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.

Seismic Response of Adjacent Structure to Inter-Story Isolated Structure

Currently, land resources are becoming more and more constrained and structures are getting closer to each other. To investigate the seismic response of inter-story isolated structure to adjacent structure, models considering no soil-structure interaction (SSI), considering soil-structure interaction (SSI), and considering structure-soil-structure interaction (SSSI) were established. Nonlinear seismic response comparative analysis was conducted by varying the spacing between adjacent structure and inter-story isolated structure, as well as the weight of adjacent structure, under different earthquake inputs, in order to obtain the structural response characteristics. The results indicate that the inter-story drift and inter-story shear of the inter-story isolated structure without considering SSI are smaller than those considering SSI and SSSI. The inter-story drift and inter-story shear of the inter-story isolated structure considering SSSI are further affected compared to that of the inter-story isolated structure considering only SSI. As the spacing between adjacent structure and inter-story isolated structure increases, the influence of adjacent structure on inter-story isolated structure decreases. The variation in the spacing between the two structures has a negligible effect on the isolation layer of the inter-story isolated structure. With the increase in the weight of adjacent structure, the influence of adjacent structure on inter-story isolated structure becomes more significant. The increasing weight of adjacent structure has an increasing effect on the Isolation layer of the inter-story isolated structure.

Microstructure and forming mechanism of metals subjected to ultrasonic vibration plastic forming: A mini review

Compared with traditional plastic forming,ultrasonic vibration plastic forming has the advantages of reducing the forming force and improving the surface quality of the workpiece.This technology has a very broad application prospect in industrial manufactur-ing.Researchers have conducted extensive research on the ultrasonic vibration plastic forming of metals and laid a deep foundation for the development of this field.In this review,metals were classified according to their crystal structures.The effects of ultrasonic vibration on the microstructure of face-centered cubic,body-centered cubic,and hexagonal close-packed metals during plastic forming and the mech-anism underlying ultrasonic vibration forming were reviewed.The main challenges and future research direction of the ultrasonic vibra-tion plastic forming of metals were also discussed.

Seismic Response Analysis of Steel Structure Isolation System Under Long-Period Seismic Motion

To analyze the seismic response of steel structure isolation systems under long-period seismic motion,a 9-story steel frame building was selected as the subject.Five steel structure finite element models were established using SAP2000.Response spectrum analysis was conducted on the seismic motion to determine if it adhered to the characteristics of long-period seismic motion.Modal analysis of each structural model revealed that the isolation structure significantly prolonged the structural natural vibration period and enhanced seismic performance.Base reactions and floor displacements of various structures notably increased under long-period seismic motion compared to regular seismic activity.Placing isolation bearings in the lower part of the structure proved more effective under long-period seismic motion.In seismic design engineering,it is essential to consider the impact of long-period seismic motion on structures and the potential failure of isolation bearings.

The MDOF equivalent linear system and its applications in seismic analysis and design of framed structures

This paper reviews the applications of the multi degree-of-freedom(MDOF)equivalent linear system in seismic analysis and design of planar steel and reinforced concrete framed structures.An equivalent MDOF linear structure,analogous to the original MDOF nonlinear structure,is constructed,which has the same mass and elastic stiffness as the original structure and modal damping ratios that account for the effects of geometrical and material nonlinearities.The equivalence implies a balance between the viscous damping work of the equivalent linear structure and that of the nonlinearities in the original nonlinear structure.This work balance is established with the aid of a transfer function in the frequency domain.Thus,equivalent modal damping ratios can be explicitly determined in terms of the period and deformation levels of the structure as well as the soil types.Use of these equivalent modal damping ratios can help address a variety of seismic analysis and design problems associated with planar steel and reinforced concrete framed structures in a rational and accurate manner.These include force-based seismic design with the aid of acceleration response spectra characterized by high amounts of damping,improved direct displacement-based seismic design and the development of advanced seismic intensity measures.The equivalent modal damping ratios are also utilized in the context of linear modal analysis for the definition and construction of the MDOF response spectrum.Furthermore,the equivalent modal damping ratios are employed in a seismic retrofit method for steel-framed structures with viscous dampers.Finally,it is demonstrated that modal behavior(or strength reduction)factors can be easily constructed based on these modal damping ratios for a more rational and accurate force-based seismic design,including the determination of inelastic displacement profiles.

