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

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 receptors.Mutations 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 well.However,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-secretase.In this review,we focus on recent studies of structural dynamic mechanisms ofγ-secretase.Different 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 simulations.While 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 findings.The approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-secretase.In addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is discussed.Finally,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 of theγ-secretase-substrate complexes.Comprehensive understanding of the functional mechanisms ofγ-secretase will greatly facilitate the rational design of effective drug molecules for treating familial Alzheimer’s disease and perhaps Alzheimer’s disease in general.

Study on the coupling calculation method for the launch dynamics of a self-propelled artillery multibody system considering engraving process

The launch dynamics theory for multibody systems emerges as an innovative and efficacious approach for the study of launch dynamics,capable of addressing the challenges of complex modeling,diminished computational efficiency,and imprecise analyses of system dynamic responses found in the dynamics research of intricate multi-rigid-flexible body systems,such as self-propelled artillery.This advancement aims to enhance the firing accuracy and launch safety of self-propelled artillery.Recognizing the shortfall of overlooking the band engraving process in existing theories,this study introduces a novel coupling calculation methodology for the launch dynamics of a self-propelled artillery multibody system.This method leverages the ABAQUS subroutine interface VUAMP to compute the dynamic response of the projectile and barrel during the launch process of large-caliber self-propelled artillery.Additionally,it examines the changes in projectile resistance and band deformation in relation to projectile motion throughout the band engraving process.Comparative analysis of the computational outcomes with experimental data evidences that the proposed method offers a more precise depiction of the launch process of self-propelled artillery,thereby enhancing the accuracy of launch dynamics calculations for self-propelled artillery.

Community structure and species diversity dynamics of a subtropical evergreen broad-leaved forest in China:2005 to 2020

Here,we characterize the temporal and spatial dynamics of forest community structure and species diversity in a subtropical evergreen broad-leaved forest in China.We found that community structure in this forest changed over a 15-year period.Specifically,renewal and death of common species was large,with the renewal of individuals mainly concentrated within a few populations,especially those of Aidia canthioides and Cryptocarya concinna.The numbers of individual deaths for common species were concentrated in the small and mid-diameter level.The spatial distribution of community species diversity fluctuated in each monitoring period,showing a more dispersed diversity after the 15-year study period,and the coefficient of variation on quadrats increased.In 2010,the death and renewal of the community and the spatial variation of species diversity were different compared to other survey years.Extreme weather may have affected species regeneration and community stability in our subtropical monsoon evergreen broad-leaved forests.Our findings suggest that strengthening the monitoring and management of the forest community will help better understand the long-and short-term causes of dynamic fluctuations of community structure and species diversity,and reveal the factors that drive changes in community structure.

Time-domain dynamic constitutive model suitable for mucky soil site seismic response

Soil nonlinear behavior displays noticeable effects on the site seismic response.This study proposes a new functional expression of the skeleton curve to replace the hyperbolic skeleton curve.By integrating shear modulus and combining the dynamic skeleton curve and the damping degradation coefficient,the constitutive equation of the logarithmic dynamic skeleton can be obtained,which considers the damping effect in a soil dynamics problem.Based on the finite difference method and the multi-transmitting boundary condition,a 1D site seismic response analysis program called Soilresp1D has been developed herein and used to analyze the time-domain seismic response in three types of sites.At the same time,this study also provides numerical simulation results based on the hyperbolic constitutive model and the equivalent linear method.The results verify the rationality of the new soil dynamic constitutive model.It can analyze the mucky soil site nonlinear seismic response,reflecting the deformation characteristics and damping effect of the silty soil.The hysteresis loop area is more extensive,and the residual strain is evident.

Ultrafast magneto-optical dynamics in nickel(111)single crystal studied by the integration of ultrafast reflectivity and polarimetry probes

With the integration of ultrafast reflectivity and polarimetry probes,we observed carrier relaxation and spin dynamics induced by ultrafast laser excitation of Ni(111)single crystals.The carrier relaxation time within the linear excitation range reveals that electron-phonon coupling and dissipation of photon energy into the bulk of the crystal take tens of picoseconds.On the other hand,the observed spin dynamics indicate a longer time of about 120 ps.To further understand how the lattice degree of freedom is coupled with these dynamics may require the integration of an ultrafast diffraction probe.

