TY - GEN A1 - Bittracher, Andreas A1 - Schütte, Christof T1 - A probabilistic algorithm for aggregating vastly undersampled large Markov chains N2 - Model reduction of large Markov chains is an essential step in a wide array of techniques for understanding complex systems and for efficiently learning structures from high-dimensional data. We present a novel aggregation algorithm for compressing such chains that exploits a specific low-rank structure in the transition matrix which, e.g., is present in metastable systems, among others. It enables the recovery of the aggregates from a vastly undersampled transition matrix which in practical applications may gain a speedup of several orders of mag- nitude over methods that require the full transition matrix. Moreover, we show that the new technique is robust under perturbation of the transition matrix. The practical applicability of the new method is demonstrated by identifying a reduced model for the large-scale traffic flow patterns from real-world taxi trip data. T3 - ZIB-Report - 20-21 Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-78688 UR - https://opus4.kobv.de/opus4-zib/frontdoor/index/index/docId/7587 SN - 1438-0064 ER - TY - JOUR A1 - Boltz, Horst-Holger A1 - Sirbu, Alexei A1 - Stelzer, Nina A1 - Lohse, Martin J. A1 - Schütte, Christof A1 - Annibale, Paolo T1 - Quantitative spectroscopy of single molecule interaction times JF - Optic Letters N2 - Single molecule fluorescence tracking provides information at nanometer-scale and millisecond-temporal resolution about the dynamics and interaction of individual molecules in a biological environment. While the dynamic behavior of isolated molecules can be characterized well, the quantitative insight is more limited when interactions between two indistinguishable molecules occur. We address this aspect by developing a theoretical foundation for a spectroscopy of interaction times, i.e., the inference of interaction from imaging data. A non-trivial crossover between a power law to an exponential behavior of the distribution of the interaction times is highlighted, together with the dependence of the exponential term upon the microscopic reaction affinity. Our approach is validated with simulated and experimental datasets. Y1 - 2021 U6 - https://doi.org/10.1364/OL.413030 VL - 46 IS - 7 SP - 1538 EP - 1541 ER - TY - JOUR A1 - Thies, Arne A1 - Sunkara, Vikram A1 - Ray, Sourav A1 - Wulkow, Hanna A1 - Celik, M. Özgür A1 - Yergöz, Fatih A1 - Schütte, Christof A1 - Stein, Christoph A1 - Weber, Marcus A1 - Winkelmann, Stefanie T1 - Modelling altered signalling of G-protein coupled receptors in inflamed environment to advance drug design JF - Scientific Reports N2 - We previously reported the successful design, synthesis and testing of the prototype opioid painkiller NFEPP that does not elicit adverse side effects. The design process of NFEPP was based on mathematical modelling of extracellular interactions between G-protein coupled receptors (GPCRs) and ligands, recognizing that GPCRs function differently under pathological versus healthy conditions. We now present an additional and novel stochastic model of GPCR function that includes intracellular dissociation of G-protein subunits and modulation of plasma membrane calcium channels and their dependence on parameters of inflamed and healthy tissue (pH, radicals). The model is validated against in vitro experimental data for the ligands NFEPP and fentanyl at different pH values and radical concentrations. We observe markedly reduced binding affinity and calcium channel inhibition for NFEPP at normal pH compared to lower pH, in contrast to the effect of fentanyl. For increasing radical concentrations, we find enhanced constitutive G-protein activation but reduced ligand binding affinity. Assessing the different effects, the results suggest that, compared to radicals, low pH is a more important determinant of overall GPCR function in an inflamed environment. Future drug design efforts should take this into account. Y1 - 2023 U6 - https://doi.org/10.1038/s41598-023-27699-w VL - 13 IS - 607 ER - TY - JOUR A1 - Bauer, Wolfgang A1 - Weber, Marcus A1 - Diehl-Wiesenecker, Eva A1 - Galtung, Noa A1 - Prpic, Monika A1 - Somasundaram, Rajan A1 - Tauber, Rudolf A1 - Schwenk, Jochen A1 - Micke, Patrick A1 - Kappert, Kai T1 - Plasma Proteome Fingerprints Reveal Distinctiveness and Clinical Outcome of SARS-CoV-2 Infection JF - Viruses N2 - We evaluated how plasma proteomic signatures in patients with suspected COVID-19 can unravel the pathophysiology, and determine kinetics and clinical outcome of the infection. We identified distinct plasma proteins linked to the presence and course of COVID-19. These plasma proteomic findings may translate to a protein fingerprint, helping to assist clinical management decisions. Y1 - 2021 U6 - https://doi.org/10.3390/v13122456 VL - 13 IS - 12 SP - 2456 ER - TY - JOUR A1 - Bittracher, Andreas A1 - Moschner, Johann A1 - Koksch, Beate A1 - Netz, Roland A1 - Schütte, Christof T1 - Exploring the locking stage of NFGAILS amyloid fibrillation via transition manifold analysis JF - The European Physical Journal B Y1 - 2021 U6 - https://doi.org/10.1140/epjb/s10051-021-00200-0 VL - 94 ER -