{"9ea232cf947b61f5a35902124baac4dbsimtech":{"DOI":"","ISBN":"","ISSN":"2835-8856","URL":"https://openreview.net/pdf?id=aVSoQXbfy1","abstract":"","annote":"","author":[{"family":"Scheurer","given":"Stefania"},{"family":"Reiser","given":"Philipp"},{"family":"Brünnette","given":"Tim"},{"family":"Nowak","given":"Wolfgang"},{"family":"Guthke","given":"Anneli"},{"family":"Bürkner","given":"Paul-Christian"}],"citation-label":"scheurer2026uncertainty","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Transactions on Machine Learning Research","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2026","jan"]],"literal":"2026"},"event-place":"","id":"9ea232cf947b61f5a35902124baac4dbsimtech","interhash":"5a4875d858175206d6f85d84a00a0456","intrahash":"9ea232cf947b61f5a35902124baac4db","issue":"","issued":{"date-parts":[["2026","jan"]],"literal":"2026"},"keyword":"EXC2075 PN2 PN2-7 PN5 PN5-6(II) curated","misc":{"issn":"2835-8856"},"note":"","number":"","page":"","page-first":"","publisher":"","publisher-place":"","status":"","title":"Uncertainty-Aware Surrogate-based Amortized Bayesian Inference for Computationally Expensive Models","type":"article-journal","username":"simtech","version":"","volume":""},"13d070ca717db4ad910b6f698ff75056simtech":{"DOI":"10.1038/s41419-025-08258-9","ISBN":"","ISSN":"20414889","URL":"https://doi.org/10.1038/s41419-025-08258-9","abstract":"Apoptosis dysfunction is linked to diseases like cancer and neurodegenerative disorders. A key event during apoptosis is mitochondrial outer membrane permeabilization (MOMP), which typically proceeds in a rapid all-or-none fashion. If MOMP occurs only in a subset of mitochondria (minority MOMP), it can be sublethal and contribute to tumorigenesis and cancer progression. Similarly, individual mitochondria escaping widespread MOMP (majority MOMP) can allow cancer cells to recover if apoptosis execution fails. How such heterogeneities in mitochondrial MOMP responsiveness arise within cells is incompletely understood. In particular, whether stochasticity in subcellular protein distributions and interactions across cytosol and mitochondria can realistically contribute to mitochondrial MOMP heterogeneity has not yet been studied. To assess this, we sequentially built and experimentally parameterized a particle-based, cell-sized model including cytosolic and mitochondrial compartments, and that featured a reduced interactome of MCL-1, BAK and tBID. High-performance computing enabled cell-scale simulations of protein distributions and interactions to understand how and under which conditions stochasticity could contribute to heterogeneity in MOMP susceptibility. Our results show that stochastic effects strongly predispose sub-pools of fragmented mitochondria to MOMP under low apoptotic stress. At higher apoptotic stress, fractions of small mitochondria were more likely to escape MOMP than large mitochondria. Retrospective quantification of mitochondrial sizes in experimental scenarios of minority and majority MOMP confirmed these findings. We therefore conclude that stochasticity substantially contributes to enabling small or fragmented mitochondria to undergo MOMP in minority MOMP scenarios and to escape MOMP in majority MOMP scenarios.","annote":"","author":[{"family":"Geiger","given":"Jenny"},{"family":"Klötzer","given":"Fabian"},{"family":"Pollak","given":"Nadine"},{"family":"Fullstone","given":"Gavin"},{"family":"Rehm","given":"Markus"}],"citation-label":"geiger2025stochasticity","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Cell Death & Disease","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2025"]],"literal":"2025"},"event-place":"","id":"13d070ca717db4ad910b6f698ff75056simtech","interhash":"f4e9c4247e6172bfe4a2c1d3d3b1202b","intrahash":"13d070ca717db4ad910b6f698ff75056","issue":"1","issued":{"date-parts":[["2025"]],"literal":"2025"},"keyword":"EXC2075 PN2 PN2-1A curated","misc":{"issn":"20414889","refid":"Geiger2025","doi":"10.1038/s41419-025-08258-9"},"note":"","number":"1","page":"893--","page-first":"893","publisher":"","publisher-place":"","status":"","title":"Stochasticity contributes to explaining minority and majority MOMP during apoptosis","type":"article-journal","username":"simtech","version":"","volume":"16"},"68637f883b4bfc6a7d8dc12397ae0f83simtech":{"DOI":"10.1007/s11222-025-10597-8","ISBN":"","ISSN":"","URL":"","abstract":"","annote":"","author":[{"family":"Reiser","given":"Philipp"},{"family":"Aguilar","given":"Javier Enrique"},{"family":"Guthke","given":"Anneli"},{"family":"Bürkner","given":"Paul-Christian"}],"citation-label":"reiser2023uncertainty","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Statistics and Computing","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2025"]],"literal":"2025"},"event-place":"","id":"68637f883b4bfc6a7d8dc12397ae0f83simtech","interhash":"969d1c2fbe22848311d4151d231c2a60","intrahash":"68637f883b4bfc6a7d8dc12397ae0f83","issue":"(3)","issued":{"date-parts":[["2025"]],"literal":"2025"},"keyword":"EXC2075 PN2 PN2-7 curated","misc":{"doi":"10.1007/s11222-025-10597-8"},"note":"","number":"(3)","page":"66","page-first":"66","publisher":"","publisher-place":"","status":"","title":"Uncertainty Quantification and Propagation in Surrogate-based Bayesian