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.

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.

Spatiotemporal dynamics of the social structure of Indo-Pacific humpback dolphins(Sousa chinensis)in Xiamen waters from 2007 to 2019

As highly social animals,Indo-Pacific humpback dolphins(Sousa chinensis)exhibit community differentiation.Nevertheless,our understanding of the external and internal factors influencing these dynamics,as well as their spatiotemporal variations,is still limited.In the present study,variations in the social structure of an endangered Indo-Pacific humpback dolphin population in Xiamen Bay,China,were monitored over two distinct periods(2007–2010 and 2017–2019)to analyze the effects of habitat utilization and the composition of individuals within the population.In both periods,the population demonstrated a strikingly similar pattern of social differentiation,characterized by the division of individuals into two main clusters and one small cluster.Spatially,the two primary clusters occupied the eastern and western waters,respectively,although the core distribution area of the eastern cluster shifted further eastward between the two periods.Despite this distribution shift,the temporal stability of the social structure and inter-associations within the eastern cluster remained unaffected.A subset of 16individuals observed in both periods,comprising 51.6%and 43.2%of the population in each respective period,emerged as a foundational element of the social structure and may be responsible for sustaining social structure stability,especially during the 2007–2010 period.These observations suggest that the composition of dominant individuals,an internal factor,had a more substantial influence on the formation of the social network than changes in habitat use,an external factor.Consequently,the study proposes distinct conservation measures tailored to each of the two main clusters.

Deep structure of the Southeast Asian curved subduction system and its dynamic process

The deep structure,material circulation,and dynamic processes in the Southeast Asia have long been an elusive scientific puzzle due to the lack of systematic scientific observations and recognized theoretical models.Based on the deep seismic tomography using long-period natural earthquake data,in this study,the deep structure and material circulation of the curved subduction system in Southeast Asia was studied,and the dynamic processes since 100 million years ago was reconstructed.It is pointed out that challenges still exist in the precise reconstruction of deep mantle structures of the study area,the influence of multi-stage subduction on deep material exchange and shallow magma activity,as well as the spatiotemporal evolution and coupling mechanism of multi-plate convergence.Future work should focus on high-resolution land-sea joint 3-D seismic tomography imaging of the curved subduction system in the Southeast Asia,combined with geochemical analysis and geodynamic modelling works.

The chemical environment and structural ordering in liquid Mg-Y-Zn system:An ab-initio molecular dynamics investigation of melt for the formation mechanism of LPSO structure

In an effort to clarify the formation mechanism of LPSO structure in Mg-Y-Zn alloy,the chemical environment and structural ordering in liquid Mg-rich Mg-Y-Zn system are investigated with the aid of ab-initio molecular dynamics simulation.In liquid Mg-rich Mg-Y alloys,the strong Mg-Y interaction is determined,which promotes the formation of fivefold symmetric local structure.For Mg-Zn alloys,the weak Mg-Zn interaction results in the fivefold symmetry weakening in the liquid structure.Due to the coexistence of Y and Zn,the strong attractive interaction is introduced in liquid Mg-Y-Zn ternary alloy,and contributes to the clustering of Mg,Y,Zn launched from Zn.What is more,the distribution of local structures becomes closer to that in pure Mg compared with that in binary Mg-Y and Mg-Zn alloys.These results should relate to the origins of the Y/Zn segregation zone and close-packed stacking mode in LPSO structure,which provides a new insight into the formation mechanism of LPSO structure at atomic level.

Evolutionary game dynamics of combining two different aspiration-driven update rules in structured populations

In evolutionary games,most studies on finite populations have focused on a single updating mechanism.However,given the differences in individual cognition,individuals may change their strategies according to different updating mechanisms.For this reason,we consider two different aspiration-driven updating mechanisms in structured populations:satisfied-stay unsatisfied shift(SSUS)and satisfied-cooperate unsatisfied defect(SCUD).To simulate the game player’s learning process,this paper improves the particle swarm optimization algorithm,which will be used to simulate the game player’s strategy selection,i.e.,population particle swarm optimization(PPSO)algorithms.We find that in the prisoner’s dilemma,the conditions that SSUS facilitates the evolution of cooperation do not enable cooperation to emerge.In contrast,SCUD conditions that promote the evolution of cooperation enable cooperation to emerge.In addition,the invasion of SCUD individuals helps promote cooperation among SSUS individuals.Simulated by the PPSO algorithm,the theoretical approximation results are found to be consistent with the trend of change in the simulation results.

