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1、DigestOfThe.Economist.2006(4-5)HottotrotAnewservicehopestodofortextingwhatSkypedidforvoicecallsTALKischeapparticularlysincetheappearanceofvoice-over-internetservicessuchasSkype.Suchservices,whichmakepossibleverycheap(orevenfree)callsbyroutingpartorallofeachcallovertheinternet,haveforcedtraditionalte
2、lecomsfirmstocuttheirprices.Andnowthesamethingcouldbeabouttohappentomobilephonetextmessages,followingthelaunchthisweekofHotxt,aBritishstart-up.UsersdownloadtheHotxtsoftwaretotheirhandsets,justastheywouldagameoraringtone.Theychooseausername,andcanthenexchangeasmanymessagesastheylikewithotherHotxtuser
3、sfor1($1.75)perweek.Themessagesaresentasdatapacketsacrosstheinternet,ratherthanbeingroutedthroughoperatorstextmessaginginfrastructure.Asaresult,userspayonlyatinydata-transportcharge,typicallyofapennyorsopermessage.Sincetextmessagestypicallycost10p,thisisabigsavingparticularlyforthecost-consciousteen
4、agersatwhomtheserviceisaimed.MostteenagersinBritain,andelsewhereinEurope,payfortheirmobilephonesona“pre-paid”basis,ratherthanhavingamonthlycontractwitharegularbill.Pre-paidtariffsarefarmoreexpensive:bundlesoffreetextsandotherspecialdeals,whichcanreducethecostoftextmessaging,aregenerallynotavailable.
5、Forateenagerwhosendssevenmessagesaday,Hotxtcancutthecostoftextingby75%,saving210peryear,saysDougRichard,thefirmsco-founder.Forreallyintensivetext-messagers,thesavingscouldbeevenbigger:JoshDhaliwalofmobileYouth,amarket-researchfirm,saysthatsometeenagerschieflyboysaged15-16andgirlsaged14-15are“superte
6、xters”whosendasmanyas50messagesperday.Whilethissoundslikegoodnewsforusers,itcouldprovepainfulformobileoperators.Text-messagingaccountsforaround20%ofatypicaloperatorsrevenues.Withmarginsontextmessagesinexcessof90%,textingalsoaccountsfornearlyhalfofanoperatorsprofits.MrRichardisconfidentthatthereisnol
7、egalwaythatoperatorscanblockhisservice;theycouldraisedata-transportcosts,butthatwouldunderminetheirowneffortstopushnewservices.Hotxtplanstolaunchinothercountriessoon.“Thechallengeisgettingthatinitialmomentum,”saysMrDhaliwal.Hotxtneedstopersuadepeopletosignup,sothattheywillpersuadetheirfriendstosignu
8、p,andsoon.UnlikeSkype,Hotxtisnotfree,sousersmaybelessinclinedtogiveitatry.ButasSkypehasalsoshown,onceadisruptive,low-costcommunicationsservicestartstospread,itcanquicklybecomeverybigindeed.Andthatinturncanleadtolowerprices,notjustforitsusers,butforeveryone.AdiscerningviewAnewwayofprocessingX-raysgiv
9、esmuchclearerimagesX-RAYSarethemysteriousphenomenonforwhichWilhelmRentgenwasawardedthefirstNobelprizeinphysics,in1901.Sincethen,theyhaveshedtheirmysteryandfoundwidespreaduseinmedicineandindustry,wheretheyareusedtorevealtheinnerpropertiesofsolidbodies.Someproperties,however,aremoreeasilydiscernedthan
10、others.ConventionalXrayimagingreliesonthefactthatdifferentmaterialsabsorbtheradiationtodifferentdegrees.Inamedicalcontext,forexample,bonesabsorbX-raysreadily,andsoshowupwhiteonanX-radiograph,whichisaphotographicnegative.ButXraysarelessgoodatdiscriminatingbetweendifferentformsofsofttissue,suchasmuscl
