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In 1914 Bohr proved that there is an r ∈ (0, 1) such that if a power series converges in the unit disk and its sum has modulus less than 1 then, for |z| < r, the sum of absolute values of its terms is again less than 1. Recently analogous results were obtained for functions of several variables. The aim of this paper is to comprehend the theorem of Bohr in the context of solutions to second order elliptic equations meeting the maximum principle.
The paper is devoted to pseudodifferential boundary value problems in domains with singular points on the boundary. The tangent cone at a singular point is allowed to degenerate. In particular, the boundary may rotate and oscillate in a neighbourhood of such a point. We show a criterion for the Fredholm property of a boundary value problem and derive estimates of solutions close to singular points.
We consider a class of ergodic Hamilton-Jacobi-Bellman (HJB) equations, related to large time asymptotics of non-smooth multiplicative functional of difusion processes. Under suitable ergodicity assumptions on the underlying difusion, we show existence of these asymptotics, and that they solve the related HJB equation in the viscosity sense.
For each compact subset K of the complex plane C which does not surround zero, the Riemann surface Sζ of the Riemann zeta function restricted to the critical half-strip 0 < Rs < 1/2 contains infinitely many schlicht copies of K lying ‘over’ K. If Sζ also contains at least one such copy, for some K which surrounds zero, then the Riemann hypothesis fails.
A function has vanishing mean oscillation (VMO) on R up(n) if its mean oscillation - the local average of its pointwise deviation from its mean value - both is uniformly bounded over all cubes within R up(n) and converges to zero with the volume of the cube. The more restrictive class of functions with vanishing lower oscillation (VLO) arises when the mean value is replaced by the minimum value in this definition. It is shown here that each VMO function is the difference of two functions in VLO.
We show a Lefschetz fixed point formula for holomorphic functions in a bounded domain D with smooth boundary in the complex plane. To introduce the Lefschetz number for a holomorphic map of D, we make use of the Bergman kernal of this domain. The Lefschetz number is proved to be the sum of usual contributions of fixed points of the map in D and contributions of boundary fixed points, these latter being different for attracting and repulsing fixed points.
We elaborate a boundary Fourier method for studying an analogue of the Hilbert problem for analytic functions within the framework of generalised Cauchy-Riemann equations. The boundary value problem need not satisfy the Shapiro-Lopatinskij condition and so it fails to be Fredholm in Sobolev spaces. We show a solvability condition of the Hilbert problem, which looks like those for ill-posed
problems, and construct an explicit formula for approximate solutions.
We are interested in modeling some two-level population dynamics, resulting from the interplay of ecological interactions and phenotypic variation of individuals (or hosts) and the evolution of cells (or parasites) of two types living in these individuals. The ecological parameters of the individual dynamics depend on the number of cells of each type contained by the individual and the cell dynamics depends on the trait of the invaded individual. Our models are rooted in the microscopic description of a random (discrete) population of individuals characterized by one or several adaptive traits and cells characterized by their type. The population is modeled as a stochastic point process whose generator captures the probabilistic dynamics over continuous time of birth, mutation and death for individuals and birth and death for cells. The interaction between individuals (resp. between cells) is described by a competition between individual traits (resp. between cell types). We look for tractable large population approximations. By combining various scalings on population size, birth and death rates and mutation step, the single microscopic model is shown to lead to contrasting nonlinear macroscopic limits of different nature: deterministic approximations, in the form of ordinary, integro- or partial differential equations, or probabilistic ones, like stochastic partial differential equations or superprocesses. The study of the long time behavior of these processes seems very hard and we only develop some simple cases enlightening the difficulties involved.
In a recent paper with N. Tarkhanov, the Lefschetz number for endomorphisms (modulo trace class operators) of sequences of trace class curvature was introduced. We show that this is a well defined, canonical extension of the classical Lefschetz number and establish the homotopy invariance of this number. Moreover, we apply the results to show that the Lefschetz fixed point formula holds for geometric quasiendomorphisms of elliptic quasicomplexes.
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.
This thesis focuses on the study of marked Gibbs point processes, in particular presenting some results on their existence and uniqueness, with ideas and techniques drawn from different areas of statistical mechanics: the entropy method from large deviations theory, cluster expansion and the Kirkwood--Salsburg equations, the Dobrushin contraction principle and disagreement percolation.
We first present an existence result for infinite-volume marked Gibbs point processes. More precisely, we use the so-called entropy method (and large-deviation tools) to construct marked Gibbs point processes in R^d under quite general assumptions. In particular, the random marks belong to a general normed space S and are not bounded. Moreover, we allow for interaction functionals that may be unbounded and whose range is finite but random. The entropy method relies on showing that a family of finite-volume Gibbs point processes belongs to sequentially compact entropy level sets, and is therefore tight.
We then present infinite-dimensional Langevin diffusions, that we put in interaction via a Gibbsian description. In this setting, we are able to adapt the general result above to show the existence of the associated infinite-volume measure. We also study its correlation functions via cluster expansion techniques, and obtain the uniqueness of the Gibbs process for all inverse temperatures β and activities z below a certain threshold. This method relies in first showing that the correlation functions of the process satisfy a so-called Ruelle bound, and then using it to solve a fixed point problem in an appropriate Banach space. The uniqueness domain we obtain consists then of the model parameters z and β for which such a problem has exactly one solution.
Finally, we explore further the question of uniqueness of infinite-volume Gibbs point processes on R^d, in the unmarked setting. We present, in the context of repulsive interactions with a hard-core component, a novel approach to uniqueness by applying the discrete Dobrushin criterion to the continuum framework. We first fix a discretisation parameter a>0 and then study the behaviour of the uniqueness domain as a goes to 0. With this technique we are able to obtain explicit thresholds for the parameters z and β, which we then compare to existing results coming from the different methods of cluster expansion and disagreement percolation.
Throughout this thesis, we illustrate our theoretical results with various examples both from classical statistical mechanics and stochastic geometry.
