Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

Role of methoxy and C_(α)-based substituents in electrochemical oxidation mechanisms and bond cleavage selectivity of β-O-4 lignin model compounds

In order to better understand the specific substituent effects on the electrochemical oxidation process of β-O-4 bond, a series of methoxyphenyl type β-O-4 dimer model compounds with different localized methoxyl groups, including 2-(2-methoxyphenoxy)-1-phenylethanone, 2-(2-methoxyphenoxy)-1-phenylethanol, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanol, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanol have been selected and their electrochemical properties have been studied experimentally by cyclic voltammetry, and FT-IR spectroelectrochemistry. Combining with electrolysis products distribution analysis and density functional theory calculations, oxidation mechanisms of all six model dimers have been explored. In particular, a total effect from substituents of both para-methoxy(on the aryl ring closing to Cα) and Cα-OH on the oxidation mechanisms has been clearly observed, showing a significant selectivity on the Cα-Cβbond cleavage induced by electrochemical oxidations.

Calculation of the Standard Model Parameters and Particles Based on a SU(4) Preon Model

This paper describes an extension and a new foundation of the Standard Model of particle physics based on a SU(4)-force called hyper-color, and on preon subparticles. The hyper-color force is a generalization of the SU(2)-based weak interaction and the SU(1)-based right-chiral self-interaction, in which the W-and the Z-bosons are Yukawa residual-field-carriers of the hyper-color force, in the same sense as the pions are the residual-field-carriers of the color SU(3) interaction. Using the method of numerical minimization of the SU(4)-action based on this model, the masses and the inner structure of leptons, quarks and weak bosons are calculated: the mass results are very close to the experimental values. We calculate also precisely the value of the Cabibbo angle, so the mixing matrices of the Standard model, CKM matrix for quarks and PMNS matrix for neutrinos can also be calculated. In total, we reduce the 29 parameters of the Standard Model to a total of 7 parameters.

Research on Track Fastener Service Status Detection Based on Improved Yolov4 Model

As an important part of railway lines, the healthy service status of track fasteners was very important to ensure the safety of trains. The application of deep learning algorithms was becoming an important method to realize its state detection. However, there was often a deficiency that the detection accuracy and calculation speed of model were difficult to balance, when the traditional deep learning model is used to detect the service state of track fasteners. Targeting this issue, an improved Yolov4 model for detecting the service status of track fasteners was proposed. Firstly, the Mixup data augmentation technology was introduced into Yolov4 model to enhance the generalization ability of model. Secondly, the MobileNet-V2 lightweight network was employed in lieu of the CSPDarknet53 network as the backbone, thereby reducing the number of algorithm parameters and improving the model’s computational efficiency. Finally, the SE attention mechanism was incorporated to boost the importance of rail fastener identification by emphasizing relevant image features, ensuring that the network’s focus was primarily on the fasteners being inspected. The algorithm achieved both high precision and high speed operation of the rail fastener service state detection, while realizing the lightweight of model. The experimental results revealed that, the MAP value of the rail fastener service state detection algorithm based on the improved Yolov4 model reaches 83.2%, which is 2.83% higher than that of the traditional Yolov4 model, and the calculation speed was improved by 67.39%. Compared with the traditional Yolov4 model, the proposed method achieved the collaborative optimization of detection accuracy and calculation speed.

Effect of pre-deformation on aging creep of Al-Li-S4 alloy and its constitutive modeling

A set of uniaxial tensile creep tests at different pre-deformations, aging temperatures and stress levels were carried out for Al-Li-S4 alloy, and the creep behavior and the effects of pre-deformation on mechanical properties and microstructures were determined under basic thermodynamics conditions of aging forming. The results show that pre-deformation shortens the time of primary creep and raises the second steady-state creep rate. Then, the total creep strain is greater, but in the range of test parameters it is still smaller than that without pre-deformation. In addition, transmission electron microscopy（TEM） observation shows that pre-deformation promotes the formation of T1 phase and θ′ phase and makes them distribute more dispersively, while inhibits the generation of δ′ phase, which leads to the improvement of mechanical properties of the alloy. A unified constitutive model reflecting the effects of aging mechanism, stress levels and different pre-deformations was established. The fitting results agree with the experimental data well.

