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.

Web Layout Design of Large Cavity Structures Based on Topology Optimization

Large cavity structures are widely employed in aerospace engineering, such as thin-walled cylinders, blades andwings. Enhancing performance of aerial vehicles while reducing manufacturing costs and fuel consumptionhas become a focal point for contemporary researchers. Therefore, this paper aims to investigate the topologyoptimization of large cavity structures as a means to enhance their performance, safety, and efficiency. By usingthe variable density method, lightweight design is achieved without compromising structural strength. Theoptimization model considers both concentrated and distributed loads, and utilizes techniques like sensitivityfiltering and projection to obtain a robust optimized configuration. The mechanical properties are checked bycomparing the stress distribution and displacement of the unoptimized and optimized structures under the sameload. The results confirm that the optimized structures exhibit improved mechanical properties, thus offering keyinsights for engineering lightweight, high-strength large cavity structures.

OptoGPT: A foundation model for inverse design in optical multilayer thin film structures

Optical multilayer thin film structures have been widely used in numerous photonic applications.However,existing inverse design methods have many drawbacks because they either fail to quickly adapt to different design targets,or are difficult to suit for different types of structures,e.g.,designing for different materials at each layer.These methods also cannot accommodate versatile design situations under different angles and polarizations.In addition,how to benefit practical fabrications and manufacturing has not been extensively considered yet.In this work,we introduce OptoGPT(Opto Generative Pretrained Transformer),a decoder-only transformer,to solve all these drawbacks and issues simultaneously.

Resistive switching behavior and mechanism of HfO_(x) films with large on/off ratio by structure design

Different bilayer structures of HfO_(x)/Ti(TiO_(x)) are designed for hafnium-based memory to investigate the switching characteristics. The chemical states in the films and near the interface are characterized by x-ray photoelectron spectroscopy,and the oxygen vacancies are analyzed. Highly improved on/off ratio(~104) and much uniform switching parameters are observed for bilayer structures compared to single layer HfO_(x) sample, which can be attributed to the modulation of oxygen vacancies at the interface and better control of the growth of filaments. Furthermore, the reliability of the prepared samples is investigated. The carrier conduction behaviors of HfO_(x)-based samples can be attributed to the trapping and de-trapping process of oxygen vacancies and a filamentary model is proposed. In addition, the rupture of filaments during the reset process for the bilayer structures occur at the weak points near the interface by the recovery of oxygen vacancies accompanied by the variation of barrier height. The re-formation of fixed filaments due to the residual filaments as lightning rods results in the better switching performance of the bilayer structure.

Design,preparation,application of advanced array structured materials and their action mechanism analyses for high performance lithium-sulfur batteries

Lithium-sulfur battery(LSB)has brought much attention and concern because of high theoretical specific capacity and energy density as one of main competitors for next-generation energy storage systems.The widely commercial application and development of LSB is mainly hindered by serious“shuttle effect”of lithium polysulfides(Li PSs),slow reaction kinetics,notorious lithium dendrites,etc.In various structures of LSB materials,array structured materials,possessing the composition of ordered micro units with the same or similar characteristics of each unit,present excellent application potential for various secondary cells due to some merits such as immobilization of active substances,high specific surface area,appropriate pore sizes,easy modification of functional material surface,accommodated huge volume change,enough facilitated transportation for electrons/lithium ions,and special functional groups strongly adsorbing Li PSs.Thus many novel array structured materials are applied to battery for tackling thorny problems mentioned above.In this review,recent progresses and developments on array structured materials applied in LSBs including preparation ways,collaborative structural designs based on array structures,and action mechanism analyses in improving electrochemical performance and safety are summarized.Meanwhile,we also have detailed discussion for array structured materials in LSBs and constructed the structure-function relationships between array structured materials and battery performances.Lastly,some directions and prospects about preparation ways,functional modifications,and practical applications of array structured materials in LSBs are generalized.We hope the review can attract more researchers'attention and bring more studying on array structured materials for other secondary batteries including LSB.