Experimental crushing behavior and energy absorption of angular gradient honeycomb structures under quasi-static and dynamic compression

The high variability of shock in terrorist attacks poses a threat to people's lives and properties,necessitating the development of more effective protective structures.This study focuses on the angle gradient and proposes four different configurations of concave hexagonal honeycomb structures.The structures'macroscopic deformation behavior,stress-strain relationship,and energy dissipation characteristics are evaluated through quasi-static compression and Hopkinson pressure bar impact experiments.The study reveals that,under varying strain rates,the structures deform starting from the weak layer and exhibit significant interlayer separation.Additionally,interlayer shear slip becomes more pronounced with increasing strain rate.In terms of quasi-static compression,symmetric gradient structures demonstrate superior energy absorption,particularly the symmetric negative gradient structure(SNG-SMS)with a specific energy absorption of 13.77 J/cm~3.For dynamic impact,unidirectional gradient structures exhibit exceptional energy absorption,particularly the unidirectional positive gradient honeycomb structure(UPG-SML)with outstanding mechanical properties.The angle gradient design plays a crucial role in determining the structure's stability and deformation mode during impact.Fewer interlayer separations result in a more pronounced negative Poisson's ratio effect and enhance the structure's energy absorption capacity.These findings provide a foundation for the rational design and selection of seismic protection structures in different strain rate impact environments.

A process monitoring method for autoregressive-dynamic inner total latent structure projection

As a dynamic projection to latent structures(PLS)method with a good output prediction ability,dynamic inner PLS(DiPLS)is widely used in the prediction of key performance indi-cators.However,due to the oblique decomposition of the input space by DiPLS,there are false alarms in the actual industrial process during fault detection.To address the above problems,a dynamic modeling method based on autoregressive-dynamic inner total PLS(AR-DiTPLS)is proposed.The method first uses the regression relation matrix to decompose the input space orthogonally,which reduces useless information for the predic-tion output in the quality-related dynamic subspace.Then,a vector autoregressive model(VAR)is constructed for the predic-tion score to separate dynamic information and static informa-tion.Based on the VAR model,appropriate statistical indicators are further constructed for online monitoring,which reduces the occurrence of false alarms.The effectiveness of the method is verified by a Tennessee-Eastman industrial simulation process and a three-phase flow system.

Molecular dynamics simulation of relationship between local structure and dynamics during glass transition of Mg_7Zn_3 alloy

The rapid solidification process of Mg7Zn3 alloy was simulated by the molecular dynamics method. The relationship between the local structure and the dynamics during the liquid-glass transition was deeply investigated. It was found that the Mg-centered FK polyhedron and the Zn-centered icosahedron play a critical role in the formation of Mg7Zn3 metallic glass. The self-diffusion coefficients of Mg and Zn atoms deviate from the Arrhenius law near the melting temperature and then satisfy the power law. According to the time correlation functions of mean-square displacement, incoherent intermediate scattering function and non-Gaussian parameter, it was found that the β-relaxation in Mg7Zn3 supercooled liquid becomes more and more evident with decreasing temperature, and the α-relaxation time rapidly increases in the VFT law. Moreover, the smaller Zn atom has a faster relaxation behavior than the Mg atom. Some local atomic structures with short-range order have lower mobility, and they play a critical role in the appearance of cage effect in theβ-relaxation regime. The dynamics deviates from the Arrhenius law just at the temperature as the number of local atomic structures begins to rapidly increase. The dynamic glass transition temperature （Tc） is close to the glass transition point in structure （TgStr）.

DYNAMIC RESPONSE OPTIMIZATION DESIGN FOR ENGINEERING STRUCTURES BASED ON RELIABILITY

In many practical structures, physical parameters of material and applied loads have random property.To optimize this kind of structures,an optimum mathematical model was built.This model has reliability constraints on dynamic stress and displacement and upper & lower limits of the design variables. The numerical characteristic of dynamic response and sensitivity of dynamic response based on probability of structure were deduced respectively. By equivalent disposing, the reliability constraints were changed into conventional forms. The SUMT method was used in the optimization process.Two examples illustrate the correctness and practicability of the optimum model and solving approach.

