TY - GEN A1 - Keller, Matthias A1 - Pinchover, Yehuda A1 - Pogorzelski, Felix T1 - From hardy to rellich inequalities on graphs T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - We show how to deduce Rellich inequalities from Hardy inequalities on infinite graphs. Specifically, the obtained Rellich inequality gives an upper bound on a function by the Laplacian of the function in terms of weighted norms. These weights involve the Hardy weight and a function which satisfies an eikonal inequality. The results are proven first for Laplacians and are extended to Schrodinger operators afterwards. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1379 KW - 35R02 KW - 39A12 (primary) KW - 26D15 KW - 31C20 KW - 35B09 KW - 58E35 (secondary) Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-542140 SN - 1866-8372 IS - 3 ER - TY - JOUR A1 - Kürschner, Patrick A1 - Freitag, Melina A. T1 - Inexact methods for the low rank solution to large scale Lyapunov equations JF - BIT : numerical mathematics ; the leading applied mathematics journal for all computational mathematicians N2 - The rational Krylov subspace method (RKSM) and the low-rank alternating directions implicit (LR-ADI) iteration are established numerical tools for computing low-rank solution factors of large-scale Lyapunov equations. In order to generate the basis vectors for the RKSM, or extend the low-rank factors within the LR-ADI method, the repeated solution to a shifted linear system of equations is necessary. For very large systems this solve is usually implemented using iterative methods, leading to inexact solves within this inner iteration (and therefore to "inexact methods"). We will show that one can terminate this inner iteration before full precision has been reached and still obtain very good accuracy in the final solution to the Lyapunov equation. In particular, for both the RKSM and the LR-ADI method we derive theory for a relaxation strategy (e.g. increasing the solve tolerance of the inner iteration, as the outer iteration proceeds) within the iterative methods for solving the large linear systems. These theoretical choices involve unknown quantities, therefore practical criteria for relaxing the solution tolerance within the inner linear system are then provided. The theory is supported by several numerical examples, which show that the total amount of work for solving Lyapunov equations can be reduced significantly. KW - Lyapunov equation KW - alternating direction implicit KW - rational Krylov KW - subspaces KW - low-rank approximations Y1 - 2019 U6 - https://doi.org/10.1007/s10543-020-00813-4 SN - 0006-3835 SN - 1572-9125 VL - 60 IS - 4 SP - 1221 EP - 1259 PB - Springer CY - Dordrecht ER - TY - JOUR A1 - Flad, Heinz-Jürgen A1 - Flad-Harutyunyan, Gohar A1 - Schulze, Bert-Wolfgang T1 - Explicit Green operators for quantum mechanical Hamiltonians BT - II. edge-type singularities of the helium atom JF - Asian-European journal of mathematics : AEJM N2 - We extend our approach of asymptotic parametrix construction for Hamiltonian operators from conical to edge-type singularities which is applicable to coalescence points of two particles of the helium atom and related two electron systems including the hydrogen molecule. Up to second-order, we have calculated the symbols of an asymptotic parametrix of the nonrelativistic Hamiltonian of the helium atom within the Born-Oppenheimer approximation and provide explicit formulas for the corresponding Green operators which encode the asymptotic behavior of the eigenfunctions near an edge. KW - Singular analysis KW - Schrodinger equation KW - many-electron systems KW - asymptotic properties of eigenfunctions Y1 - 2020 U6 - https://doi.org/10.1142/S1793557120501223 SN - 1793-5571 SN - 1793-7183 VL - 13 IS - 7 PB - World Scientific CY - Singapore ER - TY - CHAP A1 - Rungrottheera, Wannarut A1 - Chang, Der-Chen A1 - Schulze, Bert-Wolfgang T1 - The edge calculus of singularity order >3 T2 - Journal of nonlinear and convex analysis : an international journal N2 - We study Mellin pseudo-differential algebras on singular straight cones and manifolds with singularity of order >= 3. Those are necessary to express parametrices of elliptic differential operators with a corresponding cornerdegenerate behavior, and we obtain regularity in weighted spaces. KW - Pseudo-differential algebras KW - symbols KW - singular manifolds KW - Mellin KW - operator calculus Y1 - 2020 SN - 1345-4773 SN - 1880-5221 VL - 21 IS - 2 SP - 387 EP - 401 PB - Yokohama Publishers CY - Yokohama ER - TY - JOUR A1 - Zöller, Gert A1 - Hainzl, Sebastian A1 - Tilmann, Frederik A1 - Woith, Heiko A1 - Dahm, Torsten T1 - Comment on: Wikelski, Martin; Müller, Uschi; Scocco, Paola; Catorci, Andrea; Desinov, Lev V.; Belyaev, Mikhail Y.; Keim, Daniel A.; Pohlmeier, Winfried; Fechteler, Gerhard; Mai, Martin P. : Potential short-term earthquake forecasting by farm animal monitoring. - Ethology. - 126 (2020), 9. - S. 931 - 941. -ISSN 0179-1613. - eISSN 1439-0310. - doi 10.1111/eth.13078 JF - Ethology N2 - Based on an analysis of continuous monitoring of farm animal behavior in the region of the 2016 M6.6 Norcia earthquake in Italy, Wikelski et al., 2020; (Seismol Res Lett, 89, 2020, 1238) conclude that animal activity can be anticipated with subsequent seismic activity and that this finding might help to design a "short-term earthquake forecasting method." We show that this result is based on an incomplete analysis and misleading interpretations. Applying state-of-the-art methods of statistics, we demonstrate that the proposed anticipatory patterns cannot be distinguished from random patterns, and consequently, the observed anomalies in animal activity do not have any forecasting