[{"date_updated":"2023-09-20T11:06:03Z","ddc":["006","576"],"department":[{"_id":"ToHe"},{"_id":"CaGu"},{"_id":"NiBa"}],"file_date_updated":"2020-07-14T12:44:46Z","_id":"1351","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","pubrep_id":"649","publication_identifier":{"issn":["00015903"]},"publication_status":"published","file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"5841","checksum":"4e661d9135d7f8c342e8e258dee76f3e","creator":"dernst","date_updated":"2020-07-14T12:44:46Z","file_size":755241,"date_created":"2019-01-17T15:57:29Z","file_name":"2017_ActaInformatica_Giacobbe.pdf"}],"language":[{"iso":"eng"}],"volume":54,"issue":"8","related_material":{"record":[{"relation":"earlier_version","id":"1835","status":"public"}]},"ec_funded":1,"abstract":[{"lang":"eng","text":"The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs—an important problem of interest in evolutionary biology—more efficiently than the classical simulation method. We specify the property in linear temporal logic. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights."}],"oa_version":"Published Version","scopus_import":"1","month":"12","intvolume":" 54","citation":{"mla":"Giacobbe, Mirco, et al. “Model Checking the Evolution of Gene Regulatory Networks.” Acta Informatica, vol. 54, no. 8, Springer, 2017, pp. 765–87, doi:10.1007/s00236-016-0278-x.","apa":"Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., & Petrov, T. (2017). Model checking the evolution of gene regulatory networks. Acta Informatica. Springer. https://doi.org/10.1007/s00236-016-0278-x","ama":"Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. Model checking the evolution of gene regulatory networks. Acta Informatica. 2017;54(8):765-787. doi:10.1007/s00236-016-0278-x","ieee":"M. Giacobbe, C. C. Guet, A. Gupta, T. A. Henzinger, T. Paixao, and T. Petrov, “Model checking the evolution of gene regulatory networks,” Acta Informatica, vol. 54, no. 8. Springer, pp. 765–787, 2017.","short":"M. Giacobbe, C.C. Guet, A. Gupta, T.A. Henzinger, T. Paixao, T. Petrov, Acta Informatica 54 (2017) 765–787.","chicago":"Giacobbe, Mirco, Calin C Guet, Ashutosh Gupta, Thomas A Henzinger, Tiago Paixao, and Tatjana Petrov. “Model Checking the Evolution of Gene Regulatory Networks.” Acta Informatica. Springer, 2017. https://doi.org/10.1007/s00236-016-0278-x.","ista":"Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. 2017. Model checking the evolution of gene regulatory networks. Acta Informatica. 54(8), 765–787."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publist_id":"5898","author":[{"id":"3444EA5E-F248-11E8-B48F-1D18A9856A87","first_name":"Mirco","full_name":"Giacobbe, Mirco","orcid":"0000-0001-8180-0904","last_name":"Giacobbe"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"},{"first_name":"Ashutosh","id":"335E5684-F248-11E8-B48F-1D18A9856A87","last_name":"Gupta","full_name":"Gupta, Ashutosh"},{"last_name":"Henzinger","orcid":"0000−0002−2985−7724","full_name":"Henzinger, Thomas A","first_name":"Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Tiago","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","last_name":"Paixao"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","first_name":"Tatjana","full_name":"Petrov, Tatjana","orcid":"0000-0002-9041-0905","last_name":"Petrov"}],"article_processing_charge":"No","external_id":{"isi":["000414343200003"]},"title":"Model checking the evolution of gene regulatory networks","project":[{"call_identifier":"FP7","_id":"25EE3708-B435-11E9-9278-68D0E5697425","name":"Quantitative Reactive Modeling","grant_number":"267989"},{"_id":"25832EC2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"S 11407_N23","name":"Rigorous Systems Engineering"},{"grant_number":"Z211","name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25F42A32-B435-11E9-9278-68D0E5697425"},{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"},{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"_id":"25B07788-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"250152","name":"Limits to selection in biology and in evolutionary computation"}],"has_accepted_license":"1","isi":1,"year":"2017","day":"01","publication":"Acta Informatica","page":"765 - 787","date_published":"2017-12-01T00:00:00Z","doi":"10.1007/s00236-016-0278-x","date_created":"2018-12-11T11:51:32Z","quality_controlled":"1","publisher":"Springer","oa":1},{"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Paixao, Tiago, Jorge Pérez Heredia, Dirk Sudholt, and Barbora Trubenova. “Towards a Runtime Comparison of Natural and Artificial Evolution.” Algorithmica. Springer, 2017. https://doi.org/10.1007/s00453-016-0212-1.","ista":"Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. 2017. Towards a runtime comparison of natural and artificial evolution. Algorithmica. 78(2), 681–713.","mla":"Paixao, Tiago, et al. “Towards a Runtime Comparison of Natural and Artificial Evolution.” Algorithmica, vol. 78, no. 2, Springer, 2017, pp. 681–713, doi:10.1007/s00453-016-0212-1.","short":"T. Paixao, J. Pérez Heredia, D. Sudholt, B. Trubenova, Algorithmica 78 (2017) 681–713.","ieee":"T. Paixao, J. Pérez Heredia, D. Sudholt, and B. Trubenova, “Towards a runtime comparison of natural and artificial evolution,” Algorithmica, vol. 78, no. 2. Springer, pp. 681–713, 2017.","ama":"Paixao T, Pérez Heredia J, Sudholt D, Trubenova B. Towards a runtime comparison of natural and artificial evolution. Algorithmica. 2017;78(2):681-713. doi:10.1007/s00453-016-0212-1","apa":"Paixao, T., Pérez Heredia, J., Sudholt, D., & Trubenova, B. (2017). Towards a runtime comparison of natural and artificial evolution. Algorithmica. Springer. https://doi.org/10.1007/s00453-016-0212-1"},"title":"Towards a runtime comparison of natural and artificial evolution","article_processing_charge":"No","external_id":{"isi":["000400379500013"]},"author":[{"full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","first_name":"Tiago"},{"full_name":"Pérez Heredia, Jorge","last_name":"Pérez Heredia","first_name":"Jorge"},{"first_name":"Dirk","last_name":"Sudholt","full_name":"Sudholt, Dirk"},{"first_name":"Barbora","id":"42302D54-F248-11E8-B48F-1D18A9856A87","full_name":"Trubenova, Barbora","orcid":"0000-0002-6873-2967","last_name":"Trubenova"}],"publist_id":"5931","project":[{"name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","grant_number":"618091","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"publication":"Algorithmica","day":"01","year":"2017","isi":1,"has_accepted_license":"1","date_created":"2018-12-11T11:51:27Z","doi":"10.1007/s00453-016-0212-1","date_published":"2017-06-01T00:00:00Z","page":"681 - 713","oa":1,"quality_controlled":"1","publisher":"Springer","ddc":["576"],"date_updated":"2023-09-20T11:14:42Z","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"file_date_updated":"2020-07-14T12:44:44Z","_id":"1336","pubrep_id":"658","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","language":[{"iso":"eng"}],"file":[{"date_created":"2018-12-12T10:10:19Z","file_name":"IST-2016-658-v1+1_s00453-016-0212-1.pdf","creator":"system","date_updated":"2020-07-14T12:44:44Z","file_size":710206,"file_id":"4805","checksum":"7873f665a0c598ac747c908f34cb14b9","access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"publication_status":"published","publication_identifier":{"issn":["01784617"]},"ec_funded":1,"volume":78,"issue":"2","oa_version":"Published Version","abstract":[{"text":"Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse the runtimes of EAs on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrences of new mutations is much longer than the time it takes for a mutated genotype to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a stochastic process evolving one genotype by means of mutation and selection between the resident and the mutated genotype. The probability of accepting the mutated genotype then depends on the change in fitness. We study this process, SSWM, from an algorithmic perspective, quantifying its expected optimisation time for various parameters and investigating differences to a similar evolutionary algorithm, the well-known (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient.","lang":"eng"}],"intvolume":" 78","month":"06","scopus_import":"1"},{"title":"Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis","publist_id":"6294","author":[{"last_name":"Fang","full_name":"Fang, Chong","first_name":"Chong"},{"last_name":"Nagy-Staron","orcid":"0000-0002-1391-8377","full_name":"Nagy-Staron, Anna A","first_name":"Anna A","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Martin","full_name":"Grafe, Martin","last_name":"Grafe"},{"last_name":"Heermann","full_name":"Heermann, Ralf","first_name":"Ralf"},{"first_name":"Kirsten","full_name":"Jung, Kirsten","last_name":"Jung"},{"first_name":"Susanne","last_name":"Gebhard","full_name":"Gebhard, Susanne"},{"full_name":"Mascher, Thorsten","last_name":"Mascher","first_name":"Thorsten"}],"article_processing_charge":"No","external_id":{"isi":["000398059200002"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Fang C, Nagy-Staron AA, Grafe M, Heermann R, Jung K, Gebhard S, Mascher T. 2017. Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. 104(1), 16–31.","chicago":"Fang, Chong, Anna A Nagy-Staron, Martin Grafe, Ralf Heermann, Kirsten Jung, Susanne Gebhard, and Thorsten Mascher. “Insulation and Wiring Specificity of BceR like Response Regulators and Their Target Promoters in Bacillus Subtilis.” Molecular Microbiology. Wiley-Blackwell, 2017. https://doi.org/10.1111/mmi.13597.","ama":"Fang C, Nagy-Staron AA, Grafe M, et al. Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. 