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.

In-situ additive manufacturing of high strength yet ductility titanium composites with gradient layered structure using N_(2)

It has always been challenging work to reconcile the contradiction between the strength and plasticity of titanium materials.Laser powder bed fusion(LPBF) is a convenient method to fabricate innovative composites including those inspired by gradient layered materials.In this work,we used LPBF to selectively prepare Ti N/Ti gradient layered structure(GLSTi)composites by using different N_(2)–Ar ratios during the LPBF process.We systematically investigated the mechanisms of in-situ synthesis Ti N,high strength and ductility of GLSTi composites using microscopic analysis,TEM characterization,and tensile testing with digital image correlation.Besides,a digital correspondence was established between the N_(2) concentration and the volume fraction of LPBF in-situ synthesized Ti N.Our results show that the GLSTi composites exhibit superior mechanical properties compared to pure titanium fabricated by LPBF under pure Ar.Specifically,the tensile strength of GLSTi was more than 1.5times higher than that of LPBF-formed pure titanium,reaching up to 1100 MPa,while maintaining a high elongation at fracture of 17%.GLSTi breaks the bottleneck of high strength but low ductility exhibited by conventional nanoceramic particle-strengthened titanium matrix composites,and the hetero-deformation induced strengthening effect formed by the Ti N/Ti layered structure explained its strength-plasticity balanced principle.The microhardness exhibits a jagged variation of the relatively low hardness of 245 HV0.2 for the pure titanium layer and a high hardness of 408 HV0.2 for the N_(2) in-situ synthesis layer.Our study provides a new concept for the structure-performance digital customization of 3D-printed Ti-based composites.

Utilizing a defective MgO layer for engineering multifunctional Co-MOF hybrid materials with tailored leaf-like and polyhedral structures for optimal electrochemical and photocatalytic activities

The hybridization of metal-organic framework(MOF)with inorganic layers would lead to the discovery of novel hybrid materials that can provide a compelling strategy for enhancing its photocatalytic and electrochemical response.In the present study,a highly efficient multifunctional hybrid material was developed by exploiting the defective layer formed on AZ31 Mg alloy through plasma electrolytic oxidation(PEO)as a nucleation and growth site for Co-MOF.The concentrations of the organic linker 2-Methylimidazole(2,MIm)and cobalt nitrate as a source of Co^(2+) ions were varied to control the growth of the obtained Co-MOF.Lower concentrations of the 2,MIm ligand favored the formation of leaf-like MOF structures through an anisotropic,two-dimensional growth,while higher concentrations led to rapid,isotropic nucleation and the creation of polyhedral Co-MOF structures.The sample characterized by polyhedral Co-MOF structures exhibited superior electrochemical stability,with the lowest corrosion current density(3.11×10^(-9) A/cm^(2))and the highest top layer resistance(2.34×10^(6)Ωcm^(2)),and demonstrated outstanding photocatalytic efficiency,achieving a remarkable 99.98%degradation of methylene blue,an organic pollutant,in model wastewater.To assess the active adsorption sites of the Co-MOF,density functional theory(DFT)was utilized.This study explores the changes in morphologies of the coatings of Co-MOF with the change of solution concentration to form coatings with enhanced properties on the metallic substrate,which could establish the groundwork for the development of next-generation multifunctional frameworks with diverse applications.

Reversible Mn^(2+)/Mn^(4+)double-electron redox in P3-type layer-structured sodium-ion cathode

The balance between cationic redox and oxygen redox in layer-structured cathode materials is an important issue for sodium batteries to obtain high energy density and considerable cycle stability.Oxygen redox can contribute extra capacity to increase energy density,but results in lattice instability and capacity fading caused by lattice oxygen gliding and oxygen release.In this work,reversible Mn^(2+)/Mn^(4+)redox is realized in a P3-Na_(0.65)Li_(0.2)Co_(0.05)Mn_(0.75)O_(2)cathode material with high specific capacity and structure stability via Co substitution.The contribution of oxygen redox is suppressed significantly by reversible Mn^(2+)/Mn^(4+)redox without sacrificing capacity,thus reducing lattice oxygen release and improving the structure stability.Synchrotron X-ray techniques reveal that P3 phase is well maintained in a wide voltage window of 1.5-4.5 V vs.Na^(+)/Na even at 10 C and after long-term cycling.It is disclosed that charge compensation from Co/Mn-ions contributes to the voltage region below 4.2 V and O-ions contribute to the whole voltage range.The synergistic contributions of Mn^(2+)/Mn^(4+),Co^(2+)/Co^(3+),and O^(2-)/(O_n)^(2-)redox in P3-Na_(0.65)Li_(0.2)Co_(0.05)Mn_(0.75)O_(2)lead to a high reversible capacity of 215.0 m A h g^(-1)at 0.1 C with considerable cycle stability.The strategy opens up new opportunities for the design of high capacity cathode materials for rechargeable batteries.

