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Emerging s.ructures.and dynamic mechanis.s.ofγ-s.cretas. for Alzheimer’s.dis.as.

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Neural Regeneration Res.arch 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael s.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemis.ry University of KansasLawrenceKSUSA

γ-s.cretas.,called“the proteas.me of the membrane,”is.a membrane-embedded proteas. complex that cleaves.150+peptide s.bs.rates.with central roles.in biology and medicine,including amyloid precurs.r protein and the Notch family of cell-s.rface *** inγ-s.cretas. and amyloid precurs.r protein lead to early-ons.t familial Alzheimer’s.dis.as..γ-s.cretas. has.thus.s.rved as.a critical drug target for treating familial Alzheimer’s.dis.as. and the more common late-ons.t Alzheimer’s.dis.as. as.***,critical gaps.remain in unders.anding the mechanis.s.of proces.ive proteolys.s.of s.bs.rates.the effects.of familial Alzheimer’s.dis.as. mutations.and allos.eric modulation of s.bs.rate cleavage byγ-*** this.review,we focus.on recent s.udies.of s.ructural dynamic mechanis.s.ofγ-*** mechanis.s.including the“Fit-s.ay-Trim,”“s.iding-Unwinding,”and“Tilting-Unwinding,”have been propos.d for s.bs.rate proteolys.s.of amyloid precurs.r protein byγ-s.cretas. bas.d on all-atom molecular dynamics.*** an incorrect regis.ry of the Notch1 s.bs.rate was.identified in the cryo-electron micros.opy s.ructure of Notch1-boundγ-s.cretas.,molecular dynamics.s.mulations.on a res.lved model of Notch1-boundγ-s.cretas. that was.recons.ructed us.ng the amyloid precurs.r protein-boundγ-s.cretas. as.a template s.cces.fully capturedγ-s.cretas. activation for proper cleavages.of both wildtype and mutant Notch,being cons.s.ent with biochemical experimental *** approach could be potentially applied to decipher the proces.ing mechanis.s.of various.s.bs.rates.byγ-*** addition,controvers. over the effects.of familial Alzheimer’s.dis.as. mutations.particularly the is.ue of whether they s.abilize or des.abilizeγ-s.cretas.-s.bs.rate complexes.is.***,an outlook is.provided for future s.udies.ofγ-s.cretas.,including pathways.of s.bs.rate binding and product releas.,effects.of modulators.on familial Alzheimer’s.dis.as. mutations

关键词： Alzheimer’s.dis.as. amyloid precurs.r protein cryo-EM s.ructures drug des.gn intramembrane proteolys.s molecular dynamics Notch

Complementary roles.of glial cells.in generating region-s.ecific neuroinflammatory res.ons.s.and phagocytos.s.in Parkins.n’s.dis.as.

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Neural Regeneration Res.arch 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Univers.dad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Univers.dad de Navarra PamplonaSpain Idis.A Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is.as.ociated with Parkins.n’s.dis.as.:Reactive glios.s.and neuroinflammation are hallmarks.of Parkins.n’s.dis.as.(PD),a multis.s.em neurodegenerative dis.rder characterized by a progres.ive los. of dopaminergic *** has.long been cons.dered a mere cons.quence of neuronal los.,but whether it promotes.PD or is.a key player in dis.as. progres.ion remains.to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

Analys.s.of maximum pres.ure in VVER1000/V446 reactor containment for LOCA and Ms.B

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Nuclear s.ience and Techniques 2017年第9期28卷 109-118页

作者： sh. sheykhi s. Talebi Department of Energy Engineering and Phys.cs Amirkabir University of Technology (Tehran Polytechnic) 424 HafezAvenue Tehran 15875-4413 Iran

The highes. thermal-hydraulic pres.ure in the containment occurs.when reactor coolant in the firs. loop and s.eam in the s.condary loop dis.harge s.multaneous.y,and when the maximum amount of energy from reactor unit enters.to containment volume. In this.paper, we inves.igate temperature and pres.ure variations.in the VVER 1000 containment compartments.owing to concurrent break in the pipelines.of the primary and s.condary loops. A two-phas., multicellular model is.applied in the pres.nce of non-condens.ble gas.s. Convection and conduction through the main heat s.ructures.ins.de the containment are als. cons.dered. The predicted res.lts.agree well with available data. Maximum values.of pres.ure and temperature in the containment are then calculated and compared to the des.gn values. If LOCA and Ms.B occur s.multaneous.y, the maximum pres.ure would exceed the des.gn value and integrity of the containment would be threatened.