Inference","type":"article-journal","username":"simtech","version":"","volume":"35"},"2ea9b17dfb5a097ef392c40fe653019dsimtech":{"DOI":"10.1080/19420862.2025.2563758","ISBN":"","ISSN":"19420862","URL":"https://doi.org/10.1080/19420862.2025.2563758","abstract":"","annote":"","author":[{"family":"Kuhn","given":"Philipp"},{"family":"Petralla","given":"Sabrina"},{"family":"Dabbagh","given":"Fatemeh"},{"family":"Pegoretti","given":"Valentina"},{"family":"Muranyi","given":"Walter"},{"family":"Ishikawa","given":"Hiroshi"},{"family":"Schroten","given":"Horst"},{"family":"Fischer","given":"Roman"},{"family":"Frenzel","given":"André"},{"family":"Schirrmann","given":"Thomas"},{"family":"Rehm","given":"Markus"},{"family":"Schwerk","given":"Christian"},{"family":"Fricker","given":"Gert"},{"family":"Kontermann","given":"Roland"},{"family":"Fullstone","given":"Gavin"}],"citation-label":"kuhn2025phsensitive","collection-editor":[],"collection-title":"","container-author":[],"container-title":"mAbs","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2025","dec"]],"literal":"2025"},"event-place":"","id":"2ea9b17dfb5a097ef392c40fe653019dsimtech","interhash":"9344d4546a208948b4213b3abcd7c8de","intrahash":"2ea9b17dfb5a097ef392c40fe653019d","issue":"1","issued":{"date-parts":[["2025","dec"]],"literal":"2025"},"keyword":"EXC2075 PN2 PN2-1A curated","misc":{"issn":"19420862","comment":"doi: 10.1080/19420862.2025.2563758","doi":"10.1080/19420862.2025.2563758"},"note":"","number":"1","page":"2563758--","page-first":"2563758","publisher":"Taylor & Francis","publisher-place":"","status":"","title":"A pH-sensitive binding modality allows successful transferrin receptor-mediated transcytosis of a bivalent antibody across brain barriers","type":"article-journal","username":"simtech","version":"","volume":"17"},"508330b0e707cab72cde85d5372b57b3simtech":{"DOI":"https://doi.org/10.1016/bs.mie.2025.01.040","ISBN":"","ISSN":"0076-6879","URL":"https://www.sciencedirect.com/science/article/pii/S0076687925000606","abstract":"The digitalization of biocatalysis presents significant opportunities for advancing research by improving data management, fostering transparency, and enabling more efficient, reproducible experiments. However, this transformation brings challenges, particularly in standardizing and sharing data across diverse platforms and laboratory settings. Managing experimental data and metadata in structured, machine-readable formats is fundamental for integrating automation, while mechanistic modeling and artificial intelligence applications further benefit from well-curated datasets. Creating sustainable, reusable software is also key to the long-term success of biocatalysis projects. Yet, efficient data acquisition remains limited by the lack of universally accepted data formats for analytical instruments. To address these barriers, the best practices presented here focus on optimizing biocatalysis workflows for the FAIR (Findable, Accessible, Interoperable, Reusable) data principles. This includes adopting standardized data exchange formats and sharing reproducible datasets in public repositories, thus enhancing interoperability and reusability. By following these guidelines, researchers can contribute to the digitalization of biocatalysis, facilitating the knowledge sharing and data reuse necessary to support the transition of biocatalysis into a more data-driven field.","annote":"","author":[{"family":"Giess","given":"Torsten"},{"family":"Pleiss","given":"Jürgen"}],"citation-label":"GIESS2025","collection-editor":[],"collection-title":"Methods in Enzymology","container-author":[],"container-title":"","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2025"]],"literal":"2025"},"event-place":"","id":"508330b0e707cab72cde85d5372b57b3simtech","interhash":"ad7bfdc8362fd60c6ac228ce98e15c8c","intrahash":"508330b0e707cab72cde85d5372b57b3","issue":"","issued":{"date-parts":[["2025"]],"literal":"2025"},"keyword":"EXC2075 PN2 PN2-6 PN2-6(II) curated","misc":{"issn":"0076-6879","doi":"https://doi.org/10.1016/bs.mie.2025.01.040"},"note":"","number":"","page":"","page-first":"","publisher":"Academic Press","publisher-place":"","status":"","title":"Digitalization of biocatalysis: Best practices to research data management","type":"chapter","username":"simtech","version":"","volume":""},"152183f0edd23d3a6b697219f2c6ca41simtech":{"DOI":"10.14814/phy2.70187","ISBN":"","ISSN":"2051-817X","URL":"http://dx.doi.org/10.14814/phy2.70187","abstract":"AbstractThe maintenance of an appropriate ratio of body fat to muscle mass is essentialfor the preservation of health and performance, as excessive body fat is associatedwith an increased risk of various diseases. Accurate body composition assessmentrequires precise segmentation of structures. In this study we developed a novelautomatic machine learning approach for volumetric segmentation and quantita-tive assessment of MRI volumes and investigated the efficacy of using a machinelearning algorithm to assess muscle, subcutaneous adipose tissue (SAT), and bonevolume of the thigh before and after a strength training. Eighteen healthy, young,female volunteers were randomly allocated to two groups: intervention group(IG) and control group (CG). The IG group followed an 8-week strength endur-ance training plan that was conducted two times per week. Before and after thetraining, the subjects of both groups underwent MRI scanning. The evaluation ofthe image data was performed by a machine learning system which is based ona 3D U-Net- based Convolutional Neural Network. The volumes of muscle, bone,and SAT were each examined using a 2 (GROUP [IG vs. CG]) × 2 (TIME [pre-intervention vs. post-intervention]) analysis of variance (ANOVA) with repeatedmeasures for the factor TIME. The results of the ANOVA demonstrate significantTIME × GROUP