Quantitative Identification of Delamination Damage in Composite Structure Based on Distributed Optical Fiber Sensors and Model Updating

Delamination is a prevalent type of damage in composite laminate structures.Its accumulation degrades structural performance and threatens the safety and integrity of aircraft.This study presents a method for the quantitative identification of delamination identification in composite materials,leveraging distributed optical fiber sensors and a model updating approach.Initially,a numerical analysis is performed to establish a parameterized finite element model of the composite plate.Then,this model subsequently generates a database of strain responses corresponding to damage of varying sizes and locations.The radial basis function neural network surrogate model is then constructed based on the numerical simulation results and strain responses captured from the distributed fiber optic sensors.Finally,a multi-island genetic algorithm is employed for global optimization to identify the size and location of the damage.The efficacy of the proposed method is validated through numerical examples and experiment studies,examining the correlations between damage location,damage size,and strain responses.The findings confirm that the model updating technique,in conjunction with distributed fiber optic sensors,can precisely identify delamination in composite structures.

Characterization and Modeling of Mechanical Properties of Additively Manufactured Coconut Fiber-Reinforced Polypropylene Composites

In the face of the increased global campaign to minimize the emission of greenhouse gases and the need for sustainability in manufacturing, there is a great deal of research focusing on environmentally benign and renewable materials as a substitute for synthetic and petroleum-based products. Natural fiber-reinforced polymeric composites have recently been proposed as a viable alternative to synthetic materials. The current work investigates the suitability of coconut fiber-reinforced polypropylene as a structural material. The coconut fiber-reinforced polypropylene composites were developed. Samples of coconut fiber/polypropylene (PP) composites were prepared using Fused Filament Fabrication (FFF). Tests were then conducted on the mechanical properties of the composites for different proportions of coconut fibers. The results obtained indicate that the composites loaded with 2 wt% exhibited the highest tensile and flexural strength, while the ones loaded with 3 wt% had the highest compression strength. The ultimate tensile and flexural strength at 2 wt% were determined to be 34.13 MPa and 70.47 MPa respectively. The compression strength at 3 wt% was found to be 37.88 MPa. Compared to pure polypropylene, the addition of coconut fibers increased the tensile, flexural, and compression strength of the composite. In the study, an artificial neural network model was proposed to predict the mechanical properties of polymeric composites based on the proportion of fibers. The model was found to predict data with high accuracy.

Numerical Analysis of Fiber Reinforced Polymer-Confined Concrete under Cyclic Compression Using Cohesive Zone Models

This paper examines the mechanical behavior offiber reinforced polymer(FRP)-confined concrete under cyclic compression using the 3D cohesive zone model(CZM).A numerical modeling method was developed,employing zero-thickness cohesive elements to represent the stress-displacement relationship of concrete potential fracture surfaces and FRP-concrete interfaces.Additionally,mixed-mode damage plastic constitutive models were pro-posed for the concrete potential fracture surfaces and FRP-concrete interface,considering interfacial friction.Furthermore,an anisotropic plastic constitutive model was developed for the FRP composite jacket.The CZM model proposed in this study was validated using experimental data from plain concrete and large rupture strain(LRS)FRP-confined concrete subjected to cyclic compression.The simulation results demonstrate that the pro-posed model accurately predicts the mechanical response of both concrete and FRP-confined concrete under cyc-lic compression.Lastly,various parametric studies were conducted to investigate the internal failure mechanism of FRP-confined concrete under cyclic loading to analyze the influence of the inner friction plasticity of different components.

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-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。

Modeling, Simulation and Experimental Studies of Refractometric Fiber Optic Sensor

Refractometric fiber optic sensors have a number of applications in industry due to advantages like remote sensing ability, compact size, easy to fit, etc. A refractometric sensor contains a pair of parallel fibers and a gap between the sensor probe and reflector, wherein the liquid whose refractive index is to be measured is filled. This paper describes the importance of mathematical modeling of this sensor. Ray tracing approach is used to model the sensor mathematically. This mathematical model is generalized for any scenario which is useful to avoid tedious trial and error techniques to design the sensor prototype. Mathematical modelling is a useful tool to optimize the gap distance for a detection of refractive index of liquid. The model is developed and analyzed rigorously considering adulteration of diesel by kerosene where refractive index varies from 1.44 to 1.46. Simulation experiments are carried out to optimize the gap distance which is found to be 6.8 mm using both models. Experiments are carried out where sensor probe is fabricated and results are analyzed. It is observed that for suggested gap distance sensor output varies almost linear over the entire range.

