Releasing Wolbachia-infected Aedes aegypti to prevent the spread of dengue virus: A mathematical study.

Wolbachia is a bacterium that is present in 60% of insects but it is not generally found in Aedes aegypti, the primary vector responsible for the transmission of dengue virus, Zika virus, and other human diseases caused by RNA viruses. Wolbachia has been shown to stop the growth of a variety of RNA viruses in Drosophila and in mosquitoes. Wolbachia-infected Ae. aegypti have both reproductive advantages and disadvantages over wild types. If Wolbachia-infected females are fertilized by either normal or infected males, the offspring are healthy and Wolbachia-positive. On the other hand, if Wolbachia-negative females are fertilized by Wolbachia-positive males, the offspring do not hatch. This phenomenon is called cytoplasmic incompatibility. Thus, Wolbachia-positive females have a reproductive advantage, and the Wolbachia is expanded in the population. On the other hand, Wolbachia-infected mosquitoes lay fewer eggs and generally have a shorter lifespan. In recent years, scientists have successfully released these Wolbachia-adapted mosquitoes into the wild in several countries and have achieved a high level of replacement with Wolbachia-positive mosquitoes. Here, we propose a minimal mathematical model to investigate the feasibility of such a release method. The model has five steady-states two of which are locally asymptotically stable. One of these stable steady-states has no Wolbachia-infected mosquitoes while for the other steady-state, all mosquitoes are infected with Wolbachia. We apply optimal control theory to find a release method that will drive the mosquito population close to the steady-state with only Wolbachia-infected mosquitoes in a two-year time period. Because some of the model parameters cannot be accurately measured or predicted, we also perform uncertainty and sensitivity analysis to quantify how variations in our model parameters affect our results.

Inside dynamics for stage-structured integrodifference equations.

A stage-structured model of integrodifference equations is used to study the asymptotic neutral genetic structure of populations undergoing range expansion. That is, we study the inside dynamics of solutions to stage-structured integrodifference equations. To analyze the genetic consequences for long term population spread, we decompose the solution into neutral genetic components called neutral fractions. The inside dynamics are then given by the spatiotemporal evolution of these neutral fractions. We show that, under some mild assumptions on the dispersal kernels and population projection matrix, the spread is dominated by individuals at the leading edge of the expansion. This result is consistent with the founder effect. In the case where there are multiple neutral fractions at the leading edge we are able to explicitly calculate the asymptotic proportion of these fractions found in the long-term population spread. This formula is simple and depends only on the right and left eigenvectors of the population projection matrix evaluated at zero and the initial proportion of each neutral fraction at the leading edge of the range expansion. In the absence of a strong Allee effect, multiple neutral fractions can drive the long-term population spread, a situation not possible with the scalar model.

Neutral Genetic Patterns for Expanding Populations with Nonoverlapping Generations.

We investigate the inside dynamics of solutions to integrodifference equations to understand the genetic consequences of a population with nonoverlapping generations undergoing range expansion. To obtain the inside dynamics, we decompose the solution into neutral genetic components. The inside dynamics are given by the spatiotemporal evolution of the neutral genetic components. We consider thin-tailed dispersal kernels and a variety of per capita growth rate functions to classify the traveling wave solutions as either pushed or pulled fronts. We find that pulled fronts are synonymous with the founder effect in population genetics. Adding overcompensation to the dynamics of these fronts has no impact on genetic diversity in the expanding population. However, growth functions with a strong Allee effect cause the traveling wave solution to be a pushed front preserving the genetic variation in the population. In this case, the contribution of each neutral fraction can be computed by a simple formula dependent on the initial distribution of the neutral fractions, the traveling wave solution, and the asymptotic spreading speed.

Dynamics of two-strain influenza model with cross-immunity and no quarantine class.