Large Eddy Simulation of Vertical Structure and Size Density of Deep Layer Clouds

In a convective scheme featuring a discretized cloud size density, the assumed lateral mixing rate is inversely proportional to the exponential coefficient of plume size. This follows a typical assumption of-1, but it has unveiled inherent uncertainties, especially for deep layer clouds. Addressing this knowledge gap, we conducted comprehensive large eddy simulations and comparative analyses focused on terrestrial regions. Our investigation revealed that cloud formation adheres to the tenets of Bernoulli trials, illustrating power-law scaling that remains consistent regardless of the inherent deep layer cloud attributes existing between cloud size and the number of clouds. This scaling paradigm encompasses liquid, ice, and mixed phases in deep layer clouds. The exponent characterizing the interplay between cloud scale and number in the deep layer cloud, specifically for liquid, ice, or mixed-phase clouds, resembles that of shallow convection,but converges closely to zero. This convergence signifies a propensity for diminished cloud numbers and sizes within deep layer clouds. Notably, the infusion of abundant moisture and the release of latent heat by condensation within the lower atmospheric strata make substantial contributions. However, this role in ice phase formation is limited. The emergence of liquid and ice phases in deep layer clouds is facilitated by the latent heat and influenced by the wind shear inherent in the middle levels. These interrelationships hold potential applications in formulating parameterizations and post-processing model outcomes.

Formation mechanism of periodic layered structure in Ni_3Si/Zn system

The formation of periodic layered structure in Ni3Si/Zn diffusion couples with Zn in vapor or liquid state was investigated by SEM-EDS, FESEM and XRD. The results show that the diffusion path in solid-liquid reaction is Ni3Si/（T＋γ）/γ/…T/γ/Ni4Zn12Si3/γ/…Ni4Zn12Si3/γ/Ni4Zn12Si3/δ…/Ni4Zn12Si3/δ/liquid-Zn, and the diffusion path in solid-vapor reaction is Ni3Si/θ/（T＋γ）/γ/…/T/γ/…T/γ/vapor-Zn. With increasing Zn diffusion flux, the diffusion reaction path moves toward the Zn-rich direction, and the distance from the Ni3Si substrate to the periodic layer pair nearest to the interface decreases. In the initial stage of both reactions,γphase nucleates and grows within T matrix phase at first, and then conjuncts together to form a band to reduce the surface energy. Based on the experimental results and diffusion kinetics analysis, the microstructure differences were compared and the formation mechanism of the periodic layered structure in Ni3Si/Zn system was discussed.

NONLINEAR EFFECT OF LOCAL ROUGH WALL ON LARGE EDDY STRUCTURE IN BOUNDARY LAYER

Based on the building of a theoretical model for the large eddy structure, the nonlinear effect of the local rough wall on the large eddy structure in the boundary layer is studied by direct numerical simulation. Numerical results show that factors of the local rough feature, the distributing structure and the intensity, etc. play an important role in the evolution of the large eddy structure in the boundary layer.

Layered Structural PBAT Composite Foams for Efficient Electromagnetic Interference Shielding

The utilization of eco-friendly,lightweight,high-efficiency and high-absorbing electromagnetic interference(EMI)shielding composites is imperative in light of the worldwide promotion of sustainable manufacturing.In this work,magnetic poly(butyleneadipate-coterephthalate)(PBAT)microspheres were firstly synthesized via phase separation method,then PBAT composite foams with layered structure was constructed through the supercritical carbon dioxide foaming and scraping techniques.The merits of integrating ferroferric oxideloaded multi-walled carbon nanotubes(Fe3O4@MWCNTs)nanoparticles,a microcellular framework,and a highly conductive silver layer have been judiciously orchestrated within this distinctive layered configuration.Microwaves are consumed throughout the process of“absorption-reflection-reabsorption”as much as possible,which greatly declines the secondary radiation pollution.The biodegradable PBAT composite foams achieved an EMI shielding effectiveness of up to 68 dB and an absorptivity of 77%,and authenticated favorable stabilization after the tape adhesion experiment.