2017;104(1):16-31. doi:10.1111/mmi.13597","apa":"Fang, C., Nagy-Staron, A. A., Grafe, M., Heermann, R., Jung, K., Gebhard, S., & Mascher, T. (2017). Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis. Molecular Microbiology. Wiley-Blackwell. https://doi.org/10.1111/mmi.13597","ieee":"C. Fang et al., “Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis,” Molecular Microbiology, vol. 104, no. 1. Wiley-Blackwell, pp. 16–31, 2017.","short":"C. Fang, A.A. Nagy-Staron, M. Grafe, R. Heermann, K. Jung, S. Gebhard, T. Mascher, Molecular Microbiology 104 (2017) 16–31.","mla":"Fang, Chong, et al. “Insulation and Wiring Specificity of BceR like Response Regulators and Their Target Promoters in Bacillus Subtilis.” Molecular Microbiology, vol. 104, no. 1, Wiley-Blackwell, 2017, pp. 16–31, doi:10.1111/mmi.13597."},"publisher":"Wiley-Blackwell","quality_controlled":"1","doi":"10.1111/mmi.13597","date_published":"2017-04-01T00:00:00Z","date_created":"2018-12-11T11:50:03Z","page":"16 - 31","day":"01","publication":"Molecular Microbiology","isi":1,"year":"2017","status":"public","type":"journal_article","_id":"1084","department":[{"_id":"CaGu"}],"date_updated":"2023-09-20T11:48:43Z","month":"04","intvolume":" 104","scopus_import":"1","oa_version":"None","abstract":[{"lang":"eng","text":"BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross-regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high-affinity, low-specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low-affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities."}],"volume":104,"issue":"1","language":[{"iso":"eng"}],"publication_identifier":{"issn":[" 0950382X"]},"publication_status":"published"},{"project":[{"grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"article_number":"e25192","title":"On the mechanistic nature of epistasis in a canonical cis-regulatory element","external_id":{"isi":["000404024800001"]},"article_processing_charge":"Yes","author":[{"full_name":"Lagator, Mato","last_name":"Lagator","first_name":"Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87"},{"id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","first_name":"Tiago","orcid":"0000-0003-2361-3953","full_name":"Paixao, Tiago","last_name":"Paixao"},{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas H","last_name":"Barton","full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","last_name":"Bollback"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet"}],"publist_id":"6460","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Lagator, Mato, et al. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife, vol. 6, e25192, eLife Sciences Publications, 2017, doi:10.7554/eLife.25192.","apa":"Lagator, M., Paixao, T., Barton, N. H., Bollback, J. P., & Guet, C. C. (2017). On the mechanistic nature of epistasis in a canonical cis-regulatory element. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25192","ama":"Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 2017;6. doi:10.7554/eLife.25192","ieee":"M. Lagator, T. Paixao, N. H. Barton, J. P. Bollback, and C. C. Guet, “On the mechanistic nature of epistasis in a canonical cis-regulatory element,” eLife, vol. 6. eLife Sciences Publications, 2017.","short":"M. Lagator, T. Paixao, N.H. Barton, J.P. Bollback, C.C. Guet, ELife 6 (2017).","chicago":"Lagator, Mato, Tiago Paixao, Nicholas H Barton, Jonathan P Bollback, and Calin C Guet. “On the Mechanistic Nature of Epistasis in a Canonical Cis-Regulatory Element.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25192.","ista":"Lagator M, Paixao T, Barton NH, Bollback JP, Guet CC. 2017. On the mechanistic nature of epistasis in a canonical cis-regulatory element. eLife. 6, e25192."},"oa":1,"quality_controlled":"1","publisher":"eLife Sciences Publications","date_created":"2018-12-11T11:49:23Z","doi":"10.7554/eLife.25192","date_published":"2017-05-18T00:00:00Z","publication":"eLife","day":"18","year":"2017","isi":1,"has_accepted_license":"1","pubrep_id":"841","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","_id":"954","department":[{"_id":"CaGu"},{"_id":"NiBa"},{"_id":"JoBo"}],"file_date_updated":"2020-07-14T12:48:16Z","ddc":["576"],"date_updated":"2023-09-22T10:01:17Z","intvolume":" 6","month":"05","scopus_import":"1","oa_version":"Published Version","abstract":[{"text":"Understanding the relation between genotype and phenotype remains a major challenge. The difficulty of predicting individual mutation effects, and particularly the interactions between them, has prevented the development of a comprehensive theory that links genotypic changes to their phenotypic effects. We show that a general thermodynamic framework for gene regulation, based on a biophysical understanding of protein-DNA binding, accurately predicts the sign of epistasis in a canonical cis-regulatory element consisting of overlapping RNA polymerase and repressor binding sites. Sign and magnitude of individual mutation effects are sufficient to predict the sign of epistasis and its environmental dependence. Thus, the thermodynamic model offers the correct null prediction for epistasis between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for.","lang":"eng"}],"ec_funded":1,"volume":6,"language":[{"iso":"eng"}],"file":[{"file_id":"5306","checksum":"59cdd4400fb41280122d414fea971546","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"IST-2017-841-v1+1_elife-25192-v2.pdf","date_created":"2018-12-12T10:17:49Z","creator":"system","file_size":2441529,"date_updated":"2020-07-14T12:48:16Z"},{"file_size":3752660,"date_updated":"2020-07-14T12:48:16Z","creator":"system","file_name":"IST-2017-841-v1+2_elife-25192-figures-v2.pdf","date_created":"2018-12-12T10:17:50Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_id":"5307","checksum":"b69024880558b858eb8c5d47a92b6377"}],"publication_status":"published","publication_identifier":{"issn":["2050084X"]}},{"publication_status":"published","publication_identifier":{"issn":["0005-1098"]},"language":[{"iso":"eng"}],"file":[{"file_size":1401954,"date_updated":"2018-12-12T10:11:29Z","creator":"system","file_name":"IST-2017-813-v1+1_ZerosOfNonlinearSystems.pdf","date_created":"2018-12-12T10:11:29Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_id":"4884"}],"ec_funded":1,"volume":"81C","abstract":[{"lang":"eng","text":"A nonlinear system possesses an invariance with respect to a set of transformations if its output dynamics remain invariant when transforming the input, and adjusting the initial condition accordingly. Most research has focused on invariances with respect to time-independent pointwise transformations like translational-invariance (u(t) -> u(t) + p, p in R) or scale-invariance (u(t) -> pu(t), p in R>0). In this article, we introduce the concept of s0-invariances with respect to continuous input transformations exponentially growing/decaying over time. We show that s0-invariant systems not only encompass linear time-invariant (LTI) systems with transfer functions having an irreducible zero at s0 in R, but also that the input/output relationship of nonlinear s0-invariant systems possesses properties well known from their linear counterparts. Furthermore, we extend the concept of s0-invariances to second- and higher-order s0-invariances, corresponding to invariances with respect to transformations of the time-derivatives of the input, and encompassing LTI systems with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant systems realize – under mild conditions – nth-order nonlinear differential operators: when excited by an input of a characteristic functional form, the system’s output converges to a constant value only depending on the nth (nonlinear) derivative of the input."}],"oa_version":"Published Version","scopus_import":"1","month":"06","date_updated":"2023-10-17T08:51:18Z","ddc":["000"],"file_date_updated":"2018-12-12T10:11:29Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"_id":"1007","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","pubrep_id":"813","status":"public","year":"2017","isi":1,"has_accepted_license":"1","publication":"Automatica","day":"01","page":"46 - 55","date_created":"2018-12-11T11:49:39Z","doi":"10.1016/j.automatica.2017.03.030","date_published":"2017-06-01T00:00:00Z","oa":1,"quality_controlled":"1","publisher":"International Federation of Automatic Control","citation":{"ieee":"M. Lang and E. Sontag, “Zeros of nonlinear systems with input invariances,” Automatica, vol. 81C. International Federation of Automatic Control, pp. 46–55, 2017.","short":"M. Lang, E. Sontag, Automatica 81C (2017) 46–55.","apa":"Lang, M., & Sontag, E. (2017). Zeros of nonlinear systems with input invariances. Automatica. International Federation of Automatic Control. https://doi.org/10.1016/j.automatica.2017.03.030","ama":"Lang M, Sontag E. Zeros of nonlinear systems with input invariances. Automatica. 2017;81C:46-55. doi:10.1016/j.automatica.2017.03.030","mla":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica, vol. 81C, International Federation of Automatic Control, 2017, pp. 46–55, doi:10.1016/j.automatica.2017.03.030.","ista":"Lang M, Sontag E. 2017. Zeros of nonlinear systems with input invariances. Automatica. 81C, 46–55.","chicago":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica. International Federation of Automatic Control, 2017. https://doi.org/10.1016/j.automatica.2017.03.030."