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n this paper we study invasion probabilities and invasion times of cooperative parasites spreading in spatially structured host populations. The spatial structure of the host population is given by a random geometric graph on [0,1]n, n∈N, with a Poisson(N)-distributed number of vertices and in which vertices are connected over an edge when they have a distance of at most rN∈Θ(Nβ−1n) for some 0<β<1 and N→∞. At a host infection many parasites are generated and parasites move along edges to neighbouring hosts. We assume that parasites have to cooperate to infect hosts, in the sense that at least two parasites need to attack a host simultaneously. We find lower and upper bounds on the invasion probability of the parasites in terms of survival probabilities of branching processes with cooperation. Furthermore, we characterize the asymptotic invasion time.
An important ingredient of the proofs is a comparison with infection dynamics of cooperative parasites in host populations structured according to a complete graph, i.e. in well-mixed host populations. For these infection processes we can show that invasion probabilities are asymptotically equal to survival probabilities of branching processes with cooperation.
Furthermore, we build in the proofs on techniques developed in [BP22], where an analogous invasion process has been studied for host populations structured according to a configuration model.
We substantiate our results with simulations.
Muller's ratchet, in its prototype version, models a haploid, asexual population whose size~N is constant over the generations. Slightly deleterious mutations are acquired along the lineages at a constant rate, and individuals carrying less mutations have a selective advantage. The classical variant considers {\it fitness proportional} selection, but other fitness schemes are conceivable as well. Inspired by the work of Etheridge et al. ([EPW09]) we propose a parameter scaling which fits well to the ``near-critical'' regime that was in the focus of [EPW09] (and in which the mutation-selection ratio diverges logarithmically as N→∞). Using a Moran model, we investigate the``rule of thumb'' given in [EPW09] for the click rate of the ``classical ratchet'' by putting it into the context of new results on the long-time evolution of the size of the best class of the ratchet with (binary) tournament selection, which (other than that of the classical ratchet) follows an autonomous dynamics up to the time of its extinction. In [GSW23] it was discovered that the tournament ratchet has a hierarchy of dual processes which can be constructed on top of an Ancestral Selection graph with a Poisson decoration. For a regime in which the mutation/selection-ratio remains bounded away from 1, this was used in [GSW23] to reveal the asymptotics of the click rates as well as that of the type frequency profile between clicks. We will describe how these ideas can be extended to the near-critical regime in which the mutation-selection ratio of the tournament ratchet converges to 1 as N→∞.
The category of abelian varieties over Fq is shown to be anti-equivalent to a category of Z-lattices that are modules for a non-commutative pro-ring of endomorphisms of a suitably chosen direct system of abelian varieties over Fq. On full subcategories cut out by a finite set w of conjugacy classes of Weil q-numbers, the anti-equivalence is represented by what we call w-locally projective abelian varieties.
We consider ground state solutions u ∈ H2(RN) of biharmonic (fourth-order) nonlinear Schrodinger equations of the form ¨2u + 2au + bu − |u| p−2u = 0 in RN with positive constants a, b > 0 and exponents 2 < p < 2∗, where 2∗ = 2N N−4 if N > 4 and 2∗ = ∞ if N ≤ 4. By exploiting a connection to the adjoint Stein–Tomas inequality on the unit sphere and by using trial functions due to Knapp, we prove a general symmetry breaking result by showing that all ground states u ∈ H2(RN) in dimension N ≥ 2 fail to be radially symmetric for all exponents 2 < p < 2N+2 N−1 in a suitable regime of a, b > 0. As applications of our main result, we also prove symmetry breaking for a minimization problem with constrained L2-mass and for a related problem on the unit ball in RN subject to Dirichlet boundary conditions.
Using limit linear series on chains of curves, we show that closures of certain Brill-Noether loci contain a product of pointed Brill-Noether loci of small codimension. As a result, we obtain new non-containments of Brill-Noether loci, in particular that dimensionally expected non-containments hold for expected maximal Brill-Noether loci. Using these degenerations, we also give a new proof that Brill-Noether loci with expected codimension −ρ≤⌈g/2⌉ have a component of the expected dimension. Additionally, we obtain new non-containments of Brill-Noether loci by considering the locus of the source curves of unramified double covers.
We prove that the projectivized strata of differentials are not contained in pointed Brill-Noether divisors, with only a few exceptions. For a generic element in a stratum of differentials, we show that many of the associated pointed Brill-Noether loci are of expected dimension. We use our results to study the Auel-Haburcak Conjecture: We obtain new non-containments between maximal Brill-Noether loci in Mg. Our results regarding quadratic differentials imply that the quadratic strata in genus 6 are uniruled.