Difficulties, strategies, and recent research and development of layered sodium transition metal oxide cathode materials for high-energy sodium-ion batteries

Energy-storage systems and their production have attracted significant interest for practical applications.Batteries are the foundation of sustainable energy sources for electric vehicles(EVs),portable electronic devices(PEDs),etc.In recent decades,Lithium-ion batteries(LIBs) have been extensively utilized in largescale energy storage devices owing to their long cycle life and high energy density.However,the high cost and limited availability of Li are the two main obstacles for LIBs.In this regard,sodium-ion batteries(SIBs) are attractive alternatives to LIBs for large-scale energy storage systems because of the abundance and low cost of sodium materials.Cathode is one of the most important components in the battery,which limits cost and performance of a battery.Among the classified cathode structures,layered structure materials have attracted attention because of their high ionic conductivity,fast diffusion rate,and high specific capacity.Here,we present a comprehensive review of the classification of layered structures and the preparation of layered materials.Furthermore,the review article discusses extensively about the issues of the layered materials,namely(1) electrochemical degradation,(2) irreversible structural changes,and(3) structural instability,and also it provides strategies to overcome the issues such as elemental phase composition,a small amount of elemental doping,structural design,and surface alteration for emerging SIBs.In addition,the article discusses about the recent research development on layered unary,binary,ternary,quaternary,quinary,and senary-based O3-and P2-type cathode materials for high-energy SIBs.This review article provides useful information for the development of high-energy layered sodium transition metal oxide P2 and O3-cathode materials for practical SIBs.

Influence of topography on the fine structures of stratospheric gravity waves:An analysis using COSMIC-2 temperature data

We derive the potential energy of gravity waves(GWs)in the upper troposphere and stratosphere at 45°S-45°N from December 2019 to November 2022 by using temperature profiles retrieved from the Constellation Observing System for Meteorology,Ionosphere,and Climate-2(COSMIC-2)satellite.Owing to the dense sampling of COSMIC-2,in addition to the strong peaks of gravity wave potential energy(GWPE)above the Andes and Tibetan Plateau,we found weak peaks above the Rocky,Atlas,Caucasus,and Tianshan Mountains.The land-sea contrast is responsible for the longitudinal variations of the GWPE in the lower and upper stratosphere.At 40°N/S,the peaks were mainly above the topographic regions during the winter.At 20°N/S,the peaks were a slight distance away from the topographic regions and might be the combined effect of nontopographic GWs and mountain waves.Near the Equator,the peaks were mainly above the regions with the lowest sea level altitude and may have resulted from convection.Our results indicate that even above the local regions with lower sea level altitudes compared with the Andes and Tibetan Plateau,the GWPE also exhibits fine structures in geographic distributions.We found that dissipation layers above the tropopause jet provide the body force to generate secondary waves in the upper stratosphere,especially during the winter months of each hemisphere and at latitudes of greater than 20°N/S.

Characteristics of the Boundary Layer Structure of Sea Fog on the Coast of Southern China

Using boundary layer data with regard to sea fog observed at the Science Experiment Base for Marine Meteorology at Bohe,Guangdong Province,the structure of the atmospheric boundary layer and the characteristics of the tops of the fog and the clouds were analyzed.In addition,the effects of advection,radiation,and turbulence during sea fog were also investigated.According to the stability definition of saturated,wet air,the gradient of the potential pseudo-equivalent temperature equal to zero was defined as the thermal turbulence interface.There is evidence to suggest that two layers of turbulence exist in sea fog.Thermal turbulence produced by long-wave radiation is prevalent above the thermal turbulence interface,whereas mechanical turbulence aroused by wind shear is predominant below the interface.The height of the thermal turbulence interface was observed between 180 m and 380 m.Three important factors are closely related to the development of the top of the sea fog：（1） the horizontal advection of the water vapor,（2） the long-wave radiation of the fog top,and（3） the movement of the vertical turbulence.Formation,development,and dissipation are the three possible phases of the evolution of the boundary-layer structure during the sea fog season.In addition,the thermal turbulence interface is the most significant turbulence interface during the formation and development periods;it is maintained after sea fog rises into the stratus layer.

