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.

Nanograting‑Based Dynamic Structural Colors Using Heterogeneous Materials

Dynamic structuralcolors can change in response todifferent environmental stimuli.This ability remains effectiveeven when the size of the speciesresponsible for the structural coloris reduced to a few micrometers,providing a promising sensingmechanism for solving microenvironmentalsensing problems inmicro-robotics and microfluidics.However, the lack of dynamicstructural colors that can encoderapidly, easily integrate, and accuratelyreflect changes in physical quantities hinders their use in microscale sensing applications. Herein, we present a 2.5-dimensionaldynamic structural color based on nanogratings of heterogeneous materials, which were obtained by interweaving a pH-responsive hydrogelwith an IP-L photoresist. Transverse gratings printed with pH-responsive hydrogels elongated the period of longitudinal grating in the swollenstate, resulting in pH-tuned structural colors at a 45° incidence. Moreover, the patterned encoding and array printing of dynamic structuralcolors were achieved using grayscale stripe images to accurately encode the periods and heights of the nanogrid structures. Overall, dynamicstructural color networks exhibit promising potential for applications in information encryption and in situ sensing for microfluidic chips.

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.

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.

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.

Design of Ocean Floating Structures:Prediction of Hydrodynamic Coefficients

[Introduction] Accurate calculation of the hydrodynamic coefficients for floating structures and the investigation of the flow field distribution around floating bodies on the marine free surface are essential for improving the engineering design and application of marine structures.[Method] This study utilized the computational fluid dynamics(CFD) approach and the Reynolds Averaged NavierStokes(RANS) method and considered the effects of viscosity and free surface interactions on the hydrodynamic behavior of floating structures.By employing the dynamic mesh technique,this study simulated the periodic movements of simplified three-dimensional(3D)shapes:spheres,cylinders,and cubes,which were representative of complex marine structures.The volume of fluid(VOF) method was leveraged to accurately track the nonlinear behavior of the free surface.In this analysis,the added mass and damping coefficients for the fundamental modes of motion(surge,heave,and roll) were calculated across a spectrum of frequencies,facilitating the fast determination of hydrodynamic forces and moments exerted on floating structures.[Result] The results of this study are not only consistent with the results of the 3D potential flow theory but also further reflect the role of viscosity.This method can be used for precise calculation of the hydrodynamic coefficients of floating structures and for describing the flow field of such structures in motion on a free surface.[Conclusion] The methodology presented goes beyond the traditional potential flow approach.

Dynamic Response of Tensile Membrane Structure under Coupling Effect of Wind and Rain

Because of the small stiffness and high flexibility, the tension membrane structure is easy to relax and damage or even destroy under the action of external load, which leads to the occurrence of engineering accidents. In this paper, the damped nonlinear vibration of tensioned membrane structure under the coupling action of wind and rain is approximately solved, considering the geometric nonlinearity of membrane surface deformation and the influence of air damping. Applying von Karman’s large deflection theory and D’Alembert’s principle, the governing equations are established for an analytical solution, and the experimental results are compared with the analytical results. The feasibility of this method is verified, which provides some theoretical reference for practical membrane structure engineering design and maintenance.

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.

Unveiling structural and dynamical features of chromatin using NMR spectroscopy This article is part of the virtual special issue“Solid-state NMR studies on polymers and biological solids”

Eukaryotic deoxyribonucleic acid(DNA)is wrapped around histone octamers(HOs)to form nucleosome core particles(NCPs),which in turn interact with linker DNA and linker histones to assemble chromatin fibers with more complex,high-order structures.The molecular properties of chromatin are dynamically regulated by several factors,such as post-translational modifications and effector proteins,to maintain genome stability.In the past two decades,high-resolution techniques have led to many breakthroughs in understanding the molecular mechanisms that govern chromatin regulation.Nuclear magnetic resonance(NMR)has emerged as one of the major techniques in this field,providing new insights into the nucleosomes and nucleosome-protein complexes in different states ranging from soluble form to condensed states.Solution-state NMR has proven valuable in elucidating the conformational dynamics and molecular interactions for histone N-terminal tails,histone core regions and DNA with the combination of specific isotopic labeling.Solid-state NMR,which is not constrained by the high molecular weights of complexes like nucleosomes,has been applied to capture the structural and dynamical characteristics of both flexible tails and rigid histone core regions in nucleosomes and their complexes with effector proteins.Furthermore,the combination of the two techniques allows tracking molecular properties of nucleosomes during phase separation processes,which potentially play essential roles in chromatin regulation.This review summarizes recent advances in NMR studies of chromatin structure and dynamics.It highlighted that NMR revealed unique molecular characteristics for nucleosomes that are often invisible experimentally by other techniques like cryogenic electron microscopy(cryo-EM)and X-ray diffraction(XRD).I envision that,with future ef-forts such as the development of NMR methods and optimization of sample production protocols,solution-state NMR and solid-state NMR will provide invaluable information to expand our understanding of chromatin activity and its regulatory processes.

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.

Enhancing Na^(+) diffusion dynamics and structural stability of O3-NaMn_(0.5)Ni_(0.5)O_(2)cathode by Sc and Zn dual-substitution

Sc and Zn were introduced into O3-NaMn_(0.5)Ni_(0.5)O_(2)(NaMN)using the combination of solution combustion and solid-state method.The effect of Sc and Zn dual-substitution on Na^(+) diffusion dynamics and structural stability of NaMN was investigated.The physicochemical characterizations suggest that the introduction of Sc and Zn broaden Na^(+) diffusion channels and weaken the Na—O bonds,thereby facilitating the diffusion of sodium ions.Simulations indicate that the Sc and Zn dual-substitution decreases the diffusion barrier of Na-ions and improves the conductivity of the material.The dual-substituted NaMn_(0.5)Ni_(0.4)Sc_(0.04)Zn_(0.04)O_(2)(Na MNSZ44)cathode delivers impressive cycle stability with capacity retention of 71.2%after 200 cycles at 1C and 54.8%after 400 cycles at 5C.Additionally,the full cell paired with hard carbon anode exhibits a remarkable long-term cycling stability,showing capacity retention of 64.1%after 250 cycles at 1C.These results demonstrate that Sc and Zn dual-substitution is an effective strategy to improve the Na^(+) diffusion dynamics and structural stability of NaMN.