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.

Effect of Crystalline Structure of Wood on Liquefaction

By means of X ray and gas chromatography analysis, the crystalline structure of untreated wood , alkali treated wood and benzylated wood and their liquefaction in toluene and tetrahydrofufan with HCl as a catalyst were studied .The upper solution of benzylated wood was also studied by GC MS analysis. It proved that the introduction of bulky benzyl group in wood significantly changed the crystalline structure of wood ,enlarging the free volume which facilitated the penetration of solvent into the matrix of treated wood, thus tremendously enhancing thesolubility in solvent,compared to untreated wood and alkali treated wood. The percentage of residue decreased and the combined solvent increased with the increase of weight gain revealed that the liquefaction process became easy. Furthermore, the factors that influenced the liquefaction of benzylated wood were investigated. It showed that the liquefaction performance was improved with the increase of liquefaction time and the amount of catalyst when toluene was used as a solvent, especially in the presence of THF as solvent, there existed the optimum liquefaction time and the amount of catalyst .

Discussion on Selection of Wood Structure of Ancient Buildings in China

Based on wood structure of ancient buildings in China,the paper considers that Chinese ancient people have selected wood as the architectural material due to its characteristics and some necessity.After the analysis of architectural features of traditional settlements,it has found that Chinese ancient people tend to draw on local materials for construction.Then,it further analyzes the adaptability of Chinese wood structure,and the flexibility and complexity of its plane layout.By combining with Chinese's life value,the eternal significance contained in wood structure has been explained based on material and spiritual level.From the perspective of natural selection,technological advancement,spatial advantage,spiritual value and aesthetic need,the paper tries to find causes for wood structure as architectural materials,aiming to objectively treat the effort of Chinese ancient people made in the progress history of human civilization.

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.

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.

A feasibility study of using two-component polyurethane adhesive in constructing wooden structures

This investigation was conducted to determine the feasibility of using a two-component polyurethane （PUR） adhesive, with special waterproof properties, in constructing wooden structures. We designed and conducted tests to compare the shear strength and adhesion performance of PUR with polyvinyl acetate （PVAc） adhesive on block-shear specimens constructed of oriental beech （Fagus orientalis L.）, fir （Abies alba Mill.）, poplar （Populus deltoides Bartr.）, white oak （Quercus alba L.）, sycamore （Platanus orientalis L.） and white walnut （Juglans cinerea L.）. The values of the percentage of wood failure were also determined in specimens constructed with each adhesive. The highest shear strength values of both adhesives were obtained in specimens constructed of beech, while the lowest shear strength values were obtained in fir and poplar specimens. Average shear strength of the PUR adhesive was 16.5% higher than that of the PVAc adhesive. Specimens constructed of fir, poplar and sycamore were characterised by the highest percentages of wood failure, whereas the lowest average percentages of wood failure were obtained in beech and oak specimens. With the exception of oak specimens, there was no statistically significant difference between percentage of wood failure among the PUR and PVAc adhesives. Generally, the PUR adhesive showed an acceptable adhesion performance on wood materials used in our study.

Experimental study on large wood filtration performance by herringbone water-sediment separation structure

A herringbone water-sediment separation structure(hereinafter referred to as "herringbone structure") has been shown to be effective in separating coarse inorganic debris; however, less is known regarding the large wood(LW) filtration effect in this structure. This paper presents preliminary research on the wood filtration effect of the herringbone structure based on physical model tests.The results show that the herringbone structure exhibited effective performance in large wood size segregation, with a 100% component filtration rate for LW that diameter(D) larger than ribbed beam opening width(a). The total filtration rate also exceeded 80% when the Fraud number(Fr) is larger than 2.64 and increased with the increase of Fr. After exceeding Frmax, total filtration rate would be decreased due to overflow. Beside flow condition,structure parameters influence significantly on LW filtration rate. We attempt to explain the filtration process via particle contact trajectory and particle movement trajectory. The inclined angle of ribbed beam(γ) contributed the most variation to the filtration rate via influencing the coincidence with particle contact trajectory and particle movement trajectory. The high sensitivity coefficient of ribbed beam(θ) under relatively low Fr conditions implies remarkable influences on LW filtration effects by causing clogging problem. The ribbed beam opening width(a) together with LW diameter(D) influenced the size segregation performance.

Relations Between Permeability and Structure of Wood

The permeability and the structure of heartwood and sapwood of the solvent-exchange dried and the air-dried greenwood of Chinese-fir (Cunninghamia lanceolata (Lamb.) Hook.) and masson pine (Pinus massoniana Lamb.) were measured in order to study the relations between the permeability and the structure. The results showed that the permeability of sapwood of both the air-dried and the solvent-exchange dried wood was higher than that of heartwood, and the permeability of the solvent-exchanged dried heartwood and sapwood was higher than that of the air-dried. A higher permeability of wood was attributed to, on the one hand, a bigger number of flow path per unit area of the wood perpendicular to the flow direction resulted from a bigger number of unaspirated pits per unit area and a bigger number of effective pit openings per membrane, and on the other hand, a smaller number of tracheid in series connection per unit length parallel to flow direction resulted from a longer tracheid length and an effective tracheid length for permeability.

THE DETECTION OF THE BOUNDARY OF IMAGE OF WOODANATOMICAL STRUCTURE MOLECULAR

Basing on a lot of examinations, according to the fundamental inage processing theories and methods, getting touch with the property of wood anatomical structure image,we put forward the optimum method and theory which are suitable for the binary processing of the wood anatomical structure image. After the wood image has been processed binary, with the help of computer vision technology, the boundary of wood anatomical structure molecular binary image was sought This kind of theory and method lay a solid foundaion on the collection of feature and the pottern recognition and other high level processing of wood anatomical structure molecular image.

