Advanced Dialogues with Multiple Choice Questions - Milk and Aesthetics

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新闻英语测试题及答案一、选择题（每题1分，共10分）1. What is the main topic of the news article?A. The economic situationB. A new technological breakthroughC. A political eventD. A cultural festival2. According to the article, which of the following statements is NOT true?A. The event attracted a large audience.B. The speaker emphasized the importance of education.C. The event was held in a remote area.D. The speaker called for environmental protection.3. What is the purpose of the new policy mentioned in the article?A. To reduce traffic congestion.B. To increase tax revenue.C. To promote tourism.D. To improve public health.4. The article suggests that the company has:A. Expanded its market share.B. Faced financial difficulties.C. Launched a new product line.D. Merged with a competitor.5. What does the term "sustainable development" refer to in the context of the article?A. Economic growth without environmental harm.B. The development of new technologies.C. The increase in population.D. The improvement of living standards.6. The article reports that the government has:A. Introduced new regulations.B. Allocated additional funding.C. Imposed a new tax.D. Announced a public inquiry.7. The author of the article seems to have a(n) ________ attitude towards the issue discussed.A. PositiveB. NegativeC. NeutralD. Critical8. Which of the following is NOT mentioned as a benefit of the new technology?A. Increased efficiency.B. Reduced costs.C. Improved safety.D. Decreased demand.9. According to the article, the majority of the public:A. Supports the proposed changes.B. Opposes the proposed changes.C. Is indifferent to the proposed changes.D. Has mixed opinions about the proposed changes.10. The article concludes by highlighting the need for:A. Greater international cooperation.B. Stricter domestic regulations.C. More public awareness campaigns.D. Additional scientific research.二、填空题（每空1分，共10分）11. The ________ of the new law has been met with mixed reactions from the public.[答案] introduction12. The company has seen a ________ in profits over the past year.[答案] decline13. The ________ of the old bridge has been postponed due to budget constraints.[答案] construction14. The ________ of the new policy is expected to have a significant impact on the industry.[答案] implementation15. The ________ of the event was attended by numerous dignitaries and celebrities.[答案] inauguration16. The ________ of the project is scheduled for next month. [答案] completion17. The ________ of the company has been attributed to its innovative approach.[答案] success18. The ________ of the new initiative has been widely praised by the media.[答案] launch19. The ________ of the old factory site has been approved by the city council.[答案] redevelopment20. The ________ of the new technology is expected to revolutionize the industry.[答案] introduction三、简答题（每题5分，共20分）21. What are the key points of the new policy discussed in the article?[答案] The key points of the new policy include a focus on environmental sustainability, incentives for businesses to adopt green practices, and penalties for non-compliance.22. How does the article describe the impact of the recent economic downturn on the job market?[答案] The article describes the impact as significant, with many industries facing layoffs and a rise in unemployment rates, particularly among young professionals.23. What are the main features of the new technologyintroduced in the article?[答案] The main features of the new technology include advanced data processing capabilities, user-friendly interface, and compatibility with various platforms.24. How does the article summarize the public's reaction to the proposed changes?[答案] The article summarizes the public's reaction as generally positive, with many expressing support for the changes and their potential benefits to society.四、阅读理解题（每题5分，共20分）25. Read the following excerpt from the article and answer the question:"The new initiative aims to bridge the gap between traditional and modern education methods, providing students with a more holistic learning experience."What does the initiative aim to achieve?[答案] The initiative aims to achieve a more holistic learning experience by integrating traditional and modern education methods.26. According to the article。

Artificial Intelligence AI has been a rapidly evolving field with profound implications for society,economy,and technology.Heres an essay on AI and its development:Introduction to Artificial IntelligenceArtificial Intelligence refers to the simulation of human intelligence in machines that are programmed to think like humans and mimic their actions.The term was coined in1956 at a conference at Dartmouth College,and since then,AI has been a subject of fascination and research.Historical DevelopmentThe development of AI can be traced back to the1950s with the advent of the first AI program,the Logic Theorist,developed by Allen Newell and Herbert A.Simon.This was followed by the development of the General Problem Solver and the creation of the first AI laboratory at MIT.However,the field faced a period of stagnation in the1970s, known as the AI winter,due to a lack of funding and overestimation of AI capabilities.Renaissance of AIThe field saw a resurgence in the1990s with the introduction of machine learning,a subset of AI that focuses on the development of algorithms that can learn from and make predictions or decisions based on data.The availability of big data,advancements in computational power,and the development of new algorithms have all contributed to this renaissance.Current State of AIToday,AI is pervasive in various sectors,from healthcare,where it assists in diagnosing diseases,to finance,where it is used for fraud detection and algorithmic trading.In the consumer market,AI is evident in virtual assistants like Siri and Alexa,which can perform tasks and answer questions through natural language processing.Machine Learning and Deep LearningMachine learning,a core component of AI,has further evolved with the advent of deep learning,which uses neural networks with many layers to analyze complex patterns in data.This has led to significant advancements in image and speech recognition,as well as natural language processing.Ethical Considerations and ChallengesDespite the benefits,AI development has raised ethical concerns,such as privacy issues, the potential for job displacement,and the need for transparency in AI decisionmaking processes.There is also a debate on the potential risks of AI becoming too powerful andthe need for regulation to ensure its safe and beneficial use.Future ProspectsThe future of AI is promising,with ongoing research into areas such as autonomous vehicles,advanced robotics,and personalized AI assistants.However,it is crucial to address the ethical and societal implications to ensure that AI development aligns with human values and contributes positively to society.ConclusionArtificial Intelligence is a transformative technology that continues to push the boundaries of what machines can do.As it develops,it is essential to foster a multidisciplinary approach that includes technologists,ethicists,and policymakers to guide its responsible and beneficial integration into all aspects of life.。

展望未来英语教程学生用书：引领语言学习的革新之路In the ever-evolving landscape of language education, "Looking Forward English Course for Students" stands as a beacon of innovation, guiding learners towards a brighter future in communication and cultural understanding. This comprehensive textbook, with its blend of contemporary content, engaging activities, and cutting-edge teaching methods, offers a unique and dynamic approach to language acquisition.The textbook's emphasis on real-world applications is particularly noteworthy. Through immersive scenarios and practical exercises, students are encouraged to apply their language skills to real-life situations, fostering a deeper understanding of the language's cultural and social context. This approach not only enhances the learning experience but also prepares students for the challenges they mayencounter in the globalized world.Moreover, the integration of technology into thelearning process is a testament to the textbook's forward-thinking approach. With digital resources and interactivefeatures, students can engage with the material in a more dynamic and engaging way, enhancing their learning outcomes. This blend of traditional and modern learning methods ensures that students are not only kept engaged but also equipped with the tools they need to excel in today'sdigital age.The content of the textbook is also carefully craftedto cater to the diverse needs of students. With a focus on building a strong foundation in language skills, the textbook gradually introduces more complex concepts and vocabulary, ensuring a gradual and steady progression through the course. This gradual approach not only ensures that students retain the information better but also helps them build confidence in their language abilities.The inclusion of cultural insights and comparisons throughout the textbook is also a valuable addition. By exploring the similarities and differences betweendifferent cultures, students are able to gain a broader perspective on the world and develop a deeper understanding of the language they are learning. This cultural awarenessnot only enhances their language skills but also prepares them to become global citizens.In conclusion, "Looking Forward English Course for Students" is a comprehensive and innovative textbook that offers a unique approach to language learning. Its focus on real-world applications, integration of technology, diverse content, and cultural insights make it an invaluable resource for students seeking to excel in the globalized world. With this textbook as their guide, students are sure to embark on a journey of linguistic discovery and cultural understanding that will prepare them for the challenges and opportunities of the future.**展望未来英语教程学生用书：引领语言学习的革新之路** 在不断变化的语言教育领域中，《展望未来英语教程学生用书》犹如一盏指引灯，引领学习者走向更加光明的沟通与文化理解之路。

高一英语学科国际学术交流合作的障碍与解决方案分析单选题80题(答案解析)1.The biggest obstacle in international academic exchanges is _____.nguage differenceB.cultural diversityC.time differenceD.geographical distance答案：A。

本题考查国际学术交流中的主要障碍。

语言差异是国际学术交流中最大的障碍之一，因为不同的语言可能导致沟通困难。

选项B 文化多样性虽然也会带来一些挑战，但不是最大的障碍。

选项 C 时间差异和选项 D 地理距离也会对交流产生影响，但相对语言差异来说不是最主要的。

2.International academic exchanges often face problems of _____.A.misunderstanding due to languageB.different research methodsC.diverse academic backgroundsD.various teaching styles答案：A。

国际学术交流中经常面临由于语言而产生的误解问题。

选项B 不同的研究方法、选项C 多样的学术背景和选项 D 不同的教学风格虽然也可能存在，但语言问题往往是最直接和常见的障碍。

3.The main difficulty in language communication in international academic exchanges is _____.A.vocabulary shortageB.grammar mistakesC.pronunciation inaccuracyck of fluency答案：A。

在国际学术交流的语言沟通中，主要困难是词汇量不足。

语法错误、发音不准确和缺乏流利度也会有影响，但词汇量不足会更严重地阻碍交流。

IDL Advanced及其详细功能介绍(2011-03-27 18:23:43)转载▼标签：分类：IDL数值分析idladvancedanalyst杂谈IDL Advanced是IDL的一个新的增值模块，它全面集成了IMSL TM C Numerical Library 的数学和统计程序，在IDL原有的交互式数据分析和可视化功能基础上增加了复杂的数学和统计功能。

IMSL（International Mathematics and Statistics Library）是由Visual Numerics,Inc 从20世纪70年代开始开发的包含全面的数学和统计函数的软件包，拥有超过300个已证明且精准的数学统计算法，IDL Advanced中包含了除金融方面函数之外的整个C语言库。

IDL Advanced为科学家和专业领域的工程师提供了185个经过证明的运算函数，在IDL 环境下，用户只需要简单地调用这些函数到自己的应用程序中，就可以实现复杂的数学和统计运算，并可以进行运算结果的快速可视化。

