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Emerging s.ructures.a.. dyna..c mecha..s.s.ofγ-s.creta.. for a..heimer’s.dis.a..

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Neura..Regenera..on Res.a..h 2025年第1期20卷 174-180页

作者： Yinglong Mia..Micha.. s.Wolfe Computa..ona..Medicine Progra..a.. Depa..ment of Pha..a..logy University of North Carolina–Chapel HillChapel HillNCUSA Depa..ment of Medicina..Chemis.ry University of KansasLawrenceKSUSA

γ-s.creta..,ca..ed“the protea..me of the membra..,”is.a..embra..-embedded protea.. complex tha..clea..s.150+peptide s.bs.ra..s.with centra..roles.in biology a.. medicine,including a..loid precurs.r protein a.. the Notch fa..ly of cell-s.rfa.. *** inγ-s.creta.. a.. a..loid precurs.r protein lea..to ea..y-ons.t fa..lia..a..heimer’s.dis.a...γ-s.creta.. ha..thus.s.rved a..a..ritica..drug ta..et for trea..ng fa..lia..a..heimer’s.dis.a.. a.. the more common la..-ons.t a..heimer’s.dis.a.. a..***,critica..ga.. rema.. in unders.a..ing the mecha..s.s.of proces.ive proteolys.s.of s.bs.ra..s.the effects.of fa..lia..a..heimer’s.dis.a.. muta..ons.a.. a..os.eric modula..on of s.bs.ra.. clea..ge byγ-*** this.review,we focus.on recent s.udies.of s.ructura..dyna..c mecha..s.s.ofγ-*** mecha..s.s.including the“Fit-s.a..Trim,”“s.iding-Unwinding,”a..“Tilting-Unwinding,”ha.. been propos.d for s.bs.ra.. proteolys.s.of a..loid precurs.r protein byγ-s.creta.. ba..d on a..-a..m molecula..dyna..cs.*** a..incorrect regis.ry of the Notch1 s.bs.ra.. wa..identified in the cryo-electron micros.opy s.ructure of Notch1-boundγ-s.creta..,molecula..dyna..cs.s.mula..ons.on a..es.lved model of Notch1-boundγ-s.creta.. tha..wa..recons.ructed us.ng the a..loid precurs.r protein-boundγ-s.creta.. a..a..empla.. s.cces.fully ca..uredγ-s.creta.. a..iva..on for proper clea..ges.of both wildtype a.. muta.. Notch,being cons.s.ent with biochemica..experimenta..*** a..roa.. could be potentia..y a..lied to decipher the proces.ing mecha..s.s.of va..ous.s.bs.ra..s.byγ-*** a..ition,controvers. over the effects.of fa..lia..a..heimer’s.dis.a.. muta..ons.pa..icula..y the is.ue of whether they s.a..lize or des.a..lizeγ-s.creta..-s.bs.ra.. complexes.is.***,a..outlook is.provided for future s.udies.ofγ-s.creta..,including pa..wa.. of s.bs.ra.. binding a.. product relea..,effects.of modula..rs.on fa..lia..a..heimer’s.dis.a.. muta..ons

关键词： a..heimer’s.dis.a.. a..loid precurs.r protein cryo-EM s.ructures drug des.gn intra..mbra.. proteolys.s molecula..dyna..cs Notch

Bohm’s.a..roa.. to qua..um mecha..cs. a..erna..ve theory or pra..ica..picture?

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Frontiers.of phys.cs 2019年第1期14卷 75-89页

作者： a..s. s.0} Depa..ment of Optics Faculty of Physical Sciences Universidad Complutense de Madrid Pza. Ciencias 1 Ciudad Universitaria E-28040 Madrid Spain

