TY - CHAP A1 - Skibina, Julia A1 - Iliew, Rumen A1 - Bethge, Jens A1 - Bock, Martin A1 - Fischer, Dorit A1 - Beloglazov, Valentin A1 - Wedell, Reiner A1 - Burger, Sven A1 - Steinmeyer, Günter T1 - A chirped photonic crystal fiber for high-fidelity guiding of sub-100 fs pluses T2 - CLEO/QELS Y1 - 2009 U6 - https://doi.org/10.1364/CLEO.2009.CMHH1 SP - CMHH1 ER - TY - JOUR A1 - Fischer, Alexander A1 - Cordes, Frank A1 - Schütte, Christof T1 - Hybrid Monte Carlo with Adaptive Temperature in Mixed–Canonical Ensemble: Efficient conformational analysis of RNA JF - J. Comp. Chem. Y1 - 1998 U6 - https://doi.org/10.1002/(SICI)1096-987X(19981130)19:15<1689::AID-JCC2>3.0.CO;2-J VL - 19 IS - 15 SP - 1689 EP - 1697 ER - TY - CHAP A1 - Fischer, Alexander A1 - Schütte, Christof A1 - Deuflhard, Peter A1 - Cordes, Frank ED - Schlick, T. ED - Gan, H. T1 - Hierarchical Uncoupling-Coupling of Metastable Conformations T2 - Computational Methods for Macromolecules Y1 - 2002 UR - http://www.zib.de/PaperWeb/abstracts/ZR-01-03 IS - 24 SP - 235 EP - 259 PB - Springer ER - TY - JOUR A1 - Schütte, Christof A1 - Fischer, Alexander A1 - Huisinga, Wilhelm A1 - Deuflhard, Peter T1 - A Direct Approach to Conformational Dynamics Based on Hybrid Monte Carlo JF - J. Comput. Phys. Y1 - 1999 UR - http://www.zib.de/PaperWeb/abstracts/SC-98-45 VL - 151 SP - 146 EP - 168 ER - TY - JOUR A1 - Bock, Martin A1 - Skibina, Julia A1 - Fischer, Dorit A1 - Bretschneider, Mario A1 - Wedell, Reiner A1 - Grunwald, Rüdiger A1 - Burger, Sven A1 - Beloglazov, Valentin A1 - Steinmeyer, Günter T1 - Nanostructured fibers for sub-10 fs optical pulse delivery JF - Laser & Photonics Reviews Y1 - 2013 U6 - https://doi.org/10.1002/lpor.201300006 VL - 7 SP - 566 EP - 570 ER - TY - CHAP A1 - Skibina, Julia A1 - Iliew, Rumen A1 - Bethge, Jens A1 - Bock, Martin A1 - Fischer, Dorit A1 - Beloglazov, Valentin A1 - Wedell, Reiner A1 - Burger, Sven A1 - Steinmeyer, Günter T1 - A chirped photonic crystal fiber for ultrashort laser pulse delivery T2 - CLEO Europe - EQEC Y1 - 2009 U6 - https://doi.org/10.1109/CLEOE-EQEC.2009.5196579 ER - TY - JOUR A1 - Gorgulla, Christoph A1 - Boeszoermnyi, Andras A1 - Wang, Zi-Fu A1 - Fischer, Patrick D. A1 - Coote, Paul A1 - Das, Krishna M. Padmanabha A1 - Malets, Yehor S. A1 - Radchenko, Dmytro S. A1 - Moroz, Yurii A1 - Scott, David A. A1 - Fackeldey, Konstantin A1 - Hoffmann, Moritz A1 - Iavniuk, Iryna A1 - Wagner, Gerhard A1 - Arthanari, Haribabu T1 - An open-source drug discovery platform enables ultra-large virtual screens JF - Nature N2 - On average, an approved drug today costs $2-3 billion and takes over ten years to develop1. In part, this is due to expensive and time-consuming wet-lab experiments, poor initial hit compounds, and the high attrition rates in the (pre-)clinical phases. Structure-based virtual screening (SBVS) has the potential to mitigate these problems. With SBVS, the quality of the hits improves with the number of compounds screened2. However, despite the fact that large compound databases exist, the ability to carry out large-scale SBVSs on computer clusters in an accessible, efficient, and flexible manner has remained elusive. Here we designed VirtualFlow, a highly automated and versatile open-source platform with perfect scaling behaviour that is able to prepare and efficiently screen ultra-large ligand libraries of compounds. VirtualFlow is able to use a variety of the