北师大版三年级上册英语《review -word and picture》PPT课件

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北师大英语必修1unit 1Lesson 1(共42张PPT)

北师大英语必修1unit 1Lesson 1(共42张PPT)

3. Brian always takes his portable TV while going out for a walk every afternoon.
4. Brian has a good wife, and they live a happy life.
5. Bob normally wakes up about five minutes after his alarm clock goes off.
5. Bob normally wakes up about five minutes after his alarm clock goes off. F
6. Bob is very busy all day. T
7. Bob seldom has time for fun and other leisure activities with his family, but his family doesn’t complain. F
Careful Reading
1. Is Brian a lazy person ? Can you find two examples of his lazy behavior? Yes, he is. For example, he watches the children’s programs until about half-past ten. Then he gets up. He doesn’t work but his wife works and she makes his meals.
Words Preview
urgent personal document midnight
bored
adj.急迫的,紧急的 adj.私人的,个人的 n.公文,文件 n.午夜,半夜 adj.厌烦的,不感兴趣 的

Electron-Positron colliders

Electron-Positron colliders

a r X i v :h e p -e x /0111070v 1 22 N o v 2001ELECTRON-POSITRON-COLLIDERSR.-D.HEUERInstitut f¨u r Experimentalphysik,Universit¨a t Hamburg,Luruper Chaussee 149,22761Hamburg GermanyE-mail:rolf-dieter.heuer@desy.deAn electron-positron linear collider in the energy range between 500and 1000GeV is of crucial importance to precisely test the Standard Model and to explore the physics beyond it.The physics program is complementary to that of the Large Hadron Collider.Some of the main physics goals and the expected accuracies of the anticipated measurements at such a linear collider are discussed.A short review of the different collider designs presently under study is given including possible upgrade paths to the multi-TeV region.Finally a framework is presented within which the realisation of such a project could be achieved as a global international project.1IntroductionA coherent picture of matter and forces has emerged in the past decades through in-tensive theoretical and experimental studies.It is adequately described by the Standard Model of particle physics.In the last few years many aspects of the model have been stringently tested,some to the per-mille level,with e +e −,ep and p ¯p machines making com-plementary contributions,especially to the determination of the electroweak bining the results with neutrino scatter-ing data and low energy measurements,the experimental analysis is in excellent concor-dance with the electroweak part of the Stan-dard Model.Also the predictions of QCD have been thoroughly tested,examples being precise measurements of the strong coupling αs and probing the proton structure to the shortest possible distances.Despite these great successes there are many gaps in our understanding.The clearest one is the present lack of any direct evidence for the dynamics of electroweak symmetry breaking and the generation of the masses of gauge bosons and fermions.The Higgs mechanism which generates the masses of the fundamental particles in the Standard Model,has not been experimentally estab-lished though the indirect evidence from pre-cision measurements is very strong.Even ifsuccessfully completed,the Standard Model does not provide a comprehensive theory of matter.There is no explanation for the wide range of masses of the fermions,the grand unification between the two gauge theories,electroweak and QCD,is not realised and gravity is not incorporated at the quantum level.Several alternative scenarios have been de-veloped for the physics which may emerge beyond the Standard Model as energies are increased.The Supersymmetric extension of the Standard Model provides a stable bridge from the presently explored energy scales up to the grand unification scale.Alternatively,new strong interactions give rise to strong forces between W bosons at high energies.Quite general arguments suggest that such new phenomena must appear below a scale of approximately 3TeV.Extra space dimen-sions which alter the high energy behaviour in such a way that the energy scale of gravity is in the same order as the electroweak scale are another proposed alternative.There are two ways of exploring the new scales,through attaining the highest possible energy in a hadron collider and through high precision measurements at the energy fron-tier of lepton colliders.This article is based on the results ofmany workshops on physics and detector studies for linear colliders.Much more can be found in the respective publications1,2,3,4 and on the different Web sites5,6,7,8.Many people have contributed to these studies and the references to their work can be found in the documents quoted above.2Complementarity of Lepton and Hadron MachinesIt is easier to accelerate protons to very high energies than leptons,but the detailed colli-sion process cannot be well controlled or se-lected.Electron-positron colliders offer a well√defined initial state.The collision energying generation of colliders.The physics case for such a machine will depend on the results from the LHC and the linear collider in the sub-TeV range.3Selected Physics TopicsIn this chapter,some of the main physics top-ics to be studied at a linear collider will bediscussed.Emphasis is given to the study of the Higgs mechanism in the Standard Model,the measurements of properties of su-persymmetric particles,and precision tests of the electroweak theory.More details about these topics as well as information about the numerous topics not presented here can be found in the physics books published in the studies of the physicspotential offuture lin-ear colliders 1,2,3,4.3.1Standard Model Higgs BosonThe main task of a linear electron-positron collider will be to establish experimentally the Higgs mechanism as the mechanism for generating the masses of fundamental parti-cles:•The Higgs boson must be discovered.•The couplings of the Higgs boson to gauge bosons and to fermions must be proven to increase with their masses.•The Higgs potential which generates the non-zero field in the vacuum must be reconstructed by determining the Higgs self-coupling.•The quantum numbers (J P C =0++)must be confirmed.The main production mechanisms for Higgs bosons in e +e −collisions are Higgs-strahlung e +e −→HZ and WW-fusion e +e −→νe ¯νe H ,and the corresponding cross-sections as a function of M H are depicted in figure 2for three different centre of mass en-ergies.With an integrated luminosity of 500Figure 2.The Higgs-strahlung and WW fusion pro-duction cross-sections as a function of M H for differ-ent√sof about 800GeV;for 1000fb −1an accuracyof 6%can be expected.The Higgs boson quantum numbers can be determined through the rise of the cross sec-tion close to the production threshold and through the angular distributions of the H and Z bosons in the continuum.Recoil Mass [GeV ]N u m b e r o f E v e n t s / 1.5 G e VFigure 3.The µ+µ−recoil mass distribution in theprocess e +e −→HZ →µ+µ−for M H =120GeV,500fb −1at√2of the self potential of the Higgs field V =λ(φ2−14λH4.The trilinearHiggs coupling λHHH =6λv can be mea-sured directly in the double Higgs-strahlung process e +e −→HHZ →q ¯q b ¯bb ¯b .The fi-nal state contains six partons resulting in a rather complicated experimental signature with six jets,a challenging task calling for ex-cellent granularity of the tracking device and the calorimeter 9.Despite the low cross sec-tion of the order of 0.2fb for M H =120GeV at√s =500GeV with an integrated luminosity of 1ab −1as shown in figure 6.Measurements of Higgs boson properties and their anticipated accuracies are sum-marised in table 1.In summary,the Higgs mechanism can be established in an unambiguous way at a high luminosity electron-positron collider with a centre-of-mass energy up to around one TeV as the mechanism responsible for the sponta-neous symmetry breaking of the electroweak interactions.3.2Supersymmetric ParticlesSupersymmetry (SUSY)is considered the most attractive extension of the Standardg c /g c (SM)g b /g b (S M )0.80.850.90.9511.051.11.151.2Figure 5.Higgs coupling determination:The con-tours for g b vs.g c for a 120GeV Higgs boson normalised to their Standard Model expectations as measured with 500fb −1.Model,which cannot be the ultimate the-ory for many reasons.The most impor-tant feature of SUSY is that it can explain the hierarchy between the electroweak scale of ≈100GeV,responsible for the W and Z masses,and the Planck scale M P l ≃1019GeV.When embedded in a grand-unified the-ory,it makes a very precise prediction of the electroweak mixing angle sin 2θW in excellent concordance with the precision electroweak measurement.In the following,only the min-imal supersymmetric extension to the Stan-dard Model (MSSM)will be considered and measurements of the properties of the super-symmetric particles will be discussed.Stud-ies of the supersymmetric Higgs sector can be found elsewhere 1,2,3,4.In addition to the particles of the Stan-dard Model,the MSSM contains their su-persymmetric partners:sleptons ˜l ±,˜νl (l =e,µ,τ),squarks ˜q ,and gauginos ˜g ,˜χ±,˜χ0.In the MSSM the multiplicative quantum num-ber R-parity is conserved,R p =+1for par-10012014016018000.20.10.3M H [GeV ]SM Double Higgs-strahlung: e + e - → ZHH σ [fb ]√s = 800 GeV√s = 500 GeVFigure 6.The cross-section for doubleHiggs-strahlung in the Standard Model at√120GeVmass 0.05%spin yes CPyes6%g HZZ 1%g HW W 2%g Hbb 2%g Hcc 10%g Hττ5%g Htt 6%λHHH∼30%ticles and R p =−1for sparticles.Spar-ticles are therefore produced in pairs and they eventually decay into the lightest spar-ticle which has to be stable.As an example,smuons are produced and decay through theprocess e +e −→˜µ+˜µ−→µ+µ−χ01χ01with χ01as the lightest sparticle being stable and,therefore,escaping detection.The mass scale of sparticles is only vaguely known.In most scenarios some spar-ticles,in particular charginos and neutrali-nos,are expected to lie in the energy region accessible by the next generation of e +e −200400600800Figure 7.Examples of mass spectra in mSUGRA,GMSB and AMSB models.colliders alsosupported bythe recentmea-surement of (g −2)µ10.Examples of massspectra for three SUSY breaking mechanisms (mSUGRA,GMSB,AMSB)are given in fig-ure 7.The most fundamental problem of super-symmetric theories is how SUSY is broken and in which way this breaking is communi-cated to the particles.Several scenarios have been proposed in which the mass spectra are generally quite different as illustrated in fig-ure 7.High precision measurements of the particle properties are therefore expected to distinguish between some of these scenarios.The study and exploration of Supersymmetry will proceed in the following steps:•Reconstruction of the kinematically ac-cessible spectrum of sparticles and the measurement of their properties,masses and quantum numbers•Extraction of the basic low-energy pa-rameters such as mass parameters,cou-plings,and mixings•Analysis of the breaking mechanism and reconstruction of the underlying theory.While it is unlikely that the complete spectrum of sparticles will be accessible at acollider with√Figure 9.Cross section near threshold for the processe +e −→˜χ+1˜χ−1,10fb−1per point.approach,the measured electroweak scaleSUSY parameters are extrapolated to high energies using these RGE’s.Due to the high precision of the measured input variables,only possible at the linear collider,an accurate test can be performed at which energy scale certain parameters be-come equal.Most interesting,the assump-tion of grand unification of forces requires the gaugino mass parameters M 1,M 2,M 3to meet at the GUT scale (figure 10(left)).Different SUSY breaking mechanisms predict different unification patterns of the sfermion mass parameters at high energy.With the high accuracy of the linear collider measure-ments these models can be distinguished as shown in figure 10for the case of mSUGRA (middle)and GMSB (right).In summary,the high precision studies of supersymmetric particles and their properties can open a window to energy scales far above the scales reachable with future accelerators,possibly towards the Planck scale where grav-ity becomes important.3.3Precision MeasurementsThe primary goal of precision measurements of gauge boson properties is to establish the non-abelian nature of electroweak interac-tions.The gauge symmetries of the Stan-dard Model determine the form and the strength of the self-interactions of the elec-troweak bosons,the triple couplings W W γand W W Z and the quartic couplings.Devi-ations from the Standard Model expectations for these couplings could be expected in sev-eral scenarios,for example in models where there exists no light Higgs boson and where the W and Z bosons are generated dynam-ically and interact strongly at high scales.Also for the extrapolation of couplings to high scales to test theories of grand unifi-cation such high precision measurements are mandatory.For the study of the couplings between gauge bosons the best precision is reached at the highest possible centre of mass energies.These couplings are especially sen-sitive to models of strong electroweak sym-metry breaking.W bosons are produced either in pairs,e +e −→W +W −or singly,e +e −→W eνwith both processes being sensitive to the triple gauge couplings.In general the total errors estimated on the anomalous couplings are in the range of few ×10−4.Figure 11com-pares the precision obtainable for ∆κγand ∆λγat different machines.The measurements at a linear collider are sensitive to strong symmetry breaking be-yond Λof the order of 5TeV,to be com-pared with the electroweak symmetry break-ing scale ΛEW SB =4πv ≈3TeV.One of the most sensitive quantities to loop corrections from the Higgs boson is the effective weak mixing angle in Z boson de-cays.By operating the collider at ener-gies close to the Z -pole with high luminos-ity (GigaZ)to collect at least 109Z bosons in particular the accuracy of the measure-Figure 10.Extrapolation of SUSY parameters measured at the electroweak scale to high energies.10-410-310-2∆κγLEP TEV LHCTESLA TESLA 50080010-410-310-2∆λγLEP TEV LHCTESLA TESLA500800Figure parison of constraints on the anomalous couplings ∆κγand ∆λγat different machinesment of sin 2θleff can be improved by one or-der of magnitude wrt.the precision obtained today 11.With both electron and positronbeams longitudinally polarised,sin 2θleff can be determined most accurately by measur-ing the left-right asymmetry A LR =A e =2v e a e /(v 2e +a 2e )with v e (a e )being the vec-tor (axialvector)couplings of the Z boson tothe electron and v e /a e =1-4sin 2θleff for pure Z exchange.Particularly demanding is the precision of 2×10−4with which the po-larisation needs to be known to match the statistical accuracy.An error in the weakmixing angle of ∆sin 2θleff =0.000013can be expected.Together with an improved de-termination of the mass of the W boson toa precision of some 6MeV through a scan of the W W production threshold and with the measurements obtained at high energy run-ning of the collider this will allow many high precision tests of the Standard Model at the loop level.As an example,figure 12shows the variation of the fit χ2to the electroweak measurements as a function of M H for the present data and for the data expected at a linear collider.The mass of the Higgs bo-son can indirectly be constraint at a level of 5%.Comparing this prediction with the di-rect measurement of M H consistency tests of the Standard Model can be performed at the quantum level or to measure free parameters in extensions of the Standard Model.This is5101520101032000LCm hχ2Figure 12.