Geometry is part of the core of mathematics. It has been relevant ever since people have interacted with nature and its phenomena. Geometry’s relevance to the teaching and learning of mathematics can be emphasized, too. Nevertheless, a current potential shift in the topics of mathematics education to the detriment of geometry might be emerging. That is, other topics related to mathematics are seeming to grow in importance in comparison to geometry. Despite this, or perhaps because of it, geometry is an important component of current research in mathematics education. In the literature review, we elaborate relevant foci on the basis of current conference proceedings. By means of about 50 journal articles, five main topics are elaborated in more detail: geometric thinking and practices, geometric contents and topics, teacher education in geometry, argumentation and proof in geometry, as well as the use of digital tools for the teaching and learning of geometry. Conclusions and limitations for current and future research on geometry are formulated at the end of the article. In particular, the transfer to the practices of geometric teaching is explored on the basis of the elaborated research findings in order to combine both aspects of the teaching and learning of geometry.
The free energy of TAP-solutions for the SK-model of mean field spin glasses can be expressed as a nonlinear functional of local terms: we exploit this feature in order to contrive abstract REM-like models which we then solve by a classical large deviations treatment. This allows to identify the origin of the physically unsettling quadratic (in the inverse of temperature) correction to the Parisi free energy for the SK-model, and formalizes the true cavity dynamics which acts on TAP-space, i.e. on the space of TAP-solutions. From a non-spin glass point of view, this work is the first in a series of refinements which addresses the stability of hierarchical structures in models of evolving populations.
The free energy of TAP-solutions for the SK-model of mean field spin glasses can be expressed as a nonlinear functional of local terms: we exploit this feature in order to contrive abstract REM-like models which we then solve by a classical large deviations treatment. This allows to identify the origin of the physically unsettling quadratic (in the inverse of temperature) correction to the Parisi free energy for the SK-model, and formalizes the true cavity dynamics which acts on TAP-space, i.e. on the space of TAP-solutions. From a non-spin glass point of view, this work is the first in a series of refinements which addresses the stability of hierarchical structures in models of evolving populations.
During my initial days here in Frankfurt, in October 2020 amidst the pandemic crisis, all my notes revolved around three articles by Bolthausen and Kistler, which now form the starting point of this work.
The ones introduced by Bolthausen and Kistler are abstract mean field spin glass models, reminiscent of Derrida’s Generalized Random Energy Model (GREM), which generalize the GREM while remaining rigorously solvable through large deviations methods and within a classical Boltzmann-Gibbs formalism. This allows to establish, by means of a second moment method, the associated free energy at the thermodynamic limit as an orthodox, infinite-dimensional, Boltzmann-Gibbs variational principle.
Dual Parisi formulas for the limiting free energy associated with these Hamiltonians hold, and are revealed to be the finite-dimensional (”collapsed”) versions of the classical, infinite-dimensional Boltzmann-Gibbs principles.
In the 2nd chapter of this thesis, we uncover the hidden yet essential connection between real-world spin glasses, like the Sherrington-Kirkpatrick (SK) model and the random energy models. The crucial missing element is that of TAP-free energies: integrating it with the framework introduced by Bolthausen and Kistler results in a correction to the Parisi formula for the free energy, which brings it much, much closer to the ”true” Parisi solution for the SK-model. In other words, we can identify the principles that transform the classical Boltzmann-Gibbs maximization into the unorthodox (and puzzling) Parisi minimization.
This arguably stands as the primary achievement of this work.
Komplexität und Zufälligkeit
(1978)
Muller's ratchet, in its prototype version, models a haploid, asexual population whose size~N is constant over the generations. Slightly deleterious mutations are acquired along the lineages at a constant rate, and individuals carrying less mutations have a selective advantage. The classical variant considers {\it fitness proportional} selection, but other fitness schemes are conceivable as well. Inspired by the work of Etheridge et al. ([EPW09]) we propose a parameter scaling which fits well to the ``near-critical'' regime that was in the focus of [EPW09] (and in which the mutation-selection ratio diverges logarithmically as N→∞). Using a Moran model, we investigate the``rule of thumb'' given in [EPW09] for the click rate of the ``classical ratchet'' by putting it into the context of new results on the long-time evolution of the size of the best class of the ratchet with (binary) tournament selection, which (other than that of the classical ratchet) follows an autonomous dynamics up to the time of its extinction. In [GSW23] it was discovered that the tournament ratchet has a hierarchy of dual processes which can be constructed on top of an Ancestral Selection graph with a Poisson decoration. For a regime in which the mutation/selection-ratio remains bounded away from 1, this was used in [GSW23] to reveal the asymptotics of the click rates as well as that of the type frequency profile between clicks. We will describe how these ideas can be extended to the near-critical regime in which the mutation-selection ratio of the tournament ratchet converges to 1 as N→∞.
