TY - GEN A1 - Winkelmann, Stefanie A1 - Schütte, Christof T1 - Hybrid Models for Chemical Reaction Networks: Multiscale Theory and Application to Gene Regulatory Systems N2 - 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. T3 - ZIB-Report - 17-29 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-64264 ER - TY - GEN A1 - Rohr, Ulrich-Peter A1 - Herrmann, Pia A1 - Ilm, Katharina A1 - Zhang, Hai A1 - Lohmann, Sabine A1 - Reiser, Astrid A1 - Muranyi, Andrea A1 - Smith, Janice A1 - Burock, Susen A1 - Osterland, Marc A1 - Leith, Katherine A1 - Singh, Shalini A1 - Brunhoeber, Patrick A1 - Bowermaster, Rebecca A1 - Tie, Jeanne A1 - Christie, Michael A1 - Wong, Hui-Li A1 - Waring, Paul A1 - Shanmugam, Kandavel A1 - Gibbs, Peter A1 - Stein, Ulrike T1 - Prognostic value of MACC1 and proficient mismatch repair status for recurrence risk prediction in stage II colon cancer patients: the BIOGRID studies N2 - Background We assessed the novel MACC1 gene to further stratify stage II colon cancer patients with proficient mismatch repair (pMMR). Patients and methods Four cohorts with 596 patients were analyzed: Charité 1 discovery cohort was assayed for MACC1 mRNA expression and MMR in cryo-preserved tumors. Charité 2 comparison cohort was used to translate MACC1 qRT- PCR analyses to FFPE samples. In the BIOGRID 1 training cohort MACC1 mRNA levels were related to MACC1 protein levels from immunohistochemistry in FFPE sections; also analyzed for MMR. Chemotherapy-naïve pMMR patients were stratified by MACC1 mRNA and protein expression to establish risk groups based on recurrence-free survival (RFS). Risk stratification from BIOGRID 1 was confirmed in the BIOGRID 2 validation cohort. Pooled BIOGRID datasets produced a best effect-size estimate. Results In BIOGRID 1, using qRT-PCR and immunohistochemistry for MACC1 detection, pMMR/MACC1-low patients had a lower recurrence probability versus pMMR/MACC1-high patients (5-year RFS of 92% and 67% versus 100% and 68%, respectively). In BIOGRID 2, longer RFS was confirmed for pMMR/MACC1-low versus pMMR/MACC1-high patients (5-year RFS of 100% versus 90%, respectively). In the pooled dataset, 6.5% of patients were pMMR/MACC1-low with no disease recurrence, resulting in a 17% higher 5-year RFS (95% CI (12.6-21.3%)) versus pMMR/MACC1-high patients (P=0.037). Outcomes were similar for pMMR/MACC1-low and deficient MMR (dMMR) patients (5-year RFS of 100% and 96%, respectively). Conclusions MACC1 expression stratifies colon cancer patients with unfavorable pMMR status. Stage II colon cancer patients with pMMR/MACC1-low tumors have a similar favorable prognosis to those with dMMR with potential implications for the role of adjuvant therapy. T3 - ZIB-Report - 17-28 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-64184 SN - 1438-0064 ER - TY - GEN A1 - Beckenbach, Isabel A1 - Peis, Britta A1 - Schaudt, Oliver A1 - Scheidweiler, Robert T1 - A Combinatorial Proof of a König-type Theorem for Unimodular Hypergraphs N2 - We state purely combinatorial proofs for König- and Hall-type theorems for a wide class of combinatorial optimization problems. Our methods rely on relaxations of the matching and vertex cover problem and, moreover, on the strong coloring properties admitted by bipartite graphs and their generalizations. T3 - ZIB-Report - 17-27 KW - Packing KW - Covering KW - Total Unimodularity KW - König's Theorem KW - Factors Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-64017 SN - 1438-0064 ER - TY - GEN A1 - Homberg, Ulrike A1 - Baum, Daniel A1 - Prohaska, Steffen A1 - Günster, Jens A1 - Krauß-Schüler, Stefanie T1 - Adapting trabecular structures for 3D printing: an image processing approach based on µCT data N2 - Materials with a trabecular structure notably combine advantages such as lightweight, reasonable strength, and permeability for fluids. This combination of advantages is especially interesting for tissue engineering in trauma surgery and orthopedics. Bone-substituting scaffolds for instance are designed with a trabecular structure in order to allow cell migration for bone ingrowth and vascularization. An emerging and recently very popular technology to produce such complex, porous structures is 3D printing. However, several technological aspects regarding the scaffold architecture, the printable resolution, and the feature size have to be considered when fabricating scaffolds for bone tissue replacement and regeneration. Here, we present a strategy to assess and prepare realistic trabecular structures for 3D printing using image analysis with the aim of preserving the structural elements. We discuss critical conditions of the printing system and present