We consider a Cauchy problem for the heat equation in a cylinder X x (0,T) over a domain X in the n-dimensional space with data on a strip lying on the lateral surface. The strip is of the form
S x (0,T), where S is an open subset of the boundary of X. The problem is ill-posed. Under natural restrictions on the configuration of S we derive an explicit formula for solutions of this problem.
We consider the problem of testing whether the density of a mul- tivariate random variable can be expressed by a prespecified copula function and the marginal densities. The proposed test procedure is based on the asymptotic normality of the properly standardized integrated squared distance between a multivariate kernel density estimator and an estimator of its expectation under the hypothesis. The test of independence is a special case of this approach.
We reconsider the fundamental work of Fichtner ([2]) and exhibit the permanental structure of the ideal Bose gas again, using another approach which combines a characterization of infinitely divisible random measures (due to Kerstan,Kummer and Matthes [5, 6] and Mecke [8, 9]) with a decomposition of the moment measures into its factorial measures due to Krickeberg [4]. To be more precise, we exhibit the moment measures of all orders of the general ideal Bose gas in terms of certain path integrals. This representation can be considered as a point process analogue of the old idea of Symanzik [11] that local times and self-crossings of the Brownian motion can be used as a tool in quantum field theory. Behind the notion of a general ideal Bose gas there is a class of infinitely divisible point processes of all orders with a Levy-measure belonging to some large class of measures containing the one of the classical ideal Bose gas considered by Fichtner. It is well known that the calculation of moments of higher order of point processes are notoriously complicated. See for instance Krickeberg's calculations for the Poisson or the Cox process in [4].
Transport Molecules play a crucial role for cell viability. Amongst others, linear motors transport cargos along rope-like structures from one location of the cell to another in a stochastic fashion. Thereby each step of the motor, either forwards or backwards, bridges a fixed distance. While moving along the rope the motor can also detach and is lost. We give here a mathematical formalization of such dynamics as a random process which is an extension of Random Walks, to which we add an absorbing state to model the detachment of the motor from the rope. We derive particular properties of such processes that have not been available before. Our results include description of the maximal distance reached from the starting point and the position from which detachment takes place. Finally, we apply our theoretical results to a concrete established model of the transport molecule Kinesin V.
Let A be a nonlinear differential operator on an open set X in R^n and S a closed subset of X. Given a class F of functions in X, the set S is said to be removable for F relative to A if any weak solution of A (u) = 0 in the complement of S of class F satisfies this equation weakly in all of X. For the most extensively studied classes F we show conditions on S which guarantee that S is removable for F relative to A.
We introduce a natural symmetry condition for a pseudodifferential operator on a manifold with cylindrical ends ensuring that the operator admits a doubling across the boundary. For such operators we prove an explicit index formula containing, apart from the Atiyah-Singer integral, a finite number of residues of the logarithmic derivative of the conormal symbol.
In a bounded domain with smooth boundary in R^3 we consider the stationary Maxwell equations
for a function u with values in R^3 subject to a nonhomogeneous condition
(u,v)_x = u_0 on
the boundary, where v is a given vector field and u_0 a function on the boundary. We specify this problem within the framework of the Riemann-Hilbert boundary value problems for the Moisil-Teodorescu system. This latter is proved to satisfy the Shapiro-Lopaniskij condition if an only if the vector v is at no point tangent to the boundary. The Riemann-Hilbert problem for the Moisil-Teodorescu system fails to possess an adjoint boundary value problem with respect to the Green formula, which satisfies the Shapiro-Lopatinskij condition. We develop the construction of Green formula to get a proper concept of adjoint boundary value problem.
The Riemann hypothesis is equivalent to the fact the the reciprocal function 1/zeta (s) extends from the interval (1/2,1) to an analytic function in the quarter-strip 1/2 < Re s < 1 and Im s > 0. Function theory allows one to rewrite the condition of analytic continuability in an elegant form amenable to numerical experiments.
The zero-noise limit of differential equations with singular coefficients is investigated for the first time in the case when the noise is a general alpha-stable process. It is proved that extremal solutions are selected and the probability of selection is computed. Detailed analysis of the characteristic function of an exit time form on the half-line is performed, with a suitable decomposition in small and large jumps adapted to the singular drift.
Adiabatic vacuum states are a well-known class of physical states for linear quantum fields n Robertson-Walker spacetimes. We extend the definition of adiabatic vacua to general spacetime manifolds by using the notion of the Sobolev wavefront set. This definition is also applicable to interacting field theories. Hadamard states form a special subclass of the adiabatic vacua. We analyze physical properties of adiabatic vacuum representations of the Klein-Gordon field on globally hyperbolic spacetme manifolds (factoriality, quasiequivalence, local definteness, Haag duality) and construct them explicitly, if the manifold has a compact Cauchy surface.
In the limit we analyze the generators of families of reversible jump processes in the n-dimensional space associated with a class of symmetric non-local Dirichlet forms and show exponential decay of the eigenfunctions. The exponential rate function is a Finsler distance, given as solution of certain eikonal equation. Fine results are sensitive to the rate functions being twice differentiable or just Lipschitz. Our estimates are similar to the semiclassical Agmon estimates for differential operators of second order. They generalize and strengthen previous results on the lattice.
We construct an algebra of pseudo-differential boundary value problems that contains the classical Shapiro-Lopatinskij elliptic problems as well as all differential elliptic problems of Dirac type with APS boundary conditions, together with their parametrices. Global pseudo-differential projections on the boundary are used to define ellipticity and to show the Fredholm property in suitable scales of spaces.
