@phdthesis{Sareeto2024, author = {Sareeto, Apatsara}, title = {Algebraic proberties of a subsemigroup of the symmetric inverse semigroup}, school = {Universit{\"a}t Potsdam}, pages = {92}, year = {2024}, language = {en} } @phdthesis{Günther2023, author = {G{\"u}nther, Claudia-Susanne}, title = {Das Eigene und das Fremde}, school = {Universit{\"a}t Potsdam}, pages = {245}, year = {2023}, abstract = {Die vorliegende Arbeit stellt eine Untersuchung des Fremdverstehens von Lehrkr{\"a}ften im Mathematikunterricht dar. Mit ‚Fremdverstehen' soll dabei - in Anlehnung an den Soziologen Alfred Sch{\"u}tz - der Prozess bezeichnet werden, in welchem eine Lehrkraft versucht, das Verhalten einer Sch{\"u}lerin oder eines Sch{\"u}lers zu verstehen, indem sie dieses Verhalten auf ein Erleben zur{\"u}ckf{\"u}hrt, das ihm zugrunde gelegen haben k{\"o}nnte. Als ein wesentliches Merkmal des Prozesses stellt Sch{\"u}tz 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 zun{\"a}chst die mathematikbezogenen Erlebnisse zweier Lehrkr{\"a}fte nachgezeichnet, bevor dann ihr Fremdverstehen in konkreten Situationen im Mathematikunterricht rekonstruiert wird. In der ersten Teiluntersuchung (= der Rekonstruktion eigener Erlebnisse der untersuchten Lehrkr{\"a}fte) erfolgt die Datenerhebung mit Hilfe biographisch-narrativer Interviews, in denen die untersuchten Lehrkr{\"a}fte angeregt werden, ihre mathematikbezogene Lebensgeschichte zu erz{\"a}hlen. Die Analyse dieser Interviews wird im Sinne der rekonstruktiven Fallanalyse vorgenommen. Insgesamt f{\"u}hrt die erste Teiluntersuchung zu textlichen Darstellungen der rekonstruierten mathematikbezogenen Lebensgeschichte der untersuchten Mathematiklehrkr{\"a}fte. In der zweiten Teiluntersuchung (= der Rekonstruktion des Fremdverstehens der untersuchten Lehrkr{\"a}fte) werden dann narrative Interviews gef{\"u}hrt, in denen die untersuchten Lehrkr{\"a}fte von ihrem Fremdverstehen in konkreten Situationen im Mathematikunterricht erz{\"a}hlen. 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 Lehrkr{\"a}fte 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 {\"u}ber f{\"u}nf Merkmale des Fremdverstehens von Lehrkr{\"a}ften im Mathematikunterricht im Allgemeinen gewonnen. Mit diesen Aussagen vermag die Arbeit eine erste Beschreibung davon hervorzubringen, wie sich das Ph{\"a}nomen des Fremdverstehens von Lehrkr{\"a}ften im Mathematikunterricht ausgestalten kann.}, language = {de} } @misc{Dahl2023, type = {Master Thesis}, author = {Dahl, Dorothee Sophie}, title = {Zahlen in den Fingern}, doi = {10.25932/publishup-60762}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-607629}, school = {Universit{\"a}t Potsdam}, pages = {118}, year = {2023}, abstract = {Die Debatte {\"u}ber den Einsatz von digitalen Werkzeugen in der mathematischen Fr{\"u}hf{\"o}rderung ist hoch aktuell. Lernspiele werden konstruiert, mit dem Ziel, mathematisches, informelles Wissen aufzubauen und so einen besseren Schulstart zu erm{\"o}glichen. Doch allein die digitale und spielerische Aufarbeitung f{\"u}hrt nicht zwingend zu einem Lernerfolg. Daher ist es umso wichtiger, die konkrete Implementation der theoretischen Konstrukte und Interaktionsm{\"o}glichkeiten mit den Werkzeugen zu analysieren und passend aufzubereiten. In dieser Masterarbeit wird dazu exemplarisch ein mathematisches Lernspiel namens „Fingu" f{\"u}r den Einsatz im vorschulischen Bereich theoretisch und empirisch im Rahmen der Artifact-Centric Activity Theory (ACAT) untersucht. Dazu werden zun{\"a}chst die theoretischen Hintergr{\"u}nde zum Zahlensinn, Zahlbegriffserwerb, Teil-Ganze-Verst{\"a}ndnis, der Anzahlwahrnehmung und -bestimmung, den Anzahlvergleichen und der Anzahldarstellung mithilfe von Fingern gem{\"a}ß der Embodied Cognition sowie der Verwendung von digitalen Werkzeugen und Multi-Touch-Ger{\"a}ten umfassend beschrieben. Anschließend wird die App Fingu erkl{\"a}rt und dann theoretisch entlang des ACAT-Review-Guides analysiert. Zuletzt wird die selbstst{\"a}ndig durchgef{\"u}hrte Studie mit zehn Vorschulkindern erl{\"a}utert und darauf aufbauend Verbesserungs- und Entwicklungsm{\"o}glichkeiten der App auf wissenschaftlicher Grundlage beigetragen. F{\"u}r Fingu l{\"a}sst sich abschließend festhalten, dass viele Prozesse wie die (Quasi-)Simultanerfassung oder das Z{\"a}hlen gef{\"o}rdert werden k{\"o}nnen, f{\"u}r andere wie das Teil-Ganze-Verst{\"a}ndnis aber noch Anpassungen und/oder die Begleitung durch Erwachsene n{\"o}tig ist.}, language = {de} } @phdthesis{Gehring2023, author = {Gehring, Penelope}, title = {Non-local boundary conditions for the spin Dirac operator on spacetimes with timelike boundary}, doi = {10.25932/publishup-57775}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-577755}, school = {Universit{\"a}t Potsdam}, pages = {100}, year = {2023}, abstract = {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, B{\"a}r 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 B{\"a}r 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.}, language = {en} } @phdthesis{LopezValencia2023, author = {Lopez Valencia, Diego Andres}, title = {The Milnor-Moore and Poincar{\´e}-Birkhoff-Witt theorems in the locality set up and the polar structure of Shintani zeta functions}, doi = {10.25932/publishup-59421}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-594213}, school = {Universit{\"a}t Potsdam}, pages = {147}, year = {2023}, abstract = {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 Poincar{\´e}-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 Poincar{\´e}-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 Poincar{\´e}-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.}, language = {en} } @phdthesis{MalemShinitski2023, author = {Malem-Shinitski, Noa}, title = {Bayesian inference and modeling for point processes with applications from neuronal activity to scene viewing}, doi = {10.25932/publishup-61495}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-614952}, school = {Universit{\"a}t Potsdam}, pages = {vii, 129}, year = {2023}, abstract = {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.}, language = {en} } @misc{EhlenFloegeGoebeletal.2023, author = {Ehlen, Tobias and Fl{\"o}ge, Annie and G{\"o}bel, Franziska and Keller, Peter and Rœlly, Sylvie}, title = {{\"U}bungsbuch zur Stochastik}, editor = {Keller, Peter and Rœlly, Sylvie}, publisher = {Universit{\"a}tsverlag Potsdam}, address = {Potsdam}, isbn = {978-3-86956-563-7}, doi = {10.25932/publishup-59593}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-595939}, pages = {306}, year = {2023}, abstract = {Dieses Buch stellt {\"U}bungen zu den Grundbegriffen und Grunds{\"a}tzen der Stochastik und ihre L{\"o}sungen zur Verf{\"u}gung. So wie man Tonleitern in der Musik trainiert, so berechnet man {\"U}bungsaufgaben in der Mathematik. In diesem Sinne soll dieses {\"U}bungsbuch vor allem als Vorlage dienen f{\"u}r das eigenst{\"a}ndige, eigenverantwortliche Lernen und {\"U}ben. Die Sch{\"o}nheit und Einzigartigkeit der Wahrscheinlichkeitstheorie besteht darin, dass sie eine Vielzahl von realen Ph{\"a}nomenen modellieren kann. Daher findet man hier Aufgaben mit Verbindungen zur Geometrie, zu Gl{\"u}cksspielen, zur Versicherungsmathematik, zur Demographie und vielen anderen Themen.}, language = {de} } @article{KortenkampKuzleReitzKoncebovski2023, author = {Kortenkamp, Ulrich and Kuzle, Ana and Reitz-Koncebovski, Karen}, title = {Fachdidaktisches Wissen aus dem Fachwissen generieren}, series = {PSI-Potsdam: Ergebnisbericht zu den Aktivit{\"a}ten im Rahmen der Qualit{\"a}tsoffensive Lehrerbildung (2019-2023) (Potsdamer Beitr{\"a}ge zur Lehrerbildung und Bildungsforschung ; 3)}, journal = {PSI-Potsdam: Ergebnisbericht zu den Aktivit{\"a}ten im Rahmen der Qualit{\"a}tsoffensive Lehrerbildung (2019-2023) (Potsdamer Beitr{\"a}ge zur Lehrerbildung und Bildungsforschung ; 3)}, number = {3}, publisher = {Universit{\"a}tsverlag Potsdam}, address = {Potsdam}, isbn = {978-3-86956-568-2}, issn = {2626-3556}, doi = {10.25932/publishup-61760}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-617602}, pages = {171 -- 191}, year = {2023}, abstract = {Das Mathematik-Teilprojekt SPIES-M zielt auf eine st{\"a}rkere Professionsorientierung und die Verkn{\"u}pfung von Fachwissenschaft und Fachdidaktik in der universit{\"a}ren Lehrkr{\"a}ftebildung. Zu allen großen Inhaltsgebieten der Mathematik wurden neue Lehrveranstaltungen konzipiert und in den Studienordnungen s{\"a}mtlicher Lehr{\"a}mter Mathematik an der Universit{\"a}t Potsdam implementiert. F{\"u}r die Konzeption wurden theoriebasiert Gestaltungsprinzipien herausgearbeitet, die sowohl f{\"u}r das Design als auch f{\"u}r die Evaluation und Weiterentwicklung der Lehrveranstaltungen nach dem Design-Research-Ansatz genutzt werden k{\"o}nnen. Die Umsetzung der Gestaltungsprinzipien wird am Beispiel der Fundamentalen Idee der Proportionalit{\"a}t verdeutlicht und dabei aufgezeigt, wie Studierende dazu bef{\"a}higt werden k{\"o}nnen, fachdidaktisches Wissen aus fachmathematischen Inhalten zu generieren. Die Entwicklung des Professionswissens der Studierenden wird mithilfe unterschiedlicher Instrumente untersucht, um R{\"u}ckschl{\"u}sse auf die Wirksamkeit der neu konzipierten Lehrveranstaltungen zu ziehen. F{\"u}r die Untersuchungen im Mixed-Methods-Design werden neben Beobachtungen in Lehrveranstaltungen eigens konzipierte Wissenstests, Gruppeninterviews, Unterrichtsentw{\"u}rfe aus Praxisphasen und Lerntageb{\"u}cher genutzt. Die Studierendenperspektive wird durch Befragungen zur wahrgenommenen (Berufs-)Relevanz der Lehrveranstaltungen erhoben. Weiteres wesentliches Element der Begleitforschung ist die kollegiale Supervision durch sogenannte „Spies" (Spione), die die Veranstaltungen kriteriengeleitet beobachten und anschließend gemeinsam mit den Dozierenden reflektieren. Die bisherigen Ergebnisse werden hier pr{\"a}sentiert und hinsichtlich ihrer Implikationen diskutiert. Die im Projekt entwickelten Gestaltungsprinzipien als Werkzeug f{\"u}r Design und Evaluation sowie das Spies-Konzept der kollegialen Supervision werden f{\"u}r die Qualit{\"a}tsentwicklung von Lehrveranstaltungen zum Transfer vorgeschlagen.}, language = {de} } @phdthesis{Schindler2023, author = {Schindler, Daniel}, title = {Mathematical modeling and simulation of protrusion-driven cell dynamics}, doi = {10.25932/publishup-61327}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-613275}, school = {Universit{\"a}t Potsdam}, pages = {VI, 161}, year = {2023}, abstract = {Amoeboid cell motility takes place in a variety of biomedical processes such as cancer metastasis, embryonic morphogenesis, and wound healing. In contrast to other forms of cell motility, it is mainly driven by substantial cell shape changes. Based on the interplay of explorative membrane protrusions at the front and a slower-acting membrane retraction at the rear, the cell moves in a crawling kind of way. Underlying these protrusions and retractions are multiple physiological processes resulting in changes of the cytoskeleton, a meshwork of different multi-functional proteins. The complexity and versatility of amoeboid cell motility raise the need for novel computational models based on a profound theoretical framework to analyze and simulate the dynamics of the cell shape. The objective of this thesis is the development of (i) a mathematical framework to describe contour dynamics in time and space, (ii) a computational model to infer expansion and retraction characteristics of individual cell tracks and to produce realistic contour dynamics, (iii) and a complementing Open Science approach to make the above methods fully accessible and easy to use. In this work, we mainly used single-cell recordings of the model organism Dictyostelium discoideum. Based on stacks of segmented microscopy images, we apply a Bayesian approach to obtain smooth representations of the cell membrane, so-called cell contours. We introduce a one-parameter family of regularized contour flows to track reference points on the contour (virtual markers) in time and space. This way, we define a coordinate system to visualize local geometric and dynamic quantities of individual contour dynamics in so-called kymograph plots. In particular, we introduce the local marker dispersion as a measure to identify membrane protrusions and retractions in a fully automated way. This mathematical framework is the basis of a novel contour dynamics model, which consists of three biophysiologically motivated components: one stochastic term, accounting for membrane protrusions, and two deterministic terms to control the shape and area of the contour, which account for membrane retractions. Our model provides a fully automated approach to infer protrusion and retraction characteristics from experimental cell tracks while being also capable of simulating realistic and qualitatively different contour dynamics. Furthermore, the model is used to classify two different locomotion types: the amoeboid and a so-called fan-shaped type. With the complementing Open Science approach, we ensure a high standard regarding the usability of our methods and the reproducibility of our research. In this context, we introduce our software publication named AmoePy, an open-source Python package to segment, analyze, and simulate amoeboid cell motility. Furthermore, we describe measures to improve its usability and extensibility, e.g., by detailed run instructions and an automatically generated source code documentation, and to ensure its functionality and stability, e.g., by automatic software tests, data validation, and a hierarchical package structure. The mathematical approaches of this work provide substantial improvements regarding the modeling and analysis of amoeboid cell motility. We deem the above methods, due to their generalized nature, to be of greater value for other scientific applications, e.g., varying organisms and experimental setups or the transition from unicellular to multicellular movement. Furthermore, we enable other researchers from different fields, i.e., mathematics, biophysics, and medicine, to apply our mathematical methods. By following Open Science standards, this work is of greater value for the cell migration community and a potential role model for other Open Science contributions.}, language = {en} } @article{HijaziFreitagLandwehr2023, author = {Hijazi, Saddam and Freitag, Melina A. and Landwehr, Niels}, title = {POD-Galerkin reduced order models and physics-informed neural networks for solving inverse problems for the Navier-Stokes equations}, series = {Advanced modeling and simulation in engineering sciences : AMSES}, volume = {10}, journal = {Advanced modeling and simulation in engineering sciences : AMSES}, number = {1}, publisher = {SpringerOpen}, address = {Berlin}, issn = {2213-7467}, doi = {10.1186/s40323-023-00242-2}, pages = {38}, year = {2023}, abstract = {We present a Reduced Order Model (ROM) which exploits recent developments in Physics Informed Neural Networks (PINNs) for solving inverse problems for the Navier-Stokes equations (NSE). In the proposed approach, the presence of simulated data for the fluid dynamics fields is assumed. A POD-Galerkin ROM is then constructed by applying POD on the snapshots matrices of the fluid fields and performing a Galerkin projection of the NSE (or the modified equations in case of turbulence modeling) onto the POD reduced basis. A POD-Galerkin PINN ROM is then derived by introducing deep neural networks which approximate the reduced outputs with the input being time and/or parameters of the model. The neural networks incorporate the physical equations (the POD-Galerkin reduced equations) into their structure as part of the loss function. Using this approach, the reduced model is able to approximate unknown parameters such as physical constants or the boundary conditions. A demonstration of the applicability of the proposed ROM is illustrated by three cases which are the steady flow around a backward step, the flow around a circular cylinder and the unsteady turbulent flow around a surface mounted cubic obstacle.}, language = {en} } @article{MicheletBindelliniMelinetal.2023, author = {Michelet, Robin and Bindellini, Davide and Melin, Johanna and Neumann, Uta and Blankenstein, Oliver and Huisinga, Wilhelm and Johnson, Trevor N. and Whitaker, Martin J. and Ross, Richard and Kloft, Charlotte}, title = {Insights in the maturational processes influencing hydrocortisone pharmacokinetics in congenital adrenal hyperplasia patients using a middle-out approach}, series = {Frontiers in Pharmacology}, volume = {13}, journal = {Frontiers in Pharmacology}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1663-9812}, doi = {10.3389/fphar.2022.1090554}, pages = {14}, year = {2023}, abstract = {Introduction: Hydrocortisone is the standard of care in cortisol replacement therapy for congenital adrenal hyperplasia patients. Challenges in mimicking cortisol circadian rhythm and dosing individualization can be overcome by the support of mathematical modelling. Previously, a non-linear mixed-effects (NLME) model was developed based on clinical hydrocortisone pharmacokinetic (PK) pediatric and adult data. Additionally, a physiologically-based pharmacokinetic (PBPK) model was developed for adults and a pediatric model was obtained using maturation functions for relevant processes. In this work, a middle-out approach was applied. The aim was to investigate whether PBPK-derived maturation functions could provide a better description of hydrocortisone PK inter-individual variability when implemented in the NLME framework, with the goal of providing better individual predictions towards precision dosing at the patient level. Methods: Hydrocortisone PK data from 24 adrenal insufficiency pediatric patients and 30 adult healthy volunteers were used for NLME model development, while the PBPK model and maturation functions of clearance and cortisol binding globulin (CBG) were developed based on previous studies published in the literature. Results: Clearance (CL) estimates from both approaches were similar for children older than 1 year (CL/F increasing from around 150 L/h to 500 L/h), while CBG concentrations differed across the whole age range (CBG(NLME) stable around 0.5 mu M vs. steady increase from 0.35 to 0.8 mu M for CBG (PBPK)). PBPK-derived maturation functions were subsequently included in the NLME model. After inclusion of the maturation functions, none, a part of, or all parameters were re-estimated. However, the inclusion of CL and/or CBG maturation functions in the NLME model did not result in improved model performance for the CL maturation function (\& UDelta;OFV > -15.36) and the re-estimation of parameters using the CBG maturation function most often led to unstable models or individual CL prediction bias. Discussion: Three explanations for the observed discrepancies could be postulated, i) non-considered maturation of processes such as absorption or first-pass effect, ii) lack of patients between 1 and 12 months, iii) lack of correction of PBPK CL maturation functions derived from urinary concentration ratio data for the renal function relative to adults. These should be investigated in the future to determine how NLME and PBPK methods can work towards deriving insights into pediatric hydrocortisone PK.