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The motivation for this work was the question of reliability and robustness of seismic tomography. The problem is that many earth models exist which can describe the underlying ground motion records equally well. Most algorithms for reconstructing earth models provide a solution, but rarely quantify their variability. If there is no way to verify the imaged structures, an interpretation is hardly reliable. The initial idea was to explore the space of equivalent earth models using Bayesian inference. However, it quickly became apparent that the rigorous quantification of tomographic uncertainties could not be accomplished within the scope of a dissertation.
In order to maintain the fundamental concept of statistical inference, less complex problems from the geosciences are treated instead. This dissertation aims to anchor Bayesian inference more deeply in the geosciences and to transfer knowledge from applied mathematics. The underlying idea is to use well-known methods and techniques from statistics to quantify the uncertainties of inverse problems in the geosciences. This work is divided into three parts:
Part I introduces the necessary mathematics and should be understood as a kind of toolbox. With a physical application in mind, this section provides a compact summary of all methods and techniques used. The introduction of Bayesian inference makes the beginning. Then, as a special case, the focus is on regression with Gaussian processes under linear transformations. The chapters on the derivation of covariance functions and the approximation of non-linearities are discussed in more detail.
Part II presents two proof of concept studies in the field of seismology. The aim is to present the conceptual application of the introduced methods and techniques with moderate complexity. The example about traveltime tomography applies the approximation of non-linear relationships. The derivation of a covariance function using the wave equation is shown in the example of a damped vibrating string. With these two synthetic applications, a consistent concept for the quantification of modeling uncertainties has been developed.
Part III presents the reconstruction of the Earth's archeomagnetic field. This application uses the whole toolbox presented in Part I and is correspondingly complex. The modeling of the past 1000 years is based on real data and reliably quantifies the spatial modeling uncertainties. The statistical model presented is widely used and is under active development.
The three applications mentioned are intentionally kept flexible to allow transferability to similar problems. The entire work focuses on the non-uniqueness of inverse problems in the geosciences. It is intended to be of relevance to those interested in the concepts of Bayesian inference.
In this work, we present Raman lidar data (from a Nd:YAG operating at 355 nm, 532 nm and 1064 nm) from the international research village Ny-Alesund for the time period of January to April 2020 during the Arctic haze season of the MOSAiC winter. We present values of the aerosol backscatter, the lidar ratio and the backscatter Angstrom exponent, though the latter depends on wavelength. The aerosol polarization was generally below 2%, indicating mostly spherical particles. We observed that events with high backscatter and high lidar ratio did not coincide. In fact, the highest lidar ratios (LR > 75 sr at 532 nm) were already found by January and may have been caused by hygroscopic growth, rather than by advection of more continental aerosol. Further, we performed an inversion of the lidar data to retrieve a refractive index and a size distribution of the aerosol. Our results suggest that in the free troposphere (above approximate to 2500 m) the aerosol size distribution is quite constant in time, with dominance of small particles with a modal radius well below 100 nm. On the contrary, below approximate to 2000 m in altitude, we frequently found gradients in aerosol backscatter and even size distribution, sometimes in accordance with gradients of wind speed, humidity or elevated temperature inversions, as if the aerosol was strongly modified by vertical displacement in what we call the "mechanical boundary layer". Finally, we present an indication that additional meteorological soundings during MOSAiC campaign did not necessarily improve the fidelity of air backtrajectories.
The Levenberg–Marquardt regularization for the backward heat equation with fractional derivative
(2022)
The backward heat problem with time-fractional derivative in Caputo's sense is studied. The inverse problem is severely ill-posed in the case when the fractional order is close to unity. A Levenberg-Marquardt method with a new a posteriori stopping rule is investigated. We show that optimal order can be obtained for the proposed method under a Hölder-type source condition. Numerical examples for one and two dimensions are provided.
