博哈博哈英语格式化集训12级教材

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Lecture-12_Mult-Reg

13
Interpreting the Coefficient Parameters

Now that we have multiple independent variables, how do we interpret the coefficient parameters? Suppose we have a model with two independent variables: �� = ��0 + ��1 ��1,�� + ��2 ��2,�� + ��

STAT7055 - Lecture 12
5
Multiple Regression – Advantages

Also, provided that the independent variables we choose for our model are all truly related to the dependent variable, a multiple regression model will tend to produce better predictions than a simple linear regression model. That is, for a new observation not in our sample, the predicted value will be closer to the true value.
STAT7055 - Lecture 12 7

Multiple Regression – Caveats

Book 10 博哈英语格式化集训12级教材之第十册

Unit 1
你喜欢哪间办公室？
Which office do you like?
这对我来说无所谓。我可以要大的那间吗？
It doesn't matter to me. Can I have the big one?
你喜欢哪个房间？
Which room do you like?
这对我来说无所谓。我可以要大的那间吗？
你认为他会帮你们吗？
Do you think he will help you?
如果我们把目前的状况告诉他的话，我肯定他会帮我们的。
I am sure he will help us if we tell him about our present situation.
你认为他会帮你们吗？
It doesn't matter to me. Can I have the big one?
你要哪一半？
Which half do you like?
这对我来说无所谓。我可以要较大的那半吗？
It doesn't matter to me. Can I have the bigger half?
不一定。不过为什么不学好它呢？
Not really. But why not?
Unit 5
你认为他会帮你们吗？
Do you think he will help you?
如果他有时间的话，我肯定他会帮我们的。
I am sure he will help us if he has time.
你的婚姻生活怎么样？
What do you feel about your marriage life?

李阳疯狂英语封闭强化集训营专用教材

李阳疯狂英语封闭强化集训营专用教材分级：小学1级、2级、3级；初中1级、2级；高中1级、2级内容：1.每级30个句型+3篇短文（也可以是演讲或小诗）2.所有句型最多配3个例句，每个例句都要加意群3.每篇短文除英文和译文、注释外，做一个学习版，加音标和意群4.每个级别加语法讲解：每个语法结构最多加3个简单例句小学1级：主谓结构小学2级：主谓宾小学3级：主谓宾补初1：时态（标美教程上有最常用的8~10个时态）初2：宾语从句、状语从句、表语从句、不定式高1：非谓语动词（不定式、V-ed、V-ing）高2：名词性从句、定语从句、状语从句5.初高中每级各增加一篇完形、阅读和写作小学一级I thank1 / my family2.I thank / my teachers3.I thank / my friends4.I thank / everyone5！I love6 / my family. love / my teachers.I love / my friends.I love / everyone！【李阳疯狂英语“三最”口腔肌肉训练记录为：10秒】【李阳疯狂英语“一口气”训练记录为：0.5口气】【参考译文】我感谢我的家人。

我感谢我的老师。

我感谢我的朋友。

我感谢每一个人！我爱我的家人。

我爱我的老师。

我爱我的朋友。

我爱每一个人！Most of / my classmates1 / are very shy, / but / I am not shy. / I follow/ Teacher Li Yang’s / advice4: / “Don’t be shy. / Just try5!” / I’m not afraid of6 / making mistakes7. / I’m not afraid of / being laughed at8. / I enjoy9 / losing face10. I want to speak11 / beautiful12 English!【李阳疯狂英语“三最”口腔肌肉训练记录为：12秒】【李阳疯狂英语“一口气”训练记录为：1口气】【参考译文】我大部分的同学都很害羞，但是我不害羞。

OSHA现场作业手册说明书

DIRECTIVE NUMBER: CPL 02-00-150 EFFECTIVE DATE: April 22, 2011 SUBJECT: Field Operations Manual (FOM)ABSTRACTPurpose: This instruction cancels and replaces OSHA Instruction CPL 02-00-148,Field Operations Manual (FOM), issued November 9, 2009, whichreplaced the September 26, 1994 Instruction that implemented the FieldInspection Reference Manual (FIRM). The FOM is a revision of OSHA’senforcement policies and procedures manual that provides the field officesa reference document for identifying the responsibilities associated withthe majority of their inspection duties. This Instruction also cancels OSHAInstruction FAP 01-00-003 Federal Agency Safety and Health Programs,May 17, 1996 and Chapter 13 of OSHA Instruction CPL 02-00-045,Revised Field Operations Manual, June 15, 1989.Scope: OSHA-wide.References: Title 29 Code of Federal Regulations §1903.6, Advance Notice ofInspections; 29 Code of Federal Regulations §1903.14, Policy RegardingEmployee Rescue Activities; 29 Code of Federal Regulations §1903.19,Abatement Verification; 29 Code of Federal Regulations §1904.39,Reporting Fatalities and Multiple Hospitalizations to OSHA; and Housingfor Agricultural Workers: Final Rule, Federal Register, March 4, 1980 (45FR 14180).Cancellations: OSHA Instruction CPL 02-00-148, Field Operations Manual, November9, 2009.OSHA Instruction FAP 01-00-003, Federal Agency Safety and HealthPrograms, May 17, 1996.Chapter 13 of OSHA Instruction CPL 02-00-045, Revised FieldOperations Manual, June 15, 1989.State Impact: Notice of Intent and Adoption required. See paragraph VI.Action Offices: National, Regional, and Area OfficesOriginating Office: Directorate of Enforcement Programs Contact: Directorate of Enforcement ProgramsOffice of General Industry Enforcement200 Constitution Avenue, NW, N3 119Washington, DC 20210202-693-1850By and Under the Authority ofDavid Michaels, PhD, MPHAssistant SecretaryExecutive SummaryThis instruction cancels and replaces OSHA Instruction CPL 02-00-148, Field Operations Manual (FOM), issued November 9, 2009. The one remaining part of the prior Field Operations Manual, the chapter on Disclosure, will be added at a later date. This Instruction also cancels OSHA Instruction FAP 01-00-003 Federal Agency Safety and Health Programs, May 17, 1996 and Chapter 13 of OSHA Instruction CPL 02-00-045, Revised Field Operations Manual, June 15, 1989. This Instruction constitutes OSHA’s general enforcement policies and procedures manual for use by the field offices in conducting inspections, issuing citations and proposing penalties.Significant Changes∙A new Table of Contents for the entire FOM is added.∙ A new References section for the entire FOM is added∙ A new Cancellations section for the entire FOM is added.∙Adds a Maritime Industry Sector to Section III of Chapter 10, Industry Sectors.∙Revises sections referring to the Enhanced Enforcement Program (EEP) replacing the information with the Severe Violator Enforcement Program (SVEP).∙Adds Chapter 13, Federal Agency Field Activities.∙Cancels OSHA Instruction FAP 01-00-003, Federal Agency Safety and Health Programs, May 17, 1996.DisclaimerThis manual is intended to provide instruction regarding some of the internal operations of the Occupational Safety and Health Administration (OSHA), and is solely for the benefit of the Government. No duties, rights, or benefits, substantive or procedural, are created or implied by this manual. The contents of this manual are not enforceable by any person or entity against the Department of Labor or the United States. Statements which reflect current Occupational Safety and Health Review Commission or court precedents do not necessarily indicate acquiescence with those precedents.Table of ContentsCHAPTER 1INTRODUCTIONI.PURPOSE. ........................................................................................................... 1-1 II.SCOPE. ................................................................................................................ 1-1 III.REFERENCES .................................................................................................... 1-1 IV.CANCELLATIONS............................................................................................. 1-8 V. ACTION INFORMATION ................................................................................. 1-8A.R ESPONSIBLE O FFICE.......................................................................................................................................... 1-8B.A CTION O FFICES. .................................................................................................................... 1-8C. I NFORMATION O FFICES............................................................................................................ 1-8 VI. STATE IMPACT. ................................................................................................ 1-8 VII.SIGNIFICANT CHANGES. ............................................................................... 1-9 VIII.BACKGROUND. ................................................................................................. 1-9 IX. DEFINITIONS AND TERMINOLOGY. ........................................................ 1-10A.T HE A CT................................................................................................................................................................. 1-10B. C OMPLIANCE S AFETY AND H EALTH O FFICER (CSHO). ...........................................................1-10B.H E/S HE AND H IS/H ERS ..................................................................................................................................... 1-10C.P ROFESSIONAL J UDGMENT............................................................................................................................... 1-10E. W ORKPLACE AND W ORKSITE ......................................................................................................................... 1-10CHAPTER 2PROGRAM PLANNINGI.INTRODUCTION ............................................................................................... 2-1 II.AREA OFFICE RESPONSIBILITIES. .............................................................. 2-1A.P ROVIDING A SSISTANCE TO S MALL E MPLOYERS. ...................................................................................... 2-1B.A REA O FFICE O UTREACH P ROGRAM. ............................................................................................................. 2-1C. R ESPONDING TO R EQUESTS FOR A SSISTANCE. ............................................................................................ 2-2 III. OSHA COOPERATIVE PROGRAMS OVERVIEW. ...................................... 2-2A.V OLUNTARY P ROTECTION P ROGRAM (VPP). ........................................................................... 2-2B.O NSITE C ONSULTATION P ROGRAM. ................................................................................................................ 2-2C.S TRATEGIC P ARTNERSHIPS................................................................................................................................. 2-3D.A LLIANCE P ROGRAM ........................................................................................................................................... 2-3 IV. ENFORCEMENT PROGRAM SCHEDULING. ................................................ 2-4A.G ENERAL ................................................................................................................................................................. 2-4B.I NSPECTION P RIORITY C RITERIA. ..................................................................................................................... 2-4C.E FFECT OF C ONTEST ............................................................................................................................................ 2-5D.E NFORCEMENT E XEMPTIONS AND L IMITATIONS. ....................................................................................... 2-6E.P REEMPTION BY A NOTHER F EDERAL A GENCY ........................................................................................... 2-6F.U NITED S TATES P OSTAL S ERVICE. .................................................................................................................. 2-7G.H OME-B ASED W ORKSITES. ................................................................................................................................ 2-8H.I NSPECTION/I NVESTIGATION T YPES. ............................................................................................................... 2-8 V.UNPROGRAMMED ACTIVITY – HAZARD EVALUATION AND INSPECTION SCHEDULING ............................................................................ 2-9 VI.PROGRAMMED INSPECTIONS. ................................................................... 2-10A.S ITE-S PECIFIC T ARGETING (SST) P ROGRAM. ............................................................................................. 2-10B.S CHEDULING FOR C ONSTRUCTION I NSPECTIONS. ..................................................................................... 2-10C.S CHEDULING FOR M ARITIME I NSPECTIONS. ............................................................................. 2-11D.S PECIAL E MPHASIS P ROGRAMS (SEP S). ................................................................................... 2-12E.N ATIONAL E MPHASIS P ROGRAMS (NEP S) ............................................................................... 2-13F.L OCAL E MPHASIS P ROGRAMS (LEP S) AND R EGIONAL E MPHASIS P ROGRAMS (REP S) ............ 2-13G.O THER S PECIAL P ROGRAMS. ............................................................................................................................ 2-13H.I NSPECTION S CHEDULING AND I NTERFACE WITH C OOPERATIVE P ROGRAM P ARTICIPANTS ....... 2-13CHAPTER 3INSPECTION PROCEDURESI.INSPECTION PREPARATION. .......................................................................... 3-1 II.INSPECTION PLANNING. .................................................................................. 3-1A.R EVIEW OF I NSPECTION H ISTORY .................................................................................................................... 3-1B.R EVIEW OF C OOPERATIVE P ROGRAM P ARTICIPATION .............................................................................. 3-1C.OSHA D ATA I NITIATIVE (ODI) D ATA R EVIEW .......................................................................................... 3-2D.S AFETY AND H EALTH I SSUES R ELATING TO CSHO S.................................................................. 3-2E.A DVANCE N OTICE. ................................................................................................................................................ 3-3F.P RE-I NSPECTION C OMPULSORY P ROCESS ...................................................................................................... 3-5G.P ERSONAL S ECURITY C LEARANCE. ................................................................................................................. 3-5H.E XPERT A SSISTANCE. ........................................................................................................................................... 3-5 III. INSPECTION SCOPE. ......................................................................................... 3-6A.C OMPREHENSIVE ................................................................................................................................................... 3-6B.P ARTIAL. ................................................................................................................................................................... 3-6 IV. CONDUCT OF INSPECTION .............................................................................. 3-6A.T IME OF I NSPECTION............................................................................................................................................. 3-6B.P RESENTING C REDENTIALS. ............................................................................................................................... 3-6C.R EFUSAL TO P ERMIT I NSPECTION AND I NTERFERENCE ............................................................................. 3-7D.E MPLOYEE P ARTICIPATION. ............................................................................................................................... 3-9E.R ELEASE FOR E NTRY ............................................................................................................................................ 3-9F.B ANKRUPT OR O UT OF B USINESS. .................................................................................................................... 3-9G.E MPLOYEE R ESPONSIBILITIES. ................................................................................................. 3-10H.S TRIKE OR L ABOR D ISPUTE ............................................................................................................................. 3-10I. V ARIANCES. .......................................................................................................................................................... 3-11 V. OPENING CONFERENCE. ................................................................................ 3-11A.G ENERAL ................................................................................................................................................................ 3-11B.R EVIEW OF A PPROPRIATION A CT E XEMPTIONS AND L IMITATION. ..................................................... 3-13C.R EVIEW S CREENING FOR P ROCESS S AFETY M ANAGEMENT (PSM) C OVERAGE............................. 3-13D.R EVIEW OF V OLUNTARY C OMPLIANCE P ROGRAMS. ................................................................................ 3-14E.D ISRUPTIVE C ONDUCT. ...................................................................................................................................... 3-15F.C LASSIFIED A REAS ............................................................................................................................................. 3-16VI. REVIEW OF RECORDS. ................................................................................... 3-16A.I NJURY AND I LLNESS R ECORDS...................................................................................................................... 3-16B.R ECORDING C RITERIA. ...................................................................................................................................... 3-18C. R ECORDKEEPING D EFICIENCIES. .................................................................................................................. 3-18 VII. WALKAROUND INSPECTION. ....................................................................... 3-19A.W ALKAROUND R EPRESENTATIVES ............................................................................................................... 3-19B.E VALUATION OF S AFETY AND H EALTH M ANAGEMENT S YSTEM. ....................................................... 3-20C.R ECORD A LL F ACTS P ERTINENT TO A V IOLATION. ................................................................................. 3-20D.T ESTIFYING IN H EARINGS ................................................................................................................................ 3-21E.T RADE S ECRETS. ................................................................................................................................................. 3-21F.C OLLECTING S AMPLES. ..................................................................................................................................... 3-22G.P HOTOGRAPHS AND V IDEOTAPES.................................................................................................................. 3-22H.V IOLATIONS OF O THER L AWS. ....................................................................................................................... 3-23I.I NTERVIEWS OF N ON-M ANAGERIAL E MPLOYEES .................................................................................... 3-23J.M ULTI-E MPLOYER W ORKSITES ..................................................................................................................... 3-27 K.A DMINISTRATIVE S UBPOENA.......................................................................................................................... 3-27 L.E MPLOYER A BATEMENT A SSISTANCE. ........................................................................................................ 3-27 VIII. CLOSING CONFERENCE. .............................................................................. 3-28A.P ARTICIPANTS. ..................................................................................................................................................... 3-28B.D ISCUSSION I TEMS. ............................................................................................................................................ 3-28C.A DVICE TO A TTENDEES .................................................................................................................................... 3-29D.P ENALTIES............................................................................................................................................................. 3-30E.F EASIBLE A DMINISTRATIVE, W ORK P RACTICE AND E NGINEERING C ONTROLS. ............................ 3-30F.R EDUCING E MPLOYEE E XPOSURE. ................................................................................................................ 3-32G.A BATEMENT V ERIFICATION. ........................................................................................................................... 3-32H.E MPLOYEE D ISCRIMINATION .......................................................................................................................... 3-33 IX. SPECIAL INSPECTION PROCEDURES. ...................................................... 3-33A.F OLLOW-UP AND M ONITORING I NSPECTIONS............................................................................................ 3-33B.C ONSTRUCTION I NSPECTIONS ......................................................................................................................... 3-34C. F EDERAL A GENCY I NSPECTIONS. ................................................................................................................. 3-35CHAPTER 4VIOLATIONSI. BASIS OF VIOLATIONS ..................................................................................... 4-1A.S TANDARDS AND R EGULATIONS. .................................................................................................................... 4-1B.E MPLOYEE E XPOSURE. ........................................................................................................................................ 4-3C.R EGULATORY R EQUIREMENTS. ........................................................................................................................ 4-6D.H AZARD C OMMUNICATION. .............................................................................................................................. 4-6E. E MPLOYER/E MPLOYEE R ESPONSIBILITIES ................................................................................................... 4-6 II. SERIOUS VIOLATIONS. .................................................................................... 4-8A.S ECTION 17(K). ......................................................................................................................... 4-8B.E STABLISHING S ERIOUS V IOLATIONS ............................................................................................................ 4-8C. F OUR S TEPS TO BE D OCUMENTED. ................................................................................................................... 4-8 III. GENERAL DUTY REQUIREMENTS ............................................................. 4-14A.E VALUATION OF G ENERAL D UTY R EQUIREMENTS ................................................................................. 4-14B.E LEMENTS OF A G ENERAL D UTY R EQUIREMENT V IOLATION.............................................................. 4-14C. U SE OF THE G ENERAL D UTY C LAUSE ........................................................................................................ 4-23D.L IMITATIONS OF U SE OF THE G ENERAL D UTY C LAUSE. ..............................................................E.C LASSIFICATION OF V IOLATIONS C ITED U NDER THE G ENERAL D UTY C LAUSE. ..................F. P ROCEDURES FOR I MPLEMENTATION OF S ECTION 5(A)(1) E NFORCEMENT ............................ 4-25 4-27 4-27IV.OTHER-THAN-SERIOUS VIOLATIONS ............................................... 4-28 V.WILLFUL VIOLATIONS. ......................................................................... 4-28A.I NTENTIONAL D ISREGARD V IOLATIONS. ..........................................................................................4-28B.P LAIN I NDIFFERENCE V IOLATIONS. ...................................................................................................4-29 VI. CRIMINAL/WILLFUL VIOLATIONS. ................................................... 4-30A.A REA D IRECTOR C OORDINATION ....................................................................................................... 4-31B.C RITERIA FOR I NVESTIGATING P OSSIBLE C RIMINAL/W ILLFUL V IOLATIONS ........................ 4-31C. W ILLFUL V IOLATIONS R ELATED TO A F ATALITY .......................................................................... 4-32 VII. REPEATED VIOLATIONS. ...................................................................... 4-32A.F EDERAL AND S TATE P LAN V IOLATIONS. ........................................................................................4-32B.I DENTICAL S TANDARDS. .......................................................................................................................4-32C.D IFFERENT S TANDARDS. .......................................................................................................................4-33D.O BTAINING I NSPECTION H ISTORY. .....................................................................................................4-33E.T IME L IMITATIONS..................................................................................................................................4-34F.R EPEATED V. F AILURE TO A BATE....................................................................................................... 4-34G. A REA D IRECTOR R ESPONSIBILITIES. .............................................................................. 4-35 VIII. DE MINIMIS CONDITIONS. ................................................................... 4-36A.C RITERIA ................................................................................................................................................... 4-36B.P ROFESSIONAL J UDGMENT. ..................................................................................................................4-37C. A REA D IRECTOR R ESPONSIBILITIES. .............................................................................. 4-37 IX. CITING IN THE ALTERNATIVE ............................................................ 4-37 X. COMBINING AND GROUPING VIOLATIONS. ................................... 4-37A.C OMBINING. ..............................................................................................................................................4-37B.G ROUPING. ................................................................................................................................................4-38C. W HEN N OT TO G ROUP OR C OMBINE. ................................................................................................4-38 XI. HEALTH STANDARD VIOLATIONS ....................................................... 4-39A.C ITATION OF V ENTILATION S TANDARDS ......................................................................................... 4-39B.V IOLATIONS OF THE N OISE S TANDARD. ...........................................................................................4-40 XII. VIOLATIONS OF THE RESPIRATORY PROTECTION STANDARD(§1910.134). ....................................................................................................... XIII. VIOLATIONS OF AIR CONTAMINANT STANDARDS (§1910.1000) ... 4-43 4-43A.R EQUIREMENTS UNDER THE STANDARD: .................................................................................................. 4-43B.C LASSIFICATION OF V IOLATIONS OF A IR C ONTAMINANT S TANDARDS. ......................................... 4-43 XIV. CITING IMPROPER PERSONAL HYGIENE PRACTICES. ................... 4-45A.I NGESTION H AZARDS. .................................................................................................................................... 4-45B.A BSORPTION H AZARDS. ................................................................................................................................ 4-46C.W IPE S AMPLING. ............................................................................................................................................. 4-46D.C ITATION P OLICY ............................................................................................................................................ 4-46 XV. BIOLOGICAL MONITORING. ...................................................................... 4-47CHAPTER 5CASE FILE PREPARATION AND DOCUMENTATIONI.INTRODUCTION ............................................................................................... 5-1 II.INSPECTION CONDUCTED, CITATIONS BEING ISSUED. .................... 5-1A.OSHA-1 ................................................................................................................................... 5-1B.OSHA-1A. ............................................................................................................................... 5-1C. OSHA-1B. ................................................................................................................................ 5-2 III.INSPECTION CONDUCTED BUT NO CITATIONS ISSUED .................... 5-5 IV.NO INSPECTION ............................................................................................... 5-5 V. HEALTH INSPECTIONS. ................................................................................. 5-6A.D OCUMENT P OTENTIAL E XPOSURE. ............................................................................................................... 5-6B.E MPLOYER’S O CCUPATIONAL S AFETY AND H EALTH S YSTEM. ............................................................. 5-6 VI. AFFIRMATIVE DEFENSES............................................................................. 5-8A.B URDEN OF P ROOF. .............................................................................................................................................. 5-8B.E XPLANATIONS. ..................................................................................................................................................... 5-8 VII. INTERVIEW STATEMENTS. ........................................................................ 5-10A.G ENERALLY. ......................................................................................................................................................... 5-10B.CSHO S SHALL OBTAIN WRITTEN STATEMENTS WHEN: .......................................................................... 5-10C.L ANGUAGE AND W ORDING OF S TATEMENT. ............................................................................................. 5-11D.R EFUSAL TO S IGN S TATEMENT ...................................................................................................................... 5-11E.V IDEO AND A UDIOTAPED S TATEMENTS. ..................................................................................................... 5-11F.A DMINISTRATIVE D EPOSITIONS. .............................................................................................5-11 VIII. PAPERWORK AND WRITTEN PROGRAM REQUIREMENTS. .......... 5-12 IX.GUIDELINES FOR CASE FILE DOCUMENTATION FOR USE WITH VIDEOTAPES AND AUDIOTAPES .............................................................. 5-12 X.CASE FILE ACTIVITY DIARY SHEET. ..................................................... 5-12 XI. CITATIONS. ..................................................................................................... 5-12A.S TATUTE OF L IMITATIONS. .............................................................................................................................. 5-13B.I SSUING C ITATIONS. ........................................................................................................................................... 5-13C.A MENDING/W ITHDRAWING C ITATIONS AND N OTIFICATION OF P ENALTIES. .................................. 5-13D.P ROCEDURES FOR A MENDING OR W ITHDRAWING C ITATIONS ............................................................ 5-14 XII. INSPECTION RECORDS. ............................................................................... 5-15A.G ENERALLY. ......................................................................................................................................................... 5-15B.R ELEASE OF I NSPECTION I NFORMATION ..................................................................................................... 5-15C. C LASSIFIED AND T RADE S ECRET I NFORMATION ...................................................................................... 5-16。

