Time scale interactions and the coevolution of humans and water

收稿日期：2023-09-20基金项目：国家社会科学基金项目“意义与指称理论前沿问题研究”（21BZX04）作者简介：尹均怡，南开大学哲学院，主要从事逻辑哲学研究。

E-mail ：******************刘叶涛，南开大学哲学院，主要从事逻辑哲学与哲学逻辑研究。

E-mail ：**************摘 要：查尔默斯以二维语义为视角提出了一种试图融合描述论和直接指称论的新型意义理论；通过重新把握认识论与形而上学的区分与关联，构建了一种较为系统的二维指称理论，以进一步强化“意义—理性—模态”的密切关联。

在系统阐释查尔默斯二维指称理论的建构动因、核心内容及其发展历程的基础上，通过深入考察国内外学界就此提出的质疑，并追踪查尔默斯针对这些质疑给出的回应，可为深度把握二维指称理论架构的成就与不足提供方向。

关键词：指称理论； 金三角； 二维指称理论；认知可能性；形而上学可能性中图分类号：B813文献标识码：A 文章编号：1006-2815（2024）01-0113-12DOI ： 10.19946/j.issn.1006-2815.2024.01.010二维指称理论及其发展尹均怡 刘叶涛一、背景：当代意义和指称理论的对立与交锋在当代意义理论中，描述论和直接指称论的交锋旷日持久。

弗雷格（G. Frege ）明确区分了名称的含义（sense ）和指称（reference ），强调含义在给命题赋值过程中的作用不可忽视，开创了现代指称理论的先河。

“a=a ”和“a=b ”这两种同一陈述之间存在重要区别：“a=b ”传达了一种“a=a ”无法传达的信息，这种认知意义（cognitive significance ）上的差异与被命名对象关系密切：“和一个名称相联系的，不仅具有被命名的对象（或指称），还有这个名称的含义，在其名称中包含了名称提出的方式和语境”①。

摹状词理论尽管只是为了讨论限定摹状词的意义，但罗素（B. Russell ）的基本主张经提炼，也适用于名称，从而在主要观点上与弗雷格相同：名称（专名和通名）都有含义；专名的含① Gottlob Frege, “On Sense and Nominatum Reprinted ”, in Anthony Patrick Martinich (ed.), The Philosophy of Lan-guage , Oxford: Oxford University Press, 2001, p.2.SCIENCE · ECONOMY ·SOCIETY 第42卷 总第178期Vol.42, Total No.1782024年第1 期No.1, 20241132024年第1期义指谓的是个体对象的独有属性，通常由限定摹状词表达；通名的含义指谓一类对象的共有且仅有属性，通常由非限定摹状词表达；含义是判定指称的依据和标准，含义决定指称。

IntroductionThis comprehensive work plan outlines a strategic roadmap for enhancing organizational performance through a multifaceted approach that emphasizes quality, efficiency, and continuous improvement. It is designed to provide a clear, actionable framework for achieving our objectives while fostering a culture of excellence and innovation. The plan is structured around five key pillars: (1) Leadership and Culture, (2) Operational Excellence, (3) Talent Management, (4) Customer Centricity, and (5) Technology and Innovation. Each pillar represents a distinct yet interconnected domain that, when synergistically optimized, will propel the organization towards its vision of delivering unparalleled value to stakeholders.I. Leadership and CultureA. Vision and Values Clarification1. Conduct a thorough review and refinement of the organization's vision, mission, and core values to ensure they align with our strategic direction and resonate with all stakeholders.2. Develop a communication strategy to effectively cascade these refreshed guiding principles throughout the organization, utilizing various channels such as town hall meetings, internal newsletters, and leadership workshops.B. Leadership Development1. Implement a leadership development program encompassing coaching, mentoring, and training initiatives to enhance the capabilities of current and future leaders in areas such as strategic thinking, change management, emotional intelligence, and inclusive leadership.2. Establish a robust succession planning process to identify and nurture high-potential talent, ensuring a steady pipeline of capable leaders to drive the organization forward.C. Culture Transformation1. Design and launch a culture transformation initiative focused on embedding a high-performance, customer-centric, and innovative mindset across all levels of the organization. This will involve:- Conducting a cultural audit to assess the current state and identify areas for improvement.- Formulating a culture charter that defines the desired behaviors, norms, and practices.- Implementing targeted interventions, such as workshops, team-building activities, and recognition programs, to foster the desired culture.- Regularly measuring and reporting on cultural progress using relevant metrics and employee feedback mechanisms.II. Operational ExcellenceA. Process Optimization1. Undertake a comprehensive process mapping exercise to identify bottlenecks, inefficiencies, and opportunities for standardization across allcore business processes.2. Implement Lean Six Sigma or similar methodologies to streamline workflows, eliminate waste, and enhance process quality, with a focus on reducing cycle times, minimizing errors, and boosting productivity.B. Performance Metrics and Dashboards1. Develop a robust performance measurement framework that encompasses key performance indicators (KPIs), balanced scorecards, and real-time dashboards to monitor and track progress against strategic objectives at both the organizational and departmental levels.2. Establish regular review meetings (e.g., monthly or quarterly) where senior leadership can analyze performance data, discuss trends, and make data-driven decisions to address issues and capitalize on opportunities.C. Risk Management and Compliance1. Strengthen the organization's risk management framework by conductinga thorough risk assessment, identifying potential threats, and implementing mitigation strategies across all operational domains.2. Ensure strict adherence to regulatory requirements and industry best practices by establishing a robust compliance monitoring system, providing regular training to employees, and conducting periodic audits.III. Talent ManagementA. Talent Acquisition and Retention1. Refine the recruitment strategy to attract top talent by leveraging advanced sourcing techniques, enhancing the employer brand, and streamlining the candidate experience.2. Implement a comprehensive retention strategy encompassing competitive compensation packages, career development opportunities, employee wellness initiatives, and a positive work environment to minimize turnover and maximize employee engagement.B. Learning and Development1. Design and roll out a competency-based learning and development framework that aligns individual skill sets with organizational needs, incorporates both formal training and on-the-job learning, and fosters a culture of continuous learning.2. Invest in digital learning platforms and microlearning modules to facilitate self-paced, personalized learning experiences for employees.C. Performance Management1. Transition to a more agile, continuous performance management approach that emphasizes ongoing feedback, coaching, and goal alignment, replacing traditional annual reviews with regular check-ins and development-focused conversations.2. Introduce a fair and transparent performance evaluation system linked to clearly defined performance standards and development goals, ensuring that rewards and recognition are commensurate with individual contributions and achievements.IV. Customer CentricityA. Customer Experience Strategy1. Develop a customer-centric strategy that encompasses all touchpoints and stages of the customer journey, focusing on understanding customer needs, preferences, and pain points, and designing tailored solutions and experiences to meet them.2. Establish a Voice of the Customer (VoC) program to gather and analyze customer feedback continuously, using insights to drive product/service improvements, process enhancements, and strategic decision-making.B. Customer Relationship Management (CRM)1. Implement a robust CRM system to centralize customer data, facilitate seamless interactions across channels, and enable personalized, data-driven marketing, sales, and service efforts.2. Train employees on effective CRM usage and customer engagement strategies to foster strong, long-lasting customer relationships.C. Customer Service Excellence1. Revamp the customer service function by setting high service standards, providing comprehensive training to frontline staff, and leveraging technology (e.g., chatbots, AI-powered support) to deliver fast, accurate, and empathetic assistance.2. Establish a customer satisfaction measurement system and regularly review metrics to identify areas for improvement and ensure consistent delivery of exceptional service.V. Technology and InnovationA. Digital Transformation1. Develop a digital transformation roadmap that outlines the strategic adoption of emerging technologies (e.g., cloud computing, artificial intelligence, Internet of Things) to enhance operational efficiency, customer experiences, and innovation capabilities.2. Prioritize investments in IT infrastructure upgrades, cybersecurity enhancements, and data analytics tools to create a solid foundation for digital growth.B. Innovation Management1. Establish an innovation management framework that encourages cross-functional collaboration, fosters a culture of experimentation, and supports the development, testing, and scaling of new ideas. This may include