∆χ2as a function of the Higgs boson mass for the electroweak precision data today (2000)and after GigaZ running (LC).of particular importance if M H >200GeV in contradiction to the current electroweak mea-surements.In summary,there is strong evidence for new phenomena at the TeV energy scale.Only the precision exploration at the linear collider will allow,together with the results obtained at the Large Hadron Collider,the understanding of the underlying physics and will open a new window beyond the centre-of-mass energies reachable.Whatever sce-nario is realized in nature,the linear collider will add crucial information beyond the LHC.There is global consensus in the high energy physics community that the next accelera-tor based project needs to be an electron-positron linear collider with a centre-of-mass energy of at least 500GeV.4Electron-Positron Linear CollidersThe feasibility of a linear collider has been successfully demonstrated by the operationof the SLAC Linear Collider,SLC.How-ever,aiming at centre-of-mass energies at the TeV scale with luminosities of the order of 1034cm −2s −1requires at least two orders of magnitude higher beam power and two orders of magnitude smaller beam sizes at the inter-action point.Over the past decade,several groups worldwide have been pursuing differ-ent linear collider designs for the centre-of-mass energy range up to around one TeV as well as for the multi-TeV range.Excel-lent progress has been achieved at various test facilities worldwide in international col-laborations on crucial aspects of the collider designs.At the Accelerator Test Facility at KEK 12,emittances within a factor two of the damping ring design have been achieved.At the Final Focus Test Beam at SLAC 13de-magnification of the beams has been proven;the measured spot sizes are well in agreement with the theoretically expected values.The commissioning and operation of the TESLA Test Facility at DESY 14has demonstrated the feasibility of the TESLA technology.In the following,a short review of the different approaches is given.4.1TeV rangeThree design studies are presently pursued:JLC 15,NLC 16and TESLA 17,centred around KEK,SLAC and DESY,respectively.Details about the design,the status of de-velopment and the individual test facilities can be found in the above quoted references as well as in the status reports presented at LCWS200018,19,20.A comprehensive sum-mary of the present status can be found in the Snowmass Accelerator R&D Report 21,here only a short discussion of the main features and differences of the three approaches will be given with emphasis on luminosity and en-ergy reach.One key parameter for performing the physics program at a collider is the centre-of-mass energy achievable.The energy reachof a collider with a given linac length and a certain cavityfilling factor is determined by the gradient achievable with the cavity tech-nology chosen.For normalconducting cavi-ties the maximum achievable gradient scales roughly proportional to the RF frequency used,for superconducting Niobium cavities, the fundamental limit today is around55 MV/m.The second key parameter for the physicsprogram is the luminosity L,given byL=n b N2e f rep(σ∗x+σ∗y)2.Choos-ing aflat beam size(σ∗x≫σ∗y)at the inter-action point,δE becomes independent of the vertical beam size and the luminosity can be increased by reducingσ∗y as much as possi-ble.Sinceσ∗y∝sn b N e f rep=ηP AC is obtained from themains power P AC with an efficiency η.Equation(1)can then be rewritten asL∝ηP AC s ǫy(2)High luminosity therefore requires high ef-ficiencyηand high beam quality with low emittanceǫy and low emittance dilution ∆ǫ/ǫ∝f6RF,which is largely determined by the RF frequency f RF of the chosen technol-ogy.The fundamental difference between the three designs is the choice of technology for the accelerating structures.The design of NLC is based on normalconducting cavities using f RF of11.4GHz(X-band),for JLC two options,X-band or C-band(5.7GHz)are pursued.The TESLA concept,developed by the TESLA collaboration,is using supercon-ducting cavities(1.3GHz).As an example for a linear collider facility,figure13shows the schematic layout of TESLA.Figure13.Schematic layout of TESLATable2compares some key parameters for the different technologies at√Figure 14.Evolution of superconducting cavity per-formance.The average gradient achieved with TESLA 9-cell cavities produced in industry (first test,no additional processing)is shown as dots.with N b bunches,the time ∆T b between bunches within a train which allows head on crossing of the bunches for TESLA but requires a crossing angle for the other de-signs.The design luminosity L ,beam power P beam and the required mains power P AC il-lustrate that for a given mains power the su-perconducting technology delivers higher lu-minosity.On the other hand the lower gradi-ent G acc requires a longer linac for the samecentre-of-massenergy reach.As can be seen from table 2the X-band machines call for a beam loaded (unloaded)gradient of some 50(70)MV/m for√s =500GeV,a gradient which is mean-while routinely achieved for cavities fabri-cated in industry as illustrated in figure 14.Table 2also contains the presently planned length of the facilities 17,16,22,23.AnFigure 15.Excitation curves of three electropolished single-cell cavities.Gradients well above 35MV/m are reached.upgrade in energy up to around one TeV seems possible for all designs.In the NLC case,more cavities would be installed within the existing tunnel,in the JLC case,the tunnel length would have to be increased to house more cavities.In the TESLA case,a gradient of around 35MV/m is neededto reach√Table parison of some crucial parameters at 500GeV for the different technologies under study,see text for details.NLCJLC-C51502820190337 1.4head on angle 20.7σ∗x/y [nm ]245/2.7318/4.3δE [%]4.73.93.42.64P beam [MW ]13.212.6P AC (linacs )[MW ]13222023.550.23316s of 3TeV,usinghigh frequency (30GHz)normalcon-ducting structures operating at very high ac-celerating fields (150MV/m).The present design calls for bunch separations of .67ns,a vertical spotsize of 1nm and beamstrahlung δE of 30%.For this promising concept a new test facility is under construction at CERN which should allow tests with full gradient starting in 2005.5RealisationThe new generation of high energy colliders most likely exceeds the resources of a coun-try or even a region.There is general consen-sus that the realisation has to be done in an international,interregional framework.One such framework,the so called Global Accel-erator Network (GAN),has been proposed to ICFA in March 2000.A short discussion of the principle considerations will be presented here,more details can be found in ref.25.The GAN is a global collaboration of lab-oratories and institutes in order to design,construct,commission,operate and main-tain a large accelerator facility.The model is based on the experience of large experi-mental collaborations,particularly in particle physics.Some key elements are listed below:•it is not an international permanent in-stitution,but an international project of limited duration;•the facility would be the common prop-erty of the participating countries;•there are well defined roles and obliga-tions of all partners;•partners contribute through components or subsystems;•design,construction and testing of com-ponents is done in participating institu-tions;•maintenance and running of the accel-erator would be done to a large extent from the participating institutions.The GAN would make best use of world-wide competence,ideas and resources,create a visible presence of activities in all partici-pating countries and would,hopefully,make the site selection less controversial.study general considerations of implementing a GAN and to study the technical considera-tions and influence on the design and cost of the accelerator.The reports of these working groups can be found on the web26.Their overall conclusion is that a GAN can be a fea-sible way to build and operate a new global accelerator,although many details still need to be clarified.6SummaryThere is global consensus about the next ac-celerator based project in particle physics.It has to be an electron-positron linear collider with an initial energy reach of some500GeV with the potential of an upgrade in centre-of-mass energy.The physics case is excellent, only a few highlights could be presented here. There is also global consensus that concur-rent operation with LHC is needed and fruit-ful.Therefore,a timely realisation is manda-tory.The technical realisation of a linear col-lider is now feasible,several technologies are either ripe or will be ripe soon.A fast consen-sus in the community about the technology is as a global project with the highest possible luminosity and a clear upgrade potential be-yond500GeV.AcknowledgmentsThe author would like to express his grati-tude to all people who have contributed to the studies of future electron-positron linear colliders from the machine design to physics and detector studies.Special thanks go to the organisers and their team for a very well or-ganised,inspiring conference as well as for the competent technical help in preparing this presentation.References1.J.A.Aguilar-Saavedra et al,TESLATechnical Design Report,Part III,Physics at an e+e−Linear Collider,DESY2001-011,ECFA2001-209,hep-ph/0106315.2.T.Abe et al,Linear Collider Physics Re-source Book for Snowmass2001,BNL-52627,CLNS01/1729,FERMILAB-Pub-01/058-E,LBNL-47813,SLAC-R-570,UCRL-ID-143810-DR,LC-REV-2001-074-US,hep-ex/0106055-583.K.Abe et al,Particle Physics Exper-iments at JLC,KEK-Report2001-11, hep-ph/0109166.4.Proceedings of LCWS,Physics and Ex-periments with Future Linear Colliders, eds A.Para,H.E.Fisk,(AIP Conf.Proc.,Vol578,2001).5.Worldwide Study of the Physics and De-tectors for Future e+e−Colliders/lc/6.ACFA Joint Linear Collider Physics andDetector Working Grouphttp://acfahep.kek.jp/7.2nd Joint ECFA/DESY Studyon Physics and Detectors for a Linear Electron-Positron Colliderhttp://www.desy.de/conferences/ecfa-desy-lc98.html8.A Study of the Physics and Detectors forFuture Linear e+e−Colliders:American Activities/lc/ameri-ca.html9.G.Alexander et al,TESLA TechnicalDesign Report,Part IV,A Detector for TESLA,DESY2001-011,ECFA2001-209.10.H.N.Brown et al.[Muon g-2Collabo-ration],Phys.Rev.Lett.86(2001)222711.J.Drees,these proceedings12.E.Hinode et al,eds.,KEK Internal95-4,1995,eds J.Urakawa and M.Yoshioka, Proceedings of the SLAC/KEK Linear Collider Workshop on Damping Ring, KEK92-6,199213.The FFTB Collaboration:BINP(Novosibirsk/Protvino),DESY, FNAL,KEK,LAL(Orsay),MPI Mu-nich,Rochester,and SLAC14.Proposal for a TESLA Test Facility,DESY TESLA-93-01,199215.KEK-Report97-1,1997.16.Zeroth Order Design Report for theNext Linear Collider,SLAC Report474,1996.2001Report on the Next Linear Collider,Fermilab-Conf-01-075-E,LBNL-47935,SLAC-R-571,UCRL-ID-14407717.J.Andruszkow et al,TESLA TechnicalDesign Report,Part II,The Accelerator, DESY2001-011,ECFA2001-20918.O.Napoly,TESLA Linear Collider:Sta-tus Report,in ref419.T.O.Raubenheimer,Progress in theNext Linear Collider Design,in ref4 20.Y.H.Chin et al Status of JLC Accelera-tor Development,in ref421.A.Chao et al,2001Snowmass Accelera-tor R&D Report,http://www.hep.anl.gov/pvs/dpb/Snowmass.pdf22.Y.H.Chin,private communication23.H.Matsumoto,T.Shintake,private com-munication24.I.Wilson,A Multi-TeV Compact e+e−Linear Collider,in ref425.F.Richard et al,TESLA Technical De-sign Report,Part I,Executive Summary, DESY2001-011,ECFA2001-209,hep-ph/0106314.26./directorate/icfa/icfa reports.html。

