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.

Dietary polyphenols reduced the allergenicity ofβ-lactoglobulin via non-covalent interactions:a study on the structure-allergenicity relationship

Studies showed that complexation of polyphenols with milk allergens reduced their immunogenic potential.However,the relationship between structures of polyphenols and their hypoallergenic effects on milk allergens in association with physiological and conformational changes of the complexes remain unclear.In this study,polyphenols from eight botanical sources were extracted to prepare non-covalent complexes withβ-lactoglobulin(β-LG),a major allergen in milk.The dominant phenolic compounds bound toβ-LG with a diminished allergenicity were identified to investigate their respective role on the structural and allergenic properties ofβ-LG.Extracts from Vaccinium fruits and black soybeans were found to have great inhibitory effects on the IgE-and IgG-binding abilities ofβ-LG.Among the fourteen structure-related phenolic compounds,flavonoids and tannins with larger MWs and multi-hydroxyl substituents,notably rutin,EGCG,and ellagitannins were more potent to elicit changes on the conformational structures ofβ-LG to decrease the allergenicity of complexedβ-LG.Correlation analysis further demonstrated that a destabilized secondary structure and protein depolymerization caused by polyphenol-binding were closely related to the allergenicity property of formed complexes.This study provides insights into the understanding of structure-allergenicity relationship ofβ-LG-polyphenol interactions and would benefit the development of polyphenol-fortified matrices with hypoallergenic potential.

Theoretical and experimental investigations of flexural wave propagation in periodic grid structures designed with the idea of phononic crystals

The propagation characteristics of flexural waves in periodic grid structures designed with the idea of phononic crystals are investigated by combining the Bloch theorem with the finite element method. This combined analysis yields phase constant surfaces, which predict the location and the extension of band gaps, as well as the directions and the regions of wave propagation at assigned frequencies. The predictions are validated by computation and experimental analysis of the harmonic responses of a finite structure with 11 × 11 unit cells. The flexural wave is localized at the point of excitation in band gaps, while the directional behaviour occurs at particular frequencies in pass bands. These studies provide guidelines to designing periodic structures for vibration attenuation.

Hydrothermal Synthesis and Crystal Structure of a Square Grid Coordination Copper(II) Polymer from 1,4-Bis(imidazole-1-ylmethyl)benzene

The title compound [Cu（bix）2（NO3）z·H2P]n 1 （bix = 1,4-bis（imidazole-1-ylme-thyl） benzene） has been synthesized by hydrothermal method. Its crystal structure is of monoclinic, space group P1^- with a = 8.3075（13）, b = 9.4725（13）, c = 10.0192（13） A, α = 91.088（4）, β = 104.063（6）, γ = 101.88（1）, V = 746.5（3） A^3, Z = 1, C28H30N10O7Cu1, Mr = 682.16, Dc = 1.518 g/cm^3, μ = 0.796 mm^-1, F（000） = 353, the final R = 0.0535 and wR = 0.0996 for 2921 observed reflections with I 〉 2σ（I）. Each bix ligand binds two Cu（Ⅱ） ions to form a 2-D（4,4） square grid layer, which is connected by hydrogen bonds showing large channels occupied by solvated water molecules and nitrate anions.

The Tension Cosmology, Largest Cosmic Structures and Explosions of Supernovae from SST

Here, using the Scale-Symmetric Theory (SST) we explain the cosmological tension and the origin of the largest cosmic structures. We show that a change in value of strong coupling constant for cold baryonic matter leads to the disagreement in the galaxy clustering amplitude, quantified by the parameter S8. Within the same model we described the Hubble tension. We described also the mechanism that transforms the gravitational collapse into an explosion—it concerns the dynamics of virtual fields that lead to dark energy. Our calculations concern the Type Ia supernovae and the core-collapse supernovae. We calculated the quantized masses of the progenitors of supernovae, emitted total energy during explosion, and we calculated how much of the released energy was transferred to neutrinos. Value of the speed of sound in the strongly interacting matter measured at the LHC confirms that presented here model is correct. Our calculations show that the Universe is cyclic.

