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It is "scientific folklore" coming from physical heuristics that solutions to the heat equation on a Riemannian manifold can be represented by a path integral. However, the problem with such path integrals is that they are notoriously ill-defined. One way to make them rigorous (which is often applied in physics) is finite-dimensional approximation, or time-slicing approximation: Given a fine partition of the time interval into small subintervals, one restricts the integration domain to paths that are geodesic on each subinterval of the partition. These finite-dimensional integrals are well-defined, and the (infinite-dimensional) path integral then is defined as the limit of these (suitably normalized) integrals, as the mesh of the partition tends to zero.
In this thesis, we show that indeed, solutions to the heat equation on a general compact Riemannian manifold with boundary are given by such time-slicing path integrals. Here we consider the heat equation for general Laplace type operators, acting on sections of a vector bundle. We also obtain similar results for the heat kernel, although in this case, one has to restrict to metrics satisfying a certain smoothness condition at the boundary. One of the most important manipulations one would like to do with path integrals is taking their asymptotic expansions; in the case of the heat kernel, this is the short time asymptotic expansion. In order to use time-slicing approximation here, one needs the approximation to be uniform in the time parameter. We show that this is possible by giving strong error estimates.
Finally, we apply these results to obtain short time asymptotic expansions of the heat kernel also in degenerate cases (i.e. at the cut locus). Furthermore, our results allow to relate the asymptotic expansion of the heat kernel to a formal asymptotic expansion of the infinite-dimensional path integral, which gives relations between geometric quantities on the manifold and on the loop space. In particular, we show that the lowest order term in the asymptotic expansion of the heat kernel is essentially given by the Fredholm determinant of the Hessian of the energy functional. We also investigate how this relates to the zeta-regularized determinant of the Jacobi operator along minimizing geodesics.
The main results of this thesis are formulated in a class of surfaces (varifolds) generalizing closed and connected smooth submanifolds of Euclidean space which allows singularities. Given an indecomposable varifold with dimension at least two in some Euclidean space such that the first variation is locally bounded, the total variation is absolutely continuous with respect to the weight measure, the density of the weight measure is at least one outside a set of weight measure zero and the generalized mean curvature is locally summable to a natural power (dimension of the varifold minus one) with respect to the weight measure. The thesis presents an improved estimate of the set where the lower density is small in terms of the one dimensional Hausdorff measure. Moreover, if the support of the weight measure is compact, then the intrinsic diameter with respect to the support of the weight measure is estimated in terms of the generalized mean curvature. This estimate is in analogy to the diameter control for closed connected manifolds smoothly immersed in some Euclidean space of Peter Topping. Previously, it was not known whether the hypothesis in this thesis implies that two points in the support of the weight measure have finite geodesic distance.
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.
We prove statistical rates of convergence for kernel-based least squares regression from i.i.d. data using a conjugate gradient algorithm, where regularization against overfitting is obtained by early stopping. This method is related to Kernel Partial Least Squares, a regression method that combines supervised dimensionality reduction with least squares projection. Following the setting introduced in earlier related literature, we study so-called "fast convergence rates" depending on the regularity of the target regression function (measured by a source condition in terms of the kernel integral operator) and on the effective dimensionality of the data mapped into the kernel space. We obtain upper bounds, essentially matching known minimax lower bounds, for the L^2 (prediction) norm as well as for the stronger Hilbert norm, if the true
regression function belongs to the reproducing kernel Hilbert space. If the latter assumption is not fulfilled, we obtain similar convergence rates for appropriate norms, provided additional unlabeled data are available.
Convoluted Brownian motion
(2016)
In this paper we analyse semimartingale properties of a class of Gaussian periodic processes, called convoluted Brownian motions, obtained by convolution between a deterministic function and a Brownian motion. A classical
example in this class is the periodic Ornstein-Uhlenbeck process. We compute their characteristics and show that in general, they are neither
Markovian nor satisfy a time-Markov field property. Nevertheless, by enlargement
of filtration and/or addition of a one-dimensional component, one can in some case recover the Markovianity. We treat exhaustively the case of the bidimensional trigonometric convoluted Brownian motion and the higher-dimensional monomial convoluted Brownian motion.
The human immunodeficiency virus (HIV) has resisted nearly three decades of efforts targeting a cure. Sustained suppression of the virus has remained a challenge, mainly due
to the remarkable evolutionary adaptation that the virus exhibits by the accumulation of drug-resistant mutations in its genome. Current therapeutic strategies aim at achieving and maintaining a low viral burden and typically involve multiple drugs. The choice of optimal combinations of these drugs is crucial, particularly in the background of treatment failure having occurred previously with certain other drugs. An understanding of the dynamics of viral mutant genotypes aids in the assessment of treatment failure with a certain drug
combination, and exploring potential salvage treatment regimens.
Mathematical models of viral dynamics have proved invaluable in understanding the viral life cycle and the impact of antiretroviral drugs. However, such models typically use simplified and coarse-grained mutation schemes, that curbs the extent of their application to drug-specific clinical mutation data, in order to assess potential next-line therapies. Statistical
models of mutation accumulation have served well in dissecting mechanisms of resistance evolution by reconstructing mutation pathways under different drug-environments. While these models perform well in predicting treatment outcomes by statistical learning, they do not incorporate drug effect mechanistically. Additionally, due to an inherent lack of
temporal features in such models, they are less informative on aspects such as predicting mutational abundance at treatment failure. This limits their application in analyzing the
pharmacology of antiretroviral drugs, in particular, time-dependent characteristics of HIV therapy such as pharmacokinetics and pharmacodynamics, and also in understanding the impact of drug efficacy on mutation dynamics.
In this thesis, we develop an integrated model of in vivo viral dynamics incorporating drug-specific mutation schemes learned from clinical data. Our combined modelling
approach enables us to study the dynamics of different mutant genotypes and assess mutational abundance at virological failure. As an application of our model, we estimate in vivo
fitness characteristics of viral mutants under different drug environments. Our approach also extends naturally to multiple-drug therapies. Further, we demonstrate the versatility of our model by showing how it can be modified to incorporate recently elucidated mechanisms of drug action including molecules that target host factors.
Additionally, we address another important aspect in the clinical management of HIV disease, namely drug pharmacokinetics. It is clear that time-dependent changes in in vivo
drug concentration could have an impact on the antiviral effect, and also influence decisions on dosing intervals. We present a framework that provides an integrated understanding
of key characteristics of multiple-dosing regimens including drug accumulation ratios and half-lifes, and then explore the impact of drug pharmacokinetics on viral suppression.
Finally, parameter identifiability in such nonlinear models of viral dynamics is always a concern, and we investigate techniques that alleviate this issue in our setting.
This article assesses the distance between the laws of stochastic differential equations with multiplicative Lévy noise on path space in terms of their characteristics. The notion of transportation distance on the set of Lévy kernels introduced by Kosenkova and Kulik yields a natural and statistically tractable upper bound on the noise sensitivity. This extends recent results for the additive case in terms of coupling distances to the multiplicative case. The strength of this notion is shown in a statistical implementation for simulations and the example of a benchmark time series in paleoclimate.
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 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.