冀教版小学英语三年级上册教案5篇

冀教版小学英语三年级上册教案5篇

冀教版小学英语三年级上册教案5篇冀教版小学英语三年级上册教案1教学目的:1复习巩固功能句型:Whose (pencil) is this/ that? It’s (Ken’s). Whose (books) are these/ those? They’re (Mocky’s). 2学习新单词。

教学重点:正确认读新单词,熟练听说。

教学难点: 1熟记单词,灵活反应。

2A cassette的发音。

分层要求: A类学生能够认读所学新单词。

B类学生能够听说所学新单词。

C类学生能够说所学新单词。

环境设计:教师准备:录音机,教学卡片学生准备:学生卡片桌椅摆放形式:两人一桌教学过程一、Review:1Greetings 2.收集教师、学生使用的物品,师生、生生问答。

Whose (pen) is this/ that? It’s (Ken’s). Whose (books) are these/ those? They’re (Mocky’s). 3提示:This 和these——较近 That和 those——较远在情境中让学生发现,总结规律。

二、Practice:1出示教学卡片,复习问:What’s this? 引导生回答:It’s a (robot). 2出示toys卡片,问:What are these? 引导生回答:They are toys. 1 投影“电视”,举起Television 的教学卡片: This is a television. 2学习其他单词。

三、Words to learn.1打开书P28上面的图,放录音,指相应的图。

2再放录音,生跟读(逐词停顿) 3再放录音,不停顿,生跟着重复 4师指图,引导生大声读出物品的名称。

同样的方法完成其余的图片。

5I can try.生自由举手中卡片,读单词。

6师生共同抽卡读词。

四、Listen to this1打开书P28下端。

2逐图问答:What’s this? It’s a (bike). 3放录音,师问,生答。

Unit 16 Stories—Lesson 3《Life Stories》教案(北师大选修6)

Unit 16 Stories—Lesson 3《Life Stories》教案(北师大选修6)

教学设计Unit 16 Lesson 3 Life Stories教材分析本课是16单元的第3课,以“人生故事”为主题,主课文讲述的是美国著名盲人女作家Helen Keller 童年学习语言的真实故事。

本课的难点在于文章较长、生词较多且抽象、情节脉络较复杂。

本课的教学设计分为三课时。

第一课时侧重对课文的整体理解及情感体验,引导学生清晰地整理出文章结构和事件发展脉络,提取文章细节信息并进行初步的输出活动。

第二课时在对已学课文进行复习的基础上,学生继续完成对细节信息的提取,并能够重组信息和尝试运用重点词汇进行表达,最后总结和提升所学内容。

第三课时的主要任务是(1)词汇的巩固、扩展及在新语境中的使用;(2)对情态动词过去时形式和意义的体验和理解。

教学内容话题:著名美国女作家Helen Keller童年学习语言的故事(阅读)词汇:重点词汇:severe, restriction, unbearable, stubborn, troublesome, straightforward, precise, precious, eager, gradual, complex, warmth, apparent, uncertain, breakthrough相关词汇:sweetness, now that, expand策略:通过图片、标题、开头等预测文章内容,略读等语法(体验):情态动词过去时的功能和形式第一课时First Period教学目标:在本课学习结束时,学生能够:1.理清课文故事的大体情节和发展脉络;2.说出Helen Keller学习语言过程中的1-2个事例;3.感悟并描述课文中人物的情感、态度。

*表示可灵活处理的活动。

第二课时Second Period 教学目标在本课学习结束时,学生能够:1.运用所学单词和短语描述Helen的学习语言的过程;2.讨论Helen和/或Anne成功的原因;*表示可灵活处理的活动。

