Analysis of the dynamics of a delayed HIV pathogenesis model

In this paper, considering full Logistic proliferation of CD4⁺ T cells, we study an HIV pathogenesis model with antiretroviral therapy and HIV replication time. We first analyze the existence and stability of the equilibrium, and then investigate the effect of the time delay on the stability of the infected steady state. Sufficient conditions are given to ensure that the infected steady state is asymptotically stable for all delay. Furthermore, we apply the Nyquist criterion to estimate the length of delay for which stability continues to hold, and investigate the existence of Hopf bifurcation by using a delay τ as a bifurcation parameter. Finally, numerical simulations are presented to illustrate the main results.     

Bifurcation analysis of HIV infection model with antibody and cytotoxic T‐lymphocyte immune responses and Beddington–DeAngelis functional response

In this paper, a mathematical model for HIV‐1 infection with antibody, cytotoxic T‐lymphocyte immune responses and Beddington–DeAngelis functional response is investigated. The stability of the infection‐free and infected steady states is investigated. The basic reproduction number R₀ is identified for the proposed system. If R₀ < 1, then there is an infection‐free steady state, which is locally asymptotically stable. Further, the infected steady state is locally asymptotically stable for R₀ > 1 in the absence of immune response delay. We use Nyquist criterion to estimate the length of the delay for which stability continues to hold. Also the existence of the Hopf bifurcation is investigated by using immune response delay as a bifurcation parameter. Numerical simulations are presented to justify the analytical results. Copyright © 2014 John Wiley & Sons, Ltd.     

Mathematical Analysis of SIR Epidemic Model with Piecewise Infection Rate and Control Strategies

The limitation of contact between susceptible and infected individuals plays an important role in decreasing the transmission of infectious diseases. Prevention and control strategies contribute to minimizing the transmission rate. In this paper, we propose SIR epidemic model with delayed control strategies, in which delay describes the response and effect time. We study the dynamic properties of the epidemic model from three aspects: steady states, stability and bifurcation. By eliminating the existence of limit cycles, we establish the global stability of the endemic equilibrium, when the delay is ignored. Further, we find that the delayed effect on the infection rate does not affect the stability of the disease-free equilibrium, but it can destabilize the endemic equilibrium and bring Hopf bifurcation. Theoretical results show that the prevention and control strategies can effectively reduce the final number of infected individuals in the population. Numerical results corroborate the theoretical ones.     

A delay-dependent model with HIV drug resistance during therapy

The use of combination antiretroviral therapy has proven remarkably effective in controlling HIV disease progression and prolonging survival. However, the emergence of drug resistance can occur. It is necessary that we gain a greater understanding of the evolution of drug resistance. Here, we consider an HIV viral dynamical model with general form of target cell density, drug resistance and intracellular delay incorporating antiretroviral therapy. The model includes two strains: wild-type and drug-resistant. The basic reproductive ratio for each strain is obtained for the existence of steady states. Qualitative analysis of the model such as the well-posedness of the solutions and the equilibrium stability is provided. Global asymptotic stability of the disease-free and drug-resistant steady states is shown by constructing Lyapunov functions. Furthermore, sufficient conditions related to the properties of the target cell density are obtained for the local asymptotic stability of the positive steady state. Numerical simulations are conducted to study the impact of target cell density and intracellular delay focusing on the stability of the positive steady state. The occurrence of Hopf bifurcation of periodic solutions is shown to depend on the target cell density.     

Asymptotic behavior and stability switch for a mature–immature model of cell differentiation

We consider a nonlinear age-structured model, inspired by hematopoiesis modelling, describing the dynamics of a cell population divided into mature and immature cells. Immature cells, that can be either proliferating or non-proliferating, differentiate in mature cells, that in turn control the immature cell population through a negative feedback. We reduce the system to two delay differential equations, and we investigate the asymptotic stability of the trivial and the positive steady states. By constructing a Lyapunov function, the trivial steady state is proven to be globally asymptotically stable when it is the only equilibrium of the system. The asymptotic stability of the positive steady state is related to a delay-dependent characteristic equation. Existence of a Hopf bifurcation and stability switch for the positive steady state is established. Numerical simulations illustrate the stability results.     

Stability of a stochastic SEIS model with saturation incidence and latent period

In this paper, a stochastic SEIS epidemic model with a saturation incidence rate and a time delay describing the latent period of the disease is investigated. The model inherits the endemic steady state from its corresponding deterministic counterpart. We first show the existence and uniqueness of the global positive solution of the model. Then, by constructing Lyapunov functionals, we derive sufficient conditions ensuring the stochastic stability of the endemic steady state. Numerical simulations are carried out to confirm our analytical results. Furthermore, our simulation results shows that the existence of noise and delay may cause the endemic steady state to be unstable.     

