@article{WeberFischerDamerauetal., author = {Weber, Marie-Christin and Fischer, Lisa and Damerau, Alexandra and Ponomarev, Igor and Pfeiffenberger, Moritz and Gaber, Timo and G{\"o}tschel, Sebastian and Lang, Jens and R{\"o}blitz, Susanna and Buttgereit, Frank and Ehrig, Rainald and Lang, Annemarie}, title = {In vitro and in silico modeling of cellular and matrix-related changes during the early phase of osteoarthritis}, series = {BioRxiv}, journal = {BioRxiv}, doi = {10.1101/725317}, abstract = {Understanding the pathophysiological processes of osteoarthritis (OA) require adequate model systems. Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific parts of the disease. This study aimed to combine in vitro and in silico modeling to describe cellular and matrix-related changes during the early phase of OA. We developed an in vitro OA model based on scaffold-free cartilage-like constructs (SFCCs), which was mathematically modeled using a partial differential equation (PDE) system to resemble the processes during the onset of OA. SFCCs were produced from mesenchymal stromal cells and analyzed weekly by histology and qPCR to characterize the cellular and matrix-related composition. To simulate the early phase of OA, SFCCs were treated with interleukin-1β (IL-1β), tumor necrosis factor α (TNFα) and examined after 3 weeks or cultivated another 3 weeks without inflammatory cytokines to validate the regeneration potential. Mathematical modeling was performed in parallel to the in vitro experiments. SFCCs expressed cartilage-specific markers, and after stimulation an increased expression of inflammatory markers, matrix degrading enzymes, a loss of collagen II (Col-2) and a reduced cell density was observed which could be partially reversed by retraction of stimulation. Based on the PDEs, the distribution processes within the SFCCs, including those of IL-1β, Col-2 degradation and cell number reduction was simulated. By combining in vitro and in silico methods, we aimed to develop a valid, efficient alternative approach to examine and predict disease progression and new therapeutic strategies.}, language = {en} } @article{WeberFischerDamerauetal., author = {Weber, Marie-Christin and Fischer, Lisa and Damerau, Alexandra and Ponomarev, Igor and Pfeiffenberger, Moritz and Gaber, Timo and G{\"o}tschel, Sebastian and Lang, Jens and R{\"o}blitz, Susanna and Buttgereit, Frank and Ehrig, Rainald and Lang, Annemarie}, title = {Macroscale mesenchymal condensation to study cytokine-driven cellular and matrix-related changes during cartilage degradation}, series = {Biofabrication}, volume = {12}, journal = {Biofabrication}, number = {4}, doi = {10.1088/1758-5090/aba08f}, abstract = {Understanding the pathophysiological processes of cartilage degradation requires adequate model systems to develop therapeutic strategies towards osteoarthritis (OA). Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific disease aspects. This study aimed to combine in vitro and in silico modeling based on a tissue-engineering approach using mesenchymal condensation to mimic cytokine-induced cellular and matrix-related changes during cartilage degradation. Thus, scaffold-free cartilage-like constructs (SFCCs) were produced based on self-organization of mesenchymal stromal cells (mesenchymal condensation) and i) characterized regarding their cellular and matrix composition or secondly ii) treated with interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) for 3 weeks to simulate OA-related matrix degradation. In addition, an existing mathematical model based on partial differential equations was optimized and transferred to the underlying settings to simulate distribution of IL-1β, type II collagen degradation and cell number reduction. By combining in vitro and in silico methods, we aim to develop a valid, efficient alternative approach to examine and predict disease progression and effects of new therapeutics.