1. IMSL数学和统计功能列表：Linear System （线性系统）Eigensystem Analysis （特征系统分析）Interpolation and Approximation （差值和拟合）Quadrature （积分）Differential Equations （微分方程）Transforms （变换）Nonlinear Equations （非线性方程）Optimization （最优化）Special Functions （特殊函数）Basic Statistics and Random Number Generators （基础统计和随机数产生）Regression （回归）Correlation and Covariance （相关和协方差）Analysis of Variance （变异分析）Categorical and Discrete Data Analysis （分类和离散数据分析）Nonparametric Statistics （非参数统计）Goodness of Fit （拟和优度/配合度）Time Series and Forecasting （时间序列和预测）Multivariate Analysis （多元分析）Survival Analysis （生存分析）Probability Distribution Functions and Inverses （概率分布函数和反转）Random Number Generation （随机数生成）Math and Statistics Utilities（应用数学统计）2. IDL Advanced数学功能详细介绍§1 Linear System （线性系统）Matrix Inversion 矩阵转置IMSL_INVLinear Equations with Full Matrices 全矩阵线性方程IMSL_SP_LUSOLIMSL_SP_LUFACIMSL_SP_CHSOLIMSL_SP_CHFACLinear Least Squares with Full Matrices 全矩阵线性最小二乘IMSL_QRSOLIMSL_QRFACIMSL_SVDCOMPIMSL_CHNNDSOLIMSL_CHNNDFACIMSL_LINLSQSparse Matrices 稀疏矩阵IMSL_SP_LUSOLIMSL_SP_LUFACIMSL_SP_BDSOLIMSL_SP_BDFACIMSL_SP_PDSOLIMSL_SP_PDFACIMSL_SP_BDPDSOLIMSL_SP_BDPDFACIMSL_SP_GMRESIMSL_SP_CGIMSL_SP_MVMUL§2 Eigensystem Analysis （特征系统分析）Linear Eigensystem Problems 线性特征系统问题IMSL_EIGGeneralized Eigensystem Problems 广义特征系统问题IMSL_EIGSYMGENIMSL_GENEIG§3 Interpolation and Approximation （差值和拟合）Cubic Spline Interpolation 三次样条插值IMSL_CSINTERPIMSL_CSSHAPEB-spline Interpolation B-样条插值IMSL_BSINTERPIMSL_BSKNOTSB-spline and Cubic Spline Evaluation and Integration B-样条、三次样条评价及综合 IMSL_SPVALUEIMSL_SPINTEGLeast-squares Approximation and Smoothing 最小二乘拟和及滤波IMSL_FCNLSQIMSL_BSLSQIMSL_CONLSQIMSL_CSSMOOTHIMSL_SMOOTHDATA1DScattered Data Interpolation 离散数据插值IMSL_SCAT2DINTERPIMSL_RADBFIMSL_RADBE§4 Quadrature （积分）Univariate and Bivariate Quadrature 一元积分和双重积分IMSL_INTFCNArbitrary Dimension Quadrature 任意维的积分IMSL_INTFCNHYPERIMSL_INTFCN_QMCGauss Quadrature 高斯积分IMSL_GQUADDifferentiation 区别IMSL_FCN_DERIV§5 Differential Equations （微分方程）IMSL_ODEIMSL_PDE_MOLIMSL_POISSON2D§6 Transforms （变换）IMSL_FFTCOMPIMSL_FFTINITIMSL_CONVOL1DIMSL_CORR1DIMSL_LAPLACE_INV§7 Nonlinear Equations （非线性方程）Zeros of a Polynomial 多项式的零点IMSL_ZEROPOLYZeros of a Function 函数的零点IMSL_ZEROFCNRoot of a System of Equations 方程组的根IMSL_ZEROSYS§8 Optimization （最优化）Unconstrained Minimization 无约束最小化IMSL_FMINIMSL_FMINVIMSL_NLINLSQLinearly Constrained Minimization 线性约束最小化IMSL_LINPROGIMSL_QUADPROGNonlinearly Constrained Minimization 非线性约束最小化 IMSL_MINCONGENIMSL_CONSTRAINED_NLP§9 Special Functions （特殊函数）Error Functions 误差函数IMSL_ERFIMSL_ERFCIMSL_BETAIMSL_LNBETAIMSL_BETAIGamma Functions γ函数IMSL_LNGAMMAIMSL_GAMMA_ADVIMSL_GAMMAIBessel Functions with Real Order and Complex Argument 一般和复杂的贝赛尔函数 IMSL_BESSIIMSL_BESSJIMSL_BESSKIMSL_BESSYIMSL_BESSI_EXPIMSL_BESSK_EXPElliptic Integrals 椭圆积分IMSL_ELKIMSL_ELEIMSL_ELRFIMSL_ELRDIMSL_ELRJIMSL_ELRCFresnel Integrals菲涅耳积分IMSL_FRESNEL_COSINEIMSL_FRESNEL_SINEAiry Functions Airy函数IMSL_AIRY_AIIMSL_AIRY_BIKelvin Functions开尔文函数IMSL_KELVIN_BER0IMSL_KELVIN_BEI0IMSL_KELVIN_KER0IMSL_KELVIN_KEI03. IDL Advanced统计功能详细介绍§1 Basic Statistics （基础统计）Simple Summary Statistics 简单统计概要IMSL_NORM1SAMPIMSL_NORM2SAMPTabulate, Sort, and Rank 列表、分类和排列IMSL_FREQTABLEIMSL_SORTDATAIMSL_RANKS§2 Regression （回归）Multiple Linear Regression 多线性回归IMSL_REGRESSORSIMSL_MULTIREGRESSIMSL_MULTIPREDICTVariable Selection 变量选择IMSL_ALLBESTIMSL_STEPWISEPolynomial and Nonlinear Regression 多项式和非线性回归IMSL_POLYREGRESSIMSL_POLYPREDICTIMSL_NONLINREGRESSMultivariate Linear Regression—Statistical Inference and Diagnostics 多元线性回归-统计推断和诊断IMSL_HYPOTH_PARTIALIMSL_HYPOTH_SCPHIMSL_HYPOTH_TESTPolynomial and Nonlinear Regression 多项式和非线性回归IMSL_NONLINOPTAlternatives to Least Squares Regression 可选最小二乘回归IMSL_LNORMREGRESS§3 Correlation and Covariance （相关和协方差）IMSL_COVARIANCESIMSL_PARTIAL_COVIMSL_POOLED_COVIMSL_ROBUST_COV§4 Analysis of Variance （变异分析）IMSL_ANOVA1IMSL_ANOVAFACTIMSL_ANOVANESTEDIMSL_ANOVABALANCED§5 Categorical and Discrete Data Analysis （分类和离散数据分析）Statistics in the Two-Way Contingency Table （双向列联表统计）IMSL_CONTINGENCYIMSL_EXACT_ENUMIMSL_EXACT_NETWORKGeneralized Categorical Models 广义类别模型IMSL_CAT_GLM§6 Nonparametric Statistics （非参数统计）One Sample Tests—Nonparametric Statistics 单样本检验－非参数统计IMSL_SIGNTESTIMSL_WILCOXONIMSL_NCTRENDSIMSL_CSTRENDSIMSL_TIE_STATSTwo or More Samples Tests—Nonparametric Statistics 双样本或多样本检验－非参数统计 IMSL_KW_TESTIMSL_FRIEDMANS_TESTIMSL_COCHRANQIMSL_KTRENDS§7 Goodness of Fit （拟和优度/配合度）General Goodness of Fit Tests 一般拟和优度检验IMSL_CHISQTESTIMSL_NORMALITYIMSL_KOLMOGOROV1IMSL_KOLMOGOROV2IMSL_MVAR_NORMALITYTests for Randomness 随机检验IMSL_RANDOMNESS_TEST§8 Time Series and Forecasting （时间序列和预测）IMSL_ARMA Models IMSL_ARMA 模型IMSL_ARMAIMSL_DIFFERENCEIMSL_BOXCOXTRANSIMSL_AUTOCORRELATIONIMSL_PARTIAL_ACIMSL_LACK_OF_FITIMSL_GARCHIMSL_KALMAN§9 Multivariate Analysis （多元分析）IMSL_K_MEANSIMSL_PRINC_COMPIMSL_FACTOR_ANALYSISIMSL_DISCR_ANALYSIS§10 Survival Analysis （生存分析）IMSL_SURVIVAL_GLM§11 Probability Distribution Functions and Inverses （概率分布函数和反转） IMSL_NORMALCDFIMSL_BINORMALCDFIMSL_CHISQCDFIMSL_FCDFIMSL_TCDFIMSL_GAMMACDFIMSL_BETACDFIMSL_BINOMIALCDFIMSL_BINOMIALPDFIMSL_HYPERGEOCDFIMSL_POISSONCDF§12 Random Number Generation （随机数生成）Random Numbers 随机数IMSL_RANDOMOPTIMSL_RANDOM_TABLEIMSL_RANDOMIMSL_RANDOM_NPPIMSL_RANDOM_ORDERIMSL_RAND_TABLE_2WAYIMSL_RAND_ORTH_MATIMSL_RANDOM_SAMPLEIMSL_RAND_FROM_DATAIMSL_CONT_TABLEIMSL_RAND_GET_CONTIMSL_DISCR_TABLEIMSL_RAND_GEN_DISCRStochastic Processes 随机过程IMSL_RANDOM_ARMALow-discrepancy Sequences 超均匀分布序列IMSL_FAURE_INITIMSL_FAURE_NEXT_PT§13 Math and Statistics Utilities（应用数学统计）Dates 日期IMSL_DAYSTODATEIMSL_DATETODAYSConstants and Data Sets 常量和数据集IMSL_CONSTANTIMSL_MACHINEIMSL_STATDATABinomial Coefficient 二项式系数IMSL_BINOMIALCOEFGeometry 几何排列IMSL_NORMMatrix Norm 矩阵范数IMSL_MATRIX_NORMMatrix Entry and Display 矩阵输入和显示PMRM4.需要知道的关于IDL Advanced的几点常识：I.关于license：IDL Advanced是独立注册的IDL模块，如果没有安装IDL Advanced license，那么包含IMSL函数的IDL应用程序将不能运行，也就是说每个终端用户都必须有一个IDL Advanced license。

