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The geomagnetic Kp index is one of the most extensively used indices of geomagnetic activity, both for scientific and operational purposes. This article reviews the properties of the Kp index and provides a reference for users of the Kp index and associated data products as derived and distributed by the GFZ German Research Centre for Geosciences. The near real-time production of the nowcast Kp index is of particular interest for space weather services and here we describe and evaluate its current setup.
Various particle filters have been proposed over the last couple of decades with the common feature that the update step is governed by a type of control law. This feature makes them an attractive alternative to traditional sequential Monte Carlo which scales poorly with the state dimension due to weight degeneracy. This article proposes a unifying framework that allows us to systematically derive the McKean-Vlasov representations of these filters for the discrete time and continuous time observation case, taking inspiration from the smooth approximation of the data considered in [D. Crisan and J. Xiong, Stochastics, 82 (2010), pp. 53-68; J. M. Clark and D. Crisan, Probab. Theory Related Fields, 133 (2005), pp. 43-56]. We consider three filters that have been proposed in the literature and use this framework to derive Ito representations of their limiting forms as the approximation parameter delta -> 0. All filters require the solution of a Poisson equation defined on R-d, for which existence and uniqueness of solutions can be a nontrivial issue. We additionally establish conditions on the signal-observation system that ensures well-posedness of the weighted Poisson equation arising in one of the filters.
Androulidakis-Skandalis (2009) showed that every singular foliation has an associated topological groupoid, called holonomy groupoid. In this note, we exhibit some functorial properties of this assignment: if a foliated manifold (M, FM ) is the quotient of a foliated manifold (P, FP ) along a surjective submersion with connected fibers, then the same is true for the corresponding holonomy groupoids. For quotients by a Lie group action, an analogue statement holds under suitable assumptions, yielding a Lie 2-group action on the holonomy groupoid.
Identification of unknown parameters on the basis of partial and noisy data is a challenging task, in particular in high dimensional and non-linear settings. Gaussian approximations to the problem, such as ensemble Kalman inversion, tend to be robust and computationally cheap and often produce astonishingly accurate estimations despite the simplifying underlying assumptions. Yet there is a lot of room for improvement, specifically regarding a correct approximation of a non-Gaussian posterior distribution. The tempered ensemble transform particle filter is an adaptive Sequential Monte Carlo (SMC) method, whereby resampling is based on optimal transport mapping. Unlike ensemble Kalman inversion, it does not require any assumptions regarding the posterior distribution and hence has shown to provide promising results for non-linear non-Gaussian inverse problems. However, the improved accuracy comes with the price of much higher computational complexity, and the method is not as robust as ensemble Kalman inversion in high dimensional problems. In this work, we add an entropy-inspired regularisation factor to the underlying optimal transport problem that allows the high computational cost to be considerably reduced via Sinkhorn iterations. Further, the robustness of the method is increased via an ensemble Kalman inversion proposal step before each update of the samples, which is also referred to as a hybrid approach. The promising performance of the introduced method is numerically verified by testing it on a steady-state single-phase Darcy flow model with two different permeability configurations. The results are compared to the output of ensemble Kalman inversion, and Markov chain Monte Carlo methods results are computed as a benchmark.
In a previous study, a new snapshot modeling concept for the archeomagnetic field was introduced (Mauerberger et al., 2020, ). By assuming a Gaussian process for the geomagnetic potential, a correlation-based algorithm was presented, which incorporates a closed-form spatial correlation function. This work extends the suggested modeling strategy to the temporal domain. A space-time correlation kernel is constructed from the tensor product of the closed-form spatial correlation kernel with a squared exponential kernel in time. Dating uncertainties are incorporated into the modeling concept using a noisy input Gaussian process. All but one modeling hyperparameters are marginalized, to reduce their influence on the outcome and to translate their variability to the posterior variance. The resulting distribution incorporates uncertainties related to dating, measurement and modeling process. Results from application to archeomagnetic data show less variation in the dipole than comparable models, but are in general agreement with previous findings.
Ulcerative colitis (UC) is part of the inflammatory bowels diseases, and moderate to severe UC patients can be treated with anti-tumour necrosis alpha monoclonal antibodies, including infliximab (IFX). Even though treatment of UC patients by IFX has been in place for over a decade, many gaps in modelling of IFX PK in this population remain. This is even more true for acute severe UC (ASUC) patients for which early prediction of IFX pharmacokinetic (PK) could highly improve treatment outcome. Thus, this review aims to compile and analyse published population PK models of IFX in UC and ASUC patients, and to assess the current knowledge on disease activity impact on IFX PK. For this, a semi-systematic literature search was conducted, from which 26 publications including a population PK model analysis of UC patients receiving IFX therapy were selected. Amongst those, only four developed a model specifically for UC patients, and only three populations included severe UC patients. Investigations of disease activity impact on PK were reported in only 4 of the 14 models selected. In addition, the lack of reported model codes and assessment of predictive performance make the use of published models in a clinical setting challenging. Thus, more comprehensive investigation of PK in UC and ASUC is needed as well as more adequate reports on developed models and their evaluation in order to apply them in a clinical setting.