Semiclassical approach to spin dynamics of a ferromagnetic S = 1 chain

Motivated by recent experimental progress on the quasi-one-dimensional quantum magnet Ni Nb2O6, we study the spin dynamics of an S = 1 ferromagnetic Heisenberg chain with single-ion anisotropy by using a semiclassical molecular dynamics approach. This system undergoes a quantum phase transition from a ferromagnetic to a paramagnetic state under a transverse magnetic field, and the magnetic response reflecting this transition is well described by our semiclassical method.We show that at low temperature the transverse component of the dynamical structure factor depicts clearly the magnon dispersion, and the longitudinal component exhibits two continua associated with single-and two-magnon excitations,respectively. These spin excitation spectra show interesting temperature dependence as effects of magnon interactions. Our findings shed light on the experimental detection of spin excitations in a large class of quasi-one-dimensional magnets.

Transient Response and Ionic Dynamics in Organic Electrochemical Transistors

The rapid development of organic electrochemical transistors(OECTs)has ushered in a new era in organic electronics,distinguishing itself through its application in a variety of domains,from high-speed logic circuits to sensitive biosensors,and neuromorphic devices like artificial synapses and organic electrochemical random-access memories.Despite recent strides in enhancing OECT performance,driven by the demand for superior transient response capabilities,a comprehensive understanding of the complex interplay between charge and ion transport,alongside electron–ion interactions,as well as the optimization strategies,remains elusive.This review aims to bridge this gap by providing a systematic overview on the fundamental working principles of OECT transient responses,emphasizing advancements in device physics and optimization approaches.We review the critical aspect of transient ion dynamics in both volatile and non-volatile applications,as well as the impact of materials,morphology,device structure strategies on optimizing transient responses.This paper not only offers a detailed overview of the current state of the art,but also identifies promising avenues for future research,aiming to drive future performance advancements in diversified applications.

Ab initio nonadiabatic molecular dynamics study on spin–orbit coupling induced spin dynamics in ferromagnetic metals

Understanding the photoexcitation induced spin dynamics in ferromagnetic metals is important for the design of photo-controlled ultrafast spintronic device.In this work,by the ab initio nonadiabatic molecular dynamics simulation,we have studied the spin dynamics induced by spin–orbit coupling(SOC)in Co and Fe using both spin-diabatic and spin-adiabatic representations.In Co system,it is found that the Fermi surface(E_(F))is predominantly contributed by the spin-minority states.The SOC induced spin flip will occur for the photo-excited spin-majority electrons as they relax to the E_(F),and the spin-minority electrons tend to relax to the EFwith the same spin through the electron–phonon coupling(EPC).The reduction of spin-majority electrons and the increase of spin-minority electrons lead to demagnetization of Co within100 fs.By contrast,in Fe system,the E_(F) is dominated by the spin-majority states.In this case,the SOC induced spin flip occurs for the photo-excited spin-minority electrons,which leads to a magnetization enhancement.If we move the E_(F) of Fe to higher energy by 0.6eV,the E_(F) will be contributed by the spin-minority states and the demagnetization will be observed again.This work provides a new perspective for understanding the SOC induced spin dynamics mechanism in magnetic metal systems.

Target layer state estimation in multi-layer complex dynamical networks considering nonlinear node dynamics

In many engineering networks, only a part of target state variables are required to be estimated.On the other hand,multi-layer complex network exists widely in practical situations.In this paper, the state estimation of target state variables in multi-layer complex dynamical networks with nonlinear node dynamics is studied.A suitable functional state observer is constructed with the limited measurement.The parameters of the designed functional observer are obtained from the algebraic method and the stability of the functional observer is proven by the Lyapunov theorem.Some necessary conditions that need to be satisfied for the design of the functional state observer are obtained.Different from previous studies, in the multi-layer complex dynamical network with nonlinear node dynamics, the proposed method can estimate the state of target variables on some layers directly instead of estimating all the individual states.Thus, it can greatly reduce the placement of observers and computational cost.Numerical simulations with the three-layer complex dynamical network composed of three-dimensional nonlinear dynamical nodes are developed to verify the effectiveness of the method.

