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.

Simulation of large-scale numerical substructure in real-time dynamic hybrid testing

A solution scheme is proposed in this paper for an existing RTDHT system to simulate large-scale finite element （FE） numerical substructures. The analysis of the FE numerical substructure is split into response analysis and signal generation tasks, and executed in two different target computers in real-time. One target computer implements the response analysis task, wherein a large time-step is used to solve the FE substructure, and another target computer implements the signal generation task, wherein an interpolation program is used to generate control signals in a small time-step to meet the input demand of the controller. By using this strategy, the scale of the FE numerical substructure simulation may be increased significantly. The proposed scheme is initially verified by two FE numerical substructure models with 98 and 1240 degrees of freedom （DOFs）. Thereafter, RTDHTs of a single frame-foundation structure are implemented where the foundation, considered as the numerical substructure, is simulated by the FE model with 1240 DOFs. Good agreements between the results of the RTDHT and those from the FE analysis in ABAQUS are obtained.

Early warning of coal dynamic disaster by precursor of AE and EMR"quiet period"

Efcient and accurate monitoring and early warning of coal dynamic disaster and other disasters can provide guarantee for the efcient operation of mine transportation system.However,the traditional threshold early warning method often fails to warning some accidents.To address above issues,a new early warning method was proposed based on"quiet period"phenomenon of AE and EMR during fracture.It is found that,a"quiet period"of AE and EMR was present before the load reaches the peak stress,which could be used as one of the precursors to warn the imminent failure of coal and rock specimens.MS and AE signals increased abnormally followed by the phenomenon of"quiet period"before the occurrence of coal dynamic disaster on site,and the decrease of MS events in the"quiet period"is about 57%–88%compared with that in previous abnormal increase stage.During the damage evolution of coal and rock,"quiet period"phenomenon usually occurred at 85%–90%of the peak stress,where the slope of damage parameter curve is almost zero.The"quiet period"of the AE-EMR signals and the low change rate of damage parameter before failure provide a theoretical foundation for the coal dynamic disaster warning based on the"quiet period"precursor found in MS-AE-EMR monitoring system.These fndings will help reduce the number of under-reported events and improve early warning accuracy.

Vehicle routing optimization algorithm based on time windows and dynamic demand

To provide the supplier with the minimizum vehicle travel distance in the distribution process of goods in three situations of new customer demand,customer cancellation service,and change of customer delivery address,based on the ideas of pre-optimization and real-time optimization,a two-stage planning model of dynamic demand based vehicle routing problem with time windows was established.At the pre-optimization stage,an improved genetic algorithm was used to obtain the pre-optimized distribution route,a large-scale neighborhood search method was integrated into the mutation operation to improve the local optimization performance of the genetic algorithm,and a variety of operators were introduced to expand the search space of neighborhood solutions;At the real-time optimization stage,a periodic optimization strategy was adopted to transform a complex dynamic problem into several static problems,and four neighborhood search operators were used to quickly adjust the route.Two different scale examples were designed for experiments.It is proved that the algorithm can plan the better route,and adjust the distribution route in time under the real-time constraints.Therefore,the proposed algorithm can provide theoretical guidance for suppliers to solve the dynamic demand based vehicle routing problem.

Features and physical proces of the dynamic evolution pattern of ground resistivity precursor front

In order to quantitatively describe the geoelectric precursor anomaly in the short-impending process of earthquakes, a new geoelectric precursor index — (monthly) relative change rate of ground resistivity, R ρ (t) , is designed. Using this index and choosing the internationally accepted ground resistivity data before the Tangshan M =7.8 earthquake of July 28, 1976, the features of dynamic evolution pattern of R ρ(t) are studied. The results show that: ① about 10～9 months before earthquake, the ground resistivity in a certain range around the epicentral region begins to display the anomaly of accelerating descent, and the rate of descent is higher in the epicentral region than in surrounding areas; ② with the shortening of countdown before earthquake, the R ρ(t) value in epicentral region increases gradually (ground resistivity value decreases at an increasing rate); ③ the R ρ(t) value has the epicentral area as a center and its contour lines propagate towards surrounding areas with the shortening of countdown before earthquake; ④after the R ρ(t) value in epicentral region has descended at increasing rate to reach an extremity [ R ρ(t) = (7.0], it turns to descend at decreasing rate (2～3 months) and earthquake occurs when it accelerates again. Meanwhile, earthquake occurs when the contour lines of R ρ(t) stop propagating towards surrounding areas and turn to shrink back (2～3 months later). Its physical process can be explained by the″ swollen hypothesis″ of Prof. Fu and the theory of ″Slip-weakening and rockmass instability″ of Mei, Niu, et al ..