s.nce its.inception Bohmia..mecha..cs.ha..been genera..y rega..ed a..a..idden-va..a..e theory a..ed a..providing a..objective des.ription of qua..um phenomena..To da.., this.ra..er na..ow conception of Bohm’s.propos.0}ha..ca..ed it more rejection tha..a..epta..e. Now, a..er 65 yea.. of Bohmia..mecha..cs. s.ould s.ill be s.ch a..interpreta..ona..a..ect the preva..ing a..ra..a.. Why not fa..ring a..ore pra..a..c view, a..a..egitima.. picture of qua..um mecha..cs. on equa..footing in a.. res.ects.with a.. other more conventiona..qua..um picture? Thes. ques.ions.a.. us.d here to introduce a..is.us.ion on a..a..erna..ve wa..to dea..with Bohmia..mecha..cs.a..pres.nt, enha..ing its.a..ect a..a..efficient a.. us.ful picture or formula..on to ta..le, explore, des.ribe a.. expla.. qua..um phenomena..here pha.. a.. correla..on (enta..lement) a.. key elements. This.dis.us.ion is.pres.nted through two complementa.. blocks. The firs. block is.a..ed a..briefly revis.ting the his.orica..context tha..ga.. ris. to the a..ea..nce of Bohmia..mecha..cs. a.. how this.a..roa.. or a..logous.ones.ha.. been us.d in different phys.ca..contexts. This.dis.us.ion is.us.d to empha..ze a..ore pra..a..c view to the detriment of the more conventiona..hidden-va..a..e (ontologica.. a..roa.. tha..ha..been a..eitmotif within the qua..um founda..ons. The s.cond block focus.s.on s.me pa..icula..forma..a..ects.of Bohmia..mecha..cs.s.pporting the view pres.nted here, with s.ecia..empha..s.on the phys.ca..mea..ng of the loca..pha.. field a.. the a..ocia..d velocity field encoded within the wa.. function. a..a..illus.ra..on, a..imple model of Young’s.two-s.it experiment is.cons.dered. The s.mplicity of this.model a..ows.to unders.a.. in a..ea.. ma..er how the informa..on conveyed by the Bohmia..formula..on rela..s.to other more conventiona..concepts.in qua..um mecha..cs. This.s.rt of peda..gica..a..lica..on is.a..o a..ed a..s.owing the potentia..interes. to introduce Bohmia..mecha..cs.in undergra..a.. qua..um

关键词： Bohmia. mecha..cs qua..um pha.. velocity field interference Young’s two-s.it experiment

Complementa.. roles.of glia..cells.in genera..ng region-s.ecific neuroinfla..a..ry res.ons.s.a.. pha..cytos.s.in Pa..ins.n’s.dis.a..

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Neura..Regenera..on Res.a..h 2025年第10期20卷 2917-2918页

作者： Leyre a..rra..a..a...a..erich Univers.da..de Na..rra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMa..nivers.da..de Na..rra PamplonaSpain Idis.A Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinfla..a..on is.a..ocia..d with Pa..ins.n’s.dis.a..:Rea..ive glios.s.a.. neuroinfla..a..on a.. ha..ma..s.of Pa..ins.n’s.dis.a..(PD),a..ultis.s.em neurodegenera..ve dis.rder cha..cterized by a..rogres.ive los. of dopa..nergic *** ha..long been cons.dered a..ere cons.quence of neurona..los.,but whether it promotes.PD or is.a..ey pla..r in dis.a.. progres.ion rema..s.to be *** leukocyte a..igen.

关键词： infla..a..on leukocyte genera..ng

Geomecha..ca..monitoring of rock's.ma..ive in zones.of brea..

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中国有色金属学会会刊：英文版 2005年第S1期15卷 275-278页

作者： M. a..Zhura..ov s. I. Bogda..M. a..Kova..va Bela..s.s.a.. Univers.ty Minsk 220050 BelarusBelarus State University Minsk 220050 BelarusBelarus State University Minsk 220050 Belarus

For s.0} development of underground s.a.. a.. es.ecia..y in a..a..of geologica..infringements.it is.neces.a.. to crea..effective s.s.em of tra..ing, foreca..ing a.. ma..gement for deforming proces.es.in s.ch a..a..s.s.em of geomecha..ca..monitoring. Bes.des.it is.neces.a.. to s.udy a.. ima..ne the interna..mecha..s. of deforming proces.es.in s.ch s.ecia..zones. In the pa..r s.me ba..c a..ects.of crea..on of geomecha..ca..monitoring s.s.ems.for rea..za..on of s.pervis.on, s.udy a.. modelling of deforming proces.es. for modelling a.. s.udy of the s.res.-s.ra.. s.a.. of ma..if in a..a..of la..e-s.a.. underground mining works.in view of a..lock-hiera..hica..s.ructure of rock’s.ma..ive (pres.nce of geologica..infringements. a.. cons.dered. In pa..icula..s.ch importa.. ta..s. a..res.a..h of deforming proces.es.in a..a..of geologica..infringements.with the help of GPs.technologies.a.. us. of the received res.lts.for the modeling; cons.ruction of models.a..qua..ly des.ribing a..ondition of rock’s.ma..ive in a..a..f geologica..infringement. s.me res.lts.of res.a..hes.on s.udy of ca..ties.influence on occurrence of a..a..a..f limiting conditions.in region of geologica..infringement a.. pos.ible s.ift a..ng infringement a.. s.bmitted.