Operators on manifolds with corners that have base configurations with geometric singularities can be analysed in the frame of a conormal symbolic structure which is in spirit similar to the one for conical singularities of Kondrat'ev's work. Solvability of elliptic equations and asymptotics of solutions are determined by meromorphic conormal symbols. We study the case when the base has edge singularities which is a natural assumption in a number of applications. There are new phenomena, caused by a specific kind of higher degeneracy of the underlying symbols. We introduce an algebra of meromorphic edge operators that depend on complex parameters and investigate meromorphic inverses in the parameter-dependent elliptic case. Among the examples are resolvents of elliptic differential operators on manifolds with edges.
We prove in this paper an existence result for infinite-dimensional stationary interactive Brownian diffusions. The interaction is supposed to be small in the norm ||.||∞ but otherwise is very general, being possibly non-regular and non-Markovian. Our method consists in using the characterization of such diffusions as space-time Gibbs fields so that we construct them by space-time cluster expansions in the small coupling parameter.
These lecture notes are intended as a short introduction to diffusion processes on a domain with a reflecting boundary for graduate students, researchers in stochastic analysis and interested readers. Specific results on stochastic differential equations with reflecting boundaries such as existence and uniqueness, continuity and Markov properties, relation to partial differential equations and submartingale problems are given. An extensive list of references to current literature is included. This book has its origins in a mini-course the author gave at the University of Potsdam and at the Technical University of Berlin in Winter 2013.
We establish elements of a new approach to ellipticity and parametrices within operator algebras on manifolds with higher singularities, only based on some general axiomatic requirements on parameter-dependent operators in suitable scales of spaes. The idea is to model an iterative process with new generations of parameter-dependent operator theories, together with new scales of spaces that satisfy analogous requirements as the original ones, now on a corresponding higher level. The "full" calculus involves two separate theories, one near the tip of the corner and another one at the conical exit to infinity. However, concerning the conical exit to infinity, we establish here a new concrete calculus of edge-degenerate operators which can be iterated to higher singularities.
We consider the Navier-Stokes equations in the layer R^n x [0,T] over R^n with finite T > 0. Using the standard fundamental solutions of the Laplace operator and the heat operator, we reduce the Navier-Stokes equations to a nonlinear Fredholm equation of the form (I+K) u = f, where K is a compact continuous operator in anisotropic normed Hölder spaces weighted at the point at infinity with respect to the space variables. Actually, the weight function is included to provide a finite energy estimate for solutions to the Navier-Stokes equations for all t in [0,T]. On using the particular properties of the de Rham complex we conclude that the Fréchet derivative (I+K)' is continuously invertible at each point of the Banach space under consideration and the map I+K is open and injective in the space. In this way the Navier-Stokes equations prove to induce an open one-to-one mapping in the scale of Hölder spaces.
Students of computer science studies enter university education with very different competencies, experience and knowledge. 145 datasets collected of freshmen computer science students by learning management systems in relation to exam outcomes and learning dispositions data (e. g. student dispositions, previous experiences and attitudes measured through self-reported surveys) has been exploited to identify indicators as predictors of academic success and hence make effective interventions to deal with an extremely heterogeneous group of students.
Concurrent observation technologies have made high-precision real-time data available in large quantities. Data assimilation (DA) is concerned with how to combine this data with physical models to produce accurate predictions. For spatial-temporal models, the ensemble Kalman filter with proper localisation techniques is considered to be a state-of-the-art DA methodology. This article proposes and investigates a localised ensemble Kalman Bucy filter for nonlinear models with short-range interactions. We derive dimension-independent and component-wise error bounds and show the long time path-wise error only has logarithmic dependence on the time range. The theoretical results are verified through some simple numerical tests.
We prove a theorem on analytic representation of integrable CR functions on hypersurfaces with singular points. Moreover, the behaviour of representing analytic functions near singular points is investigated. We are aimed at explaining the new effect caused by the presence of a singularity rather than at treating the problem in full generality.
Anisotropic edge problems
(2002)
We investigate elliptic pseudodifferential operators which degenerate in an anisotropic way on a submanifold of arbitrary codimension. To find Fredholm problems for such operators we adjoint to them boundary and coboundary conditions on the submanifold.The algebra obtained this way is a far reaching generalisation of Boutet de Monvel's algebra of boundary value problems with transmission property. We construct left and right regularisers and prove theorems on hypoellipticity and local solvability.
Since 1971, the Freudenthal Institute has developed an approach to mathematics education named Realistic Mathematics Education (RME). The philosophy of RME is based on Hans Freudenthal’s concept of ‘mathematics as a human activity’. Prof. Hans Freudenthal (1905-1990), a mathematician and educator, believes that ‘ready-made mathematics’ should not be taught in school. By contrast, he urges that students should be offered ‘realistic situations’ so that they can rediscover from informal to formal mathematics. Although mathematics education in Vietnam has some achievements, it still encounters several challenges. Recently, the reform of teaching methods has become an urgent task in Vietnam. It appears that Vietnamese mathematics education lacks necessary theoretical frameworks. At first sight, the philosophy of RME is suitable for the orientation of the teaching method reform in Vietnam. However, the potential of RME for mathematics education as well as the ability of applying RME to teaching mathematics is still questionable in Vietnam. The primary aim of this dissertation is to research into abilities of applying RME to teaching and learning mathematics in Vietnam and to answer the question “how could RME enrich Vietnamese mathematics education?”. This research will emphasize teaching geometry in Vietnamese middle school. More specifically, the dissertation will implement the following research tasks: • Analyzing the characteristics of Vietnamese mathematics education in the ‘reformed’ period (from the early 1980s to the early 2000s) and at present; • Implementing a survey of 152 middle school teachers’ ideas from several Vietnamese provinces and cities about Vietnamese mathematics education; • Analyzing RME, including Freudenthal’s viewpoints for RME and the characteristics of RME; • Discussing how to design RME-based lessons and how to apply these lessons to teaching and learning in Vietnam; • Experimenting RME-based lessons in a Vietnamese middle school; • Analyzing the feedback from the students’ worksheets and the teachers’ reports, including the potentials of RME-based lessons for Vietnamese middle school and the difficulties the teachers and their students encountered with RME-based lessons; • Discussing proposals for applying RME-based lessons to teaching and learning mathematics in Vietnam, including making suggestions for teachers who will apply these lessons to their teaching and designing courses for in-service teachers and teachers-in training. This research reveals that although teachers and students may encounter some obstacles while teaching and learning with RME-based lesson, RME could become a potential approach for mathematics education and could be effectively applied to teaching and learning mathematics in Vietnamese school.
