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

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

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Features on Very Peripheral Collisions of 16O-Em at 3.7A GeV

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Chinese Physics Letters 2018年第3期35卷 14-17页

作者： M.s.El-Nagdy A.abdelsalam B.M.Badawy P.i.Zarubin A.M.Abdalla A.saber Physics Department Faculty of ScienceHelwan UniversityHelwanEgypt Physics Department Faculty of ScienceCairo UniversityGizaEgypt Reactor Physics Department Atomic Energy AuthorityEgypt Joint institute for Nuclear Research DubnaMoscowRussia Department of Mathematical and Physical Engineering Faculty of Engineering in ShoubraBenha UniversityCairoEgypt

From 1540 inelastic interactions of 3. 7A GeV 160 projectile with emulsion nuclei, we select samples of 87 and 61 events carefully due to interactions of neutron （n） and singly charged particles （Z = 1）, respectively. New results concerning the topology of such events are investigated. The average multiplicities of secondary relativistic particles that appear as shower tracks for n and Z = 1 stay more or less constant when compared with analogous data on p-Em at similar energy. The multiplicity distributions and the average values of the various secondary charged particles are studied and compared with the corresponding predictions by the cascade evaporation model. The results assume that the n or Z = 1 from 16O collide peripherally with an emulsion target and are considered as an expansion to the N-N collisions.

关键词： Features on Very Peripheral Collisions of O-Em at 3.7 A GeV

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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

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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

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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

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Traveling wave solutions for shallow water equations

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Journal of Ocean Engineering and science 2017年第1期2卷 28-33页

作者： U.M.abdelsalam Department of Mathematics Faculty of ScienceFayoum UniversityAl FayoumEgypt

An extended homogeneous balance method is suggested in this *** on computerized symbolic computation and the homogeneous balance method,new exact traveling wave solutions of nonlinear partial differential equations(PDEs)are *** shallow-water equations represent a simple yet realistic set of equations typically found in atmospheric or ocean modeling applications,we consider the exact solutions of the nonlinear generalized shallow water equation and the fourth order Boussinesq *** this method,with the aid of Mathematica,many new exact traveling wave solutions are successfully obtained.

关键词： Extended homogeneous balance method shallow water equation Boussinesq equation Traveling wave solutions

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steady-state Performance Evaluation of Linux TCPs versus TCP Wave over Leaky satellite Links

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China Communications 2017年第3期14卷 17-30页

作者： Ahmed abdelsalam Cesare Roseti Francesco Zampognaro Department of Electronics Engineering University of Rome "Tor Vergata" Via del Politecnico 1 Rome 00133 Italy

internet access is becoming even more heterogeneous, including different wireless backhauling links, with Ka-band satellites as a possible alternative. since communication path is unknown a priori, adoption of PEP solutions to optimize TCP performance over satellite is discouraged to allow dynamic network reconfigurations. To opposite, an endto-end TCP performance evaluation on such a challenging scenario, with possible large latency and transmission losses, is herein considered of paramount importance. several TCP variants exist to tackle different aspects of communication networks. in Linux, the different TCP congestion control schemes differ from the theoretical formulations and RFC specifications, introducing a varying set of optimizations and options. This aspect makes difficult to identify a standard/reference TCP version for the proposed scenario, while testing with the real protocol stacks is deemed necessary to obtain consistent results. in addition, an innovative end-to-end TCP, namely TCP Wave, is introduced to replace the traditional window-based transmission with a burst-based strategy, representing a valid alternative to Linux TCP. To offer a fair, realistic and comprehensive evaluation, we configured a simulation setup where different Linux TCPs can be run within ns-3 network simulator and compared with TCP Wave.

关键词： TCP satellite internet leaky channels Linux ns-3

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Multisensory mechanisms of gait and balance in Parkinson’s disease:an integrative review

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Neural Regeneration Research 2025年第1期20卷 82-92页

作者： stiven Roytman Rebecca Paalanen Giulia Carli Uros Marusic Prabesh Kanel Teus van Laar Nico i.Bohnen Department of Radiology University of MichiganAnn ArborMIUSA Department of Neurology University of MichiganAnn ArborMIUSA Morris K.Udall Center of Excellence for Parkinson’s Disease Research University of MichiganAnn ArborMIUSA institute for Kinesiology Research Science and Research Centre KoperKoperSlovenia Department of Health sciences Alma Mater Europaea–ECMMariborSlovenia Parkinson’s Foundation Research Center of Excellence University of MichiganAnn ArborMIUSA Department of Neurology University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands Neurology service and GRECC VA Ann Arbor Healthcare SystemAnn ArborMIUSA

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging *** and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous *** effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory *** mechanisms which underpin the integration of these multisensory signals are the principal topic of the present *** multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older *** emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and *** the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s *** also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older ***,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.