new media & society

new media & society

New Media & SocietyDOI: 10.1177/14614448050491452005; 7; 64 New Media Society Joo-Young Jung, Yong-Chan Kim, Wan-Ying Lin and Pauline Hope Cheong adolescents in Seoul, Singapore and Taipei The influence of social environment on internet connectedness of /cgi/content/abstract/7/1/64The online version of this article can be found at: Published by:can be found at:New Media & Society Additional services and information for/cgi/alerts Email Alerts:/subscriptions Subscriptions:/journalsReprints.nav Reprints:/journalsPermissions.nav Permissions:/cgi/content/refs/7/1/64SAGE Journals Online and HighWire Press platforms): (this article cites 39 articles hosted on the CitationsARTICLEThe influence of socialenvironment on internetconnectedness ofadolescents in Seoul,Singapore and Taipei............................................................................................................................................................................................................................................JOO-YOUNG JUNGUniversity of T okyo, Japan............................................................................................................................................................................................................................................YONG-CHAN KIMUniversity of Alabama, USA............................................................................................................................................................................................................................................WAN-YING LINUniversity of Southern California, USA............................................................................................................................................................................................................................................PAULINE HOPE CHEONG State University of New York, USA............................................................................................................................................................................................................................................AbstractThis article examines the influence of the socialenvironment on adolescents’ connectedness to the internet inEast Asia, one of the most wired regions in the world.Connectedness is a qualitative conceptualization of anindividual’s relationship with the internet, taking intoconsideration the breadth, depth, and the importance ofindividuals’ internet experience. This study seeks to situateadolescents’ internet connectedness in three spheres ofsocial environment: (1) the general social support measuredby how easy it is to get help when adolescents encounterproblems in using the internet; (2) the parents, where weexamine parents’ socioeconomic status and their internetuse; and (3) the peer group, where we look into thenew media & societyCopyright © 2005 SAGE PublicationsLondon, Thousand Oaks, CA and New DelhiVol7(1):64–88 [DOI: 10.1177/1461444805049145]........................................................................................................................................................................................................................................................64Jung et al.: Social environment and internet connectednessproportion of friends who connect to the internet. Theresults from a survey of 1303 adolescents in Seoul,Singapore and Taipei support our major hypothesis thatamong the internet-using adolescents, their internetconnectedness patterns differ by the nature of their socialenvironments.Key wordsadolescents • digital divide • East Asia • internetconnectedness • internet use • parents • peers • socialenvironmentINTRODUCTIONThe internet population has grown rapidly in the last decade. As more and more people gain access to the internet, researchers have started to reposition the access issue as it goes beyond a ‘yes/no’ question to what kinds of relationships people build with the internet. Several studies (Jung, 2003; Jung et al., 2001) have developed a concept of internet Connectedness Index (ICI) where ‘connectedness’ is defined as the multidimensional relationship between an individual and the internet. With regards to the concept of internet connectedness, significant variations were found among people of different income, education, gender, ethnicity and age (Jung et al., 2001; Kim et al., 2002b; Loges and Jung, 2001). In this conceptualization, the digital divide is not simply reduced to the rates of internet access achieved, but endures ‘beyond access’ to the quality of people’s connections to the internet (Bonfadelli, 2002; DiMaggio et al., 2001; Gibbs et al., 2004; Hargittai, 2002; Jung et al., 2001; Lievrouw, 2000; Morino Institute, 2001; Newhagen and Bucy, 2001; Patterson and Wilson III, 2000; V an Dijk, 1997).The digital divide has been a prolific research topic in the US since the mid-1990s, but the focus has mostly been on what is happening in this country. Not many studies have introduced internet use patterns in other nations beyond the comparison of access rates between different nations. Considering that the internet has the potential to connect different parts of the world, and that its use is simultaneously increasing in different nations, only studying the digital divide in the US is not sufficient to obtain a picture of how the internet is being incorporated into diverse people’s everyday lives. This study examines the internet connectedness in the context of East Asia. In particular, three cities are chosen – Seoul, Singapore and Taipei – for reasons detailed below.1South Korea, Singapore and Taiwan have been characterized by their high rates of internet access. South Korea has about 30 million internet users, or about 70 percent of the total population (NDA, 2004). Moreover, 7865New Media & Society 7(1)percent of South Korean households have broadband connection (Shameen, 2004). Taiwan has 12.74 million internet users, accounting for 62 percent of the total population. Singapore has a household internet penetration rate of 61 percent, and 40 percent of the Singaporean households subscribe to broadband services (Infocomm Development Authority, 2004; TNIC, 2004). In particular, the authors examine the internet connectedness of adolescents in Seoul, Singapore and Taipei based on surveys conducted in the three respective cities. The adolescents are chosen because they belong to a wired generation eager to connect to the internet in a region where internet penetration rates are very high, and the issue of a digital divide based on quality connections is more salient than that of mere access. Among different age groups, adolescents represent the most rapidly growing internet population (Internet Matrix, 2000; NUA, 2001; US Department of Commerce, 2002), and the internet plays a prominent role in the lives of youths today in many parts of the world.2For example, in 2002, 38 percent of internet users in Taiwan were 15 to 24 years of age, followed by those aged 25–34 (28%) and 35–49 (25%) (Hsu, 2002). More prominently, a recent survey of the Korea Institute for Y outh Development reports that about 93 percent of Korean adolescents use the internet (Hwang et al., 2002), and about 35 percent of the total internet population in Korea is in the age group of 7 to 19 (Internet Matrix, 2002).Given the high internet penetration rates among adolescents in the respected study cities (Seoul, Singapore, Taipei), the most prominent question becomes how the adolescents are using the internet. W e believe that among the internet-using adolescents, disparities are likely to exist in terms of their ability to utilize various resources on the internet. Among the factors that are likely to affect adolescents’ internet connectedness, we attempt to examine the influence of adolescents’ social environment on the quality of their connectedness to the internet. Particularly, we examine the influence of social support that the adolescents have by asking how easy it is to get help from people around them when having problems in using computers and the internet. In addition to the general social support, we consider the influence of two key players in their social environments, parents and peer group, on their internet connectedness. These are measured by parents’ socio-economic status, parents’ internet uses, and proportions of friends who use the internet. W e hypothesize that these three aspects of social environment, internet-related help, parents, and peer group, would shape the levels and patterns of adolescents’ internet connectedness.East Asian adolescents and the internetAdolescents’ internet use patterns in the US and Europe have been examined more extensively (e.g., Cheskin Research, 1999; d’Haenens, 2001; Holloway and V alentine, 2003; Johnsson-Smaragdi et al., 1998; Lenhart et66Jung et al.: Social environment and internet connectedness al., 2001; Livingstone, 1998, 2003; Livingstone and Bovill, 2001; NPR [National Public Radio], 2000; Roper ASW, 1999; Suss, 2001) than in East Asian countries. Among the few studies, Singapore Internet Project reported that the majority of the 13-year-olds surveyed went online for everyday life information such as sports, entertainment, science and technology, and hobbies (Howard et al., 2001). A survey in Taiwan showed that teens turned to the internet mostly for games, information searching, entertainment news, and chatting (Liang et al., 2001). In addition, more than half of the 1861 Taiwanese teens surveyed believed that the internet was able to improve interpersonal relationships as well as school performance. Chen (2000) examined whether and how digital divide might exist among middle school students in Taiwan. The results showed that household income and urbanization level had significant influence on internet access and etiquette. The Korean Network and Information Center survey reported that the main activities Korean adolescents do online included seeking entertainment-related information, games, and email (Internet Matrix, 2002).Current research on adolescents’ connections to the internet, however, is limited in several ways. First, most studies stay on a descriptive level in examining the issue, mainly by reporting percentages or levels of access and use. Second, most studies isolate the internet from other activities that adolescents do in their everyday lives. Studies mainly focus on what adolescents do on the internet, but do not consider how these relate to other aspects of their lives, such as their relationships with family, school, and friends. Third, studies on East Asian adolescents’ internet use tend to limit their focus to specific facets, particularly the internet as a tool of entertainment for adolescents. For example, several studies have examined the ways in which adolescents engage in computer and internet games (e.g., Kang, 2001; Lee, 2002), and other studies have described adolescents’addictions to the internet (Kim, 2001; Kim et al., 2000; Lee, 2002).Social environment and adolescents’ internetconnectednessT o understand the nature of differences in adolescents’ internet connectedness, the authors propose that the social environment should be considered. Researchers have been eager to explore the factors that contribute to the quality of individual’s internet connection. Many studies focused on demographic characteristics, such as income, education, gender, age, and ethnicity. Studies on the adoption and use of new communication technologies found that factors related to social networks, such as influences from family or friends, were as important as individual characteristics (Fischer, 1992; Fulk et al., 1990; Marvin, 1988; Rogers, 1983; Schmitz and Fulk, 1991; Williams et al., 1986; Williams et al., 1994).67New Media & Society 7(1)Scholars conceptualized the value of the social environment in people’s lives as ‘social capital,’ a resource embedded in our social ties that can be transformed to other types of resources such as human capital or economic capital (Bourdieu, 1986; Burt, 1992; Coleman, 1988; Loury, 1997; Putnam, 1995, 2000). According to Bourdieu (1986), social capital is a resource or profit to which individuals have access as a result of their membership or participation in groups such as families, parties, or associations. Burt (1992) explained that these resources do not flow equally in each set of human relations and therefore individuals in a position to capitalize on opportunities are those who have access to personal contacts that can provide valuable information, knowledge, or expertise. Coleman (1988) argued that social capital, especially that of children, affects the level of their cognitive developments that are key to gaining human capital in various educational settings.More recently, the communication infrastructure perspective (Gibbs, 2004) directly addressed the importance of social environment in people’s internet connectedness. A communication infrastructure includes a network of communicators, including individuals, media, large and small social institutes, and also social and physical environments that either facilitate or constrain communications in the network. From this perspective, the internet, a relatively new medium, is conceptualized as entering the existing communication infrastructure, and the ways in which the internet builds relationships with individuals are influenced by the existing communication patterns in the social context. Researchers taking this communication infrastructure approach stayed away from focusing solely on the features of new media technologies or individuals’ needs for using them, but emphasized relational aspects between individuals, media and social contexts that characterize types and levels of the relationships (Ball-Rokeach et al., 2000; Jung, 2003; Kim et al., 2002b).Unlike earlier internet studies that pictured the internet as a medium that isolates people from their social environment, quite a number of recent studies emphasized the central role of the internet as a facilitator of social relationships (Baym et al., 2001; Castells, 2002; Flanagin and Metzger, 2001; Lee and Chan, 2001; Lee and Kuo, 2002; Livingstone and Lievrouw, 2002; W ellman et al., 2001; W ellman and Haythornthwaite, 2003). These studies examined the internet in relation to people’s other social activities, and found that the internet played a positive role in maintaining and extending the existing social relationships. For example, Lee and Chan (2001) found that the internet facilitated Singaporean adolescents’ communication with friends, and the majority of them arranged face-to-face social gatherings via email.A fewer number of studies examined the influence of social environments on people’s internet use (Fong et al., 2001; Matei and Ball-Rokeach, 2001; 68Jung et al.: Social environment and internet connectedness Wilhelm, 2000). Matei and Ball-Rokeach (2001) found that those who had a larger social network in offline interpersonal relations tended to make more friends online. Wilhelm argued from what he called a ‘quasi-sociological perspective’ that the ways in which one’s family members, friends, neighbors or other social contacts perceived the value of the internet and the computer affected the person’s adoption and use of the internet (2000: 65). Fong and his colleagues examined the effect of three different social characteristics – individual, household and neighborhood –on people’s internet use in Canada and in the US (Fong et al., 2001). They found that in addition to individual’s socioeconomic status, household characteristics (e.g., household size and the presence of children), and the neighborhood characteristics (e.g., the proportion of immigrants and rural-urban-suburban locations) were important factors affecting people’s internet access. Jung (2003) found that social and technological environments surrounding individuals had significant influence on individuals’ internet connectedness.Measuring the digital divideAnother important research focus of this study is to conceptualize and measure the disparities in how people connect to the internet, widely referred to as ‘digital divide’ research. Research on the digital divide follows a tradition of studies on social and individual adoption of new communication technology (Douglas, 1987; Fischer, 1992; Marvin, 1988; Rogers, 1983; Rogers and Shoemaker, 1971), social inequality and levels of access to communication media (Dervin, 1980; Donohue et al., 1987; Gaziano and Gaziano, 1999; Tichenor et al., 1970), universal service (Anderson et al., 1995; Lievrouw, 2000; Thomas, 1995), and early personal computer diffusion (Dutton et al., 1987; Dutton et al., 1989).The most common way of conceptualizing digital divide has been to divide people into ‘haves’ and ‘have-nots.’ That is, the digital divide between those who own a computer and those who do not, or the divide between those who have internet access and those who do not. Although this kind of categorization is useful in the early stage of technological diffusion, such dichotomous comparisons are not sufficient when discussing the social consequences of technology as it matures in various sectors in society (Jung et al., 2001).A set of recent research on the digital divide attempted to go beyond access to examine various aspects involved in people’s connections to the internet. In addition to the common way of measuring the intensity of internet use by asking the amount of time spent online (Kraut et al., 1998; Nie and Erbring, 2000; Robinson et al., 2000),3several studies used multivariate measures to capture a more in-depth picture of people’s internet connections (Anderson et al., 1995; Bikson and Panis, 1999; Bonfadelli,69New Media & Society 7(1)2002; Hargittai, 2002; Hindman, 2000; Howard et al., 2001; Jung et al., 2001; Shah et al., 2001a; W ellman et al., 2001; Wilhelm, 2000). Wilhelm (2000) categorized information and telecommunications ‘have-nots’ into three categories: those immune to progress, those with peripheral access and peripheral users – and argued that the groups are distinguished by the different abilities to participate in social and economic life of the larger community. W ellman and his colleagues (W ellman et al., 2001) measured people’s online communication in terms of their participation in organizations and political discussion on the internet. The authors argued that people in a disadvantaged community are situated in a ‘double digital divide’, where the lack of technical access is worsened by the lack of social support in acquiring skills and knowledge about utilizing the internet(W ellman et al., 2001). Hargittai (2002) pointed out study shortcomings that only viewed the binary disparity between those who use the internet and those who do not, and examined disparities in people’s online skills, or what she called the ‘second-level digital divide.’ By assigning search tasks to a random sample of internet users, she found a considerable difference in whether people could find various types of content on the internet and how long it took them to find it.In an attempt to systematically incorporate multiple aspects of people’s internet connectedness, Jung et al. (2001) developed a multidimensional index called the Internet Connectedness Index (ICI). ICI is composed of three dimensions for measuring the quality of people’s internet connectedness: 1) history and context of internet connectedness, mostly concerning the economic disparity; 2) scope and intensity of internet connectedness, concerning the depth and breadth of people’s internet use in terms of their goals for going online and the activities people engage in on the internet; and 3) the centrality of people’s internet connectedness, with a focus on the subjective perception of the importance of the internet in people’s lives.The ICI was developed and applied in several studies (Jung et al., 2001; Kim et al., 2002a; Kim et al., 2002b; Loges and Jung, 2001) based on the assumption that the digital divide is not a single-faceted gap, but a multi-faceted divide reflected in different aspects of people’s relationship with the internet. Jung et al. (2001) found that people’s scores of ICI had a linear positive relationship with their income and education. Kim et al. (2002b) found that an individual’s ethnicity and residential location had interaction effects on ICI after controlling for individuals’ socio-economic status. Loges and Jung (2001) examined the relationship between ICI and age and found that younger people had longer experience with the internet with better technological equipment, and they had a broader and more intense scope of goals and activities for going online than the elders. On the other hand,70Jung et al.: Social environment and internet connectedness seniors perceived the internet to be as central in their life as other age groups (Loges and Jung, 2001).HYPOTHESESBased on the previous studies, we propose three components of social environment that are likely to influence adolescents’ internet connectedness (scope and intensity of internet connectedness and centrality of internet connectedness). The first factor that shapes adolescents’ internet connectedness is the availability of help from people around them when having problems in using the internet. In other words, internet-related knowledge and expertise of other people in their social network, and the ways in which those resources are available to adolescents when they are in need are important social capital that shapes adolescents’ connections to the internet (Hall and Schaverien, 2001; Silverstone, 1996). For example, a recent report by a Silicon V alley based organization found that despite the overall high internet access rate among the youth across different social groups, the ways in which the students perceived the importance of the internet in their future career were highly influenced by whether they were located in a social environment where it was relatively easy to get internet related support whenever needed from people around them (Joint V enture, 2002).H1:The availability of help from others when having problems withcomputers and the internet is likely to affect the scope and intensityand the centrality of adolescents’ connections to the internet.H1-a.The easier the adolescents are able to get help from others on internet-related problems, the broader and more intense their internetconnectedness is.H1-b.The easier the adolescents are able to get help from others on internet-related problems, the higher the centrality of their internetconnectedness is.Second, in adolescents’ social environments, we specifically examine the relationship between parents’ internet use and the adolescents’ connectedness to the internet. Practitioners and researchers have long recognized the importance of parental involvement in students’ school performance and their daily activities such as technology use (Ramirez, 2001; Wright, 2001).A pre-internet, longitudinal study of 7–12 graders showed that parental interest and household computer ownership were the most important predictors of student’s heavy computer use (Rocheleau, 1995). Recent studies also found a positive influence of parents’ socioeconomic status on children’s internet use (Guo and Bu, 2001; Holton, 2000; Kuo et al., 2002).A study of ‘online households’ in the US with children aged 6–12 indicated that 75 percent of either parent had a college degree. In addition, 7171New Media & Society 7(1)percent of the households had an annual income of more than $50,000 and only 15 percent had an income under $15,000 (Holton, 2000). A large-scale survey conducted on 4804 students aged 10 to 18 in five cities in China showed that half of the parents of students who used the internet had a college degree or above, whereas the majority of parents of non-users had a high-school diploma or lower (Guo and Bu, 2001). In Singapore, two cross-sectional surveys in 1999 and 2000 similarly indicated that parents of internet using adolescents were likely to be more educated and reported a higher household income than those of non-users (Kuo et al., 2002).H2:Parents’ socio-economic status influences the ways in which adolescents connect to the internet.H2-a.Parents’ socio-economic status has a positive influence on the scope and intensity of the adolescents’ internet connectedness. The higher theparents’ educational and income levels, the broader and more intenseadolescents’ internet connectedness.H2-b.Parents’ socio-economic status has a positive influence on the centrality of internet connectedness. The higher the parents’ educational andincome levels, the higher the centrality of the internet connectedness. Despite the high internet access rates among the families with adolescents in our targeted East Asian countries, we expect to find significant variance among those wired families in terms of parents’ internet use. Such variations are likely to be significantly related to the ways in which adolescents connect to the internet. Parents’ internet use concerns whether either or both parents have access to the internet. W e believe that parents’ internet connections are likely to enhance adolescents’ connectedness to the internet.H3:Parents’ internet use affects the scope and intensity and the centrality of the adolescents’ internet connectedness.H3-a.Adolescents whose parents use the internet are more likely to have broader and more intense connectedness to the internet than thosewhose parents do not use the internet.H3-b.Adolescents whose parents use the internet are more likely to have higher centrality of internet connectedness than those whose parents donot use the internet.Another important social group that is likely to have significant influence on adolescents’ internet connectedness is their peer group with whom adolescents spend much of their time interacting. Particularly, the internet has become one of the major means of communication to maintain friendship among adolescents. Although several studies reported the effect of 72the internet on creating and maintaining peer group communications (Cheskin Research, 1999; Lenhart et al., 2001; Liang et al., 2001; NPR, 2000), very few of them examined the effect of their peer group’s internet use on adolescents’ internet adoption and use. W e hypothesize that proportions of their peer group’s internet connections would have significant effects on adolescents’ scope and intensity and the centrality of internet connectedness.H4:Proportions of adolescents’ peers who use the internet affect the scope and intensity and the centrality of adolescents’ connectedness to theinternet.H4-a.Adolescents who have more friends using the internet are more likely to have broader and more intense internet connectedness.H4-b.Adolescents who have more friends using the internet are more likely to have higher centrality of internet connectedness. METHODOLOGYResearch designSurveys were conducted in three East Asian cities: Seoul, Singapore, and Taipei. A survey questionnaire was first developed in English and translated into Korean and Chinese. Pilot studies were conducted in each city and revisions were made accordingly.In all of the three cities, a multistage cluster sampling method was used based on different school districts and levels of school resources. In Seoul, a total of 26 school districts were divided into three groups – rich, medium, and poor – in view of the presence of area-based inequality that leads to a difference in economic resources available in different groups of schools. In each cluster, we selected two schools, and from each of these six schools, two second-grade (equivalent to eighth grade in the US) classes were chosen. In the cases of Singapore and Taipei, where economic resources vary more prominently between public and private schools than among geographical areas, schools were categorized into public and private, and classes were chosen from each category.Researchers administered the survey for self-completion by students in classrooms. Students were not allowed to confer while completing the questionnaire. Students and schools were assured of the confidentiality of their responses. In all, we obtained a sample of 1303 students, of which 456 came from Seoul, 462 from Singapore, and 385 from Taipei. Fifty-five percent of the total respondents were male, and 45 percent were female. The survey implementation was initiated in June and completed in September 2001.。