Machine Learning-based Inverse Model for Few-Mode Fiber Designs

The medium for next-generation communication is considered as fiber for fast,secure communication and switching capability.Mode division and space division multiplexing provide an excellent switching capability with high data transmission rate.In this work,the authors have approached an inverse modeling technique using regression-based machine learning to design a weakly coupled few-mode fiber for facilitating mode division multiplexing.The technique is adapted to predict the accurate profile parameters for the proposed few-mode fiber to obtain the maximum number of modes.It is for a three-ring-core few-mode fiber for guiding five,ten,fifteen,and twenty modes.Three types of regression models namely ordinary least-square linear multi-output regression,k-nearest neighbors of multi-output regression,and ID3 algorithm-based decision trees for multi-output regression are used for predicting the multiple profile parameters.It is observed that the ID3-based decision tree for multioutput regression is the robust,highly-accurate machine learning model for fast modeling of FMFs.The proposed fiber claims to be an efficient candidate for the next-generation 5G and 6G backhaul networks using mode division multiplexing.

Modeling Date Palm Trunk Fibers (DPTF) Packed Bed Adsorption Performances for Cadmium Removal from Aqueous Wastewater

In this study,the potential of a low-cost bio-adsorbent,taken directly from Date Palm Trunk Fibers(DPTF)agricultural wastes,for cadmium ions removal from wastewaters is examined.The performances of this adsorbent are evaluated by building breakthrough curves at different bed heights and flow rates while keeping other parameters,such as the initial feed concentration,pH,and particle size,constant.The results indicate that the maximum cadmium adsorption capacity of DTPF can be obtained from the Thomas model as 51.5 mg/g with the most extended mass transfer zone of 83 min at the lowest flow rate at 5 ml/min.The saturation concentrations(NO)and the rate constant(kab)obtained from the BDST(bed depth service time)model are 7022.16 mg/l and 0.0536 l/mg.min,respectively.Using the Yon-Nelsen Model,it is found that operating at a lower flow rate leads to a larger value of the elapsed needed time to reach a 50%breakthrough.The Wolborska model indicates that the bed capacity increases with decreasing the flow rate,and the adsorbent can achieve a greater external mass transfer kinetic coefficient(2.271/min)at a higher flow rate.

Projecting Wintertime Newly Formed Arctic Sea Ice through Weighting CMIP6 Model Performance and Independence

Precipitous Arctic sea-ice decline and the corresponding increase in Arctic open-water areas in summer months give more space for sea-ice growth in the subsequent cold seasons. Compared to the decline of the entire Arctic multiyear sea ice,changes in newly formed sea ice indicate more thermodynamic and dynamic information on Arctic atmosphere–ocean–ice interaction and northern mid–high latitude atmospheric teleconnections. Here, we use a large multimodel ensemble from phase 6 of the Coupled Model Intercomparison Project(CMIP6) to investigate future changes in wintertime newly formed Arctic sea ice. The commonly used model-democracy approach that gives equal weight to each model essentially assumes that all models are independent and equally plausible, which contradicts with the fact that there are large interdependencies in the ensemble and discrepancies in models' performances in reproducing observations. Therefore, instead of using the arithmetic mean of well-performing models or all available models for projections like in previous studies, we employ a newly developed model weighting scheme that weights all models in the ensemble with consideration of their performance and independence to provide more reliable projections. Model democracy leads to evident bias and large intermodel spread in CMIP6 projections of newly formed Arctic sea ice. However, we show that both the bias and the intermodel spread can be effectively reduced by the weighting scheme. Projections from the weighted models indicate that wintertime newly formed Arctic sea ice is likely to increase dramatically until the middle of this century regardless of the emissions scenario.Thereafter, it may decrease(or remain stable) if the Arctic warming crosses a threshold(or is extensively constrained).

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.