interaction effects for the muscle volume (F1,16 = 12.80, p = 0.003,ηP2 = 0.44) with an increase of 2.93% in the IG group and no change in the CG(−0.62%, p = 0.893). There were no significant changes in bone or SAT volumebetween the groups. This study supports the use of artificial intelligence systemsto analyze MRI images  as a reliable tool for monitoring training responses onbody composition.","annote":"","author":[{"family":"Ramedani","given":"Saied"},{"family":"Kelesoglu","given":"Ebru"},{"family":"Stutzig","given":"Norman"},{"family":"Von Tengg‐Kobligk","given":"Hendrik"},{"family":"Daneshvar Ghorbani","given":"Keivan"},{"family":"Siebert","given":"Tobias"}],"citation-label":"Ramedani_2025","collection-editor":[{"family":"Siebert","given":"Tobias"}],"collection-title":"","container-author":[{"family":"Siebert","given":"Tobias"}],"container-title":"Physiological Reports","documents":[],"edition":"","editor":[{"family":"Siebert","given":"Tobias"}],"event-date":{"date-parts":[["2025","jan"]],"literal":"2025"},"event-place":"","id":"152183f0edd23d3a6b697219f2c6ca41simtech","interhash":"3afe397a451bce869962d016312aff6a","intrahash":"152183f0edd23d3a6b697219f2c6ca41","issue":"3","issued":{"date-parts":[["2025","jan"]],"literal":"2025"},"keyword":"EXC2075 PN2 curated","misc":{"issn":"2051-817X","doi":"10.14814/phy2.70187"},"note":"","number":"3","page":"","page-first":"","publisher":"Wiley","publisher-place":"","status":"","title":"Quantification of training‐induced alterations in body composition via automated machine learning analysis of MRI images in the thigh region: A pilot study in young females","type":"article-journal","username":"simtech","version":"","volume":"13"},"4386f56655faa9b7cc13322ef28d8a24simtech":{"DOI":"10.1038/s44319-024-00206-6","ISBN":"","ISSN":"1469-3178","URL":"http://dx.doi.org/10.1038/s44319-024-00206-6","abstract":"","annote":"","author":[{"family":"Beigl","given":"Tobias B"},{"family":"Paul","given":"Alexander"},{"family":"Fellmeth","given":"Thomas P"},{"family":"Nguyen","given":"Dang"},{"family":"Barber","given":"Lynn"},{"family":"Weller","given":"Sandra"},{"family":"Schäfer","given":"Benjamin"},{"family":"Gillissen","given":"Bernhard F"},{"family":"Aulitzky","given":"Walter E"},{"family":"Kopp","given":"Hans-Georg"},{"family":"Rehm","given":"Markus"},{"family":"Andrews","given":"David W"},{"family":"Pluhackova","given":"Kristyna"},{"family":"Essmann","given":"Frank"}],"citation-label":"Beigl_2024","collection-editor":[],"collection-title":"","container-author":[],"container-title":"EMBO Reports","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2024"]],"literal":"2024"},"event-place":"","id":"4386f56655faa9b7cc13322ef28d8a24simtech","interhash":"ab21830497642ce8fdb93068c809c733","intrahash":"4386f56655faa9b7cc13322ef28d8a24","issue":"9","issued":{"date-parts":[["2024"]],"literal":"2024"},"keyword":"EXC2075 PN2 PN2-1(II) PN2-1A PN3 PN3-11 curated","misc":{"issn":"1469-3178","doi":"10.1038/s44319-024-00206-6"},"note":"","number":"9","number-of-pages":"28","page":"3896–3924","page-first":"3896","publisher":"Springer Science and Business Media LLC","publisher-place":"","status":"","title":"BCL-2 and BOK regulate apoptosis by interaction of their C-terminal transmembrane domains","type":"article-journal","username":"simtech","version":"","volume":"25"},"d4c6f9a31ee0320fc3be6307a85d6c4esimtech":{"DOI":"10.1007/s00424-023-02794-z","ISBN":"","ISSN":"1432-2013","URL":"","abstract":"","annote":"","author":[{"family":"Tomalka","given":"André"}],"citation-label":"tomalka2023eccentric","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Pflügers Archiv","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2023"]],"literal":"2023"},"event-place":"","id":"d4c6f9a31ee0320fc3be6307a85d6c4esimtech","interhash":"c1587910394340ebda12596b663f7b66","intrahash":"d4c6f9a31ee0320fc3be6307a85d6c4e","issue":"","issued":{"date-parts":[["2023"]],"literal":"2023"},"keyword":"EXC2075 PN2 curated","misc":{"issn":"1432-2013","language":"eng","doi":"10.1007/s00424-023-02794-z"},"note":"","number":"","number-of-pages":"14","page":"421-435","page-first":"421","publisher":"Springer","publisher-place":"","status":"","title":"Eccentric muscle contractions : from single muscle fibre to whole muscle mechanics","type":"article-journal","username":"simtech","version":"","volume":"475"},"a3694399a83c9346ae66fe151dce7e94simtech":{"DOI":"https://doi.org/10.1016/j.fluid.2024.114324","ISBN":"","ISSN":"0378-3812","URL":"https://www.sciencedirect.com/science/article/pii/S0378381224002991","abstract":"Molecular simulations allow the prediction of a large variety of thermophysical properties for complex mixtures based on one underlying model, i.e. the force field. In the present work static and dynamic properties of aqueous 1:2 choline chloride:glycerol mixtures are computed by molecular dynamics simulations with the aim to report robust simulation protocols that allow for a thorough evaluation of the molecular model with regard to experimental data. In particular for the shear viscosity a rather strong dependence of the results on the simulation method can be found. The simulations do not only provide quantitative data but also insight into the effect of water on the microscopic structure of the fluid. The isobaric thermal expansivity shows a transition from DES-like to water-like behavior beyond a water mole fraction of 0.75. Moreover, inconsistencies in experimental datasets are identified. Molecular dynamics simulations serve as a powerful tool to support the decision for one or the other data set in case of contradictory experimental data.","annote":"","author":[{"family":"Spera","given":"Marcelle B.M."