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.

Exploiting fly models to investigate rare human neurological disorders

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.

A promising approach for quantifying focal stroke modeling and assessing stroke progression:optical resolution photoacoustic microscopy photothrombosis

To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

Prosthetic modeling for femoral head based on ellipsoid fitting

A novel modeling method which can restore the shape of the femoral head with collapse induced by ischemic necrosis is proposed. First, sequential tomograms of the hip are obtained from a CT scan; secondly, an accurate and automatic method is used to extract the profile of the acetabulum; thirdly, a hybrid method is utilized to gather fiducial marks on the acetabulum; fourthly, bulky error sampling points are removed. Finally, an ellipsoid fitting method is used to fit the ellipsoid model of the femoral head. Two male sufferers with different necrosis extents are chosen as experimental subjects for contrastive simulation. Fifty cases of different ages （from 25 to 79 years old） are utilized for statistical comparisons of matching errors. The prosthetic models highly resemble the primary shape of the femoral head in health. This new method provides not only a theoretical model for accurate operation position fixing in an orthopaedics clinic, but it is also an innovative practical means for the individual manufacture of artificial femoral heads.

采用STAMP-24Model的多组织事故分析

安全生产事故往往由多组织交互、多因素耦合造成,事故原因涉及多个组织。为预防和遏制多组织生产安全事故的发生,基于系统理论事故建模与过程模型(Systems-Theory Accident Modeling and Process,STAMP)、24Model,构建一种用于多组织事故分析的方法,并以青岛石油爆炸事故为例进行事故原因分析。结果显示:STAMP-24Model可以分组织,分层次且有效、全面、详细地分析涉及多个组织的事故原因,探究多组织之间的交互关系;对事故进行动态演化分析,可得到各组织不安全动作耦合关系与形成的事故失效链及管控失效路径,进而为预防多组织事故提供思路和参考。

基于改进24Model-ISM-SNA建筑工人不安全行为关联路径研究

建筑施工现场环境复杂,为有效控制不安全行为发生,基于行为安全“2-4”模型对360份具有代表性的建筑安全事故调查报告进行分析,提取出22个不安全行为的主要影响因素。利用灰色关联分析方法(GRA)改进的集成ISM-SNA模型,将不安全行为风险因素划分为表层、过渡层与深层,然后对风险因素进行可视化分析、中心度分析及凝聚子群分析,揭示了各致因因素间的关联关系和传导路径。结果表明,建筑工人不安全行为影响因素可划分成7级3阶的多级递阶结构,安全意识、现场监管、外部环境是建筑工人不安全行为的关键影响因素,同时现场监管和隐患排查到位能有效降低不安全行为的发生。

Analysis of reflected signal of quad rotor UAV based on model fitting in mobile communication system

In view of the many scenes of unmanned aerial vehicle(UAV)detection,a third-party signal source is used to design a receiver to monitor the UAV.It is of great significance to understand the reflection of the signal illuminating the UAV.Taking the communication base station(BS)signal as the third-party signal source,and considering the complete transmission link,reflection changes and loss fading of the communication signal,this study conducts model fitting for irregular UAV targets,simplifying complex targets into a combination of simple targets.Furthermore,the influence of the dielectric constant of the target surface and the signal irradiation angle on the signal reflection is analyzed.The analysis shows that the simulation results of this model fitting method are consistent with the results of other literature,which provides theoretical support for the detection of low and slow small targets such as UAVs.

基于24Model的地铁内涝事故原因分析与评估

为降低地铁内涝事故灾害风险,基于事故致因“2-4”模型,分析了地铁内涝事故致灾因子,采用层次分析法构建了地铁内涝事故原因分析指标体系,确定了各风险因子的权重,并利用模糊综合评价法对地铁内涝事故进行了定量评估,识别出关键的影响因素。结果表明:地铁内涝事故一级指标中不安全动作与物态因素最重要,其中影响最大的指标包括擅自更改建筑设计、未按照要求检查水位情况、未及时排水、出入口不符合防汛标准等因素;习惯性不安全行为的权重位居第二,表明该指标因素较为重要,同时安全管理体系得分位居第二,表明该指标因素较易发生。对关键指标采取防范措施,可有效降低风险,从而减少地铁内涝事故的发生。

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。

Objective Fitting Evaluation Model for Dressing Fit Based on Wrinkle Index of Dressing Image

An effective model(image to wrinkle, ITW) for garment fitting evaluation is presented. The proposed model is to improve the accuracy of garment fitting evaluation based on dressing image. The ITW model is an objective evaluation model of fitting based on the wrinkle index of dressing image. The ITW model consists of two main steps, the gray curve-fitting(GCF) threshold segmentation algorithm and Canny edge detection algorithm. In the ITW model, three types of wrinkle trends are defined. And the network dressing image is evaluated and simulated by three quantitative indexes: wrinkle number, wrinkle regularity and wrinkle unevenness. Finally, the fitness of three kinds of dress effects(tight, fit and loose) is quantified by objective fitting evaluation model.