power. KW - animal behavior KW - earthquake precursor KW - error diagram KW - prediction KW - randomness KW - statistics Y1 - 2020 U6 - https://doi.org/10.1111/eth.13105 SN - 0179-1613 SN - 1439-0310 VL - 127 IS - 3 SP - 302 EP - 306 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Mueller-Schoell, Anna A1 - Groenland, Stefanie L. A1 - Scherf-Clavel, Oliver A1 - van Dyk, Madele A1 - Huisinga, Wilhelm A1 - Michelet, Robin A1 - Jaehde, Ulrich A1 - Steeghs, Neeltje A1 - Huitema, Alwin D. R. A1 - Kloft, Charlotte T1 - Therapeutic drug monitoring of oral targeted antineoplastic drugs JF - European journal of clinical pharmacology N2 - Purpose This review provides an overview of the current challenges in oral targeted antineoplastic drug (OAD) dosing and outlines the unexploited value of therapeutic drug monitoring (TDM). Factors influencing the pharmacokinetic exposure in OAD therapy are depicted together with an overview of different TDM approaches. Finally, current evidence for TDM for all approved OADs is reviewed. Methods A comprehensive literature search (covering literature published until April 2020), including primary and secondary scientific literature on pharmacokinetics and dose individualisation strategies for OADs, together with US FDA Clinical Pharmacology and Biopharmaceutics Reviews and the Committee for Medicinal Products for Human Use European Public Assessment Reports was conducted. Results OADs are highly potent drugs, which have substantially changed treatment options for cancer patients. Nevertheless, high pharmacokinetic variability and low treatment adherence are risk factors for treatment failure. TDM is a powerful tool to individualise drug dosing, ensure drug concentrations within the therapeutic window and increase treatment success rates. After reviewing the literature for 71 approved OADs, we show that exposure-response and/or exposure-toxicity relationships have been established for the majority. Moreover, TDM has been proven to be feasible for individualised dosing of abiraterone, everolimus, imatinib, pazopanib, sunitinib and tamoxifen in prospective studies. There is a lack of experience in how to best implement TDM as part of clinical routine in OAD cancer therapy. Conclusion Sub-therapeutic concentrations and severe adverse events are current challenges in OAD treatment, which can both be addressed by the application of TDM-guided dosing, ensuring concentrations within the therapeutic window. KW - targeted antineoplastic drugs KW - tyrosine kinase inhibitors KW - therapeutic KW - drug monitoring KW - oral anticancer drugs KW - personalised medicine Y1 - 2020 U6 - https://doi.org/10.1007/s00228-020-03014-8 SN - 0031-6970 SN - 1432-1041 VL - 77 IS - 4 SP - 441 EP - 464 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Grisic, Ana-Marija A1 - Eser, Alexander A1 - Huisinga, Wilhelm A1 - Reinisch, Walter A1 - Kloft, Charlotte T1 - Quantitative relationship between infliximab exposure and inhibition of C-reactive protein synthesis to support inflammatory bowel disease management JF - British journal of clinical pharmacology N2 - Aim Quantitative and kinetic insights into the drug exposure-disease response relationship might enhance our knowledge on loss of response and support more effective monitoring of inflammatory activity by biomarkers in patients with inflammatory bowel disease (IBD) treated with infliximab (IFX). This study aimed to derive recommendations for dose adjustment and treatment optimisation based on mechanistic characterisation of the relationship between IFX serum concentration and C-reactive protein (CRP) concentration.
Methods Data from an investigator-initiated trial included 121 patients with IBD during IFX maintenance treatment. Serum concentrations of IFX, antidrug antibodies (ADA), CRP, and disease-related covariates were determined at the mid-term and end of a dosing interval. Data were analysed using a pharmacometric nonlinear mixed-effects modelling approach. An IFX exposure-CRP model was generated and applied to evaluate dosing regimens to achieve CRP remission.
Results The generated quantitative model showed that IFX has the potential to inhibit up to 72% (9% relative standard error [RSE]) of CRP synthesis in a patient. IFX concentration leading to 90% of the maximum CRP synthesis inhibition was 18.4 mu g/mL (43% RSE). Presence of ADA was the most influential factor on IFX exposure. With standard dosing strategy, >= 55% of ADA+ patients experienced CRP nonremission. Shortening the dosing interval and co-therapy with immunomodulators were found to be the most beneficial strategies to maintain CRP remission.
Conclusions With the generated model we could for the first time establish a robust relationship between IFX exposure and CRP synthesis inhibition, which could be utilised for treatment optimisation in IBD patients. KW - C‐ reactive protein remission KW - inflammatory bowel disease KW - infliximab dosing Y1 - 2020 U6 - https://doi.org/10.1111/bcp.14648 SN - 0306-5251 SN - 1365-2125 VL - 87 IS - 5 SP - 2374 EP - 2384 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Kluwe, Franziska A1 - Michelet, Robin A1 - Müller-Schöll, Anna A1 - Maier, Corinna A1 - Klopp-Schulze, Lena A1 - van Dyk, Madele A1 - Mikus, Gerd A1 - Huisinga, Wilhelm A1 - Kloft, Charlotte T1 - Perspectives on model-informed precision dosing in the digital health era BT - challenges, opportunities, and recommendations JF - Clinical pharmacology & therapeutics Y1 - 2020 U6 - https://doi.org/10.1002/cpt.2049 SN - 0009-9236 SN - 1532-6535 VL - 109 IS - 1 SP - 29 EP - 36 PB - Wiley CY - Hoboken 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 - 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 -