Determination of optimal grid opening width for herringbone water-sediment separation structures based on sediment separation efficiency

The herringbone water-sediment separation structure(HWSSS) was developed to prevent debris flows. This paper mainly focuses on evaluating the sediment separation efficiency of HWSSS in debris flow prevention and determining the grid opening width D, a crucial structure parameter for HWSSS design. Theoretical analysis on the total sediment separation rate Pt reveals that the efficiency of sediment separation is much related with sediment grain size distribution(GSD) and grid opening width. The lower limit of Pt is deduced from the perspective of safety consideration by transforming debris flow into sediment-laden flow. Hydraulic model tests were carried out. Based on the regression analysis of the experimental data, the quantitative relationships between Pt and D and GSD characteristic values were finally established. A procedure for determining optimal grid opening width is proposed based on these analyses. These results are of significance in evaluating sediment separation effect by HWSSS in debris flow prevention and contribute to a more explicit methodology for design of HWSSS.

Analysis of Reflection Characteristics for Foam Filled Grid Structure

The reflection characteristics of gird structures are calculated by the spatial network method in the case of normal incidence plane electromagnetic wave. The numerical result shows that the grid panels without electromagnetic wave absorbing foams are not ideal. However, the absorbing ability can be achieved as low as -25 dBsm from 8 GHz to 12 GHz when the grid cells are filled with foam absorbers. Also it is noted from computation that the foam filled grid structures with larger cell size, higher and thinner ribs will improve the absorbing abilities, which illustrates that they can be used as the effective light-weight stealth structures for aeronautical application.

Unstructured Grid Immersed Boundary Method for Numerical Simulation of Fluid Structure Interaction

This paper presents an improved unstructured grid immersed boundary method.The advantages of both immersed boundary method and body fitted grids which are generated by unstructured grid technology are used to enhance the computation efficiency of fluid structure interaction in complex domain.The Navier-Stokes equation was discretized spacially with collocated finite volume method and Euler implicit method in time domain.The rigid body motion was simulated by immersed boundary method in which the fluid and rigid body interface interaction was dealt with VOS(volume of solid) method.A new VOS calculation method based on graph was presented in which both immersed boundary points and cross points were collected in arbitrary order to form a graph.The method is verified with flow past oscillating cylinder.

Study on Relation between Industrial Structure and Grid Load in Shanxi Province

The section of electric power is the foundation of national economy. The paper analyzes the relation between industrial structure and grid load in Shanxi province, and finds out that electricity demand and grid load relate linearly to value added of industry. In the end, the paper predicts electricity demand and grid load via the model.

An Overset Grid Method for Fluid-Structure Interaction

An overset grid methodology is developed for the fully coupled analysis of fluid-structure interaction (FSI) problems. The overset grid approach alleviates some of the computational geometry difficulties traditionally associated with Arbitrary-Lagrangian-Eulerian (ALE) based, moving mesh methods for FSI. Our partitioned solution algorithm uses separate solvers for the fluid (finite volume method) and the structure (finite element method), with mesh motion computed only on a subset of component grids of our overset grid assembly. Our results indicate a significant reduction in computational cost for the mesh motion, and element quality is improved. Numerical studies of the benchmark test demonstrate the benefits of our overset mesh method over traditional approaches.

Allozyme Diversity and Population Genetic Structure of Three Medicinal Epimedium Species from Hubei

Three Epimedium species, E. pubescens Maxim., E. sagittatum （Sieb. ＆ Zucc.） Maxim., and E. wushanense T. S. Ying, which are sympatrically distributed in the western Hubei Province, have been used in traditional Chinese medicine （TCM） for about 2,000 years. Genetic variability and population genetic structure of 11 natural populations of these Epimedium species were investigated using isoelectric focusing in thin-layer polyacrylamide slab gels. Of the 22 enzyme systems prescreened, six coding for 13 loci and 45 alleles were resolved, which were used for analyzing genetic diversity and population structure at both intraspecific and interspecific levels. The results showed that： l） high levels of genetic diversity were observed in all three species （A = 2.6-3.2, P = 69.2%-84.6%, Ho= 0.274-0.377, HE= 0.282-0.369）, which were higher than that of other herbaceous and aulmal-pollinated species with similar life-history characteristics; 2） there was significant deviation from Hardy-Weinberg Equilibrium, with one half of the loci showing heterozygote excess and the other homozygote excess, in all populations, suggesting the complicated breeding system of Epimedium species; 3） the low level of intraspecific and interspecific genetic differentiation （GST= 0.0246-0.0409 and 0.0495-0.1213, respectively） indicated a high level of gene flow among populations and close genetic relationship among the three species; and 4） UPGMA cluster analysis further showed that E. pubescens was more closely related to E. sagittatum than to E. wushanense, which was in good agreement with the morphological characters and the recent phylogenetic analysis of these species. On the basis of these results, it was concluded that the mixed breeding system, long-lived perennial life form, ancient evolutionary history, and seed dispersal by ants in Epimedium are responsible for the genetic variation and population structure of these species.