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"isi":["000403513900006"]},"article_processing_charge":"Yes (in subscription journal)","publist_id":"6391","author":[{"first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz","last_name":"Lang"},{"first_name":"Eduardo","full_name":"Sontag, Eduardo","last_name":"Sontag"}],"title":"Zeros of nonlinear systems with input invariances","project":[{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425"}]},{"project":[{"name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"author":[{"first_name":"Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias","last_name":"Bergmiller"},{"id":"2B8A40DA-F248-11E8-B48F-1D18A9856A87","first_name":"Anna M","last_name":"Andersson","orcid":"0000-0003-2912-6769","full_name":"Andersson, Anna M"},{"last_name":"Tomasek","full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","first_name":"Kathrin"},{"first_name":"Enrique","last_name":"Balleza","full_name":"Balleza, Enrique"},{"full_name":"Kiviet, Daniel","last_name":"Kiviet","first_name":"Daniel"},{"orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","last_name":"Hauschild","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tkacik","full_name":"Tkacik, Gasper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gasper"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"}],"publist_id":"7064","article_processing_charge":"No","title":"Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity","citation":{"short":"T. Bergmiller, A.M. Andersson, K. Tomasek, E. Balleza, D. Kiviet, R. Hauschild, G. Tkačik, C.C. Guet, Science 356 (2017) 311–315.","ieee":"T. Bergmiller et al., “Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity,” Science, vol. 356, no. 6335. American Association for the Advancement of Science, pp. 311–315, 2017.","ama":"Bergmiller T, Andersson AM, Tomasek K, et al. Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. Science. 2017;356(6335):311-315. doi:10.1126/science.aaf4762","apa":"Bergmiller, T., Andersson, A. M., Tomasek, K., Balleza, E., Kiviet, D., Hauschild, R., … Guet, C. C. (2017). Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aaf4762","mla":"Bergmiller, Tobias, et al. “Biased Partitioning of the Multidrug Efflux Pump AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.” Science, vol. 356, no. 6335, American Association for the Advancement of Science, 2017, pp. 311–15, doi:10.1126/science.aaf4762.","ista":"Bergmiller T, Andersson AM, Tomasek K, Balleza E, Kiviet D, Hauschild R, Tkačik G, Guet CC. 2017. Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity. Science. 356(6335), 311–315.","chicago":"Bergmiller, Tobias, Anna M Andersson, Kathrin Tomasek, Enrique Balleza, Daniel Kiviet, Robert Hauschild, Gašper Tkačik, and Calin C Guet. “Biased Partitioning of the Multidrug Efflux Pump AcrAB TolC Underlies Long Lived Phenotypic Heterogeneity.” Science. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/science.aaf4762."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","publisher":"American Association for the Advancement of Science","page":"311 - 315","date_published":"2017-04-21T00:00:00Z","doi":"10.1126/science.aaf4762","date_created":"2018-12-11T11:47:48Z","year":"2017","day":"21","publication":"Science","article_type":"original","type":"journal_article","status":"public","_id":"665","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"Bio"}],"date_updated":"2024-02-21T13:49:00Z","scopus_import":1,"month":"04","intvolume":" 356","abstract":[{"lang":"eng","text":"The molecular mechanisms underlying phenotypic variation in isogenic bacterial populations remain poorly understood.We report that AcrAB-TolC, the main multidrug efflux pump of Escherichia coli, exhibits a strong partitioning bias for old cell poles by a segregation mechanism that is mediated by ternary AcrAB-TolC complex formation. Mother cells inheriting old poles are phenotypically distinct and display increased drug efflux activity relative to daughters. Consequently, we find systematic and long-lived growth differences between mother and daughter cells in the presence of subinhibitory drug concentrations. A simple model for biased partitioning predicts a population structure of long-lived and highly heterogeneous phenotypes. This straightforward mechanism of generating sustained growth rate differences at subinhibitory antibiotic concentrations has implications for understanding the emergence of multidrug resistance in bacteria."}],"oa_version":"None","issue":"6335","volume":356,"related_material":{"record":[{"relation":"popular_science","id":"5560","status":"public"}]},"publication_identifier":{"issn":["00368075"]},"publication_status":"published","language":[{"iso":"eng"}]},{"date_created":"2018-12-11T11:49:46Z","doi":"10.1002/anie.201611998","date_published":"2017-03-20T00:00:00Z","page":"4608-4611","publication":"Angewandte Chemie - International Edition","day":"20","year":"2017","isi":1,"has_accepted_license":"1","oa":1,"quality_controlled":"1","publisher":"Wiley-Blackwell","acknowledgement":"This work was supported by a grant from the European Unions Seventh Framework Programme (CIG-303564). E.R. was supported by the graduate program MolecularDrugTargets (Austrian Science Fund (FWF), W1232) and a FemTech fellowship (Austrian Research Promotion Agency, 3580812)","title":"Green-light-induced inactivation of receptor signaling using cobalamin-binding domains","article_processing_charge":"No","external_id":{"isi":["000398154000038"]},"author":[{"first_name":"Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","full_name":"Kainrath, Stephanie","last_name":"Kainrath"},{"first_name":"Manuela","last_name":"Stadler","full_name":"Stadler, Manuela"},{"first_name":"Eva","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7218-7738","full_name":"Gschaider-Reichhart, Eva","last_name":"Gschaider-Reichhart"},{"full_name":"Distel, Martin","last_name":"Distel","first_name":"Martin"},{"full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","last_name":"Janovjak","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","first_name":"Harald L"}],"publist_id":"6362","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Kainrath, Stephanie, Manuela Stadler, Eva Gschaider-Reichhart, Martin Distel, and Harald L Janovjak. “Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition. Wiley-Blackwell, 2017. https://doi.org/10.1002/anie.201611998.","ista":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. 2017. Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. 56(16), 4608–4611.","mla":"Kainrath, Stephanie, et al. “Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains.” Angewandte Chemie - International Edition, vol. 56, no. 16, Wiley-Blackwell, 2017, pp. 4608–11, doi:10.1002/anie.201611998.","apa":"Kainrath, S., Stadler, M., Gschaider-Reichhart, E., Distel, M., & Janovjak, H. L. (2017). Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. Wiley-Blackwell. https://doi.org/10.1002/anie.201611998","ama":"Kainrath S, Stadler M, Gschaider-Reichhart E, Distel M, Janovjak HL. Green-light-induced inactivation of receptor signaling using cobalamin-binding domains. Angewandte Chemie - International Edition. 2017;56(16):4608-4611. doi:10.1002/anie.201611998","ieee":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, and H. L. Janovjak, “Green-light-induced inactivation of receptor signaling using cobalamin-binding domains,” Angewandte Chemie - International Edition, vol. 56, no. 16. Wiley-Blackwell, pp. 4608–4611, 2017.","short":"S. Kainrath, M. Stadler, E. Gschaider-Reichhart, M. Distel, H.L. Janovjak, Angewandte Chemie - International Edition 56 (2017) 4608–4611."},"project":[{"call_identifier":"FP7","_id":"25548C20-B435-11E9-9278-68D0E5697425","grant_number":"303564","name":"Microbial Ion Channels for Synthetic Neurobiology"},{"name":"Molecular Drug Targets [do not use to be deleted]","grant_number":"W1232-B24","call_identifier":"FWF","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425"}],"ec_funded":1,"volume":56,"issue":"16","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"418"},{"status":"public","id":"7680","relation":"part_of_dissertation"}]},"language":[{"iso":"eng"}],"file":[{"success":1,"file_id":"5845","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2017_communications_Kainrath.pdf","date_created":"2019-01-18T09:39:55Z","file_size":2614942,"date_updated":"2019-01-18T09:39:55Z","creator":"dernst"}],"publication_status":"published","publication_identifier":{"issn":["14337851"]},"intvolume":" 56","month":"03","scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Optogenetics and photopharmacology provide spatiotemporally precise control over protein interactions and protein function in cells and animals. Optogenetic methods that are sensitive to green light and can be used to break protein complexes are not broadly available but would enable multichromatic experiments with previously inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12) binding domains of bacterial CarH transcription factors for green-light-induced receptor dissociation. In cultured cells, we observed oligomerization-induced cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding domains in the dark that was rapidly eliminated upon illumination. In zebrafish embryos expressing fusion receptors, green light endowed control over aberrant fibroblast growth factor signaling during development. Green-light-induced domain dissociation and light-inactivated receptors will critically expand the optogenetic toolbox for control of biological processes."