consideration factors such as human color perception and perceptual range, and the image is partitioned into a set of regions by using a simple classifying scheme. The compact color feature vector and the spatial color histogram, which are extracted from the seqmented image region, are used for representing the color and spatial information in the image. We have also developed the region-based distance measures to compare the similarity of two images. Extensive tests on a large image collection were conducted to demonstrate the effectiveness of the proposed approach. 展开更多
关键词 color distribution spatial color histogram region-based image representation and retrieval similarity matching integrating of single features
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New Numerical Integration Formulations for Ordinary Differential Equations
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作者 Serdar Beji 《Advances in Pure Mathematics》 2024年第8期650-666,共17页
An entirely new framework is established for developing various single- and multi-step formulations for the numerical integration of ordinary differential equations. Besides polynomials, unconventional base-functions ... An entirely new framework is established for developing various single- and multi-step formulations for the numerical integration of ordinary differential equations. Besides polynomials, unconventional base-functions with trigonometric and exponential terms satisfying different conditions are employed to generate a number of formulations. Performances of the new schemes are tested against well-known numerical integrators for selected test cases with quite satisfactory results. Convergence and stability issues of the new formulations are not addressed as the treatment of these aspects requires a separate work. The general approach introduced herein opens a wide vista for producing virtually unlimited number of formulations. 展开更多
关键词 Single- and Multi-Step Numerical integration Unconventional base-Functions Ordinary Differential Equations
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ON THE ERROR OF QUADRATURE FORMULAE FOR CAUCHY PRINCIPAL VALUE INTEGRALS BASED ON PIECEWISE INTERPOLATION
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作者 P. Khler 《Analysis in Theory and Applications》 1997年第3期58-69,共12页
We consider the computation of the. Cauchy principal value mtegral by quadrature formulaeof compound type, which are obtained by replacing f by a piecewise defined function F,[;]. The behaviour of the constants m the ... We consider the computation of the. Cauchy principal value mtegral by quadrature formulaeof compound type, which are obtained by replacing f by a piecewise defined function F,[;]. The behaviour of the constants m the estimates where quadrature error) is determined for fixed i and which means that not only the. order, but also the coefficient of the main term of is determined. The behaviour of these error constants is compared -with the corresponding ones obtained for the. method of subtraction of the singularity. As it turns out, these error constants have, in general, the same asymptotic behaviour. 展开更多
关键词 ON THE ERROR OF QUADRATURE FORMULAE FOR CAUCHY PRINCIPAL VALUE integrALS based ON PIECEWISE INTERPOLATION
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Managing Value-Based Activity Flexibility on Integrated ERP 被引量:1
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作者 WANG Manling, YANG Deli (Insutution of System Engineering, Dalian University of Technology Shandong Dalian 116024 China) 《Journal of Electronic Science and Technology of China》 2004年第3期128-133,共6页
On the background of integrated ERP development, activity-value-flexibility management (AVFM) is defined. By using economic-value-added (EVA) and corporate value creation as the objective of AVFM, custom value deviati... On the background of integrated ERP development, activity-value-flexibility management (AVFM) is defined. By using economic-value-added (EVA) and corporate value creation as the objective of AVFM, custom value deviating rate, capital cost deviating rate, cash-flow-out per purchase deviating rate and cash-flow-in per sell deviating rate are developed to be the key responding variates for AVFM, and they also decide the rational quantity range for AVFM tactics. Method for rational AVFM tactics solution could be got by means of redesigning activity information process on integrated ERP. 展开更多
关键词 integrated ERP value-based activity flexibility-management information-integration
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The Calculation of Parameters for DNA Kinetic Structure Based on Monte-Carlo Multiple Integrals 被引量:1
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作者 崔向军 蔡禄 《Agricultural Science & Technology》 CAS 2010年第5期5-6,16,共3页
