TY - JOUR A1 - Weber, Marcus A1 - Kube, Susanna A1 - Walter, Lionel A1 - Deuflhard, Peter T1 - Stable Computation of Probability Densities of Metastable Dynamical Systems JF - SIAM J. Multiscale Model. Simul. Y1 - 2007 VL - 6 IS - 2 SP - 396 EP - 416 ER - TY - JOUR A1 - Kube, Susanna A1 - Lasser, Caroline A1 - Weber, Marcus T1 - Monte Carlo sampling of Wigner functions and surface hopping quantum dynamics JF - Journal of Computational Physics Y1 - 2008 U6 - https://doi.org/10.1016/j.jcp.2008.11.016 VL - 228 IS - 6 SP - 1947 EP - 1962 ER - TY - JOUR A1 - Deuflhard, Peter A1 - Röblitz, Susanna A1 - Stötzel, Claudia T1 - Mathematical Systems Biology at Zuse Institute Berlin (ZIB) JF - BioTOPics - Journal of Biotechnology in Berlin-Brandenburg Y1 - 2010 VL - 39 ER - TY - JOUR A1 - Röblitz, Susanna A1 - Weber, Marcus T1 - Fuzzy Spectral Clustering by PCCA+ JF - Classification and Clustering: Models, Software and Applications Y1 - 2009 UR - http://www.wias-berlin.de/publications/wias-publ/run.jsp?template=abstract&type=Report&year=2009&number=26 IS - WIAS Report No. 26 SP - 73 EP - 79 ER - TY - THES A1 - Knöchel, Jane T1 - Mathematische Modellierung metabolischer Einflussfaktoren auf den Milchkuhzyklus N2 - In den letzten Jahren ist die reproduktive Leistung von Milchkühen parallel zur steigenden Milchleistung drastisch gesunken. Um die zu Grunde liegenden biologischen Mechanismen besser zu verstehen, wurde in dieser Arbeit eine Modellerweiterung des vorhandenen Modells von Stötzel et al. (2011) um metabolische Einflussfaktoren angestrebt. Hierfür wurde zuerst aus veröffentlichten, experimentell gewonnen Erkenntnissen herausgearbeitet, wie die metabolischen Faktoren auf das periodische Zyklusverfahren der Milchkuh Einfluss nehmen. Daraus wurde ersichtlich, dass Glukose, Insulin und IGF-I die wichtigsten metabolischen Faktoren sind, aber lediglich IGF-I als dynamische Größe in das Modell eingeht. Zur Validierung des erweiterten Modells, wurden im Rahmen dieser Arbeit Szenarien aus der Literatur entwickelt, welche eine negative Energiebilanz oder den Effekt von Diätrestriktionen auf den Milchkuhzyklus simulieren sollten. Ferner wurden Messdaten für IGF, E2 und P4 von Kawashima et al. (2007) und Cerri et al. (2011) bereit gestellt. Das erweiterte Modell umfasst lediglich 8 Parameter mehr als das Ursprungsmodell, wobei gezeigt werden konnte, dass weder die Bedingung für die Lösbarkeit noch die Stabilität in den Anfangswerten eingebüßt wurde. Die Modellkurven konnten mittels des NLSCON erfolgreich an die bereitgestellten Messdaten für IGF, E2 und P4 angepasst werden. Anhand der Ergebnisse aus den Szenarien ließ sich zeigen, dass es teilweise gelingt über die metabolischen Einflussfaktoren eine negative Energiebilanz für unterernährte Kühe darzustellen. Die Rückführung in das periodische Zyklusverhalten verlief jedoch im Vergleich zu in vivo Beobachtungen zu schnell ab. Eine mögliche Erklärung hierfür ist ein zu geringer Einfluss von IGF-I auf das Modell. Darüber hinaus kam es trotz (stark) reduzierter LH-Konzentration zur Ovulation. Auf diesen Erkenntnissen aufbauend könnte in Zukunft die Follikelmodellierung modifiziert oder die Hillfunktion, die die Ovulation darstellt, überarbeitet werden. N2 - During the last few years there has been a drastic decline in the fertility of dairy cows. Therefore the goal of this work is to identify the underlying mechanisms for this problem by extending the model from Stötzel et al. (2011) to include the influence of metabolic factors. For this purpose the influence of the metabolic factors was determined based on published, experimentally obtained findings. The important metabolic factors were glucose, insulin and IGF-I, but only IGF-I was shown to be dynamic over the course of a cycle and therefore implemented into the model. To validate the chosen model extension we developed scenarios from the literature in order to simulate the impact of negative energy balance as well as the effect of diet restrictions on the bovine oestrous cycle. Furthermore we got measurement data from Kawashima et al. (2007) and Cerri et al. (2011) for IGF, E2 and P4. The new model has just 8 parameters more, while maintaining the same solvability and stability in the initial values. It was possible to fit the model with the use of NLSCON to the measurement data for IGF, E2 and P4. In addition the scenarios allowed us to show that the model is able to simulate a negative energy balance in parts. Merely the return into the cyclic behaviour was faster than observed in vivo. One possible explanation would be, that the influence of IGF-I on the model is not strong enough. The model showed a deficit while simulating the