Wave localization in randomly disordered periodic layered piezoelectric structures

Considering the mechnoelectrical coupling, the localization of SH-waves in disordered periodic layered piezoelectric structures is studied. The waves propagating in directions normal and tangential to the layers are considered. The transfer matrices between two consecutive unit cells are obtained according to the continuity conditions. The expressions of localization factor and localization length in the disordered periodic structures are presented. For the disordered periodic piezoelectric structures, the numerical results of localization factor and localization length are presented and discussed. It can be seen from the results that the frequency passbands and stopbands appear for the ordered periodic structures and the wave localization phenomenon occurs in the disordered periodic ones, and the larger the coefficient of variation is, the greater the degree of wave localization is. The widths of stopbands in the ordered periodic structures are very narrow when the properties of the consecutive piezoelectric materials are similar and the intervals of stopbands become broader when a certain material parameter has large changes. For the wave propagating in the direction normal to the layers the localization length has less dependence on the frequency, but for the wave propagating in the direction tangential to the layers the localization length is strongly dependent on the frequency.

Tomographic PIV investigation of coherent structures in a turbulent boundary layer flow

Tomographic particle image velocimetry was used to quantitatively visualize the three-dimensional co- herent structures in the logarithmic region of the turbulent boundary layer in a water tunnel. The Reynolds number based on momentum thickness is Reo = 2 460. The in- stantaneous velocity fields give evidence of hairpin vortices aligned in the streamwise direction forming very long zones of low speed fluid, which is flanked on either side by high- speed ones. Statistical support for the existence of hairpins is given by conditional averaged eddy within an increasing spanwise width as the distance from the wall increases, and the main vortex characteristic in different wall-normal re- gions can be reflected by comparing the proportion of ejec- tion and its contribution to Reynolds stress with that of sweep event. The pre-multiplied power spectra and two-point cor- relations indicate the presence of large-scale motions in the boundary layer, which are consistent with what have been termed very large scale motions （VLSMs）. The three dimen-sional spatial correlations of three components of veloc- ity further indicate that the elongated low-speed and high- speed regions will be accompanied by a counter-rotating roll modes, as the statistical imprint of hairpin packet structures, all of which together make up the characteristic of coherent structures in the logarithmic region of the turbulent boundary layer （TBL）.

Numerical Study of Boundary Layer Structure and Rainfall after Landfall of Typhoon Fitow(2013): Sensitivity to Planetary Boundary Layer Parameterization

The boundary layer structure and related heavy rainfall of Typhoon Fitow(2013), which made landfall in Zhejiang Province, China, are studied using the Advanced Research version of the Weather Research and Forecasting model, with a focus on the sensitivity of the simulation to the planetary boundary layer parameterization. Two groups of experiments—one with the same surface layer scheme and including the Yonsei University(YSU), Mellor–Yamada–Nakanishi–Niino Level 2.5,and Bougeault and Lacarrere schemes; and the other with different surface layer schemes and including the Mellor–Yamada–Janjic′ and Quasi-Normal Scale Elimination schemes—are investigated. For the convenience of comparative analysis, the simulation with the YSU scheme is chosen as the control run because this scheme successfully reproduces the track, intensity and rainfall as a whole. The maximum deviations in the peak tangential and peak radial winds may account for 11% and 33%of those produced in the control run, respectively. Further diagnosis indicates that the vertical diffusivity is much larger in the first group, resulting in weaker vertical shear of the tangential and radial winds in the boundary layer and a deeper inflow layer therein. The precipitation discrepancies are related to the simulated track deflection and the differences in the simulated low-level convergent flow among all tests. Furthermore, the first group more efficiently transfers moisture and energy and produces a stronger ascending motion than the second, contributing to a deeper moist layer, stronger convection and greater precipitation.

A KIND OF FAST CHANGING COHERENT STRUCTURE IN A TURBULENT BOUNDARY LAYER

Coherent structures of a turbulent boundary layer were investigated by hydrogen bubble method. A kind of fast changing structure was observed. That is a spot in which all the hydrogen bubbles vanish much faster than in other regions. This investigation verified that dark-spot is formed by a strong sweep from outer layer. Inside a dark-spot the local instantaneous flow speed might be four times of its neighboring high-speed streaks. Comparing with the low/high speed streaks, both dark-spot and the vortical structures around it are changing very fast. Around dark-spot intensive shear layers are formed and indications of the generation of small-scale structures could be observed.