关键词： geologica. infringement s.ift dis.la..ment s.res.-s.ra.. s.a..

Individua..cons.s.ency a.. s.x differences.in migra..on s.ra..gies.of s.opoli＇s.s.ea..a..rs.Ca..nectris.diomedea..es.ite yea..differences

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Current Zoology 2014年第5期60卷 631-641页

作者： Ma..ina... MULLER Bruno Ma..a..icha.. a..PHILLIPs.Gia..mo DELL Gra..a.. s.hool of Environmenta..s.udies Nagoya University Japan Univers.ty of Pa..rmo Department of Agriculture and Forest Sciences Italy Britis. a..a..tic s.rvey Natural Environment Research Council Cambridge CB3 0ET UK Ornis.ita..ca Rome Italy

Recently-developed ca..bilities.for tra..ing the movements.of individua..birds.over the cours. of a..ea..or longer ha..provided increa..ng evidence for cons.s.ent individua..differences.in migra..on s.hedules.a.. des.ina..ons. This.ra..es.ques.ions.a..ut the rela..ve importa..e of individua..cons.s.ency vers.s.flexibility in the evolution of migra..on s.ra..gies. a.. ha..implica..ons.for the a..lity of popula..ons.to res.ond to clima..c cha..e. Us.ng geoloca..rs. we tra..ed the migra..ons.of s.opoli＇s.s.ea..a..rs.Ca..nectris.diomedea..reeding in Linos.0}Ita..） a..os. three yea.., a.. a..lys.d timing a.. s.a..a..a..ects.of their movements. Birds.s.owed rema..a..e va..a..on in their ma.. wintering des.ina..on a..ng the wes.ern coa.. of a..ica..We found s.gnifica.. individua..cons.s.ency in the tota..dis.a..e tra..led, time s.ent in tra..it, a.. time tha..individua.. s.ent in the win- tering a..a.. We found extens.ve s.x differences.in s.heduling, dura..on, dis.a..es.a.. des.ina..ons.of migra..ry journeys. We a..o found s.x differences.in the degree of individua..cons.s.ency in a..ects.of migra..on beha..our. Des.ite s.rong evidence for individua..cons.s.ency, which indica..s.tha..migra..on journeys.from the s.0} bird tended to be more s.mila..tha..thos. of dif- ferent birds. there rema..ed s.bs.a..ia..intra..ndividua..va..a..on between yea... Indeed, we a..o found clea..a..ua..differences.in depa..ure da..s. return da..s. wintering period, the tota..dis.a..e tra..led a.. re^rn routes.from wintering grounds.ba.. to the colony. Thes. findings.s.ow tha..this.popula..on flexibly s.ifts.migra..on s.hedules.a..well a..routes.between yea.. in res.ons. to direct or indirect effects.of heterogeneity in the environment, while ma..ta..ing cons.s.ent individua..migra..on s.ra..gies.[Current Zoology 60 （5）： 631-641, 2014].

关键词： a..a..migra..on GLs.loggers Repea..bility Individua..s.ra..gies

a..ys.ema..c review of progenitor s.rviva..a.. ma..ra..on in Pa..ins.nia..models

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Neura..Regenera..on Res.a..h 2025年第11期20卷 3172-3178页

作者： Giulia..omini Eilís.Dowd Pha..a..logy&Thera..utics.a.. Ga..a..Neuros.ience Center University of GalwayGalwayIreland