},{"family":"Darouich","given":"Samir"},{"family":"Pleiss","given":"Jürgen"},{"family":"Hansen","given":"Niels"}],"citation-label":"SPERA2025114324","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Fluid Phase Equilibria","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2025"]],"literal":"2025"},"event-place":"","id":"a3694399a83c9346ae66fe151dce7e94simtech","interhash":"975d837ae55dd9dd3eb9e564fd6913c5","intrahash":"a3694399a83c9346ae66fe151dce7e94","issue":"","issued":{"date-parts":[["2025"]],"literal":"2025"},"keyword":"EXC2075 PN2 PN2-6 PN2-6(II) PN3 PN3-8 curated","misc":{"issn":"0378-3812","orcid":"0000-0003-1045-8202","doi":"https://doi.org/10.1016/j.fluid.2024.114324"},"note":"","number":"","page":"114324","page-first":"114324","publisher":"","publisher-place":"","status":"","title":"Influence of water content on thermophysical properties of aqueous glyceline solutions predicted by molecular dynamics simulations","type":"article-journal","username":"simtech","version":"","volume":"592"},"b962af03d0e70e2009b457665c691400simtech":{"DOI":"10.1038/s41929-024-01261-x","ISBN":"","ISSN":"25201158","URL":"https://doi.org/10.1038/s41929-024-01261-x","abstract":"Biocatalysis needs improved reproducibility and quality of research reporting. Our interdisciplinary team has developed a flexible and extensible metadata catalogue based on STRENDA guidelines, essential for describing complex experimental setups in biocatalysis. The catalogue is available online via GitHub for community use.","annote":"","author":[{"family":"Malzacher","given":"Stephan"},{"family":"Meißner","given":"Dominik"},{"family":"Range","given":"Jan"},{"family":"Findrik Blažević","given":"Zvjezdana"},{"family":"Rosenthal","given":"Katrin"},{"family":"Woodley","given":"John M."},{"family":"Wohlgemuth","given":"Roland"},{"family":"Wied","given":"Peter"},{"family":"Nidetzky","given":"Bernd"},{"family":"Giessmann","given":"Robert T."},{"family":"Prakinee","given":"Kridsadakorn"},{"family":"Chaiyen","given":"Pimchai"},{"family":"Bommarius","given":"Andreas S."},{"family":"Rohwer","given":"Johann M."},{"family":"de Souza","given":"Rodrigo O. M. A."},{"family":"Halling","given":"Peter J."},{"family":"Pleiss","given":"Jürgen"},{"family":"Kettner","given":"Carsten"},{"family":"Rother","given":"Dörte"}],"citation-label":"malzacher2024strenda","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Nature Catalysis","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2024"]],"literal":"2024"},"event-place":"","id":"b962af03d0e70e2009b457665c691400simtech","interhash":"43db653083278be6b42b11b2642d61c9","intrahash":"b962af03d0e70e2009b457665c691400","issue":"12","issued":{"date-parts":[["2024"]],"literal":"2024"},"keyword":"PN2 PN2-6(II) curated","misc":{"orcid":"0000-0003-1045-8202","issn":"25201158","refid":"Malzacher2024","doi":"10.1038/s41929-024-01261-x"},"note":"","number":"12","number-of-pages":"4","page":"1245--1249","page-first":"1245","publisher":"","publisher-place":"","status":"","title":"The STRENDA Biocatalysis Guidelines for cataloguing metadata","type":"article-journal","username":"simtech","version":"","volume":"7"},"4a122061de06137fc1895607c95226f1simtech":{"DOI":"10.1007/s13222-024-00475-4","ISBN":"","ISSN":"16101995","URL":"https://doi.org/10.1007/s13222-024-00475-4","abstract":"Research Data Management (RDM) has gained significant traction in recent years, being essential to allowing research data to be, e.g., findable, accessible, interoperable, and reproducible (FAIR), thereby fostering collaboration or accelerating scientific findings. We present solutions for RDM developed within the DFG-Funded Cluster of Excellence EXC2075 Data-Integrated Simulation Science (SimTech). After an introduction to the scientific context and challenges faced by simulation scientists, we outline the general data management infrastructure and present tools that address these challenges. Exemplary domain applications demonstrate the use and benefits of the proposed data management software solutions. These are complemented by additional measures for enablement and dissemination to foster the adoption of these techniques.","annote":"","author":[{"family":"Flemisch","given":"Bernd"},{"family":"Hermann","given":"Sibylle"},{"family":"Herschel","given":"Melanie"},{"family":"Pflüger","given":"Dirk"},{"family":"Pleiss","given":"Jürgen"},{"family":"Range","given":"Jan"},{"family":"Roy","given":"Sarbani"},{"family":"Takamoto","given":"Makoto"},{"family":"Uekermann","given":"Benjamin"}],"citation-label":"flemisch2024research","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Datenbank-Spektrum","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2024"]],"literal":"2024"},"event-place":"","id":"4a122061de06137fc1895607c95226f1simtech","interhash":"c95189d52d2ce9bdf72132f187c89b32","intrahash":"4a122061de06137fc1895607c95226f1","issue":"","issued":{"date-parts":[["2024"]],"literal":"2024"},"keyword":"PN2 PN2-6 curated","misc":{"orcid":"0000-0003-1045-8202","issn":"16101995","refid":"Flemisch2024","doi":"10.1007/s13222-024-00475-4"},"note":"","number":"","number-of-pages":"8","page":"97–105","page-first":"97","publisher":"","publisher-place":"","status":"","title":"Research Data Management in Simulation Science: Infrastructure, Tools, and