MATHEMATICAL MODEL OF ~4He QUANTUM INTERFEROMETER GYROSCOPE

The mathematical model of 4He quantum interferometer gyroscope is presented. The model includes the driven equation, the current equation and the position equation. Therefore, it can sufficiently describe the gyro- scope system. The driven equation shows the thermally driven gyroscope can work for a long time but the pres- sure driven one cannot. From the current equation, the superfluid currents passing through the weak link contain the AC currents which show the rotation flux, and other currents caused by drive. As shown in the position equa- tion, the displacement of diaphragm is the only detectable parameter in the gyroscope system. The model is tested by the simulations based on experimental parameters, and can be used to research performance of the gyroscope and analyse the gyroscope error.

A modified Johnson-Cook model for NC warm bending of large diameter thin-walled Ti-6Al-4V tube in wide ranges of strain rates and temperatures

Numerical control（NC） warm bending is a proven strategy to form the large diameter thin-walled（LDTW） Ti-6 Al-4 V tubes, which are typical light-weight and high-performance structural components urgently required in many industries. In virtue of unveiling the thermo-mechanical coupled deformation behaviors, uniaxial tensile tests were conducted on Ti-6 Al-4 V tube within wide ranges of temperatures（25-600 ℃） and strain rates（0.00067-0.1 s～（-1））. Moreover, a modified Johnson-Cook（JC） model is proposed with a consideration of nonlinear strain rate hardening and the interaction between strain hardening and thermal softening. Resultantly, the present model gives more accurate predictions for flow stress over the entire deformation ranges and the maximum error decreases by about 90%. By employing proposed model to NC warm bending, preferable precision is obtained in predicting forming defects including fracture, wrinkling and over thinning. The present work lays foundation for the forming limit prediction and process optimization in NC warm bending of LDTW Ti-6 Al-4 V tubes.

基于24Model-D-ISM的地铁站火灾疏散影响因素研究

为预防地铁站火灾事故,深入了解地铁站火灾人员疏散影响因素间的内在联系与层次结构,基于第6版“2-4”模型(24Model)分析63起地铁站火灾疏散事故,充分考虑各个因素之间的交互作用,提取19个影响地铁站人员疏散的关键因素,建立地铁站火灾人员疏散影响因素指标体系;采用算子客观赋权法(C-OWA)改进决策试验与评价实验法(DEMATEL),确定地铁站火灾人员疏散的重要影响因素;在此基础上,采用解释结构模型(ISM)分析各个因素间的层次结构及相互作用路径,构建地铁站火灾人员疏散影响因素的多级递阶结构模型。研究结果表明:疏散引导、恐慌从众行为、人员拥挤为地铁站火灾人员疏散的关键影响因素;地铁站火灾人员疏散受表层因素、中间层因素、深层因素共同作用的影响,其中,疏散教育与培训、设施维护与检查、疏散预案等因素是根源影响因素,重视根源影响因素的改善有利于从本质上预防和控制事故的发生。

Decomposition of a β-O-4 lignin model compound over solid Cs-substituted polyoxometalates in anhydrous ethanol: acidity or redox property dependence?

Production o f aromatics from lignin has attracted much attention. Because of the coexistence of C-O and C-C bonds and their complex combinations in the lignin macromolecular network, a plausible roadmap for developing a lignin catalytic decomposition process could be developed by exploring the transformation mechanisms of various model compounds. Herein, decomposition of a lignin model compound, 2-phenoxyacetophenone （2-PAP）, was investigated over several ce-sium-exchanged polyoxometalate （Cs-POM） catalysts. Decomposition of 2-PAP can follow two dif-ferent mechanisms： an active hydrogen transfer mechanism or an oxonium cation mechanism. The mechanism for most reactions depends on the competition between the acidity and redox proper-ties of the catalysts. The catalysts of POMs perform the following functions： promoting active hy-drogen liberated from ethanol and causing formation of and then temporarily stabilizing oxonium cations from 2-PAP. The use of Cs-PMo, which with strong redox ability, enhances hydrogen libera-tion and promotes liberated hydrogen transfer to the reaction intermediates. As a consequence, complete conversion of 2-PAP （〉99%） with excellent selectivities to the desired products （98.6% for phenol and 91.1% for acetophenone） can be achieved.

