[{"date_created":"2018-12-11T11:49:16Z","intvolume":" 93","volume":93,"language":[{"iso":"eng"}],"article_processing_charge":"No","publication":"Physical Review E Statistical Nonlinear and Soft Matter Physics","year":"2016","publisher":"American Institute of Physics","date_published":"2016-02-28T00:00:00Z","title":"Interplay of migratory and division forces as a generic mechanism for stem cell patterns","month":"02","type":"journal_article","author":[{"last_name":"Hannezo","full_name":"Hannezo, Edouard B","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"},{"last_name":"Coucke","full_name":"Coucke, Alice","first_name":"Alice"},{"first_name":"Jean","full_name":"Joanny, Jean","last_name":"Joanny"}],"extern":"1","citation":{"mla":"Hannezo, Edouard B., et al. “Interplay of Migratory and Division Forces as a Generic Mechanism for Stem Cell Patterns.” Physical Review E Statistical Nonlinear and Soft Matter Physics, vol. 93, no. 2, American Institute of Physics, 2016, doi:10.1103/PhysRevE.93.022405.","apa":"Hannezo, E. B., Coucke, A., & Joanny, J. (2016). Interplay of migratory and division forces as a generic mechanism for stem cell patterns. Physical Review E Statistical Nonlinear and Soft Matter Physics. American Institute of Physics. https://doi.org/10.1103/PhysRevE.93.022405","ista":"Hannezo EB, Coucke A, Joanny J. 2016. Interplay of migratory and division forces as a generic mechanism for stem cell patterns. Physical Review E Statistical Nonlinear and Soft Matter Physics. 93(2).","chicago":"Hannezo, Edouard B, Alice Coucke, and Jean Joanny. “Interplay of Migratory and Division Forces as a Generic Mechanism for Stem Cell Patterns.” Physical Review E Statistical Nonlinear and Soft Matter Physics. American Institute of Physics, 2016. https://doi.org/10.1103/PhysRevE.93.022405.","ama":"Hannezo EB, Coucke A, Joanny J. Interplay of migratory and division forces as a generic mechanism for stem cell patterns. Physical Review E Statistical Nonlinear and Soft Matter Physics. 2016;93(2). doi:10.1103/PhysRevE.93.022405","short":"E.B. Hannezo, A. Coucke, J. Joanny, Physical Review E Statistical Nonlinear and Soft Matter Physics 93 (2016).","ieee":"E. B. Hannezo, A. Coucke, and J. Joanny, “Interplay of migratory and division forces as a generic mechanism for stem cell patterns,” Physical Review E Statistical Nonlinear and Soft Matter Physics, vol. 93, no. 2. American Institute of Physics, 2016."},"day":"28","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledgement":"The authors thank Jacques Prost and Pierre Recho for helpful discussions, as well as the Labex CelTisPhyBio and all its members. E.H. acknowledges for funding a Young Researcher Prize from the Bettencourt-Schueller Fondation, and a Junior Research Fellowship from Trinity College, Cambridge.","oa_version":"None","publication_status":"published","date_updated":"2021-01-12T08:22:00Z","_id":"931","status":"public","abstract":[{"text":"In many adult tissues, stem cells and differentiated cells are not homogeneously distributed: stem cells are arranged in periodic "niches," and differentiated cells are constantly produced and migrate out of these niches. In this article, we provide a general theoretical framework to study mixtures of dividing and actively migrating particles, which we apply to biological tissues. We show in particular that the interplay between the stresses arising from active cell migration and stem cell division give rise to robust stem cell patterns. The instability of the tissue leads to spatial patterns which are either steady or oscillating in time. The wavelength of the instability has an order of magnitude consistent with the biological observations. We also discuss the implications of these results for future in vitro and in vivo experiments.","lang":"eng"}],"doi":"10.1103/PhysRevE.93.022405","publist_id":"6509","issue":"2"},{"date_published":"2016-01-12T00:00:00Z","title":"Emergence of an Apical Epithelial Cell Surface In Vivo","publisher":"Cell Press","publication":"Developmental Cell","article_processing_charge":"No","language":[{"iso":"eng"}],"volume":36,"year":"2016","page":"24 - 35","intvolume":" 36","date_created":"2018-12-11T11:49:16Z","doi":"10.1016/j.devcel.2015.12.013","publist_id":"6510","abstract":[{"lang":"eng","text":"Epithelial sheets are crucial components of all metazoan animals, enclosing organs and protecting the animal from its environment. Epithelial homeostasis poses unique challenges, as addition of new cells and loss of old cells must be achieved without disrupting the fluid-tight barrier and apicobasal polarity of the epithelium. Several studies have identified cell biological mechanisms underlying extrusion of cells from epithelia, but far less is known of the converse mechanism by which new cells are added. Here, we combine molecular, pharmacological, and laser-dissection experiments with theoretical modeling to characterize forces driving emergence of an apical surface as single nascent cells are added to a vertebrate epithelium in vivo. We find that this process involves the interplay between cell-autonomous actin-generated pushing forces in the emerging cell and mechanical properties of neighboring cells. Our findings define the forces driving this cell behavior, contributing to a more comprehensive understanding of epithelial homeostasis."}],"issue":"1","status":"public","_id":"932","citation":{"ama":"Sedzinski J, Hannezo EB, Tu F, Biro M, Wallingford J. Emergence of an Apical Epithelial Cell Surface In Vivo. Developmental Cell. 2016;36(1):24-35. doi:10.1016/j.devcel.2015.12.013","short":"J. Sedzinski, E.B. Hannezo, F. Tu, M. Biro, J. Wallingford, Developmental Cell 36 (2016) 24–35.","chicago":"Sedzinski, Jakub, Edouard B Hannezo, Fan Tu, Maté Biro, and John Wallingford. “Emergence of an Apical Epithelial Cell Surface In Vivo.” Developmental Cell. Cell Press, 2016. https://doi.org/10.1016/j.devcel.2015.12.013.","ieee":"J. Sedzinski, E. B. Hannezo, F. Tu, M. Biro, and J. Wallingford, “Emergence of an Apical Epithelial Cell Surface In Vivo,” Developmental Cell, vol. 36, no. 1. Cell Press, pp. 24–35, 2016.","ista":"Sedzinski J, Hannezo EB, Tu F, Biro M, Wallingford J. 2016. Emergence of an Apical Epithelial Cell Surface In Vivo. Developmental Cell. 36(1), 24–35.","apa":"Sedzinski, J., Hannezo, E. B., Tu, F., Biro, M., & Wallingford, J. (2016). Emergence of an Apical Epithelial Cell Surface In Vivo. Developmental Cell. Cell Press. https://doi.org/10.1016/j.devcel.2015.12.013","mla":"Sedzinski, Jakub, et al. “Emergence of an Apical Epithelial Cell Surface In Vivo.” Developmental Cell, vol. 36, no. 1, Cell Press, 2016, pp. 24–35, doi:10.1016/j.devcel.2015.12.013."},"day":"12","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Sedzinski, Jakub","first_name":"Jakub","last_name":"Sedzinski"},{"last_name":"Hannezo","first_name":"Edouard B","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6005-1561"},{"full_name":"Tu, Fan","first_name":"Fan","last_name":"Tu"},{"last_name":"Biro","full_name":"Biro, Maté","first_name":"Maté"},{"last_name":"Wallingford","first_name":"John","full_name":"Wallingford, John"}],"extern":"1","acknowledgement":"We thank J. Bear, B. Goldstein, A. Ewald, and D. Soroldoni for critical reading. This work was funded by an EMBO Long Term Fellowship to J.S., a Research Fellowship from Trinity College, Cambridge and a Bettencourt-Schueller Foundation Young Researcher Prize to E.H., a Cancer Institute NSW Early Career Researcher fellowship (13/ECF/1–25) and a Cancer Australia/Cure Cancer Australia Foundation project grant (1070498) to M.B., and grants from the NHLBI (HL117164) and NIGMS (GM074104) to J.B.W. J.B.W. was an early career scientist of the Howard Hughes Medical Institute. This work was initiated at the New Quantitative Approaches to Morphogenesis Workshop at UCSB, which is funded in part by the National Science Foundation (PHY11-25915) and the NIGMS (GM067110-05).","publication_status":"published","oa_version":"None","date_updated":"2021-01-12T08:22:00Z","type":"journal_article","month":"01"},{"type":"journal_article","oa_version":"Submitted Version","date_updated":"2021-12-14T07:55:30Z","department":[{"_id":"DaZi"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"short":"J.T. Huff, D. Zilberman, S.W. Roy, Nature 538 (2016) 533–536.","ama":"Huff JT, Zilberman D, Roy SW. Mechanism for DNA transposons to generate introns on genomic scales. Nature. 2016;538(7626):533-536. doi:10.1038/nature20110","chicago":"Huff, Jason T., Daniel Zilberman, and Scott W. Roy. “Mechanism for DNA Transposons to Generate Introns on Genomic Scales.” Nature. Springer Nature , 2016. https://doi.org/10.1038/nature20110.","ieee":"J. T. Huff, D. Zilberman, and S. W. Roy, “Mechanism for DNA transposons to generate introns on genomic scales,” Nature, vol. 538, no. 7626. Springer Nature , pp. 533–536, 2016.","ista":"Huff JT, Zilberman D, Roy SW. 2016. Mechanism for DNA transposons to generate introns on genomic scales. Nature. 538(7626), 533–536.","apa":"Huff, J. T., Zilberman, D., & Roy, S. W. (2016). Mechanism for DNA transposons to generate introns on genomic scales. Nature. Springer Nature . https://doi.org/10.1038/nature20110","mla":"Huff, Jason T., et al. “Mechanism for DNA Transposons to Generate Introns on Genomic Scales.” Nature, vol. 538, no. 7626, Springer Nature , 2016, pp. 533–36, doi:10.1038/nature20110."},"author":[{"full_name":"Huff, Jason T.","first_name":"Jason T.","last_name":"Huff"},{"orcid":"0000-0002-0123-8649","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1","first_name":"Daniel","full_name":"Zilberman, Daniel","last_name":"Zilberman"},{"last_name":"Roy","first_name":"Scott W.","full_name":"Roy, Scott W."}],"oa":1,"_id":"9456","external_id":{"pmid":["27760113"]},"scopus_import":"1","date_created":"2021-06-04T11:34:55Z","year":"2016","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684705/","open_access":"1"}],"publication":"Nature","volume":538,"article_processing_charge":"No","date_published":"2016-10-27T00:00:00Z","title":"Mechanism for DNA transposons to generate introns on genomic scales","quality_controlled":"1","month":"10","publication_status":"published","day":"27","extern":"1","status":"public","pmid":1,"publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"issue":"7626","abstract":[{"text":"The discovery of introns four decades ago was one of the most unexpected findings in molecular biology. Introns are sequences interrupting genes that must be removed as part of messenger RNA production. Genome sequencing projects have shown that most eukaryotic genes contain at least one intron, and frequently many. Comparison of these genomes reveals a history of long evolutionary periods during which few introns were gained, punctuated by episodes of rapid, extensive gain. However, although several detailed mechanisms for such episodic intron generation have been proposed, none has been empirically supported on a genomic scale. Here we show how short, non-autonomous DNA transposons independently generated hundreds to thousands of introns in the prasinophyte Micromonas pusilla and the pelagophyte Aureococcus anophagefferens. Each transposon carries one splice site. The other splice site is co-opted from the gene sequence that is duplicated upon transposon insertion, allowing perfect splicing out of the RNA. The distributions of sequences that can be co-opted are biased with respect to codons, and phasing of transposon-generated introns is similarly biased. These transposons insert between pre-existing nucleosomes, so that multiple nearby insertions generate nucleosome-sized intervening segments. Thus, transposon insertion and sequence co-option may explain the intron phase biases and prevalence of nucleosome-sized exons observed in eukaryotes. Overall, the two independent examples of proliferating elements illustrate a general DNA transposon mechanism that can plausibly account for episodes of rapid, extensive intron gain during eukaryotic evolution.","lang":"eng"}],"doi":"10.1038/nature20110","intvolume":" 538","page":"533-536","article_type":"letter_note","language":[{"iso":"eng"}],"publisher":"Springer Nature "},{"_id":"9473","external_id":{"pmid":["27956643"]},"scopus_import":"1","type":"journal_article","oa_version":"Published Version","date_updated":"2023-05-08T11:00:40Z","department":[{"_id":"DaZi"},{"_id":"XiFe"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"apa":"Hsieh, P.