Applications","type":"article-journal","username":"simtech","version":"","volume":"24"},"1ad96e0232adfc011d13023ff6e39376simtech":{"DOI":"10.1038/s41419-024-07273-6","ISBN":"","ISSN":"2041-4889","URL":"https://doi.org/10.1038/s41419-024-07273-6","abstract":"","annote":"","author":[{"family":"Entrop","given":"Kristin"},{"family":"Wieske","given":"Senait"},{"family":"Rehm","given":"Markus"}],"citation-label":"Entrop2024","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Cell Death & Disease","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2024","dec","05"]],"literal":"2024"},"event-place":"","id":"1ad96e0232adfc011d13023ff6e39376simtech","interhash":"11d95a9a5753703baaf16b3b75e3ab6c","intrahash":"1ad96e0232adfc011d13023ff6e39376","issue":"12","issued":{"date-parts":[["2024","dec","05"]],"literal":"2024"},"keyword":"EXC2075 PN2 PN2-1(II) PN2-1A curated","misc":{"issn":"2041-4889","doi":"10.1038/s41419-024-07273-6"},"note":"","number":"12","page":"880","page-first":"880","publisher":"","publisher-place":"","status":"","title":"Why Bax detection in >1400 publications might be flawed","type":"article-journal","username":"simtech","version":"","volume":"15"},"1ba781404619589ae488cb37851e45a6simtech":{"DOI":"10.1021/acs.biochem.4c00501","ISBN":"","ISSN":"00062960","URL":"https://doi.org/10.1021/acs.biochem.4c00501","abstract":"","annote":"","author":[{"family":"Pleiss","given":"Jürgen"}],"citation-label":"pleiss2024modeling","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Biochemistry","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2024","sep"]],"literal":"2024"},"event-place":"","id":"1ba781404619589ae488cb37851e45a6simtech","interhash":"a09cf079d6fccb01943e3dbb28409185","intrahash":"1ba781404619589ae488cb37851e45a6","issue":"20","issued":{"date-parts":[["2024","sep"]],"literal":"2024"},"keyword":"EXC2075 PN2 PN2-6(II) curated","misc":{"orcid":"0000-0003-1045-8202","issn":"00062960","comment":"doi: 10.1021/acs.biochem.4c00501","doi":"10.1021/acs.biochem.4c00501"},"note":"","number":"20","number-of-pages":"8","page":"2533-2541","page-first":"2533","publisher":"American Chemical Society","publisher-place":"","status":"","title":"Modeling Enzyme Kinetics: Current Challenges and Future Perspectives for Biocatalysis","type":"article-journal","username":"simtech","version":"","volume":"63"},"112b47e516f3b08e53d295d89027127asimtech":{"DOI":"10.1038/s41598-024-75795-2","ISBN":"","ISSN":"2045-2322","URL":"https://doi.org/10.1038/s41598-024-75795-2","abstract":"During muscle contraction, not only are the fascicles shortening but also the pennation angle changes, which leads to a faster contraction of the muscle than of its fascicles. This phenomenon is called muscle gearing, and it has a direct influence on the force output of the muscle. There are few studies showing pennation angle changes during isometric and concentric contractions for different contraction intensities and muscle lengths. Therefore, the aim was to determine these influences over a wide range of contraction intensities and ankle joint angles for human triceps surae. Additionally, the influence of contraction intensity and ankle joint angle on muscle gearing was evaluated. Ten sport students performed concentric and isometric contractions with intensities between 0 and 90\\% of the maximum voluntary contraction and ankle joint angles from 50° to 120°. During these contractions, the m. gastrocnemius medialis and lateralis and the m. soleus were recorded via ultrasound imaging. A nonlinear relationship between fascicle length and pennation angle was discovered, which can be described with a quadratic fit for each of the muscles during isometric contraction. A nearly identical relationship was detected during dynamic contraction. The muscle gearing increased almost linearly with contraction intensity and ankle joint angle.","annote":"","author":[{"family":"Coenning","given":"Corinna"},{"family":"Rieg","given":"Volker"},{"family":"Siebert","given":"Tobias"},{"family":"Wank","given":"Veit"}],"citation-label":"Coenning2024","collection-editor":[{"family":"Siebert","given":"Tobias"}],"collection-title":"","container-author":[{"family":"Siebert","given":"Tobias"}],"container-title":"Scientific Reports","documents":[],"edition":"","editor":[{"family":"Siebert","given":"Tobias"}],"event-date":{"date-parts":[["2024","oct","22"]],"literal":"2024"},"event-place":"","id":"112b47e516f3b08e53d295d89027127asimtech","interhash":"7118ef30d9e0d0109338f9b611d56769","intrahash":"112b47e516f3b08e53d295d89027127a","issue":"1","issued":{"date-parts":[["2024","oct","22"]],"literal":"2024"},"keyword":"EXC2075 PN2 PN2-8Siebert curated","misc":{"issn":"2045-2322","doi":"10.1038/s41598-024-75795-2"},"note":"","number":"1","page":"24929","page-first":"24929","publisher":"","publisher-place":"","status":"","title":"Impact of contraction intensity and ankle joint angle on calf muscle fascicle length and pennation angle during isometric and dynamic contractions","type":"article-journal","username":"simtech","version":"","volume":"14"},"e081e01c6fc7c13b601050bfc0f1ab99simtech":{"DOI":"10.1016/j.ifacol.2024.10.004","ISBN":"","ISSN":"2405-8963","URL":"http://dx.doi.org/10.1016/j.ifacol.2024.10.004","abstract":"","annote":"","author":[{"family":"Höpfl","given":"Sebastian"},{"family":"Tautenhahn","given":"Hans-Michael"},{"family":"Wagner","given":"Vincent"},{"family":"Radde","given":"Nicole