The overall program "arborescent numbers" is to similarly perform the constructions from the natural numbers (N) to the positive fractional numbers (Q+) to positive real numbers (R+) beginning with (specific) binary trees instead of natural numbers. N can be regarded as the associative binary trees. The binary trees B and the left-commutative binary trees P allow the hassle-free definition of arbitrary high arithmetic operations (hyper ... hyperpowers). To construct the division trees the algebraic structure "coppice" is introduced which is a group with an addition over which the multiplication is right-distributive. Q+ is the initial associative coppice. The present work accomplishes one step in the program "arborescent numbers". That is the construction of the arborescent equivalent(s) of the positive fractional numbers. These equivalents are the "division binary trees" and the "fractional trees". A representation with decidable word problem for each of them is given. The set of functions f:R1->R1 generated from identity by taking powers is isomorphic to P and can be embedded into a coppice by taking inverses.
Asymptotic algebras
(2001)
In this paper, a global existence result of smooth solutions to the multidimen- sional nonisentropic hydrodynamic model for semiconductors is proved, under the assumption that the initial data is a perturbation of the stationary solutions for the thermal equilibrium state. The resulting evolutionary solutions converge to the stationary solutions in time asymptotically exponentially fast.
It is shown that bounded solutions to semilinear elliptic Fuchsian equations obey complete asymptoic expansions in terms of powers and logarithms in the distance to the boundary. For that purpose, Schuze's notion of asymptotic type for conormal asymptotics close to a conical point is refined. This in turn allows to perform explicit calculations on asymptotic types - modulo the resolution of the spectral problem for determining the singular exponents in the asmptotic expansions.
We study the asymptotic regularity of solutions of Hartree-Fock equations for Coulomb systems. In order to deal with singular Coulomb potentials, Fock operators are discussed within the calculus of pseudo-differential operators on conical manifolds. First, the non-self-consistent-field case is considered which means that the functions that enter into the nonlinear terms are not the eigenfunctions of the Fock operator itself. We introduce asymptotic regularity conditions on the functions that build up the Fock operator which guarantee ellipticity for the local part of the Fock operator on the open stretched cone R+ × S². This proves existence of a parametrix with a corresponding smoothing remainder from which it follows, via a bootstrap argument, that the eigenfunctions of the Fock operator again satisfy asymptotic regularity conditions. Using a fixed-point approach based on Cances and Le Bris analysis of the level-shifting algorithm, we show via another bootstrap argument, that the corresponding self-consistent-field solutions of the Hartree-Fock equation have the same type of asymptotic regularity.
Asymptotic solutions of the Dirichlet problem for the heat equation at a characteristic point
(2012)
The Dirichlet problem for the heat equation in a bounded domain is characteristic, for there are boundary points at which the boundary touches a characteristic hyperplane t = c, c being a constant. It was I.G. Petrovskii (1934) who first found necessary and sufficient conditions on the boundary which guarantee that the solution is continuous up to the characteristic point, provided that the Dirichlet data are continuous. This paper initiated standing interest in studying general boundary value problems for parabolic equations in bounded domains. We contribute to the study by constructing a formal solution of the Dirichlet problem for the heat equation in a neighbourhood of a characteristic boundary point and showing its asymptotic character.
We analyze the asymptotic behavior in the limit epsilon to zero for a wide class of difference operators H_epsilon = T_epsilon + V_epsilon with underlying multi-well potential. They act on the square summable functions on the lattice (epsilon Z)^d. We start showing the validity of an harmonic approximation and construct WKB-solutions at the wells. Then we construct a Finslerian distance d induced by H and show that short integral curves are geodesics and d gives the rate for the exponential decay of Dirichlet eigenfunctions. In terms of this distance, we give sharp estimates for the interaction between the wells and construct the interaction matrix.
We study pseudodifferential operators on a cylinder IR x B with cross section B that conical singularities. Configurations of that kind are the local model of cornere singularities with base spaces B. Operators A in our calculus are assumed to have symbols α which are meromorphic in the complex covariable with values in the space of all cone operators on B. In case α is dependent of the axial variable t ∈ IR, we show an explicit formula for solutions of the homogeneous equation. Each non-bjectivity point of the symbol in the complex plane corresponds to a finite-dimensional space of solutions. Moreover, we give a relative index formula.
Boundary value problems on manifolds with conical singularities or edges contain potential operators as well as trace and Green operators which play a similar role as the corresponding operators in (pseudo-differential) boundary value problems on a smooth manifold. There is then a specific asymptotic behaviour of these operators close to the singularities. We characterise potential operators in terms of actions of cone or edge pseudo-differential operators (in the neighbouring space) on densities supported by sbmanifolds which also have conical or edge singularities. As a byproduct we show the continuity of such potentials as continuous perators between cone or edge Sobolev spaces and subspaces with asymptotics.
We consider an SDE driven by a Lévy noise on a foliated manifold, whose trajectories stay on compact leaves. We determine the effective behavior of the system subject to a small smooth transversal perturbation of positive order epsilon. More precisely, we show that the average of the transversal component of the SDE converges to the solution of a deterministic ODE, according to the average of the perturbing vector field with respect to the invariant measures on the leaves (of the unpertubed system) as epsilon goes to 0. In particular we give upper bounds for the rates of convergence. The main results which are proved for pure jump Lévy processes complement the result by Gargate and Ruffino for Stratonovich SDEs to Lévy driven SDEs of Marcus type.
