Species tree estimation faces many significant hurdles. Chief among them is that the trees describing the ancestral lineages of each individual gene-the gene trees-often differ from the species tree. The multispecies coalescent is commonly used to model this gene tree discordance, at least when it is believed to arise from incomplete lineage sorting, a population-genetic effect. Another significant challenge in this area is that molecular sequences associated to each gene typically provide limited information about the gene trees themselves. While the modeling of sequence evolution by single-site substitutions is well-studied, few species tree reconstruction methods with theoretical guarantees actually address this latter issue. Instead, a standard-but unsatisfactory-assumption is that gene trees are perfectly reconstructed before being fed into a so-called summary method. Hence much remains to be done in the development of inference methodologies that rigorously account for gene tree estimation error-or completely avoid gene tree estimation in the first place. In previous work, a data requirement trade-off was derived between the number of loci m needed for an accurate reconstruction and the length of the locus sequences k. It was shown that to reconstruct an internal branch of length f, one needs m to be of the order of [Formula: see text]. That previous result was obtained under the restrictive assumption that mutation rates as well as population sizes are constant across the species phylogeny. Here we further generalize this result beyond this assumption. Our main contribution is a novel reduction to the molecular clock case under the multispecies coalescent, which we refer to as a stochastic Farris transform. As a corollary, we also obtain a new identifiability result of independent interest: for any species tree with [Formula: see text] species, the rooted topology of the species tree can be identified from the distribution of its unrooted weighted gene trees even in the absence of a molecular clock.

Inference of network-like evolutionary relationships between species from genomic data must address the interwoven signals from both gene flow and incomplete lineage sorting. The heavy computational demands of standard approaches to this problem severely limit the size of datasets that may be analyzed, in both the number of species and the number of genetic loci. Here we provide a theoretical pointer to more efficient methods, by showing that logDet distances computed from genomic-scale sequences retain sufficient information to recover network relationships in the level-1 ultrametric case. This result is obtained under the Network Multispecies Coalescent model combined with a mixture of General Time-Reversible sequence evolution models across individual gene trees. It applies to both unlinked site data, such as for SNPs, and to sequence data in which many contiguous sites may have evolved on a common tree, such as concatenated gene sequences. Thus under standard stochastic models statistically justifiable inference of network relationships from sequences can be accomplished without consideration of individual genes or gene trees.

Cholera is a water- and food-borne infectious disease caused by V. cholerae. To investigate multiple effects of human behavior change, seasonality and spatial heterogeneity on cholera spread, we propose a reaction-advection-diffusion model that incorporates human hosts and aquatic reservoir of V. cholerae. We derive the basic reproduction number [Formula: see text] for this system and then establish a threshold type result on its global dynamics in terms of [Formula: see text]. Further, we show that the bacterial loss at the downstream end of the river due to water flux can reduce the disease risk, and describe the asymptotic behavior of [Formula: see text] for small and large diffusion in a special case (where the diffusion rates of infected human and the pathogen are constant). We also study the transmission dynamics at the early stage of cholera outbreak numerically, and find that human behavior change may lower the infection level and delay the disease peak. Moreover, the relative rate of bacterial loss, together with convection rate, plays an important role in identifying the severely infected areas. Meanwhile spatial heterogeneity may dilute or amplify cholera infection, which in turn would increase the complexity of disease spread.

We consider a class of density-dependent branching processes which generalises exponential, logistic and Gompertz growth. A population begins with a single individual, grows exponentially initially, and then growth may slow down as the population size moves towards a carrying capacity. At a time while the population is still growing superlinearly, a fixed number of individuals are sampled and their coalescent tree is drawn. Taking the sampling time and carrying capacity simultaneously to infinity, we prove convergence of the coalescent tree to a limiting tree which is in a sense universal over our class of models.

Genetic diversity at population scale, depends on species life-history traits, population dynamics and local and global environmental factors. We first investigate the effect of life-history traits on the neutral genetic diversity of a single population using a deterministic mathematical model. When the population is stable, we show that semelparous species with precocious maturation and iteroparous species with delayed maturation exhibit higher diversity because their life history traits tend to balance the lifetimes of non reproductive individuals (juveniles) and adults which reproduce. Then, we extend our model to a metapopulation to investigate the additional effect of dispersal on diversity. We show that dispersal may truly modify the local effect of life history on diversity. As a result, the diversity at the global scale of the metapopulation differ from the local diversity which is only described through local life history traits of the populations. In particular, dispersal usually promotes diversity at the global metapopulation scale.

