A TWO-PARAMETER MODEL FOR THREE TYPES OF NUCLEPORE FILTRATION OF LEUKOCYTES

Micropore filtration of leukocytes is one of the main methods for evaluating leukocytes' deformability. Here a biofluid mechanical model was proposed for three cases: (i) filtration under gravity; (ii) constant pressure filtration; (iii) constant flow rate filtration. In previous models, constant blood cell resistance was assumed. In this paper, when evaluating the filter resistance to leukocytes, not only the effect of the change in the driving pressure but also the difference in the deformability of individual leukocytes are taken into consideration. Moreover, based on Moessmer's experimental results, a probability distribution function for the transit time of polymorphonuclear cells (PMNs) through the filter is assumed. Finally, numerical curves are obtained for the above three types of filtration and the comparison between the theoretical and experimental results of PMNs for case (i) turns out to be satisfactory. The two parameters in the model, A and B represent leukocytes' deformability under low and high pressure respectively.

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.

A two-parameter mathematical model for immobilizedenzymes and Homotopy analysis method

A two parameter mathematical model was developed to find the concentration for immobilized enzyme systems in porous spherical particles. This model contains a non-linear term related to reversible Michaelies-Menten kinetics. Analytical expression pertaining to the substrate concentration was reported for all possible values of Thiele module φ and α . In this work, we report the theoretically evaluated steady-state effectiveness factor for immobilized enzyme systems in porous spherical particles. These analytical results were found to be in good agreement with numerical results. Moreover, herein we employ new “Homotopy analysis method” (HAM) to solve non-linear reaction/diffusion equation.

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.

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。

Prestack migration velocity analysis based on simplified two-parameter moveout equation

Stacking velocity V_（C2）,vertical velocity ratio γ_0,effective velocity ratio γ_（eff）,and anisotropic parameter x_（eff） are correlated in the PS-converted-wave（PS-wave） anisotropic prestack Kirchhoff time migration（PKTM） velocity model and are thus difficult to independently determine.We extended the simplified two-parameter（stacking velocity V_（C2） and anisotropic parameter k_（eff）） moveout equation from stacking velocity analysis to PKTM velocity model updating and formed a new four-parameter（stacking velocity V_（C2）,vertical velocity ratio γ_0,effective velocity ratio γ_（eff）,and anisotropic parameter k_（eff）） PS-wave anisotropic PKTM velocity model updating and process flow based on the simplified twoparameter moveout equation.In the proposed method,first,the PS-wave two-parameter stacking velocity is analyzed to obtain the anisotropic PKTM initial velocity and anisotropic parameters;then,the velocity and anisotropic parameters are corrected by analyzing the residual moveout on common imaging point gathers after prestack time migration.The vertical velocity ratio γ_0 of the prestack time migration velocity model is obtained with an appropriate method utilizing the P- and PS-wave stacked sections after level calibration.The initial effective velocity ratio γ_（eff） is calculated using the Thomsen（1999） equation in combination with the P-wave velocity analysis;ultimately,the final velocity model of the effective velocity ratio γ_（eff） is obtained by percentage scanning migration.This method simplifies the PS-wave parameter estimation in high-quality imaging,reduces the uncertainty of multiparameter estimations,and obtains good imaging results in practice.

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。

A GENERAL FORM OF THE INCREMENTS OF A TWO-PARAMETER WIENER PROCESS

In this paper, we consider a general form of the increments for a two-parameter Wiener process. Both the Csorgo-Revesz's increments and a class of the lag increments are the special cases of this general form of increments. Our results imply the theorem that have been given by Csorgo and Revesz (1978), and some of their conditions are removed.

Buckling analysis of shear deformable composite conical shells reinforced by CNTs subjected to combined loading on the two-parameter elastic foundation

The main objective of this study is to investigate the buckling analysis of CCSs reinforced by CNTs subjected to combined loading of hydrostatic pressure and axial compression resting on the twoparameter elastic foundation(T-P-EF).It is one of the first attempts to derive the governing equations of the CCSs reinforced with CNTs,based on a generalized first-order shear deformation shell theory(FSDST)which includes shell-foundation interaction.By adopting the extended mixing rule,the effective material properties of CCSs reinforced by CNTs with linear distributions are approximated by introducing some efficiency parameters.Three carbon nanotube distribution in the matrix,i.e.uniform distribution(U)and V and X-types linear distribution are taken into account.The stability equations are solved by using the Galerkin procedure to determine the combined buckling loads(CBLs)of the structure selected here.The numerical illustrations cover CBLs characteristics of CCSs reinforced by CNTs in the presence of the T-P-EF.Finally,a parametric study is carried out to study the influences of the foundation parameters,the volume fraction of carbon nanotubes and the types of reinforcement on the CBLs.

