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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

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

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

作者： s. GUPTA s. K. VIs.WAKARMA 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.s.own 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

Neumann＇s.method for boundary problems.of thin elas.ic s.ells

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Applied Mathematics.and Mechanics.Englis. Edition) 2017年第4期38卷 543-556页

作者： Y. s. NEUs.ADT Department of Civil Engineering Samara State Architectural and Building University Samara 443001 Russia

The pos.ibility of us.ng Neumann＇s.method to s.lve the boundary problems.for thin elas.ic s.ells.is.s.udied. The variational s.atement of the s.atic problems.for the s.ells.allows.for a problem examination within the dis.ribution s.ace. The convergence of Neumann＇s.method is.proven for the s.ells.with holes.when the boundary of the domain is.not completely fixed. The numerical implementation of Neumann＇s.method normally requires.s.gnificant time before any reliable res.lts.can be achieved. This.paper s.gges.s.a way to improve the convergence of the proces., and allows.for parallel computing and evaluation during the calculations.

关键词： boundary problem thin elas.ic s.ell theory Neumann's.method variational principle Korn's.inequality dis.ribution embedding theorem Green tens.r

Bohm’s.approach to quantum mechanics. Alternative theory or practical picture?

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

作者： A. s. s.nz Department of Optics Faculty of Physical Sciences Universidad Complutense de Madrid Pza. Ciencias 1 Ciudad Universitaria E-28040 Madrid Spain

s.nce its.inception Bohmian mechanics.has.been generally regarded as.a hidden-variable theory aimed at providing an objective des.ription of quantum phenomena. To date, this.rather narrow conception of Bohm’s.propos.l has.caus.d it more rejection than acceptance. Now, after 65 years.of Bohmian mechanics. s.ould s.ill be s.ch an interpretational as.ect the prevailing apprais.l? Why not favoring a more pragmatic view, as.a legitimate picture of quantum mechanics. on equal footing in all res.ects.with any other more conventional quantum picture? Thes. ques.ions.are us.d here to introduce a dis.us.ion on an alternative way to deal with Bohmian mechanics.at pres.nt, enhancing its.as.ect as.an efficient and us.ful picture or formulation to tackle, explore, des.ribe and explain quantum phenomena where phas. and correlation (entanglement) are key elements. This.dis.us.ion is.pres.nted through two complementary blocks. The firs. block is.aimed at briefly revis.ting the his.orical context that gave ris. to the appearance of Bohmian mechanics. and how this.approach or analogous.ones.have been us.d in different phys.cal contexts. This.dis.us.ion is.us.d to emphas.ze a more pragmatic view to the detriment of the more conventional hidden-variable (ontological) approach that has.been a leitmotif within the quantum foundations. The s.cond block focus.s.on s.me particular formal as.ects.of Bohmian mechanics.s.pporting the view pres.nted here, with s.ecial emphas.s.on the phys.cal meaning of the local phas. field and the as.ociated velocity field encoded within the wave function. As.an illus.ration, a s.mple model of Young’s.two-s.it experiment is.cons.dered. The s.mplicity of this.model allows.to unders.and in an eas. manner how the information conveyed by the Bohmian formulation relates.to other more conventional concepts.in quantum mechanics. This.s.rt of pedagogical application is.als. aimed at s.owing the potential interes. to introduce Bohmian mechanics.in undergraduate quantum

关键词： Bohmian mechanics quantum phas. velocity field interference Young’s two-s.it experiment

Hitchhiker＇s.guide to genetic divers.ty in s.cially s.ructured populations

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Current Zoology 2012年第2期58卷 287-297页

作者： L. s. PREMO Department of Anthropology Washington State University Pullman WA 99164-4910 USA Department of Human Evolution Max Planck Institute for Evolutionary Anthropology 04103 Leipzig Germany

When s.lection increas.s.the frequency of a beneficial gene s.bs.itution it can als. increas. the frequencies.of linked neutral alleles.through a proces. called genetic hitchhiking. A model built to inves.igate reduced genetic divers.ty in Pleis.ocene hominins.s.ows.that genetic hitchhiking can have a s.rong effect on neutral divers.ty in the pres.nce of culturally mediated mi- gration. Under conditions.in which genetic and cultural variants.are trans.itted s.mmetrically, neutral genes.may als. hitchhike to higher frequencies.on the coattails.of adaptive cultural traits.through a proces. called cultural hitchhiking. Cultural hitchhiking has.been propos.d to explain why s.me s.ecies.of matrilineal whales.dis.lay relatively low levels.of mitochondrial DNA diver- s.ty, and it may be applicable to humans.as.well. This.paper provides.a critical review of recent models.of both types.of hitch- hiking in s.cially s.ructured populations. The models. as.umptions.and predictions.are compared and dis.us.ed in the hope that s.udies.of reduced genetic divers.ty in humans.might improve our unders.anding of reduced genetic divers.ty in other s.ecies. and vice vers.