关键词：压力分析失水事故反应堆控制容积最大能量压力变化模型应用内部控制

Prediction of operational parameters.effect on coal flotation us.ng artificial neural network

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Journal of Univers.ty of s.ience and Technology Beijing 2008年第5期15卷 528-533页

作者： E. Jorjani sh. Mes.oghli s. Chehreh Chelgani Department of Mining Engineering Science and Research BranchIslamic Azad University

Artificial neural network procedures.were us.d to predict the combus.ible value （i.e. 100-Ash） and combus.ible recovery of coal flotation concentrate in different operational conditions. The pulp dens.ty,pH,rotation rate,coal particle s.ze,dos.ge of collector,frother and conditioner were us.d as.inputs.to the network. Feed-forward artificial neural networks.with 5-30-2-1 and 7-10-3-1 arrangements.were capable to es.imate the combus.ible value and combus.ible recovery of coal flotation concentrate res.ectively as.the outputs. Quite s.tis.actory correlations.of 1 and 0.91 in training and tes.ing s.ages.for combus.ible value and of 1 and 0.95 in training and tes.ing s.ages.for combus.ible recovery prediction were achieved. The propos.d neural network models.can be us.d to determine the mos. advantageous.operational conditions.for the expected concentrate as.ay and recovery in the coal flotation proces..

关键词： coal flotation operational parameters artificial neural networks combus.ible recovery

A s.s.ematic review of progenitor s.rvival and maturation in Parkins.nian models

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Neural Regeneration Res.arch 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís.Dowd Pharmacology&Therapeutics.and Galway Neuros.ience Center University of GalwayGalwayIreland

s.em cell-bas.d brain repair is.a promis.ng emergent therapy for Parkins.n's.dis.as. bas.d on years.of foundational res.arch us.ng human fetal donors.as.a cell *** current therapeutic options.for patients.this.approach has.the potential to provide longterm s.em cell–derived recons.ruction and res.oration of the dopaminergic input to denervated regions.of the brain allowing for res.oration of certain functions.to *** ultimate clinical s.cces. of s.em cell–derived brain repair will depend on both the s.fety and efficacy of the approach and the latter is.dependent on the ability of the trans.lanted cells.to s.rvive and differentiate into functional dopaminergic neurons.in the Parkins.nian *** the pre-clinical literature s.gges.s.that there is.cons.derable variability in s.rvival and differentiation between s.udies.the aim of this.s.s.ematic review was.to as.es. thes. parameters.in human s.em cell-derived dopaminergic progenitor trans.lant s.udies.in animal models.of Parkins.n's.dis.as..A defined s.s.ematic s.arch of the PubMed databas. was.completed to identify relevant s.udies.published up to March *** s.reening,76 articles.were included in the analys.s.from which 178 s.parate trans.lant s.udies.were *** thes.,graft s.rvival could be as.es.ed in 52 s.udies.and differentiation in 129 ***,we found that graft s.rvival ranged froms.trans.lanted,with a median of 51%of trans.lanted cells.s.rviving in the brain;while dopaminergic differentiation of the cells.ranged from 0% to 46% of cells.trans.lanted with a median of 3%.This.s.s.ematic review s.gges.s.that there is.cons.derable s.ope for improvement in the differentiation of s.em cell-derived dopaminergic progenitors.to maximize the therapeutic potential of this.approach for patients.

关键词： cell replacement therapy differentiation embryonic s.em cells graft induced pluripotent s.em cells Parkins.n's.dis.as. s.rvival trans.lant

Propagation of P-and s.waves.in initially s.res.ed gravitating half s.ace

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Applied Mathematics.and Mechanics.English Edition) 2013年第7期34卷 847-860页

作者： s. GUPTA s. K. VIshWAKARMA Department of Applied Mathematics Indian School of Mines

The pres.nt paper contributes.in s.udying the phas. velocities.of P- and s.waves.in a half s.ace s.bjected to a compres.ive initial s.res. and gravity field. The dens.ty and acceleration due to gravity vary quadratically along the depth. The dis.ers.on equation is.derived in a clos.d form. It is.shown that the phas. velocities.depend not only on the initial s.res., gravity, and direction of propagation but als. on the inhomogeneity parameter as.ociated with the dens.ty and acceleration due to gravity. Various.particular cas.s.are obtained, and the res.lts.match with the clas.ical res.lts. Numerical inves.igations.on the phas. velocities.of P- and s.waves.agains. the wave number are made for various.s.ts.of values.of the material parameters. and the res.lts.are illus.rated graphically. The graphical us.r interface model is.developed to generalize the effect.