Erika"}],"citation-label":"Hoepfl2024FOSBE","collection-editor":[{"family":"Klapa","given":"Maria"},{"family":"Bernaerts","given":"Kristel"},{"family":"Vignoni","given":"Alejandro"}],"collection-title":"","container-author":[{"family":"Klapa","given":"Maria"},{"family":"Bernaerts","given":"Kristel"},{"family":"Vignoni","given":"Alejandro"}],"container-title":"IFAC-PapersOnLine","documents":[],"edition":"","editor":[{"family":"Klapa","given":"Maria"},{"family":"Bernaerts","given":"Kristel"},{"family":"Vignoni","given":"Alejandro"}],"event-date":{"date-parts":[["2024"]],"literal":"2024"},"event-place":"","id":"e081e01c6fc7c13b601050bfc0f1ab99simtech","interhash":"e28d46677fd5e50b334e2cc620cd3c5c","intrahash":"e081e01c6fc7c13b601050bfc0f1ab99","issue":"23","issued":{"date-parts":[["2024"]],"literal":"2024"},"keyword":"EXC2075 PN2A-5 PN2","misc":{"issn":"2405-8963","doi":"10.1016/j.ifacol.2024.10.004"},"note":"","number":"23","number-of-pages":"5","page":"19–24","page-first":"19","publisher":"Elsevier BV","publisher-place":"","status":"","title":"Marginal Percentile Intervals in Bayesian Inference are Overconfident","type":"article-journal","username":"simtech","version":"","volume":"58"},"f5ab63441ede21fa42abc43d88a66090simtech":{"DOI":"10.1038/s41419-024-07134-2","ISBN":"","ISSN":"2041-4889","URL":"https://doi.org/10.1038/s41419-024-07134-2","abstract":"Evasion of cell death is a hallmark of cancer, and consequently the induction of cell death is a common strategy in cancer treatment. However, the molecular mechanisms regulating different types of cell death are poorly understood. We have formerly shown that in the epidermis of hypomorphic zebrafish hai1a mutant embryos, pre-neoplastic transformations of keratinocytes caused by unrestrained activity of the type II transmembrane serine protease Matriptase-1 heal spontaneously. This healing is driven by Matriptase-dependent increased sphingosine kinase (SphK) activity and sphingosine-1-phosphate (S1P)-mediated keratinocyte loss via apical cell extrusion. In contrast, amorphic hai1afr26 mutants with even higher Matriptase-1 and SphK activity die within a few days. Here we show that this lethality is not due to epidermal carcinogenesis, but to aberrant tp53-independent apoptosis of keratinocytes caused by increased levels of pro-apoptotic C16 ceramides, sphingolipid counterparts to S1P within the sphingolipid rheostat, which severely compromises the epidermal barrier. Mathematical modelling of sphingolipid rheostat homeostasis, combined with in vivo manipulations of components of the rheostat or the ceramide de novo synthesis pathway, indicate that this unexpected overproduction of ceramides is caused by a negative feedback loop sensing ceramide levels and controlling ceramide replenishment via de novo synthesis. Therefore, despite their initial decrease due to increased conversion to S1P, ceramides eventually reach cell death-inducing levels, making transformed pre-neoplastic keratinocytes die even before they are extruded, thereby abrogating the normally barrier-preserving mode of apical live cell extrusion. Our results offer an in vivo perspective of the dynamics of sphingolipid homeostasis and its relevance for epithelial cell survival versus cell death, linking apical cell extrusion and apoptosis. Implications for human carcinomas and their treatments are discussed.","annote":"","author":[{"family":"Armistead","given":"Joy"},{"family":"Höpfl","given":"Sebastian"},{"family":"Goldhausen","given":"Pierre"},{"family":"Müller-Hartmann","given":"Andrea"},{"family":"Fahle","given":"Evelin"},{"family":"Hatzold","given":"Julia"},{"family":"Franzen","given":"Rainer"},{"family":"Brodesser","given":"Susanne"},{"family":"Radde","given":"Nicole E."},{"family":"Hammerschmidt","given":"Matthias"}],"citation-label":"Armistead2024","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Cell Death & Disease","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2024","oct","14"]],"literal":"2024"},"event-place":"","id":"f5ab63441ede21fa42abc43d88a66090simtech","interhash":"f966f7ced6d0d8dbd5f6fdf8eaf10d82","intrahash":"f5ab63441ede21fa42abc43d88a66090","issue":"10","issued":{"date-parts":[["2024","oct","14"]],"literal":"2024"},"keyword":"PN2 PN2A-5 EXC2075","misc":{"issn":"2041-4889","doi":"10.1038/s41419-024-07134-2"},"note":"","number":"10","page":"746","page-first":"746","publisher":"","publisher-place":"","status":"","title":"A sphingolipid rheostat controls apoptosis versus apical cell extrusion as alternative tumour-suppressive mechanisms","type":"article-journal","username":"simtech","version":"","volume":"15"},"36d0787264e7b25210ec22590dc26a34simtech":{"DOI":"","ISBN":"","ISSN":"","URL":"https://elib.uni-stuttgart.de/handle/11682/13594","abstract":"Vehicle accidents can cause neck injuries which are costly for individuals and society. Safety systems could be designed to reduce the risk of neck injury if it were possible to accurately simulate the tissue-level injuries that later lead to chronic pain. During a crash, reflexes cause the muscles of the neck to be actively lengthened. Although the muscles of the neck are often only mildly injured, the forces developed by the neck’s musculature affect the tissues that are more severely injured. In this work, we compare the forces developed by MAT_156, LS-DYNA’s Hill-type model, and the newly proposed VEXAT muscle model during active lengthening. The results show that Hill-type muscle models underestimate forces developed during active lengthening, while the VEXAT model can more faithfully reproduce experimental measurements.","annote":"","author":[{"family":"Millard","given":"Matthew"},{"family":"Kempter","given":"Fabian"},{"family":"Stutzig","given":"Norman"},{"family":"Siebert","given":"Tobias"},{"family":"Fehr","given":"Jörg"}],"citation-label":"siebert2023improving","collection-editor":[{"family":"Siebert","given":"T."