We present a new model of the geomagnetic field spanning the last 20 years and called Kalmag. Deriving from the assimilation of CHAMP and Swarm vector field measurements, it separates the different contributions to the observable field through parameterized prior covariance matrices. To make the inverse problem numerically feasible, it has been sequentialized in time through the combination of a Kalman filter and a smoothing algorithm. The model provides reliable estimates of past, present and future mean fields and associated uncertainties. The version presented here is an update of our IGRF candidates; the amount of assimilated data has been doubled and the considered time window has been extended from [2000.5, 2019.74] to [2000.5, 2020.33].
Data assimilation algorithms are used to estimate the states of a dynamical system using partial and noisy observations. The ensemble Kalman filter has become a popular data assimilation scheme due to its simplicity and robustness for a wide range of application areas. Nevertheless, this filter also has limitations due to its inherent assumptions of Gaussianity and linearity, which can manifest themselves in the form of dynamically inconsistent state estimates. This issue is investigated here for balanced, slowly evolving solutions to highly oscillatory Hamiltonian systems which are prototypical for applications in numerical weather prediction. It is demonstrated that the standard ensemble Kalman filter can lead to state estimates that do not satisfy the pertinent balance relations and ultimately lead to filter divergence. Two remedies are proposed, one in terms of blended asymptotically consistent time-stepping schemes, and one in terms of minimization-based postprocessing methods. The effects of these modifications to the standard ensemble Kalman filter are discussed and demonstrated numerically for balanced motions of two prototypical Hamiltonian reference systems.
Background
Cytochrome P450 (CYP) 3A contributes to the metabolism of many approved drugs. CYP3A perpetrator drugs can profoundly alter the exposure of CYP3A substrates. However, effects of such drug-drug interactions are usually reported as maximum effects rather than studied as time-dependent processes. Identification of the time course of CYP3A modulation can provide insight into when significant changes to CYP3A activity occurs, help better design drug-drug interaction studies, and manage drug-drug interactions in clinical practice.
Objective
We aimed to quantify the time course and extent of the in vivo modulation of different CYP3A perpetrator drugs on hepatic CYP3A activity and distinguish different modulatory mechanisms by their time of onset, using pharmacologically inactive intravenous microgram doses of the CYP3A-specific substrate midazolam, as a marker of CYP3A activity.
Methods
Twenty-four healthy individuals received an intravenous midazolam bolus followed by a continuous infusion for 10 or 36 h. Individuals were randomized into four arms: within each arm, two individuals served as a placebo control and, 2 h after start of the midazolam infusion, four individuals received the CYP3A perpetrator drug: voriconazole (inhibitor, orally or intravenously), rifampicin (inducer, orally), or efavirenz (activator, orally). After midazolam bolus administration, blood samples were taken every hour (rifampicin arm) or every 15 min (remaining study arms) until the end of midazolam infusion. A total of 1858 concentrations were equally divided between midazolam and its metabolite, 1'-hydroxymidazolam. A nonlinear mixed-effects population pharmacokinetic model of both compounds was developed using NONMEM (R). CYP3A activity modulation was quantified over time, as the relative change of midazolam clearance encountered by the perpetrator drug, compared to the corresponding clearance value in the placebo arm.
Results
Time course of CYP3A modulation and magnitude of maximum effect were identified for each perpetrator drug. While efavirenz CYP3A activation was relatively fast and short, reaching a maximum after approximately 2-3 h, the induction effect of rifampicin could only be observed after 22 h, with a maximum after approximately 28-30 h followed by a steep drop to almost baseline within 1-2 h. In contrast, the inhibitory impact of both oral and intravenous voriconazole was prolonged with a steady inhibition of CYP3A activity followed by a gradual increase in the inhibitory effect until the end of sampling at 8 h. Relative maximum clearance changes were +59.1%, +46.7%, -70.6%, and -61.1% for efavirenz, rifampicin, oral voriconazole, and intravenous voriconazole, respectively.
Conclusions
We could distinguish between different mechanisms of CYP3A modulation by the time of onset. Identification of the time at which clearance significantly changes, per perpetrator drug, can guide the design of an optimal sampling schedule for future drug-drug interaction studies. The impact of a short-term combination of different perpetrator drugs on the paradigm CYP3A substrate midazolam was characterized and can define combination intervals in which no relevant interaction is to be expected.
The purpose of this paper is to build an algebraic framework suited to regularize branched structures emanating from rooted forests and which encodes the locality principle. This is achieved by means of the universal properties in the locality framework of properly decorated rooted forests. These universal properties are then applied to derive the multivariate regularization of integrals indexed by rooted forests. We study their renormalization, along the lines of Kreimer's toy model for Feynman integrals.
Übungsbuch zur Stochastik
(2023)
Dieses Buch stellt Übungen zu den Grundbegriffen und Grundsätzen der Stochastik und ihre Lösungen zur Verfügung. So wie man Tonleitern in der Musik trainiert, so berechnet man Übungsaufgaben in der Mathematik. In diesem Sinne soll dieses Übungsbuch vor allem als Vorlage dienen für das eigenständige, eigenverantwortliche Lernen und Üben.
Die Schönheit und Einzigartigkeit der Wahrscheinlichkeitstheorie besteht darin, dass sie eine Vielzahl von realen Phänomenen modellieren kann. Daher findet man hier Aufgaben mit Verbindungen zur Geometrie, zu Glücksspielen, zur Versicherungsmathematik, zur Demographie und vielen anderen Themen.
We show that local deformations, near closed subsets, of solutions to open partial differential relations can be extended to global deformations, provided all but the highest derivatives stay constant along the subset. The applicability of this general result is illustrated by a number of examples, dealing with convex embeddings of hypersurfaces, differential forms, and lapse functions in Lorentzian geometry.