recent initiaatives by the basel-based r_qt0806

BIS Quarterly ReviewJune 2008 International banking and financial market developmentsBIS Quarterly ReviewMonetary and Economic DepartmentEditorial Committee:Claudio Borio Frank Packer Paul Van den BerghWhite Már Gudmundsson Eli Remolona William Robert McCauley Philip TurnerGeneral queries concerning this commentary should be addressed to Frank Packer(tel +41 61 280 8449, e-mail: frank.packer@), queries concerning specific parts to theauthors, whose details appear at the head of each section, and queries concerning the statisticsto Philippe Mesny (tel +41 61 280 8425, e-mail: philippe.mesny@).Requests for copies of publications, or for additions/changes to the mailing list, should be sent to:Bank for International SettlementsPress & CommunicationsCH-4002 Basel, SwitzerlandE-mail: publications@Fax: +41 61 280 9100 and +41 61 280 8100This publication is available on the BIS website ().©Bank for International Settlements 2008. All rights reserved. Brief excerpts may be reproduced or translated provided the source is cited.ISSN 1683-0121 (print)ISSN 1683-013X (online)BIS Quarterly ReviewJune 2008International banking and financial market developmentsOverview : a cautious return of risk tolerance (1)Credit market turmoil gives way to fragile recovery (1)Box: Estimating valuation losses on subprime MBS with theABX HE index – some potential pitfalls (6)Bond yields recover as markets stabilise (8)A turning point for equity prices? (11)Emerging market investors discount growth risks (12)Tensions in interbank markets remain high (13)Highlights of international banking and financial market activity (17)The international banking market (17)The international debt securities market (23)Derivatives markets (24)Box: An update on local currency debt securities marketsin emerging market economies (28)Special featuresInternational banking activity amidst the turmoil (31)Patrick McGuire and Goetz von PeterThe build-up of international bank balance sheets (32)Developments in the second half of 2007 (36)Bilateral exposures of national banking systems (39)Concluding remarks (42)Managing international reserves: how does diversification affect financial costs? 45 Srichander RamaswamyFramework of the analysis (46)Risk-return trade-offs (48)Financial cost of acquiring reserves through FX intervention (49)Box: Methodology for computing estimates of financial cost (51)Central bank objectives and FX reserve allocation (53)Conclusions (54)Credit derivatives and structured credit: the nascent markets of Asiaand the Pacific (57)Eli M Remolona and Ilhyock ShimCredit default swaps (58)Traded CDS indices (60)Collaterised debt obligations (61)How the region’s markets have fared in the global turmoil (63)Conclusion (65)Asian banks and the international interbank market (67)Robert N McCauley and Jens ZukunftAsian banks’ international interbank liquidity: where do we stand? (68)Foreign banks and the local funding gap (73)Box: The Asian financial crisis: international liquidity lessons (76)Conclusions (78)BIS Quarterly Review, June 2008 iiiRecent initiatives by Basel-based committees and groupsBasel Committee on Banking Supervision (81)Joint Forum (84)Financial Stability Forum (87)Statistical Annex ........................................................................................ A1 Special features in the BIS Quarterly Review ................................ B1 List of recent BIS publications .............................................................. B2Notations used in this Reviewe estimatedlhs, rhs left-hand scale, right-hand scalemillionbillion thousand… notavailableapplicable. not– nil0 negligible$ US dollar unless specified otherwiseDifferences in totals are due to rounding.iv BIS Quarterly Review, June 2008BIS Quarterly Review, June 20081Ingo Fender +41 61 280 8415ingo.fender@Peter Hördahl+41 61 280 8434peter.hoerdahl@Overview: a cautious return of risk toleranceFollowing deepening turmoil and rising concerns about systemic risks in the first two weeks of March, financial markets witnessed a cautious return of investor risk tolerance over the remainder of the period to end-May 2008. The process of disorderly deleveraging which had started in 2007 intensified from end-February, with asset markets becoming increasingly illiquid and valuations plunging to levels implying severe stress. However, markets subsequently rebounded in the wake of repeated central bank action and the Federal Reserve-facilitated takeover of a large US investment bank. In sharp contrast to these favourable developments, interbank money markets failed to recover, as liquidity demand remained elevated.Mid-March was a turning point for many asset classes. Amid signs of short covering, credit spreads rallied back to their mid-January values before fluctuating around these levels throughout May. Market liquidity improved, allowing for better price differentiation across instruments. The stabilisation of financial markets and the emergence of a somewhat less pessimistic economic outlook also contributed to a turnaround in equity markets. In this environment, government bond yields bottomed out and subsequently rose considerably. A reduction in the demand for safe government securities contributed to this, as did growing perceptions among investors that the impact from the financial turmoil on real economic activity might turn out to be less severe than had been anticipated. Emerging market assets, in turn, performed broadly in line with assets in the industrialised economies, as the balance of risk shifted from concerns about economic growth to those about inflation.Credit market turmoil gives way to fragile recoveryFollowing two weeks of increasingly unstable conditions in early March, credit markets were buoyed by a cautious return of risk tolerance, with spreads recovering from the very wide levels reached during the first quarter of 2008. Sentiment turned in mid-March, following repeated interventions by the Federal Reserve to improve market functioning and to help avert the collapse of a major US investment bank. As these actions alleviated earlier concerns about risks to the financial system, previously dysfunctional markets resumed trading and prices rallied across a variety of risky assets.2BIS Quarterly Review, June 2008Between end-February and end-May, the US five-year CDX high-yield index spread tightened by about 144 basis points to 573, while corresponding investment grade spreads fell by 63 basis points to 102. European and Japanese spreads broadly mirrored the performance of the major US indices, declining by between 25 and 153 basis points overall. Between 10 and 17 March, all five major indices had been pushed out to or near the widest levels seen since their inception. They then rallied back and seemed to stabilise around their mid-January values, remaining significantly above the levels prevailing before the start of the market turmoil in mid-2007 (Graph 1).business lines, tightening repo haircuts caused a number of hedge funds and other leveraged investors to unwind existing positions. As a result, concerns underlying exposures are almost entirely protected by federal guarantees, as summer of 2007 (Graph 3, right-hand panel).BIS Quarterly Review, June 20083Fears about collapsing financial markets reached a peak in the week March, triggering repeated policy actions by the US authorities. investment grade credit default swap (CDS) indices underperforming lower-quality benchmarks (Graph 4, left-hand and centre panels). Spreads were temporarily arrested when, on 11 March, the Federal Reserve announced an expansion of its securities lending activities targeting the large US dealer banks (see section on money markets and Table 1 below). European CDS indices tightened by more than 10 basis points on the news, while the two key basis points down, respectively (Graph 1). allowing it to make secured advance payments to the troubled investment These developments appeared to herald a turning point in the market, funds target down to 2.25%. Earnings announcements by major investment banks on 18 and 19 March that were better than anticipated provided further support, with investors increasingly adopting the view that various central bank initiatives aimed at reliquifying previously dysfunctional markets were gradually gaining traction. Consistent with perceptions of a considerable reduction in systemic risk, spreads, and particularly those for financial sector and other investment grade firms, tightened from the peaks reached in early March(Graph 4). Movements were partially driven by the unwinding of speculative short positions, as suggested by changes in pricing differentials across products with similar exposures, according to the ease with which such positions can be opened or closed. For example, spreads on CDS contracts referencing the major credit indices moved more strongly than those on the same indices’ constituent names (Graph 1, centre and right-hand panels). Similarly, CDS markets outperformed those for comparable cash bonds, as market participants adjusted their synthetic trades.risks (Graph 1, centre and right-hand panels). Similarly, implied volatilities from CDS index options eased into the second quarter, indicating a somewhat reduced uncertainty about shorter-run credit spread movements (Graph 3, centre and right-hand panels).losses based on ABX prices (see box). This was despite the lack of a recovery for the index series with lower original ratings, whose prices continued to4 BIS Quarterly Review, June 2008BIS Quarterly Review, June 20085suggest expectations of complete writedowns of all underlying bonds by mid-2009 (Graph 2, centre panel). At these low levels, and with none of the ABX indices having experienced any principal writedowns so far, investors appeared to be pricing in the possibility of legislation writing down mortgage principal. Against this background, issuance of private-label mortgage-backed securities remained depressed, with volume growth coming mainly from US agency-Supported by optimism about banks’ recapitalisation efforts, spreads pace of capital replenishment. Following news of a rights issue on 31 March, CDS spreads referencing debt issued by Lehman Brothers tightened. UBS announced large first quarter losses and a fully underwritten capital increase on 1 April, and other institutions followed over the rest of the month. Globally, banks managed to raise more than $100 billion of new capital in April alone, stemming the deterioration in capital ratios. Financial CDS spreads, the monoline segment excluded, outperformed corresponding equity prices in the process (Graph 4, right-hand panel), reflecting diminishing concerns about imminent financial sector risk as well as the dilutory effects of equity financing. Markets retraced some of these gains in early May, partially driven by strong supply flows from corporate issuers that included, at $9 billion, the largest US dollar deal by a non-US borrower in seven years. Volumes were dominated by6 BIS Quarterly Review, June 2008Pitfalls in using the ABX. Estimated mark to market losses and actual writedowns made by banks and other investors can differ for a variety of reasons. Analysts, depending on their objective, thus have to be mindful of potential sources of bias. At least three such sources can be identified, of which two are specific to the ABX index:•Accounting treatment. Subprime MBS are held by a variety of investors and for different purposes. While large amounts of outstanding subprime MBS are known to reside inbanks’ trading books, banks and other investors may also hold these securities tomaturity. This can result in different accounting treatments, which would tend to deflateactual writedowns and impairment charges relative to estimates of mark to market losseson the basis of market indices, such as the ABX. The size of this effect, however, isdifficult to determine. Further complexities are added once securities cease to be tradedin active markets, implying the use of valuation techniques, which may differ acrossinvestors, in establishing fair value.5•Market coverage. ABX prices may not be representative of the total subprime universe, due to limited index coverage of the overall market. Original balance across all four serieshas averaged about $31 billion. This compares to average monthly MBS issuance ofsome $36 billion over the 10 quarters up to mid-2007, ie almost a month’s worth ofsubprime MBS supply per index series. Similarly, with 2004–07 vintage subprime MBSvolumes estimated at around $600 billion in outstanding amounts, each series representssome 5% of the overall universe on average. At the same time, ABX deal composition isknown to be quite similar in terms of collateral attributes (such as FICO scores and loan-to-value ratios) to the overall market (by vintage).6 Therefore, despite somewhat limitedcoverage, this particular source of bias may not be large.•Deal-level coverage. Similarly, ABX prices may not be representative because each index series covers only part of the capital structure of the 20 deals included in the index(see Graph A, right-hand panel, for an illustration).7 In particular, tranches referenced bythe AAA indices are not the most senior pieces in the capital structure, but those with thelongest duration (expected average life) – the so-called “last cash flow bonds”. Theseclaims will receive any cash flow allocations sequentially after all other AAA trancheshave been paid; and tend to switch to pro rata pay only when the highest mezzaninebond has been written down. It follows that AAA ABX index prices are going to reflectdurations that are longer, and effective subordinations that are lower, than those of theremaining AAA subprime MBS universe. As a result, using newly available data for MBStranches with shorter durations, the $119 billion of losses implied by the ABX AAA indicesas of end-May would be some 62% larger than those implied under more realisticassumptions.8_________________________________1 See, for example, International Monetary Fund, Global Financial Stability Report, April 2008, pp 46–52, and Box 1 in Bank of England, Financial Stability Report, April 2008.2 Supplementary indices, called ABX HE PENAAA, were introduced in May 2008 to provide additional pricing information for all four existing vintages.3 An alternative approach, likely to lead to very different results, would estimate future default-related cash flow shortfalls on the basis of deal-level or aggregate data for subprime securities. To obtain these estimates, such methodologies rely on information about collateral performance and require the analyst to make assumptions about structural relationships and model parameters. Typical subprime loss projections, for example, use delinquency data and assumptions about factors such as delinquency-to-default transitions, default timing, and losses-given-default. See Box 1 in the Overview section of the December 2007 BIS Quarterly Review for an example on the basis of an approach devised by UBS. 4Mark to market losses (relative to par) are calculated assuming that unrated tranches are written down completely; ABX prices for the BBB– indices are used to mark BB collateral; rated tranches from the 2004 vintage are assumed unimpaired; outstanding amounts remain static.5 For details, see Global Public Policy Committee, Determining fair value of financial instruments under IFRS in current market conditions, December 2007.6 See, for example, UBS, Mortgage Strategist, 17 October 2006. 7 Incomplete coverage at the deal level further reduces effective market coverage: typical subprime MBS structures have some 15 tranches per deal, of which only five were originally included in the ABX indices. As a result, each series references less than 15% of the underlying deal volume at issuance.8 Duration effects at the AAA level are bound to be significant for overall loss estimates as the AAA classes account for the lion’s share of MBS capital structures. Using prices for the newly instituted PENAAA indices, which reference “second to last” AAA bonds, to calculate AAA mark to market losses generates an estimate of $73 billion. This, in turn, translates into an overall valuation loss of $205 billion (ie some 18% below the unadjusted estimate of $250 billion).capitalisation had recovered, while remaining weaker than before the crisis. At the same time, still-elevated implied volatilities suggested ongoing investor uncertainty over the future trajectory of credit markets. With the credit cycle continuing to deteriorate and related losses on exposures outside the residential mortgage sector looming, it was thus unclear whether liquidity supply and risk tolerance had recovered to an extent that would help maintain this improved environment on a sustained basis.Bond yields recover as markets stabiliseFrom its low point on 17 March, the 10-year US Treasury bond yield rose by 75 basis points to reach 4.05% at the end of May. During this period, 10-year yields in the euro area and Japan climbed by around 70 and 50 basis points, respectively, to 4.40% and 1.75% (Graph 5, left-hand panel). In US and euro area bond markets, the increase in yields was particularly pronounced for short maturities, with two-year yields rising by 130 basis points in the United States and by almost 120 basis points in the euro area (Graph 5, centre panel). Two-year yields went up in Japan too, but by a more modest 35 basis points. In addition to reduced safe haven demand for government securities, the rise in short-term yields reflected a reassessment among investors of the need for monetary easing, following the stabilisation of financial markets.In the first two weeks of March, as the financial turmoil deepened and forward rates dropping (Graph 6, right-hand panel). While flight to safety and other effects relating to the volatility in financial markets may have influenced consistent with the observed fall at the short end of the forward break-evencurve. At the same time, these same concerns led investors to increasinglyexpect the Federal Reserve to maintain a more accommodative policy stancethan normal in an effort to contain the fallout on economic growth. Insofar asthis was seen as likely to lead to higher prices down the road, it could explainthe rise in distant forward break-even rates at the time.As the situation in financial markets stabilised after the rescue of BearStearns in mid-March, and perceptions of the economic outlook improvedsomewhat, the US forward break-even curve shifted in the opposite directionand flattened considerably. To a large extent, this shift in the forward curve islikely to have reflected a reversal of the same influences that had been at playin the first two weeks of March: the dampening effect on prices coming from theturmoil was perceived to be weaker after mid-March, while the Federal Reservewas seen to be less likely to deliver further sharp rate cuts. Moreover, upwardprice pressures appeared to intensify in the short to medium term, with foodprices rising continuously and oil prices reaching new all-time highs during thisperiod (Graph 5, right-hand panel), pushing near-term forward break-evenrates further upwards.real yields reflected a combination of expectations of higher average realinterest rates in coming years and a reversal of flight to safety pressures. Theformer component, in turn, was due to perceptions among investors that thereal economic fallout from the financial turmoil was likely to be less severe thanhad previously been anticipated. This was despite indications of deterioratingconsumer confidence amid tighter bank lending standards and continuedweakness in US housing markets. The revival in investor confidence seemedinstead to follow from the stabilisation in markets and from a number ofrelatively upbeat macroeconomic announcements. These included better thangovernment securities.In line with perceptions that the stabilisation of markets had reduced therisks to economic growth somewhat, prices of short-term interest rateindicating expectations of a period of stable rates, followed by rising rates inthe first half of 2009 (Graph 7, left-hand panel). In the euro area, EONIA swapprices at the beginning of March had signalled expectations of sizeable ECBrate cuts, but by end-May prices had shifted to reflect expectations of graduallyincreasing policy rates (Graph 7, centre panel). Meanwhile in Japan,expectations of mildly falling policy rates in March had by May been revised toindicate rising rates (Graph 7, right-hand panel).A turning point for equity prices?to end-2007 levels, gained almost 10% between 17 March and end-May. Equity markets in Europe and Japan, which had seen losses in excess of 20% between the turn of the year and 17 March, subsequently also displayed a strong recovery, with the EURO STOXX gaining 11% and the Nikkei 225 rising Reflecting the improved situation in financial markets during this period, by almost 20% and 34%, respectively. These gains occurred despiteannouncements by several banks of record losses during the first quarter amidcontinued credit-related write-offs. Investors obviously took solace from the factthat losses – although big – were no worse than expected, and that a numberof banks had been successful in their recapitalisation efforts (see credit marketsection above).surprises remained well above that of negative surprises, provided somesupport for equity prices. In addition, as fears failed to materialise that economic growth might slow dramatically in the first few months of the year,investors increasingly began to see equity valuations as attractive following thesharp price declines in late 2007 and early 2008. markets recovered after a sharp dip in March (Graph 8, right-hand panel).Emerging market investors discount growth risksequities fell up to mid-March, before rebounding in the wake of the change inmarket sentiment following the Bear Stearns rescue in the United States.Between end-February and end-May, the MSCI emerging market indexgained about 4% in local currency terms, and was up more than 14% from thelows established in mid-March. Latin American markets, which had seen ahigh trading volumes in commodity derivatives (see the Highlights section inthis issue) and speculative demand as a source of part of that strength, otherspointed to low supply elasticities and expectations of sustained rates ofindustrialisation throughout the emerging markets. With the region being amajor net commodities importer and natural disaster contributing to weakerequity prices in China, Asian markets were broadly flat over the period.Emerging Europe, in turn, remained exposed to the risk of a reversal in privatecapital flows, owing to large current account deficits and associated financingneeds in a number of countries. Nevertheless, strong gains in Russia and thebetter than expected growth performance of major European economies in thefirst quarter seemed to aid equity markets in May.Emerging market credit spreads, as measured by the EMBIG index,accounting for most of the spread tightening, the EMBIG remained almost flatin return terms, gaining about 1.1% between end-February and end-May(Graph 9, left-hand panel). Large stocks of foreign reserves and favourablemacroeconomic performance in key emerging market economies continued toprovide support, aiding the market recovery. Spread dispersion remained high,pointing to ongoing price differentiation according to credit quality (Graph 10,centre panel). At the same time, with inflation running well above target in anumber of major emerging market economies, policy credibility appeared tobecome more of a concern, putting pressure on local bond markets. Risinginflation expectations, combined with increasing US Treasury yields andrelatively resilient markets during the earlier stages of the recent marketturmoil, may thus have contributed to a somewhat more muted performancefrom emerging market bonds relative to other asset markets over the periodsince mid-March.Tensions in interbank markets remain highas high at the end of May as three months earlier, across most horizons and inall three major markets (Graph 10). This appeared to imply expectations thatinterbank strains were likely to remain severe well into the future.After a relatively smooth turn of the year, interbank market tensions hadappeared to ease somewhat until early March 2008, and Libor-OIS spreadshad shown some signs of stabilising. However, as the financial turmoilsuddenly deepened in the second week of March, following an acceleration inmargin calls and rapid unwinding of trades (see the credit section above),interbank market pressures quickly increased. With market rumoursproliferating about imminent liquidity problems in one or more large investmentbanks, banks became increasingly wary of lending to others. At the same time,their own demand for funds jumped as they sought to avoid being perceived ashaving a shortage of liquidity.Selected central bank liquidity measures during the period under review7 March The Federal Reserve increases the size of its Term Auction Facility (TAF) to $100 billion andextends the maturity of its repos to up to one month.11 March The Federal Reserve introduces the Term Securities Lending Facility (TSLF), which allowsprimary dealers to borrow up to $200 billion of Treasury securities against collateral. Theexisting dollar swap arrangements between the Federal Reserve and the ECB and the SNB areincreased from a total of $24 billion to $36 billion.16 March The Federal Reserve introduces the Primary Dealer Credit Facility (PDCF), which providesovernight funding for primary dealers in exchange for collateral. The Federal Reserve alsolowers the spread between the discount rate and the federal funds rate from 50 to 25 basispoints, and lengthens the maximum maturity from 30 to 90 days.28 March The ECB announces that the maturity of its longer-term refinancing operations (LTROs) wouldbe extended from up to three months to a maximum of six months.21 April The Bank of England introduces the Special Liquidity Scheme, under which banks can swapilliquid assets for Treasury bills.2 May The Federal Reserve boosts the size of its TAF programme to $150 billion, and announces abroadening of the collateral eligible for the TSLF auctions. The dollar swap arrangements withthe ECB and the SNB are increased further, from $36 billion to $62 billion.Source: Central bank press releases. Table 1The near collapse and subsequent takeover of Bear Stearns onMarch highlighted the risks that banks face in such situations. On the would not be allowed to fail, and this helped restore order in other markets. On the other hand, the speed with which Bear Stearns’ access to market liquidity had collapsed underscored the vulnerability of other banks in this regard, which kept Libor-OIS spreads high even as CDS spreads on banks and brokerages Throughout the period, central banks maintained and even stepped up activity from central banks seemed to have limited immediate impact oninterbank rates. To some extent, this may have reflected the fact that while thesums involved in central bank liquidity schemes were large in absolute terms,they were still rather limited compared to banks’ assessment of their overallliquidity needs against the background of a sharp decline in traditional sourcesof funding. One significant source of short-term funding for banks in the pasthas been money market mutual funds. Such funds have seen substantialinflows since the outbreak of the financial turmoil (Graph 11, left-hand panel),reflecting a noticeable reduction in investors’ appetite for risk. However, thisloss of risk appetite also resulted in money market funds shifting theirinvestments increasingly into treasury bills and other safe short-term securities,hence depriving banks of a key funding source (Graph 11, centre panel). Thissuggests that determining how persistent the interbank tensions will be maydepend significantly, among other things, on how long the risk appetite ofmoney market fund managers, and investors more broadly, will continue to bedepressed.。