}],"collection-title":"","container-author":[{"family":"Siebert","given":"T."}],"container-title":"","documents":[],"edition":"","editor":[{"family":"Siebert","given":"T."}],"event-date":{"date-parts":[["2023"]],"literal":"2023"},"event-place":"","id":"36d0787264e7b25210ec22590dc26a34simtech","interhash":"2a76571d45f9e0508f29fe5f5e899b06","intrahash":"36d0787264e7b25210ec22590dc26a34","issue":"","issued":{"date-parts":[["2023"]],"literal":"2023"},"keyword":"EXC2075 PN2 curated","misc":{"eventtitle":"Ircobi","venue":"Zürich","eventdate":"2023"},"note":"","number":"","number-of-pages":"8","page":"533-541","page-first":"533","publisher":"","publisher-place":"","status":"","title":"Improving the accuracy of musculotendon models for the simulation of active lengthening","type":"paper-conference","username":"simtech","version":"","volume":""},"16b5ea1f1bb5147f2f92564d1767c724simtech":{"DOI":"10.1007/s10439-022-03087-9","ISBN":"","ISSN":"","URL":"https://link.springer.com/article/10.1007/s10439-022-03087-9","abstract":"Occupants exposed to low or moderate crash events can already suffer from whiplash-associated disorders leading to severe and long-lasting symptoms. However, the underlying injury mechanisms and the role of muscle activity are not fully clear. Potential increases in injury risk of non-nominal postures, i.e., rotated head, cannot be evaluated in detail due to the lack of experimental data. Examining changes in neck muscle activity to hold and stabilize the head in a rotated position during pre-crash scenarios might provide a deeper understanding of muscle reflex contributions and injury mechanisms. In this study, the influence of two different head postures (nominal vs. rotation of the head by about 63 ± 9° to the right) on neck muscle activity and head kinematics was investigated in simulated braking experiments inside a driving simulator. The braking scenario was implemented by visualization of the virtual scene using head-mounted displays and a combined translational-rotational platform motion. Kinematics of seventeen healthy subjects was tracked using 3D motion capturing. Surface electromyography were used to quantify muscle activity of left and right sternocleidomastoideus (SCM) and trapezius (TRP) muscles. The results show clear evidence that rotated head postures affect the static as well as the dynamic behavior of muscle activity during the virtual braking event. With head turned to the right, the contralateral left muscles yielded higher base activation and delayed muscle onset times. In contrast, right muscles had much lower activations and showed no relevant changes in muscle activation between nominal and rotated head position. The observed delayed muscle onset times and increased asymmetrical muscle activation patterns in the rotated head position are assumed to affect injury mechanisms. This could explain the prevalence of rotated head postures during a crash reported by patients suffering from WAD. The results can be used for validating the active behavior of human body models in braking simulations with nominal and rotated head postures, and to gain a deeper understanding of neck injury mechanisms.","annote":"","author":[{"family":"Kempter","given":"Fabian"},{"family":"Lantella","given":"Lorena"},{"family":"Stutzig","given":"Norman"},{"family":"Fehr","given":"Jörg"},{"family":"Siebert","given":"Tobias"}],"citation-label":"noauthororeditor2024rotated","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Springer Link","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2024","April"]],"literal":"2024"},"event-place":"","id":"16b5ea1f1bb5147f2f92564d1767c724simtech","interhash":"958da81d5faeafe01668d01f4a237c19","intrahash":"16b5ea1f1bb5147f2f92564d1767c724","issue":"","issued":{"date-parts":[["2024","April"]],"literal":"2024"},"keyword":"EXC2075 PN2 curated","misc":{"doi":"10.1007/s10439-022-03087-9"},"note":"","number":"","number-of-pages":"11","page":"771–782","page-first":"771","publisher":"","publisher-place":"","status":"","title":"Role of Rotated Head Postures on Volunteer Kinematics and Muscle Activity in Braking Scenarios Performed on a Driving Simulator","type":"article-journal","username":"simtech","version":"","volume":"51"},"c7e68ae5f3894d810752300311254adesimtech":{"DOI":"10.1016/j.jmbbm.2024.106740","ISBN":"","ISSN":"","URL":"https://www.sciencedirect.com/science/article/pii/S1751616124003722?via%3Dihub","abstract":"Digital human body models are used to simulate injuries that occur as a result of vehicle collisions, vibration, sports, and falls. Given enough time the body’s musculature can generate force, affect the body’s movements, and change the risk of some injuries. The finite-element code LS-DYNA is often used to simulate the movements and injuries sustained by the digital human body models as a result of an accident. In this work, we evaluate the accuracy of the three muscle models in LS-DYNA (MAT_156, EHTM, and the VEXAT) when simulating a range of experiments performed on isolated muscle: force-length-velocity experiments on maximally and sub-maximally stimulated muscle, active-lengthening experiments, and vibration experiments. The force-length-velocity experiments are included because these conditions are typical of the muscle activity that precedes an accident, while the active-lengthening and vibration experiments mimic conditions that can cause injury. The three models perform similarly