Structure-controlled slow dynamics in Al−Mg melts

Molecular dynamics simulation was employed to investigate the dynamical and structural properties of Al−Mg melts with the Al concentration systematically changed.The results show that the viscosity of Al67Mg33 abnormally surpasses that of Al85Mg15 below 550 K,inconsistent with the tendency at high temperatures.The evolution of the icosahedral order population is found to account for this dynamic behavior.Structural analysis shows a preferred bonding between Al and Mg atoms in the nearest neighbor shells,while a repelling tendency between them in the second shells,leading to the prepeak emergence in the partial static structure factors.The formation of icosahedral clusters is constrained in the Al-rich compositions because of the lack of sufficient Mg atoms to stabilize the clusters geometrically.These results demonstrate the structural consequence through the interplay between geometric packing and chemical interaction.These findings are crucial to understanding the structure−dynamic properties in Al−Mg melts.

Microstructural evolution and dynamic recrystallization mechanisms of additively manufactured TiAl alloy with heterogeneous microstructure during hot compression

Microstructural evolution and dynamic recrystallization(DRX)mechanisms of a Ti-48Al-2Cr-2Nb(at.%)alloy prepared by selective electron beam melting(SEBM)during hot deformation at 1150℃and 0.1 s^(-1)were investigated by hot compression tests,optical microscope(OM),scanning electron microscope(SEM),electron back-scattered diffraction(EBSD)and transmission electron microscope(TEM).The results show that the initial microstructure of the as-SEBMed alloy exhibits layers of coarseγgrains and fineγ+α_(2)+(α_(2)/γ)lamellar mixture grains alternately along the building direction.During the early stage of hot deformation,deformation twins tend to form within the coarse grains,facilitating subsequent deformation,and a small number of DRX grains appear in the fine-grained regions.With the increase of strain,extensive DRX grains are formed through different DRX mechanisms in both coarse and fine-grained regions,involving discontinuous dynamic recrystallization mechanism(DDRX)in the fine-grained regions and a coexistence of DDRX and continuous dynamic recrystallization(CDRX)in the coarsegrained regions.

The impact of demographic dynamics on food consumption and its environmental outcomes:Evidence from China

With increasing population and changing demographics,food consumption has experienced a significant transition in quantity and quality.However,a dearth of knowledge remains regarding its environmental impacts and how it responds to demographic dynamics,particularly in emerging economies like China.Using the two-stage Quadratic Almost Demand System(QUAIDS)model,this study empirically examines the impact of demographic dynamics on food consumption and its environmental outcomes based on the provincial data from 2000 to 2020 in China.Under various scenarios,according to changes in demographics,we extend our analysis to project the long-term trend of food consumption and its environmental impacts,including greenhouse gas(GHG)emissions,water footprint(WF),and land appropriation(LA).The results reveal that an increase in the proportion of senior people significantly decreases the consumption of grain and livestock meat and increases the consumption of poultry,egg,and aquatic products,particularly for urban residents.Moreover,an increase in the proportion of males in the population leads to higher consumption of poultry and aquatic products.Correspondingly,in the current scenario of an increased aging population and sex ratio,it is anticipated that GHG emissions,WF,and LA are likely to decrease by 1.37,2.52,and 3.56%,respectively.More importantly,in the scenario adhering to the standards of nutritional intake according to the Dietary Guidelines for Chinese Residents in 2022,GHG emissions,WF,and LA in urban areas would increase by 12.78,20.94,and 18.32%,respectively.Our findings suggest that changing demographics should be considered when designing policies to mitigate the diet-environment-health trilemma and achieve sustainable food consumption.

Analysis of CH_(4) and H_(2) Adsorption on Heterogeneous Shale Surfaces Using aMolecular Dynamics Approach

Determining the adsorption of shale gas on complex surfaces remains a challenge in molecular simulation studies.Difficulties essentially stem from the need to create a realistic shale structure model in terms of mineral heterogeneityand multiplicity.Moreover,precise characterization of the competitive adsorption of hydrogen andmethane in shale generally requires the experimental determination of the related adsorptive capacity.In thisstudy,the adsorption of adsorbates,methane(CH_(4)),and hydrogen(H_(2))on heterogeneous shale surface modelsof Kaolinite,Orthoclase,Muscovite,Mica,C_(60),and Butane has been simulated in the frame of a moleculardynamic’s numerical technique.The results show that these behaviors are influenced by pressure and potentialenergy.On increasing the pressure from 500 to 2000 psi,the sorption effect for CH_(4)significantly increasesbut shows a decline at a certain stage(if compared to H_(2)).The research findings also indicate that raw shalehas a higher capacity to adsorb CH_(4)compared to hydrogen.However,in shale,this difference is negligible.