Glioblastoma multiforme is a brain cancer that still shows poor prognosis for patients despite the active research for new treatments. In this work, the goal is to model and simulate the evolution of tumour associated angiogenesis and the therapeutic response to glioblastoma multiforme. Multiple phenomena are modelled in order to fit different biological pathways, such as the cellular cycle, apoptosis, hypoxia or angiogenesis. This leads to a nonlinear system with 4 equations and 4 unknowns: the density of tumour cells, the [Formula: see text] concentration, the density of endothelial cells and the vascular endothelial growth factor concentration. This system is solved numerically on a mesh fitting the geometry of the brain and the tumour of a patient based on a 2D slice of MRI. We show that our numerical scheme is positive, and we give the energy estimates on the discrete solution to ensure its existence. The numerical scheme uses nonlinear control volume finite elements in space and is implicit in time. Numerical simulations have been done using the different standard treatments: surgery, chemotherapy and radiotherapy, in order to conform to the behaviour of a tumour in response to treatments according to empirical clinical knowledge. We find that our theoretical model exhibits realistic behaviours.

We consider a reaction-diffusion system of densities of two types of particles, introduced by Hannezo et al. (Cell 171(1):242-255.e27, 2017). It is a simple model for a growth process: active, branching particles form the growing boundary layer of an otherwise static tissue, represented by inactive particles. The active particles diffuse, branch and become irreversibly inactive upon collision with a particle of arbitrary type. In absence of active particles, this system is in a steady state, without any a priori restriction on the amount of remaining inactive particles. Thus, while related to the well-studied FKPP-equation, this system features a game-changing continuum of steady state solutions, where each corresponds to a possible outcome of the growth process. However, simulations indicate that this system self-organizes: traveling fronts with fixed shape arise under a wide range of initial data. In the present work, we describe all positive and bounded traveling wave solutions, and obtain necessary and sufficient conditions for their existence. We find a surprisingly simple symmetry in the pairs of steady states which are joined via heteroclinic wave orbits. Our approach is constructive: we first prove the existence of almost constant solutions and then extend our results via a continuity argument along the continuum of limiting points.

Human papillomavirus (HPV) infection can spread between regions. What is the impact of disassortative geographical mixing on the dynamics of HPV transmission? Vaccination is effective in preventing HPV infection. How to allocate HPV vaccines between genders within each region and between regions to reduce the total infection? Here we develop a two-patch two-sex model to address these questions. The control reproduction number [Formula: see text] under vaccination is obtained and shown to provide a critical threshold for disease elimination. Both analytical and numerical results reveal that disassortative geographical mixing does not affect [Formula: see text] and only has a minor impact on the disease prevalence in the total population given the vaccine uptake proportional to the population size for each gender in the two patches. When the vaccine uptake is not proportional to the population size, sexual mixing between the two patches can reduce [Formula: see text] and mitigate the consequence of disproportionate vaccine coverage. Using parameters calibrated from the data of a case study, we find that if the two patches have the same or similar sex ratios, allocating vaccines proportionally according to the new recruits in two patches and giving priority to the gender with a smaller recruit rate within each patch will bring the maximum benefit in reducing the total prevalence. We also show that a time-variable vaccination strategy between the two patches can further reduce the disease prevalence. This study provides some quantitative information that may help to develop vaccine distribution strategies in multiple regions with disassortative mixing.

We analyze the harvesting and stocking of a population that is affected by random and seasonal environmental fluctuations. The main novelty comes from having three layers of environmental fluctuations. The first layer is due to the environment switching at random times between different environmental states. This is similar to having sudden environmental changes or catastrophes. The second layer is due to seasonal variation, where there is a significant change in the dynamics between seasons. Finally, the third layer is due to the constant presence of environmental stochasticity-between the seasonal or random regime switches, the species is affected by fluctuations which can be modelled by white noise. This framework is more realistic because it can capture both significant random and deterministic environmental shifts as well as small and frequent fluctuations in abiotic factors. Our framework also allows for the price or cost of harvesting to change deterministically and stochastically, something that is more realistic from an economic point of view. The combined effects of seasonal and random fluctuations make it impossible to find the optimal harvesting-stocking strategy analytically. We get around this roadblock by developing rigorous numerical approximations and proving that they converge to the optimal harvesting-stocking strategy. We apply our methods to multiple population models and explore how prices, or costs, and environmental fluctuations influence the optimal harvesting-stocking strategy. We show that in many situations the optimal way of harvesting and stocking is not of threshold type.