setting up innovation labs, organizing hackathons, or implementing an idea management platform.2. Integrate innovation metrics into the performance measurement framework, rewarding teams and individuals who contribute to successful innovation projects and driving accountability for innovation outcomes across the organization.C. Data-Driven Decision Making1. Enhance data literacy across the organization through targeted training programs and the creation of user-friendly dashboards and reports thatdemocratize access to meaningful data insights.2. Embed data-driven decision making into all aspects of the business by establishing a Center of Excellence (CoE) for business intelligence and analytics, providing expert guidance and support to departments in leveraging data to inform strategy and operations.ConclusionThis comprehensive work plan outlines a holistic approach to enhancing organizational performance, addressing critical dimensions such as leadership and culture, operational excellence, talent management, customer centricity, and technology and innovation. By diligently executing this plan, the organization will be well-positioned to achieve its strategic objectives, maintain a competitive edge, and deliver sustained value to all stakeholders. Regular monitoring, review, and adjustment of the plan will be crucial to ensure its continued relevance and effectiveness in a rapidly changing business landscape.。

Communicative Competence ScaleWiemann (1977) created the Communicative Competence Scale (CCS) to measure communicative competence, an ability "to choose among available communicative behaviors" to accomplish one's own "interpersonal goals during an encounter while maintaining the face and line" of "fellow interactants within the constraints of the situation" (p. 198). Originally, 57 Likert-type items were created to assess five dimensions of interpersonal competence (General Competence, Empathy Affiliation/Support, Behavioral Flexibility, and Social Relaxation) and a dependent measure- (interaction Management). Some 239 college students used the scale to rate videotaped confederates enacting one of four role-play interaction management conditions (high, medium, low, rude). The 36 items that discriminated the best between conditions were used in the final instrument. Factor analysis resulted in two main factors-general and relaxation-indicating that the subjects did not differentiate among the dimensions as the model originally predicted.Subjects use the CCS to assess another person's communicative competence by responding to 36 items using Likert scales that range from strongly agree (5) to strongly disagree (1). The scale takes less than 5 minutes to complete. Some researchers have adapted the other-report format to self-report and partner-report. These formats are available from the author.RELIABILITYThe CCS appears to be internally consistent. Wiemann (1977) reported a .96 coefficient alpha (and .74 magnitude of experimental effect) for the 36item revised instrument. McLaughlin and Cody (1982) used a 30-item version for college students to rate their partners after 30 minutes of conversation and reported an alpha of .91. Jones and Brunner (1984) had college students rate audio-taped interactions and reported an overall alpha of .94 to .95; subscale scores had alphas ranging from .68 to .82. Street, Mulac, and Wiemann (1988) had college students rate each other on communicative competence and reported an alpha of .84. The 36-item self-report format version is also reliable: Cupach and Spitz berg (1983) reported an alpha of .90, Hazleton and Cupach (1986) reported an alpha of .91, Cegala, Savage, Brunner, and Conrad (1982) reported an alpha of .85, and Query, Parry, and Flint (1992) reported an alpha of .86,Profile by Rebecca R. Rubin.VALIDITYTwo studies found evidence of construct validity. First, McLaughlin and Cody (1982) found that interactants in conversations in which there were multiple lapses of time rated each other lower on communicative competence. Second, Street et al. (1988) found that conversants' speech rate, vocal back channeling, duration of speech, and rate of interruption were related to their communicative competence scores; they also found that conversants rated their partners significantly more favorably than did observers.Various studies have provided evidence of concurrent validity. Cupach and Spitzberg (1983) used the dispositional self-report format and found that the CCS was strongly correlated with two other dispositions: communication adaptability and trait self-rated competence. The CCS was also modestly related to situational, conversation-specific measures of feeling good and self-rated competence. Hazleton and Cupach (1986) found a moderate relationship between communicative competence and both ontological knowledge about interpersonal communication and interpersonal communication apprehension. Backlund (1978) found communicative competence was related to social insight and open-mindedness. Douglas (1991) reported inverse relationships between communication competence and uncertainty and apprehension during initial meetings, And Query et al. (1992) found that nontraditional students, those high in communication competence, had more social supports and were more satisfied with these supports.In addition, Cegala et al. (1982) compared 326 college students' CCS and Interaction Involvement Scalescores. All three dimensions of interaction involvement were positively correlated with the CCS, but onlyperceptiveness correlated significantly with all five dimensions for both men and women. Responsiveness was related to behavioral flexibility, affiliation/support, and social relaxation, and attentiveness was related toimpression management.COMMENTSAlthough this scale has existed for a number of years and the original article has been cited numerous times,relatively few research studies have actually used the CCS. As reported by Perotti and De Wine (1987), problems with the factor structure and the Likert-type format may be reasons why. They suggested that theinstrument be used as a composite measure of communicative competence rather than breaking the scale into subscales, and this appears to be good advice. Spitzberg (1988, 1989) viewed the instrument as well conceived, suitable for observant or conversant rating situations, and aimed at "normal" adolescent or adult populations, yet Backlund (1978) found little correlation between peer-perceived competence and expert-perceived competence when using the CCS. The scale has been used only with college student populations.LOCATIONWiemann; J. M. (1977). Explication and test of a model of communicative competence. Human Communication Research, 3, 195-213.REFERENCESBacklund, P. M. (1978). Speech communication correlates of perceived communication competence (Doctoral dissertation, University of Denver, 1977). Dissertation Abstracts International, 38, 3800A.Cegala, D. J, Savage, G. T., Brunner, C. c., & Conrad, A. B. (1982). An elaboration of the meaning of interaction involvement: Toward the development of a theoretical concept. Communication Monographs, 49,229-248. Cupach, W. R., & Spitzberg, B. H. (1983). Trait versus state: A comparison of dispositional and situational measures of interpersonal communication competence. Western Journal o/SPeech Communication, 47,364-379.Douglas, W. (1991). Expectations aboUt initial interaction: An examination of rheeffects of global uncertainty. Human Communication Research, 17,355-384.Hazleton, V., Jr., & Cupach, W. R. (1986). An exploration of ontological knowledge: Communication competence as a function of the ability to describe,predict, and explain. Western Journal o/Speech Communication, 50,119-132.Jones, T. S., & Brunner, C. C. (1984). The effects of self-disclosure and sex on perceptions of interpersonal communication competence. Women's Studies in Communication, 7, 23-37.McLaughlin, M. 1., & Cody, M. J. (1982). Awkward silences: Behavioral antecedents and consequences of the conversational lapse. Human Communication Research, 8,299-316.Perotti, V. S., & DeWine, S. (1987). Competence in communication: An examination of three instruments.Management Communication Quarterly, 1,272-287.Query, J. 1., Parry, D., & Flint, 1. J. (1992). The relationship among social support, communication competence, and cognitive depression for nontraditional students. Journal 0/ Applied Communication Research, 20, 78-94.Spitzberg, B. H. (1988). Communication competence: Measures of perceived effectiveness. In C. H. Tardy (Ed.),A handbook for the study of human communication: Methods and instruments for observing, measuring, andassessing communication processes (pp. 67-105). Norwood, NJ: Ablex.Spitzberg, B. H. (1989). Handbook of interpersonal competence research. New York: Springer-Verlag.Street, R. 1., Jr., Mulac, A., & Wiemann, J. M. (1988). Speech evaluation differences as a function of perspective (participant versus observer) and presentational medium. Human Communication Research, 14,333-363.Communicative Competence Scale*Instructions: Complete the following questionnaire/scale with the subject (S) in mind. Write in one of the sets of letters before each numbered question based upon whether you:strongly agree (SA), agree (A), are undecided or neutral (?),disagree (D), or strongly disagree (SD).Always keep the subject in mind as you answer.