DOI 10.1212/WNL.0b013e3182695882 2012;79;S119Neurology Jawad F. Kirmani, Ammar Alkawi, Spozhmy Panezai, et al.Advances in thrombolytics for treatment of acute ischemic strokeSeptember 24, 2012This information is current as of/content/79/13_Supplement_1/S119.full.html located on the World Wide Web at:The online version of this article, along with updated information and services, isrights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.All since 1951, it is now a weekly with 48 issues per year. Copyright © 2012 by AAN Enterprises, Inc. ® is the official journal of the American Academy of Neurology. Published continuously NeurologyAdvances in thrombolytics for treatment of acute ischemic strokeJawad F.Kirmani,MD Ammar Alkawi,MD Spozhmy Panezai,MD Martin Gizzi,MD,PhD ABSTRACTOver the past50years,thrombolytic agents have been devised with the aim of recanalizing occluded coronary vessels,and later on,applied in the setting of acute ischemic stroke.Pharma-cologic agents have generally targeted the plasminogen–plasmin transformation,facilitating the natural process of fibrinolysis.Newer agents with varying degrees of fibrin selectivity and phar-macologic half-life have influenced both recanalization rates and hemorrhagic complications,in-side and outside the CNS.Intra-arterial(IA)administration of fibrinolytic agents increases delivery of the drug to the thrombus at a higher concentration with smaller quantities and therefore lowers systemic exposure.Mechanical thrombus disruption or extraction allows for drug delivery to a greater surface area of the thrombus.Delays associated with IA therapy may worsen the risk/ benefit ratio of thrombolysis;therefore,combinations of IA-IV treatments have been studied.To date,there are no direct comparative trials to show that endovascular administration is more efficacious or carries a lower risk of hemorrhagic complications than IV tissue plasminogen acti-vator.Neurology®2012;79(Suppl1):S119–S125GLOSSARYAISϭacute ischemic stroke;DIASϭDesmoteplase in Acute Ischemic Stroke Trial;ECASSϭEuropean Cooperative Acute Stroke Studies;FDAϭUS Food and Drug Administration;IAϭintra-arterial;ICHϭintracerebral hemorrhage;MCAϭmiddle cerebral artery;MMPsϭmatrix metalloproteinases;MRAϭmagnetic resonance angiography;NIHSSϭNIH Stroke Scale;NINDSϭNational Institute of Neurological Disorders and Stroke;PROACTϭProlyse in Acute Cerebral Thromboembolism;rtPAϭrecom-binant tissue plasminogen activator;TIMIϭthrombolysis in myocardial ischemia;tPAϭtissue plasminogen activator.Stroke is the fourth leading cause of death in the United States and is a major cause of disability worldwide.1–3Over the past20years,many advances in the treatment of stroke have been directed at better prevention and acute intervention in an effort to improve clinical outcomes and decrease associated mortality.Most of the acute interventions target the salvageable isch-emic penumbra.This is best achieved by IV or intra-arterial(IA)thrombolysis.Ongoing development of thrombolytic agents has produced4generations of drugs based on fibrin specificity and pharmacologic half-life.In addition,interventional mechanical devices can en-hance the performance of thrombolytic agents.THROMBOLYTICS Vessel occlusion,caused by a blood clot,interrupts cerebral blood flow and results in an acute ischemic stroke(AIS).Most commonly,the clot comprises a mesh of fibrin and platelets.The resultant cerebral infarct has a core lesion containing dead tissue and a surrounding viable ischemic penumbra.The ischemic penumbra is a region of hypoperfused and dysfunctional cerebral tissue,which may be salvageable. The stability and size of the penumbra are dependent mainly on the collateral blood supply.4Rapid restora-tion of blood flow through dissolution of the obstructing clot allows recovery of the penumbra.Thrombolytic agents aim at disrupting the fibrin-rich clot that is created in response to injury of the endothelium.5By activating plasminogen,the administration of thrombolytics leads to an increased produc-tion of plasmin,which dissolves the fibrin bonds in the clot(figure1).When IV thrombolysis occurs,rapid local and systemic complications may be minimized.However,this time constraint is one of the major limitations of thrombolytic use,and penumbral imaging becomes of paramount significance in triaging AISFrom the New Jersey Neurological Institute,JFK Neuroscience Institute,Edison.Go to for full disclosures.Disclosures deemed relevant by the authors,if any,are provided at the end of this article.Correspondence&reprint requests to Dr.Kirmani: jkirmani@patients for thrombolytic therapy,which is addressed elsewhere in the supplement.First generation.Streptokinase and urokinase are the first generation of thrombolytics.Although they are effective in clot lysis,they are not fibrin-specific.Streptokinase is the oldest thrombolytic agent.It is naturally produced by bacteria and was isolated and manufactured in the1950s.6Streptokinase is known to have immunogenic properties that may re-duce its effectiveness or induce an allergic reaction.7 Early trials of streptokinase as a treatment for AIS had poor outcomes and were all terminated early be-cause of increased mortality related to the develop-ment of intracerebral hemorrhage(ICH)after treatment.8During these early trials,investigators were unable to recruit patients within the first few hours of symptom onset,and many patients were en-rolled days later.This delay,among other factors,con-tributed to the increased incidence of hemorrhages.8 More trials using streptokinase were conducted in the late1980s and early1990s.These included the Australian Streptokinase Trial(AST),the Multi-center Acute Stroke Trial(MAST),and the Multi-center Acute Stroke Trial in Italy(MAST-I).7,9In these trials,IV streptokinase was administered within 4to6hours of symptom onset.The results failed to show clear benefit and led to abandonment of its use in the treatment of AIS.Urokinase was developed and studied in the 1970s.In the early1980s,3trials tested IV urokinase in AIS.Again,these trials recruited patients up to several days after stroke onset and,as a result,had high rates of ICH.In1980,the NIH consensus rec-ommended that thrombolysis of acute cerebrovascu-lar disorders be contraindicated,10thus limiting its use in treatment of AIS.Second generation.Alteplase is a protease that is thought to exert a neurotoxic effect on the brain pa-renchyma when it crosses the blood–brain barrier.It also amplifies calcium currents through the NMDA receptor leading to neuroexcitotoxicity and cell death.11,12Alteplase directly activates matrix metallo-proteinases(MMPs),which have been found to play a role in blood–brain barrier breakdown and neuro-nal injury in a stroke.Because these proteases may increase the risk of ICH and cerebral edema,early administration of the drug prior to natural MMP activation is ideal.The second-generation thrombolytics include re-combinant tissue plasminogen activator(rtPA),also known as alteplase,and prourokinase.These agents are more fibrin-selective and have been studied ex-tensively in ischemic stroke.13–16The National Insti-tute of Neurological Disorders and Stroke(NINDS) tissue plasminogen activator(tPA)trial was the first study to demonstrate efficacy of alteplase in patients with AIS.The efficacy was based on administering tPA,0.9mg/kg IV,given within3hours of symptom onset.16On the basis of the results of this study,the US Food and Drug Administration(FDA)approved IV alteplase for treatment of AIS.Patients who re-ceived treatment within the first90minutes had a more favorable outcome at3months than patients who were treated after90minutes.17The European Cooperative Acute Stroke Studies (ECASS I,II,and II)looked at the efficacy of IV alteplase within6hours of symptom onset.These studies did not show significant improvement in neurologic outcomes at3months in comparison with placebo.ECASS I used a dose of1.1mg/kg,a higher dose than the NINDS rtPA study,which led to a higher incidence of ICH(19.8%).13A lower dose of0.9mg/kg was used in ECASS II,and a lower ICH rate(8%)was observed,as well as a trend to-ward better outcome.14The ATLANTIS study began as an investigation of alteplase used within6hours of symptom onset.Because of safety concerns,the time window was shortened to5hours.15A pooled analy-sis of the ATLANTIS,ECASS,and NINDS trials showed beneficial effects of IV alteplase up to4.5 hours after symptom onset.There was no significant benefit when it was given between4.5to6hours.18 ECASS III showed that although overall symptom-atic ICH was higher in treated patients,the rate was not higher in patients treated within the approved 3-hour window and was not associated with in-First,streptokinase and urokinase;second,alteplase and prourokinase;third/fourth,rete-plase,tenecteplase,monteplase,desmoteplase,and lanoteplase(t-PAϭtissue plasmino-gen activator;PAI-1ϭplasminogen activator inhibitor1).creased mortality.The results were significant across multiple endpoints and showed efficacy of treatment despite an increased rate of hemorrhage within3to 4.5hours of symptom onset.19There is evidence from MRI protocols and several studies that IV thrombolysis beyond3hours in selected patients can be effective.20,21Prourokinase is a proenzyme precursor of uroki-nase.When activated by fibrin-associated plasmin,2 single-chain prourokinase units bind at the surface of the thrombus to form an active2-chain urokinase molecule.22The thrombolytic effect is enhanced by heparin,possibly through neutralization of thrombin or by stimulating tPA from the endothelium.23,24 Prourokinase was utilized for IA thrombolysis stud-ies in the mid-1990s.The Prolyse in Acute Cere-bral Thromboembolism(PROACT)trial evaluated IA infusion of prourokinase(6mg)vs placebo for treatment of middle cerebral artery(MCA)occlusion in patients who presented within6hours of symptom onset.25At90days,there was a10%to12%absolute increase in excellent neurologic outcome,defined as a modified Rankin Scale score of2or less,in the patients who received prourokinase compared with placebo.Symptomatic hemorrhages within the first 24hours occurred in15.4%of patients who received prourokinase,vs7.1%in the placebo group.The PROACT II trial compared patients who received an IA infusion of prourokinase(9mg)and low-dose heparin vs low-dose heparin alone within6hours of symptom onset for treatment of angiographically proven MCA occlusion.26Although early symptom-atic hemorrhage occurred in10%of the IA prouroki-nase group vs2%in the control group,there was a 15%absolute increase in favorable outcome with IA prourokinase.However,despite these results,prou-rokinase did not gain FDA approval for use in AIS.Although these second-generation agents may be beneficial,there are still a significant number of pa-tients who did not respond to treatment,had low recanalization rates,or had high rates of reocclusion.5 In addition,hemorrhagic complications occurred frequently when these agents were used.Due to the potentially poor clinical outcome,the need for newer thrombolytic agents with lower adverse profiles and possibly longer therapeutic windows remained. Third/fourth generation.Several third-and fourth-generation thrombolytics are being developed,in-cluding mutants of scuPA and tPA;chimeric plasminogen activators of these2molecules(ame-diplase);conjugates of plasminogen activators with monoclonal antibodies against fibrin,platelets,or thrombomodulin;and plasminogen activators of an-imal(vampire bat)or bacterial(Staphylococcus aureus) origin.27These agents have longer half-lives in plasma,allowing for single or repeated bolus injec-tions,as opposed to the continuous infusion required with the first-and second-generation thrombolytics. They have higher fibrin specificity and lower or no neurotoxicity,which may in turn lead to lower hem-orrhagic complications.5,12Staphylokinase is a highly fibrin-selective agent.It has a low affinity for plasminogen that is free or bound to intact fibrin,but it binds strongly to plas-min and to plasminogen that is bound to partially degraded fibrin.28This feature enables it to concen-trate on the surface of a lysing thrombus.The staphylokinase-plasmin complex is rapidly inhibited by␣2-antiplasmin in the absence of circulating fi-brin.When bound to fibrin,the complex is pro-tected from inhibition.Thus,staphylokinase acts as an indirect activator of plasminogen within a throm-bus.12,28Nevertheless,this agent has not been exten-sively studied for use in AIS.Tenecteplase is another third-generation agent that is more fibrin-specific than alteplase and may reduce the risk of systemic complications.29,30It has a longer half-life(15to19minutes)and greater resis-tance to plasminogen-activator inhibitor.5The“plas-minogen steal”effect that is seen with alteplase is not seen with tenecteplase,thus making it more effec-tive.30This phenomenon occurs when high levels of alteplase lower systemic plasminogen levels,which leads to a paradoxical diffusion of plasminogen out of the clot,thereby reducing clot lysis.12,31Tenecteplase has been tested in AIS patients in phase II trials.32,33At this point,the most beneficial dose of tenecteplase is unclear.A small pilot study using magnetic resonance angiography(MRA)and MRI perfusion-weighted imaging showed improved recanalization and reperfusion rates in15patients re-ceiving0.1mg/kg tenecteplase and35patients re-ceiving standard doses of tPA.32There were no cerebral hemorrhages in the tenecteplase group,but 4were seen in the tPA group.A recent phase IIB/III trial comparing0.1mg/kg,0.25mg/kg,and0.4 mg/kg tenecteplase with tPA was ended prematurely because of poor enrollment.34A total of112patients were randomized,and the0.4-mg/kg dose was dis-carded early because of inferiority and a higher rate of ICH.Optimal dose selection could not be made between the0.1mg/kg and0.25mg/kg doses be-cause of the termination of the study.34Reteplase is a deletion mutant of tPA5that lacks the