DRX rules during extrusion process of large-scale thick-walled Inconel 625 pipe by FE method

A thermal-mechanical and micro-macro coupled finite element（FE） model for the hot extrusion process of large-scale thick-walled Inconel 625 pipe was developed based on the DEFORM-2D platform.Then,the influence rules of the key extrusion parameters on the average grain size and grain uniformity of the extruded pipe were revealed.The results show that with the increase of initial billet temperature,extrusion speed and friction coefficient,the grain uniformity is firstly improved and then deteriorated.Larger extrusion ratio leads to more uniform grain distribution.With the increase of initial billet temperature,the average grain size of the pipe first decreases and then increases.Additionally,larger extrusion ratio can bring smaller average grain size.The extrusion speed and friction coefficient have slight effects on the average grain size of the extruded pipe.

Dynamics of Spreading of Liquid on Solid Surface

Based on assuming that there is the precursor film in the front of the apparent contact line （ACL）, a model was proposed to understand the dynamic wetting process and associated dynamic contact angle. The present model indicated that a new dimensionless characteristic parameter, 2, attects the dynamic wetting process and associated dynamic contact angle as well. However, the previous model suggested that the dynamic contact angle is dependent＇on the capillary number and static contact angle only. An experimental investigation was conducted to measure the dynamic wetting behavior of silicon oil moving over glass, aluminum and stainless steel surfaces. It concluded that when the value of 2 was selected as 0.07, 0.16 and 0.35 for glass, aluminum and stainless steel, respectively, the experimental results were in good accordance with the prediction of the model. Furthermore, the comparison of the model with Strom＇s experimental data showed that 2 is independent on the species of liquids. Apparently, 2 should be interpreted as the effect of the solid surface properties on the dynamic wetting process.Meanwhile, it is found in the present experiment that the Hoffman-Voinov-Tanner law, which is valid at very low capillary number （Ca 〈〈 1 or 80〈 10°） recommend by Cazabat, still holds for higher contact angles, even up to 70°-80°. This is explained by （he present model very well.

Filter-based iterative learning control for linear large-scale industrial processes

In the procedure of the steady-state hierarchical optimization with feedback for large-scale industrial processes, a sequence of set-point changes with different magnitudes is carried out on the optimization layer. To improve the dynamic performance of transient response driven by the set-point changes, a filter-based iterative learning control strategy is proposed. In the proposed updating law, a local-symmetric-integral operator is adopted for eliminating the measurement noise of output information,a set of desired trajectories are specified according to the set-point changes sequence, the current control input is iteratively achieved by utilizing smoothed output error to modify its control input at previous iteration, to which the amplified coefficients related to the different magnitudes of set-point changes are introduced. The convergence of the algorithm is conducted by incorporating frequency-domain technique into time-domain analysis. Numerical simulation demonstrates the effectiveness of the proposed strategy,

Temperature control for thermal treatment of aluminum alloy in a large-scale vertical quench furnace

The temperature control of the large-scale vertical quench furnace is very difficult due to its huge volume and complex thermal exchanges. To meet the technical requirement of the quenching process, a temperature control system which integrates temperature calibration and temperature uniformity control is developed for the thermal treatment of aluminum alloy workpieces in the large-scale vertical quench furnace. To obtain the aluminum alloy workpiece temperature, an air heat transfer model is newly established to describe the temperature gradient distribution so that the immeasurable workpiece temperature can be calibrated from the available thermocouple temperature. To satisfy the uniformity control of the furnace temperature, a second order partial differential equation(PDE) is derived to describe the thermal dynamics inside the vertical quench furnace. Based on the PDE, a decoupling matrix is constructed to solve the coupling issue and decouple the heating process into multiple independent heating subsystems. Then, using the expert control rule to find a compromise of temperature rising time and overshoot during the quenching process. The developed temperature control system has been successfully applied to a 31 m large-scale vertical quench furnace, and the industrial running results show the significant improvement of the temperature uniformity, lower overshoot and shortened processing time.