a 3-stage approach to adapt a trabecular structure from $\mu$CT data while incorporating knowledge about the printing system. In the first stage, an image-based extraction of solid and void structures is performed, which results in voxel- and graph-based representations of the extracted structures. These representations not only allow us to quantify geometrical properties such as pore size or strut geometry and length. But, since the graph represents the geometry and the topology of the initial structure, it can be used in the second stage to modify and adjust feature size, volume and sample size in an easy and consistent way. In the final reconstruction stage, the graph is then converted into a voxel representation preserving the topology of the initial structure. This stage generates a model with respect to the printing conditions to ensure a stable and controlled voxel placement during the printing process. T3 - ZIB-Report - 17-26 KW - trabecular structures KW - image-based analysis KW - additive manufacturing KW - printability Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-64004 SN - 1438-0064 ER - TY - GEN A1 - Fischer, Lisa A1 - Götschel, Sebastian A1 - Weiser, Martin T1 - Lossy data compression reduces communication time in hybrid time-parallel integrators N2 - Parallel in time methods for solving initial value problems are a means to increase the parallelism of numerical simulations. Hybrid parareal schemes interleaving the parallel in time iteration with an iterative solution of the individual time steps are among the most efficient methods for general nonlinear problems. Despite the hiding of communication time behind computation, communication has in certain situations a significant impact on the total runtime. Here we present strict, yet no sharp, error bounds for hybrid parareal methods with inexact communication due to lossy data compression, and derive theoretical estimates of the impact of compression on parallel efficiency of the algorithms. These and some computational experiments suggest that compression is a viable method to make hybrid parareal schemes robust with respect to low bandwidth setups. T3 - ZIB-Report - 17-25 KW - parallel-in-time integration KW - hybrid parareal KW - convergence KW - lossy compression KW - MPI Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-63961 SN - 1438-0064 ER - TY - GEN A1 - Grimm, Boris A1 - Borndörfer, Ralf A1 - Reuther, Markus A1 - Schade, Stanley A1 - Schlechte, Thomas T1 - A Propagation Approach to Acyclic Rolling Stock Rotation Optimization N2 - The rolling stock, i.e., railway vehicles, are one of the key ingredients of a running railway system. As it is well known, the offer of a railway company to their customers, i.e., the railway timetable, changes from time to time. Typical reasons for that are different timetables associated with different seasons, maintenance periods or holidays. Therefore, the regular lifetime of a timetable is split into (more or less) irregular periods where parts of the timetable are changed. In order to operate a railway timetable most railway companies set up sequences that define the operation of timetabled trips by a single physical railway vehicle called (rolling stock) rotations. Not surprisingly, the individual parts of a timetable also affect the rotations. More precisely, each of the parts brings up an acyclic rolling stock rotation problem with start and end conditions associated with the beginning and ending of the corresponding period. In this paper, we propose a propagation approach to deal with large planning horizons that are composed of many timetables with shorter individual lifetimes. The approach is based on an integer linear programming formulation that propagates rolling stock rotations through the irregular parts of the timetable while taking a large variety of operational requirements into account. This approach is implemented within the rolling stock rotation optimization framework ROTOR used by DB Fernverkehr AG, one of the leading railway operators in Europe. Computational results for real world scenarios are presented to evaluate the approach. T3 - ZIB-Report - 17-24 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-63930 SN - 1438-0064 ER - TY - GEN A1 - Lange, Alexander A1 - Schwieger, Robert A1 - Plöntzke, Julia A1 - Schäfer, Stefan A1 - Röblitz, Susanna T1 - Follicular competition: the selection of dominant follicles as a synergistic effect N2 - 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. T3 - ZIB-Report - 17-21 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-63863 SN - 1438-0064 ER - TY - GEN A1 - Gilg, Brady A1 - Klug, Torsten A1 - Martienssen, Rosemarie