Study on curved surface fitting model using GPS and leveling in local area

The height anomaly surface is fitt and the quasi-geoid can be obtained when the height anomaly is determined with the geometric analytic method. Therefore, some mathematical models to fit height anomaly surface using GPS, leveling and terrain data in a local area, including the polynomial fitting model, the multi-surface function fitting model, the motion surface fitting model and the fitting model of little flexibility deformation of thin board, are given. Then the digital characteristics are analyzed with the curved surface theory. The General curvature and the mean curvature of surface are concluded. The advantage, disadvantage and application of the above models are discussed. The effect of terrain undulation on height anomaly is considered in the surface fitting models. The practical case indicates that these models are of validity and practicability. It is concluded that the above models can give the good fitting results at the centimeter level. But the polynomial fitting model is worse than the other models.

A Robust Indoor Localization Algorithm Based on Polynomial Fitting and Gaussian Mixed Model

Wireless sensor network(WSN)positioning has a good effect on indoor positioning,so it has received extensive attention in the field of positioning.Non-line-of sight(NLOS)is a primary challenge in indoor complex environment.In this paper,a robust localization algorithm based on Gaussian mixture model and fitting polynomial is proposed to solve the problem of NLOS error.Firstly,fitting polynomials are used to predict the measured values.The residuals of predicted and measured values are clustered by Gaussian mixture model(GMM).The LOS probability and NLOS probability are calculated according to the clustering centers.The measured values are filtered by Kalman filter(KF),variable parameter unscented Kalman filter(VPUKF)and variable parameter particle filter(VPPF)in turn.The distance value processed by KF and VPUKF and the distance value processed by KF,VPUKF and VPPF are combined according to probability.Finally,the maximum likelihood method is used to calculate the position coordinate estimation.Through simulation comparison,the proposed algorithm has better positioning accuracy than several comparison algorithms in this paper.And it shows strong robustness in strong NLOS environment.

Function fitting for modeling seasonal normalized difference vegetation index time series and early forecasting of soybean yield

Forecasting crop yields based on remote sensing data is one of the most important tasks in agriculture.Soybean is the main crop in the Russian Far East.It is desirable to forecast soybean yield as early as possible while maintaining high accuracy.This study aimed to investigate seasonal time series of the normalized difference vegetation index(NDVI) to achieve early forecasting of soybean yield.This research used data from the Moderate Resolution Image Spectroradiometer(MODIS),an arable-land mask obtained from the VEGA-Science web service,and soybean yield data for 2008-2017 for the Jewish Autonomous Region(JAR) districts.Four approximating functions were fitted to model the NDVI time series:Gaussian,double logistic(DL),and quadratic and cubic polynomials.In the period from calendar weeks 22-42(end of May to mid-October),averaged over two districts,the model using the DL function showed the highest accuracy(mean absolute percentage error-4.0%,root mean square error(RMSE)-0.029,P <0.01).The yield forecast accuracy of prediction in the period of weeks 25-30 in JAR municipalities using the parameters of the Gaussian function was higher(P <0.05) than that using the other functions.The mean forecast error for the Gaussian function was 14.9% in week 25(RMSE was0.21 t ha) and 5.1%-12.9% in weeks 26-30(RMSE varied from 0.06 to 0.15 t ha) according to the2013-2017 data.In weeks 31-32,the error was 5.0%-5.4%(RMSE was 0.07 t ha) using the Gaussian parameters and 7.4%-7.7%(RMSE was 0.09-0.11 t ha) for the DL function.When the method was applied to municipal districts of other soy-producing regions of the Russian Far East.RMSE was0.14-0.32 t hain weeks 25-26 and did not exceed 0.20 t hain subsequent weeks.