24Model与LCM原因因素定义对比研究

为探究损失致因模型(LCM)原因因素定义与事故致因“2-4”模型(24Model)存在的异同和优缺点,梳理2个模型各层面原因和结果的定义,对比定义内容及其对事故原因分析等安全实务的指导作用,并以一起瓦斯爆炸事故为例加以实证分析,获得二者分析结果之间的差异。研究结果表明:LCM是首个将管理因素纳入事故致因分析的一维事件序列模型,可明确各层面原因因素的定义和因素间的逻辑关系,但部分定义存在交叉重复的问题,并没有揭示安全工作指导思想等深层次事故致因因素;24Model作为系统性事故致因模型,对各类因素的定义均以组织为主体,描述事件、事故、安全的概念内涵,划分个体安全动作、安全能力和组织安全管理体系的类别并给出含义解析,探究组织安全文化层面的问题并以32个元素体现;2个模型的事故原因分析方法均建立在对各层级原因因素定义的基础上,并适用于模型理论体系本身。

氨基修饰g-C_(3)N_(4)材料的制备及其光催化去除U(Ⅵ)

以三聚氰胺为前驱体,焙烧制得g-C_(3)N_(4)。g-C_(3)N_(4)经过与乙二胺水热反应得到氨基修饰的g-C_(3)N_(4)/NH_(2)改性光催化剂。研究g-C_(3)N_(4)/NH_(2)改性光催化剂对废水中U(Ⅵ)的去除能力,并采用XRD、SEM、XPS、FT-IR等技术对改性样品的形貌、结构、光催化去除U(Ⅵ)能力等进行表征。结果表明,在模拟光源下,其中加入30 mL乙二胺的样品表现出最佳性能,可以在15 min将U(Ⅵ)浓度为10 mg·L^(-1)的U(Ⅵ)完全去除,150 min对U(Ⅵ)浓度为50 mg·L^(-1)的U(Ⅵ)去除率达76.5%。经表面修饰的材料表现出对U(Ⅵ)溶液优异的吸附和催化性能的原因是:水热过程使g-C_(3)N_(4)纳米片层剥离,提高了材料的比表面积;成功引入的氨基基团使g-C_(3)N_(4)提高了对U(Ⅵ)的捕获能力,提高了对光生电子的利用率,进而提高了g-C_(3)N_(4)/NH_(2)材料的催化性能。

Comparison of convective parameterizations in RegCM4 experiments over China with CLM as the land surface model

in the latest version of the international Centre for Theoretical Physics＇ regional climate model, RegCM4, CLM was introduced as a new land surface scheme. The performance over China of RegCM4-CLM with different convection schemes is analyzed in this study, based on a series of short- term experiments.The model is driven by ERA-Interim data at a grid spacing of 25 km.The convection schemes employed are： Emanuel; Grell; Emanuel over land and Grell over ocean; Grell over land and Emanuel over ocean; and Tiedtke. The simulated mean surface air temperature and precipitation in December-February-January and June-July-August are compared against observation. In general, better performance of Emanuel is found both for temperature and precipitation, and in both seasons. Thus, the model physics of CLM and Emanuel for the land surface processes and convection, respectively, are recommended for further application of RegCM4 over the China region. The de^ciencies that remain in the model arealso outlined and discussed.

