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.

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。

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.

基于24Model的煤炭企业安全文化提升实践研究

为了发挥安全文化在事故预防中的重要作用,运用基于事故致因“2-4”模型的安全文化水平提升方法研究某煤炭企业的安全文化建设现状并提出改进措施。首先,明确了24Model视域下的安全文化水平提升方法在我国的适用性;然后,从安全文化水平现状和安全理念2方面开展了针对该企业的实践研究;最后,提出改进措施。结果表明:该企业安全文化水平总体上要比国内或同行业的安全业绩较差的企业好,比安全业绩较好的企业差;该企业安全理念涉及32元素的13个方面;一线人员、班组长、专业人员和领导层对部分元素的理解程度不佳,并且这些元素中仅有元素3、元素4、元素6、元素13、元素16的内容在企业的安全理念有所体现。提出了14条改进的安全理念用于提高企业的安全文化水平。

Thermodynamic modeling and phase diagram prediction of salt lake brine systemsⅡ.Aqueous Li^(+)-Na^(+)-K^(+)-SO_(4)^(2-) and its subsystems

It is still a challenging task to accurately and temperature-continuously express the thermodynamic properties and phase equilibrium behaviors of the salt-lake brine with multi-component,multitemperature and high concentration.The essential subsystem of sulfate type brine,aqueous Li^(+)-Na^(+)-K^(+)-SO_(4)^(2-) and its subsystems across a temperature range from 250 K to 643 K are investigated with the improved comprehensive thermodynamic model.Liquid parameters(Δg_(IJ),Δh_(IJ),and ΔC_(p,IJ))associated with the contributions of Gibbs energy,enthalpy,and heat capacity to the binary interaction parameters,i.e.the temperature coefficients of eNRTL parameters formulated with a Gibbs Helmholtz expression,are determined via multi-objective optimization method.The solid constantsΔ_(f)G_(k)°^((298.15))andΔ_(f)H_(k)°^((298.15))of11 solid species occurred in the quaternary system are rebuilt from multi-temperature solubilities.The modeling results show the accurate representation of(1)solution properties and binary phase diagram at temperature ranges from eutectic points to 643 K;(2)isothermal phase diagrams for Li_(2)SO_(4)-Na_(2)SO_(4)-H_(2)O,Li_(2)SO_(4)-K_(2)SO_(4)-H_(2)O and Na_(2)SO_(4)-K_(2)SO_(4)-H_(2)O ternary systems.The predicted results of complete structure and polythermal phase diagram of ternary systems and the isothermal phase diagrams of quaternary system excellently match with the experimental data.

24 Model在道路运输事故成因中的应用

为预防道路运输事故,基于事故致因“2-4”(24 Model)模型,对2015—2021年发生的215起道路运输事故的行为原因进行研究。从个人层面和组织层面分析导致事故发生的直接原因、间接原因、根本原因及其根源原因。结果表明:发生频次最多的不安全动作是驾驶员超速行驶(占10.67%);22.33%的道路运输事故存在管理者违章安排无资质员工上岗作业;管理者和领导者对57.67%的道路运输事故的发生有重要影响;由人为因素产生的不安全物态占比达71.53%;驾驶员、车辆安全生产管理制度欠缺或执行不到位在根本原因中尤为突出(占20.92%)。基于此,提出道路运输事故预防对策并构建出道路运输系统各因素关系图。

Modelling of Turbulent Nonpremixed CH4/H2 Flame Using Second-Moment Turbulence Closure Models

Turbulent nonpremixed CH4/H2 flame has been simulated using several typical differential secondmoment turbulence closure (SMTC) models. To clarify the applicability of the various models, the LRR-IP model,JM model, SSG model as well as two modified LRR-IP models were tested. Some of above-mentioned SMTC models cannot provide the overall satisfactory predictions of this challenging case. It is confirmed again that the standard LRR-IP model considerably overpredict the centerline velocity decay rate, and therefore performs not well. Also it is interesting to observe that the JM model does not perform well in this challenging test case, although it has already been proved successful in other cases. The SSG model produces quite satisfactory prediction and performs equally well or better than the two modified LRR-IP models in the reacting case. It can be concluded that the modified LRR-IP models as well as the SSG model are superior to the other SMTC models in the turbulent nonpremixed CH4/H2 flame.