-H., He, S., Buttress, T., Gao, H., Couchman, M., Fischer, R. L., … Feng, X. (2016). Arabidopsis male sexual lineage exhibits more robust maintenance of CG methylation than somatic tissues. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1619074114","mla":"Hsieh, Ping-Hung, et al. “Arabidopsis Male Sexual Lineage Exhibits More Robust Maintenance of CG Methylation than Somatic Tissues.” Proceedings of the National Academy of Sciences, vol. 113, no. 52, National Academy of Sciences, 2016, pp. 15132–37, doi:10.1073/pnas.1619074114.","ista":"Hsieh P-H, He S, Buttress T, Gao H, Couchman M, Fischer RL, Zilberman D, Feng X. 2016. Arabidopsis male sexual lineage exhibits more robust maintenance of CG methylation than somatic tissues. Proceedings of the National Academy of Sciences. 113(52), 15132–15137.","ieee":"P.-H. Hsieh et al., “Arabidopsis male sexual lineage exhibits more robust maintenance of CG methylation than somatic tissues,” Proceedings of the National Academy of Sciences, vol. 113, no. 52. National Academy of Sciences, pp. 15132–15137, 2016.","chicago":"Hsieh, Ping-Hung, Shengbo He, Toby Buttress, Hongbo Gao, Matthew Couchman, Robert L. Fischer, Daniel Zilberman, and Xiaoqi Feng. “Arabidopsis Male Sexual Lineage Exhibits More Robust Maintenance of CG Methylation than Somatic Tissues.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2016. https://doi.org/10.1073/pnas.1619074114.","ama":"Hsieh P-H, He S, Buttress T, et al. Arabidopsis male sexual lineage exhibits more robust maintenance of CG methylation than somatic tissues. Proceedings of the National Academy of Sciences. 2016;113(52):15132-15137. doi:10.1073/pnas.1619074114","short":"P.-H. Hsieh, S. He, T. Buttress, H. Gao, M. Couchman, R.L. Fischer, D. Zilberman, X. Feng, Proceedings of the National Academy of Sciences 113 (2016) 15132–15137."},"author":[{"first_name":"Ping-Hung","full_name":"Hsieh, Ping-Hung","last_name":"Hsieh"},{"full_name":"He, Shengbo","first_name":"Shengbo","last_name":"He"},{"last_name":"Buttress","full_name":"Buttress, Toby","first_name":"Toby"},{"last_name":"Gao","first_name":"Hongbo","full_name":"Gao, Hongbo"},{"first_name":"Matthew","full_name":"Couchman, Matthew","last_name":"Couchman"},{"full_name":"Fischer, Robert L.","first_name":"Robert L.","last_name":"Fischer"},{"orcid":"0000-0002-0123-8649","first_name":"Daniel","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1","full_name":"Zilberman, Daniel","last_name":"Zilberman"},{"orcid":"0000-0002-4008-1234","full_name":"Feng, Xiaoqi","first_name":"Xiaoqi","id":"e0164712-22ee-11ed-b12a-d80fcdf35958","last_name":"Feng"}],"oa":1,"title":"Arabidopsis male sexual lineage exhibits more robust maintenance of CG methylation than somatic tissues","date_published":"2016-12-27T00:00:00Z","quality_controlled":"1","date_created":"2021-06-07T06:21:39Z","year":"2016","main_file_link":[{"url":"https://doi.org/10.1073/pnas.1619074114","open_access":"1"}],"publication":"Proceedings of the National Academy of Sciences","volume":113,"article_processing_charge":"No","pmid":1,"status":"public","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"issue":"52","doi":"10.1073/pnas.1619074114","abstract":[{"text":"Cytosine DNA methylation regulates the expression of eukaryotic genes and transposons. Methylation is copied by methyltransferases after DNA replication, which results in faithful transmission of methylation patterns during cell division and, at least in flowering plants, across generations. Transgenerational inheritance is mediated by a small group of cells that includes gametes and their progenitors. However, methylation is usually analyzed in somatic tissues that do not contribute to the next generation, and the mechanisms of transgenerational inheritance are inferred from such studies. To gain a better understanding of how DNA methylation is inherited, we analyzed purified Arabidopsis thaliana sperm and vegetative cells-the cell types that comprise pollen-with mutations in the DRM, CMT2, and CMT3 methyltransferases. We find that DNA methylation dependency on these enzymes is similar in sperm, vegetative cells, and somatic tissues, although DRM activity extends into heterochromatin in vegetative cells, likely reflecting transcription of heterochromatic transposons in this cell type. We also show that lack of histone H1, which elevates heterochromatic DNA methylation in somatic tissues, does not have this effect in pollen. Instead, levels of CG methylation in wild-type sperm and vegetative cells, as well as in wild-type microspores from which both pollen cell types originate, are substantially higher than in wild-type somatic tissues and similar to those of H1-depleted roots. Our results demonstrate that the mechanisms of methylation maintenance are similar between pollen and somatic cells, but the efficiency of CG methylation is higher in pollen, allowing methylation patterns to be accurately inherited across generations.","lang":"eng"}],"month":"12","publication_status":"published","day":"27","extern":"1","publisher":"National Academy of Sciences","intvolume":" 113","page":"15132-15137","article_type":"original","language":[{"iso":"eng"}]},{"publication_status":"published","day":"27","extern":"1","month":"12","issue":"52","abstract":[{"text":"Cytosine methylation is a DNA modification with important regulatory functions in eukaryotes. In flowering plants, sexual reproduction is accompanied by extensive DNA demethylation, which is required for proper gene expression in the endosperm, a nutritive extraembryonic seed tissue. Endosperm arises from a fusion of a sperm cell carried in the pollen and a female central cell. Endosperm DNA demethylation is observed specifically on the chromosomes inherited from the central cell in Arabidopsis thaliana, rice, and maize, and requires the DEMETER DNA demethylase in Arabidopsis. DEMETER is expressed in the central cell before fertilization, suggesting that endosperm demethylation patterns are inherited from the central cell. Down-regulation of the MET1 DNA methyltransferase has also been proposed to contribute to central cell demethylation. However, with the exception of three maize genes, central cell DNA methylation has not been directly measured, leaving the origin and mechanism of endosperm demethylation uncertain. Here, we report genome-wide analysis of DNA methylation in the central cells of Arabidopsis and rice—species that diverged 150 million years ago—as well as in rice egg cells. We find that DNA demethylation in both species is initiated in central cells, which requires DEMETER in Arabidopsis. However, we do not observe a global reduction of CG methylation that would be indicative of lowered MET1 activity; on the contrary, CG methylation efficiency is elevated in female gametes compared with nonsexual tissues. Our results demonstrate that locus-specific, active DNA demethylation in the central cell is the origin of maternal chromosome hypomethylation in the endosperm.","lang":"eng"}],"doi":"10.1073/pnas.1619047114","status":"public","pmid":1,"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"language":[{"iso":"eng"}],"intvolume":" 113","page":"15138-15143","article_type":"original","publisher":"National Academy of Sciences","date_updated":"2023-05-08T11:00:07Z","oa_version":"Published Version","department":[{"_id":"DaZi"},{"_id":"XiFe"}],"citation":{"ama":"Park K, Kim MY, Vickers M, et al. DNA demethylation is initiated in the central cells of Arabidopsis and rice. Proceedings of the National Academy of Sciences. 2016;113(52):15138-15143. doi:10.1073/pnas.1619047114","short":"K. Park, M.Y. Kim, M. Vickers, J.-S. Park, Y. Hyun, T. Okamoto, D. Zilberman, R.L. Fischer, X. Feng, Y. Choi, S. Scholten, Proceedings of the National Academy of Sciences 113 (2016) 15138–15143.","chicago":"Park, Kyunghyuk, M. Yvonne Kim, Martin Vickers, Jin-Sup Park, Youbong Hyun, Takashi Okamoto, Daniel Zilberman, et al. “DNA Demethylation Is Initiated in the Central Cells of Arabidopsis and Rice.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2016. https://doi.org/10.1073/pnas.1619047114.","ieee":"K. Park et al., “DNA demethylation is initiated in the central cells of Arabidopsis and rice,” Proceedings of the National Academy of Sciences, vol. 113, no. 52. National Academy of Sciences, pp. 15138–15143, 2016.","ista":"Park K, Kim MY, Vickers M, Park J-S, Hyun Y, Okamoto T, Zilberman D, Fischer RL, Feng X, Choi Y, Scholten S. 2016. DNA demethylation is initiated in the central cells of Arabidopsis and rice. Proceedings of the National Academy of Sciences. 113(52), 15138–15143.","apa":"Park, K., Kim, M. Y., Vickers, M., Park, J.-S., Hyun, Y., Okamoto, T., … Scholten, S. (2016). DNA demethylation is initiated in the central cells of Arabidopsis and rice. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1619047114","mla":"Park, Kyunghyuk, et al. “DNA Demethylation Is Initiated in the Central Cells of Arabidopsis and Rice.” Proceedings of the National Academy of Sciences, vol. 113, no. 52, National Academy of Sciences, 2016, pp. 15138–43, doi:10.1073/pnas.1619047114."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Kyunghyuk","full_name":"Park, Kyunghyuk","last_name":"Park"},{"first_name":"M. Yvonne","full_name":"Kim, M. Yvonne","last_name":"Kim"},{"first_name":"Martin","full_name":"Vickers, Martin","last_name":"Vickers"},{"full_name":"Park, Jin-Sup","first_name":"Jin-Sup","last_name":"Park"},{"full_name":"Hyun, Youbong","first_name":"Youbong","last_name":"Hyun"},{"first_name":"Takashi","full_name":"Okamoto, Takashi","last_name":"Okamoto"},{"last_name":"Zilberman","orcid":"0000-0002-0123-8649","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1","first_name":"Daniel","full_name":"Zilberman, Daniel"},{"last_name":"Fischer","first_name":"Robert L.","full_name":"Fischer, Robert L."