3D numerical simulation of avascular tumour growth: effect of hypoxic micro-environment in host tissue

A three-dimensional （3D） mathematical model of tumour growth at the avascular phase and vessel remodelling in host tissues is proposed with emphasis on the study of the interactions of tumour growth and hypoxic micro-environment in host tissues. The hybrid based model includes the continuum part, such as the distributions of oxygen and vascular endothelial growth factors （VEGFs）, and the discrete part of tumour cells （TCs） and blood vessel networks. The simulation shows the dynamic process of avascular tumour growth from a fewinitial cells to an equilibrium state with varied vessel networks. After a phase of rapidly increasing numbers of the TCs, more and more host vessels collapse due to the stress caused by the growing tumour. In addition, the consumption of oxygen expands with the enlarged tumour region. The study also discusses the effects of certain factors on tumour growth, including the density and configuration of pre- existing vessel networks and the blood oxygen content. The model enables us to examine the relationship between early tumour growth and hypoxic micro-environment in host tissues, which can be useful for further applications, such as tumour metastasis and the initialization of tumour angiogenesis.     

Numerical simulation of inhibiting effects on solid tumour cells in anti-angiogenic therapy: application of coupled mathematical model of angiogenesis with tumour growth

To investigate the inhibiting effects of the anti-angiogenic factor andostatin and the anti-angiogenic drug endostatin on tumour angiogenesis and tumour cells, a coupled mathematical model of tumor angiogenesis with tumour growth and blood perfusion is developed. Simulation results show that angiostatin and endostatin can improve the abnormal microenvironment inside the tumour tissue by effectively inhibiting the process of tumor angiogenesis and decreasing tumour cells. The present model can be used as a valid theoretical method in the investigation of the tumour anti-angiogenic therapy.     

实体肿瘤血管生成和肿瘤生长的耦合研究

研究宏观尺度上肿瘤向外浸润式生长的动态变化对微观尺度上肿瘤内部微血管网生成过程产生的影响。建立肿瘤组织生长动力学模型与促血管生成的二维离散数学模型,模型考虑促血管生成因子诱导下血管内皮细胞的随机性、趋化性和趋触性运动以及血管内皮细胞与胞外基质的相互作用,并且肿瘤组织的生长满足经典的Compertz函数形式,通过耦合研究模拟了肿瘤组织动态生长过程中微脉管系统生成的时空演化,数值生成肿瘤动态生长下内外异构的微血管网和肿瘤内部分层的网络结构。该模型可以产生相对真实的具有接近肿瘤病理生理特性的血管网,为临床研究提供有益的信息。     

A model for cell migration in tumour growth

Tumour growth results, in particular, from cell–cell interaction and tumour and healthy cell proliferation. The complexity of the cellular microenvironment may then be framed within the theory of mixtures by looking at cell populations as the constituents of a mixture. In this paper the balance equations are reviewed to account for directionality onto a collective migration of the tumour cell population, via an attractive force of the chemotactic type, in addition to the customary pressure term. The density of tumour cells turns out to be governed by a hyperbolic differential equation. By neglecting, as usual, the inertia term it follows that the density satisfies a backward, or forward, diffusion equation according as the attraction, or pressure effect, prevails. Uniqueness of the solution to the backward equation is investigated and a family of solutions is described. An estimate is given for the growth rate of a tumour profile.     

Instability of sloshing motion in a vessel undergoing pivoted oscillations

Suspending a rectangular vessel partially filled with an inviscid fluid from a single rigid pivoting rod produces an interesting physical model for investigating the dynamic coupling between the fluid and vessel motion. The fluid motion is governed by the Euler equations relative to the moving frame of the vessel, and the vessel motion is given by a modified forced pendulum equation. The fully nonlinear, two-dimensional, equations of motion are derived and linearised for small-amplitude vessel and free-surface motions, and the natural frequencies of the system analysed. It is found that the linear problem exhibits an unstable solution if the rod length is shorter than a critical length which depends on the length of the vessel, the fluid height and the ratio of the fluid and vessel masses. In addition, we identify the existence of 1:1 resonances in the system where the symmetric sloshing modes oscillate with the same frequency as the coupled fluid/vessel motion. The implications of instability and resonance on the nonlinear problem are also briefly discussed.     

