TY - JOUR A1 - Kucharski, Maciej A1 - Ergintav, Arzu A1 - Ahmad, Wael Abdullah A1 - Krstić, Miloš A1 - Ng, Herman Jalli A1 - Kissinger, Dietmar T1 - A Scalable 79-GHz Radar Platform Based on Single-Channel Transceivers JF - IEEE Transactions on Microwave Theory and Techniques N2 - This paper presents a scalable E-band radar platform based on single-channel fully integrated transceivers (TRX) manufactured using 130-nm silicon-germanium (SiGe) BiCMOS technology. The TRX is suitable for flexible radar systems exploiting massive multiple-input-multipleoutput (MIMO) techniques for multidimensional sensing. A fully integrated fractional-N phase-locked loop (PLL) comprising a 39.5-GHz voltage-controlled oscillator is used to generate wideband frequency-modulated continuous-wave (FMCW) chirp for E-band radar front ends. The TRX is equipped with a vector modulator (VM) for high-speed carrier modulation and beam-forming techniques. A single TRX achieves 19.2-dBm maximum output power and 27.5-dB total conversion gain with input-referred 1-dB compression point of -10 dBm. It consumes 220 mA from 3.3-V supply and occupies 3.96 mm(2) silicon area. A two-channel radar platform based on full-custom TRXs and PLL was fabricated to demonstrate high-precision and high-resolution FMCW sensing. The radar enables up to 10-GHz frequency ramp generation in 74-84-GHz range, which results in 1.5-cm spatial resolution. Due to high output power, thus high signal-to-noise ratio (SNR), a ranging precision of 7.5 mu m for a target at 2 m was achieved. The proposed architecture supports scalable multichannel applications for automotive FMCW using a single local oscillator (LO). KW - Automotive KW - E-band KW - frequency-modulated continuous-wave (FMCW) KW - patch antenna KW - phase-locked loop (PLL) KW - power amplifier (PA) KW - radar KW - scalable KW - transceiver (TRX) Y1 - 2019 U6 - https://doi.org/10.1109/TMTT.2019.2914104 SN - 0018-9480 SN - 1557-9670 VL - 67 IS - 9 SP - 3882 EP - 3896 PB - Inst. of Electr. and Electronics Engineers CY - Piscataway ER - TY - JOUR A1 - Sharma, Shubham A1 - Hainzl, Sebastian A1 - Zöller, Gert A1 - Holschneider, Matthias T1 - Is Coulomb stress the best choice for aftershock forecasting? JF - Journal of geophysical research : Solid earth N2 - The Coulomb failure stress (CFS) criterion is the most commonly used method for predicting spatial distributions of aftershocks following large earthquakes. However, large uncertainties are always associated with the calculation of Coulomb stress change. The uncertainties mainly arise due to nonunique slip inversions and unknown receiver faults; especially for the latter, results are highly dependent on the choice of the assumed receiver mechanism. Based on binary tests (aftershocks yes/no), recent studies suggest that alternative stress quantities, a distance-slip probabilistic model as well as deep neural network (DNN) approaches, all are superior to CFS with predefined receiver mechanism. To challenge this conclusion, which might have large implications, we use 289 slip inversions from SRCMOD database to calculate more realistic CFS values for a layered half-space and variable receiver mechanisms. We also analyze the effect of the magnitude cutoff, grid size variation, and aftershock duration to verify the use of receiver operating characteristic (ROC) analysis for the ranking of stress metrics. The observations suggest that introducing a layered half-space does not improve the stress maps and ROC curves. However, results significantly improve for larger aftershocks and shorter time periods but without changing the ranking. We also go beyond binary testing and apply alternative statistics to test the ability to estimate aftershock numbers, which confirm that simple stress metrics perform better than the classic Coulomb failure stress calculations and are also better than the distance-slip probabilistic model. Y1 - 2020 U6 - https://doi.org/10.1029/2020JB019553 SN - 2169-9313 SN - 2169-9356 VL - 125 IS - 9 PB - American Geophysical Union CY - Washington ER - TY - THES A1 - Maier, Corinna T1 - Bayesian data assimilation and reinforcement learning for model-informed precision dosing in oncology T1 - Bayes’sche Datenassimilation und Reinforcement Learning für die modellinformierte Präzisionsdosierung in der Onkologie N2 - 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. N2 - Obwohl Patienten sehr unterschiedlich auf medikamentöse Therapien ansprechen, werden in der klinischen Praxis häufig noch standardisierte Dosierungsschemata angewendet. Bei Arzneimitteln mit engen therapeutischen Fenstern zwischen minimal wirksamen und toxischen Konzentrationen kann dieser Ansatz bei hoher interindividueller Variabilität zu häufigem Auftreten von Toxizitäten oder subtherapeutischen Konzentrationen führen. Die modellinformierte Präzisionsdosierung (MIPD) ist ein quantitativer Ansatz zur Dosisindividualisierung, der auf der mathematischen Modellierung von Dosis-Wirkungs-Beziehungen beruht und Daten aus dem therapeutischen Drug/Biomarker-Monitoring (TDM) einbezieht. Die derzeitigen MIPD-Ansätze verwenden entweder Dosierungstabellen oder einfache Punkt-Vorhersagen des Therapieverlaufs. Diesen Ansätzen fehlt eine Quantifizierung der Unsicherheiten, verzögerte Effekte werden nicht berücksichtigt und die zugrunde liegenden Modelle werden im Laufe der Anwendung nicht verbessert. Daher sind die derzeitigen Ansätze nicht ideal für eine fundierte klinische Entscheidungsfindung auf Grundlage eines differenzierten Verständnisses des individuell vorhergesagten Therapieverlaufs. Das Ziel dieser Arbeit ist es, mathematische Ansätze für das MIPD zu entwickeln, die (i) eine effiziente, vollständig Bayes’sche Vorhersage des individuellen Therapieverlaufs einschließlich der damit verbundenen Unsicherheiten ermöglichen, (ii) Markov-Entscheidungsprozesse mittels Reinforcement Learning (RL) in einen umfassenden Entscheidungsrahmen zur Dosisindividualisierung integrieren, und (iii) ein kontinuierliches Lernen