While patients are known to respond differently to drug therapies, current clinical practice often still follows a standardized dosage regimen for all patients. For drugs with a narrow range of both effective and safe concentrations, this approach may lead to a high incidence of adverse events or subtherapeutic dosing in the presence of high patient variability. Model-informedprecision dosing (MIPD) is a quantitative approach towards dose individualization based on mathematical modeling of dose-response relationships integrating therapeutic drug/biomarker monitoring (TDM) data. MIPD may considerably improve the efficacy and safety of many drug therapies. Current MIPD approaches, however, rely either on pre-calculated dosing tables or on simple point predictions of the therapy outcome. These
approaches lack a quantification of uncertainties and the ability to account for effects that are delayed. In addition, the underlying models are not improved while applied to patient data. Therefore, current approaches are not well suited for informed clinical decision-making based on a differentiated understanding of the individually predicted therapy outcome.
The objective of this thesis is to develop mathematical approaches for MIPD, which (i) provide efficient fully Bayesian forecasting of the individual therapy outcome including associated uncertainties, (ii) integrate Markov decision processes via reinforcement learning (RL) for a comprehensive decision framework for dose individualization, (iii) allow for continuous learning across patients and hospitals. Cytotoxic anticancer chemotherapy with its major dose-limiting toxicity, neutropenia, serves as a therapeutically relevant application example.
For more comprehensive therapy forecasting, we apply Bayesian data assimilation (DA) approaches, integrating patient-specific TDM data into mathematical models of chemotherapy-induced neutropenia that build on prior population analyses. The value of uncertainty quantification is demonstrated as it allows reliable computation of the patient-specific probabilities of relevant clinical quantities, e.g., the neutropenia grade. In view of novel home monitoring devices that increase the amount of TDM data available, the data processing of
sequential DA methods proves to be more efficient and facilitates handling of the variability between dosing events.
By transferring concepts from DA and RL we develop novel approaches for MIPD. While DA-guided dosing integrates individualized uncertainties into dose selection, RL-guided dosing provides a framework to consider delayed effects of dose selections. The combined
DA-RL approach takes into account both aspects simultaneously and thus represents a holistic approach towards MIPD. Additionally, we show that RL can be used to gain insights into important patient characteristics for dose selection. The novel dosing strategies substantially reduce the occurrence of both subtherapeutic and life-threatening neutropenia grades in a simulation study based on a recent clinical study (CEPAC-TDM trial) compared to currently used MIPD approaches.
If MIPD is to be implemented in routine clinical practice, a certain model bias with respect to the underlying model is inevitable, as the models are typically based on data from comparably small clinical trials that reflect only to a limited extent the diversity in real-world patient populations. We propose a sequential hierarchical Bayesian inference framework that enables continuous cross-patient learning to learn the underlying model parameters of the target patient population. It is important to note that the approach only requires summary information of the individual patient data to update the model. This separation of the individual inference from population inference enables implementation across different centers of care.
The proposed approaches substantially improve current MIPD approaches, taking into account new trends in health care and aspects of practical applicability. They enable progress towards more informed clinical decision-making, ultimately increasing patient benefits beyond the current practice.
Point processes are a common methodology to model sets of events. From earthquakes to social media posts, from the arrival times of neuronal spikes to the timing of crimes, from stock prices to disease spreading -- these phenomena can be reduced to the occurrences of events concentrated in points. Often, these events happen one after the other defining a time--series.
Models of point processes can be used to deepen our understanding of such events and for classification and prediction. Such models include an underlying random process that generates the events. This work uses Bayesian methodology to infer the underlying generative process from observed data. Our contribution is twofold -- we develop new models and new inference methods for these processes.
We propose a model that extends the family of point processes where the occurrence of an event depends on the previous events. This family is known as Hawkes processes. Whereas in most existing models of such processes, past events are assumed to have only an excitatory effect on future events, we focus on the newly developed nonlinear Hawkes process, where past events could have excitatory and inhibitory effects. After defining the model, we present its inference method and apply it to data from different fields, among others, to neuronal activity.
The second model described in the thesis concerns a specific instance of point processes --- the decision process underlying human gaze control. This process results in a series of fixated locations in an image. We developed a new model to describe this process, motivated by the known Exploration--Exploitation dilemma. Alongside the model, we present a Bayesian inference algorithm to infer the model parameters.
Remaining in the realm of human scene viewing, we identify the lack of best practices for Bayesian inference in this field. We survey four popular algorithms and compare their performances for parameter inference in two scan path models.
The novel models and inference algorithms presented in this dissertation enrich the understanding of point process data and allow us to uncover meaningful insights.
The aim of this paper is to bring together two areas which are of great importance for the study of overdetermined boundary value problems. The first area is homological algebra which is the main tool in constructing the formal theory of overdetermined problems. And the second area is the global calculus of pseudodifferential operators which allows one to develop explicit analysis.
We study boundary value problems for linear elliptic differential operators of order one. The underlying manifold may be noncompact, but the boundary is assumed to be compact. We require a symmetry property of the principal symbol of the operator along the boundary. This is satisfied by Dirac type operators, for instance. We provide a selfcontained introduction to (nonlocal) elliptic boundary conditions, boundary regularity of solutions, and index theory. In particular, we simplify and generalize the traditional theory of elliptic boundary value problems for Dirac type operators. We also prove a related decomposition theorem, a general version of Gromov and Lawson's relative index theorem and a generalization of the cobordism theorem.
The index theorem for elliptic operators on a closed Riemannian manifold by Atiyah and Singer has many applications in analysis, geometry and topology, but it is not suitable for a generalization to a Lorentzian setting.