LOW-FREQUENCY RESPONSES OF NONLINEARLY MOORED VESSELS IN RANDOM WAVES: COUPLED SURGE,PITCH AND HEAVE MOTIONS

The responses of a multi-degree-of-freedom model of a moored vessel are analysed, accounting for the hydroelastic interaction between the nonlinear wave hydrodynamics and the nonlinear mooring stiffness. A two-scale perturbation method developed by Sarkar & Eatock Taylor to determine low-frequency hydrodynamic forces on a single-degree-of-freedom model of a nonlinearly moored vessel has been extended to analyse the nonlinear multi-degree-of-freedom dynamics of the system. Surge, heave and pitch motions are considered. The perturbation equations of successive orders are derived. To illustrate the approach, semi-analytical expressions for the higher-order hydrodynamic force components have been obtained for a truncated circular cylinder in finite water depth. In addition to conventional quadratic force transfer functions, a new type of higher-order force transfer function is introduced. This is used to characterize the hydrodynamic forces on the vessel which arise due to nonlinearity of the mooring stiffness. These are a type of radiation force, generated by the nonlinear interaction of the fluid–structure coupled system. Based on a Volterra series model, the power spectral densities of the new higher-order forces are then derived for the case of Gaussian random seas. It is shown that the additional response arising due to nonlinear dynamics of the mooring system can significantly contribute to low-frequency drift forces and responses of the vessel. Unlike conventional non-Gaussian second-order forces which are quadratic transformations of a Gaussian random process, the new higher-order forces arising due to the nonlinear mooring stiffness are polynomials of a Gaussian random process (up to fourth order for a Duffing oscillator model). This may significantly influence the extreme responses.     

基于动态预测的深水爆炸试验容器可靠性分析

为了确保深水爆炸试验容器在服役期间的安全性,提出了一种基于智能预测的随机-区间动态可靠性模型,通过动态测试数据建立了容器响应的广义回归神经网络（general regression neural network,GRNN）预测模型,获得了容器的最大应变区间变量,同时考虑容器结构的随机特性,开展了现役深水爆炸试验容器的可靠性分析,并分别采用3种方法进行了可靠性指标计算。分析结果表明,对于深水爆炸试验容器这类高可靠性且缺乏样本数据的结构,建立基于动态预测的混合可靠性模型,并通过区间计算可靠性指标的方法简便、可行;模型的区间变量随着结构动态测试数据的变化而变化,且对结构的不确定性分析也是动态的,因此得到的容器可靠性也随着其服役过程不断推进,具有动态特性,可以更好地反映容器在服役期间的性能变化,为容器的使用维护提供决策依据。     

The pendulum-slosh problem: Simulation using a time-dependent conformal mapping

Suspending a rectangular vessel which is partially filled with fluid from a single rigid pivoting pole produces an interesting theoretical model with which to investigate the dynamic coupling between fluid motion and vessel rotation. The exact equations for this coupled system are derived with the fluid motion governed by the Euler equations relative to the moving frame of the vessel, and the vessel motion governed by a modified forced pendulum equation. The nonlinear equations of motion for the fluid are solved numerically via a time-dependent conformal mapping, which maps the physical domain to a rectangle in the computational domain with a time dependent conformal modulus. The numerical scheme expresses the implicit free-surface boundary conditions as two explicit partial differential equations which are then solved via a pseudo-spectral method in space. The coupled system is integrated in time with a fourth-order Runge–Kutta method. The starting point for the simulations is the linear neutral stability contour discovered by Turner et al. (2015, Journal of Fluid & Structures 52, 166–180). Near the contour the nonlinear results confirm the instability boundary, and far from the neutral curve (parameterized by longer pole lengths) nonlinearity is found to significantly alter the vessel response. Results are also presented for an initial condition given by a superposition of two sloshing modes with approximately the same frequency from the linear characteristic equation. In this case the fluid initial conditions generate large nonlinear vessel motions, which may have implications for systems designed to oscillate in a confined space or on the slosh-induced-rolling of a ship.     