zwischen Patienten erlauben. Die antineoplastische Chemotherapie mit ihrer wichtigen dosislimitierenden Toxizität, der Neutropenie, dient als therapeutisch relevantes Anwendungsbeispiel. Für eine umfassendere Therapievorhersage wenden wir Bayes’sche Datenassimilationsansätze (DA) an, um TDM-Daten in mathematische Modelle der Chemotherapie-induzierten Neutropenie zu integrieren. Wir zeigen, dass die Quantifizierung von Unsicherheiten einen großen Mehrwert bietet, da sie eine zuverlässige Berechnung der Wahrscheinlichkeiten relevanter klinischer Größen, z.B. des Neutropeniegrades, ermöglicht. Im Hinblick auf neue Home-Monitoring-Geräte, die die Anzahl der verfügbaren TDM-Daten erhöhen, erweisen sich sequenzielle DA-Methoden als effizienter und erleichtern den Umgang mit der Unsicherheit zwischen Dosierungsereignissen. Basierend auf Konzepten aus DA und RL, entwickeln wir neue Ansätze für MIPD. Während die DA-geleitete Dosierung individualisierte Unsicherheiten in die Dosisauswahl integriert, berücksichtigt die RL-geleitete Dosierung verzögerte Effekte der Dosisauswahl. Der kombinierte DA-RL-Ansatz vereint beide Aspekte und stellt somit einen ganzheitlichen Ansatz für MIPD dar. Zusätzlich zeigen wir, dass RL Informationen über die für die Dosisauswahl relevanten Patientencharakteristika liefert. Der Vergleich zu derzeit verwendeten MIPD Ansätzen in einer auf einer klinischen Studie (CEPAC-TDM-Studie) basierenden Simulationsstudie zeigt, dass die entwickelten Dosierungsstrategien das Auftreten subtherapeutischer Konzentrationen sowie lebensbedrohlicher Neutropenien drastisch reduzieren. Wird MIPD in der klinischen Routine eingesetzt, ist eine gewisse Modellverzerrung unvermeidlich. Die Modelle basieren in der Regel auf Daten aus vergleichsweise kleinen klinischen Studien, die die Heterogenität realer Patientenpopulationen nur begrenzt widerspiegeln. Wir schlagen einen sequenziellen hierarchischen Bayes’schen Inferenzrahmen vor, der ein kontinuierliches patientenübergreifendes Lernen ermöglicht, um die zugrunde liegenden Modellparameter der Ziel-Patientenpopulation zu erlernen. Zur Aktualisierung des Modells erfordert dieser Ansatz lediglich zusammenfassende Informationen der individuellen Patientendaten, was eine Umsetzung über verschiedene Versorgungszentren hinweg erlaubt. Die vorgeschlagenen Ansätze verbessern die derzeitigen MIPD-Ansätze erheblich, wobei neue Trends in der Gesundheitsversorgung und Aspekte der praktischen Anwendbarkeit berücksichtigt werden. Damit stellen sie einen Fortschritt in Richtung einer fundierteren klinischen Entscheidungsfindung dar. KW - data assimilation KW - Datenassimilation KW - reinforcement learning KW - model-informed precision dosing KW - pharmacometrics KW - oncology KW - modellinformierte Präzisionsdosierung KW - Onkologie KW - Pharmakometrie KW - Reinforcement Learning Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-515870 ER - TY - JOUR A1 - Michelet, Robin A1 - Bindellini, Davide A1 - Melin, Johanna A1 - Neumann, Uta A1 - Blankenstein, Oliver A1 - Huisinga, Wilhelm A1 - Johnson, Trevor N. A1 - Whitaker, Martin J. A1 - Ross, Richard A1 - Kloft, Charlotte T1 - Insights in the maturational processes influencing hydrocortisone pharmacokinetics in congenital adrenal hyperplasia patients using a middle-out approach JF - Frontiers in Pharmacology N2 - 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. KW - hydrocortisone KW - congenital adrenal hyperplasia KW - population pharmacokinetics KW - middle-out approach KW - pediatrics KW - physiologically-based pharmacokinetics (PBPK) KW - non-linear mixed effects modelling (NLME); KW - maturation Y1 - 2023 U6 - https://doi.org/10.3389/fphar.2022.1090554 SN - 1663-9812 VL - 13 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Krippendorff, Ben-Fillippo A1 - Oyarzún, Diego A. A1 - Huisinga, Wilhelm T1 - Predicting the F(ab)-mediated effect of monoclonal antibodies in vivo by combining cell-level kinetic and pharmacokinetic modelling JF - Journal of pharmacokinetics and pharmacodynamics N2 - Cell-level kinetic models for therapeutically relevant processes increasingly benefit the early stages of drug development. Later stages of the drug development processes, however, rely on pharmacokinetic compartment models while cell-level dynamics are typically neglected. We here present a systematic approach to integrate cell-level kinetic models and pharmacokinetic compartment models. Incorporating target dynamics into pharmacokinetic models is especially useful for the development of therapeutic antibodies because their effect and pharmacokinetics are inherently interdependent. The approach is illustrated by analysing the F(ab)-mediated inhibitory effect of therapeutic antibodies targeting the epidermal growth factor receptor. We build a multi-level model for anti-EGFR antibodies by combining a systems biology model with in vitro determined parameters and a pharmacokinetic model based on in vivo pharmacokinetic data. Using this model, we investigated in silico the impact of biochemical properties of anti-EGFR antibodies on their F(ab)-mediated inhibitory effect. The multi-level model suggests that the F(ab)-mediated inhibitory effect saturates with increasing drug-receptor affinity, thereby limiting the impact of increasing antibody affinity on improving the effect. This indicates that observed differences in the therapeutic effects of high affinity antibodies in the market and in clinical development may result mainly from Fc-mediated indirect mechanisms such as antibody-dependent cell cytotoxicity. KW - Cell-level kinetics KW - Pharmacokinetic models KW - Therapeutic proteins KW - EGFR Y1 - 2012 U6 - https://doi.org/10.1007/s10928-012-9243-7 SN - 1567-567X VL - 39 IS - 2 SP - 125 EP - 139 PB - Springer CY - New York ER - TY - JOUR A1 - Weiss, Andrea Y. A1 - Huisinga, Wilhelm T1 - Error-controlled global sensitivity analysis of ordinary differential equations JF - Journal of computational physics N2 - We propose a novel strategy for