Travel restrictions, while delaying the spread of an emerging disease from the source, could inflict substantial socioeconomic burden. Travel-related policies, such as quarantine and testing of travelers, may be considered as alternative strategies to mitigate the negative impact of travel bans. We developed a meta-population, delay-differential model to evaluate a strategy that combines testing of travelers prior to departure from the source of infection with quarantine and testing at exit from quarantine in the destination population. Our results, based on early parameter estimates of SARS-CoV-2 infection, indicate that testing travelers at exit from quarantine is more effective in delaying case importation than testing them before departure or upon arrival. We show that a 1-day quarantine with an exit test could outperform a longer, 3-day quarantine without testing in delaying the outbreak peak. Rapid, large-scale testing capacities with short turnaround times provide important means of detecting infectious cases and reducing case importation, while shortening quarantine duration for travelers at destination.

During development, spatio-temporal patterns ranging from checkerboard to engulfing occur with precise proportions of the respective cell fates. Key developmental regulators are intracellular transcriptional interactions and intercellular signaling. We present an analytically tractable mathematical model based on signaling that reliably generates different cell type patterns with specified proportions. Employing statistical mechanics, We derived a cell fate decision model for two cell types. A detailed steady state analysis on the resulting dynamical system yielded necessary conditions to generate spatially heterogeneous patterns. This allows the cell type proportions to be controlled by a single model parameter. Cell-cell communication is realized by local and global signaling mechanisms. These result in different cell type patterns. A nearest neighbor signal yields checkerboard patterns. Increasing the signal dispersion, cell fate clusters and an engulfing pattern can be generated. Altogether, the presented model allows us to reliably generate heterogeneous cell type patterns of different kinds as well as desired proportions.

The current rapid extinction of species leads not only to their loss but also the disappearance of the unique features they harbour, which have evolved along the branches of the underlying evolutionary tree. One proxy for estimating the feature diversity (FD) of a set S of species at the tips of a tree is 'phylogenetic diversity' (PD): the sum of the branch lengths of the subtree connecting the species in S. For a phylogenetic tree that evolves under a standard birth-death process, and which is then subject to a sudden extinction event at the present (the simple 'field of bullets' model with a survival probability of s per species) the proportion of the original PD that is retained after extinction at the present is known to converge quickly to a particular concave function [Formula: see text] as t grows. To investigate how the loss of FD mirrors the loss of PD for a birth-death tree, we model FD by assuming that distinct discrete features arise randomly and independently along the branches of the tree at rate r and are lost at a constant rate [Formula: see text]. We derive an exact mathematical expression for the ratio [Formula: see text] of the two expected feature diversities (prior to and following an extinction event at the present) as t becomes large. We find that although [Formula: see text] has a similar behaviour to [Formula: see text] (and coincides with it for [Formula: see text]), when [Formula: see text], [Formula: see text] is described by a function that is different from [Formula: see text]. We also derive an exact expression for the expected number of features that are present in precisely one extant species. Our paper begins by establishing some generic properties of FD in a more general (non-phylogenetic) setting and applies this to fixed trees, before considering the setting of random (birth-death) trees.

We derive rigorous estimates on the speed of invasion of an advantageous trait in a spatially advancing population in the context of a system of one-dimensional F-KPP equations. The model was introduced and studied heuristically and numerically in a paper by Venegas-Ortiz et al. (Genetics 196:497-507, 2014). In that paper, it was noted that the speed of invasion by the mutant trait is faster when the resident population is expanding in space compared to the speed when the resident population is already present everywhere. We use the Feynman-Kac representation to provide rigorous estimates that confirm these predictions.

Biological events are often initiated when a random "searcher" finds a "target," which is called a first passage time (FPT). In some biological systems involving multiple searchers, an important timescale is the time it takes the slowest searcher(s) to find a target. For example, of the hundreds of thousands of primordial follicles in a woman's ovarian reserve, it is the slowest to leave that trigger the onset of menopause. Such slowest FPTs may also contribute to the reliability of cell signaling pathways and influence the ability of a cell to locate an external stimulus. In this paper, we use extreme value theory and asymptotic analysis to obtain rigorous approximations to the full probability distribution and moments of slowest FPTs. Though the results are proven in the limit of many searchers, numerical simulations reveal that the approximations are accurate for any number of searchers in typical scenarios of interest. We apply these general mathematical results to models of ovarian aging and menopause timing, which reveals the role of slowest FPTs for understanding redundancy in biological systems. We also apply the theory to several popular models of stochastic search, including search by diffusive, subdiffusive, and mortal searchers.