全国体育舞蹈等级考试培训教材.doc

全国体育舞蹈等级考试培训教材（中英文对照）WALTZ bronze华尔兹铜牌（11小节）1 .L.F closed change 左足并换步，1232.Natural Turn 右转步，123 4563.R.F closed change 右足并换步，1234.ReverseTurn 左转步，123 4565.Whisk 拂步，1236.Chasse From PP 由侧行至追步，12&37.Natural Spin Turn At The Corner 右旋转在角落里123 4568.（4-6） Reverse Turn 左转步456QUICKSTEP bronze 快步铜牌（12 小节）1.Left foot forward 左足常步，S2.Quarter Turn to Right 直角右转步，SQQS3.Progressive Chasse 直行追步，SQQS4.Forward Lock Step 前进锁步，SQQS5.Natural Turn With Hesitation 踌躇右转步，SQQ SSS6.Chasse Reverse Turn 追并左转步，SQQ7.Progressive Chasse 直行追步，SQQS8.U/T Spin Turn 减弱右旋转步，SQQ SSSTANGO bronze探戈铜牌（8小节）1.TwoWalks2 常步，SS2.Progressive Side Step 直行侧步，QQS3.Walks 常步，SS4.0pen Reverse Turn（Lady Outside closed finish）分式左转步（女士女士外侧并步结束)，QQS QQS5.Two Walks 2 常步，SS6.Natural Rock Turn 右摇转步，QQS QQSWALTZ sliver华尔兹银牌(12小节)l.Intor L.F左足预备步(3)2.Underturned natural spin turn 减弱的右旋转123 4563.(4-6)Reverse turn 左转步4564.Double reverse spin 双左旋转步1235.Progressive chasse to right 直行追步向右12&36.Back lock step 后退锁步12&37.Back whisk 后退拂步1238.Chasse from PP由侧行至追步12&39.Weave(ended PP)迂I可步结束于侧行位置10.Hover(end weave 456)盘旋步123 (迂回步456)QUICKSTEP silver 快步银牌(12 小节)l.Intro.L.F左足前进S2.U/T Natural spin turn 减弱的右旋转SQQ SSS3.Progressive chasse 直行追少SQQS4.Walk on R.F in C.B.M.P右足走步，反身动作位置S5.Quick open reverse 快分式左转步SQQ6.Four quick run 四快跑步SQQQQS7.U/T Natural spin turn at the corner 角落里的减弱右旋转SQQ SSS8.V6V6 步，QQS SQQFOXTROT silver狐步银牌（9小节）1.Feather step 羽步SQQ2.Reverse turn 左转步SQQ SQQ3.Three step 三步SQQ4.Natural turn 右转步SQQ SSS5.Feather step 羽步SQQ6.Change of direction 换向步SSSTANGO silver探戈银牌（12小节）1 .Two walks2 常步SS2.Open reverse turn lady outside closed finish 分式左转女士外侧并步结束QQS QQS3.Two walks 2 常步SS4.Progressive link 直行串步QQ5.Natural twist turn 右扭转步SQQ SQQ6.Fallaway promenade 并退滑行步SQQ SQQ7.Natural promenade turn to Rock turn end pp 右滑形转至摇转步侧行完SQQ SQQ SQQWALTZ gold华尔兹（金牌）16小节l.U/T Natural spin turn 减弱右旋转步123 4562.4-6 Reverse turn 4-6 左转步4563.Double reverse spin 双左旋转步1234.Progressive chasse to right 直行追步向右12&35.Backward lock step 后退锁步12&36.U/T Outside spin减弱外侧旋转步1237.Turning lock 旋转锁步1&238.Back whisk（After 1-3 of nat turn）后退拂步在1-3 右转步之后123 4569.Chasse from PP由侧行至追步12&310.U/T Natural spin turn 右旋转步123 45611.Turning lock to right 右旋转锁步1&2312.Weave from PP侧行位置的迂回步123 456QUICKSTEP gold快步（金牌）16小节1 .Natural turn 右转步SQQ2.Open impetus turn 分式激转步SSS3.Chasse from PP由侧行至追步SQQS4.Walk on RF in CBMP右足走步（反身动作位置）S5.Quick open reverse 快分式左转SQQ6.4 Quick run 四快跑步SQQQQS7.Running right turn 跑步右转SQQ SSQQ SQQ8.Check抑制步SS9.V 6 V 6 步QQS SQQ10.Fish-tail 鱼尾步SQQQQSFOXTROT gold狐步（金牌）16小节1 .Feather step 羽步SQQ2.Reverse turn 左转步SQQ SQQ3.Three step 三步SQQ4.Natural twist turn feather finish 右扭转步接羽步完成SQ&QQQ SQQ5.1-4 Reverse wave 1-4 左转波纹步SQQS6.Weave 迂回步QQQQQQ7.Re verse weave 左转波纹步SQQ SQQ SSS8.Feather step 羽步SQQ9.Change of Direction 换向步SSSTANGO gold探戈（金牌）16小节I.Two walks 2 常步SS2.Progressive link 直行串步QQ3.Closed promenade 并式滑行步SQQS4.Four step 四快步QQQQ5.Fallaway promenade 并退滑行步SQQ SQQ6.Promenade turn to rock turn back check to PP 右滑行转至摇转步接后抑制步成侧行位置SQQ SQQ SQQ7.Chase whisk fan（end PP）追逐步接拂步接扇形步结束于侧行位置SQQQQ Q&Q SQQ8.Promenade link 侧行连步SQQ9.Fallaway reverse turn slip pivot 并退左滑轴转步QQQQ10.Basic reverse turn 基本左转步QQ&QQ&II.Contra check（end PP）反抑制步侧行完成SQQVIENNESE-WALTZ gold维也纳华尔兹（金牌）1.Natural turn 右转步2.Reverse turn 左转步3.For ward and backward change 前进后退换向步WALTZ gold 1华尔兹金星一级（24小节）l.U/T natural spin turn 减弱右旋转步123 4562.4-6 Reverse turn 左转步4563.Fallaway reverse turn and slip pivot 并退左转接滑轴转步1&234.Open telemark open natural turn 分式滑行步接分式右转步123 1235.U/T outside spin减弱外侧旋转步1236.Turning lock 旋转锁步1&237.Back whisk(After 1-3 nat turn)后退拂步在1-3 右转步之后123 4568.Chasse from PP由侧行至追步12&39.U/T natural spin turn 右旋转步123 45610.Turning lock to the right 右旋转锁步1&2311 .Chasse from PP 由侧行至追步12&312.1- 3 Weave from PP 1-3侧行位置的迂回步12313.Back lock 后退锁步12&314.Impetus and 4-6 reverse turn 激转步接4-6 左转步123 45615.Double reverse spin 双左旋转步12316.Whisk 拂步12317.Wing 翼步12318.Progressive chasse to right and weave 4-6 ended PP 直行追步向右迂回步456结束于侧行位置12&3 456QUICKSTEP gold 1快步金星一级(26小节)1 .Natural turn 右转步SQQ2.Open impetus turn 分式激转步SSS3.Chasse from PP由侧行至追步SQQS4.Walk on RF in C.B.M.P 右足走步S5.Quick open reverse 快分式左转步S QQ6.4 Quick run 四快跑步SQQQQ S7.Running right turn 跑步右转SQQ SSQQ SQQ8.Natural spin turn 右旋转步 SQQ SSS9.V 6 V6 QQS SQQ10.Fish-tail 鱼尾步SQQQQS11.1-3 Nat turn back lock 1-3 右转步接后退锁步SQQ SQQ S12.Running finish 跑步结束QQS13.Tipple chasse to left 晃追步向左SQQS14.Back lock 后退锁步QQS!5.Tipple chasse to right 晃追步向右SQQS QQSFOXTROT gold 1狐步金星一级(24小节)I.Feather step 羽步SQQ2.Reverse turn 左转步SQQSQQ3.Three step 三步SQQ4.Hover cross 盘旋交叉步SQQQQQQ5.Open telemark 分式滑形步SQQ6.Feather ending 羽步结束SQQ 8 Bars7.1- 4 Reverse wave 1-4 左转波纹步SQQS8.Weave 迂I可步QQQQQQ9.The extended reverse weave 延长左转波纹步1-9 SQQ SQQ SQQ10.Reverse pivot 左轴转步 &II.Change of direction 换向步SSS12.Contra check 反抑制步S□.Natural pivot turn 右轴转步QQ 8 Bars14.Natural twist turn feather finish 右扭转步接羽步完成SQ&QQQ,S QQ15.Hover telemark(Ending PP)盘旋滑形步以侧行结束：SQQ16.Natural zig-zag from PP 侧行右曲折步SQQQQ17.Fallaway reverse and slip pivot 并退左转至滑轴步S&QQ18.Change of direction 换向步SSS 8 BarsTANGO gold 1探戈金星一级(24小节)1.Two walks 2 常步SS2.Progressive link 直行串步QQ3.Open promenade 分式侧行步SQQS4.Outside swivel followed by step 2&3 of promenade link 夕卜侧回旋步侧行串步2和3步SQQ5.Brush tap 刷踏步QQ&S6.Promenade turn to rock turn back check to P.P 右滑行转步至摇转步接后抑制步成侧行SQQ SQQ SQQ 8 Bars7.Chase whisk fan(End P.P)追逐步接拂步接扇形步结束于侧行位SQQQQQ&Q s QQ8.Drop or tilt oversway 点剑点SQ&Q9.Chasse L.F back in fallaway slip pivot 追步接并退左滑轴转步Q&Q QQ lO.Open reverse in Q time 快分式左转步QQQQ S11.Right lunge 右剑步S12.Drag西班牙拉步S-S 8 Bars13.Back open promenade and nature pivot 后退分式滑行步接右轴转SQQQQQQ14.Twist turn(3-6)扭转步SQ&Q15.Chasse from P.P closed promenade 追步侧行并步S&SQQS16.Back corte 1-2 step S &17.Mini five step 缩小五快步QQSQQ18.Promenade link 侧步串步SQQ 8 BarsVIENNESE-WALTZ gold 1维也纳华尔兹金星一级1 .Natural turn 右转步2.Reverse turn 左转步3.Forward and backward change 前进后退换向步4.Reverse flicker 左原地转步5.Contra check 反抑制步WAITZ gold 2 华尔兹金星二级（24小节）I.Overturned natural spin turn 强度右旋转步，123 4562.Turning lock to right 右旋转锁步，1&233.Chasse from P.P weave from P.P 由侧行追步至侧行迂回步，12&3,123 4564.Natural spin turn 右旋转步，123 456 8 Bars5.Double lock oversway hover to P.P 双锁步强度倾斜步侧行完成，1&23J23 4566.Chasse from P.P top spin 由侧行追步至陀螺转步，12&3,1&237.Natural spin turn 右旋转步，123 4568.Turning lock to side lock 旋转锁步至侧向锁步，1&23& 8 Bars9.Fallaway reverse slip pivot, double reverse spin 并退左转与滑轴步，双左旋转步，1&23,12310.Curved 3 step progressive chasse 曲转3 步接直行追步，123,12&3II.Natural pivot to hairpin 右轴转至U 形步，123 12&312.Syncopated double back lock 切音双退锁步，12&3&113.Syncopated outside change 切音外侧换步，2&3 8BarsQUICKSTEP gold 2 快步金星二级(24小节)1 .Overturned natural spin turn 强度右旋转步，SQQ SSS2.Turning lock to right 旋转锁步向右，QQSS3.Double lock 双锁步，SQQQQ4.Quick open reverse 快分式左转步，SQQ5.4 Quick run 4 快跑步，SQQQQS 8 1/2 Bars6.Natural turn back lock running finish 右转步后退锁步跑步结束，SQQ SQQS QQS7.1-3 Natural turn to open impetus 1・3 右转步分式激转步，SQQ SQQ (SQQ, SSS)8.(Variation)Step R.F and slipL tipsyCoupe pointStep R.F.& slipL tipsy. Step cross(花步组合)右足滑步，S&蹒跚追步向左，Q&Q双点步，QQ右足滑步，S& 7 1/2 Bars蹒跚追步向左交又，Q&QQQ9.Natural pivot to hairpin run 右轴转至U 形跑步,SQQ SS QQ10.V-6, fishtail V-6,鱼尾步，SQQS SQQ,S QQQQS 8 BarsFOXTROT gold 2 狐步金星二级（24小节）1.Feather step fallaway reverse slip pivot 羽步并退左转步与滑轴步，SQQ S&QQ2.Curved 3 step feather finish 曲转3 步羽步完成，SQQ,SQQ3.3 Step hover cross, chasse to right 3 步盘旋交叉追步向右，SQQ,SQQQQQQ,SQ&Q 8Bars4.3-6 Weave 3-6 迂回步，QQQQ5.Travelling contra check to P.P.游走反抑制步至侧行完，SQQ6.Natural fall away. Back link to （Mans outside swivel）（Lady developed'kick）右并退步，后退串步（男士外侧回旋,女士踢步），SQQ,S&SSQQ7.Weave from P.P.由侧行至迂回步，SQQQQQQ8.Syncopated L.side feather 切音左侧羽步，SQ & QQQ 8Bars9.Quick open reverse 快分式左转步，SQ & QQQ10.1- 4 Reverse wave 1-4 左转波纹步，SQQS11.Weave, 3 step il回步，3 步，QQQQQQ, SQQ12.Natural twist turn 右扭转步,SQ&QSQQ 8BarsTANGO gold 2 探戈金星二级（24小节）1.2 Walks,L,R.2 常步，左足，右足，SS2.Progressive link chase with chasse to right progressive link 直行串步，追逐步，追步向右，直行串步，QQ.SQQQQ.Q&Q.QQ3.L.F to side in P.P.RF forward and across in P.P.左足向侧右足交叉侧行，S.S and across in P.P.4.Jelpoint 点剑步，&S5.Chasse l.f. back in fallaway, slip pivot 追步接并退左滑轴转步，Q&Q QQ6.Open reverse in Q time 快分式左转，QQQQS 8Bars7.Right lunge 右剑步，S8.Rock and drag 摇步接西班牙拉步，QQ SS9.Slip pivot, chasse break 滑轴步，追步停，QQQ&Q10.Contra check.to P.P.反抑制步侧行完成，S QQ11.Natural promenade turn rock turn 右滑行转接摇转步，SQQ SQQS12.Syncopated back locks & chasse 切音后退锁步接追步，Q&QS, &QQ&8Bars13.Viennese waltz reverse turn 维也纳华尔兹左转步，QQ&QQ&14.Throwaway oversway 抛开式倾斜，QQSS15.Appel to point 顿足至点步，&S16.Double to point(kick)双点踢步，QQS.&S17.Open reverse to outside swivel 分式左转至外侧回旋步，QQS18.Syncopated lock 切音锁步，Q&QS19.Promenade link to 4 step change 滑行串步接四快换步，SQQQQ&S 8BarsVIENNESE-WALTZ gold 2维也纳华尔兹金星二级1 .Natural turn 右转步2.Reverse turn 左转步3.Forward and backward change 前进后退换向步4.Natural flicker 右原地转步5.Reverse flicker 左原地转步6.Contra check 反抑制步。