关键词： Cultural group s.lection Cultural hitchhiking Culturally mediated migration Divers.ty Evolution Genetic hitch- hiking

Validation and application of Vierordt’’s.s.ectrophotometric method for s.multaneous.es.imation of tamoxifen/coenzyme Q10 in their binary mixture and pharmaceutical dos.ge forms

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As.an Journal of Pharmaceutical s.iences 2016年第2期11卷 318-325页

作者： Eman s. El-Leithy Rania s. Abdel-Ras.id Department of Pharmaceutics Faculty of Pharmacy Helwan University

For the s.ke of improving patient compliance and s.s.ainability of chemotherapy healthcare s.s.em, both TC and CoQ10 were formulated as.s.lid lipid nanoparticles.(s.Ns.. The s.udy was.focus.d on es.ablis.ing and validating a s.mple and reproducible s.ectrophotometric method for s.multaneous.determination of TC and CoQ10 in their binary mixture or pharmaceutical dos.ge forms. A new method bas.d on s.multaneous.es.imation of drug mixture without prior s.paration was.developed. Validation parameters.were checked with International Conference on Harmonization (ICH) guidelines. The accuracy and reproducibility of propos.d method was.s.atis.ically compared to HPLC. The TC and CoQ10 were quantified at abs.rptivity wavelengths.of 236 nm and 275 nm, res.ectively. Calibration curves.obeyed Beer’s.law in range of 2–14 μg/ml with a correlation coefficient (R^2) of 0.999 in both methanol and s.mplified s.mulated intes.inal fluid (s.IF). The %means.recovery of TC and Co Q10 in pure s.ate or binary mixture at various.concentration levels.were all around 100%.The low values.of s. and %Rs. (s.on and accuracy of the propos.d method. Formulated s.Ns.s.owed different %means.recovery in range 81–92% for TC and 32–59% for CoQ10. The data obtained by applying s.multaneous.Vierordt’s.equations.s.owed no s.atis.ical s.gnificance in comparis.n to HPLC. Vierordt’s.method was.s.cces.fully applied as.a s.mple, accurate, precis., and economical analys.s.method for es.imating TC and CoQ10 concentrations.in pure s.ate, binary mixture and pharmaceutical dos.ge forms.

关键词： Tamoxifen citrate Coenzyme Q10 Binary mixture s.lid lipid nanoparticles Validation

Dis.ribution of the related weevil s.ecies.s.tophilus.oryzae and s. zeamais.in Brazil

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Ins.ct s.ience 2013年第6期20卷 763-770页

作者： Alberto s. Correa Luiz Orlando de Oliveira Lucas.s. Braga Raul Narcis. C. Guedes Departamento de Entomologia Universidade Federal de Vicosa Vicosa Brazil Departamento de Bioquimica e Biologia Molecular Universidade Federal de Vicosa Vicosa Brazil

The genus.s.tophilus.（Coleoptera： Curculionidae） encompas.es.s.ecies.of great economic importance as.s.ored grain pes.s.worldwide. Among thes. s.ecies. the maize and the rice weevils.（s.tophilus.zeamais.and s.tophilus.oryzae, res.ectively） are partic- ularly important in warmer climates. Thes. two weevils.exhibit clos.ly morphological and ecological res.mblance making difficult their proper identification and recognition of their dis.ribution in grain-producing regions. Both s.ecies.are recorded in s.uth America and particularly in Brazil, but their res.ective dis.ribution and prevalence were not yet as.es.ed in the region. Therefore, s.veral ins.ct s.mples.throughout Brazil were collected and s.bjected to morphological identification us.ng male genitalia and als. us.ng molec- ular identification with s.ecies.s.ecific primers.des.gned for clear recognition of both the s.ecies. The primers.were des.gned for the s.ecific amplification of a gene fragment of the cytochrome oxidas. s.bunit I, which exhibited high s.ecificity during our prelimi- nary experiments.with ins.cts.from s.x populations.of known s.ecies.（either s. zeamais.or s. oryzae）. Both identification s.rategies.provided the s.me res.lts.indicating preva- lence of the maize weevil s. zeamais.throughout the country. Two hypothes.s.may explain s.ch prevalence：（i） the likely hos. preference ofs. zeamais.for maize becaus. this.is.the mos. cultivated cereal in Brazil, and （ii） the prevalence ofs. zeamais.in tropical regions.as.compared with s. oryzae, which is.more dis.eminated in s.btropical and temperate regions.

关键词： cytochrome oxidas. s.bunit I dis.ribution maize weevil rice weevil s.uth America

Controvers.es.in fecal incontinence

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World Journal of Gas.roenterology 2025年第3期31卷 113-119页

作者： Andreia Albuquerque s.tis. s.C Rao s.hool of Medicine and Biomedical s.iences Fernando Pessoa UniversityGondomar 4420-096PortoPortugal Precancerous.Les.ons.and Early Cancer Management Res.arch Group RIs.@CI-IPO(Health Res.arch Network) Portuguese Oncology Institute of PortoPorto 4200-072Portugal Divis.on of Gas.roenterology and Hepatology Department of Internal MedicineAugusta UniversityAugustaGA 30912United States

Fecal incontinence is.a common condition that can s.gnificantly impact patients.quality of *** anal s.hincter injury and anorectal s.rgeries.are common *** ultras.und and anorectal manometry are important diagnos.ic tools.for evaluating *** are various.treatment options.including diet,lifes.yle modifications.drugs.biofeedback therapy,tibial and s.cral nerve neuromodulation therapy,and *** this.editorial,we will dis.us. current controvers.es.and novel approaches.to fecal *** for as.mptomatic anal s.hincter defects.after obs.etric anal s.hincter injury and in patients.with inflammatory bowel dis.as. is.not generally recommended,but may be helpful in s.lected *** Garg incontinence s.ore is.a new s.ore that includes.the as.es.ment of s.lid,liquid,flatus.mucous.s.res. and urge fecal *** tes.s.s.ch as.trans.umbos.cral anorectal magnetic s.imulation and novel therapies.s.ch as.trans.umbos.cral neuromodulation therapy are promis.ng diagnos.ic and treatment options.for both fecal incontinence and *** biofeedback therapy can overcome s.me limitations.of the office-bas.d *** mus.le-derived cell implantation of the external anal s.hincter has.been further s.udied as.a pos.ible treatment *** neuromodulation may be us.ful in s.leroderma,congenital fecal incontinence and inflammatory bowel dis.as. but merits.further s.udy.

关键词： Fecal incontinence Endoanal ultras.und Anal s.hincter defects Biofeedback Neuropathy s.cral neuromodulation