Based on protein-DNA complex crystal structural data in up-to-date Nucleic Acid Database,the related parameters of DNA Kinetic Structure were investigated by Monte-Carlo Multiple Integrals on the base of modified DNA ... Based on protein-DNA complex crystal structural data in up-to-date Nucleic Acid Database,the related parameters of DNA Kinetic Structure were investigated by Monte-Carlo Multiple Integrals on the base of modified DNA structure statistical mechanical model,and time complexity and precision were analyzed on the calculated results. 展开更多
关键词 Monte-Carlo method Multiple integrals DNA Time complexity Precision
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BBACIMA:A Trustworthy Integrity Measurement Architecture through Behavior-Based TPM Access Control
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作者 YU Aimin FENG Dengguo 《Wuhan University Journal of Natural Sciences》 CAS 2008年第5期513-518,共6页
Two limitations of current integrity measurement architectures are pointed out: (1) a reference value is required for every measured entity to verify the system states, as is impractical however; (2) malicious us... Two limitations of current integrity measurement architectures are pointed out: (1) a reference value is required for every measured entity to verify the system states, as is impractical however; (2) malicious user can forge proof of inexistent system states. This paper proposes a trustworthy integrity measurement architecture, BBACIMA, through enforcing behavior-based access control for trusted platform module (TPM). BBACIMA introduces a TPM reference monitor (TPMRM) to ensure the trustworthiness of integrity measurement. TPMRM enforces behavior-based access control for the TPM and is isolated from other entities which may be malicious. TPMRM is the only entity manipulating TPM directly and all PCR (platform configuration register) operation requests must pass through the security check of it so that only trusted processes can do measurement and produce the proof of system states. Through these mechanisms malicious user can not enforce attack which is feasible in current measurement architectures. 展开更多
关键词 integrity measurement behavior-based access control trusted platform module (TPM) trusted computing remoteattestation
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Discussion on Theme-based Design of Road Landscape in Scenic Area——A Case Study of Five Dragon Temple Cultural Park in Yingcheng City
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作者 李忠博 李江风 《Journal of Landscape Research》 2011年第2期22-24,共3页
The combination of ornamental function and recreational function should be taken into account in road landscape design of scenic area.The theme characteristic should be highlighted by designing techniques.Roads in sce... The combination of ornamental function and recreational function should be taken into account in road landscape design of scenic area.The theme characteristic should be highlighted by designing techniques.Roads in scenic area should be used to lead tourists' behavior according to people's behavioral psychology.With Five Dragon Temple Cultural Park as case study,starting from its geographic location and establishment concept,the paper had extracted design theme of Five Dragon Temple Cultural Park.Profound religious cultural connotation had been given to the cultural park with Chinese traditional religion and "Five Elements" theory as the inspiration.It designed five main roads with different colors which represented five elements covering "gold,wood,water,fire and earth".Different scenic areas had been linked together by five man roads,forming a road landscape pattern of "meeting of five dragons".Then,flowering plants had been collocated along the five roads which were Vatica astrotricha,Punica granatum,Prunus serrulata,Morus alba and Osmanthus fragrans,creating theme-based road landscape not only representing religious significance but also corresponding with "Five Elements" theory. 展开更多
关键词 Landscape based on THEME Road in SCENIC area integration of ORNAMENTAL and RECREATIONAL function Tour route
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基于LON网络Host-based节点的CIMS系统的应用 被引量:1
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作者 束保华 温阳东 《合肥工业大学学报(自然科学版)》 CAS CSCD 2000年第5期694-697,共4页
首先简要介绍了 CIMS系统的体系结构和 L on Works的技术特点 ,以及在 CIMS系统中采用 L on Works技术所具有的优势。对基于 L on Works的 Host- based节点与 Neuron Chip- hosted节点进行了比较 ,并给出实例展示了该系统由单片机80 C19... 首先简要介绍了 CIMS系统的体系结构和 L on Works的技术特点 ,以及在 CIMS系统中采用 L on Works技术所具有的优势。对基于 L on Works的 Host- based节点与 Neuron Chip- hosted节点进行了比较 ,并给出实例展示了该系统由单片机80 C196KB为主处理器 Neuron,芯片 MC14312 0为从处理器 ;两处理器协同工作 ,主处理器采样控制 ,从处理器负责通信。以Host- based节点为基础的 CIMS系统。 展开更多
关键词 现场总线 HOS-based节点 网络集成 LON网络 CIMS系统
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Hybrid event based control architecture for tele-robotic systems controlled through Internet 被引量:1
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作者 李晓明 杨灿军 +1 位作者 陈鹰 胡旭东 《Journal of Zhejiang University-Science A(Applied Physics & Engineering)》 SCIE EI CAS CSCD 2004年第3期47-53,共7页