We construct and examine the prototype of a deep learning-based ground-motion model (GMM) that is both fully data driven and nonergodic. We formulate ground-motion modeling as an image processing task, in which a specific type of neural network, the U-Net, relates continuous, horizontal maps of earthquake predictive parameters to sparse observations of a ground-motion intensity measure (IM). The processing of map-shaped data allows the natural incorporation of absolute earthquake source and observation site coordinates, and is, therefore, well suited to include site-, source-, and path-specific amplification effects in a nonergodic GMM. Data-driven interpolation of the IM between observation points is an inherent feature of the U-Net and requires no a priori assumptions. We evaluate our model using both a synthetic dataset and a subset of observations from the KiK-net strong motion network in the Kanto basin in Japan. We find that the U-Net model is capable of learning the magnitude???distance scaling, as well as site-, source-, and path-specific amplification effects from a strong motion dataset. The interpolation scheme is evaluated using a fivefold cross validation and is found to provide on average unbiased predictions. The magnitude???distance scaling as well as the site amplification of response spectral acceleration at a period of 1 s obtained for the Kanto basin are comparable to previous regional studies.
Hidden semi-Markov models generalise hidden Markov models by explicitly modelling the time spent in a given state, the so-called dwell time, using some distribution defined on the natural numbers. While the (shifted) Poisson and negative binomial distribution provide natural choices for such distributions, in practice, parametric distributions can lack the flexibility to adequately model the dwell times. To overcome this problem, a penalised maximum likelihood approach is proposed that allows for a flexible and data-driven estimation of the dwell-time distributions without the need to make any distributional assumption. This approach is suitable for direct modelling purposes or as an exploratory tool to investigate the latent state dynamics. The feasibility and potential of the suggested approach is illustrated in a simulation study and by modelling muskox movements in northeast Greenland using GPS tracking data. The proposed method is implemented in the R-package PHSMM which is available on CRAN.
Ground motion with strong-velocity pulses can cause significant damage to buildings and structures at certain periods; hence, knowing the period and velocity amplitude of such pulses is critical for earthquake structural engineering.
However, the physical factors relating the scaling of pulse periods with magnitude are poorly understood.
In this study, we investigate moderate but damaging earthquakes (M-w 6-7) and characterize ground- motion pulses using the method of Shahi and Baker (2014) while considering the potential static-offset effects.
We confirm that the within-event variability of the pulses is large. The identified pulses in this study are mostly from strike-slip-like earthquakes. We further perform simulations using the freq uency-wavenumber algorithm to investigate the causes of the variability of the pulse periods within and between events for moderate strike-slip earthquakes.
We test the effect of fault dips, and the impact of the asperity locations and sizes. The simulations reveal that the asperity properties have a high impact on the pulse periods and amplitudes at nearby stations.
Our results emphasize the importance of asperity characteristics, in addition to earthquake magnitudes for the occurrence and properties of pulses produced by the forward directivity effect.
We finally quantify and discuss within- and between-event variabilities of pulse properties at short distances.
The spatio-temporal epidemic type aftershock sequence (ETAS) model is widely used to describe the self-exciting nature of earthquake occurrences. While traditional inference methods provide only point estimates of the model parameters, we aim at a fully Bayesian treatment of model inference, allowing naturally to incorporate prior knowledge and uncertainty quantification of the resulting estimates. Therefore, we introduce a highly flexible, non-parametric representation for the spatially varying ETAS background intensity through a Gaussian process (GP) prior. Combined with classical triggering functions this results in a new model formulation, namely the GP-ETAS model. We enable tractable and efficient Gibbs sampling by deriving an augmented form of the GP-ETAS inference problem. This novel sampling approach allows us to assess the posterior model variables conditioned on observed earthquake catalogues, i.e., the spatial background intensity and the parameters of the triggering function. Empirical results on two synthetic data sets indicate that GP-ETAS outperforms standard models and thus demonstrate the predictive power for observed earthquake catalogues including uncertainty quantification for the estimated parameters. Finally, a case study for the l'Aquila region, Italy, with the devastating event on 6 April 2009, is presented.