Worldwide, the recent SARS-CoV-2 virus has infected more than 670 million people and killed nearly 67.0 million. In Africa, the number of confirmed COVID-19 cases was approximately 12.7 million as of January 11, 2023, that is about 2% of the infections around the world. Many theories and modeling techniques have been used to explain this lower-than-expected number of reported COVID-19 cases in Africa relative to the high disease burden in most developed countries. We noted that most epidemiological mathematical models are formulated in continuous-time interval, and taking Cameroon in Sub-Saharan Africa, and New York State in the USA as case studies, in this paper we developed parameterized hybrid discrete-time-continuous-time models of COVID-19 in Cameroon and New York State. We used these hybrid models to study the lower-than-expected COVID-19 infections in developing countries. We then used error analysis to show that a time scale for a data-driven mathematical model should match that of the actual data reporting.

A stochastic hierarchical model for the evolution of low grade gliomas is proposed. Starting with the description of cell motion using a piecewise diffusion Markov process (PDifMP) at the cellular level, we derive an equation for the density of the transition probability of this Markov process based on the generalised Fokker-Planck equation. Then, a macroscopic model is derived via parabolic limit and Hilbert expansions in the moment equations. After setting up the model, we perform several numerical tests to study the role of the local characteristics and the extended generator of the PDifMP in the process of tumour progression. The main aim focuses on understanding how the variations of the jump rate function of this process at the microscopic scale and the diffusion coefficient at the macroscopic scale are related to the diffusive behaviour of the glioma cells and to the onset of malignancy, i.e., the transition from low-grade to high-grade gliomas.

Reconstructing the ancestral state of a group of species helps answer many important questions in evolutionary biology. Therefore, it is crucial to understand when we can estimate the ancestral state accurately. Previous works provide a necessary and sufficient condition, called the big bang condition, for the existence of an accurate reconstruction method under discrete trait evolution models and the Brownian motion model. In this paper, we extend this result to a wide range of continuous trait evolution models. In particular, we consider a general setting where continuous traits evolve along the tree according to stochastic processes that satisfy some regularity conditions. We verify these conditions for popular continuous trait evolution models including Ornstein-Uhlenbeck, reflected Brownian Motion, bounded Brownian Motion, and Cox-Ingersoll-Ross.

Some genes can promote or repress their own expressions, which is called autoregulation. Although gene regulation is a central topic in biology, autoregulation is much less studied. In general, it is extremely difficult to determine the existence of autoregulation with direct biochemical approaches. Nevertheless, some papers have observed that certain types of autoregulations are linked to noise levels in gene expression. We generalize these results by two propositions on discrete-state continuous-time Markov chains. These two propositions form a simple but robust method to infer the existence of autoregulation from gene expression data. This method only needs to compare the mean and variance of the gene expression level. Compared to other methods for inferring autoregulation, our method only requires non-interventional one-time data, and does not need to estimate parameters. Besides, our method has few restrictions on the model. We apply this method to four groups of experimental data and find some genes that might have autoregulation. Some inferred autoregulations have been verified by experiments or other theoretical works.

Recombination is a fundamental evolutionary force, but it is difficult to quantify because the effect of a recombination event on patterns of variation in a sample of genetic data can be hard to discern. Estimators for the recombination rate, which are usually based on the idea of integrating over the unobserved possible evolutionary histories of a sample, can therefore be noisy. Here we consider a related question: how would an estimator behave if the evolutionary history actually was observed? This would offer an upper bound on the performance of estimators used in practice. In this paper we derive an expression for the maximum likelihood estimator for the recombination rate based on a continuously observed, multi-locus, Wright-Fisher diffusion of haplotype frequencies, complementing existing work for an estimator of selection. We show that, contrary to selection, the estimator has unusual properties because the observed information matrix can explode in finite time whereupon the recombination parameter is learned without error. We also show that the recombination estimator is robust to the presence of selection in the sense that incorporating selection into the model leaves the estimator unchanged. We study the properties of the estimator by simulation and show that its distribution can be quite sensitive to the underlying mutation rates.

We present a phase field model for vesicle growth or shrinkage induced by an osmotic pressure due to a chemical potential gradient. The model consists of an Allen-Cahn equation describing the evolution of the phase field parameter that describes the shape of the vesicle and a Cahn-Hilliard-type equation describing the evolution of the ionic fluid. We establish conditions for vesicle growth or shrinkage via a common tangent construction using free energy curves. During the membrane deformation, the model ensures total mass conservation of the ionic fluid, and we weakly enforce a surface area constraint of the vesicle. We develop a stable numerical scheme and an efficient nonlinear multigrid solver to evolve the phase and concentration fields, and we use this to evolve the fields to near equilibrium for 2D vesicles. Convergence tests confirm an [Formula: see text] accuracy for our scheme and near-optimal convergence for our multigrid solver. Numerical results reveal that the diffuse interface model captures the main features of cell shape dynamics: for a growing vesicle, there exist circle-like equilibrium shapes if the concentration difference across the membrane and the initial osmotic pressure are large enough; while for a shrinking vesicle, there exists a rich collection of finger-like equilibrium morphologies.