Modeling and simulation of circulating fluidized bed reactors applied to a carbonation/calcination loop

A fluid dynamic model for a gas-solid circulating fluidized bed (CFB) designed using two coupled riser reactors is developed and implemented numerically with code programmed in Matlab. The fluid dynamic model contains heat and species mass balances to calculate temperatures and compositions for a carbonation/calcination loop process.Because of the high computational costs required to resolve the three-dimensional phenomena, a model representing a trade-off between computational time requirements and accuracy is developed. For dynamic processes with a solid flux between the two reactor units that depends on the fluid dynamics of both risers, a dynamic one-dimensional two-fluid model is sufficient.A two-fluid model using the constant particle viscosity closure for the stress term is used for the solid phase, and an algebraic turbulence model is applied to the gas phase. The numerical model implementation is based on the finite volume method with a staggered grid scheme. The exchange of solids between the reactor units constituting the circulating fluidized bed (solid flux) is implemented through additional mass source/sink terms in the continuity equations of the two phases.For model validation, a relevant experimental analysis provided in the literature is reproduced by the numerical simulations. The numerical analysis indicates that sufficient heat integration between the two reactor units is important for the performance of the circulating fluidized bed system.The two-fluid model performs fairly well for this chemical process operated in a CFB designed as two coupled riser reactors. Further analysis and optimization of the solution algorithms and the reactor coupling strategy is warranted.     

An ALE approach to mechano‐chemical processes in fluid–structure interactions

Mathematical modeling and simulation of fluid–structure interaction problems are in the focus of research already for a longer period. However, taking into account also chemical reactions, leading to structural changes, including changes of mechanical properties of the solid phase, is rather new but for many applications is highly important area. This paper formulates a model system for reactive flow and transport in a vessel system, the penetration of chemical substances into the solid wall. Inside the wall, reactions take place that lead to changes of volume and of the mechanical properties of the wall. Numerical algorithms are developed and used to simulate the dynamics of such a mechano‐chemical fluid–structure interaction problem. As a proof of concept scenario, plaque formation in blood vessels is chosen. The arbitrary Lagrangian Eulerian approach (ALE) is chosen to solve the systems numerically. Temporal discretization of the fully coupled monolithic model is accomplished by backward Euler scheme and spatial discretization by stabilized finite elements. The numerical approach is verified by numerical tests, and effective methods to maintain mesh qualities under large deformations are described. For realistic system parameters, the simulations show that the plaque formation in blood vessel is a long‐time effect. The time scale of the formation is in the simulation of comparable order as in reality. Copyright © 2016 John Wiley & Sons, Ltd.     

Modeling and simulation of circulating fluidized bed reactors applied to a carbonation/calcination loop

A fluid dynamic model for a gas-solid circulating fluidized bed （CFB） designed using two coupled riser reactors is developed and implemented numerically with code programmed in Matlab. The fluid dynamic model contains heat and species mass balances to calculate temperatures and compositions for a carbonation/calcination loop process. Because of the high computational costs required to resolve the three-dimensional phenomena, a model representing a trade-offbetween computational time requirements and accuracy is developed. For dynamic processes with a solid flux between the two reactor units that depends on the fluid dynamics of both risers, a dynamic one-dimensional two-fluid model is sufficient. A two-fluid model using the constant particle viscosity closure for the stress term is used for the solid phase, and an algebraic turbulence model is applied to the gas phase. The numerical model implementa- tion is based on the finite volume method with a staggered grid scheme. The exchange of solids between the reactor units constituting the circulating fluidized bed （solid flux） is implemented through additional mass source/sink terms in the continuity equations of the two phases, For model validation, a relevant experimental analysis provided in the literature is reproduced by the numerical simulations, The numerical analysis indicates that sufficient heat integration between the two reactor units is important for the performance of the circulating fluidized bed system, The two-fluid model performs fairly well for this chemical process operated in a CFB designed as two coupled riser reactors. Further analysis and optimization of the solution algorithms and the reactor coupling strategy is warranted.     

