Cellular models for human cardiomyopathy:What is the best option?

The genetic cardiomyopathies are a group of disorders related by abnormal myocardial structure and function.Although individually rare,these diseases collectively represent a significant health burden since they usually develop early in life and are a major cause of morbidity and mortality amongst affected children.The heterogeneity and rarity of these disorders requires the use of an appropriate model system in order to characterize the mechanism of disease and develop useful therapeutics since standard drug trials are infeasible.A common approach to study human disease involves the use of animal models,especially rodents,but due to important biological and physiological differences,this model system may not recapitulate human disease.An alternative approach for studying the metabolic cardiomyopathies relies on the use of cellular models which have most frequently been immortalized cell lines or patient-derived fibroblasts.However,the recent introduction of induced pluripotent stem cells(iPSCs),which have the ability to differentiate into any cell type in the body,is of great interest and has the potential to revolutionize the study of rare diseases.In this paper we review the advantages and disadvantages of each model system by comparing their utility for the study of mitochondrial cardiomyopathy with a particular focus on the use of iPSCs in cardiovascular biology for the modeling of rare genetic or metabolic diseases.

Cellular models for disease exploring and drug screening

The biopharmaceutical industry has been greatly promoted by the application of drug and disease models,including both animal and cellular models.In particular,the emergence of induced pluripotent stem cells(iPSC)makes it possible to create a large number of diseasespecific cells in vitro.This review introduces the most widely applied models and their specialties.

NEURO PROTECTIVE EFFECT OF SCHISANDRA B ON AD-RELATED CELLULAR MODEL INVOLVES THE ATTENUATION OF APOPTOSIS

Schisandrin B(Sch B),the major lignans isolated from Schisandra chinensis,exerts high arntioxidant activities.However,it is unknown whether SchB protects neural cell against Aβinduced cellular apoptosis.This study aims to investigate the neuroprotective action of SchB on cellular model of AD,and revealed the underlying mechanisms.

Modernising autism spectrum disorder model engineering and treatment via CRISPR-Cas9:A gene reprogramming approach

A neurological abnormality called autism spectrum disorder(ASD)affects how a person perceives and interacts with others,leading to social interaction and communication issues.Limited and recurring behavioural patterns are another feature of the illness.Multiple mutations throughout development are the source of the neurodevelopmental disorder autism.However,a well-established model and perfect treatment for this spectrum disease has not been discovered.The rising era of the clustered regularly interspaced palindromic repeats(CRISPR)-associated protein 9(Cas9)system can streamline the complexity underlying the pathogenesis of ASD.The CRISPR-Cas9 system is a powerful genetic engineering tool used to edit the genome at the targeted site in a precise manner.The major hurdle in studying ASD is the lack of appropriate animal models presenting the complex symptoms of ASD.Therefore,CRISPR-Cas9 is being used worldwide to mimic the ASD-like pathology in various systems like in vitro cell lines,in vitro 3D organoid models and in vivo animal models.Apart from being used in establishing ASD models,CRISPR-Cas9 can also be used to treat the complexities of ASD.The aim of this review was to summarize and critically analyse the CRISPRCas9-mediated discoveries in the field of ASD.

A dynamic cellular vertex model of growing epithelial tissues

Intercellular interactions play a significant role in a wide range of biological functions and processes at both the cellular and tissue scales, for example, embryogenesis, organogenesis, and cancer invasion. In this paper, a dynamic cellular vertex model is presented to study the morphomechanics of a growing epithelial monolayer. The regulating role of stresses in soft tissue growth is revealed. It is found that the cells originating from the same parent cell in the monolayer can orchestrate into clustering patterns as the tissue grows. Collective cell migration exhibits a feature of spatial correlation across multiple cells. Dynamic intercellular interactions can engender a variety of distinct tissue behaviors in a social context. Uniform cell proliferation may render high and heterogeneous residual compressive stresses, while stress-regulated proliferation can effectively release the stresses, reducing the stress heterogeneity in the tissue. The results highlight the critical role of mechanical factors in the growth and morphogenesis of epithelial tissues and help understand the development and invasion of epithelial tumors.