},{"last_name":"Feng","id":"e0164712-22ee-11ed-b12a-d80fcdf35958","first_name":"Xiaoqi","full_name":"Feng, Xiaoqi","orcid":"0000-0002-4008-1234"},{"last_name":"Choi","full_name":"Choi, Yeonhee","first_name":"Yeonhee"},{"last_name":"Scholten","full_name":"Scholten, Stefan","first_name":"Stefan"}],"oa":1,"type":"journal_article","external_id":{"pmid":["27956642"]},"scopus_import":"1","_id":"9477","main_file_link":[{"url":"https://doi.org/10.1073/pnas.1619047114","open_access":"1"}],"year":"2016","publication":"Proceedings of the National Academy of Sciences","volume":113,"article_processing_charge":"No","date_created":"2021-06-07T07:10:59Z","title":"DNA demethylation is initiated in the central cells of Arabidopsis and rice","date_published":"2016-12-27T00:00:00Z","keyword":["Multidisciplinary"],"quality_controlled":"1"},{"publisher":"Neural Information Processing Systems","page":"4285 - 4293","intvolume":" 29","language":[{"iso":"eng"}],"status":"public","publist_id":"6469","abstract":[{"lang":"eng","text":"Experience constantly shapes neural circuits through a variety of plasticity mechanisms. While the functional roles of some plasticity mechanisms are well-understood, it remains unclear how changes in neural excitability contribute to learning. Here, we develop a normative interpretation of intrinsic plasticity (IP) as a key component of unsupervised learning. We introduce a novel generative mixture model that accounts for the class-specific statistics of stimulus intensities, and we derive a neural circuit that learns the input classes and their intensities. We will analytically show that inference and learning for our generative model can be achieved by a neural circuit with intensity-sensitive neurons equipped with a specific form of IP. Numerical experiments verify our analytical derivations and show robust behavior for artificial and natural stimuli. Our results link IP to non-trivial input statistics, in particular the statistics of stimulus intensities for classes to which a neuron is sensitive. More generally, our work paves the way toward new classification algorithms that are robust to intensity variations."}],"month":"01","alternative_title":["Advances in Neural Information Processing Systems"],"day":"01","ec_funded":1,"publication_status":"published","acknowledgement":"DFG Cluster of Excellence EXC 1077/1 (Hearing4all) and LU 1196/5-1 (JL and TM), People Programme (Marie Curie Actions) FP7/2007-2013 grant agreement no. 291734 (CS)","conference":{"name":"NIPS: Neural Information Processing Systems","end_date":"2016-12-10","start_date":"2016-12-05","location":"Barcelona, Spaine"},"quality_controlled":"1","project":[{"name":"International IST Postdoc Fellowship Programme","grant_number":"291734","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"title":"Neurons equipped with intrinsic plasticity learn stimulus intensity statistics","date_published":"2016-01-01T00:00:00Z","date_created":"2018-12-11T11:49:21Z","volume":29,"main_file_link":[{"url":"https://papers.nips.cc/paper/6582-neurons-equipped-with-intrinsic-plasticity-learn-stimulus-intensity-statistics"}],"year":"2016","_id":"948","scopus_import":1,"type":"conference","citation":{"ieee":"T. Monk, C. Savin, and J. Lücke, “Neurons equipped with intrinsic plasticity learn stimulus intensity statistics,” presented at the NIPS: Neural Information Processing Systems, Barcelona, Spaine, 2016, vol. 29, pp. 4285–4293.","ama":"Monk T, Savin C, Lücke J. Neurons equipped with intrinsic plasticity learn stimulus intensity statistics. In: Vol 29. Neural Information Processing Systems; 2016:4285-4293.","short":"T. Monk, C. Savin, J. Lücke, in:, Neural Information Processing Systems, 2016, pp. 4285–4293.","chicago":"Monk, Travis, Cristina Savin, and Jörg Lücke. “Neurons Equipped with Intrinsic Plasticity Learn Stimulus Intensity Statistics,” 29:4285–93. Neural Information Processing Systems, 2016.","ista":"Monk T, Savin C, Lücke J. 2016. Neurons equipped with intrinsic plasticity learn stimulus intensity statistics. NIPS: Neural Information Processing Systems, Advances in Neural Information Processing Systems, vol. 29, 4285–4293.","mla":"Monk, Travis, et al. Neurons Equipped with Intrinsic Plasticity Learn Stimulus Intensity Statistics. Vol. 29, Neural Information Processing Systems, 2016, pp. 4285–93.","apa":"Monk, T., Savin, C., & Lücke, J. (2016). Neurons equipped with intrinsic plasticity learn stimulus intensity statistics (Vol. 29, pp. 4285–4293). Presented at the NIPS: Neural Information Processing Systems, Barcelona, Spaine: Neural Information Processing Systems."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Monk, Travis","first_name":"Travis","last_name":"Monk"},{"last_name":"Savin","first_name":"Cristina","id":"3933349E-F248-11E8-B48F-1D18A9856A87","full_name":"Savin, Cristina"},{"last_name":"Lücke","first_name":"Jörg","full_name":"Lücke, Jörg"}],"oa_version":"None","date_updated":"2021-01-12T08:22:08Z","department":[{"_id":"GaTk"}]},{"type":"journal_article","oa_version":"Preprint","date_updated":"2023-02-23T14:02:07Z","oa":1,"author":[{"last_name":"Krivelevich","first_name":"Michael","full_name":"Krivelevich, Michael"},{"full_name":"Kwan, Matthew Alan","id":"5fca0887-a1db-11eb-95d1-ca9d5e0453b3","first_name":"Matthew Alan","orcid":"0000-0002-4003-7567","last_name":"Kwan"},{"last_name":"Sudakov","first_name":"Benny","full_name":"Sudakov, Benny"}],"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","citation":{"ista":"Krivelevich M, Kwan MA, Sudakov B. 2016. Cycles and matchings in randomly perturbed digraphs and hypergraphs. Combinatorics, Probability and Computing. 25(6), 909–927.","apa":"Krivelevich, M., Kwan, M. A., & Sudakov, B. (2016). Cycles and matchings in randomly perturbed digraphs and hypergraphs. Combinatorics, Probability and Computing. Cambridge University Press. https://doi.org/10.1017/s0963548316000079","mla":"Krivelevich, Michael, et al. “Cycles and Matchings in Randomly Perturbed Digraphs and Hypergraphs.” Combinatorics, Probability and Computing, vol. 25, no. 6, Cambridge University Press, 2016, pp. 909–27, doi:10.1017/s0963548316000079.","ama":"Krivelevich M, Kwan MA, Sudakov B. Cycles and matchings in randomly perturbed digraphs and hypergraphs. Combinatorics, Probability and Computing. 2016;25(6):909-927. doi:10.1017/s0963548316000079","short":"M. Krivelevich, M.A. Kwan, B. Sudakov, Combinatorics, Probability and Computing 25 (2016) 909–927.","chicago":"Krivelevich, Michael, Matthew Alan Kwan, and Benny Sudakov. “Cycles and Matchings in Randomly Perturbed Digraphs and Hypergraphs.” Combinatorics, Probability and Computing. Cambridge University Press, 2016. https://doi.org/10.1017/s0963548316000079.","ieee":"M. Krivelevich, M. A. Kwan, and B. Sudakov, “Cycles and matchings in randomly perturbed digraphs and hypergraphs,” Combinatorics, Probability and Computing, vol. 25, no. 6. Cambridge University Press, pp. 909–927, 2016."},"_id":"9591","external_id":{"arxiv":["1501.04816"]},"scopus_import":"1","date_created":"2021-06-22T12:35:13Z","year":"2016","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1501.04816"}],"volume":25,"article_processing_charge":"No","publication":"Combinatorics, Probability and Computing","title":"Cycles and matchings in randomly perturbed digraphs and hypergraphs","date_published":"2016-11-01T00:00:00Z","quality_controlled":"1","month":"11","publication_status":"published","extern":"1","day":"01","status":"public","publication_identifier":{"issn":["0963-5483"],"eissn":["1469-2163"]},"issue":"6","doi":"10.1017/s0963548316000079","abstract":[{"text":"We give several results showing that different discrete structures typically gain certain spanning substructures (in particular, Hamilton cycles) after a modest random perturbation. First, we prove that adding linearly many random edges to a dense k-uniform hypergraph ensures the (asymptotically almost sure) existence of a perfect matching or a loose Hamilton cycle. The proof involves an interesting application of Szemerédi's Regularity Lemma, which might be independently useful. We next prove that digraphs with certain strong expansion properties are pancyclic, and use this to show that adding a linear number of random edges typically makes a dense digraph pancyclic. Finally, we prove that perturbing a certain (minimum-degree-dependent) number of random edges in a tournament typically ensures the existence of multiple edge-disjoint Hamilton cycles. All our results are tight.","lang":"eng"}],"intvolume":" 25","page":"909-927","article_type":"original","arxiv":1,"language":[{"iso":"eng"}],"publisher":"Cambridge University Press"},{"publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"pmid":1,"status":"public","abstract":[{"lang":"eng","text":"RNA polymerase I (Pol I) is a highly processive enzyme that transcribes ribosomal DNA (rDNA) and regulates growth of eukaryotic cells. Crystal structures of free Pol I from the yeast Saccharomyces cerevisiae have revealed dimers of the enzyme stabilized by a 'connector' element and an expanded cleft containing the active centre in an inactive conformation. The central bridge helix was unfolded and a Pol-I-specific 'expander' element occupied the DNA-template-binding site. The structure of Pol I in its active transcribing conformation has yet to be determined, whereas structures of Pol II and Pol III have been solved with bound DNA template and RNA transcript. Here we report structures of active transcribing Pol I from yeast solved by two different cryo-electron microscopy approaches. A single-particle structure at 3.8 Å resolution reveals a contracted active centre cleft with bound DNA and RNA, and a narrowed pore beneath the active site that no longer holds the RNA-cleavage-stimulating domain of subunit A12.2. A structure at 29 Å resolution that was determined from cryo-electron tomograms of Pol I enzymes transcribing cellular rDNA confirms contraction of the cleft and reveals that incoming and exiting rDNA enclose an angle of around 150°. The structures suggest a model for the regulation of transcription elongation in which contracted and expanded polymerase conformations are associated with active and inactive states, respectively."}],"doi":"10.1038/nature20561","issue":"7634","month":"12","day":"22","extern":"1","publication_status":"published","publisher":"Springer Nature","article_type":"letter_note","page":"607-610","intvolume":" 540","language":[{"iso":"eng"}],"_id":"9654","scopus_import":"1","external_id":{"pmid":["27842382"]},"type":"journal_article","citation":{"ieee":"S. Neyer et al., “Structure of RNA polymerase I transcribing ribosomal DNA genes,” Nature, vol. 540, no. 7634. Springer Nature, pp. 607–610, 2016.","ama":"Neyer S, Kunz M, Geiss C, et al. Structure of RNA polymerase I transcribing ribosomal DNA genes. Nature. 2016;540(7634):607-610. doi:10.1038/nature20561","short":"S. Neyer, M. Kunz, C. Geiss, M. Hantsche, V.-V. Hodirnau, A. Seybert, C. Engel, M.P. Scheffer, P. Cramer, A.S. Frangakis, Nature 540 (2016) 607–610.","chicago":"Neyer, Simon, Michael Kunz, Christian Geiss, Merle Hantsche, Victor-Valentin Hodirnau, Anja Seybert, Christoph Engel, Margot P. Scheffer, Patrick Cramer, and Achilleas S. Frangakis. “Structure of RNA Polymerase I Transcribing Ribosomal DNA Genes.” Nature. Springer Nature, 2016. https://doi.org/10.1038/nature20561.","ista":"Neyer S, Kunz M, Geiss C, Hantsche M, Hodirnau V-V, Seybert A, Engel C, Scheffer MP, Cramer P, Frangakis AS. 2016. Structure of RNA polymerase I transcribing ribosomal DNA genes. Nature. 540(7634), 607–610.","mla":"Neyer, Simon, et al. “Structure of RNA Polymerase I Transcribing Ribosomal DNA Genes.” Nature, vol. 540, no. 7634, Springer Nature, 2016, pp. 607–10, doi:10.1038/nature20561.","apa":"Neyer, S., Kunz, M., Geiss, C., Hantsche, M., Hodirnau, V.