In the case where a boundary is present Atiyah, Patodi and Singer provide an index theorem for compact Riemannian manifolds by introducing non-local boundary conditions obtained via the spectral decomposition of an induced boundary operator, so called APS boundary conditions. Bär and Strohmaier prove a Lorentzian version of this index theorem for the Dirac operator on a manifold with boundary by utilizing results from APS and the characterization of the spectral flow by Phillips. In their case the Lorentzian manifold is assumed to be globally hyperbolic and spatially compact, and the induced boundary operator is given by the Riemannian Dirac operator on a spacelike Cauchy hypersurface. Their results show that imposing APS boundary conditions for these boundary operator will yield a Fredholm operator with a smooth kernel and its index can be calculated by a formula similar to the Riemannian case.
Back in the Riemannian setting, Bär and Ballmann provide an analysis of the most general kind of boundary conditions that can be imposed on a first order elliptic differential operator that will still yield regularity for solutions as well as Fredholm property for the resulting operator. These boundary conditions can be thought of as deformations to the graph of a suitable operator mapping APS boundary conditions to their orthogonal complement.
This thesis aims at applying the boundary conditions found by Bär and Ballmann to a Lorentzian setting to understand more general types of boundary conditions for the Dirac operator, conserving Fredholm property as well as providing regularity results and relative index formulas for the resulting operators. As it turns out, there are some differences in applying these graph-type boundary conditions to the Lorentzian Dirac operator when compared to the Riemannian setting. It will be shown that in contrast to the Riemannian case, going from a Fredholm boundary condition to its orthogonal complement works out fine in the Lorentzian setting. On the other hand, in order to deduce Fredholm property and regularity of solutions for graph-type boundary conditions, additional assumptions for the deformation maps need to be made.
The thesis is organized as follows. In chapter 1 basic facts about Lorentzian and Riemannian spin manifolds, their spinor bundles and the Dirac operator are listed. These will serve as a foundation to define the setting and prove the results of later chapters.
Chapter 2 defines the general notion of boundary conditions for the Dirac operator used in this thesis and introduces the APS boundary conditions as well as their graph type deformations. Also the role of the wave evolution operator in finding Fredholm boundary conditions is analyzed and these boundary conditions are connected to notion of Fredholm pairs in a given Hilbert space.
Chapter 3 focuses on the principal symbol calculation of the wave evolution operator and the results are used to proof Fredholm property as well as regularity of solutions for suitable graph-type boundary conditions. Also sufficient conditions are derived for (pseudo-)local boundary conditions imposed on the Dirac operator to yield a Fredholm operator with a smooth solution space.
In the last chapter 4, a few examples of boundary conditions are calculated applying the results of previous chapters. Restricting to special geometries and/or boundary conditions, results can be obtained that are not covered by the more general statements, and it is shown that so-called transmission conditions behave very differently than in the Riemannian setting.
The paper is devoted to pseudodifferential boundary value problems in domains with cuspidal wedges. Concerning the geometry we even admit a more general behaviour, namely oscillating cuspidal wedges. We show a criterion for the Fredholm property of a boundary value problem and derive estimates of solutions close to edges.
Edge representations of operators on closed manifolds are known to induce large classes of operators that are elliptic on specific manifolds with edges, cf. [9]. We apply this idea to the case of boundary value problems. We establish a correspondence between standard ellipticity and ellipticity with respect to the principal symbolic hierarchy of the edge algebra of boundary value problems, where an embedded submanifold on the boundary plays the role of an edge. We first consider the case that the weight is equal to the smoothness and calculate the dimensions of kernels and cokernels of the associated principal edge symbols. Then we pass to elliptic edge operators for arbitrary weights and construct the additional edge conditions by applying relative index results for conormal symbols.
We study elliptic boundary value problems in a wedge with additional edge conditions of trace and potential type. We compute the (difference of the) number of such conditions in terms of the Fredholm index of the principal edge symbol. The task will be reduced to the case of special opening angles, together with a homotopy argument.
We construct a new calculus of boundary value problems with the transmission property on a non-compact smooth manifold with boundary and conical exits to infinity. The symbols are classical both in covariables and variables. The operators are determined by principal symbol tuples modulo operators of lower orders and weights (such remainders are compact in weighted Sobolev spaces). We develop the concept of ellipticity, construct parametrices within the algebra and obtain the Fredholm property. For the existence of Shapiro-Lopatinskij elliptic boundary conditions to a given elliptic operator we prove an analogue of the Atiyah-Bott condition.
In the thesis there are constructed new quantizations for pseudo-differential boundary value problems (BVPs) on manifolds with edge. The shape of operators comes from Boutet de Monvel’s calculus which exists on smooth manifolds with boundary. The singular case, here with edge and boundary, is much more complicated. The present approach simplifies the operator-valued symbolic structures by using suitable Mellin quantizations on infinite stretched model cones of wedges with boundary. The Mellin symbols themselves are, modulo smoothing ones, with asymptotics, holomorphic in the complex Mellin covariable. One of the main results is the construction of parametrices of elliptic elements in the corresponding operator algebra, including elliptic edge conditions.
We give a survey on the calculus of (pseudo-differential) boundary value problems with the transmision property at the boundary, and ellipticity in the Shapiro-Lopatinskij sense. Apart from the original results of the work of Boutet de Monvel we present an approach based on the ideas of the edge calculus. In a final section we introduce symbols with the anti-transmission property.
We describe a new algebra of boundary value problems which contains Lopatinskii elliptic as well as Toeplitz type conditions. These latter are necessary, if an analogue of the Atiyah-Bott obstruction does not vanish. Every elliptic operator is proved to admit up to a stabilisation elliptic conditions of such a kind. Corresponding boundary value problems are then Fredholm in adequate scales of spaces. The crucial novelty consists of the new type of weighted Sobolev spaces which serve as domains of pseudodifferential operators and which fit well to the nature of operators.
We study boundary-contact problems for elliptic equations (and systems) with interfaces that have edge singularities. Such problems represent continuous operators between weighted edge spaces and subspaces with asymptotics. Ellipticity is formulated in terms of a principal symbolic hierarchy, containing interior, transmission, and edge symbols. We construct parametrices, show regularity with asymptotics of solutions in weighted edge spaces and illustrate the results by boundary-contact problems for the Laplacian with jumping coefficients.
