@article{Winkelmann2017, author = {Winkelmann, Stefanie}, title = {Markov Control with Rare State Observation: Average Optimality}, volume = {23}, journal = {Markov Processes and Related Fields}, pages = {1 -- 34}, year = {2017}, abstract = {This paper investigates the criterion of long-term average costs for a Markov decision process (MDP) which is not permanently observable. Each observation of the process produces a fixed amount of information costs which enter the considered performance criterion and preclude from arbitrarily frequent state testing. Choosing the rare observation times is part of the control procedure. In contrast to the theory of partially observable Markov decision processes, we consider an arbitrary continuous-time Markov process on a finite state space without further restrictions on the dynamics or the type of interaction. Based on the original Markov control theory, we redefine the control model and the average cost criterion for the setting of information costs. We analyze the constant of average costs for the case of ergodic dynamics and present an optimality equation which characterizes the optimal choice of control actions and observation times. For this purpose, we construct an equivalent freely observable MDP and translate the well-known results from the original theory to the new setting.}, language = {en} } @article{GuptaGramatkeEinspanieretal.2017, author = {Gupta, Pooja and Gramatke, Annika and Einspanier, Ralf and Sch{\"u}tte, Christof and von Kleist, Max and Sharbati, Jutta}, title = {In silico cytotoxicity assessment on cultured rat intestinal cells deduced from cellular impedance measurements}, volume = {41}, journal = {Toxicology in Vitro}, issn = {1438-0064}, pages = {179 -- 188}, year = {2017}, abstract = {Early and reliable identification of chemical toxicity is of utmost importance. At the same time, reduction of animal testing is paramount. Therefore, methods that improve the interpretability and usability of in vitro assays are essential. xCELLigence's real-time cell analyzer (RTCA) provides a novel, fast and cost effective in vitro method to probe compound toxicity. We developed a simple mathematical framework for the qualitative and quantitative assessment of toxicity for RTCA measurements. Compound toxicity, in terms of its 50\% inhibitory concentration IC50 on cell growth, and parameters related to cell turnover were estimated on cultured IEC-6 cells exposed to 10 chemicals at varying concentrations. Our method estimated IC50 values of 113.05, 7.16, 28.69 and 725.15 μM for the apparently toxic compounds 2-acetylamino-fluorene, aflatoxin B1, benzo-[a]-pyrene and chloramphenicol in the tested cell line, in agreement with literature knowledge. IC50 values of all apparent in vivo non-toxic compounds were estimated to be non-toxic by our method. Corresponding estimates from RTCA's in-built model gave false positive (toxicity) predictions in 5/10 cases. Taken together, our proposed method reduces false positive predictions and reliably identifies chemical toxicity based on impedance measurements. The source code for the developed method including instructions is available at https://git.zib.de/bzfgupta/toxfit/tree/master.}, language = {en} } @misc{WinkelmannSchuette2017, author = {Winkelmann, Stefanie and Sch{\"u}tte, Christof}, title = {Hybrid Models for Chemical Reaction Networks: Multiscale Theory and Application to Gene Regulatory Systems}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-64264}, year = {2017}, abstract = {Well-mixed stochastic chemical kinetics are properly modelled by the chemical master equation (CME) and associated Markov jump processes in molecule number space. If the reactants are present in large amounts, however, corresponding simulations of the stochastic dynamics become computationally expensive and model reductions are demanded. The classical model reduction approach uniformly rescales the overall dynamics to obtain deterministic systems characterized by ordinary differential equations, the well-known mass action reaction rate equations. For systems with multiple scales there exist hybrid approaches that keep parts of the system discrete while another part is approximated either using Langevin dynamics or deterministically. This paper aims at giving a coherent overview of the different hybrid approaches, focusing on their basic concepts and the relation between them. We derive a novel general description of such hybrid models that allows to express various forms by one type of equation. We also check in how far the approaches apply to model extensions of the CME for dynamics which do not comply with the central well-mixed condition and require some spatial resolution. A simple but meaningful gene expression system with negative self-regulation is analysed to illustrate the different approximation qualities of some of the hybrid approaches discussed.