Research on dynamics patterns and parameter characters of crustal deformation field before and after strong earthquake

Based on the dynamic monitoring data of crustal deformation, the parameter evolution for the dynamics pattern and fractal dimension of crustal deformation field and the integral activity level of many faults etc. before and after the Tangshan (1976) and Lijiang (1996) strong earthquakes and others are studied by using the method of pattern dynamics. It is exposed that two time space characters, the ordered dimension drop of the deformation field and the accelerated motion of multi fault before an earthquake, are probably caused by the deformation localization and fault softening after the seismogenic process enters the nonlinear stage. They could be an important seismic precursor if they occurred repeatedly before strong earthquakes.

An approach on dynamic earthquake prediction by georesistivitymeasurements

Experiences on earthquake prediction accumulated by the Chinese scientists in the last 20 years were synthetically analyzed. A prediction program was set up to demonstrate the development of the georesistivity anomaly by using of the dynamic image, accordingly the earthquake prone area can be recognized. By revising the DYBS Ⅰ, which was developed in 1989, and adding some latest achievements, we worked out a software on earthquake prediction by the geoelectric method the DYBS Ⅱ. Some new feature of DYBS Ⅱ are: the anomalous area may be determined by the space distribution and its time variation of geoelectric parameters; The dynamic process that is associated with the development of earthquake anomaly can be displayed on the computer screen; Technique for the prediction of an impending earthquake was included too. Some results of the Tangshan earthquake were presented at the end of this paper.

An Adaptive Sliding Mode Tracking Controller Using BP Neural Networks for a Class of Large-scale Nonlinear Systems

A new type controller, BP neural-networks-based sliding mode controller is developed for a class of large-scale nonlinear systems with unknown bounds of high-order interconnections in this paper. It is shown that decentralized BP neural networks are used to adaptively learn the uncertainty bounds of interconnected subsystems in the Lyapunov sense, and the outputs of the decentralized BP neural networks are then used as the parameters of the sliding mode controller to compensate for the effects of subsystems uncertainties. Using this scheme, not only strong robustness with respect to uncertainty dynamics and nonlinearities can be obtained, but also the output tracking error between the actual output of each subsystem and the corresponding desired reference output can asymptotically converge to zero. A simulation example is presented to support the validity of the proposed BP neural-networks-based sliding mode controller.

On the conjunction practical stability and controllability of large-scale impulsive control systems

We studied the conjunction practical stability and controllability of large-scale impulsive control systems by using the comparison systems and vector Lyapunov fimctions. Then the less conservative sufficient conditions for conjunction practical stability and controllability of large-scale impulsive control system were obtained.

Free-Interface Dual-Compatibility Modal Synthesis Substructure Method in Large-Scale Structures

Free-interface dual-compatibility modal synthesis method(compatibility of both force and displacement on interfaces)is introduced to large-scale civil engineering structure to enhance computation efficiency. The basic equations of the method are first set up, and then the mode cut-off principle and the dividing principle are proposed. MATLAB is used for simulation in different frame structures. The simulation results demonstrate the applicability of this substructure method to civil engineering structures and the correctness of the proposed mode cut-off principle. Studies are also conducted on how to divide the whole structure for better computation efficiency while maintaining better precision. It is observed that the geometry and material properties should be considered, and the synthesis results would be more precise when the inflection points of the mode shapes are taken into consideration. Furthermore, the simulation performed on a large-scale high-rise connected structure further proves the feasibility and efficiency of this modal synthesis method compared with the traditional global method. It is also concluded from the simulation results that the fewer number of DOFs in each substructure will result in better computation efficiency, but too many substructures will be time-consuming due to the tedious synthesis procedures. Moreover, the substructures with free interface will introduce errors and reduce the precision dramatically, which should be avoided.

Research on Control Method of Inverters for Large-scale Grid Connected Photovoltaic Power System

A grid-connected inverter controlling method to analyze dynamic process of large-scale and grid-connected photovoltaic power station is proposed. The reference values of control variables are composed of maximum power which is the output of the photovoltaic array of the photovoltaic power plant, and power factor specified by dispatching, the control strategy of dynamic feedback linearization is adopted. Nonlinear decoupling controller is designed for realizing decoupling control of active and reactive power. The cascade PI regulation is proposed to avoid inaccurate parameter estimation which generates the system static error. Simulation is carried out based on the simplified power system with large-scale photovoltaic plant modelling, and the power factor, solar radiation strength, and bus fault are considered for the further research. It’s demonstrated that the parameter adjustment of PI controller is simple and convenient, dynamic response of system is transient, and the stability of the inverter control is verified.

