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.

Rigorous and integrated self-calibration model for a large-field-of-view camera using a star image

This paper proposes a novel self-calibration method for a large-FoV(Field-of-View)camera using a real star image.First,based on the classic equisolid-angle projection model and polynomial distortion model,the inclination of the optical axis is thoroughly considered with respect to the image plane,and a rigorous imaging model including 8 unknown intrinsic parameters is built.Second,the basic calibration equation based on star vector observations is presented.Third,the partial derivative expressions of all 11 camera parameters for linearizing the calibration equation are deduced in detail,and an iterative solution using the least squares method is given.Furtherly,simulation experiment is designed,results of which shows the new model has a better performance than the old model.At last,three experiments were conducted at night in central China and 671 valid star images were collected.The results indicate that the new method obtains a mean magnitude of reprojection error of 0.251 pixels at a 120°FoV,which improves the calibration accuracy by 38.6%compared with the old calibration model(not considering the inclination of the optical axis).When the FoV drops below 20°,the mean magnitude of the reprojection error decreases to 0.15 pixels for both the new model and the old model.Since stars instead of manual control points are used,the new method can realize self-calibration,which might be significant for the long-duration navigation of vehicles in some unfamiliar or extreme environments,such as those of Mars or Earth’s moon.

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.

A Fractional-N CMOS DPLL with Self-Calibration

A digital phase-locked loop （DPLL） based on a new digital phase-frequency detector is presented. The self-calibration technique is employed to acquire wide lock range,low jitter, and fast acquisition. The DPLL works from 60 to 600MHz at a supply voltage of 1.8V. It also features a fraetional-N synthesizer with digital 2nd-order sigma-delta noise shaping, which can achieve a short lock time,a high frequency resolution,and an improved phase-noise spectrum. The DPLL has been implemented in SMIC 0. 18μm 1.8V 1P6M CMOS technology. The peak-to-peak jitter is less than 0. 8% of the output clock period and the lock time is less than 150 times of the reference clock period after the pre-divider.

Capacitor self-calibration technique used in time-interleaved successive approximation ADC

A capacitor self-calibration circuit used in a successive approximation analog-to-digital converter （SA-ADC） is presented. This capacitor self-calibration circuit can calibrate erroneous data and work with the ADC by adding an additional clock period. This circuit is used in a 10 bit 32 Msample/s time-interleaved SA- ADC. The chip is implemented with Chart 0. 25 μm 2. 5 V process and totally occupies an area of 1.4 mm× 1.3 mm. After calibration, the simulated signal-to-noise ratio （SNR） is 59. 586 1 dB and the spurious-free dynamic range （SFDR） is 70. 246 dB at 32 MHz. The measured signal-to-noise and distortion ratio （SINAD） is 44. 82 dB and the SFDR is 63. 760 4 dB when the ADC samples a 5.8 MHz sinusoid wave.

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。

Self-calibration and Compensation of Setting Errors for Surface Profile Measurement of a Microstructured Roll Workpiece

Microstructured roll workpieces have been widely used as functional components in the precision industries. Current researches on quality control have focused on surface profile measurement of microstructured roll workpieces, and types of measurement systems and measurement methods have been developed. However, low measurement efficiency and low measurement accuracy caused by setting errors are the common disadvantages for surface profile measurement of microstructured roll workpieces. In order to shorten the measurement time and enhance the measurement accuracy, a method for self-calibration and compensation of setting errors is proposed for surface profile measurement of microstructured roll workpieces. A measurement system is constructed for the measurement, in which a precision spindle is employed to rotate the roll workpiece and an air-bearing displacement sensor with a micro-stylus probe is employed to scan the microstructured surface of the roll workpiece. The resolution of the displacement sensor is 0.14 nm and that of the rotary encoder of the spindle was 0.15r~. Geometrical and mathematical models are established for analyzing the influences of the setting errors of the roll workpiece and the displacement sensor with respect to the axis of the spindle, including the eccentric error of the roll workpiece, the offset error of the sensor axis and the zero point error of the sensor output. Measurement experiments are carded out on a roll workpiece on which periodic microstructures are a period of 133 i^m along the circumferential direction. Experimental results demonstrate the feasibility of the self-compensation method. The proposed method can be used to detect and compensate the setting errors without using any additional accurate artifact.

Integration of Tracer Test Data to Refine Geostatistical Hydraulic Conductivity Fields Using Sequential Self-Calibration Method

On the basis of local measurements of hydraulic conductivity, geostatistical methods have been found to be useful in heterogeneity characterization of a hydraulic conductivity field on a regional scale. However, the methods are not suited to directly integrate dynamic production data, such as, hydraulic head and solute concentration, into the study of conductivity distribution. These data, which record the flow and transport processes in the medium, are closely related to the spatial distribution of hydraulic conductivity. In this study, a three-dimensional gradient-based inverse method--the sequential self-calibration （SSC） method--is developed to calibrate a hydraulic conductivity field, initially generated by a geostatistical simulation method, conditioned on tracer test results. The SSC method can honor both local hydraulic conductivity measurements and tracer test data. The mismatch between the simulated hydraulic conductivity field and the reference true one, measured by its mean square error （MSE）, is reduced through the SSC conditional study. In comparison with the unconditional results, the SSC conditional study creates the mean breakthrough curve much closer to the reference true curve, and significantly reduces the prediction uncertainty of the solute transport in the observed locations. Further, the reduction of uncertainty is spatially dependent, which indicates that good locations, geological structure, and boundary conditions will affect the efficiency of the SSC study results.