The question about whether a periodic solution can exists for a given epidemiological model is a complicated one and has a long history (Hethcote and Levin, Applied math. ecology, biomathematics, vol 18. Springer, Berlin, pp 193-211, 1989). For influenza models, it is well known that a periodic solution can exists for a single-strain model with periodic contact rate (Aron and Schwartz, J Math Biol 110:665-679, 1984; Kuznetsov and Piccardi, J Math Biol 32:109-121, 1994), or a multiple-strain model with cross-immunity and quarantine class or age-structure (Nuño et al., Mathematical epidemiology. Lecture notes in mathematics, vol 1945. Springer, Berlin, 2008, chapter 13). In this paper, we prove the local asymptotic stability of the interior steady-state of a two-strain influenza model with sufficiently close cross-immunity and no quarantine class or age-structure. We also show that if the cross-immunity between two strains are far apart; then it is possible for the interior steady-state to lose its stability and bifurcation of periodic solutions can occur. Our results extend those obtained by Nuño et.al. (SIAM J Appl Math 65:964-982, 2005). This problem is important because understanding the reasons behind periodic outbreaks of seasonal flu is an important issue in public health.

Modelling the biological invasion of Carcinus maenas (the European green crab).

This paper proposes a system of integro-difference equations to model the spread of Carcinus maenas, commonly called the European green crab, that causes severe damage to coastal ecosystems. A model with juvenile and adult classes is first studied. Here, standard theory of monotone operators for integro-difference equations can be applied and yields explicit formulas for the asymptotic spreading speeds of the juvenile and adult crabs. A second model including an infected class is considered by introducing a castrating parasite Sacculina carcini as a biological control agent. The dynamics are complicated and simulations reveal the occurrence of periodic solutions and stacked fronts. In this case, only conjectures can be made for the asymptotic spreading speeds because of the lack of mathematical theory for non-monotone operators. This paper also emphasizes the need for mathematical studies of non-monotone operators in heterogeneous environments and the existence of stacked front solutions in biological invasion models.

Global Spatio-temporal Patterns of Influenza in the Post-pandemic Era.

We study the global spatio-temporal patterns of influenza dynamics. This is achieved by analysing and modelling weekly laboratory confirmed cases of influenza A and B from 138 countries between January 2006 and January 2015. The data were obtained from FluNet, the surveillance network compiled by the the World Health Organization. We report a pattern of skip-and-resurgence behavior between the years 2011 and 2013 for influenza H1N1pdm, the strain responsible for the 2009 pandemic, in Europe and Eastern Asia. In particular, the expected H1N1pdm epidemic outbreak in 2011/12 failed to occur (or "skipped") in many countries across the globe, although an outbreak occurred in the following year. We also report a pattern of well-synchronized wave of H1N1pdm in early 2011 in the Northern Hemisphere countries, and a pattern of replacement of strain H1N1pre by H1N1pdm between the 2009 and 2012 influenza seasons. Using both a statistical and a mechanistic mathematical model, and through fitting the data of 108 countries, we discuss the mechanisms that are likely to generate these events taking into account the role of multi-strain dynamics. A basic understanding of these patterns has important public health implications and scientific significance.

Advance of advantageous genes for a multiple-allele population genetics model.

This paper extends the classical result of Fisher (1937) from the case of two alleles to the case of multiple alleles. Consider a population living in a homogeneous one-dimensional infinite habitat. Individuals in this population carry a gene that occurs in k forms, called alleles. Under the joint action of migration and selection and some additional conditions, the frequencies of the alleles, p(i),i=1,…,k, satisfy a system of differential equations of the form (1.2). In this paper, we first show that under the conditions A(1)A(1) is the most fit among the homozygotes, (1.2) is cooperative, the state that only allele A(1) is present in the population is stable, and the state that allele A(1) is absent and all other alleles are present in the population is unstable, then there exists a positive constant, c(*), such that allele A(1) propagates asymptotically with speed c(*) in the population as t→∞. We then show that traveling wave solutions connecting these two states exist for |c|≥c(*). Finally, we show that under certain additional conditions, there exists an explicit formula for c(*). These results allow us to estimate how fast an advantageous gene propagates in a population under selection and migration forces as t→∞. Selection is one of the major evolutionary forces and understanding how it works will help predict the genetic makeup of a population in the long run.

Patterns for four-allele population genetics model.