global sensitivity analysis of ordinary differential equations. It is based on an error-controlled solution of the partial differential equation (PDE) that describes the evolution of the probability density function associated with the input uncertainty/variability. The density yields a more accurate estimate of the output uncertainty/variability, where not only some observables (such as mean and variance) but also structural properties (e.g., skewness, heavy tails, bi-modality) can be resolved up to a selected accuracy. For the adaptive solution of the PDE Cauchy problem we use the Rothe method with multiplicative error correction, which was originally developed for the solution of parabolic PDEs. We show that, unlike in parabolic problems, conservation properties necessitate a coupling of temporal and spatial accuracy to avoid accumulation of spatial approximation errors over time. We provide convergence conditions for the numerical scheme and suggest an implementation using approximate approximations for spatial discretization to efficiently resolve the coupling of temporal and spatial accuracy. The performance of the method is studied by means of low-dimensional case studies. The favorable properties of the spatial discretization technique suggest that this may be the starting point for an error-controlled sensitivity analysis in higher dimensions. KW - ODE with random initial conditions KW - Global sensitivity analysis KW - Cauchy problem KW - Error control/adaptivity KW - Rothe method KW - Approximate approximations Y1 - 2011 U6 - https://doi.org/10.1016/j.jcp.2011.05.011 SN - 0021-9991 VL - 230 IS - 17 SP - 6824 EP - 6842 PB - Elsevier CY - San Diego ER - TY - JOUR A1 - Weiße, Andrea Y. A1 - Middleton, Richard H. A1 - Huisinga, Wilhelm T1 - Quantifying uncertainty, variability and likelihood for ordinary differential equation models N2 - Background: In many applications, ordinary differential equation (ODE) models are subject to uncertainty or variability in initial conditions and parameters. Both, uncertainty and variability can be quantified in terms of a probability density function on the state and parameter space. Results: The partial differential equation that describes the evolution of this probability density function has a form that is particularly amenable to application of the well- known method of characteristics. The value of the density at some point in time is directly accessible by the solution of the original ODE extended by a single extra dimension (for the value of the density). This leads to simple methods for studying uncertainty, variability and likelihood, with significant advantages over more traditional Monte Carlo and related approaches especially when studying regions with low probability. Conclusions: While such approaches based on the method of characteristics are common practice in other disciplines, their advantages for the study of biological systems have so far remained unrecognized. Several examples illustrate performance and accuracy of the approach and its limitations. Y1 - 2010 UR - http://www.biomedcentral.com/1752-0509/ U6 - https://doi.org/10.1186/1752-0509-4-144 SN - 1752-0509 ER - TY - JOUR A1 - Pilari, Sabine A1 - Preusse, Cornelia A1 - Huisinga, Wilhelm T1 - Gestational influences on the pharmacokinetics of gestagenic drugs a combined in silico, in vitro and in vivo analysis JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, EUFEPS N2 - During preclinical development of a gestagenic drug, a significant increase of the total plasma concentration was observed after multiple dosing in pregnant rabbits, but not in (non-pregnant) rats or monkeys. We used a PBPK modeling approach in combination with in vitro and in vivo data to address the question to what extent the pharmacologically active free drug concentration is affected by pregnancy induced processes. In human, a significant increase in sex hormone binding globulin (SHBG), and an induction of hepatic CYP3A4 as well as plasma esterases is observed during pregnancy. We find that the observed increase in total plasma trough levels in rabbits can be explained as a combined result of (i) drug accumulation due to multiple dosing, (ii) increase of the binding protein SHBG, and (iii) clearance induction. For human, we predict that free drug concentrations in plasma would not increase during pregnancy above the steady state trough level for non-pregnant women. KW - PBPK KW - Pregnancy KW - Gestagenic drug KW - Protein binding KW - SHBG KW - Clearance induction Y1 - 2011 U6 - https://doi.org/10.1016/j.ejps.2010.12.003 SN - 0928-0987 VL - 42 IS - 4 SP - 318 EP - 331 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - von Kleist, Max A1 - Menz, Stephan A1 - Stocker, Hartmut A1 - Arasteh, Keikawus A1 - Schuette, Christof A1 - Huisinga, Wilhelm T1 - HIV quasispecies dynamics during pro-active treatment switching impact on multi-drug resistance and resistance archiving in latent reservoirs JF - PLoS one N2 - The human immunodeficiency virus (HIV) can be suppressed by highly active anti-retroviral therapy (HAART) in the majority of infected patients. Nevertheless, treatment interruptions inevitably result in viral rebounds from persistent, latently infected cells, necessitating lifelong treatment. Virological failure due to resistance development is a frequent event and the major threat to treatment success. Currently, it is recommended to change treatment after the confirmation of virological failure. However, at the moment virological failure is detected, drug resistant mutants already replicate in great numbers. They infect numerous cells, many of which will turn into latently infected cells. This pool of cells represents an archive of resistance, which has the potential of limiting future treatment options. The objective of this study was to design a treatment strategy for treatment-naive patients that decreases the likelihood of early treatment failure and preserves future treatment options. We propose to apply a