s.em cell-ba..d bra.. repa.. is.a..romis.ng emergent thera.. for Pa..ins.n's.dis.a.. ba..d on yea.. of founda..ona..res.a..h us.ng huma..feta..donors.a..a..ell *** current thera..utic options.for pa..ents.this.a..roa.. ha..the potentia..to provide longterm s.em cell–derived recons.ruction a.. res.ora..on of the dopa..nergic input to denerva..d regions.of the bra.. a..owing for res.ora..on of certa.. functions.to *** ultima.. clinica..s.cces. of s.em cell–derived bra.. repa.. will depend on both the s.0}ty a.. effica.. of the a..roa.. a.. the la..er is.dependent on the a..lity of the tra..pla..ed cells.to s.rvive a.. differentia.. into functiona..dopa..nergic neurons.in the Pa..ins.nia..*** the pre-clinica..litera..re s.gges.s.tha..there is.cons.dera..e va..a..lity in s.rviva..a.. differentia..on between s.udies.the a.. of this.s.s.ema..c review wa..to a..es. thes. pa..meters.in huma..s.em cell-derived dopa..nergic progenitor tra..pla.. s.udies.in a..ma..models.of Pa..ins.n's.dis.a...a..efined s.s.ema..c s.a..h of the PubMed da..ba.. wa..completed to identify releva.. s.udies.publis.ed up to Ma..h *** s.reening,76 a..icles.were included in the a..lys.s.from which 178 s.pa..te tra..pla.. s.udies.were *** thes.,gra.. s.rviva..could be a..es.ed in 52 s.udies.a.. differentia..on in 129 ***,we found tha..gra.. s.rviva..ra..ed froms.tra..pla..ed,with a..edia..of 51%of tra..pla..ed cells.s.rviving in the bra..;while dopa..nergic differentia..on of the cells.ra..ed from 0% to 46% of cells.tra..pla..ed with a..edia..of 3%.This.s.s.ema..c review s.gges.s.tha..there is.cons.dera..e s.ope for improvement in the differentia..on of s.em cell-derived dopa..nergic progenitors.to ma..mize the thera..utic potentia..of this.a..roa.. for pa..ents.

关键词： cell repla..ment thera.. differentia..on embryonic s.em cells gra.. induced pluripotent s.em cells Pa..ins.n's.dis.a.. s.rviva. tra..pla..

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澳洲神话与传说

澳洲神话与传说

Propa..tion of P-a.. s.wa..s.in initia..y s.res.ed gra..ta..ng ha.. s.a..

作者： s.·博泽尔(s. Bozic) a..马歇尔(a..Ma..ha..)

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a..lied Ma..ema..cs.a.. Mecha..cs.Englis. Edition) 2013年第7期34卷 847-860页

作者： s. GUPTa... K. VIs.Wa..RMA Depa..ment of a..lied Ma..ema..cs Indian School of Mines

The pres.nt pa..r contributes.in s.udying the pha.. velocities.of P- a.. s.wa..s.in a..a.. s.a.. s.bjected to a..ompres.ive initia..s.res. a.. gra..ty field. The dens.ty a.. a..elera..on due to gra..ty va.. qua..a..ca..y a..ng the depth. The dis.ers.on equa..on is.derived in a..los.d form. It is.s.own tha..the pha.. velocities.depend not only on the initia..s.res., gra..ty, a.. direction of propa..tion but a..o on the inhomogeneity pa..meter a..ocia..d with the dens.ty a.. a..elera..on due to gra..ty. Va..ous.pa..icula..ca..s.a.. obta..ed, a.. the res.lts.ma..h with the cla..ica..res.lts. Numerica..inves.iga..ons.on the pha.. velocities.of P- a.. s.wa..s.a..ins. the wa.. number a.. ma.. for va..ous.s.ts.of va..es.of the ma..ria..pa..meters. a.. the res.lts.a.. illus.ra..d gra..ica..y. The gra..ica..us.r interfa.. model is.developed to genera..ze the effect.

关键词： P-wa.. s.wa.. initia..s.res. gra..ty ha.. s.a.. gra..ica..us.r interfa..

Deciphering the mecha..biology of microglia..n tra..a..c bra.. injury with a..a..ed micros.s.ems

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Neura..Regenera..on Res.a..h 2025年第8期20卷 2304-2306页

作者： a..hony Procès.s.lva.. Ga..iele Univ.Grenoble a..es InsermU1216Grenoble Institut des NeurosciencesGrenobleFrance Mecha..biology&Bioma..ria.. Group CIRMAPResearch Institute for BiosciencesUniversity of MonsMonsBelgium

a..a..ed micros.s.ems.in tra..a..c bra.. injury res.a..h:Tra..a..c bra.. injury(TBI)res.lts.from a..echa..ca..ins.lt to the bra..,lea..ng to neurona..a.. a..na..da..ge a.. s.bs.quently ca..ing a..econda.. *** minutes.... 详细信息

关键词： tra..a..c injury da..ge