Geostatistical seismic inversion and 3D modelling of metric flow units,porosity and permeability in Brazilian presalt reservoir

Flow units(FU)rock typing is a common technique for characterizing reservoir flow behavior,producing reliable porosity and permeability estimation even in complex geological settings.However,the lateral extrapolation of FU away from the well into the whole reservoir grid is commonly a difficult task and using the seismic data as constraints is rarely a subject of study.This paper proposes a workflow to generate numerous possible 3D volumes of flow units,porosity and permeability below the seismic resolution limit,respecting the available seismic data at larger scales.The methodology is used in the Mero Field,a Brazilian presalt carbonate reservoir located in the Santos Basin,who presents a complex and heterogenic geological setting with different sedimentological processes and diagenetic history.We generated metric flow units using the conventional core analysis and transposed to the well log data.Then,given a Markov chain Monte Carlo algorithm,the seismic data and the well log statistics,we simulated acoustic impedance,decametric flow units(DFU),metric flow units(MFU),porosity and permeability volumes in the metric scale.The aim is to estimate a minimum amount of MFU able to calculate realistic scenarios porosity and permeability scenarios,without losing the seismic lateral control.In other words,every porosity and permeability volume simulated produces a synthetic seismic that match the real seismic of the area,even in the metric scale.The achieved 3D results represent a high-resolution fluid flow reservoir modelling considering the lateral control of the seismic during the process and can be directly incorporated in the dynamic characterization workflow.

耦合优化蚁群算法与P-Median model的选址模型设计

为节省城建部门对于公共体育设施的投入成本以及提高城市人民生活质量,以运动场所优化选址为例,提出一种新型设施选址模型。该模型主要基于P-Median model(最小化阻抗模型)根据需求点数量从全部候选设施选址中选择设施空间位置,让用户达到离自己最近设施距离成本总和最小的目的,对选址的基本原则和实际情况提出要求,构造目标函数用于优化后蚁群算法求解进行选址工作。优化蚁群算法实现基于Python语言模块,通过改进蚁群原始信息素,提升原有算法的收敛速度,求出目标函数最优解,可以很好地模拟对于运动场所的选址。用二者耦合进行优势互补所设计的选址模型来搜寻研究区蚁群信息素浓度残留最大的栅格像元,从而确定未被已有设施点服务半径覆盖的最佳设施点建立位置。实验结果表明,该新型选址模型相较于最小化阻抗模型与最大化覆盖模型,新增优化设施点使整体服务半径覆盖率分别高出10.42%和6.95%,适合求解较为精确且小规模空间下的选址问题。

Thermo-hydro-poro-mechanical responses of a reservoir-induced landslide tracked by high-resolution fiber optic sensing nerves

Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond the slip surface to progressive failure.Here,we aim to investigate the subsurface multiphysics of reservoir landslides under two extreme hydrologic conditions(i.e.wet and dry),particularly within sliding masses.Based on ultra-weak fiber Bragg grating(UWFBG)technology,we employ specialpurpose fiber optic sensing cables that can be implanted into boreholes as“nerves of the Earth”to collect data on soil temperature,water content,pore water pressure,and strain.The Xinpu landslide in the middle reach of the Three Gorges Reservoir Area in China was selected as a case study to establish a paradigm for in situ thermo-hydro-poro-mechanical monitoring.These UWFBG-based sensing cables were vertically buried in a 31 m-deep borehole at the foot of the landslide,with a resolution of 1 m except for the pressure sensor.We reported field measurements covering the period 2021 and 2022 and produced the spatiotemporal profiles throughout the borehole.Results show that wet years are more likely to motivate landslide motions than dry years.The annual thermally active layer of the landslide has a critical depth of roughly 9 m and might move downward in warmer years.The dynamic groundwater table is located at depths of 9e15 m,where the peaked strain undergoes a periodical response of leap and withdrawal to annual hydrometeorological cycles.These interface behaviors may support the interpretation of the contribution of reservoir regulation to slope stability,allowing us to correlate them to local damage events and potential global destabilization.This paper also offers a natural framework for interpreting thermo-hydro-poro-mechanical signatures from creeping reservoir bank slopes,which may form the basis for a landslide monitoring and early warning system.