We study the minimal and maximal closed extension of a differential operator A on a manifold B with conical singularities, when A acts as an unbounded operator on weighted Lp-spaces over B,1 < p < ∞. Under suitable ellipticity assumptions we can define a family of complex powers A up(z), z ∈ C. We also obtain sufficient information on the resolvent of A to show the boundedness of the pure imaginary powers. Examples concern unique solvability and maximal regularity of the solution of the Cauchy problem u' - Δu = f, u(0) = 0, for the Laplacian on conical manifolds.
We consider an infinite system of hard balls in Rd undergoing Brownian motions and submitted to a pair potential with infinite range and quasi polynomial decay. It is modelized by an infinite-dimensional Stochastic Differential Equation with an infinite-dimensional local time term. Existence and uniqueness of a strong solution is proven for such an equation with deterministic initial condition. We also show that the set of all equilibrium measures, solution of a Detailed Balance Equation, coincides with the set of canonical Gibbs measures associated to the hard core potential.
For a domain D subset of IRn with singular points on the boundary and a weight function ω infinitely differentiable away from the singularpoints in D, we consider a C*-algebra G (D; ω) of operators acting in the weighted space L² (D, ω). It is generated by the operators XD F-¹ σ F XD where σ is a homogeneous function. We show that the techniques of limit operators apply to define a symbol algebra for G (D; ω). When combined with the local principle, this leads to describing the Fredholm operators in G (D; ω).
We consider the norm closure A of the algebra of all operators of order and class zero in Boutet de Monvel's calculus on a manifold X with boundary ∂X. We first describe the image and the kernel of the continuous extension of the boundary principal symbol homomorphism to A. If X is connected and ∂X is not empty, we then show that the K-groups of A are topologically determined. In case the manifold, its boundary, and the cotangent space of its interior have torsion free K-theory, we get Ki(A,k) congruent Ki(C(X))⊕Ksub(1-i)(Csub(0)(T*X)),i = 0,1, with k denoting the compact ideal, and T*X denoting the cotangent bundle of the interior. Using Boutet de Monvel's index theorem, we also prove that the above formula holds for i = 1 even without this torsion-free hypothesis. For the case of orientable, two-dimensional X, Ksub(0)(A) congruent Z up(2g+m) and Ksub(1)(A) congruent Z up(2g+m-1), where g is the genus of X and m is the number of connected components of ∂X. We also obtain a composition sequence 0 ⊂ k ⊂ G ⊂ A, with A/G commutative and G/k isomorphic to the algebra of all continuous functions on the cosphere bundle of ∂X with values in compact operators on L²(R+).
Processes with independent increments are characterized via a duality formula, including Malliavin derivative and difference operators. This result is based on a characterization of infinitely divisible random vectors by a functional equation. A construction of the difference operator by a variational method is introduced and compared to approaches used by other authors for L´evy processes involving the chaos decomposition. Finally we extend our method to characterize infinitely divisible random measures.
We consider orthogonal connections with arbitrary torsion on compact Riemannian manifolds. For the induced Dirac operators, twisted Dirac operators and Dirac operators of Chamseddine-Connes type we compute the spectral action. In addition to the Einstein-Hilbert action and the bosonic part of the Standard Model Lagrangian we find the Holst term from Loop Quantum Gravity, a coupling of the Holst term to the scalar curvature and a prediction for the value of the Barbero-Immirzi parameter.
The aim of these lectures is a reformulation and generalization of the fundamental investigations of Alexander Bach [2, 3] on the concept of probability in the work of Boltzmann [6] in the language of modern point process theory. The dominating point of view here is its subordination under the disintegration theory of Krickeberg [14]. This enables us to make Bach's consideration much more transparent. Moreover the point process formulation turns out to be the natural framework for the applications to quantum mechanical models.
This thesis is concerned with the issue of extinction of populations composed of different types of individuals, and their behavior before extinction and in case of a very late extinction. We approach this question firstly from a strictly probabilistic viewpoint, and secondly from the standpoint of risk analysis related to the extinction of a particular model of population dynamics. In this context we propose several statistical tools. The population size is modeled by a branching process, which is either a continuous-time multitype Bienaymé-Galton-Watson process (BGWc), or its continuous-state counterpart, the multitype Feller diffusion process. We are interested in different kinds of conditioning on non-extinction, and in the associated equilibrium states. These ways of conditioning have been widely studied in the monotype case. However the literature on multitype processes is much less extensive, and there is no systematic work establishing connections between the results for BGWc processes and those for Feller diffusion processes. In the first part of this thesis, we investigate the behavior of the population before its extinction by conditioning the associated branching process X_t on non-extinction (X_t≠0), or more generally on non-extinction in a near future 0≤θ<∞ (X_{t+θ}≠0), and by letting t tend to infinity. We prove the result, new in the multitype framework and for θ>0, that this limit exists and is non-degenerate. This reflects a stationary behavior for the dynamics of the population conditioned on non-extinction, and provides a generalization of the so-called Yaglom limit, corresponding to the case θ=0. In a second step we study the behavior of the population in case of a very late extinction, obtained as the limit when θ tends to infinity of the process conditioned by X_{t+θ}≠0. The resulting conditioned process is a known object in the monotype case (sometimes referred to as Q-process), and has also been studied when X_t is a multitype Feller diffusion process. We investigate the not yet considered case where X_t is a multitype BGWc process and prove the existence of the associated Q-process. In addition, we examine its properties, including the asymptotic ones, and propose several interpretations of the process. Finally, we are interested in interchanging the limits in t and θ, as well as in the not yet studied commutativity of these limits with respect to the high-density-type relationship between BGWc processes and Feller processes. We prove an original and exhaustive list of all possible exchanges of limit (long-time limit in t, increasing delay of extinction θ, diffusion limit). The second part of this work is devoted to the risk analysis related both to the extinction of a population and to its very late extinction. We consider a branching population model (arising notably in the epidemiological context) for which a parameter related to the first moments of the offspring distribution is unknown. We build several estimators adapted to different stages of evolution of the population (phase growth, decay phase, and decay phase when extinction is expected very late), and prove moreover their asymptotic properties (consistency, normality). In particular, we build a least squares estimator adapted to the Q-process, allowing a prediction of the population development in the case of a very late extinction. This would correspond to the best or to the worst-case scenario, depending on whether the population is threatened or invasive. These tools enable us to study the extinction phase of the Bovine Spongiform Encephalopathy epidemic in Great Britain, for which we estimate the infection parameter corresponding to a possible source of horizontal infection persisting after the removal in 1988 of the major route of infection (meat and bone meal). This allows us to predict the evolution of the spread of the disease, including the year of extinction, the number of future cases and the number of infected animals. In particular, we produce a very fine analysis of the evolution of the epidemic in the unlikely event of a very late extinction.