11、es,tendons,fatandbloodvessels.That,however,couldsoonchange.ForFranzPfeifferofthePaulScherrerInstituteinVilligen,Switzerland,andhiscolleaguesreport,intheAprileditionofNaturePhysic,sthattheyhavemanipulatedstandardX-rayimagingtechniquestoshowmanymoredetailsoftheinnerbody.Thetrickneededtodiscernthisfine
12、detail,accordingtoDrPfeiffer,isasimpleone.TheresearcherstookadvantagenotonlyofhowtissuesabsorbX-raysbutalsoofhowmuchtheyslowtheirpassage.ThisslowingcanbeseenaschangesinthephaseoftheradiationthatemergesinotherwordsoftherelativepositionsofthepeaksandtroughsofthewavesofwhichX-raysarecomposed.Subtlechan
13、gesinphaseareeasilypickedup,sodoctorscandetectevensmallvariationsinthecompositionofthetissueunderinvestigation,suchasmightbecausedbytheearlystagesofbreastcancer.Indeed,thistrickknownasphase-contrastimagingisalreadyusedroutinelyinopticalmicroscopyandtransmissionelectronmicroscopy.Untilnow,however,noo
14、nehadthoughttouseitformedicalX-radiography.Toperformtheirtrick,theresearchersusedaseriesofthreedevicescalledtransmissiongratings.TheyplacedonebetweenthesourceoftheX-raysandthebodyunderexamination,andtwobetweenthebodyandtheX-raydetectorthatformstheimage.Thefirstgratinggathersinformationonthephasesoft
15、heX-rayspassingthroughit.Thesecondandthirdworktogethertoproducethedetailedphase-contrastedimage.TheapproachgeneratestwoseparateimagestheclassicX-rayimageandthephase-contrastedimagewhichcanthenbecombinedtoproduceahigh-resolutionpicture.TheresearcherstestedtheirtechniqueonaCardinaltetra,atinyiridescen
16、tfishcommonlyfoundinfishtanksandaquariums.TheconventionalX-rayimageshowedthebonesandthegutofthefish,whilethephase-contrastedimageshoweddetailsofthefins,theearandtheeye.DrPfeifferstechniquewouldthusappeartoofferawaytogetmuchgreaterdetailforthesameamountofradiationexposure.Moreover,sinceitusesstandard
17、hospitalequipment,itshouldbeeasytointroduceintomedicalpractice.X-raysmaynolongerbethestuffofNobelprizes,buttheirusefulnessmayjusthaveincreasedsignificantly.HerebedragonsWithluck,youmaysoonbeabletobuyamythologicalpetPAOLOFRIL,chairmanandchiefscientificofficerofGeneDupe,basedinSanMelito,California,isa
18、manwithadream.Thatdreamisadragonineveryhome.GeneDupesbusinessisbiotechpets.NotforDrFril,though,themundanecloningofdeadmoggiesandpooches.Heplansarangeofentirelynewanimalsor,rather,ofreallyquiteoldanimals,withthetwistthatevenwhentheydidexist,itwasonlyintheimagination.Makingamythicalcreaturerealisnotea
19、sy.ButGeneDupesteamofbiologistsandcomputerscientistsreckontheyareequaltothetask.Theirsecretisanewfield,whichtheycall“virtualcellbiology”.Biologyandcomputinghavealotincommon,sincebothareaboutprocessinginformationinonecaseelectronic;intheother,biochemical.Virtualcellbiologyaspirestomakeasoftwaremodelo
20、facellthatisaccurateineverybiochemicaldetail.Thatispossiblebecauseallanimalcellsusethesamepartslistmitochondriaforenergyprocessing,theendoplasmicreticulumformakingproteins,Golgibodyforproteinassembly,andsoon.Armedwiththeirvirtualcell,GeneDupesscientistscancustomisetheresultsothatitbelongstoaparticul