New self-calibration approach to space robots based on hand-eye vision

To overcome the influence of on-orbit extreme temperature environment on the tool pose(position and orientation) accuracy of a space robot,a new self-calibration method based on a measurement camera(hand-eye vision) attached to its end-effector was presented.Using the relative pose errors between the two adjacent calibration positions of the space robot,the cost function of the calibration was built,which was different from the conventional calibration method.The particle swarm optimization algorithm(PSO) was used to optimize the function to realize the geometrical parameter identification of the space robot.The above calibration method was carried out through self-calibration simulation of a six-DOF space robot whose end-effector was equipped with hand-eye vision.The results showed that after calibration there was a significant improvement of tool pose accuracy in a set of independent reference positions,which verified the feasibility of the method.At the same time,because it was unnecessary for this method to know the transformation matrix from the robot base to the calibration plate,it reduced the complexity of calibration model and shortened the error propagation chain,which benefited to improve the calibration accuracy.

Camera Self-Calibration in Computer Vision with Precise Estimation of Initial Parameters

A key problem that plagues camera self-calibration, namely that the classical self-calibration algorithms are very sensitive to the initial values of the camera intrinsic parameters, is analyzed and a practical solution is provided. The effect of the camera intrinsic parameters, mainly the principal point and the skew factor is first discussed. Then a practical method via a controlled motion of the camera is introduced so as to obtain an accurate estimation of these parameters. Feasibility of this approach is illustrated by carrying out comprehensive experiments using synthetic data as well as real image sequences. Unreasonable initial values can often make self-calibration impossible, yet a precise initialization guarantees a better and successful reconstruction. Trying to obtain a more reasonable initialization is worthwhile the effort in camera self-calibration.

A Self-calibration Bundle Adjustment Algorithm Based on Block Matrix Cholesky Decomposition Technology

In this study,the problem of bundle adjustment was revisited,and a novel algorithm based on block matrix Cholesky decomposition was proposed to solve the thorny problem of self-calibration bundle adjustment.The innovation points are reflected in the following aspects:①The proposed algorithm is not dependent on the Schur complement,and the calculation process is simple and clear;②The complexities of time and space tend to O(n)in the context of world point number is far greater than that of images and cameras,so the calculation magnitude and memory consumption can be reduced significantly;③The proposed algorithm can carry out self-calibration bundle adjustment in single-camera,multi-camera,and variable-camera modes;④Some measures are employed to improve the optimization effects.Experimental tests showed that the proposed algorithm has the ability to achieve state-of-the-art performance in accuracy and robustness,and it has a strong adaptability as well,because the optimized results are accurate and robust even if the initial values have large deviations from the truth.This study could provide theoretical guidance and technical support for the image-based positioning and 3D reconstruction in the fields of photogrammetry,computer vision and robotics.

An improved self-calibration approach based on adaptive genetic algorithm for position-based visual servo

An improved self-calibrating algorithm for visual servo based on adaptive genetic algorithm is proposed in this paper. Our approach introduces an extension of Mendonca-Cipolla and G. Chesi＇s self-calibration for the positionbased visual servo technique which exploits the singular value property of the essential matrix. Specifically, a suitable dynamic online cost function is generated according to the property of the three singular values. The visual servo process is carried out simultaneous to the dynamic self-calibration, and then the cost function is minimized using the adaptive genetic algorithm instead of the gradient descent method in G. Chesi＇s approach. Moreover, this method overcomes the limitation that the initial parameters must be selected close to the true value, which is not constant in many cases. It is not necessary to know exactly the camera intrinsic parameters when using our approach, instead, coarse coding bounds of the five parameters are enough for the algorithm, which can be done once and for all off-line. Besides, this algorithm does not require knowledge of the 3D model of the object. Simulation experiments are carried out and the results demonstrate that the proposed approach provides a fast convergence speed and robustness against unpredictable perturbations of camera parameters, and it is an effective and efficient visual servo algorithm.

NOVEL METHOD FOR ERROR ANALYSIS AND SELF-CALIBRATION OF LASER TRACKING MIRROR MECHANISM

Laser tracking system （LTS） is an advanced device for large size 3D coordinates measuring with the advantages of broad range, high speed and high accuracy. However, its measuring accuracy is highly dominated by the geometric errors of the tracking mirror mechanism. Proper calibration of LTS is essential prior to the use of it for metrology. A kinematics model that describes not only the motion but also the geometric variations of LTS is developed. Through error analysis of the proposed model, it is claimed that gimbals axis misalignments and tracking mirror center off-set are the key contributors to measuring errors of LTS. A self-calibration method is presented of calibrating LTS with planar constraints. Various calibration strategies utilizing single-plane and multiple-plane constraints are proposed for different situations. For each calibration strategy, issues about the error parameter estimation of LTS are exploded to find out in which conditions these parameters can be uniquely estimated. Moreover, these conditions reveal the applicability of the planar constraints to LTS self-calibration. Intensive studies have been made to check validity of the theoretical results. The results show that the measuring accuracy of LTS has increased by 5 times since this technique for calibration is used.

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。

Self-calibration Applied in Converting Simulation Surveying

In the field of converting simulation surveying and traditional close range photogrammetry, it has been developed so far to survey objects by commercial digital camera and this technique is applied widely in every part of production. In order to get three-dimensional information of objects, commercial digital camera must be examined. For a long time, digital camera has been examined by DLT. Then there must be a high-precision control field. For realizing surveying without control points, a method for self-calibration is proposed.