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emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 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 Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-eM structures drug design intramembrane proteolysis molecular dynamics Notch

Quantum dynamics in ultracold atomic physics

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Frontiers of physics 2012年第1期7卷 16-30页

作者： Qiong-Yi He (1) Margaret D. Reid (1) Bogdan Opanchuk (1) Rodney Polkinghorne (1) Laura e. C. Rosales-Zárate (1) Peter D. Drummond (1) 1. Centre for Atom Optics and Ultrafast spectroscopy Swinburne University of Technology Melbourne 3122 Australia

We review recent developments in the theory of quantum dynamics in ultracold atomic physics, including exact techniques and methods based on phase-space mappings that are applicable when the complexity becomes exponentially large. Phase-space representations include the truncated Wigner, positive-P and general Gaussian operator representations which can treat both bosons and fermions. These phase-space methods include both traditional approaches using a phase-space of classical dimension, and more recent methods that use a non-classical phase-space of increased dimensionality. examples used include quantum einstein Podolsky-Rosen （ePR） entanglement of a four-mode BeC, time-reversal tests of dephasing in single-mode traps, BeC quantum collisions with up to 106 modes and 105 interacting particles, quantum interferometry in a multi-mode trap with nonlinear absorption, and the theory of quantum entropy in phase-space. We also treat the approach of variational optimization of the sampling error, giving an elementary example of a nonlinear oscillator.

关键词： quantum dynamics atomic ultracold collisions entanglement phase-space

Modulational instability of a weakly relativistic ion acoustic wave in a warm plasma with nonthermal electrons

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Chinese Physics B 2003年第7期12卷 759-764页

作者： s.K.e1-Labany M.s.AbdelKrim s.A.el-Warraki W.F.e1-Taibany PhysicsDepartment FacultyofScience-DamiettaMansouraUniversityDamiettaEI-GedidaEgypt

An investigation has been made of modulational instability of a nonlinear ion acoustic wave in a weakly relativis-tic warm unmagnetized nonthermal plasma whose constituents are an inertial ion fluid and nonthermally distributedelectrons. Up to the second order of the perturbation theory, a nonlinear schrodinger type (NsT) equation for thecomplex amplitude of the perturbed ion density is obtained. The coefficients of this equation show that the relativisticeffect, the finite ion temperature and the nonthermal electrons modify the condition of the modulational stability. Theassociation between the small-wavenumber limit of the NsT equation and the oscillatory solution of the Korteweg-deVaries equation, obtained by a reductive perturbation theory, is satisfied.

关键词： derivative expansion method warm plasma ion acoustic waves modulational instability

Modeling natural convection boundary layer flow of micropolar nanofluid over vertical permeable cone with variable wall temperature

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Applied Mathematics and Mechanics(english edition) 2017年第8期38卷 1171-1180页

作者： s.e.AHMeD Department of Mathematics Faculty of ScienceSouth Valley UniversityQena 83523Egypt

This paper discusses the natural convection boundary layer flow of a micropo- lax nanofluid over a vertical permeable cone with variable wall temperatures. Non-similax solutions are obtained. The nonlineaxly coupled differential equations under the boundary layer approximations governing the flow axe solved numerically using an efficient, itera- tive, tri-diagonal, implicit finite difference method. Different experimental correlations for both nanofluid effective viscosity and nanofluid thermal conductivity are considered. It is found that as the vortex-viscosity parameter increases, both the velocity profiles and the local Nusselt number decrease. Also, among all the nanoparticles considered in this investigation, Cu gives a good convection.