single, pro-active treatment switch, following a period of treatment with an induction regimen. The main goal of the induction regimen is to decrease the abundance of randomly generated mutants that confer resistance to the maintenance regimen, thereby increasing subsequent treatment success. Treatment is switched before the overgrowth and archiving of mutant strains that carry resistance against the induction regimen and would limit its future re-use. In silico modelling shows that an optimal trade-off is achieved by switching treatment at & 80 days after the initiation of antiviral therapy. Evaluation of the proposed treatment strategy demonstrated significant improvements in terms of resistance archiving and virological response, as compared to conventional HAART. While continuous pro-active treatment alternation improved the clinical outcome in a randomized trial, our results indicate that a similar improvement might also be reached after a single pro-active treatment switch. The clinical validity of this finding, however, remains to be shown by a corresponding trial. Y1 - 2011 U6 - https://doi.org/10.1371/journal.pone.0018204 SN - 1932-6203 VL - 6 IS - 3 PB - PLoS CY - San Fransisco ER - TY - CHAP A1 - Steenholdt, Casper A1 - Edlund, Helena A1 - Ainsworth, Mark A. A1 - Brynskov, Jorn A1 - Thomsen, Ole Ostergaard A1 - Huisinga, Wilhelm A1 - Kloft, Charlotte T1 - Relationship between measures of infliximab exposure and clinical outcome of infliximab intensification at therapeutic failure in Crohn's disease T2 - JOURNAL OF CROHNS & COLITIS Y1 - 2015 SN - 1873-9946 SN - 1876-4479 VL - 9 SP - S330 EP - S330 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Menz, Stephan A1 - Latorre, Juan C. A1 - Schütte, Christof A1 - Huisinga, Wilhelm T1 - Hybrid stochastic-deterministic solution of the chemical master equation JF - Multiscale modeling & simulation : a SIAM interdisciplinary journal N2 - The chemical master equation (CME) is the fundamental evolution equation of the stochastic description of biochemical reaction kinetics. In most applications it is impossible to solve the CME directly due to its high dimensionality. Instead, indirect approaches based on realizations of the underlying Markov jump process are used, such as the stochastic simulation algorithm (SSA). In the SSA, however, every reaction event has to be resolved explicitly such that it becomes numerically inefficient when the system's dynamics include fast reaction processes or species with high population levels. In many hybrid approaches, such fast reactions are approximated as continuous processes or replaced by quasi-stationary distributions in either a stochastic or a deterministic context. Current hybrid approaches, however, almost exclusively rely on the computation of ensembles of stochastic realizations. We present a novel hybrid stochastic-deterministic approach to solve the CME directly. Our starting point is a partitioning of the molecular species into discrete and continuous species that induces a partitioning of the reactions into discrete-stochastic and continuous-deterministic processes. The approach is based on a WKB (Wentzel-Kramers-Brillouin) ansatz for the conditional probability distribution function (PDF) of the continuous species (given a discrete state) in combination with Laplace's method of integral approximation. The resulting hybrid stochastic-deterministic evolution equations comprise a CME with averaged propensities for the PDF of the discrete species that is coupled to an evolution equation of the related expected levels of the continuous species for each discrete state. In contrast to indirect hybrid methods, the impact of the evolution of discrete species on the dynamics of the continuous species has to be taken into account explicitly. The proposed approach is efficient whenever the number of discrete molecular species is small. We illustrate the performance of the new hybrid stochastic-deterministic approach in an application to model systems of biological interest. KW - chemical master equation KW - hybrid model KW - multiscale analysis KW - partial averaging KW - asymptotic approximation KW - WKB ansatz Y1 - 2012 U6 - https://doi.org/10.1137/110825716 SN - 1540-3459 VL - 10 IS - 4 SP - 1232 EP - 1262 PB - Society for Industrial and Applied Mathematics CY - Philadelphia ER - TY - CHAP A1 - Andersson, H. A1 - Keunecke, A. A1 - Eser, A. A1 - Huisinga, Wilhelm A1 - Reinisch, W. A1 - Kloft, Charlotte T1 - Pharmacokinetic considerations for optimising dosing regimens of a potsdam univ infliximab in patients with Crohn's disease T2 - JOURNAL OF CROHNS & COLITIS Y1 - 2014 U6 - https://doi.org/10.1016/S1873-9946(14)60086-6 SN - 1873-9946 SN - 1876-4479 VL - 8 SP - S44 EP - S44 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Kaminski, Jakob A. A1 - Schlagenhauf, Florian A1 - Rapp, Michael A. A1 - Awasthi, Swapnil A1 - Ruggeri, Barbara A1 - Deserno, Lorenz A1 - Banaschewski, Tobias A1 - Bokde, Arun L. W. A1 - Bromberg, Uli A1 - Büchel, Christian A1 - Quinlan, Erin Burke A1 - Desrivieres, Sylvane A1 - Flor, Herta A1 - Frouin, Vincent A1 - Garavan, Hugh A1 - Gowland, Penny A1 - Ittermann, Bernd A1 - Martinot, Jean-Luc A1 - Martinot, Marie-Laure Paillere A1 - Nees, Frauke A1 - Orfanos, Dimitri Papadopoulos A1 - Paus, Tomas A1 - Poustka, Luise A1 - Smolka, Michael N. A1 - Fröhner, Juliane H. A1 - Walter, Henrik A1 - Whelan, Robert A1 - Ripke, Stephan A1 - Schumann, Gunter A1 - Heinz, Andreas T1 - Epigenetic variance in dopamine D2 receptor BT - a marker of IQ malleability? JF - Translational Psychiatry N2 - Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure. Y1 - 2018 U6 - https://doi.org/10.1038/s41398-018-0222-7 SN - 2158-3188 VL - 8 PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Gerlach, Moritz A1 - Glück, Jochen A1 - Kunze, Markus T1 - Stability of transition semigroups and applications to parabolic equations JF - Transactions of the American Mathematical Society N2 - 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. KW - Transition probabilities KW - strong Feller property KW - asymptotic KW - behavior KW - invariant measure KW - parabolic equations Y1 - 2023 U6 - https://doi.org/10.1090/tran/8620 SN - 0002-9947 SN - 1088-6850 VL - 376 IS - 1 SP - 153 EP - 180 PB - American Mathematical Soc. CY - Providence ER - TY - JOUR A1 - Dimitrova, Ilinka A1 - Koppitz, Jörg T1 - On relative ranks of the semigroup of orientation-preserving transformations on infinite chain with restricted range JF - Communications in algebra N2 - 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. KW - Order-preserving transformations KW - orientation-preserving KW - transformations KW - relative rank KW - restricted range KW - transformation KW - semigroups on infinite chain Y1 - 2022 U6 - https://doi.org/10.1080/00927872.2021.2000998 SN - 0092-7872 SN - 1532-4125 VL - 50 IS - 5 SP - 2157 EP - 2168 PB - Taylor & Francis Group CY - Philadelphia ER - TY - JOUR A1 - Dimitrova, Ilinka A1 - Koppitz, Jörg T1 - On relative ranks of the semigroup of orientation-preserving transformations on infinite chains JF - Asian-European journal of mathematics N2 - In this paper, we determine the relative rank of the semigroup OP(X) of all orientation-preserving transformations on infinite chains modulo the semigroup O(X) of all order-preserving transformations. KW - Transformation semigroups on infinite chains KW - order-preserving KW - transformations KW - orientation-preserving transformations KW - relative rank Y1 - 2020 U6 - https://doi.org/10.1142/S1793557121501461 SN - 1793-5571 SN - 1793-7183 VL - 14 IS - 08 PB - World Scientific CY - Singapore ER - TY - JOUR A1 - Sharma, Shubham A1 - Hainzl, Sebastian A1 - Zöller, Gert T1 - Seismicity parameters dependence on main shock-induced co-seismic stress JF - Geophysical journal international N2 - 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. KW - earthquake hazards KW - earthquake interaction KW - forecasting and prediction KW - statistical seismology KW - b-value Y1 - 2023 U6 - https://doi.org/10.1093/gji/ggad201 SN - 0956-540X SN - 1365-246X VL - 235 IS - 1 SP - 509 EP - 517 PB - Oxford Univ. Press CY - Oxford ER - TY - THES A1 - Sareeto, Apatsara T1 - Algebraic properties of a subsemigroup of the symmetric inverse semigroup Y1 - 2024 ER - TY - JOUR A1 - Gerlach, Moritz Reinhardt A1 - Glück, Jochen T1 - On a convergence theorem for semigroups of positive integral operators JF - Comptes Rendus Mathematique N2 - We give a new and very short proof of a theorem of Greiner asserting that a positive and contractive -semigroup on an -space is strongly convergent in case it has a strictly positive fixed point and contains an integral operator. Our proof is a streamlined version of a much more general approach to the asymptotic theory of positive semigroups developed recently by the authors. Under the assumptions of Greiner's theorem, this approach becomes particularly elegant and simple. We also give an outlook on several generalisations of this result. Y1 - 2017 U6 - https://doi.org/10.1016/j.crma.2017.07.017 SN - 1631-073X SN - 1778-3569 VL - 355 SP - 973 EP - 976 PB - Elsevier CY - Paris ER - TY - JOUR A1 - Gerlach, Moritz Reinhardt T1 - Convergence of dynamics and the Perron-Frobenius operator JF - Israel Journal of Mathematics N2 - We complete the picture how the asymptotic behavior of a dynamical system is reflected by properties of the associated Perron-Frobenius operator. Our main result states that strong convergence of the powers of the Perron-Frobenius operator is equivalent to setwise convergence of the underlying dynamic in the measure algebra. This situation is furthermore characterized by uniform mixing-like properties of the system. Y1 - 2018 U6 - https://doi.org/10.1007/s11856-018-1671-7 SN - 0021-2172 SN - 1565-8511 VL - 225 IS - 1 SP - 451 EP - 463 PB - Hebrew univ magnes press CY - Jerusalem ER - TY - JOUR A1 - Gerlach, Moritz Reinhardt A1 - Glück, Jochen T1 - Convergence of positive operator semigroups JF - Transactions of the American Mathematical Society N2 - We present new conditions for semigroups of positive operators to converge strongly as time tends to infinity. Our proofs are based on a novel approach combining the well-known splitting theorem by Jacobs, de Leeuw, and Glicksberg with a purely algebraic result about positive group representations. Thus, we obtain convergence theorems not only for one-parameter semigroups but also for a much larger class of semigroup representations. Our results allow for a unified treatment of various theorems from the literature that, under technical assumptions, a bounded positive C-0-semigroup containing or dominating a kernel operator converges strongly as t ->infinity. We gain new insights into the structure theoretical background of those theorems and generalize them in several respects; especially we drop any kind of continuity or regularity assumption with respect to the time parameter. KW - Positive semigroups KW - semigroup representations KW - asymptotic behavior KW - kernel operator Y1 - 2019 U6 - https://doi.org/10.1090/tran/7836 SN - 0002-9947 SN - 1088-6850 VL - 372 IS - 9 SP - 6603 EP - 6627 PB - American Mathematical Soc. CY - Providence ER - TY - JOUR A1 - Edeko, Nikolai A1 - Gerlach, Moritz Reinhardt A1 - Kühner, Viktoria T1 - Measure-preserving semiflows and one-parameter Koopman semigroups JF - Semigroup forum N2 - For a finite measure space X, we characterize strongly continuous Markov lattice semigroups on Lp(X) by showing that their generator A acts as a derivation on the dense subspace D(A)L(X). We then use this to characterize Koopman semigroups on Lp(X) if X is a standard probability space. In addition, we show that every measurable and measure-preserving flow on a standard probability space is isomorphic to a continuous flow on a compact Borel probability space. KW - Measure-preserving semiflow KW - Koopman semigroup KW - Derivation KW - Topological model Y1 - 2019 U6 - https://doi.org/10.1007/s00233-018-9960-3 SN - 0037-1912 