Alpine ecosystems on the Tibetan Plateau are being threatened by ongoing climate warming and intensified human activities. Ecological time-series obtained from sedimentary ancient DNA (sedaDNA) are essential for understanding past ecosystem and biodiversity dynamics on the Tibetan Plateau and their responses to climate change at a high taxonomic resolution. Hitherto only few but promising studies have been published on this topic. The potential and limitations of using sedaDNA on the Tibetan Plateau are not fully understood. Here, we (i) provide updated knowledge of and a brief introduction to the suitable archives, region-specific taphonomy, state-of-the-art methodologies, and research questions of sedaDNA on the Tibetan Plateau; (ii) review published and ongoing sedaDNA studies from the Tibetan Plateau; and (iii) give some recommendations for future sedaDNA study designs. Based on the current knowledge of taphonomy, we infer that deep glacial lakes with freshwater and high clay sediment input, such as those from the southern and southeastern Tibetan Plateau, may have a high potential for sedaDNA studies. Metabarcoding (for microorganisms and plants), metagenomics (for ecosystems), and hybridization capture (for prehistoric humans) are three primary sedaDNA approaches which have been successfully applied on the Tibetan Plateau, but their power is still limited by several technical issues, such as PCR bias and incompleteness of taxonomic reference databases. Setting up high-quality and open-access regional taxonomic reference databases for the Tibetan Plateau should be given priority in the future. To conclude, the archival, taphonomic, and methodological conditions of the Tibetan Plateau are favorable for performing sedaDNA studies. More research should be encouraged to address questions about long-term ecological dynamics at ecosystem scale and to bring the paleoecology of the Tibetan Plateau into a new era.
The objectives of this study were the identification in (morbidly) obese and nonobese patients of (i) the most appropriate body size descriptor for fosfomycin dose adjustments and (ii) adequacy of the currently employed dosing regimens. Plasma and target site (interstitial fluid of subcutaneous adipose tissue) concentrations after fosfomycin administration (8 g) to 30 surgery patients (15 obese/15 nonobese) were obtained from a prospective clinical trial. After characterization of plasma and microdialysis-derived target site pharmacokinetics via population analysis, short-term infusions of fosfomycin 3 to 4 times daily were simulated. The adequacy of therapy was assessed by probability of pharmacokinetic/pharmacodynamic target attainment (PTA) analysis based on the unbound drug-related targets of an %fT(>= MIC) (the fraction of time that unbound fosfomycin concentrations exceed the MIC during 24 h) of 70 and an fAUC(0-24h)/MIC (the area under the concentration-time curve from 0 to 24 h for the unbound fraction of fosfomycin relative to the MIC) of 40.8 to 83.3. Lean body weight, fat mass, and creatinine clearance calculated via adjusted body weight (ABW) (CLCRCG_ABW) of all patients (body mass index [BMI] = 20.1 to 52.0 kg/m(2)) explained a considerable proportion of between-patient pharmacokinetic variability (up to 31.0% relative reduction). The steady-state unbound target site/plasma concentration ratio was 26.3% lower in (morbidly) obese than nonobese patients. For infections with fosfomycin-susceptible pathogens (MIC <= 16 mg/L), intermittent "high-dosage" intravenous (i.v.) fosfomycin (8 g, three times daily) was sufficient to treat patients with a CLCRCG_ABW of,130 mL/min, irrespective of the pharmacokinetic/pharmacodynamic indices considered. For infections by Pseudomonas aeruginosa with a MIC of 32 mg/L, when the index fAUC0-24h/MIC is applied, fosfomycin might represent a promising treatment option in obese and nonobese patients, especially in combination therapy to complement beta-lactams, in which carbapenem-resistant P. aeruginosa is critical. In conclusion, fosfomycin showed excellent target site penetration in obese and nonobese patients. Dosing should be guided by renal function rather than obesity status.
