An Age-structured Mathematical Model for the Within Host Dynamics of Malaria and the Immune System

In the paper, we use a mathematical model to study the population dyna mics of replicating malaria parasites and their interaction with the immune cells within a human host. The model is formulated as a system of age-structured partial differential equations that are then integrated over age to obtain a system of nonlinear delay differential equations. Our model incorporates an intracellular time delay between the infection of the red blood cells by the merozoites that grow and replicate within the infected cells to produce new merozoites. The infected red blood cells burst approximately every 48 h releasing daughter parasites to renew the cycle. The dynamical processes of the parasites within the human host are subjected to pressures exerted by the human immunological responses. The system is then solved using a first-order, finite difference method to give a discrete system. Numerical simulations carried out to illustrate stability of the system reveal that the populations undergo damped oscillations that stabilise to steady states.      

Bifurcation analysis of a multidelayed HIV model in presence of immune response and understanding of in‐host viral dynamics

In this paper, we proposed a multidelayed in‐host HIV model to represent the interaction between human immunodeficiency virus and immune response. One delay was considered to incorporate the time required by the virus for various intracellular events to make a host cell productively infective, and the second delay was introduced to take into account the time required for adaptive immune system to respond against infection. We extensively analyzed this multidelayed model analytically and numerically. We show that delay may have both destabilizing and stabilizing effects even when the system contains a single immune response delay. It happens when there exists two sequences of critical values of this delay. If the system starts with stable state in absence of delay, then the smallest value of these critical delays causes instability and the next higher value causes stability. The system may also show stability switching for different values of the virus replication factor. These results demonstrate the possible reasons of intrapatients and interpatients variability of CD4⁺ T cells and virus counts in HIV‐infected patients.     

Allee effects in a Ricker-type predator–prey system

We study a discrete host–parasitoid system where the host population follows the classical Ricker functional form and is also subject to Allee effects. We determine basins of attraction of the local attractors of the single population model when the host intrinsic growth rate is not large. In this situation, existence and local stability of the interior steady states for the host–parasitoid interaction are completely analysed. If the host's intrinsic growth rate is large, then the interaction may support multiple interior steady states. Linear stability of these steady states is provided.     

Stability and bifurcation analysis of a mathematical model for tumor–immune interaction with piecewise constant arguments of delay

In this paper, we propose and analyze a Lotka–Volterra competition like model which consists of system of differential equations with piecewise constant arguments of delay to study of interaction between tumor cells and Cytotoxic T lymphocytes (CTLs). In order to get local and global behaviors of the system, we use Schur–Cohn criterion and constructed a Lyapunov function. Some algebraic conditions which satisfy local and global stability of the system are obtained. In addition, we investigate the possible bifurcation types for the system and observe that the system may undergo Neimark–Sacker bifurcation. Moreover, it is predicted a threshold value above which there is uncontrollable tumor growth, and below periodic solutions that leading to tumor dormant state occur.     

Stability and bifurcation analysis of a nutrient-phytoplankton model with time delay

We proposed a nutrient-phytoplankton interaction model with a discrete and distributed time delay to provide a better understanding of phytoplankton growth dynamics and nutrient-phytoplankton oscillations induced by delay. Standard linear analysis indicated that delay can induce instability of a positive equilibrium via Hopf bifurcation. We derived the conditions guaranteeing the existence of Hopf bifurcation and tracked its direction and the stability of the bifurcating periodic solutions. We also obtained the sufficient conditions for the global asymptotic stability of the unique positive steady state. Numerical analysis in the fully nonlinear regime showed that the stability of the positive equilibrium is sensitive to changes in delay values under select conditions. Numerical results were consistent with results predicted by linear analysis.     

Modeling the role of constant and time varying recycling delay on an ecological food chain

We consider a mathematical model of nutrient-autotroph-herbivore interaction with nutrient recycling from both autotroph and herbivore. Local and global stability criteria of the model are studied in terms of system parameters. Next we incorporate the time required for recycling of nutrient from herbivore as a constant discrete time delay. The resulting DDE model is analyzed regarding stability and bifurcation aspects. Finally, we assume the recycling delay in the oscillatory form to model the daily variation in nutrient recycling and deduce the stability criteria of the variable delay model. A comparison of the variable delay model with the constant delay one is performed to unearth the biological relevance of oscillating delay in some real world ecological situations. Numerical simulations are done in support of analytical results.     