during the maximally and sub-maximally activated force-length-velocity experiments, but noticeably differ in response to the active-lengthening and vibration experiments. The VEXAT model is able to generate the enhanced forces of biological muscle during active lengthening, while both the MAT_156 and EHTM produce too little force. In response to vibration, the stiffness and damping of the VEXAT model closely follows the experimental data while the MAT_156 and EHTM models differ substantially. The accuracy of the VEXAT model comes from two additional mechanical structures that are missing in the MAT_156 and EHTM models: viscoelastic cross-bridges, and an active titin filament. To help others build on our work we have made our simulation code publicly available.","annote":"","author":[{"family":"Millard","given":"Matthew"},{"family":"Stutzig","given":"Norman"},{"family":"Fehr","given":"Jörg"},{"family":"Siebert","given":"Tobias"}],"citation-label":"millard2024benchmark","collection-editor":[],"collection-title":"","container-author":[],"container-title":"ScienceDirect Elsevier","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2024","september 2024"]],"literal":"2024"},"event-place":"","id":"c7e68ae5f3894d810752300311254adesimtech","interhash":"f87d2c872f2e6f474113b724ada23083","intrahash":"c7e68ae5f3894d810752300311254ade","issue":"","issued":{"date-parts":[["2024","september 2024"]],"literal":"2024"},"keyword":"EXC2075 PN2 curated","misc":{"language":"English","doi":"10.1016/j.jmbbm.2024.106740"},"note":"","number":"","page":"","page-first":"","publisher":"","publisher-place":"","status":"","title":"A benchmark of muscle models to length changes great and small","type":"article-journal","username":"simtech","version":"","volume":""},"6d5194ffec57a10698f14e4eb9cafefdsimtech":{"DOI":"10.1016/j.bpj.2023.05.026","ISBN":"","ISSN":"","URL":"https://www.sciencedirect.com/science/article/abs/pii/S0006349523003387?via%3Dihub","abstract":"Section snippets\r\nThe Rode model's explanation of the FLR's ascending limb allegedly involves pushing forces in thin filaments\r\nThe main Rockenfeller et al. argument to dismiss the Rode model is the wrong assertion that the Rode model describes the FLR’s ascending limb based on pushing or compressive forces in thin filaments. The thin filaments would be too soft to transmit relevant pushing forces. However, in the Rode model, thin filaments are always pulled away from the Z-disk.\r\n\r\nFurthermore, Rockenfeller et al. wrongly assert that swXBs generate pushing forces on thin filaments in the Rode model and that the\r\n\r\nThe Rockenfeller model ignores geometrical changes developing on the FLR’s ascending limb\r\nThe Rockenfeller model assumes a hexagonal filament lattice as in optimal overlap down to 0.4-μm half-sarcomere length (with about 1 μm being the optimal length) and that the lattice distances progressively increase with shortening due to volume constancy. These assumptions ignore several geometrical changes in the half-sarcomere that occur during shortening and hamper the predictive power of the model in the range of the FLR’s ascending limb. For example, the Rockenfeller model predicts noThe Rockenfeller model assumes effective force in the region of double thin-filament overlap\r\nDouble thin-filament overlap starts to develop when thin filaments slide through the M-line near optimal half-sarcomere length (left-hand side of the FLR plateau). The Rockenfeller model assumes that XBs are formed in the region of double thin-filament overlap. This assumption leads to effective force in this region and cannot explain Trombitás and Tigyi-Sebes’ experiments (8).\r\n\r\nTrombitás and Tigyi-Sebes stretched rigor muscle fibers leading to the detachment of thin filaments from the Z-disk.\r\n\r\nThe Rockenfeller model's effective overlap function is mechanically inconsistent on the FLR's ascending limb\r\nOne basis of the Rockenfeller model’s force calculation is the effective filament overlap, the theoretical capacity to produce isometric force depending on half-sarcomere length without effects of interfilament spacing. Surprisingly, the effective filament overlap (their Figure 1 in (3)) is straight at about 0.8-μm half-sarcomere length. First, when thick-filament tips slide through the Z-disk at this length, the myosin heads meet thin filaments of opposite polarity and form swXBs in their","annote":"","author":[{"family":"Rode","given":"Christian"},{"family":"Tomalka","given":"André"},{"family":"Blickhan","given":"Reinhard"},{"family":"Siebert","given":"Tobias"}],"citation-label":"noauthororeditor","collection-editor":[{"family":"Tobias","given":"Siebert"}],"collection-title":"","container-author":[{"family":"Tobias","given":"Siebert"}],"container-title":"Biophysical Journal 1","documents":[],"edition":"","editor":[{"family":"Tobias","given":"Siebert"}],"event-date":{"date-parts":[["2023","09"]],"literal":"2023"},"event-place":"","id":"6d5194ffec57a10698f14e4eb9cafefdsimtech","interhash":"d8e89594eb96e38b9322adfc8d9b4e9a","intrahash":"6d5194ffec57a10698f14e4eb9cafefd","issue":"17","issued":{"date-parts":[["2023","09"]],"literal":"2023"},"keyword":"PN2 EXC2075","misc":{"language":"English","doi":"10.1016/j.bpj.2023.05.026"},"note":"","number":"17","number-of-pages":"2","page":"3541-3543","page-first":"3541","publisher":"","publisher-place":"","status":"","title":"Structurally motivated models to explain the muscle’s force-length relationship","type":"article-journal","username":"simtech","version":"","volume":"122"}}