A Hybrid Level Set Optimization Design Method of Functionally Graded Cellular Structures Considering Connectivity

With the continuous advancement in topology optimization and additive manufacturing(AM)technology,the capability to fabricate functionally graded materials and intricate cellular structures with spatially varying microstructures has grown significantly.However,a critical challenge is encountered in the design of these structures–the absence of robust interface connections between adjacent microstructures,potentially resulting in diminished efficiency or macroscopic failure.A Hybrid Level Set Method(HLSM)is proposed,specifically designed to enhance connectivity among non-uniform microstructures,contributing to the design of functionally graded cellular structures.The HLSM introduces a pioneering algorithm for effectively blending heterogeneous microstructure interfaces.Initially,an interpolation algorithm is presented to construct transition microstructures seamlessly connected on both sides.Subsequently,the algorithm enables the morphing of non-uniform unit cells to seamlessly adapt to interconnected adjacent microstructures.The method,seamlessly integrated into a multi-scale topology optimization framework using the level set method,exhibits its efficacy through numerical examples,showcasing its prowess in optimizing 2D and 3D functionally graded materials(FGM)and multi-scale topology optimization.In essence,the pressing issue of interface connections in complex structure design is not only addressed but also a robust methodology is introduced,substantiated by numerical evidence,advancing optimization capabilities in the realm of functionally graded materials and cellular structures.

Multi-Scale Design and Optimization of Composite Material Structure for Heavy-Duty Truck Protection Device

In this paper,to present a lightweight-developed front underrun protection device(FUPD)for heavy-duty trucks,plain weave carbon fiber reinforced plastic(CFRP)is used instead of the original high-strength steel.First,the mechanical and structural properties of plain carbon fiber composite anti-collision beams are comparatively analyzed from a multi-scale perspective.For studying the design capability of carbon fiber composite materials,we investigate the effects of TC-33 carbon fiber diameter(D),fiber yarn width(W)and height(H),and fiber yarn density(N)on the front underrun protective beam of carbon fiber compositematerials.Based on the investigation,a material-structure matching strategy suitable for the front underrun protective beam of heavy-duty trucks is proposed.Next,the composite material structure is optimized by applying size optimization and stack sequence optimization methods to obtain the higher performance carbon fiber composite front underrun protection beam of commercial vehicles.The results show that the fiber yarn height(H)has the greatest influence on the protective beam,and theH1matching scheme for the front underrun protective beamwith a carbon fiber composite structure exhibits superior performance.The proposed method achieves a weight reduction of 55.21% while still meeting regulatory requirements,which demonstrates its remarkable weight reduction effect.

Design of a Novel Robotic Fish Structure Utilizing PVC Gel Actuators

In this research work, it has been designed a bionic robot fish structure, can swim underwater. The active compact body is powered by eight sets of symmetric PVC gel actuators with a caudal fin. The robot’s 200 mm-long, fish structure design incorporates a 55.52 angle to optimize the fish dynamics movement. It’s a fast and smooth operation and can swim. The robot can swim fast and quietly by using the right positions and the appropriate actuators on PVC gel actuators. This design entails a unique architecture that enables the robot to move safely and unobtrusively at the same time, which makes it suitable equipment for different exploration and surveillance missions in the water with speed and silent operation as the foremost concern.

Design and Engineering of Urban Interchange Ramp Bridge Structure

This paper analyzes the structural design of an urban interchange ramp bridge from four aspects,which are the superstructure,pier structure,foundation structure,and deck structure design to summarize the structural design ideas of this urban interchange ramp bridge,which can be used as a reference for future construction of the same bridge.

Optimization method of reef structure design based on hydrodynamic model

Artificial fish reef is a kind of artificial structure in water,which provides a necessary and safe place for aquatic life such as fish to inhabit,grow,and breed,and creates an environment suitable for fish growth,so as to protect and multiply fishery resources.In a large time scale,the physical process of sea area can deeply affect the chemical process and biological process,so the structure characteristics of artificial reef are the key factors affecting the flow field effect around the reef.In this study,through the hydrodynamic experiments of four kinds of reef models,including big windows box reef,big and small windows box reef,"(卐)"shaped reef and double-layer shellfish breeding reef,the influence of single reef structure on the flow field effect is analyzed,and the force conditions of different reefs under the same incoming current velocity are obtained.According to the simulation results,the safety research and calculation of five kinds of reef models are carried out,and the volumes of vortex area and upwelling area behind four kinds of reef are obtained.Using hydrodynamic model to simulate the flow field effect of reef area,optimizing the reef structure design,improving the maximum biological trapping and proliferation effect of reef,can provide theoretical guidance and scientific and technological support for the construction of reef area.