21、arspecies,byloadingitwithavirtualcopyofthatanimalsgenome.Then,ifthecellisalsoloadedwiththerightvirtualmolecules,itwillbehavelikeafertilisedegg,andstartdividinganddevelopingfirstintoanembryo,andultimatelyintoanadult.Becausethis“growth”isgoingoninacomputer,ithappensfast.PassingfromeggtoadultinoneofGen
22、eDupesenormousMythmakercomputerstakeslessthanaminute.AnditisherethatCharlesDarwingetsalookin.Withsuchashortgenerationtime,GeneDupesscientistscanaddalittleevolutiontotheirproducts.Eachcomputerstartswithasearchimage(dragon,unicorn,gryphon,etc),andthegenomeoftherealanimalmostcloselyresemblingit(alizard
23、forthedragon,ahorsefortheunicornand,mosttaxingly,thesplicedgenomesofalionandaneagleforthegryphon).Thevirtualgenomesoftheserealanimalsarethentweakedbyrandomelectronicmutations.Whentheyhavematured,thevirtualadultsmostcloselyresemblingthetargetsarepickedandcross-bred,whiletheothersareculled.Usingthisra
24、pidevolutionaryprocess,GeneDupesscientistshavearrivedatgenomesforarangeofmythologicalcreaturesinacomputer,atleast.Thenextstage,onwhichtheyarejustembarking,istodoitforreal.Thisinvolvessynthesising,withactualDNA,thegeneticmaterialthatthecomputermodelspredictwillproducethemythicalcreatures.Thesynthetic
25、DNAistheninsertedintoacellthathashaditsnaturalnucleusremoved.Theresult,DrFrilandhiscommercialbackershope,willbeareallivedragon,unicornorwhathaveyou.TalesoftheunexpectedWhyadrugtrialwentsobadlywrongINANYsortoftest,notleastadrugstrial,oneshouldexpecttheunexpected.Evenso,onMarch13th,sixvolunteerstaking
26、partinasmallclinicaltrialofatreatmentknownasTGN1412gotfarmorethantheybargainedfor.Allendedupseriouslyill,withmultipleorganfailure,soonafterbeinginjectedwiththedrugataspecialtestingunitatNorthwickParkHospitalinLondon,runbyacompanycalledParexel.Onemanremainsillinhospital.Small,preliminarytrialsofthiss
27、ortareintendedtofindoutwhetheradrugistoxic.Nevertheless,themishapwassoseriousthatBritainsMedicinesandHealthcareproductsRegulatoryAgency(MHRA),agovernmentbody,swiftlylaunchedafullinquiry.OnApril5thitannounceditspreliminaryfindings.Thesewerethatthetrialwasruncorrectly,dosesofthedrugweregivenastheywere
28、supposedtohavebeen,andtherewasnocontaminationduringmanufacturing.Inotherwords,itseemsthatdespiteextensivetestsonanimalsandhuman-cellcultures,anddespitethefactthatthedosesinthehumantrialwereonlyafive-hundredthofthosegiventotheanimals,TGN1412istoxicinpeopleinawaythatsimplyhadnotshownup.Thisisadifficul
29、tresultforthedrugbusinessbecauseitraisesquestionsabouttherightwayoftestingmedicinesofthiskind.TGN1412isunusualinthatitisanantibody.Mostdrugsarewhatareknownas“smallmolecules”.Antibodiesarebig,powerfulproteinsthataretheworkhorsesoftheimmunesystem.Amere20ofthemhavebeenapprovedforhumantherapy,orareinlat
30、estageclinicaltrails,inAmericaandEurope,buthundredsareinpre-clinicaldevelopment,andwillsoonneedtobetriedoutonpeople.Mostantibodydrugsaredesignedtoworkinoneofthreeways:byrecruitingpartsoftheimmunesystemtokillcancercells;bydeliveringasmall-moleculedrugoraradioactiveatomspecificallytoacancer;orbyblocki
