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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.
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.
For genus g=r(r+1)2+1, we prove that via the forgetful map, the universal Prym-Brill-Noether locus Rrg has a unique irreducible component dominating the moduli space Rg of Prym curves.
For genus g=2i≥4 and the length g−1 partition μ=(4,2,…,2,−2,…,−2) of 0, we compute the first coefficients of the class of D¯¯¯¯(μ) in PicQ(R¯¯¯¯g), where D(μ) is the divisor consisting of pairs [C,η]∈Rg with η≅OC(2x1+x2+⋯+xi−1−xi−⋯−x2i−1) for some points x1,…,x2i−1 on C. We further provide several enumerative results that will be used for this computation.
For genus g=2i≥4 and the length g−1 partition μ=(4,2,…,2,−2,…,−2) of 0, we compute the first coefficients of the class of D¯¯¯¯(μ) in PicQ(R¯¯¯¯g), where D(μ) is the divisor consisting of pairs [C,η]∈Rg with η≅OC(2x1+x2+⋯+xi−1−xi−⋯−x2i−1) for some points x1,…,x2i−1 on C. We further provide several enumerative results that will be used for this computation.
Between his arrival in Frankfurt in 1922 and and his proof of his famous finiteness theorem for integral points in 1929, Siegel had no publications. He did, however, write a letter to Mordell in 1926 in which he explained a proof of the finiteness of integral points on hyperelliptic curves. Recognizing the importance of this argument (and Siegel's views on publication), Mordell sent the relevant extract to be published under the pseudonym "X".
The purpose of this note is to explain how to optimize Siegel's 1926 technique to obtain the following bound. Let K be a number field, S a finite set of places of K, and f∈oK,S[t] monic of degree d≥5 with discriminant Δf∈o×K,S. Then: #|{(x,y):x,y∈oK,S,y2=f(x)}|≤2rankJac(Cf)(K)⋅O(1)d3⋅([K:Q]+#|S|).
This improves bounds of Evertse-Silverman and Bombieri-Gubler from 1986 and 2006, respectively.
The main point underlying our improvement is that, informally speaking, we insist on "executing the descents in the presence of only one root (and not three) until the last possible moment".
For genus g=2i≥4 and the length g−1 partition μ=(4,2,…,2,−2,…,−2) of 0, we compute the first coefficients of the class of D¯¯¯¯(μ) in PicQ(R¯¯¯¯g), where D(μ) is the divisor consisting of pairs [C,η]∈Rg with η≅OC(2x1+x2+⋯+xi−1−xi−⋯−x2i−1) for some points x1,…,x2i−1 on C. We further provide several enumerative results that will be used for this computation.
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.
Using the notion of a root datum of a reductive group G we propose a tropical analogue of a principal G-bundle on a metric graph. We focus on the case G=GLn, i.e. the case of vector bundles. Here we give a characterization of vector bundles in terms of multidivisors and use this description to prove analogues of the Weil--Riemann--Roch theorem and the Narasimhan--Seshadri correspondence. We proceed by studying the process of tropicalization. In particular, we show that the non-Archimedean skeleton of the moduli space of semistable vector bundles on a Tate curve is isomorphic to a certain component of the moduli space of semistable tropical vector bundles on its dual metric graph.
In this article we provide a stack-theoretic framework to study the universal tropical Jacobian over the moduli space of tropical curves. We develop two approaches to the process of tropicalization of the universal compactified Jacobian over the moduli space of curves -- one from a logarithmic and the other from a non-Archimedean analytic point of view. The central result from both points of view is that the tropicalization of the universal compactified Jacobian is the universal tropical Jacobian and that the tropicalization maps in each of the two contexts are compatible with the tautological morphisms. In a sequel we will use the techniques developed here to provide explicit polyhedral models for the logarithmic Picard variety.
Foundations of geometry
(2020)
In an earlier paper we proposed a recursive model for epidemics; in the present paper we generalize this model to include the asymptomatic or unrecorded symptomatic people, which we call dark people (dark sector). We call this the SEPARd-model. A delay differential equation version of the model is added; it allows a better comparison to other models. We carry this out by a comparison with the classical SIR model and indicate why we believe that the SEPARd model may work better for Covid-19 than other approaches.
In the second part of the paper we explain how to deal with the data provided by the JHU, in particular we explain how to derive central model parameters from the data. Other parameters, like the size of the dark sector, are less accessible and have to be estimated more roughly, at best by results of representative serological studies which are accessible, however, only for a few countries. We start our country studies with Switzerland where such data are available. Then we apply the model to a collection of other countries, three European ones (Germany, France, Sweden), the three most stricken countries from three other continents (USA, Brazil, India). Finally we show that even the aggregated world data can be well represented by our approach.
At the end of the paper we discuss the use of the model. Perhaps the most striking application is that it allows a quantitative analysis of the influence of the time until people are sent to quarantine or hospital. This suggests that imposing means to shorten this time is a powerful tool to flatten the curves.
We deal with the reconstruction of inclusions in elastic bodies based on monotonicity methods and construct conditions under which a resolution for a given partition can be achieved. These conditions take into account the background error as well as the measurement noise. As a main result, this shows us that the resolution guarantees depend heavily on the Lamé parameter μ and only marginally on λ.
The Calderón problem with finitely many unknowns is equivalent to convex semidefinite optimization
(2023)
We consider the inverse boundary value problem of determining a coefficient function in an elliptic partial differential equation from knowledge of the associated Neumann-Dirichlet-operator. The unknown coefficient function is assumed to be piecewise constant with respect to a given pixel partition, and upper and lower bounds are assumed to be known a-priori.
We will show that this Calderón problem with finitely many unknowns can be equivalently formulated as a minimization problem for a linear cost functional with a convex non-linear semidefinite constraint. We also prove error estimates for noisy data, and extend the result to the practically relevant case of finitely many measurements, where the coefficient is to be reconstructed from a finite-dimensional Galerkin projection of the Neumann-Dirichlet-operator.
Our result is based on previous works on Loewner monotonicity and convexity of the Neumann-Dirichlet-operator, and the technique of localized potentials. It connects the emerging fields of inverse coefficient problems and semidefinite optimization.
The purpose of the paper is to initiate the development of the theory of Newton Okounkov bodies of curve classes. Our denition is based on making a fundamental property of NewtonOkounkov bodies hold also in the curve case: the volume of the NewtonOkounkov body of a curve is a volume-type function of the original curve. This construction allows us to conjecture a new relation between NewtonOkounkov bodies, we prove it in certain cases.
Motivation: The topic of this paper is the estimation of alignments and mutation rates based on stochastic sequence-evolution models that allow insertions and deletions of subsequences ("fragments") and not just single bases. The model we propose is a variant of a model introduced by Thorne, Kishino, and Felsenstein (1992). The computational tractability of the model depends on certain restrictions in the insertion/deletion process; possible effects we discuss.
Results: The process of fragment insertion and deletion in the sequence-evolution model induces a hidden Markov structure at the level of alignments and thus makes possible efficient statistical alignment algorithms. As an example we apply a sampling procedure to assess the variability in alignment and mutation parameter estimates for HVR1 sequences of human and orangutan, improving results of previous work. Simulation studies give evidence that estimation methods based on the proposed model also give satisfactory results when applied to data for which the restrictions in the insertion/deletion process do not hold.
Availability: The source code of the software for sampling alignments and mutation rates for a pair of DNA sequences according to the fragment insertion and deletion model is freely available from www.math.uni-frankfurt.de/~stoch/software/mcmcsalut under the terms of the GNU public license (GPL, 2000).