Biochemomechanical poroelastic theory of avascular tumor growth

Tumor growth is a complex process involving genetic mutations, biochemical regulations, and mechanical deformations. In this paper, a thermodynamics-based nonlinear poroelastic theory is established to model the coupling among the mechanical, chemical, and biological mechanisms governing avascular tumor growth. A volumetric growth law accounting for mechano-chemo-biological coupled effects is proposed to describe the development of solid tumors. The regulating roles of stresses and nutrient transport in the tumor growth are revealed under different environmental constraints. We show that the mechano-chemo-biological coupling triggers anisotropic and heterogeneous growth, leading to the formation of layered structures in a growing tumor. There exists a steady state in which tumor growth is balanced by resorption. The influence of external confinements on tumor growth is also examined. A phase diagram is constructed to illustrate how the elastic modulus and thickness of the confinements jointly dictate the steady state of tumor volume. Qualitative and quantitative agreements with experimental observations indicate the developed model is capable of capturing the essential features of avascular tumor growth in various environments.     

Particle-scale and sub-grid drag models coupled CFD for simulating the CO methanation in a CFB riser

The diffusion and chemical reactions inside the catalyst particles and the heterogeneous flow structure in the computational cells are key factors to affect the accuracy of the coarse-grid simulation in circulating fluidized bed (CFB) methanation reactors. In this work, a particle-scale model is developed to calculate the effective reaction rate considering the transient diffusion and chemical reactions in the particle scale, i.e., the scale of the single catalyst particle. A modified sub-grid drag model is proposed to consider the effects of the meso-scale and chemical reactions on the heterogeneous gas-solid interaction, where the meso-scale is between the single particle and the whole reactor and featured with the particle cluster. Subsequently, a coupled model is developed by integrating the particle-scale and modified sub-grid drag models into CFD. Moreover, the coupled model is validated to achieve accurate predictions on the CO methanation process in a CFB riser. Notably, the coupled model can be performed with a coarse grid (∼58 times particle diameter) and a large time step (0.005 s) to accelerate the simulation. By simply changing the reaction kinetics, different gas-solid catalytic reaction systems can be simulated by using the coupled model.     

双层球壳结构准静态线性化学弹性问题的位移势函数解

本文研究了各向同性固体的化学-力学耦合问题,在传统化学弹性理论描述的扩散-变形耦合关系基础上,进一步考虑了化学反应与固体变形的相互作用关系,发展了等温状态下固体-扩散-反应-变形耦合的线性化学弹性理论,拓展了化学弹性力学的应用范围．该理论能够同时描述固体内介质扩散和固体与介质之间化学反应两个不同时间尺度的化学过程,并给出由此引起的弹性范围内的应变和应力．为应用该模型求解具体化学弹性问题,本文通过构造扩散-反应位移势函数来获得位移特解形式,再与齐次Lamé方程通解叠加获得完整解;针对反应控制问题,引入化学弹性准静态假设,将反应-扩散-变形全耦合的瞬态过程分解为两个可解耦的相继过程,从而获得相应位移解．基于此解法,本文获得了反应控制的双层球壳结构化学弹性问题的解析解,并分析了化学反应、几何结构和弹性模量对应力分布的影响．     

Blast from explosive evaporation of carbon dioxide: experiment, modeling and physics

Explosive evaporation of a superheated liquid is a relevant hazard in the process industry. A vessel rupture during storage, transport or handling may lead to devastating blast effects. In order to assess the risk associated with this hazard or to design protective measures, an accurate prediction model for the blast generated after vessel rupture is needed. For this reason a fundamental understanding of the effects of a boiling liquid expanding vapor explosion (BLEVE) is essential. In this paper, we report on a number of well-defined BLEVE experiments with 40-l liquid CO₂ bottles. The existing inertia-limited BLEVE model has been validated by its application to these experiments. Good qualitative agreement between model and experiment was found, while quantitatively the results provide a safe estimate. Possible model improvements taking into account the finite rate of evaporation are described. These comprise phenomena such as bubble nucleation and growth rate, and the two-phase flow regime. Suggestions for improved experiments are given as well.     