-V., Seybert, A., … Frangakis, A. S. (2016). Structure of RNA polymerase I transcribing ribosomal DNA genes. Nature. Springer Nature. https://doi.org/10.1038/nature20561"},"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","author":[{"last_name":"Neyer","full_name":"Neyer, Simon","first_name":"Simon"},{"full_name":"Kunz, Michael","first_name":"Michael","last_name":"Kunz"},{"last_name":"Geiss","first_name":"Christian","full_name":"Geiss, Christian"},{"full_name":"Hantsche, Merle","first_name":"Merle","last_name":"Hantsche"},{"last_name":"Hodirnau","id":"3661B498-F248-11E8-B48F-1D18A9856A87","full_name":"Hodirnau, Victor-Valentin","first_name":"Victor-Valentin"},{"full_name":"Seybert, Anja","first_name":"Anja","last_name":"Seybert"},{"full_name":"Engel, Christoph","first_name":"Christoph","last_name":"Engel"},{"full_name":"Scheffer, Margot P.","first_name":"Margot P.","last_name":"Scheffer"},{"first_name":"Patrick","full_name":"Cramer, Patrick","last_name":"Cramer"},{"first_name":"Achilleas S.","full_name":"Frangakis, Achilleas S.","last_name":"Frangakis"}],"oa_version":"None","date_updated":"2021-07-22T09:22:20Z","quality_controlled":"1","date_published":"2016-12-22T00:00:00Z","title":"Structure of RNA polymerase I transcribing ribosomal DNA genes","date_created":"2021-07-14T09:04:24Z","publication":"Nature","volume":540,"article_processing_charge":"No","year":"2016"},{"intvolume":" 7","article_type":"letter_note","page":"2210-2215","language":[{"iso":"eng"}],"publisher":"American Chemical Society","month":"06","publication_status":"published","extern":"1","day":"16","pmid":1,"status":"public","publication_identifier":{"eissn":["1948-7185"]},"issue":"12","doi":"10.1021/acs.jpclett.6b00729","abstract":[{"lang":"eng","text":"One of the most prominent consequences of the quantum nature of light atomic nuclei is that their kinetic energy does not follow a Maxwell–Boltzmann distribution. Deep inelastic neutron scattering (DINS) experiments can measure this effect. Thus, the nuclear quantum kinetic energy can be probed directly in both ordered and disordered samples. However, the relation between the quantum kinetic energy and the atomic environment is a very indirect one, and cross-validation with theoretical modeling is therefore urgently needed. Here, we use state of the art path integral molecular dynamics techniques to compute the kinetic energy of hydrogen and oxygen nuclei in liquid, solid, and gas-phase water close to the triple point, comparing three different interatomic potentials and validating our results against equilibrium isotope fractionation measurements. We will then show how accurate simulations can draw a link between extremely precise fractionation experiments and DINS, therefore establishing a reliable benchmark for future measurements and providing key insights to increase further the accuracy of interatomic potentials for water."}],"date_created":"2021-07-19T08:57:32Z","year":"2016","article_processing_charge":"No","volume":7,"publication":"The Journal of Physical Chemistry Letters","title":"Nuclear quantum effects in water at the triple point: Using theory as a link between experiments","date_published":"2016-06-16T00:00:00Z","quality_controlled":"1","type":"journal_article","date_updated":"2023-02-23T14:04:49Z","oa_version":"None","author":[{"last_name":"Cheng","full_name":"Cheng, Bingqing","id":"cbe3cda4-d82c-11eb-8dc7-8ff94289fcc9","first_name":"Bingqing","orcid":"0000-0002-3584-9632"},{"last_name":"Behler","full_name":"Behler, Jörg","first_name":"Jörg"},{"last_name":"Ceriotti","full_name":"Ceriotti, Michele","first_name":"Michele"}],"citation":{"ista":"Cheng B, Behler J, Ceriotti M. 2016. Nuclear quantum effects in water at the triple point: Using theory as a link between experiments. The Journal of Physical Chemistry Letters. 7(12), 2210–2215.","apa":"Cheng, B., Behler, J., & Ceriotti, M. (2016). Nuclear quantum effects in water at the triple point: Using theory as a link between experiments. The Journal of Physical Chemistry Letters. American Chemical Society. https://doi.org/10.1021/acs.jpclett.6b00729","mla":"Cheng, Bingqing, et al. “Nuclear Quantum Effects in Water at the Triple Point: Using Theory as a Link between Experiments.” The Journal of Physical Chemistry Letters, vol. 7, no. 12, American Chemical Society, 2016, pp. 2210–15, doi:10.1021/acs.jpclett.6b00729.","ama":"Cheng B, Behler J, Ceriotti M. Nuclear quantum effects in water at the triple point: Using theory as a link between experiments. The Journal of Physical Chemistry Letters. 2016;7(12):2210-2215. doi:10.1021/acs.jpclett.6b00729","short":"B. Cheng, J. Behler, M. Ceriotti, The Journal of Physical Chemistry Letters 7 (2016) 2210–2215.","chicago":"Cheng, Bingqing, Jörg Behler, and Michele Ceriotti. “Nuclear Quantum Effects in Water at the Triple Point: Using Theory as a Link between Experiments.” The Journal of Physical Chemistry Letters. American Chemical Society, 2016. https://doi.org/10.1021/acs.jpclett.6b00729.","ieee":"B. Cheng, J. Behler, and M. Ceriotti, “Nuclear quantum effects in water at the triple point: Using theory as a link between experiments,” The Journal of Physical Chemistry Letters, vol. 7, no. 12. American Chemical Society, pp. 2210–2215, 2016."},"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","_id":"9681","external_id":{"pmid":["27203358"]},"scopus_import":"1"},{"publisher":"American Physical Society","intvolume":" 6","article_number":"031016","language":[{"iso":"eng"}],"status":"public","issue":"3","publist_id":"7954","abstract":[{"lang":"eng","text":"We introduce a scheme for preparation, manipulation, and read out of Majorana zero modes in semiconducting wires with mesoscopic superconducting islands. Our approach synthesizes recent advances in materials growth with tools commonly used in quantum-dot experiments, including gate control of tunnel barriers and Coulomb effects, charge sensing, and charge pumping. We outline a sequence of milestones interpolating between zero-mode detection and quantum computing that includes (1) detection of fusion rules for non-Abelian anyons using either proximal charge sensors or pumped current, (2) validation of a prototype topological qubit, and (3) demonstration of non-Abelian statistics by braiding in a branched geometry. The first two milestones require only a single wire with two islands, and additionally enable sensitive measurements of the system\\'s excitation gap, quasiparticle poisoning rates, residual Majorana zero-mode splittings, and topological-qubit coherence times. These pre-braiding experiments can be adapted to other manipulation and read out schemes as well."}],"doi":"10.1103/PhysRevX.6.031016","month":"08","acknowledgement":"We acknowledge support from Microsoft Research, the National Science Foundation through Grant No. DMR-1341822 (J. A.); the Alfred P. Sloan Foundation (J. A.); the Caltech Institute for Quantum Information and Matter, an NSF Physics Frontiers Center with support of the Gordon and Betty Moore Foundation through Grant No. GBMF1250; the Walter Burke Institute for Theoretical Physics at Caltech; the NSERC PGSD program (D. A.); the Crafoord Foundation (M. L. and M. H.) and the Swedish Research Council (M. L.); The Danish National Research Foundation, and the Villum Foundation (C. M.); The Danish Council for Independent Research/Natural Sciences, and Danmarks Nationalbank (J. F.). Part of this work was performed at the Aspen Center for Physics, which is supported by National Science Foundation Grant No. PHY-1066293 (R. V. M.).","publication_status":"published","extern":"1","day":"03","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2016-08-03T00:00:00Z","title":"Milestones toward Majorana-based quantum computing","quality_controlled":"1","date_created":"2018-12-11T11:44:37Z","ddc":["530"],"year":"2016","volume":6,"publication":"Physical Review X","_id":"100","file_date_updated":"2019-05-15T14:12:31Z","type":"journal_article","file":[{"file_name":"2016_PhysRevX_Aasen.pdf","file_size":2142676,"date_updated":"2019-05-15T14:12:31Z","content_type":"application/pdf","access_level":"open_access","success":1,"date_created":"2019-05-15T14:12:31Z","file_id":"6458","relation":"main_file","creator":"kschuh"}],"oa_version":"Published Version","date_updated":"2021-01-12T06:47:33Z","author":[{"last_name":"Aasen","full_name":"Aasen, David","first_name":"David"},{"last_name":"Hell","first_name":"Michael","full_name":"Hell, Michael"},{"last_name":"Mishmash","first_name":"Ryan","full_name":"Mishmash, Ryan"},{"first_name":"Andrew P","full_name":"Higginbotham, Andrew P","id":"4AD6785A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2607-2363","last_name":"Higginbotham"},{"first_name":"Jeroen","full_name":"Danon, Jeroen","last_name":"Danon"},{"full_name":"Leijnse, Martin","first_name":"Martin","last_name":"Leijnse"},{"first_name":"Thomas","full_name":"Jespersen, Thomas","last_name":"Jespersen"},{"first_name":"Joshua","full_name":"Folk, Joshua","last_name":"Folk"},{"first_name":"Charles","full_name":"Marcs, Charles","last_name":"Marcs"},{"full_name":"Flensberg, Karsten","first_name":"Karsten","last_name":"Flensberg"},{"full_name":"Alicea, Jason","first_name":"Jason","last_name":"Alicea"}],"oa":1,"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","citation":{"ista":"Aasen D, Hell M, Mishmash R, Higginbotham AP, Danon J, Leijnse M, Jespersen T, Folk J, Marcs C, Flensberg K, Alicea J. 2016. Milestones toward Majorana-based quantum computing. Physical Review X. 6(3), 031016.","apa":"Aasen, D., Hell, M., Mishmash, R., Higginbotham, A. P., Danon, J., Leijnse, M., … Alicea, J. (2016). Milestones toward Majorana-based quantum computing. Physical Review X. American Physical Society. https://doi.org/10.1103/PhysRevX.6.031016","mla":"Aasen, David, et al. “Milestones toward Majorana-Based Quantum Computing.” Physical Review X, vol. 6, no. 3, 031016, American Physical Society, 2016, doi:10.1103/PhysRevX.6.031016.","ieee":"D. Aasen et al., “Milestones toward Majorana-based quantum computing,” Physical Review X, vol. 6, no. 3. American Physical Society, 2016.","short":"D. Aasen, M. Hell, R. Mishmash, A.P. Higginbotham, J. Danon, M. Leijnse, T. Jespersen, J. Folk, C. Marcs, K. Flensberg, J. Alicea, Physical Review X 6 (2016).","ama":"Aasen D, Hell M, Mishmash R, et al. Milestones toward Majorana-based quantum computing. Physical Review X. 2016;6(3). doi:10.1103/PhysRevX.6.031016","chicago":"Aasen, David, Michael Hell, Ryan Mishmash, Andrew P Higginbotham, Jeroen Danon, Martin Leijnse, Thomas Jespersen, et al. “Milestones toward Majorana-Based Quantum Computing.” Physical Review X. American Physical Society, 2016. https://doi.org/10.1103/PhysRevX.6.031016."}},{"year":"2016","publication":"ACS Synthetic Biology","language":[{"iso":"eng"}],"volume":5,"date_created":"2018-12-11T11:49:40Z","intvolume":" 5","page":"1098 - 1107","title":"An orthogonal permease–inducer–repressor feedback loop shows bistability","date_published":"2016-05-05T00:00:00Z","quality_controlled":"1","publisher":"American Chemical Society","oa_version":"None","acknowledgement":"We thank Julio Polaina (Instituto de Agroqu ı ́ mica y Tecnolog ı ́ a de Alimentos, C.S.I.C., Paterna, Spain) for the gift of plasmid pMR4, Gregor W. Schmidt for provision of and support with the micro fl uidic device, Markus Du ̈ rr for the cell tracking R script, and Lukas Widmer for the script for MEIGO using “ parfor ” in MATLAB. We acknowledge the members of the Stelling group for discussions, comments, and support.","publication_status":"published","date_updated":"2021-01-12T06:47:37Z","department":[{"_id":"CaGu"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","day":"05","citation":{"ista":"Gnügge R, Dharmarajan L, Lang M, Stelling J. 2016. An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. 5(10), 1098–1107.","mla":"Gnügge, Robert, et al. “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS Synthetic Biology, vol. 5, no. 10, American Chemical Society, 2016, pp. 1098–107, doi:10.1021/acssynbio.6b00013.","apa":"Gnügge, R., Dharmarajan, L., Lang, M., & Stelling, J. (2016). An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. American Chemical Society. https://doi.org/10.1021/acssynbio.6b00013","ieee":"R. Gnügge, L. Dharmarajan, M. Lang, and J. Stelling, “An orthogonal permease–inducer–repressor feedback loop shows bistability,” ACS Synthetic Biology, vol. 5, no. 10. American Chemical Society, pp. 1098–1107, 2016.","ama":"Gnügge R, Dharmarajan L, Lang M, Stelling J. An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. 