terminal domains of alteplase,including the ter-minal finger,epidermal growth factor,and kringle1 domains.27As a result,reteplase does not bind strongly to fibrin,allowing unbound reteplase to penetrate the thrombus and promote lysis.It has a reduced affinity for binding to endothelial cells andmonocytes,which in turn leads to higher levels in the bloodstream.Reteplase has a longer half-life(15to18 minutes)than alteplase and may be given as a bolus.5It is used for IA thrombolysis in AIS.The first human clinical trial using this agent intra-arterially was reported in2001.35Sixteen patients who were poor candidates for IV alteplase were selected for therapy.Selection cri-teria included a time interval of3hours or longer from symptom onset or severe neurologic deficit on presenta-tion(NIH Stroke Scale[NIHSS]scores ranged from10 to26).This was primarily a dose escalation safety trial. Of the16treated patients,1had symptomatic ICH.A modified thrombolysis in myocardial infarction(TIMI) grading system was used,and the authors reported TIMI3or4(equivalent to the original TIMI grade3) recanalization rates in88%of patients.This high rate of recanalization was achieved even though8of16pa-tients presented with occlusion of either the cervical (nϭ4)or intracranial(nϭ4)internal carotid artery. Forty-four percent of patients had early neurologic im-provement(defined as a decrease of4or more points in the NIHSS score at24hours).However,further studies are necessary to evaluate the proper dosage and durabil-ity of reteplase for IA thrombolysis in AIS.Desmoteplase is a serine protease that naturally occurs in the saliva of the bat Desmodus rotundus.12It has pharmacologic and toxicologic properties supe-rior to human tPA,including a higher fibrin selectiv-ity,lower hemorrhagic transformation profile,longer half-life,and lack of NMDA-mediated neurotoxic-ity,in comparison with alteplase.12,35,36The Des-moteplase in Acute Ischemic Stroke Trial(DIAS) was an MRI-based phase II study.DIAS was con-ducted to explore the safety and efficacy of various doses of IV desmoteplase in patients with AIS and evidence of perfusion/diffusion mismatch with symptom onset between3and9hours.37Results showed a higher rate of reperfusion(71.4%)and a favorable90-day clinical outcome(60.0%)com-pared to placebo(19.2%and22.2%,respectively), and a low rate of symptomatic intracranial hemor-rhage using doses up to125␮g/kg.37The phase III DIAS-2study failed to show the same benefits.This was believed to be related to the inclusion of a large number of patients with mild strokes at baseline and no vessel occlusion,as well as a high response rate among placebo-treated patients.38However,post hoc analysis showed a positive response in patients who had a proximal cerebral vessel occlusion or high-grade stenosis on baseline angiography.39DIAS-3 and DIAS-4phase III trials are currently underway to evaluate patients with AIS related to occlusion or high-grade stenosis of proximal arteries,as assessed by MRA or CT angiogram.40Ancrod is a biological agent extracted from the venom of the Malayan pit viper that reduces blood fibrinogen levels.41It induces defibrinogenation in humans by cleaving fibrinopeptide A from fibrino-gen,thus depleting the substrate needed for throm-bus formation.This substrate depletion indirectlyThe left internal carotid injection demonstrated complete occlusion of the middle cerebral artery M1segment(thrombolysis in cerebral ischemia score[TICI]0),treated with intra-arterial recombinant tissue plasminogen activator for a total of22mg,with complete recanalization (TICI3)and near-complete clinical improvement to an NIH Stroke Scale score of2.The middle illustration depicts a disrupted clot with a greater surface area.A longer half-life may further enhance clot lysis,as is the case with newer-generation thrombolytics.leads to anticoagulation and decreased blood viscos-ity,which later helps with improving circulation to affected areas.12,42–45Products of defibrinogenation may also enhance local clot-specific thrombolysis by stimulating endogenous plasminogen activators.46 Two small trials of ancrod for AIS in the1980s sug-gested that it was safe and beneficial in stroke pa-tients.47,48On the basis of these promising results,the Stroke Treatment with Ancrod Trial(STAT)was conducted.44In this study,500patients who pre-sented within3hours of symptom onset were ran-domized to receive ancrod or placebo as a continuous infusion over72hours and1-hour infusions at96 and120hours.Patients in the ancrod group had a more favorable functional outcome(42.2%)than the placebo group(34.4%)(pϭ0.04).There appeared to be more symptomatic intracranial hemorrhages in the ancrod group(5.2%)vs placebo recipients (2.0%)(pϭ0.06),but the difference was not statis-tically significant.A follow-up clinical trial,in which 500subjects with AIS were randomized within6 hours of symptoms to ancrod at0.167IU/kg IV per hour vs placebo for2to3hours,showed no differ-ence in clinical outcome between the2groups.49A favorable functional outcome at39.6%in the treat-ment arm vs37.2%(pϭ0.47)was found.49Intra-arterial delivery.Despite the improvement in functional outcome in stroke patients who receive IV rtPA,a large number of patients(57%to58%)die or become dependent despite treatment.13,16,50,51This has prompted a search for better drugs and modali-ties of delivery that will achieve higher and quicker rates of recanalization with minimal risk to the pa-tient.IA thrombolysis involves administration of high concentrations of thrombolytic agents near the thrombus,utilizing lower doses than systemic ad-ministration.This may result in lower systemic com-plications,including extracranial hemorrhages (figure2),and minimizing local neurotoxic effects of these agents.5This approach also allows the simulta-neous use of mechanical devices to facilitate throm-bolysis(figure3).5,52,53Combining the IA delivery with mechanical thrombectomy increases the surface area exposed to the thrombolytic agents(figure2). The disadvantages of the IA modality include the potential delay required to obtain initial cerebral an-giography and position of the microcatheter for ad-ministration of the thrombolytic agent.These concerns led to the initiative of delivering the IA thrombolysis following IV thrombolysis.The Emer-gency Management of Stroke(EMS)bridging trial, which had a randomized,double-blind,placebo-control design,demonstrated higher recanalization rates(53%)in the combined IV/IA alteplase treat-ment group than in the IA alteplase group(28%).54 There was no difference in clinical outcomes be-tween the2groups and no significant difference in the rate of symptomatic ICH.This suggested the fea-sibility of the combined treatment.Although in some centers the IA approach is favored in a subset of pa-tients who are expected to have limited response to IV treatment,including those with severe neurologic deficits,those presenting between3and6hours of symptom onset,those who have a history of major surgery within the previous2weeks,and those with occlusion of major cervical or intracranial vessels,this has yet to be proven in controlled trials.51Another combined approach involves using IA treatment initially to maximize the rate of recanaliza-tion,followed by IV infusion to increase the efficacy of the treatment.55This approach was studied but the results were inconclusive.12Thrombolytics are also known to activate throm-bin,which promotes platelet adhesion and poten-tially reocclusion of patent vessels.56No conclusive data on combining the IA thrombolysis delivery with a glycoprotein IIb/IIIa platelet receptor inhibitor via an IA or IV route exist.However,a glycoprotein IIb/ IIIa receptor inhibitor,abciximab,was evaluated for safety and efficacy in AIS.The Abciximab in Isch-emic Stroke pilot study was a randomized,double-blind,placebo-controlled,dose-escalation trial, where4escalated doses of IV abciximab were admin-istered up to24hours after stroke onset.57It showed a relatively low risk of ICH(7%)and a trend toward improved outcome after30days.It was concluded that abciximab was safe to use within24hours after stroke onset.However,the trial failed toCtlϭcontrol;IAϭintra-arterial;IMSϭInterventional Management of Stroke;MELTϭMiddle cerebral artery Embolism Local fibrinolytic intervention Trial;mRSϭmodified Rankin Scale score;NINDSϭNational Institute of Neurological Disorders and Stroke;PRO-ACTϭProlyse in Acute Cerebral Thromboembolism.demonstrate safety or efficacy of IV abciximab;in fact,there was an increased rate of symptomatic or fatal hemorrhage.58DISCUSSION IA fibrinolysis is an effective AIS therapy within6hours of symptom onset,in comparison with placebo.A meta-analysis of IA thrombolysis studies showed that this approach substantially increases recan-alization rates and good clinical outcomes in AIS.59A higher rate of ICH was not associated with any increase in mortality(figure4).59Future directions.The best way of delivering IA fi-brinolysis—alone,in combination with mechanical thrombectomy,as systemic thrombolysis,or fol-lowed by antiplatelet therapy—remains to be deter-mined after further study.The development of newer-generation thrombo-lytic agents,safer and more effective for treating AIS, is needed.This may be accomplished by increased fibrin specificity,rapid onset of action,and shorter half-life to improve on safety.AUTHOR CONTRIBUTIONSDr.Kirmani:study concept or design,study supervision.Dr.Alkawi: drafting/revising the manuscript,study concept or design,analysis or in-terpretation of data,acquisition of data,study supervision.Dr.Panezai: drafting/revising the manuscript.Dr.Gizzi:drafting/revising the manu-script,study supervision.DISCLOSUREDr.Kirmani has served on the Editorial Board of Frontiers in Endovascular and Interventional Neurology.Dr.Alkawi,Dr.Panezai,and Dr.Gizzi re-port no disclosures.Go to for full disclosures.Received July9,2011.Accepted in final form February23,2012.REFERENCES1.National Center for Health Statistics.Deaths:leadingcauses(data for US in2009).Available at:http://www.cdc.gov/nchs/fastats/lcod.htm.2.Kalache A,Aboderin I.Stroke:the global burden.HealthPolicy Plan1995;10:1–21.3.Murray CJ,Lopez AD.Global mortality,disability,andthe contribution of risk factors:Global Burden of Disease ncet1997;349:1436–1442.4.Liebeskind DS.Reperfusion for acute ischemic stroke:ar-terial revascularization and collateral therapeutics.Curr Opin Neurol2010;23:36–45.5.Qureshi AI,Pande RU,Kim SH,Hanel RA,Kirmani JF,Yahia AM.Third generation thrombolytics for the treat-ment of ischemic stroke.Curr Opin Investig Drugs2002;3:1729–1732.6.Zivin JA.Thrombolytic stroke therapy:past,present,andfuture.Neurology1999;53:14–19.7.Cornu C,Boutitie F,Candelise L,et al.Streptokinase inacute ischemic stroke:an individual patient data met-analysis.Stroke2000;31:1555–1560.8.MAST-I Trial Investigators.Randomised controlled trial ofstreptokinase,aspirin,and combination of both in treatment of acute ischaemic stroke:Multicentre Acute Stroke Trial–Italy(MAST-I)ncet1995;346:1509–1514.9.Donnan GA,Hommel M,Davis SM,McNeil JJ.Strepto-kinase in acute ischaemic stroke:Steering Committees of the ASK and MAST-E trials:Australian Streptokinase ncet1995;346:56.10.Thrombolytic therapy in thrombosis:a National Institutesof Health consensus development conference.Ann Intern Med1980;93:141–144.11.Kaur J,Zhao Z,Klein GM,Lo EH,Buchan AM.Theneurotoxicity of tissue plasminogen activator?J Cereb Blood Flow Metab2004;24:945–963.12.Donnan GA,Howells DW,Markus R,Toni D,Davis SM.Can the time window for administration of thrombolytics in stroke be increased?CNS Drugs2003;17:995–1011.13.Hacke W,Kaste M,Fieschi C,et al.Intravenous thrombolysiswith recombinant tissue plasminogen activator for acute hemispheric stroke:The European Cooperative Acute Stroke Study(ECASS)[see comment].JAMA1995;274:1017–1025.14.Hacke W,Kaste M,Fieschi C,et al.Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke(ECASS II): Second European-Australasian Acute Stroke Study Investi-gators[see comment].Lancet1998;352:1245–1251. 15.Clark WM,Wissman S,Albers GW,Jhamandas JH,Mad-den KP,Hamilton S.Recombinant tissue-type plasmino-gen activator(alteplase)for ischemic stroke3to5hours after symptom onset:the ATLANTIS study:a randomized controlled trial:Alteplase Thrombolysis for Acute Nonin-terventional Therapy in Ischemic Stroke[see comment].JAMA1999;282:2019–2026.16.The National Institute of Neurological Disorders and Strokert-PA Stroke Study Group.Tissue plasminogen activator for acute ischemic stroke.N Engl J Med1995;333:1581–1587.17.Marler JR,Tilley BC,Lu M,et al.Early stroke treatmentassociated with better outcome:the NINDS rt-PA Stroke Study.Neurology2000;55:1649–1655.18.Hacke W,Donnan G,Fieschi C,et al.Association of out-come with early stroke treatment:pooled analysis of ATLANTIS,ECASS,and NINDS ncet2004;363:768–774.19.Hacke W,Kaste M,Bluhmki E,et al.,for ECASS III Investi-gators.Thrombolysis with alteplase3to4.5hours after acute ischemic stroke.N Engl J Med2008;359:1317–1329. 20.Schellinger PD,Kaste M,Hacke W.An update on throm-bolytic therapy for acute stroke.Curr Opin Neurol2004;17:69–77.21.The Internet Stroke Center,Stroke Trials Directory.Avail-able at:/trials/TrialDetail.asp?refϭ475&browseϭsearch.Accessed December28,2009. 22.Pannell R,Gurewich V.Pro-urokinase:a study of its sta-bility in plasma and of a mechanism for its selective fi-brinolytic effect.Blood1986;67:1215–1223.23.Tebbe U,Windeler J,Boesl I,et al.Thrombolysis withrecombinant unglycosylated single-chain urokinase-type plasminogen activator(saruplase)in acute myocardial infarction:influence of heparin on early patency rate (LIMITS study):Liquemin in Myocardial Infarction During Thrombolysis With Saruplase.J Am Coll Car-diol1995;26:365–373.24.Gurewich V,Liu JN.Intra-arterial pro-urokinase in isch-emic stroke.Stroke1998;29:1255–1256.25.del Zoppo GJ,Higashida RT,Furlan AJ,Pessin MS,Row-ley HA,Gent M.PROACT:a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in。