Lesson Twelve

• Case 2 Crisis of Barbie Doll in the Intercultural marketing
虽然Mattel公司在开拓国际市场时，一向注意跨文化的技巧，比如为了迎合美国国内的少数民族裔群体，引进了黑色肤色的芭比；在国外，Mattel公司在保持芭比核心形象的前提下，让芭比点上朱砂痣穿上莎丽，成功的进入印度市场，但是在中东，芭比却遭遇惨败。
（3）Developing the Market What are our areas for growth? What sectors have the most potential? We have to address spreading out to new markets. The customers still don’t trust in our brand. Which of the steps are you focusing on in brand growth? We’re working on different steps in different areas. Understanding comes from product differentiation. How can we make product differentiation?
How are sales abroad? Asia is booming now. Is the Asian market available to us? Take the marketing report and compare it with our survey
of consumer buying habits. At a discounted introductory price, we landed more sales. We’ve got to come up with a few clever strategies in order

Article1

Evidence of the voice-related cortical potential:An electroencephalographic studyJessica Galgano and Karen Froud ⁎Department of Biobehavioral Sciences,Teachers College,Columbia University,USA Received 1October 2007;revised 4March 2008;accepted 12March 2008Available online 21March 2008The Bereitschaftspotential (BP)is a slow negative-going cortical potential associated with preparation for volitional movement.Studies since the 1960s have provided evidence for a BP preceding speech-related volitional motor acts.However,the BP associated specifically with voice initiation (i.e.a volitional motor act involving bilateral true vocal fold adduction)has not to date been systematically investigated.The current investigation utilizes a novel experimental design to address methodological confounds typically found in studies of movement-related cortical potentials,to demonstrate the existence and localization of generators for the voice-related cortical potential (VRCP).Using high-density EEG,we recorded scalp potentials in preparation for voice onset and for exhalation in a stimulus-induced voluntary movement task.Results showed a slow,increasingly negative cortical potential in the time window of up to 2500ms prior to the mean onset of phonation.This VRCP peaked at a greater amplitude and shorter latency than the BP associated with exhalation alone.VRCP sources were localized to the anterior rostral regions of the medial frontal gyrus (Supplementary Motor Area (SMA))and in bilateral laryngeal motor areas before and immediately following the mean initiation of phonation.Additional sources were localized to the bilateral cerebellum and occipital lobe in the time window following the mean onset of phonation.We speculate that these results provide additional support for fine somatotopic organization of the SMA.Further examination of the spatiotemporal change of the VRCP yielded source models which indicated involvement of the laryngeal motor cortices and cerebellum,likely responsible for the initiation and continuation of phonation.©2008Elsevier Inc.All rights reserved.IntroductionThe event-preceding brain component associated with prepara-tion for volitional movement,referred to as the Bereitschaftspo-tential (BP),has been described in detail over many years of research (Kornhuber and Deecke,1965;Deecke et al.,1969,1976).Several studies have attempted to identify and isolate the BP related specifically to preparation for speech.For example,Brooker and Donald (1980)put a significant amount of consideration into matching the time constants of instrumentation,and included EMG recordings of several muscles that are active during speech.Wohlert (1993)and Wohlert and Larson (1991)investigated the BP preceding speech and nonspeech movements of various levels of complexity.Both experiments controlled for respiratory artifact by having subjects hold their breath prior to task initiation.In addition,electro-ocular and EMG activity were monitored,and (in the 1993study)a pneumatic respiration transducer was utilized to monitor breathing patterns.Additionally,EMG activity from the orbicularis oris muscle was used to trigger and average segments.More recent advances in electroencephalo-graphic and electromyographic techniques have made it possible for examinations of this nature to more accurately identify BPs associated with vocalization and oral movements.These advances have also permitted investigations aiming to specify the cortical and subcortical pathways involved in volitional control of exhalation,which is required for voice production.Kuna et al.(1988)found thyroarytenoid muscle activity during exhalation,suggesting that cortical control of volitional respiration may be related,in part,to the requirement for precise management of vocal fold position during respiration.Although a significant amount is understood about the BP,it has been difficult to extract these components from EEG recordings,since the BP is typically a slow change in amplitude with a wide bilateral distribution (Brooker and Donald,1980;Deecke et al.,1986;Ertl and Schafer,1967;Grabow and Elliott,1974;McAdam and Whitaker,1971;Morrell and Huntington,1971;Schafer,1967),representing shifts of only a few microvolts.Thus,accurate triggering by the exact onset of movement is extremely important.Studies attempting to identify the BP associated with the volitional motor act of laryngeal or vocal fold movement (which we will refer to as the V oice-Related Cortical Potential,or VRCP)have encountered other obstacles too:in particular,difficulties withco-/locate/ynimg NeuroImage 41(2008)1313–1323Corresponding author.Department of Biobehavioral Sciences,Box 180,Teachers College,Columbia University,New York,NY 10027,USA.Fax:+12126788233.E-mail address:kfroud@ (K.Froud).Available online on ScienceDirect ().1053-8119/$-see front matter ©2008Elsevier Inc.All rights reserved.doi:10.1016/j.neuroimage.2008.03.019registration between physiological measurements and electrophy-siological instrumentation,inaccurate identification of vocal fold movement onset,and methodological confounds between voice, speech and language(Brooker and Donald,1980;Deecke et al., 1986;Ertl and Schafer,1967;Grabow and Elliott,1974;McAdam and Whitaker,1971;Morrell and Huntington,1971;Schafer,1967). In addition,respiratory artifact or R-wave contamination of the BP preceding speech has proven a major difficulty,particularly in early studies(Deecke et al.,1986).Larger-amplitude artifacts due to head-,eye-,lip-,mouth movements and respiration must also be eliminated before signal averaging(Grözinger et al.,1980).Earlier studies investigating voice-related brain activations typically confounded the distinctions between voice,speech and language.Voice refers to the sound produced by action of the vocal organs,in particular the larynx and its associated musculature. Speech is concerned with articulation,and the movement of organs responsible for the production of the sounds of language—in particular,those of the oral tract,including the lips,tongue and nguage refers to the complex set of cognitive operations involved in producing and understanding the systematic processes which underpin communication.Therefore,studies which have at-tempted to isolate voice or speech-related activity by the use of word production instead have described activation relating to a combina-tion of these cognitive and motor operations(for example,Grözinger et al.(1975)used word utterances amongst their tasks designed to elicit speech-related activations;Ikeda and Shibasaki(1995)used single words as well as nonspeech-related movements like lingual protrusion;McAdam and Whitaker(1971)used unspecified three-syllable words to elicit ostensibly speech-related activity).Con-versely,in a magnetoencephalography(MEG)study,Gunji et al. (2000)examined the vocalization-related cortical fields(VRCF) associated with repeated production of the vowel[u].Microphones placed close to the mouth were used to capture the sound waveform from the vocalization;the onset of the waveform provided the trigger for segmenting and averaging epochs.This design carefully attempts to identify vocalization-related fields;however,operationalizing a procedure which is able to most closely capture the onset of voicing is particularly difficult.Difficulty stems,in part,from the limited number of compatible neuroimaging techniques and instruments able to capture these phenomena.The present study contributes to understanding of the timing and distribution of the VRCP by addressing two major sources of methodological confound:the blurring of distinctions between voice, speech and language;and the accurate identification of movement onset for triggering and epoch segmentation.Furthermore,we use high-density EEG recordings,providing an increased level of detail in terms of the scalp topography,and additionally enabling the application of source modeling techniques to ensure accurate identification of the VRCP.Our results provide novel insight into voice generation by addressing the following research question: Can the true VRCP,associated only with laryngeal activity,be isolated from related movement potentials,by utilizing the right combination of control and experimental tasks?We predicted that a stimulus-induced voluntary movement paradigm would yield significant differences in the characteristics of the Readiness Potentials associated with(a)initiation of phonation and(b)respiration.To be specific,we predicted the existence of an isolable voice-related cortical potential associated only with prepara-tion for initiation of phonation and greater amplitude of the VRCP vs. the respiration-related cortical potential.We also predicted that VRCP sources would be localized to the Supplementary Motor Area, primary motor cortices,and sensori-motor regions.Elucidation of the neural mechanisms of normal voice is a crucial step towards understanding the role of functional reorganization in cortical and subcortical networks associated with voice production, both for changes in the normal aging voice,and in pathological populations.This approach to determining the neural correlates of voice initiation could provide a foundation for creating neurophy-siologic models of normal and disordered voice,ultimately informing our understanding of the effects of surgical,medicinal and/or behavioral interventions in voice-disordered populations. The findings could ultimately provide us with new basic science information regarding the relative benefit of different treatment approaches in the clinical management of neurogenic voice disorders.In addition,the larger significance of this work is related to the fact that voice disorders are currently recognized as the most common cause of communication difficulty across the lifespan,with a lifetime prevalence of almost30%(Roy et al.,2005). Materials and methodsA stimulus-induced voluntary movement paradigm in which trials of different types were presented in subject-specific rando-mized orders was utilized.This method addressed the documented problem of the classic BP paradigm which involves self-paced movements separated by short breaks:the person is already conscious of and preparing for a particular movement and there is a known repetition rate of the movements(Libet et al.,1982,1983). This can lead to automatic movements,which change the presentation of the VRCP.In our procedure,it is not possible for the participant to predict ahead of time which task they have to perform,which allows for a spontaneous movement.The movements were chosen to avoid another methodological confound,between voice,speech and language tasks.Requiring subjects to produce linguistically complex units,such as sounds or words(e.g.Ikeda and Shibasaki,1995;Wohlert and Larson,1991; Wohlert,1993)led to some debate concerning whether BPs for speech might be lateralized to the dominant hemisphere for language.This problem is avoided in the current study,and the problem of movement artifacts involved in speech and speech-like movements such as lip-pursing or vowel-production(Gunji et al., 2000;Wohlert and Larson,1991;Wohlert,1993),in particular of back,tense,rounded vowels(such as the[u]used in Gunji et al's experiments),by utilizing a task which involves voicing only,and has no related speech or language overlay.The actions of breathing out through the nose,and gentle-onset humming of the bilabial nasal [m]without labial pressing,are equivalent actions in terms of involvement of the articulatory tract,the only difference being the initiation of vocal fold movement in the humming condition.By having participants breathe or hum following a period of breath-holding,the possibility of R-wave contamination is also reduced (Deecke et al.,1986).Onset of phonation is established by mea-suring vocal fold closure using electroglottography(EGG),and a telethermometer attached to a trans-nasal temperature probe was used for the earliest possible identification of exhalation onset. Subjects24healthy subjects(21females and3males)with an age range of21–35years of age(mean age=26years)participated in the study.All subjects were informed of the purpose of the study and1314J.Galgano,K.Froud/NeuroImage41(2008)1313–1323gave informed consent to participate,following procedures ap-proved by the local Institutional Review Board.All participants took part in a training phase,which was identical to the experi-mental procedure and served to train participants on the expected response to each screen.Each step of the procedure was discussed and explained as it was occurring,and there was ample opportunity for feedback to be provided to ensure accurate task performance.EEG/ERP experimental set-up and proceduresEEG data acquisitionScalp voltages were collected with a 128channel Geodesic Sensor Net (Tucker,1993)connected to a high-input impedance amplifier (Net Amps200,Electrical Geodesics Inc.,Eugene,OR).Amplified analog voltages (.1–100Hz bandpass)were digitized at 250Hz.Individual sensors were adjusted until impedances were less than 30–50k Ω,and all electrodes were referenced to the vertex (Cz)during recording.The net included channels above and below the eyes,and at the outer canthi,for identification of EOG.The EEG,EOG,stimulus triggered responses,EGG and telethermometer data were acquired simultaneously and later processed offline.Recording of respirationA nasal telethermometer (YSI Model 43single-channel)with a small sensor (YSI Precision 4400Series probe,style 4491A)was placed 2–4cm inside one nostril transnasally and used to measure the temperature of inhaled and exhaled air.Readings from the telethermometer were digitally recorded by interfacing the teletherm-ometer with one outrider channel input to the EEG net amplifier connection,for co-registration of the time course of respiration with the continuous EEG.Recording of voice onsetA Kay Telemetric Computerized Speech Lab,Model 4500(housing a Computerized Speech Lab Main Program Model 6103Electroglottography)with 2electrodes placed bilaterally on the thyroid cartilage,adjacent to the thyroid notch,was used to measurevocal fold closure and opening.The EGG trace was acquired in the Computerized Speech Lab (CSL)proprietary software and co registered offline with EEG and telethermometer recordings,in order to determine error trial locations and confirm onset of vocal fold adduction and controlled exhalation.V oice sounds were also recorded by microphone on a sound track acquired on the CSL computer,sampling at 44.1kHz.A response button box permitted participant regulation of the start of each trial.At each button press,an audible “beep ”was generated by the system which provided an additional point of co-registration between the EGG system and the time of trial onset.In addition,pressing the button permitted the subject to move to the next trial set from a screen that allowed physical adjustment into a more comfortable position if needed in between tasks (to reduce movement artifact).Instructions and experimental taskThe experimental task required subjects to hold their breath for 4s,followed by breathing out or humming through the nose.The action carried out was determined by presentation of a “Go ”screen after the breath-holding interval;the “Go ”screen randomly presented either a “Breathe ”or “Hum ”instruction.To avoid using language-based stimuli in this experiment,the instructions to breath or hum were represented instead by letter symbols:a large 0for breathing,and a large M for humming.There were eighty trials altogether (forty voice and forty breathe).Experimental stimuli were presented using Eprime stimulus presentation software (Psychology Software Tools,Pittsburgh,PA).Subjects were visually monitored via a closed circuit visual surveillance system,to ensure compliance with experimental conditions.Each trial (breathe or hum)was followed by a black screen,which indicated to participants that they could take a break before the next trial,swallow,blink and make themselves comfortable (this was intended to reduce movement artifacts during trials).Participants used button presses to indicate when they were ready to continue on to the next trial (Fig.1).Data analysisRecorded EEG was digitally low-pass filtered at 30Hz.Trials were discarded from analyses if they contained incorrectresponses,Fig.1.The following experimental control module display shows the timeline of stimulus presentation during the experiment.Initially,a red screen instructed the subject to hold their breath with a closed mouth (4s).This was followed by a green screen which displayed either an “M ”or “0”,prompting the subject to hum or breathe out,respectively.Following each trial,a black screen instructed the subjects to make themselves comfortable to minimize movement artifact before moving onto the next trial.When subjects were ready,a button press triggered an audio beep which allowed for co-registration of instrumentation being utilized.1315J.Galgano,K.Froud /NeuroImage 41(2008)1313–1323eye movements (EOG over 70µV),or more than 20%of the channels were bad (average amplitude over 100µV).This resulted in rejection of less than 5%of trials for any individual.EEG was rereferenced offline to the average potential over the scalp (Picton et al.,2000).EEG epochs were segmented from −3000to +500ms from onset of voicing or exhalation,and averaged within subjects.Data were baseline-corrected to a 100ms period from the start of the segment,to provide additional control for drift or other low amplitude artifact.For identification of ERPs and for further statistical analyses,two regions of interest (ROIs)were selected:the Supplementary Motor Area (SMA)ROI,and the Primary Motor Region (M1)ROI.The 7SMA sensors were centered around FCz,where SMA activations have previously been reported (e.g.Deecke et al.,1986).The M1ROI consisted of 25sensors,centered anterior to the central sulcus and located around the 10–20system electrodes F7,F3,Fz,F4,F8,A1,T3,C3,Cz,C4,T4,A2(listed left-to-right,anterior-to-posterior),where Motor-Related Potentials have been previously identified (Jahanshahi et al.,1995).See Fig.2.Statistical analysesData from averaged segments were exported to standard statistical software packages (Microsoft Excel and SPSS),permit-ting further analysis of the ERP data.Repeated measures Analysis of Variance (ANOV A)was used to evaluate interactions and main effects in a 2(Condition:voicing vs.breathing)×2(region:SMA vs.M1)×3(time window:pre-stimulus,stimulus to voice onset,and post-voice onset)comparison.The dependent variable was grand-averaged voltages across relevant sensor arrays,determined following data preprocessing.The ANOV A was followed by planned comparisons,and all statistical analyses employed the Greenhouse –Geisser epsilon as needed to deal with violations of assumptions of sphericity.Point-to-point differences in mean amplitude between the 2conditions (humming vs.breathing)were evaluated for statistical significance,using separate repeated measures t -tests performed on mean amplitude measures within a 4ms sliding analysis window.Bonferroni corrections were employed to control for type 1error arising from multiplecomparisons.Fig.2.This sensor layout displays the 128-channel Geodesic Sensor Net utilized in the current experiment.Legend:Black=SMA montage;Grey=M1montage;Black+Grey=Channels entered into Grand Average.1316J.Galgano,K.Froud /NeuroImage 41(2008)1313–1323VRCP.Time-locking of the segmented EEG to the onset of true vocal fold adduction as recorded from the electroglottograph enabled identification of the standard BP topography,with a peak at the time of the movement onset,followed by a positive reafferent potential.The topography of the VRCP was examined using true vocal fold (TVF)adduction onset obtained from the EGG recording,and is subject-specific.Individual averaged files were placed into group grand-averages.The VRCP was identified in individual averaged data and in group grand-averages,based on the distribution and latency of ponent duration and mean amplitude for each subject(and for grand-averaged data)in each experimental condition were calculated.Three pre-movement components of the VRCP were measured, i.e.early(−1500to−1000ms prior to movement onset),late(about −500ms prior to movement onset),and peak VRCP(coincides with or occurs approximately50ms prior to movement onset)(Deecke et al.,1969,1976,1984;Barret et al.,1986).To determine the onset of each VRCP component,mean amplitude traces from individual and grand-averaged voice trials were examined independently by scientists with BP experience(Jahanshahi et al.,1995;Fuller et al., 1999).The mean latency of the early VRCP(rise of the slope from the baseline),the late VRCP(point of change in slope),and the peak VRCP(most negative point at or prior to vocal fold closure)were measured.The slope of the early VRCP was calculated(in microvolts per second)between the point of onset of the early VRCP and the onset of the late VRCP.The slope of the late component was calculated from the point of onset of the late VRCP to the onset of the peak VRCP.A2(region:SMA vs.M1)×2(time window:early VRCP te VRCP/late VRCP vs.peak VRCP)repeated measures ANOV A,followed up with planned comparisons,was used to examine interactions and main effects.BESA.In order to model the spatiotemporal properties of the VRCP sources,we used Brain Electrical Source Analysis(BESA: Scherg and Berg,1991).Source modeling procedures were applied to the voice produc-tion condition only(not to the exhalation condition).This is because a telethermometer was used to record changes in temperature associated with inhalation and exhalation;however,these associated changes do not reliably correlate with the true onset of exhalation or thyroarytenoid muscle activity associated with exhalation,as evidenced by the wide variety of measures reported in the literature for determination of respiration onset(e.g.Macefield and Gandevia (1991)used EMG measured over scalene and lateral abdominal muscles;Pause et al.(1999)used a thermistor placed at the nostril to determine onset of respiration based on changes to air temperature; Gross et al.(2003)determined onset of respiration to be associated with highest cyclic subglottal pressure;and other methods have also been reported).Source localization approaches are therefore not appropriate for the exhalation condition;consequently,we con-ducted comparisons between potentials associated with exhalation and voice using statistical analyses of differences in amplitude only. Source localization procedures were conducted on the voice pro-duction condition,because in that condition we were able to identify the initiation of voicing,using electroglottography.BESA attempts to separate and image the principal components of the recorded waveform as well as localizing multiple equivalent current dipoles(ECDs).Any equivalent current dipole was fit to the data over a specified time window,and the goodness of fit was expressed as a percentage of the variance.Our procedure for developing the ECD model was closely based on procedures detailed in Gunji et al.(2000),as follows.First,we selected an interval for analyzing the data in terms of a spatiotemporal dipole model.Following Gunji et al.,we selected the interval of−150ms to+100ms,because this interval covered the approximate period from the onset of the instruction screen to preparation to move the vocal folds,through to onset of phonation and the start of auditory feedback.Gunji et al.further recommend a dipole modeling approach limited to this time interval in order to focus on brain activations just before and after vocalization,rather than attempting to model the complex and persistent sources associated with Readiness Potentials.We therefore seeded sources and fit them for orientation and location in the time window from −150ms to0ms(the averaged time of the start of phonation).The time window from0to+100ms was examined separately.Sources seeded in both time windows are described below.ResultsIndividual data were grand-averaged and component identifica-tion was based on distribution,topography,and latency of activations (individual subjects and grand-averaged data).AVRCP was identified in all subjects,maximized over fronto-central electrodes(overlying the SMA).For grand-averaged data,all electrodes overlying the SMA showed a large VRCP in the specified time window(see Fig.3). Voicing vs.Controlled Exhalation ConditionsThe ANOV A revealed that the triple Condition×Region×Time interaction was significant(F(1,124)=2488.463,p b.0001),as were both two-way interactions(Condition×Region,F(1,124)=68.428, p b.0001;Condition×Time,F(1,124)=1808.242,p b.0001; Region×Time,F(1,124)=6651.504,p b.0001).Planned compar-isons revealed that the mean amplitudes of the VRCP were significantly more negative than the BP associated with the controlled exhalation condition,and SMA amplitudes were significantly more negative than M1.The significant interaction between Condition and Region for all subjects was found to be due to the fact that,although SMA sensors were always significantly more negative than M1 sensors(t(1939.233)=26.272,p b.0001),there was a greater difference in the measured negativities in V oice trials compared to Breathe trials(see Fig.4).Further examination of the main effect of Time revealed that,as time progressed,mean amplitudes became significantly more negative(i.e.VRCPs became significantly more negative from the pre-stimulus time window to the time of voice onset and beyond). Investigations of the Condition by Time interaction revealed sig-nificant progressive increases in the measured negativities from early to late time windows for the V oice condition.However, subjects showed a greater degree of negativity in the pre-and post-screen time windows for the breathe condition only(see Fig.5).For the Controlled Exhalation/Breathing Condition,the SMA BPs from stimulus to exhalation were significantly more negative than in the pre-stimulus interval.The M1region,however,showed no significant increase in negativity until the later time windows.In other words,over the SMA sensors the movement-related negativity increased in the period leading to exhalation,as well as later;over the M1sensors,however,readings did not become significantly more negative until after movement.Investigations of the Region×Time interaction for the voicing trials showed a significant increase in the negativity over both the SMA and M11317J.Galgano,K.Froud/NeuroImage41(2008)1313–1323regions between the pre-stimulus interval and the time to voice onset.Mean amplitudes continued to become significantly more negative across time intervals post-voice onset for both regions.This is summarized in Table 1and shown in Fig.5below.To summarize,several significant findings were revealed.The voicing condition was significantly more negative than the exhalation condition,activation over SMA sensors was significantly more negative than over M1sensors,and negativities significantly increased over the three time windows for the voice condition only.VRCP slope changesThe 2×3repeated measures ANOV A examining changes in the VRCP slope (microvolts per second)revealed a significant main effect of time,with the earlier time window being associated with ashallower slope than the later time window in both Regions.No other main effects or interactions were significant.Source localization using BESAUsing BESA,we fit dipoles to the grand-averaged data from 23subjects'responses to the V oice condition.We accepted an ECD model as a good fit when the residual variance dropped to 25%or below (standard for fitting to data from individuals is 10%RV).We began by seeding pairs of dipole sources to the left and right laryngeal motor areas,and in the middle frontal gyri,known to be associated with oro-facial movement planning in humans (Chainay et al.,2004)and the origination of human motor readiness potentials (Pedersen et al.,1998),respectively.A final pair of dipoleswasFig.3.The above waveform demonstrates grand-averages of 24subjects.In the voice condition,a peak negativity of the VRCP (SMA:−10.0086,V;M1:−5.2983,V)was found at bilateral TVF adduction,evidenced by onset movement shown in the Lx (EGG)waveform.A standard BP topography in M1is revealed.The late VRCP in M1shows a steeper slope,positive deflection preceding movement onset,and longer latency when compared to SMA.In the breathe condition,peaks showed longer latencies over both M1and SMA sensors,and reduced amplitude over SMA.Steps in the stimulus presentation/analysis procedure are superimposed:the breath-holding screen starts at −4000ms,and the “Go ”screen (instruction to hum through the nose)appears after 4s of breath-holding and is shown for a further 4s period.Initiation of phonation (recorded by EGG)was established for each individual trial within each subject.The interval between the onset of the “Go ”screen and phonation is where the specific VRCP could be identified.1318J.Galgano,K.Froud /NeuroImage 41(2008)1313–1323。