A1 - Paat, Joseph A1 - Schlechte, Thomas A1 - Schulz, Christof A1 - Seymen, Sinan A1 - Tesch, Alexander T1 - Conflict-Free Railway Track Assignment at Depots N2 - Managing rolling stock with no passengers aboard is a critical component of railway operations. In particular, one problem is to park the rolling stock on a given set of tracks at the end of a day or service. Depending on the parking assignment, shunting may be required in order for a parked train to depart or for an incoming train to park. Given a collection of tracks M and a collection of trains T with fixed arrival-departure timetable, the train assignment problem (TAP) is to determine the maximum number of trains from T that can be parked on M according to the timetable and without the use of shunting. Hence, efficiently solving the TAP allows to quickly compute feasible parking schedules that do not require further shunting adjustments. In this paper, we present two integer programming models for solving the TAP. To our knowledge, this is the first integrated approach that considers track lengths along with the three most common types of parking tracks. We compare these models on a theoretical level. We also prove that a decision version of the TAP is NP-complete, justifying the use of integer programming techniques. Using stochastic and robust modelling techniques, both models produce parking assignments that are optimized and robust according to random train delays. We conclude with computational results for both models, observing that they perform well on real timetables. T3 - ZIB-Report - 17-23 KW - Depot Planning KW - Railway Track Assignment Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-63843 SN - 1438-0064 ER - TY - GEN A1 - Bittracher, Andreas A1 - Koltai, Péter A1 - Klus, Stefan A1 - Banisch, Ralf A1 - Dellnitz, Michael A1 - Schütte, Christof T1 - Transition manifolds of complex metastable systems: Theory and data-driven computation of effective dynamics N2 - We consider complex dynamical systems showing metastable behavior but no local separation of fast and slow time scales. The article raises the question of whether such systems exhibit a low-dimensional manifold supporting its effective dynamics. For answering this question, we aim at finding nonlinear coordinates, called reaction coordinates, such that the projection of the dynamics onto these coordinates preserves the dominant time scales of the dynamics. We show that, based on a specific reducibility property, the existence of good low-dimensional reaction coordinates preserving the dominant time scales is guaranteed. Based on this theoretical framework, we develop and test a novel numerical approach for computing good reaction coordinates. The proposed algorithmic approach is fully local and thus not prone to the curse of dimension with respect to the state space of the dynamics. Hence, it is a promising method for data-based model reduction of complex dynamical systems such as molecular dynamics. T3 - ZIB-Report - 17-22 KW - metastability KW - slow dynamics KW - effective dynamics KW - transition manifold KW - embedding KW - transfer operator KW - reaction coordinate Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-63822 SN - 1438-0064 ER - TY - GEN A1 - Weiser, Martin A1 - Erdmann, Bodo A1 - Schenkl, Sebastian A1 - Muggenthaler, Holger A1 - Hubig, Michael A1 - Mall, Gita A1 - Zachow, Stefan T1 - Uncertainty in Temperature-Based Determination of Time of Death N2 - Temperature-based estimation of time of death (ToD) can be per- formed either with the help of simple phenomenological models of corpse cooling or with detailed mechanistic (thermodynamic) heat transfer mod- els. The latter are much more complex, but allow a higher accuracy of ToD estimation as in principle all relevant cooling mechanisms can be taken into account. The potentially higher accuracy depends on the accuracy of tissue and environmental parameters as well as on the geometric resolution. We in- vestigate the impact of parameter variations and geometry representation on the estimated ToD based on a highly detailed 3D corpse model, that has been segmented and geometrically reconstructed from a computed to- mography (CT) data set, differentiating various organs and tissue types. From that we identify the most crucial parameters to measure or estimate, and obtain a local uncertainty quantifcation for the ToD. T3 - ZIB-Report - 17-18 KW - forensic medicine KW - determination of time of death KW - heat transfer equation KW - sensitivity i.r.t. thermal parameters KW - sensitivity i.r.t. geometric resolution Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-63818 SN - 1438-0064 ER -