A study on deep structure using teleseismic receiver function in Western Yunnan

s Western Yunnan is located at the boundary of collision or underthrusting zone of Eurasian plate and is influenced by many times tectonic movements. With very complex geological environment and tectonic background, it is one of the seismically active areas. In the paper, the teleseismic records were selected from 16 national, local and mo-bile stations, including 4 very-wide-band mobile stations of PASSCAL. And nearly 2 000 receiver functions were extracted. Two measuring lines are 650 km and 450 km, respectively and across some major tectonic units in Western Yunnan. It is indicated that Nujiang might be a seam characterized by underthrusting. The western and eastern boundaries of Sichuan-Yunnan rhombus block, i.e., Honghe and Xiaojiang faults, might be an erection seam or collision belt. Panxi tectonic zone still has the characteristics of continental rift valley, that is, the surface is hollow and the upper mantle is upwarping. The tectonic situation in Western Yunnan is of certain regulation with the interlacing distribution of orogenic zone and seam. The crustal thickness decreases gradually from the north to the south and the S wave velocity is globally lower here.

Analysis of the Structure of Shakespeare's Sonnets

The sonnet is a kind of lyrics with restrict forms which cannot depart from the contents. Shakespeare's sonnets are like a valuable flower blossoming in the England poetry garden during the age of Renaissance and a bright pearl sparkling in the world's poetry treasury. This paper will analyze his sonnets from the perspective of the structure and then interpret the meanings behind those words, which can demonstrate the importance of the connection between the forms and the contents.

Effect of C/S Ratio on Morphology and Structure of Hydrothermally Synthesized Calcium Silicate Hydrate

The samples of the C-S-H series were synthesized by hydrothermal reaction of fumed silica, CaO and deionized water at initial C/S ratios between 1.0-1.7. Phase composition and structural and morphology characteristics of C-S-H samples were analyzed by XRD, IR and SEM. The experimental results showed that the d-spacing of （002）, （110） and （020） decreased, the d-spacing of （200） increased, and the d-spacing of （310） varied randomly, the polymerization of silica tetrahedra of C-S-H decreased, and morphology of C-S-H samples varied from sheet shapes to long reticular fibers as C/S ratio increased.

A welding document management software package based on a Client/Server structure

According to specifications for Welding Procedure Qualification of ASME IX Section and Chinese code, JB 4708 2000, a software package for managing welding documents has been rebuilt. Consequently, the new software package can be used in a Limited Area Network (LAN) with 4 different levels of authorities for different users. Therefore, the welding documents, including DWPS (Design for Welding Procedure Specifications), PQRs (Procedure Qualification Records) and WPS (Welding Procedure Specifications) can be shared within a company. At the same time, the system provides users various functions such as browsing, copying, editing, searching and printing records, and helps users to make decision of whether a new PQR test is necessary or not according to the codes above as well. Furthermore, super users can also browse the history of record modification and retrieve the records when needed.

A study on deep structure using teleseismic receiver function in Western Yunnan

s Western Yunnan is located at the boundary of collision or underthrusting zone of Eurasian plate and is influenced by many times tectonic movements. With very complex geological environment and tectonic background, it is one of the seismically active areas. In the paper, the teleseismic records were selected from 16 national, local and mo-bile stations, including 4 very-wide-band mobile stations of PASSCAL. And nearly 2 000 receiver functions were extracted. Two measuring lines are 650 km and 450 km, respectively and across some major tectonic units in Western Yunnan. It is indicated that Nujiang might be a seam characterized by underthrusting. The western and eastern boundaries of Sichuan-Yunnan rhombus block, i.e., Honghe and Xiaojiang faults, might be an erection seam or collision belt. Panxi tectonic zone still has the characteristics of continental rift valley, that is, the surface is hollow and the upper mantle is upwarping. The tectonic situation in Western Yunnan is of certain regulation with the interlacing distribution of orogenic zone and seam. The crustal thickness decreases gradually from the north to the south and the S wave velocity is globally lower here.

