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.

Quantum Mechanics: Harmonic Wave-Packets, Localized by Resonant Response in Dispersion Dynamics

From a combination of Maxwell’s electromagnetism with Planck’s law and the de Broglie hypothesis, we arrive at quantized photonic wave groups whose constant phase velocity is equal to the speed of light c = ω/k and to their group velocity dω/dk. When we include special relativity expressed in simplest units, we find that, for particulate matter, the square of rest mass , i.e., angular frequency squared minus wave vector squared. This equation separates into a conservative part and a uniform responsive part. A wave function is derived in manifold rank 4, and from it are derived uncertainties and internal motion. The function solves four anomalies in quantum physics: the point particle with prescribed uncertainties;spooky action at a distance;time dependence that is consistent with the uncertainties;and resonant reduction of the wave packet by localization during measurement. A comparison between contradictory mathematical and physical theories leads to similar empirical conclusions because probability amplitudes express hidden variables. The comparison supplies orthodox postulates that are compared to physical principles that formalize the difference. The method is verified by dual harmonics found in quantized quasi-Bloch waves, where the quantum is physical;not axiomatic.

A Framework for Exploring the Dynamics of Autonomous Work Groups in Manufacturing Organizations

Nowadays, new paradigm of enterprise organization i s constantly changing due to the emergence of the global marketplace, the rise of information technology, and the emphasis of the social developments. This re quires a more flexible form of organization that are more adaptable to rapid cha nges in business environment such as autonomous work groups (AWGs) in order to achieve higher productivity and effectiveness. AWGs are work units responsib le for the production of goods and the provision of services. They involve team members in making decisions that are traditionally the responsibility of the sup ervisors and managers (Cohen & Bailey, 1997). Team members of AWGs are allowed t o self-regulate their behavior on jobs such as task assignments, methods for ca rrying out the work, and scheduling of activities etc. (Cohen & Ledford, 1994). For example, Motorola achieved a high organizational performance due to the succ essful implementation of AWGs in quality management (Piczak & Hauser, 1996). Xer ox also reported their operational successes based on the team-oriented work gr oups (Wageman, 1997). In recent years many organizations have replaced the traditional layers of manag ement with autonomous team-based work arrangements. Surveys indicated that the adoption of AWGs has soared in responding to the competitive business challenges . Many enterprises are making a deliberate effort to use AWGs to carry out work and operational processes as an alternative for hierarchical approaches (Lawler et al., 1995). There is a growing body of evidence that AWGs are more effective than traditionally managed groups and they contributes to organizational perform ance, such as improvement in operational performance, productivity, quality, cos t savings, employee attitude and behavior, and employee satisfaction (e.g. Pears on, 1992; Cohen & Ledford, 1994; Seers et al. 1995). Given the complexity and cognitive nature of team-based organizations, the mech anisms that the enterprises use in the development of the increasingly sophistic ated models, which can contribute to the effective functioning of AWGs, are extr emely important. The process of developing effective AWGs enables enterprises to inherent built-in intelligence of the organizations so that they will be more able to accommodate to external pressures and changes. The context of this paper is the construction of a dynamics framework and a stra tegic path for autonomous work groups in the technology-oriented manufacturing organization re-design. The framework is a conceptual one drawn from the litera ture survey. The importance of studying autonomous work groups for today’s manuf acturing organizations is claimed. Based on the General System Theory (GST), the characterization of AWGs is addressed. Three-dimensional domains such as t echnical content, service content, and relationship content are identified. A st rategic path is proposed to guide the organizations how the development of AWGs progresses at different levels of maturity that are associated with organization al effectiveness and performance. The utility of the model for AWGs is expected to provide technology-oriented organizations with a strategic path to achieve h igher organizational performance.