Coupled model of coating formation on a cylindrical substrate

A coupled model of coating formation on the surface of a part of a cylindrical shape during deposition from the plasma is proposed. This model takes into account the phenomena of thermal diffusion, diffusive thermal conductivity, and mass transfer under the action of the stress gradient, and the formation of chemical compounds. The coating growth rate is considered to be a given function of the particle velocity and particle concentration near the surface of the growing coating. The problem is solved numerically. It is shown that diffusion cross-fluxes, diffusive thermal conductivity, and thermal diffusion during the growth process reduce the width of the transition zone between the substrate and the coating. This effect becomes most essential if the substrate has a low thermal conductivity. Accounting for stresses arising in the coating-substrate system during the deposition process changes the effective transfer coefficients and significantly affects the result of modeling the distribution of chemical elements and their compounds in the coating.     

On the role of the process zone in dynamic fracture

The evolution of the fracture process zone and its influence on dynamic crack propagation are investigated using a simple constitutive assumption to model the material in the fracture process zone. The mode III problem of anti-plane shear is examined using a finite difference scheme to obtain the full field solution. Unlike the classical approach of determining the steady state solutions for imposed constant speed of crack propagation, here the fracture criterion is imposed along with the formulation of the boundary-initial value problem and the coupled equations are solved numerically to determine the generation and growth of the fracture process zone as well as the crack tip. The results of the simulation indicate that the constitutive behavior of the process zone material (or equivalently the evolution of the process zone itself) plays a key role in determining the dynamics of fast fracture.     

Modelling the curing process in magneto-sensitive polymers: Rate-dependence and shrinkage

This paper deals with a phenomenologically motivated magneto-viscoelastic coupled finite strain framework for simulating the curing process of polymers under the application of a coupled magneto-mechanical load. Magneto-sensitive polymers are prepared by mixing micron-sized ferromagnetic particles in uncured polymers. Application of a magnetic field during the curing process causes the particles to align and form chain-like structures lending an overall anisotropy to the material. The polymer curing is a viscoelastic complex process where a transformation from fluid to solid occurs in the course of time. During curing, volume shrinkage also occurs due to the packing of polymer chains by chemical reactions. Such reactions impart a continuous change of magneto-mechanical properties that can be modelled by an appropriate constitutive relation where the temporal evolution of material parameters is considered. To model the shrinkage during curing, a magnetic-induction-dependent approach is proposed which is based on a multiplicative decomposition of the deformation gradient into a mechanical and a magnetic-induction-dependent volume shrinkage part. The proposed model obeys the relevant laws of thermodynamics. Numerical examples, based on a generalised Mooney–Rivlin energy function, are presented to demonstrate the model capacity in the case of a magneto-viscoelastically coupled load.     

油气在持续热壁下热着火发生的数值模拟

为了对油气在持续热壁下热着火发生过程进行数值模拟,耦合化学动力学模型、流体动力学模型及辐射传热模型,建立了油气热着火的统一模型。基于实验工况,模拟了受限空间中油气在持续热壁条件下热着火发生过程,并分析了温度、压力流场的演变特征,以及不同位置处温度、压力、层流速度、湍流速度和组分质量分数的变化曲线。通过模拟,发现油气热着火过程存在3个阶段,分别为加热初始阶段、加热中间阶段和热着火发生阶段。不同阶段存在的主要原因是化学反应和流动的主导作用不同。     

Homogenization in non-linear dynamics due to frictional contact

This work is devoted to a study of the classical homogenization process and its influence on the behavior of a composite under non-linear dynamic loading due to contact and friction. First, the general problem of convergence of numerical models subjected to dynamic contact with friction loading is addressed. The use of a regularized friction law allows obtaining good convergence of such models. This study shows that for a dynamic contact with friction loading, the classical homogenization process, coupled with an homogenization of the frictional contact, enables replacing the entire heterogeneous model by a homogenized one. The dynamic part of the frictional contact must be homogenized by modifying the dynamic parameter of the friction law. Modification of the dynamic parameter of the friction law is function of the type and regime of instability. A calculation of a homogenized friction coefficient is presented in view to homogenizing the static part of the frictional contact when the friction coefficient is not constant over the contact surface. Finally matrix and heterogeneities stresses in the heterogeneous models are identified by using the relocalization process and a frictional contact dynamic analysis of a homogeneous model.