______ 1. S finds it easy to get along with others.______ 2. S can adapt to changing situations.______ 3. S treats people as individuals.______ 4. S interrupts others too much.______ 5. S is "rewarding" to talk to.______ 6. S can deal with others effectively.______ 7. S is a good listener.______ 8. S's personal relations are cold and distant.______ 9. S is easy to talk to.______ 10. S won't argue with someone just to prove he/she is right.______ 11. S's conversation behavior is not "smooth.”______ 12. S ignores other people's feelings.______ 13. S generally knows how others feel.______ 14. S lets others know he/she understands them.______ 15. S understands other people.______ 16. S is relaxed and comfortable when speaking.______ 17. S listens to what people say to him/her.______ 18. S likes to be close and personal with people.______ 19. S generally knows what type of behavior is appropriate in any given situation.______ 20. S usually does not make unusual demands on his/her friends.______ 21. S is an effective conversationalist.______ 22. S is supportive of others.______ 23. S does not mind meeting strangers.______ 24. S can easily put himself/herself in another person's shoes.______ 25. S pays attention to the conversation.______ 26. S is generally relaxed when conversing with a new acquaintance. 27. S is interested in what others have to say.______ 27. S doesn't follow the conversation very well.______ 28. S enjoys social gatherings where he/she can meet new people.______ 29. S is a likeable person.______ 30. S is flexible.______ 31. S is not afraid to speak with people in authority.______ 32. People can go to S with their problems.______ 33. S generally says the right thing at the right time.______ 34. S likes to use his/her voice and body expressively.______ 35. S is sensitive to others' needs of the moment.Note. Items 4, 8, 11, 12, and 28 are reverse-coded before summing the 36 items. For "Partner" version, "S" is replaced by "My partner" and by "my long-standing relationship partner" in the instructions. For the "Self-Report" version, "S" is replaced by "I" and statements are adjusted forfirst-person singular.。

Unit 2History and MemorySection 1Unit MaterialsQuestions To ConsiderQuestion 1.What are some of the different ways individuals and groups remember and represent the past? Question 2.What are some of the causes that prompt professional historians to reinterpret and ask new questions of the past?Question 3.What are some of the ways twentieth-century world historians have helped to shape collective memories of the past?Question 4.Why is commemoration of the past a source of conflict, and how do individuals and groups challenge the collective memories of other individuals and groups?The Big PictureHow is this topic related to Increasing Integration?Shared remembrance, also called social memory, integrates people at many different levels —from the family to the nation to the international arena.How is this topic related to Proliferating Difference?Different individuals and groups often have competing social memories because of their different experiences and perspectives. These competing social memories (also called counter-memories) can challenge and even change dominant versions of the past.Unit PurposeßIndividual and collective memories are the substance of history, whether that history is of the family, community, nation, or world.ßRepresentations of the past — including written archives, monuments, museums, and oral stories — help construct social memory, but they can also be challenged bycompeting counter-memories.ßHistory, as a form of social memory, is dynamic and always changing because different people record it for different purposes and audiences.Unit Content OverviewAll people seek their origins in what came before them; they derive their identities from both individual and collective memories. The past can be recalled and retold in many ways, whether it is through the written word, history, myth, legend, oral tradition, art, or performance. History is often told as a linear narrative, with a beginning, middle, and end. Human memory is more elusive – vivid for some experiences, faint for others – and not necessarily linear. However, both history and memory are selective, changeable, and open to contestation and competition. Both are expressed in multiple voices and are continually altered. Just as social memory is molded by community experiences and contemporary concerns, historians too reinterpret the past in response to shifting concerns and questions shaped by the world they inhabit. In the ever-changing landscapes of history and memory, it is as important to know what has been forgotten as to understand why and how an event or a person has been remembered.This unit explores questions about how our notions of historical memory have changed over time and in different places. Both individual and collective identities are closely tied to how the past is remembered. Individual identities derive in part from family experiences recalled and recounted over generations, along with genealogical records – from handwritten names in family bibles to computerized official documents that certify birth, marriage, and death. Community identities –from village to nation to planet – are rooted in shared remembrance of collective experiences, and are defined by the ways that remembrance is reconstructed and represented. Nations in particular make use of – and often reinvent – the past to construct national identities. Textbooks teach national history in schools; national museums house historical artifacts; and national libraries archive written records of the past. People also collect and preserve artifacts and records of local histories, and they display these community histories in local museums, on the World Wide Web, and even in school classrooms.Unit ReferencesSusan E. Alcock,“Archaeologies of Memory” in Archaeologies of the Greek Past: Landscape, Monuments, and Memories (Cambridge: Cambridge University Press, 2002): 1-35. Michael D. Coe, Breaking the Maya Code (London: Thames and Hudson, 1992).David Lowenthal, “Distorted Mirrors,” History Today 44, no.2 (February 1994): 8-12.William D. Phillips, Jr. and Carla Rahn Phillips, The Worlds of Christopher Columbus (Cambridge: Cambridge University Press, 1992).Mary Nooter Roberts and Allen F. Roberts, “Luba Art and the Making of History,” African Arts 29, no. 1 (Winter 1996)Linda Schele and Mary Ellen Miller, Blood of Kings: Dynasty and Ritual in Maya Art (New York: George Braziller, 1986).Stephen J. Summerhill and John Alexander Williams, Sinking Columbus: Contested History, Cultural Politics, and Mythmaking during the Quincentenary (Gainesville: University ofFlorida Press, 1992).Global Historical ContextßTime Period: 1500–presentßLike Unit 1, this unit is designed to provide an overall framework for the study of world history. However, most of the case studies concern the period after 1500, and can beused to illustrate issues resulting from European-American contact (Columbus and thereinterpretation of the Maya) or the competing historical memories of colonialism andWorld War II (Korean National Museum).AP ThemesßExplores interactions in economics and politics through the international exchanges brought about by the Columbian encounter and World War II.