Many-body dissipative particle dynamics with energy conservation:temperature-dependent long-term attractive interaction

Heat and mass transfer during the process of liquid droplet dynamic behaviors has attracted much attention in decades.At mesoscopic scale,numerical simulations of liquid droplets motion,such as impacting,sliding,and coalescence,have been widely studied by using the particle-based method named many-body dissipative particle dynamics(MDPD).However,the detailed information on heat transfer needs further description.This paper develops a modified MDPD with energy conservation(MDPDE)by introducing a temperature-dependent long-term attractive interaction.By fitting or deriving the expressions of the strength of the attractive force,the exponent of the weight function in the dissipative force,and the mesoscopic heat friction coefficient about temperature,we calculate the viscosity,self-diffusivity,thermal conductivity,and surface tension,and obtain the Schmidt number Sc,the Prandtl number P r,and the Ohnesorge number Oh for 273 K to 373 K.The simulation data of MDPDE coincide well with the experimental data of water,indicating that our model can be used to simulate the dynamic behaviors of liquid water.Furthermore,we compare the equilibrium contact angle of droplets wetting on solid surfaces with that calculated from three interfacial tensions by MDPDE simulations.The coincident results not only stand for the validation of Young’s equation at mesoscale,but manifest the reliability of our MDPDE model and applicability to the cases with free surfaces.Our model can be extended to study the multiphase flow withcomplex heat and mass transfer.

基于数据流的K-S变化检测的动态多目标规划算法

为了更加准确地判断环境是否发生变化并快速追踪动态多目标规划问题(dynamicmulti-objectiveoptimization problem,DMOP)当前时刻的Pareto前沿,提出了一种基于数据流的Kolmogorov-Smirnov(K-S)变化检测的动态多目标规划(DSK-SDMOP)算法。该算法以NSGA-Ⅱ为基础,通过数据流建立2个时刻的检验窗口,再利用K-S检验基于数据流的Pareto最优前沿是否发生变化,检测2个窗口的数据是否服从同一分布来判断环境是否发生变化,并就环境变化的剧烈程度实行相应的应答机制,以提高对环境的适应程度。利用基于数据流的K-S检测方法,对环境变化不会过于敏感,而且不用提前假设对应目标值的分布,易于操作。通过5个动态多目标规划标准测试函数对该算法进行测试,并和现有的2种算法进行对比分析,结果表明该算法处理动态多目标规划问题具有良好的性能。

Dynamic Modeling and Investigation of Maneuver Characteristics of A Deep-Sea Manned Submarine Vehicle

A deep-sea Manned Submarine Vehicle （MSV） is usually required to move at a low forward speed and a low rotational speed when it executes investigation tasks. In this condition, the motion is in large drift angles, and the maneuverability hydrodynamic forces cannot be expressed properly in the conventional mathematical model of submersible motion. In this paper, firstly, a general equation of MSV with six-freedom motion is presented, and the numerical simulation of descent/ascent motion and helix motion is conducted to reveal the general maneuver characteristics of MSV. Secondly, according to the data of captive model tests of large drift angles of MSV, the regression analysis of position hydrodynamic forces and rotation hydrodynamic forces is carried out, and the results of regression analysis of maneuverability hydrody- namic characteristics are analyzed to reveal the special maneuver characteristics. Thirdly, a special new mathematical model of MSV with the whole range of drift angles motion is presented, which can be used to predict hydrodynamic performance of motion in the 0° - 180° range of drift angles. The results are applied to the design of maneuverability hydrodynamic forces, development of control system and simulator of a practical MSV.

Dynamics and adaptive control of a dual-arm space robot with closed-loop constraints and uncertain inertial parameters

A dynamics-based adaptive control approach is proposed for a planar dual-arm space robot in the presence of closed-loop constraints and uncertain inertial parameters of the payload. The controller is capable of controlling the po- sition and attitude of both the satellite base and the payload grasped by the manipulator end effectors. The equations of motion in reduced-order form for the constrained system are derived by incorporating the constraint equations in terms of accelerations into Kane＇s equations of the unconstrained system. Model analysis shows that the resulting equations perfectly meet the requirement of adaptive controller design. Consequently, by using an indirect approach, an adaptive control scheme is proposed to accomplish position/attitude trajectory tracking control with the uncertain parameters be- ing estimated on-line. The actuator redundancy due to the closed-loop constraints is utilized to minimize a weighted norm of the joint torques. Global asymptotic stability is proven by using Lyapunov＇s method, and simulation results are also presented to demonstrate the effectiveness of the proposed approach.