The main application is a general approximation result by sections that have very restrictive local properties on open dense subsets. This shows, for instance, that given any K is an element of Double-struck capital R every manifold of dimension at least 2 carries a complete C-1,C- 1-metric which, on a dense open subset, is smooth with constant sectional curvature K. Of course, this is impossible for C-2-metrics in general.
For a closed, connected direct product Riemannian manifold (M, g) = (M-1, g(1)) x ... x (M-l, g(l)), we define its multiconformal class [[g]] as the totality {integral(2)(1)g(1) circle plus center dot center dot center dot integral(2)(l)g(l)} of all Riemannian metrics obtained from multiplying the metric gi of each factor Mi by a positive function fi on the total space M. A multiconformal class [[ g]] contains not only all warped product type deformations of g but also the whole conformal class [(g) over tilde] of every (g) over tilde is an element of[[ g]]. In this article, we prove that [[g]] contains a metric of positive scalar curvature if and only if the conformal class of some factor (Mi, gi) does, under the technical assumption dim M-i = 2. We also show that, even in the case where every factor (M-i, g(i)) has positive scalar curvature, [[g]] contains a metric of scalar curvature constantly equal to -1 and with arbitrarily large volume, provided l = 2 and dim M = 3.
For the time stationary global geomagnetic field, a new modelling concept is presented. A Bayesian non-parametric approach provides realistic location dependent uncertainty estimates. Modelling related variabilities are dealt with systematically by making little subjective apriori assumptions. Rather than parametrizing the model by Gauss coefficients, a functional analytic approach is applied. The geomagnetic potential is assumed a Gaussian process to describe a distribution over functions. Apriori correlations are given by an explicit kernel function with non-informative dipole contribution. A refined modelling strategy is proposed that accommodates non-linearities of archeomagnetic observables: First, a rough field estimate is obtained considering only sites that provide full field vector records. Subsequently, this estimate supports the linearization that incorporates the remaining incomplete records. The comparison of results for the archeomagnetic field over the past 1000 yr is in general agreement with previous models while improved model uncertainty estimates are provided.
We provide an overview of the tools and techniques of resurgence theory used in the Borel-ecalle resummation method, which we then apply to the massless Wess-Zumino model. Starting from already known results on the anomalous dimension of the Wess-Zumino model, we solve its renormalisation group equation for the two-point function in a space of formal series. We show that this solution is 1-Gevrey and that its Borel transform is resurgent. The Schwinger-Dyson equation of the model is then used to prove an asymptotic exponential bound for the Borel transformed two-point function on a star-shaped domain of a suitable ramified complex plane. This proves that the two-point function of the Wess-Zumino model is Borel-ecalle summable.
Zahlen in den Fingern
(2023)
Die Debatte über den Einsatz von digitalen Werkzeugen in der mathematischen Frühförderung ist hoch aktuell. Lernspiele werden konstruiert, mit dem Ziel, mathematisches, informelles Wissen aufzubauen und so einen besseren Schulstart zu ermöglichen. Doch allein die digitale und spielerische Aufarbeitung führt nicht zwingend zu einem Lernerfolg. Daher ist es umso wichtiger, die konkrete Implementation der theoretischen Konstrukte und Interaktionsmöglichkeiten mit den Werkzeugen zu analysieren und passend aufzubereiten.
In dieser Masterarbeit wird dazu exemplarisch ein mathematisches Lernspiel namens „Fingu“ für den Einsatz im vorschulischen Bereich theoretisch und empirisch im Rahmen der Artifact-Centric Activity Theory (ACAT) untersucht. Dazu werden zunächst die theoretischen Hintergründe zum Zahlensinn, Zahlbegriffserwerb, Teil-Ganze-Verständnis, der Anzahlwahrnehmung und -bestimmung, den Anzahlvergleichen und der Anzahldarstellung mithilfe von Fingern gemäß der Embodied Cognition sowie der Verwendung von digitalen Werkzeugen und Multi-Touch-Geräten umfassend beschrieben. Anschließend wird die App Fingu erklärt und dann theoretisch entlang des ACAT-Review-Guides analysiert. Zuletzt wird die selbstständig durchgeführte Studie mit zehn Vorschulkindern erläutert und darauf aufbauend Verbesserungs- und Entwicklungsmöglichkeiten der App auf wissenschaftlicher Grundlage beigetragen. Für Fingu lässt sich abschließend festhalten, dass viele Prozesse wie die (Quasi-)Simultanerfassung oder das Zählen gefördert werden können, für andere wie das Teil-Ganze-Verständnis aber noch Anpassungen und/oder die Begleitung durch Erwachsene nötig ist.
Data-driven prediction and physics-agnostic machine-learning methods have attracted increased interest in recent years achieving forecast horizons going well beyond those to be expected for chaotic dynamical systems. In a separate strand of research data-assimilation has been successfully used to optimally combine forecast models and their inherent uncertainty with incoming noisy observations. The key idea in our work here is to achieve increased forecast capabilities by judiciously combining machine-learning algorithms and data assimilation. We combine the physics-agnostic data -driven approach of random feature maps as a forecast model within an ensemble Kalman filter data assimilation procedure. The machine-learning model is learned sequentially by incorporating incoming noisy observations. We show that the obtained forecast model has remarkably good forecast skill while being computationally cheap once trained. Going beyond the task of forecasting, we show that our method can be used to generate reliable ensembles for probabilistic forecasting as well as to learn effective model closure in multi-scale systems. (C) 2021 Elsevier B.V. All rights reserved.