Effects of rainy weather on traffic accidents of a freeway using cellular automata model

The aim of this work is to investigate the influence of rainy weather on traffic accidents of a freeway. The micro-scale driving behaviors in rainy weather and possible vehicle rear-end and sideslip accidents are analyzed. An improved CA model of two lanes one-way freeway is presented, where some vehicle accidents will occur when the necessary conditions are simultaneously satisfied. The characteristics of traffic flow under different rainfall intensities are discussed and the accident probabilities are analyzed via the simulation experiments by using variable speed limit （VSL） and incoming flow control. The results indicate that the measures are effective especially during heavy rainstorms or short-time heavy rainfall. According to different rainfall intensities, an appropriate strategy should be adopted in order to reduce the probability of vehicle accidents and enhance traffic flux as well.

An extended cellular automata model with modified floor field for evacuation

The floor field model has been widely used in evacuation simulation research based on cellular automata model. However, conventional methods of setting floor field will lead to highly insufficient utilization of the exit area when people gather on one side of the exit. In this study, an extended cellular automata model with modified floor field is proposed to solve this problem. Additionally, a congestion judgment mechanism is integrated in our model, whereby people can synthetically judge the degree of congestion and distance in front of them to determine whether they need to change another exit to evacuate or not. We contrasted the simulation results of the conventional floor field model, the extended model proposed in this paper, and Pathfinder software in a same scenario. It is demonstrated that this extended model can ameliorate the problem of insufficient utilization of the exit area and the trajectory of pedestrian movement and the crowd shape of pedestrians in front of exit in this new model are more realistic than those of the other two models. The findings have implications for modeling pedestrian evacuation.

A traffic flow cellular automaton model to considering drivers' learning and forgetting behaviour

It is known that the commonly used NaSch cellular automaton （CA） model and its modifications can help explain the internal causes of the macro phenomena of traffic flow. However, the randomization probability of vehicle velocity used in these models is assumed to be an exogenous constant or a conditional constant, which cannot reflect the learning and forgetting behaviour of drivers with historical experiences. This paper further modifies the NaSch model by enabling the randomization probability to be adjusted on the bases of drivers＇ memory. The Markov properties of this modified model are discussed. Analytical and simulation results show that the traffic fundamental diagrams can be indeed improved when considering drivers＇ intelligent behaviour. Some new features of traffic are revealed by differently combining the model parameters representing learning and forgetting behaviour.

A cellular automaton model for a bridge traffic bottleneck

A cellular automaton （CA） model is proposed in this paper to analyze a bridge traffic bottleneck. The simulation results with this model show that there are several phase transitions in the traffic average density, velocity and flow for each lane under a periodic boundary condition. An unstable phase in the traffic average density and velocity for the upstream and downstream lanes of the bridge is shown in a range of initial traffic densities. The critical points of the phase transitions and the phenomenon of the unstable phase found in the simulation are also explained with the mean-field theory.

Cellular automata modeling of pedestrian＇s crossing dynamics

Cellular automata modeling techniques and the characteristics of mixed traffic flow were used to derive the 2-dimensional model presented here for simulation of pedestrian's crossing dynamics. A conception of "stop point" is introduced to deal with traffic obstacles and resolve conflicts among pedestrians or between pedestrians and the other vehicles on the crosswalk. The model can be easily extended, is very efficient for simulation of pedestrian's crossing dy-namics, can be integrated into traffic simulation software, and has been proved feasible by simulation

An implementation of cellular automaton model for single-line train working diagram

According to the railway transportation system＇s characteristics, a new cellular automaton model for the single- line railway system is presented in this paper. Based on this model, several simulations were done to imitate the train operation under three working diagrams. From a different angle the results show how the organization of train operation impacts on the railway carrying capacity. By using the non-parallel train working diagram the influence of fast-train on slow-train is found to be the strongest. Many slow-trains have to wait in-between neighbouring stations to let the fast-train（s） pass through first. So the slow-train will advance like a wave propagating from the departure station to the arrival station. This also resembles the situation of a highway jammed traffic flow. Furthermore, the nonuniformity of travel times between the sections also greatly limits the railway carrying capacity. After converting the nonuniform sections into the sections with uniform travel times while the total travel time is kept unchanged, all three carrying capacities are improved greatly as shown by simulation. It also shows that the cellular automaton model is an effective and feasible way to investigate the railway transportation system.