WAVELET ANALYSIS OF COHERENT STRUCTURES IN A THREE-DIMENSIONAL MIXING LAYER

Wavelet analysis is applied to the results obtained by the direct numerical simulation of a three-dimensional (3D) mixing layer in order to investigate coherent structures in dimension of scale. First, 3D orthonormal wavelet bases are constructed, and the corresponding decomposition algorithm is developed. Then the Navier-Stokes equations are transformed into the wavelet space and the architecture for multi-scale analysis is established. From this architecture, the coarse field images in different scales are obtained and some local statistical quantities are calculated. The results show that, with the development of a mixing layer, the energy spectrum densities for different wavenumbers increase and the energy is transferred from the average flow to vortex structures in different scales. Due to the non-linear interactions between different scales, cascade processes of energy are very complex. Because vortices always roll and pair at special areas, for a definite scale, the energy is obtained from other scales at some areas while it is transferred to other scales at other areas. In addition, energy dissipation and transfer always occur where an intense interaction between vortices exists.

The transient fracture behavior for a functionally graded layered structure subjected to an in-plane impact load

The transient fracture behavior of a functionally graded layered structure subjected to an in-plane impact load is investigated. The studied structure is composed of two homogeneous layers and a functionally gradedinterlayer with a crack perpendicular to the boundaries. The impact load is applied on the face of the crack. Fourier transform and Laplace transform methods are used to formulate the present problem in terms of a singular integral equation in Laplace transform domain. Considering variations of parameters such as the nonhomogeneity constant, the thickness ratio and the crack length, the dynamic stress intensity factors （DSIFs） in time domain are studied and some meaningful conclusions are obtained.

PROPAGATION OF SURFACE ACOUSTIC WAVES IN PRESTRESSED ANISOTROPIC LAYERED PIEZOELECTRIC STRUCTURES

The propagation of surface acoustic waves in layered piezoelectric structureswith initial stresses is investigated. The phase velocity equations are obtained for electricallyfree and shorted cases, respectively. Effects of the initial stresses on the phase velocity and theelectromechanical coupling coefficient for the fundamental mode of the layered piezoelectricstructures are discussed. Numerical results for the c-axis oriented film of LiNbO_3 on a sapphiresubstrate are given. It is found that the fractional change in phase velocity is a linear functionwith the initial stresses, and the electromechanical coupling factor increases with an increase ofthe absolute values of the compressive initial stresses. The results are useful for the design ofsurface acoustic wave devices.

A review:Modification strategies of nickel-rich layer structure cathode(Ni≥0.8)materials for lithium ion power batteries

Lithium ion power batteries have undoubtedly become one of the most promising rechargeable batteries at present;nonetheless,they still suffer from the challenges such as requirement of even higher energy density and capacity retention.Nickel-rich layer oxides(Ni≥0.8)become ideal cathode materials to achieve the high specific capacity.Integration of optimization of synthesis process and modification of crystal structure to suppress the capacity fading can obviously improve the performance of the lithium ion batteries.This review presents the recent modification strategies of the nickel-rich layered oxide materials.Unlike in previous reviews and related papers,the specific mechanism about each type of the modification strategies is specially discussed in detail,which is mainly about inhibiting the anisotropic lattice strain and adjusting the cation mixing degree to maintain crystal structure.Based on the recent progress,the prospects and challenges of the modified nickel-rich layer cathodes to upgrade the property of lithium ion batteries are also comprehensively analyzed,and the potential applications in the field of plug-in hybrid vehicles and electric vehicles are further discussed.

The tuning of pore structures and acidity for Zn/Al layered double hydroxides:The application on selective hydrodesulfurization for FCC gasoline

Co–Mo catalysts applied on the hydrodesulfurization（HDS） for FCC gasoline were prepared with Zn–Al layered double hydroxides（LDHs） to improve their performances,and the effects of pore structures and acidity on HDS performances were studied in detail. A series of Zn–Al/LDHs samples with different pore structures and acidities are synthesized on the bases of co-precipitation of OH-,CO2-,Al3＋,and Zn2＋. The neutralization p H is a main factor to affect the pore structures and acidity of Zn–Al/LDHs,and a series of Zn–Al/LDHs with different pore structures and acidities are obtained. Based on the representative samples with different specific surface areas（SBET） and acidities,three Co Mo/LDHs catalysts were prepared,and their HDS performances were compared with traditional Co Mo/Al2O3 catalysts. The results indicated that catalysts prepared with high SBETpossessed high HDS activity,and Br？nsted acid sites could reduce the thiol content in the product to some extent. All the three catalysts prepared with LDHs displayed little lower HDS activity but higher selectivity than Co Mo/Al2O3,and could restrain the reactions of re-combination between olefin and H2 S which could be due to the existence of Br？nsted acid sites.