ßExamines change and continuity through the various ways historical memory has changed over time about Christopher Columbus, the bombing of Hiroshima andNagasaki, and the legacy of Japanese imperialism in Korea. Change and continuity arealso addressed through the way scholarly opinion about ancient Mayan society haschanged in light of new archaeological and linguistic evidence.ßDiscusses cultural and intellectual developments in the Americas and Korea by looking at the cultural impact of shifting historical memories about Columbus, World War II, andJapanese imperialism, and by looking at the intellectual impact of scholarly reevaluations about Mayan culture.Related UnitsßUnit 1. Maps, Time, and World History: What tools do world historians use in the study of history? This unit begins the study of world history by examining how geographical andchronological frameworks have shaped the understanding of world history and been used to chart the past. It is related to Unit 2 because it demonstrates that historians — and the histories they tell — are shaped by their own world’s concerns and intellectualframeworks.ßUnit 6. Order and Early Societies: How do diverse political structures and relationships distribute power and material resources? Through the rise of the Chinese empire, Mayan regional kingdoms, and the complex society of Igbo Ukwu, this unit considers the origins of centralized states and alternative political and social orders. It is related to Unit 2because it demonstrates how historians can learn new things about the past througharchaeology.ßUnit 13. Family and Household: What does the study of families and households tell us about our global past? In this unit examining West Asia, Europe, and China, historiansfocus on how families and households provide windows into the private experiences ofworld societies — and explore how these private experiences sometimes become models for ordering the outside world. It is related to Unit 2 because it illustrates the importantrole of the family as an entity with its own memory and history.ßUnit 26. World History and Identity: How have global forces redefined both individual and group identities in the modern world? This unit examines the transnational identity thatemerged from the Chinese diaspora and compares it to a newly re-defined nationalChechen identity forged through war with Russia. It is related to Unit 2 because itdemonstrates how individual and collective memories are important components of identity even — or especially — in our own time.Section 2Video-Related MaterialsVideo Segment 1: Commemorating ColumbusThis segment looks at the changing ways Christopher Columbus has been remembered and commemorated in the Americas and in the world. Until recently, Columbus was revered as an intrepid explorer and civilizer in many parts of the world, not least the United States. But in the last four decades the historical record — once based solely on Columbus’s own words — began to be enriched by new scientific and archaeological evidence. This evidence helped scholars understand the dramatic impact Columbus’s voyages had on the indigenous peoples of the Americas. Increasingly, Columbus became symbolic of an encounter that raised uncomfortable questions about conquest, colonialism, and destruction of peoples and habitats. These new interpretations ensured that the 1992 American quincentenary celebration of Columbus’s arrival in the Americas was a highly contested affair. Indigenous groups from the Americas refused to celebrate Columbus Day, and they actively protested its commemoration. Overall, this segment demonstrates how changing historical views can change or revise even long-held shared historical memories.Video Segment 2: Changing Views of the MayaThis segment demonstrates both how new evidence can transform the ways historians interpret the past and how history and memory can be recalled and represented in ways alien to most westernized scholars. It looks first at historical interpretations of the Maya, who were once believed to be a peace-loving rural people. This interpretation, however, was based only on material evidence at Mayan ruins and on the opinions of a few scholars, and it did not take into account the meanings in Mayan glyphs. Once scholars were able to decipher Mayan glyphs —beginning in the 1970s — historical interpretations of the Maya shifted dramatically. Today, historians view the ancient Maya as a bellicose urban people. They were ruled by deified kings obsessed with lineage and conquest, who resided in densely populated cities supported by sophisticated farming that included extensive canals and raised-field agriculture. This change in historical interpretation was made possible through the study of Mayan written language — even though it was centuries old — and the change has revolutionized this field of historical study. Video Segment 3: Memory and MuseumsMemory can be preserved in many ways. This unit explores some methods of remembering, including physical devices, architecture, and museums. It begins with the Luba people of central Congo, who use elaborate carvings, memory boards, and scarification to mark, remember, and retell the past. Until recently, professional historians viewed peoples without written records as “without history” because the historians’ perceptions of history were shaped overwhelmingly by their own experiences in a literate culture. This segment then moves to monuments and museums to explore how they can collect, preserve, and interpret the past. First, it looks at the destruction of South Korea’s National Museum on August 15, 1995, during the fiftieth anniversary celebration of Korea’s independence from Japan. The museum edifice was built during Japan’s colonial rule of Korea with the labor of more than 50,000 Koreans. Although the building had once housed Korea’s national treasures, from a Korean point of view it was a monument to the Japanese oppression of the Korean people, and its destruction was presented in Korea as a restoration of Korean national pride.Perspectives on the Past: Rigoberta Menchu’s StoryWhat is the relationship between individual and collective memories? Where is the line between truth and fiction in these memories? The case of Rigoberta Menchu, a Guatemalan resistance fighter whose autobiography details the struggles of her people, raises both of these questions. Menchu’s story has been attacked for making claims that go beyond her personal experience, butit has been defended as true to the collective memory of her people. It demonstrates that, frequently, what is “true” is often a matter of perspective, both in memory and in history.Video DetailsWho Is Interviewed•Peter Winn•Gary Nash•Candice GoucherPrimary Source Materials Featured in the Video•Samuel Eliot Morison, historian•Linda Schele, art historian and epigrapher•Rigoberta Menchu, recipient of Nobel Peace PrizeProgram ContentsBegins Ends Contents00:0001:33Show tease, show opening credits01:3404:05Program overview/introduction04:0612:45Video Segment 1: Commemorating Columbus12:4617:37Video Segment 2: Changing Views of the Maya 17:3823:54Video Segment 3: Memory and Museums23:5526:15Perspectives on the Past: Rigoberta Menchu’s Story 26:1628:25Show close and program credits。