飞博k12教材目录 20180910

飞博K12课程–类别目录一、听口综合1、小童星Gogo Star 幼儿园，4-6岁2、剑桥少儿英语Cambridge Young Learners English (CYLE) 幼儿园至小学5年级，4-11岁3、剑桥国际少儿英语Kid’s Box (KB) 第一版剑桥国际少儿英语Kid’s Box (KB) 新版（开发中）小学，6-12岁小学，6-12岁4、新概念英语第1册 New Concept English (NCE1) 第一版新概念英语第1册 New Concept English (NCE1) 第二版（开发中）小学3年级至初中2年级，9-14岁小学3年级至初中2年级，9-14岁5、新概念英语第2册 New Concept English (NCE2) 第一版新概念英语第2册 New Concept English (NCE2) 第二版（开发中）初中2年级至高中3年级，14-18岁初中2年级至高中3年级，14-18岁6、新概念英语青少版 New Concept English Junior 1A, 1B（其他级别开发中）小学3年级至4年级，9-10岁7、剑桥国际英语教程青少版Connect 初中，13-15岁8、朗文国际英语线上口语Side by Side 小学4年级至初中，10-15岁9、公立校外研社版FLTRP 小学1年级至高中3年级，6-18岁10、公立校人教版PEP 小学3年级至高中3年级，9-18岁11、看听学3L- Look Listen and Learn 小学3年级至5年级，9-11岁12、牛津少儿英语Let’s Go! 小学4年级至6年级，10-12岁二、自然拼读17、魔法拼读 Magic Phonics 幼儿园至小学3年级，4-9岁18、自然拼读(速成版) Phonics 幼儿园至小学3年级，4-9岁19、少儿预备级Get Ready 幼儿园至小学3年级，4-9岁三、阅读13、绘本阅读Wise Reading 小学3年级至初中，9-15岁14、世界历史History 高中，16-18岁四、写作15、初级写作 Initial Writing 小学6年级至初中，12-15岁16、中级写作Intermediate Writing 初中和高中，13-18岁五、应试20、三一口语GESE (3-9级) 小学3年级至高中，9-18岁21、剑桥五级证书口语备考第1级 KET 小学4年级至初中1年级，10-13岁22、剑桥五级证书口语备考第2级 PET 小学5年级至初中3年级，11-15岁23、剑桥五级证书口语备考第3级 FCE 小学5年级至高中，11-18岁24、剑桥五级证书口语备考测试版1级KET 小学4年级至初中1年级，10-13岁25、剑桥五级证书口语备考测试版2级PET 小学5年级至初中3年级，11-15岁26、美国高中口语入学面试短训 International High School EntranceInterview初中，13-15岁27、中国高考口语能力测评课 Sprinting Speaking 高中，16-18岁28、中国高考听说能力测评课Sprinting Listening&Speaking 高中，16-18岁29、美国高考读写备考 SAT 高中，16-18岁31、雅思口语备考IELTS 高中，16-18岁六、主题课/短期课32、爆款体验课Lightning （K2, A, B, C）幼儿园至小学，4-12岁33、学唱英文歌Super Songs 小学1 至3年级，7-9岁34、口语短训课 English Corner 小学1至4年级，7-10岁35、中西方节日 Chinese and Western Festivals 小学1至4年级，7-10岁36、趣味英语Delish English 初中和高中，13-18岁37、旅行口语Travel 初中和高中，13-18岁38、交换生短训Exchange students 高中，16-18岁39、西方话题Western Outlook 高中，16-18岁一、剑桥剑桥少儿英语Cambridge Young Learners English (CYLE) 幼儿园至小学5年级，4-11岁剑桥国际少儿英语Kid’s Box (KB) 小学，6-12岁剑桥国际英语教程青少版Connect 初中，13-15岁剑桥五级证书口语备考第1级 (KET) 小学4年级至初中1年级，10-13岁剑桥五级证书口语备考第2级 (PET) 小学5年级至初中3年级，11-15岁剑桥五级证书口语备考第3级 (FCE) 小学5年级至高中，11-18岁二、新概念新概念英语第1册 New Concept English (NCE) 小学3年级至初中2年级，9-14岁新概念英语第2册New Concept English (NCE) 初中2年级至高中，14-18岁新概念英语青少版 New Concept English Junior 1A, 1B小学3年级至4年级，9-10岁三、公立校公立校外研社版FLTRP 小学1年级至高中3年级，6-18岁公立校人教版PEP 小学3年级至高中3年级，9-18岁四、其他朗文国际英语线上口语Side by Side 小学4年级至初中，10-15岁看听学3L- Look Listen and Learn 小学3年级至5年级，9-11岁牛津少儿英语Let’s Go! 小学4年级至6年级，10-12岁应试三一口语(3-9级)GESE 小学3年级至高中，9-18岁初中和高中，13-18岁美国高中口语入学面试短训 International High School EntranceInterview中国高考口语能力测评课Sprinting Speaking 高中，16-18岁美国高考读写备考SAT 高中，16-18岁托福听说模拟TOEFL 高中，16-18岁雅思口语备考IELTS 高中，16-18岁阅读绘本阅读Wise Reading 小学3年级至初中，9-15岁世界历史History 高中，16-18岁写作初级写作 Initial Writing 小学6年级至初中，12-15岁中级写作 Intermediate Writing 初中和高中，13-18岁主题课/短期课爆款体验课Lightning （K2, A, B, C）幼儿园至小学，4-12岁学唱英文歌Super Songs 小学1至3年级，6-9岁口语短训课 English Corner 小学1至4年级，6-9岁中西方节日 Chinese and Western Festivals 小学1至4年级，6-9岁趣味英语Delish English 初中和高中，13-18岁旅行口语Travel 初中和高中，13-18岁交换生短训Exchange students 高中，16-18岁西方话题Western Outlook 高中，16-18岁小童星Gogo Star飞博类别：听口综合适用年龄：幼儿园，3-6岁课程简介该课程适合3-6岁幼儿园儿童，内容为字母、与主题相关的词汇和句型。

《哈利波特与火焰杯》第12章《三强争霸赛》中英文对照学习版

中英文对照学习版Harry Potter and the Goblet of Fire《哈利波特与火焰杯》Chapter TwelveThe Triwizard Tournament第12章三强争霸赛Through the gates, flanked with statues of winged boars, and up the sweeping drive the carriages trundl ed, swaying dangerously in what was fast becoming a gale. Leaning against the wind ow, Harry coul d see Hogwarts coming nearer, its many lighted wind ows blurred and shimmering behind the thick curtain of rain. Lightning flashed across the sky as their carriage came to a halt before the great oak front doors, which stood at the top of a flight of stone steps. Peopl e who had occupied the carriages in front were already hurrying up the stone steps into the castle; Harry, Ron, Hermione and Nevill e jumped d own from their carriage and dashed up the steps too, l ooking up only when they were safely insid e the cavernous, torch-lit Entrance Hall, with its magnificent marbl e staircase.马车穿过两边带翅膀野猪雕塑的大门，顺着宽敞的车道行驶，由于狂风大作，马车剧烈地摇晃着。