An optimized fitting function with least square approximation in InAs/AlSb HFET small-signal model for characterizing the frequency dependency of impact ionization effect

An enhanced small-signal model is introduced to model the influence of the impact ionization effect on the performance of In As/Al Sb HFET, in which an optimized fitting function D（ωτi） in the form of least square approximation is proposed in order to further enhance the accuracy in modeling the frequency dependency of the impact ionization effect.The enhanced model with D（ωτi） can accurately characterize the key S parameters of In As/Al Sb HFET in a wide frequency range with a very low error function EF. It is demonstrated that the new fitting function D（ωτi） is helpful in further improving the modeling accuracy degree.

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。

Model fitting of the seasonal population dynamics of the soybean aphid, Aphis glycines Matsumura, in the field

The soybean aphid, Aphis glycines Matsumura(Hemiptera: Aphididae), is one of the greatest threats to soybean production, and both trend analysis and periodic analysis of its population dynamics are important for integrated pest management(IPM). Based on systematically investigating soybean aphid populations in the field from 2018 to 2020, this study adopted the inverse logistic model for the first time, and combined it with the classical logistic model to describe the changes in seasonal population abundance from colonization to extinction in the field. Then, the increasing and decreasing phases of the population fluctuation were divided by calculating the inflection points of the models, which exhibited distinct seasonal trends of the soybean aphid populations in each year. In addition, multifactor logistic models were then established for the first time, in which the abundance of soybean aphids in the field changed with time and relevant environmental conditions. This model enabled the prediction of instantaneous aphid abundance at a given time based on relevant meteorological data. Taken as a whole, the successful approaches implemented in this study could be used to build a theoretical framework for practical IPM strategies for controlling soybean aphids.

Least squares fitting of coordinate parameters model

This paper starts with untime-diversification of the time-diversification deformation model and gives displacement distribution model of untime-diversification and simplifies further the study of deformation model. The paper discusses the problem of least squares fitting of coordinate parameters model—parameters of deformation model. During discussion, the basic means of cubic B splines and two steps of multidimensional disorder datum fitting are adopted which can make fitting function calculated mostly approximate coordinate parameters model and it can make calculation easier.

Splitting and Merging Based Multi-model Fitting for Point Cloud Segmentation

This paper deals with the massive point cloud segmentation processing technology on the basis of machine vision, which is the second essential factor for the intelligent data processing of three dimensional conformation in digital photogrammetry. In this paper, multi-model fitting method is used to segment the point cloud according to the spatial distribution and spatial geometric structure of point clouds by fitting the point cloud into different geometric primitives models. Because point cloud usually possesses large amount of 3D points, which are uneven distributed over various complex structures, this paper proposes a point cloud segmentation method based on multi-model fitting. Firstly, the pre-segmentation of point cloud is conducted by using the clustering method based on density distribution. And then the follow fitting and segmentation are carried out by using the multi-model fitting method based on split and merging. For the plane and the arc surface, this paper uses different fitting methods, and finally realizing the indoor dense point cloud segmentation. The experimental results show that this method can achieve the automatic segmentation of the point cloud without setting the number of models in advance. Compared with the existing point cloud segmentation methods, this method has obvious advantages in segmentation effect and time cost, and can achieve higher segmentation accuracy. After processed by method proposed in this paper, the point cloud even with large-scale and complex structures can often be segmented into 3D geometric elements with finer and accurate model parameters, which can give rise to an accurate 3D conformation.

Fitting and evaluation of height-diameter models for Alnus japonica in La Trinidad, Benguet, Philippines

The study was conducted to develop height-diameter at breast height(HT-DBH) models for Alnus japonica in La Trinidad, Benguet,Philippines and evaluate their predictive capability.The six widely used nonlinear growth models that were selected in this study were the ChapmanRichards, Schnute, Modified logistic, Korf/Lundqvist,Weibull and Exponential. A total of 208 Alnus japonica trees were measured using standard diameter tape for DBH(1.3 m above the ground) and Vertex and transponder was used for the total height measurement. The performance of the developed models were evaluated using the fit statistics including coefficient of determination(R^2), root mean square error(RMSE), mean bias(ē), absolute mean difference(AMD), and Akaike Information Criterion(AIC). The lack-of-fit statistics was also performed for further evaluation of the performance of the models.Based on the evaluation criteria, all six models were able to determine the DBH-height relationships and fitted the data well. Using the rank analysis, the Weibull HT-DBH model had the best performance among the six commonly used nonlinear growth models. The results of this study will help forest managers especially in La Trinidad, Benguet to easily predict the total height using the Weibull model for Alnus japonica utilizing the DBH as the predicting variable.