scenarios since a marked reduction of the LH concentration still led to ovulation. Thus future research could be done in this direction, where it would probably be necessary to modify the follicle function or the hill function responsible for ovulation. KW - Systembiologie Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-46170 N1 - Diplomarbeit ER - TY - JOUR A1 - Röblitz, Susanna A1 - Weber, Marcus T1 - Fuzzy spectral clustering by PCCA+: application to Markov state models and data classification JF - Advances in Data Analysis and Classification Y1 - 2013 U6 - https://doi.org/10.1007/s11634-013-0134-6 VL - 7 IS - 2 SP - 147 EP - 179 ER - TY - JOUR A1 - Haack, Fiete A1 - Fackeldey, Konstantin A1 - Röblitz, Susanna A1 - Scharkoi, Olga A1 - Weber, Marcus A1 - Schmidt, Burkhard T1 - Adaptive spectral clustering with application to tripeptide conformation analysis JF - The Journal of Chemical Physics Y1 - 2013 U6 - https://doi.org/10.1063/1.4830409 VL - 139 SP - 110 EP - 194 ER - TY - CHAP A1 - Schäfer, Stefan A1 - Plöntzke, Julia A1 - Röblitz, Susanna T1 - Mathematical Modelling of Follicular Maturation in Cows and Women T2 - 49. Jahrestagung der Physiologie und Pathologie der Fortpflanzung und gleichzeitig 41. Veterinär-Humanmedizinische Gemeinschaftstagung 2016, Leipzig. Y1 - 2016 ER - TY - CHAP A1 - Igde, Sinaida A1 - Wölk, Hendrik A1 - Röblitz, Susanna A1 - Reidelbach, Marco A1 - Weber, Marcus A1 - Hartmann, Laura T1 - Identifying Multivalent Binding Kinetics of Precision Glycomacromolecules: A Kinetic Study Using kinITC T2 - Münster Symposium on Cooperative Effects 2015 - SFB 858, at Westfälische Wilhelms-Universität Münster, 2015 N2 - Multivalent sugar/protein interactions are well-known to proceed through different binding modes 1-5 which in turn can be described by their binding kinetics 3-5. This study provides additional insight into the association and dissociation reaction rates of complex multivalent sugar/protein interactions. Binding kinetics of recently introduced multivalent precision glycomacromolecules 6-8 to Concanavalin A (Con A) were studied by " kinetic Isothermal Titration Calorimetry " (kinITC) 9-11. The effect of multivalency is evaluated by comparing rate constants of glycomacromolecules obtaining the same and different valency of mannose ligands and by variation of the overall backbone properties, such as hydrophilic/ hydrophoboc. In addition, binding kinetics were studied using different conformations of Con A (homodimer vs.-tetramer) and thus a different protein valency. Our results show that precision glycomacromolecule/Con A binding proceeds non-cooperatively. Further, association and dissociation rates are mainly described by intermolecular complex formation. Together with the so-called functional valency, we can discriminate between " bound " and " unbound " states for macroscopic on-and off-rates, even for such complex glycooligomer/protein systems. By comparing e.g. a mono-to a divalent glycomacromolecule for their binding to dimeric Con A, we see a lower dissociation rate for the latter. As both bind monovalently to Con A, this is a strong indication for a statistical rebinding event. Further, there is a strong dependence of multivalent binding kinetics on the ligand density of glycomacromolecules as well as the Con A conformation and thus the overall on-and off-rates. Y1 - 2015 ER - TY - JOUR A1 - Klebanov, Ilja A1 - Sikorski, Alexander A1 - Schütte, Christof A1 - Röblitz, Susanna T1 - Objective priors in the empirical Bayes framework JF - Scandinavian Journal of Statistics N2 - When dealing with Bayesian inference the choice of the prior often remains a debatable question. Empirical Bayes methods offer a data-driven solution to this problem by estimating the prior itself from an ensemble of data. In the nonparametric case, the maximum likelihood estimate is known to overfit the data, an issue that is commonly tackled by regularization. However, the majority of regularizations are ad hoc choices which lack invariance under reparametrization of the model and result in inconsistent estimates for equivalent models. We introduce a nonparametric, transformation-invariant estimator for the prior distribution. Being defined in terms of the missing information similar to the reference prior, it can be seen as an extension of the latter to the data-driven setting. This implies a natural interpretation as a trade-off between choosing the least informative prior and incorporating the information provided by the data, a symbiosis between the objective and empirical Bayes methodologies. Y1 - 2021 U6 - https://doi.org/10.1111/sjos.12485 VL - 48 IS - 4 SP - 1212 EP - 1233 PB - Wiley Online Library ER -