}, language = {en} } @article{FalkenhagenKnoechelKloftetal.2023, author = {Falkenhagen, Undine and Kn{\"o}chel, Jane and Kloft, Charlotte and Huisinga, Wilhelm}, title = {Deriving mechanism-based pharmacodynamic models by reducing quantitative systems pharmacology models}, series = {CPT: Pharmacometrics \& Systems Pharmacology}, volume = {12}, journal = {CPT: Pharmacometrics \& Systems Pharmacology}, number = {4}, publisher = {Wiley}, address = {Hoboken}, issn = {2163-8306}, doi = {10.1002/psp4.12903}, pages = {432 -- 443}, year = {2023}, abstract = {Quantitative systems pharmacology (QSP) models integrate comprehensive qualitative and quantitative knowledge about pharmacologically relevant processes. We previously proposed a first approach to leverage the knowledge in QSP models to derive simpler, mechanism-based pharmacodynamic (PD) models. Their complexity, however, is typically still too large to be used in the population analysis of clinical data. Here, we extend the approach beyond state reduction to also include the simplification of reaction rates, elimination of reactions, and analytic solutions. We additionally ensure that the reduced model maintains a prespecified approximation quality not only for a reference individual but also for a diverse virtual population. We illustrate the extended approach for the warfarin effect on blood coagulation. Using the model-reduction approach, we derive a novel small-scale warfarin/international normalized ratio model and demonstrate its suitability for biomarker identification. Due to the systematic nature of the approach in comparison with empirical model building, the proposed model-reduction algorithm provides an improved rationale to build PD models also from QSP models in other applications.}, language = {en} } @article{StueblerKloftHuisinga2023, author = {St{\"u}bler, Sabine and Kloft, Charlotte and Huisinga, Wilhelm}, title = {Cell-level systems biology model to study inflammatory bowel diseases and their treatment options}, series = {CPT: pharmacometrics \& systems pharmacology}, volume = {12}, journal = {CPT: pharmacometrics \& systems pharmacology}, number = {5}, publisher = {Nature Publ. Group}, address = {London}, issn = {2163-8306}, doi = {10.1002/psp4.12932}, pages = {690 -- 705}, year = {2023}, abstract = {To help understand the complex and therapeutically challenging inflammatory bowel diseases (IBDs), we developed a systems biology model of the intestinal immune system that is able to describe main aspects of IBD and different treatment modalities thereof. The model, including key cell types and processes of the mucosal immune response, compiles a large amount of isolated experimental findings from literature into a larger context and allows for simulations of different inflammation scenarios based on the underlying data and assumptions. In the context of a large and diverse virtual IBD population, we characterized the patients based on their phenotype (in contrast to healthy individuals, they developed persistent inflammation after a trigger event) rather than on a priori assumptions on parameter differences to a healthy individual. This allowed to reproduce the enormous diversity of predispositions known to lead to IBD. Analyzing different treatment effects, the model provides insight into characteristics of individual drug therapy. We illustrate for anti-TNF-alpha therapy, how the model can be used (i) to decide for alternative treatments with best prospects in the case of nonresponse, and (ii) to identify promising combination therapies with other available treatment options.}, language = {en} } @article{GerlachGlueckKunze2023, author = {Gerlach, Moritz and Gl{\"u}ck, Jochen and Kunze, Markus}, title = {Stability of transition semigroups and applications to parabolic equations}, series = {Transactions of the American Mathematical Society}, volume = {376}, journal = {Transactions of the American Mathematical Society}, number = {1}, publisher = {American Mathematical Soc.}, address = {Providence}, issn = {0002-9947}, doi = {10.1090/tran/8620}, pages = {153 -- 180}, year = {2023}, abstract = {This paper deals with the long-term behavior of positive operator semigroups on spaces of bounded functions and of signed measures, which have applications to parabolic equations with unbounded coefficients and to stochas-tic analysis. The main results are a Tauberian type theorem characterizing the convergence to equilibrium of strongly Feller semigroups and a generalization of a classical convergence theorem of Doob. None of these results requires any kind of time regularity of the semigroup.}, language = {en} } @article{SharmaHainzlZoeller2023, author = {Sharma, Shubham and Hainzl, Sebastian and Z{\"o}ller, Gert}, title = {Seismicity parameters dependence on main shock-induced co-seismic stress}, series = {Geophysical journal international}, volume = {235}, journal = {Geophysical journal international}, number = {1}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0956-540X}, doi = {10.1093/gji/ggad201}, pages = {509 -- 517}, year = {2023}, abstract = {The Gutenberg-Richter (GR) and the Omori-Utsu (OU) law describe the earthquakes' energy release and temporal clustering and are thus of great importance for seismic hazard assessment. Motivated by experimental results, which indicate stress-dependent parameters, we consider a combined global data set of 127 main shock-aftershock sequences and perform a systematic study of the relationship between main shock-induced stress changes and associated seismicity patterns. For this purpose, we calculate space-dependent Coulomb Stress (\& UDelta;CFS) and alternative receiver-independent stress metrics in the surrounding of the main shocks. Our results indicate a clear positive correlation between the GR b-value and the induced stress, contrasting expectations from laboratory experiments and suggesting a crucial role of structural heterogeneity and strength variations. Furthermore, we demonstrate that the aftershock productivity increases nonlinearly with stress, while the OU parameters c and p systematically decrease for increasing stress changes. Our partly unexpected findings can have an important impact on future estimations of the aftershock hazard.}, language = {en} } @article{Lewandowski2022, author = {Lewandowski, Max}, title = {Hadamard states for bosonic quantum field theory on globally hyperbolic spacetimes}, series = {Journal of mathematical physics}, volume = {63}, journal = {Journal of mathematical physics}, number = {1}, publisher = {American Institute of Physics}, address = {Melville}, issn = {0022-2488}, doi = {10.1063/5.0055753}, pages = {34}, year = {2022}, abstract = {According to Radzikowski's celebrated results, bisolutions of a wave operator on a globally hyperbolic spacetime are of the Hadamard form iff they are given by a linear combination of distinguished parametrices i2(G˜aF-G˜F+G˜A-G˜R) in the sense of Duistermaat and H{\"o}rmander [Acta Math. 128, 183-269 (1972)] and Radzikowski [Commun. Math. Phys. 179, 529 (1996)]. Inspired by the construction of the corresponding advanced and retarded Green operator GA, GR as done by B{\"a}r, Ginoux, and Pf{\"a}ffle {Wave Equations on Lorentzian Manifolds and Quantization [European Mathematical Society (EMS), Z{\"u}rich, 2007]}, we construct the remaining two Green operators GF, GaF locally in terms of Hadamard series. Afterward, we provide the global construction of i2(G˜aF-G˜F), which relies on new techniques such as a well-posed Cauchy problem for bisolutions and a patching argument using Čech cohomology. This leads to global bisolutions of the Hadamard form, each of which can be chosen to be a Hadamard two-point-function, i.e., the smooth part can be adapted such that, additionally, the symmetry and the positivity condition are exactly satisfied.}, language = {en} } @article{Zoeller2022, author = {Z{\"o}ller, Gert}, title = {A note on the estimation of the maximum possible earthquake magnitude based on extreme value theory for the Groningen Gas Field}, series = {The bulletin of the Seismological Society of America : BSSA}, volume = {112}, journal = {The bulletin of the Seismological Society of America : BSSA}, number = {4}, publisher = {Seismological Society of America}, address = {El Cerito, Calif.}, issn = {0037-1106}, doi = {10.1785/0120210307}, pages = {1825 -- 1831}, year = {2022}, abstract = {Extreme value statistics is a popular and frequently used tool to model the occurrence of large earthquakes. The problem of poor statistics arising from rare events is addressed by taking advantage of the validity of general statistical properties in asymptotic regimes. In this note, I argue that the use of extreme value statistics for the purpose of practically modeling the tail of the frequency-magnitude distribution of earthquakes can produce biased and thus misleading results because it is unknown to what degree the tail of the true distribution is sampled by data. Using synthetic data allows to quantify this bias in detail. The implicit assumption that the true M-max is close to the maximum observed magnitude M-max,M-observed restricts the class of the potential models a priori to those with M-max = M-max,M-observed + Delta M with an increment Delta M approximate to 0.5... 1.2. This corresponds to the simple heuristic method suggested by Wheeler (2009) and labeled :M-max equals M-obs plus an increment." The incomplete consideration of the entire model family for the frequency-magnitude distribution neglects, however, the scenario of a large so far unobserved earthquake.}, language = {en} } @article{KayaFreitag2022, author = {Kaya, Adem and Freitag, Melina A.}, title = {Conditioning analysis for discrete Helmholtz problems}, series = {Computers and mathematics with applications : an international journal}, volume = {118}, journal = {Computers and mathematics with applications : an international journal}, publisher = {Elsevier Science}, address = {Amsterdam}, issn = {0898-1221}, doi = {10.1016/j.camwa.2022.05.016}, pages = {171 -- 182}, year = {2022}, abstract = {In this paper, we examine conditioning of the discretization of the Helmholtz problem. Although the discrete Helmholtz problem has been studied from different perspectives, to the best of our knowledge, there is no conditioning analysis for it. We aim to fill this gap in the literature. We propose a novel method in 1D to observe the near-zero eigenvalues of a symmetric indefinite matrix. Standard classification of ill-conditioning based on the matrix condition number is not true for the discrete Helmholtz problem. We relate the ill-conditioning of the discretization of the Helmholtz problem with the condition number of the matrix. We carry out analytical conditioning analysis in 1D and extend our observations to 2D with numerical observations. We examine several discretizations. We find different regions in which the condition number of the problem shows different characteristics. We also explain the general behavior of the solutions in these regions.}, language = {en} } @article{HoudebertZass2022, author = {Houdebert, Pierre and Zass, Alexander}, title = {An explicit Dobrushin uniqueness region for Gibbs point processes with repulsive interactions}, series = {Journal of applied probability / Applied Probability Trust}, volume = {59}, journal = {Journal of applied probability / Applied Probability Trust}, number = {2}, publisher = {Cambridge Univ. Press}, address = {Cambridge}, issn = {0021-9002}, doi = {10.1017/jpr.2021.70}, pages = {541 -- 555}, year = {2022}, abstract = {We present a uniqueness result for Gibbs point processes with interactions that come from a non-negative pair potential; in particular, we provide an explicit uniqueness region in terms of activity z and inverse temperature beta. The technique used relies on applying to the continuous setting the classical Dobrushin criterion. We also present a comparison to the two other uniqueness methods of cluster expansion and disagreement percolation, which can also be applied for this type of interaction.}, language = {en} } @article{EvansHyde2022, author = {Evans, Myfanwy E. and Hyde, Stephen T.}, title = {Symmetric Tangling of Honeycomb Networks}, series = {Symmetry}, volume = {14}, journal = {Symmetry}, edition = {9}, publisher = {MDPI}, address = {Basel, Schweiz}, issn = {2073-8994}, doi = {10.3390/sym14091805}, pages = {1 -- 13}, year = {2022}, abstract = {Symmetric, elegantly entangled structures are a curious mathematical construction that has found their way into the heart of the chemistry lab and the toolbox of constructive geometry. Of particular interest are those structures—knots, links and weavings—which are composed locally of simple twisted strands and are globally symmetric. This paper considers the symmetric tangling of multiple 2-periodic honeycomb networks. We do this using a constructive methodology borrowing elements of graph theory, low-dimensional topology and geometry. The result is a wide-ranging enumeration of symmetric tangled honeycomb networks, providing a foundation for their exploration in both the chemistry lab and the geometers toolbox.}, language = {en} } @article{HydeEvans2022, author = {Hyde, Stephen T. and Evans, Myfanwy E.}, title = {Symmetric tangled Platonic polyhedra}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {119}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {1}, publisher = {National Acad. of Sciences}, address = {Washington}, issn = {0027-8424}, doi = {10.1073/pnas.2110345118}, pages = {10}, year = {2022}, abstract = {Conventional embeddings of the edge-graphs of Platonic polyhedra, {f,z}, where f,z denote the number of edges in each face and the edge-valence at each vertex, respectively, are untangled in that they can be placed on a sphere (S-2) such that distinct edges do not intersect, analogous to unknotted loops, which allow crossing-free drawings of S-1 on the sphere. The most symmetric (flag-transitive) realizations of those polyhedral graphs are those of the classical Platonic polyhedra, whose symmetries are *2fz, according to Conway's two-dimensional (2D) orbifold notation (equivalent to Schonflies symbols I-h, O-h, and T-d). Tangled Platonic {f,z} polyhedra-which cannot lie on the sphere without edge-crossings-are constructed as windings of helices with three, five, seven,... strands on multigenus surfaces formed by tubifying the edges of conventional Platonic polyhedra, have (chiral) symmetries 2fz (I, O, and T), whose vertices, edges, and faces are symmetrically identical, realized with two flags. The analysis extends to the "theta(z)" polyhedra, {2,z}. The vertices of these symmetric tangled polyhedra overlap with those of the Platonic polyhedra; however, their helicity requires curvilinear (or kinked) edges in all but one case. We show that these 2fz polyhedral tangles are maximally symmetric; more symmetric embeddings are necessarily untangled. On one hand, their topologies are very constrained: They are either self-entangled graphs (analogous to knots) or mutually catenated entangled compound polyhedra (analogous to links). On the other hand, an endless variety of entanglements can be realized for each topology. Simpler examples resemble patterns observed in synthetic organometallic materials and clathrin coats in vivo.}, language = {en} } @phdthesis{Hain2022, author = {Hain, Tobias Martin}, title = {Structure formation and identification in geometrically driven soft matter systems}, doi = {10.25932/publishup-55880}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-558808}, school = {Universit{\"a}t Potsdam}, pages = {xviii, 171}, year = {2022}, abstract = {Subdividing space through interfaces leads to many space partitions that are relevant to soft matter self-assembly. Prominent examples include cellular media, e.g. soap froths, which are bubbles of air separated by interfaces of soap and water, but also more complex partitions such as bicontinuous minimal surfaces. Using computer simulations, this thesis analyses soft matter systems in terms of the relationship between the physical forces between the system's constituents and the structure of the resulting interfaces or partitions. The focus is on two systems, copolymeric self-assembly and the so-called Quantizer problem, where the driving force of structure formation, the minimisation of the free-energy, is an interplay of surface area minimisation and stretching contributions, favouring cells of uniform thickness. In the first part of the thesis we address copolymeric phase formation with sharp interfaces. We analyse a columnar copolymer system "forced" to assemble on a spherical surface, where the perfect solution, the hexagonal tiling, is topologically prohibited. For a system of three-armed copolymers, the resulting structure is described by solutions of the so-called Thomson problem, the search of minimal energy configurations of repelling charges on a sphere. We find three intertwined Thomson problem solutions on a single sphere, occurring at a probability depending on the radius of the substrate. We then investigate the formation of amorphous and crystalline structures in the Quantizer system, a particulate model with an energy functional without surface tension that favours spherical cells of equal size. We find that quasi-static equilibrium cooling allows the Quantizer system to crystallise into a BCC ground state, whereas quenching and non-equilibrium cooling, i.e. cooling at slower rates then quenching, leads to an approximately hyperuniform, amorphous state. The assumed universality of the latter, i.e. independence of energy minimisation method or initial configuration, is strengthened by our results. We expand the Quantizer system by introducing interface tension, creating a model that we find to mimic polymeric micelle systems: An order-disorder phase transition is observed with a stable Frank-Caspar phase. The second part considers bicontinuous partitions of space into two network-like domains, and introduces an open-source tool for the identification of structures in electron microscopy images. We expand a method of matching experimentally accessible projections with computed projections of potential structures, introduced by Deng and Mieczkowski (1998). The computed structures are modelled using nodal representations of constant-mean-curvature surfaces. A case study conducted on etioplast cell membranes in chloroplast precursors establishes the double Diamond surface structure to be dominant in these plant cells. We automate the matching process employing deep-learning methods, which manage to identify structures with excellent accuracy.