Vegetation landscape structure and dynamics in sandy forest-steppe ecotone

Sandy forest-steppe ecotone in Baiyinaobao Natural Reserve of Inner Mongolia Autonomous Region of China is one of the special landscape types in forest-steppe vegetation zone in China. Vegetation landscape types, landscape patches, and patch size were measured by the field investigation, forest photograph, and airscape. The structure of landscape patches in sandy forest-steppe ecotone, including composition structure, and size structure, was studied and the dynamics and transformation of landscape patches were analyzed. The data obtained in this study could provide theoretical basis for the research on vegetation landscape in forest-steppe ecotones and other vegetation types.

Dynamic Interaction Analysis of Coupled Axial-Torsional-Lateral Mechanical Vibrations in Rotary Drilling Systems

Maintaining the integrity and longevity of structures is essential in many industries,such as aerospace,nuclear,and petroleum.To achieve the cost-effectiveness of large-scale systems in petroleum drilling,a strong emphasis on structural durability and monitoring is required.This study focuses on the mechanical vibrations that occur in rotary drilling systems,which have a substantial impact on the structural integrity of drilling equipment.The study specifically investigates axial,torsional,and lateral vibrations,which might lead to negative consequences such as bit-bounce,chaotic whirling,and high-frequency stick-slip.These events not only hinder the efficiency of drilling but also lead to exhaustion and harm to the system’s components since they are difficult to be detected and controlled in real time.The study investigates the dynamic interactions of these vibrations,specifically in their high-frequency modes,usingfield data obtained from measurement while drilling.Thefindings have demonstrated the effect of strong coupling between the high-frequency modes of these vibrations on drilling sys-tem performance.The obtained results highlight the importance of considering the interconnected impacts of these vibrations when designing and implementing robust control systems.Therefore,integrating these compo-nents can increase the durability of drill bits and drill strings,as well as improve the ability to monitor and detect damage.Moreover,by exploiting thesefindings,the assessment of structural resilience in rotary drilling systems can be enhanced.Furthermore,the study demonstrates the capacity of structural health monitoring to improve the quality,dependability,and efficiency of rotary drilling systems in the petroleum industry.

Self‑Healing Dynamic Hydrogel Microparticles with Structural Color for Wound Management

Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing circumstances.It is vital to develop multifunctional hydrogel dressings,with well-designed morphology and structure to enhance flexibility and effectiveness in wound management.To achieve these,we propose a self-healing hydrogel dressing based on structural color microspheres for wound management.The microsphere comprised a photothermal-responsive inverse opal framework,which was constructed by hyaluronic acid methacryloyl,silk fibroin methacryloyl and black phosphorus quantum dots(BPQDs),and was further re-filled with a dynamic hydrogel.The dynamic hydrogel filler was formed by Knoevenagel condensation reaction between cyanoacetate and benzaldehyde-functionalized dextran(DEX-CA and DEX-BA).Notably,the composite microspheres can be applied arbitrarily,and they can adhere together upon near-infrared irradiation by leveraging the BPQDs-mediated photothermal effect and the thermoreversible stiffness change of dynamic hydrogel.Additionally,eumenitin and vascular endothelial growth factor were co-loaded in the microspheres and their release behavior can be regulated by the same mechanism.Moreover,effective monitoring of the drug release process can be achieved through visual color variations.The microsphere system has demonstrated desired capabilities of controllable drug release and efficient wound management.These characteristics suggest broad prospects for the proposed composite microspheres in clinical applications.