In this paper, we bring together the worlds of model order reduction for stochastic linear systems and H-2-optimal model order reduction for deterministic systems. In particular, we supplement and complete the theory of error bounds for model order reduction of stochastic differential equations. With these error bounds, we establish a link between the output error for stochastic systems (with additive and multiplicative noise) and modified versions of the H-2-norm for both linear and bilinear deterministic systems. When deriving the respective optimality conditions for minimizing the error bounds, we see that model order reduction techniques related to iterative rational Krylov algorithms (IRKA) are very natural and effective methods for reducing the dimension of large-scale stochastic systems with additive and/or multiplicative noise. We apply modified versions of (linear and bilinear) IRKA to stochastic linear systems and show their efficiency in numerical experiments.
In this paper Lie group method in combination with Magnus expansion is utilized to develop a universal method applicable to solving a Sturm–Liouville problem (SLP) of any order with arbitrary boundary conditions. It is shown that the method has ability to solve direct regular (and some singular) SLPs of even orders (tested for up to eight), with a mix of (including non-separable and finite singular endpoints) boundary conditions, accurately and efficiently. The present technique is successfully applied to overcome the difficulties in finding suitable sets of eigenvalues so that the inverse SLP problem can be effectively solved. The inverse SLP algorithm proposed by Barcilon (1974) is utilized in combination with the Magnus method so that a direct SLP of any (even) order and an inverse SLP of order two can be solved effectively.
In this paper Lie group method in combination with Magnus expansion is utilized to develop a universal method applicable to solving a Sturm–Liouville problem (SLP) of any order with arbitrary boundary conditions. It is shown that the method has ability to solve direct regular (and some singular) SLPs of even orders (tested for up to eight), with a mix of (including non-separable and finite singular endpoints) boundary conditions, accurately and efficiently. The present technique is successfully applied to overcome the difficulties in finding suitable sets of eigenvalues so that the inverse SLP problem can be effectively solved. The inverse SLP algorithm proposed by Barcilon (1974) is utilized in combination with the Magnus method so that a direct SLP of any (even) order and an inverse SLP of order two can be solved effectively.
In this paper, we investigate the continuous version of modified iterative Runge–Kutta-type methods for nonlinear inverse ill-posed problems proposed in a previous work. The convergence analysis is proved under the tangential cone condition, a modified discrepancy principle, i.e., the stopping time T is a solution of ∥𝐹(𝑥𝛿(𝑇))−𝑦𝛿∥=𝜏𝛿+ for some 𝛿+>𝛿, and an appropriate source condition. We yield the optimal rate of convergence.
In this paper, we investigate the continuous version of modified iterative Runge–Kutta-type methods for nonlinear inverse ill-posed problems proposed in a previous work. The convergence analysis is proved under the tangential cone condition, a modified discrepancy principle, i.e., the stopping time T is a solution of ∥𝐹(𝑥𝛿(𝑇))−𝑦𝛿∥=𝜏𝛿+ for some 𝛿+>𝛿, and an appropriate source condition. We yield the optimal rate of convergence.
Global numerical weather prediction (NWP) models have begun to resolve the mesoscale k(-5/3) range of the energy spectrum, which is known to impose an inherently finite range of deterministic predictability per se as errors develop more rapidly on these scales than on the larger scales. However, the dynamics of these errors under the influence of the synoptic-scale k(-3) range is little studied. Within a perfect-model context, the present work examines the error growth behavior under such a hybrid spectrum in Lorenz's original model of 1969, and in a series of identical-twin perturbation experiments using an idealized two-dimensional barotropic turbulence model at a range of resolutions. With the typical resolution of today's global NWP ensembles, error growth remains largely uniform across scales. The theoretically expected fast error growth characteristic of a k(-5/3) spectrum is seen to be largely suppressed in the first decade of the mesoscale range by the synoptic-scale k(-3) range. However, it emerges once models become fully able to resolve features on something like a 20-km scale, which corresponds to a grid resolution on the order of a few kilometers.
This work provides a necessary and sufficient condition for a symbolic dynamical system to admit a sequence of periodic approximations in the Hausdorff topology. The key result proved and applied here uses graphs that are called De Bruijn graphs, Rauzy graphs, or Anderson-Putnam complex, depending on the community. Combining this with a previous result, the present work justifies rigorously the accuracy and reliability of algorithmic methods used to compute numerically the spectra of a large class of self-adjoint operators. The so-called Hamiltonians describe the effective dynamic of a quantum particle in aperiodic media. No restrictions on the structure of these operators other than general regularity assumptions are imposed. In particular, nearest-neighbor correlation is not necessary. Examples for the Fibonacci and the Golay-Rudin-Shapiro sequences are explicitly provided illustrating this discussion. While the first sequence has been thoroughly studied by physicists and mathematicians alike, a shroud of mystery still surrounds the latter when it comes to spectral properties. In light of this, the present paper gives a new result here that might help uncovering a solution.
This thesis bridges two areas of mathematics, algebra on the one hand with the Milnor-Moore theorem (also called Cartier-Quillen-Milnor-Moore theorem) as well as the Poincaré-Birkhoff-Witt theorem, and analysis on the other hand with Shintani zeta functions which generalise multiple zeta functions.