}, language = {en} } @phdthesis{Fischer2022, author = {Fischer, Jens Walter}, title = {Random dynamics in collective behavior - consensus, clustering \& extinction of populations}, doi = {10.25932/publishup-55372}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-553725}, school = {Universit{\"a}t Potsdam}, pages = {242}, year = {2022}, abstract = {The echo chamber model describes the development of groups in heterogeneous social networks. By heterogeneous social network we mean a set of individuals, each of whom represents exactly one opinion. The existing relationships between individuals can then be represented by a graph. The echo chamber model is a time-discrete model which, like a board game, is played in rounds. In each round, an existing relationship is randomly and uniformly selected from the network and the two connected individuals interact. If the opinions of the individuals involved are sufficiently similar, they continue to move closer together in their opinions, whereas in the case of opinions that are too far apart, they break off their relationship and one of the individuals seeks a new relationship. In this paper we examine the building blocks of this model. We start from the observation that changes in the structure of relationships in the network can be described by a system of interacting particles in a more abstract space. These reflections lead to the definition of a new abstract graph that encompasses all possible relational configurations of the social network. This provides us with the geometric understanding necessary to analyse the dynamic components of the echo chamber model in Part III. As a first step, in Part 7, we leave aside the opinions of the inidividuals and assume that the position of the edges changes with each move as described above, in order to obtain a basic understanding of the underlying dynamics. Using Markov chain theory, we find upper bounds on the speed of convergence of an associated Markov chain to its unique stationary distribution and show that there are mutually identifiable networks that are not apparent in the dynamics under analysis, in the sense that the stationary distribution of the associated Markov chain gives equal weight to these networks. In the reversible cases, we focus in particular on the explicit form of the stationary distribution as well as on the lower bounds of the Cheeger constant to describe the convergence speed. The final result of Section 8, based on absorbing Markov chains, shows that in a reduced version of the echo chamber model, a hierarchical structure of the number of conflicting relations can be identified. We can use this structure to determine an upper bound on the expected absorption time, using a quasi-stationary distribution. This hierarchy of structure also provides a bridge to classical theories of pure death processes. We conclude by showing how future research can exploit this link and by discussing the importance of the results as building blocks for a full theoretical understanding of the echo chamber model. Finally, Part IV presents a published paper on the birth-death process with partial catastrophe. The paper is based on the explicit calculation of the first moment of a catastrophe. This first part is entirely based on an analytical approach to second degree recurrences with linear coefficients. The convergence to 0 of the resulting sequence as well as the speed of convergence are proved. On the other hand, the determination of the upper bounds of the expected value of the population size as well as its variance and the difference between the determined upper bound and the actual value of the expected value. For these results we use almost exclusively the theory of ordinary nonlinear differential equations.}, language = {en} } @phdthesis{Schanner2022, author = {Schanner, Maximilian Arthus}, title = {Correlation based modeling of the archeomagnetic field}, doi = {10.25932/publishup-55587}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-555875}, school = {Universit{\"a}t Potsdam}, pages = {vii, 146}, year = {2022}, abstract = {The geomagnetic main field is vital for live on Earth, as it shields our habitat against the solar wind and cosmic rays. It is generated by the geodynamo in the Earth's outer core and has a rich dynamic on various timescales. Global models of the field are used to study the interaction of the field and incoming charged particles, but also to infer core dynamics and to feed numerical simulations of the geodynamo. Modern satellite missions, such as the SWARM or the CHAMP mission, support high resolution reconstructions of the global field. From the 19 th century on, a global network of magnetic observatories has been established. It is growing ever since and global models can be constructed from the data it provides. Geomagnetic field models that extend further back in time rely on indirect observations of the field, i.e. thermoremanent records such as burnt clay or volcanic rocks and sediment records from lakes and seas. These indirect records come with (partially very large) uncertainties, introduced by the complex measurement methods and the dating procedure. Focusing on thermoremanent records only, the aim of this thesis is the development of a new modeling strategy for the global geomagnetic field during the Holocene, which takes the uncertainties into account and produces realistic estimates of the reliability of the model. This aim is approached by first considering snapshot models, in order to address the irregular spatial distribution of the records and the non-linear relation of the indirect observations to the field itself. In a Bayesian setting, a modeling algorithm based on Gaussian process regression is developed and applied to binned data. The modeling algorithm is then extended to the temporal domain and expanded to incorporate dating uncertainties. Finally, the algorithm is sequentialized to deal with numerical challenges arising from the size of the Holocene dataset. The central result of this thesis, including all of the aspects mentioned, is a new global geomagnetic field model. It covers the whole Holocene, back until 12000 BCE, and we call it ArchKalmag14k. When considering the uncertainties that are produced together with the model, it is evident that before 6000 BCE the thermoremanent database is not sufficient to support global models. For times more recent, ArchKalmag14k can be used to analyze features of the field under consideration of posterior uncertainties. The algorithm for generating ArchKalmag14k can be applied to different datasets and is provided to the community as an open source python package.}, language = {en} } @misc{EvansHyde2022, author = {Evans, Myfanwy E. and Hyde, Stephen T.}, title = {Symmetric Tangling of Honeycomb Networks}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1282}, issn = {1866-8372}, doi = {10.25932/publishup-57084}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-570842}, pages = {13}, year = {2022}, abstract = {Symmetric, elegantly entangled structures are a curious mathematical construction that has found their way into the heart of the chemistry lab and the toolbox of constructive geometry. Of particular interest are those structures—knots, links and weavings—which are composed locally of simple twisted strands and are globally symmetric. This paper considers the symmetric tangling of multiple 2-periodic honeycomb networks. We do this using a constructive methodology borrowing elements of graph theory, low-dimensional topology and geometry. The result is a wide-ranging enumeration of symmetric tangled honeycomb networks, providing a foundation for their exploration in both the chemistry lab and the geometers toolbox.}, language = {en} } @phdthesis{Hannes2022, author = {Hannes, Sebastian}, title = {Boundary Value Problems for the Lorentzian Dirac Operator}, doi = {10.25932/publishup-54839}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-548391}, school = {Universit{\"a}t Potsdam}, pages = {67}, year = {2022}, abstract = {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. B{\"a}r 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, B{\"a}r 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 B{\"a}r 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.}, language = {en} } @article{BaerBandara2022, author = {B{\"a}r, Christian and Bandara, Lashi}, title = {Boundary value problems for general first-order elliptic differential operators}, series = {Journal of functional analysis}, volume = {282}, journal = {Journal of functional analysis}, number = {12}, publisher = {Elsevier}, address = {Amsterdam [u.a.]}, issn = {0022-1236}, doi = {10.1016/j.jfa.2022.109445}, pages = {69}, year = {2022}, abstract = {We study boundary value problems for first-order elliptic differential operators on manifolds with compact boundary. The adapted boundary operator need not be selfadjoint and the boundary condition need not be pseudo-local.We show the equivalence of various characterisations of elliptic boundary conditions and demonstrate how the boundary conditions traditionally considered in the literature fit in our framework. The regularity of the solutions up to the boundary is proven. We show that imposing elliptic boundary conditions yields a Fredholm operator if the manifold is compact. We provide examples which are conveniently treated by our methods.}, language = {en} } @article{MeraTarkhanov2022, author = {Mera, Azal Jaafar Musa and Tarkhanov, Nikolai}, title = {An elliptic equation of finite index in a domain}, series = {Boletin de la Sociedad Matem{\´a}tica Mexicana}, volume = {28}, journal = {Boletin de la Sociedad Matem{\´a}tica Mexicana}, number = {2}, publisher = {Springer International}, address = {New York [u.a.]}, issn = {1405-213X}, doi = {10.1007/s40590-022-00442-7}, pages = {10}, year = {2022}, abstract = {We give an example of first order elliptic equation for a complex-valued function in a plane domain which has a finite number of linearly independent solutions for any right-hand side. No boundary value conditions are thus required.}, language = {en} } @article{EngbertRabeSchwetlicketal.2022, author = {Engbert, Ralf and Rabe, Maximilian Michael and Schwetlick, Lisa and Seelig, Stefan A. and Reich, Sebastian and Vasishth, Shravan}, title = {Data assimilation in dynamical cognitive science}, series = {Trends in cognitive sciences}, volume = {26}, journal = {Trends in cognitive sciences}, number = {2}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1364-6613}, doi = {10.1016/j.tics.2021.11.006}, pages = {99 -- 102}, year = {2022}, abstract = {Dynamical models make specific assumptions about cognitive processes that generate human behavior. In data assimilation, these models are tested against timeordered data. Recent progress on Bayesian data assimilation demonstrates that this approach combines the strengths of statistical modeling of individual differences with the those of dynamical cognitive models.}, language = {en} } @article{HinzSchwarz2022, author = {Hinz, Michael and Schwarz, Michael}, title = {A note on Neumann problems on graphs}, series = {Positivity}, volume = {26}, journal = {Positivity}, number = {4}, publisher = {Springer}, address = {Dordrecht}, issn = {1385-1292}, doi = {10.1007/s11117-022-00930-0}, pages = {23}, year = {2022}, abstract = {We discuss Neumann problems for self-adjoint Laplacians on (possibly infinite) graphs. Under the assumption that the heat semigroup is ultracontractive we discuss the unique solvability for non-empty subgraphs with respect to the vertex boundary and provide analytic and probabilistic representations for Neumann solutions. A second result deals with Neumann problems on canonically compactifiable graphs with respect to the Royden boundary and provides conditions for unique solvability and analytic and probabilistic representations.}, language = {en} } @article{BaerHanke2022, author = {B{\"a}r, Christian and Hanke, Bernhard}, title = {Local flexibility for open partial differential relations}, series = {Communications on pure and applied mathematics / issued by the Courant Institute of Mathematical Sciences, New York Univ.}, volume = {75}, journal = {Communications on pure and applied mathematics / issued by the Courant Institute of Mathematical Sciences, New York Univ.}, number = {6}, publisher = {Wiley}, address = {Hoboken}, issn = {0010-3640}, doi = {10.1002/cpa.21982}, pages = {1377 -- 1415}, year = {2022}, abstract = {We show that local deformations, near closed subsets, of solutions to open partial differential relations can be extended to global deformations, provided all but the highest derivatives stay constant along the subset. The applicability of this general result is illustrated by a number of examples, dealing with convex embeddings of hypersurfaces, differential forms, and lapse functions in Lorentzian geometry. The main application is a general approximation result by sections that have very restrictive local properties on open dense subsets. This shows, for instance, that given any K is an element of Double-struck capital R every manifold of dimension at least 2 carries a complete C-1,C- 1-metric which, on a dense open subset, is smooth with constant sectional curvature K. Of course, this is impossible for C-2-metrics in general.}, language = {en} } @article{HanischLudewig2022, author = {Hanisch, Florian and Ludewig, Matthias}, title = {A rigorous construction of the supersymmetric path integral associated to a compact spin manifold}, series = {Communications in mathematical physics}, volume = {391}, journal = {Communications in mathematical physics}, number = {3}, publisher = {Springer}, address = {Berlin ; Heidelberg}, issn = {0010-3616}, doi = {10.1007/s00220-022-04336-7}, pages = {1209 -- 1239}, year = {2022}, abstract = {We give a rigorous construction of the path integral in N = 1/2 supersymmetry as an integral map for differential forms on the loop space of a compact spin manifold. It is defined on the space of differential forms which can be represented by extended iterated integrals in the sense of Chen and Getzler-Jones-Petrack. Via the iterated integral map, we compare our path integral to the non-commutative loop space Chern character of Guneysu and the second author. Our theory provides a rigorous background to various formal proofs of the Atiyah-Singer index theorem for twisted Dirac operators using supersymmetric path integrals, as investigated by Alvarez-Gaume, Atiyah, Bismut and Witten.}, language = {en} } @article{SchannerKorteHolschneider2022, author = {Schanner, Maximilian and Korte, Monika and Holschneider, Matthias}, title = {ArchKalmag14k: A kalman-filter based global geomagnetic model for the holocene}, series = {Journal of geophysical research : Solid earth}, volume = {127}, journal = {Journal of geophysical research : Solid earth}, number = {2}, publisher = {American Geophysical Union}, address = {Washington}, issn = {2169-9313}, doi = {10.1029/2021JB023166}, pages = {17}, year = {2022}, abstract = {We propose a global geomagnetic field model for the last 14 thousand years, based on thermoremanent records. We call the model ArchKalmag14k. ArchKalmag14k is constructed by modifying recently proposed algorithms, based on space-time correlations. Due to the amount of data and complexity of the model, the full Bayesian posterior is numerically intractable. To tackle this, we sequentialize the inversion by implementing a Kalman-filter with a fixed time step. Every step consists of a prediction, based on a degree dependent temporal covariance, and a correction via Gaussian process regression. Dating errors are treated via a noisy input formulation. Cross correlations are reintroduced by a smoothing algorithm and model parameters are inferred from the data. Due to the specific statistical nature of the proposed algorithms, the model comes with space and time-dependent uncertainty estimates. The new model ArchKalmag14k shows less variation in the large-scale degrees than comparable models. Local predictions represent the underlying data and agree with comparable models, if the location is sampled well. Uncertainties are bigger for earlier times and in regions of sparse data coverage. We also use ArchKalmag14k to analyze the appearance and evolution of the South Atlantic anomaly together with reverse flux patches at the core-mantle boundary, considering the model uncertainties. While we find good agreement with earlier models for recent times, our model suggests a different evolution of intensity minima prior to 1650 CE. In general, our results suggest that prior to 6000 BCE the data is not sufficient to support global models.}, language = {en} } @article{BellingeriFrizPaychaetal.2022, author = {Bellingeri, Carlo and Friz, Peter and Paycha, Sylvie and Preiß, Rosa Lili Dora}, title = {Smooth rough paths, their geometry and algebraic renormalization}, series = {Vietnam journal of mathematics}, volume = {50}, journal = {Vietnam journal of mathematics}, number = {3}, publisher = {Springer}, address = {Singapore}, issn = {2305-221X}, doi = {10.1007/s10013-022-00570-7}, pages = {719 -- 761}, year = {2022}, abstract = {We introduce the class of "smooth rough paths" and study their main properties. Working in a smooth setting allows us to discard sewing arguments and focus on algebraic and geometric aspects. Specifically, a Maurer-Cartan perspective is the key to a purely algebraic form of Lyons' extension theorem, the renormalization of rough paths following up on [Bruned et al.: A rough path perspective on renormalization, J. Funct. Anal. 277(11), 2019], as well as a related notion of "sum of rough paths". We first develop our ideas in a geometric rough path setting, as this best resonates with recent works on signature varieties, as well as with the renormalization of geometric rough paths. We then explore extensions to the quasi-geometric and the more general Hopf algebraic setting.}, language = {en} } @article{LieStahnSullivan2022, author = {Lie, Han Cheng and Stahn, Martin and Sullivan, Tim J.}, title = {Randomised one-step time integration methods for deterministic operator differential equations}, series = {Calcolo}, volume = {59}, journal = {Calcolo}, number = {1}, publisher = {Springer}, address = {Milano}, issn = {0008-0624}, doi = {10.1007/s10092-022-00457-6}, pages = {33}, year = {2022}, abstract = {Uncertainty quantification plays an important role in problems that involve inferring a parameter of an initial value problem from observations of the solution. Conrad et al. (Stat Comput 27(4):1065-1082, 2017) proposed randomisation of deterministic time integration methods as a strategy for quantifying uncertainty due to the unknown time discretisation error. We consider this strategy for systems that are described by deterministic, possibly time-dependent operator differential equations defined on a Banach space or a Gelfand triple. Our main results are strong error bounds on the random trajectories measured in Orlicz norms, proven under a weaker assumption on the local truncation error of the underlying deterministic time integration method. Our analysis establishes the theoretical validity of randomised time integration for differential equations in infinite-dimensional settings.}, language = {en} } @article{MalemShinitskiOjedaOpper2022, author = {Malem-Shinitski, Noa and Ojeda, Cesar and Opper, Manfred}, title = {Variational bayesian inference for nonlinear hawkes process with gaussian process self-effects}, series = {Entropy}, volume = {24}, journal = {Entropy}, number = {3}, publisher = {MDPI}, address = {Basel}, issn = {1099-4300}, doi = {10.3390/e24030356}, pages = {22}, year = {2022}, abstract = {Traditionally, Hawkes processes are used to model time-continuous point processes with history dependence. Here, we propose an extended model where the self-effects are of both excitatory and inhibitory types and follow a Gaussian Process. Whereas previous work either relies on a less flexible parameterization of the model, or requires a large amount of data, our formulation allows for both a flexible model and learning when data are scarce. We continue the line of work of Bayesian inference for Hawkes processes, and derive an inference algorithm by performing inference on an aggregated sum of Gaussian Processes. Approximate Bayesian inference is achieved via data augmentation, and we describe a mean-field variational inference approach to learn the model parameters. To demonstrate the flexibility of the model we apply our methodology on data from different domains and compare it to previously reported results.