most powerful docking programs. Using VirtualFlow, we have prepared the largest and freely available ready-to-dock ligand library available, with over 1.4 billion commercially available molecules. To demonstrate the power of VirtualFlow, we screened over 1 billion compounds and discovered a small molecule inhibitor (iKeap1) that engages KEAP1 with nanomolar affinity (Kd = 114 nM) and disrupts the interaction between KEAP1 and the transcription factor NRF2. We also identified a set of structurally diverse molecules that bind to KEAP1 with submicromolar affinity. This illustrates the potential of VirtualFlow to access vast regions of the chemical space and identify binders with high affinity for target proteins. Y1 - 2020 U6 - https://doi.org/https://doi.org/10.1038/s41586-020-2117-z VL - 580 SP - 663 EP - 668 PB - Springer Nature ER - TY - JOUR A1 - Gorgulla, Christoph A1 - Das, Krishna M. Padmanabha A1 - Leigh, Kendra E A1 - Cespugli, Marco A1 - Fischer, Patrick D. A1 - Wang, Zi-Fu A1 - Tesseyre, Guilhem A1 - Pandita, Shreya A1 - Shnapir, Alex A1 - Calderaio, Anthony A1 - Hutcheson, Colin A1 - Gechev, Minko A1 - Rose, Alexander A1 - Lewis, Noam A1 - Yaffe, Erez A1 - Luxenburg, Roni A1 - Herce, Henry D. A1 - Durmaz, Vedat A1 - Halazonetis, Thanos D. A1 - Fackeldey, Konstantin A1 - Patten, Justin J. A1 - Chuprina, Alexander A1 - Dziuba, Igor A1 - Plekhova, Alla A1 - Moroz, Yurii A1 - Radchenko, Dmytro A1 - Tarkhanova, Olga A1 - Yavnyuk, Irina A1 - Gruber, Christian C. A1 - Yust, Ryan A1 - Payne, Dave A1 - Näär, Anders M. A1 - Namchuk, Mark N. A1 - Davey, Robert A. A1 - Wagner, Gerhard A1 - Kinney, Jamie A1 - Arthanari, Haribabu T1 - A Multi-Pronged Approach Targeting SARS-CoV-2 Proteins Using Ultra-Large Virtual Screening JF - iScience N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019 novel coronavirus (2019-nCoV), has spread rapidly across the globe, creating an unparalleled global health burden and spurring a deepening economic crisis. As of July 7th, 2020, almost seven months into the outbreak, there are no approved vaccines and few treatments available. Developing drugs that target multiple points in the viral life cycle could serve as a strategy to tackle the current as well as future coronavirus pandemics. Here we leverage the power of our recently developed in silico screening platform, VirtualFlow, to identify inhibitors that target SARS-CoV-2. VirtualFlow is able to efficiently harness the power of computing clusters and cloud-based computing platforms to carry out ultra-large scale virtual screens. In this unprecedented structure-based multi-target virtual screening campaign, we have used VirtualFlow to screen an average of approximately 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets in the cloud. In addition to targeting the active sites of viral enzymes, we also target critical auxiliary sites such as functionally important protein-protein interaction interfaces. This multi-target approach not only increases the likelihood of finding a potent inhibitor, but could also help identify a collection of anti-coronavirus drugs that would retain efficacy in the face of viral mutation. Drugs belonging to different regimen classes could be combined to develop possible combination therapies, and top hits that bind at highly conserved sites would be potential candidates for further development as coronavirus drugs. Here, we present the top 200 