Comparative study of HFACS and the 24Model accident causation models

A comparative study is conducted to compare the theory and application effect of two accident causation models, the human factors analysis and classification system（HFACS） and the accident causation ＂2-4＂ model（24 Model）, as well as to provide a reference for safety researchers and accident investigators to select an appropriate accident analysis method. The two models are compared in terms of their theoretical foundations, cause classifications, accident analysis processes, application ranges, and accident prevention strategies. A coal and gas outburst accident is then analyzed using both models, and the application results are compared. This study shows that both the 24 Model and HFACS have strong theoretical foundations, and they can each be applied in various domains. In addition, the cause classification in HFACS is more practical, and its accident analysis process is more convenient. On the other hand, the 24 Model includes external factors, which makes the cause analysis more systematic and comprehensive. Moreover, the 24 Model puts forward more corresponding measures to prevent accidents.

Impact of Probiotics on Toll-like Receptor 4 Expression in an Experimental Model of Ulcerative Colitis

Toll-like receptors （TLRs） are key components of the innate immune system which trigger antimicrobial host defense responses. This study aimed to investigate the impact of probiotics （Lactoba- cillus, Bifiidobacterium） on the expression of TLR4 and tumor necrosis factor-alpha （TNF-α in the co- lon mucosa of rat experimental ulcerative colitis model induced by trinitrobenzene sulfonic acid （TNBS）/ethanol and immune complexes. The gross and histological changes of the colonic mucosa were observed and assessed by the means-standard deviation and independent samples t-test. The pro- tein expression levels of TLR4 and TNF-α were detected by using immunohistochemistry and Westem blotting, respectively. It was revealed that there was visible infiltration of inflammatory cells, formation of crypt abscess, and the reduction of goblet cells in the colon tissue of experimental models. As com- pared with the control group, the levels of TLR4 and TNF-α protein were significantly increased in the model group （P〈0.01 for both）. No significant difference was found in the expression of TLR4 and TNF-α between the two-week probiotics treatment group and the model group （P〉0.05）, whereas sig- nificant reductions were shown in rats which were treated with probiotics for four weeks as compared with the model group （P〈0.01）. There was no significant difference between two probiotics-treated groups. Our results implied that probiotics were likely to play a key role in protecting ulcerative colitis by reducing the inflammatory factor TNF-α expression through inhibiting the TLR4 expression in the colon tissue of experimental models.

Idealized Experiments for Optimizing Model Parameters Using a 4D-Variational Method in an Intermediate Coupled Model of ENSO

Large biases exist in real-time ENSO prediction, which can be attributed to uncertainties in initial conditions and model parameters. Previously, a 4D variational （4D-Vat） data assimilation system was developed for an intermediate coupled model （ICM） and used to improve ENSO modeling through optimized initial conditions. In this paper, this system is further applied to optimize model parameters. In the ICM used, one important process for ENSO is related to the anomalous temperature of subsurface water entrained into the mixed layer （Te）, which is empirically and explicitly related to sea level （SL） variation. The strength of the thermocline effect on SST （referred to simply as ＂the thermocline effect＂） is represented by an introduced parameter, （l＇Te. A numerical procedure is developed to optimize this model parameter through the 4D-Var assimilation of SST data in a twin experiment context with an idealized setting. Experiments having their initial condition optimized only, and having their initial condition plus this additional model parameter optimized, are compared. It is shown that ENSO evolution can be more effectively recovered by including the additional optimization of this parameter in ENSO modeling. The demonstrated feasibility of optimizing model parameters and initial conditions together through the 4D-Var method provides a modeling platform for ENSO studies. Further applications of the 4D-Vat data assimilation system implemented in the ICM are also discussed.