新北师大高中英语必修一课件Unit3 Lesson 3

新北师大高中英语必修一课件Unit3 Lesson 3
The writer didn’t notice it at that time. The writer thinks of her often and misses her very much.
Intensive Reading
Discuss the following questions with your partner 3. Read the last paragraph. Why does the writer think Christmas is “magical”?
Read the passage and locate the dates or time words in the passage.
November
December
Christmas Eve
Christmas Day
Complete the timeline.
November
bh
December
Intensive Reading: Fill in the blanks
Christmas Day
Memories of Christmas
I was on my best behaviour as we 8. _o_p_e_n_e_d__th_e__p_r_e_se_n_t_s__. And then we had a Christmas lunch. During lunch, we 9. __p_u_t_o_n__s_il_ly__p_a_p_e_r_h_a_t_s_ and had a big turkey.
Intensillowing questions with your partner
2. Did the writer notice it at that time? How did she feel after

The Monte Carlo method in quantum field theory

The Monte Carlo method in quantum field theory
1
arXiv:hep-lat/0702020v1 20 Feb 2007
THE MONTE CARLO METHOD IN QUANTUM FIELD THEORY
COLIN MORNINGSTAR Department of Physics, Carnegie Mellon University, Pittsburgh, PA 15213, USA E-mail: colin morningstar@ This series of six lectures is an introduction to using the Monte Carlo method to carry out nonperturbative studies in quantum field theories. Path integrals in quantum field theory are reviewed, and their evaluation by the Monte Carlo method with Markov-chain based importance sampling is presented. Properties of Markov chains are discussed in detail and several proofs are presented, culminating in the fundamental limit theorem for irreducible Markov chains. The example of a real scalar field theory is used to illustrate the MetropolisHastings method and to demonstrate the effectiveness of an action-preserving (microcanonical) local updating algorithm in reducing autocorrelations. The goal of these lectures is to provide the beginner with the basic skills needed to start carrying out Monte Carlo studies in quantum field theories, as well as to present the underlying theoretical foundations of the method. Keywords : Monte Carlo, Markov chains, Lattice QCD.