Seismic response of a mid-story isolated structure considering SSI in mountainous areas under long-period earthquakes

At present,there is not much research on mid-story isolated structures in mountainous areas.In this study,a model of a mid-story isolated structure considering soil-structure interaction(SSI)in mountainous areas is established along with a model that does not consider SSI.Eight long-period earthquake waves and two ordinary earthquake waves are selected as inputs for the dynamic time history analysis of the structure.The results show that the seismic response of a mid-story isolated structure considering SSI in mountainous areas can be amplified when compared with a structure that does not consider SSI.The structure response under long-period earthquakes is larger than that of ordinary earthquakes.The structure response under far-field harmonic-like earthquakes is larger than that of near-fault pulse-type earthquakes.The structure response under near-fault pulse-type earthquakes is larger than that of far-field non-harmonic earthquakes.When subjected to long-period earthquakes,the displacement of the isolated bearings exceeded the limit value,which led to instability and overturning of the structure.The structure with dampers in the isolated story could adequately control the nonlinear response of the structure,effectively reduce the displacement of the isolated bearings,and provide a convenient,efficient and economic method not only for new construction but also to retrofit existing structures.

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.

Equivalent linear model for seismic damage evaluation of single-degree-of-freedom systems representing reinforced concrete structures considering cyclic degradation behavior

In this study,a novel equivalent damping ratio model that is suitable for reinforced concrete(RC)structures considering cyclic degradation behavior is developed,and a new equivalent linearization analysis method for implementing the proposed equivalent damping ratio model for use in seismic damage evaluation is presented.To this end,Ibarra’s peak-oriented model,which incorporates an energy-based degradation rule,is selected for representing hysteretic behavior of RC structure,and the optimized equivalent damping for predicting the maximum displacement response is presented by using the empirical method,in which the effect of cyclic degradation is considered.Moreover,the relationship between the hysteretic energy dissipation of the inelastic system and the elastic strain energy of the equivalent linear system is established so that the proposed equivalent linear system can be directly integrated with the Park-Ang seismic model to implement seismic damage evaluation.Due to the simplicity of the equivalent linearization method,the proposed method provides an efficient and reliable way of obtaining comprehensive insight into the seismic performance of RC structures.The verification demonstrates the validity of the proposed method.

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.

Structure and 2p decay mechanism of^(18)Mg

The recently discovered,extremely proton-rich nuclide 18 Mg exhibits ground-state decay via two sequential two-proton(2p)emissions through the intermediate nucleus,16Ne.This study investigates the structure and the initial 2p decay mechanism of^(18)Mgby examining the density and correlations of the valence protons using a three-body Gamow coupled-channel method.The results show that the ground state of^(18)Mgis significantly influenced by the continuum,resulting in a significant s-wave component.However,based on the current framework,this does not lead to a significant deviation in mirror symmetry in either the structure or spectroscopy of the 18Mg-18C pair.Additionally,the time evolution analysis of the^(18)Mgground state suggests a simultaneous 2p emission during the first step of decay.The observed nucleon-nucleon correlations align with those of the light-mass 2p emitters,indicating a consistent decay behavior within this nuclear region.

Advances in seismological methods for characterizing fault zone structure

Large earthquakes frequently occur along complex fault systems.Understanding seismic rupture and long-term fault evolution requires constraining the geometric and material properties of fault zone structures.We provide a comprehensive overview of recent advancements in seismological methods used to study fault zone structures,including seismic tomography,fault zone seismic wave analysis,and seismicity analysis.Observational conditions limit our current ability to fully characterize fault zones,for example,insufficient imaging resolution to discern small-scale anomalies,incomplete capture of crucial fault zone seismic waves,and limited precision in event location accuracy.Dense seismic arrays can overcome these limitations and enable more detailed investigations of fault zone structures.Moreover,we present new insights into the structure of the Anninghe-Xiaojiang fault zone in the southeastern margin of the Qinghai-Xizang Plateau based on data collected from a dense seismic array.We found that utilizing a dense seismic array can identify small-scale features within fault zones,aiding in the interpretation of fault zone geometry and material properties.

Effect of pore structure on seismic rock-physics characteristics of dense carbonates

The Ordovician carbonate rocks of the Yingshan formation in the Tarim Basin have a complex pore structure owing to diagenetic and secondary structures. Seismic elastic parameters（e.g., wave velocity） depend on porosity and pore structure. We estimated the average specific surface, average pore-throat radius, pore roundness, and average aspect ratio of carbonate rocks from the Tazhong area. High P-wave velocity samples have small average specific surface, small average pore-throat radius, and large average aspect ratio. Differences in the pore structure of dense carbonate samples lead to fluid-related velocity variability. However, the relation between velocity dispersion and average specific surface, or the average aspect ratio, is not linear. For large or small average specific surface, the pore structure of the rock samples becomes uniform, which weakens squirt fl ow and minimizes the residuals of ultrasonic data and predictions with the Gassmann equation. When rigid dissolved（casting mold） pores coexist with less rigid microcracks, there are significant P-wave velocity differences between measurements and predictions.