31、ngunwantedimmuneresponses.Inthatsense,TGN1412wasunusualbecauseitworkedinafourthway.Itiswhatiscalleda“superagonistic”antibody,designedtoincreasethenumbersofatypeofimmunecellknownasregulatoryT-cells.Reducednumbers,orimpairedfunction,ofregulatoryT-cellshasbeenimplicatedinanumberofillnesses,suchastype1d
32、iabetes,multiplesclerosisandrheumatoidarthritis.Boostingthepooloftheseantibodiesseemedlikeagoodtreatmentstrategy.Unfortunately,thatstrategyfelldisastrouslytopiecesanditwilltakealittlelongertofindoutwhy.TheresulthighlightsconcernsraisedinapaperjustpublishedbytheAcademyofMedicalSciences,agroupofexpert
33、sbasedinLondon.Itsaystherearespecialrisksassociatedwithnovelantibodytherapies.Forexample,theirchemicalspecificitymeansthattheymightnotbindtotheirtargetsinhumansastheydoinotherspecies.AccidenceandsubstanceTwopossibleexplanationsforthebulkofrealityTHEunknownpervadestheuniverse.Thatwhichpeoplecansee,wi
34、ththeaidofvarioussortsoftelescope,accountsforjust4%ofthetotalmass.Therest,however,mustexist.Withoutit,galaxieswouldnotsurviveandtheuniversewouldnotbegentlyexpanding,aswitnessedbyastronomers.Whatexactlyconstitutesthisdarkmatteranddarkenergyremainsmysterious,butphysicistshaverecentlyuncoveredsomemorec
35、lues,abouttheformer,atleast.Onepossibleexplanationfordarkmatterisagroupofsubatomicparticlescalledneutrinos.Theseobjectsaresodifficulttocatchthatascreenmadeofleadalight-yearthickwouldstoponlyhalftheneutrinosbeamedatitfromgettingthrough.Yetneutrinosarethoughttobethemostabundantparticlesintheuniverse.S
36、ometenthousandtrilliontrillionmostofthemproducedbynuclearreactionsinthesunreachEartheverysecond.Allbutahandfulpassstraightthroughtheplanetasifitwasntthere.AccordingtotheStandardModel,themostsuccessfuldescriptionofparticlephysicstodate,neutrinoscomeinthreevarieties,called“flavours”.Theseareknownasele
37、ctronneutrinos,tauneutrinosandmuonneutrinos.Again,accordingtotheStandardModel,theyarepoint-like,electricallyneutralandmassless.Butinrecentyears,thisviewhasbeenchallenged,asphysicistsrealisedthatneutrinosmighthavemass.Thefirststrongevidencecamein1998,whenresearchersatanexperimentcalledSuperKamiokande
38、,basedatKamioka,inJapan,showedthatmuonneutrinosproducedbycosmicrayshittingtheupperatmospherehadgonemissingbythetimetheyshouldhavereachedanundergrounddetector.SuperKamiokandesoperatorssuspectthatthemissingmuonneutrinoshadchangedflavour,becomingelectronneutrinosormorelikelytauneutrinos.Theorysuggestst
39、hatthisprocess,calledoscillation,canhappenonlyifneutrinoshavemass.Sincethen,therehavebeenotherreportsofoscillation.ResultsfromtheSudburyNeutrinoObservatoryinCanadasuggestthatelectronneutrinosproducedbynuclearreactionsinthesunchangeintoeithermuonortauneutrinosontheirjourneytoEarth.TwootherJapaneseexp
40、eriments,oneconductedatKamiokaandoneinvolvingtheKEKparticle-acceleratorlaboratoryinTsukuba,nearTokyo,alsohintatoscillation.Lastweek,researchersworkingontheMINOSexperimentatFermilab,nearChicago,confirmedtheseresults.Overthecomingmonthsandyears,theyhopetoproducethemostaccuratemeasurementsyet.Theresear