Theory and practice for assessing structural integrity and dynamical integrity of high-speed trains

Purpose–The safety and reliability of high-speed trains rely on the structural integrity of their components and the dynamic performance of the entire vehicle system.This paper aims to define and substantiate the assessment of the structural integrity and dynamical integrity of high-speed trains in both theory and practice.The key principles and approacheswill be proposed,and their applications to high-speed trains in Chinawill be presented.Design/methodology/approach–First,the structural integrity and dynamical integrity of high-speed trains are defined,and their relationship is introduced.Then,the principles for assessing the structural integrity of structural and dynamical components are presented and practical examples of gearboxes and dampers are provided.Finally,the principles and approaches for assessing the dynamical integrity of highspeed trains are presented and a novel operational assessment method is further presented.Findings–Vehicle system dynamics is the core of the proposed framework that provides the loads and vibrations on train components and the dynamic performance of the entire vehicle system.For assessing the structural integrity of structural components,an open-loop analysis considering both normal and abnormal vehicle conditions is needed.For assessing the structural integrity of dynamical components,a closed-loop analysis involving the influence of wear and degradation on vehicle system dynamics is needed.The analysis of vehicle system dynamics should follow the principles of complete objects,conditions and indices.Numerical,experimental and operational approaches should be combined to achieve effective assessments.Originality/value–The practical applications demonstrate that assessing the structural integrity and dynamical integrity of high-speed trains can support better control of critical defects,better lifespan management of train components and better maintenance decision-making for high-speed trains.

Dynamic behavior of new cutting subgrade structure of expensive soil under train loads coupling with service environment

Expansive soil is sensitive to dry and wet environment change. And the volume deformation and inflation pressure of expansive soil may induce to cause the deformation failure of roadbed or many other adverse effects. Aimed at a high-speed railway engineering practice in the newly built Yun-Gui high-speed railway expansive soil section in China, indoor vibration test on a full-scaled new cutting subgrade model is carried out. Based on the established track-subgrade-foundation of expansive soil system dynamic model test platform, dynamic behavior of new cutting subgrade structure under train loads coupling with extreme service environment(dry, raining, and groundwater level rising) is analyzed comparatively. The results show that the subgrade dynamic response is significantly influenced by service conditions and the dynamic response of subgrade gradually becomes stable with the increasing vibration times under various service environment conditions. The vertical dynamic soil stress is related with the depth in an approximate exponential function, and the curves of vertical dynamic soil stress present a "Z" shape distribution along transverse distance. The peak value of dynamic soil stress appears below the rail, and it increases more obviously near the roadbed surface. However, the peak value of dynamic soil stress is little affected outside 5.0 m of center line. The vibration velocity and acceleration are in a quadratic curve with an increase in depth, and the raining and groundwater level rising increase both the vibration velocity and the acceleration. The vertical deformations at different depths are differently affected by service environment in roadbed. The deformation of roadbed increases sharply when the water gets in the foundation of expansive soil, and more than 60% of the total deformation of roadbed occurs in expansive soil foundation. The laid waterproofing and drainage structure layer, which weakens the dynamic stress and improves the track regularity, presents a positive effect on the control deformation of roadbed surface. An improved empirical formula is then proposed to predict the dynamic stress of ballasted tracks subgrade of expansive soil.

Research on the Agriculture Production Structure in Shandong Province Based on the Grey Relational Dynamic Analysis

In accordance with grey relational dynamic analysis, overall structure and inner structure of agriculture were analyzed and the grey relational sequence inte- grals were concluded of Shandong agriculture during 2003-2014. Besides, the re- search analyzed the contributions by specific agricultural sectors and Shandong a- gricultural structure from natural endowments, policy, and agricultural modernization. Finally, the development countermeasures and suggestions were proposed.

λ-PDF AND GEGENBAUER POLYNOMIAL APPROXIMATION FOR DYNAMIC RESPONSE PROBLEMS OF RANDOM STRUCTURES

A bounded,mono-peak,and symmetrically distributed probability density function, called λ-PDF,together with the Gegenbauer polynomial approximation,is used in dynamic response problems of random structures.The λ-PDF can reasonably model a variety of random parameters in engineering random structures.The Gegenbauer polynomial approximation can be viewed as a new extension of the weighted residual method into the random space.Both of them can be easily used by scientists and engineers,and applied to a variety of response problems of random structures.The numerical example shows the effectiveness of the proposed method to study dynamic phenomena in random structures.