Analysis of Multistage Amplifier–FrequencyCompensationKa Nang Leung and Philip K.T.Mok,Member,IEEEAbstract—Frequency-compensation techniques of single-,two-and three-stage amplifiers based on Miller pole splitting and pole–zero cancellation are reanalyzed.The assumptions made, transfer functions,stability criteria,bandwidths,and important design issues of most of the reported topologies are included. Several proposed methods to improve the published topologies are given.In addition,simulations and experimental results are provided to verify the analysis and to prove the effectiveness of the proposed methods.Index Terms—Damping-factor-control frequency compen-sation,multipath nested Miller compensation,multipath zero cancellation,multistage amplifier,nested Gm-C compensation, nested Miller compensation,simple Miller compensation.I.I NTRODUCTIONM ULTISTAGE amplifiers are urgently needed with the advance in technologies,due to the fact that single-stage cascode amplifier is no longer suitable in low-voltage designs. Moreover,short-channel effect of the sub-micron CMOS transistor causes output-impedance degradation and hence gain of an amplifier is reduced dramatically.Therefore,many frequency-compensation topologies have been reported to stabilize the multistage amplifiers[1]–[26].Most of these topologies are based on pole splitting and pole–zero can-cellation using capacitor and resistor.Both analytical and experimental works have been given to prove the effectiveness of these topologies,especially on two-stage Miller compen-sated amplifiers.However,the discussions in some topologies are focused only on the stability criteria,but detailed design information such as some important assumptions are missing. As a result,if the provided stability criteria cannot stabilize the amplifier successfully,circuit designers usually choose the parameters of the compensation network by trial and error and thus optimum compensation cannot be achieved.In fact,there are not many discussions on the comparison of the existing compensation topologies.Therefore,the differences as well as the pros and cons of the topologies should be inves-tigated in detail.This greatly helps the designers in choosing a suitable compensation technique for a particular design condi-tion such as low-power design,variable output capacitance or variable output current.Manuscript received March9,2000;revised February6,2001.This work was supported by the Research Grant Council of Hong Kong,China under grant HKUST6007/97E.This paper was recommended by Associate Editor N.M.K. Rao.The authors are with the Department of Electrical and Electronic Engineering, The Hong Kong University of Science and Technology,Clear Water Bay,Hong Kong(e-mail:eemok@t.hk).Publisher Item Identifier S1057-7122(01)07716-9.Moreover,practical considerations on the compensation tech-niquesof(a)(b)(c)(d)(e)(f)(g)(h)(i)(j)Fig.1.Studied and proposed frequency-compensation topologies.(a)SMC.(b)SMCNR.(c)MZC.(d)NMC.(e)NMCNR.(f)MNMC.(g)NGCC.(h)NMCF.(i)DFCFC1.(j)DFCFC2.accuracy.In this paper,there are three common assumptionsmade for all studied and proposed topologies.1)The gains of all stages are much greater than one(i.e.,LEUNG et al.:ANALYSIS OF MULTISTAGE AMPLIFIER–FREQUENCY COMPENSATION1043 Assumption1holds true in amplifier designs for most ampli-fiers except those driving small load resistance.If this assump-tion cannot be satisfied,numerical analysis using computers isrequired.Moreover,the parasitic capacitances of the tiny-geom-etry transistors in advanced technologies are small and this val-idates assumptions2)and3).III.R EVIEW ON S INGLE-S TAGE A MPLIFIERThe single-stage amplifier is said to have excellent frequencyresponse and is widely used in many commercial products.Infact,the advantages can be illustrated by its transferfunctiondue to the single pole,assuming thatGBW(i.e.,andminimum.Therefore,a higher bias current and smaller size for all transis-tors in the signal path are required tolocateand the RHP zeroislocates beforepp pp ppz ppp p1044IEEE TRANSACTIONS ON CIRCUITS AND SYSTEMS—I:FUNDAMENTAL THEORY AND APPLICATIONS,VOL.48,NO.9,SEPTEMBER2001Fig.3.PM versus g=gof a SMC amplifier.From (6)and Fig.3,the PM of a SMC amplifier strongly de-pends ontheto ratio and this,in fact,shows the RHP zero effect on the PM.Physically,the presence of the RHP zero is due to the feedforward small-signal current flowing throughthe compensation capacitor to the output [1]–[11].Ifis large,the small-signal output current is larger than the feed-forward current and the effect of the RHP zero appears only at very high frequencies.Thus,asmallis preferable.However,is limited bythe bias current and size of the input differential pair.To have a good slew rate,the bias current cannot be small.In addition,to have a small offset voltage,the size of input differential pair cannot be too small.Emitter/source degeneration technique isalso not feasible toreducesince it reduces the limited input common-mode range in low-voltage design.Therefore,asmallcannot be obtained easily.From the previous analysis,it is known that the RHP zero degrades the stability significantly.There are many methods to eliminate the RHP zero and improve the bandwidth.The methods involve using voltage buffer [4]–[6]and current buffer [7],[8],a nulling resistor [2],[3],[9]–[11],and MZC technique [12].In this paper,the techniques to be discussed are:1)SMC using nulling resistor (SMCNR)and 2)SMC using MZC.A.SMCNRThe presence of the RHP zero is due to the feedforward small-signal current.One method for reducing the feedforward current and thus eliminating the RHP zero is to increase the impedance of the capacitive path.This can be done by inserting a resistor,called nulling resistor,in series with the compensation capacitor,as shown in Fig.1(b).Most published analyses only focus on the effect of the nulling resistor to the position of the zero but not to the positions of the poles.In fact,when the nulling resistor isincreased to infinity,the compensation network is open-circuit and no pole splitting takes place.Thus,the target of this section is to investigate the limit of the nulling resistor.The transfer function of the SMNCR(,,respectively.It is well-known thatwhenis generally much smallerthananddue to theabsence of the RHP zero.However,many designers prefer to use a nulling resistor withvalue largerthansince an accurate valueofandis not a con-stant and a precise cancellation of the RHP zero by afixed)to cancel the feedforward small-signal current(,,which is independentof.(7)LEUNG et al.:ANALYSIS OF MULTISTAGE AMPLIFIER–FREQUENCY COMPENSATION1045 Moreover,since MZC does not change the positions of thepoles,the same dimension condition ofwhich is obtained by neglecting the RHP zerophase shifting term in(6).Besides,when the output current isincreased,is increased accordingly.The nondominant pole()will move to a higher frequency and a largerPM is obtained.Thus,this compensation topology can stabilizethe amplifier within the quiescent to maximum loading currentrange.In some applications,whereand the PM is about90andand.Apparently,the GBW can be increased to infinity bydecreasingto validate the assumptions on deriving(8),so the fol-lowing condition is required as a compromise:,the transfer function is rewritten as(11),shownat the bottom of the page.The dominant pole is1046IEEE TRANSACTIONS ON CIRCUITS AND SYSTEMS—I:FUNDAMENTAL THEORY AND APPLICATIONS,VOL.48,NO.9,SEPTEMBER2001Fig.5.Equivalent small-signal model of three-stage NMC.From the above equation,GBW.Assuming,and are fixed for a given power consumption,largeand are required.This increases the PM but itreduces the GBW and also increases the capacitor values andthe required chip area simultaneously.For the complex-pole approach,the NMC amplifier in unity-feedback configuration should have the third-order Butterworthfrequency response.Let be the closed-loop transferfunctionandshould be in the followingformat:and areobtained:(or)and the damping factor of the complexpoleis(17)which is one-fourth the bandwidth of a single-stage amplifier.This shows the bandwidth reduction effect of nesting compen-sation.Similar to SMC,the GBW can be improved by alargerand asmaller and asmaller.The PM under the effect of a complex pole[28]is givenbyPM(18)Comparing the required compensation capacitors,the GBWand PM under the same power consumption(i.e.,same,and)of the two approaches,it is concluded that thecomplex-pole approach is better.Moreover,from(15)and(16),smallerand are neededwhen.This validates the previous assumption on neglecting the zerossince the coefficients of the function of zero in(10)are smalland the zeros locate at high frequencies.From another pointof view,therequiredand are small,so the feedfor-ward small-signal current can pass to the output only at veryhigh frequencies.In addition,the output small-signal current ismuch larger than the feedforward currentas.Thus,the zeros give negligible effect to the stability.If theseparate-pole approach is applied,the stability is doubtful sincelarger compensation capacitors are required and this generateszeros close to the unity-gain frequency of the amplifier.To further provethat is necessary inNMC,a HSPICE simulation using the equivalent small-signalmodel of NMC,which is shown in Fig.5,is performed.The cir-cuit parametersare A/V,A/V,is satisfied)and10pF.and,which is set according to(15)and(16),are4pFand1pF,respectively.The simulation result is shown in Fig.6by the solid line.A GBW of4.2MHz and a PM of58from100is notmuch largerthan),therequired is changed from4pFto40pF,according to(15).The frequency response is shownby the dotted line in Fig.6.A RHP zero appears before theunity-gain frequency and causes the magnitude plot to curveupwards.The PM is degraded to30ischanged from50is not much largerthan)and is changed from1pF to20pF accordingto(16).As shown by the dashed line in Fig.6,a frequencypeak,due to small damping factor of the complex pole,appearsand makes the amplifier unstable.The phenomenon can be ex-plained from(10).When is not much largerthan,theterm()of the second-order function in the denomi-nator is small and this causes the complex poles to have a smallLEUNG et al.:ANALYSIS OF MULTISTAGE AMPLIFIER–FREQUENCY COMPENSATION1047Fig.6.HSPICE simulation of NMC (solid:g g and g ;dotted:g is not much larger than g ;dash:g is not much larger than g ).damping factor.Ifis very important and critical to the stability of an NMCamplifier.However,this condition is very difficult to achieve,especially in low-power design.Ifdoes not hold true,the analysis should be re-started from (10).Fromthis equation,sincetheterm is negative,there are one RHP zero and one LHP zero.The RHP zero locates at a lower fre-quency astheand only a LHPzeroand any value closedto is able to locate the RHP zero to a high frequency.Bydefining,the transfer function is rewritten as (20)shownat the bottom of the page.It is notedthatand are obtained as in NMC usingcomplex-pole approach and are givenby(i.e.,1048IEEE TRANSACTIONS ON CIRCUITS AND SYSTEMS—I:FUNDAMENTAL THEORY AND APPLICATIONS,VOL.48,NO.9,SEPTEMBER2001Fig.7.Circuit diagram of the amplifiers(a)NMCNR.(b)NMCF.(c)DFCFC1.(d)DFCFC2.).The GBW is given byGBWdue to the LHP zero.A larger GBW can be obtained byslightly reducing but this reduces the PM.To prove the proposed structure,NMC and NMCNR am-plifiers were implemented in AMS10.8.The circuit diagram of the NMCNR amplifiersare shown in Fig.7(a)and the NMC counterpart has the samecircuitry without the nulling resistor.The chip micrograph isshown in Fig.8.Both amplifiers drive a100pF//25knulling resistor,which is made of poly,is used in the NMCNRamplifier.In NMC,the required is99pF,but inNMCNR is63pF.As presented before,the PM of NMCNRamplifier is larger,so a smaller is used in the implemen-tation to obtain a similar PM as in NMC and a larger GBW.Moreover,this greatly reduces the chip area from0.23mm.The measured results and improvement comparison are tabu-lated in Tables I and II,respectively.Both amplifiers haveW power consumption and)are improvedby+39%,+3is improvedLEUNG et al.:ANALYSIS OF MULTISTAGE AMPLIFIER–FREQUENCY COMPENSATION 1049TABLE IM EASURED R ESULTS OF THE AMPLIFIERSTABLE III MPROVEMENT OF THE P ROPOSED AND P UBLISHED T OPOLOGIES W ITH NMC (,and the chip area.VI.MNMCBesides increasing the power,the multipath technique can be used to increase the bandwidth of an amplifier.In MNMC[12],[16],[19],and [26],a feedforward transconductance stage (FTS)is added to the NMC structure to create a low-fre-quency LHP zero.This zero,called multipath zero,cancels the second nondominant pole to extend the bandwidth.The structure of MNMC is shown in Fig.1(f)and it is limited to three-stage amplifiers but it has potential to extend to more stages.However,power consumption and circuit complexity are increased accordingly since a feedforward input differ-ential stage,as same as MZC,is needed,so this will not be discussed here.The input of the FTS,withtransconductanceand the output is connected to the input of theoutput stage.Again,with the conditionthat,the transfer function is given by (23)at the bottom of the next page.The nondominant poles are givenby1050IEEE TRANSACTIONS ON CIRCUITS AND SYSTEMS—I:FUNDAMENTAL THEORY AND APPLICATIONS,VOL.48,NO.9,SEPTEMBER2001Fig.9.Simulation results of an MNMC amplifier using equivalent small-signal circuit under the change of g andC =20pF;dash:g =10mA/V andC =1pF)..The explicit dimensionconditionofis,therefore,givenbyin MNMC is much larger thanthat in NMC.This increases the required chip area and reduces the SR dramatically.Therefore,emitter degeneration technique was used in the design of [16].This can reduce theeffective so thatthe is,as a result,smaller.With (24),the positionsofis thefollowing:.The above analysis gives the required valuesof,and,,and.In fact,if this assumption does nothold true,the positions of the poles and the LHP zero are not those previously stated.Moreover,a RHP zero exists and the stability is greatly affected.The analysis and dimension conditions are obtained in static state.Since there is a pole–zero doublet before the unity-gain frequency,the dynamic-state stability should also be consid-ered.Since,in practice,the loading current andcapacitancemay change in some general-purpose amplifiers with Class-AB output stage,it is necessary to consider the stability of theMNMC amplifierwhenis increasedand ,where the ratio isobtained from (24)and (26).Besides,the multipath zero is notchangedwhenand with the condition in (27).It is obviousthat,so MNMC is not affected by changing the loading current and capacitance.To prove the above arguments,a simulation using HSPICE is performed with the equivalent small-signal circuit of an MNMCamplifier.The circuit parametersareA/V,,1M25k 20p F.T h u s,111.25i s c h a n g e d f r o m 1m A /V t o 10m A /V ;a n d 2)a nd i s i n c re a s e d or a r e r e q u i r e d .T h i s c o n d i t i o n n o t o n l y i m -p r o v e s t h e s t a b i l i t y b u t i t a l s o s i m p l i f i e s t h e t r a n s f e r f u n c t i o n .I n f a c t ,a s m e n t i o n e d b e f o r e ,t h i s c o n d i t i o n i s d i f f i c u l t t o a c h i e v e i n l o w -p o w e r d e s i g n ,s o Y o u e t a l .i n t r o d u c e d N G C C [20].N G C C i s a n-s t a g e N G C Ca m p l i f i e r.W i t h t h e c o n d i t i o n t h at w e re ,t h e g e n e r a lf o r m o f a n-s t a g e a m p l i f i e r t h a n N M C .I n t h e s t a b i l i t