}, language = {en} } @article{HengartnerKruegerGeraedtsetal.2017, author = {Hengartner, Michael and Kr{\"u}ger, Tillmann H. C. and Geraedts, Kirsten and Tronci, Enrico and Mancini, Toni and Ille, Fabian and Egli, Marcel and R{\"o}blitz, Susanna and Ehrig, Rainald and Saleh, Lanja and Spanaus, Katharina and Schippert, Cordula and Zhang, Yuanyuan and Leeners, Brigitte}, title = {Negative affect is unrelated to fluctuations in hormone levels across the menstrual cycle: evidence from a multisite observational study across two successive cycles}, volume = {99}, journal = {Journal of Psychosomatic Research}, doi = {10.1016/j.jpsychores.2017.05.018}, pages = {21 -- 27}, year = {2017}, language = {en} } @misc{LangeSchwiegerPloentzkeetal.2017, author = {Lange, Alexander and Schwieger, Robert and Pl{\"o}ntzke, Julia and Sch{\"a}fer, Stefan and R{\"o}blitz, Susanna}, title = {Follicular competition: the selection of dominant follicles as a synergistic effect}, issn = {1438-0064}, doi = {https://doi.org/10.1007/s00285-018-1284-0}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-63863}, year = {2017}, abstract = {The estrous cycle of mono-ovulatory species such as cows or humans, is known to show two or more waves of follicular growth and decline between two successive ovulations. Within each wave, there is one dominant follicle escorted by subordinate follicles of varying number. Under the surge of the luteinizing hormone a growing dominant follicle ovulates. Rarely the number of ovulating follicles exceeds one. In the biological literature, the change of hormonal concentrations and individually varying numbers of follicular receptors are made responsible for the selection of exactly one dominant follicle, yet a clear cause has not been identified. In this paper, we suggest a synergistic explanation based on competition, formulated by a parsimoniously defined system of ordinary differential equations (ODEs) that quantifies the time evolution of multiple follicles and their competitive interaction during one wave. Not discriminating between follicles, growth and decline are given by fixed rates. Competition is introduced via a growth-suppressing term, equally supported by all follicles. We prove that the number of dominant follicles is determined exclusively by the ratio of follicular growth and competition. This number turns out to be independent of the number of subordinate follicles. The asymptotic behavior of the corresponding dynamical system is investigated rigorously, where we demonstrate that the omega-limit set only contains fixed points. When also including follicular decline, our ODEs perfectly resemble ultrasound data of bovine follicles. Implications for the involved but not explicitly modeled hormones are discussed.}, language = {en} } @article{LeenersKruegerGeraedtsetal.2017, author = {Leeners, Brigitte and Kr{\"u}ger, Tillmann H. C. and Geraedts, Kirsten and Tronci, Enrico and Mancini, Toni and Ille, Fabian and Egli, Marcel and R{\"o}blitz, Susanna and Saleh, Lanja and Spanhaus, K. and Schippert, Cordula and Zhang, Y. and Hengartner, M. P.}, title = {Lack of association between female hormone levels and visuospatial working memory, divided attention and cognitive bias across two consecutive menstrual cycles}, journal = {Front. Behav. Neurosci.}, doi = {10.3389/fnbeh.2017.00120}, year = {2017}, language = {en} } @article{BergPloentzkeLeonhardMareketal.2017, author = {Berg, Mascha and Pl{\"o}ntzke, Julia and Leonhard-Marek, Sabine and M{\"u}ller, Kerstin-Elisabeth and R{\"o}blitz, Susanna}, title = {A dynamic model to simulate potassium balance in dairy cows}, volume = {100}, journal = {Journal of Dairy Science}, number = {12}, doi = {10.3168/jds.2016-12443}, pages = {9799 -- 9814}, year = {2017}, abstract = {High-performing dairy cows require a particular composition of nutritional ingredients, adapted to their individual requirements and depending on their production status. The optimal dimensioning of minerals in the diet, one being potassium, is indispensable for the prevention of imbalances. Potassium balance in cows is the result of potassium intake, distribution in the organism, and excretion, and it is closely related to glucose and electrolyte metabolism. In this paper, we present a dynamical model for potassium balance in lactating and nonlactating dairy cows based on ordinary differential equations. Parameter values were obtained from clinical trial data and from the literature. To verify the consistency of the model, we present simulation outcomes for 3 different scenarios: potassium balance in (1) nonlactating cows with varying feed intake, (2) nonlactating cows with varying potassium fraction in the diet, and (3) lactating cows with varying milk production levels. The results give insights into the short- and long-term potassium metabolism, providing an important step toward the understanding of the potassium network, the design of prophylactic feed additives, and possible treatment strategies.}, language = {en} } @article{IgdeRoeblitzMuelleretal.2017, author = {Igde, Sinaida and R{\"o}blitz, Susanna and M{\"u}ller, Anne and Kolbe, Katharina and Boden, Sophia and Fessele, Claudia and Lindhorst, Thisbe and Weber, Marcus and Hartmann, Laura}, title = {Linear Precision Glycomacromolecules with Varying Interligand Spacing and Linker Functionalities Binding to Concanavalin A and the Bacterial Lectin FimH}, volume = {17}, journal = {Marcomolecular Bioscience}, number = {12}, doi = {10.1002/mabi.201700198}, pages = {1700198}, year = {2017}, language = {en} }