Aseismic performances of constrained damping lining structures made of rubber-sand-concrete

Flexible damping technology considering aseismic materials and aseismic structures seems be a good solution for engineering structures.In this study,a constrained damping structure for underground tunnel lining,using a rubber-sand-concrete(RSC)as the aseismic material,is proposed.The aseismic performances of constrained damping structure were investigated by a series of hammer impact tests.The damping layer thickness and shape effects on the aseismic performance such as effective duration and acceleration amplitude of time-domain analysis,composite loss factor and damping ratio of the transfer function analysis,and total vibration level of octave spectrum analysis were discussed.The hammer impact tests revealed that the relationship between the aseismic performance and damping layer thickness was not linear,and that the hollow damping layer had a better aseismic performance than the flat damping layer one.The aseismic performances of constrained damping structure under different seismicity magnitudes and geological conditions were investigated.The effects of the peak ground acceleration(PGA)and tunnel overburden depth on the aseismic performances such as the maximum principal stress and equivalent plastic strain(PEEQ)were discussed.The numerical results show the constrained damping structure proposed in this paper has a good aseismic performance,with PGA in the range(0.2-1.2)g and tunnel overburden depth in the range of 0-300 m.

Numerical analysis on seismic performance of underground structures in liquefiable interlayer sites from centrifuge shaking table test

When an underground structure passes through a liquefiable soil layer,the soil liquefaction may pose a significant threat to the structure.A centrifuge shaking table test was performed to research the seismic response of underground structures in liquefiable interlayer sites,and a valid numerical model was obtained through simulation model test.Finally,the calibrated numerical model was used to perform further research on the influence of various distribution characteristics of liquefiable interlayers on the seismic reaction of underground structures.The key findings are as follows.The structure faces the most unfavorable condition once a liquefiable layer is located in the middle of the underground structure.When a liquefiable layer exists in the middle of the structure,the seismic reactions of both the underground structure and model site will increase with the rise of the thickness of the liquefiable interlayer.The inter-story drift of the structure in the non-liquefiable site is much smaller than that in the liquefiable interlayer site.The inter-story drift of the structure is not only associated with the site displacement and the soil-structure stiffness ratio but also closely associated with the slippage of the soil-structure contact interface under the condition of large deformation of the site.

Viscosity and structure relationship with equimolar substitution of CaO with MgO in the CaO–MgO–Al_(2)O_(3)–SiO_(2)slag melts

Currently,the Al_(2)O_(3)content in the high-alumina slag systems within blast furnaces is generally limited to 16wt%–18.5wt%,making it challenging to overcome this limitation.Unlike most studies that concentrated on managing the MgO/Al_(2)O_(3)ratio or basicity,this paper explored the effect of equimolar substitution of MgO for CaO on the viscosity and structure of a high-alumina CaO-MgO-Al_(2)O_(3)-SiO_(2)slag system,providing theoretical guidance and data to facilitate the application of high-alumina ores.The results revealed that the viscosity first decreased and then increased with higher MgO substitution,reaching a minimum at 15mol%MgO concentration.Fourier transform infrared spectroscopy(FTIR)results found that the depths of the troughs representing[SiO_(4)]tetrahedra,[AlO_(4)]tetrahedra,and Si-O-Al bending became progressively deeper with increased MgO substitution.Deconvolution of the Raman spectra showed that the average number of bridging oxygens per Si atom and the X_(Q^(3))/X_(Q^(2))(X_(Q^(i))is the molar fraction of Q^(i) unit,and i is the number of bridging oxygens in a[SiO_(4)]tetrahedral unit)ratio increased from 2.30 and 1.02 to 2.52 and 2.14,respectively,indicating a progressive polymerization of the silicate structure.X-ray photoelectron spectroscopy(XPS)results highlighted that non-bridging oxygen content decreased from 77.97mol% to 63.41mol% with increasing MgO concentration,whereas bridging oxygen and free oxygen contents increased.Structural analysis demonstrated a gradual increase in the polymerization degree of the tetrahedral structure with the increase in MgO substitution.However,bond strength is another important factor affecting the slag viscosity.The occurrence of a viscosity minimum can be attributed to the complex evolution of bond strengths of non-bridging oxygens generated during depolymerization of the[SiO_(4)]and[AlO_(4)]tetrahedral structures by CaO and MgO.