The first part is devoted to an algebraic formulation of the locality principle in physics and generalisations of classification theorems such as Milnor-Moore and Poincaré-Birkhoff-Witt theorems to the locality framework. The locality principle roughly says that events that take place far apart in spacetime do not infuence each other. The algebraic formulation of this principle discussed here is useful when analysing singularities which arise from events located far apart in space, in order to renormalise them while keeping a memory of the fact that they do not influence each other. We start by endowing a vector space with a symmetric relation, named the locality relation, which keeps track of elements that are "locally independent". The pair of a vector space together with such relation is called a pre-locality vector space. This concept is extended to tensor products allowing only tensors made of locally independent elements. We extend this concept to the locality tensor algebra, and locality symmetric algebra of a pre-locality vector space and prove the universal properties of each of such structures. We also introduce the pre-locality Lie algebras, together with their associated locality universal enveloping algebras and prove their universal property. We later upgrade all such structures and results from the pre-locality to the locality context, requiring the locality relation to be compatible with the linear structure of the vector space. This allows us to define locality coalgebras, locality bialgebras, and locality Hopf algebras. Finally, all the previous results are used to prove the locality version of the Milnor-Moore and the Poincaré-Birkhoff-Witt theorems. It is worth noticing that the proofs presented, not only generalise the results in the usual (non-locality) setup, but also often use less tools than their counterparts in their non-locality counterparts.
The second part is devoted to study the polar structure of the Shintani zeta functions. Such functions, which generalise the Riemman zeta function, multiple zeta functions, Mordell-Tornheim zeta functions, among others, are parametrised by matrices with real non-negative arguments. It is known that Shintani zeta functions extend to meromorphic functions with poles on afine hyperplanes. We refine this result in showing that the poles lie on hyperplanes parallel to the facets of certain convex polyhedra associated to the defining matrix for the Shintani zeta function. Explicitly, the latter are the Newton polytopes of the polynomials induced by the columns of the underlying matrix. We then prove that the coeficients of the equation which describes the hyperplanes in the canonical basis are either zero or one, similar to the poles arising when renormalising generic Feynman amplitudes. For that purpose, we introduce an algorithm to distribute weight over a graph such that the weight at each vertex satisfies a given lower bound.
Analysis of protrusion dynamics in amoeboid cell motility by means of regularized contour flows
(2021)
Amoeboid cell motility is essential for a wide range of biological processes including wound healing, embryonic morphogenesis, and cancer metastasis. It relies on complex dynamical patterns of cell shape changes that pose long-standing challenges to mathematical modeling and raise a need for automated and reproducible approaches to extract quantitative morphological features from image sequences. Here, we introduce a theoretical framework and a computational method for obtaining smooth representations of the spatiotemporal contour dynamics from stacks of segmented microscopy images. Based on a Gaussian process regression we propose a one-parameter family of regularized contour flows that allows us to continuously track reference points (virtual markers) between successive cell contours. We use this approach to define a coordinate system on the moving cell boundary and to represent different local geometric quantities in this frame of reference. In particular, we introduce the local marker dispersion as a measure to identify localized membrane expansions and provide a fully automated way to extract the properties of such expansions, including their area and growth time. The methods are available as an open-source software package called AmoePy, a Python-based toolbox for analyzing amoeboid cell motility (based on time-lapse microscopy data), including a graphical user interface and detailed documentation. Due to the mathematical rigor of our framework, we envision it to be of use for the development of novel cell motility models. We mainly use experimental data of the social amoeba Dictyostelium discoideum to illustrate and validate our approach. <br /> Author summary Amoeboid motion is a crawling-like cell migration that plays an important key role in multiple biological processes such as wound healing and cancer metastasis. This type of cell motility results from expanding and simultaneously contracting parts of the cell membrane. From fluorescence images, we obtain a sequence of points, representing the cell membrane, for each time step. By using regression analysis on these sequences, we derive smooth representations, so-called contours, of the membrane. Since the number of measurements is discrete and often limited, the question is raised of how to link consecutive contours with each other. In this work, we present a novel mathematical framework in which these links are described by regularized flows allowing a certain degree of concentration or stretching of neighboring reference points on the same contour. This stretching rate, the so-called local dispersion, is used to identify expansions and contractions of the cell membrane providing a fully automated way of extracting properties of these cell shape changes. We applied our methods to time-lapse microscopy data of the social amoeba Dictyostelium discoideum.
We show how to deduce Rellich inequalities from Hardy inequalities on infinite graphs. Specifically, the obtained Rellich inequality gives an upper bound on a function by the Laplacian of the function in terms of weighted norms. These weights involve the Hardy weight and a function which satisfies an eikonal inequality. The results are proven first for Laplacians and are extended to Schrodinger operators afterwards.
Model-informed precision dosing (MIPD) is a quantitative dosing framework that combines prior knowledge on the drug-disease-patient system with patient data from therapeutic drug/ biomarker monitoring (TDM) to support individualized dosing in ongoing treatment. Structural models and prior parameter distributions used in MIPD approaches typically build on prior clinical trials that involve only a limited number of patients selected according to some exclusion/inclusion criteria. Compared to the prior clinical trial population, the patient population in clinical practice can be expected to also include altered behavior and/or increased interindividual variability, the extent of which, however, is typically unknown. Here, we address the question of how to adapt and refine models on the level of the model parameters to better reflect this real-world diversity. We propose an approach for continued learning across patients during MIPD using a sequential hierarchical Bayesian framework. The approach builds on two stages to separate the update of the individual patient parameters from updating the population parameters. Consequently, it enables continued learning across hospitals or study centers, because only summary patient data (on the level of model parameters) need to be shared, but no individual TDM data. We illustrate this continued learning approach with neutrophil-guided dosing of paclitaxel. The present study constitutes an important step toward building confidence in MIPD and eventually establishing MIPD increasingly in everyday therapeutic use.