Stochastic stability and state shifts for a time-delayed cancer growth system subjected to correlated multiplicative and additive noises

In the present paper, we investigate the stationary probability distribution(SPD) and the mean treatment time of a time-delayed cancer growth system induced by cross-correlated intrinsic and extrinsic noises. Our main results show that the resonant-like phenomenon of the mean first-passage time (MFPT) appears in the tumor cell growth model due to the interaction of all kinds of noises and time delay. Due to the existence of the resonant-like peak value, by increasing the intensity of multiplicative noise and time delay, it is possible to restrain effectively the development of the cancer cells and enhance the stability of the system. During the process of controlling the diffusion of the tumor cells, it contributes to inhibiting the development of cancer by increasing the cross-correlated noise strength and weakening the additive noise intensity and time delay. Meanwhile, the proper multiplicative noise intensity is conducive to the process of inhibition. Conversely, in the process of exterminating cancer cells of a large density, it can exert positive effects on eliminating the tumor cells by increasing noises intensities and the value of time delay.     

Effects of environmental fluctuation and time delay on ratio dependent hyperparasitism model

A model of host–parasitoid–hyperparasitoid is considered with ratio dependence between parasitoid and hyperparasitoid. First, the conditions for local stability and increasing host fitness due to the effect of hyperparasitism are deduced. Next, we study the effects of stochastic environmental fluctuations and discrete time delay on the system behavior and calculate the corresponding populations variances. Numerical simulations illustrate that populations densities oscillate randomly around equilibrium points. Also, in contrast to previous literature, the simulations carried out here indicate that populations variances oscillate with the increase of time delay.     

Geometric stability switch criteria in delay differential equations with two delays and delay dependent parameters

Most modeling efforts involve multiple physical or biological processes. All physical or biological processes take time to complete. Therefore, multiple time delays occur naturally and shall be considered in more advanced modeling efforts. Carefully formulated models of such natural processes often involve multiple delays and delay dependent parameters. However, a general and practical theory for the stability analysis of models with more than one discrete delay and delay dependent parameters is nonexistent. The main purpose of this paper is to present a practical geometric method to study the stability switching properties of a general transcendental equation which may result from a stability analysis of a model with two discrete time delays and delay dependent parameters that dependent only on one of the time delay. In addition to simple and illustrative examples, we present a detailed application of our method to the study of a two discrete delay SIR model.     

Stability analysis of mathematical models for nonlinear growth kinetics of breast cancer stem cells

Cancer stem cells are responsible for tumor survival and resurgence and are thus essential in developing novel therapeutic strategies against cancer. Mathematical models can help understand cancer stem and differentiated cell interaction in tumor growth, thus having the potential to help in designing experiments to develop novel therapeutic strategies against cancer. In this paper, by using theory of functional and ordinary differential equations, we study the existence and stability of nonlinear growth kinetics of breast cancer stem cells. First, we provide a sufficient condition for the existence and uniqueness of the solution for nonlinear growth kinetics of breast cancer stem cells. Then we study the uniform asymptotic stability of the zero solution. By using linearization techniques, we also provide a criteria for uniform asymptotic stability of a nontrivial steady‐state solution with and without time delays. We present a theorem from complex analysis that gives certain conditions that allow for this criteria to be satisfied. Next, we apply these theorems to a special case of the system of functional differential equations that has been used to model nonlinear growth kinetics of breast cancer stem cells. The theoretical results are further justified by numerical testing examples. Consistent with the theories, our numerical examples show that the time delays can disrupt the stability. All the results can be easily extended to study more general cell lineage models. Copyright © 2017 John Wiley & Sons, Ltd.     

Effect of time delay in an autotroph-herbivore system with nutrient cycling

In the present study we consider a mathematical model of a non-interactive type autotroph-herbivore system in which the amount of autotroph biomass consumed by the herbivore is assumed to follow a Holling type II functional response. We have also incorporated discrete time delays in the numerical response term to represent a delay due to gestation, and in the recycling term which represents the time required for bacterial decomposition. We have derived conditions for global asymptotic stability of the model in the absence of delays. Conditions for delay-induced asymptotic stability of the steady state are also derived. The length of the delay preserving stability has been estimated and interpreted ecologically.     

Temporal and spatiotemporal variations in a mathematical model of macrophage–tumor interaction

In the present paper we study a three-component mathematical model of tumor–immune system interaction. A number of solid tumors contain a high proportion of macrophages and these immune cells are known to have a remarkable impact on the progression and dormancy of such tumors. We assume these macrophages as the main immune system component facilitating tumor destruction. Stability criteria of the basic model around the steady state of coexistence are derived. Next, we consider the process of macrophage activation as non-instantaneous by using a distributed delay with a weak kernel and obtain a range for the macrophage death rate that ensures system stability. Finally, we incorporate the spatial irregularity of solid tumors by making the delay nonlocal. Analysis of the resulting spatiotemporal model gives a number of thresholds in terms of different system parameters that guarantee tumor stability. Numerical simulations are performed to justify analytical findings.     