Impacts of Wood Poaching on Vegetation Structure and Composition in Mukuvisi Woodland, Zimbabwe

Our study focused on the effects of wood poaching on the vegetation structure and composition in Mukuvisi Woodland, Zimbabwe. Mukuvisi Woodland, located within the precincts of Harare urban area, Zimbabwe, suffers from high illegal wood utilization pressure stemming from the need to fulfill alternative energy demands created by persistent electricity shortages and an unstable economic environment, particularly between 2000 and 2008. This results in a continuous flux of vegetation and a disturbed animal habitat driven mainly by anthropogenic activities. Due to the heterogeneity in vegetation utilisation trends, we used the stratified systematic random sampling technique, where the site was divided into two strata, central and boundary. Twelve 30 × 20 m permanent plots were established in which species name, species diversity, height, basal area, plant status, fire evidence, number of stems and saplings were recorded and assessed in April and May 2012. A total of 968 woody plants were assessed representing 47 woody plant species. All woody vegetation variables recorded and assessed showed no significant difference (P > 0.05) between the two strata, i.e., central and boundary, in Mukuvisi Woodland, except sapling density (P = 0.022). Principal Component Analysis indicated evidence of fire impacts on vegetation structure. The study concludes that illegal wood harvesting in Mukuvisi Woodland has not yet reached alarming proportions and can be contained. The study recommends collaborative arrangements with key stakeholders, promotion of the use of alternative energy sources and increased environmental education and awareness campaigns.

Aristotle and Hollywood： Dramatic Structure From Ancient Greece to Avatar ＆ Beyond

It is fascinating to realize that even while Hollywood continually comes up with incredible special effects in films such as Avatar （2009）, the basic structure and development closely ＂follows＂ the guidelines for drama and storytelling laid out by Aristotle in his The Poetics, written several thousand years ago. We are specifically speaking of three act （beginning, middle, and ending） structure, focusing more on plot than character, and the need for a final resolution （catharsis）. But throughout literary and cinematic history, not everyone has followed these rules. Ironically, we take a close look at the award-winning Greek director Theo Angelopoulos＇ Ulysse＇s Gaze （1995） staring Harvey Keitel, as an example of a very non-Aristotelian approach to filmmaking and storytelling. Angelopoulos＇ film is character rather than plot centered on the Harvey Keitel figure and the journey of the narrative can be broken down to between 8-10 acts, depending how you describe them. We discuss many of the standard American ＂how to write screenplay book＂ authors such as Syd Field, while bringing a variety of authors such as Lajos Egri （The Art of Dramatic Writing） who criticize both Aristotle＇s Poetics and the way it has been interpreted for centuries especially in Hollywood. We conclude that there is a middle ground as well, for while Casablanca （1942） has a clear three act structure, it does not give us a happy romantic ＂Hollywood＂ ending/resolution as Rick insists that Lisa leave with her husband.

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.

Synthesis, performance and structure characterization of glyoxal-monomethylolurea-melamine (G-MMU-M) co-condensed resin

In order to reduce the formaldehyde emission of formaldehyde-based wood adhesive from the source,it is aimed to develop a novel co-condensed resin of glyoxal-monomethylolurea-melamine(G-MMU-M).A series of G-MMU-M resins with various formulations of raw materials were successfully prepared.The basic properties and bonding performance of the G-MMU-M resins were determined.Furthermore,the structures of resins were characterized by FTIR,^(13)C NMR,XPS,and ESI-MS.The results show that the prepared G-MMU-M resin remains stable for 30 d,meanwhile,the dry and wet bonding strength of the plywoods bonded with the resins,solid content and viscosity are influenced greatly by the addition amount of melamine and MMU/G molar ratio.The G-MMU-M resins with MMU/G molar ratio of 0.9:1.0 and 8% melamine exhibit the highest dry and bonding strength of 1.98 MPa and 1.27 MPa,increased by 34% and 63%,respectively,in comparison with glyoxal-monomethylolurea(G-MMU)resin.In the G-MMU-M resins,there were four main oligomers including M—CH(—^(+)CH-MMU)-O-MMU,M-CH(—CH_(2)OH)-MMU-O-MMU,M—CH(—OH)—^(+)CH-MMU-O-MMU,and M—CH(—^(+)CH-MMU)-MMU-p-G.

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）.

Configuring single-layer MXene nanosheet onto natural wood fiber via C-Ti-C covalent bonds for high-stability Li-S batteries

Lithium-sulfur batteries(LSBs)are considered promising candidates for next-generation battery technologies owing to their outstanding theoretical energy density and cost-effectiveness.However,the low conductivity and polysulfide shuttling effect of S cathodes severely hamper the practical performance of LSBs.Herein,in situ-generated single layer MXene nanosheet/hierarchical porous carbonized wood fiber(MX/PCWF)composites are prepared via a nonhazardous eutectic activation strategy coupled with pyrolysis-induced gas diffusion.The unique architecture,wherein single layer MXene nanosheets are constructed on carbonized wood fiber walls,ensures rapid polysulfide conversion and continuous electron transfer for redox reactions.The C-Ti-C bonds formed between MXene and PCWF can considerably expedite the conversion of polysulfides,effectively suppressing the shuttle effect.An impressive capacity of 1301.1 m A h g^(-1)at 0.5 C accompanied by remarkable stability is attained with the MX/PCWF host,as evidenced by the capacity maintenance of 722.6 m A h g^(-1)after 500 cycles.Notably,the MX/PCWF/S cathode can still deliver a high capacity of 886.8 m A h g^(-1)at a high S loading of 5.6 mg cm^(-2).The construction of two-dimensional MXenes on natural wood fiber walls offers a competitive edge over S-based cathode materials and demonstrates a novel strategy for developing high-performance batteries.