}, language = {en} } @article{PathirajaLeeuwen2022, author = {Pathiraja, Sahani Darschika and Leeuwen, Peter Jan van}, title = {Multiplicative Non-Gaussian model error estimation in data assimilation}, series = {Journal of advances in modeling earth systems : JAMES}, volume = {14}, journal = {Journal of advances in modeling earth systems : JAMES}, number = {4}, publisher = {American Geophysical Union}, address = {Washington}, issn = {1942-2466}, doi = {10.1029/2021MS002564}, pages = {23}, year = {2022}, abstract = {Model uncertainty quantification is an essential component of effective data assimilation. Model errors associated with sub-grid scale processes are often represented through stochastic parameterizations of the unresolved process. Many existing Stochastic Parameterization schemes are only applicable when knowledge of the true sub-grid scale process or full observations of the coarse scale process are available, which is typically not the case in real applications. We present a methodology for estimating the statistics of sub-grid scale processes for the more realistic case that only partial observations of the coarse scale process are available. Model error realizations are estimated over a training period by minimizing their conditional sum of squared deviations given some informative covariates (e.g., state of the system), constrained by available observations and assuming that the observation errors are smaller than the model errors. From these realizations a conditional probability distribution of additive model errors given these covariates is obtained, allowing for complex non-Gaussian error structures. Random draws from this density are then used in actual ensemble data assimilation experiments. We demonstrate the efficacy of the approach through numerical experiments with the multi-scale Lorenz 96 system using both small and large time scale separations between slow (coarse scale) and fast (fine scale) variables. The resulting error estimates and forecasts obtained with this new method are superior to those from two existing methods.}, language = {en} } @article{KolbeEvans2022, author = {Kolbe, Benedikt Maximilian and Evans, Myfanwy E.}, title = {Enumerating isotopy classes of tilings guided by the symmetry of triply}, series = {Siam journal on applied algebra and geometry}, volume = {6}, journal = {Siam journal on applied algebra and geometry}, number = {1}, publisher = {Society for Industrial and Applied Mathematics}, address = {Philadelphia}, issn = {2470-6566}, doi = {10.1137/20M1358943}, pages = {1 -- 40}, year = {2022}, abstract = {We present a technique for the enumeration of all isotopically distinct ways of tiling a hyperbolic surface of finite genus, possibly nonorientable and with punctures and boundary. This generalizes the enumeration using Delaney--Dress combinatorial tiling theory of combinatorial classes of tilings to isotopy classes of tilings. To accomplish this, we derive an action of the mapping class group of the orbifold associated to the symmetry group of a tiling on the set of tilings. We explicitly give descriptions and presentations of semipure mapping class groups and of tilings as decorations on orbifolds. We apply this enumerative result to generate an array of isotopically distinct tilings of the hyperbolic plane with symmetries generated by rotations that are commensurate with the threedimensional symmetries of the primitive, diamond, and gyroid triply periodic minimal surfaces, which have relevance to a variety of physical systems.}, language = {en} } @phdthesis{Mauerberger2022, author = {Mauerberger, Stefan}, title = {Correlation based Bayesian modeling}, doi = {10.25932/publishup-53782}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-537827}, school = {Universit{\"a}t Potsdam}, pages = {x, 128}, year = {2022}, abstract = {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.}, language = {en} } @article{DubeBoeckmannRitter2022, author = {Dube, Jonas and B{\"o}ckmann, Christine and Ritter, Christoph}, title = {Lidar-Derived Aerosol Properties from Ny-{\AA}lesund, Svalbard during the MOSAiC Spring 2020}, series = {Remote sensing / Molecular Diversity Preservation International (MDPI)}, volume = {14}, journal = {Remote sensing / Molecular Diversity Preservation International (MDPI)}, number = {11}, publisher = {MDPI}, address = {Basel}, issn = {2072-4292}, doi = {10.3390/rs14112578}, pages = {17}, year = {2022}, abstract = {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.}, language = {en} } @article{PornsawadBoeckmannPanitsupakamon2022, author = {Pornsawad, Pornsarp and B{\"o}ckmann, Christine and Panitsupakamon, Wannapa}, title = {The Levenberg-Marquardt regularization for the backward heat equation with fractional derivative}, series = {Electronic transactions on numerical analysis - ETNA}, volume = {57}, journal = {Electronic transactions on numerical analysis - ETNA}, publisher = {Kent State University}, address = {Kent}, isbn = {978-3-7001-8258-0}, issn = {1068-9613}, doi = {10.1553/etna_vol57s67}, pages = {67 -- 79}, year = {2022}, abstract = {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 H{\"o}lder-type source condition. Numerical examples for one and two dimensions are provided.}, language = {en} } @article{LilienkampvonSpechtWeatherilletal.2022, author = {Lilienkamp, Henning and von Specht, Sebastian and Weatherill, Graeme and Caire, Giuseppe and Cotton, Fabrice}, title = {Ground-Motion modeling as an image processing task}, series = {Bulletin of the Seismological Society of America}, volume = {112}, journal = {Bulletin of the Seismological Society of America}, number = {3}, publisher = {Seismological Society of America}, address = {Albany}, issn = {0037-1106}, doi = {10.1785/0120220008}, pages = {1565 -- 1582}, year = {2022}, abstract = {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.}, language = {en} } @article{PohleAdamBeumer2022, author = {Pohle, Jennifer and Adam, Timo and Beumer, Larissa}, title = {Flexible estimation of the state dwell-time distribution in hidden semi-Markov models}, series = {Computational statistics \& data analysis}, volume = {172}, journal = {Computational statistics \& data analysis}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0167-9473}, doi = {10.1016/j.csda.2022.107479}, pages = {15}, year = {2022}, abstract = {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.}, language = {en} } @article{YenvonSpechtLinetal.2022, author = {Yen, Ming-Hsuan and von Specht, Sebastian and Lin, Yen-Yu and Cotton, Fabrice and Ma, Kuo-Fong}, title = {Within- and between-event variabilities of strong-velocity pulses of moderate earthquakes within dense seismic arrays}, series = {Bulletin of the Seismological Society of America}, volume = {112}, journal = {Bulletin of the Seismological Society of America}, number = {1}, publisher = {Seismological Society of America}, address = {El Cerito, Calif.}, issn = {0037-1106}, doi = {10.1785/0120200376}, pages = {361 -- 380}, year = {2022}, abstract = {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.}, language = {en} } @article{MaierWiljesHartungetal.2022, author = {Maier, Corinna Sabrina and Wiljes, Jana de and Hartung, Niklas and Kloft, Charlotte and Huisinga, Wilhelm}, title = {A continued learning approach for model-informed precision dosing}, series = {CPT: pharmacometrics \& systems pharmacology}, volume = {11}, journal = {CPT: pharmacometrics \& systems pharmacology}, number = {2}, publisher = {London}, address = {Nature Publ. Group}, issn = {2163-8306}, doi = {10.1002/psp4.12745}, pages = {185 -- 198}, year = {2022}, abstract = {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.}, language = {en} } @article{DemarisWidigsonIlvemarketal.2022, author = {D{\´e}maris, Alix and Widigson, Ella S. K. and Ilvemark, Johan F. K. F. and Steenholdt, Casper and Seidelin, Jakob B. and Huisinga, Wilhelm and Michelet, Robin and Aulin, Linda B. S. and Kloft, Charlotte}, title = {Ulcerative colitis and acute severe ulcerative colitis patients are overlooked in infliximab population pharmacokinetic models}, series = {Pharmaceutics / Molecular Diversity Preservation International}, volume = {14}, journal = {Pharmaceutics / Molecular Diversity Preservation International}, number = {10}, publisher = {MDPI}, address = {Basel}, issn = {1999-4923}, doi = {10.3390/pharmaceutics14102095}, pages = {32}, year = {2022}, abstract = {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.}, language = {en} } @article{NassarHohmannMicheletetal.2022, author = {Nassar, Yomna M. and Hohmann, Nicolas and Michelet, Robin and Gottwalt, Katharina and Meid, Andreas D. and Burhenne, J{\"u}rgen and Huisinga, Wilhelm and Haefeli, Walter E. and Mikus, Gerd and Kloft, Charlotte}, title = {Quantification of the Time Course of CYP3A Inhibition, Activation, and Induction Using a Population Pharmacokinetic Model of Microdosed Midazolam Continuous Infusion}, series = {Clinical Pharmacokinetics}, volume = {61}, journal = {Clinical Pharmacokinetics}, number = {11}, publisher = {Springer}, address = {Northcote}, issn = {0312-5963}, doi = {10.1007/s40262-022-01175-6}, pages = {1595 -- 1607}, year = {2022}, abstract = {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.}, language = {en} } @article{JiaAnslanChenetal.2022, author = {Jia, Weihan and Anslan, Sten and Chen, Fahu and Cao, Xianyong and Dong, Hailiang and Dulias, Katharina and Gu, Zhengquan and Heinecke, Liv and Jiang, Hongchen and Kruse, Stefan and Kang, Wengang and Li, Kai and Liu, Sisi and Liu, Xingqi and Liu, Ying and Ni, Jian and Schwalb, Antje and Stoof-Leichsenring, Kathleen R. and Shen, Wei and Tian, Fang and Wang, Jing and Wang, Yongbo and Wang, Yucheng and Xu, Hai and Yang, Xiaoyan and Zhang, Dongju and Herzschuh, Ulrike}, title = {Sedimentary ancient DNA reveals past ecosystem and biodiversity changes on the Tibetan Plateau: overview and prospects}, series = {Quaternary science reviews : the international multidisciplinary research and review journal}, volume = {293}, journal = {Quaternary science reviews : the international multidisciplinary research and review journal}, publisher = {Elsevier}, address = {Oxford}, issn = {0277-3791}, doi = {10.1016/j.quascirev.2022.107703}, pages = {14}, year = {2022}, abstract = {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.}, language = {en} } @article{BusseSimonPetroffetal.2022, author = {Busse, David and Simon, Philipp and Petroff, David and El-Najjar, Nahed and Schmitt, Lisa and Bindellini, Davide and Dietrich, Arne and Zeitlinger, Markus and Huisinga, Wilhelm and Michelet, Robin and Wrigge, Hermann and Kloft, Charlotte}, title = {High-dosage fosfomycin results in adequate plasma and target-site exposure in morbidly obese and nonobese nonhyperfiltration patients}, series = {Antimicrobial agents and chemotherapy}, volume = {66}, journal = {Antimicrobial agents and chemotherapy}, number = {6}, publisher = {American Society for Microbiology}, address = {Washington}, issn = {0066-4804}, doi = {10.1128/aac.02302-21}, pages = {12}, year = {2022}, abstract = {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.}, language = {en} } @article{WeineltStegemannTheloeetal.2022, author = {Weinelt, Ferdinand Anton and Stegemann, Miriam Songa and Theloe, Anja and Pf{\"a}fflin, Frieder and Achterberg, Stephan and Weber, Franz and D{\"u}bel, Lucas and Mikolajewska, Agata and Uhrig, Alexander and Kiessling, Peggy and Huisinga, Wilhelm and Michelet, Robin and Hennig, Stefanie and Kloft, Charlotte}, title = {Evaluation of a meropenem and piperacillin monitoring program in intensive care unit patients calls for the regular assessment of empirical targets and easy-to-use dosing decision tools}, series = {Antibiotics : open access journal}, volume = {11}, journal = {Antibiotics : open access journal}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {2079-6382}, doi = {10.3390/antibiotics11060758}, pages = {17}, year = {2022}, abstract = {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.}, language = {en} } @article{StachanowNeumannBlankensteinetal.2022, author = {Stachanow, Viktoria and Neumann, Uta and Blankenstein, Oliver and Bindellini, Davide and Melin, Johanna and Ross, Richard and Whitaker, Martin J. J. and Huisinga, Wilhelm and Michelet, Robin and Kloft, Charlotte}, title = {Exploring dried blood spot cortisol concentrations as an alternative for monitoring pediatric adrenal insufficiency patients}, series = {Frontiers in pharmacology}, volume = {13}, journal = {Frontiers in pharmacology}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1663-9812}, doi = {10.3389/fphar.2022.819590}, pages = {8}, year = {2022}, abstract = {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.}, language = {en} } @article{MolkenthinDonnerReichetal.2022, author = {Molkenthin, Christian and Donner, Christian and Reich, Sebastian and Z{\"o}ller, Gert and Hainzl, Sebastian and Holschneider, Matthias and Opper, Manfred}, title = {GP-ETAS: semiparametric Bayesian inference for the spatio-temporal epidemic type aftershock sequence model}, series = {Statistics and Computing}, volume = {32}, journal = {Statistics and Computing}, number = {2}, publisher = {Springer}, address = {Dordrecht}, issn = {0960-3174}, doi = {10.1007/s11222-022-10085-3}, pages = {25}, year = {2022}, abstract = {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.}, language = {en} } @article{DimitrovaKoppitz2022, author = {Dimitrova, Ilinka and Koppitz, J{\"o}rg}, title = {On relative ranks of the semigroup of orientation-preserving transformations on infinite chain with restricted range}, series = {Communications in algebra}, volume = {50}, journal = {Communications in algebra}, number = {5}, publisher = {Taylor \& Francis Group}, address = {Philadelphia}, issn = {0092-7872}, doi = {10.1080/00927872.2021.2000998}, pages = {2157 -- 2168}, year = {2022}, abstract = {Let X be an infinite linearly ordered set and let Y be a nonempty subset of X. We calculate the relative rank of the semigroup OP(X,Y) of all orientation-preserving transformations on X with restricted range Y modulo the semigroup O(X,Y) of all order-preserving transformations on X with restricted range Y. For Y = X, we characterize the relative generating sets of minimal size.}, language = {en} } @article{FischerKeller2021, author = {Fischer, Florian and Keller, Matthias}, title = {Riesz decompositions for Schr{\"o}dinger operators on graphs}, series = {Journal of mathematical analysis and applications}, volume = {495}, journal = {Journal of mathematical analysis and applications}, number = {1}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0022-247X}, doi = {10.1016/j.jmaa.2020.124674}, pages = {22}, year = {2021}, abstract = {We study superharmonic functions for Schrodinger operators on general weighted graphs. Specifically, we prove two decompositions which both go under the name Riesz decomposition in the literature. The first one decomposes a superharmonic function into a harmonic and a potential part. The second one decomposes a superharmonic function into a sum of superharmonic functions with certain upper bounds given by prescribed superharmonic functions. As application we show a Brelot type theorem.}, language = {en} } @article{Baer2021, author = {B{\"a}r, Christian}, title = {The Faddeev-LeVerrier algorithm and the Pfaffian}, series = {Linear algebra and its applications}, volume = {630}, journal = {Linear algebra and its applications}, publisher = {Elsevier}, address = {New York}, issn = {0024-3795}, doi = {10.1016/j.laa.2021.07.023}, pages = {39 -- 55}, year = {2021}, abstract = {We adapt the Faddeev-LeVerrier algorithm for the computation of characteristic polynomials to the computation of the Pfaffian of a skew-symmetric matrix. This yields a very simple, easy to implement and parallelize algorithm of computational cost O(n(beta+1)) where nis the size of the matrix and O(n(beta)) is the cost of multiplying n x n-matrices, beta is an element of [2, 2.37286). We compare its performance to that of other algorithms and show how it can be used to compute the Euler form of a Riemannian manifold using computer algebra.}, language = {en} } @article{Bandara2021, author = {Bandara, Lashi}, title = {Functional calculus and harmonic analysis in geometry}, series = {S{\~a}o Paulo journal of mathematical sciences / Instituto de Matem{\´a}tica e Estat{\´i}stica da Universidade de S{\~a}o Paulo}, volume = {15}, journal = {S{\~a}o Paulo journal of mathematical sciences / Instituto de Matem{\´a}tica e Estat{\´i}stica da Universidade de S{\~a}o Paulo}, number = {1}, publisher = {Springer}, address = {Cham}, issn = {1982-6907}, doi = {10.1007/s40863-019-00149-0}, pages = {20 -- 53}, year = {2021}, abstract = {In this short survey article, we showcase a number of non-trivial geometric problems that have recently been resolved by marrying methods from functional calculus and real-variable harmonic analysis. We give a brief description of these methods as well as their interplay. This is a succinct survey that hopes to inspire geometers and analysts alike to study these methods so that they can be further developed to be potentially applied to a broader range of questions.}, language = {en} } @article{KleinRosenberger2021, author = {Klein, Markus and Rosenberger, Elke}, title = {The tunneling effect for Schr{\"o}dinger operators on a vector bundle}, series = {Analysis and mathematical physics}, volume = {11}, journal = {Analysis and mathematical physics}, number = {2}, publisher = {Springer International Publishing AG}, address = {Cham (ZG)}, issn = {1664-2368}, doi = {10.1007/s13324-021-00485-5}, pages = {35}, year = {2021}, abstract = {In the semiclassical limit (h) over bar -> 0, we analyze a class of self-adjoint Schrodinger operators H-(h) over bar = (h) over bar L-2 + (h) over barW + V center dot id(E) acting on sections of a vector bundle E over an oriented Riemannian manifold M where L is a Laplace type operator, W is an endomorphism field and the potential energy V has non-degenerate minima at a finite number of points m(1),... m(r) is an element of M, called potential wells. Using quasimodes of WKB-type near m(j) for eigenfunctions associated with the low lying eigenvalues of H-(h) over bar, we analyze the tunneling effect, i.e. the splitting between low lying eigenvalues, which e.g. arises in certain symmetric configurations. Technically, we treat the coupling between different potential wells by an interaction matrix and we consider the case of a single minimal geodesic (with respect to the associated Agmon metric) connecting two potential wells and the case of a submanifold of minimal geodesics of dimension l + 1. This dimension l determines the polynomial prefactor for exponentially small eigenvalue splitting.