BCR-ABL genes and leukemic phenotype

BCR-ABL genes and leukemic phenotype

BCR/ABL genes and leukemic phenotype:from molecular mechanisms to clinical correlationsFabrizio Pane*,1,Mariano Intrieri 1,2,Concetta Quintarelli 1,Barbara Izzo 1,Giada Casadei Muccioli 1and Francesco Salvatore 11CEINGE Biotechnologie Avanzate,and Dipartimento di Biochimica e Biotecnologie Mediche,Facolta `di Medicina,Universita `di Napoli Federico II,Italy;2Dipartimento STAT,Facolta `di Scienze MFN,Universita `degli Studi del Molise -Isernia,ItalyThe Philadelphia chromosome (Ph),a minute chromo-some that derives from the balanced translocation between chromosomes 9and 22,was first described in 1960and was for a long time the only genetic lesion consistently associated with human cancer.This chro-mosomal translocation results in the fusion between the 5’part of BCR gene,normally located on chromosome 22,and the 3’part of the ABL gene on chromosome 9giving origin to a BCR/ABL fusion gene which is transcribed and then translated into a hybrid protein.Three main variants of the BCR/ABL gene have been described,that,depending on the length of the sequence of the BCR gene included,encode for the p190BCR/ABL ,P210BCR/ABL ,and P230BCR/ABL proteins.These three main variants are associated with distinct clinical types of human leukemias.Herein we review the data on the correlations between the type of BCR/ABL gene and the corresponding leukemic clinical stly,drawing on experimental data,we provide insight into the different transforming power of the three hybrid BCR/ABL proteins.Oncogene (2002)21,8652–8667.doi:10.1038/sj.onc.1206094Keywords:Philadelphia chromosome;Ph positive leu-kemias;molecular pathogenesis;phenotype of leukemia IntroductionPh-positive leukemias have been the object of extensive studies to define at molecular and cellular level the complex mechanisms whereby the hybrid BCR/ABL protein may disrupt,in hemopoietic precursors,the maturation and replication processes and the physiological response to cytokines and growth factor leading,ultimately,to their neoplastic transformation.Although the expression of the hybrid BCR/ABL protein is presumed to be an early pathogenic event and its elevated tyrosine kinase activity to be a central event in Ph positiveleukemias,the intimate role of the BCR/ABL protein in leukemic transformation has not yet been completely elucidated.The knowledge of the role of BCR/ABL fusion gene in leukemia is further complicated by cytogenetic and epidemiological observations.This hybrid gene was originally described in a chronic type of leukemia affecting the myeloid compartment,the chronic myelogenous leukemia (CML),and is present in almost all the CML cases with a classical clinical picture,which is now considered the hallmark (Bennett et al .,1994).However,unlike other genetic lesions that are specifically associated with particular types of leuke-mias (Rowley,1998),the BCR/ABL hybrid gene is not restricted to CML,but it can also be found in a significant proportion of acute lymphoblastic leuke-mia (ALL)and less frequently in other chronic and acute hemopoietic tumors (Melo,1996).We described a relatively benign and rather rare form of myeloproliferative disease that we called ‘Neutrophi-lic-chronic myeloid leukemia’(CML-N),which is also associated with a BCR/ABL gene,that shows a novel position for the breakpoint in the BCR gene far downstream from the breakpoints already described (Pane et al .,1996b).Therefore,the identification of this subset of patients carrying the novel type of BCR/ABL gene led to the hypothesis that the structure of this gene and,in particular,the location of the breakpoint on the BCR sequences correlates with the leukemic phenotype (Pane et al .,1996b).A masterly account of these data and their far reaching implications can be found in Melo (1996).To minimize overlapping with the excellent reviews devoted to the intracellular interactions of BCR/ABL proteins that have appeared in recent years (Faderl et al .,1999;Holyoake,2001)or that are included in this issue of the journal,we first trace the milestones that have culminated in today’s state of the art,and then discuss:(i)the molecular structure of BCR/ABL fusion genes;(ii)the correlation between leukemic clinical features and the position of the breakpoint in the BCR gene;(iii)the clinical characteristics of the CML-N cases described so far;and (iv)the hypothesis that could explain at molecular level the differential transforming power of the various BCR/ABL fusion proteins.*Correspondence:F Pane,CEINGE and Dipartimento di Biochimicae Biotecnologie Mediche,Universitadi Napoli Federico II,Via S.Pansini 5,80131Naples,Italy;E-mail:fabpane@unina.itMilestonesThe history of the hybrid BCR/ABL gene started in 1960,when an abnormal,shortened chromosome22, termed the Philadelphia chromosome,was described in the leukemic cells of a patient affected by chronic myeloid leukemia(Nowell and Hungerford,1960). Only13years later,the use of quinacrinefluorescence and Giemsa banding in chromosome studying,allowed to clarify that Ph chromosome is the result of a translocation of part of chromosome22to chromo-some9(Rowley,1973).The molecular characterization of this translocation was facilitated when the c-ABL gene,the human homologous of v-ABL,an oncogene originally identified in the Abelson murine leukemia virus,was localized to the long arm of the chromosome 9(Heisterkamp et al.,1982).Two ABL probes,which normally map to chromosome9,were shown to hybridize on chromosome22q-(the Ph chromosome) of somatic cell hybrids originating from human CML leukocytes and rodent cells(de Klein et al.,1982), while sequences of the c-sis oncogene,generally found on chromosome22,were shown to be translocated to the chromosome9in CML cells(Groffen et al.,1983). These studies indicated a reciprocal translocation for the Ph chromosome,and suggested that activation of the transforming potential of the c-ABL proto-oncogene was an important consequence of the translocation.The cloning of the BCR/ABL break-point was the subsequent milestone.Heisterkamp and colleagues applied the‘chromosome walking’technique to show a chromosomal breakpoint within a14kb sequence of chromosome9homologous to the v-ABL, in one of three patients with CML(Heisterkamp et al., 1983).However,the chromosome9rearrangement was not evident in the remaining two patients,and this prompted Groffen et al.(1984)to direct their attention to chromosome22breakpoints.They used the sequences complementary to chromosome22 previously isolated from the genomic clone of the positive CML patients as probe to screen for genomic rearrangements,and found a rearrangement of chro-mosome22in a second CML patient.Noteworthy,this second rearrangement of chromosome22mapped very closely(1kb)to that identified in thefirst positive CML patient.When the same probe and restriction analysis was applied to a series of17leukemic patients, all but two cases(both Ph chromosome negative) showed a chromosome22rearrangement clustered within a5.8kb Bgl II–Bgl II genomic fragment,which was thus named the‘bcr’or breakpoint cluster region (Figure1)(Groffen et al.,1984).This region was later renamed‘M-bcr’(major breakpoint cluster region)to distinguish it from the‘minor breakpoint region’(m-bcr)–a chromosome22fragment located further upstream,which appeared to harbor breakpoints of Ph-positive acute leukemias(Hermans et al.,1987).It was rapidly evident that the involvement of M-bcr was highly specific for CML,as the rearrangement of this chromosome region were consistently found only in this type of leukemia and not in other hemopoietic neoplasias.The identification of an abnormally large (8.0kb)v-ABL related mRNA in Ph positive cell lines and in CML cells,but not in normal cells and in Ph negative leukemias(Gale and Canaani,1984),and the characterization of a large(210kDa)ABL related phosphoprotein,the P210(Konopka et al.,1984), reinforced the concept that CML was related to a fusion gene.Importantly,the tyrosine kinase activity of P210resembled that of protein v-ABL(Witte et al., 1980;Davis et al.,1985),which was phosphorylated, whereas the145kDa c-ABL protein which was not phosphorylated in vivo,in normal cells(Konopka and Witte,1985).The definitive proof of the presence of a fusion gene in CML cells,came from the studies of Shtivelman et al.(1995)thatfirst cloned the full length cDNA corresponding to the6.0kb cABL encoding transcript, and used the5’part of this cDNA to clone the CML-specific transcript from cDNA libraries prepared from both K562and EM2PH positive cell lines.The sequence analysis of these transcripts isolated from both cell lines revealed that they contain a novel5’sequence fused in frame with c-ABl exon2,and interestingly,a genomic fragment which hybridized to these non-ABL sequences contained the M-bcr region previously identified by Groffen et al.(1984).Taken together,these data suggested that the8kb CML-specific mRNA contains the BCR joined to the c-ABL sequences that was transcribed from a BCR/ABL fusion gene.In addition the authors suggested that the amino terminal substitution was responsible for the increased tyrosine kinase activity of the ABL-derived sequences.Thesefirst but extremely important data open the way to a huge amount of studies on the structure of this hybrid gene and on molecular mechanisms of Ph positive leukemias.Molecular structure of BCR/ABL genesAt molecular level,the Ph translocation results in the juxtaposing of the5’part of the BCR gene to the3’part of the ABL gene,and,depending on chromosomal breakpoint locations,different parts of these two genes may be included in the oncogenic fusion gene(Table 1).The ABL gene is a gene encoding a non receptor tyrosine kinase,which spans a230kb region at band q34of chromosome9and consists of11exons,with twofirst alternative exons i.e.exons Ia and Ib (Kurzrock et al.,1988).In the vast majority of the Ph positive patients,breakpoints in the ABL gene appeared to be distributed over a rather large300kb fragment of chromosome9at band q34,which comprises the5’end of this gene,and may occur either upstream of the alternativefirst exon(exon Ib), or downstream of the otherfirst exon(Ia)or more frequently between these two(Melo et al.,1993a).By the effect of the Ph chromosomal translocation,ABL sequences sited downstream(telomeric)of breakpoint move to the der(22)and are joined to the5’part of the BCR/ABL genes and leukemic phenotypeF Pane etalFigure1Breakpoint locations at the BCR and ABL loci.The sporadic breakpoints are indicated by small arrows(see also Table1)Table1Breakpoints at the BCR and ABL locus in human Philadelphia positive leukemias(see also text for details)Genomic breakpoints No of ChimericBCR locus ABL locus cases mRNA junctions protein ReferenceMinor bcr5’end of ABL(*300Kb)Common e1a2185KDa(Fainstein et al.,1987;Clark et al.,1987;and this review) Minor bcr Intron2or5’end of ABL4e1a3180KDa(Soekarman et al.,1990;Iwata et al.,1994;Wilson et al.,2000;Mancini et al.,2001)Exon25’end of ABL(intron Ib)1e2-int ABL1b-a2187KDa(Okamoto et al.,1997)Intron65’end of ABL(*300Kb)1e6a2195KDa(Hochhaus et al.,1996)Intron85’end of ABL(*300Kb)4Not tested?(Saglio et al.,1988;Negrini et al.,1992)2e8-int-a2197.5KDa(How et al.,1999;Martinelli et al.,2002)Intron105’end of ABL(*300Kb)1Not tested?(Erikson et al.,1986)Major bcr5’end of ABL(*300Kb)Common e13a2and/or e14a2210KDa(Heisterkamp et al.,1985;Kawasaki et al.,1988and this review)Major bcr Intron2or5’end of ABL*4e13a3203KDa(Soekarman et al.,1990;van der Plas et al.,1991;3e14a3Tuszynski et al.,1993;Wilson et al.,2000)(Inukai et al.,1993;Iwata et al.,1994)Intron15Exon2(nt78)2e15a2210KDa(Moreno Mdel et al.,2001)Micro bcr5’end of ABL(*300Kb)24e19a2230KDa(Saglio et al.,1990and this review)BCR gene(Figure1).Sequences of the exons Ia and/or Ib,which may be included in the fusion gene,are spliced out from the primary hybrid transcript.Indeed, they are never detected in the mature BCR/ABL mRNAs,which,with very rare exceptions(see below), contain only the last10exons,from exon2to exon11, of ABL gene(Morris et al.,1991;Melo et al.,1993b). Breakpoints on the BCR gene are usually clustered in three well defined regions(Table1and Figure1). Thefirst,now known as major breakpoint cluster region(M-bcr),is a 5.8kb chromosomal region spanning exons12–16(originally named b1to b5) (Heisterkamp et al.,1985;Stam et al.,1985).M-bcr breakpoints are detectable in more than95%of cases (Faderl et al.,1999,however,breakpoints in this region can be detected in about one third of adult acute lymphoid leukemias(ALLs)with the t(9;22)transloca-tion and in a small fraction of Ph positive ALL childhood cases(Arico et al.,2000;Gleissner et al., 2002).Depending on the position of breakpoint in this region,the5’end of the BCR gene comprising either the exon13(formerly b2)or exon14(formerly b3)is joined to the3’part of ABL gene,giving rise to a BCR/ABL hybrid gene encoding the chimeric210kDa protein(P210BCR/ABL).The corresponding fusion mRNAs shows either the b2a2or the b3a2type of junctions(Kawasaki et al.,1988).Together with Saglio’s group,we reported alternative splicing of the primary BCR/ABL transcript which leads in all CML patients to the production of also the P190-encoding mRNA(e1a2junction),(Saglio et al.,1996).This finding was subsequently confirmed by other groups (van Rhee et al.,1996;Lichty et al.,1998;Serrano et al.,2000).In addition,alternative splicing allows the simultaneous expression of both b2a2and b3a2types of transcripts(Melo,1996).In70–80%of Ph positive ALLs(Arico et al.,2000; Gleissner et al.,2002),and in rare cases of CML(Melo et al.,1994),breakpoints of chromosome22span a 55kb intronic sequence between the two alternative exons e2’and e2(Chissoe et al.,1995),called minor breakpoint cluster region(m-bcr)(Clark et al.,1987; Fainstein et al.,1987).In these cases only the extreme 5’end of the BCR gene is joined to the3’sequences of the ABL gene,and although the deriving BCR/ABL fusion gene contains both the e1’and the e2’BCR exons and may contain ABL alternativefirst exons,all these exonic sequences are removed by splicing and the hybrid transcript shows a junction between the BCR exon e1and ABL exon a2.This type of ela2transcript is smaller(7.4kb)than that normally found in CML patients and encodes a185kDa chimeric protein (P190BCR/ABL)(Clark et al.,1987;Hermans et al., 1987;Kurzrock et al.,1987).More recently Saglio et al.