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.

Landslide Susceptibility Mapping Using RBFN-Based Ensemble Machine Learning Models

This study was aimed to prepare landslide susceptibility maps for the Pithoragarh district in Uttarakhand,India,using advanced ensemble models that combined Radial Basis Function Networks(RBFN)with three ensemble learning techniques:DAGGING(DG),MULTIBOOST(MB),and ADABOOST(AB).This combination resulted in three distinct ensemble models:DG-RBFN,MB-RBFN,and AB-RBFN.Additionally,a traditional weighted method,Information Value(IV),and a benchmark machine learning(ML)model,Multilayer Perceptron Neural Network(MLP),were employed for comparison and validation.The models were developed using ten landslide conditioning factors,which included slope,aspect,elevation,curvature,land cover,geomorphology,overburden depth,lithology,distance to rivers and distance to roads.These factors were instrumental in predicting the output variable,which was the probability of landslide occurrence.Statistical analysis of the models’performance indicated that the DG-RBFN model,with an Area Under ROC Curve(AUC)of 0.931,outperformed the other models.The AB-RBFN model achieved an AUC of 0.929,the MB-RBFN model had an AUC of 0.913,and the MLP model recorded an AUC of 0.926.These results suggest that the advanced ensemble ML model DG-RBFN was more accurate than traditional statistical model,single MLP model,and other ensemble models in preparing trustworthy landslide susceptibility maps,thereby enhancing land use planning and decision-making.

Global Piecewise Analysis of HIV Model with Bi-Infectious Categories under Ordinary Derivative and Non-Singular Operator with Neural Network Approach

This study directs the discussion of HIV disease with a novel kind of complex dynamical generalized and piecewise operator in the sense of classical and Atangana Baleanu(AB)derivatives having arbitrary order.The HIV infection model has a susceptible class,a recovered class,along with a case of infection divided into three sub-different levels or categories and the recovered class.The total time interval is converted into two,which are further investigated for ordinary and fractional order operators of the AB derivative,respectively.The proposed model is tested separately for unique solutions and existence on bi intervals.The numerical solution of the proposed model is treated by the piece-wise numerical iterative scheme of Newtons Polynomial.The proposed method is established for piece-wise derivatives under natural order and non-singular Mittag-Leffler Law.The cross-over or bending characteristics in the dynamical system of HIV are easily examined by the aspect of this research having a memory effect for controlling the said disease.This study uses the neural network(NN)technique to obtain a better set of weights with low residual errors,and the epochs number is considered 1000.The obtained figures represent the approximate solution and absolute error which are tested with NN to train the data accurately.

Prognostic model for esophagogastric variceal rebleeding after endoscopic treatment in liver cirrhosis: A Chinese multicenter study

BACKGROUND Rebleeding after recovery from esophagogastric variceal bleeding(EGVB)is a severe complication that is associated with high rates of both incidence and mortality.Despite its clinical importance,recognized prognostic models that can effectively predict esophagogastric variceal rebleeding in patients with liver cirrhosis are lacking.AIM To construct and externally validate a reliable prognostic model for predicting the occurrence of esophagogastric variceal rebleeding.METHODS This study included 477 EGVB patients across 2 cohorts:The derivation cohort(n=322)and the validation cohort(n=155).The primary outcome was rebleeding events within 1 year.The least absolute shrinkage and selection operator was applied for predictor selection,and multivariate Cox regression analysis was used to construct the prognostic model.Internal validation was performed with bootstrap resampling.We assessed the discrimination,calibration and accuracy of the model,and performed patient risk stratification.RESULTS Six predictors,including albumin and aspartate aminotransferase concentrations,white blood cell count,and the presence of ascites,portal vein thrombosis,and bleeding signs,were selected for the rebleeding event prediction following endoscopic treatment(REPET)model.In predicting rebleeding within 1 year,the REPET model ex-hibited a concordance index of 0.775 and a Brier score of 0.143 in the derivation cohort,alongside 0.862 and 0.127 in the validation cohort.Furthermore,the REPET model revealed a significant difference in rebleeding rates(P<0.01)between low-risk patients and intermediate-to high-risk patients in both cohorts.CONCLUSION We constructed and validated a new prognostic model for variceal rebleeding with excellent predictive per-formance,which will improve the clinical management of rebleeding in EGVB patients.

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.