2016;5(10):1098-1107. doi:10.1021/acssynbio.6b00013","short":"R. Gnügge, L. Dharmarajan, M. Lang, J. Stelling, ACS Synthetic Biology 5 (2016) 1098–1107.","chicago":"Gnügge, Robert, Lekshmi Dharmarajan, Moritz Lang, and Jörg Stelling. “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS Synthetic Biology. American Chemical Society, 2016. https://doi.org/10.1021/acssynbio.6b00013."},"author":[{"last_name":"Gnügge","first_name":"Robert","full_name":"Gnügge, Robert"},{"full_name":"Dharmarajan, Lekshmi","first_name":"Lekshmi","last_name":"Dharmarajan"},{"first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz","last_name":"Lang"},{"last_name":"Stelling","full_name":"Stelling, Jörg","first_name":"Jörg"}],"type":"journal_article","month":"05","issue":"10","publist_id":"6390","doi":"10.1021/acssynbio.6b00013","abstract":[{"lang":"eng","text":"Feedback loops in biological networks, among others, enable differentiation and cell cycle progression, and increase robustness in signal transduction. In natural networks, feedback loops are often complex and intertwined, making it challenging to identify which loops are mainly responsible for an observed behavior. However, minimal synthetic replicas could allow for such identification. Here, we engineered a synthetic permease-inducer-repressor system in Saccharomyces cerevisiae to analyze if a transport-mediated positive feedback loop could be a core mechanism for the switch-like behavior in the regulation of metabolic gene networks such as the S. cerevisiae GAL system or the Escherichia coli lac operon. We characterized the synthetic circuit using deterministic and stochastic mathematical models. Similar to its natural counterparts, our synthetic system shows bistable and hysteretic behavior, and the inducer concentration range for bistability as well as the switching rates between the two stable states depend on the repressor concentration. Our results indicate that a generic permease–inducer–repressor circuit with a single feedback loop is sufficient to explain the experimentally observed bistable behavior of the natural systems. We anticipate that the approach of reimplementing natural systems with orthogonal parts to identify crucial network components is applicable to other natural systems such as signaling pathways."}],"status":"public","_id":"1008"},{"external_id":{"arxiv":["1603.03217"]},"_id":"101","author":[{"last_name":"Albrecht","first_name":"S M","full_name":"Albrecht, S M"},{"orcid":"0000-0003-2607-2363","id":"4AD6785A-F248-11E8-B48F-1D18A9856A87","full_name":"Higginbotham, Andrew P","first_name":"Andrew P","last_name":"Higginbotham"},{"last_name":"Jespersen","first_name":"Thomas","full_name":"Jespersen, Thomas"},{"first_name":"Morten","full_name":"Madsen, Morten","last_name":"Madsen"},{"last_name":"Kuemmeth","first_name":"Ferdinand","full_name":"Kuemmeth, Ferdinand"},{"last_name":"Nygård","first_name":"Jesper","full_name":"Nygård, Jesper"},{"first_name":"Peter","full_name":"Krogstrup, Peter","last_name":"Krogstrup"},{"full_name":"Marcus, Charles","first_name":"Charles","last_name":"Marcus"}],"oa":1,"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"short":"S.M. Albrecht, A.P. Higginbotham, T. Jespersen, M. Madsen, F. Kuemmeth, J. Nygård, P. Krogstrup, C. Marcus, Nature 531 (2016) 206–209.","ama":"Albrecht SM, Higginbotham AP, Jespersen T, et al. Exponential protection of zero modes in Majorana islands. Nature. 2016;531(7593):206-209. doi:10.1038/nature17162","chicago":"Albrecht, S M, Andrew P Higginbotham, Thomas Jespersen, Morten Madsen, Ferdinand Kuemmeth, Jesper Nygård, Peter Krogstrup, and Charles Marcus. “Exponential Protection of Zero Modes in Majorana Islands.” Nature. Nature Publishing Group, 2016. https://doi.org/10.1038/nature17162.","ieee":"S. M. Albrecht et al., “Exponential protection of zero modes in Majorana islands,” Nature, vol. 531, no. 7593. Nature Publishing Group, pp. 206–209, 2016.","ista":"Albrecht SM, Higginbotham AP, Jespersen T, Madsen M, Kuemmeth F, Nygård J, Krogstrup P, Marcus C. 2016. Exponential protection of zero modes in Majorana islands. Nature. 531(7593), 206–209.","apa":"Albrecht, S. M., Higginbotham, A. P., Jespersen, T., Madsen, M., Kuemmeth, F., Nygård, J., … Marcus, C. (2016). Exponential protection of zero modes in Majorana islands. Nature. Nature Publishing Group. https://doi.org/10.1038/nature17162","mla":"Albrecht, S. M., et al. “Exponential Protection of Zero Modes in Majorana Islands.” Nature, vol. 531, no. 7593, Nature Publishing Group, 2016, pp. 206–09, doi:10.1038/nature17162."},"date_updated":"2021-01-12T06:47:37Z","oa_version":"Submitted Version","type":"journal_article","quality_controlled":"1","date_published":"2016-03-10T00:00:00Z","title":"Exponential protection of zero modes in Majorana islands","volume":531,"publication":"Nature","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1603.03217"}],"year":"2016","date_created":"2018-12-11T11:44:38Z","doi":"10.1038/nature17162","publist_id":"7953","abstract":[{"text":"Majorana zero modes are quasiparticle excitations in condensed matter systems that have been proposed as building blocks of fault-tolerant quantum computers. They are expected to exhibit non-Abelian particle statistics, in contrast to the usual statistics of fermions and bosons, enabling quantum operations to be performed by braiding isolated modes around one another. Quantum braiding operations are topologically protected insofar as these modes are pinned near zero energy, with the departure from zero expected to be exponentially small as the modes become spatially separated. Following theoretical proposals, several experiments have identified signatures of Majorana modes in nanowires with proximity-induced superconductivity and atomic chains, with small amounts of mode splitting potentially explained by hybridization of Majorana modes. Here, we use Coulomb-blockade spectroscopy in an InAs nanowire segment with epitaxial aluminium, which forms a proximity-induced superconducting Coulomb island (a â ∼ Majorana islandâ (tm)) that is isolated from normal-metal leads by tunnel barriers, to measure the splitting of near-zero-energy Majorana modes. We observe exponential suppression of energy splitting with increasing wire length. For short devices of a few hundred nanometres, sub-gap state energies oscillate as the magnetic field is varied, as is expected for hybridized Majorana modes. Splitting decreases by a factor of about ten for each half a micrometre of increased wire length. For devices longer than about one micrometre, transport in strong magnetic fields occurs through a zero-energy state that is energetically isolated from a continuum, yielding uniformly spaced Coulomb-blockade conductance peaks, consistent with teleportation via Majorana modes. Our results help to explain the trivial-to-topological transition in finite systems and to quantify the scaling of topological protection with end-mode separation.","lang":"eng"}],"issue":"7593","status":"public","extern":"1","day":"10","acknowledgement":"This research was supported by Microsoft Project Q, the Danish National Research Foundation, the Lundbeck Foundation, the Carlsberg Foundation and the European Commission. C.M.M. acknowledges support from the Villum Foundation.","publication_status":"published","month":"03","publisher":"Nature Publishing Group","arxiv":1,"language":[{"iso":"eng"}],"page":"206 - 209","intvolume":" 531"},{"type":"journal_article","oa_version":"Preprint","date_updated":"2021-01-12T06:47:42Z","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"apa":"Mishmash, R., Aasen, D., Higginbotham, A. P., & Alicea, J. (2016). Approaching a topological phase transition in Majorana nanowires. Physical Review B. American Physical Society. https://doi.org/10.1103/PhysRevB.93.245404","mla":"Mishmash, Ryan, et al. “Approaching a Topological Phase Transition in Majorana Nanowires.” Physical Review B, vol. 93, no. 24, 245404, American Physical Society, 2016, doi:10.1103/PhysRevB.93.245404.","ista":"Mishmash R, Aasen D, Higginbotham AP, Alicea J. 2016. Approaching a topological phase transition in Majorana nanowires. Physical Review B. 93(24), 245404.","chicago":"Mishmash, Ryan, David Aasen, Andrew P Higginbotham, and Jason Alicea. “Approaching a Topological Phase Transition in Majorana Nanowires.” Physical Review B. American Physical Society, 2016. https://doi.org/10.1103/PhysRevB.93.245404.","short":"R. Mishmash, D. Aasen, A.P. Higginbotham, J. Alicea, Physical Review B 93 (2016).","ama":"Mishmash R, Aasen D, Higginbotham AP, Alicea J. Approaching a topological phase transition in Majorana nanowires. Physical Review B. 2016;93(24). doi:10.1103/PhysRevB.93.245404","ieee":"R. Mishmash, D. Aasen, A. P. Higginbotham, and J. Alicea, “Approaching a topological phase transition in Majorana nanowires,” Physical Review B, vol. 93, no. 24. American Physical Society, 2016."},"oa":1,"author":[{"last_name":"Mishmash","first_name":"Ryan","full_name":"Mishmash, Ryan"},{"first_name":"David","full_name":"Aasen, David","last_name":"Aasen"},{"last_name":"Higginbotham","orcid":"0000-0003-2607-2363","id":"4AD6785A-F248-11E8-B48F-1D18A9856A87","first_name":"Andrew P","full_name":"Higginbotham, Andrew P"},{"first_name":"Jason","full_name":"Alicea, Jason","last_name":"Alicea"}],"_id":"102","external_id":{"arxiv":["1601.07908"]},"date_created":"2018-12-11T11:44:38Z","year":"2016","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1601.07908"}],"publication":"Physical Review B","volume":93,"date_published":"2016-06-08T00:00:00Z","title":"Approaching a topological phase transition in Majorana nanowires","quality_controlled":"1","month":"06","publication_status":"published","day":"08","extern":"1","status":"public","issue":"24","publist_id":"7952","abstract":[{"lang":"eng","text":"Recent experiments have produced mounting evidence of Majorana zero modes in nanowire-superconductor hybrids. Signatures of an expected topological phase transition accompanying the onset of these modes nevertheless remain elusive. We investigate a fundamental question concerning this issue: Do well-formed Majorana modes necessarily entail a sharp phase transition in these setups? Assuming reasonable parameters, we argue that finite-size effects can dramatically smooth this putative transition into a crossover, even in systems large enough to support well-localized Majorana modes. We propose overcoming such finite-size effects by examining the behavior of low-lying excited states through tunneling spectroscopy. In particular, the excited-state energies exhibit characteristic field and density dependence, and scaling with system size, that expose an approaching topological phase transition. We suggest several experiments for extracting the predicted behavior. As a useful byproduct, the protocols also allow one to measure the wire's spin-orbit coupling directly in its superconducting environment."}],"doi":"10.1103/PhysRevB.93.245404","article_number":"245404","intvolume":" 93","arxiv":1,"language":[{"iso":"eng"}],"publisher":"American Physical Society"},{"extern":"1","day":"01","publication_status":"published","acknowledgement":"We acknowledge support from the Human Frontier Science Program and Emmanuel College (A.