Forest landscape patterns dynamics of Yihe-Luohe river basin

Based on the information from forest resources distribution maps of Luoning County of 1983 and 1999, six indices were used to analyze spatial patterns and dynamics of forest landscapes of the typical region in the middle of the Yihe-Luohe river basin. These indices include patch number, mean patch area, fragment index, patch extension index, etc. The results showed that: (1) There was a rapid increase in the number of patch and total area from 1983 to 1999 in the study area. The fragment degree became very high. (2) The area of all the forest patch types had witnessed great changes. The fractal degree of each forest patch type became big from 1983 to 1999. The mean extension index of Robinia pseudoacacia forest, non-forest, shrub forest, sparse forest, and Quercus species forest increased rapidly, but that of economic forest became zero. The fractal dimension each showed that forest coverage has been promoted. (3) The changes of landscape patterns were different in different geomorphic regions. From 1983 to 1999 the vegetation cover area, the gross number and the density of patch, diversity and evenness of landscape were all reduced greatly in gullies and ravines, but the maximum area and the mean area of patch types were increased. In hilly region, both the forest cover area and the number of patch increased from 1983 to 1999, but the mean area of patch was reduced greatly. In mountain region, even though the area under forest canopy reduced from 1983 to 1999, the patch number was increased greatly, the mean area of all patch types was reduced, the extension index, diversity index and evenness index of landscape were all increased. Furthermore, because of different types of land use, human activity and terrain, the vegetation changes on northern and southern mountain slopes were different. According to these analyses, the main driving forces, such as the policies of management, market economy, influence of human activities etc. are brought out.

A numerical study on the effect of tidal flat's slope on tidal dynamics in the Xiangshan Bay, China

The Xiangshan Bay is a semi-enclosed and narrow bay, which is characterized by large scale tidal flats and has been historically utilized through coastal construction and aquaculture engineering. The hydrodynamic model using the Finite Volume Coastal Ocean Model（FVCOM） was constructed to examine the changes of tidal dynamics due to the variation of tidal flat slopes. According to the model results, a decreased slope of a tidal flat would amplify the M2 tidal amplitude and delay the M2 tidal phase in the inner harbor, due to an increased tidal prism, and vice versa. The amplitude of the main shallow-water tide M4 would be amplified/dampened in the entire bay due to the changed bottom friction, if the tidal flat＇s slope were reduced/increased at the Tie inlet. The phase was advanced. The change of a tidal flat＇s slope at the Tie inlet had greater impacts on tidal amplitude,phase and duration asymmetry, than that at the Xihu inlet. The impact of changes of the tidal flat slope at the Xihu inlet was small and was constrained locally. Changes in the tidal flats＇ slopes at the Tie and Xihu inlets changed the tidal duration asymmetry, residual current and tidal energy via modulating tides. The ebb dominance decreased when the tidal flat＇s slope at the Tie inlet was changed. Decreased/increased ebb dominance occurred when the tidal flat＇s slope was reduced/increased at the Xihu inlet. The residual current and tidal energy density was amplified/dampened and more/less tidal energy was dissipated, with reduced/increased slope at both of the inlets. The findings in this study are instructive to coastal engineering and estuarine management.

Size dependency and potential field influence on deriving mechanical properties of carbon nanotubes using molecular dynamics

A thorough understanding on the mechanical properties of carbon nanotube （CNT） is essential in extending the advanced applications of CNT based systems. However, conducting experiments to estimate mechanical properties at this scale is extremely challenging. Therefore, development of mechanistic models to estimate the mechanical properties of CNTs along with the integration of existing continuum mechanics concepts is critically important. This paper presents a comprehensive molecular dynamics simulation study on the size dependency and potential function influence of mechanical properties of CNT. Commonly used reactive bond order （REBO） and adaptive intermolecular reactive bond order （A1REBO） potential functions were considered in this regard. Young＇s modulus and shear modulus of CNTs are derived by integrating classical continuum mechanics concepts with molecular dynamics simulations. The results indicate that the potential function has a significant influence on the estimated mechanical properties of CNTs, and the influence of potential field is much higher when studying the torsional behaviour of CNTs than the tensile behaviour.