LoRa Sense:Sensing and Optimization of LoRa Link Behavior Using Path-Loss Models in Open-Cast Mines

The Internet of Things(IoT)has orchestrated various domains in numerous applications,contributing significantly to the growth of the smart world,even in regions with low literacy rates,boosting socio-economic development.This study provides valuable insights into optimizing wireless communication,paving the way for a more connected and productive future in the mining industry.The IoT revolution is advancing across industries,but harsh geometric environments,including open-pit mines,pose unique challenges for reliable communication.The advent of IoT in the mining industry has significantly improved communication for critical operations through the use of Radio Frequency(RF)protocols such as Bluetooth,Wi-Fi,GSM/GPRS,Narrow Band(NB)-IoT,SigFox,ZigBee,and Long Range Wireless Area Network(LoRaWAN).This study addresses the optimization of network implementations by comparing two leading free-spreading IoT-based RF protocols such as ZigBee and LoRaWAN.Intensive field tests are conducted in various opencast mines to investigate coverage potential and signal attenuation.ZigBee is tested in the Tadicherla open-cast coal mine in India.Similarly,LoRaWAN field tests are conducted at one of the associated cement companies(ACC)in the limestone mine in Bargarh,India,covering both Indoor-toOutdoor(I2O)and Outdoor-to-Outdoor(O2O)environments.A robust framework of path-loss models,referred to as Free space,Egli,Okumura-Hata,Cost231-Hata and Ericsson models,combined with key performance metrics,is employed to evaluate the patterns of signal attenuation.Extensive field testing and careful data analysis revealed that the Egli model is the most consistent path-loss model for the ZigBee protocol in an I2O environment,with a coefficient of determination(R^(2))of 0.907,balanced error metrics such as Normalized Root Mean Square Error(NRMSE)of 0.030,Mean Square Error(MSE)of 4.950,Mean Absolute Percentage Error(MAPE)of 0.249 and Scatter Index(SI)of 2.723.In the O2O scenario,the Ericsson model showed superior performance,with the highest R^(2)value of 0.959,supported by strong correlation metrics:NRMSE of 0.026,MSE of 8.685,MAPE of 0.685,Mean Absolute Deviation(MAD)of 20.839 and SI of 2.194.For the LoRaWAN protocol,the Cost-231 model achieved the highest R^(2)value of 0.921 in the I2O scenario,complemented by the lowest metrics:NRMSE of 0.018,MSE of 1.324,MAPE of 0.217,MAD of 9.218 and SI of 1.238.In the O2O environment,the Okumura-Hata model achieved the highest R^(2)value of 0.978,indicating a strong fit with metrics NRMSE of 0.047,MSE of 27.807,MAPE of 27.494,MAD of 37.287 and SI of 3.927.This advancement in reliable communication networks promises to transform the opencast landscape into networked signal attenuation.These results support decision-making for mining needs and ensure reliable communications even in the face of formidable obstacles.

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.

Physiology and health assessment,risk balance,and model for endstage liver disease scores:Postoperative outcome of liver transplantation

BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To provide fair organ distribution,predictive mortality scores have been developed.AIM To compare the Acute Physiology and Chronic Health Evaluation IV(APACHE IV),balance of risk(BAR),and model for end-stage liver disease(MELD)scores as predictors of mortality.METHODS Retrospective cohort study,which included 283 adult patients in the postoperative period of deceased donor liver transplantation from 2014 to 2018.RESULTS The transplant recipients were mainly male,with a mean age of 58.1 years.Donors were mostly male,with a mean age of 41.6 years.The median cold ischemia time was 3.1 hours,and the median intensive care unit stay was 5 days.For APACHE IV,a mean of 59.6 was found,BAR 10.7,and MELD 24.2.The 28-day mortality rate was 9.5%,and at 90 days,it was 3.5%.The 28-day mortality prediction for APACHE IV was very good[area under the curve(AUC):0.85,P<0.001,95%CI:0.76-0.94],P<0.001,BAR(AUC:0.70,P<0.001,95%CI:0.58–0.81),and MELD(AUC:0.66,P<0.006,95%CI:0.55-0.78),P<0.008.At 90 days,the data for APACHE IV were very good(AUC:0.80,P<0.001,95%CI:0.71–0.90)and moderate for BAR and MELD,respectively,(AUC:0.66,P<0.004,95%CI:0.55–0.77),(AUC:0.62,P<0.026,95%CI:0.51–0.72).All showed good discrimination between deaths and survivors.As for the best value for liver transplantation,it was significant only for APACHE IV(P<0.001).CONCLUSION The APACHE IV assessment score was more accurate than BAR and MELD in predicting mortality in deceased donor liver transplant recipients.

Modeling and Comprehensive Review of Signaling Storms in 3GPP-Based Mobile Broadband Networks:Causes,Solutions,and Countermeasures

Control signaling is mandatory for the operation and management of all types of communication networks,including the Third Generation Partnership Project(3GPP)mobile broadband networks.However,they consume important and scarce network resources such as bandwidth and processing power.There have been several reports of these control signaling turning into signaling storms halting network operations and causing the respective Telecom companies big financial losses.This paper draws its motivation from such real network disaster incidents attributed to signaling storms.In this paper,we present a thorough survey of the causes,of the signaling storm problems in 3GPP-based mobile broadband networks and discuss in detail their possible solutions and countermeasures.We provide relevant analytical models to help quantify the effect of the potential causes and benefits of their corresponding solutions.Another important contribution of this paper is the comparison of the possible causes and solutions/countermeasures,concerning their effect on several important network aspects such as architecture,additional signaling,fidelity,etc.,in the form of a table.This paper presents an update and an extension of our earlier conference publication.To our knowledge,no similar survey study exists on the subject.

