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FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival

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Neural Regeneration Research 2025年第7期20卷 2108-2115页

作者： Yuhui Kou Zongxue Jin Yusong Yuan Bo Ma Wenyong Xie na Han Department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina national Center for Trauma Medicine Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Trauma Medicine Center Peking University People’s HospitalBeijingChina Department of Orthopedics China-Japan Friendship HospitalBeijingChina

FK506(Tacrolimus)is a systemic immunosuppressant approved by the *** and Drug ***506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain *** this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function *** findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

关键词： FK506 inflammation motor neurons nerve regeneration neuron peripheral nerve injury sensory neurons

Revisiting cerebral endothelial cells in Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2911-2912页

作者： Amira s.Hanafy Department of Neurosurgery University Hospital BonnBonnGermany

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory *** only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the *** amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

关键词： Alzheimer Aβ cerebral

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

Limsup Results and LIL for Partial sum Processes of a Gaussian Random Field

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Acta Mathematica sinica,English series 2008年第9期24卷 1497-1506页

作者： Yong-kab CHOI Mikls CsRG Department of Mathematics and RINs Gyeongsang National University Jinju 660-701 Republic of Korea school of Mathematics and statistics Carleton University 1125 Colonel By DriveOttawa K1S 5B6 Canada

Let {ξ j ; j ∈ ℤ+ d be a centered stationary Gaussian random field, where ℤ+ d is the d-dimensional lattice of all points in d-dimensional Euclidean space ℝd, having nonnegative integer coordinates. For each j = (j ... 详细信息

Let {ξsUB> j sUB>; j ∈ ℤsUB>+sUB>sUP> d sUP>be a centered stationary Gaussian random field, where ℤsUB>+sUB>sUP> d sUP>is the d-dimensional lattice of all points in d-dimensional Euclidean space ℝsUP>dsUP>, having nonnegative integer coordinates. For each j = (j sUB>1 sUB>, ..., jd) in ℤsUB>+sUB>sUP> d sUP>, we denote |j| = j sUB>1 sUB>... j sUB>d sUB>and for m, n ∈ ℤsUB>+sUB>sUP> d sUP>, define s(m, n] = ΣsUB> msUB>ζsUB> j sUB>, σsUP>2sUP>(|n−m|) = Es sUP>2 sUP>(m, n], s sUB>n sUB>= s(0, n] and s sUB>0 sUB>= 0. Assume that σ(|n|) can be extended to a continuous function σ(t) of t > 0, which is nondecreasing and regularly varying with exponent α at b ≥ 0 for some 0 some additional conditions, we study limsup results for increments of partial sum processes and prove as well the law of the iterated logarithm for such partial sum processes.

关键词： stationary Gaussian random field regularly varying function large deviation probability law of the iterated logarithm

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

Chung＇s Law of the Iterated Logarithm for subfractional Brownian Motion

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Acta Mathematica sinica,English series 2017年第6期33卷 839-850页

作者： na na LUAN school of Insurance and Economics University of International Business and Economics Beijing 100029 P. R. China

Let XH = {xH（t）,t ∈ R＋} be a subfractional Brownian motion in Rd. We provide asufficient condition for a self-similar Gaussian process to be strongly locally nondeterministic and show that XH has the property of strong local nondeterminism. Applying this property and a stochastic integral representation of XH, we establish Chung＇s law of the iterated logarithm for XH.

关键词： subfractional Brownian motion self-similar Gaussian processes small ball probability,Chung's law of the iterated logarithm

Path properties of l_p-valued Gaussian random fields

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science China Mathematics 2007年第10期50卷 1501-1520页

作者： Yong-kab CHOI Miklós CsRGO Department of Mathematics Gyeongsang National UniversityJinju 660-701Korea school of Mathematics and statistics Carleton University1125 Colonel By DriveOttawaK1S 5B6Canada

General limit theorems are established for l^p-valued Gaussian random fields indexed by a multidimensional parameter,which contain both almost sure moduli of continuity and limits of large increments for the l^p-value... 详细信息

关键词： l^p-valued Gaussian random field modulus of continuity large deviation probability regularly varying function

Large-scale Estimation of Distribution Algorithms with Adaptive Heavy Tailed Random Pro jection Ensembles

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Journal of Computer science & Technology 2019年第6期34卷 1241-1257页

作者： Momodou L.sanyang Ata kabán school of Computer science University of BirminghamEdgbastonBirmingham B152TTU.K. school of Information Technology and Communication University of The GambiaSerekundaThe Gambia

We present new variants of Estimation of Distribution Algorithms (EDA) for large-scale continuous optimisation that extend and enhance a recently proposed random projection (RP) ensemble based approach. The main novelty here is to depart from the theory of RPs that require (sub-)Gaussian random matrices for norm-preservation, and instead for the purposes of high-dimensional search we propose to employ random matrices with independent and identically distributed entries drawn from a t-distribution. We analytically show that the implicitly resulting high-dimensional covariance of the search distribution is enlarged as a result. Moreover, the extent of this enlargement is controlled by a single parameter, the degree of freedom. For this reason, in the context of optimisation, such heavy tailed random matrices turn out to be preferable over the previously employed (sub-)Gaussians. Based on this observation, we then propose novel covariance adaptation schemes that are able to adapt the degree of freedom parameter during the search, and give rise to a flexible approach to balance exploration versus exploitation. We perform a thorough experimental study on high-dimensional benchmark functions, and provide statistical analyses that demonstrate the state-of-the-art performance of our approach when compared with existing alternatives in problems with 1000 search variables.

关键词： covariance adaptation estimation of distribution algorithm random projection ensemble t-distribution

Effect of a Traffic speed Based Cruise Control on an Electric Vehicle’s Performance and an Energy Consumption Model of an Electric Vehicle

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IEEE/CAA Journal of Automatica sinica 2020年第2期7卷 386-394页

作者： Anil K.Madhusudhanan Xiaoxiang na Department of Engineering University of Cambridge

This paper proposes a cruise control system(CCs)to improve an electric vehicle's range,which is a significant hurdle in market penetration of electric vehicles.A typical driver or a conventional adaptive cruise control(ACC)controls an electric vehicle(EV)such that it follows a lead vehicle or drives close to the speed *** driving behaviour may cause the EV to cruise significantly above the average traffic *** may later require the EV to slow down due to the traffic ripples,wasting a part of the EV's kinetic *** addition,the EV will also waste higher speed dependent dissipative energies,which are spent to overcome the aerodynamic drag force and rolling *** paper proposes a CCs to address this *** proposed CCs controls an EV's speed such that it prevents the vehicle from speeding significantly above the average traffic *** addition,it maintains a safe inter-vehicular distance from the lead *** design and simulation analysis of the proposed CCs were in a MATLAB simulation *** simulation environment includes an energy consumption model of an EV,which was developed using data collected from an electric bus operation in *** the simulation analysis,the proposed system reduced the EV's energy consumption by approximately 36.6%in urban drive cycles and 15.4%in motorway drive ***,the experimental analysis using a Nissan e-NV200on two urban routes showed approximately 30.8%energy savings.

关键词： Cruise control electric vehicle(EV) energy performance safety traffic