Global stability and Hopf bifurcation of a plankton model with time delay

A differential delay equation model with a discrete time delay and a distributed time delay is introduced to simulate zooplankton–nutrient interaction. The differential inequalities’ methods and standard Hopf bifurcation analysis are applied. Some sufficient conditions are obtained for persistence and for the global stability of the unique positive steady state, respectively. It was shown that there is a Hopf bifurcation in the model by using the discrete time delay as a bifurcation parameter.     

Effect of time delay on a harvested predator-prey model

The predator-prey systems with harvesting have received a great deal of attentions for last few decades. Incorporating discrete time delays into predator-prey models could induce instability and bifurcation. In this paper we are interested in studying the combined effects of harvesting and discrete time delay on the dynamics of a predator-prey model. A comparative analysis is provided for stability behaviour in absence as well as in presence of time delay. The length of discrete time delay to preserve stability of the model system is obtained. Existence of Hopf-bifurcating small amplitude periodic solutions is derived by taking discrete time delay as a bifurcation parameter.     

Dynamical analysis of a delay model of phytoplankton-zooplankton interaction

The interaction of toxic-phytoplankton-zooplankton systems and their dynamical behavior will be considered in this paper based upon nonlinear ordinary differential equation model system. We induced a discrete time delay to the both of the consume response function and distribution of toxic substance term to describe the delay in the conversion of nutrient consumed to species and the fact that the time required for the phytoplankton species to mature before they can produce toxic substances. We generalized the model in [1] and explicit results are derived for globally asymptotically stability of the boundary equilibrium. Using numerical simulation method, we determine there is a parameter range for the delay parameter τ where more complicated dynamics occurs, and this appears to be a new result. Significant outcomes of our numerical findings and their interpretations from ecological point of view are provided in this paper.     

Analysis of an elliptic-parabolic free boundary problem modelling the growth of non-necrotic tumor cord

We study a free boundary problem modelling the growth of a tumor cord in which tumor cells live around and receive nutrient from a central blood vessel. The evolution of the tumor cord surface is governed by Darcy's law together with a surface tension equation. The concentration of nutrient in the tumor cord satisfies a reaction-diffusion equation. In this paper we first establish a well-posedness result for this free boundary problem in some Sobolev-Besov spaces with low regularity by using the analytic semigroup theory. We next study asymptotic stability of the unique radially symmetric stationary solution. By making delicate spectrum analysis for the linearized problem, we prove that this stationary solution is locally asymptotically stable provided that the constant c representing the ratio between the diffusion time of nutrient and the birth time of new cells is sufficiently small.     

Ratio dependent predation :A bifurcation analysis

In this study, we have considered a prey-predator model reflecting the predator interference with discrete time delay. This delay is regarded as the lag due to gestation. In absence of delay, the criteria for existence of interior equilibrium and its global stability are derived. By choosing the delay as a bifurcation parameter, we have shown that a Hopf bifurcation may occur when the delay passes its critical value. Finally, we have derived the criteria for stability switches and verified the results through computer simulation.     

Dynamical behavior in a stage-structured differential-algebraic prey-predator model with discrete time delay and harvesting

A differential-algebraic model system which considers a prey-predator system with stage structure for prey and harvest effort on predator is proposed. By using the differential-algebraic system theory and bifurcation theory, dynamic behavior of the proposed model system with and without discrete time delay is investigated. Local stability analysis of the model system without discrete time delay reveals that there is a phenomenon of singularity induced bifurcation due to variation of the economic interest of harvesting, and a state feedback controller is designed to stabilize the proposed model system at the interior equilibrium; Furthermore, local stability of the model system with discrete time delay is studied. It reveals that the discrete time delay has a destabilizing effect in the population dynamics, and a phenomenon of Hopf bifurcation occurs as the discrete time delay increases through a certain threshold. Finally, numerical simulations are carried out to show the consistency with theoretical analysis obtained in this paper.     

Stability and bifurcations of equilibria in a delayed Kirschner–Panetta model

In this paper, a delay differential equation model of immunotherapy for tumor-immune response is presented. The dynamics that interplays between the three model factors, namely, effector cells, tumor cells and interleukin-2 is studied and the quantitative analysis is performed. We estimate the length of delay to preserve the stability of an equilibrium state of biological significance. The impact of delay in the immunotherapy with interleukin-2, especially, at different antigenicity levels, is discussed, along with the scenarios under which the tumor remission can be prolonged.     

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.