Analyses of Reaction Mechanisms among Different Sulfonation Reagents and m-Diphenylamine and Crystal Structures of the Formed Compounds

In the traditional process, m-phenylenediamine reacts with fuming sulfuric acid at high temperature to get intermediates, and then after dehydration occurs intramolecular rearrangement to get 2,4-diaminobenzenesulfonic acid. Traditional methods need to consume a lot of fuming sulfuric acid or concentrated sulfuric acid, resulting in high industrial large-scale production cost, more waste, and posing a serious environmental pollution risk. In this thesis, three different sulfonation reagents were used for the sulfonation reaction of m-phenylenediamine, and the reaction mechanisms and crystal structures of the three pathways were investigated. The three routes are: 1) one-step synthesis of monosulfonated compound 1 from raw material and sulfur trioxide (SO3);2) rapid reaction of raw material and chlorosulfonic acid to synthesize bisulfonated compound 2;3) direct eutectic crystallization of raw material and ordinary sulfuric acid to obtain compound 3. The crystal structure of the compounds synthesized by three paths was analyzed by X-ray single crystal diffraction, and compound 1 was characterized by NMR, Fourier infrared spectra, UV-visible spectrum and Mass spectrometry. The one-step synthesis of SO3 as a sulfonation reagent has the advantages of mild reaction conditions, simple operation and low cost.

Study on the Influence of Aspect Ratio on the Seismic Response and Overturning Resistance of a New Staggered Story Isolated Structure

The aspect ratio of the structure has a significant impact on the overall stability of the ultra high-rise building. A large aspect ratio of the structure increases the risk of overturning and reduces the lateral stiffness of the structure, leading to significant tensile and compressive stresses in the isolated bearings. To study the effect of aspect ratio on the seismic response and overturning resistance of a new staggered story isolated structure, three models with different aspect ratios were established. Nonlinear time-history analysis of the three models was conducted using ETABS finite element software. The results indicate that the overturning moment and overturning resistance moment of the superstructure in the new staggered story isolated structure increase with an increasing aspect ratio. However, the increase in the overturning moment of the superstructure is much greater than the increase in the overturning resistance moment, resulting in a decrease in the overturning resistance ratio of the superstructure with an increasing aspect ratio. The overturning moment and overturning resistance moment of the substructure in the new staggered story isolated structure decrease with an increasing aspect ratio. However, the decrease in the overturning moment of the substructure is greater than the decrease in the overturning resistance moment, leading to an increase in the overturning resistance ratio of the substructure with an increasing aspect ratio. The decrease in the overturning resistance ratio of the superstructure in the new staggered story isolated structure is much greater than the increase in the overturning resistance ratio of the substructure. Therefore, as the aspect ratio of the overall structure increases, the overturning resistance ratio of the superstructure and the entire structure decreases.

Advanced Functional Electromagnetic Shielding Materials:A Review Based on Micro‑Nano Structure Interface Control of Biomass Cell Walls

Research efforts on electromagnetic interference(EMI)shielding materials have begun to converge on green and sustainable biomass materials.These materials offer numerous advantages such as being lightweight,porous,and hierarchical.Due to their porous nature,interfacial compatibility,and electrical conductivity,biomass materials hold significant potential as EMI shielding materials.Despite concerted efforts on the EMI shielding of biomass materials have been reported,this research area is still relatively new compared to traditional EMI shielding materials.In particular,a more comprehensive study and summary of the factors influencing biomass EMI shielding materials including the pore structure adjustment,preparation process,and micro-control would be valuable.The preparation methods and characteristics of wood,bamboo,cellulose and lignin in EMI shielding field are critically discussed in this paper,and similar biomass EMI materials are summarized and analyzed.The composite methods and fillers of various biomass materials were reviewed.this paper also highlights the mechanism of EMI shielding as well as existing prospects and challenges for development trends in this field.

Molecular Structure Tailoring of Organic Spacers for High‑Performance Ruddlesden–Popper Perovskite Solar Cells

Layer-structured Ruddlesden–Popper(RP)perovskites(RPPs)with decent stability have captured the imagination of the photovoltaic research community and bring hope for boosting the development of perovskite solar cell(PSC)technology.However,two-dimensional(2D)or quasi-2D RP PSCs are encountered with some challenges of the large exciton binding energy,blocked charge transport and poor film quality,which restrict their photovoltaic performance.Fortunately,these issues can be readily resolved by rationally designing spacer cations of RPPs.This review mainly focuses on how to design the molecular structures of organic spacers and aims to endow RPPs with outstanding photovoltaic applications.We firstly elucidated the important roles of organic spacers in impacting crystallization kinetics,charge transporting ability and stability of RPPs.Then we brought three aspects to attention for designing organic spacers.Finally,we presented the specific molecular structure design strategies for organic spacers of RPPs aiming to improve photovoltaic performance of RP PSCs.These proposed strategies in this review will provide new avenues to develop novel organic spacers for RPPs and advance the development of RPP photovoltaic technology for future applications.

3D Printing of Tough Hydrogel Scaffolds with Functional Surface Structures for Tissue Regeneration

Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.