41、cherscreatedabeamofmuonneutrinosbyfiringanintensestreamofprotonsintoablockofcarbon.OntheothersideofthetargetsataparticledetectorthatmonitoredthenumberofmuonneutrinosleavingtheFermilabsite.Theneutrinosthentraveled750km(450miles)throughtheEarthtoadetectorinaformerironmineinSoudan,Minnesota.Mythsandmig
42、rationDoimmigrantsreallyhurtAmericanworkerswages?EVERYnowandagainAmerica,anationlargelymadeupofimmigrantsandtheirdescendants,isgrippedbyafuriouspoliticalrowoverwhetherandhowitshouldstemthefloodofpeoplewantingtoenterthecountry.Itisinthemidstofjustsuchaquarrelnow.Congressiscontemplatingtheerectionofaw
43、allalongstretchesoftheMexicanborderandacrackdownonillegalworkers,aswellassofterpoliciessuchasaguest-workerprogrammeforillegalimmigrants.Someoftheargumentsareplainsilly.ImmigrationsdefendersclaimthatforeignerscometodojobsthatAmericanswontasifcitieswithfewimmigrantshadnogardeners.Itsopponentssaythatim
44、migrantsstealAmericanjobssuccumbingtothefallacythatthereareonlyafixednumberofjobstogoaround.Onecommonargument,thoughnotsilly,isoftenoverstated:thatimmigrationpushesdownAmericanworkerswages,especiallyamonghigh-schooldropouts.Itisnthardtoseewhythismightbe.Overthepast25yearsAmericanincomeshavebecomeles
45、sequallydistributed,typicalwageshavegrownsurprisinglyslowlyforsuchahealthyeconomyandtherealwagesoftheleastskilledhaveactuallyfallen.Itisplausiblethatimmigrationisatleastpartlytoblame,especiallybecauserecentarrivalshavedisproportionatelypoorskills.Inthe2000censusimmigrantsmadeup13%ofAmericaspoolofwor
46、kers,but28%ofthosewithoutahigh-schooleducationandoverhalfofthosewitheightyearsschoolingorless.Infact,therelationshipbetweenimmigrationandwagesisnotclear-cut,evenintheory.Thatisbecausewagesdependonthesupplyofcapitalaswellaslabour.Alone,aninfluxofimmigrantsraisesthesupplyofworkersandhencereduceswages.
47、Butcheaperlabourincreasesthepotentialreturntoemployersofbuildingnewfactoriesoropeningnewvalet-parkingcompanies.Insodoing,theycreateextrademandforworkers.Oncecapitalhasfullyadjusted,thefinalimpactonoverallwagesshouldbeawash,aslongastheimmigrantshavenotchangedtheproductivityoftheworkforceasawhole.Howe
48、ver,evenifwagesdonotchangeonaverage,immigrationcanstillshifttherelativepayofworkersofdifferenttypes.Alargeinflowoflow-skilledpeoplecouldpushdowntherelativewagesoflow-skillednatives,assumingthattheycompeteforthesamejobs.Ontheotherhand,iftheimmigrantshadcomplementaryskills,nativeswouldberelativelybett
49、eroff.Togaugethefulleffectofimmigrationonwages,therefore,youneedtoknowhowquicklycapitaladjustsandhowfarthenewcomersaresubstitutesforlocalworkers.RoamingholidayTheEUhopestoslashthepriceofcross-bordermobilecalls“TODAYitisonlywhenusingyourmobilephoneabroadthatyourealisetherearestillbordersinEurope,”lam
50、entedVivianeReding,theEuropeancommissionerresponsiblefortelecomsandmediaregulation,assheannouncedplanstoslashthecostofmobileroaminglastmonth.Itisalaudableaim:Europeanconsumerstypicallypay1.25($1.50)perminutetocallhomefromanotherEuropeancountry,and1perminutetoreceivecallsfromhomewhileabroad.Withroami