In insect respiration, oxygen from the air diffuses through a branching system of air-filled tubes to the cells of the body and carbon dioxide produced in cellular respiration diffuses out. The tracheal system has a very large surface area, so water loss is a potential threat and the question of how insects regulate oxygen uptake and water loss has been an important issue in insect physiology for the past century. The tracheal system starts at spiracles on the surface of the body that insects can open and close, and three phases are observed experimentally, open or closed for relatively long periods of time and opening and closing rapidly, which is called fluttering. In previous work we have shown that during this flutter phase, no matter how small the percentage of time that the spiracles are open, the insect can absorb almost as much oxygen as if the spiracle were always open, if the insect flutters fast enough. This left open the question of water loss during the flutter phase, which is the question addressed in this paper. We formulate a stochastic diffusion-convection model for the concentration of water vapor in the tracheae. Mathematical analysis of the model yields an explicit formula for water loss as a function of six non-dimensional parameters and we use experimental data from various insects to show that, for parameters in the physiological ranges, water loss during the flutter phase is approximately proportional to the percentage of time open. This means that the insect can solve the oxygen uptake versus water loss problem by choosing to have their spiracles open a small percentage of time during the flutter phase and fluttering rapidly.

We derive an alternative expression for a delayed logistic equation in which the rate of change in the population involves a growth rate that depends on the population density during an earlier time period. In our formulation, the delay in the growth term is consistent with the rate of instantaneous decline in the population given by the model. Our formulation is a modification of Arino et al. (J Theor Biol 241(1):109-119, 2006) by taking the intraspecific competition between the adults and juveniles into account. We provide a complete global analysis showing that no sustained oscillations are possible. A threshold giving the interface between extinction and survival is determined in terms of the parameters in the model. The theory of chain transitive sets and the comparison theorem for cooperative delay differential equations are used to determine the global dynamics of the model. We extend our delayed logistic equation to a system modeling the competition between two species. For the competition model, we provide results on local stability, bifurcation diagrams, and adaptive dynamics. Assuming that the species with shorter delay produces fewer offspring at a time than the species with longer delay, we show that there is a critical value, [Formula: see text], such that the evolutionary trend is for the delay to approach [Formula: see text].

We develop general heterogeneous nonlocal diffusion models and investigate their connection to local diffusion models by taking a singular limit of focusing kernels. We reveal the link between the two groups of diffusion equations which include both spatial heterogeneity and anisotropy. In particular, we introduce the notion of deciding factors which single out a nonlocal diffusion model and typically consist of the total jump rate and the average jump length. In this framework, we also discuss the dependence of the profile of the steady state solutions on these deciding factors, thus shedding light on the preferential position of individuals.

In this work, we provide a general mathematical formalism to study the optimal control of an epidemic, such as the COVID-19 pandemic, via incentives to lockdown and testing. In particular, we model the interplay between the government and the population as a principal-agent problem with moral hazard, à la Cvitanić et al. (Finance Stoch 22(1):1-37, 2018), while an epidemic is spreading according to dynamics given by compartmental stochastic SIS or SIR models, as proposed respectively by Gray et al. (SIAM J Appl Math 71(3):876-902, 2011) and Tornatore et al. (Phys A Stat Mech Appl 354(15):111-126, 2005). More precisely, to limit the spread of a virus, the population can decrease the transmission rate of the disease by reducing interactions between individuals. However, this effort-which cannot be perfectly monitored by the government-comes at social and monetary cost for the population. To mitigate this cost, and thus encourage the lockdown of the population, the government can put in place an incentive policy, in the form of a tax or subsidy. In addition, the government may also implement a testing policy in order to know more precisely the spread of the epidemic within the country, and to isolate infected individuals. In terms of technical results, we demonstrate the optimal form of the tax, indexed on the proportion of infected individuals, as well as the optimal effort of the population, namely the transmission rate chosen in response to this tax. The government's optimisation problems then boils down to solving an Hamilton-Jacobi-Bellman equation. Numerical results confirm that if a tax policy is implemented, the population is encouraged to significantly reduce its interactions. If the government also adjusts its testing policy, less effort is required on the population side, individuals can interact almost as usual, and the epidemic is largely contained by the targeted isolation of positively-tested individuals.