IFAM与24Model的对比研究

为完善和推动事故致因理论的发展,提高事故防控水平,在对信息流事故致因模型(IFAM)和事故致因2-4模型(24Model)理论基础、组成要素和分析过程对比研究的基础上,通过实例分析辨识二者之间的异同。研究结果表明:IFAM与24Model都有较强的理论基础,部分组成要素存在对应关系,但原因类别划分存在差异。IFAM以信息流和组织为研究对象,研究过程相对复杂,更适用于分析单起事故;24Model以组织为研究对象,事故原因模块通用性和逻辑性强,适用于分析单起或某类事故。在实际应用中,IFAM与24Model均可用于事故调查分析和事故分级定责,具有一定的理论和实践价值。IFAM通过信息流表征事故致因,直观描述组织外部原因因素,但对个体能力的深入研究欠缺;而24Model认为组织外部因素需要通过组织内部原因模块的欠缺体现,认为个体能力是引发事故的间接原因并进行细致分析,但对组织间相关关系的探究欠缺。研究结果可为事故预防工作提供新视角和理论支撑。

基于24Model的房屋市政工程事故致因组态研究

为探索房屋市政工程事故的影响因素与关联组态路径,依据案例的完整性、代表性与可靠性选取2018—2022年发生的70起较大及以上规模房屋市政工程生产安全事故作为研究对象,运用定性比较分析方法和“2-4”模型寻找该类事故的致因组态。研究结果表明:组织安全管理体系的执行情况是导致事故发生的重要影响因素;安全文化型和不安全动作型是事故的主要发生机制;事故致因与结果之间存在多重并发的因果关系。房屋市政工程生产安全管理需夯实安全管理体系,利用致因组态强化事故预防措施,以改善工程的经济与社会效益。

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.

Bayesian Joint Modelling of Survival Time and Longitudinal CD4 Cell Counts Using Accelerated Failure Time and Generalized Error Distributions

Survival of HIV/AIDS patients is crucially dependent on comprehensive and targeted medical interventions such as supply of antiretroviral therapy and monitoring disease progression with CD4 T-cell counts. Statistical modelling approaches are helpful towards this goal. This study aims at developing Bayesian joint models with assumed generalized error distribution (GED) for the longitudinal CD4 data and two accelerated failure time distributions, Lognormal and loglogistic, for the survival time of HIV/AIDS patients. Data are obtained from patients under antiretroviral therapy follow-up at Shashemene referral hospital during January 2006-January 2012 and at Bale Robe general hospital during January 2008-March 2015. The Bayesian joint models are defined through latent variables and association parameters and with specified non-informative prior distributions for the model parameters. Simulations are conducted using Gibbs sampler algorithm implemented in the WinBUGS software. The results of the analyses of the two different data sets show that distributions of measurement errors of the longitudinal CD4 variable follow the generalized error distribution with fatter tails than the normal distribution. The Bayesian joint GED loglogistic models fit better to the data sets compared to the lognormal cases. Findings reveal that patients’ health can be improved over time. Compared to the males, female patients gain more CD4 counts. Survival time of a patient is negatively affected by TB infection. Moreover, increase in number of opportunistic infection implies decline of CD4 counts. Patients’ age negatively affects the disease marker with no effects on survival time. Improving weight may improve survival time of patients. Bayesian joint models with GED and AFT distributions are found to be useful in modelling the longitudinal and survival processes. Thus we recommend the generalized error distributions for measurement errors of the longitudinal data under the Bayesian joint modelling. Further studies may investigate the models with various types of shared random effects and more covariates with predictions.

Reducing the Range of Cancer Risk on BI-RADS 4 Subcategories via Mathematical Modelling

Breast Imaging Reporting and Data System,also known as BI-RADS is a universal system used by radiologists and doctors.It constructs a comprehensive language for the diagnosis of breast cancer.BI-RADS 4 category has a wide range of cancer risk since it is divided into 3 categories.Mathematicalmodels play an important role in the diagnosis and treatment of cancer.In this study,data of 42 BI-RADS 4 patients taken fromthe Center for Breast Health,Near East University Hospital is utilized.Regarding the analysis,a mathematical model is constructed by dividing the population into 4 compartments.Sensitivity analysis is applied to the parameters with the desired outcome of a reduced range of cancer risk.Numerical simulations of the parameters are demonstrated.The results of the model have revealed that an increase in the lactation rate and earlymenopause have a negative correlation with the chance of being diagnosed with BI-RADS 4 whereas a positive correlation increase in age,the palpable mass,and family history is distinctive.Furthermore,the negative effects of smoking and late menopause on BI-RADS 4C diagnosis are vehemently outlined.Consequently,the model showed that the percentages of parameters play an important role in the diagnosis of BI-RADS 4 subcategories.All things considered,with the assistance of the most effective parameters,the range of cancer risks in BI-RADS 4 subcategories will decrease.