Numerical Solution of Constrained Mechanical System Motions Equations and Inverse Problems of Dynamics

In this paper the method of design of kinematical and dynamical equations of mechanical systems, applied to numerical ealization, is proposed. The corresponding difference equations, which are obtained, give a guarantee of computations with a given precision. The equations of programmed constraints and those of constraint perturbations are defined. The stability of the programmed manifold for numerical solutions of the kinematical and dynamical equations is obtained by corresponding construction of the constraint perturbation equations. The dynamical equations of system with programmed constraints are set up in the form of Lagrange’s equations in generalized coordinates. Certain inverse problems of rigid body dynamics are examined.

Approximate expression of Young's equation and molecular dynamics simulation for its applicability

In 1805, Thomas Young was the first to propose an equation(Young's equation) to predict the value of the equilibrium contact angle of a liquid on a solid. On the basis of our predecessors, we further clarify that the contact angle in Young's equation refers to the super-nano contact angle. Whether the equation is applicable to nanoscale systems remains an open question. Zhu et al. [College Phys. 4 7(1985)] obtained the most simple and convenient approximate formula, known as the Zhu–Qian approximate formula of Young's equation. Here, using molecular dynamics simulation, we test its applicability for nanodrops. Molecular dynamics simulations are performed on argon liquid cylinders placed on a solid surface under a temperature of 90 K, using Lennard–Jones potentials for the interaction between liquid molecules and between a liquid molecule and a solid molecule with the variable coefficient of strength a. Eight values of a between 0.650 and 0.825 are used. By comparison of the super-nano contact angles obtained from molecular dynamics simulation and the Zhu–Qian approximate formula of Young's equation, we find that it is qualitatively applicable for nanoscale systems.

Dynamics of vehicles with high gravity centre

The vehicles with high gravity centre are more prone to roll over. The paper deals with a method of dynamics analysis of fire engines which is an example of these types of vehicle. Algorithms for generating the equations of motion have been formulated by homogenous transformations and Lagrange＇s equation. The model presented in this article consists of a system of rigid bodies connected one with another forming an open kinematic chain. Road maneuvers such as a lane change and negotiating a circular track have been presented as the main simulations when a car loses its stability. The method has been verified by comparing numerical results with results obtained by experimental measurements performed during road tests.

A typical slow reaction H(~2S) + S_2(X^3-Σ_g^-) → SH(X^2Π)+S(~3P) on a new surface:Quantum dynamics calculations

Quantum dynamics calculations for the title reaction H（2S） ＋ S2（X3∑g） → SH（X2П） ＋S（3P） are performed byusing a globally accurate double many-body expansion potential energy surface [J. Phys. Chem. A 115 5274 （2011）]. The Chebyshev real wave packet propagation method is employed to obtain the dynamical information, such as reaction probability, initial state-specified integral cross section, and thermal rate constant. It is found not only that there is a reaction threshold near 0.7 eV in both reaction probabilities and integral cross section curves, but also that both the probability and cross section increase firstly and then decrease as the collision energy increases. The existence of the resonance structure in both the probability and cross section curves is ascribed to the deep potential well. The calculation of the rate constant reveals that the reaction occurring on the potential energy surface of the ground-state HS2 is slow to take place.

A high resolution inversion method for fluid factor with dynamic dryrock V_(P)/V_(S) ratio squared

As an important indicator parameter of fluid identification,fluid factor has always been a concern for scholars.However,when predicting Russell fluid factor or effective pore-fluid bulk modulus,it is necessary to introduce a new rock skeleton parameter which is the dry-rock VP/VS ratio squared(DVRS).In the process of fluid factor calculation or inversion,the existing methods take this parameter as a static constant,which has been estimated in advance,and then apply it to the fluid factor calculation and inversion.The fluid identification analysis based on a portion of the Marmousi 2 model and numerical forward modeling test show that,taking the DVRS as a static constant will limit the identification ability of fluid factor and reduce the inversion accuracy.To solve the above problems,we proposed a new method to regard the DVRS as a dynamic variable varying with depth and lithology for the first time,then apply it to fluid factor calculation and inversion.Firstly,the exact Zoeppritz equations are rewritten into a new form containing the fluid factor and DVRS of upper and lower layers.Next,the new equations are applied to the four parameters simultaneous inversion based on the generalized nonlinear inversion(GNI)method.The testing results on a portion of the Marmousi 2 model and field data show that dynamic DVRS can significantly improve the fluid factor identification ability,effectively suppress illusion.Both synthetic and filed data tests also demonstrate that the GNI method based on Bayesian deterministic inversion(BDI)theory can successfully solve the above four parameter simultaneous inversion problem,and taking the dynamic DVRS as a target inversion parameter can effectively improve the inversion accuracy of fluid factor.All these results completely verified the feasibility and effectiveness of the proposed method.