in silico hits for each target site. While in-house experimental validation of some of these compounds is currently underway, we want to make this array of potential inhibitor candidates available to researchers worldwide in consideration of the pressing need for fast-tracked drug development. Y1 - 2021 U6 - https://doi.org/10.26434/chemrxiv.12682316 VL - 24 IS - 2 SP - 102021 PB - CellPress ER - TY - JOUR A1 - Weber, Marie-Christin A1 - Fischer, Lisa A1 - Damerau, Alexandra A1 - Ponomarev, Igor A1 - Pfeiffenberger, Moritz A1 - Gaber, Timo A1 - Götschel, Sebastian A1 - Lang, Jens A1 - Röblitz, Susanna A1 - Buttgereit, Frank A1 - Ehrig, Rainald A1 - Lang, Annemarie T1 - Macroscale mesenchymal condensation to study cytokine-driven cellular and matrix-related changes during cartilage degradation JF - Biofabrication N2 - 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. Y1 - 2020 U6 - https://doi.org/10.1088/1758-5090/aba08f VL - 12 IS - 4 ER - TY - JOUR A1 - Fischer, Sophie A1 - Ehrig, Rainald A1 - Schäfer, Stefan A1 - Tronci, Enrico A1 - Mancini, Toni A1 - Egli, Marcel A1 - Ille, Fabian A1 - Krüger, Tillmann H. C. A1 - Leeners, Brigitte A1 - Röblitz, Susanna T1 - Mathematical Modelling and Simulation Provides Evidence for New Strategies of Ovarian Stimulation JF - Frontiers in Endocrinology N2 - New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle which is especially useful when time for assisted reproductive technology is limited, e.g. for emergency fertility preservation in cancer patients. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts ("waves") of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modelling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle. Y1 - 2021 U6 - https://doi.org/10.3389/fendo.2021.613048 VL - 12 ER - TY - JOUR A1 - Weber, Marie-Christin A1 - Fischer, Lisa A1 - Damerau, Alexandra A1 - Ponomarev, Igor A1 - Pfeiffenberger, Moritz A1 - Gaber, Timo A1 - Götschel, Sebastian A1 - Lang, Jens A1 - Röblitz, Susanna A1 - Buttgereit, Frank A1 - Ehrig, Rainald A1 - Lang, Annemarie T1 - In vitro and in silico modeling of cellular and matrix-related changes during the early phase of osteoarthritis JF - BioRxiv N2 - 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. Y1 - 2019 U6 - https://doi.org/10.1101/725317 ER - TY - JOUR A1 - Lang, Annemarie A1 - Fischer, Lisa A1 - Weber, Marie-Christin A1 - Gaber, Timo A1 - Ehrig, Rainald A1 - Röblitz, Susanna A1 - Buttgereit, Frank T1 - Combining in vitro simulation and in silico modelling towards a sophisticated human osteoarthritis model JF - Osteoarthritis and Cartilage N2 - 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. Y1 - 2019 U6 - https://doi.org/10.1016/j.joca.2019.02.277 VL - 27 SP - S183 ER - TY - CHAP A1 - Bock, Martin A1 - Skibina, Julia A1 - Fischer, Dorit A1 - Grunwald, Rüdiger A1 - Burger, Sven A1 - Beloglazov, Valentin A1 - Steinmeyer, Günter T1 - 10-fs pulse delivery through a fiber T2 - CLEO Y1 - 2012 U6 - https://doi.org/10.1364/CLEO_SI.2012.CTh3G.3 SP - CTh3G.3 PB - Optical Society of America ER - TY - JOUR A1 - Deuflhard, Peter A1 - Huisinga, Wilhelm A1 - Fischer, Alexander A1 - Schütte, Christof T1 - Identification of Almost Invariant Aggregates in Reversible Nearly Uncoupled Markov Chains JF - Lin. Alg. Appl. Y1 - 2000 VL - 315 SP - 39 EP - 59 ER - TY - JOUR A1 - Koschek, A1 - Durmaz, Vedat A1 - Krylova, A1 - Wieczorek, A1 - Gupta, Pooja A1 - Richter, A1 - Bujotzek, Alexander A1 - Fischer, A1 - Haag, Rainer A1 - Freund, A1 - Weber, Marcus A1 - Rademann, T1 - Peptide polymer ligands for a tandem WW-domain, a soft multivalent protein-protein interaction: lessons on the thermodynamic fitness of flexible ligands JF - Beilstein J. Org. Chem. Y1 - 2015 VL - 11 SP - 837 EP - 847 ER - TY - CHAP A1 - Skibina, Julia A1 - Bock, Martin A1 - Fischer, Dorit A1 - Grunwald, Rüdiger A1 - Steinmeyer, Günter A1 - Wedell, Reiner A1 - Bretschneider, Mario A1 - Burger, Sven A1 - Beloglazov, Valentin T1 - 10-fs fiber based pulse delivery T2 - Conference on Lasers, Applications, and Technologies (LAT) Y1 - 2013 SP - LWF5 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 - JOUR A1 - Fischer, Lisa A1 - Götschel, Sebastian A1 - Weiser, Martin T1 - Lossy data compression reduces communication time in hybrid time-parallel integrators JF - Comput. Vis. Sci. 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. Y1 - 2018 U6 - https://doi.org/10.1007/s00791-018-0293-2 VL - 19 IS - 1 SP - 19 EP - 30 ER - TY - THES A1 - Fischer, Lisa T1 - On the convergence of inexact time parallel time integration Y1 - 2017 ER - TY - JOUR A1 - Garcia Santiago, Xavier A1 - Hammerschmidt, Martin A1 - Sachs, Johannes A1 - Burger, Sven A1 - Kwon, Hyunah A1 - Knöller, Marvin A1 - Arens, Tilo A1 - Fischer, Peer A1 - Fernandez-Corbaton, Ivan A1 - Rockstuhl, Carsten T1 - Toward maximally electromagnetically chiral scatterers at optical frequencies JF - ACS Photonics Y1 - 2022 U6 - https://doi.org/10.1021/acsphotonics.1c01887 VL - 9 SP - 1954 ER - TY - JOUR A1 - Schimunek, Johannes A1 - Seidl, Philipp A1 - Elez, Katarina A1 - Hempel, Tim A1 - Le, Tuan A1 - Noé, Frank A1 - Olsson, Simon A1 - Raich, Lluís A1 - Winter, Robin A1 - Gokcan, Hatice A1 - Gusev, Filipp A1 - Gutkin, Evgeny M. A1 - Isayev, Olexandr A1 - Kurnikova, Maria G. A1 - Narangoda, Chamali H. A1 - Zubatyuk, Roman A1 - Bosko, Ivan P. A1 - Furs, Konstantin V. A1 - Karpenko, Anna D. A1 - Kornoushenko, Yury V. A1 - Shuldau, Mikita A1 - Yushkevich, Artsemi A1 - Benabderrahmane, Mohammed B. A1 - Bousquet-Melou, Patrick A1 - Bureau, Ronan A1 - Charton, Beatrice A1 - Cirou, Bertrand C. A1 - Gil, Gérard A1 - Allen, William J. A1 - Sirimulla, Suman A1 - Watowich, Stanley A1 - Antonopoulos, Nick A1 - Epitropakis, Nikolaos A1 - Krasoulis, Agamemnon A1 - Itsikalis, Vassilis A1 - Theodorakis, Stavros A1 - Kozlovskii, Igor A1 - Maliutin, Anton A1 - Medvedev, Alexander A1 - Popov, Petr A1 - Zaretckii, Mark A1 - Eghbal-Zadeh, Hamid A1 - Halmich, Christina A1 - Hochreiter, Sepp A1 - Mayr, Andreas A1 - Ruch, Peter A1 - Widrich, Michael A1 - Berenger, Francois A1 - Kumar, Ashutosh A1 - Yamanishi, Yoshihiro A1 - Zhang, Kam Y. J. A1 - Bengio, Emmanuel A1 - Bengio, Yoshua A1 - Jain, Moksh J. A1 - Korablyov, Maksym A1 - Liu, Cheng-Hao A1 - Marcou, Gilles A1 - Glaab, Enrico A1 - Barnsley, Kelly A1 - Iyengar, Suhasini M. A1 - Ondrechen, Mary Jo A1 - Haupt, V. Joachim A1 - Kaiser, Florian A1 - Schroeder, Michael A1 - Pugliese, Luisa A1 - Albani, Simone A1 - Athanasiou, Christina A1 - Beccari, Andrea A1 - Carloni, Paolo A1 - D’Arrigo, Giulia A1 - Gianquinto, Eleonora A1 - Goßen, Jonas A1 - Hanke, Anton A1 - Joseph, Benjamin P. A1 - Kokh, Daria B. A1 - Kovachka, Sandra A1 - Manelfi, Candida A1 - Mukherjee, Goutam A1 - Muñiz-Chicharro, Abraham A1 - Musiani, Francesco A1 - Nunes-Alves, Ariane A1 - Paiardi, Giulia A1 - Rossetti, Giulia A1 - Sadiq, S. Kashif A1 - Spyrakis, Francesca A1 - Talarico, Carmine A1 - Tsengenes, Alexandros A1 - Wade, Rebecca C. A1 - Copeland, Conner A1 - Gaiser, Jeremiah A1 - Olson, Daniel R. A1 - Roy, Amitava A1 - Venkatraman, Vishwesh A1 - Wheeler, Travis J. A1 - Arthanari, Haribabu A1 - Blaschitz, Klara A1 - Cespugli, Marco A1 - Durmaz, Vedat A1 - Fackeldey, Konstantin A1 - Fischer, Patrick D. A1 - Gorgulla, Christoph A1 - Gruber, Christian A1 - Gruber, Karl A1 - Hetmann, Michael A1 - Kinney, Jamie E. A1 - Padmanabha Das, Krishna M. A1 - Pandita, Shreya A1 - Singh, Amit A1 - Steinkellner, Georg A1 - Tesseyre, Guilhem A1 - Wagner, Gerhard A1 - Wang, Zi-Fu A1 - Yust, Ryan J. A1 - Druzhilovskiy, Dmitry S. A1 - Filimonov, Dmitry A. A1 - Pogodin, Pavel V. A1 - Poroikov, Vladimir A1 - Rudik, Anastassia V. A1 - Stolbov, Leonid A. A1 - Veselovsky, Alexander V. A1 - De Rosa, Maria A1 - De Simone, Giada A1 - Gulotta, Maria R. A1 - Lombino, Jessica A1 - Mekni, Nedra A1 - Perricone, Ugo A1 - Casini, Arturo A1 - Embree, Amanda A1 - Gordon, D. Benjamin A1 - Lei, David A1 - Pratt, Katelin A1 - Voigt, Christopher A. A1 - Chen, Kuang-Yu A1 - Jacob, Yves A1 - Krischuns, Tim A1 - Lafaye, Pierre A1 - Zettor, Agnès A1 - Rodríguez, M. Luis A1 - White, Kris M. A1 - Fearon, Daren A1 - Von Delft, Frank A1 - Walsh, Martin A. A1 - Horvath, Dragos A1 - Brooks III, Charles L. A1 - Falsafi, Babak A1 - Ford, Bryan A1 - García-Sastre, Adolfo A1 - Yup Lee, Sang A1 - Naffakh, Nadia A1 - Varnek, Alexandre A1 - Klambauer, Günter A1 - Hermans, Thomas M. T1 - A community effort in SARS-CoV-2 drug discovery JF - Molecular Informatics KW - COVID-19 KW - drug discovery KW - machine learning KW - SARS-CoV-2 Y1 - 2023 U6 - https://doi.org/https://doi.org/10.1002/minf.202300262 VL - 43 IS - 1 SP - e202300262 ER - TY - JOUR A1 - Fischer-Holzhausen, Sophie A1 - Röblitz, Susanna T1 - Hormonal regulation of ovarian follicle growth in humans: Model-based exploration of cycle variability and parameter sensitivities JF - Journal of Theoretical Biology N2 - We present a modelling and simulation framework for the dynamics of ovarian follicles and key hormones along the hypothalamic-pituitary-gonadal axis throughout consecutive human menstrual cycles. All simulation results (hormone concentrations and ovarian follicle sizes) are in biological units and can easily be compared to clinical data. The model takes into account variability in follicles' response to stimulating hormones, which introduces variability between cycles. The growth of ovarian follicles in waves is an emergent property in our model simulations and further supports the hypothesis that follicular waves are also present in humans. We use Approximate Bayesian Computation and cluster analysis to construct a population of virtual subjects and to study parameter distributions and sensitivities. The model can be used to compare and optimize treatment protocols for ovarian hyperstimulation, thus potentially forming the integral part of a clinical decision support system in reproductive endocrinology. Y1 - 2022 U6 - https://doi.org/https://doi.org/10.1016/j.jtbi.2022.111150 ER - TY - JOUR A1 - Fischer-Holzhausen, Sophie A1 - Röblitz, Susanna T1 - Mathematical modelling of follicular growth and ovarian stimulation JF - Current Opinion in Endocrine and Metabolic Research Y1 - 2022 U6 - https://doi.org/https://doi.org/10.1016/j.coemr.2022.100385 ER -