More informationPhase Noise and Frequency Stability in OscillatorsPresenting a comprehensive account of oscillator phase noise and frequency stability,this practical text is both mathematically rigorous and accessible.An in-depth treatmentof the noise mechanism is given,describing the oscillator as a physical system,andshowing that simple general laws govern the stability of a large variety of oscillatorsdiffering in technology and frequency range.Inevitably,special attention is given to am-plifiers,resonators,delay lines,feedback,andflicker(1/f)noise.The reverse engineeringof oscillators based on phase-noise spectra is also covered,and end-of-chapter exercisesare given.Uniquely,numerous practical examples are presented,including case studiestaken from laboratory prototypes and commercial oscillators,which allow the oscillatorinternal design to be understood by analyzing its phase-noise spectrum.Based on tuto-rials given by the author at the Jet Propulsion Laboratory,international IEEE meetings,and in industry,this is a useful reference for academic researchers,industry practitioners,and graduate students in RF engineering and communications engineering.Additional materials are available via /rubiola.Enrico Rubiola is a Senior Scientist at the CNRS FEMTO-ST Institute and a Professorat the Universit´e de Franche Comt´e.With previous positions as a Professor at theUniversit´e Henri Poincar´e,Nancy,and in Italy at the University Parma and thePolitecnico di Torino,he has also consulted at the NASA/Caltech Jet PropulsionLaboratory.His research interests include low-noise oscillators,phase/frequency-noisemetrology,frequency synthesis,atomic frequency standards,radio-navigation systems,precision electronics from dc to microwaves,optics and gravitation.More informationThe Cambridge RF and Microwave Engineering SeriesSeries EditorSteve C.CrippsPeter Aaen,Jaime Pl´a and John Wood,Modeling and Characterization of RF andMicrowave Power FETsEnrico Rubiola,Phase Noise and Frequency Stability in OscillatorsDominique Schreurs,M´a irt´ın O’Droma,Anthony A.Goacher and Michael Gadringer,RF Amplifier Behavioral ModelingFan Y ang and Y ahya Rahmat-Samii,Electromagnetic Band Gap Structures in AntennaEngineeringForthcoming:Sorin V oinigescu and Timothy Dickson,High-Frequency Integrated CircuitsDebabani Choudhury,Millimeter W aves for Commercial ApplicationsJ.Stephenson Kenney,RF Power Amplifier Design and LinearizationDavid B.Leeson,Microwave Systems and EngineeringStepan Lucyszyn,Advanced RF MEMSEarl McCune,Practical Digital Wireless Communications SignalsAllen Podell and Sudipto Chakraborty,Practical Radio Design TechniquesPatrick Roblin,Nonlinear RF Circuits and the Large-Signal Network AnalyzerDominique Schreurs,Microwave Techniques for MicroelectronicsJohn L.B.Walker,Handbook of RF and Microwave Solid-State Power AmplifiersPhase Noise and Frequency Stability in OscillatorsENRICO RUBIOLAProfessor of Electronics FEMTO-ST Institute CNRS and Universit´e de Franche Comt´e Besanc ¸on,FranceMore informationMore informationCAMBRIDGE UNIVERSITY PRESSCambridge,New Y ork,Melbourne,Madrid,Cape Town,Singapore,S˜a o Paulo,DelhiCambridge University PressThe Edinburgh Building,Cambridge CB28RU,UKPublished in the United States of America by Cambridge University Press,New Y orkInformation on this title:/9780521886772C Cambridge University Press2009This publication is in copyright.Subject to statutory exceptionand to the provisions of relevant collective licensing agreements,no reproduction of any part may take place withoutthe written permission of Cambridge University Press.First published2009Printed in the United Kingdom at the University Press,CambridgeA catalog record for this publication is available from the British LibraryISBN978-0-521-88677-2hardbackCambridge University Press has no responsibility for the persistence oraccuracy of URLs for external or third-party internet websites referred toin this publication,and does not guarantee that any content on suchwebsites is,or will remain,accurate or appropriate.More informationContentsForeword by Lute Maleki page ixForeword by David Leeson xiiPreface xv How to use this book xviSupplementary material xviii Notation xix 1Phase noise and frequency stability11.1Narrow-band signals11.2Physical quantities of interest51.3Elements of statistics91.4The measurement of power spectra131.5Linear and time-invariant(LTI)systems191.6Close-in noise spectrum221.7Time-domain variances251.8Relationship between spectra and variances291.9Experimental techniques30Exercises33 2Phase noise in semiconductors and amplifiers352.1Fundamental noise phenomena352.2Noise temperature and noisefigure372.3Phase noise and amplitude noise422.4Phase noise in cascaded amplifiers492.5 Low-flicker amplifiers522.6 Detection of microwave-modulated light62Exercises65 3Heuristic approach to the Leeson effect673.1Oscillator fundamentals673.2The Leeson formula72More informationvi Contents3.3The phase-noise spectrum of real oscillators753.4Other types of oscillator824Phase noise and feedback theory884.1Resonator differential equation884.2Resonator Laplace transform924.3The oscillator964.4Resonator in phase space1014.5Proof of the Leeson formula1114.6Frequency-fluctuation spectrum and Allan variance1164.7 A different,more general,derivation of the resonatorphase response1174.8 Frequency transformations1215Noise in delay-line oscillators and lasers1255.1Basic delay-line oscillator1255.2Optical resonators1285.3Mode selection1305.4The use of a resonator as a selectionfilter1335.5Phase-noise response1385.6Phase noise in lasers1435.7Close-in noise spectra and Allan variance1455.8Examples1466Oscillator hacking1506.1General guidelines1506.2About the examples of phase-noise spectra1546.3Understanding the quartz oscillator1546.4Quartz oscillators156Oscilloquartz OCXO8600(5MHz AT-cut BV A)156Oscilloquartz OCXO8607(5MHz SC-cut BV A)159RAKON PHARAO5MHz quartz oscillator162FEMTO-ST LD-cut quartz oscillator(10MHz)164Agilent10811quartz(10MHz)166Agilent noise-degeneration oscillator(10MHz)167Wenzel501-04623(100MHz SC-cut quartz)1716.5The origin of instability in quartz oscillators1726.6Microwave oscillators175Miteq DRO mod.D-210B175Poseidon DRO-10.4-FR(10.4GHz)177Poseidon Shoebox(10GHz sapphire resonator)179UWA liquid-N whispering-gallery9GHz oscillator182More informationContents vii6.7Optoelectronic oscillators185NIST10GHz opto-electronic oscillator(OEO)185OEwaves Tidalwave(10GHz OEO)188 Exercises190Appendix A Laplace transforms192References196Index202More informationForeword by Lute MalekiGiven the ubiquity of periodic phenomena in nature,it is not surprising that oscillatorsplay such a fundamental role in sciences and technology.In physics,oscillators are thebasis for the understanding of a wide range of concepts spanningfield theory and linearand nonlinear dynamics.In technology,oscillators are the source of operation in everycommunications system,in sensors and in radar,to name a few.As man’s study ofnature’s laws and human-made phenomena expands,oscillators have found applicationsin new realms.Oscillators and their interaction with each other,usually as phase locking,and withthe environment,as manifested by a change in their operational parameters,form thebasis of our understanding of a myriad phenomena in biology,chemistry,and evensociology and climatology.It is very difficult to account for every application in whichthe oscillator plays a role,either as an element that supports understanding or insight oran entity that allows a given application.In all thesefields,what is important is to understand how the physical parametersof the oscillator,i.e.its phase,frequency,and amplitude,are affected,either by theproperties of its internal components or by interaction with the environment in whichthe oscillator resides.The study of oscillator noise is fundamental to understanding allphenomena in which the oscillator model is used in optimization of the performance ofsystems requiring an oscillator.Simply stated,noise is the unwanted part of the oscillator signal and is unavoidablein practical systems.Beyond the influence of the environment,and the non-ideality ofthe physical elements that comprise the oscillator,the fundamental quantum nature ofelectrons and photons sets the limit to what may be achieved in the spectral purity of thegenerated signal.This sets the fundamental limit to the best performance that a practicaloscillator can produce,and it is remarkable that advanced oscillators can reach it.The practitioners who strive to advance thefield of oscillators in time-and-frequencyapplications cannot be content with knowledge of physics alone or engineering alone.The reason is that oscillators and clocks,whether of the common variety or the advancedtype,are complex“systems”that interact with their environment,sometimes in waysthat are not readily obvious or that are highly nonlinear.Thus the physicist is needed toidentify the underlying phenomenon and the parameters affecting performance,and theengineer is needed to devise the most effective and practical approach to deal with them.The present monograph by Professor Enrico Rubiola is unique in the extent to which itsatisfies both the physicist and the engineer.It also serves the need to understand bothMore informationx Forewordsthe fundamentals and the practice of phase-noise metrology,a required tool in dealingwith noise in oscillators.Rubiola’s approach to the treatment of noise in this book is based on the input–output transfer functions.While