Š.), St John’s and Peterhouse Colleges (T.C.T.M.), the Swiss National Science Foundation (T.C.T.M.), the Biotechnology and Biological Sciences Research Council (T.P.J.K.), the Frances and Augustus Newman Foundation (T.P.J.K.), the European Research Council (T.C.T.M., T.P.J.K., and D.F.), and the Engineering and Physical Sciences Research Council (D.F.).","month":"12","doi":"10.1063/1.4965040","abstract":[{"lang":"eng","text":"Nucleation processes are at the heart of a large number of phenomena, from cloud formation to protein crystallization. A recently emerging area where nucleation is highly relevant is the initiation of filamentous protein self-assembly, a process that has broad implications in many research areas ranging from medicine to nanotechnology. As such, spontaneous nucleation of protein fibrils has received much attention in recent years with many theoretical and experimental studies focusing on the underlying physical principles. In this paper we make a step forward in this direction and explore the early time behaviour of filamentous protein growth in the context of nucleation theory. We first provide an overview of the thermodynamics and kinetics of spontaneous nucleation of protein filaments in the presence of one relevant degree of freedom, namely the cluster size. In this case, we review how key kinetic observables, such as the reaction order of spontaneous nucleation, are directly related to the physical size of the critical nucleus. We then focus on the increasingly prominent case of filament nucleation that includes a conformational conversion of the nucleating building-block as an additional slow step in the nucleation process. Using computer simulations, we study the concentration dependence of the nucleation rate. We find that, under these circumstances, the reaction order of spontaneous nucleation with respect to the free monomer does no longer relate to the overall physical size of the nucleating aggregate but rather to the portion of the aggregate that actively participates in the conformational conversion. Our results thus provide a novel interpretation of the common kinetic descriptors of protein filament formation, including the reaction order of the nucleation step or the scaling exponent of lag times, and put into perspective current theoretical descriptions of protein aggregation."}],"issue":"21","publication_identifier":{"issn":["0021-9606"],"eissn":["1089-7690"]},"status":"public","pmid":1,"language":[{"iso":"eng"}],"arxiv":1,"article_type":"original","intvolume":" 145","article_number":"211926","publisher":"American Institute of Physics","oa":1,"author":[{"full_name":"Šarić, Anđela","first_name":"Anđela","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","orcid":"0000-0002-7854-2139","last_name":"Šarić"},{"last_name":"Michaels","full_name":"Michaels, Thomas C. T.","first_name":"Thomas C. T."},{"first_name":"Alessio","full_name":"Zaccone, Alessio","last_name":"Zaccone"},{"last_name":"Knowles","first_name":"Tuomas P. J.","full_name":"Knowles, Tuomas P. J."},{"last_name":"Frenkel","first_name":"Daan","full_name":"Frenkel, Daan"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"ieee":"A. Šarić, T. C. T. Michaels, A. Zaccone, T. P. J. Knowles, and D. Frenkel, “Kinetics of spontaneous filament nucleation via oligomers: Insights from theory and simulation,” The Journal of Chemical Physics, vol. 145, no. 21. American Institute of Physics, 2016.","chicago":"Šarić, Anđela, Thomas C. T. Michaels, Alessio Zaccone, Tuomas P. J. Knowles, and Daan Frenkel. “Kinetics of Spontaneous Filament Nucleation via Oligomers: Insights from Theory and Simulation.” The Journal of Chemical Physics. American Institute of Physics, 2016. https://doi.org/10.1063/1.4965040.","short":"A. Šarić, T.C.T. Michaels, A. Zaccone, T.P.J. Knowles, D. Frenkel, The Journal of Chemical Physics 145 (2016).","ama":"Šarić A, Michaels TCT, Zaccone A, Knowles TPJ, Frenkel D. Kinetics of spontaneous filament nucleation via oligomers: Insights from theory and simulation. The Journal of Chemical Physics. 2016;145(21). doi:10.1063/1.4965040","mla":"Šarić, Anđela, et al. “Kinetics of Spontaneous Filament Nucleation via Oligomers: Insights from Theory and Simulation.” The Journal of Chemical Physics, vol. 145, no. 21, 211926, American Institute of Physics, 2016, doi:10.1063/1.4965040.","apa":"Šarić, A., Michaels, T. C. T., Zaccone, A., Knowles, T. P. J., & Frenkel, D. (2016). Kinetics of spontaneous filament nucleation via oligomers: Insights from theory and simulation. The Journal of Chemical Physics. American Institute of Physics. https://doi.org/10.1063/1.4965040","ista":"Šarić A, Michaels TCT, Zaccone A, Knowles TPJ, Frenkel D. 2016. Kinetics of spontaneous filament nucleation via oligomers: Insights from theory and simulation. The Journal of Chemical Physics. 145(21), 211926."},"oa_version":"Preprint","date_updated":"2021-11-29T10:33:11Z","type":"journal_article","scopus_import":"1","external_id":{"pmid":["28799382"],"arxiv":["1610.02320"]},"_id":"10376","volume":145,"article_processing_charge":"No","publication":"The Journal of Chemical Physics","year":"2016","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1610.02320"}],"date_created":"2021-11-29T10:01:57Z","quality_controlled":"1","keyword":["physical and theoretical chemistry","general physics and astronomy"],"title":"Kinetics of spontaneous filament nucleation via oligomers: Insights from theory and simulation","date_published":"2016-12-01T00:00:00Z"},{"publisher":"Springer Nature","article_number":"32825","intvolume":" 6","article_type":"original","arxiv":1,"language":[{"iso":"eng"}],"status":"public","pmid":1,"publication_identifier":{"issn":["2045-2322"]},"issue":"1","doi":"10.1038/srep32825","abstract":[{"lang":"eng","text":"The interplay of membrane proteins is vital for many biological processes, such as cellular transport, cell division, and signal transduction between nerve cells. Theoretical considerations have led to the idea that the membrane itself mediates protein self-organization in these processes through minimization of membrane curvature energy. Here, we present a combined experimental and numerical study in which we quantify these interactions directly for the first time. In our experimental model system we control the deformation of a lipid membrane by adhering colloidal particles. Using confocal microscopy, we establish that these membrane deformations cause an attractive interaction force leading to reversible binding. The attraction extends over 2.5 times the particle diameter and has a strength of three times the thermal energy (−3.3 kBT). Coarse-grained Monte-Carlo simulations of the system are in excellent agreement with the experimental results and prove that the measured interaction is independent of length scale. Our combined experimental and numerical results reveal membrane curvature as a common physical origin for interactions between any membrane-deforming objects, from nanometre-sized proteins to micrometre-sized particles."}],"related_material":{"link":[{"url":"https://doi.org/10.1038/srep37382","relation":"erratum"}]},"month":"09","publication_status":"published","acknowledgement":"This work was supported by the Netherlands Organisation for Scientific Research (NWO/OCW), as part of the Frontiers of Nanoscience program and VENI grant 680-47-431. We thank Jeroen Appel and Wim Pomp for advice on the protocol design and Marcel Winter and Ruben Verweij for experimental support.","day":"13","extern":"1","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"title":"Lipid membrane-mediated attraction between curvature inducing objects","date_published":"2016-09-13T00:00:00Z","keyword":["multidisciplinary"],"quality_controlled":"1","ddc":["540"],"date_created":"2021-11-29T10:34:08Z","year":"2016","main_file_link":[{"open_access":"1","url":"https://www.nature.com/articles/srep32825"}],"publication":"Scientific Reports","volume":6,"article_processing_charge":"No","_id":"10377","external_id":{"pmid":["27618764"],"arxiv":["1603.04644"]},"file_date_updated":"2021-11-29T10:50:00Z","scopus_import":"1","type":"journal_article","oa_version":"Published Version","date_updated":"2021-11-29T11:08:15Z","file":[{"file_name":"2016_SciRep_vanderWel.pdf","file_size":1598289,"content_type":"application/pdf","date_updated":"2021-11-29T10:50:00Z","access_level":"open_access","success":1,"date_created":"2021-11-29T10:50:00Z","file_id":"10379","relation":"main_file","checksum":"d6cf16dd511e15726b001e7cc287cf1d","creator":"cchlebak"}],"citation":{"mla":"van der Wel, Casper, et al. “Lipid Membrane-Mediated Attraction between Curvature Inducing Objects.” Scientific Reports, vol. 6, no. 1, 32825, Springer Nature, 2016, doi:10.1038/srep32825.","apa":"van der Wel, C., Vahid, A., Šarić, A., Idema, T., Heinrich, D., & Kraft, D. J. (2016). Lipid membrane-mediated attraction between curvature inducing objects. Scientific Reports. Springer Nature. https://doi.org/10.1038/srep32825","ista":"van der Wel C, Vahid A, Šarić A, Idema T, Heinrich D, Kraft DJ. 2016. Lipid membrane-mediated attraction between curvature inducing objects. Scientific Reports. 6(1), 32825.","chicago":"Wel, Casper van der, Afshin Vahid, Anđela Šarić, Timon Idema, Doris Heinrich, and Daniela J. Kraft. “Lipid Membrane-Mediated Attraction between Curvature Inducing Objects.” Scientific Reports. Springer Nature, 2016. https://doi.org/10.1038/srep32825.","short":"C. van der Wel, A. Vahid, A. Šarić, T. Idema, D. Heinrich, D.J. Kraft, Scientific Reports 6 (2016).","ama":"van der Wel C, Vahid A, Šarić A, Idema T, Heinrich D, Kraft DJ. Lipid membrane-mediated attraction between curvature inducing objects. Scientific Reports. 2016;6(1). doi:10.1038/srep32825","ieee":"C. van der Wel, A. Vahid, A. Šarić, T. Idema, D. Heinrich, and D. J. Kraft, “Lipid membrane-mediated attraction between curvature inducing objects,” Scientific Reports, vol. 6, no. 1. Springer Nature, 2016."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","has_accepted_license":"1","author":[{"last_name":"van der Wel","first_name":"Casper","full_name":"van der Wel, Casper"},{"full_name":"Vahid, Afshin","first_name":"Afshin","last_name":"Vahid"},{"last_name":"Šarić","orcid":"0000-0002-7854-2139","full_name":"Šarić, Anđela","first_name":"Anđela","id":"bf63d406-f056-11eb-b41d-f263a6566d8b"},{"first_name":"Timon","full_name":"Idema, Timon","last_name":"Idema"},{"last_name":"Heinrich","full_name":"Heinrich, Doris","first_name":"Doris"},{"last_name":"Kraft","first_name":"Daniela J.","full_name":"Kraft, Daniela J."}],"oa":1},{"pmid":1,"status":"public","publication_identifier":{"issn":["1745-2473"],"eissn":["1745-2481"]},"issue":"9","abstract":[{"lang":"eng","text":"The ability of biological molecules to replicate themselves is the foundation of life, requiring a complex cellular machinery. However, a range of aberrant processes involve the self-replication of pathological protein structures without any additional assistance. One example is the autocatalytic generation of pathological protein aggregates, including amyloid fibrils, involved in neurodegenerative disorders. Here, we use computer simulations to identify the necessary requirements for the self-replication of fibrillar assemblies of proteins. We establish that a key physical determinant for this process is the affinity of proteins for the surfaces of fibrils. We find that self-replication can take place only in a very narrow regime of inter-protein interactions, implying a high level of sensitivity to system parameters and experimental conditions. We then compare our theoretical predictions with kinetic and biosensor measurements of fibrils formed from the Aβ peptide associated with Alzheimer’s disease. Our results show a quantitative connection between the kinetics of self-replication and the surface coverage of fibrils by monomeric proteins. These findings reveal the fundamental physical requirements for the formation of supra-molecular structures able to replicate themselves, and shed light on mechanisms in play in the proliferation of protein aggregates in nature."