Performance-based seismic design of nonstructural building components:The next frontier of earthquake engineering

With the development and implementation of performance-based earthquake engineering,harmonization of performance levels between structural and nonstructural components becomes vital. Even if the structural components of a building achieve a continuous or immediate occupancy performance level after a seismic event,failure of architectural,mechanical or electrical components can lower the performance level of the entire building system. This reduction in performance caused by the vulnerability of nonstructural components has been observed during recent earthquakes worldwide. Moreover,nonstructural damage has limited the functionality of critical facilities,such as hospitals,following major seismic events. The investment in nonstructural components and building contents is far greater than that of structural components and framing. Therefore,it is not surprising that in many past earthquakes,losses from damage to nonstructural components have exceeded losses from structural damage. Furthermore,the failure of nonstructural components can become a safety hazard or can hamper the safe movement of occupants evacuating buildings,or of rescue workers entering buildings. In comparison to structural components and systems,there is relatively limited information on the seismic design of nonstructural components. Basic research work in this area has been sparse,and the available codes and guidelines are usually,for the most part,based on past experiences,engineering judgment and intuition,rather than on objective experimental and analytical results. Often,design engineers are forced to start almost from square one after each earthquake event: to observe what went wrong and to try to prevent repetitions. This is a consequence of the empirical nature of current seismic regulations and guidelines for nonstructural components. This review paper summarizes current knowledge on the seismic design and analysis of nonstructural building components,identifying major knowledge gaps that will need to be filled by future research. Furthermore,considering recent trends in earthquake engineering,the paper explores how performance-based seismic design might be conceived for nonstructural components,drawing on recent developments made in the field of seismic design and hinting at the specific considerations required for nonstructural components.

Research on the Course of Principles of Concrete Structure Design

Nowadays,education and teaching have become a hot topic,and teaching in colleges and universities is facing a brand-new development direction.Principles of Concrete Structure Design,as one of the main courses,transmits professional knowledge for students,enhances the students’professional ability,and further carries out in-depth research on the course to bring a better teaching effect for students.The article mainly focuses on the research of the principles of concrete structure design course,conducts an analysis of the teaching characteristics of the principles of concrete structure design course,and reasonably sets the teaching content from the optimization of the course teaching objectives;innovative course teaching methods can deepen the effect of knowledge understanding;reform of experimental practice teaching can lay down the effect of the internalization of knowledge,etc.The in-depth description and discussion of the relevant aspects of the research aim to provide guidelines for related research.

Performance-based global reliability assessment of a high-rise frame-core tube structure subjected to multi-dimensional stochastic earthquakes

When evaluating the seismic safety and reliability of complex engineering structures,it is a critical problem to reasonably consider the randomness and multi-dimensional nature of ground motions.To this end,a proposed modeling strategy of multi-dimensional stochastic earthquakes is addressed in this study.This improved seismic model has several merits that enable it to better provide seismic analyses of structures.Specifically,at first,the ground motion model is compatible with the design response spectrum.Secondly,the evolutionary power spectrum involved in the model and the design response spectrum are constructed accordingly with sufficient consideration of the correlation between different seismic components.Thirdly,the random function-based dimension-reduction representation is applied,by which seismic modeling is established,with three elementary random variables.Numerical simulations of multi-dimensional stochastic ground motions in a specific design scenario indicate the effectiveness of the proposed modeling strategy.Moreover,the multi-dimensional seismic response and the global reliability of a high-rise frame-core tube structure is discussed in detail to further illustrate the engineering applicability of the proposed method.The analytical investigations demonstrate that the suggested stochastic model of multi-dimensional ground motion is available for accurate seismic response analysis and dynamic reliability assessment of complex engineering structures for performance-based seismic resistance design.