}],"file_date_updated":"2019-01-18T09:39:55Z","department":[{"_id":"CaGu"},{"_id":"HaJa"}],"ddc":["540"],"date_updated":"2024-03-27T23:30:13Z","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","_id":"1028"},{"_id":"704","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","pubrep_id":"890","status":"public","date_updated":"2024-03-27T23:30:27Z","ddc":["576"],"file_date_updated":"2020-07-14T12:47:48Z","department":[{"_id":"CaGu"}],"abstract":[{"lang":"eng","text":"How the organization of genes on a chromosome shapes adaptation is essential for understanding evolutionary paths. Here, we investigate how adaptation to rapidly increasing levels of antibiotic depends on the chromosomal neighborhood of a drug-resistance gene inserted at different positions of the Escherichia coli chromosome. Using a dual-fluorescence reporter that allows us to distinguish gene amplifications from other up-mutations, we track in real-time adaptive changes in expression of the drug-resistance gene. We find that the relative contribution of several mutation types differs systematically between loci due to properties of neighboring genes: essentiality, expression, orientation, termination, and presence of duplicates. These properties determine rate and fitness effects of gene amplification, deletions, and mutations compromising transcriptional termination. Thus, the adaptive potential of a gene under selection is a system-property with a complex genetic basis that is specific for each chromosomal locus, and it can be inferred from detailed functional and genomic data."}],"oa_version":"Published Version","scopus_import":1,"intvolume":" 6","month":"07","publication_status":"published","publication_identifier":{"issn":["2050084X"]},"language":[{"iso":"eng"}],"file":[{"checksum":"6b908b5db9f61f6820ebd7f8fa815571","file_id":"4975","content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2018-12-12T10:12:54Z","file_name":"IST-2017-890-v1+1_elife-25100-v1.pdf","date_updated":"2020-07-14T12:47:48Z","file_size":2092088,"creator":"system"},{"file_id":"4976","checksum":"ca21530389b720243552678125fdba35","content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2018-12-12T10:12:55Z","file_name":"IST-2017-890-v1+2_elife-25100-figures-v1.pdf","date_updated":"2020-07-14T12:47:48Z","file_size":3428681,"creator":"system"}],"related_material":{"record":[{"id":"5564","status":"public","relation":"popular_science"},{"relation":"dissertation_contains","id":"26","status":"public"}]},"volume":6,"article_number":"e25100","citation":{"chicago":"Steinrück, Magdalena, and Calin C Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25100.","ista":"Steinrück M, Guet CC. 2017. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. eLife. 6, e25100.","mla":"Steinrück, Magdalena, and Calin C. Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” ELife, vol. 6, e25100, eLife Sciences Publications, 2017, doi:10.7554/eLife.25100.","apa":"Steinrück, M., & Guet, C. C. (2017). Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25100","ama":"Steinrück M, Guet CC. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. eLife. 2017;6. doi:10.7554/eLife.25100","short":"M. Steinrück, C.C. Guet, ELife 6 (2017).","ieee":"M. Steinrück and C. C. Guet, “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection,” eLife, vol. 6. eLife Sciences Publications, 2017."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Magdalena","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","full_name":"Steinrück, Magdalena","orcid":"0000-0003-1229-9719","last_name":"Steinrück"},{"last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"6990","title":"Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection","oa":1,"publisher":"eLife Sciences Publications","quality_controlled":"1","year":"2017","has_accepted_license":"1","publication":"eLife","day":"25","date_created":"2018-12-11T11:48:01Z","date_published":"2017-07-25T00:00:00Z","doi":"10.7554/eLife.25100"},{"abstract":[{"text":"Mutator strains are expected to evolve when the availability and effect of beneficial mutations are high enough to counteract the disadvantage from deleterious mutations that will inevitably accumulate. As the population becomes more adapted to its environment, both availability and effect of beneficial mutations necessarily decrease and mutation rates are predicted to decrease. It has been shown that certain molecular mechanisms can lead to increased mutation rates when the organism finds itself in a stressful environment. While this may be a correlated response to other functions, it could also be an adaptive mechanism, raising mutation rates only when it is most advantageous. Here, we use a mathematical model to investigate the plausibility of the adaptive hypothesis. We show that such a mechanism can be mantained if the population is subjected to diverse stresses. By simulating various antibiotic treatment schemes, we find that combination treatments can reduce the effectiveness of second-order selection on stress-induced mutagenesis. We discuss the implications of our results to strategies of antibiotic therapy.","lang":"eng"}],"oa_version":"Published Version","scopus_import":1,"month":"07","intvolume":" 13","publication_identifier":{"issn":["1553734X"]},"publication_status":"published","file":[{"date_updated":"2020-07-14T12:47:46Z","file_size":3775716,"creator":"system","date_created":"2018-12-12T10:15:01Z","file_name":"IST-2017-894-v1+1_journal.pcbi.1005609.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"5117","checksum":"9143c290fa6458ed2563bff4b295554a"}],"language":[{"iso":"eng"}],"volume":13,"related_material":{"record":[{"relation":"research_data","status":"public","id":"9849"},{"relation":"research_data","status":"public","id":"9850"},{"id":"9851","status":"public","relation":"research_data"},{"id":"9852","status":"public","relation":"research_data"},{"id":"6263","status":"public","relation":"dissertation_contains"}]},"issue":"7","ec_funded":1,"_id":"696","article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","pubrep_id":"894","date_updated":"2024-03-27T23:30:28Z","ddc":["576"],"department":[{"_id":"ToBo"},{"_id":"NiBa"},{"_id":"CaGu"}],"file_date_updated":"2020-07-14T12:47:46Z","publisher":"Public Library of Science","quality_controlled":"1","oa":1,"has_accepted_license":"1","year":"2017","day":"18","publication":"PLoS Computational Biology","date_published":"2017-07-18T00:00:00Z","doi":"10.1371/journal.pcbi.1005609","date_created":"2018-12-11T11:47:58Z","article_number":"e1005609","project":[{"call_identifier":"FP7","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","grant_number":"618091","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation"}],"citation":{"apa":"Lukacisinova, M., Novak, S., & Paixao, T. (2017). Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1005609","ama":"Lukacisinova M, Novak S, Paixao T. Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. 2017;13(7). doi:10.1371/journal.pcbi.1005609","ieee":"M. Lukacisinova, S. Novak, and T. Paixao, “Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes,” PLoS Computational Biology, vol. 13, no. 7. Public Library of Science, 2017.","short":"M. Lukacisinova, S. Novak, T. Paixao, PLoS Computational Biology 13 (2017).","mla":"Lukacisinova, Marta, et al. “Stress Induced Mutagenesis: Stress Diversity Facilitates the Persistence of Mutator Genes.” PLoS Computational Biology, vol. 13, no. 7, e1005609, Public Library of Science, 2017, doi:10.1371/journal.pcbi.1005609.","ista":"Lukacisinova M, Novak S, Paixao T. 2017. Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes. PLoS Computational Biology. 13(7), e1005609.","chicago":"Lukacisinova, Marta, Sebastian Novak, and Tiago Paixao. “Stress Induced Mutagenesis: Stress Diversity Facilitates the Persistence of Mutator Genes.” PLoS Computational Biology. Public Library of Science, 2017. https://doi.org/10.1371/journal.pcbi.1005609."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Marta","id":"4342E402-F248-11E8-B48F-1D18A9856A87","full_name":"Lukacisinova, Marta","orcid":"0000-0002-2519-8004","last_name":"Lukacisinova"},{"first_name":"Sebastian","id":"461468AE-F248-11E8-B48F-1D18A9856A87","last_name":"Novak","full_name":"Novak, Sebastian","orcid":"0000-0002-2519-824X"},{"id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","first_name":"Tiago","last_name":"Paixao","orcid":"0000-0003-2361-3953","full_name":"Paixao, Tiago"}],"publist_id":"7004","title":"Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes"},{"status":"public","type":"journal_article","_id":"735","department":[{"_id":"CaHe"},{"_id":"CaGu"},{"_id":"GaTk"}],"date_updated":"2024-03-27T23:30:38Z","intvolume":" 43","month":"10","scopus_import":"1","oa_version":"None","abstract":[{"text":"Cell-cell contact formation constitutes an essential step in evolution, leading to the differentiation of specialized cell types. However, remarkably little is known about whether and how the interplay between contact formation and fate specification affects development. Here, we identify a positive feedback loop between cell-cell contact duration, morphogen signaling, and mesendoderm cell-fate specification during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for ppl cell-fate specification. We further show that Nodal signaling promotes ppl cell-cell contact duration, generating a positive feedback loop between ppl cell-cell contact duration and cell-fate specification. Finally, by combining mathematical modeling and experimentation, we show that this feedback determines whether anterior axial mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the interdependent activities of cell-cell signaling and contact formation control fate diversification within the developing embryo.","lang":"eng"}],"ec_funded":1,"related_material":{"record":[{"relation":"dissertation_contains","id":"961","status":"public"},{"relation":"dissertation_contains","id":"8350","status":"public"}]},"volume":43,"issue":"2","language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"issn":["15345807"]},"project":[{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"call_identifier":"FWF","_id":"252DD2A6-B435-11E9-9278-68D0E5697425","grant_number":"I2058","name":"Cell segregation in gastrulation: the role of cell fate specification"}],"title":"An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate","article_processing_charge":"No","external_id":{"isi":["000413443700011"]},"author":[{"first_name":"Vanessa","id":"419EECCC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2676-3367","full_name":"Barone, Vanessa","last_name":"Barone"},{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz","last_name":"Lang","full_name":"Lang, Moritz"},{"orcid":"0000-0003-4761-5996","full_name":"Krens, Gabriel","last_name":"Krens","id":"2B819732-F248-11E8-B48F-1D18A9856A87","first_name":"Gabriel"},{"last_name":"Pradhan","full_name":"Pradhan, Saurabh","first_name":"Saurabh"},{"id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","first_name":"Shayan","last_name":"Shamipour","full_name":"Shamipour, Shayan"},{"orcid":"0000-0002-6453-8075","full_name":"Sako, Keisuke","last_name":"Sako","id":"3BED66BE-F248-11E8-B48F-1D18A9856A87","first_name":"Keisuke"},{"id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","first_name":"Mateusz K","full_name":"Sikora, Mateusz K","last_name":"Sikora"},{"last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg"}],"publist_id":"6934","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Barone V, Lang M, Krens G, Pradhan S, Shamipour S, Sako K, Sikora MK, Guet CC, Heisenberg C-PJ. 2017. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 43(2), 198–211.","chicago":"Barone, Vanessa, Moritz Lang, Gabriel Krens, Saurabh Pradhan, Shayan Shamipour, Keisuke Sako, Mateusz K Sikora, Calin C Guet, and Carl-Philipp J Heisenberg. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell. Cell Press, 2017. https://doi.org/10.1016/j.devcel.2017.09.014.","ama":"Barone V, Lang M, Krens G, et al. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 2017;43(2):198-211. doi:10.1016/j.devcel.2017.09.014","apa":"Barone, V., Lang, M., Krens, G., Pradhan, S., Shamipour, S., Sako, K., … Heisenberg, C.-P. J. (2017). An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. Cell Press. https://doi.org/10.1016/j.devcel.2017.09.014","short":"V. Barone, M. Lang, G. Krens, S. Pradhan, S. Shamipour, K. Sako, M.K. Sikora, C.C. Guet, C.-P.J. Heisenberg, Developmental Cell 43 (2017) 198–211.","ieee":"V. Barone et al., “An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate,” Developmental Cell, vol. 43, no. 2. Cell Press, pp. 198–211, 2017.","mla":"Barone, Vanessa, et al. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell, vol. 43, no. 2, Cell Press, 2017, pp. 198–211, doi:10.1016/j.devcel.2017.09.014."},"quality_controlled":"1","publisher":"Cell Press","date_created":"2018-12-11T11:48:13Z","date_published":"2017-10-23T00:00:00Z","doi":"10.1016/j.devcel.2017.09.014","page":"198 - 211","publication":"Developmental Cell","day":"23","year":"2017","isi":1},{"publication":"ACS Synthetic Biology","language":[{"iso":"eng"}],"day":"05","publication_status":"published","year":"2016","date_created":"2018-12-11T11:49:40Z","doi":"10.1021/acssynbio.6b00013","volume":5,"date_published":"2016-05-05T00:00:00Z","issue":"10","page":"1098 - 1107","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.","oa_version":"None","abstract":[{"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.","lang":"eng"}],"intvolume":" 5","month":"05","publisher":"American Chemical Society","quality_controlled":"1","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","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.","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.","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.","short":"R. Gnügge, L. Dharmarajan, M. Lang, J. Stelling, ACS Synthetic Biology 5 (2016) 1098–1107.","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","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","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."},"date_updated":"2021-01-12T06:47:37Z","department":[{"_id":"CaGu"}],"title":"An orthogonal permease–inducer–repressor feedback loop shows bistability","author":[{"first_name":"Robert","full_name":"Gnügge, Robert","last_name":"Gnügge"},{"full_name":"Dharmarajan, Lekshmi","last_name":"Dharmarajan","first_name":"Lekshmi"},{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz","full_name":"Lang, Moritz","last_name":"Lang"},{"first_name":"Jörg","full_name":"Stelling, Jörg","last_name":"Stelling"}],"publist_id":"6390","_id":"1008","status":"public","type":"journal_article"},{"publication_status":"published","language":[{"iso":"eng"}],"file":[{"file_id":"5095","checksum":"781bc3ffd30b2dd65b7727c5a285fc78","relation":"main_file","access_level":"local","content_type":"application/pdf","file_name":"IST-2017-811-v1+1_modular_parameter_identification.pdf","date_created":"2018-12-12T10:14:41Z","creator":"system","file_size":871964,"date_updated":"2020-07-14T12:44:37Z"}],"volume":38,"issue":"6","abstract":[{"text":"The increasing complexity of dynamic models in systems and synthetic biology poses computational challenges especially for the identification of model parameters. While modularization of the corresponding optimization problems could help reduce the “curse of dimensionality,” abundant feedback and crosstalk mechanisms prohibit a simple decomposition of most biomolecular networks into subnetworks, or modules. Drawing on ideas from network modularization and multiple-shooting optimization, we present here a modular parameter identification approach that explicitly allows for such interdependencies. Interfaces between our modules are given by the experimentally measured molecular species. This definition allows deriving good (initial) estimates for the inter-module communication directly from the experimental data. Given these estimates, the states and parameter sensitivities of different modules can be integrated independently. To achieve consistency between modules, we iteratively adjust the estimates for inter-module communication while optimizing the parameters. After convergence to an optimal parameter set---but not during earlier iterations---the intermodule communication as well as the individual modules\\' state dynamics agree with the dynamics of the nonmodularized network. Our modular parameter identification approach allows for easy parallelization; it can reduce the computational complexity for larger networks and decrease the probability to converge to suboptimal local minima. We demonstrate the algorithm\\'s performance in parameter estimation for two biomolecular networks, a synthetic genetic oscillator and a mammalian signaling pathway.","lang":"eng"}],"oa_version":"Submitted Version","scopus_import":1,"intvolume":" 38","month":"11","date_updated":"2021-01-12T06:48:49Z","ddc":["003","518","570","621"],"file_date_updated":"2020-07-14T12:44:37Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"_id":"1170","type":"journal_article","pubrep_id":"811","status":"public","year":"2016","has_accepted_license":"1","publication":"SIAM Journal on Scientific Computing","day":"15","page":"B988 - B1008","date_created":"2018-12-11T11:50:31Z","date_published":"2016-11-15T00:00:00Z","doi":"10.1137/15M103306X","quality_controlled":"1","publisher":"Society for Industrial and Applied Mathematics ","citation":{"ista":"Lang M, Stelling J. 2016. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 38(6), B988–B1008.","chicago":"Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics , 2016. https://doi.org/10.1137/15M103306X.","ama":"Lang M, Stelling J. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 2016;38(6):B988-B1008. doi:10.1137/15M103306X","apa":"Lang, M., & Stelling, J. (2016). Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics . https://doi.org/10.1137/15M103306X","ieee":"M. Lang and J. Stelling, “Modular parameter identification of biomolecular networks,” SIAM Journal on Scientific Computing, vol. 38, no. 6. Society for Industrial and Applied Mathematics , pp. B988–B1008, 2016.","short":"M. Lang, J. Stelling, SIAM Journal on Scientific Computing 38 (2016) B988–B1008.","mla":"Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing, vol. 38, no. 6, Society for Industrial and Applied Mathematics , 2016, pp. B988–1008, doi:10.1137/15M103306X."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","author":[{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz","last_name":"Lang","full_name":"Lang, Moritz"},{"first_name":"Jörg","last_name":"Stelling","full_name":"Stelling, Jörg"}],"publist_id":"6186","title":"Modular parameter identification of biomolecular networks"},{"oa_version":"Preprint","abstract":[{"lang":"eng","text":"Theoretical and numerical aspects of aerodynamic efficiency of propulsion systems coupled to the boundary layer of a fuselage are studied. We discuss the effects of local flow fields, which are affected both by conservative flow acceleration as well as total pressure losses, on the efficiency of boundary layer immersed propulsion devices. We introduce the concept of a boundary layer retardation turbine that helps reduce skin friction over the fuselage. We numerically investigate efficiency gains offered by boundary layer and wake interacting devices. We discuss the results in terms of a total energy consumption framework and show that efficiency gains of any device depend on all the other elements of the propulsion system."