Travelling waves of a predator–prey model with a spatiotemporal delay

This paper is concerned with the existence of traveling waves to a predator–prey model with a spatiotemporal delay. By analyzing the corresponding characteristic equations, the local stability of a positive steady state and each of boundary steady states are established, and the existence of Hopf bifurcation at the positive steady state is also discussed. By constructing a pair of upper–lower solutions and by using the cross‐iteration method as well as the Schauder's fixed‐point theorem, the existence of a traveling wave solution connecting the semi‐trivial steady state and the positive steady state is proved. Numerical simulations are carried out to illustrate the main theoretical results. Copyright © 2013 John Wiley & Sons, Ltd.     

Global dynamics of a spatial heterogeneous viral infection model with intracellular delay and nonlocal diffusion

In this paper, we propose a spatial heterogeneous viral infection model, where heterogeneous parameters, the intracellular delay and nonlocal diffusion of free virions are considered. The global well-posedness, compactness and asymptotic smoothness of the semiflow generated by the system are established. It is shown that the principal eigenvalue problem of a perturbation of the nonlocal diffusion operator has a principal eigenvalue associated with a positive eigenfunction. The principal eigenvalue plays the same role as the basic reproduction number being defined as the spectral radius of the next generation operator. The existence of the unique chronic-infection steady state is established by the super-sub solution method. Furthermore, the uniform persistence of the model is investigated by using the persistence theory of infinite dimensional dynamical systems. By setting the eigenfunction as the integral kernel of Lyapunov functionals, the global threshold dynamics of the system is established. More precisely, the infection-free steady state is globally asymptotically stable if the basic reproduction number is less than one; while the chronic-infection steady state is globally asymptotically stable if the basic reproduction number is larger than one. Numerical simulations are carried out to illustrate the effects of intracellular delay and diffusion rate on the final concentrations of infected cells and free virions, respectively.     

Analysis of stability and Hopf bifurcation for HIV-1 dynamics with PI and three intracellular delays

Mathematical model for the effects of protease inhibitor on the dynamics of HIV-1 infection model with three delays is proposed and analyzed. Some analytical results on the global stability of viral free steady state and infected steady state are obtained. The stability/instability of the positive steady state and associated Hopf bifurcation are investigated by analyzing the characteristic equations.     

Global properties of a class of HIV infection models with Beddington–DeAngelis functional response

In this paper, the global properties of a class of human immunodeficiency virus (HIV) models with Beddington–DeAngelis functional response are investigated. Lyapunov functions are constructed to establish the global asymptotic stability of the uninfected and infected steady states of three HIV infection models. The first model considers the interaction process of the HIV and the CD4 ⁺ T cells and takes into account the latently and actively infected cells. The second model describes two co‐circulation populations of target cells, representing CD4 ⁺ T cells and macrophages. The third model is a two‐target‐cell model taking into account the latently and actively infected cells. We have proven that if the basic reproduction number R₀ is less than unity, then the uninfected steady state is globally asymptotically stable, and if R₀ > 1, then the infected steady state is globally asymptotically stable. Copyright © 2012 John Wiley & Sons, Ltd.     

Long term dynamics in a mathematical model of HIV-1 infection with delay in different variants of the basic drug therapy model

Infection with HIV-1, degrading the human immune system and recent advances of drug therapy to arrest HIV-1 infection, has generated considerable research interest in the area. Bonhoeffer et al. (1997) [1], introduced a population model representing long term dynamics of HIV infection in response to available drug therapies. We consider a similar type of approximate model incorporating time delay in the process of infection on the healthy T cells which, in turn, implies inclusion of a similar delay in the process of viral replication. The model is studied both analytically and numerically. We also include a similar delay in the killing rate of infected CD4⁺ T cells by Cytotoxic T-Lymphocyte (CTL) and in the stimulation of CTL and analyse two resulting models numerically.The models with no time delay present have two equilibria: one where there is no infection and a non-trivial equilibrium where the infection can persist. If there is no time delay then the non-trivial equilibrium is locally asymptotically stable. Both our analytical results (for the first model) and our numerical results (for all three models) indicate that introduction of a time delay can destabilize the non-trivial equilibrium. The numerical results indicate that such destabilization occurs at realistic time delays and that there is a threshold time delay beneath which the equilibrium with infection present is locally asymptotically stable and above which this equilibrium is unstable and exhibits oscillatory solutions of increasing amplitude.     

Localization of compact invariant sets and global stability in analysis of one tumor growth model

In this paper, we study some features of global behavior of the four‐dimensional superficial bladder cancer model with Bacillus Calmette‐Guérin (BCG) immunotherapy described by Bunimovich‐Mendrazitsky et al. in 2007 with the help of localization analysis of its compact invariant sets. Its dynamics is defined by the BCG treatment and by densities of three cells populations: effector cells, tumor infected cells by BCG, and tumor uninfected cells. We find upper bounds for ultimate dynamics of the whole state vector in the positive orthant and also under condition that there are no uninfected tumor cells. Further, we prove the existence of the bounded positively invariant domain in both of these two situations. Finally, by using these assertions, we derive our main result: sufficient conditions of global asymptotic stability of the tumor‐free equilibrium point in the positive orthant. Copyright © 2013 John Wiley & Sons, Ltd.     