We present a supervised learning method to learn the propagator map of a dynamical system from partial and noisy observations. In our computationally cheap and easy-to-implement framework, a neural network consisting of random feature maps is trained sequentially by incoming observations within a data assimilation procedure. By employing Takens's embedding theorem, the network is trained on delay coordinates. We show that the combination of random feature maps and data assimilation, called RAFDA, outperforms standard random feature maps for which the dynamics is learned using batch data.
The superposition operation S-n,S-A, n >= 1, n is an element of N, maps to each (n + 1)-tuple of n-ary operations on a set A an n-ary operation on A and satisfies the so-called superassociative law, a generalization of the associative law. The corresponding algebraic structures are Menger algebras of rank n. A partial algebra of type (n + 1) which satisfies the superassociative law as weak identity is said to be a partial Menger algebra of rank n. As a generalization of linear terms we define r-terms as terms where each variable occurs at most r-times. It will be proved that n-ary r-terms form partial Menger algebras of rank n. In this paper, some algebraic properties of partial Menger algebras such as generating systems, homomorphic images and freeness are investigated. As generalization of hypersubstitutions and linear hypersubstitutions we consider r-hypersubstitutions.U
Purpose The anatomy of the circle of Willis (CoW), the brain's main arterial blood supply system, strongly differs between individuals, resulting in highly variable flow fields and intracranial vascularization patterns. To predict subject-specific hemodynamics with high certainty, we propose a data assimilation (DA) approach that merges fully 4D phase-contrast magnetic resonance imaging (PC-MRI) data with a numerical model in the form of computational fluid dynamics (CFD) simulations. Methods To the best of our knowledge, this study is the first to provide a transient state estimate for the three-dimensional velocity field in a subject-specific CoW geometry using DA. High-resolution velocity state estimates are obtained using the local ensemble transform Kalman filter (LETKF). Results Quantitative evaluation shows a considerable reduction (up to 90%) in the uncertainty of the velocity field state estimate after the data assimilation step. Velocity values in vessel areas that are below the resolution of the PC-MRI data (e.g., in posterior communicating arteries) are provided. Furthermore, the uncertainty of the analysis-based wall shear stress distribution is reduced by a factor of 2 for the data assimilation approach when compared to the CFD model alone. Conclusion This study demonstrates the potential of data assimilation to provide detailed information on vascular flow, and to reduce the uncertainty in such estimates by combining various sources of data in a statistically appropriate fashion.
The Rarita-Schwinger operator is the twisted Dirac operator restricted to 3/2-spinors. Rarita-Schwinger fields are solutions of this operator which are in addition divergence-free. This is an overdetermined problem and solutions are rare; it is even more unexpected for there to be large dimensional spaces of solutions. In this paper we prove the existence of a sequence of compact manifolds in any given dimension greater than or equal to 4 for which the dimension of the space of Rarita-Schwinger fields tends to infinity. These manifolds are either simply connected Kahler-Einstein spin with negative Einstein constant, or products of such spaces with flat tori. Moreover, we construct Calabi-Yau manifolds of even complex dimension with more linearly independent Rarita-Schwinger fields than flat tori of the same dimension.
The estimation of a log-concave density on R is a canonical problem in the area of shape-constrained nonparametric inference. We present a Bayesian nonparametric approach to this problem based on an exponentiated Dirichlet process mixture prior and show that the posterior distribution converges to the log-concave truth at the (near-) minimax rate in Hellinger distance. Our proof proceeds by establishing a general contraction result based on the log-concave maximum likelihood estimator that prevents the need for further metric entropy calculations. We further present computationally more feasible approximations and both an empirical and hierarchical Bayes approach. All priors are illustrated numerically via simulations.
Conventional embeddings of the edge-graphs of Platonic polyhedra, {f,z}, where f,z denote the number of edges in each face and the edge-valence at each vertex, respectively, are untangled in that they can be placed on a sphere (S-2) such that distinct edges do not intersect, analogous to unknotted loops, which allow crossing-free drawings of S-1 on the sphere. The most symmetric (flag-transitive) realizations of those polyhedral graphs are those of the classical Platonic polyhedra, whose symmetries are *2fz, according to Conway's two-dimensional (2D) orbifold notation (equivalent to Schonflies symbols I-h, O-h, and T-d). Tangled Platonic {f,z} polyhedra-which cannot lie on the sphere without edge-crossings-are constructed as windings of helices with three, five, seven,... strands on multigenus surfaces formed by tubifying the edges of conventional Platonic polyhedra, have (chiral) symmetries 2fz (I, O, and T), whose vertices, edges, and faces are symmetrically identical, realized with two flags. The analysis extends to the "theta(z)" polyhedra, {2,z}. The vertices of these symmetric tangled polyhedra overlap with those of the Platonic polyhedra; however, their helicity requires curvilinear (or kinked) edges in all but one case. We show that these 2fz polyhedral tangles are maximally symmetric; more symmetric embeddings are necessarily untangled. On one hand, their topologies are very constrained: They are either self-entangled graphs (analogous to knots) or mutually catenated entangled compound polyhedra (analogous to links). On the other hand, an endless variety of entanglements can be realized for each topology. Simpler examples resemble patterns observed in synthetic organometallic materials and clathrin coats in vivo.