other approaches lead to some of the same results,this treatment allows the introduction of a mathematical rigor that is easily tractable byanyone with an introductory knowledge of Fourier and Laplace transforms.In particular,Rubiola uses this approach to obtain a derivation,fromfirst principles,of the Leesonformula.This formula has been used in the engineering literature for the noise analysisof the RF oscillator since its introduction by Leeson in1966.Leeson evidently arrivedat it without realizing that it was known earlier in the physics literature in a differentform as the Schawlow–Townes linewidth for the laser oscillator.While a number ofother approaches based on linear and nonlinear models exist for analyzing noise inan oscillator,the Leeson formula remains particularly useful for modeling the noisein high-performance oscillators.Given its relation to the Schawlow–Townes formula,it is not surprising that the Leeson model is so useful for analyzing the noise in theoptoelectronic oscillator,a newcomer to the realm of high-performance microwave andmillimeter-wave oscillators,which are also treated in this book.Starting in the Spring of2004,Professor Rubiola began a series of limited-timetenures in the Quantum Sciences and Technologies group at the Jet Propulsion Labo-ratory.Evidently,this can be regarded as the time when the initial seed for this bookwas conceived.During these visits,Rubiola was to help architect a system for themeasurement of the noise of a high-performance microwave oscillator,with the sameexperimental care that he had previously applied and published for the RF oscillators.Characteristically,Rubiola had to know all the details about the oscillator,its principleof operation,and the sources of noise in its every component.It was only then that hecould implement the improvement needed on the existing measurement system,whichwas based on the use of a longfiber delay in a homodyne setup.Since Rubiola is an avid admirer of the Leeson model,he was interested in applyingit to the optoelectronic oscillator,as well.In doing so,he developed both an approachfor analyzing the performance of a delay-line oscillator and a scheme based on Laplacetransforms to derive the Leeson formula,advancing the original,heuristic,approach.These two treatments,together with the range of other topics covered,should makethis unique book extremely useful and attractive to both the novice and experiencedpractitioners of thefield.It is delightful to see that in writing the monograph,Enrico Rubiola has so openlybared his professional persona.He pursues the subject with a blatant passion,andhe is characteristically not satisfied with“dumbing down,”a concept at odds withmathematical rigor.Instead,he provides visuals,charts,and tables to make his treatmentaccessible.He also shows his commensurate tendencies as an engineer by providingnumerical examples and details of the principles behind instruments used for noisemetrology.He balances this with the physicist in him that looks behind the obvious forthe fundamental causation.All this is enhanced with his mathematical skill,of which healways insists,with characteristic modesty,he wished to have more.Other ingredients,missing in the book,that define Enrico Rubiola are his knowledge of ancient languagesMore informationForewords xi and history.But these could not inform further such a comprehensive and extremelyuseful book on the subject of oscillator noise.Lute MalekiNASA/Caltech Jet Propulsion Laboratoryand OEwaves,Inc.,February2008More informationForeword by David LeesonPermit me to place Enrico Rubiola’s excellent book Phase Noise and Frequency Stabilityin Oscillators in context with the history of the subject over the pastfive decades,goingback to the beginnings of my own professional interest in oscillator frequency stability.Oscillator instabilities are a fundamental concern for systems tasked with keeping anddistributing precision time or frequency.Also,oscillator phase noise limits the demod-ulated signal-to-noise ratio in communication systems that rely on phase modulation,such as microwave relay systems,including satellite and deep-space parablyimportant are the dynamic range limits in multisignal systems resulting from the mask-ing of small signals of interest by oscillator phase noise on adjacent large signals.Forexample,Doppler radar targets are masked by ground clutter noise.These infrastructure systems have been well served by what might now be termedthe classical theory and measurement of oscillator noise,of which this volume is acomprehensive and up-to-date tutorial.Rubiola also exposes a number of significantconcepts that have escaped prior widespread notice.My early interest in oscillator noise came as solid-state signal sources began to beapplied to the radars that had been under development since the days of the MIT RadiationLaboratory.I was initiated into the phase-noise requirements of airborne Doppler radarand the underlying arts of crystal oscillators,power amplifiers,and nonlinear-reactancefrequency multipliers.In1964an IEEE committee was formed to prepare a standard on frequency stability.Thanks to a supportive mentor,W.K.Saunders,I became a member of that group,whichincluded leaders such as J.A.Barnes and L.S.Cutler.It was noted that the independentuse of frequency-domain and time-domain definitions stood in the way of the develop-ment of a common standard.To promote focused interchange the group sponsored theNovember1964NASA/IEEE Conference on Short Term Frequency Stability and editedthe February1966Special Issue on Frequency Stability of the Proceedings of the IEEE.The context of that time included the appreciation that self-limiting oscillators andmany systems(FM receivers with limiters,for example)are nonlinear in that theylimit amplitude variations(AM noise);hence the focus on phase noise.The modestfrequency limits of semiconductor devices of that period dictated the common usage ofnonlinear-reactance frequency multipliers,which multiply phase noise to the point whereit dominates the output noise spectrum.These typical circuit conditions were secondnature then to the“short-term stability community”but might not come so readily tomind today.More informationForewords xiii Thefirst step of the program to craft a standard that would define frequency stabilitywas to understand and meld the frequency-and time-domain descriptions of phaseinstability to a degree that was predictive and permitted analysis and optimization.Bythe time the subcommittee edited the Proc.IEEE special issue,the wide exchange ofviewpoints and concepts made it possible to synthesize concise summaries of the workin both domains,of which my own model was one.The committee published its“Characterization of frequency stability”in IEEE Trans.Instrum.Meas.,May1971.This led to the IEEE1139Standards that have served thecommunity well,with advances and revisions continuing since their initial publication.Rubiola’s book,based on his extensive seminar notes,is a capstone tutorial on thetheoretical basis and experimental measurements of oscillators for which phase noiseand frequency stability are primary issues.In hisfirst chapter Rubiola introduces the reader to the fundamental statistical de-scriptions of oscillator instabilities and discusses their role in the standards.Then in thesecond chapter he provides an exposition of the sources of noise in devices and circuits.In an instructive analysis of cascaded stages,he shows that,for modulative or parametricflicker noise,the effect of cascaded stages is cumulative without regard to stage gain.This is in contrast with the well-known treatment of additive noise using the Friisformula to calculate an equivalent input noise power representing noise that may originateanywhere in a cascade of real amplifiers.This example highlights the concept that“themodel is not the actual thing.”He also describes concepts for the reduction offlickernoise in amplifier stages.In his third chapter Rubiola then combines the elements of thefirst two chapters toderive models and techniques useful in characterizing phase noise arising in resonatorfeedback oscillators,adding mathematical formalism to these in the fourth chapter.Inthefifth chapter he extends the reader’s view to the case of delay-line oscillators suchas lasers.In his sixth chapter,Rubiola offers guidance for the