}, language = {en} } @article{SchimunekSeidlElezetal.2023, author = {Schimunek, Johannes and Seidl, Philipp and Elez, Katarina and Hempel, Tim and Le, Tuan and No{\´e}, Frank and Olsson, Simon and Raich, Llu{\´i}s and Winter, Robin and Gokcan, Hatice and Gusev, Filipp and Gutkin, Evgeny M. and Isayev, Olexandr and Kurnikova, Maria G. and Narangoda, Chamali H. and Zubatyuk, Roman and Bosko, Ivan P. and Furs, Konstantin V. and Karpenko, Anna D. and Kornoushenko, Yury V. and Shuldau, Mikita and Yushkevich, Artsemi and Benabderrahmane, Mohammed B. and Bousquet-Melou, Patrick and Bureau, Ronan and Charton, Beatrice and Cirou, Bertrand C. and Gil, G{\´e}rard and Allen, William J. and Sirimulla, Suman and Watowich, Stanley and Antonopoulos, Nick and Epitropakis, Nikolaos and Krasoulis, Agamemnon and Itsikalis, Vassilis and Theodorakis, Stavros and Kozlovskii, Igor and Maliutin, Anton and Medvedev, Alexander and Popov, Petr and Zaretckii, Mark and Eghbal-Zadeh, Hamid and Halmich, Christina and Hochreiter, Sepp and Mayr, Andreas and Ruch, Peter and Widrich, Michael and Berenger, Francois and Kumar, Ashutosh and Yamanishi, Yoshihiro and Zhang, Kam Y. J. and Bengio, Emmanuel and Bengio, Yoshua and Jain, Moksh J. and Korablyov, Maksym and Liu, Cheng-Hao and Marcou, Gilles and Glaab, Enrico and Barnsley, Kelly and Iyengar, Suhasini M. and Ondrechen, Mary Jo and Haupt, V. Joachim and Kaiser, Florian and Schroeder, Michael and Pugliese, Luisa and Albani, Simone and Athanasiou, Christina and Beccari, Andrea and Carloni, Paolo and D'Arrigo, Giulia and Gianquinto, Eleonora and Goßen, Jonas and Hanke, Anton and Joseph, Benjamin P. and Kokh, Daria B. and Kovachka, Sandra and Manelfi, Candida and Mukherjee, Goutam and Mu{\~n}iz-Chicharro, Abraham and Musiani, Francesco and Nunes-Alves, Ariane and Paiardi, Giulia and Rossetti, Giulia and Sadiq, S. Kashif and Spyrakis, Francesca and Talarico, Carmine and Tsengenes, Alexandros and Wade, Rebecca C. and Copeland, Conner and Gaiser, Jeremiah and Olson, Daniel R. and Roy, Amitava and Venkatraman, Vishwesh and Wheeler, Travis J. and Arthanari, Haribabu and Blaschitz, Klara and Cespugli, Marco and Durmaz, Vedat and Fackeldey, Konstantin and Fischer, Patrick D. and Gorgulla, Christoph and Gruber, Christian and Gruber, Karl and Hetmann, Michael and Kinney, Jamie E. and Padmanabha Das, Krishna M. and Pandita, Shreya and Singh, Amit and Steinkellner, Georg and Tesseyre, Guilhem and Wagner, Gerhard and Wang, Zi-Fu and Yust, Ryan J. and Druzhilovskiy, Dmitry S. and Filimonov, Dmitry A. and Pogodin, Pavel V. and Poroikov, Vladimir and Rudik, Anastassia V. and Stolbov, Leonid A. and Veselovsky, Alexander V. and De Rosa, Maria and De Simone, Giada and Gulotta, Maria R. and Lombino, Jessica and Mekni, Nedra and Perricone, Ugo and Casini, Arturo and Embree, Amanda and Gordon, D. Benjamin and Lei, David and Pratt, Katelin and Voigt, Christopher A. and Chen, Kuang-Yu and Jacob, Yves and Krischuns, Tim and Lafaye, Pierre and Zettor, Agn{\`e}s and Rodr{\´i}guez, M. Luis and White, Kris M. and Fearon, Daren and Von Delft, Frank and Walsh, Martin A. and Horvath, Dragos and Brooks III, Charles L. and Falsafi, Babak and Ford, Bryan and Garc{\´i}a-Sastre, Adolfo and Yup Lee, Sang and Naffakh, Nadia and Varnek, Alexandre and Klambauer, G{\"u}nter and Hermans, Thomas M.}, title = {A community effort in SARS-CoV-2 drug discovery}, series = {Molecular Informatics}, volume = {43}, journal = {Molecular Informatics}, number = {1}, doi = {https://doi.org/10.1002/minf.202300262}, pages = {e202300262}, year = {2023}, language = {en} } @article{LangFischerWeberetal., author = {Lang, Annemarie and Fischer, Lisa and Weber, Marie-Christin and Gaber, Timo and Ehrig, Rainald and R{\"o}blitz, Susanna and Buttgereit, Frank}, title = {Combining in vitro simulation and in silico modelling towards a sophisticated human osteoarthritis model}, series = {Osteoarthritis and Cartilage}, volume = {27}, journal = {Osteoarthritis and Cartilage}, doi = {10.1016/j.joca.2019.02.277}, pages = {S183}, abstract = {Our project aimed at building an in silico model based on our recently developed in vitro osteoarthritis (OA) model seeking for refinement of the model to enhance validity and translatability towards the more sophisticated simulation of OA. In detail, the previously 3D in vitro model is based on 3D chondrogenic constructs generated solely from human bone marrow derived mesenchymal stromal cells (hMSCs). Besides studying the normal state of the model over 3 weeks, the in vitro model was treated with interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNFα) to mimic an OA-like environment.