(1990)described the presence of a novel type of BCR breakpoint located at the3’end of the gene in two cases of chronic myeloid leukemia.The breakpoints of these two patients were both comprised in the intron19and,hence,19of the 23BCR exons were included in the resulting fusion mRNA,which show an in frame e19a2type junction encoding for the largest BCR/ABL chimeric protein of predicted230kDa.This protein(P230BCR/ABL)was subsequently purified from a Ph positive cell line expressing this type of BCR/ABL fusion gene(Wada et al.,1995).Afterwards,we described three additional patients affected by a Ph positive leukemia carrying the e19a2type of BCR/ABL gene(Pane et al.,1996a). Interestingly,the leukemic phenotype in these three patients was very close to that of the chronic neutrophilic leukemia(CNL),and,in retrospect,also the clinical features of thefirst two cases described by Saglio et al.(1990)might be considered much closer to CNL than the classical CML.Therefore,we proposed the name of m BCR(Micro-BCR)for the breakpoints located at the intron19of the BCR gene,which were associated to a distinct form of mild Ph positive myeloproliferative disease,the neutrophilic-chronic myeloid leukemia(CML-N)(Pane et al.,1996b). Over the past15years,additional types of BCR/ ABL genes have been described mainly as single case reports(Table1).Eight cases concerning patients with a breakpoint comprised between the minor and major BCR regions,mainly located at,or around,the BCR intron8.The fused mRNA was detected in only three of these patients,being the in frame e6a2junction in one case(Hochhaus et al.,1996)and an e8a2junction which was in frame by the inclusion of an intronic sequence,in the other two patients(How et al.,1999; Martinelli et al.,2002).In other11patients,the hybrid transcript had an unusual junction between BCR sequences(exons e1,e13or e14)and the ABL exon 3,thus showing that the174bp sequences of the ABL exon2,which encode for58amino acids,the last17of which are part of the SH3domain,were not essential for the transformation of cells(Table1).In only one of these cases the Southern analysis made it possible to detect a breakpoint at the0.6kb ABL intron2, whereas in the other two cases the restriction analysis excluded the presence of a breakpoint in the second ABL intron,therefore,most likely,the unusual junctions derive in these latter cases,from the splicing out of the ABL exon2from the primary hybrid transcript(van der Plas et al.,1991;Iwata et al.,1994). Correlation of BCR breakpoint positions with the leukemic phenotypeClinical variability among the main cluster regions Table2shows the different types of leukemia and the corresponding BCR/ABL breakpoints found in the Ph positive patients,which shows the relationship between the amount of BCR sequences included in the hybrid gene and the leukemic phenotypes.In ALL,the Philadelphia chromosome and the corresponding BCR/ABL gene shows a different epidemiological distribution between adults and chil-dren cases(see Table2).The incidence of this genetic abnormality seems to correlate with age and it is relatively common in adults where it is found in up to 35%of cases(Maurer et al.,1991;Westbrook et al., BCR/ABL genes and leukemic phenotypeF Pane etal1992;Annino et al .,1994;Gleissner et al .,2002).Interestingly,among ALL cases,this genetic abnorm-ality is tightly associated to the B lineage and the cases of true T-ALL containing the BCR/ABL gene are very rare.Moreover,most of the Ph positive B-ALL cases express CD34and CD10antigens (Kantarjian et al .,1991;Westbrook et al .,1992;Gleissner et al .,2002).The relative proportion of adult ALL patients with the P210-and P190-encoding genes is variable in the various studies.The bias among the various studies is largely due to the selection of cases and the low number of patients analysed in some reports.Indeed,two studies,based on retrospective analysis,reported a higher percentage of adult ALL cases with M-bcr breakpoint (P210+ALL)compared to those with m-bcr type of breakpoint (P190+ALL)(Annino et al .,1994;Radich et al .,1994).Kantarjian et al .(1991)found the m-bcr type of breakpoint in 12out of 24adult ALL patients and the M-bcr in 11patients,and both the P210and the P190-encoding mRNA in the remaining patient.Most likely,this latter patient had a hybrid BCR/ABL gene with the M-bcr type of breakpoint,which gave origin to the two types of mature mRNAs by alternative splicing of a primary transcript (Dhingra et al .,1991;Saglio et al .,1996;van Rhee et al .,1996).In other studies,including a large prospective report on 175cases of Ph positive adult ALL,the percentage of adult ALL expressing the P190-encoding gene is much higher and accounts for 70–75%of the total number of Ph positive cases (Maurer et al .,1991;Westbrook et al .,1992;Gleissner et al .,2002).On the clinical ground,none of these studies provided evidence of hematological differences between the two types of breakpoints,with the exception of a trend,not statistically significant,toward a longer survival probability at 3years of the P190+ALL compared to the P210+ALL patients (0.19%vs 0.03%;P =0.7)found in the 175Ph positive ALL cases published by Gleisser et al .(2002).It is to be stressed,however,that the dire prognosis of adult ALL patients with the BCR/ABL gene might hide the clinical differences between the P190+ALL and the P210+ALL cases at least as regarding the treatment outcome aspects.Noteworthy,when aggressive treat-ments such as allogeneic stem cell transplant (SCT),were applied to the Ph positive ALL,the type of transcript seems to predict the clinical outcome.Indeed,Radich et al .(1992)showed that the PCR analysis made it possible to detect BCR/ABL positive cells,at least once after SCT,in bone marrow samples of 23out of 36Ph positive ALL patients,and that the PCR positivity predicted an overt clinical relapse with a relative risk of 5.7compared to a PCR negative assay.Interestingly,these authors showed that seven out of 10patients with the P190positive ALL and a post-transplant PCR positive assay relapsed,in contrast to only one out of eight patients with the P210positive ALL and a post-SCT PCR positive assay (Radich et al .,1997).In childhood ALL cases,the BCR/ABL gene is detectable in a limited proportion (up to 5–6%)of newly diagnosed patients (Suryanarayan et al .,1991;Pui and Evans,1998).As for the adult patients,the Ph defect is restricted to the pre-B ALL (Schrappe et al .,1998;Arico et al .,2000),and the cases of T-ALL with the BCR/ABL gene are very rare (Arico et al .,2000).The P210+ALL in children is less frequent than in adults and represents a small minority of cases (10–20%)of all childhood Ph positive ALL when tested in large groups of patients (Maurer et al .,1991;Schrappe et al .,1998;Arico et al .,2000).Although no clinical differences have been found between P210+ALL and P190+ALL pediatric patients,two large retrospective studies provided evidence that childhood Ph positive ALL comprises patients with heterogeneous responses to the intensive treatments (Schrappe et al .,1998;Arico et al .,2000).In particular,a good response to initial prednisone treatment and low WBC count predict those patients who will benefit from the treatment (Arico et al .,2000;Schrappe et al .,1998).At the moment,however,the biological background of these clinical heterogeneity is not known.The Ph chromosome is only rarely detected in acute myeloid leukemia (AML),and most of the patients represent myeloid blast crisis of CML following a clinically silent chronic phase.In the few bona fide Ph positive AML cases for which molecular studies were available,the P190-,differently to the P210-encoding gene,was always associated with the myelomonocytic phenotype (FAB M4or M5),thus suggesting a pivotal role of the BCR sequences located downstream from the m-bcr breakpoint,in the transformation of myeloidTable 2BCR/ABL junctions and leukemic phenotypeBCR breakpointJunction BCR/ABL mRNAProteinDiseases FrequencyALL85%of childhood Ph positive ALL 50–70%of adult Ph positive ALL Minor (m)e1/a2P185CML Very rare AMLVery rare Multiple myelomaOne case Non Hodgkin Lymphoma One caseCML 100%of casesMajor (M)b2/a2or b3/a2P210ALL 15%of childhood Ph positive ALL 30–50%of adult Ph positive ALL AML Very rare Micro (m )c3/a2P230CML-NRarelineage cells(Kurzrock et al.,1987;Preudhomme et al., 1992;Secker-Walker et al.,1992;Alimena et al.,1995). The impact of the amount of BCR sequences on leukemic phenotype is further supported by chronic leukemias predominantly affecting the myeloid lineage. Classical CML usually shows,at least in the initial chronic phase,a prominent,but often asymptomatic increase in peripheral blood of WBC,and in some cases of platelet count associated with the presence of immature granulocytic elements.This leukemia is almost invariably derived by the P210-encoding BCR/ ABL gene,and is the prototype of a stem cell neoplasia,in which all the hemopoietic lineages derive from a staminal transformed cell and have the Ph chromosome(Fialkow et al.,1977;Jonas et al.,1992; Maguer-Satta et al.,1996).In the classical CML, however,only the myeloid and megakaryotytic compartments show a neoplastic expansion,and the granulocytic progenitors have a moderate degree of impairment of their differentiation and maturation capacity,whereas the erythroid,monocytic and B-and T-lymphoid lineages do not reveal any functional damage(Clarkson and Strife,1993).By contrast,the rare cases of CML with the P-190encoding BCR/ABL gene are characterized by a prominent monocytosis, with a low neutrophil-to-monocyte ratio in both bone marrow and peripheral blood.In addition,these patients show a relative higher proportion of immature cells in peripheral blood and lower neutrophil alkaline phosphatase(NAP)score than those affected by P210 CML(Melo et al.,1994;Roumier et al.,1999). Therefore,as for the P190positive AML,when the BCR/ABL gene with the m-BCR type of breakpoint is expressed in the early myeloid compartment,the monocytic precursors are consistently included in the neoplastic expansion,whereas the M-BCR breakpoint results in the restriction of the expansion to the granulocytic precursors.The importance of the length of BCR sequence in the BCR/ABL fusion gene was corroborated by the CML-N patients with the P230encoding BCR/ABL gene and the m BCR type of breakpoint.The CML-N wasfirst described by us in1996infive patients as a clinical entity characterized by primary chronic,non progressive leukocytosis(Pane et al.,1996b).The original description required the following criteria:(1) moderate neutrophilic leukocytosis,(2)rare circulating immature myeloid cells without a myelocyte peak,(3) excess marrow mature myeloid cells,and(4)absent or minimal splenomegaly.Thesefirst cases suggested that CML-N might have a more benign clinical course than classical CML.This was disputed after the report of three new cases of Ph positive leukemia with the m BCR type of breakpoint whose clinical features were similar to those usually observed in the classical P210-expressing CML and of a single case of AML with this type of BCR/ABL gene(Briz et al.,1997;Wilson et al.,1997;Haskovec et al.,1998;Kojima et al.,1999). Twenty-four patients with the P230-encoding BCR:ABL gene have thus far been reported(Verstov-sek et al.,2002).Overall,the clinical features of these patients are different to the classical CML(Table3): out of the24CML-N patients,18were females,17 had no palpable splenomegaly(in one case thisfinding was not reported),and only three had WBC counts greater than1006109/L.The mean platelet count of all the patients was6616109/L and thrombocytosis was present in16cases,withfive patients presenting with very high platelet count(410006109/L).Note-worthy,in15patients the m BCR type of BCR/ABL gene was the sole detectable genetic abnormality (Table3,upper panel),whereas in nine patients the BCR/ABL gene rearrangement was associated with other cytogenetic abnormalities beside the Ph chromo-some(Table3,lower panel),and at least in the case reported by Wada et al.(1995),the associated chromosomal lesion,the isochromosome17,was proven to precede the t(9;22)translocation.Interest-ingly,14out of the15patients belonging to thefirst group showed a clinical picture typical of what we have termed CML-N(i.e.,a Ph-positive chronic neutrophilic leukemia).Indeed,all patients except one did not show splenomegaly,the mean WBC count in these patients was rather low(346109/L),and12of the15patients are alive and well,in some instances after a prolonged period of observation(Verstovsek et al.,2002).Only one patient of this group had a blastic transformation,while the other two patients died from unrelated causes(Saglio et al.,1990;Pane et al., 1996b),and the median survival probability of this group of patient is projected at190months by the actuarial analysis.By contrast,in the remaining nine patients who had,at presentation of disease,additional cytogenetic abnormalities,clinical and hematological features were more similar to the classical CML:the spleen was enlarged in four of these patients,the mean WBC count was significantly higher(926109/L),and a transition to the more advanced phase of disease was observed in four of this group of patients who showed a median survival probability of37months.Interest-ingly,all these chromosomal abnormalities have been described in acute myeloid leukemia and among these, both the trisomy of chromosome8and the isochromo-some17,which has been found in three patients,may be the sole genetic lesion in acute myeloid leukemias (Schoch et al.,1997;Fioretos et al.,1999;Paulsson et al.,2001).Furthermore,the hybrid AML/ETO gene of the t(8;21)detected in patient#23,has proven to transform myeloid precursors(Nucifora and Rowley, 1995).We then investigated for the presence of the P230BCR/ABL protein and for the amount of P230-encoding transcript copies in the bone marrow cells of all the available CML-N patients(Verstovsek et al., 2002).Interestingly,in all the patients analysed,the level of expression of the P230BCR/ABL protein was always very low and below the detection limit of the very sensitive technique used in this study.The presence of the P230BCR/ABL protein was reported in only one patient(#24of Table3),however,his leukemic blasts carried two copies of Ph chromosome (Haskovec et al.,1998).In addition,in all but two patients,we measured,by using both the real time and BCR/ABL genes and leukemic phenotypeF Pane etal。