SN - 1432-2137 VL - 98 IS - 1 SP - 48 EP - 63 PB - Springer CY - New York ER - TY - JOUR A1 - Gerlach, Moritz Reinhardt A1 - Glück, Jochen T1 - Lower bounds and the asymptotic behaviour of positive operator semigroups JF - Ergodic theory and dynamical systems N2 - If (T-t) is a semigroup of Markov operators on an L-1-space that admits a nontrivial lower bound, then a well-known theorem of Lasota and Yorke asserts that the semigroup is strongly convergent as t -> infinity. In this article we generalize and improve this result in several respects. First, we give a new and very simple proof for the fact that the same conclusion also holds if the semigroup is merely assumed to be bounded instead of Markov. As a main result, we then prove a version of this theorem for semigroups which only admit certain individual lower bounds. Moreover, we generalize a theorem of Ding on semigroups of Frobenius-Perron operators. We also demonstrate how our results can be adapted to the setting of general Banach lattices and we give some counterexamples to show optimality of our results. Our methods combine some rather concrete estimates and approximation arguments with abstract functional analytical tools. One of these tools is a theorem which relates the convergence of a time-continuous operator semigroup to the convergence of embedded discrete semigroups. Y1 - 2017 U6 - https://doi.org/10.1017/etds.2017.9 SN - 0143-3857 SN - 1469-4417 VL - 38 SP - 3012 EP - 3041 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Gerlach, Moritz Reinhardt A1 - Glück, Jochen T1 - Mean ergodicity vs weak almost periodicity JF - Studia mathematica N2 - We provide explicit examples of positive and power-bounded operators on c(0) and l(infinity) which are mean ergodic but not weakly almost periodic. As a consequence we prove that a countably order complete Banach lattice on which every positive and power-bounded mean ergodic operator is weakly almost periodic is necessarily a KB-space. This answers several open questions from the literature. Finally, we prove that if T is a positive mean ergodic operator with zero fixed space on an arbitrary Banach lattice, then so is every power of T . KW - positive operators KW - weakly almost periodic KW - order continuous norm KW - KB-space KW - mean ergodic Y1 - 2019 U6 - https://doi.org/10.4064/sm170918-20-3 SN - 0039-3223 SN - 1730-6337 VL - 248 IS - 1 SP - 45 EP - 56 PB - Polska Akademia Nauk, Instytut Matematyczny CY - Warszawa ER - TY - JOUR A1 - Lilienkamp, Henning A1 - von Specht, Sebastian A1 - Weatherill, Graeme A1 - Caire, Giuseppe A1 - Cotton, Fabrice T1 - Ground-Motion modeling as an image processing task BT - introducing a neural network based, fully data-driven, and nonergodic JF - Bulletin of the Seismological Society of America N2 - 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. Y1 - 2022 U6 - https://doi.org/10.1785/0120220008 SN - 0037-1106 SN - 1943-3573 VL - 112 IS - 3 SP - 1565 EP - 1582 PB - Seismological Society of America CY - Albany ER - TY - JOUR A1 - Julien, Bärenzung A1 - Matthias, Holschneider A1 - Saynisch-Wagner, Jan A1 - Thomas, Maik T1 - Kalmag: a high spatio-temporal model of the geomagnetic field JF - Earth, planets and space N2 - We present the extension of the Kalmag model, proposed as a candidate for IGRF-13, to the twentieth century. The dataset serving its derivation has been complemented by new measurements coming from satellites, ground-based observatories and land, marine and airborne surveys. As its predecessor, this version is derived from a combination of a Kalman filter and a smoothing algorithm, providing mean models and associated uncertainties. These quantities permit a precise estimation of locations where mean solutions can be considered as reliable or not. The temporal resolution of the core field and the secular variation was set to 0.1 year over the 122 years the model is spanning. Nevertheless, it can be shown through ensembles a posteriori sampled, that this resolution can be effectively achieved only by a limited amount of spatial scales and during certain time periods. Unsurprisingly, highest accuracy in both space and time of the core field and the secular variation is achieved during the CHAMP and Swarm era. In this version of Kalmag, a particular effort was made for resolving the small-scale lithospheric field. Under specific statistical assumptions, the latter was modeled up to spherical harmonic degree and order 1000, and signal from both satellite and survey measurements contributed to its development. External and induced fields were jointly estimated with the rest of the model. We show that their large scales could be accurately extracted from direct measurements whenever the latter exhibit a sufficiently high temporal coverage. Temporally resolving these fields down to 3 hours during the CHAMP and Swarm missions, gave us access to the link between induced and magnetospheric fields. In particular, the period dependence of the driving signal on the induced one could be directly observed. The model is available through various physical and statistical quantities on a dedicated website at https://ionocovar.agnld.uni-potsdam.de/Kalmag/. KW - geomagnetic field KW - lithospheric field KW - secular variation KW - magnetospheric field KW - induced field KW - assimilation KW - Kalman filter KW - machine learning Y1 - 2022 U6 - https://doi.org/10.1186/s40623-022-01692-5 SN - 1880-5981 VL - 74 IS - 1 PB - Springer CY - New York ER - TY - THES A1 - Reimann, Hans T1 - Towards robust inference for Bayesian filtering of linear Gaussian dynamical systems subject to additive change T1 - Hin zu einer robusten Inferenz für Bayes'sche Filterung linearer gaußscher dynamischer Systeme bei additiver Veränderung N2 - State space models enjoy wide popularity in mathematical and statistical modelling across disciplines and research fields. Frequent solutions to problems of estimation and forecasting of a latent signal such as the celebrated Kalman filter hereby rely on a