}, language = {en} } @article{HeinzeDipankarHenkenetal., author = {Heinze, Rieke and Dipankar, Anurag and Henken, Cintia Carbajal and Moseley, Christopher and Sourdeval, Odran and Tr{\"o}mel, Silke and Xie, Xinxin and Adamidis, Panos and Ament, Felix and Baars, Holger and Barthlott, Christian and Behrendt, Andreas and Blahak, Ulrich and Bley, Sebastian and Brdar, Slavko and Brueck, Matthias and Crewell, Susanne and Deneke, Hartwig and Di Girolamo, Paolo and Evaristo, Raquel and Fischer, J{\"u}rgen and Frank, Christopher and Friederichs, Petra and G{\"o}cke, Tobias and Gorges, Ksenia and Hande, Luke and Hanke, Moritz and Hansen, Akio and Hege, Hans-Christian and Hose, Corinna and Jahns, Thomas and Kalthoff, Norbert and Klocke, Daniel and Kneifel, Stefan and Knippertz, Peter and Kuhn, Alexander and van Laar, Thriza and Macke, Andreas and Maurer, Vera and Mayer, Bernhard and Meyer, Catrin I. and Muppa, Shravan K. and Neggers, Roeland A. J. and Orlandi, Emiliano and Pantillon, Florian and Pospichal, Bernhard and R{\"o}ber, Niklas and Scheck, Leonhard and Seifert, Axel and Seifert, Patric and Senf, Fabian and Siligam, Pavan and Simmer, Clemens and Steinke, Sandra and Stevens, Bjorn and Wapler, Kathrin and Weniger, Michael and Wulfmeyer, Volker and Z{\"a}ngl, G{\"u}nther and Zhang, Dan and Quaas, Johannes}, title = {Large-eddy simulations over Germany using ICON: a comprehensive evaluation}, series = {Quarterly Journal of the Royal Meteorological Society}, volume = {143}, journal = {Quarterly Journal of the Royal Meteorological Society}, number = {702}, doi = {10.1002/qj.2947}, pages = {69 -- 100}, abstract = {Large-eddy simulations (LES) with the new ICOsahedral Non-hydrostatic atmosphere model (ICON) covering Germany are evaluated for four days in spring 2013 using observational data from various sources. Reference simulations with the established Consortium for Small-scale Modelling (COSMO) numerical weather prediction model and further standard LES codes are performed and used as a reference. This comprehensive evaluation approach covers multiple parameters and scales, focusing on boundary-layer variables, clouds and precipitation. The evaluation points to the need to work on parametrizations influencing the surface energy balance, and possibly on ice cloud microphysics. The central purpose for the development and application of ICON in the LES configuration is the use of simulation results to improve the understanding of moist processes, as well as their parametrization in climate models. The evaluation thus aims at building confidence in the model's ability to simulate small- to mesoscale variability in turbulence, clouds and precipitation. The results are encouraging: the high-resolution model matches the observed variability much better at small- to mesoscales than the coarser resolved reference model. In its highest grid resolution, the simulated turbulence profiles are realistic and column water vapour matches the observed temporal variability at short time-scales. Despite being somewhat too large and too frequent, small cumulus clouds are well represented in comparison with satellite data, as is the shape of the cloud size spectrum. Variability of cloud water matches the satellite observations much better in ICON than in the reference model. In this sense, it is concluded that the model is fit for the purpose of using its output for parametrization development, despite the potential to improve further some important aspects of processes that are also parametrized in the high-resolution model.}, language = {en} } @misc{FischerSchlechte, author = {Fischer, Frank and Schlechte, Thomas}, title = {Strong Relaxations for the Train Timetabling Problem using Connected Configurations}, issn = {1438-0064}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-64743}, abstract = {The task of the train timetabling problem or track allocation problem is to find conflict free schedules for a set of trains with predefined routes in a railway network. Especially for non-periodic instances models based on time expanded networks are often used. Unfortunately, the linear programming relaxation of these models is often extremely weak because these models do not describe combinatorial relations like overtaking possibilities very well. In this paper we extend the model by so called connected configuration subproblems. These subproblems perfectly describe feasible schedules of a small subset of trains (2-3) on consecutive track segments. In a Lagrangian relaxation approach we solve several of these subproblems together in order to produce solutions which consist of combinatorially compatible schedules along the track segments. The computational results on a mostly single track corridor taken from the INFORMS RAS Problem Solving Competition 2012 data indicate that our new solution approach is rather strong. Indeed, for this instance the solution of the Lagrangian relaxation is already integral.