}],"month":"06","oa":1,"main_file_link":[{"url":"https://ntrs.nasa.gov/search.jsp?R=20160010167&hterms=Fuselage+boundary+layer+ingestion+propulsion+applied+thin+haul+commuter+aircraft+optimal+efficiency&qs=N%3D0%26Ntk%3DAll%26Ntt%3DFuselage%2520boundary%2520layer%2520ingestion%2520propulsion%2520applied%2520to%2520a%2520thin%2520haul%2520commuter%2520aircraft%2520for%2520optimal%2520efficiency%26Ntx%3Dmode%2520matchallpartial%26Nm%3D123%7CCollection%7CNASA%2520STI%7C%7C17%7CCollection%7CNACA","open_access":"1"}],"publisher":"AIAA","quality_controlled":"1","scopus_import":1,"language":[{"iso":"eng"}],"day":"01","year":"2016","publication_status":"published","date_created":"2018-12-11T11:50:47Z","date_published":"2016-06-01T00:00:00Z","doi":"10.2514/6.2016-3764","page":"1 - 19","_id":"1220","status":"public","conference":{"start_date":"2016-06-13","location":"Washington, D.C., USA","end_date":"2016-06-17","name":"AIAA: Aviation Technology, Integration, and Operations Conference"},"type":"conference","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Mikić G, Stoll A, Bevirt J, Grah R, Moore M. 2016. Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency. AIAA: Aviation Technology, Integration, and Operations Conference, 1–19.","chicago":"Mikić, Gregor, Alex Stoll, Joe Bevirt, Rok Grah, and Mark Moore. “Fuselage Boundary Layer Ingestion Propulsion Applied to a Thin Haul Commuter Aircraft for Optimal Efficiency,” 1–19. AIAA, 2016. https://doi.org/10.2514/6.2016-3764.","short":"G. Mikić, A. Stoll, J. Bevirt, R. Grah, M. Moore, in:, AIAA, 2016, pp. 1–19.","ieee":"G. Mikić, A. Stoll, J. Bevirt, R. Grah, and M. Moore, “Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency,” presented at the AIAA: Aviation Technology, Integration, and Operations Conference, Washington, D.C., USA, 2016, pp. 1–19.","ama":"Mikić G, Stoll A, Bevirt J, Grah R, Moore M. Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency. In: AIAA; 2016:1-19. doi:10.2514/6.2016-3764","apa":"Mikić, G., Stoll, A., Bevirt, J., Grah, R., & Moore, M. (2016). Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency (pp. 1–19). Presented at the AIAA: Aviation Technology, Integration, and Operations Conference, Washington, D.C., USA: AIAA. https://doi.org/10.2514/6.2016-3764","mla":"Mikić, Gregor, et al. Fuselage Boundary Layer Ingestion Propulsion Applied to a Thin Haul Commuter Aircraft for Optimal Efficiency. AIAA, 2016, pp. 1–19, doi:10.2514/6.2016-3764."},"date_updated":"2023-02-21T10:17:50Z","title":"Fuselage boundary layer ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publist_id":"6114","author":[{"last_name":"Mikić","full_name":"Mikić, Gregor","first_name":"Gregor"},{"last_name":"Stoll","full_name":"Stoll, Alex","first_name":"Alex"},{"full_name":"Bevirt, Joe","last_name":"Bevirt","first_name":"Joe"},{"id":"483E70DE-F248-11E8-B48F-1D18A9856A87","first_name":"Rok","last_name":"Grah","orcid":"0000-0003-2539-3560","full_name":"Grah, Rok"},{"full_name":"Moore, Mark","last_name":"Moore","first_name":"Mark"}]},{"title":"Compounds that select against the tetracycline-resistance efflux pump","author":[{"last_name":"Stone","full_name":"Stone, Laura","first_name":"Laura"},{"first_name":"Michael","full_name":"Baym, Michael","last_name":"Baym"},{"first_name":"Tami","last_name":"Lieberman","full_name":"Lieberman, Tami"},{"orcid":"0000-0003-0876-3187","full_name":"Chait, Remy P","last_name":"Chait","first_name":"Remy P","id":"3464AE84-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Clardy, Jon","last_name":"Clardy","first_name":"Jon"},{"first_name":"Roy","last_name":"Kishony","full_name":"Kishony, Roy"}],"publist_id":"6026","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"apa":"Stone, L., Baym, M., Lieberman, T., Chait, R. P., Clardy, J., & Kishony, R. (2016). Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. Nature Publishing Group. https://doi.org/10.1038/nchembio.2176","ama":"Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. 2016;12(11):902-904. doi:10.1038/nchembio.2176","short":"L. Stone, M. Baym, T. Lieberman, R.P. Chait, J. Clardy, R. Kishony, Nature Chemical Biology 12 (2016) 902–904.","ieee":"L. Stone, M. Baym, T. Lieberman, R. P. Chait, J. Clardy, and R. Kishony, “Compounds that select against the tetracycline-resistance efflux pump,” Nature Chemical Biology, vol. 12, no. 11. Nature Publishing Group, pp. 902–904, 2016.","mla":"Stone, Laura, et al. “Compounds That Select against the Tetracycline-Resistance Efflux Pump.” Nature Chemical Biology, vol. 12, no. 11, Nature Publishing Group, 2016, pp. 902–04, doi:10.1038/nchembio.2176.","ista":"Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. 2016. Compounds that select against the tetracycline-resistance efflux pump. Nature Chemical Biology. 12(11), 902–904.","chicago":"Stone, Laura, Michael Baym, Tami Lieberman, Remy P Chait, Jon Clardy, and Roy Kishony. “Compounds That Select against the Tetracycline-Resistance Efflux Pump.” Nature Chemical Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/nchembio.2176."},"oa":1,"quality_controlled":"1","publisher":"Nature Publishing Group","acknowledgement":"This work was supported in part by National Institute of Allergy and Infectious Diseases grant U54 AI057159, US National Institutes of Health grants R01 GM081617 (to R.K.) and GM086258 (to J.C.), European Research Council FP7 ERC grant 281891 (to R.K.) and a National Science Foundation Graduate Fellowship (to L.K.S.).\r\n","date_created":"2018-12-11T11:51:10Z","doi":"10.1038/nchembio.2176","date_published":"2016-11-01T00:00:00Z","page":"902 - 904","publication":"Nature Chemical Biology","day":"01","year":"2016","status":"public","type":"journal_article","_id":"1290","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"date_updated":"2021-01-12T06:49:39Z","intvolume":" 12","month":"11","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069154/","open_access":"1"}],"scopus_import":1,"oa_version":"Preprint","abstract":[{"lang":"eng","text":"We developed a competition-based screening strategy to identify compounds that invert the selective advantage of antibiotic resistance. Using our assay, we screened over 19,000 compounds for the ability to select against the TetA tetracycline-resistance efflux pump in Escherichia coli and identified two hits, β-thujaplicin and disulfiram. Treating a tetracycline-resistant population with β-thujaplicin selects for loss of the resistance gene, enabling an effective second-phase treatment with doxycycline."}],"issue":"11","volume":12,"language":[{"iso":"eng"}],"publication_status":"published"},{"project":[{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"}],"article_number":"7526722","title":"Scale-invariant systems realize nonlinear differential operators","publist_id":"5950","author":[{"full_name":"Lang, Moritz","last_name":"Lang","first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sontag","full_name":"Sontag, Eduardo","first_name":"Eduardo"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Lang, Moritz, and Eduardo Sontag. “Scale-Invariant Systems Realize Nonlinear Differential Operators,” Vol. 2016–July. IEEE, 2016. https://doi.org/10.1109/ACC.2016.7526722.","ista":"Lang M, Sontag E. 2016. Scale-invariant systems realize nonlinear differential operators. ACC: American Control Conference vol. 2016–July, 7526722.","mla":"Lang, Moritz, and Eduardo Sontag. Scale-Invariant Systems Realize Nonlinear Differential Operators. Vol. 2016–July, 7526722, IEEE, 2016, doi:10.1109/ACC.2016.7526722.","ieee":"M. Lang and E. Sontag, “Scale-invariant systems realize nonlinear differential operators,” presented at the ACC: American Control Conference, Boston, MA, USA, 2016, vol. 2016–July.","short":"M. Lang, E. Sontag, in:, IEEE, 2016.","apa":"Lang, M., & Sontag, E. (2016). Scale-invariant systems realize nonlinear differential operators (Vol. 2016–July). Presented at the ACC: American Control Conference, Boston, MA, USA: IEEE. https://doi.org/10.1109/ACC.2016.7526722","ama":"Lang M, Sontag E. Scale-invariant systems realize nonlinear differential operators. In: Vol 2016-July. IEEE; 2016. doi:10.1109/ACC.2016.7526722"},"quality_controlled":"1","publisher":"IEEE","acknowledgement":"The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n° [291734]. Work supported in part by grants AFOSR FA9550-14-1-0060 and NIH 1R01GM100473.","doi":"10.1109/ACC.2016.7526722","date_published":"2016-07-28T00:00:00Z","date_created":"2018-12-11T11:51:21Z","day":"28","has_accepted_license":"1","year":"2016","status":"public","pubrep_id":"810","type":"conference","conference":{"name":"ACC: American Control Conference","location":"Boston, MA, USA","end_date":"2016-07-08","start_date":"2016-07-06"},"_id":"1320","file_date_updated":"2020-07-14T12:44:43Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"ddc":["003","621"],"date_updated":"2021-01-12T06:49:51Z","month":"07","scopus_import":1,"oa_version":"Preprint","abstract":[{"text":"In recent years, several biomolecular systems have been shown to be scale-invariant (SI), i.e. to show the same output dynamics when exposed to geometrically scaled input signals (u → pu, p > 0) after pre-adaptation to accordingly scaled constant inputs. In this article, we show that SI systems-as well as systems invariant with respect to other input transformations-can realize nonlinear differential operators: when excited by inputs obeying functional forms characteristic for a given class of invariant systems, the systems' outputs converge to constant values directly quantifying the speed of the input.","lang":"eng"}],"volume":"2016-July","ec_funded":1,"file":[{"checksum":"7219432b43defc62a0d45f48d4ce6a19","file_id":"5203","content_type":"application/pdf","access_level":"local","relation":"main_file","date_created":"2018-12-12T10:16:17Z","file_name":"IST-2017-810-v1+1_root.pdf","date_updated":"2020-07-14T12:44:43Z","file_size":539166,"creator":"system"}],"language":[{"iso":"eng"}],"publication_status":"published"},{"volume":7,"file":[{"file_id":"5039","checksum":"ef147bcbb8bd37e9079cf3ce06f5815d","content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2018-12-12T10:13:52Z","file_name":"IST-2016-662-v1+1_ncomms10333.pdf","date_updated":"2020-07-14T12:44:44Z","file_size":1844107,"creator":"system"}],"language":[{"iso":"eng"}],"publication_status":"published","month":"01","intvolume":" 