A Dynamic Active-Set Method for Linear Programming

An efficient active-set approach is presented for both nonnegative and general linear programming by adding varying numbers of constraints at each iteration. Computational experiments demonstrate that the proposed approach is significantly faster than previous active-set and standard linear programming algorithms.

Understanding the Dynamics Location of Very Large Populations Interacted with Service Points

This paper offers preliminary work on system dynamics and Data mining tools. It tries to understand the dynamics of carrying out large-scale events, such as Hajj. The study looks at a large, recurring problem as a variable to consider, such as how the flow of people changes over time as well as how location interacts with placement. The predicted data is analyzed using Vensim PLE 32 modeling software, GIS Arc Map 10.2.1, and AnyLogic 7.3.1 software regarding the potential placement of temporal service points, taking into consideration the three dynamic constraints and behavioral aspects: a large population, limitation in time, and space. This research proposes appropriate data analyses to ensure the optimal positioning of the service points with limited time and space for large-scale events. The conceptual framework would be the output of this study. Knowledge may be added to the insights based on the technique.

Engineering and dynamics of heterogeneous catalysts via metal single atoms as promoters/precursors

Metal single-atom catalysts(SACs) have emerged as a focal point of research, captivating the scientific community due to their distinctive electronic properties and unparalleled catalytic prowess in the realm of heterogeneous catalysis. However, their significance transcends their role as mere active sites. Recent investigations have illuminated the multifaceted capabilities of metal single atoms as catalyst promoters and precursors, paving the way for the engineering of highly efficient heterogeneous catalysts. Single-atom promoters not only enhance the stabilization of active metals and tailor the support material, but regulate the reactive interfacial structure, eventually tuning the catalytic performance. Furthermore, SACs were also used as catalyst precursors to design new catalyst active sites. During the pretreatment or catalytic reaction, the structure of the metal single sites is changed significantly and transformed into the new and more active state, which improve the adsorption and reactive ability of reactants or intermediates. In this critical review, we comment the recent development of metal SACs used as catalyst promoters/precursors in engineering heterogeneous catalysts, including thermal catalysis and electrocatalysis. Furthermore, the dynamic evolution of the SACs during the pretreatment or catalytic reaction is also discussed. Finally, we provide our insight to potentially guide the future development on this emerging field.

Improving Simulation of a Tropical Cyclone Using Dynamical Initialization and Large-Scale Spectral Nudging: A Case Study of Typhoon Megi (2010)

In this study, an approach combining dynamical initialization and large-scale spectral nudging is proposed to achieve improved numerical simulations of tropical cyclones （TCs）, including track, structure, intensity, and their changes, based on the Advanced Weather Research and Forecasting （ARW-WRF） model. The effectiveness of the approach has been demonstrated with a case study of Typhoon Megi （2010）. The ARW-WRF model with the proposed approach realistically reproduced many aspects of Typhoon Megi in a 7-day-long simulation. In particular, the model simulated quite well not only the storm track and intensity changes but also the structure changes before, during, and after its landfall over the Luzon Island in the northern Philippines, as well as after it reentered the ocean over the South China Sea （SCS）. The results from several sensitivity experiments demonstrate that the proposed approach is quite effective and ideal for achieving realistic simulations of real TCs, and thus is useful for understanding the TC inner-core dynamics, and structure and intensity changes.

A study of boundary vorticity dynamics and identification of large-scale structures in flow field based on two-dimensional flow around a bluff body

A method based on decomposition of acceleration field and Lie derivative is introduced to identify shearing and rotational domains.This method is validated on two typical kinds of model flows.Vorticity dynamics of flow around bluff body is studied,illustrated by numerical examples of flow around an elliptic cylinder,a slanted elliptic cylinder and an elliptic cylinder with a pair of bumps on the front side.To explain the generation of vortical structures and how they evolve into inner flow field,boundary vorticity dynamics analysis is performed.Boundary vorticity flux as well as the enstrophy diffusion flux creates vorticity sources and vorticity sinks,which generate or consume boundary vorticity,then shearing layers are generated and interact with each other finally create vortices.The results provide potential in accurate flow control by boundary deformation,and show that relevant theoretical conclusions can be effectively applied in revealing the flow mechanisms.