Durability zonation standard of concrete structure design

Durability zonation standard （DZS） is proposed to provide useful parameters for durable concrete structure design. It deals not only with the influence of environment on structures, but also with types, functions and importance of structures based on the theory of life cycle cost（LCC）. First, the basic concept of DZS for concrete structure design is defined. Then the basic principles for DZS are established. The factors for zonation according to natural environmental conditions and structural importance are identified. The usefulness of DZS by citing a real application for concrete highway bridges in Zhejiang Province is demonstrated. Finally, durability regulations are provided accordingly to zonation.

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.

Integrated Assembly Structure Design Within Concurrent Engineering

Taking a microwave product as an example, a system of integrated assembly structure design is presented. Getting design constraints from the upstream design section through product data management(PDM), the system generates the assembly scheme using the case? based method, then assigns the design requirements into each component of the assembly. The detail design for each component can be performed under these design constraints. In order to practise concurrent design, the system sends the final design result to the upstream section and downstream section through PDM to achieve information sharing and integration.

Molecular Design and Electronic Structure Investigation of Novel Nitrogen Heteroatom 2-β-Naphthylbenzoxazoles

For the aim of finding new available functional materials, a series of nitrogen heteroatom 2 β naphthylbenzoxazole molecules were designed based on the experiment and theoretical studies of 2 β naphthylbenzoxazole molecule. Geometry optimization of the 2 β naphthylbenzoxazole was carried out by using Hyperchem Molecular Mechanics plus MM+. The planar molecular structure was obtained. The quantum chemistry calculating method PPP SCF CI, which is specially available to treat electron spectrum, was applied to investigate each novel designed molecules. Their electronic structures were analyzed in detail, it shows that total π electron energy decreased linearly with the number of replaced nitrogen. Single nitrogen atom located in benzoxazole ring or naphthalene ring results in contrary changes of level difference of FMO; multiple nitrogen atoms located in different molecular positions will lead to polarization of extremum in the level difference of FMO; and 5 nitrogen heteroatoms reach the culmination. Considering other electronic structure information, some favorable designed molecules were identified.

Structure Design Considerations of a Sub-50nm Self-Aligned Double-Gate MOSFET

A comprehensive way to design a sub 50nm SADG MOSFET with the ability of being fabricated by improved CMOS technique is described.Under this way,the gate length and thickness of Si island of DG device show many different scaling limits for various elements.Meanwhile,the spacer insulator shows a kind of width thickness on device drain current and circuit speed.A model about that effect is developed and offers design consideration for future.A new design of channel doping profile,called SCD,is also discussed here in detail.The DG device with SCD can achieve a good balance between the volume inversion operation mode and the control of V th .Finally,a guideline to make a SADG MOSFET is presented.

Logical-Structure Modeling for Conceptual Design

Based on the definition of a logic structure feature to relate logically functional requirements to geometric representation independent upon detailed geometric representation, this paper presents an idea of logical structure modeling for computer aided conceptual design and makes attempt to establish a representation formalism of logic structure modeling. The definition and representation of logical structure feature are given and an assembly module definition for supporting top down conceptual design is also proposed. The proposed scheme contributes to several aspects of conceptual design research, especially to provide elementarily a formal methodology for computer aided conceptual design system development and operation.

Structure optimal design research on backfill hydraulic support

Backfill hydraulic support is the key equipment in achieving coal mining and solid backfilling simultaneously in solid backfill mining technology.Based on the summary and analysis of main types,basic structural properties and filed application of backfill hydraulic support,this work has firstly proposed the basic principle of backfill hydraulic support optimization design and provided the method of optimal design of key structural components,like four-bar linkage,rear canopy and tamping structure;the method is further elaborated as changing hinging position of upper bar to optimize four-bar linkage,by lengthening or shortening the rear canopy to optimize length ratio of canopy;and by changing length and hinging position of tamping structure as well as suspension height of backfill scrape conveyor to realize optimization of tamping structure.On this basis,the process of optimal design of backfill hydraulic support is built.The optimal design case of ZC5200/14.5/30 six columns-four bar linkage used in 7203 W workface of Zhaizhen Coal Mine shows that the backfill properties like horizontal roof gap,vertical horizontal gap,tamping angle and tamping head gap are improved obviously through optimizing four-bar linkage,canopy length and tamping structure according to the optimal design method proposed in this work.