Instantaneous information propagation in free flow,synchronized flow,stop-and-go waves in a cellular automaton model

Recently, a number of efforts are underway to investigate inter-vehicle communications （IVC）. This paper studies the instantaneous information propagation behaviours based on IVC in three different tragic situations （free flow, synchronized flow and stop-and-go waves） in a cellular automaton model. It is shown that different behaviours appear in stop-and-go waves from those in free flow and synchronized flow. While the distribution of Multi-hop Communication Distance （MhCD） is either exponential or uniform in free flow and synchronized flow, the distribution of MhCD is either exponential or with a single peak in stop-and-go waves.

Urban rail departure capacity analysis based on a cellular automaton model

As an important traffic mode, urban rail transit is constantly developing toward improvement in service capacity and quality. When an urban rail transit system is evaluated in terms of its service capacity, the train departure capacity is an important index that can objectively reflect the service level of an urban rail transit facility. In light of the existing cellular automaton models, this paper proposes a suitable cellular automaton model to analyze the train departure capacity of urban rail transit under different variable factors and conditions. The established model can demonstrate the train operating processes by implementing the proposed sound rules, including the rules of train departure at the origin and intermediate stations, and the velocity and position updating rules. The properties of train traffic are analyzed via numerical experiments. The numerical results show that the departure capacity is negatively affected by the train departure control manner. In addition, （i） the real-time signal control can offer a higher train service frequency; （ii） the departure capacity gradually rises with the decrease in the line design speed to a limited extent; （iii） the departure capacity decreases with extension in the train length; （iv） the number of departed trains decreases as the train stop time increases; （v） the departure capacity is not affected by the section length. However, the longer the length, the worse the service quality of the urban rail transit line. The experiments show that the proposed cellular automaton model can be used to analyze the train service capacity of an urban rail transit system by performing quantitative analysis under various considered factors, conditions, and management modes.

Simulation of traffic flow with traffic light strategies via a modified cellular automaton model

Traffic flows controlled by traffic light strategies were investigated via a cellular automaton model with anticipation, which is suitable for describing urban traffic. Three kinds of strategies, i. e., synchronized, green-wave and random switching lights, were designed, simulated and compared with each other. It is shown that the green-wave strategy is only valid at lower density and there is not an effective way with the three strategies to improve the efficiency of traffic flow at high density.

A Modified Sensitive Driving Cellular Automaton Model

A modified cellular automaton model for traffic flow on highway is proposed with a novel concept about the variable security gap. The concept is first introduced into the original Nagel-Schreckenberg model, which is called the non-sensitive driving cellular automaton model. And then it is incorporated with a sensitive driving NaSch model,in which the randomization brake is arranged before the deterministic deceleration. A parameter related to the variable security gap is determined through simulation. Comparison of the simulation results indicates that the variable security gap has different influence on the two models. The fundamental diagram obtained by simulation with the modified sensitive driving NaSch model shows that the maximumflow are in good agreement with the observed data, indicating that the presented model is more reasonable and realistic.

Numerical simulation of solidification morphologies of Cu-0.6Cr casting alloy using modified cellular automaton model

The purpose of this study is to predict the morphologies in the solidification process for Cu-0.6Cr(mass fraction,%)alloy by vacuum continuous casting(VCC)and verify its accuracy by the observed experimental results.In numerical simulation aspect, finite difference(FD)method and modified cellular automaton(MCA)model were used to simulate the macro-temperature field, micro-concentration field,nucleation and grain growth of Cu-0.6Cr alloy using real data from actual casting operations.From the observed casting experiment,the preliminary grain morphologies are the directional columnar grains by the VCC process.The solidification morphologies by MCAFD model are in agreement with the result of actual casting experiment well.

