TY - JOUR A1 - Strader, Anne A1 - Schneider, Max A1 - Schorlemmer, Danijel T1 - Prospective and retrospective evaluation of five-year earthquake forecast models for California JF - Geophysical journal international KW - Probabilistic forecasting KW - Statistical methods KW - Earthquake interaction KW - fore-casting KW - and prediction KW - Statistical seismology Y1 - 2017 U6 - https://doi.org/10.1093/gji/ggx268 SN - 0956-540X SN - 1365-246X VL - 211 SP - 239 EP - 251 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Hartung, Niklas A1 - Benary, Uwe A1 - Wolf, Jana A1 - Kofahl, Bente T1 - Paracrine and autocrine regulation of gene expression by Wnt-inhibitor Dickkopf in wild-type and mutant hepatocytes JF - BMC systems biology N2 - Background: Cells are able to communicate and coordinate their function within tissues via secreted factors. Aberrant secretion by cancer cells can modulate this intercellular communication, in particular in highly organised tissues such as the liver. Hepatocytes, the major cell type of the liver, secrete Dickkopf (Dkk), which inhibits Wnt/beta-catenin signalling in an autocrine and paracrine manner. Consequently, Dkk modulates the expression of Wnt/beta-catenin target genes. We present a mathematical model that describes the autocrine and paracrine regulation of hepatic gene expression by Dkk under wild-type conditions as well as in the presence of mutant cells. Results: Our spatial model describes the competition of Dkk and Wnt at receptor level, intra-cellular Wnt/beta-catenin signalling, and the regulation of target gene expression for 21 individual hepatocytes. Autocrine and paracrine regulation is mediated through a feedback mechanism via Dkk and Dkk diffusion along the porto-central axis. Along this axis an APC concentration gradient is modelled as experimentally detected in liver. Simulations of mutant cells demonstrate that already a single mutant cell increases overall Dkk concentration. The influence of the mutant cell on gene expression of surrounding wild-type hepatocytes is limited in magnitude and restricted to hepatocytes in close proximity. To explore the underlying molecular mechanisms, we perform a comprehensive analysis of the model parameters such as diffusion coefficient, mutation strength and feedback strength. Conclusions: Our simulations show that Dkk concentration is elevated in the presence of a mutant cell. However, the impact of these elevated Dkk levels on wild-type hepatocytes is confined in space and magnitude. The combination of inter-and intracellular processes, such as Dkk feedback, diffusion and Wnt/beta-catenin signal transduction, allow wild-type hepatocytes to largely maintain their gene expression. KW - Wnt/beta-catenin signalling pathway KW - Dickkopf diffusion and feedback regulation KW - APC concentration gradient KW - Mathematical model KW - Paracrine and autocrine regulation KW - Reaction-diffusion system Y1 - 2017 U6 - https://doi.org/10.1186/s12918-017-0470-9 SN - 1752-0509 VL - 11 PB - BioMed Central CY - London ER - TY - JOUR A1 - Benini, Marco A1 - Schenkel, Alexander T1 - Quantum Field Theories on Categories Fibered in Groupoids JF - Communications in mathematical physics N2 - We introduce an abstract concept of quantum field theory on categories fibered in groupoids over the category of spacetimes. This provides us with a general and flexible framework to study quantum field theories defined on spacetimes with extra geometric structures such as bundles, connections and spin structures. Using right Kan extensions, we can assign to any such theory an ordinary quantum field theory defined on the category of spacetimes and we shall clarify under which conditions it satisfies the axioms of locally covariant quantum field theory. The same constructions can be performed in a homotopy theoretic framework by using homotopy right Kan extensions, which allows us to obtain first toy-models of homotopical quantum field theories resembling some aspects of gauge theories. Y1 - 2017 U6 - https://doi.org/10.1007/s00220-017-2986-7 SN - 0010-3616 SN - 1432-0916 VL - 356 SP - 19 EP - 64 PB - Springer CY - New York ER - TY - JOUR A1 - Chang, D. -C. A1 - Schulze, Bert-Wolfgang T1 - Calculus on spaces with higher singularities JF - Journal of pseudo-differential operators and applications N2 - We establish extensions of the standard pseudo-differential calculus to specific classes of operators with operator-valued symbols occurring in symbolic hierarchies motivated by manifolds with higher singularities or stratified spaces. KW - Pseudo-differential operators KW - Operator-valued symbols KW - Fourier and Mellin transform Y1 - 2017 U6 - https://doi.org/10.1007/s11868-016-0180-x SN - 1662-9981 SN - 1662-999X VL - 8 SP - 585 EP - 622 PB - Springer CY - Basel ER -