Let M be a compact manifold of dimension n. In this paper, we introduce the Mass Function a >= 0 bar right arrow X-+(M)(a) (resp. a >= 0 bar right arrow X--(M)(a)) which is defined as the supremum (resp. infimum) of the masses of all metrics on M whose Yamabe constant is larger than a and which are flat on a ball of radius 1 and centered at a point p is an element of M. Here, the mass of a metric flat around p is the constant term in the expansion of the Green function of the conformal Laplacian at p. We show that these functions are well defined and have many properties which allow to obtain applications to the Yamabe invariant (i.e. the supremum of Yamabe constants over the set of all metrics on M).
We present a technique for the enumeration of all isotopically distinct ways of tiling a hyperbolic surface of finite genus, possibly nonorientable and with punctures and boundary. This generalizes the enumeration using Delaney--Dress combinatorial tiling theory of combinatorial classes of tilings to isotopy classes of tilings. To accomplish this, we derive an action of the mapping class group of the orbifold associated to the symmetry group of a tiling on the set of tilings. We explicitly give descriptions and presentations of semipure mapping class groups and of tilings as decorations on orbifolds. We apply this enumerative result to generate an array of isotopically distinct tilings of the hyperbolic plane with symmetries generated by rotations that are commensurate with the threedimensional symmetries of the primitive, diamond, and gyroid triply periodic minimal surfaces, which have relevance to a variety of physical systems.
We prove a Feynman path integral formula for the unitary group exp(-itL(nu,theta)), t >= 0, associated with a discrete magnetic Schrodinger operator L-nu,L-theta on a large class of weighted infinite graphs. As a consequence, we get a new Kato-Simon estimate
vertical bar exp(- itL(nu,theta))(x,y)vertical bar <= exp( -tL(-deg,0))(x,y),
which controls the unitary group uniformly in the potentials in terms of a Schrodinger semigroup, where the potential deg is the weighted degree function of the graph.
The canonical trace and the Wodzicki residue on classical pseudo-differential operators on a closed manifold are characterised by their locality and shown to be preserved under lifting to the universal covering as a result of their local feature. As a consequence, we lift a class of spectral zeta-invariants using lifted defect formulae which express discrepancies of zeta-regularised traces in terms of Wodzicki residues. We derive Atiyah's L-2-index theorem as an instance of the Z(2)-graded generalisation of the canonical lift of spectral zeta-invariants and we show that certain lifted spectral zeta-invariants for geometric operators are integrals of Pontryagin and Chern forms.
An explicit Dobrushin uniqueness region for Gibbs point processes with repulsive interactions
(2022)
We present a uniqueness result for Gibbs point processes with interactions that come from a non-negative pair potential; in particular, we provide an explicit uniqueness region in terms of activity z and inverse temperature beta. The technique used relies on applying to the continuous setting the classical Dobrushin criterion. We also present a comparison to the two other uniqueness methods of cluster expansion and disagreement percolation, which can also be applied for this type of interaction.
Interacting particle solutions of Fokker–Planck equations through gradient–log–density estimation
(2020)
Fokker-Planck equations are extensively employed in various scientific fields as they characterise the behaviour of stochastic systems at the level of probability density functions. Although broadly used, they allow for analytical treatment only in limited settings, and often it is inevitable to resort to numerical solutions. Here, we develop a computational approach for simulating the time evolution of Fokker-Planck solutions in terms of a mean field limit of an interacting particle system. The interactions between particles are determined by the gradient of the logarithm of the particle density, approximated here by a novel statistical estimator. The performance of our method shows promising results, with more accurate and less fluctuating statistics compared to direct stochastic simulations of comparable particle number. Taken together, our framework allows for effortless and reliable particle-based simulations of Fokker-Planck equations in low and moderate dimensions. The proposed gradient-log-density estimator is also of independent interest, for example, in the context of optimal control.
In the limit (h) over bar -> 0, we analyze a class of Schrödinger operators H-(h) over bar = (h) over bar L-2 + (h) over barW + V .id(epsilon) acting on sections of a vector bundle epsilon over a Riemannian manifold M where L is a Laplace type operator, W is an endomorphism field and the potential energy V has a non-degenerate minimum at some point p is an element of M. We construct quasimodes of WKB-type near p for eigenfunctions associated with the low-lying eigenvalues of H-(h) over bar. These are obtained from eigenfunctions of the associated harmonic oscillator H-p,H-(h) over bar at p, acting on smooth functions on the tangent space.