}],"doi":"10.1038/nphys3828","month":"07","publication_status":"published","acknowledgement":"We acknowledge support from the Human Frontier Science Program and Emmanuel College (A.Š.), the Leverhulme Trust and Magdalene College (A.K.B.), St John’s College (T.C.T.M.), the Biotechnology and Biological Sciences Research Council (T.P.J.K. and C.M.D.), the Frances and Augustus Newman Foundation (T.P.J.K.), the European Research Council (T.P.J.K., T.C.T.M., S.L. and D.F.), and the Engineering and Physical Sciences Research Council (D.F.).","extern":"1","day":"18","publisher":"Springer Nature","intvolume":" 12","page":"874-880","article_type":"original","language":[{"iso":"eng"}],"_id":"10378","external_id":{"pmid":["31031819"]},"scopus_import":"1","type":"journal_article","date_updated":"2021-11-29T11:07:25Z","oa_version":"Preprint","oa":1,"author":[{"full_name":"Šarić, Anđela","first_name":"Anđela","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","orcid":"0000-0002-7854-2139","last_name":"Šarić"},{"full_name":"Buell, Alexander K.","first_name":"Alexander K.","last_name":"Buell"},{"last_name":"Meisl","full_name":"Meisl, Georg","first_name":"Georg"},{"last_name":"Michaels","first_name":"Thomas C. T.","full_name":"Michaels, Thomas C. T."},{"full_name":"Dobson, Christopher M.","first_name":"Christopher M.","last_name":"Dobson"},{"last_name":"Linse","first_name":"Sara","full_name":"Linse, Sara"},{"full_name":"Knowles, Tuomas P. J.","first_name":"Tuomas P. J.","last_name":"Knowles"},{"full_name":"Frenkel, Daan","first_name":"Daan","last_name":"Frenkel"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"short":"A. Šarić, A.K. Buell, G. Meisl, T.C.T. Michaels, C.M. Dobson, S. Linse, T.P.J. Knowles, D. Frenkel, Nature Physics 12 (2016) 874–880.","ama":"Šarić A, Buell AK, Meisl G, et al. Physical determinants of the self-replication of protein fibrils. Nature Physics. 2016;12(9):874-880. doi:10.1038/nphys3828","chicago":"Šarić, Anđela, Alexander K. Buell, Georg Meisl, Thomas C. T. Michaels, Christopher M. Dobson, Sara Linse, Tuomas P. J. Knowles, and Daan Frenkel. “Physical Determinants of the Self-Replication of Protein Fibrils.” Nature Physics. Springer Nature, 2016. https://doi.org/10.1038/nphys3828.","ieee":"A. Šarić et al., “Physical determinants of the self-replication of protein fibrils,” Nature Physics, vol. 12, no. 9. Springer Nature, pp. 874–880, 2016.","ista":"Šarić A, Buell AK, Meisl G, Michaels TCT, Dobson CM, Linse S, Knowles TPJ, Frenkel D. 2016. Physical determinants of the self-replication of protein fibrils. Nature Physics. 12(9), 874–880.","mla":"Šarić, Anđela, et al. “Physical Determinants of the Self-Replication of Protein Fibrils.” Nature Physics, vol. 12, no. 9, Springer Nature, 2016, pp. 874–80, doi:10.1038/nphys3828.","apa":"Šarić, A., Buell, A. K., Meisl, G., Michaels, T. C. T., Dobson, C. M., Linse, S., … Frenkel, D. (2016). Physical determinants of the self-replication of protein fibrils. Nature Physics. Springer Nature. https://doi.org/10.1038/nphys3828"},"keyword":["general physics and astronomy"],"title":"Physical determinants of the self-replication of protein fibrils","date_published":"2016-07-18T00:00:00Z","quality_controlled":"1","date_created":"2021-11-29T10:36:11Z","year":"2016","main_file_link":[{"open_access":"1","url":"https://discovery.ucl.ac.uk/id/eprint/1517406/"}],"article_processing_charge":"No","volume":12,"publication":"Nature Physics"},{"pmid":1,"status":"public","publication_identifier":{"issn":["0021-9606"],"eissn":["1089-7690"]},"issue":"22","doi":"10.1063/1.4953036","abstract":[{"text":"Using non-equilibrium molecular dynamics simulations, it has been recently demonstrated that water molecules align in response to an imposed temperature gradient, resulting in an effective electric field. Here, we investigate how thermally induced fields depend on the underlying treatment of long-ranged interactions. For the short-ranged Wolf method and Ewald summation, we find the peak strength of the field to range between 2 × 107 and 5 × 107 V/m for a temperature gradient of 5.2 K/Å. Our value for the Wolf method is therefore an order of magnitude lower than the literature value [J. A. Armstrong and F. Bresme, J. Chem. Phys. 139, 014504 (2013); J. Armstrong et al., J. Chem. Phys. 143, 036101 (2015)]. We show that this discrepancy can be traced back to the use of an incorrect kernel in the calculation of the electrostatic field. More seriously, we find that the Wolf method fails to predict correct molecular orientations, resulting in dipole densities with opposite sign to those computed using Ewald summation. By considering two different multipole expansions, we show that, for inhomogeneous polarisations, the quadrupole contribution can be significant and even outweigh the dipole contribution to the field. Finally, we propose a more accurate way of calculating the electrostatic potential and the field. In particular, we show that averaging the microscopic field analytically to obtain the macroscopic Maxwell field reduces the error bars by up to an order of magnitude. As a consequence, the simulation times required to reach a given statistical accuracy decrease by up to two orders of magnitude.","lang":"eng"}],"month":"06","acknowledgement":"The authors should like to dedicate this paper to the memory of Simon de Leeuw, who was a pioneer in the calculation of Coulomb effects in simulations. P.W. would like to thank the Austrian Academy of Sciences for financial support through a DOC Fellowship, and for covering the travel expenses for the CECAM workshop in Zaragoza in May 2015, where these results were first presented. P.W. would also like to thank Chao Zhang for pointing out the equivalence of the two expressions for the electric field discussed in Sec. VI D, Michiel Sprik for emphasising the importance of the quadrupole contribution in experimental studies of interfacial systems, as well as Aleks Reinhardt and other members of the Frenkel and Dellago groups for their advice. We further acknowledge support from the Federation of Austrian Industry (IV) Carinthia (P.W.), the University of Zagreb and Erasmus SMP (D. Fijan), the Human Frontier Science Program and Emmanuel College (A.Š.), the Austrian Science Fund FWF within the SFB Vicom project F41 (C.D.), and the Engineering and Physical Sciences Research Council Programme Grant No. EP/I001352/1 (D.F.). Additional data related to this publication are available at the University of Cambridge data repository (http://dx.doi.org/10.17863/CAM.118).","publication_status":"published","day":"10","extern":"1","publisher":"American Institute of Physics","article_number":"224102","intvolume":" 144","article_type":"original","arxiv":1,"language":[{"iso":"eng"}],"_id":"10380","external_id":{"arxiv":["1602.02734"],"pmid":["27305991"]},"scopus_import":"1","type":"journal_article","date_updated":"2021-11-29T13:09:08Z","oa_version":"Preprint","citation":{"ista":"Wirnsberger P, Fijan D, Šarić A, Neumann M, Dellago C, Frenkel D. 2016. Non-equilibrium simulations of thermally induced electric fields in water. The Journal of Chemical Physics. 144(22), 224102.","mla":"Wirnsberger, P., et al. “Non-Equilibrium Simulations of Thermally Induced Electric Fields in Water.” The Journal of Chemical Physics, vol. 144, no. 22, 224102, American Institute of Physics, 2016, doi:10.1063/1.4953036.","apa":"Wirnsberger, P., Fijan, D., Šarić, A., Neumann, M., Dellago, C., & Frenkel, D. (2016). Non-equilibrium simulations of thermally induced electric fields in water. The Journal of Chemical Physics. American Institute of Physics. https://doi.org/10.1063/1.4953036","ieee":"P. Wirnsberger, D. Fijan, A. Šarić, M. Neumann, C. Dellago, and D. Frenkel, “Non-equilibrium simulations of thermally induced electric fields in water,” The Journal of Chemical Physics, vol. 144, no. 22. American Institute of Physics, 2016.","ama":"Wirnsberger P, Fijan D, Šarić A, Neumann M, Dellago C, Frenkel D. Non-equilibrium simulations of thermally induced electric fields in water. The Journal of Chemical Physics. 2016;144(22). doi:10.1063/1.4953036","short":"P. Wirnsberger, D. Fijan, A. Šarić, M. Neumann, C. Dellago, D. Frenkel, The Journal of Chemical Physics 144 (2016).","chicago":"Wirnsberger, P., D. Fijan, Anđela Šarić, M. Neumann, C. Dellago, and D. Frenkel. “Non-Equilibrium Simulations of Thermally Induced Electric Fields in Water.” The Journal of Chemical Physics. American Institute of Physics, 2016. https://doi.org/10.1063/1.4953036."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","oa":1,"author":[{"last_name":"Wirnsberger","first_name":"P.","full_name":"Wirnsberger, P."},{"last_name":"Fijan","full_name":"Fijan, D.","first_name":"D."},{"first_name":"Anđela","full_name":"Šarić, Anđela","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","orcid":"0000-0002-7854-2139","last_name":"Šarić"},{"last_name":"Neumann","full_name":"Neumann, M.","first_name":"M."},{"last_name":"Dellago","first_name":"C.","full_name":"Dellago, C."},{"last_name":"Frenkel","first_name":"D.","full_name":"Frenkel, D."}],"title":"Non-equilibrium simulations of thermally induced electric fields in water","keyword":["physical and theoretical chemistry","general physics and astronomy"],"date_published":"2016-06-10T00:00:00Z","quality_controlled":"1","date_created":"2021-11-29T11:08:52Z","year":"2016","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1602.02734"}],"publication":"The Journal of Chemical Physics","article_processing_charge":"No","volume":144},{"page":"7804-7817","article_type":"original","intvolume":" 12","language":[{"iso":"eng"}],"arxiv":1,"publisher":"Royal Society of Chemistry","month":"08","extern":"1","day":"19","publication_status":"published","publication_identifier":{"eissn":["1744-6848"],"issn":["1744-683X"]},"pmid":1,"status":"public","abstract":[{"lang":"eng","text":"We study phase behaviour of lipid-bilayer vesicles functionalised by ligand–receptor complexes made of synthetic DNA by introducing a modelling framework and a dedicated experimental platform. In particular, we perform Monte Carlo simulations that combine a coarse grained description of the lipid bilayer with state of art analytical models for multivalent ligand–receptor interactions. Using density of state calculations, we derive the partition function in pairs of vesicles and compute the number of ligand–receptor bonds as a function of temperature. Numerical results are compared to microscopy and fluorimetry experiments on large unilamellar vesicles decorated by DNA linkers carrying complementary overhangs. We find that vesicle aggregation is suppressed when the total number of linkers falls below a threshold value. Within the model proposed here, this is due to the higher configurational costs required to form inter-vesicle bridges as compared to intra-vesicle loops, which are in turn related to membrane deformability. Our findings and our numerical/experimental methodologies are applicable to the rational design of liposomes used as functional materials and drug delivery applications, as well as to study inter-membrane interactions in living systems, such as cell adhesion."