Fixed-Bed Column Adsorption Modeling of MnO4- Ions from Acidic Aqueous Solutions on Activated Carbons Prepared with the Biomass

Activated carbons calcined at 400˚C and 600˚C (AC-400 and AC-600), prepared using palm nuts, collected in the town of Franceville in Gabon, were used to study the dynamic adsorption of MnO4- ions in acidic media on fixed bed column and on the kinetic modeling of experimental data of breakthrough curves of MnO4- ions obtained. Results on the adsorption of MnO4- ions in fixed-bed dynamics obtained on AC-400 and AC-600 adsorbents beds indicated that the AC-400 bed appears to be the most efficient in removing MnO4- ions in acidic media. Indeed, the adsorbed amounts, the adsorbed capacities at saturation and the elimination percentage of MnO4- ions obtained with AC-400 (31.24 mg;52.06 mg·g-1 and 41.65% respectively) were higher compared to those obtained with AC-600 (9.87 mg;16.45 mg·g-1 and 17.79% respectively). The breakthrough curves kinetic modeling revealed that the Thomas model and the pseudo-first-order kinetic model were the most suitable models to describe the adsorption of MnO4- ions on adsorbents studied in our experimental conditions. The results of the intraparticle diffusion model showed that intraparticle diffusion was involved in the adsorption mechanism of MnO4- ions on investigated adsorbents and was not the limiting step and the only process controlling MnO4- ions adsorption. In contrast to AC-400, the intraparticle diffusion on AC-600 bed plays an important role in the adsorption mechanism of MnO4- ions.

基于24model的建筑施工机械伤害事故脆弱性分析

为预防建筑施工机械伤害事故,本研究采用事故致因2-4模型(24model)和复杂网络理论(CN)对施工机械事故进行分析整理。首先采用24model梳理86起典型机械事故报告中各层次事故的致因,对伤害事故中的安全管理体系、习惯性行为、不安全动作和不安全物态进行定性分析;随后根据复杂网络理论构建风险要素网络模型,通过网络攻击的手段找到导致事故的关键要素。研究结果表明:未经允许冒险作业、无相关施工资质、作业环境恶劣是事故关键致因。通过对关键节点的防控,可有效提升建筑施工安全水平。

Energy Level Statistics of SO（5） Limit of Super-symmetry U（6/4） in Interacting Boson-Fermion Model

We study the energy level statistics of the SO(5) limit of super-symmetry U(6/4) in odd-A nucleus using the interacting boson-fermion model. The nearest neighbor spacing distribution (NSD) and the spectral rigidity (△3)are investigated, and the factors that affect the properties of level statistics are also discussed. The results show that the boson number N is a dominant factor. If N is small, both the interaction strengths of subgroups SOB(5) and SOBF(5)and the spin play important roles in the energy level statistics, however, along with the increase of N, the statistics distribution would tend to be in Poisson form.

雄黄诱导人弥漫性大B淋巴瘤SU-DHL-4细胞凋亡及其机制的初步研究

本研究旨在探讨雄黄(Realgar,As4S4)诱导人弥漫性大B淋巴瘤SU-DHL-4细胞凋亡及其可能的机制。采用MTT法观测雄黄对SU-DHL-4细胞的增殖抑制作用,应用流式细胞术检测药物对SU-DHL-4细胞周期的影响及其诱导凋亡情况,利用琼脂糖凝胶电泳方法观察凋亡细胞的DNA降解情况,通过透射电子显微镜技术观察药物作用前后细胞超微结构的变化,采用Western blot方法检测药物诱导SU-DHL-4细胞48 h后Caspase-3、Bcl-2以及Bax蛋白表达情况。结果表明:20、40、80μmol/L的雄黄均可抑制SU-DHL-4细胞增殖,抑制率呈时间-剂量依赖性(r=0.982;P<0.05);AnnexinV/PI双染流式细胞术检测细胞凋亡率显示雄黄作用SU-DHL-4细胞48 h后,随着药物浓度的增加,早期凋亡细胞所占比率增高(P<0.05);PI单染流式细胞术检测细胞周期发现,雄黄作用SU-DHL-4细胞48 h后处于细胞周期S期的细胞显著减少(P<0.05);透射电子显微镜下观察雄黄作用SU-DHL-4细胞48 h后各浓度组细胞,均呈典型凋亡的改变,偶见坏死细胞;琼脂糖凝胶电泳结果显示,各浓度实验组雄黄干预SU-DHL-4细胞48 h后,细胞核DNA降解呈梯状;Western blot结果显示,雄黄作用SU-DHL-4细胞48 h后,Bcl-2蛋白表达降低,Bax和Caspase-3蛋白表达增加。结论:雄黄可以诱导人弥漫性大B淋巴瘤细胞凋亡,其作用机制可能是通过抑制细胞增殖、阻滞细胞周期、上调Caspase-3和Bax蛋白,下调Bcl-2蛋白而诱导细胞凋亡。