}, language = {en} } @phdthesis{Etzold2021, author = {Etzold, Heiko}, title = {Neue Zug{\"a}nge zum Winkelbegriff}, doi = {10.25932/publishup-50418}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-504187}, school = {Universit{\"a}t Potsdam}, pages = {300}, year = {2021}, abstract = {Die Vielf{\"a}ltigkeit des Winkelbegriffs ist gleichermaßen spannend wie herausfordernd in Hinblick auf seine Zug{\"a}nge im Mathematikunterricht der Schule. Ausgehend von verschiedenen Vorstellungen zum Winkelbegriff wird in dieser Arbeit ein Lehrgang zur Vermittlung des Winkelbegriffs entwickelt und letztlich in konkrete Umsetzungen f{\"u}r den Schulunterricht {\"u}berf{\"u}hrt. Dabei erfolgt zun{\"a}chst eine stoffdidaktische Auseinandersetzung mit dem Winkelbegriff, die von einer informationstheoretischen Winkeldefinition begleitet wird. In dieser wird eine Definition f{\"u}r den Winkelbegriff unter der Fragestellung entwickelt, welche Informationen man {\"u}ber einen Winkel ben{\"o}tigt, um ihn beschreiben zu k{\"o}nnen. So k{\"o}nnen die in der fachdidaktischen Literatur auftretenden Winkelvorstellungen aus fachmathematischer Perspektive erneut abgeleitet und validiert werden. Parallel dazu wird ein Verfahren beschrieben, wie Winkel - auch unter dynamischen Aspekten - informationstechnisch verarbeitet werden k{\"o}nnen, so dass Schlussfolgerungen aus der informationstheoretischen Winkeldefinition beispielsweise in dynamischen Geometriesystemen zur Verf{\"u}gung stehen. Unter dem Gesichtspunkt, wie eine Abstraktion des Winkelbegriffs im Mathematikunterricht vonstatten gehen kann, werden die Grundvorstellungsidee sowie die Lehrstrategie des Aufsteigens vom Abstrakten zum Konkreten miteinander in Beziehung gesetzt. Aus der Verkn{\"u}pfung der beiden Theorien wird ein grunds{\"a}tzlicher Weg abgeleitet, wie im Rahmen der Lehrstrategie eine Ausgangsabstraktion zu einzelnen Winkelaspekten aufgebaut werden kann, was die Generierung von Grundvorstellungen zu den Bestandteilen des jeweiligen Winkelaspekts und zum Operieren mit diesen Begriffsbestandteilen erm{\"o}glichen soll. Hierf{\"u}r wird die Lehrstrategie angepasst, um insbesondere den {\"U}bergang von Winkelsituationen zu Winkelkontexten zu realisieren. Explizit f{\"u}r den Aspekt des Winkelfeldes werden, anhand der Untersuchung der Sichtfelder von Tieren, Lernhandlungen und Forderungen an ein Lernmodell beschrieben, die Sch{\"u}lerinnen und Sch{\"u}ler bei der Begriffsaneignung unterst{\"u}tzen. Die T{\"a}tigkeitstheorie, der die genannte Lehrstrategie zuzuordnen ist, zieht sich als roter Faden durch die weitere Arbeit, wenn nun theoriebasiert Designprinzipien generiert werden, die in die Entwicklung einer interaktiven Lernumgebung m{\"u}nden. Hierzu wird u. a. das Modell der Artifact-Centric Activity Theory genutzt, das das Beziehungsgef{\"u}ge aus Sch{\"u}lerinnen und Sch{\"u}lern, dem mathematischen Gegenstand und einer zu entwickelnden App als vermittelndes Medium beschreibt, wobei der Einsatz der App im Unterrichtskontext sowie deren regelgeleitete Entwicklung Bestandteil des Modells sind. Gem{\"a}ß dem Ansatz der Fachdidaktischen Entwicklungsforschung wird die Lernumgebung anschließend in mehreren Zyklen erprobt, evaluiert und {\"u}berarbeitet. Dabei wird ein qualitatives Setting angewandt, das sich der Semiotischen Vermittlung bedient und untersucht, inwiefern sich die Qualit{\"a}t der von den Sch{\"u}lerinnen und Sch{\"u}lern gezeigten Lernhandlungen durch die Designprinzipien und deren Umsetzung erkl{\"a}ren l{\"a}sst. Am Ende der Arbeit stehen eine finale Version der Designprinzipien und eine sich daraus ergebende Lernumgebung zur Einf{\"u}hrung des Winkelfeldbegriffs in der vierten Klassenstufe.}, language = {de} } @phdthesis{Zass2021, author = {Zass, Alexander}, title = {A multifaceted study of marked Gibbs point processes}, doi = {10.25932/publishup-51277}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-512775}, school = {Universit{\"a}t Potsdam}, pages = {vii, 104}, year = {2021}, abstract = {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.}, language = {en} } @phdthesis{Oancea2021, author = {Oancea, Marius-Adrian}, title = {Spin Hall effects in general relativity}, doi = {10.25932/publishup-50229}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-502293}, school = {Universit{\"a}t Potsdam}, pages = {vii, 123}, year = {2021}, abstract = {The propagation of test fields, such as electromagnetic, Dirac or linearized gravity, on a fixed spacetime manifold is often studied by using the geometrical optics approximation. In the limit of infinitely high frequencies, the geometrical optics approximation provides a conceptual transition between the test field and an effective point-particle description. The corresponding point-particles, or wave rays, coincide with the geodesics of the underlying spacetime. For most astrophysical applications of interest, such as the observation of celestial bodies, gravitational lensing, or the observation of cosmic rays, the geometrical optics approximation and the effective point-particle description represent a satisfactory theoretical model. However, the geometrical optics approximation gradually breaks down as test fields of finite frequency are considered. In this thesis, we consider the propagation of test fields on spacetime, beyond the leading-order geometrical optics approximation. By performing a covariant Wentzel-Kramers-Brillouin analysis for test fields, we show how higher-order corrections to the geometrical optics approximation can be considered. The higher-order corrections are related to the dynamics of the spin internal degree of freedom of the considered test field. We obtain an effective point-particle description, which contains spin-dependent corrections to the geodesic motion obtained using geometrical optics. This represents a covariant generalization of the well-known spin Hall effect, usually encountered in condensed matter physics and in optics. Our analysis is applied to electromagnetic and massive Dirac test fields, but it can easily be extended to other fields, such as linearized gravity. In the electromagnetic case, we present several examples where the gravitational spin Hall effect of light plays an important role. These include the propagation of polarized light rays on black hole spacetimes and cosmological spacetimes, as well as polarization-dependent effects on the shape of black hole shadows. Furthermore, we show that our effective point-particle equations for polarized light rays reproduce well-known results, such as the spin Hall effect of light in an inhomogeneous medium, and the relativistic Hall effect of polarized electromagnetic wave packets encountered in Minkowski spacetime.}, language = {en} } @misc{Moehring2021, type = {Master Thesis}, author = {M{\"o}hring, Jan}, title = {Stochastic inversion for core field modeling using satellite data}, doi = {10.25932/publishup-49807}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-498072}, school = {Universit{\"a}t Potsdam}, pages = {vii, 55}, year = {2021}, abstract = {Magnetfeldmodellierung mit Kugelfl{\"a}chenfunktionen basiert auf der Inversion nach hunderten bis tausenden von Parametern. Dieses hochdimensionale Problem kann grunds{\"a}tzlich als ein Optimierungsproblem formuliert werden, bei dem ein globales Minimum einer gewissen Zielfunktion berechnet werden soll. Um dieses Problem zu l{\"o}sen, gibt es eine Reihe bekannter Ans{\"a}tze, dazu z{\"a}hlen etwa gradientenbasierte Verfahren oder die Methode der kleinsten Quadrate und deren Varianten. Jede dieser Methoden hat verschiedene Vor- und Nachteile, beispielsweise bez{\"u}glich der Anwendbarkeit auf nicht-differenzierbare Funktionen oder der Laufzeit zugeh{\"o}riger Algorithmen. In dieser Arbeit verfolgen wir das Ziel, einen Algorithmus zu finden, der schneller als die etablierten Verfahren ist und sich auch f{\"u}r nichtlineare Probleme anwenden l{\"a}sst. Solche nichtlinearen Probleme treten beispielsweise bei der Absch{\"a}tzung von Euler-Winkeln oder bei der Verwendung der robusteren L_1-Norm auf. Dazu untersuchen wir die Anwendbarkeit stochastischer Optimierungsverfahren aus der CMAES-Familie auf die Modellierung des geomagnetischen Feldes des Erdkerns. Es werden sowohl die Grundlagen der Kernfeldmodellierung und deren Parametrisierung anhand einiger Beispiele aus der Literatur besprochen, als auch die theoretischen Hintergr{\"u}nde der stochastischen Verfahren gegeben. Ein CMAES-Algorithmus wurde erfolgreich angewendet, um Daten der Swarm-Satellitenmission zu invertieren und daraus das Magnetfeldmodell EvoMag abzuleiten. EvoMag zeigt gute {\"U}bereinstimmung mit etablierten Modellen, sowie mit Observatoriumsdaten aus Niemegk. Wir thematisieren einige beobachtete Schwierigkeiten und pr{\"a}sentieren und diskutieren die Ergebnisse unserer Modellierung.}, language = {en} } @article{BaerMazzeo2021, author = {B{\"a}r, Christian and Mazzeo, Rafe}, title = {Manifolds with many Rarita-Schwinger fields}, series = {Communications in mathematical physics}, volume = {384}, journal = {Communications in mathematical physics}, number = {1}, publisher = {Springer}, address = {Berlin}, issn = {0010-3616}, doi = {10.1007/s00220-021-04030-0}, pages = {533 -- 548}, year = {2021}, abstract = {The Rarita-Schwinger operator is the twisted Dirac operator restricted to 3/2-spinors. Rarita-Schwinger fields are solutions of this operator which are in addition divergence-free. This is an overdetermined problem and solutions are rare; it is even more unexpected for there to be large dimensional spaces of solutions. In this paper we prove the existence of a sequence of compact manifolds in any given dimension greater than or equal to 4 for which the dimension of the space of Rarita-Schwinger fields tends to infinity. These manifolds are either simply connected Kahler-Einstein spin with negative Einstein constant, or products of such spaces with flat tori. Moreover, we construct Calabi-Yau manifolds of even complex dimension with more linearly independent Rarita-Schwinger fields than flat tori of the same dimension.}, language = {en} } @phdthesis{Zadorozhnyi2021, author = {Zadorozhnyi, Oleksandr}, title = {Contributions to the theoretical analysis of the algorithms with adversarial and dependent data}, school = {Universit{\"a}t Potsdam}, pages = {144}, year = {2021}, abstract = {In this work I present the concentration inequalities of Bernstein's type for the norms of Banach-valued random sums under a general functional weak-dependency assumption (the so-called \$\cC-\$mixing). The latter is then used to prove, in the asymptotic framework, excess risk upper bounds of the regularised Hilbert valued statistical learning rules under the τ-mixing assumption on the underlying training sample. These results (of the batch statistical setting) are then supplemented with the regret analysis over the classes of Sobolev balls of the type of kernel ridge regression algorithm in the setting of online nonparametric regression with arbitrary data sequences. Here, in particular, a question of robustness of the kernel-based forecaster is investigated. Afterwards, in the framework of sequential learning, the multi-armed bandit problem under \$\cC-\$mixing assumption on the arm's outputs is considered and the complete regret analysis of a version of Improved UCB algorithm is given. Lastly, probabilistic inequalities of the first part are extended to the case of deviations (both of Azuma-Hoeffding's and of Burkholder's type) to the partial sums of real-valued weakly dependent random fields (under the type of projective dependence condition).}, language = {en} } @article{GottwaldReich2021, author = {Gottwald, Georg A. and Reich, Sebastian}, title = {Combining machine learning and data assimilation to forecast dynamical systems from noisy partial observations}, series = {Chaos : an interdisciplinary journal of nonlinear science}, volume = {31}, journal = {Chaos : an interdisciplinary journal of nonlinear science}, number = {10}, publisher = {AIP}, address = {Melville}, issn = {1054-1500}, doi = {10.1063/5.0066080}, pages = {8}, year = {2021}, abstract = {We present a supervised learning method to learn the propagator map of a dynamical system from partial and noisy observations. In our computationally cheap and easy-to-implement framework, a neural network consisting of random feature maps is trained sequentially by incoming observations within a data assimilation procedure. By employing Takens's embedding theorem, the network is trained on delay coordinates. We show that the combination of random feature maps and data assimilation, called RAFDA, outperforms standard random feature maps for which the dynamics is learned using batch data.}, language = {en} } @article{Clavier2021, author = {Clavier, Pierre J.}, title = {Borel-{\´E}calle resummation of a two-point function}, series = {Annales Henri Poincar{\´e} : a journal of theoretical and mathematical physics / ed. jointly by the Institut Henri Poincar{\´e} and by the Swiss Physical Society}, volume = {22}, journal = {Annales Henri Poincar{\´e} : a journal of theoretical and mathematical physics / ed. jointly by the Institut Henri Poincar{\´e} and by the Swiss Physical Society}, number = {6}, publisher = {Springer}, address = {Cham}, issn = {1424-0637}, doi = {10.1007/s00023-021-01057-w}, pages = {2103 -- 2136}, year = {2021}, abstract = {We provide an overview of the tools and techniques of resurgence theory used in the Borel-ecalle resummation method, which we then apply to the massless Wess-Zumino model. Starting from already known results on the anomalous dimension of the Wess-Zumino model, we solve its renormalisation group equation for the two-point function in a space of formal series. We show that this solution is 1-Gevrey and that its Borel transform is resurgent. The Schwinger-Dyson equation of the model is then used to prove an asymptotic exponential bound for the Borel transformed two-point function on a star-shaped domain of a suitable ramified complex plane. This proves that the two-point function of the Wess-Zumino model is Borel-ecalle summable.}, language = {en} } @masterthesis{Dahl2021, type = {Bachelor Thesis}, author = {Dahl, Dorothee Sophie}, title = {Let's have FUN! Gamification im Mathematikunterricht}, doi = {10.25932/publishup-51593}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-515937}, school = {Universit{\"a}t Potsdam}, pages = {78}, year = {2021}, abstract = {Spiele und spieltypische Elemente wie das Sammeln von Treuepunkten sind aus dem Alltag kaum wegzudenken. Zudem werden sie zunehmend in Unternehmen oder in Lernumgebungen eingesetzt. Allerdings ist die Methode Gamification bisher f{\"u}r den p{\"a}dagogischen Kontext wenig klassifiziert und f{\"u}r Lehrende kaum zug{\"a}nglich gemacht worden. Daher zielt diese Bachelorarbeit darauf ab, eine systematische Strukturierung und Aufarbeitung von Gamification sowie innovative Ans{\"a}tze f{\"u}r die Verwendung spieltypischer Elemente im Unterricht, konkret dem Mathematikunterricht, zu pr{\"a}sentieren. Dies kann eine Grundlage f{\"u}r andere Fachgebiete, aber auch andere Lehrformen bieten und so die Umsetzbarkeit von Gamification in eigenen Lehrveranstaltungen aufzeigen. In der Arbeit wird begr{\"u}ndet, weshalb und mithilfe welcher Elemente Gamification die Motivation und Leistungsbereitschaft der Lernenden langfristig erh{\"o}hen, die Sozial- und Personalkompetenzen f{\"o}rdern sowie die Lernenden zu mehr Aktivit{\"a}t anregen kann. Zudem wird Gamification explizit mit grundlegenden mathematikdidaktischen Prinzipien in Verbindung gesetzt und somit die Relevanz f{\"u}r den Mathematikunterricht hervorgehoben. Anschließend werden die einzelnen Elemente von Gamification wie Punkte, Level, Abzeichen, Charaktere und Rahmengeschichte entlang einer eigens f{\"u}r den p{\"a}dagogischen Kontext entwickelten Klassifikation „FUN" (Feedback - User specific elements - Neutral elements) schematisch beschrieben, ihre Funktionen und Wirkung dargestellt sowie Einsatzm{\"o}glichkeiten im Unterricht aufgezeigt. Dies beinhaltet Ideen zu lernf{\"o}rderlichem Feedback, Differenzierungsm{\"o}glichkeiten und Unterrichtsrahmengestaltung, die in Lehrveranstaltungen aller Art umsetzbar sein k{\"o}nnen. Die Bachelorarbeit umfasst zudem ein spezifisches Beispiel, einen Unterrichtsentwurf einer gamifizierten Mathematikstunde inklusive des zugeh{\"o}rigen Arbeitsmaterials, anhand dessen die Verwendung von Gamification deutlich wird. Gamification offeriert oftmals Vorteile gegen{\"u}ber dem traditionellen Unterricht, muss jedoch wie jede Methode an den Inhalt und die Zielgruppe angepasst werden. Weiterf{\"u}hrende Forschung k{\"o}nnte sich mit konkreten motivationalen Strukturen, personenspezifischen Unterschieden sowie mit mathematischen Inhalten wie dem Probleml{\"o}sen oder dem Wechsel zwischen verschiedenen Darstellungen hinsichtlich gamifizierter Lehrformen besch{\"a}ftigen.