Asymptotic profiles of positive steady states for a diffusive predator–prey model with predator interference

This paper is concerned with positive steady states for a diffusive predator–prey model with predator interference in a spatially heterogeneous environment. We first establish the necessary and sufficient conditions for the existence of positive steady states. In order to get a better understanding of the structure of positive steady states, we further investigate the asymptotic profiles of positive steady states as some parameter tends to zero or infinity.     

A microbial continuous culture system with diffusion and diversified growth

A reaction-diffusion model is presented to describe the microbial continuous culture with diversified growth. The existence of nonnegative solutions and attractors for the system is obtained, the stability of steady states and the steady state bifurcation are studied under three growth conditions. In the case of no growth inhibition or only product inhibition, the system admits one positive constant steady state which is stable; in the case of growth inhibition only by substrate, the system can have two positive constant steady states, explicit conditions of the stability and the steady state bifurcation are also determined. In addition, numerical simulations are given to exhibit the theoretical results.     

Effects of the self- and cross-diffusion on positive steady states for a generalized predator–prey system

This paper deals with a generalized predator–prey system with cross-diffusion and homogeneous Neumann boundary condition, where the cross-diffusion is included in such a way that the prey runs away from the predator. We first give a priori estimate for positive steady states to the system. Then we obtain the non-existence result of non-constant positive steady states. Finally, we investigate the stability of constant equilibrium point and the existence of non-constant positive steady states. It is shown that the system admits a non-constant positive steady state provided that either of the self-diffusions is large or the cross-diffusion is small.     

The global dynamics of a model about HIV-1 infection in vivo

A four dimension ODE model is built to study the infection of human immunodeficiency virus (HIV) in vivo. We include in this model four components: the healthy T cells, the latent-infected T cells, the active-infected T cells and the HIV virus. Two types of HIV transmissions in vivo are also included in the model: the virus-to-cell transmission, and the cell-to-cell HIV transmission. There are two possible equilibriums: the healthy equilibrium, and the infected steady state. The basic reproduction number R ₀ is introduced. When R ₀ < 1, the healthy equilibrium is globally stable and when R ₀ > 1, the infected equilibrium exists and is globally stable. Through simulations, we find that, the cell-to-cell HIV transmission is very important for the final outcome of the HIV attacking. Some important clinical observations about the HIV infection situation in lymph node are also verified.      

Positive Steady States of a Prey-predator Model with Diffusion and Non-monotone Conversion Rate

In this paper, we study the positive steady states of a prey-predator model with diffusion throughout and a non-monotone conversion rate under the homogeneous Dirichlet boundary condition. We obtain some results of the existence and non-existence of positive steady states. The stability and uniqueness of positive steady states are also discussed.     

具有阶段结构的Lotka-Volterra合作系统的稳定性和行波解

文建立并研究了一个两物种成年个体相互合作的时滞反应扩散模型.利用线性化稳定性方法和Redlinger上、下解方法证明了该模型具有简单的动力学行为,即零平衡点和边界平衡点是不稳定的,而唯一的正平衡点是全局渐近稳定的.同时, 利用Wang, Li 和Ruan建立的具有非局部时滞的反应扩散系统的波前解的存在性,证明了该模型连接零平衡点与唯一正平衡点的波前解的存在性.     

Mathematical description of the interactions of CycE/Cdk2, Cdc25A,and P27Kip1 in a core cancer subnetwork

Recent studies have shown that the initiation of human cancer is due to the malfunction of some genes (such as E2F, CycE, CycD, Cdc25A, P27^Kip1, and Rb) at the R‐checkpoint during the G₁‐to‐S transition of the cell cycle. Identifying and modeling the dynamics of these genes provide new insight into the initiation and progression of many types of cancers. In this study, a cancer subnetwork that has a mutual activation between phosphatase Cdc25A and the CycE/Cdk2 complex and a mutual inhibition between the Cdk inhibitor P27^Kip1 and the CycE/Cdk2 complex is identified. A new mathematical model for the dynamics of this cancer subnetwork is developed. Positive steady states are determined and rigorously analyzed. We have found a condition for the existence of positive steady states from the activation, inhibition, and degradation parameter values of the dynamical system. We also found a robust condition that needs to be satisfied for the steady states to be asymptotically stable. We determine the parameter value(s) under which the system exhibits a saddle–node bifurcation. We also identify the condition for which the system exhibits damped oscillation solutions. We further explore the possibility of Hopf and homoclinic bifurcations from the saddle–focus steady state of the system. Our analytic and numerical results confirm experimental results in the literature, thus validating our model. Copyright © 2016 John Wiley & Sons, Ltd.