Modeling of dynamic recrystallization volume fraction evolution for AlCu4SiMg alloy and its application in FEM

To improve the understanding of coupling effect between dynamic recrystallization(DRX)behaviors and flow behaviors of as-cast AlCu4 SiMg, a finite element(FE) simulation equipped with the models of DRX evolution was implemented. A series of isothermal compression tests were performed primarily on a Gleeble-3500 thermo-mechanical simulator in a temperature range of 648-748 K and a strain rate range of 0.01-10 s-1.According to the measured true stress-strain data,the strain hardening rate curves(dσ/dε versus σ) were plotted to identify the critical strains for DRX initiation(εc). By further derivation of the related material constants, the DRX volume fraction equation and the strain for 50% DRX(ε0.5) equation were solved. Accordingly, the aforementioned DRX equations were implanted into the FE model to conduct a series of simulations for the isothermal compression tests. The results show that during the evolution of DRX volume fraction at a fixed strain rate, the strain required for the same amount of DRX volume fraction increases with decreasing temperature. In contrast, at a fixed temperature, it increases with increasing strain rate. Ultimately, the DRX kinetics model of AlCu4 SiMg alloy and the consequence of the FE analysis were validated by microstructure observations.

Domain-specific modeling and verification for C4ISR capability requirements

An approach was proposed to specify the C4ISR capability of domain-specific modeling language.To confine the domain modeling within a standard architecture framework,formally a C4ISR capability meta-ontology was defined according to the meta-model of DoD Architecture Framework.The meta-ontology is used for extending UML Profile so that the domain experts can model the C4ISR domains using the C4ISR capability meta-concepts to define a domain-specific modeling language.The domain models can be then checked to guarantee the consistency and completeness through converting the UML models into the Description Logic ontology and making use of inference engine Pellet to verify the ontology.

Constitutive Modeling for Ti-6Al-4V Alloy Machining Based on the SHPB Tests and Simulation

A constitutive model is critical for the prediction accuracy of a metal cutting simulation. The highest strain rate involved in the cutting process can be in the range of 104-106 s 1. Flow stresses at high strain rates are close to that of cutting are difficult to test via experiments. Split Hopkinson compression bar （SHPB） technology is used to study the deformation behavior of Ti-6Al-4V alloy at strain rates of 10 -4-10 4s- 1. The Johnson Cook （JC） model was applied to characterize the flow stresses of the SHPB tests at various conditions. The parameters of the JC model are optimized by using a genetic algorithm technology. The JC plastic model and the energy density-based ductile failure criteria are adopted in the proposed SHPB finite element simulation model. The simulated flow stresses and the failure characteristics, such as the cracks along the adiabatic shear bands agree well with the experimental results. Afterwards, the SHPB simulation is used to simulate higher strain rate（approximately 3 × 10 4 s -1） conditions by minimizing the size of the specimen. The JC model parameters covering higher strain rate conditions which are close to the deformation condition in cutting were calculated based on the flow stresses obtained by using the SHPB tests （10 -4 - 10 4 s- 1） and simulation （up to 3 × 10 4 s - 1）. The cutting simulation using the constitutive parameters is validated by the measured forces and chip morphology. The constitutive model and parameters for high strain rate conditions that are identical to those of cutting were obtained based on the SHPB tests and simulation.

A CAD oriented quasi-analytical large-signal drain current model for 4H-SiC MESFETs

This paper reports that a 4H-SiC MESFET （Metal Semiconductor Field Effect Transistor） large signal drain current model based on physical expressions has been developed to be used in CAD tools. The form of drain current model is based on semi-empirical MESFET model, and all parameters in this model are determined by physical parameters of 4H-SiC MESFET. The verification of the present model embedded in CAD tools is made, which shows a good agreement with measured data of large signal DC I-V characteristics, PAE （power added efficiency）, output power and gain.

An executable modeling and analyzing approach to C4ISR architecture

To analyze the behavioral model of the command,control,communication,computer,intelligence,surveillance,reconnaissance(C4ISR)architecture,we propose an executable modeling and analyzing approach to it.First,the meta concept model of the C4ISR architecture is introduced.According to the meta concept model,we construct the executable meta models of the C4ISR architecture by extending the meta models of fUML.Then,we define the concrete syntax and executable activity algebra(EAA)semantics for executable models.The semantics functions are introduced to translating the syntax description of executable models into the item of EAA.To support the execution of models,we propose the executable rules which are the structural operational semantics of EAA.Finally,an area air defense of the C4ISR system is used to illustrate the feasibility of the approach.