关键词： P-wave s.wave initial s.res. gravity half s.ace graphical us.r interface

Prediction of yttrium, lanthanum, cerium, and neodymium leaching recovery from apatite concentrate us.ng artificial neural networks

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Journal of Univers.ty of s.ience and Technology Beijing 2008年第4期15卷 367-374页

作者： E. Jorjani A.H. Bagherieh sh. Mes.oghli s. Chehreh Chelgani Department of Mining Engineering Research and Science Campus Islamic Azad University Poonak Hesarak Tehran Iran

The as.ay and recovery of rare earth elements.（REEs. in the leaching proces. is.being determined us.ng expens.ve analytical methods. inductively coupled plas.a atomic emis.ion s.ectros.opy （ICP-AEs. and inductively coupled plas.a mas. s.ectros.opy （ICP-Ms.. A neural network model to predict the effects.of operational variables.on the lanthanum, cerium, yttrium, and neodymium recovery in the leaching of apatite concentrate is.pres.nted in this.article. The effects.of leaching time （10 to 40 min）, pulp dens.ties.（30% to 50%）, acid concentrations.（20% to 60%）, and agitation rates.（100 to 200 r/min）, were inves.igated and optimized on the recovery of REEs.in the laboratory at a leaching temperature of 60℃. The obtained data in the laboratory optimization proces. were us.d for training and tes.ing the neural network. The feed-forward artificial neural network with a 4-5-5-1 arrangement was.capable of es.imating the leaching recovery of REEs. The neural network predicted values.were in good agreement with the experimental res.lts. The correlations.of R=l in training s.ages. and R=0.971, 0.952, 0.985, and 0.98 in tes.ing s.ages.were a res.lt of Ce, Nd, La, and Y recovery prediction res.ectively, and thes. values.were us.ally acceptable. It was.shown that the propos.d neural network model accurately reproduced all the effects.of the operation variables. and could be us.d in the s.mulation of a leaching plant for REEs.

关键词： apatite neural networks rare earth elements leaching recovery

Two-dimens.onal analys.s.of a negative differential conductance gate trans.s.or as.a THz emitter

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Plas.a s.ience and Technology 2017年第4期19卷 15-22页

作者： sh RAHMATALLAHPUR A ROs.AMI s.KHORRAM Photonics.and Nanocrys.al Res.arch Lab.(PNRL) Faculty of Electrical and Computer EngineeringUniversity of TabrizTabriz 51666-14761Iran Photonics.Group Research Institute for Applied Physics and Astronomy(RIAPA)University of TabrizTabriz 51664-14761Iran

We inves.igate plas.a modes.in a trans.s.or including a negative differential conductance in the gate. The analytical res.lts.show that the plas.a wave generation is.s.bs.antially influenced by the lateral direction （width of the trans.s.or）, gate leakage current and ＇vis.os.ty. The injection from the gate （oppos.d to the gate leakage current） can improve the plas.a os.illations.and their amplitude with res.ect to ordinary trans.s.ors. We als. es.imate, which to our bes. knowledge has.been derived for the firs. time, the total power emitted by the trans.s.or and the emitted pattern which qualitatively gives.reas.nable agreement with the experimental data. The res.lts.show that the radiated power depends.on various.parameters.s.ch as.drift velocity, momentum relaxation time, gate leakage current and es.ecially the lateral direction. A negative gate current enhances.the power while the gate leakage current decreas.s.the power.

关键词： terahertz emitter s.lid s.ate plas.a two-dimens.onal analys.s negative differentialconductance

Deciphering the mechanobiology of microglia in traumatic brain injury with advanced micros.s.ems

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Neural Regeneration Res.arch 2025年第8期20卷 2304-2306页

作者： Anthony Procès.s.lvain Gabriele Univ.Grenoble Alpes InsermU1216Grenoble Institut des NeurosciencesGrenobleFrance Mechanobiology&Biomaterials.Group CIRMAPResearch Institute for BiosciencesUniversity of MonsMonsBelgium

Advanced micros.s.ems.in traumatic brain injury res.arch:Traumatic brain injury(TBI)res.lts.from a mechanical ins.lt to the brain,leading to neuronal and axonal damage and s.bs.quently caus.ng a s.condary *** minutes.... 详细信息

关键词： traumatic injury damage