Molecular dynamics studies of the inhibitory mechanism of copper(Ⅱ) on aggregation of amyloid β-peptide

The inhibitory mechanism of copper（Ⅱ） on the aggegation of amyloid β-peptide （Aβ） was investigated by molecular dynamics simulations. The binding mode ofcopper（Ⅱ） with Aβ is characterized by the imidazole nitrogen atom, Nπ, of the histidine residue H 13, acting as the anchoring site, and the backbone＇s deprotoned amide nitogen atoms as the main binding sites. Drove by the coordination bonds and their induced hydrogen bond net, the conformations of Aβ converted from β-sheet non-β-sheet conformations, which destabilized the aggregation of Aβ into fibrils.

Spatio-temporal Dynamics of Urbanization in China Using DMSP/OLS Nighttime Light Data from 1992–2013

Understanding the dynamics of urbanization is essential to the sustainable development of cities. Meanwhile the analysis of urban development can also provide scientifically and effective information for decision-making. With the long-term Defense Meteorological Satellite Program’s Operational Linescan System(DMSP/OLS) nighttime light images, a pixel level assessment of urbanization of China from 1992 to 2013 was conducted in this study, and the spatio-temporal dynamics and future trends of urban development were fully detected. The results showed that the urbanization and urban dynamics of China experienced drastic fluctuations from 1992 to 2013, especially for those in the coastal and metropolitan areas. From a regional perspective, it was found that the urban dynamics and increasing trends in North Coast China, East Coast China and South Coast China were much more stable and significant than that in other regions. Moreover, with the sustainability estimating of nighttime light dynamics, the regional agglomeration trends of urban regions were also detected. The light intensity in nearly 50% of lighted pixels may continuously decrease in the future, indicating a severe situation of urbanization within these regions. In this study, The results revealed in this study can provided a new insight in long time urbanization detecting and is thus beneficial to the better understanding of trends and dynamics of urban development.

Demage Spreading in the Ising Model with a special Metropolis Dynamics Approach

The time evolution of the Hamming distance (damage spreading)for the S=1/2 and S=1 Ising models on the square lattice is performed with a special metropolis dynamics algorithm.Two distinct regimes are observed according to the temperature range for both models:a low-temperature one where the distance in the long-time limit is finite and seems not to depend on the initial distance and the system size;a high- temperature one where the distance vanishes in the long-time limit.Using the finite size scaling method,the dynamical phase transition(damage spreading transition) temperature is obtained as Tc ≈1.675±0.025 for the S=1 lsing model.

Electromechanical dynamics analysis and simulation on rollforming equipment with both sides variable cross-section

Electromechanical dynamics analysis and simulation on a rollforming equipment with both sides variable cross-section are discussed in this study.The system includes mechanical parts and electromagnetism parts,and it is a strongly coupled electromechanical system.Based on a virtual work principle and given power,generalized forces of this system are obtained.By using Lagrange-Maxwell equations,a model of electromechanical dynamics is established.Differential equations of two-phase winding on d-q axis are obtained by Park transformation,which comes from three-phase winding equations on the A-B-C axis.This system is solved with the 4th order Runge-Kutta's method,and discrete solutions of all variables are obtained.Finally,by using Matlab language,the system is simulated.The results show that the proposed method works very well.

Motion State Modification of Coulomb’s Law and Dynamic Gravitation

As we know, Coulomb’s law describes the interaction between static charges. In this paper, the modified formula of Coulomb’s law in the state of charge motion is given. Based on this formula, Ampere’s law and Lorentz’s law of force are derived by pure mathematics. According to the similarity between the formula of universal gravitation and Coulomb’s law, the correction of the formula of universal gravitation under the state of motion is assumed boldly, and some inferences are made on the motion law of celestial bodies.