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。

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。

High performance“non-local”generic face reconstruction model using the lightweight Speckle-Transformer(SpT)UNet

Significant progress has been made in computational imaging(CI),in which deep convolutional neural networks(CNNs)have demonstrated that sparse speckle patterns can be reconstructed.However,due to the limited“local”kernel size of the convolutional operator,for the spatially dense patterns,such as the generic face images,the performance of CNNs is limited.Here,we propose a“non-local”model,termed the Speckle-Transformer(SpT)UNet,for speckle feature extraction of generic face images.It is worth noting that the lightweight SpT UNet reveals a high efficiency and strong comparative performance with Pearson Correlation Coefficient(PCC),and structural similarity measure(SSIM)exceeding 0.989,and 0.950,respectively.

Generic creep behavior and creep modeling of an aged surface support liner under tension

Polymer-based materials have been motivated to be an alternative support system element in the mining/tunneling industry due to their logistic and geotechnical benefits.Thin spray-on liner(TSL),a term to define the application of the material on the rock surface with a layer ranging from 2 mm to10 mm in thickness,shows some promising results.TSLs are mainly composed of plastic,polymer,or cement-based ingredients to a certain proportion.This study intends to reveal the time-dependent response of TSL specimens,cured throughout 500 d,under four constant stress levels for stable laboratory conditions.The results were correlated using two interrelated equations to predict the material’s service life(creep-rupture envelopes).The proposed correlations offered an insight into both the effective permanent support time and the strain amount at the liner failure.The time-dependent deformation of TSL,whose performance is highly responsive to creep behavior,was obtained so that the design engineers may use the findings to avoid the severe problems of material creep.Experimental data were also used to develop a Burgers(four-element)creep model.Since the liner has a nonlinear time-dependent behavior,creep models were built for each stress level separately.Subsequently,a generic equation was obtained using the nonlinear parametric dependencies.There is a good agreement between the proposed model and the experimental results.The proposed model can be used as a basis for future numerical studies related to the support behavior of aged surface support liners.

Generic-Model-Based Description Scheme for MPEG-7

We propose a new description scheme for MPEG-7:Generic-model-based Description Scheme to describe contents of audio, video, text and other sorts of multimedia. It uses a generic model as the description frame, which provides a simple but useful object\|based structure. The main components of the description scheme are generic model, objects and object features. The proposed description scheme is illustrated and exemplified by Extensible Markup Language. It aims at clarity and flexibility to support MPEG\|7 applications such as query and edit. We demonstrate its feasibility and efficiency by presenting applications: Digital Broadcasting and Edit System (DEBS) and Non\|linear Edit System (NLES) that already used the generic structure or will greatly benefit from it.

A Generic Design Model for Evolutionary Algorithms

A generic design model for evolutionary algorithms is proposed in this paper. The model, which was described by UML in details, focuses on the key concepts and mechanisms in evolutionary algorithms. The model not only achieves separation of concerns and encapsulation of implementations by classification and abstraction of those concepts, it also has a flexible architecture due to the application of design patterns. As a result, the model is reusable, extendible, easy to understand, easy to use, and easy to test. A large number of experiments applying the model to solve many different problems adequately illustrate the generality and effec-tivity of the model.

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。

A Generic Battery Model and Its Parameter Identification

A new dynamic model is developed in this paper based on the generic MATLAB battery model. The battery capacity is expressed as a function of the self-discharge rate, the discharge current, the cycling life and the temperature of the battery. The dependence of the model parameters on cycle life and temperature are estimated from the first order approximation. The detailed procedures and formula to extract the model parameters are presented and the extraction relies only on the discharge curves at two different discharge currents, at two different life cycles, and at two different temperatures. These discharge curves are typically provided in the battery manufacturer’s datasheet. The proposed model is verified for both nickel-metal hydride and lithium-ion batteries by comparing the calculated discharge curves with the results from the generic MATLAB model. The model is further validated for the Sinopoly lithium-ion battery (SP-LFP1000AHA) by comparing the model results with the discharge curves from the manufacturer’s datasheet at different discharge currents, different cycling numbers, and different temperatures. Simulation results show that the new model can correctly predict voltage separation beyond the nominal zone while maintaining the same level of accuracy as the generic MATLAB model in the exponential and nominal zones.