7","scopus_import":1,"oa_version":"Published Version","abstract":[{"text":"Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized antibiotic sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected by resistance to the antibiotic. How do such mixed and heterogeneous conditions influence the selective advantage or disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels of tetracyclines potentiate selection for or against tetracycline resistance around localized sources of almost any toxin or stress. Furthermore, certain stresses generate alternating rings of selection for and against resistance around a localized source of the antibiotic. In these conditions, localized antibiotic sources, even at high strengths, can actually produce a net selection against resistance to the antibiotic. Our results show that interactions between the effects of an antibiotic and other stresses in inhomogeneous environments can generate pervasive, complex patterns of selection both for and against antibiotic resistance.","lang":"eng"}],"file_date_updated":"2020-07-14T12:44:44Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"ddc":["570","579"],"date_updated":"2021-01-12T06:49:57Z","status":"public","pubrep_id":"662","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"1332","doi":"10.1038/ncomms10333","date_published":"2016-01-20T00:00:00Z","date_created":"2018-12-11T11:51:25Z","day":"20","publication":"Nature Communications","has_accepted_license":"1","year":"2016","publisher":"Nature Publishing Group","quality_controlled":"1","oa":1,"acknowledgement":"This work was partially supported by US National Institutes of Health grant R01-GM081617, Israeli Centers of Research Excellence I-CORE Program ISF Grant No. 152/11, and the European Research Council FP7 ERC Grant 281891.","title":"Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments","author":[{"full_name":"Chait, Remy P","orcid":"0000-0003-0876-3187","last_name":"Chait","first_name":"Remy P","id":"3464AE84-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Palmer","full_name":"Palmer, Adam","first_name":"Adam"},{"first_name":"Idan","last_name":"Yelin","full_name":"Yelin, Idan"},{"full_name":"Kishony, Roy","last_name":"Kishony","first_name":"Roy"}],"publist_id":"5936","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Chait, Remy P, Adam Palmer, Idan Yelin, and Roy Kishony. “Pervasive Selection for and against Antibiotic Resistance in Inhomogeneous Multistress Environments.” Nature Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms10333.","ista":"Chait RP, Palmer A, Yelin I, Kishony R. 2016. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. 7, 10333.","mla":"Chait, Remy P., et al. “Pervasive Selection for and against Antibiotic Resistance in Inhomogeneous Multistress Environments.” Nature Communications, vol. 7, 10333, Nature Publishing Group, 2016, doi:10.1038/ncomms10333.","short":"R.P. Chait, A. Palmer, I. Yelin, R. Kishony, Nature Communications 7 (2016).","ieee":"R. P. Chait, A. Palmer, I. Yelin, and R. Kishony, “Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments,” Nature Communications, vol. 7. Nature Publishing Group, 2016.","ama":"Chait RP, Palmer A, Yelin I, Kishony R. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. 2016;7. doi:10.1038/ncomms10333","apa":"Chait, R. P., Palmer, A., Yelin, I., & Kishony, R. (2016). Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms10333"},"article_number":"10333"},{"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Baym M, Lieberman T, Kelsic E, Chait RP, Gross R, Yelin I, Kishony R. 2016. Spatiotemporal microbial evolution on antibiotic landscapes. Science. 353(6304), 1147–1151.","chicago":"Baym, Michael, Tami Lieberman, Eric Kelsic, Remy P Chait, Rotem Gross, Idan Yelin, and Roy Kishony. “Spatiotemporal Microbial Evolution on Antibiotic Landscapes.” Science. American Association for the Advancement of Science, 2016. https://doi.org/10.1126/science.aag0822.","short":"M. Baym, T. Lieberman, E. Kelsic, R.P. Chait, R. Gross, I. Yelin, R. Kishony, Science 353 (2016) 1147–1151.","ieee":"M. Baym et al., “Spatiotemporal microbial evolution on antibiotic landscapes,” Science, vol. 353, no. 6304. American Association for the Advancement of Science, pp. 1147–1151, 2016.","ama":"Baym M, Lieberman T, Kelsic E, et al. Spatiotemporal microbial evolution on antibiotic landscapes. Science. 2016;353(6304):1147-1151. doi:10.1126/science.aag0822","apa":"Baym, M., Lieberman, T., Kelsic, E., Chait, R. P., Gross, R., Yelin, I., & Kishony, R. (2016). Spatiotemporal microbial evolution on antibiotic landscapes. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aag0822","mla":"Baym, Michael, et al. “Spatiotemporal Microbial Evolution on Antibiotic Landscapes.” Science, vol. 353, no. 6304, American Association for the Advancement of Science, 2016, pp. 1147–51, doi:10.1126/science.aag0822."},"date_updated":"2021-01-12T06:50:01Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"title":"Spatiotemporal microbial evolution on antibiotic landscapes","author":[{"full_name":"Baym, Michael","last_name":"Baym","first_name":"Michael"},{"first_name":"Tami","last_name":"Lieberman","full_name":"Lieberman, Tami"},{"first_name":"Eric","last_name":"Kelsic","full_name":"Kelsic, Eric"},{"first_name":"Remy P","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","last_name":"Chait","orcid":"0000-0003-0876-3187","full_name":"Chait, Remy P"},{"full_name":"Gross, Rotem","last_name":"Gross","first_name":"Rotem"},{"first_name":"Idan","full_name":"Yelin, Idan","last_name":"Yelin"},{"first_name":"Roy","last_name":"Kishony","full_name":"Kishony, Roy"}],"publist_id":"5911","_id":"1342","status":"public","type":"journal_article","language":[{"iso":"eng"}],"publication":"Science","day":"09","year":"2016","publication_status":"published","date_created":"2018-12-11T11:51:29Z","volume":353,"date_published":"2016-09-09T00:00:00Z","issue":"6304","doi":"10.1126/science.aag0822","page":"1147 - 1151","oa_version":"Preprint","abstract":[{"text":"A key aspect of bacterial survival is the ability to evolve while migrating across spatially varying environmental challenges. Laboratory experiments, however, often study evolution in well-mixed systems. Here, we introduce an experimental device, the microbial evolution and growth arena (MEGA)-plate, in which bacteria spread and evolved on a large antibiotic landscape (120 × 60 centimeters) that allowed visual observation of mutation and selection in a migrating bacterial front.While resistance increased consistently, multiple coexisting lineages diversified both phenotypically and genotypically. Analyzing mutants at and behind the propagating front,we found that evolution is not always led by the most resistant mutants; highly resistant mutants may be trapped behindmore sensitive lineages.TheMEGA-plate provides a versatile platformfor studying microbial adaption and directly visualizing evolutionary dynamics.","lang":"eng"}],"intvolume":" 353","month":"09","oa":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534434/","open_access":"1"}],"scopus_import":1,"publisher":"American Association for the Advancement of Science","quality_controlled":"1"},{"oa":1,"quality_controlled":"1","publisher":"ACM","date_created":"2018-12-11T11:51:31Z","doi":"10.1145/2908812.2908909","date_published":"2016-07-20T00:00:00Z","page":"1163 - 1170","publication":"Proceedings of the Genetic and Evolutionary Computation Conference 2016 ","day":"20","year":"2016","has_accepted_license":"1","project":[{"_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","grant_number":"618091"}],"title":"When non-elitism outperforms elitism for crossing fitness valleys","publist_id":"5900","author":[{"last_name":"Oliveto","full_name":"Oliveto, Pietro","first_name":"Pietro"},{"full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","last_name":"Paixao","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","first_name":"Tiago"},{"first_name":"Jorge","last_name":"Heredia","full_name":"Heredia, Jorge"},{"full_name":"Sudholt, Dirk","last_name":"Sudholt","first_name":"Dirk"},{"orcid":"0000-0002-6873-2967","full_name":"Trubenova, Barbora","last_name":"Trubenova","first_name":"Barbora","id":"42302D54-F248-11E8-B48F-1D18A9856A87"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"short":"P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, B. Trubenova, in:, Proceedings of the Genetic and Evolutionary Computation Conference 2016 , ACM, 2016, pp. 1163–1170.","ieee":"P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, and B. Trubenova, “When non-elitism outperforms elitism for crossing fitness valleys,” in Proceedings of the Genetic and Evolutionary Computation Conference 2016 , Denver, CO, USA, 2016, pp. 1163–1170.","ama":"Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. When non-elitism outperforms elitism for crossing fitness valleys. In: Proceedings of the Genetic and Evolutionary Computation Conference 2016 . ACM; 2016:1163-1170. doi:10.1145/2908812.2908909","apa":"Oliveto, P., Paixao, T., Heredia, J., Sudholt, D., & Trubenova, B. (2016). When non-elitism outperforms elitism for crossing fitness valleys. In Proceedings of the Genetic and Evolutionary Computation Conference 2016 (pp. 1163–1170). Denver, CO, USA: ACM. https://doi.org/10.1145/2908812.2908909","mla":"Oliveto, Pietro, et al. “When Non-Elitism Outperforms Elitism for Crossing Fitness Valleys.” Proceedings of the Genetic and Evolutionary Computation Conference 2016 , ACM, 2016, pp. 1163–70, doi:10.1145/2908812.2908909.","ista":"Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. 