A modified stochastic model for LS+AR hybrid method and its application in polar motion short-term prediction

Short-term(up to 30 days)predictions of Earth Rotation Parameters(ERPs)such as Polar Motion(PM:PMX and PMY)play an essential role in real-time applications related to high-precision reference frame conversion.Currently,least squares(LS)+auto-regressive(AR)hybrid method is one of the main techniques of PM prediction.Besides,the weighted LS+AR hybrid method performs well for PM short-term prediction.However,the corresponding covariance information of LS fitting residuals deserves further exploration in the AR model.In this study,we have derived a modified stochastic model for the LS+AR hybrid method,namely the weighted LS+weighted AR hybrid method.By using the PM data products of IERS EOP 14 C04,the numerical results indicate that for PM short-term forecasting,the proposed weighted LS+weighted AR hybrid method shows an advantage over both the LS+AR hybrid method and the weighted LS+AR hybrid method.Compared to the mean absolute errors(MAEs)of PMX/PMY sho rt-term prediction of the LS+AR hybrid method and the weighted LS+AR hybrid method,the weighted LS+weighted AR hybrid method shows average improvements of 6.61%/12.08%and 0.24%/11.65%,respectively.Besides,for the slopes of the linear regression lines fitted to the errors of each method,the growth of the prediction error of the proposed method is slower than that of the other two methods.

Mshpy23:a user-friendly,parameterized model of magnetosheath conditions

Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind−Magnetosphere−Ionosphere Link Explorer(SMILE)will observe magnetosheath and its boundary motion in soft X-rays for understanding magnetopause reconnection modes under various solar wind conditions after their respective launches in 2024 and 2025.Magnetosheath conditions,namely,plasma density,velocity,and temperature,are key parameters for predicting and analyzing soft X-ray images from the LEXI and SMILE missions.We developed a userfriendly model of magnetosheath that parameterizes number density,velocity,temperature,and magnetic field by utilizing the global Magnetohydrodynamics(MHD)model as well as the pre-existing gas-dynamic and analytic models.Using this parameterized magnetosheath model,scientists can easily reconstruct expected soft X-ray images and utilize them for analysis of observed images of LEXI and SMILE without simulating the complicated global magnetosphere models.First,we created an MHD-based magnetosheath model by running a total of 14 OpenGGCM global MHD simulations under 7 solar wind densities(1,5,10,15,20,25,and 30 cm)and 2 interplanetary magnetic field Bz components(±4 nT),and then parameterizing the results in new magnetosheath conditions.We compared the magnetosheath model result with THEMIS statistical data and it showed good agreement with a weighted Pearson correlation coefficient greater than 0.77,especially for plasma density and plasma velocity.Second,we compiled a suite of magnetosheath models incorporating previous magnetosheath models(gas-dynamic,analytic),and did two case studies to test the performance.The MHD-based model was comparable to or better than the previous models while providing self-consistency among the magnetosheath parameters.Third,we constructed a tool to calculate a soft X-ray image from any given vantage point,which can support the planning and data analysis of the aforementioned LEXI and SMILE missions.A release of the code has been uploaded to a Github repository.

Development and validation of a prediction model for early screening of people at high risk for colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.

Model-based deep learning for fiber bundle infrared image restoration

As the representative of flexibility in optical imaging media,in recent years,fiber bundles have emerged as a promising architecture in the development of compact visual systems.Dedicated to tackling the problems of universal honeycomb artifacts and low signal-to-noise ratio(SNR)imaging in fiber bundles,the iterative super-resolution reconstruction network based on a physical model is proposed.Under the constraint of solving the two subproblems of data fidelity and prior regularization term alternately,the network can efficiently“regenerate”the lost spatial resolution with deep learning.By building and calibrating a dual-path imaging system,the real-world dataset where paired low-resolution(LR)-high-resolution(HR)images on the same scene can be generated simultaneously.Numerical results on both the United States Air Force(USAF)resolution target and complex target objects demonstrate that the algorithm can restore high-contrast images without pixilated noise.On the basis of super-resolution reconstruction,compound eye image composition based on fiber bundle is also embedded in this paper for the actual imaging requirements.The proposed work is the first to apply a physical model-based deep learning network to fiber bundle imaging in the infrared band,effectively promoting the engineering application of thermal radiation detection.

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。

Genetically modified non-human primate models for research on neurodegenerative diseases

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.