Author summary <br /> The use of orally inhaled drugs for treating lung diseases is appealing since they have the potential for lung selectivity, i.e. high exposure at the site of action -the lung- without excessive side effects. However, the degree of lung selectivity depends on a large number of factors, including physiochemical properties of drug molecules, patient disease state, and inhalation devices. To predict the impact of these factors on drug exposure and thereby to understand the characteristics of an optimal drug for inhalation, we develop a predictive mathematical framework (a "pharmacokinetic model"). In contrast to previous approaches, our model allows combining knowledge from different sources appropriately and its predictions were able to adequately predict different sets of clinical data. Finally, we compare the impact of different factors and find that the most important factors are the size of the inhaled particles, the affinity of the drug to the lung tissue, as well as the rate of drug dissolution in the lung. In contrast to the common belief, the solubility of a drug in the lining fluids is not found to be relevant. These findings are important to understand how inhaled drugs should be designed to achieve best treatment results in patients. <br /> The fate of orally inhaled drugs is determined by pulmonary pharmacokinetic processes such as particle deposition, pulmonary drug dissolution, and mucociliary clearance. Even though each single process has been systematically investigated, a quantitative understanding on the interaction of processes remains limited and therefore identifying optimal drug and formulation characteristics for orally inhaled drugs is still challenging. To investigate this complex interplay, the pulmonary processes can be integrated into mathematical models. However, existing modeling attempts considerably simplify these processes or are not systematically evaluated against (clinical) data. In this work, we developed a mathematical framework based on physiologically-structured population equations to integrate all relevant pulmonary processes mechanistically. A tailored numerical resolution strategy was chosen and the mechanistic model was evaluated systematically against data from different clinical studies. Without adapting the mechanistic model or estimating kinetic parameters based on individual study data, the developed model was able to predict simultaneously (i) lung retention profiles of inhaled insoluble particles, (ii) particle size-dependent pharmacokinetics of inhaled monodisperse particles, (iii) pharmacokinetic differences between inhaled fluticasone propionate and budesonide, as well as (iv) pharmacokinetic differences between healthy volunteers and asthmatic patients. Finally, to identify the most impactful optimization criteria for orally inhaled drugs, the developed mechanistic model was applied to investigate the impact of input parameters on both the pulmonary and systemic exposure. Interestingly, the solubility of the inhaled drug did not have any relevant impact on the local and systemic pharmacokinetics. Instead, the pulmonary dissolution rate, the particle size, the tissue affinity, and the systemic clearance were the most impactful potential optimization parameters. In the future, the developed prediction framework should be considered a powerful tool for identifying optimal drug and formulation characteristics.
We extend our approach of asymptotic parametrix construction for Hamiltonian operators from conical to edge-type singularities which is applicable to coalescence points of two particles of the helium atom and related two electron systems including the hydrogen molecule. Up to second-order, we have calculated the symbols of an asymptotic parametrix of the nonrelativistic Hamiltonian of the helium atom within the Born-Oppenheimer approximation and provide explicit formulas for the corresponding Green operators which encode the asymptotic behavior of the eigenfunctions near an edge.
When trying to cast the free fermion in the framework of functorial field theory, its chiral anomaly manifests in the fact that it assigns the determinant of the Dirac operator to a top-dimensional closed spin manifold, which is not a number as expected, but an element of a complex line. In functorial field theory language, this means that the theory is twisted, which gives rise to an anomaly theory. In this paper, we give a detailed construction of this anomaly theory, as a functor that sends manifolds to infinite-dimensional Clifford algebras and bordisms to bimodules.
We consider rough metrics on smooth manifolds and corresponding Laplacians induced by such metrics. We demonstrate that globally continuous heat kernels exist and are Holder continuous locally in space and time. This is done via local parabolic Harnack estimates for weak solutions of operators in divergence form with bounded measurable coefficients in weighted Sobolev spaces.
In this paper, we develop the mathematical tools needed to explore isotopy classes of tilings on hyperbolic surfaces of finite genus, possibly nonorientable, with boundary, and punctured. More specifically, we generalize results on Delaney-Dress combinatorial tiling theory using an extension of mapping class groups to orbifolds, in turn using this to study tilings of covering spaces of orbifolds. Moreover, we study finite subgroups of these mapping class groups. Our results can be used to extend the Delaney-Dress combinatorial encoding of a tiling to yield a finite symbol encoding the complexity of an isotopy class of tilings. The results of this paper provide the basis for a complete and unambiguous enumeration of isotopically distinct tilings of hyperbolic surfaces.
This paper further improves the Lie group method with Magnus expansion proposed in a previous paper by the authors, to solve some types of direct singular Sturm-Liouville problems. Next, a concrete implementation to the inverse Sturm-Liouville problem algorithm proposed by Barcilon (1974) is provided. Furthermore, computational feasibility and applicability of this algorithm to solve inverse Sturm-Liouville problems of higher order (for n=2,4) are verified successfully. It is observed that the method is successful even in the presence of significant noise, provided that the assumptions of the algorithm are satisfied. In conclusion, this work provides a method that can be adapted successfully for solving a direct (regular/singular) or inverse Sturm-Liouville problem (SLP) of an arbitrary order with arbitrary boundary conditions.
LetH be a Schrodinger operator defined on a noncompact Riemannianmanifold Omega, and let W is an element of L-infinity (Omega; R). Suppose that the operator H + W is critical in Omega, and let phi be the corresponding Agmon ground state. We prove that if u is a generalized eigenfunction ofH satisfying vertical bar u vertical bar <= C-phi in Omega for some constant C > 0, then the corresponding eigenvalue is in the spectrum of H. The conclusion also holds true if for some K is an element of Omega the operator H admits a positive solution in (Omega) over bar = Omega \ K, and vertical bar u vertical bar <= C psi in (Omega) over bar for some constant C > 0, where psi is a positive solution of minimal growth in a neighborhood of infinity in Omega. Under natural assumptions, this result holds also in the context of infinite graphs, and Dirichlet forms.