}, language = {de} } @masterthesis{Engelhardt2021, type = {Bachelor Thesis}, author = {Engelhardt, Max Angel Ronan}, title = {Zwischen Simulation und Beweis - eine mathematische Analyse des Bienaym{\´e}-Galton-Watson-Prozesses und sein Einsatz innerhalb des Mathematikunterrichts}, doi = {10.25932/publishup-52447}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-524474}, school = {Universit{\"a}t Potsdam}, pages = {117}, year = {2021}, abstract = {Die Bienaym{\´e}-Galton-Watson Prozesse k{\"o}nnen f{\"u}r die Untersuchung von speziellen und sich entwickelnden Populationen verwendet werden. Die Populationen umfassen Individuen, welche sich identisch, zuf{\"a}llig, selbstst{\"a}ndig und unabh{\"a}ngig voneinander fortpflanzen und die jeweils nur eine Generation existieren. Die n-te Generation ergibt sich als zuf{\"a}llige Summe der Individuen der (n-1)-ten Generation. Die Relevanz dieser Prozesse begr{\"u}ndet sich innerhalb der Historie und der inner- und außermathematischen Bedeutung. Die Geschichte der Bienaym{\´e}-Galton-Watson-Prozesse wird anhand der Entwicklung des Konzeptes bis heute dargestellt. Dabei werden die Wissenschaftler:innen verschiedener Disziplinen angef{\"u}hrt, die Erkenntnisse zu dem Themengebiet beigetragen und das Konzept in ihren Fachbereichen angef{\"u}hrt haben. Somit ergibt sich die außermathematische Signifikanz. Des Weiteren erh{\"a}lt man die innermathematische Bedeutsamkeit mittels des Konzeptes der Verzweigungsprozesse, welches auf die Bienaym{\´e}-Galton-Watson Prozesse zur{\"u}ckzuf{\"u}hren ist. Die Verzweigungsprozesse stellen eines der aussagekr{\"a}ftigsten Modelle f{\"u}r die Beschreibung des Populationswachstums dar. Dar{\"u}ber hinaus besteht die derzeitige Wichtigkeit durch die Anwendungsm{\"o}glichkeit der Verzweigungsprozesse und der Bienaym{\´e}-Galton-Watson Prozesse innerhalb der Epidemiologie. Es werden die Ebola- und die Corona-Pandemie als Anwendungsfelder angef{\"u}hrt. Die Prozesse dienen als Entscheidungsst{\"u}tze f{\"u}r die Politik und erm{\"o}glichen Aussagen {\"u}ber die Auswirkungen von Maßnahmen bez{\"u}glich der Pandemien. Neben den Prozessen werden ebenfalls der bedingte Erwartungswert bez{\"u}glich diskreter Zufallsvariablen, die wahrscheinlichkeitserzeugende Funktion und die zuf{\"a}llige Summe eingef{\"u}hrt. Die Konzepte vereinfachen die Beschreibung der Prozesse und bilden somit die Grundlage der Betrachtungen. Außerdem werden die ben{\"o}tigten und weiterf{\"u}hrenden Eigenschaften der grundlegenden Themengebiete und der Prozesse aufgef{\"u}hrt und bewiesen. Das Kapitel erreicht seinen H{\"o}hepunkt bei dem Beweis des Kritikalit{\"a}tstheorems, wodurch eine Aussage {\"u}ber das Aussterben des Prozesses in verschiedenen F{\"a}llen und somit {\"u}ber die Aussterbewahrscheinlichkeit get{\"a}tigt werden kann. Die F{\"a}lle werden anhand der zu erwartenden Anzahl an Nachkommen eines Individuums unterschieden. Es zeigt sich, dass ein Prozess bei einer zu erwartenden Anzahl kleiner gleich Eins mit Sicherheit ausstirbt und bei einer Anzahl gr{\"o}ßer als Eins, die Population nicht in jedem Fall aussterben muss. Danach werden einzelne Beispiele, wie der linear fractional case, die Population von Fibroblasten (Bindegewebszellen) von M{\"a}usen und die Entstehungsfragestellung der Prozesse, angef{\"u}hrt. Diese werden mithilfe der erlangten Ergebnisse untersucht und einige ausgew{\"a}hlte zuf{\"a}llige Dynamiken werden im nachfolgenden Kapitel simuliert. Die Simulationen erfolgen durch ein in Python erstelltes Programm und werden mithilfe der Inversionsmethode realisiert. Die Simulationen stellen beispielhaft die Entwicklungen in den verschiedenen Kritikalit{\"a}tsf{\"a}llen der Prozesse dar. Zudem werden die H{\"a}ufigkeiten der einzelnen Populationsgr{\"o}ßen in Form von Histogrammen angebracht. Dabei l{\"a}sst sich der Unterschied zwischen den einzelnen F{\"a}llen best{\"a}tigen und es wird die Anwendungsm{\"o}glichkeit der Bienaym{\´e}-Galton-Watson Prozesse bei komplexeren Problemen deutlich. Histogramme bekr{\"a}ftigen, dass die einzelnen Populationsgr{\"o}ßen nur endlich oft vorkommen. Diese Aussage wurde von Galton aufgeworfen und in der Extinktions-Explosions-Dichotomie verwendet. Die dargestellten Erkenntnisse {\"u}ber das Themengebiet und die Betrachtung des Konzeptes werden mit einer didaktischen Analyse abgeschlossen. Die Untersuchung beinhaltet die Ber{\"u}cksichtigung der Fundamentalen Ideen, der Fundamentalen Ideen der Stochastik und der Leitidee „Daten und Zufall". Dabei ergibt sich, dass in Abh{\"a}ngigkeit der gew{\"a}hlten Perspektive die Anwendung der Bienaym{\´e}-Galton-Watson Prozesse innerhalb der Schule plausibel ist und von Vorteil f{\"u}r die Sch{\"u}ler:innen sein kann. F{\"u}r die Behandlung wird exemplarisch der Rahmenlehrplan f{\"u}r Berlin und Brandenburg analysiert und mit dem Kernlehrplan Nordrhein-Westfalens verglichen. Die Konzeption des Lehrplans aus Berlin und Brandenburg l{\"a}sst nicht den Schluss zu, dass die Bienaym{\´e}-Galton-Watson Prozesse angewendet werden sollten. Es l{\"a}sst sich feststellen, dass die zugrunde liegende Leitidee nicht vollumf{\"a}nglich mit manchen Fundamentalen Ideen der Stochastik vereinbar ist. Somit w{\"u}rde eine Modifikation hinsichtlich einer st{\"a}rkeren Orientierung des Lehrplans an den Fundamentalen Ideen die Anwendung der Prozesse erm{\"o}glichen. Die Aussage wird durch die Betrachtung und {\"U}bertragung eines nordrhein-westf{\"a}lischen Unterrichtsentwurfes f{\"u}r stochastische Prozesse auf die Bienaym{\´e}-Galton-Watson Prozesse unterst{\"u}tzt. Dar{\"u}ber hinaus werden eine Concept Map und ein Vernetzungspentagraph nach von der Bank konzipiert um diesen Aspekt hervorzuheben.}, language = {de} } @article{RoosOtoba2021, author = {Roos, Saskia and Otoba, Nobuhiko}, title = {Scalar curvature and the multiconformal class of a direct product Riemannian manifold}, series = {Geometriae dedicata}, volume = {214}, journal = {Geometriae dedicata}, number = {1}, publisher = {Springer}, address = {Dordrecht}, issn = {0046-5755}, doi = {10.1007/s10711-021-00636-9}, pages = {801 -- 829}, year = {2021}, abstract = {For a closed, connected direct product Riemannian manifold (M, g) = (M-1, g(1)) x ... x (M-l, g(l)), we define its multiconformal class [[g]] as the totality {integral(2)(1)g(1) circle plus center dot center dot center dot integral(2)(l)g(l)} of all Riemannian metrics obtained from multiplying the metric gi of each factor Mi by a positive function fi on the total space M. A multiconformal class [[ g]] contains not only all warped product type deformations of g but also the whole conformal class [(g) over tilde] of every (g) over tilde is an element of[[ g]]. In this article, we prove that [[g]] contains a metric of positive scalar curvature if and only if the conformal class of some factor (Mi, gi) does, under the technical assumption dim M-i = 2. We also show that, even in the case where every factor (M-i, g(i)) has positive scalar curvature, [[g]] contains a metric of scalar curvature constantly equal to -1 and with arbitrarily large volume, provided l = 2 and dim M = 3.}, language = {en} } @article{GottwaldReich2021, author = {Gottwald, Georg A. and Reich, Sebastian}, title = {Supervised learning from noisy observations}, series = {Physica : D, Nonlinear phenomena}, volume = {423}, journal = {Physica : D, Nonlinear phenomena}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0167-2789}, doi = {10.1016/j.physd.2021.132911}, pages = {15}, year = {2021}, abstract = {Data-driven prediction and physics-agnostic machine-learning methods have attracted increased interest in recent years achieving forecast horizons going well beyond those to be expected for chaotic dynamical systems. In a separate strand of research data-assimilation has been successfully used to optimally combine forecast models and their inherent uncertainty with incoming noisy observations. The key idea in our work here is to achieve increased forecast capabilities by judiciously combining machine-learning algorithms and data assimilation. We combine the physics-agnostic data -driven approach of random feature maps as a forecast model within an ensemble Kalman filter data assimilation procedure. The machine-learning model is learned sequentially by incorporating incoming noisy observations. We show that the obtained forecast model has remarkably good forecast skill while being computationally cheap once trained. Going beyond the task of forecasting, we show that our method can be used to generate reliable ensembles for probabilistic forecasting as well as to learn effective model closure in multi-scale systems. (C) 2021 Elsevier B.V. All rights reserved.}, language = {en} } @article{RedmannFreitag2021, author = {Redmann, Martin and Freitag, Melina A.}, title = {Optimization based model order reduction for stochastic systems}, series = {Applied mathematics and computation}, volume = {398}, journal = {Applied mathematics and computation}, publisher = {Elsevier}, address = {New York}, issn = {0096-3003}, doi = {10.1016/j.amc.2020.125783}, pages = {18}, year = {2021}, abstract = {In this paper, we bring together the worlds of model order reduction for stochastic linear systems and H-2-optimal model order reduction for deterministic systems. In particular, we supplement and complete the theory of error bounds for model order reduction of stochastic differential equations. With these error bounds, we establish a link between the output error for stochastic systems (with additive and multiplicative noise) and modified versions of the H-2-norm for both linear and bilinear deterministic systems. When deriving the respective optimality conditions for minimizing the error bounds, we see that model order reduction techniques related to iterative rational Krylov algorithms (IRKA) are very natural and effective methods for reducing the dimension of large-scale stochastic systems with additive and/or multiplicative noise. We apply modified versions of (linear and bilinear) IRKA to stochastic linear systems and show their efficiency in numerical experiments.}, language = {en} } @article{RuchiDubinkinaWiljes2021, author = {Ruchi, Sangeetika and Dubinkina, Svetlana and Wiljes, Jana de}, title = {Fast hybrid tempered ensemble transform filter formulation for Bayesian elliptical problems via Sinkhorn approximation}, series = {Nonlinear processes in geophysics / European Geosciences Union ; American Geophysical Union}, volume = {28}, journal = {Nonlinear processes in geophysics / European Geosciences Union ; American Geophysical Union}, number = {1}, publisher = {Copernicus}, address = {G{\"o}ttingen}, issn = {1023-5809}, doi = {10.5194/npg-28-23-2021}, pages = {23 -- 41}, year = {2021}, abstract = {Identification of unknown parameters on the basis of partial and noisy data is a challenging task, in particular in high dimensional and non-linear settings. Gaussian approximations to the problem, such as ensemble Kalman inversion, tend to be robust and computationally cheap and often produce astonishingly accurate estimations despite the simplifying underlying assumptions. Yet there is a lot of room for improvement, specifically regarding a correct approximation of a non-Gaussian posterior distribution. The tempered ensemble transform particle filter is an adaptive Sequential Monte Carlo (SMC) method, whereby resampling is based on optimal transport mapping. Unlike ensemble Kalman inversion, it does not require any assumptions regarding the posterior distribution and hence has shown to provide promising results for non-linear non-Gaussian inverse problems. However, the improved accuracy comes with the price of much higher computational complexity, and the method is not as robust as ensemble Kalman inversion in high dimensional problems. In this work, we add an entropy-inspired regularisation factor to the underlying optimal transport problem that allows the high computational cost to be considerably reduced via Sinkhorn iterations. Further, the robustness of the method is increased via an ensemble Kalman inversion proposal step before each update of the samples, which is also referred to as a hybrid approach. The promising performance of the introduced method is numerically verified by testing it on a steady-state single-phase Darcy flow model with two different permeability configurations. The results are compared to the output of ensemble Kalman inversion, and Markov chain Monte Carlo methods results are computed as a benchmark.}, language = {en} } @article{ShlapunovTarchanov2021, author = {Shlapunov, Alexander and Tarchanov, Nikolaj Nikolaevič}, title = {An open mapping theorem for the Navier-Stokes type equations associated with the de Rham complex over R-n}, series = {Siberian electronic mathematical reports = Sibirskie ėlektronnye matematičeskie izvestija}, volume = {18}, journal = {Siberian electronic mathematical reports = Sibirskie ėlektronnye matematičeskie izvestija}, number = {2}, publisher = {Institut Matematiki Imeni S. L. Soboleva}, address = {Novosibirsk}, issn = {1813-3304}, doi = {10.33048/semi.2021.18.108}, pages = {1433 -- 1466}, year = {2021}, abstract = {We consider an initial problem for the Navier-Stokes type equations associated with the de Rham complex over R-n x[0, T], n >= 3, with a positive time T. We prove that the problem induces an open injective mappings on the scales of specially constructed function spaces of Bochner-Sobolev type. In particular, the corresponding statement on the intersection of these classes gives an open mapping theorem for smooth solutions to the Navier-Stokes equations.}, language = {en} } @article{BeckusEliaz2021, author = {Beckus, Siegfried and Eliaz, Latif}, title = {Eigenfunctions growth of R-limits on graphs}, series = {Journal of spectral theory / European Mathematical Society}, volume = {11}, journal = {Journal of spectral theory / European Mathematical Society}, number = {4}, publisher = {EMS Press, an imprint of the European Mathematical Society - EMS - Publishing House GmbH, Institut f{\"u}r Mathematik, Technische Universit{\"a}t}, address = {Berlin}, issn = {1664-039X}, doi = {10.4171/JST/389}, pages = {1895 -- 1933}, year = {2021}, abstract = {A characterization of the essential spectrum of Schrodinger operators on infinite graphs is derived involving the concept of R-limits. This concept, which was introduced previously for operators on N and Z(d) as "right-limits," captures the behaviour of the operator at infinity. For graphs with sub-exponential growth rate, we show that each point in sigma(ss)(H) corresponds to a bounded generalized eigenfunction of a corresponding R-limit of H. If, additionally, the graph is of uniform sub-exponential growth, also the converse inclusion holds.}, language = {en} } @article{SchannerMauerbergerKorteetal.2021, author = {Schanner, Maximilian Arthus and Mauerberger, Stefan and Korte, Monika and Holschneider, Matthias}, title = {Correlation based time evolution of the archeomagnetic field}, series = {Journal of geophysical research : JGR ; an international quarterly. B, Solid earth}, volume = {126}, journal = {Journal of geophysical research : JGR ; an international quarterly. B, Solid earth}, number = {7}, publisher = {American Geophysical Union}, address = {Washington}, issn = {2169-9313}, doi = {10.1029/2020JB021548}, pages = {22}, year = {2021}, abstract = {In a previous study, a new snapshot modeling concept for the archeomagnetic field was introduced (Mauerberger et al., 2020, ). By assuming a Gaussian process for the geomagnetic potential, a correlation-based algorithm was presented, which incorporates a closed-form spatial correlation function. This work extends the suggested modeling strategy to the temporal domain. A space-time correlation kernel is constructed from the tensor product of the closed-form spatial correlation kernel with a squared exponential kernel in time. Dating uncertainties are incorporated into the modeling concept using a noisy input Gaussian process. All but one modeling hyperparameters are marginalized, to reduce their influence on the outcome and to translate their variability to the posterior variance. The resulting distribution incorporates uncertainties related to dating, measurement and modeling process. Results from application to archeomagnetic data show less variation in the dipole than comparable models, but are in general agreement with previous findings.}, language = {en} } @article{ReichWeissmann2021, author = {Reich, Sebastian and Weissmann, Simon}, title = {Fokker-Planck particle systems for Bayesian inference: computational approaches}, series = {SIAM ASA journal on uncertainty quantification}, volume = {9}, journal = {SIAM ASA journal on uncertainty quantification}, number = {2}, publisher = {Society for Industrial and Applied Mathematics}, address = {Philadelphia}, issn = {2166-2525}, doi = {10.1137/19M1303162}, pages = {446 -- 482}, year = {2021}, abstract = {Bayesian inference can be embedded into an appropriately defined dynamics in the space of probability measures. In this paper, we take Brownian motion and its associated Fokker-Planck equation as a starting point for such embeddings and explore several interacting particle approximations. More specifically, we consider both deterministic and stochastic interacting particle systems and combine them with the idea of preconditioning by the empirical covariance matrix. In addition to leading to affine invariant formulations which asymptotically speed up convergence, preconditioning allows for gradient-free implementations in the spirit of the ensemble Kalman filter. While such gradient-free implementations have been demonstrated to work well for posterior measures that are nearly Gaussian, we extend their scope of applicability to multimodal measures by introducing localized gradient-free approximations. Numerical results demonstrate the effectiveness of the considered methodologies.}, language = {en} } @article{CozzoniMaibaumHamm2021, author = {Cozzoni, Barbara and Maibaum, Michael and Hamm, Maximilian}, title = {Thermal analysis and constraints for the MASCOT landing site selection on the asteroid Ryugu}, series = {Planetary and space science}, volume = {205}, journal = {Planetary and space science}, publisher = {Elsevier}, address = {Oxford}, issn = {0032-0633}, doi = {10.1016/j.pss.2021.105286}, pages = {11}, year = {2021}, abstract = {In June 2018, after 4 years of cruise, the Japanese space probe Hayabusa2 [1-Watanabe S. et al.: Hayabusa2 Mission Overview. (2017)] reached the Near-Earth Asteroid (162173) Ryugu. Hayabusa2 carried a small Lander named MASCOT (Mobile Asteroid Surface Scout) [2-Ho T. M. et al.: MASCOT-The Mobile Asteroid Surface Scout onboard the Hayabusa2 mission. (2017)], jointly developed by the German Aerospace Center (DLR) and the French Space Agency (CNES), to investigate Ryugu's surface structure, composition and physical properties including its thermal behaviour and magnetization in-situ. The Microgravity User Support Centre (DLR-MUSC) in Cologne was in charge of providing all thermal conditions and constraints necessary for the selection of the final landing site and for the final operations of the Lander MASCOT on the surface of the asteroid Ryugu. This article provides a comprehensive assessment of these thermal conditions and constraints, based on predictions performed with the Thermal Mathematical Model (TMM) of MASCOT using different asteroid surface thermal models, ephemeris data for approach as well as descent and hopping trajectories, the related operation sequences and scenarios and the possible environmental conditions driven by the Hayabusa2 spacecraft. A comparison with the real telemetry data confirms the analysis and provides further information about the asteroid characteristics.}, language = {en} } @article{HastermannReinhardtKleinetal.2021, author = {Hastermann, Gottfried and Reinhardt, Maria and Klein, Rupert and Reich, Sebastian}, title = {Balanced data assimilation for highly oscillatory mechanical systems}, series = {Communications in applied mathematics and computational science : CAMCoS}, volume = {16}, journal = {Communications in applied mathematics and computational science : CAMCoS}, number = {1}, publisher = {Mathematical Sciences Publishers}, address = {Berkeley}, issn = {1559-3940}, doi = {10.2140/camcos.2021.16.119}, pages = {119 -- 154}, year = {2021}, abstract = {Data assimilation algorithms are used to estimate the states of a dynamical system using partial and noisy observations. The ensemble Kalman filter has become a popular data assimilation scheme due to its simplicity and robustness for a wide range of application areas. Nevertheless, this filter also has limitations due to its inherent assumptions of Gaussianity and linearity, which can manifest themselves in the form of dynamically inconsistent state estimates. This issue is investigated here for balanced, slowly evolving solutions to highly oscillatory Hamiltonian systems which are prototypical for applications in numerical weather prediction. It is demonstrated that the standard ensemble Kalman filter can lead to state estimates that do not satisfy the pertinent balance relations and ultimately lead to filter divergence. Two remedies are proposed, one in terms of blended asymptotically consistent time-stepping schemes, and one in terms of minimization-based postprocessing methods. The effects of these modifications to the standard ensemble Kalman filter are discussed and demonstrated numerically for balanced motions of two prototypical Hamiltonian reference systems.