}, language = {en} } @inproceedings{FischerSchlechte, author = {Fischer, Frank and Schlechte, Thomas}, title = {Strong Relaxations for the Train Timetabling Problem using Connected Configurations}, series = {17th Workshop on Algorithmic Approaches for Transportation Modelling, Optimization, and Systems (ATMOS 2017)}, volume = {59}, booktitle = {17th Workshop on Algorithmic Approaches for Transportation Modelling, Optimization, and Systems (ATMOS 2017)}, editor = {D'Angelo, Gianlorenzo and Dollevoet, Twan}, isbn = {978-3-95977-042-2}, doi = {10.4230/OASIcs.ATMOS.2017.11}, abstract = {The task of the train timetabling problem or track allocation problem is to find conflict free schedules for a set of trains with predefined routes in a railway network. Especially for non-periodic instances models based on time expanded networks are often used. Unfortunately, the linear programming relaxation of these models is often extremely weak because these models do not describe combinatorial relations like overtaking possibilities very well. In this paper we extend the model by so called connected configuration subproblems. These subproblems perfectly describe feasible schedules of a small subset of trains (2-3) on consecutive track segments. In a Lagrangian relaxation approach we solve several of these subproblems together in order to produce solutions which consist of combinatorially compatible schedules along the track segments. The computational results on a mostly single track corridor taken from the INFORMS RAS Problem Solving Competition 2012 data indicate that our new solution approach is rather strong. Indeed, for this instance the solution of the Lagrangian relaxation is already integral.}, language = {en} } @inproceedings{FischerSchlechte2015, author = {Fischer, Frank and Schlechte, Thomas}, title = {Comparing two dual relaxations of large scale train timetabling problems}, series = {Proceedings of Conference on Advanced Systems in Public Transport 2015}, booktitle = {Proceedings of Conference on Advanced Systems in Public Transport 2015}, year = {2015}, abstract = {Railway transportation and in particular train timetabling is one of the basic and source application areas of combinatorial optimization and integer programming. We will discuss two well established modeling techniques for the train timetabling problem. In this paper we focus on one major ingredient - the bounding by dual relaxations. We compare two classical dual relaxations of large scale time expanded train timetabling problems - the Lagrangean Dual and Lagrangean Decomposition. We discuss the convergence behavior and show limitations of the Lagrangean Decomposition approach for a configuration based model. We introduce a third dualization approach to overcome those limitations. Finally, we present promising preliminary computational experiments that show that our new approach indeed has superior convergence properties.}, language = {en} } @misc{FischerSchlechte, author = {Fischer, Frank and Schlechte, Thomas}, title = {Comparing two dual relaxations of large scale train timetabling problems}, issn = {1438-0064}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-56068}, abstract = {Railway transportation and in particular train timetabling is one of the basic and source application areas of combinatorial optimization and integer programming. We will discuss two well established modeling techniques for the train timetabling problem. In this paper we focus on one major ingredient - the bounding by dual relaxations. We compare two classical dual relaxations of large scale time expanded train timetabling problems - the Lagrangean Dual and Lagrangean Decomposition. We discuss the convergence behavior and show limitations of the Lagrangean Decomposition approach for a configuration based model. We introduce a third dualization approach to overcome those limitations. Finally, we present promising preliminary computational experiments that show that our new approach indeed has superior convergence properties.}, language = {en} } @inproceedings{FischerGrimmKlugetal., author = {Fischer, Frank and Grimm, Boris and Klug, Torsten and Schlechte, Thomas}, title = {A Re-optimization Approach for Train Dispatching}, series = {Operations Research Proceedings 2016}, booktitle = {Operations Research Proceedings 2016}, doi = {10.1007/978-3-319-55702-1_85}, pages = {645 -- 651}, abstract = {The Train Dispatching Problem (TDP) is to schedule trains through a network in a cost optimal way. Due to disturbances during operation existing track allocations often have to be re-scheduled and integrated into the timetable. This has to be done in seconds and with minimal timetable changes to guarantee smooth and conflict free operation. We present an integrated modeling approach for the re-optimization task using Mixed Integer Programming. Finally, we provide computational results for scenarios provided by the INFORMS RAS Problem Soling Competition 2012.}, language = {en} }