The drug concentrations targeted in meropenem and piperacillin/tazobactam therapy also depend on the susceptibility of the pathogen. Yet, the pathogen is often unknown, and antibiotic therapy is guided by empirical targets. To reliably achieve the targeted concentrations, dosing needs to be adjusted for renal function. We aimed to evaluate a meropenem and piperacillin/tazobactam monitoring program in intensive care unit (ICU) patients by assessing (i) the adequacy of locally selected empirical targets, (ii) if dosing is adequately adjusted for renal function and individual target, and (iii) if dosing is adjusted in target attainment (TA) failure. In a prospective, observational clinical trial of drug concentrations, relevant patient characteristics and microbiological data (pathogen, minimum inhibitory concentration (MIC)) for patients receiving meropenem or piperacillin/tazobactam treatment were collected. If the MIC value was available, a target range of 1-5 x MIC was selected for minimum drug concentrations of both drugs. If the MIC value was not available, 8-40 mg/L and 16-80 mg/L were selected as empirical target ranges for meropenem and piperacillin, respectively. A total of 356 meropenem and 216 piperacillin samples were collected from 108 and 96 ICU patients, respectively. The vast majority of observed MIC values was lower than the empirical target (meropenem: 90.0%, piperacillin: 93.9%), suggesting empirical target value reductions. TA was found to be low (meropenem: 35.7%, piperacillin 50.5%) with the lowest TA for severely impaired renal function (meropenem: 13.9%, piperacillin: 29.2%), and observed drug concentrations did not significantly differ between patients with different targets, indicating dosing was not adequately adjusted for renal function or target. Dosing adjustments were rare for both drugs (meropenem: 6.13%, piperacillin: 4.78%) and for meropenem irrespective of TA, revealing that concentration monitoring alone was insufficient to guide dosing adjustment. Empirical targets should regularly be assessed and adjusted based on local susceptibility data. To improve TA, scientific knowledge should be translated into easy-to-use dosing strategies guiding antibiotic dosing.
Congenital adrenal hyperplasia (CAH) is the most common form of adrenal insufficiency in childhood; it requires cortisol replacement therapy with hydrocortisone (HC, synthetic cortisol) from birth and therapy monitoring for successful treatment. In children, the less invasive dried blood spot (DBS) sampling with whole blood including red blood cells (RBCs) provides an advantageous alternative to plasma sampling.
Potential differences in binding/association processes between plasma and DBS however need to be considered to correctly interpret DBS measurements for therapy monitoring. While capillary DBS samples would be used in clinical practice, venous cortisol DBS samples from children with adrenal insufficiency were analyzed due to data availability and to directly compare and thus understand potential differences between venous DBS and plasma. A previously published HC plasma pharmacokinetic (PK) model was extended by leveraging these DBS concentrations.
In addition to previously characterized binding of cortisol to albumin (linear process) and corticosteroid-binding globulin (CBG; saturable process), DBS data enabled the characterization of a linear cortisol association with RBCs, and thereby providing a quantitative link between DBS and plasma cortisol concentrations. The ratio between the observed cortisol plasma and DBS concentrations varies highly from 2 to 8. Deterministic simulations of the different cortisol binding/association fractions demonstrated that with higher blood cortisol concentrations, saturation of cortisol binding to CBG was observed, leading to an increase in all other cortisol binding fractions.
In conclusion, a mathematical PK model was developed which links DBS measurements to plasma exposure and thus allows for quantitative interpretation of measurements of DBS samples.
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.
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.
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.