set of strong assumptions such as linearity of system dynamics and Gaussianity of noise terms. We investigate fallacy in mis-specification of the noise terms, that is signal noise and observation noise, regarding heavy tailedness in that the true dynamic frequently produces observation outliers or abrupt jumps of the signal state due to realizations of these heavy tails not considered by the model. We propose a formalisation of observation noise mis-specification in terms of Huber’s ε-contamination as well as a computationally cheap solution via generalised Bayesian posteriors with a diffusion Stein divergence loss resulting in the diffusion score matching Kalman filter - a modified algorithm akin in complexity to the regular Kalman filter. For this new filter interpretations of novel terms, stability and an ensemble variant are discussed. Regarding signal noise mis-specification, we propose a formalisation in the frame work of change point detection and join ideas from the popular CUSUM algo- rithm with ideas from Bayesian online change point detection to combine frequent reliability constraints and online inference resulting in a Gaussian mixture model variant of multiple Kalman filters. We hereby exploit open-end sequential probability ratio tests on the evidence of Kalman filters on observation sub-sequences for aggregated inference under notions of plausibility. Both proposed methods are combined to investigate the double mis-specification problem and discussed regarding their capabilities in reliable and well-tuned uncertainty quantification. Each section provides an introduction to required terminology and tools as well as simulation experiments on the popular target tracking task and the non-linear, chaotic Lorenz-63 system to showcase practical performance of theoretical considerations. N2 - Modelle im Zustandsraum finden breite Anwendung in der mathematischen und statistischen Modellierung verschiedener Disziplinen und Forschungsgebiete. Häufige Lösung von Problemen der Schätzung und Vorhersage von latenten Signalen wie der populäre Kalman Filter benötigen hierbei eine Reihe von starken annahmen wie Linearität der Dynamiken des Systems und Normalität der Fehlerterme. Wir untersuchen Hürden in der Modellierung durch Mis-Spezifizierung der Fehlerterme, hier des Signalfehlers und des Beobachtungsfehlers, bezüglich schweren Rändern. Die wahre Dynamik produziert häufig Beobachtungsausreißer oder plötzliche Sprünge des Signals als Realisationen dieser schweren Ränder, diese werden aber nicht durch das Modell berücksichtigt. Wir schlagen eine Formalisierung der Mis-Spezifizierung des Beobachtungsfehlers im Sinne von Hubers Epsilon-Kontaminierung sowie eine rechnerisch kosteneffiziente Lösung vor. Diese Lösung durch generalisierte Bayes'sche a-posteriori Verteilungen mit einer Diffusion Stein Divergenz resultiert in dem Diffusion-Score-Matching Kalman Filter - ein modifizierter Algorithmus ähnlich dem regulären Kalman Filter in Komplexität. Für diesen neuen Filter diskutieren wir Interpretationen neuer Terme, der Langzeitstabilität und eine Ensemble Variante. Bezüglich der Mis-Spezifizierung des Signalfehlers schlagen wir eine Formalisierung durch Wechselpunktdetektierung vor und verknüpfen Ideen des populären CUSUM Algorithmus mit Ideen der Bayes'schen Online Wechselpunktdetektierung um Eigenschaften in Zuverlässigkeit und Online-Inferenz zu erhalten. Das Ergebnis ist eine Gaussian-Mixture-Model Variante aus mehreren Kalman Filtern. Hierbei nutzen wir explizit die Open-End sequentielle Probability-Ratio-Tests zwischen den verschiedenen Kalman Filtern, um Inferenzen unter Plausibiltätsargumenten zu aggregieren. Beide vorgeschlagenen Ansätze werden gemeinsam untersucht für den Fall der zweifachen Mis-Spezifizierung und die Ergebnisse werden diskutiert bezüglich ihrer Zuverlässigkeit und Unsicherheitsquantifizierung. Jedes Kapitel beinhaltet eine Einführung in die notwendige Terminologie und mathematischen Werkzeuge, sowie Simulationsexperimente für das populäre Beispiel des Target Trackings und das nicht-lineare, chaotische Lorenz-63 System, um die praktische Performance die Theorie zu veranschaulichen. KW - statistical model Mis-specification KW - robust filtering KW - state space change point detection KW - Bayesian filtering KW - Bayesian modelling KW - Bayes'sche Modellierung KW - robustes Filtern KW - Zustandsraum Wechselpunktdetektierung KW - Mis-Spezifizierung statistischer Modelle Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-649469 ER - TY - JOUR A1 - Hanisch, Florian A1 - Strohmaier, Alexander A1 - Waters, Alden T1 - A relative trace formula for obstacle scattering JF - Duke mathematical journal N2 - We consider the case of scattering by several obstacles in Rd for d ≥ 2. In this setting, the absolutely continuous part of the Laplace operator Δ with Dirichlet boundary conditions and the free Laplace operator Δ0 are unitarily equivalent. For suitable functions that decay sufficiently fast, we have that the difference g(Δ) - g(Δ0) is a trace-class operator and its trace is described by the Krein spectral shift function. In this article, we study the contribution to the trace (and hence the Krein spectral shift function) that arises from assembling several obstacles relative to a setting where the obstacles are completely separated. In the case of two obstacles, we consider the Laplace operators Δ1 and Δ2 obtained by imposing Dirichlet boundary conditions only on one of the objects. Our main result in this case states that then g(Δ) - g(Δ1) - g(Δ2) C g(Δ0) is a trace-class operator for a much larger class of functions (including functions of polynomial growth) and that this trace may still be computed by a modification of the Birman–Krein formula. In case g(x) D x 2 , 1 the relative trace has a physical meaning as the vacuum energy of the massless scalar field and is expressible as an integral involving boundary layer operators. Such integrals have been derived in the physics literature using nonrigorous