y c o n d i t i o n s p r o p o s e d b y Y o u e t a l .,t h e s e p a r a t e d -p o l e a p p r o a c h i s u s e d a n d t h e n o n d o m a r e s e t t o s o m e f r e q u e n c i e s s u c h t h a t t h e G B W ,T s a nd p o we r c o n s u m p t i o n a r e a l l o p t i m i z e d .U n d o u b t e d l y ,t h c a t e d t o d o o p t i m i z a t i o n a n a l y t i c a l l y ,s o n u m e u s i n g M A T L A B i s r e q u i r e d .H o w e v e r ,q u e s t i o n s o n p r a c t i c a l c o n s i d e r a t i o n s ,s i n c e i t i s p r ef e r a m i n i m u m s t ag e s a s p o s s i b l e .A s s t a t e d b e f o r e ,t a n o p t i m u m n u m b e r o n d c g a i n ,b a n d w i d th ,a n d s u m p ti o n .T h e r e f o r e ,t h e a n a l y s i s i n t h i s s e c t i o n t h e t h r e e -s t a g e N G C C a m p l i f i e r.T h e s t r u c t u r e oN G C C a m p l i f i e r i s s h o w n i n F i g .1(g )a n d t h e t r a ni s g i v e n b y (29)s h o w n a t t h e b o t t o m o f t h e p a g eb e f o r e a n d a l s o f r o m t h e n u m e r a t o r o f (29),t h e b e e l i m i n a t e d b y s e t t i n g a nd .T h et r a n s f e r f u n c t i o n i s t h e n s i m p l i f i e d t o (30)s h o wo f t h e p a g e .T h e a r r a n g e m e n t o f t h e p o l e s c a n u ss e p a r a t e -p o l e o r c o m p l e x -p o l e a p p r o a c h b u t t h ep r e f e r r e d .I t i s o b v i o u s t h a t t h e d e n o m i n a t o r o s a m e a s (11)b u t t h e d i f f e r e n c e i s t h a t i s n o t r e q u i r e d i n N G C C .T h u s,.A l t h o u g h N G C C i s g o o d i n l o w -p o w e r d e s i g n s ,s t a g e F T S (i .e .,some of them are LHP zeros which,in fact,help to increase the PM.With regard to the above considerations,a new structure, called NMC with feedforward Gm stage(NMCF),is proposed and shown in Fig.1(h).There are only two differences betweenNMCF and NGCC:1)the input-stage FTS is removed and2).Bydefiningand are obtained using thecomplex-pole approach and they are givenby,are smaller than those in NMC,MNMC and NGCCsinceterm is positive andthe term is negative,the LHPzerolocates before the RHPzerofor stability purpose,so the following condition isrequired:(34)The condition states the minimum valueof to obtain anoptimum control of LHP zero.From(31)to(33),the GBW and PM are given byGBW(35)andPM(36)It is shown in(35)that the bandwidth is improved by the pres-enceofmCMOS process was done to prove the proposed structure.TheNMCF amplifier is shown in Fig.7(b)and it is basically thesame as the NMC amplifier.It is noted that the gate of M32,which is the FTS,is connected to the output of the first stage.The output stage is of push-pull typeand,from(35),to double the GBW.The measured results and improvement comparison areshown in Tables I and II,respectively.It is obvious that theimprovement of NMCF over NMC on GBW(),PM()and occupied chip area()are much larger than those in MNMC and NGCCin other designs,which are shown in Table II.The powerconsumption is only increased by6and inverselyproportionaltois removed and the bandwidth of the ampli-fier can be extended substantially.However,the damping factorof the nondominant complex poles,which is originally con-trolledby,cannot be controlled and a frequency peak,which causes the closed-loop amplifier to be unstable,appearsin the magnitude Bode plot[23].To control the damping factorand make the amplifier stable,a damping-factor-control(DFC)block is added.The DFC block is basically a gain stage withdc gain greater than one(i.e.,.The DFC block functions as a frequency-de-pendent capacitor and the amount of the small-signal currentinjected into the DFC block depends on the valueofand(transconductance of the gain stage inside the DFC block).Hence,the damping factor of the nondominant complex polescan be controlled byoptimumand and this makesthe amplifier stable.There are two possible positions to add theDFC block and they are shown in Fig.1(i)for DFCFC1andFig.1(j)for DFCFC2.In addition,both structures have a feed-forward transconductance stage to form a push-pull output stagefor improving large-signal slewing performance.For DFCFC1,the transfer function is given by(37)shown atthe bottom of the next page.It can be seen from(37)that thedamping factor of the nondominant poles can be controlledby.Moreover,the effectofandtransfer functionbut is limitedto tovalidate (37).Sinceis small,the amplifier is not slowed downby.From (37),there are three poles,so the com-plex-pole approach is used.Moreover,since it is preferable to have the same output current capability for boththe -transistor of the output stage,the sizes ofthe -tran-sistor are used in ratio of 3to 1to compensate for the differ-ence in the mobilities of the carriers.Thus,it is reasonable toset,so the dimension conditions are givenby (39)whereis much smaller thanthat in the previous nesting topologies,so the SR is also greatly improved,assuming that the SR is not limited by the outputstage.Moreover,is a decreasing functionof (41)and the PM is about 60times.Ifa little,butthis reduces the PM as a tradeoff.For DFCFC2,bysettingwith the same reason stated previously,the transfer function is given by (42)shown at the bottom of the page.Similar to DFCFC1,the complex-poleapproach is used to achieve the stability.Therefore,the dimen-sion conditions are givenby(43)is a fixed value and is four timesof.Thus,the power consumption of DFCFC2amplifier with certain valueof.Although it is difficult to comparethe GBW of DFCFC2with other topologies since the format is different,it is in general better than others.It is due to the fact that the GBW is inversely proportion to the geometric meanof,which gives a smaller valuethan mdouble-metal double-poly CMOS process.The circuit diagrams are shown in Fig.7(c)for DFCFC1and Fig.7(d)for DFCFC2.The micrograph is,again,shown in Fig.8.In both amplifiers,M41andform the DFC block and M32is the FTS.Moreover,from Table II,the GBW,PM,SR,TIX.S UMMARY OF S TUDIED F REQUENCY C OMPENSATIONT OPOLOGIESA summary on the required stability conditions,resultant GBW and PM for all studied and proposed topologies are given in Table parisons on the topologies are tabulated in Table IV.Moreover,some important points derived from the previous analyzes are summarized as follows.1)The stability-dimension conditions of all topologies arebased on the assumptions stated in Section II.If the as-sumptions cannot be met,numerical method should be used to stabilize the amplifiers.2)With the exception of the single-stage amplifier,alargerandlargestandreducingto ratio and asmallerto ratio.6)For high-speed applications,a larger bias current shouldbe applied to the output stage toincrease.Fig.10.Local feedback circuitry to control the dc operating point of the DFCblock.X.R OBUSTNESS OF THE S TUDIED F REQUENCY C OMPENSATION In IC technologies,the circuit parameters such as transcon-ductance,capacitance and resistance vary from run to run,lot to lot and also according to temperature.The robustness of fre-quency compensation is very important to ensure the stabilities of multistage amplifiers.From the summary in Table III,the required values of com-pensation capacitors depend on the ratio of transconductances of gain stages explicitly for SMC,SMCNR,MZC1,MZC2,NMC,NMCNR,MNMC,NGCC,NMCF,and DFCFC1and implicitly for DFCFC2.The ratio maintains constant for any process varia-tion and temperature effect with good bias current matching and transistor size matching (due to design).One important point is that the valueof50%,in general is not significantto the stability.In MNMC,pole–zero cancellation is used.However,the su-perior tracking technique in MNMC is due to the pole–zero can-cellation based on the ratios of transconductances and compen-sation capacitances.Thus,process variations do not affect the compression of the pole–zero doublet.Although the robustness of the studied topologies are good,the exact value of the GBW will be affected by process varia-tions.Referring to Table III,the GBW’s of all topologies,in-cluding commonly used single-stage and Miller-compensated amplifiers,depend on the transconductance of the output stage.Thus,the GBW will change under the effect of process varia-tions and temperature.XI.C ONCLUSIONSeveral frequency-compensation topologies have been investigated analytically.The pros and cons as well as the design requirements are discussed.To improve NMC and NGCC,NMCNR,and NMCF are proposed and the improved performance is verified by experimental results.In addition,DFCFC has been introduced and it has much better frequency and transient performances than the other published topologies for driving large capacitive loads.Finally,robustness of the studied topologies has been discussed.R EFERENCES[1]J.E.Solomon,“The monolithic op amp:A tutorial study,”IEEE J.Solid-State Circuits ,vol.9,pp.314–332,Dec.1974.[2]P.R.Gray and R.G.Meyer,Analysis and Design of Analog IntegratedCircuits ,2ed.New York:Wiley,1984.[3]W.-H.Ki,L.Der,and m,“Re-examination of pole splitting of ageneric single stage amplifier,”IEEE Trans.Circuits Syst.I ,vol.44,pp.70–74,Jan.1997.[4]Y.P.Tsividis and P.R.Gray,“An integrated NMOS operational amplifierwith internal compensation,”IEEE J.Solid-State Circuits,vol.SC-11, pp.748–753,Dec.1976.[5]G.Smarandoiu,D.A.Hodges,P.R.Gray,and ndsburg,“CMOSpulse-code-modulation voice codec,”IEEE J.Solid-State Circuits,vol.SC-13,pp.504–510,Aug.1978.[6]G.Palmisano and G.Palumbo,“An optimized compensation strategyfor two-stage CMOS OP AMPS,”IEEE Trans.Circuits Syst.I,vol.42, pp.178–182,Mar.1995.[7] B.K.Ahuja,“An improved frequency compensation technique forCMOS operational amplifiers,”IEEE J.Solid-State Circuits,vol.SC-18,no.6,pp.629–633,Dec.1983.[8]G.Palmisano and G.Palumbo,“A compensation strategy for two-stageCMOS opamps based on current buffer,”IEEE Trans.Circuits Syst.I, vol.44,pp.257–262,Mar.1997.[9] D.Senderowicz,D.A.Hodges,and P.R.Gray,“High-performanceNMOS operational amplifier,”IEEE J.Solid-State Circuits,vol.SC-13, pp.760–766,Dec.1978.[10]W.C.Black Jr,D.J.Allstot,and R.A.Reed,“A high performance lowpower CMOS channel filter,”IEEE J.Solid-State Circuits,vol.15,pp.929–938,Dec.1980.[11]P.R.Gray and R.G.Meyer,“MOS operational amplifier design—a tu-torial overview,”IEEE J.Solid-State Circuits,vol.SC-17,pp.969–982, Dec.1982.[12]R.G.H.Eschauzier and J.H.Huijsing,Frequency Compensation Tech-niques for Low-Power Operational Amplifiers.Boston,MA:Kluwer, 1995.[13] E.M.Cherry,“A new result in negative feedback theory and its applica-tions to audio power amplifier,”Int.J.Circuit Theory Appl.,vol.6,no.3,pp.265–288,1978.[14],“Feedback systems,”U.S.Patent4243943,Jan.1981.[15] F.N.L.Op’t Eynde,P.F.M.Ampe,L.Verdeyen,and W.M.C.Sansen,“A CMOS large-swing low-distortion three-stage class AB power am-plifier,”IEEE J.Solid-State Circuits,vol.25,pp.265–273,Feb.1990.[16]R.G.H.Eschauzier,L.P.T.Kerklaan,and J.H.Huijsing,“A100MHz100dB operational amplifier with multipath nested miller compensation structure,”IEEE J.Solid-State Circuits,vol.27,pp.1709–1717,Dec.1992.[17] E.M.Cherry,“Comment on a100MHz100dB operational amplifierwith multipath nested miller compensation structure,”IEEE J.Solid-State Circuits,vol.31,pp.753–754,May1996.[18]S.Pernici,G.Nicollini,and R.Castello,“A CMOS low-distortion fullydifferential power amplifier with double nested Miller compensation,”IEEE J.Solid-State Circuits,vol.28,pp.758–763,July1993.[19]K.-J.de Langen,R.G.H.Eschauzier,G.J.A.van Dijk,and J.H.Hui-jsing,“A1GHz bipolar class-AB operational amplifier with multipath nested Miller compensation for76dB gain,”IEEE J.Solid-State Cir-cuits,vol.32,pp.488–498,Apr.1997.[20] F.You,S.H.K.Embabi,and E.Sánchez-Sinencio,“Multistage ampli-fier topologies with nested gm-C compensation,”IEEE J.Solid-State Circuits,vol.32,pp.2000–2011,Dec.1997.[21]H.-T.Ng,R.M.Ziazadeh,and D.J.Allstot,“A mulitstage amplifiertechnique with embedded frequency compensation,”IEEE J.Solid-State Circuits,vol.34,pp.339–341,Mar.1999.[22]K.N.Leung,P.K.T.Mok,W.H.Ki,and J.K.O.Sin,“Damping-factor-control frequency compensation technique for low-voltage low-power large capacitive load applications,”in Dig.Tech.Papers ISSCC’99,1999, pp.158–159.[23],“Three-stage large capacitive load amplifier with damping-factor-control frequency compensation,”IEEE J.Solid-State Circuits,vol.35, pp.221–230,Feb.2000.[24],“Analysis on alternative structure of damping-factor-control fre-quency compensation,”in Proc.IEEE ISCAS’00,vol.II,May2000,pp.545–548.[25]K.N.Leung,P.K.T.Mok,and W.H.Ki,“Right-half-plane zero re-moval technique for low-voltage low-power nested miller compensation CMOS amplifiers,”in Proc.ICECS’99,vol.II,1999,pp.599–602. [26]J.H.Huijsing,R.Hogervorst,and K.-J.de Langen,“Low-power low-voltage VLSI operational amplifier cells,”IEEE Trans.Circuits Syst.I, vol.42,pp.841–852,Nov.1995.[27]G.C.Temes and Patra,Introduction to Circuit Synthesis andDesign,1ed.New York:McGraw-Hill,1977.[28]J.W.Nilsson,Electric Circuits,4ed.New York:Addison Wesley,1993.[29] B.Y.Kamath,R.G.Meyer,and P.R.Gray,“Relationship between fre-quency response and settling time of operational amplifier,”IEEE J.Solid-State Circuits,vol.SC-9,pp.247–352,Dec.1974.[30] C.T.Chuang,“Analysis of the settling behavior of an operational am-plifier,”IEEE J.Solid-State Circuits,vol.SC-17,pp.74–80,Feb.1982. Ka Nang Leung received the B.Eng.and M.Phil.degrees in electronic engi-neering from the Hong Kong University of Science and Technology(HKUST), Clear Water Bay,Hong Kong,in1996and1998,respectively.He is now working toward the Ph.D.degree in the same department.During the B.Eng.studies,he joined Motorola,Hong Kong,to develop a PDA system as his final year project.In addition,he has developed several frequency-compensation topologies for multistage amplifiers and low dropout regulators in his M.Phil studies.He was a Teaching Assistant in courses on analogue integrated circuits and CMOS VLSI design.His research interests are low-voltage low-power analog designs on low-dropout regulators,bandgap voltage references and CMOS voltage references.In addition,he is interested in developing frequency-compensation topologies for multistage amplifiers and for linear regulators.In1996,he received the Best Teaching Assistant Award from the Department of Electrical and Electronic Engineering at theHKUST.Philip K.T.Mok(S’86–M’95)received theB.A.Sc.,M.A.Sc.,and Ph.D.degrees in electricaland computer engineering from the University ofToronto,Toronto,Canada,in1986,1989,and1995,respectively.From1986to1992,he was a Teaching Assistant,at the University of Toronto,in the electrical engi-neering and industrial engineering departments,andtaught courses in circuit theory,IC engineering andengineering economics.He was also a Research As-sistant in the Integrated Circuit Laboratory at the Uni-versity of Toronto,from1992to1994.He joined the Department of Electrical and Electronic Engineering,the Hong Kong University of Science and Tech-nology,Hong Kong,in January1995as an Assistant Professor.His research interests include semiconductor devices,processing technologies and circuit de-signs for power electronics and telecommunications applications,with current emphasis on power-integrated circuits,low-voltage analog integrated circuits and RF integrated circuits design.Dr.Mok received the Henry G.Acres Medal,the W.S.Wilson Medal and Teaching Assistant Award from the University of Toronto and the Teaching Ex-cellence Appreciation Award twice from the Hong Kong University of Science and Technology.。