Effects of Joint on Dynamics of Space Deployable Structure

Joints are necessary components in large space deployable truss structures which have significant effects on dynamic behavior of these joint dominated structures.Previous researches usually analyzed effects of one or fewer joint characters on dynamics of jointed structures.Effects of joint stiffness,damping,location,number,clearance and contact stiffness on dynamics of jointed structures are systematically analyzed.Cantilever beam model containing linear joints is developed based on finite element method,influence of joint on natural frequencies and mode shapes of the jointed system are analyzed.Analytical results show that frequencies of jointed system decrease dramatically when peak mode shapes occur at joint locations,and there are cusp shapes present in mode shapes.System frequencies increase with joint damping increasing,there are different joint damping to achieve maximum system damping for different joint stiffness.Joint nonlinear force-displacement is described by describing function method,one-DOF model containing nonlinear joints is established to analyze joints freeplay and hysteresis nonlinearities.Analysis results show that nonlinear effects of freeplay and hysteresis make dynamic responses switch from one resonance frequency to another frequency when amplitude exceed demarcation values.Joint contact stiffness determine degree of system nonlinearity,while exciting force level,clearance and slipping force affect amplitude of dynamic response.Dynamic responses of joint dominated deployable truss structure under different sinusoidal exciting force levels are tested.The test results show obvious nonlinear behaviors contributed by joints,dynamic response shifts to lower frequency and higher amplitude as exciting force increasing.The test results are further compared with analytical results,and joint nonlinearity tested is coincident with hysteresis nonlinearity.Analysis method of joint effects on dynamic characteristics of jointed system is proposed,which can be used in optimal design of joint parameters to achieve optimum dynamic performance of jointed system.

TOPOLOGY OPTIMIZATION OF TRUSS STRUCTURE WITH FUNDAMENTAL FREQUENCY AND FREQUENCY DOMAIN DYNAMIC RESPONSE CONSTRAINTS

In this paper, adaptive genetic algorithm （AGA） is applied to topology optimization of truss structure with frequency domain excitations. The optimization constraints include fundamental frequency, displacement responses under force excitations and acceleration responses under foundation acceleration excitations. The roulette wheel selection operator, adaptive crossover and mutation operators are used as genetic operators. Some heuristic strategies are put forward to direct the deletion of the extra bars and nodes on truss structures. Three examples demonstrate that the proposed method can yield the optimum structure form and the lightest weight of the given ground structure while satisfying dynamic response constraints.

Phytosociology, structure and dynamics of Pinus roxburghii associations from Northern Pakistan

We investigated the phytosociology, structure and dynamics of Pinus roxburghii in 40 stands in northern areas of Pakistan by using cluster analysis （Ward’s agglomerative clustering） and ordination （Non-metric Multidimensional Scaling）. Cluster analysis revealed three major groups associated with specific environmental characteristics： （1） P. roxburghii （2） Pinus-Quercus baloot and （3） Pinus-Olea ferruginea community types. NMS-ordination showed the major gradient as an amalgam of elevation （r2=0.441, p＆lt;0.01） and slope （r2=0.391, p＆lt;0.05） as the two topographic factors correlated with species distribution. The first ordination axis also showed positive correlation with soil variables like pH and electrical conductivity, suggesting that soil chemistry was related to topographic characteristics and probably acted as a secondary gradient. We also examined size class distributions, age structures and growth rates of the three communities in order to describe community development and dynamics. Total tree density was 14700 plants/ha, with P. roxburghii having a relative density of 82%to 100%. Density of juve-nile and total density and basal area of the subordinate tree species were low. The low density of trees in the smallest diameter size-class sug-gested that the recruitment of small P. roxburghii plants into the adult population may be lower than the required replacement rate for the stands. Pooled size-class distributions for the species showed a multimo-dal pattern with some regeneration gaps. Browsing, heavy logging and＆amp;nbsp;other anthropogenic activities were the overriding factors responsible for the poor recruitment of P. roxburghii. We concluded from the age struc-ture that the forests were characterized by the dominance of young trees. Growth rate analysis revealed that P. roxburghii was the fastest growing species among the conifers species in Pakistan. In view of its relatively fast growth and longevity, P. roxburghii seems to be a suitable choice for short-term cultural practices in order to enhance wood production in lesser Himalaya and Hindukush ranges of Pakistan.