A new hybrid event based control architecture for tele-robotic systems controlled through the Internet is pro-posed in this paper. Different from the traditional event based control method, the new framework does not ... A new hybrid event based control architecture for tele-robotic systems controlled through the Internet is pro-posed in this paper. Different from the traditional event based control method, the new framework does not require every part of the system to be strictly event synchronized. Instead, it allows time referenced control components to be integrated into this framework, which makes it more convenient to develop Internet based control systems. Since there are two reference variables, time and event, in this architecture, how to coordinate these components with different references to keep the stability of the whole system is discussed in detail in this paper. To verify this new idea, an experiment was conducted to control the end effector of a PUMA robot tracking a continuous state trajectory given on-line by the remote operator. Ex-perimental results confirmed the stability of such systems being controlled through the Internet in real-time. 展开更多
关键词 Tele-robot EVENT based control System integration
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Experimental study on vibration suppression in a rotor system under base excitation using an integral squeeze film damper 被引量:4
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作者 Yan Wei He Lidong +2 位作者 Zhu Gang Wang Shengli Deng Zhe 《High Technology Letters》 EI CAS 2020年第4期349-359,共11页
Base excitation is one of common excitations in rotor system.In order to study the dynamic characteristics of rotor systems under base excitation and the effect of integral squeeze film dampers(ISFDs)on their dynamic ... Base excitation is one of common excitations in rotor system.In order to study the dynamic characteristics of rotor systems under base excitation and the effect of integral squeeze film dampers(ISFDs)on their dynamic characteristics,a single-disk rotor test rig,where mass imbalance and base excitation could be applied,is developed.Experimental research on the rotor system response under sinusoidal base excitation conditions with different frequencies and excitation forces is performed and the effect of ISFD on the dynamic characteristics of the rotor is investigated.The experimental results demonstrate that when the sinusoidal base excitation frequency approaches the first critical speed of the rotor system or the natural frequency of the rotor system base,strong vibration occurs in the rotor,indicating that the base excitation of the two frequencies has a greater impact on rotor system response.In addition,with the increase of the base excitation force,the vibration of the rotor will be increased.ISFDs can significantly inhibit the vibration due to unbalanced forces and sinusoidal base excitation in rotor systems.To a certain extent,ISFDs can improve the effect of sinusoidal base excitation with most frequencies on rotor system response,and they have a good vibration reduction effect for sinusoidal base excitation with different excitation forces. 展开更多
关键词 Jeffcott rotor dynamic characteristics base excitation integral squeeze film damper(ISFD) vibration suppression
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Progress in Antimonide Based III-V Compound Semiconductors and Devices 被引量:1
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作者 Chao Liu Yanbo Li Yiping Zeng 《Engineering(科研)》 2010年第8期617-624,共8页
In recent years, the narrow bandgap antimonide based compound semiconductors (ABCS) are widely regarded as the first candidate materials for fabrication of the third generation infrared photon detectors and integrated... In recent years, the narrow bandgap antimonide based compound semiconductors (ABCS) are widely regarded as the first candidate materials for fabrication of the third generation infrared photon detectors and integrated circuits with ultra-high speed and ultra-low power consumption. Due to their unique bandgap structure and physical properties, it makes a vast space to develop various novel devices, and becomes a hot research area in many developed countries such as USA, Japan, Germany and Israel etc. Research progress in the preparation and application of ABCS materials, existing problems and some latest results are briefly introduced. 展开更多
关键词 ANTIMONIDE based COMPOUND SEMICONDUCTORS (ABCS) IR Laser IR DETECTOR integrated Circuit Functional Device
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Nursing Based on Syndrome Differentiation Combined with Auricular Plaster Therapy in Alleviating Insomnia 被引量:4
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作者 Ning WANG Shu-Li MA +1 位作者 Xi LI Li-Xia YANG 《Journal of Integrative Nursing》 2019年第1期27-34,共8页