This thesis is concerned with the issue of extinction of populations composed of different types of individuals, and their behavior before extinction and in case of a very late extinction. We approach this question firstly from a strictly probabilistic viewpoint, and secondly from the standpoint of risk analysis related to the extinction of a particular model of population dynamics. In this context we propose several statistical tools. The population size is modeled by a branching process, which is either a continuous-time multitype Bienaymé-Galton-Watson process (BGWc), or its continuous-state counterpart, the multitype Feller diffsion process. We are interested in different kinds of conditioning on nonextinction, and in the associated equilibrium states. These ways of conditioning have been widely studied in the monotype case. However the literature on multitype processes is much less extensive, and there is no systematic work establishing connections between the results for BGWc processes and those for Feller diffusion processes. In the first part of this thesis, we investigate the behavior of the population before its extinction by conditioning the associated branching process Xt on non-extinction (Xt 6= 0), or more generally on non-extinction in a near future 0 < 1 (Xt+ 0 = 0), and by letting t tend to infinity. We prove the result, new in the multitype framework and for 0 > 0, that this limit exists and is nondegenerate. This re ects a stationary behavior for the dynamics of the population conditioned on non-extinction, and provides a generalization of the so-called Yaglom limit, corresponding to the case 0 = 0. In a second step we study the behavior of the population in case of a very late extinction, obtained as the limit when 0 tends to infinity of the process conditioned by Xt+ 0 = 0. The resulting conditioned process is a known object in the monotype case (sometimes referred to as Q-process), and has also been studied when Xt is a multitype Feller diffusion process. We investigate the not yet considered case where Xt is a multitype BGWc process and prove the existence of the associated Q-process. In addition, we examine its properties, including the asymptotic ones, and propose several interpretations of the process. Finally, we are interested in interchanging the limits in t and 0, as well as in the not yet studied commutativity of these limits with respect to the high-density-type relationship between BGWc processes and Feller processes. We prove an original and exhaustive list of all possible exchanges of limit (long-time limit in t, increasing delay of extinction 0, diffusion limit). The second part of this work is devoted to the risk analysis related both to the extinction of a population and to its very late extinction. We consider a branching population model (arising notably in the epidemiological context) for which a parameter related to the first moments of the offspring distribution is unknown. We build several estimators adapted to different stages of evolution of the population (phase growth, decay phase, and decay phase when extinction is expected very late), and prove moreover their asymptotic properties (consistency, normality). In particular, we build a least squares estimator adapted to the Q-process, allowing a prediction of the population development in the case of a very late extinction. This would correspond to the best or to the worst-case scenario, depending on whether the population is threatened or invasive. These tools enable us to study the extinction phase of the Bovine Spongiform Encephalopathy epidemic in Great Britain, for which we estimate the infection parameter corresponding to a possible source of horizontal infection persisting after the removal in 1988 of the major route of infection (meat and bone meal). This allows us to predict the evolution of the spread of the disease, including the year of extinction, the number of future cases and the number of infected animals. In particular, we produce a very fine analysis of the evolution of the epidemic in the unlikely event of a very late extinction.
We consider the Dirichlet, Neumann and Zaremba problems for harmonic functions in a bounded plane domain with nonsmooth boundary. The boundary curve belongs to one of the following three classes: sectorial curves, logarithmic spirals and spirals of power type. To study the problem we apply a familiar method of Vekua-Muskhelishvili which consists in using a conformal mapping of the unit disk onto the domain to pull back the problem to a boundary problem for harmonic functions in the disk. This latter is reduced in turn to a Toeplitz operator equation on the unit circle with symbol bearing discontinuities of second kind. We develop a constructive invertibility theory for Toeplitz operators and thus derive solvability conditions as well as explicit formulas for solutions.
The derivation of the standard model from a higher-dimensional action suggests a further study of the fibre bundle formulation of gauge theories to determine the variations in the choice of structure group that are allowed in this geometrical setting. The action of transformations on the projection of fibres to their submanifolds are characteristic of theories with fewer gauge vector bosons, and specific examples are given, which may have phenomenological relevance. The spinor space for the three generations of fermions in the standard model is described algebraically.
Mixed elliptic problems are characterised by conditions that have a discontinuity on an interface of the boundary of codimension 1. The case of a smooth interface is treated in [3]; the investigation there refers to additional interface conditions and parametrices in standard Sobolev spaces. The present paper studies a necessary structure for the case of interfaces with conical singularities, namely, corner conormal symbols of such operators. These may be interpreted as families of mixed elliptic problems on a manifold with smooth interface. We mainly focus on second order operators and additional interface conditions that are holomorphic in an extra parameter. In particular, for the case of the Zaremba problem we explicitly obtain the number of potential conditions in this context. The inverses of conormal symbols are meromorphic families of pseudo-differential mixed problems referring to a smooth interface. Pointwise they can be computed along the lines [3].