[{"day":"01","publication_status":"published","related_material":{"record":[{"status":"public","id":"963","relation":"earlier_version"}]},"month":"08","alternative_title":["LIPIcs"],"doi":"10.4230/LIPICS.MFCS.2018.23","abstract":[{"lang":"eng","text":"Network games are widely used as a model for selfish resource-allocation problems. In the classicalmodel, each player selects a path connecting her source and target vertices. The cost of traversingan edge depends on theload; namely, number of players that traverse it. Thus, it abstracts the factthat different users may use a resource at different times and for different durations, which playsan important role in determining the costs of the users in reality. For example, when transmittingpackets in a communication network, routing traffic in a road network, or processing a task in aproduction system, actual sharing and congestion of resources crucially depends on time.In [13], we introducedtimed network games, which add a time component to network games.Each vertexvin the network is associated with a cost function, mapping the load onvto theprice that a player pays for staying invfor one time unit with this load. Each edge in thenetwork is guarded by the time intervals in which it can be traversed, which forces the players tospend time in the vertices. In this work we significantly extend the way time can be referred toin timed network games. In the model we study, the network is equipped withclocks, and, as intimed automata, edges are guarded by constraints on the values of the clocks, and their traversalmay involve a reset of some clocks. We argue that the stronger model captures many realisticnetworks. The addition of clocks breaks the techniques we developed in [13] and we developnew techniques in order to show that positive results on classic network games carry over to thestronger timed setting."}],"license":"https://creativecommons.org/licenses/by/4.0/","publication_identifier":{"issn":["1868-8969"]},"status":"public","language":[{"iso":"eng"}],"article_number":"23","intvolume":" 117","publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"apa":"Avni, G., Guha, S., & Kupferman, O. (2018). Timed network games with clocks (Vol. 117). Presented at the MFCS: Mathematical Foundations of Computer Science, Liverpool, United Kingdom: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. https://doi.org/10.4230/LIPICS.MFCS.2018.23","mla":"Avni, Guy, et al. Timed Network Games with Clocks. Vol. 117, 23, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2018, doi:10.4230/LIPICS.MFCS.2018.23.","ista":"Avni G, Guha S, Kupferman O. 2018. Timed network games with clocks. MFCS: Mathematical Foundations of Computer Science, LIPIcs, vol. 117, 23.","ieee":"G. Avni, S. Guha, and O. Kupferman, “Timed network games with clocks,” presented at the MFCS: Mathematical Foundations of Computer Science, Liverpool, United Kingdom, 2018, vol. 117.","chicago":"Avni, Guy, Shibashis Guha, and Orna Kupferman. “Timed Network Games with Clocks,” Vol. 117. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2018. https://doi.org/10.4230/LIPICS.MFCS.2018.23.","short":"G. Avni, S. Guha, O. Kupferman, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2018.","ama":"Avni G, Guha S, Kupferman O. Timed network games with clocks. In: Vol 117. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2018. doi:10.4230/LIPICS.MFCS.2018.23"},"author":[{"last_name":"Avni","full_name":"Avni, Guy","id":"463C8BC2-F248-11E8-B48F-1D18A9856A87","first_name":"Guy","orcid":"0000-0001-5588-8287"},{"full_name":"Guha, Shibashis","first_name":"Shibashis","last_name":"Guha"},{"last_name":"Kupferman","first_name":"Orna","full_name":"Kupferman, Orna"}],"oa":1,"oa_version":"Published Version","date_updated":"2023-02-23T14:02:58Z","department":[{"_id":"ToHe"}],"file":[{"file_size":542889,"content_type":"application/pdf","date_updated":"2020-07-14T12:47:15Z","file_name":"2018_LIPIcs_Avni.pdf","date_created":"2019-02-14T14:22:04Z","file_id":"6007","access_level":"open_access","creator":"dernst","relation":"main_file","checksum":"41ab2ae9b63f5eb49fa995250c0ba128"}],"type":"conference","file_date_updated":"2020-07-14T12:47:15Z","scopus_import":"1","_id":"6005","article_processing_charge":"No","volume":117,"year":"2018","ddc":["000"],"date_created":"2019-02-14T14:12:09Z","quality_controlled":"1","project":[{"grant_number":"S 11407_N23","name":"Rigorous Systems Engineering","call_identifier":"FWF","_id":"25832EC2-B435-11E9-9278-68D0E5697425"},{"grant_number":"Z211","name":"The Wittgenstein Prize","_id":"25F42A32-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"M02369","name":"Formal Methods meets Algorithmic Game Theory","_id":"264B3912-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"date_published":"2018-08-01T00:00:00Z","title":"Timed network games with clocks","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"conference":{"name":"MFCS: Mathematical Foundations of Computer Science","start_date":"2018-08-27","location":"Liverpool, United Kingdom","end_date":"2018-08-31"}},{"language":[{"iso":"eng"}],"article_number":"39","intvolume":" 9","publisher":"MDPI AG","publication_status":"published","day":"01","month":"09","related_material":{"record":[{"id":"1003","relation":"earlier_version","status":"public"}]},"issue":"3","abstract":[{"text":"Network games (NGs) are played on directed graphs and are extensively used in network design and analysis. Search problems for NGs include finding special strategy profiles