}],"doi":"10.1039/c6sm01515h","issue":"37","date_created":"2021-11-29T11:09:55Z","article_processing_charge":"No","volume":12,"publication":"Soft Matter","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1608.05788"}],"year":"2016","quality_controlled":"1","date_published":"2016-08-19T00:00:00Z","keyword":["condensed matter physics","general chemistry"],"title":"Melting transition in lipid vesicles functionalised by mobile DNA linkers","type":"journal_article","author":[{"last_name":"Bachmann","first_name":"Stephan Jan","full_name":"Bachmann, Stephan Jan"},{"last_name":"Kotar","first_name":"Jurij","full_name":"Kotar, Jurij"},{"full_name":"Parolini, Lucia","first_name":"Lucia","last_name":"Parolini"},{"last_name":"Šarić","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","first_name":"Anđela","full_name":"Šarić, Anđela","orcid":"0000-0002-7854-2139"},{"full_name":"Cicuta, Pietro","first_name":"Pietro","last_name":"Cicuta"},{"first_name":"Lorenzo","full_name":"Di Michele, Lorenzo","last_name":"Di Michele"},{"first_name":"Bortolo Matteo","full_name":"Mognetti, Bortolo Matteo","last_name":"Mognetti"}],"oa":1,"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"ista":"Bachmann SJ, Kotar J, Parolini L, Šarić A, Cicuta P, Di Michele L, Mognetti BM. 2016. Melting transition in lipid vesicles functionalised by mobile DNA linkers. Soft Matter. 12(37), 7804–7817.","mla":"Bachmann, Stephan Jan, et al. “Melting Transition in Lipid Vesicles Functionalised by Mobile DNA Linkers.” Soft Matter, vol. 12, no. 37, Royal Society of Chemistry, 2016, pp. 7804–17, doi:10.1039/c6sm01515h.","apa":"Bachmann, S. J., Kotar, J., Parolini, L., Šarić, A., Cicuta, P., Di Michele, L., & Mognetti, B. M. (2016). Melting transition in lipid vesicles functionalised by mobile DNA linkers. Soft Matter. Royal Society of Chemistry. https://doi.org/10.1039/c6sm01515h","ieee":"S. J. Bachmann et al., “Melting transition in lipid vesicles functionalised by mobile DNA linkers,” Soft Matter, vol. 12, no. 37. Royal Society of Chemistry, pp. 7804–7817, 2016.","ama":"Bachmann SJ, Kotar J, Parolini L, et al. Melting transition in lipid vesicles functionalised by mobile DNA linkers. Soft Matter. 2016;12(37):7804-7817. doi:10.1039/c6sm01515h","short":"S.J. Bachmann, J. Kotar, L. Parolini, A. Šarić, P. Cicuta, L. Di Michele, B.M. Mognetti, Soft Matter 12 (2016) 7804–7817.","chicago":"Bachmann, Stephan Jan, Jurij Kotar, Lucia Parolini, Anđela Šarić, Pietro Cicuta, Lorenzo Di Michele, and Bortolo Matteo Mognetti. “Melting Transition in Lipid Vesicles Functionalised by Mobile DNA Linkers.” Soft Matter. Royal Society of Chemistry, 2016. https://doi.org/10.1039/c6sm01515h."},"oa_version":"Preprint","date_updated":"2021-11-29T13:09:00Z","_id":"10381","scopus_import":"1","external_id":{"arxiv":["1608.05788"],"pmid":["27722701"]}},{"year":"2016","publication":"Nature Photonics","language":[{"iso":"eng"}],"volume":10,"article_processing_charge":"No","intvolume":" 10","date_created":"2018-12-11T11:49:55Z","page":"122 - 128","title":"Coordinate-targeted fluorescence nanoscopy with multiple off states","date_published":"2016-02-01T00:00:00Z","publisher":"Nature Publishing Group","date_updated":"2021-01-12T06:47:58Z","publication_status":"published","oa_version":"None","acknowledgement":"We thank T. Gilat and E. Rothermel (both MPI) for help with preparing samples, and J. Keller for discussion. J.G.D. acknowledges support by the European Union through a Marie Curie fellowship PIEF-GA-2011-299283. S.W.H. acknowledges support by the Körber Foundation.","day":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ama":"Danzl JG, Sidenstein S, Gregor C, et al. Coordinate-targeted fluorescence nanoscopy with multiple off states. Nature Photonics. 2016;10(2):122-128. doi:10.1038/nphoton.2015.266","short":"J.G. Danzl, S. Sidenstein, C. Gregor, N. Urban, P. Ilgen, S. Jakobs, S. Hell, Nature Photonics 10 (2016) 122–128.","chicago":"Danzl, Johann G, Sven Sidenstein, Carola Gregor, Nicolai Urban, Peter Ilgen, Stefan Jakobs, and Stefan Hell. “Coordinate-Targeted Fluorescence Nanoscopy with Multiple off States.” Nature Photonics. Nature Publishing Group, 2016. https://doi.org/10.1038/nphoton.2015.266.","ieee":"J. G. Danzl et al., “Coordinate-targeted fluorescence nanoscopy with multiple off states,” Nature Photonics, vol. 10, no. 2. Nature Publishing Group, pp. 122–128, 2016.","ista":"Danzl JG, Sidenstein S, Gregor C, Urban N, Ilgen P, Jakobs S, Hell S. 2016. Coordinate-targeted fluorescence nanoscopy with multiple off states. Nature Photonics. 10(2), 122–128.","apa":"Danzl, J. G., Sidenstein, S., Gregor, C., Urban, N., Ilgen, P., Jakobs, S., & Hell, S. (2016). Coordinate-targeted fluorescence nanoscopy with multiple off states. Nature Photonics. Nature Publishing Group. https://doi.org/10.1038/nphoton.2015.266","mla":"Danzl, Johann G., et al. “Coordinate-Targeted Fluorescence Nanoscopy with Multiple off States.” Nature Photonics, vol. 10, no. 2, Nature Publishing Group, 2016, pp. 122–28, doi:10.1038/nphoton.2015.266."},"extern":"1","author":[{"full_name":"Danzl, Johann G","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","last_name":"Danzl"},{"first_name":"Sven","full_name":"Sidenstein, Sven","last_name":"Sidenstein"},{"full_name":"Gregor, Carola","first_name":"Carola","last_name":"Gregor"},{"last_name":"Urban","full_name":"Urban, Nicolai","first_name":"Nicolai"},{"first_name":"Peter","full_name":"Ilgen, Peter","last_name":"Ilgen"},{"last_name":"Jakobs","full_name":"Jakobs, Stefan","first_name":"Stefan"},{"last_name":"Hell","full_name":"Hell, Stefan","first_name":"Stefan"}],"type":"journal_article","month":"02","issue":"2","doi":"10.1038/nphoton.2015.266","publist_id":"6331","abstract":[{"lang":"eng","text":"Far-field super-resolution fluorescence microscopy discerns fluorophores residing closer than the diffraction barrier by briefly transferring them in different (typically ON and OFF) states before detection. In coordinate-targeted super-resolution variants, such as stimulated emission depletion (STED) microscopy, this state difference is created by the intensity minima and maxima of an optical pattern, causing all fluorophores to assume the off state, for instance, except at the minima. Although strong spatial confinement of the on state enables high resolution, it also subjects the fluorophores to excess intensities and state cycles at the maxima. Here, we address these issues by driving the fluorophores into a second off state that is inert to the excess light. By using reversibly switchable fluorescent proteins as labels, our approach reduces bleaching and enhances resolution and contrast in live-cell STED microscopy. Using two or more transitions to off states is a useful strategy for augmenting the power of coordinate-targeted super-resolution microscopy."}],"status":"public","_id":"1057"},{"month":"03","type":"journal_article","date_updated":"2021-01-12T06:47:59Z","oa_version":"None","publication_status":"published","acknowledgement":"We thank Prof. Y. Okada (RIKEN Quantitative Biology Center, Osaka, Japan) for the gift of β-tubulin-Halo plasmid, T. Gilat and Dr. E. Rothermel (MPIBPC, Göttingen, Germany) for cell culture and transfection, M. Pulst, J. Bienert (MPIBPC), Dr. M. John, Dr. H. Frauendorf, and co-workers (Institut für Organische und Biomolekulare Chemie, Georg-August-Universität, Göttingen, Germany) for UV/Vis, NMR, and ESI-MS spectra, Prof. M. L. Bossi (University of Buenos-Aires, Argentina) for measuring fluorescence lifetimes, and Dr. S. Vos and Prof. P. Cramer (MPIBPC) for access to a Tecan microplate reader. S.W.H. acknowledges a grant from the Bundesministerium für Bildung und Forschung (BMBF 513) within the program “Optische Technologien für Biowissenschaften und Gesundheit” (FKZ 13N11066). J.G.D. was supported by funds from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007–2013; REA grant agreement PIEF-GA-2011-299283).","author":[{"first_name":"Alexey","full_name":"Butkevich, Alexey","last_name":"Butkevich"},{"full_name":"Mitronova, Gyuzel","first_name":"Gyuzel","last_name":"Mitronova"},{"last_name":"Sidenstein","full_name":"Sidenstein, Sven","first_name":"Sven"},{"full_name":"Klocke, Jessica","first_name":"Jessica","last_name":"Klocke"},{"last_name":"Kamin","first_name":"Dirk","full_name":"Kamin, Dirk"},{"first_name":"Dirk","full_name":"Meineke, Dirk","last_name":"Meineke"},{"last_name":"D'Este","first_name":"Elisa","full_name":"D'Este, Elisa"},{"last_name":"Kraemer","full_name":"Kraemer, Philip","first_name":"Philip"},{"last_name":"Danzl","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973"},{"first_name":"Vladimir","full_name":"Belov, Vladimir","last_name":"Belov"},{"first_name":"Stefan","full_name":"Hell, Stefan","last_name":"Hell"}],"extern":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"01","citation":{"chicago":"Butkevich, Alexey, Gyuzel Mitronova, Sven Sidenstein, Jessica Klocke, Dirk Kamin, Dirk Meineke, Elisa D’Este, et al. “Fluorescent Rhodamines and Fluorogenic Carbopyronines for Super-Resolution STED Microscopy in Living Cells.” Angewandte Chemie - International Edition. Wiley-Blackwell, 2016. https://doi.org/10.1002/anie.201511018.","short":"A. Butkevich, G. Mitronova, S. Sidenstein, J. Klocke, D. Kamin, D. Meineke, E. D’Este, P. Kraemer, J.G. Danzl, V. Belov, S. Hell, Angewandte Chemie - International Edition 55 (2016) 3290–3294.","ama":"Butkevich A, Mitronova G, Sidenstein S, et al. Fluorescent rhodamines and fluorogenic carbopyronines for super-resolution STED microscopy in living cells. Angewandte Chemie - International Edition. 2016;55(10):3290-3294. doi:10.1002/anie.201511018","ieee":"A. Butkevich et al., “Fluorescent rhodamines and fluorogenic carbopyronines for super-resolution STED microscopy in living cells,” Angewandte Chemie - International Edition, vol. 55, no. 10. Wiley-Blackwell, pp. 3290–3294, 2016.","apa":"Butkevich, A., Mitronova, G., Sidenstein, S., Klocke, J., Kamin, D., Meineke, D., … Hell, S. (2016). Fluorescent rhodamines and fluorogenic carbopyronines for super-resolution STED microscopy in living cells. Angewandte Chemie - International Edition. Wiley-Blackwell. https://doi.org/10.1002/anie.201511018","mla":"Butkevich, Alexey, et al. “Fluorescent Rhodamines and Fluorogenic Carbopyronines for Super-Resolution STED Microscopy in Living Cells.” Angewandte Chemie - International Edition, vol. 55, no. 10, Wiley-Blackwell, 2016, pp. 3290–94, doi:10.1002/anie.201511018.","ista":"Butkevich A, Mitronova G, Sidenstein S, Klocke J, Kamin D, Meineke D, D’Este E, Kraemer P, Danzl JG, Belov V, Hell S. 2016. Fluorescent rhodamines and fluorogenic carbopyronines for super-resolution STED microscopy in living cells. Angewandte Chemie - International Edition. 55(10), 3290–3294."},"_id":"1059","status":"public","issue":"10","doi":"10.1002/anie.201511018","abstract":[{"text":"A range of bright and photostable rhodamines and carbopyronines with absorption maxima in the range of λ=500-630 nm were prepared, and enabled the specific labeling of cytoskeletal filaments using HaloTag technology followed by staining with 1 μm solutions of the dye-ligand conjugates. The synthesis, photophysical parameters, fluorogenic behavior, and structure-property relationships of the new dyes are discussed. Light microscopy with stimulated emission depletion (STED) provided one- and two-color images of living cells with an optical resolution of 40-60 nm.","lang":"eng"}],"publist_id":"6330","date_created":"2018-12-11T11:49:55Z","intvolume":" 55","page":"3290 - 3294","year":"2016","volume":55,"article_processing_charge":"No","language":[{"iso":"eng"}],"publication":"Angewandte Chemie - International Edition","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"publisher":"Wiley-Blackwell","title":"Fluorescent rhodamines and fluorogenic carbopyronines for super-resolution STED microscopy in living cells","date_published":"2016-03-01T00:00:00Z"}]