A New Two-Parameter Heteromorphic Elliptic Equation: Properties and Applications

The ellipse and the superellipse are both planar closed curves with a double axis of symmetry. Here we show the isoconcentration contour of the simplified two-dimensional advection-diffusion equation from a stable line source in the center of a wide river. A new two-parameter heteromorphic elliptic equation with a single axis of symmetry is defined. The values of heights, at the point of the maximum width and that of the centroid of the heteromorphic ellipse, are derived through mathematical analysis. Taking the compression coefficient θ = b/a = 1 as the criterion, the shape classification of H-type, Standard-type and W-type for heteromorphic ellipse have been given. The area formula, the perimeter theorem, and the radius of curvature of heteromorphic ellipses, and the geometric properties of the rotating body are subsequently proposed. An illustrative analysis shows that the inner contour curve of a heteromorphic elliptic tunnel has obvious advantages over the multiple- arc splicing cross section. This work demonstrates that the heteromorphic ellipses have extensive prospects of application in all categories of tunnels, liquid transport tanks, aircraft and submarines, bridges, buildings, furniture, and crafts.

Relation between Fresnel transform of input light field and the two-parameter Radon transform of Wigner function of the field

This paper proves a new theorem on the relationship between optical field Wigner function＇s two-parameter Radon transform and optical Fresnel transform of the field, i.e., when an input field ψ （x＇） propagates through an optical [D （-B） （-C） A] system, the energy density of the output field is equal to the Radon transform of the Wigner function of the input field, where the Radon transform parameters are D, B. It prove this theorem in both spatial-domain and frequency-domain, in the latter case the Radon transform parameters are A, C.

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 New Two-Parameter Formula for Rotational Spectra

A new two-parameter formula for the rotational spectra of well deformed nuclei isproposed. The formula is deduced from experimental level systematics and alternatively fromnuclear hydrodynamics. Comparisons with a great number of rotational spectra of even-even nu-clei in rare-earth and actinides region show that the formula is the best one among all two-pa-rameter formulas. It is pointed out that this formula can be applied to the spin assignment forsuperdeformed band.

Description of Rotational Molecular Spectra by the Two-Parameter Universal Equation

The n-power two-parameter universal equation for rotational spectra which we deduced recently is appliedto the description of the rotational bands of several diatomic and tetra-atomic molecules. Excellent agreement withexperimental data can be obtained with small n values. The relation between our equation and the famous Dunhamformula is discussed.

Anisotropic time-dependent behaviors of shale under direct shearing and associated empirical creep models

Understanding the anisotropic creep behaviors of shale under direct shearing is a challenging issue.In this context,we conducted shear-creep and steady-creep tests on shale with five bedding orientations (i.e.0°,30°,45°,60°,and 90°),under multiple levels of direct shearing for the first time.The results show that the anisotropic creep of shale exhibits a significant stress-dependent behavior.Under a low shear stress,the creep compliance of shale increases linearly with the logarithm of time at all bedding orientations,and the increase depends on the bedding orientation and creep time.Under high shear stress conditions,the creep compliance of shale is minimal when the bedding orientation is 0°,and the steady-creep rate of shale increases significantly with increasing bedding orientations of 30°,45°,60°,and 90°.The stress-strain values corresponding to the inception of the accelerated creep stage show an increasing and then decreasing trend with the bedding orientation.A semilogarithmic model that could reflect the stress dependence of the steady-creep rate while considering the hardening and damage process is proposed.The model minimizes the deviation of the calculated steady-state creep rate from the observed value and reveals the behavior of the bedding orientation's influence on the steady-creep rate.The applicability of the five classical empirical creep models is quantitatively evaluated.It shows that the logarithmic model can well explain the experimental creep strain and creep rate,and it can accurately predict long-term shear creep deformation.Based on an improved logarithmic model,the variations in creep parameters with shear stress and bedding orientations are discussed.With abovementioned findings,a mathematical method for constructing an anisotropic shear creep model of shale is proposed,which can characterize the nonlinear dependence of the anisotropic shear creep behavior of shale on the bedding orientation.

BOUNDARY INTEGRAL EQUATIONS FOR BENDING PROBLEM OF REISSNER'S PLATES ONTWO-PARAMETER FOUNDATION

Two fundamental solutions for bending problem of Reissner's plates on twoparameter foundation are derived by means of Fouier integral transformation of generalized function in this paper.On the basis of virtual work principles, three boundary integral equations which fit for arbitrary shapes, loads and boundary conditions of thick plates are presented according to Hu Haichang's theory about Reissner's plates. It provides the fundamental theories for the application of BEM. A numerical example is given for clamped, simply supported and free boundary conditions. The results obtained are satisfactory as compared with the analytical methods.