关键词： aging balance encephalography functional magnetic resonance imaging gait multisensory integration Parkinson’s disease positron emission tomography somatosensory vestibular visual

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intrumer:A Multi Module Distributed Explainable iDs/iPs for securing Cloud Environment

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Computers, Materials & Continua 2025年第1期82卷 579-607页

作者： Nazreen Banu A s.K.B.sangeetha Department of Computer science and Engineering SRM Institute of Science and TechnologyVadapalani CampusChennai600026Tamil NaduIndia

The increasing use of cloud-based devices has reached the critical point of cybersecurity and unwanted network *** environments pose significant challenges in maintaining privacy and *** approaches,such as iDs,have been developed to tackle these ***,most conventional intrusion Detection system(iDs)models struggle with unseen cyberattacks and complex high-dimensional *** fact,this paper introduces the idea of a novel distributed explainable and heterogeneous transformer-based intrusion detection system,named iNTRUMER,which offers balanced accuracy,reliability,and security in cloud settings bymultiplemodulesworking together within *** traffic captured from cloud devices is first passed to the TC&TM module in which the Falcon Optimization Algorithm optimizes the feature selection process,and Naie Bayes algorithm performs the classification of *** selected features are classified further and are forwarded to the Heterogeneous Attention Transformer(HAT)*** this module,the contextual interactions of the network traffic are taken into account to classify them as normal or malicious *** classified results are further analyzed by the Explainable Prevention Module(XPM)to ensure trustworthiness by providing interpretable *** the explanations fromthe classifier,emergency alarms are transmitted to nearby iDsmodules,servers,and underlying cloud devices for the enhancement of preventive *** experiments on benchmark iDs datasets CiCiDs 2017,Honeypots,and NsL-KDD were conducted to demonstrate the efficiency of the iNTRUMER model in detecting network trafficwith high accuracy for different *** outperforms state-of-the-art approaches,obtaining better performance metrics:98.7%accuracy,97.5%precision,96.3%recall,and 97.8%*** results validate the robustness and effectiveness of iNTRUMER in securing diverse cloud environments against sophisticated cyber threats.

关键词： Cloud computing intrusion detection system transformers and explainable artificial intelligence(XAi)

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Artificial intelligence-Driven FVM-ANNModel for Entropy Analysis ofMHD Natural Bioconvection in Nanofluid-Filled Porous Cavities

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Frontiers in Heat and Mass Transfer 2024年第5期22卷 1277-1307页

作者： Noura Alsedais Mohamed Ahmed Mansour Abdelraheem M.Aly sara i.abdelsalam Department of Mathematical sciences College of SciencePrincess Nourah bint Abdulrahman UniversityRiyadh11671Saudi Arabia Mathematics Department Faculty of SciencesAssiut UniversityAssiut71515Egypt Department of Mathematics College of ScienceKing Khalid UniversityAbha62529Saudi Arabia Basic science Faculty of EngineeringThe British University in EgyptAl-Shorouk CityCairo11837Egypt instituto de Ciencias Matemáticas iCMAT CSICUAMUCMUC3MMadrid28049Spain

The research examines fluid behavior in a porous box-shaped *** fluid contains nanoscale particles and swimming microbes and is subject to magnetic forces at an *** circulation driven by biological factors is *** analysis combines a traditional numerical approach with machine learning *** equations describing the system are transformed into a dimensionless form and then solved using computational *** artificial neural network(ANN)model,trained with the Levenberg-Marquardt method,accurately predicts(Nu)values,showing high correlation(R=1),low mean squared error(MsE),and minimal error *** analysis reveals significant effects of parameters,length and location of source(B),(D),heat generation/absorption coefficient(Q),and porosity parameter(ε).increasing the cooling area length(B)reduces streamline intensity and local Nusselt and sherwood numbers,while decreasing isotherms,isoconcentrations,and *** Bejan number(Be+)decreases with increasing(B),whereas(Be+++),and global entropy(e+++)*** in(Q)slightly affect streamlines but reduce isotherm intensity and average Nusselt ***(D)significantly impacts isotherms,iso-concentrations,andmicro-rotation,altering streamline contours and local Bejan number ***(ε)enhances streamline strength and local Nusselt number profiles but has mixed effects on average Nusselt *** findings highlight the complex interactions between cooling area length,fluid flow,and heat transfer *** combining finite volume method(FVM)with machine learning technique,this study provides valuable insights into the complex interactions between key parameters and heat transfer,contributing to the development of more efficient designs in applications such as cooling systems,energy storage,and bioengineering.

关键词： ANN model finite volume method natural bioconvection flow magnetohydrodynamics(MHD) porous media

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