In this paper, we find and classify all existing patterns for a single-locus four-allele population genetics models in continuous time. An existing pattern for a k-allele model means a set of all coexisting asymptotically stable equilibria with respect to the flow defined by the system of equations p(i)=p(i)(r(i)-r),i=1,…,k, where p(i) and r(i) are the frequency and marginal fitness of allele A(i), respectively, and r is the mean fitness of the population. It is well known that for the two-allele model there are only three existing patterns, depending on the relative fitness between the homozygotes and the heterozygote. For the three-allele model there are 14 existing patterns, and we shall show in this paper that for the four-allele model there are 117 existing patterns. We also describe the domains of attraction for coexisting asymptotically stable equilibria. The problem of finding existing patterns has been studied in the past, and it is an important problem because the results can be used to predict the long-term genetic makeup of a population. It should be pointed out that this continuous-time model is only an approximation to the corresponding discrete-time model. However, the set of equilibria and their stability properties are the same for the two models.

One-dimensional viscoelastic cell motility models.

In this paper we consider a class of one-dimensional cell motility models with increasing complexities beginning with a kinematic model and ending with a model based on viscoelastic theory. In many of these models, we establish the existence of traveling cell solutions and show numerically that the solutions of the time-dependent problem converge to the traveling cell solutions as t → ∞. As a result, we are able to predict the eventual length and speed of the cell.

Traveling wave solutions from microscopic to macroscopic chemotaxis models.

In this paper, we study the existence and nonexistence of traveling wave solutions for the one-dimensional microscopic and macroscopic chemotaxis models. The microscopic model is based on the velocity jump process of Othmer et al. (SIAM J Appl Math 57:1044-1081, 1997). The macroscopic model, which can be shown to be the parabolic limit of the microscopic model, is the classical Keller-Segel model, (Keller and Segel in J Theor Biol 30:225-234; 377-380, 1971). In both models, the chemosensitivity function is given by the derivative of a potential function, Phi(v), which must be unbounded below at some point for the existence of traveling wave solutions. Thus, we consider two examples: Phi(v) = ln V and Phi(v) = ln[v/(1 - v)]. The mathematical problem reduces to proving the existence or nonexistence of solutions to a nonlinear boundary value problem with variable coefficient on R. The main purpose of this paper is to identify the relationships between the two models through their traveling waves, from which we can observe how information are lost, retained, or created during the transition from the microscopic model to the macroscopic model. Moreover, the underlying biological implications of our results are discussed.

Exploring the control circuit of cell migration by mathematical modeling.

We have developed a top-down, rule-based mathematical model to explore the basic principles that coordinate mechanochemical events during animal cell migration, particularly the local-stimulation-global-inhibition model suggested originally for chemotaxis. Cells were modeled as a shape machine that protrudes or retracts in response to a combination of local protrusion and global retraction signals. Using an optimization algorithm to identify parameters that generate specific shapes and migration patterns, we show that the mechanism of local stimulation global inhibition can readily account for the behavior of Dictyostelium under a large collection of conditions. Within this collection, some parameters showed strong correlation, indicating that a normal phenotype may be maintained by complementation among functional modules. In addition, comparison of parameters for control and nocodazole-treated Dictyostelium identified the most prominent effect of microtubules as regulating the rates of retraction and protrusion signal decay, and the extent of global inhibition. Other changes in parameters can lead to profound transformations from amoeboid cells into cells mimicking keratocytes, neurons, or fibroblasts. Thus, a simple circuit of local stimulation-global inhibition can account for a wide range of cell behaviors. A similar top-down approach may be applied to other complex problems and combined with molecular manipulations to define specific protein functions.

Traveling wave solutions for a one-dimensional crawling nematode sperm cell model.

In this paper, we proved that the one-dimensional crawling nematode sperm cell model proposed by Mogilner and Verzi (2003) supports traveling wave solutions if there is no disassembly of unbundled filaments in the cell. Uniqueness of traveling wave is established under additional assumptions and numerical examples are also given in the paper. Mathematical methods used include dynamical system techniques, implicit function theorem and global bifurcation theory.