path integral derivations and our formula provides both a rigorous justification as well as a generalization. KW - Birman–Krein formula KW - Casimir energy KW - obstacle scattering KW - trace formula Y1 - 2022 U6 - https://doi.org/10.1215/00127094-2022-0053 SN - 0012-7094 SN - 1547-7398 VL - 171 IS - 11 SP - 2233 EP - 2274 PB - Duke Univ. Press CY - Durham, NC ER - TY - JOUR A1 - Maoutsa, Dimitra Despoina A1 - Opper, Manfred T1 - Deterministic particle flows for constraining stochastic nonlinear systems JF - Physical Review Research / American Physical Society N2 - Devising optimal interventions for constraining stochastic systems is a challenging endeavor that has to confront the interplay between randomness and dynamical nonlinearity. Existing intervention methods that employ stochastic path sampling scale poorly with increasing system dimension and are slow to converge. Here we propose a generally applicable and practically feasible methodology that computes the optimal interventions in a noniterative scheme. We formulate the optimal dynamical adjustments in terms of deterministically sampled probability flows approximated by an interacting particle system. Applied to several biologically inspired models, we demonstrate that our method provides the necessary optimal controls in settings with terminal, transient, or generalized collective state constraints and arbitrary system dynamics. Y1 - 2022 U6 - https://doi.org/10.1103/PhysRevResearch.4.043035 SN - 2643-1564 VL - 4 IS - 4 PB - American Physical Society CY - College Park ER - TY - JOUR A1 - Fischer, Florian A1 - Keller, Matthias T1 - Riesz decompositions for Schrödinger operators on graphs JF - Journal of mathematical analysis and applications N2 - 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. KW - Potential theory KW - Green's function KW - Schrödinger operator KW - Weighted KW - graph KW - Subcritical KW - Greatest harmonic minorant Y1 - 2021 U6 - https://doi.org/10.1016/j.jmaa.2020.124674 SN - 0022-247X SN - 1096-0813 VL - 495 IS - 1 PB - Elsevier CY - Amsterdam ER - TY - THES A1 - Fischer, Florian T1 - Hardy inequalities on graphs T1 - Hardy-Ungleichungen auf Graphen N2 - Die Dissertation befasst sich mit einer zentralen Ungleichung der nicht-linearen Potentialtheorie, der Hardy-Ungleichung. Sie besagt, dass das nicht-lineare Energiefunktional von unten durch eine p-te Potenz einer gewichteten p-Norm abgeschätzt werden kann, p>1. Das Energiefunktional besteht dabei aus einem Divergenz- und einem beliebigen Potentialteil. Als zugrundeliegender Raum wurden hier lokal summierbare unendliche Graphen gewählt. Bisherige Veröffentlichungen zu Hardy-Ungleichungen auf Graphen haben vor allem den Spezialfall p=2 betrachtet, oder lokal endliche Graphen ohne Potentialteil. Zwei grundlegende Fragestellungen ergeben sich nun ganz natürlich: Für welche Graphen gibt überhaupt es eine Hardy-Ungleichung? Und, wenn es sie gibt, gibt es einen Weg um ein optimales Gewicht zu erhalten? Antworten auf diese Fragen werden in Theorem 10.1 und Theorem 12.1 gegeben. Theorem 10.1 gibt eine Reihe an Charakterisierungen an; unter anderem gibt es eine Hardy-Ungleichung auf einem Graphen genau dann, wenn es eine Greensche Funktion gibt. Theorem 12.1 gibt eine explizite Formel an, um optimale Hardy-Gewichte für lokal endliche Graphen unter einigen technischen Zusatzannahmen zu berechnen. In Beispielen wird gezeigt, dass Greensche Funktionen gute Kandidaten sind um in die Formel eingesetzt zu werden. Um diese beiden Theoreme beweisen zu können, müssen eine Vielzahl an Techniken erarbeitet werden, welche in den ersten Kapiteln behandelt werden. Dabei sind eine Verallgemeinerung der Grundzustandstransformation (Theorem 4.1), ein Agmon-Allegretto-Piepenbrink-artiges Resultat (Theorem 6.1) und das Vergleichsprinzip (Proposition 7.3) besonders hervorzuheben, da diese Resultate sehr häufig angewendet werden und somit das Fundament der Dissertation bilden. Es wird zudem darauf Wert gelegt die Theorie durch Beispiele zu veranschaulichen. Hierbei wird der Fokus auf die natürlichen Zahlen, Euklidische Gitter, Bäume und Sterne gelegt. Als Abschluss werden noch eine nicht-lineare Version der Heisenbergschen Unschärferelation und eine Rellich-Ungleichung aus der Hardy-Ungleichung geschlussfolgert. N2 - The dissertation deals with a central inequality of non-linear potential theory, the Hardy inequality. It states that the non-linear energy functional can be estimated from below by a pth power of a weighted p-norm, p>1. The energy functional consists of a divergence part and an arbitrary potential part. Locally summable infinite graphs were chosen as the underlying space. Previous publications on Hardy inequalities on graphs have mainly considered the special case p=2, or locally finite graphs without a potential part. Two fundamental questions now arise quite naturally: For which graphs is there a Hardy inequality at all? And, if it exists, is there a way to obtain an optimal weight? Answers to these questions are given in Theorem 10.1 and Theorem 12.1. Theorem 10.1 gives a number of characterizations; among others, there is a Hardy inequality on a graph if and only if there is a Green's function. Theorem 12.1 gives an explicit formula to compute optimal Hardy weights for locally finite graphs under some additional technical assumptions. Examples show that Green's functions are good candidates to be used in the formula. Emphasis is also placed on illustrating the theory with examples. The focus is on natural numbers, Euclidean lattices, trees and star graphs. Finally, a non-linear version of the Heisenberg uncertainty principle and a Rellich inequality are derived from the Hardy inequality. KW - graph theory KW - Hardy inequality KW - quasi-linear potential theory KW - p-Laplacian KW - criticality theory KW - Graphentheorie KW - Hardy-Ungleichung KW - quasilineare Potentialtheorie KW - p-Laplace-Operator KW - Kritikalitätstheorie Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-647730 ER -