advances in mathematics介绍Advances in mathematics refer to the progress made in the field of mathematics that has greatly impacted various areas of science, technology, engineering, and even everyday life. These advances include discoveries, theories, techniques, algorithms, and computational methods that have broadened the understanding and application of mathematical concepts.One significant advance in mathematics is the development of calculus by Sir Isaac Newton and Gottfried Wilhelm Leibniz in the 17th century. Calculus allows for the study of change and the analysis of various mathematical functions, making it essential in physics, engineering, economics, and other sciences.Another important advance is the creation of non-Euclidean geometries, such as hyperbolic and elliptic geometries. These non-Euclidean geometries challenge the traditional Euclidean geometry and have applications in fields like relativity, computer graphics, and cryptography.The introduction of number theory and abstract algebra has also been a significant advancement in mathematics. Number theory deals with the properties and relationships of numbers, while abstract algebra studiesalgebraic structures such as groups, rings, and fields. These areas of mathematics have paved the way for cryptography, coding theory, and other fields related to secure communication and data encryption.Advances in mathematical modeling and simulation have greatly impacted various scientific disciplines. Mathematical models help scientists and researchers understand complex phenomena and make predictions about real-world systems. Simulation techniques, such as Monte Carlo methods and numerical optimization, allow for the analysis of large datasets and the implementation of mathematical models into computer algorithms.Furthermore, the development of computational methods and algorithms has greatly expanded the capabilities of mathematical analysis. Techniques such as linear programming, network optimization, and numerical analysis have revolutionized fields such as operations research, data analysis, and computer science.Advances in mathematics have also led to breakthroughs in cryptography, data compression, image processing, machine learning, and artificial intelligence. These advancements have influenced various technological advancements, including the development of fastercomputers, improved data storage, and advanced algorithms.In summary, advances in mathematics have transformed various fields of science, technology, and everyday life by providing tools and concepts for understanding and solving complex problems. The continuous progress in mathematics continues to shape our understanding of the world and drive innovation in various disciplines.。