Dinuclear Copper(Ⅱ) Complex with a New Polycarboxylate Ligand:Syntheses,Characterization and Crystal Structure

A dinuclear copper（Ⅱ） complex,[Cu2（HL）2（H2O）6] 1（H3L = 2,4,6-tri（3-carboxy-phenylthio）-1,3,5-triazine）,was synthesized hydrothermally and characterized by single-crystal X-ray diffraction,IR and thermal analysis.Single-crystal X-ray diffraction reveals that complex 1 is a dinuclear copper（Ⅱ） complex,which is further extended to a 3D network by weak interactions such as O…H-O hydrogen bonds and noncovalent S...S interactions.The crystal of compound 1 belongs to monoclinic,space group C2/c,with a = 50.15（2）,b = 6.789（3）,c =15.667（8） ,β = 90.588（9）o,V = 5334（4） 3,Z = 4,C48H38Cu2N6O18S6,Mr = 1306.28,Dc = 1.627 g/cm3,F（000） = 2664,Rint = 0.0631,T = 293（2） K,μ = 1.112 mm-1,the final R = 0.0661 and wR = 0.1850 for 3782 observed reflections with I 2σ（I）.

PERTURBATIONAL FINITE VOLUME METHOD FOR THE SOLUTION OF 2-D NAVIER-STOKES EQUATIONS ON UNSTRUCTURED AND STRUCTURED COLOCATED MESHES

Based on the first-order upwind and second-order central type of finite volume (UFV and CFV) scheme, upwind and central type of perturbation finite volume (UPFV and CPFV) schemes of the Navier-Stokes equations were developed. In PFV method, the mass fluxes of across the cell faces of the control volume (CV) were expanded into power series of the grid spacing and the coefficients of the power series were determined by means of the conservation equation itself. The UPFV and CPFV scheme respectively uses the same nodes and expressions as those of the normal first-order upwind and second-order central scheme, which is apt to programming. The results of numerical experiments about the flow in a lid-driven cavity and the problem of transport of a scalar quantity in a known velocity field show that compared to the first-order UFV and second-order CFV schemes, upwind PFV scheme is higher accuracy and resolution, especially better robustness. The numerical computation to flow in a lid-driven cavity shows that the under-relaxation factor can be arbitrarily selected ranging from (0.3) to (0.8) and convergence perform excellent with Reynolds number variation from 10~2 to 10~4.

Spatial distribution characteristics of bacterial community structure and gene abundance in sediments of the Bohai Sea

This study investigated differences in the community structure and environmental responses of the bacterial community in sediments of the Bohai Sea.Illumina high-throughput sequencing technology and real-time PCR were used to assay the bacterial 16S rRNA genes in the surface sediments of 13 sampling stations in the Bohai Sea.The results showed that sediments at the majority of the 13 sampling stations were contaminated by heavy metal mercury.The main phyla of bacteria recorded included Proteobacteria(52.92%),Bacteroidetes(11.76%),Planctomycetes(7.39%),Acidobacteria(6.53%)and Chloroflexi(4.97%).The genus with the highest relative abundance was Desulfobulbus(4.99%),which was the dominant genus at most sampling stations,followed by Lutimonas and Halioglobus.The main factors influencing bacterial community structure were total organic carbon,followed by depth and total phosphorus.The content of lead,cadmium,chromium,copper and zinc had a consistent effect on community structure.Arsenic showed a negative correlation with bacterial community structure in most samples,while the impact of mercury on community structure was not significant.The bacterial community in sediment samples from the Bohai Sea was rich in diversity and displayed an increase in diversity from high to low latitudes.The data indicated that the Bohai Sea had abundant microbial resources and was rich in bacteria with the potential to metabolize many types of pollutants.

The quadratic-form identity for constructing Hamiltonian structures of the Guo hierarchy

The trace identity is extended to the quadratic-form identity. The Hamiltonian structures of the multi-component Guo hierarchy, integrable coupling of Guo hierarchy and （2＋l）-dimensional Guo hierarchy are obtained by the quadraticform identity. The method can be used to produce the Hamiltonian structures of the other integrable couplings or multi-component hierarchies.