51、ngmarginsabove90%,Europeanmobileoperatorsmakeprofitsofaround10billionayearfromthetrade,thecommissionestimates.MsRedingsplan,unveiledonMarch28thandupfordiscussionuntilMay12th,istoimposea“homepricing”scheme.Evenwhileroaming,callerswouldbechargedwhatevertheywouldnormallypaytousetheirphonesintheirhomeco
52、untries;chargesforincomingcallswhileroamingwouldbeabolished.Thatmaysoundgood.But,astheindustryisunderstandablyatpainstopointout,itcouldhavesomecuriousknock-oneffects.Inparticular,consumerscouldsignupwithoperatorsinforeigncountriestotakeadvantageoflowerprices.Everyonewouldtakeoutsubscriptionstotheche
53、apestsupplierandbringthembackhome,saysJohnTysoeoftheMobileWorld,aconsultancy.“Youdendupwithacompletemuddle.Anoperatormighthaveanetwork,butnocustomers,becausetheyveallmigrated.”AnotherproblemwithMsRedingsplan,hesays,isthatoperatorswouldcompensateforthelossofroamingfeesthoughttoaccountforaround3%ofthe
54、irrevenuesand5%ofprofitsbyraisingpriceselsewhere.Thiswouldhavetheperverseeffectofloweringpricesforinternationalbusinesstravellers,abigchunkofroamingtraffic,whileraisingpricesformostconsumers.Thecommissionsproposalsare“economicallyincoherent”,saysRichardFeaseyofVodafone,whichoperatesmobilenetworksinm
55、anyEuropeancountries.Imposingpricecapsonroamingislegallyquestionable,hesays,andVodafonehas,inanycase,beensteadilyreducingitsroamingcharges.(EuropeanregulatorspreventeditfromdoingsoforthreeyearsonantitrustgroundsafteritstakeoverofMannesmannin2000.)Orange,anothermultinationaloperator,saysitisplanningt
56、omakepricecuts,too.“Ofcourse,noweverybodysgotpricecuts,”saysStefanoNicolettiofOvum,aconsultancy.ButperhapsMsRedingsunspokenplanistousethethreatofregulationasawaytopromptaction.Operatorsarerightthatherproposalsmakenosense,buttheyarechargingtoomuchallthesame.Soexpectthemtolobbyhardagainsttheproposalso
57、verthenextcoupleofyears,whilequietlycuttingtheirpricesanoutcomethatwould,ofcourse,allowbothsidestoclaimvictory.DevicesandtheirdesiresEngineersandchemistsgettogetherTHEREusedtobeaworldofdifferencebetweentreatingapatientwithadevicesuchasafakehiporapacemakerandusingbiologyandbiochemistry.Differentailme
58、ntsrequiredwhollydifferenttreatments,oftenwithlittleincommon.ButthatischangingasmedicaladvancessuchasthosebeingtrumpetedatthebiotechnologyindustrysannualgatheringthisweekinChicagofostercombinationsofsurgicalimplantsandotherhardwarewithsupportfrommedicines.Drug-releasingstentswereoneofthefirstfruitso
59、fthistrend,whichincreasinglyrequiresvastlydifferentsortsofhealth-carefirmstomeshtheirresearchefforts.Thatwillbeachallenge.Whilepharmaceuticalandbiotechfirmsarealwaysinsearchofthenextbigthing,devicemakersprefergradualprogress.InsteadofhangingoutwithbreathlessentrepreneursnearAmericaseastandwestcoasts
60、,wheremostdrugandbiotechnologyfirmsarebased,manyofthedevice-makershuddleinmidwesterncitiessuchasMinneapolis,IndianapolisandKalamazoo.AndunlikeBigPharma,whichusesmarketingblitzestotellailingconsumersaboutitsnewdrugs,medical-devicesalesteamsactmoreasinstructors,showingdoctorshowtoinstalltheirlatestcre
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