Das Eigene und das Fremde
(2023)
Die vorliegende Arbeit stellt eine Untersuchung des Fremdverstehens von Lehrkräften im Mathematikunterricht dar. Mit ‚Fremdverstehen‘ soll dabei – in Anlehnung an den Soziologen Alfred Schütz – der Prozess bezeichnet werden, in welchem eine Lehrkraft versucht, das Verhalten einer Schülerin oder eines Schülers zu verstehen, indem sie dieses Verhalten auf ein Erleben zurückführt, das ihm zugrunde gelegen haben könnte. Als ein wesentliches Merkmal des Prozesses stellt Schütz in seiner Theorie des Fremdverstehens heraus, dass das Fremdverstehen eines Menschen immer auch auf seinen eigenen Erlebnissen basiert. Aus diesem Grund wird in der Arbeit ein methodischer Zweischritt vorgenommen: Es werden zunächst die mathematikbezogenen Erlebnisse zweier Lehrkräfte nachgezeichnet, bevor dann ihr Fremdverstehen in konkreten Situationen im Mathematikunterricht rekonstruiert wird. In der ersten Teiluntersuchung (= der Rekonstruktion eigener Erlebnisse der untersuchten Lehrkräfte) erfolgt die Datenerhebung mit Hilfe biographisch-narrativer Interviews, in denen die untersuchten Lehrkräfte angeregt werden, ihre mathematikbezogene Lebensgeschichte zu erzählen. Die Analyse dieser Interviews wird im Sinne der rekonstruktiven Fallanalyse vorgenommen. Insgesamt führt die erste Teiluntersuchung zu textlichen Darstellungen der rekonstruierten mathematikbezogenen Lebensgeschichte der untersuchten Mathematiklehrkräfte. In der zweiten Teiluntersuchung (= der Rekonstruktion des Fremdverstehens der untersuchten Lehrkräfte) werden dann narrative Interviews geführt, in denen die untersuchten Lehrkräfte von ihrem Fremdverstehen in konkreten Situationen im Mathematikunterricht erzählen. Die Analyse dieser Interviews erfolgt mit Hilfe eines dreischrittigen Analyseverfahrens, welches die Autorin eigens zum Zweck der Rekonstruktion von Fremdverstehen entwickelte. Am Ende dieser zweiten Teiluntersuchung werden sowohl das rekonstruierte Fremdverstehen der Lehrkräfte in verschiedenen Unterrichtssituationen dargestellt als auch Strukturen, die sich in ihrem Fremdverstehen abzeichnen. Mit Hilfe einer theoretischen Verallgemeinerung werden schließlich – auf Basis der Ergebnisse der zweiten Teiluntersuchung – Aussagen über fünf Merkmale des Fremdverstehens von Lehrkräften im Mathematikunterricht im Allgemeinen gewonnen. Mit diesen Aussagen vermag die Arbeit eine erste Beschreibung davon hervorzubringen, wie sich das Phänomen des Fremdverstehens von Lehrkräften im Mathematikunterricht ausgestalten kann.
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.
Non-local boundary conditions for the spin Dirac operator on spacetimes with timelike boundary
(2023)
Non-local boundary conditions – for example the Atiyah–Patodi–Singer (APS) conditions – for Dirac operators on Riemannian manifolds are rather well-understood, while not much is known for such operators on Lorentzian manifolds. Recently, Bär and Strohmaier [15] and Drago, Große, and Murro [27] introduced APS-like conditions for the spin Dirac operator on Lorentzian manifolds with spacelike and timelike boundary, respectively. While Bär and Strohmaier [15] showed the Fredholmness of the Dirac operator with these boundary conditions, Drago, Große, and Murro [27] proved the well-posedness of the corresponding initial boundary value problem under certain geometric assumptions.
In this thesis, we will follow the footsteps of the latter authors and discuss whether the APS-like conditions for Dirac operators on Lorentzian manifolds with timelike boundary can be replaced by more general conditions such that the associated initial boundary value problems are still wellposed.
We consider boundary conditions that are local in time and non-local in the spatial directions. More precisely, we use the spacetime foliation arising from the Cauchy temporal function and split the Dirac operator along this foliation. This gives rise to a family of elliptic operators each acting on spinors of the spin bundle over the corresponding timeslice. The theory of elliptic operators then ensures that we can find families of non-local boundary conditions with respect to this family of operators. Proceeding, we use such a family of boundary conditions to define a Lorentzian boundary condition on the whole timelike boundary. By analyzing the properties of the Lorentzian boundary conditions, we then find sufficient conditions on the family of non-local boundary conditions that lead to the well-posedness of the corresponding Cauchy problems. The well-posedness itself will then be proven by using classical tools including energy estimates and approximation by solutions of the regularized problems.
Moreover, we use this theory to construct explicit boundary conditions for the Lorentzian Dirac operator. More precisely, we will discuss two examples of boundary conditions – the analogue of the Atiyah–Patodi–Singer and the chirality conditions, respectively, in our setting. For doing this, we will have a closer look at the theory of non-local boundary conditions for elliptic operators and analyze the requirements on the family of non-local boundary conditions for these specific examples.
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.
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.
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.