}, language = {en} } @article{DeneckeHounnon2021, author = {Denecke, Klaus-Dieter and Hounnon, Hippolyte}, title = {Partial Menger algebras of terms}, series = {Asian-European journal of mathematics}, volume = {14}, journal = {Asian-European journal of mathematics}, number = {06}, publisher = {World Scientific}, address = {Singapore}, issn = {1793-5571}, doi = {10.1142/S1793557121500923}, pages = {14}, year = {2021}, abstract = {The superposition operation S-n,S-A, n >= 1, n is an element of N, maps to each (n + 1)-tuple of n-ary operations on a set A an n-ary operation on A and satisfies the so-called superassociative law, a generalization of the associative law. The corresponding algebraic structures are Menger algebras of rank n. A partial algebra of type (n + 1) which satisfies the superassociative law as weak identity is said to be a partial Menger algebra of rank n. As a generalization of linear terms we define r-terms as terms where each variable occurs at most r-times. It will be proved that n-ary r-terms form partial Menger algebras of rank n. In this paper, some algebraic properties of partial Menger algebras such as generating systems, homomorphic images and freeness are investigated. As generalization of hypersubstitutions and linear hypersubstitutions we consider r-hypersubstitutions.U}, language = {en} } @article{DeOliveiraGomesHoegele2021, author = {De Oliveira Gomes, Andr{\´e} and H{\"o}gele, Michael Anton}, title = {The Kramers problem for SDEs driven by small, accelerated L{\´e}vy noise with exponentially light jumps}, series = {Stochastics and dynamics}, volume = {21}, journal = {Stochastics and dynamics}, number = {04}, publisher = {World Scientific}, address = {Singapore}, issn = {0219-4937}, doi = {10.1142/S0219493721500192}, pages = {44}, year = {2021}, abstract = {We establish Freidlin-Wentzell results for a nonlinear ordinary differential equation starting close to the stable state 0, say, subject to a perturbation by a stochastic integral which is driven by an epsilon-small and (1/epsilon)-accelerated Levy process with exponentially light jumps. For this purpose, we derive a large deviations principle for the stochastically perturbed system using the weak convergence approach developed by Budhiraja, Dupuis, Maroulas and collaborators in recent years. In the sequel, we solve the associated asymptotic first escape problem from the bounded neighborhood of 0 in the limit as epsilon -> 0 which is also known as the Kramers problem in the literature.}, language = {en} } @article{GarmendiaZambon2021, author = {Garmendia, Alfonso and Zambon, Marco}, title = {Quotients of singular foliations and Lie 2-group actions}, series = {Journal of noncommutative geometry}, volume = {15}, journal = {Journal of noncommutative geometry}, number = {4}, publisher = {EMS Press, an imprint of the European Mathematical Society - EMS - Publishing House GmbH, Institut f{\"u}r Mathematik, Technische Universit{\"a}t Berlin}, address = {Berlin}, issn = {1661-6952}, doi = {10.4171/JNCG/434}, pages = {1251 -- 1283}, year = {2021}, abstract = {Androulidakis-Skandalis (2009) showed that every singular foliation has an associated topological groupoid, called holonomy groupoid. In this note, we exhibit some functorial properties of this assignment: if a foliated manifold (M, FM ) is the quotient of a foliated manifold (P, FP ) along a surjective submersion with connected fibers, then the same is true for the corresponding holonomy groupoids. For quotients by a Lie group action, an analogue statement holds under suitable assumptions, yielding a Lie 2-group action on the holonomy groupoid.}, language = {en} } @article{SchickSeyedhosseini2021, author = {Schick, Thomas and Seyedhosseini, Mehran}, title = {On an index theorem of Chang, Weinberger and Yu}, series = {M{\"u}nster journal of mathematics}, volume = {14}, journal = {M{\"u}nster journal of mathematics}, number = {1}, publisher = {WWU, Fachbereich Mathematik und Informatik}, address = {M{\"u}nster}, issn = {1867-5778}, doi = {10.17879/59019522628}, pages = {123 -- 154}, year = {2021}, abstract = {In this paper we prove a strengthening of a theorem of Chang, Weinberger and Yu on obstructions to the existence of positive scalar curvature metrics on compact manifolds with boundary. They construct a relative index for the Dirac operator, which lives in a relative K-theory group, measuring the difference between the fundamental group of the boundary and of the full manifold. Whenever the Riemannian metric has product structure and positive scalar curvature near the boundary, one can define an absolute index of the Dirac operator taking value in the K-theory of the C*-algebra of fundamental group of the full manifold. This index depends on the metric near the boundary. We prove that (a slight variation of) the relative index of Chang, Weinberger and Yu is the image of this absolute index under the canonical map of K-theory groups. This has the immediate corollary that positive scalar curvature on the whole manifold implies vanishing of the relative index, giving a conceptual and direct proof of the vanishing theorem of Chang, Weinberger and Yu (rather: a slight variation). To take the fundamental groups of the manifold and its boundary into account requires working with maximal C*-completions of the involved *-algebras. A significant part of this paper is devoted to foundational results regarding these completions. On the other hand, we introduce and propose a more conceptual and more geometric completion, which still has all the required functoriality.}, language = {en} } @article{MatzkaStolleYamazakietal.2021, author = {Matzka, J{\"u}rgen and Stolle, Claudia and Yamazaki, Yosuke and Bronkalla, Oliver and Morschhauser, Achim}, title = {The geomagnetic Kp index and derived indices of geomagnetic activity}, series = {Space weather : the international journal of research and applications}, volume = {19}, journal = {Space weather : the international journal of research and applications}, number = {5}, publisher = {Wiley}, address = {New York}, issn = {1542-7390}, doi = {10.1029/2020SW002641}, pages = {21}, year = {2021}, abstract = {The geomagnetic Kp index is one of the most extensively used indices of geomagnetic activity, both for scientific and operational purposes. This article reviews the properties of the Kp index and provides a reference for users of the Kp index and associated data products as derived and distributed by the GFZ German Research Centre for Geosciences. The near real-time production of the nowcast Kp index is of particular interest for space weather services and here we describe and evaluate its current setup.}, language = {en} } @article{KemptonMuenchYau2021, author = {Kempton, Mark and M{\"u}nch, Florentin and Yau, Shing-Tung}, title = {A homology vanishing theorem for graphs with positive curvature}, series = {Communications in analysis and geometry}, volume = {29}, journal = {Communications in analysis and geometry}, number = {6}, publisher = {International Press of Boston}, address = {Somerville}, issn = {1019-8385}, doi = {10.4310/CAG.2021.v29.n6.a5}, pages = {1449 -- 1473}, year = {2021}, abstract = {We prove a homology vanishing theorem for graphs with positive Bakry-' Emery curvature, analogous to a classic result of Bochner on manifolds [3]. Specifically, we prove that if a graph has positive curvature at every vertex, then its first homology group is trivial, where the notion of homology that we use for graphs is the path homology developed by Grigor'yan, Lin, Muranov, and Yau [11]. We moreover prove that the fundamental group is finite for graphs with positive Bakry-' Emery curvature, analogous to a classic result of Myers on manifolds [22]. The proofs draw on several separate areas of graph theory, including graph coverings, gain graphs, and cycle spaces, in addition to the Bakry-Emery curvature, path homology, and graph homotopy. The main results follow as a consequence of several different relationships developed among these different areas. Specifically, we show that a graph with positive curvature cannot have a non-trivial infinite cover preserving 3-cycles and 4-cycles, and give a combinatorial interpretation of the first path homology in terms of the cycle space of a graph. Furthermore, we relate gain graphs to graph homotopy and the fundamental group developed by Grigor'yan, Lin, Muranov, and Yau [12], and obtain an alternative proof of their result that the abelianization of the fundamental group of a graph is isomorphic to the first path homology over the integers.}, language = {en} } @article{PathirajaReichStannat2021, author = {Pathiraja, Sahani Darschika and Reich, Sebastian and Stannat, Wilhelm}, title = {McKean-Vlasov SDEs in nonlinear filtering}, series = {SIAM journal on control and optimization : a publication of the Society for Industrial and Applied Mathematics}, volume = {59}, journal = {SIAM journal on control and optimization : a publication of the Society for Industrial and Applied Mathematics}, number = {6}, publisher = {Society for Industrial and Applied Mathematics}, address = {Philadelphia}, issn = {0363-0129}, doi = {10.1137/20M1355197}, pages = {4188 -- 4215}, year = {2021}, abstract = {Various particle filters have been proposed over the last couple of decades with the common feature that the update step is governed by a type of control law. This feature makes them an attractive alternative to traditional sequential Monte Carlo which scales poorly with the state dimension due to weight degeneracy. This article proposes a unifying framework that allows us to systematically derive the McKean-Vlasov representations of these filters for the discrete time and continuous time observation case, taking inspiration from the smooth approximation of the data considered in [D. Crisan and J. Xiong, Stochastics, 82 (2010), pp. 53-68; J. M. Clark and D. Crisan, Probab. Theory Related Fields, 133 (2005), pp. 43-56]. We consider three filters that have been proposed in the literature and use this framework to derive Ito representations of their limiting forms as the approximation parameter delta -> 0. All filters require the solution of a Poisson equation defined on R-d, for which existence and uniqueness of solutions can be a nontrivial issue. We additionally establish conditions on the signal-observation system that ensures well-posedness of the weighted Poisson equation arising in one of the filters.}, language = {en} } @article{LeungLeutbecherReichetal.2021, author = {Leung, Tsz Yan and Leutbecher, Martin and Reich, Sebastian and Shepherd, Theodore G.}, title = {Forecast verification}, series = {Quarterly journal of the Royal Meteorological Society}, volume = {147}, journal = {Quarterly journal of the Royal Meteorological Society}, number = {739}, publisher = {Wiley}, address = {Hoboken}, issn = {0035-9009}, doi = {10.1002/qj.4120}, pages = {3124 -- 3134}, year = {2021}, abstract = {The philosophy of forecast verification is rather different between deterministic and probabilistic verification metrics: generally speaking, deterministic metrics measure differences, whereas probabilistic metrics assess reliability and sharpness of predictive distributions. This article considers the root-mean-square error (RMSE), which can be seen as a deterministic metric, and the probabilistic metric Continuous Ranked Probability Score (CRPS), and demonstrates that under certain conditions, the CRPS can be mathematically expressed in terms of the RMSE when these metrics are aggregated. One of the required conditions is the normality of distributions. The other condition is that, while the forecast ensemble need not be calibrated, any bias or over/underdispersion cannot depend on the forecast distribution itself. Under these conditions, the CRPS is a fraction of the RMSE, and this fraction depends only on the heteroscedasticity of the ensemble spread and the measures of calibration. The derived CRPS-RMSE relationship for the case of perfect ensemble reliability is tested on simulations of idealised two-dimensional barotropic turbulence. Results suggest that the relationship holds approximately despite the normality condition not being met.}, language = {en} } @article{AyanbayevKlebanovLietal.2021, author = {Ayanbayev, Birzhan and Klebanov, Ilja and Li, Han Cheng and Sullivan, Tim J.}, title = {Gamma-convergence of Onsager-Machlup functionals}, series = {Inverse problems : an international journal of inverse problems, inverse methods and computerised inversion of data}, volume = {38}, journal = {Inverse problems : an international journal of inverse problems, inverse methods and computerised inversion of data}, number = {2}, publisher = {IOP Publ. Ltd.}, address = {Bristol}, issn = {0266-5611}, doi = {10.1088/1361-6420/ac3f81}, pages = {32}, year = {2021}, abstract = {The Bayesian solution to a statistical inverse problem can be summarised by a mode of the posterior distribution, i.e. a maximum a posteriori (MAP) estimator. The MAP estimator essentially coincides with the (regularised) variational solution to the inverse problem, seen as minimisation of the Onsager-Machlup (OM) functional of the posterior measure. An open problem in the stability analysis of inverse problems is to establish a relationship between the convergence properties of solutions obtained by the variational approach and by the Bayesian approach. To address this problem, we propose a general convergence theory for modes that is based on the Gamma-convergence of OM functionals, and apply this theory to Bayesian inverse problems with Gaussian and edge-preserving Besov priors. Part II of this paper considers more general prior distributions.}, language = {en} } @article{AyanbayevKlebanovLieetal.2021, author = {Ayanbayev, Birzhan and Klebanov, Ilja and Lie, Han Cheng and Sullivan, Tim J.}, title = {Gamma-convergence of Onsager-Machlup functionals}, series = {Inverse problems : an international journal of inverse problems, inverse methods and computerised inversion of data}, volume = {38}, journal = {Inverse problems : an international journal of inverse problems, inverse methods and computerised inversion of data}, number = {2}, publisher = {IOP Publ. Ltd.}, address = {Bristol}, issn = {0266-5611}, doi = {10.1088/1361-6420/ac3f82}, pages = {35}, year = {2021}, abstract = {We derive Onsager-Machlup functionals for countable product measures on weighted l(p) subspaces of the sequence space R-N. Each measure in the product is a shifted and scaled copy of a reference probability measure on R that admits a sufficiently regular Lebesgue density. We study the equicoercivity and Gamma-convergence of sequences of Onsager-Machlup functionals associated to convergent sequences of measures within this class. We use these results to establish analogous results for probability measures on separable Banach or Hilbert spaces, including Gaussian, Cauchy, and Besov measures with summability parameter 1 <= p <= 2. Together with part I of this paper, this provides a basis for analysis of the convergence of maximum a posteriori estimators in Bayesian inverse problems and most likely paths in transition path theory.}, language = {en} } @article{EshghiMachReichel2021, author = {Eshghi, Nasim and Mach, Thomas and Reichel, Lothar}, title = {New matrix function approximations and quadrature rules based on the Arnoldi process}, series = {Journal of computational and applied mathematics}, volume = {391}, journal = {Journal of computational and applied mathematics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0377-0427}, doi = {10.1016/j.cam.2021.113442}, pages = {12}, year = {2021}, abstract = {The Arnoldi process can be applied to inexpensively approximate matrix functions of the form f (A)v and matrix functionals of the form v*(f (A))*g(A)v, where A is a large square non-Hermitian matrix, v is a vector, and the superscript * denotes transposition and complex conjugation. Here f and g are analytic functions that are defined in suitable regions in the complex plane. This paper reviews available approximation methods and describes new ones that provide higher accuracy for essentially the same computational effort by exploiting available, but generally not used, moment information. Numerical experiments show that in some cases the modifications of the Arnoldi decompositions proposed can improve the accuracy of v*(f (A))*g(A)v about as much as performing an additional step of the Arnoldi process.}, language = {en} } @misc{Huebner2021, type = {Master Thesis}, author = {H{\"u}bner, Andrea}, title = {Ein multityper Verzweigungsprozess als Modell zur Untersuchung der Ausbreitung von Covid-19}, doi = {10.25932/publishup-50922}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-509225}, school = {Universit{\"a}t Potsdam}, year = {2021}, abstract = {Im Zuge der Covid-19 Pandemie werden zwei Werte t{\"a}glich diskutiert: Die zuletzt gemeldete Zahl der neu Infizierten und die sogenannte Reproduktionsrate. Sie gibt wieder, wie viele weitere Menschen ein an Corona erkranktes Individuum im Durchschnitt ansteckt. F{\"u}r die Sch{\"a}tzung dieses Wertes gibt es viele M{\"o}glichkeiten - auch das Robert Koch-Institut gibt in seinem t{\"a}glichen Situationsbericht stets zwei R-Werte an: Einen 4-Tage-R-Wert und einen weniger schwankenden 7-Tage-R-Wert. Diese Arbeit soll eine weitere M{\"o}glichkeit vorstellen, einige Aspekte der Pandemie zu modellieren und die Reproduktionsrate zu sch{\"a}tzen. In der ersten H{\"a}lfte der Arbeit werden die mathematischen Grundlagen vorgestellt, die man f{\"u}r die Modellierung ben{\"o}tigt. Hierbei wird davon ausgegangen, dass der Leser bereits ein Basisverst{\"a}ndnis von stochastischen Prozessen hat. Im Abschnitt Grundlagen werden Verzweigungsprozesse mit einigen Beispielen eingef{\"u}hrt und die Ergebnisse aus diesem Themengebiet, die f{\"u}r diese Arbeit wichtig sind, pr{\"a}sentiert. Dabei gehen wir zuerst auf einfache Verzweigungsprozesse ein und erweitern diese dann auf Verzweigungsprozesse mit mehreren Typen. Um die Notation zu erleichtern, beschr{\"a}nken wir uns auf zwei Typen. Das Prinzip l{\"a}sst sich aber auf eine beliebige Anzahl von Typen erweitern. Vor allem soll die Wichtigkeit des Parameters λ herausgestellt werden. Dieser Wert kann als durchschnittliche Zahl von Nachfahren eines Individuums interpretiert werden und bestimmt die Dynamik des Prozesses {\"u}ber einen l{\"a}ngeren Zeitraum. In der Anwendung auf die Pandemie hat der Parameter λ die gleiche Rolle wie die Reproduktionsrate R. In der zweiten H{\"a}lfte dieser Arbeit stellen wir eine Anwendung der Theorie {\"u}ber Multitype Verzweigungsprozesse vor. Professor Yanev und seine Mitarbeiter modellieren in ihrer Ver{\"o}ffentlichung Branching stochastic processes as models of Covid-19 epidemic development die Ausbreitung des Corona Virus' {\"u}ber einen Verzweigungsprozess mit zwei Typen. Wir werden dieses Modell diskutieren und Sch{\"a}tzer daraus ableiten: Ziel ist es, die Reproduktionsrate zu ermitteln. Außerdem analysieren wir die M{\"o}glichkeiten, die Dunkelziffer (die Zahl nicht gemeldeter Krankheitsf{\"a}lle) zu sch{\"a}tzen. Wir wenden die Sch{\"a}tzer auf die Zahlen von Deutschland an und werten diese schließlich aus.