Motivated by the question of the impact of selective advantage in populations with skewed reproduction mechanims, we study a Moran model with selection. We assume that there are two types of individuals, where the reproductive success of one type is larger than the other. The higher reproductive success may stem from either more frequent reproduction, or from larger numbers of offspring, and is encoded in a measure Λ for each of the two types. Our approach consists of constructing a Λ-asymmetric Moran model in which individuals of the two populations compete, rather than considering a Moran model for each population. Under certain conditions, that we call the "partial order of adaptation", we can couple these measures. This allows us to construct the central object of this paper, the Λ−asymmetric ancestral selection graph, leading to a pathwise duality of the forward in time Λ-asymmetric Moran model with its ancestral process. Interestingly, the construction also provides a connection to the theory of optimal transport. We apply the ancestral selection graph in order to obtain scaling limits of the forward and backward processes, and note that the frequency process converges to the solution of an SDE with discontinous paths. Finally, we derive a Griffiths representation for the generator of the SDE and use it to find a semi-explicit formula for the probability of fixation of the less beneficial of the two types.
Motivated by the question of the impact of selective advantage in populations with skewed reproduction mechanims, we study a Moran model with selection. We assume that there are two types of individuals, where the reproductive success of one type is larger than the other. The higher reproductive success may stem from either more frequent reproduction, or from larger numbers of offspring, and is encoded in a measure Λ for each of the two types. Our approach consists of constructing a Λ-asymmetric Moran model in which individuals of the two populations compete, rather than considering a Moran model for each population. Under certain conditions, that we call the ``partial order of adaptation'', we can couple these measures. This allows us to construct the central object of this paper, the Λ−asymmetric ancestral selection graph, leading to a pathwise duality of the forward in time Λ-asymmetric Moran model with its ancestral process. Interestingly, the construction also provides a connection to the theory of optimal transport. We apply the ancestral selection graph in order to obtain scaling limits of the forward and backward processes, and note that the frequency process converges to the solution of an SDE with discontinous paths. Finally, we derive a Griffiths representation for the generator of the SDE and use it to find a semi-explicit formula for the probability of fixation of the less beneficial of the two types.
Motivated by the question of the impact of selective advantage in populations with skewed reproduction mechanisms, we study a Moran model with selection. We assume that there are two types of individuals, where the reproductive success of one type is larger than the other. The higher reproductive success may stem from either more frequent reproduction, or from larger numbers of offspring, and is encoded in a measure Λ for each of the two types. Λ-reproduction here means that a whole fraction of the population is replaced at a reproductive event. Our approach consists of constructing a Λ-asymmetric Moran model in which individuals of the two populations compete, rather than considering a Moran model for each population. Provided the measure are ordered stochastically, we can couple them. This allows us to construct the central object of this paper, the Λ−asymmetric ancestral selection graph, leading to a pathwise duality of the forward in time Λ-asymmetric Moran model with its ancestral process. We apply the ancestral selection graph in order to obtain scaling limits of the forward and backward processes, and note that the frequency process converges to the solution of an SDE with discontinuous paths. Finally, we derive a Griffiths representation for the generator of the SDE and use it to find a semi-explicit formula for the probability of fixation of the less beneficial of the two types.
Therapy evasion – and subsequent disease progression – is a major challenge in current oncology. An important role in this context seems to be played by various forms of cancer cell dormancy. For example, therapy-induced dormancy, over short timescales, can create serious obstacles to aggressive treatment approaches such as chemotherapy, and long-term dormancy may lead to relapses and metastases even many years after an initially successful treatment. The underlying dormancy-related mechanisms are complex and highly diverse, so that the analysis even of basic patterns of the population-level consequences of dormancy requires abstraction and idealization, as well as the identification of the relevant specific scenarios.
In this paper, we focus on a situation in which individual cancer cells may switch into and out of a dormant state both spontaneously as well as in response to treatment, and over relatively short time-spans. We introduce a mathematical ‘toy model’, based on stochastic agent-based interactions, for the dynamics of cancer cell populations involving individual short-term dormancy, and allow for a range of (multi-drug) therapy protocols. Our analysis shows that in our idealized model, even a small initial population of dormant cells can lead to therapy failure under classical (and in the absence of dormancy successful) single-drug treatments. We further investigate the effectiveness of several multidrug regimes (manipulating dormant cancer cells in specific ways) and provide some basic rules for the design of (multi-)drug treatment protocols depending on the types and parameters of dormancy mechanisms present in the population.