北师大版初中英语七年级上册巩固练习--- Review of Get ready and Units 1-2

北师大版初中英语七年级上册巩固练习---  Review of Get ready and Units 1-2

Review of Get ready and Units 1-2巩固练习::I. 单项选择。

(每小题1分,共15分)1.Jackie Chan is from _______.He is _______.A.China;Chinese B.China;ChinaC.Chinese;China D.Chinese;Chinese2.—Where _______ you from?—Lily _______ from England and I _______ from China.A.is;are;am B.are;is;am C.is;is;am D.are;is;are3.—What’s _______ over there(在那边)?—It’s a car.A.that B.this C.these D.those4.—_______—He’s a doctor.A.What is he like? B.Where does he work? C.What does he do? D.What does he look like? 5.This is Jack.That is Mary._______ are my cousins.A.He B.It C.She D.They6.—_______—He is tall and he has short blond hair.A.What does he like? B.Does he look cool?C.What does he look like? D.How does he feel?7.—________ do you spell“classroom”?—I’m sorry.I don’t know.A.What B.When C.How D.Where8.—_______ is the best singer in your team?—The one in red.A.What B.Where C.Who D.How9.Here _______ my family photos.A.am B.are C.is D.he10._______ office building is _______ the left of the classroom building.A.An;in B.A;on C.A;in D.An;on11.These doctors and nurses are from a big ______.They can help you.A.farm B.school C.station D.hospital12.Let Simon and ______ friends.A.I be B.I am C.me be D.me are13.—What’s your favourite _______?(2015广东深圳期中)—I like English best,and I’m good _______ it.A.subject;at B.food;for C.fruit;at D.sport;for14.Can you play _______ basketball?(2016安徽合肥包河区期中)A.a B.the C./D.an15.—Are those your good friends?(2016北京二十四中期中)—No, _______.A.they aren’t B.he isn’t C.she isn’t D.it isn’tII. 完形填空。

2019-2020年三年级英语上册 unit3 lesson19In,Out教案2 冀教版

2019-2020年三年级英语上册 unit3 lesson19In,Out教案2 冀教版

2019-2020年三年级英语上册 unit3 lesson19In,Out教案2 冀教版教材分析:本课继续学习身体部位的词汇。

通过演示让学生认识表示方位的单词:left right in out 。

知识和能力目标:1. 四会掌握单词:eye , ear ,nose ,mouth 以及 in , out2. 认读单词:left , right3. 会表演唱歌曲:Do the Hokey Pokey重点和难点:1. 人体部位词汇2. 能正确分清in 和out情感态度和价值观:培养学生良好的学习方法和学习英语的兴趣,使学生养成初步的自主学习的习惯。

教具准备:单词卡、空盒子、Danny 手偶、录音机教学过程:一、热身/复习(Warm up / Revision)1. Greetings :Hello,boys and girls! How are you today? Are you happy?Do you feel tired ? Do you feel hot?2. Sing a song : If You’re Sad and You Know It3. Review:Play a game “Simon Says” to review parts of the body.二、新授:(New Concepts)1. 介绍身体部位词汇:(Introduce parts of the body)教师指着自己的眼睛、耳朵、鼻子、嘴介绍新单词:eye ear nose mouth ,讨论我们在通常说eyes 和 ears 是为什么要在后面加-s。

2. 用左手和右手介绍left 和 right 。

练习说:left eye left ear left hand right arm right leg 等。

3. Play a game : “Do this quickly.”教师发指令,让学生快速做出相应的动作,复习学过的身体部位和left right 等词汇。

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