Cellular automation model for analyzing capacity of branch road section

In order to reduce the traffic pressure of urban arterial road with the rational utilization of the branch road,the vehicle meeting behavior on the branch road without divided lane was described,and the cellular automation (CA) model was put forward by introducing meeting behavior to reflect the relation between safe meeting speed and road width.The numerical simulation results depict several relation curves between road section capacity,speed and road width under different directional distributions of traffic flow,as well as the curves between the major and minor direction saturation flow,speed and road width.These relation characteristics indicate that except the one-way road section capacity and speed remaining unchanged,other road section capacities and speeds under different directional distributions increase with the increase of road width.On narrow road,the two-way traffic capacity and speed are less than those of one-way traffic;on wide road,the two-way traffic capacity doubles that of one-way traffic,but their speeds are almost the same.As the directional distribution moves to an even distribution of 50/50,the major direction saturation flows and speeds as well as the minor direction speeds tend to decease,while the minor direction saturation flow tends to increase.

Modeling Passengers Boarding in Aircraft Using Cellular Automata

Aircraft are profitable to their owners as long as they are in the air transporting passengers to their destinations;therefore it is vital to minimize as much as possible their preparation time on the ground.In this paper we simulate different boarding strategies with the help of a model based on cellular automata parallel computational tool,attempting to find the most efficient way to deliver each passenger to her/his assigned seat.Two seat arrangements are used,a small one based on Airbus A320/ Boeing 737 and a larger one based on Airbus A380/ Boeing777-300.A wide variety of parameters,including time delay for luggage storing,the frequency by which the passengers enter the plane,different walking speeds of passengers depending on sex,age and height,and the possibility of walking past their seat,are simulated in order to achieve realistic results,as well as monitor their effects on boarding time.The simulation results indicate that the boarding time can be significantly reduced by the simple grouping and prioritizing of passengers.In accordance with previous papers and the examined strategies,the outside-in and reverse pyramid boarding methods outperform all the others for both the small and large airplane seat layout.In the latter,the examined strategies are introduced for first time in an analogous way to the initial small seat arrangement of Airbus A320/ Boeing737 aircraft family.Moreover,since in real world scenarios,the compliance of all the passengers to the suggested group division and boarding strategy cannot be guaranteed,further simulations were conducted.It is clear that as the number of passengers disregarding the priority of the boarding groups increases,the time needed for the boarding to complete tends towards that of the random boarding strategy,thus minimizing the possible advantages gained by the proposed boarding strategies.

Blast response of continuous-density graded cellular material based on the 3D Voronoi model

One-dimensional blast response of continuous-density graded cellular rods was investigated theoretically and numerically. Analytical model based on the rigid-plastic hardening(R-PH) model was used to predict the blast response of density-graded cellular rods. Finite element(FE) analysis was performed using a new model based on the 3 D Voronoi technique. The FE results have a good agreement with the analytical predictions. The blast response and energy absorption of cellular rods with the same mass but different density distributions were examined under different blast loading. As a blast resistance structure, cellular materials with high energy absorption and low impulse transmit is attractive. However, high energy absorption and low impulse transmit cannot be achieved at the same time by changing the density distribution. The energy absorption capacity increases with the initial blast pressure and characteristic time of the exponentially decaying blast loading. By contract, when the blast loading exceeds the resistance capacity of cellular material, the transmitted stress will be enhanced which is detrimental to the structure being protected.

Cellular Automaton Models of Highway Traffic Flow Considering Lane-Control and Speed-Control

As two kinds of management modes of highway traffic control,lane-control,and speed-control produce different effect under different conditions.In this paper,traffic flow cellular automaton models for four-lane highway system with two opposing directions under the above two modes are established considering car and truck mixed running. Through computer numerical simulating,the fundamental diagrams with different parameters are obtained,and after the analysis of density-flux diagrams,the variation discipline of flux with traffic density under different control models is gained.The results indicate that,compared with lane-control,utilization ratio of road can be further improved with speed-control when the truck number increases.The research result is of great significance for reasonable providing theoretical guidance for highway traffic control.