2016. When non-elitism outperforms elitism for crossing fitness valleys. Proceedings of the Genetic and Evolutionary Computation Conference 2016 . GECCO: Genetic and evolutionary computation conference, 1163–1170.","chicago":"Oliveto, Pietro, Tiago Paixao, Jorge Heredia, Dirk Sudholt, and Barbora Trubenova. “When Non-Elitism Outperforms Elitism for Crossing Fitness Valleys.” In Proceedings of the Genetic and Evolutionary Computation Conference 2016 , 1163–70. ACM, 2016. https://doi.org/10.1145/2908812.2908909."},"month":"07","scopus_import":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Crossing fitness valleys is one of the major obstacles to function optimization. In this paper we investigate how the structure of the fitness valley, namely its depth d and length ℓ, influence the runtime of different strategies for crossing these valleys. We present a runtime comparison between the (1+1) EA and two non-elitist nature-inspired algorithms, Strong Selection Weak Mutation (SSWM) and the Metropolis algorithm. While the (1+1) EA has to jump across the valley to a point of higher fitness because it does not accept decreasing moves, the non-elitist algorithms may cross the valley by accepting worsening moves. We show that while the runtime of the (1+1) EA algorithm depends critically on the length of the valley, the runtimes of the non-elitist algorithms depend crucially only on the depth of the valley. In particular, the expected runtime of both SSWM and Metropolis is polynomial in ℓ and exponential in d while the (1+1) EA is efficient only for valleys of small length. Moreover, we show that both SSWM and Metropolis can also efficiently optimize a rugged function consisting of consecutive valleys."}],"ec_funded":1,"language":[{"iso":"eng"}],"file":[{"file_name":"IST-2016-650-v1+1_p1163-oliveto.pdf","date_created":"2018-12-12T10:16:27Z","creator":"system","file_size":979026,"date_updated":"2020-07-14T12:44:45Z","checksum":"a1896e39e4113f2711e46b435d5f3e69","file_id":"5214","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"publication_status":"published","pubrep_id":"650","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"conference":{"start_date":"2016-07-20","location":"Denver, CO, USA","end_date":"2016-07-24","name":"GECCO: Genetic and evolutionary computation conference"},"type":"conference","_id":"1349","file_date_updated":"2020-07-14T12:44:45Z","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"ddc":["576"],"date_updated":"2021-01-12T06:50:03Z"},{"page":"4422 - 4427","date_created":"2018-12-11T11:51:34Z","doi":"10.1073/pnas.1518830113","date_published":"2016-04-19T00:00:00Z","year":"2016","publication":"PNAS","day":"19","oa":1,"publisher":"National Academy of Sciences","quality_controlled":"1","article_processing_charge":"No","external_id":{"pmid":["27044080"]},"publist_id":"5886","author":[{"last_name":"Paixao","full_name":"Paixao, Tiago","orcid":"0000-0003-2361-3953","id":"2C5658E6-F248-11E8-B48F-1D18A9856A87","first_name":"Tiago"},{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas H","last_name":"Barton","orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H"}],"title":"The effect of gene interactions on the long-term response to selection","citation":{"chicago":"Paixao, Tiago, and Nicholas H Barton. “The Effect of Gene Interactions on the Long-Term Response to Selection.” PNAS. National Academy of Sciences, 2016. https://doi.org/10.1073/pnas.1518830113.","ista":"Paixao T, Barton NH. 2016. The effect of gene interactions on the long-term response to selection. PNAS. 113(16), 4422–4427.","mla":"Paixao, Tiago, and Nicholas H. Barton. “The Effect of Gene Interactions on the Long-Term Response to Selection.” PNAS, vol. 113, no. 16, National Academy of Sciences, 2016, pp. 4422–27, doi:10.1073/pnas.1518830113.","ama":"Paixao T, Barton NH. The effect of gene interactions on the long-term response to selection. PNAS. 2016;113(16):4422-4427. doi:10.1073/pnas.1518830113","apa":"Paixao, T., & Barton, N. H. (2016). The effect of gene interactions on the long-term response to selection. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1518830113","short":"T. Paixao, N.H. Barton, PNAS 113 (2016) 4422–4427.","ieee":"T. Paixao and N. H. Barton, “The effect of gene interactions on the long-term response to selection,” PNAS, vol. 113, no. 16. National Academy of Sciences, pp. 4422–4427, 2016."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"grant_number":"250152","name":"Limits to selection in biology and in evolutionary computation","_id":"25B07788-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"call_identifier":"FP7","_id":"25B1EC9E-B435-11E9-9278-68D0E5697425","name":"Speed of Adaptation in Population Genetics and Evolutionary Computation","grant_number":"618091"}],"ec_funded":1,"volume":113,"issue":"16","publication_status":"published","language":[{"iso":"eng"}],"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843425/","open_access":"1"}],"scopus_import":1,"intvolume":" 113","month":"04","abstract":[{"lang":"eng","text":"The role of gene interactions in the evolutionary process has long\r\nbeen controversial. Although some argue that they are not of\r\nimportance, because most variation is additive, others claim that\r\ntheir effect in the long term can be substantial. Here, we focus on\r\nthe long-term effects of genetic interactions under directional\r\nselection assuming no mutation or dominance, and that epistasis is\r\nsymmetrical overall. We ask by how much the mean of a complex\r\ntrait can be increased by selection and analyze two extreme\r\nregimes, in which either drift or selection dominate the dynamics\r\nof allele frequencies. In both scenarios, epistatic interactions affect\r\nthe long-term response to selection by modulating the additive\r\ngenetic variance. When drift dominates, we extend Robertson\r\n’\r\ns\r\n[Robertson A (1960)\r\nProc R Soc Lond B Biol Sci\r\n153(951):234\r\n−\r\n249]\r\nargument to show that, for any form of epistasis, the total response\r\nof a haploid population is proportional to the initial total genotypic\r\nvariance. In contrast, the total response of a diploid population is\r\nincreased by epistasis, for a given initial genotypic variance. When\r\nselection dominates, we show that the total selection response can\r\nonly be increased by epistasis when s\r\nome initially deleterious alleles\r\nbecome favored as the genetic background changes. We find a sim-\r\nple approximation for this effect and show that, in this regime, it is\r\nthe structure of the genotype - phenotype map that matters and not\r\nthe variance components of the population."}],"pmid":1,"oa_version":"Published Version","department":[{"_id":"NiBa"},{"_id":"CaGu"}],"date_updated":"2021-01-12T06:50:08Z","type":"journal_article","article_type":"original","status":"public","_id":"1359"},{"ddc":["570","576"],"date_updated":"2021-01-12T06:50:39Z","department":[{"_id":"CaGu"},{"_id":"JoBo"}],"file_date_updated":"2020-07-14T12:44:53Z","_id":"1427","pubrep_id":"588","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","language":[{"iso":"eng"}],"file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"1f456ce1d2aa2f67176a1709f9702ecf","file_id":"4751","creator":"system","date_updated":"2020-07-14T12:44:53Z","file_size":648115,"date_created":"2018-12-12T10:09:27Z","file_name":"IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf"}],"publication_status":"published","ec_funded":1,"volume":33,"issue":"3","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner."}],"intvolume":" 33","month":"03","scopus_import":1,"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ama":"Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 2016;33(3):761-769. doi:10.1093/molbev/msv269","apa":"Lagator, M., Igler, C., Moreno, A., Guet, C. C., & Bollback, J. P. (2016). Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv269","short":"M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology and Evolution 33 (2016) 761–769.","ieee":"M. Lagator, C. Igler, A. Moreno, C. C. Guet, and J. P. Bollback, “Epistatic interactions in the arabinose cis-regulatory element,” Molecular Biology and Evolution, vol. 33, no. 3. Oxford University Press, pp. 761–769, 2016.","mla":"Lagator, Mato, et al. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University Press, 2016, pp. 761–69, doi:10.1093/molbev/msv269.","ista":"Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. 2016. Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology and Evolution. 33(3), 761–769.","chicago":"Lagator, Mato, Claudia Igler, Anaisa Moreno, Calin C Guet, and Jonathan P Bollback. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.” Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv269."},"title":"Epistatic interactions in the arabinose cis-regulatory element","publist_id":"5772","author":[{"last_name":"Lagator","full_name":"Lagator, Mato","first_name":"Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Igler","full_name":"Igler, Claudia","first_name":"Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Anaisa","full_name":"Moreno, Anaisa","last_name":"Moreno"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"},{"first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","last_name":"Bollback"}],"project":[{"name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"publication":"Molecular Biology and Evolution","day":"01","year":"2016","has_accepted_license":"1","date_created":"2018-12-11T11:51:57Z","doi":"10.1093/molbev/msv269","date_published":"2016-03-01T00:00:00Z","page":"761 - 769","oa":1,"quality_controlled":"1","publisher":"Oxford University Press"}]