The effects of habitat heterogeneity on a diffusing population are investigated here. We formulate a reaction-diffusion system of partial differential equations to analyze the effect of resource allocation in an ecosystem with resource having its own dynamics in space and time. We show a priori estimates to prove the existence of state solutions given a control. We formulate an optimal control problem of our ecosystem model such that the abundance of a single species is maximized while minimizing the cost of inflow resource allocation. In addition, we show the existence and uniqueness of the optimal control as well as the optimal control characterization. We also establish the existence of an optimal intermediate diffusion rate. Moreover, we illustrate several numerical simulations with Dirichlet and Neumann boundary conditions with the space domain in 1D and 2D.

Theory predicts that the additive genetic covariance ([Formula: see text]) matrix determines a population's short-term (in)ability to respond to directional selection-evolvability in the Hansen-Houle sense-which is typically quantified and compared via certain scalar indices called evolvability measures. Often, interest is in obtaining the averages of these measures across all possible selection gradients, but explicit formulae for most of these average measures have not been known. Previous authors relied either on approximations by the delta method, whose accuracy is generally unknown, or Monte Carlo evaluations (including the random skewers analysis), which necessarily involve random fluctuations. This study presents new, exact expressions for the average conditional evolvability, average autonomy, average respondability, average flexibility, average response difference, and average response correlation, utilizing their mathematical structures as ratios of quadratic forms. The new expressions are infinite series involving top-order zonal and invariant polynomials of matrix arguments, and can be numerically evaluated as their partial sums with, for some measures, known error bounds. Whenever these partial sums numerically converge within reasonable computational time and memory, they will replace the previous approximate methods. In addition, new expressions are derived for the average measures under a general normal distribution for the selection gradient, extending the applicability of these measures into a substantially broader class of selection regimes.

In this paper, we revisit a predator-prey model with specialist and generalist predators proposed by Hanski et al. (J Anim Ecol 60:353-367, 1991) , where the density of generalist predators is assumed to be a constant. It is shown that the model admits a nilpotent cusp of codimension 4 or a nilpotent focus of codimension 3 for different parameter values. As the parameters vary, the model can undergo cusp type (or focus type) degenerate Bogdanov-Takens bifurcations of codimension 4 (or 3). Our results indicate that generalist predation can induce more complex dynamical behaviors and bifurcation phenomena, such as three small-amplitude limit cycles enclosing one equilibrium, one or two large-amplitude limit cycles enclosing one or three equilibria, three limit cycles appearing in a Hopf bifurcation of codimension 3 and dying in a homoclinic bifurcation of codimension 3. In addition, we show that generalist predation stabilizes the limit cycle driven by specialist predators to a stable equilibrium, which clearly explains the famous Fennoscandia phenomenon.

This study investigates the dynamics of tuberculosis transmission through mathematical modeling, incorporating exogenous reinfections and different treatment approaches for latent tuberculosis infections. We examine three types of treatment rates: saturated, unsaturated, and mass screening-then-treatment. Our results reveal that both saturated treatment and mass screening-then-treatment can lead to a backward bifurcation, while unsaturated treatment does not. To determine the global dynamics of the models, we employ a persistent approach that avoids classifying the steady mode. By applying the models to China, we demonstrate that the data favors the use of unsaturated treatment. If unsaturated treatment is not feasible, the optimal strategy is to screen high-risk groups, identify LTBIs, and administer unsaturated treatment. Saturated treatments are not recommended.

NaV1.1 (SCN1A) is a voltage-gated sodium channel mainly expressed in GABAergic neurons. Loss of function mutations of NaV1.1 lead to epileptic disorders, while gain of function mutations cause a migraine in which cortical spreading depolarizations (CSDs) are involved. It is still debated how these opposite effects initiate two different manifestations of neuronal hyperactivity: epileptic seizures and CSD. To investigate this question, we previously built a conductance-based model of two neurons (GABAergic and pyramidal), with dynamic ion concentrations (Lemaire et al. in PLoS Comput Biol 17(7):e1009239, 2021. https://doi.org/10.1371/journal.pcbi.1009239 ). When implementing either NaV1.1 migraine or epileptogenic mutations, ion concentration modifications acted as slow processes driving the system to the corresponding pathological firing regime. However, the large dimensionality of the model complicated the exploitation of its implicit multi-timescale structure. Here, we substantially simplify our biophysical model to a minimal version more suitable for bifurcation analysis. The explicit timescale separation allows us to apply slow-fast theory, where slow variables are treated as parameters in the fast singular limit. In this setting, we reproduce both pathological transitions as dynamic bifurcations in the full system. In the epilepsy condition, we shift the spike-terminating bifurcation to lower inputs for the GABAergic neuron, to model an increased susceptibility to depolarization block. The resulting failure of synaptic inhibition triggers hyperactivity of the pyramidal neuron. In the migraine scenario, spiking-induced release of potassium leads to the abrupt increase of the extracellular potassium concentration. This causes a dynamic spike-terminating bifurcation of both neurons, which we interpret as CSD initiation.