关键词： micropolar nanofluid non-similar solution cone finite difference method,non-uniform heating

Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

Understanding activity of butyrate at a cellular level

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Neural Regeneration Research 2025年第8期20卷 2323-2324页

作者： Prapti Chakraborty Angela s.Laird Macquarie University Motor Neuron Disease Research Centre Macquarie Medical SchoolFaculty of MedicineHealth and Human SciencesMacquarie UniversitySydneyAustralia

Butyrate is a short-chain fatty acid of four carbons in length that is a by-product produced by the microbial fermentation of dietary fiber and undigested carbohydrates within the *** the years,butyrate has attracted ... 详细信息

关键词： carbons butyrate fiber

Microglial dysfunction and genetic risk for neurodegenerative disease

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Neural Regeneration Research 2025年第5期20卷 1401-1402页

作者： Debra s.MacDonald Jay Penney Department of Biomedical sciences AVCUniversity of Prince Edward IslandCharlottetownPECanada

Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases a re increasing in prevalence as world populations *** tremendous progress has been made,our understanding of the mechanisms that underlie the development of these diseases remains far from com *** troubling,despite the growing emotional and financial toll being to ken by neurodegenerative disorders,existing treatment options are limited almost exclusively to those that help manage symptoms but that lack the ability to alter the progression of the disease(Liu et al.,2022).

关键词： degenerative diseases

Performance of the Aluminide Coating of someLow Alloy steels

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Journal of Materials science & Technology 1997年第6期13卷 462-466页

作者： H.M.soliman and M.e.Abd e1-Azim(Metallurgy Dept., Atomic energy Authority, Cairo, egypt ) Metallurgy Dept. Atomic Energy Authority Cairo Egypt

Two low alloy steels 0.5Cr-0.5Mo-0.25V and H85 were pack-aluminized at 900°for 4 h by using Fe-Al powder mixture containing 48% Fe, 20.6% Al- 29.4% Al2O3 and 2% NH4Cl by weight. The microhardness and oxidation resistance at 900℃ of the aluminide coatings were studied. It was found that pack-aluminizing improves the microhardness of the 0.5Cro.5Mo-0.25V steel while it reduces the microhardness of the H85 steel. Pack aluminizing highly improves the oxidation resistance after 20h exposure at 900℃ in air for the investigated steels.

关键词： Cr Performance of the Aluminide Coating of someLow Alloy steels

Antimicrobial activity of metal-substituted cobalt ferrite nanoparticles synthesized by sol-gel technique

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Particuology 2018年第5期16卷 141-151页

作者： A.H.Ashour Ahmed I.e1-Batal M.I.A.Abdel Maksoud Gharieb s.el-sayyad sh.Labib e.Abdeltwab M.M.el-Okr Materials science Laboratory Radiation Physics Department.National Center for Radiation Research and TechnologyAtomic Energy AuthorityCairoEgypt Drug Microbiology Laboratory Drug Radiation Research DepartmentNational Center for Radiation Research and TechnologyAtomic Energy Authority CairoEgypt Nuclear Chemistry Department Hot Laboratories CenterAtomic Energy AuthorityCairoEgypt Physics Department Faculty of Science (Girls Branch)Al-Azhar UniversityCairo.Egypt Physics Department.Faculty of science (Boys Branch) Al-Azhar UniversityCairoEgypt

Metal-substituted cobalt ferrites [MxCo(1-x)Fe2O4(M=Zn,Cu,Mn;x=0.0,0.25,0.5,and 0.75)]were synthesized via a sol-gel *** ferrite structures were confirmed by X-ray diffraction, Fourier transform infrared spectroscopy,scanning electron microscopy,surface analysis using the Brunauer-emmett-Teller method,and energy-dispersive X-ray *** activity of these ferrites against selected pathogenic microbes was *** structures remained cubic spinel phases after substitution of *** strongly influenced the microstructure and homoge- neous grain *** particle size of the ferrites increased linearly with increase in their annealing *** surface area of zinc cobalt ferrite nanoparticles (ZCFO)was 52.56m^2/g,the average pore size was 1.84nm,and pore volume was 0.136mL/*** ferrites showed antimicrobial activity toward all pathogens *** these,the most powerful was ZCFO,showing zones of inhibition of 13.0mm against Bacillus subtilis and staphylococcus aureus and 12.0mm against Candida ***-irradiated ZCFO nanoparticles (150.0kGy)maintained higher antimicrobial activity than non-irradiated particles,e.g. being active toward *** (16.0mm).ZCFO is proposed as a candidate material for industrial and biomedical purposes.

关键词： Antibacterial Antifungal Zone of inhibition Zinc cobalt ferrite nanoparticles Gamma irradiation