Millisecond dynamics of colloidal suspension studied by X-ray photon correlation spectroscopy at the Shanghai Synchrotron Radiation Facility

X-ray photon correlation spectroscopy(XPCS)has emerged as a powerful tool for probing the nanoscale dynamics of soft condensed matter and strongly correlated materials owing to its high spatial resolution and penetration capabilities.This technique requires high brilliance and beam coherence,which are not directly available at modern synchrotron beamlines in China.To facilitate future XPCS experiments,we modified the optical setup of the newly commissioned BL10U1 USAXS beamline at the Shanghai Synchrotron Radiation Facility(SSRF).Subsequently,we performed XPCS measurements on silica suspensions in glycerol,which were opaque owing to their high concentrations.Images were collected using a high frame rate area detector.A comprehensive analysis was performed,yielding correlation functions and several key dynamic parameters.All the results were consistent with the theory of Brownian motion and demonstrated the feasibility of XPCS at SSRF.Finally,by carefully optimizing the setup and analyzing the algorithms,we achieved a time resolution of 2 ms,which enabled the characterization of millisecond dynamics in opaque systems.

Hybrid Dynamic Variables-Dependent Event-Triggered Fuzzy Model Predictive Control

This article focuses on dynamic event-triggered mechanism(DETM)-based model predictive control(MPC) for T-S fuzzy systems.A hybrid dynamic variables-dependent DETM is carefully devised,which includes a multiplicative dynamic variable and an additive dynamic variable.The addressed DETM-based fuzzy MPC issue is described as a “min-max” optimization problem(OP).To facilitate the co-design of the MPC controller and the weighting matrix of the DETM,an auxiliary OP is proposed based on a new Lyapunov function and a new robust positive invariant(RPI) set that contain the membership functions and the hybrid dynamic variables.A dynamic event-triggered fuzzy MPC algorithm is developed accordingly,whose recursive feasibility is analysed by employing the RPI set.With the designed controller,the involved fuzzy system is ensured to be asymptotically stable.Two examples show that the new DETM and DETM-based MPC algorithm have the advantages of reducing resource consumption while yielding the anticipated performance.

Uncertainty quantification of mechanism motion based on coupled mechanism—motor dynamic model for ammunition delivery system

In this paper,a dynamic modeling method of motor driven electromechanical system is presented,and the uncertainty quantification of mechanism motion is investigated based on this method.The main contribution is to propose a novel mechanism-motor coupling dynamic modeling method,in which the relationship between mechanism motion and motor rotation is established according to the geometric coordination of the system.The advantages of this include establishing intuitive coupling between the mechanism and motor,facilitating the discussion for the influence of both mechanical and electrical parameters on the mechanism,and enabling dynamic simulation with controller to take the randomness of the electric load into account.Dynamic simulation considering feedback control of ammunition delivery system is carried out,and the feasibility of the model is verified experimentally.Based on probability density evolution theory,we comprehensively discuss the effects of system parameters on mechanism motion from the perspective of uncertainty quantization.Our work can not only provide guidance for engineering design of ammunition delivery mechanism,but also provide theoretical support for modeling and uncertainty quantification research of mechatronics system.

Energy mechanism of bolt supporting effect to fissured rock under static and dynamic loads in deep coal mines

The stability control of fissured rock is difficult,especially under static and dynamic loads in deep coal mines.In this paper,the dynamic mechanical properties,strain rate evolution and energy dissipation of fissured and anchored rocks were respectively obtained by SHPB tests.It was found that bolt can provide supporting efficiency-improving effect for fissured rock against dynamic disturbance,and this effect increased quadratically with decrease in anchoring angles.Then,the energy dissipation mechanism of anchored rock was obtained by slipping model.Furthermore,bolt energy-absorbing mechanism by instantaneous tensile-shear deformation was expressed based on material mechanics,which was the larger the anchoring angle,the smaller the energy absorption,and the less the contribution to supporting efficiency improvement.On this basis,the functional relationship between energy dissipation of anchored rock and energy absorption of bolt was established.Taking the coal-gangue separation system of Longgu coal mine as an example,the optimal anchoring angle can be determined as 57.5°–67.5°.Field monitoring showed fissured rock with the optimal anchoring angle,can not only effectively control the deformation,but also fully exert the energy-absorbing and efficiency-improving effect of bolt itself.This study provides guidance to the stability control and supporting design for deep engineering under the same or similar conditions.