新标准英语第十二册

新标准英语第十二册新标准英语（New Standard English）是一套广为流行的英语教材，旨在帮助学生提高英语水平，提升语言能力。

第十二册作为其中的一部分，内容丰富多样，涵盖了语法、阅读、写作、听力等多个方面。

本文将对新标准英语第十二册进行全面介绍，希望能够帮助学生更好地理解和应用这一教材。

首先，新标准英语第十二册的语法部分涵盖了各种语法知识，包括时态、语态、句型转换等内容。

通过系统的讲解和大量的练习，学生可以逐渐掌握英语语法的要领，提高语言表达能力。

此外，教材还提供了丰富的例句和练习题，帮助学生更好地理解和掌握所学内容。

其次，新标准英语第十二册的阅读部分包括了各种题材的文章，涵盖了社会、文化、科技等多个领域。

通过阅读这些文章，学生不仅可以扩大词汇量，还可以了解世界各地的风土人情，培养自己的阅读能力。

同时，教材还提供了相关的阅读理解题目，帮助学生检验自己的理解能力。

另外，新标准英语第十二册的写作部分注重培养学生的写作能力，包括了各种写作类型，如记叙文、议论文、说明文等。

通过学习这些写作类型，学生可以提高自己的写作水平，培养逻辑思维能力，提高表达能力。

同时，教材还提供了大量的写作范例和写作技巧，帮助学生更好地掌握写作要领。

最后，新标准英语第十二册的听力部分包括了各种听力材料，涵盖了日常生活、学习、工作等多个方面。

通过听力训练，学生可以提高自己的听力水平，培养自己的语感，提高听力理解能力。

同时，教材还提供了相关的听力练习题目，帮助学生巩固所学内容。

综上所述，新标准英语第十二册作为一套优秀的英语教材，内容丰富多样，涵盖了语法、阅读、写作、听力等多个方面。

通过学习这一教材，学生可以全面提高自己的英语水平，提升语言能力。

希望学生们能够认真学习，不断提高自己的英语水平，取得更好的学习成绩。

Act-Iceland_110-2000

ACT ON BIOBANKS NUM.110/2000S ECTION IG ENERAL PROVISIONS Article1.ObjectivesThe objective of the Act is to authori-ze the collection,keeping,handling and utilization of biological samples from human beings,in such a way that confidentiality is ensured,the interests of donors of biological samples is safe-guarded and that the utilization of the biological samples serves the purposes of science and medicine,and is condu-cive to the public good.The interests of science and of the community shall never be given prio-rity over the interests of the donor of a biological sample.It is prohibited to discriminate against a donor of a biolo-gical sample on the grounds of data derived from a biological sample. Article2.ScopeThis Act applies to the collection of biological samples,and their keeping, handling,utilisation and storage in bio-banks.The Act does not apply to tempo-rary keeping of biological samples ta-ken for purposes of clinical testing, treatment,or for specific scientific study,provided such samples are des-troyed when the tests,treatment or re-search are completed.Temporary kee-ping means storage for up to five years,unless the National Bioethics Committee authorises a longer period of storage.Should the long-term pre-servation of such samples be desired, they shall be stored in a biobank.The Act does not apply to the sto-rage of gametes and embryos under the provisions of the Act on Artificial Procreation,to organs under the pro-visions of the Act on Organ Removal, or to bodily remains under the terms of the National Heritage Act.Article3.DefinitionsIn this Act the following terms ha-ve the following meanings:1.Biological sample:organic ma-terial from a human being,alive or deceased,which may provide biologi-cal information about him/her.2.Biobank:a collection of biologi-cal samples which are permanently preserved.3.Scientific study:a study whose primary aim is to add to knowledge, with the purpose among other things of improving health and curing disease.4.Clinical test:test carried out in order to provide health service to an individual.5.Free,informed consent:consent granted in writing of the person’s own free will,after the donor of a biological sample has been informed of the purpose of taking the biological sample,its usefulness,risks attendant upon the process,and that the biologi-cal sample will be permanently pre-712served in a biobank for use under the terms of article9.6.Assumed consent:Consent that consists in the donor of a biological sample not expressing any unwilling-ness for a biological sample taken from him/her for a clinical test to be permanently preserved in a biobank for use by the terms of article9;infor-mation in writing on this possibility having been available to him/her.7.Donor of a biological sample:A person from whom a biological sample is taken.8.Licensee:Individual or legal en-tity granted a licence by the minister to operate a biobank under the terms of article4of this Act.S ECTION IIE STABLISHMENT AND O PERATIONOF B IOBANKSArticle4.Authority to Found and Ope-rate a BIobankThe establishment and operation of a biobank,i.e.collection,keeping, handling,utilisation and storage of biological samples,is permissible only for those who have been granted a li-cence from the minister under the pro-visions of this Act,following the re-ceipt of recommendations from the director general of Health and the Na-tional Bioethics Committee.Article5.Conditions of LicenceA licence for the establishment and operation of a biobank is contingent upon he following conditions:1.The terms of this Act,and go-vernment directives on the basis of the Act,shall be complied with.2.The biobank shall be located in Iceland.3.The objectives of the operation of the biobank,and the operational basis of the bank,shall be clearly defined.4.Conditions of storage for biolo-gical samples shall be described.5.Protocols of the biobank shall have been drawn up,including regu-lations of the biobank on arrange-ments for collaboration with foreign parties.6.A governing board shall be no-minated,as provided in article6,and one individual shall be nominated to be answerable for the biobank.7.The answerable party for the biobank shall be a physician and shall have practised independent research and development work within the health sector.In the case of the bio-bank comprising exclusively biologi-cal samples gathered for purposes of scientific study,the answerable party is not required to be a physician.8.That evaluation of security,and security measures in gathering of bio-logical samples,shall be consistent with the rules laid down by the Data Protection Authority on security of personal data in biobanks.The minister may lay down further conditions.Article6.Board of a BiobankThe licensee shall appoint a board of at least three people for each biobank, which shall monitor its operations.The board shall be under an obligation to keep the director general of Health, the Data Protection Authority and the National Bioethics Committee infor-med regarding the biological samples and operations of the biobank.ACT ON BIOBANKS NUM.110/2000713ISLANDIA 714S ECTION IIIC OLLECTION,HANDLING AND AC-CESS TO BIOLOGICAL SAMPLESArticle7.Consent of Donor of a Biolo-gical Sample and Withdrawal of ConsentIn connection with collection of a biological sample for preservation in a biobank,the free,informed consent of the person giving the biological sample shall be sought.This consent shall be given freely and in writing after the donor of a biological sample has been informed of the objective of the sam-ple collection,the benefits,risks asso-ciated with it’s collection,and that the biological sample will be permanently stored at a biobank for use as provided in article9.In addition the provisions of article20of the Act on personal pri-vacy and handling of personal data shall be observed where applicable.A donor of a biological sample can at any time withdraw his/her consent under the terms of paragraph1,and the biological sample shall then be destro-yed.Material that has been produced from a biological sample by perfor-mance of a study or the results of stu-dies already carried out shall,however, not be destroyed.If biological samples have been co-llected for the purpose of clinical tests or treatment,the consent of the patient may be assumed for the storage of the biological sample in a biobank for use as provided in article9,provided that general information on this is provided by a health care professional or health institution.A donor of a biological sample may at any time withdraw his/her assumed consent for his/her biological sample to be stored in a biobank for use as provided in article9,in which case it shall thereafter only be used in the in-terests of the donor of a biological sample or by his/her specific permis-sion,but see also paragraph4article 9.The request of a donor of a biologi-cal sample may apply to all biological samples which have been taken or may be taken from him/her.Such a request must be complied with.The donor of a biological sample shall in-form the director general of Health of his/her request.The director general of Health shall be responsible for pre-paration of forms for giving such no-tice,and shall ensure that these are available at health institutions,and at the premises of self-employed health care professionals.The director gene-ral of Health shall ensure that a coded register of those who have opted out in this way shall always be available to the boards of biobanks.Staff of the director general of Health who carry out this work are subject to an obliga-tion of confidentiality regarding in-formation they may become aware of in the course of their work,which should remain confidential by law or by its nature.Such staff shall sign an oath of confidentiality before their employ-ment begins.The obligation of confi-dentiality remains in force after em-ployment ceases.Article8.Preservation of Biological SamplesBiological samples shall be kept se-curely and labelled,but stored without personal identification.The linking of biological samples with personal iden-tification shall be in keeping with stan-dards laid down by the Data Protection Authority.Biological samples shall be stored in such a way that they are not lost or damaged,and that they are not accessi-ble to those who are not entitled to use them.Should the licensee decide to cease operation of the biobank,the licence having been revoked as provided in article14,the minister shall,after re-ceiving recommendations from the di-rector general of Health,the Data Pro-tection Authority and the National Bioethics Committee,decide on the fu-ture of the biobank,taking into ac-count the wishes and proposals of the licensee.Article9.Access to Biobank and Use of Biological SamplesBiological samples shall be acqui-red for clearly defined and lawful pur-poses,and not used for other purposes, but see paragraph2,3and4.The answerable party for the bio-bank grants access to biological sam-ples for further diagnosis of diseases. He/she may also grant access to biolo-gical samples for purposes of quality control,development of methods and tuition,provided that they are not per-sonally identified.The board of the biobank shall ne-gotiate with scientists on access to bio-logical samples.Access to biological samples for scientific studies may not, however,be granted until the permis-sion of the Data Protection Authority has been granted on the basis of the Act on personal privacy and handling of personal data,and a research proto-col has been approved by the National Bioethics Committee or the ethics committee of the relevant health insti-tution,as provided in the Act on the Rights of Patients and of regulations issued on the basis of the Act.The board of the biobank may,if approved by the Data Protection Aut-hority and the National Bioethics Com-mittee,authorise the use of biological samples for other purposes than those for which the samples were originally collected,provided that important inte-rests are at stake,and that the potential benefit outweighs any potential incon-venience to the donor of a biological sample or other parties.The minister shall,having received proposals from the director general of Health,the National Bioethics Commit-tee and the Data Protection Authority, issue regulations defining more preci-sely the use of biological samples. Article10.Rights and FeesThe licensee shall not be counted as the owner of the biological sam-ples,but has rights over them,with the limitations laid down by law,and is responsible for their handling being consistent with the provisions of this Act,and of government directives ba-sed on it.The licensee may thus not pass the biological samples on to another party,nor use them as collate-ral for financial liabilities,and they are not subject to attachment for debt.The licensee may take a fee for a biological sample,or access to a bio-logical sample,equivalent to the cost of gathering,storage and access to the sample.Any further fee is prohibited.A biological sample may be sent out of the country in the interests ofACT ON BIOBANKS NUM.110/2000715the donor of a biological sample,for diagnosis or quality control.Other trans-portation out of the country of biologi-cal samples is subject to the approval of the National Bioethics Committee and the Data Protection Authority and on the conditions they lay down. Article11.ConfidentialityAll staff of biobanks and those who have access to them shall preserve confidentiality regarding matters rela-ting to their work which should be kept confidential,by law or by their nature.The obligation of confidentia-lity remains in force after employment, research or tuition ceases.S ECTION IVM ONITORING AND O BLIGATION TO S UPPLY I NFORMATION Article12.MonitoringThe answerable party for the bio-bank shall be responsible for the im-plementation of internal monitoring and that security assessments be ca-rried out regularly,in accord with the provisions of arts11and12of the Act on personal privacy and handling of personal data.The Data Protection Authority shall monitor the security of personal data in biobanks.The Data Protection Aut-hority’s monitoring of biobanks is subject to the terms of paragraph.4 article35,paragraphs2and4,article 37and articles38-43of the Act on personal privacy and handling of per-sonal data.The director general of Health shall monitor biobanks in so far as this monitoring does not fall within the ambit of the Data Protection Aut-hority or the National Bioethics Com-mittee.Article13.Obligation to supply Infor-mation:Government and Biobank BoardsThe director general of Health is under an obligation to promulgate in detail to the general public the terms of this Act on biobanks,especially the provisions on assumed consent of a donor of a biological sample regar-ding a clinical test,and also the rights of the individual by the terms of arti-cle7and of paragraph3of the article.The director general of Health shall annually issue a register of biobanks, their purposes,activities and proto-cols.The register shall contain infor-mation on the membership of the board of each bank,and the identity of the answerable party.This register shall be made public and shall be ac-cessible to the general public.The board of the biobank or the director general of Health is obliged to provide individuals with informa-tion on whether biological samples from him/her are stored in a biobank, and on the nature of such biological samples.S ECTION VP ENALTIESArticle14The minister may revoke the licen-ce under the terms of this Act,if theISLANDIA 716licensee or its employees violate the terms of the Act or government directi-ves on the basis of the Act,if the con-ditions of the licence are not fulfilled, or if the licensee proves unable to ope-rate the biobank.Should the licensee violate the terms of this legislation or not comply with the conditions of the licence,the minister shall give the li-censee a written warning,allowing a reasonable period of grace to rectify matters.Should the licensee not com-ply with such a warning,the licence shall be revoked.In the case of delibe-rate violation or gross negligence,the minister may revoke the licence wit-hout notice and without allowing time for rectification.Article15Violation of the terms of this Act or government directives based on it en-tails fines or imprisonment for up to three years,unless a more severe pe-nalty is prescribed in other legislation.A legal entity or an individual may be sentenced to pay fines due to viola-tion of this Act.A legal entity may be fined whether or not the guilt of an employee of the legal entity has been proved.Should a member of the staff of the legal entity violate the terms of this Act or of government directives based on it,the legal entity may also be fined.The legal entity shall be res-ponsible for payment of a fine imposed upon a member of its staff,for viola-tion of the terms of this Act,provided that the offence is connected to the em-ployee’s work for the legal entity.S ECTION VIV ARIOUS P ROVISIONS ernment Directives The minister may issue regulations on the further implementation of this Act.The minister shall issue regulation on how information on assumed con-sent by the terms of paragraph.3article 7shall be provided,on how to ensure that withdrawal of assumed consent by a donor of a biological sample by the terms of paragraph.4article7is com-plied with,on the register of those op-ting out and its form cp.paragraph.4 article7,and how to ensure equal treat-ment of those who request access to biobanks for purposes of scientific stu-dies,cp.paragraph.3article9.Article18.Entry into ForceThis Act shall take force on1ja-nuary2001.Provisional Clauses1.Before the Act comes into force, the minister of Health and Social Secu-rity shall assign the Directorate General of Health to carry out detailed publicity among the general public on biobanks and regulations applying to collection and utilisation of biological samples.2.Biological samples gathered be-fore this Act came into force may be stored in a biobank,unless the donor of a biological sample declares his/her opposition to this.Otherwise the pro-visions of the Act shall apply to the storage,handling and utilisation of such biological samples.ACT ON BIOBANKS NUM.110/2000717。