}, language = {de} } @article{CvetkovićConradLie2021, author = {Cvetković, Nada and Conrad, Tim and Lie, Han Cheng}, title = {A convergent discretization method for transition path theory for diffusion processes}, series = {Multiscale modeling \& simulation : a SIAM interdisciplinary journal}, volume = {19}, journal = {Multiscale modeling \& simulation : a SIAM interdisciplinary journal}, number = {1}, publisher = {Society for Industrial and Applied Mathematics}, address = {Philadelphia}, issn = {1540-3459}, doi = {10.1137/20M1329354}, pages = {242 -- 266}, year = {2021}, abstract = {Transition path theory (TPT) for diffusion processes is a framework for analyzing the transitions of multiscale ergodic diffusion processes between disjoint metastable subsets of state space. Most methods for applying TPT involve the construction of a Markov state model on a discretization of state space that approximates the underlying diffusion process. However, the assumption of Markovianity is difficult to verify in practice, and there are to date no known error bounds or convergence results for these methods. We propose a Monte Carlo method for approximating the forward committor, probability current, and streamlines from TPT for diffusion processes. Our method uses only sample trajectory data and partitions of state space based on Voronoi tessellations. It does not require the construction of a Markovian approximating process. We rigorously prove error bounds for the approximate TPT objects and use these bounds to show convergence to their exact counterparts in the limit of arbitrarily fine discretization. We illustrate some features of our method by application to a process that solves the Smoluchowski equation on a triple-well potential.}, language = {en} } @article{ChangKhalilSchulze2021, author = {Chang, Der-Chen and Khalil, Sara and Schulze, Bert-Wolfgang}, title = {Analysis on regular corner spaces}, series = {The journal of geometric analysis}, volume = {31}, journal = {The journal of geometric analysis}, number = {9}, publisher = {Springer}, address = {New York}, issn = {1050-6926}, doi = {10.1007/s12220-021-00614-3}, pages = {9199 -- 9240}, year = {2021}, abstract = {We establish a new approach of treating elliptic boundary value problems (BVPs) on manifolds with boundary and regular corners, up to singularity order 2. Ellipticity and parametrices are obtained in terms of symbols taking values in algebras of BVPs on manifolds of corresponding lower singularity orders. Those refer to Boutet de Monvel's calculus of operators with the transmission property, see Boutet de Monvel (Acta Math 126:11-51, 1971) for the case of smooth boundary. On corner configuration operators act in spaces with multiple weights. We mainly study the case of upper left entries in the respective 2 x 2 operator block-matrices of such a calculus. Green operators in the sense of Boutet de Monvel (Acta Math 126:11-51, 1971) analogously appear in singular cases, and they are complemented by contributions of Mellin type. We formulate a result on ellipticity and the Fredholm property in weighted corner spaces, with parametrices of analogous kind.}, language = {en} } @article{WormellReich2021, author = {Wormell, Caroline L. and Reich, Sebastian}, title = {Spectral convergence of diffusion maps}, series = {SIAM journal on numerical analysis / Society for Industrial and Applied Mathematics}, volume = {59}, journal = {SIAM journal on numerical analysis / Society for Industrial and Applied Mathematics}, number = {3}, publisher = {Society for Industrial and Applied Mathematics}, address = {Philadelphia}, issn = {0036-1429}, doi = {10.1137/20M1344093}, pages = {1687 -- 1734}, year = {2021}, abstract = {Diffusion maps is a manifold learning algorithm widely used for dimensionality reduction. Using a sample from a distribution, it approximates the eigenvalues and eigenfunctions of associated Laplace-Beltrami operators. Theoretical bounds on the approximation error are, however, generally much weaker than the rates that are seen in practice. This paper uses new approaches to improve the error bounds in the model case where the distribution is supported on a hypertorus. For the data sampling (variance) component of the error we make spatially localized compact embedding estimates on certain Hardy spaces; we study the deterministic (bias) component as a perturbation of the Laplace-Beltrami operator's associated PDE and apply relevant spectral stability results. Using these approaches, we match long-standing pointwise error bounds for both the spectral data and the norm convergence of the operator discretization. We also introduce an alternative normalization for diffusion maps based on Sinkhorn weights. This normalization approximates a Langevin diffusion on the sample and yields a symmetric operator approximation. We prove that it has better convergence compared with the standard normalization on flat domains, and we present a highly efficient rigorous algorithm to compute the Sinkhorn weights.}, language = {en} } @article{KellerLiuPeyerimhoff2021, author = {Keller, Matthias and Liu, Shiping and Peyerimhoff, Norbert}, title = {A note on eigenvalue bounds for non-compact manifolds}, series = {Mathematische Nachrichten}, volume = {294}, journal = {Mathematische Nachrichten}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0025-584X}, doi = {10.1002/mana.201900209}, pages = {1134 -- 1139}, year = {2021}, abstract = {In this article we prove upper bounds for the Laplace eigenvalues lambda(k) below the essential spectrum for strictly negatively curved Cartan-Hadamard manifolds. Our bound is given in terms of k(2) and specific geometric data of the manifold. This applies also to the particular case of non-compact manifolds whose sectional curvature tends to -infinity, where no essential spectrum is present due to a theorem of Donnelly/Li. The result stands in clear contrast to Laplacians on graphs where such a bound fails to be true in general.}, language = {en} } @article{SaynischWagnerBaerenzungHornschildetal.2021, author = {Saynisch-Wagner, Jan and B{\"a}renzung, Julien and Hornschild, Aaron and Irrgang, Christopher and Thomas, Maik}, title = {Tide-induced magnetic signals and their errors derived from CHAMP and Swarm satellite magnetometer observations}, series = {Earth, planets and space : EPS}, volume = {73}, journal = {Earth, planets and space : EPS}, number = {1}, publisher = {Springer}, address = {Heidelberg}, issn = {1880-5981}, doi = {10.1186/s40623-021-01557-3}, pages = {11}, year = {2021}, abstract = {Satellite-measured tidal magnetic signals are of growing importance. These fields are mainly used to infer Earth's mantle conductivity, but also to derive changes in the oceanic heat content. We present a new Kalman filter-based method to derive tidal magnetic fields from satellite magnetometers: KALMAG. The method's advantage is that it allows to study a precisely estimated posterior error covariance matrix. We present the results of a simultaneous estimation of the magnetic signals of 8 major tides from 17 years of Swarm and CHAMP data. For the first time, robustly derived posterior error distributions are reported along with the reported tidal magnetic fields. The results are compared to other estimates that are either based on numerical forward models or on satellite inversions of the same data. For all comparisons, maximal differences and the corresponding globally averaged RMSE are reported. We found that the inter-product differences are comparable with the KALMAG-based errors only in a global mean sense. Here, all approaches give values of the same order, e.g., 0.09 nT-0.14 nT for M2. Locally, the KALMAG posterior errors are up to one order smaller than the inter-product differences, e.g., 0.12 nT vs. 0.96 nT for M2.}, language = {en} } @article{RodriguezZuluagaStolleYamazakietal.2021, author = {Rodr{\´i}guez Zuluaga, Juan and Stolle, Claudia and Yamazaki, Yosuke and Xiong, Chao and England, Scott L.}, title = {A synoptic-scale wavelike structure in the nighttime equatorial ionization anomaly}, series = {Earth and Space Science : ESS}, volume = {8}, journal = {Earth and Space Science : ESS}, number = {2}, publisher = {American Geophysical Union}, address = {Malden, Mass.}, issn = {2333-5084}, doi = {10.1029/2020EA001529}, pages = {10}, year = {2021}, abstract = {Both ground- and satellite-based airglow imaging have significantly contributed to understanding the low-latitude ionosphere, especially the morphology and dynamics of the equatorial ionization anomaly (EIA). The NASA Global-scale Observations of the Limb and Disk (GOLD) mission focuses on far-ultraviolet airglow images from a geostationary orbit at 47.5 degrees W. This region is of particular interest at low magnetic latitudes because of the high magnetic declination (i.e., about -20 degrees) and proximity of the South Atlantic magnetic anomaly. In this study, we characterize an exciting feature of the nighttime EIA using GOLD observations from October 5, 2018 to June 30, 2020. It consists of a wavelike structure of a few thousand kilometers seen as poleward and equatorward displacements of the EIA-crests. Initial analyses show that the synoptic-scale structure is symmetric about the dip equator and appears nearly stationary with time over the night. In quasi-dipole coordinates, maxima poleward displacements of the EIA-crests are seen at about +/- 12 degrees latitude and around 20 and 60 degrees longitude (i.e., in geographic longitude at the dip equator, about 53 degrees W and 14 degrees W). The wavelike structure presents typical zonal wavelengths of about 6.7 x 10(3) km and 3.3 x 10(3) km. The structure's occurrence and wavelength are highly variable on a day-to-day basis with no apparent dependence on geomagnetic activity. In addition, a cluster or quasi-periodic wave train of equatorial plasma depletions (EPDs) is often detected within the synoptic-scale structure. We further outline the difference in observing these EPDs from FUV images and in situ measurements during a GOLD and Swarm mission conjunction.}, language = {en} } @article{SchindlerMoldenhawerStangeetal.2021, author = {Schindler, Daniel and Moldenhawer, Ted and Stange, Maike and Lepro, Valentino and Beta, Carsten and Holschneider, Matthias and Huisinga, Wilhelm}, title = {Analysis of protrusion dynamics in amoeboid cell motility by means of regularized contour flows}, series = {PLoS Computational Biology : a new community journal}, volume = {17}, journal = {PLoS Computational Biology : a new community journal}, number = {8}, publisher = {PLoS}, address = {San Fransisco}, issn = {1553-734X}, doi = {10.1371/journal.pcbi.1009268}, pages = {33}, year = {2021}, abstract = {Amoeboid cell motility is essential for a wide range of biological processes including wound healing, embryonic morphogenesis, and cancer metastasis. It relies on complex dynamical patterns of cell shape changes that pose long-standing challenges to mathematical modeling and raise a need for automated and reproducible approaches to extract quantitative morphological features from image sequences. Here, we introduce a theoretical framework and a computational method for obtaining smooth representations of the spatiotemporal contour dynamics from stacks of segmented microscopy images. Based on a Gaussian process regression we propose a one-parameter family of regularized contour flows that allows us to continuously track reference points (virtual markers) between successive cell contours. We use this approach to define a coordinate system on the moving cell boundary and to represent different local geometric quantities in this frame of reference. In particular, we introduce the local marker dispersion as a measure to identify localized membrane expansions and provide a fully automated way to extract the properties of such expansions, including their area and growth time. The methods are available as an open-source software package called AmoePy, a Python-based toolbox for analyzing amoeboid cell motility (based on time-lapse microscopy data), including a graphical user interface and detailed documentation. Due to the mathematical rigor of our framework, we envision it to be of use for the development of novel cell motility models. We mainly use experimental data of the social amoeba Dictyostelium discoideum to illustrate and validate our approach.
Author summary Amoeboid motion is a crawling-like cell migration that plays an important key role in multiple biological processes such as wound healing and cancer metastasis. This type of cell motility results from expanding and simultaneously contracting parts of the cell membrane. From fluorescence images, we obtain a sequence of points, representing the cell membrane, for each time step. By using regression analysis on these sequences, we derive smooth representations, so-called contours, of the membrane. Since the number of measurements is discrete and often limited, the question is raised of how to link consecutive contours with each other. In this work, we present a novel mathematical framework in which these links are described by regularized flows allowing a certain degree of concentration or stretching of neighboring reference points on the same contour. This stretching rate, the so-called local dispersion, is used to identify expansions and contractions of the cell membrane providing a fully automated way of extracting properties of these cell shape changes. We applied our methods to time-lapse microscopy data of the social amoeba Dictyostelium discoideum.}, language = {en} } @article{HartungWahlRastogietal.2021, author = {Hartung, Niklas and Wahl, Martin and Rastogi, Abhishake and Huisinga, Wilhelm}, title = {Nonparametric goodness-of-fit testing for parametric covariate models in pharmacometric analyses}, series = {CPT: pharmacometrics \& systems pharmacology}, volume = {10}, journal = {CPT: pharmacometrics \& systems pharmacology}, number = {6}, publisher = {Nature Publ. Group}, address = {London}, issn = {2163-8306}, doi = {10.1002/psp4.12614}, pages = {564 -- 576}, year = {2021}, abstract = {The characterization of covariate effects on model parameters is a crucial step during pharmacokinetic/pharmacodynamic analyses. Although covariate selection criteria have been studied extensively, the choice of the functional relationship between covariates and parameters, however, has received much less attention. Often, a simple particular class of covariate-to-parameter relationships (linear, exponential, etc.) is chosen ad hoc or based on domain knowledge, and a statistical evaluation is limited to the comparison of a small number of such classes. Goodness-of-fit testing against a nonparametric alternative provides a more rigorous approach to covariate model evaluation, but no such test has been proposed so far. In this manuscript, we derive and evaluate nonparametric goodness-of-fit tests for parametric covariate models, the null hypothesis, against a kernelized Tikhonov regularized alternative, transferring concepts from statistical learning to the pharmacological setting. The approach is evaluated in a simulation study on the estimation of the age-dependent maturation effect on the clearance of a monoclonal antibody. Scenarios of varying data sparsity and residual error are considered. The goodness-of-fit test correctly identified misspecified parametric models with high power for relevant scenarios. The case study provides proof-of-concept of the feasibility of the proposed approach, which is envisioned to be beneficial for applications that lack well-founded covariate models.}, language = {en} } @article{HetheyHartungWangorschetal.2021, author = {Hethey, Christoph Philipp and Hartung, Niklas and Wangorsch, Gaby and Weisser, Karin and Huisinga, Wilhelm}, title = {Physiology-based toxicokinetic modelling of aluminium in rat and man}, series = {Archives of toxicology : official journal of EUROTOX}, volume = {95}, journal = {Archives of toxicology : official journal of EUROTOX}, number = {9}, publisher = {Springer}, address = {Berlin ; Heidelberg}, issn = {0340-5761}, doi = {10.1007/s00204-021-03107-y}, pages = {2977 -- 3000}, year = {2021}, abstract = {A sufficient quantitative understanding of aluminium (Al) toxicokinetics (TK) in man is still lacking, although highly desirable for risk assessment of Al exposure. Baseline exposure and the risk of contamination severely limit the feasibility of TK studies administering the naturally occurring isotope Al-27, both in animals and man. These limitations are absent in studies with Al-26 as a tracer, but tissue data are limited to animal studies. A TK model capable of inter-species translation to make valid predictions of Al levels in humans-especially in toxicological relevant tissues like bone and brain-is urgently needed. Here, we present: (i) a curated dataset which comprises all eligible studies with single doses of Al-26 tracer administered as citrate or chloride salts orally and/or intravenously to rats and humans, including ultra-long-term kinetic profiles for plasma, blood, liver, spleen, muscle, bone, brain, kidney, and urine up to 150 weeks; and (ii) the development of a physiology-based (PB) model for Al TK after intravenous and oral administration of aqueous Al citrate and Al chloride solutions in rats and humans. Based on the comprehensive curated Al-26 dataset, we estimated substance-dependent parameters within a non-linear mixed-effect modelling context. The model fitted the heterogeneous Al-26 data very well and was successfully validated against datasets in rats and humans. The presented PBTK model for Al, based on the most extensive and diverse dataset of Al exposure to date, constitutes a major advancement in the field, thereby paving the way towards a more quantitative risk assessment in humans.}, language = {en} } @phdthesis{Perera2021, author = {Perera, Upeksha}, title = {Solutions of direct and inverse Sturm-Liouville problems}, doi = {10.25932/publishup-53006}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-530064}, school = {Universit{\"a}t Potsdam}, pages = {x, 109}, year = {2021}, abstract = {Lie group method in combination with Magnus expansion is utilized to develop a universal method applicable to solving a Sturm-Liouville Problem (SLP) of any order with arbitrary boundary conditions. It is shown that the method has ability to solve direct regular and some singular SLPs of even orders (tested up to order eight), with a mix of boundary conditions (including non-separable and finite singular endpoints), accurately and efficiently. The present technique is successfully applied to overcome the difficulties in finding suitable sets of eigenvalues so that the inverse SLP problem can be effectively solved. Next, a concrete implementation to the inverse Sturm-Liouville problem algorithm proposed by Barcilon (1974) is provided. Furthermore, computational feasibility and applicability of this algorithm to solve inverse Sturm-Liouville problems of order n=2,4 is verified successfully. It is observed that the method is successful even in the presence of significant noise, provided that the assumptions of the algorithm are satisfied. In conclusion, this work provides methods that can be adapted successfully for solving a direct (regular/singular) or inverse SLP of an arbitrary order with arbitrary boundary conditions.}, language = {en} } @phdthesis{Maier2021, author = {Maier, Corinna}, title = {Bayesian data assimilation and reinforcement learning for model-informed precision dosing in oncology}, doi = {10.25932/publishup-51587}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-515870}, school = {Universit{\"a}t Potsdam}, pages = {x, 138}, year = {2021}, abstract = {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.}, language = {en} }