instructive“hacking”ofexisting oscillators,using their external phase spectra and other measurables to estimatetheir internal configuration.He details cases in which resonatorfluctuations mask circuitnoise,showing that separately quantifying resonator noise can be fruitful and that devicenoisefigure and resonator Q are not merely arbitraryfitting factors.It’s interesting to consider what lies ahead in thisfield.The successes of today’sconsumer wireless products,cellular telephony,WiFi,satellite TV,and GPS,arise directlyfrom the economies of scale of highly integrated circuits.But at the same time thisintroduces compromises for active-device noise and resonator quality.A measure ofthe market penetration of multi-signal consumer systems such as cellular telephonyand WiFi is that they attract enough users to become interference-limited,often fromsubscribers much nearer than a distant base station.Hence low phase noise remainsessential to preclude an unacceptable decrease of dynamic range,but it must now beachieved within narrower bounds on the available circuit elements.A search for new understanding and techniques has been spurred by this requirementfor low phase noise in oscillators and synthesizers whose primary character is integrationand its accompanying minimal cost.This body of knowledge is advancing througha speculative and developmental phase.Today,numerical nonlinear circuit analysisMore informationxiv Forewordssupports additional design variables,such as the timing of the current pulse in nonlinearoscillators,that have become feasible because of the improved capabilities of bothsemiconductor devices and computers.Thefield is alive and well,with emerging players eager tofind a role on the stage fortheir own scenarios.Professionals and students,whether senior or new to thefield so ablydescribed by Rubiola,will benefit from his theoretical rigor,experimental viewpoint,and presentation.David B.LeesonStanford UniversityFebruary2008More informationPrefaceThe importance of oscillators in science and technology can be outlined by two mile-stones.The pendulum,discovered by Galileo Galilei in the sixteenth century,persistedas“the”time-measurement instrument(in conjunction with the Earth’s rotation period)until the piezoelectric quartz resonator.Then,it was not by chance that thefirst inte-grated circuit,built in September1958by Jack Kilby at the Bell Laboratories,was aradio-frequency oscillator.Time,and equivalently frequency,is the most precisely measured physical quantity.The wrist watch,for example,is probably the only cheap artifact whose accuracy ex-ceeds10−5,while in primary laboratories frequency attains the incredible accuracy ofa few parts in10−15.It is therefore inevitable that virtually all domains of engineeringand physics rely on time-and-frequency metrology and thus need reference oscillators.Oscillators are of major importance in a number of applications such as wireless com-munications,high-speed digital electronics,radars,and space research.An oscillator’srandomfluctuations,referred to as noise,can be decomposed into amplitude noise andphase noise.The latter,far more important,is related to the precision and accuracy oftime-and-frequency measurements,and is of course a limiting factor in applications.The main fact underlying this book is that an oscillator turns the phase noise of itsinternal parts into frequency noise.This is a necessary consequence of the Barkhausencondition for stationary oscillation,which states that the loop gain of a feedback oscillatormust be unity,with zero phase.It follows that the phase noise,which is the integral ofthe frequency noise,diverges in the long run.This phenomenon is often referred to asthe“Leeson model”after a short article published in1966by David B.Leeson[63].Onmy part,I prefer the term Leeson effect in order to emphasize that the phenomenon isfar more general than a simple model.In2001,in Seattle,Leeson received the W.G.Cady award of the IEEE International Frequency Control Symposium“for clear physicalinsight and[a]model of the effects of noise on oscillators.”In spring2004I had the opportunity to give some informal seminars on noise in oscil-lators at the NASA/Caltech Jet Propulsion Laboratory.Since then I have given lecturesand seminars on noise in industrial contexts,at IEEE symposia,and in universities andgovernment laboratories.The purpose of most of these seminars was to provide a tuto-rial,as opposed to a report on advanced science,addressed to a large-variance audiencethat included technicians,engineers,Ph.D.students,and senior scientists.Of course,capturing the attention of such a varied audience was a challenging task.The stimu-lating discussions that followed the seminars convinced me I should write a workingMore informationxvi Prefacedocument1as a preliminary step and then this book.In writing,I have made a seriouseffort to address the same broad audience.This work could not have been written without the help of many people.The gratitudeI owe to my colleagues and friends who contributed to the rise of the ideas containedin this book is disproportionate to its small size:R´e mi Brendel,Giorgio Brida,G.JohnDick,Michele Elia,Patrice F´e ron,Serge Galliou,Vincent Giordano,Charles A.(Chuck)Greenhall,Jacques Groslambert,John L.Hall,Vladimir S.(Vlad)Ilchenko,LaurentLarger,Lutfallah(Lute)Maleki,Andrey B.Matsko,Mark Oxborrow,Stefania R¨o misch,Anatoliy B.Savchenkov,Franc¸ois Vernotte,Nan Yu.Among them,I owe special thanks to the following:Lute Maleki for giving me theopportunity of spending four long periods at the NASA/Caltech Jet Propulsion Labora-tory,where I worked on noise in photonic oscillators,and for numerous discussions andsuggestions;G.John Dick,for giving invaluable ideas and suggestions during numerousand stimulating discussions;R´e mi Brendel,Mark Oxborrow,and Stefania R¨o misch fortheir personal efforts in reviewing large parts of the manuscript in meticulous detail andfor a wealth of suggestions and criticism;Vincent Giordano for supporting my effortsfor more than10years and for frequent and stimulating discussions.I wish to thank some manufacturers and their local representatives for kindness andprompt help:Jean-Pierre Aubry from Oscilloquartz;Vincent Candelier from RAKON(formerly CMAC);Art Faverio and Charif Nasrallah from Miteq;Jesse H.Searles fromPoseidon Scientific Instruments;and Mark Henderson from Oewaves.Thanks to my friend Roberto Bergonzo,for the superb picture on the front cover,entitled“The amethyst stairway.”For more information about this artist,visit the website.Finally,I wish to thank Julie Lancashire and Sabine Koch,of the Cambridge editorialstaff,for their kindness and patience during the long process of writing this book.How to use this bookLet usfirst abstract this book in one paragraph.Chapter1introduces the language ofphase noise and frequency stability.Chapter2analyzes phase noise in amplifiers,includ-ingflicker and other non-white phenomena.Chapter3explains heuristically the physicalmechanism of an oscillator and of its noise.Chapter4focuses on the mathematics thatdescribe an oscillator and its phase noise.For phase noise,the oscillator turns out to bea linear system.These concepts are extended in Chapter5to the delay-line oscillatorand to the laser,which is a special case of the latter.Finally,Chapter6analyzes indepth a number of oscillators,both laboratory prototypes and commercial products.Theanalysis of an oscillator’s phase noise discloses relevant details about the oscillator.There are other books about oscillators,though not numerous.They can be divided intothree categories:books on radio-frequency and microwave oscillators,which generallyfocus on the electronics;books about lasers,which privilege atomic physics and classical1E.Rubiola,The Leeson Effect–Phase Noise in Quasilinear Oscillators,February2005,arXiv:physics/0502143,now superseded by the present text.PrefacexviideeperreadingbasictheoreticaladvancedtheoreticallegendexperimentalistlecturerdeeperreadingFigure1Asymptotic reading paths:on the left,for someone planning lectures on oscillatornoise;on the right,for someone currently involved in practical work on oscillators.optics;books focusing on the relevant mathematical physics.The present text is uniquein that we look at the oscillator as a system consisting of more or less complex interactingblocks.Most topics are innovative,and the overlap with other books about oscillatorsor time-and-frequency metrology is surprisingly small.This may require an additionaleffort on the part of readers already familiar with the subject area.The core of this book rises from my experimentalist soul,which later became con-vinced of the importance of the mathematics.The material was originally thought anddrafted in the following(dis)order(see Fig.1):3Heuristic approach,6Oscillator hack-ing,4Feedback theory,5Delay-line oscillators.Thefinal order of subjects aims at amore understandable presentation.In seminars,I have often presented the material in the3–6–4–5order.Y et,the best reading path depends on the reader.T wo paths are suggestedin Fig.1for two“asymptotic”reader types,i.e.a lecturer and experimentalist.Whenplanning to use this book as a supplementary text for a university course,the lecturer More information。