Adenosine A1 receptor regulates osteoclast formation

ORIGINAL ARTICLEAdenosine A 1receptor regulates osteoclast formation by altering TRAF6/TAK1signalingW.He &B.N.CronsteinReceived:31October 2011/Accepted:19January 2012/Published online:5February 2012#Springer Science+Business Media B.V .2012Abstract Adenosine is an endogenous nucleoside that mod-ulates many physiological processes through four receptor subtypes (A 1,A 2a ,A 2b ,A 3).Previous work from our labora-tory has uncovered a critical role for adenosine A 1receptor (A 1R)in osteoclastogenesis both in vivo and in vitro.Our current work focuses on understanding the details of how A 1R modulates the receptor activator of NF-κB ligand (RANKL)-induced signaling in osteoclastogenesis.Osteo-clasts were generated from mouse bone marrow precursors in the presence of RANKL and macrophage-colony stimulat-ing factor.A pharmacological antagonist of A 1R (DPCPX)inhibited RANKL-induced osteoclast differentiation,including osteoclast-specific genes (Acp5,MMP9,β3Integrin ,αv Integ-rin ,and CTSK )and osteoclast-specific transcription factors such as c-fos and nuclear factor of activated Tcells cytoplasmic 1(NF ATc1)expression in a dose-dependent manner.DPCPX also inhibited RANKL-induced activation of NF-κB and JNK/c-Jun but had little effect on other mitogen-activated protein kinases (p38and Erk).Finally,immunoprecipitation analysis showed that blockade of A 1R resulted in disruption of the association of tumor necrosis factor receptor-associated factor 6(TRAF6)and transforming growth factor-β-activated kinase 1(TAK1),a signaling event that is important for activation of NF-κB and JNK,suggesting the participation of adenosine/A 1R in early signaling of RANKL.Collectively,these data demonstrated an important role of adenosine,through A 1R in RANKL-induced osteoclastogenesis.Keywords Adenosine A 1receptor .Osteoclastogenesis .TAK1.TRAF6.NF-κBIntroductionOsteoclasts,which are derived from monocytic/macrophagic hematopoietic cells in response to macrophage colony-stimulating factor (M-CSF)and receptor activator of NF-κB ligand (RANKL),a member of the tumor necrosis factor (TNF)cytokine superfamily,play a critical role in bone remod-eling.Increased osteoclast activity is seen in many osteopenic disorders,including postmenopausal osteoporosis [1,2],Paget's disease [3,4],bone metastases [5,6],periodontitis [7,8],and rheumatoid arthritis [9,10].Mature osteoclasts are giant,multinucleated cells that synthesize and directionally secrete bone matrix-degrading enzymes,including cathepsin K,matrix metalloproteinase-9(MMP9),and tartrate-resistant acid phosphatase (TRAP).The bone-resorbing activity of osteoclasts requires their adherence to the bone surface and subsequent development of ruffled borders and sealing zones.A substantial body of evidence suggests that adhesion mole-cules,including the integrin αv β3,play an important role in regulating migration,adhesion,polarization,and activation of osteoclasts [11–14].Activation of the NF-κB complex is a key early event in RANKL-induced osteoclast formation.Mammalian cells have five NF-κB family members (RelA/p65,RelB,c-Rel,NF-κB1/p105,and NF-κB2/p100)which contain an N-terminal Rel homology domain (RHD)with sequences for dimerization,DNA binding,and nuclear localization.Mice that lack both the p50and p52subunits of NF-κB developed severe osteo-petrosis due to a defect in osteoclast differentiation.Mice lacking c-Fos,a component of the transcription factor activator protein-1(AP-1),also develop osteopetrosis due to a completeElectronic supplementary material The online version of this article (doi:10.1007/s11302-012-9292-9)contains supplementary material,which is available to authorized users.W.He :B.N.Cronstein (*)New York University School of Medicine,550First Avenue,New York,NY 10016,USA e-mail:cronsb01@Purinergic Signalling (2012)8:327–337DOI 10.1007/s11302-012-9292-9block in osteoclast differentiation[15].AP-1binding sites have been identified in the promoters of several osteoclast genes including Acp5,β3integrin,carbonic anhydrase II,and NF ATc1 [16–19].Moreover,AP-1cooperates with other transcription factors(e.g.,NF-κB and NFA Tc1)to regulate RANKL-induced transcription osteoclast-specific genes[20].Binding of RANKL to RANK activates other signals that are critical for osteoclast formation as well including activation of mitogen-activated protein kinases(MAPKs),namely the extracellular signal-regulated kinase(Erk),c-Jun N-terminal kinase(JNK),and p38kinase.Genetic and biochemical studies indicate that the activation of JNK/c-Jun is indispensible for RANKL-induced osteoclast formation and mice from JNK null mice or c-Jun-deficient mice fail to form osteoclasts and suffer from osteopetrosis[21,22].Another signaling protein,transformation growth factor-β(TGF-β)activated kinase-1(TAK1)has been implicated in RANKL-induced osteoclastogenesis[23–25].Upon RANK receptor engagement,the cytoplasmic domain of RANK inter-acts with an adaptor protein,tumor necrosis factor-receptor-associated factor6(TRAF6),and endogenous TAK1is recruited to the TRAF6complex.The phosphorylation and activation of TAK1subsequently leads to MAPKs and inhib-itoryκB kinase(IKK)activation,the prerequisite event nec-essary to induce NF-κB.In this process,TAK1-associated binding protein-2(TAB2)acts as a bridge linking TRAF6to TAK1[26].Although the mechanism by which TAK1is activated is not fully understood,many studies have revealed the critical role of the lysine-63-linked polyubiquitination by TRAF6in the activation of TAK1[27,28].Adenosine is an endogenous nucleoside that modulates many physiological processes through four receptor sub-types(A1,A2a,A2b,A3).Recent studies in our laboratory have revealed a novel role for adenosine/A1receptor(A1R) in osteoclastogenesis:A1R activation is required for both osteoclast formation and function in vitro and only function in vivo,as demonstrated using pharmacologic inhibitors and mice lacking adenosine A1receptors[29,30].The disparity between in vitro and in vivo osteoclast formation is reminis-cent of a similar disparity in osteoclast formation in vitro and in vivo in mice lacking either TRAF6or Atp6v0d2in which osteoclasts are present in vivo,although functionally defec-tive[31]and do not form from precursors in vitro[32,33]). One possible explanation for these discrepancies is the pres-ence of other factors in the in vivo microenvironment which can partially compensate the A1R,TRAF6or Atp6v0d2 deficiency,such as TGF-β[32].In this work,we further probed the signaling pathways by which adenosine/A1R activation mediates its effect on osteoclastogenesis.We report here that adenosine A1R activation is required for appropriate formation of TRAF6/TAK1complexes and the resulting activation of NF-κB,the critical signaling step in osteoclastogenesis.MethodsAntibodies and reagentsCommercially available antibodies were purchased from the following resources:IκB,p-c-Jun,c-Jun,p-Erk,p65,TAK1, TRAF6,NFATc1(Santa Cruz Biotechnology Inc),p-p-38, p38,Erk,p-JNK,JNK(Cell Signaling Technology),p84, andβ-actin(abcam).Recombinant murine M-CSF and murine RANKL were from R&D System Inc.Sodium thiosul-fate and silver nitrate were purchased from Sigma.Osteoclast cultureFor generation of bone marrow-derived osteoclasts,primary bone marrow cells from6to8-week-old mice were cultured as described previously[30].Briefly,bone marrow was extracted from femora and tibia of mice.The cells were grown in completeα-MEM(Invitrogen)containing10% fetal bovine serum for24h.Then the non-adherent BMMs were collected and replated in culture dishes at1×105cells/cm2 density with murine M-CSF(30ng/ml)for2days.Cells at this stage were considered M-CSF-dependent bone marrow macro-phages(BMMs)and used as osteoclast precursors.Induction of differentiation to osteoclasts was achieved by culturing the BMM cells with the osteoclastogenic medium contain-ing M-CSF(30ng/ml)and recombinant murine RANKL (30ng/ml).The day cells were treated with differentiation medium(RANKL+M-CSF)was counted as day0.Typically, cells were TRAP-positive multinuclear at day5after the initiation of culture with RANKL.To test the effect of A1R antagonist,DPCPX,these osteoclast precursors(BMMs)were cultured in the osteoclastogenic medium with or without different doses of DPCPX for5days.The culture medium was replaced with fresh medium containing these reagents every3days.TRAP staining and bone resorption assayOsteoclast differentiation was evaluated by staining for TRAP using a leukocyte acid phosphatase kit(Sigma-Aldrich). TRAP-positive multinucleated cells(≥3nuclei)were counted as osteoclasts.For bone resorption assay,The BMMs were seeded on BD BioCoat Osteologic MultiTest slides(BD Biosciences)and cultured in the osteoclastogenic medium with or without different doses of DPCPX for8days.At the end of culture,cells were removed from chamber slides with bleach and stained by V on Kossa method.Briefly,slides were stained with5%silver nitrate for30min and then fixed in5%sodium carbonate in25%formalin for5min to remove un-reacted silver nitrate.The surface areas of resorption pits were mea-sured and analyzed using Labworks Image Acquisition and Analysis software4.0(UVP).Using the software,the percentileof pixels of white in a gray scale was measured as a represen-tation of the percentage of resorption area to total area.Real-time PCRTotal RNA was isolated from culture cells using RNeasy Kit (Qiagen).cDNAwas synthesized from1μg of total RNA using the SuperScript First-Strand Synthesis System(Invitrogen)in a volume of20μl.Real-time PCR was performed using Master SYBR Green Kit(Strategene).Primers are listed in Table1. PCR conditions were95°C for5min followed by38cycles of 95°C for30s,58°C for30s,and72°C for30s.Each experiment was done in triplicate,and results were standardized against the message level ofβ-actin.The comparative CT method was used to calculate the expression levels of RNA transcripts.Western blotFor RANKL signaling,bone marrow cells were grown in 30ng/ml M-CSF for2days.Cells were then washed with PBS and treated with30ng/ml M-CSF and50ng/ml RANKL or without different doses of DPCPX for the indicated times. Total cell lysate(30μg)were collected and subjected to western blot analysis with the indicated antibodies.Nuclear extracts (15μg)were prepared using NE-PER kit(Pierce)according to the manufacturer's instruction and loaded in10%SDS-PAGE gels and immunoblotted with different antibodies.NF-κB p65DNA-binding analysisNuclear extracts were obtained from primary osteoclast precursor cells as above and assayed for NF-κB transcription-al activity using an ELISA(Cayman Chemicals)according to the manufacturer's instruction.Nuclear extracts(15μg)were incubated into a96-well plate coated with oligonucleotide containing the consensus NF-κB response element.Absor-bance at450nm was read in a plate reader,and the data were calculated as ratio to control(BMMs treated with M-CSF only).Immunoprecipitation assayCells were washed once with ice-cold PBS and lysed in ice-cold IP lysis buffer(Pierce)according to the manufac-turer's instruction with freshly added proteinase inhibitor cocktail(Sigma)and phosphatase inhibitor(Cayman Chem-icals).Cleared lysates(3–5mg total protein)were preincubated with TRAF6antibody for overnight and complexes separated using protein G agarose(25μl per sample,Pierce)before gel electrophoresis.Statistical analysisData are shown as the means±S.D from at least three independent experiments.Statistical analysis was done by using the Prism4.02(GraphPad Software).All data was evaluated using an analysis of variance(ANOV A)followed by Bonferroni post hoc.P<0.05was considered to be significant (*P<0.05,**P<0.01,***P<0.001).ResultsA1R blockade suppresses osteoclastogenesisand bone-resorbing activity in primary BMMs cultured with RANKL and M-CSF in a dose-dependent manner We have previously demonstrated that adenosine regulates osteoclast formation through A1R[30].We therefore examinedTable1Oligonucleotides used for quantitative real-timePCR Target mouse gene Sequence Gene bank reference β-actin(F)5′-ACTATTGGCAACGAGCGGTT-3′NM_007393.3(R)5′-CAGGATTCCATACCCAAGAAGGA-3′Acp5(F)5′-CGTCTCTGCACAGATTGCAT-3′NM_007388(R)5′-TGAAGCGCAAACGGTAGTA-3′Ctsk(F)5′-GGAGGCGGCTATATGACCA-3′NM_007802(R)5′-ACAACTTTCATCCTGGGCCCA-3′MMP-9(F)5′-CCTGTGTGTTCCCGTTCATCT-3′NM_013599.2(R)5′-GCCATACAGTTTATCCTGGTCA-3′Integrinβ3(F)5′-TTTGCCCAGCCTTCCAGCCCA-3NM_016780.2(R)5′-CGGTAATCCTCCTCAGAGCA-3′Integrinαv(F)5′-AACATCACCTGGGGCATTCA-3′NM_008402.2(R)5′-TGAGGTGGTCGGACACGTTT-3NFATc1(F)5′-CTCGAAAGACAGCACTGGA-3′AF309389.1(R)5′-AGGTGCTGGAAGGTGTACT-3′c-fos(F)5′-GAACAACACACTCCATGCGG-3′NM_010234.2(R)5′-GGAGGACCTTACCTGTTCGTGA-3′the effect of A1R blockade on osteoclast formation and func-tion in vitro using pharmacological tools.After5-day culture in osteoclast differentiation medium(M-CSF and RANKL (30ng/ml each)),murine primary osteoclast precursors were differentiated into large,multinucleated TRAP+cells(Fig.1a). When the A1R-selective antagonist,DPCPX,was added at the beginning of culture(day0),a dose-dependent inhibition of osteoclastogenesis was observed,as we previously reported (Fig.1a).DPCPX at1and10μM inhibited RANKL-induced osteoclast formation by about51%and76%,respectively(P< 0.001compared with control treated with RANKL+M-CSF, for both).Even though DPCPX may also block A2A and A2B receptors,it is unlikely that interaction with these receptors plays any role in inhibiting osteoclastogenesis since stimulation of both A2A and A2B receptors inhibits osteoclast differentiation([34]and Supplemental Figure1).Consistent with the effect on osteoclast formation,resorption pit forma-tion by mature osteoclasts at day8of culture was inhibited by 1μM DPCPX by61%(Fig.1a and b,P<0.05)and nearly eliminated by10μM DPCPX(by95%)(Fig.1a,b,P<0.01). DPCPX treatment is not cytotoxic at the concentrations used (MTT assay,data not shown),indicating that the anti-osteoclastogenic effect of DPCPX was not due to toxic effects on osteoclast precursor cells.A similar pattern of dose-dependent inhibition by adenosine A1R blockade was observed with regard to RANK-induced expression of known osteoclast marker genes,including Acp5,Ctsk,MMP9,and Integrinαvβ3(Fig.1c).DPCPX ataFig.1Suppression of osteoclast formation and function by A1R-selective antagonist.Murine BMMs(1×105cell/cm2)were cultured with M-CSF and RANKL(30ng/ml each),with or without various concentrations of DPCPX for5days in48-well plates for TRAP staining(a upper panel),or8days on calcium phosphate-coated slides (BD biosciences)and for pit formation assay(a lower panel),respec-tively.b Numbers of TRAP-positive multinuclear cells containing more than three nuclei(TRAP+MNC)were counted.For pit formation assay,the slides were stained with von Kossa reagent.Bone resorption percentage was quantified using Labworks Image Acquisition and Analysis software4.0.The percentile of pixels of white in a gray scale was measured as a representation of the percentage of resorption area to total area(bone resorption,percent).c BMMs were cultured with M-CSF and RANKL(30ng/ml each),with or without various concen-trations of DPCPX in6-well plates for5days prior to RNA extraction and real-time PCR for Integrinαv,β3,Acp5,Ctsk,and MMP9.β-actin served as PCR control.Relative expression was calculated relative to M-CSF only cells(fold value1).Values are shown as means±S.D.of at least three independent experiments.*P<0.05,**P<0.01,and ***P<0.001compared to RANKL+M-CSF cellsconcentration of 1μM or more significantly reduced the transcription of these genes at day 5of culture.Similarly,rolofylline (KW3902,a more selective and potent A 1R antag-onist)inhibited RANKL-induced gene expression of Ctsk by KW3902(1μM,supplemental Figure 2,P ≤0.001compared with control treated with RANKL±M-CSF),further confirm-ing the receptor specificity of the inhibitory effect of DPCPX we observed in RANKL-induced osteoclastogenesis.Because the selective A 1receptor agonist N 6-cyclopentyladenosine neither directly affected Ctsk expression nor reversed the DPCPX-mediated inhibition of Ctsk expression (Supplemen-tal Figure 3),our results are consistent with the hypothesis that the A 1receptor is constitutively active and DPCPX acts as an inverse agonist to inhibit osteoclastogenesis.A 1R blockade diminishes induction of the transcription factors c-Fos and NFATc1in primary BMMsThe essential role of transcription factors c-Fos and NFATc1in RANKL signaling is now well established.Hence,we determined whether the inhibitory effect of A 1R blockade also leads to regulation of these factors.NFATc1is a master switch for terminal differentiation of osteoclasts;we there-fore examined the expression of NFATc1at day 4of culture.As shown in Fig.2a,b ,whereas NFATc1mRNA levels were augmented about 13.88-fold and protein levels were in-creased about 49.1-fold by RANKL treatment (relative to M-CSF only),these increases were completely abolished by DPCPX at concentrations of 1and 10μM.Previous studies of signaling pathways in osteoclast for-mation indicate that NFATc1is downstream of c-Fos in osteo-clastogenesis regulated by RANKL [17,20].We next determined whether adenosine A 1R blockade inhibits c-fos expression at day 3of culture and found that DPCPX abro-gated RANKL-induced c-fos expression was observed (Fig.2c ).The increase in the c-Fos message induced by RANKL (about twofold)was significantly decreased by DPCPX in a dose-dependent fashion.These results indicate that A 1R blockade directly diminishes the transcription of c-Fos and NFATc1byRANKL.Fig.2Suppression of the RANKL-induced expression of transcrip-tion factors NFATc1and c-fos by A 1R-selective antagonist.BMMs were cultured with M-CSF and RANKL (30ng/ml each),with or without various concentrations of DPCPX for 4days (a ,b )or 3days (c ).Total RNA was isolated and NFATc1(a )and c-fos (c )mRNA levels were quantified by real-time PCR.Relative expression in mRNA levels was calculated relative to M-CSF only cells (fold value 1).Values are shown as means±S.D.of four independent experiments.b The NFATc1protein expression was determined by immunoblotting.Pro-tein band intensities were quantified by densitometry and corrected with β-actin.Protein level (fold of change)was expressed as fold change compared with M-CSF only.Values are shown as means±S.D.of three independent experiments.*P <0.05,**P <0.01compared to RANKL+M-CSF cellsA 1R blockade inhibits RANKL-induced JNK/c-Junactivation,but not that of p38and Erk in primary BMMs An increasing body of information indicates that RANKL stimulates NF-κB and MAPK activation and subsequently elicits the activation of essential transcription factors,such as AP-1and NFATc1,required for osteoclast differentiation.Since we found that DPCPX profoundly blocks the induc-tion of c-fos and NFATc1expression by RANKL,we next examined the two major RANKL-induced signaling path-ways,MAPKs and NF-κB.Our findings confirm prior reports that RANKL induces rapid phosphorylation of the JNK,c-Jun,p38,and Erk in primary bone marrow culture (Fig.3a ).With the addition of DPCPX to the cultures,we observed a substantial suppression of the RANKL-induced phosphorylation of JNK and c-Jun at 15min (P <0.05for both,Fig.3b ),whereas the activation of p38and Erk were not affected.The activation of c-Jun by JNK is an important mechanism involved in osteoclastogenesis [21].Since the expression of c-fos was down-regulated by A 1R blockade (Fig.2c )and it is known that AP-1comprises Fos/Jun dimers,our findings indicate that blockade of adenosine A 1R impaired the RANKL-induced activation of AP-1,the critical factor in osteoclastdifferentiation.Fig.3Inhibition of RANKL-induced activation of JNK/c-Jun,but not that of Erk and p38,by A 1R-selective antagonist.BMMs were stimu-lated with RANKL/M-CSF,with or without 1μM DPCPX for various times.a Cells were lysed and equal amounts of proteins were separated by SDS-PAGE and immunoblotted with the indicated antibodies.b Protein band intensities were quantified by densitometry,and the levels of phosphorylated MAPKs were normalized to the total levels of corresponding MAPKs.The ratio of phosphorylated MAPKs/total MAPKs in the RANKL-stimulated cells was relative to that of cells treated with M-CSF only (fold value 1).The densitometry values are shown as means±S.D.of three independent experiments.The figure shows representative data from one of three replicate experiments.*P <0.05using an analysis of variance (ANOV A)followed by Bonferroni post hocA1R blockade inhibits RANKL-induced NF-κB activation in primary BMMsNF-κB signaling in osteoclasts has been extensively studied. Recent study suggests that NF-κB activation is the upstream signaling molecule of c-Fos in osteoclastogenesis[35].Dele-tion of the NF-κB subunits p50and p52causes severe osteo-petrosis through the absence of osteoclasts[36,37].We therefore examined the effects of DPCPX on the activation of NF-κB by RANKL.To this end,we stimulated BMMs with RANKL in the presence or absence of different doses of DPCPX and assessed the degradation of IκB in whole cell lysates at5min and the presence of p65in nuclei at10min by western blot analysis.As previously reported,there is cyto-solic degradation of IκB and nuclear translocation of p65in response to RANKL(Fig.4a).DPCPX markedly reduced IκB degradation in the cytosol and nuclear translocation of p65in a dose-dependent manner(Fig.4b).Consistent with these findings,we observed that RANKL induced significant p65 DNA binding activity starting from2min and continuing as long as30min(Fig.4c).With the addition of1μM of DPCPX to the cultures,we observed a significant inhibition of RANKL-induced p65transcriptional(DNA binding)activity at5min and15min(P<0.05for both).These results indicate that the A1R-mediated inhibition of RANKL-induced osteo-clastogenesis is mediated through two major pathways,inhibi-tion of NF-κB and JNK pathways,which regulate transcription of c-Fos and NFA Tc1in osteoclast precursors.A1R blockade disrupts RANKL-induced formationof TRAF6-TAK1complex in primary BMMsTAK1,a MAPK kinase kinase can form complexes with RANK and TRAF6,and was up-regulated in RANKL-induced osteoclastogenesis([23–25].RANKL-induced oste-oclast differentiation requires TAK1for NF-κB activation[25]. Herefore,we determined whether DPCPX affects the recruit-ment,and interaction of TAK1with TRAF6by RANKL.In line with previous reports,we found a striking induction of TAK1association with TRAF6following stimulationwithFig.4Inhibition of RANKL-induced activation NF-κB by A1R-se-lective antagonist.BMMs were stimulated with RANKL/M-CSF,with or without various concentrations of DPCPX.IκB degradation in whole lysates was determined at5min and nuclear localization of p65was determined at10min with western blot analysis(a).Protein band intensities were quantified by densitometry(b).For IκB degra-dation,the levels of IκB were normalized toβ-actin,and the data are expressed as percentages of control(M-CSF only).For p65nuclear translocation,the levels of p65were normalized to p84and the data are expressed as the fold changes to control(M-CSF only).The densitom-etry values are shown as means±S.D.of three independent experiments.The figure shows representative data from one of three replicate experi-ments.p65DNA binding activity was measured with an ELISA-based assay(c).BMMs were stimulated with RANKL/M-CSF,with or without 1μM DPCPX for various times.Equal amounts of nuclear proteins were collected and incubated into a96-well plate coated with oligonucleotide containing the consensus NF-κB response element.Absorbance at 450nm was read in a plate reader and the data were calculated as ratio to control(M-CSF only).Values are shown as means±S.D.of four independent experiments.*P<0.05,**P<0.01,and***P<0.001 compared to RANKL+M-CSF cellsRANKL.The addition of1μM DPCPX in culture medium completely abolished the RANKL-induced TAK1/TRAF6as-sociation without affecting the total levels of TAK1at5min (P<0.01,Fig.5a,b).Taken together,our results suggest that adenosine A1R activation is required for association of TAK1 with RANK and that blockade of A1R prevents this activation step thereby diminishing TAK1-mediated NF-κB activation. DiscussionIn the present study,we have confirmed,using the selective A1R antagonist DPCPX,that endogenous adenosine,acting via A1receptor is an important regulator of RANKL-induced osteoclastogenesis.Moreover,we found that A1R blockade impairs the activation of NF-κB by RANKL, blocks phosphorylation of JNK and inhibits the transcription of c-fos and NFATc1.These findings indicate that adenosine A1R activation is required for signaling at RANK,and A1R blockade leads to disruption in the signaling pathway for osteoclast formation.These findings also provide a solid explanation for our prior observation that A1R-selective antagonists are most effective in preventing osteoclast for-mation when included at early stages of osteoclastogenesis (before day3of culture)[30].Activation of NF-κB by RANKL is a crucial event in the early stages of osteoclastogenesis.A recent study using p50/p52double knockout splenocytes and ectopic expression of c-Fos shows that NF-κB is upstream from c-Fos and required for c-Fos activation in RANKL-stimulated osteoclast precursors[35].Similarly,in the present study,we found that induction of c-fos by RANKL was prevented by A1R blockade-mediated abrogation of NF-κB activation. Although the consensus NF-κB binding site has not been recognized in the c-Fos promoter,and there is no direct evidence of activation of c-Fos by NF-κB,our findings and others support the hypothesis that NF-κB is upstream of c-Fos in osteoclastogenesis.Adenosine has been reported to activate the JNK pathway through A1R in many other systems[38,39].Our study is the first report to demonstrate that adenosine/A1R is also required for RANKL-induced JNK/c-Jun activation in BMMs.Although the precise role of JNK/c-Jun in osteoclastogenesis has yet to be determined,there is increasing evidence that JNK/c-Jun activa-tion is essential for efficient osteoclastogenesis[22].It has been reported that osteopetrosis develops in transgenic mice with dominant-negative c-Jun in their osteoclast lineage cells[21].A more recent study showed that the JNK/c-Jun pathway is required for an anti-apoptotic effect of RANKL in multinucle-ated osteoclasts[40].However,unlike mature osteoclasts,c-Jun activation by RANKL is not involved in the anti-apoptotic effect of JNK in bone marrow macrophages[22].In line with these observations,blockade of A1R had little effect on cell viabilityinFig.5Disruption of RANKL-induced formation of TRAF6/TAK1 complex by A1R-selective antagonist.a BMMs were stimulated with RANKL/M-CSF,with or without1μM DPCPX for various times.Cell extracts were immunoprecipitated(IP)with anti-TRAF6antibody.The immunoprecipitates were then analyzed by immunoblotting with anti-TAK1antibody and anti-TRAF6antibody(upper two panels).Whole-cell extracts were immunoblotted with anti-TAK1antibody(bottom panel).Protein band intensities were quantified by densitometry(b). The level of TAK1were normalized to TRAF6and the data are expressed as fold change to control(M-CSF only).Values are shown as means±S.D.of four independent experiments.The figure shows representative data from one of four replicate experiments.**P<0.01using an analysis of variance(ANOV A)followed by Bonferroni post hocmouse BMMs(data not shown).These findings collectively argue for an essential role of JNK/c-Jun in osteoclastogenesis but not prevention of osteoclast apoptosis.Our observation that inhibition of activation of JNK and NF-κB by blockade of A1R suggests that these molecules may share a common pathway to induce osteoclast precursor dif-ferentiation.Recent studies have provided more insights into the molecular mechanism underlying the activation of these pathways.In particular,new findings reveal that TRAF6 associates with TAK1through an adaptor protein TAB2. The formation of the complex of TRAF6,TAB2,and TAK1 leads to the activation of TAK1which subsequently phosphor-ylates NF-κB-inducing kinase(NIK)and eventually leads to the activation of the NF-κB pathway[23,41,42].In addition, activated TAK1also activates the JNK pathway down-stream of RANK[24,43].In support of this hypothesis, we found that the association of RANKL/RANK in oste-oclast precursors derived from bone marrow cells evokes a rapid and dramatic accumulation of TRAF6/TAK1com-plex,which is clearly diminished by A1R blockade.This observation is consistent with the previous report that adenosine A1R blockade results in loss of cellular TRAF6 in RAW264.7cells[30].These results suggest that aden-osine A1R blockade-mediated blockade of TRAF6-TAK1 complexes triggers TRAF6degradation.We therefore pos-tulate that the pivotal effect of adenosine A1R in promo-tion of osteoclast formation is the proper formation of TRAF6-TAB2-TAK1complex(Fig.6).Further studies will be required to clarify the role of each component of this complex in mediating adenosine/A1R regulation ofosteoclastogenesis as well as the mechanism by which A1R regulates formation of this complex.Recent studies suggest that the usual classification of GPCR-active agents as agonists,antagonists,or inverse ago-nists(agents that diminish activity of a constitutively active receptor)needs refinement.Activation of GPCRs regulates cellular function by activating G proteins and,as more recently described,activatingβ-arrestin with distinct downstream sig-naling and functional consequences([44]).It has recently been recognized that some receptor active agents preferentially stimulate G protein signaling whereas others stimulate the alternative pathway and this phenomenon has recently been shown to be important for adenosine receptor physiology[44]. Because we found that stimulation of the A1receptor does not affect osteoclastogenesis whereas antagonism of A1receptors inhibits osteoclastogenesis,our results are most consistent with the hypothesis that the A1receptor is constitutively active and that blockade of the A1receptor inhibits osteoclastogen-esis by acting as an inverse agonist.Thus,it is possible that DPCPX is acting as an inverse agonist in the setting of A1R-mediated regulation of osteoclast function.Alternatively, many cell types release or generate adenosine at the cell surface and these low levels of adenosine are sufficient to activate A1R,a phenomenon blocked by DPCPX and other receptor antagonists.Previous studies have demonstrated a role for adenosine and adenosine A1R in regulating formation of multinucleated giant cells from peripheral blood monocytes[45–47],a find-ing consistent with the observations here.Similarly,in prelim-inary studies,we have observed that both DPCPX and rolofylline block osteoclast formation from human bone marrow-derived precursors(He,Mazumder and Cronstein, unpublished observations).Thus,it is likely that the observa-tions on murine osteoclast formation reported here are rele-vant to human osteoclasts as well.Adenosine may either be released from cells via bidirectional adenosine transporters on the cell membrane or adenosine may be generated by hydrolysis of extracellular adenosine nucleo-tides by such extracellular phosphohydrolases as nucleoside triphosphate phosphohydrolase(CD39),ecto-5′nucleotidase (CD73),tissue non-specific alkaline phosphatase(TNAP), among others.CD39and CD73are expressed on the surface of murine osteoclast precursors(He,W.and Cronstein,BN, unpublished),although their roles in producing extracellular adenosine have not been established.Because adenosine A1R can be fully activated by adenosine levels which are inthe Fig.6A proposed scheme of adenosine/A1R-mediated regulation of RANKL-induced osteoclast formation.During osteoclastogenesis,the critical transcription factors c-fos and NFATc1are induced by RANKL. NFATc1is known to be master switch of osteoclastogenesis.Blockade of A1R with DPCPX inhibits osteoclast formation through interfering the RANKL-induced formation of TRAF6/TAK1signaling complex followed by de-activation of NF-κB and JNK and subsequently leading to the reduction of osteoclast formation by RANKL。