Analysis of mesoscopic mechanical dynamic characteristics of ballast bed with under sleeper pads

The meso-dynamical behaviour of a high-speed rail ballast bed with under sleeper pads(USPs)was studied.The geometrically irregular refined discrete element model of the ballast particles was constructed using 3D scanning techniques,and the 3D dynamic model of the rail-sleeper-ballast bed was constructed using the coupled discrete element method-multiflexible-body dynamics(DEM-MFBD)approach.We analyse the meso-mechanical dynamics of the ballast bed with USPs under dynamic load on a train and verify the correctness of the model in laboratory tests.It is shown that the deformation of the USPs increases the contact area between the sleeper and the ballast particles,and subsequently the number of contacts between them.As the depth of the granular ballast bed increases,the contact area becomes larger,and the contact force between the ballast particles gradually decreases.Under the action of the elastic USPs,the contact forces between ballast particles are reduced and the overall vibration level of the ballast bed can be reduced.The settlement of the granular ballast bed occurs mainly at the shallow position of the sleeper bottom,and the installation of the elastic USPs can be effective in reducing the stress on the ballast particles and the settlement of the ballast bed.

Inflammatory markers,oxidative stress,and mitochondrial dynamics:Repercussions on coronary artery disease in diabetes

Inflammatory markers and mediators that affect the development of cardiovascular diseases have been the focus of recent scientific work.Thus,the purpose of this editorial is to promote a critical debate about the article titled“Nε-carboxymethyl-lysine and inflammatory cytokines,markers,and mediators of coronary artery disease progression in diabetes”,published in the World Journal of Diabetes in 2024.This work directs us to reflect on the role of advanced glycation end products,which are pro-inflammatory products arising from the metabolism of fatty acids and sugars whose main marker in tissues is Nε-carboxymethyllysine(NML).Recent studies have linked high levels of pro-inflammatory agents with the development of coronary artery disease(CAD),especially tumor necrosis factor alpha,interleukins,and C-reactive protein.These inflammatory agents increase the production of reactive oxygen species(ROS),of which people with diabetes are known to have an increased production.The increase in ROS promotes lipid peroxidation,which causes damage to myocytes,promoting myocardial damage.Furthermore,oxidative stress induces the binding of NML to its receptor RAGE,which in turn activates the nuclear factor-kB,and consequently,inflammatory cytokines.These inflammatory cytokines induce endothelial dysfunction,with increased expression of adhesion molecules,changes in endothelial permeability and changes in the expression of nitric oxide.In this sense,the therapeutic use of monoclonal antibodies(inflammatory reducers such as statins and sodium-glucose transport inhibitors)has demonstrated positive results in the regression of atherogenic plaques and consequently CAD.On the other hand,many studies have demonstrated a relationship between mitochondrial dynamics,diabetes,and cardiovascular diseases.This link occurs since ROS have their origin in the imbalance in glucose metabolism that occurs in the mitochondrial matrix,and this imbalance can have its origin in inadequate diet as well as some pathologies.Photobiomodulation(PBM)has recently been considered a possible therapeutic agent for cardiovascular diseases due to its effects on mitochondrial dynamics and oxidative stress.In this sense,therapies such as PBM that act on pro-inflammatory mediators and mitochondrial modulation could benefit those with cardiovascular diseases.

Model-driven full system dynamics estimation of PMSM-driven chain shell magazine

Based on the system dynamic model, a full system dynamics estimation method is proposed for a chain shell magazine driven by a permanent magnet synchronous motor(PMSM). An adaptive extended state observer(AESO) is proposed to estimate the unmeasured states and disturbance, in which the model parameters are adjusted in real time. Theoretical analysis shows that the estimation errors of the disturbances and unmeasured states converge exponentially to zero, and the parameter estimation error can be obtained from the extended state. Then, based on the extended state of the AESO, a novel parameter estimation law is designed. Due to the convergence of AESO, the novel parameter estimation law is insensitive to controllers and excitation signal. Under persistent excitation(PE) condition, the estimated parameters will converge to a compact set around the actual parameter value. Without PE signal, the estimated parameters will converge to zero for the extended state. Simulation and experimental results show that the proposed method can accurately estimate the unmeasured states and disturbance of the chain shell magazine, and the estimated parameters will converge to the actual value without strictly continuous PE signals.