Mixing among sub-populations, as well as heterogeneity in characteristics affecting their reproduction numbers, must be considered when evaluating public health interventions to prevent or control infectious disease outbreaks. In this overview, we apply a linear algebraic approach to re-derive some well-known results pertaining to preferential within- and proportionate among-group contacts in compartmental models of pathogen transmission. We give results for the meta-population effective reproduction number ([Formula: see text]) assuming different levels of vaccination in the sub-populations. Specifically, we unpack the dependency of [Formula: see text] on the fractions of contacts reserved for individuals within one's own subgroup and, by obtaining implicit expressions for the partial derivatives of [Formula: see text], we show that these increase as this preferential-mixing fraction increases in any sub-population.

In this paper, we propose a two-patch SIRS model with a nonlinear incidence rate: [Formula: see text] and nonconstant dispersal rates, where the dispersal rates of susceptible and recovered individuals depend on the relative disease prevalence in two patches. In an isolated environment, the model admits Bogdanov-Takens bifurcation of codimension 3 (cusp case) and Hopf bifurcation of codimension up to 2 as the parameters vary, and exhibits rich dynamics such as multiple coexistent steady states and periodic orbits, homoclinic orbits and multitype bistability. The long-term dynamics can be classified in terms of the infection rates [Formula: see text] (due to single contact) and [Formula: see text] (due to double exposures). In a connected environment, we establish a threshold [Formula: see text] between disease extinction and uniform persistence under certain conditions. We numerically explore the effect of population dispersal on disease spread when [Formula: see text] and patch 1 has a lower infection rate, our results indicate: (i) [Formula: see text] can be nonmonotonic in dispersal rates and [Formula: see text] ([Formula: see text] is the basic reproduction number of patch i) may fail; (ii) the constant dispersal of susceptible individuals (or infective individuals) between two patches (or from patch 2 to patch 1) will increase (or reduce) the overall disease prevalence; (iii) the relative prevalence-based dispersal may reduce the overall disease prevalence. When [Formula: see text] and the disease outbreaks periodically in each isolated patch, we find that: (a) small unidirectional and constant dispersal can lead to complex periodic patterns like relaxation oscillations or mixed-mode oscillations, whereas large ones can make the disease go extinct in one patch and persist in the form of a positive steady state or a periodic solution in the other patch; (b) relative prevalence-based and unidirectional dispersal can make periodic outbreak earlier.

Releasing Wolbachia-infected male mosquitoes to suppress wild female mosquitoes through cytoplasmic incompatibility has shown great promise in controlling and preventing mosquito-borne diseases. To make the release logistically and economically feasible, we propose a saturated release strategy, which is only implemented during the epidemic season of mosquito-borne diseases. Under this assumption, the model becomes a seasonally switching ordinary differential equation model. The seasonal switch brings rich dynamics, including the existence of a unique periodic solution or exactly two periodic solutions, which are proved by using the qualitative property of the Poincaré map. Sufficient conditions are also obtained for determining the stability of the periodic solutions.

The perception of susceptible individuals naturally lowers the transmission probability of an infectious disease but has been often ignored. In this paper, we formulate and analyze a diffusive SIS epidemic model with memory-based perceptive movement, where the perceptive movement describes a strategy for susceptible individuals to escape from infections. We prove the global existence and boundedness of a classical solution in an n-dimensional bounded smooth domain. We show the threshold-type dynamics in terms of the basic reproduction number [Formula: see text]: when [Formula: see text], the unique disease-free equilibrium is globally asymptotically stable; when [Formula: see text], there is a unique constant endemic equilibrium, and the model is uniformly persistent. Numerical analysis exhibits that when [Formula: see text], solutions converge to the endemic equilibrium for slow memory-based movement and they converge to a stable periodic solution when memory-based movement is fast. Our results imply that the memory-based movement cannot determine the extinction or persistence of infectious disease, but it can change the persistence manner.