英孚英语分级12级课文

英孚英语分级12级课文The English First 12th Level Coursework is a comprehensive program designed to help students achieve a high level of proficiency in the English language. This course covers a wide range of topics and skills, from advanced grammar and vocabulary to complex reading comprehension and written expression. As students progress through the program, they will be challenged to develop a deep understanding of the nuances and intricacies of the English language, preparing them for success in academic and professional settings.One of the key features of the English First 12th Level Coursework is its focus on practical application. Rather than simply memorizing rules and definitions, students are encouraged to actively engage with the language through a variety of interactive activities and real-world scenarios. This approach helps to reinforce the concepts they are learning and ensures that they are able to effectively communicate in a range of contexts.Throughout the course, students will explore a diverse array of topics, from literature and history to science and technology. They will readand analyze complex texts, engage in lively discussions, and hone their writing skills through a series of challenging assignments. This breadth of subject matter not only enhances their language proficiency but also expands their overall knowledge and critical thinking abilities.In addition to the core curriculum, the English First 12th Level Coursework also includes a strong emphasis on cultural awareness and global perspectives. Students will learn about the rich diversity of the English-speaking world, exploring the unique customs, traditions, and modes of expression that characterize different regions and communities. This understanding of cultural context is essential for effective communication and helps to prepare students for the increasingly interconnected world they will be navigating.One of the standout features of the English First 12th Level Coursework is its focus on developing advanced language skills. Students will delve into the complexities of grammar, exploring more nuanced and sophisticated structures that enable them to express themselves with greater precision and clarity. They will also expand their vocabulary, learning specialized terms and idiomatic expressions that are essential for academic and professional discourse.Perhaps most importantly, the English First 12th Level Courseworkplaces a strong emphasis on critical thinking and analytical skills. Students are challenged to engage with complex texts, extracting key ideas, evaluating arguments, and formulating their own well-reasoned perspectives. This ability to think critically and communicate effectively is a highly valued asset in today's increasingly competitive job market.As students progress through the course, they will have the opportunity to apply their language skills in a variety of practical settings. They may participate in simulated business negotiations, deliver formal presentations, or even engage in creative writing exercises. These hands-on experiences not only reinforce the concepts they have learned but also help to build their confidence and adaptability as communicators.Throughout the English First 12th Level Coursework, students will have access to a wide range of resources and support systems to help them succeed. This may include one-on-one tutoring, online learning platforms, and opportunities for peer collaboration and feedback. The instructors who guide this program are highly experienced and dedicated professionals, committed to helping students reach their full potential.One of the key benefits of the English First 12th Level Coursework is its ability to prepare students for the demands of higher educationand the global workforce. By developing a deep understanding of the English language and the ability to communicate effectively, students will be well-equipped to excel in their academic and professional pursuits. Whether they are pursuing a degree in a specialized field or seeking to advance their career, the skills and knowledge gained through this program will be invaluable.In conclusion, the English First 12th Level Coursework is a comprehensive and challenging program that is designed to help students achieve a high level of proficiency in the English language. Through a combination of rigorous academic content, practical application, and cultural awareness, this course prepares students for success in a wide range of academic and professional contexts. Whether you are a student seeking to enhance your language skills or a professional looking to take your communication abilities to the next level, the English First 12th Level Coursework is an excellent investment in your future.。

SPB Academic Publishing bv, The Hague

Landscape Ecology vol. 5 no. 3 pp 137-144 (1991)SPB Academic Publishing bv, The HagueMultiple landscape scales: An intersite comparisonR.V.V.I.T.J.M.R.ofWildlife and Ecology, P. 0. Box 84, Lyneham, ACT 2602, Australia; 3Marine Research Laboratory, Pacific Northwest Laboratory, Sequim, WA 98382;t of Environmental Sciences, University of Virginia, Charlottesville, VA22903; Research Division ER-75, Office of Health and Environmental Research, U.S. Depart-ment of Energy, Washington, DC 20545. Present Address: Department of Biology, New Mexico State University, Las Cruces, NM 88003;Sciences Department, Pacific Northwest Laboratory, P.O. Box 999, Richland, WA99352;by a single method in multiple The analyses indicated 3interactions in complexecological systems (O’Neill 1988). Interacting com-ponents operate at similar dynamic rates and arerelatively isolated from higher or lower levels (O’Neill et al. 1986). As a result, dynamics will tend to be grouped into distinct scales or levels, rather than being uniformly distributed between the fast-est and slowest rates (O’Neill 1989).Since ecological processes help determine spatial patterns in vegetation (Turner, in press), the theory predicts that the hierarchy of process rates should be reflected in a hierarchy of spatial scales on the landscape (O’Neill 1989). Biotic interactions, such as competition and grazing, can generate spatial patterns at scales characteristic of the underlying processes. Levin (1976, 1978) has shown that predator-prey interactions, combined with spatial movement of the populations, can result in a patchy spatial distribution. The scale of the distribution,i.e.,size and distance between patches, is deter-mined by the feeding and migration rates. Paine and Levin (1981) showed theoretically and138constraints, such as topography and soil, can impose additional patternsable to expect that this complex organization would be reflected in multiple scales of vegetation pattern on the landscape.A first step in determining the utility of the theo-retical framework, therefore, is the detection of multiple scales of pattern. However, detection of multiple scales cannot be considered a rigorous test of hierarchy theory. A number of landscape scales could result from independent139AnalysesThe selection of analytic methods was based on a review of statistical approaches suitable for iden-tifying spatial scale (Turner et al., in press). Based on the review, we chose four methods that we will identify as (1) Hill analysis, (2) Correlation analy-sis, (3) Ratio analysis, and (4) Spectral analysis.Turner et al. (in press) should be consulted for de-tails of the four methods briefly outlined below.Each technique has weaknesses, but the suite of four analyses complement each other. The strengths of one tend to compensate for the weak-nesses of others. Our approach was to accept a scale of pattern only if it was detected by more than one technique and/or located by a single technique inmultiple separately precluded the use of multivariate ap-proaches (e.g., Ver Hoef and Glenn-Lewis 1989,Ver Hoef et al. 1989).We also tried to make conservative interpreta-tions. Since our objective was to detect multiple scales, we combined similar scales of pattern. For example, when three different techniques indicatedpatterns atp T140no scale can be inferred. Nevertheless, whenever this approach did show a peak, this scale was invari-ably confirmed by other analyses, particularly at scales between 50 and 150 m.Spectral analysis (Ripley 1978) fits the spatial data to a model composed of sinecosine pairs of various periods. A regular pattern is indicated when an unusual amount141Table 1. Scale analyses of transect data for Bouteloua gracilis, Bouteloua eriopoda, Forbs, and Bare Ground at Sevilleta Long TermEcological Research Site, New Mexico. The analyses are based on four statistical methods and values are expressed in meters.B. gracilisForbs B. eriopodaBare Ground Hillpeak525-600350-650400-500200, 500-600troughi n t h e g r a s s e s Spectral ana 450-500 manalysis and142Table 3. Spatial analyses for transect data onAgropyron Spectral p/a’450cover75,105,1000 Ratio125patterns determined by the vegetation. Table 4 shows that, as expected, the bareground category mimics scales set by the vegetation and, for the most part, is restricted to the characteristic scales at each site (Table 4).Each site has three characteristic scales that canbe observed in all or most of the10 m, 50-60 m, and 500-700 m. Oak Ridge shows scales at 15-26 m, 350-500 m,and 500-700 m. Hanford shows scales at 60-75 m,1000 m.‘Presence/absence.Conclusions giniana at 60 m (Correlation and Ratio analyses)and is also evident in the bareground data.The bareground data introduce no additionalscales but reflect most of the scales found in thethree taxa. There are five scales: 15-24-m (Correla-tion and Spectral analyses), 60-70-m (Spectral andRatio analyses), 180-200-m (Hill and Spectral ana-lyses), 410-m (Hill and Correlation analyses), and600-m that once again shows up as a trough in theHill analysis.Table 3 presents the spatial analyses for the A.spicatum landscape in Washington. The Correla-tion analysis indicates a scale at 60 m that probablycannot be differentiated from the 75-m peak in theSpectral analysis of cover. Similarly, the 125-mpeak in the Ratio analysis is probably the same asthe 105-m peak in the spectral analysis. The largestpattern, atB. gracilisB. eriopodaForbsBare GroundOak RidgeGrassesF. virginianaJ. virginianaBare GroundHanfordA. spicatumtions. Clearly, exploration must be followed by data collections specifically designed to test hypo-theses about individual scales. Unfortunately, our analyses do not immediately reveal the underlying processes that produced the vegetation patterns. Nevertheless, a close examina-tion of Table 4 and criteria from Hierarchy Theory encourage speculations about potential causes. According to Hierarchy Theory, we would expect large-scale patterns to result from constraints im-posed by higher levels in the system. Patterns could result, for example, from large-scalelogical processes patterns in soils. Scaled patterns have been demonstrated in soils (Burrough144study (Table 4) leads us to speculate that all of these processes may be involved in the complex patterns detected on the landscape.AcknowledgementsThe authors would like to thank A. Uhl and Y. McClellan for their assistance in computer analyses and M. Cunningham, L. Mann, L. Pounds, and V. Dale for their assistance in data collection. Re-search supported in part by the Ecological Research Division, Office of Health and Environmental Research, U.S. Department of Energy under con-tract No.to the Pacific Northwest Laboratory operated by Battelle Memorial Insti-tute, in part by the National Science Foundation under grants BSR 8114822 to Colorado State University and grants to New Mexico State Univer-sity and University of New Mexico. Contribution No. 9 to the Sevilleta LTER Program. Environ-mental Sciences Publicationconcepts to nested levels of soil variation. Journal of Soil Science。

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Unit 11.有什么东西吃吗？Is there anything to eat?有啊，我马上要做早餐了。

Y es, I’m making breakfast right now.2.有什么东西吃吗？Is there anything to eat?是的，我马上做一个蛋糕。

Y es, I’m making a cake right now.3.有什么东西吃吗？Is there anything to eat?是的，我马上做面条。

Y es, I’m making noodles ri ght now.4.有什么东西吃吗？Is there anything to eat?是的，我马上包饺子。

Y es, I’m making jiaozi right now.5.有什么东西吃吗？Is there anything to eat?是的，我马上做汤圆。

Y es, I’m making dumplings right now.6.有什么东西吃吗？Is there anything to eat?是的，我马上去买汉堡包。

Y es, I’m buying hamburgers right now. Unit 21.你昨天晚上做梦了吗？Did you dream last night?哦，是的，昨天晚上我做了个美梦。

Oh, yes, I had a good dream last night.2.你昨天晚上做梦了吗？Did you dream last night?哦，是的。

我昨晚做了一个甜蜜的梦。

Oh, yes. I had a sweet dream last night.3.你昨天晚上做梦了吗？Did you dream last night?哦，是的。

我昨晚做了一个可怕的梦。

Oh, yes. I had a terrible dream last night.4.你昨天晚上做梦了吗？Did you dream last night?哦，是的。

我昨晚做了一个有意思的梦。

Oh, yes. I had an interesting dream last night.5.你昨天晚上做梦了吗？Did you dream last night?哦，是的。

我昨晚做了一个恶梦。

Oh, yes. I had a nightmare last night.6.你昨天晚上做梦了吗？Did you dream last night?我昨晚梦见你了！你真坏！I dreamed of you last night！Y ou were really bad!Unit 31.你做了什么梦？What was your dream about?我梦见我成为学校里最优秀的学生。

I dreamed that I was the best student in the school.2.你做了什么梦？What was your dream about?我梦见我是一个国家的总统。

I dreamed that I was President of a country.3.你做了什么梦？What was your dream about?我梦见我是个四个孩子的父亲。

I dreamed that I was a father of four children.4.你做了什么梦？What was your dream about?我梦见我被我爸爸打了。

I dreamed that I was beaten by my father.5.你做了什么梦？What was your dream about?我梦见我被狗追着。

I dreamed that I was chased by dogs.6.你做了什么梦？What was your dream about?我梦见我在天上飞翔。

I dreamed that I was flying in the sky.Unit 41.约翰，你早。

你昨晚睡得好吗？Morning, John. Did you sleep well last night?我睡得像个婴儿一样。

I slept like a baby.2.约翰，你早。

你昨晚睡得好吗？Morning, John. Did you sleep well last night?我睡得像块大石头。

I slept like a rock.3.约翰，你早。

你昨晚睡得好吗？Morning, John. Did you sleep well last night?我睡得像木似的。

I slept like a log.4.约翰，你早。

你昨晚睡得好吗？Morning, John. Did you sleep well last night?我睡得像小羊羔。

I slept like a lamb.5.约翰，你早。

你昨晚睡得好吗？Morning, John. Did you sleep well last night?我昨晚没有睡好。

I didn’t sleep well last night.6.约翰，你早。

你昨晚睡得好吗？Morning, John. Did you sleep well last night?我昨晚没有睡好。

你在锯木头呢！I didn’t sleep well last night. Y ou were sawing logs! Unit 51.我们今天可以去公园吗？Can we go to the park today?不,我们明天去。

No, we’ll go tomorrow.2.我们今天可以去动物园吗？Can we go to the zoo today?不,我们明天去。

No, we’ll go tomorrow.3.我们今天可以去看电影吗？Can we go to the cinema today?不,我们明天去。

No, we’ll go tomorrow.4.我们今天可以去海边吗？Can we go to the beach today?不,我们明天去。

No, we’ll go tomorrow.5.我们今天可以去爬山吗？Can we go to the mountains today? 不,我们明天去。

No, we’ll go tomorrow.6.我们今天可以去森林公园吗？Can we go to the forest park today? 不,我们明天去。

No, we’ll go tomorrow.Unit 61.我穿这条新连衣裙看起来怎么样？How do I look in this new dress?你看上去真棒！真的！Y ou look great! Really!2.我穿这件新外套看起来怎么样？How do I look in this new coat?你看上去真棒！真的！Y ou look great! Really!3.我穿这件新西装看起来怎么样？How do I look in this new suit?你看上去真棒！真的！Y ou look great! Really!4.我穿这条新裙子看起来怎么样？How do I look in this new skirt?你看上去真棒！真的！Y ou look great! Really!5.我穿这件新衬衣看起来怎么样？How do I look in this new shirt?你看上去真棒！真的！Y ou look great! Really!6.我穿这件新T恤衫看起来怎么样？How do I look in this new T-shirt?你看上去真棒！真的！Y ou look great! Really!Unit 71.你住的房子大吗？Do you live in a big house?不大。

我的房子很小。

No, my house is small.2.你住的是新房子吗？Do you live in a new house?不是，我的房子是旧的。

No, my house is old.3.你住的是旧房子吗？Do you live in an old house?不是，我的房子是新的。

No, my house is new.4.你住的是一栋漂亮的房子吗？Do you live in a beautiful house?是的，我的房子很漂亮。

Y es, my house is very beautiful.5.你住的房子干净吗？Do you live in a clean house?不，我的房子很脏。

No, my house is dirty.6.你住的是这栋房子吗？Do you live in this house?你怎么知道的？How did you know?Unit 81.你知道怎么跳舞吗？Do you know how to dance?当然了。

我在学校学过了。

Sure. I have learned it at school.2.你知道怎么写字吗？Do you know how to write?当然了。

我在学校学过了。

Sure. I have learned it at school.3.你知道怎么打字吗？Do you know how to type?当然了。

我在学校学过了。

Sure. I have learned it at school.4.你知道怎么发伊妹儿吗？Do you know how to send E-mails? 当然了，我在学校学过了。

Y es, I have learned it at school.5.你知道怎么用这个吗？Do you know how to use this?当然了。

我在学校学过了。

Sure. I have learned it at school.6.你知道怎么唱这首歌吗？Do you know how to sing this song? 当然了。

我在学校学过了。

Sure. I have learned it at school.Unit 91.你想喝点什么吗？Do you want something to drink?是的，请给我可乐。

Y es, Coke, please.2.你想喝点什么吗？Do you want something to drink?是的，请给我雪碧。

Y es, Sprite, please.3.你想喝点什么吗？Do you want something to drink? 是的，请给我椰子汁儿。

Y es, cocoanut juice, please.4.你想喝点什么吗？Do you want something to drink? 是的，请给我茶。

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