A rapid and simple assay for lamotrigine in serum/plasma by HPLC,and comparison with an immunoassayPhillip E.Morgan,*Danielle S.Fisher,Richard Evers and Robert J.Flanagan ABSTRACT:Monitoring serum/plasma concentrations of lamotrigine may be useful under certain circumstances.An HPLC column packed with strong cation-exchange(SCX)-modified microparticulate silica together with a100%methanol eluent containing an ionic modifier permits direct injection of sample extracts.An HPLC-UV method developed using this principle for the measurement of serum/plasma lamotrigine is simple,sensitive and selective.The analysis time is less than5min.Intra-and inter-assay precision and accuracy meet acceptance criteria,and sample stability,and potential interferences from other compounds have been evaluated.There was good agreement with consensus mean results from external quality assessment samples(n=32).Analysis of patient samples(n=115)using the HPLC method and the Seradyn QMS®Lamotrigine immunoas-say showed that the immunoassay over-estimated lamotrigine by21%on average.Copyright©2010John Wiley&Sons,Ltd.Keywords:lamotrigine;strong cation-exchange HPLC;non-aqueous ionic eluents;immunoassayIntroductionLamotrigine(Fig.1)is used in the treatment of epilepsy,either alone or in combination with other anticonvulsants.It is also used as a mood stabilizer in bipolar disorder,for motrigine dose adjustment is not straightforward due to(i)large inter-patient variations in dose requirement and(ii)important interac-tions with other anticonvulsants,notably phenobarbital, carbamazepine,phenytoin and valproic acid.The measurement of serum or plasma lamotrigine can therefore be useful,particu-larly during dose adjustment and when combination anticonvul-sant therapy is initiated or withdrawn(Angelis-Stoforidis et al., 1999;Johannessen et al.,2003;Subramanian et al.,2008). Published methods for serum/plasma lamotrigine measure-ment are generally based on reversed-phase HPLC(RPLC)with UV detection(Angelis-Stoforidis et al.,1999;Barbosa and Mídio, 2000;Beck et al.,2006;Saracino et al.,2007;Greiner-Sosanko et al.,2007),usually involving evaporation of sample extracts fol-lowed by reconstitution in eluent prior to chromatographic analysis.The strong cation-exchange(SCX)HPLC-UV method developed allows direct injection of sample extracts and is simple,fast,sensitive and selective.Method validation incorpo-rated a comparison with the results obtained from patient samples using the Seradyn QMS®lamotrigine immunoassay. ExperimentalChemicals and reagentsLamotrigine was a gift from GlaxoSmithKline(Stevenage,UK).Sodium hydroxide(reagent grade),tris(hydroxymethyl)aminomethane(Tris,ACS grade)and nortriptyline hydrochloride(min98%)were from Sigma (Poole,UK).Ammonium perchlorate(Ն98%)and perchloric acid(60%) were from Fluka(Poole,UK).Methanol and methyl tert-butyl ether(MTBE; both HPLC grade)were from Rathburn(Walkerburn,UK),and NIST-traceable pH reference buffer solutions were from Merck(Beeston, UK).Coarselyfiltered pooled human serum was from Scipac (Sittingbourne,UK).Tris solution(2mol/L,pH10.6)was prepared by dissolving232g Tris in deionized water(total volume2L),and the pH adjusted using aqueous hydrochloric acid(6mol/L).Internal standard solution(5mg/L nortrip-tyline free-base)was prepared by dilution of a stock solution(500mg/L free-base in0.1mol/L hydrochloric acid)with deionized water,and stored at2–8°C.A stock HPLC eluent solution(100mmol/L)was prepared by adding23.5g ammonium perchlorate to a2L volumetricflask containing20mL of sodium hydroxide(0.1mol/L)in methanol,and making up to volume with methanol.This solution was diluted with methanol to give an eluent ionic strength of35mmol/L ammonium perchlorate.The eluent was vacuumfiltered(0.45m m,nylon66)and the apparent pH(pH*)adjusted to6.0using perchloric acid(1%v/v in methanol)before use.The combi-nation pH electrode(Liq-Glass;Hamilton)was calibrated using aqueous buffers(pH4.00,7.00,and10.00).Materials and equipmentGlass test tubes(60¥7mm,Dreyer tubes)were from Esslab(Benfleet, UK).Sample/calibration solution/internal quality control(IQC)solutions were pipetted using variable volume air-displacement pipettes(BioHit, Finland),and internal standard added using a repeating volume dispens-ing pipette(Multipette®,Hamilton).Extendedfine-tipped pastettes were *Correspondence to:P.E.Morgan,Toxicology Unit,Department of Clinical Biochemistry,King’s College Hospital NHS Foundation Trust,Denmark Hill, London SE59RS,UK.E-mail:phillip.morgan@Toxicology Unit,Department of Clinical Biochemistry,King’s College Hospi-tal NHS Foundation Trust,Denmark Hill,London SE59RS,UK Abbreviations used:EQA,external quality assessment;IQC,internal quality control;MTBE,methyl tert-butyl ether;SCX,strong cation-exchange.Research articleReceived12July2010,Accepted26July2010Published online in Wiley Online Library:01September2010 ()DOI10.1002/bmc.1515775 Biomed.Chromatogr.2011;25:775–778Copyright©2010John Wiley&Sons,Ltd.P.E.Morgan et al.776Biomed.Chromatogr.2011;25:775–778/journal/bmc Copyright©2010John Wiley&Sons,Ltd.777Lamotrigine assay by SCX-HPLCBiomed.Chromatogr.2011;25:775–/journal/bmcCopyright ©2010John Wiley &Sons,Ltd.AcknowledgementsWe thank Professor Philip Patsalos for helpful comments.ReferencesAngelis-Stoforidis P,Morgan DJ,O’Brien TJ and Vajda FJE.Determination of lamotrigine in human plasma by high-performance liquid chroma-tography.Journal of Chromatography B1999;727:113–118;doi:10.1016/S0378-4347(99)00043-2.Barbosa NR and Mídio AF.Validated high-performance liquid chromato-graphic method for the determination of lamotrigine in human plasma.Journal of Chromatography B2000;741:289–293;doi:10.1016/S0378-4347(00)00102-X.Beck O,Öhman I and Nordgren HK.Determination of lamotrigine and its metabolites in human plasma by liquid chromatography-mass spec-trometry.Therapeutic Drug Monitoring2006;28:603–607;doi:10.1097/01.ftd.0000245779.64080.30.Flanagan RJ,Harvey EJ and Spencer EP.HPLC of basic drugs on micropar-ticulate strong cation-exchange materials—a review.Forensic Science International2001;121:97–102;doi:10.1016/S0379-0738(01) 00458-3.Greiner-Sosanko E,Lower DR,Virji MA and Krasowski MD.Simultaneous determination of lamotrigine,zonisamide,and carbamazepine in human plasma by high-performance liquid chromatography.Bio-medical Chromatography2007;21:225–228;doi:10.1002/bmc.753. Johannessen SI,Battino D,Berry DJ,Bialer M,Krämer G,Tomson T and Patsalos P.Therapeutic drug monitoring of the newer antiepileptic drugs.Therapeutic Drug Monitoring2003;25:347–363.Morgan PE,Manwaring V and Flanagan RJ.HPLC of basic drugs using non-aqueous ionic eluents:evaluation of a3m m strong cation-exchange material.Biomedical Chromatography2010;24:318–323;doi:10.1002/bmc.1292.Saracino MA,Bugamelli F,Conti M,Amore M and Raggi M.Rapid HPLC analysis of the antiepileptic lamotrigine and its metabolites in human plasma.Journal of Separation Science2007;30:2249–2255;doi:10.1002/jssc.200700110.Subramanian M,Birnbaum AK and Remmel RP.High-speed simul-taneous determination of nine antiepileptic drugs using liquid chromatography-mass spectrometry.Therapeutic Drug Monitoring 2008;30:347–356;doi:10.1097/FTD.0b013e3181678ecb.Westley IS and Morris RG.Seradyn quantitative microsphere system lamotrigine immunoassay on a Hitachi911analyzer compared with HPLC-UV.Therapeutic Drug Monitoring2008;30:634–637;doi:10.1097/FTD.0b013e31818580b3.778P.E.Morgan et al.Biomed.Chromatogr.2011;25:775–778 /journal/bmc Copyright©2010John Wiley&Sons,Ltd.。