Objective:To observe the effect of auricular point pressing combined with nursing based on syndrome differentiation in the treatment of insomnia patients.Methods:Totally 92 patients with insomnia were randomly divided... Objective:To observe the effect of auricular point pressing combined with nursing based on syndrome differentiation in the treatment of insomnia patients.Methods:Totally 92 patients with insomnia were randomly divided into the observation groupgiven auricular point pressing combined with nursing care based on syndrome differentiation and the control group treated with auricular point pressing alone.The improvement of Pittsburgh Sleep Quality Index(PSQI),TCM Syndrome Score and nursing satisfaction were compared between the 2 groups.Results:The time effect of PSQI total score and 6 factors in both groups were statistically significant(P<0.05).The time effect,interaction effect and inter-group effect of subjective sleep quality,PSQI total score were statistically significant(P<0.05);the 4 inter-group factors of sleep quality,sleep latency,sleep duration and daytime function were statistically significant(P<0.05).The total score of TCM syndromes in the observation group was lower than that in the control group(P<0.05),and the satisfaction rate in the observation group higher than that in the control group(80.43%vs.60.86%,P<0.05).Conclusion:Auricular point pressing combined withnursing based on syndrome differentiation can effectively improve the sleep quality of insomnia patients,and has significant advantages in improving TCM syndromes,as well as gained higher nursing satisfaction from patients. 展开更多
关键词 INSOMNIA Auricular-plaster therapy/Auricular point pressing Nursing based on syndrome differentiation/Syndrome differentiation and nursing Sleep quality Nursing of integrated traditional Chinese and western medicine
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Homologous recombination mediates stable Fah gene integration and phenotypic correction in tyrosinaemia mouse-model
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作者 Norman Junge Qinggong Yuan +8 位作者 Thu Huong Vu Simon Krooss Christien Bednarski Asha Balakrishnan Toni Cathomen Michael P Manns Ulrich Baumann Amar Deep Sharma Michael Ott 《World Journal of Hepatology》 CAS 2018年第2期277-286,共10页
AIM To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout(Fah-/-) mice by homologous-recombination-mediated targeted addition of the Fah gene.METHODS C57 BL/6 Fah?exon5 mice ... AIM To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout(Fah-/-) mice by homologous-recombination-mediated targeted addition of the Fah gene.METHODS C57 BL/6 Fah?exon5 mice served as an animal model for human tyrosinaemia type 1 in our study. The vector was created by amplifying human Fah c DNA including the TTR promoter from a lentivirus plasmid as described. The Fah expression cassette was flanked by homologous arms(620 bp and 749 bp long) of the Rosa26 gene locus. Mice were injected with 2.1 × 108 VP of this vector(r AAV8-ROSA26.HAL-TTR.FahROSA26.HAR) via the tail vein. Mice in the control group were injected with 2.1 × 108 VP of a similar vector but missing the homologous arms(r AAV8-TTR.Fah). Primary hepatocytes from Fah-/-recipient mice, treated with our vectors, were isolated and 1 × 106 hepatocytes were transplanted into secondary Fah-/-recipient mice by injection into the spleen. Upon either vector application or hepatocyte transplantation NTBC treatment was stopped in recipient mice. RESULTS Here, we report successful HR-mediated genome editing by integration of a Fah gene expression cassette into the "safe harbour locus" Rosa26 by recombinant AAV8. Both groups of mice showed long-term survival, weight gain and FAH positive clusters as determined by immunohistochemistry analysis of liver sections in the absence of NTBC treatment. In the group of C57 BL/6 Fah?exon5 mice, which have been transplanted with hepatocytes from a mouse injected with r AAV8-ROSA26.HAL-TTR.Fah-ROSA26.HAR 156 d before, 6 out of 6 mice showed long-term survival, weight gain and FAH positive clusters without need for NTBC treatment. In contrast only 1 out 5 mice, who received hepatocytes from r AAV8-TTR.Fah treated mice, survived and showed few and smaller FAH positive clusters. These results demonstrate that homologous recombinationmediated Fah gene transfer corrects the phenotype in a mouse model of human tyrosinaemia type 1(Fah-/-mice) and is long lasting in a proliferating state of the liver as shown by withdrawal of NTBC treatment and serial transplantation of isolated hepatocytes from primary Fah-/-recipient mice into secondary Fah-/-recipient mice. This long term therapeutic efficacy is clearly superior to our control mice treated with episomal r AAV8 gene therapy approach.CONCLUSION HR-mediated r AAV8 gene therapy provides targeted transgene integration and phenotypic correction in Fah-/-mice with superior long-term efficacy compared to episomal r AAV8 therapy in proliferating livers. 展开更多
关键词 Gene therapy AAV8 LIVER based METABOLIC DISEASE TARGETED integration ROSA26 PAEDIATRIC LIVER DISEASE
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