多模态磁共振成像英语Multimodal Magnetic Resonance Imaging.Magnetic resonance imaging (MRI) has revolutionized the field of medical imaging, providing doctors with detailed, non-invasive views of the internal structures of the human body. Within the vast realm of MRI, multimodal MRI stands out as a particularly advanced and versatile technique. It combines multiple imaging modalities within a single MRI scanner, enabling the acquisition of complementary information about the tissue microstructure, biochemistry, and function.The concept of multimodal MRI is based on theintegration of different MRI techniques, each sensitive to different tissue properties. For instance, structural MRI provides anatomical details of the brain's gray and white matter, while functional MRI (fMRI) reveals brain activity patterns associated with cognitive tasks or sensory stimuli. Diffusion-weighted MRI (DWI) and magnetic resonancespectroscopy (MRS) offer insights into the microstructural organization and biochemical composition of tissues, respectively.The key advantage of multimodal MRI lies in its ability to provide a comprehensive picture of the brain or any other organ. By combining the information obtained from different modalities, researchers and clinicians can gain a deeper understanding of the underlying pathophysiology of diseases such as cancer, stroke, dementia, and neurodegenerative disorders. This, in turn, can lead to more accurate diagnoses, effective treatment plans, and better patient outcomes.In addition to its diagnostic capabilities, multimodal MRI also holds great potential for research applications.It can be used to study brain development, neuroplasticity, and the neural correlates of cognition and behavior. By tracking changes in tissue properties over time, researchers can gain insights into the progression of diseases and the effects of therapeutic interventions.Technological advancements have played a crucial role in the development of multimodal MRI. The introduction of high-field MRI scanners, advanced gradient systems, and powerful computers has enabled the acquisition and processing of larger datasets with improved spatial and temporal resolution. These advancements have made it possible to perform complex multimodal MRI sequences in a clinically feasible time frame.Despite its many advantages, multimodal MRI also faces some challenges and limitations. One of the main challenges is the integration and harmonization of different imaging modalities within a single scanner. This requires careful consideration of factors such as scanner hardware, imaging sequences, and data acquisition and processing pipelines.Another limitation is the potential for signal interference between different modalities. For example, the strong magnetic fields used in MRI can affect thesensitivity and accuracy of other imaging modalities, such as positron emission tomography (PET) or computed tomography (CT). Therefore, careful planning andoptimization are essential to ensure accurate and reliable multimodal MRI data.Despite these challenges, the future of multimodal MRI looks bright. With continuous technological advancements and improved understanding of tissue properties, we can expect even more powerful and versatile multimodal MRI techniques to emerge in the coming years. These techniques will likely play a pivotal role in the early detection, diagnosis, and treatment of a wide range of diseases and disorders, leading to better patient outcomes and healthier communities.In conclusion, multimodal MRI represents a significant leap forward in medical imaging technology. By combining the strengths of different MRI modalities, it offers a comprehensive and nuanced view of the human body, enabling more accurate diagnoses, effective treatment plans, and improved patient outcomes. As we continue to push the boundaries of this remarkable technology, the potential for its application in medicine and research is limitless.。