such as a Nash equilibrium and a globally-optimal solution. The networks modeled by NGs may be huge. In formal verification, abstraction has proven to be an extremely effective technique for reasoning about systems with big and even infinite state spaces. We describe an abstraction-refinement methodology for reasoning about NGs. Our methodology is based on an abstraction function that maps the state space of an NG to a much smaller state space. We search for a global optimum and a Nash equilibrium by reasoning on an under- and an over-approximation defined on top of this smaller state space. When the approximations are too coarse to find such profiles, we refine the abstraction function. We extend the abstraction-refinement methodology to labeled networks, where the objectives of the players are regular languages. Our experimental results demonstrate the effectiveness of the methodology. ","lang":"eng"}],"doi":"10.3390/g9030039","status":"public","publication_identifier":{"issn":["2073-4336"]},"year":"2018","publication":"Games","volume":9,"ddc":["004"],"date_created":"2019-02-14T14:17:54Z","project":[{"name":"Formal Methods meets Algorithmic Game Theory","grant_number":"M02369","_id":"264B3912-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"call_identifier":"FWF","_id":"25832EC2-B435-11E9-9278-68D0E5697425","grant_number":"S 11407_N23","name":"Rigorous Systems Engineering"},{"grant_number":"Z211","name":"The Wittgenstein Prize","_id":"25F42A32-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"date_published":"2018-09-01T00:00:00Z","title":"An abstraction-refinement methodology for reasoning about network games","quality_controlled":"1","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_updated":"2023-09-22T09:48:59Z","oa_version":"Published Version","file":[{"access_level":"open_access","date_created":"2019-02-14T14:20:31Z","file_id":"6008","file_name":"2018_MDPI_Avni.pdf","file_size":505155,"content_type":"application/pdf","date_updated":"2020-07-14T12:47:16Z","relation":"main_file","checksum":"749d65ca4ce74256a029d9644a1b1cb0","creator":"kschuh"}],"department":[{"_id":"ToHe"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","citation":{"mla":"Avni, Guy, et al. “An Abstraction-Refinement Methodology for Reasoning about Network Games.” Games, vol. 9, no. 3, 39, MDPI AG, 2018, doi:10.3390/g9030039.","apa":"Avni, G., Guha, S., & Kupferman, O. (2018). An abstraction-refinement methodology for reasoning about network games. Games. MDPI AG. https://doi.org/10.3390/g9030039","ista":"Avni G, Guha S, Kupferman O. 2018. An abstraction-refinement methodology for reasoning about network games. Games. 9(3), 39.","chicago":"Avni, Guy, Shibashis Guha, and Orna Kupferman. “An Abstraction-Refinement Methodology for Reasoning about Network Games.” Games. MDPI AG, 2018. https://doi.org/10.3390/g9030039.","short":"G. Avni, S. Guha, O. Kupferman, Games 9 (2018).","ama":"Avni G, Guha S, Kupferman O. An abstraction-refinement methodology for reasoning about network games. Games. 2018;9(3). doi:10.3390/g9030039","ieee":"G. Avni, S. Guha, and O. Kupferman, “An abstraction-refinement methodology for reasoning about network games,” Games, vol. 9, no. 3. MDPI AG, 2018."},"author":[{"last_name":"Avni","full_name":"Avni, Guy","first_name":"Guy","id":"463C8BC2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5588-8287"},{"first_name":"Shibashis","full_name":"Guha, Shibashis","last_name":"Guha"},{"last_name":"Kupferman","first_name":"Orna","full_name":"Kupferman, Orna"}],"oa":1,"type":"journal_article","file_date_updated":"2020-07-14T12:47:16Z","scopus_import":1,"_id":"6006"},{"project":[{"call_identifier":"FWF","_id":"2584A770-B435-11E9-9278-68D0E5697425","grant_number":"P 23499-N23","name":"Modern Graph Algorithmic Techniques in Formal Verification"},{"name":"Rigorous Systems Engineering","grant_number":"S 11407_N23","call_identifier":"FWF","_id":"25832EC2-B435-11E9-9278-68D0E5697425"},{"_id":"2581B60A-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"279307","name":"Quantitative Graph Games: Theory and Applications"}],"title":"Algorithms for algebraic path properties in concurrent systems of constant treewidth components","date_published":"2018-08-01T00:00:00Z","quality_controlled":"1","year":"2018","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1510.07565"}],"publication":"ACM Transactions on Programming Languages and Systems","volume":40,"article_processing_charge":"No","date_created":"2019-02-14T14:31:52Z","external_id":{"isi":["000444694800001"],"arxiv":["1510.07565"]},"scopus_import":"1","_id":"6009","oa_version":"Preprint","date_updated":"2024-03-25T23:30:19Z","department":[{"_id":"KrCh"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Chatterjee, Krishnendu, et al. “Algorithms for Algebraic Path Properties in Concurrent Systems of Constant Treewidth Components.” ACM Transactions on Programming Languages and Systems, vol. 40, no. 3, 9, Association for Computing Machinery (ACM), 2018, doi:10.1145/3210257.","apa":"Chatterjee, K., Ibsen-Jensen, R., Goharshady, A. K., & Pavlogiannis, A. (2018). Algorithms for algebraic path properties in concurrent systems of constant treewidth components. ACM Transactions on Programming Languages and Systems. Association for Computing Machinery (ACM). https://doi.org/10.1145/3210257","ista":"Chatterjee K, Ibsen-Jensen R, Goharshady AK, Pavlogiannis A. 2018. Algorithms for algebraic path properties in concurrent systems of constant treewidth components. ACM Transactions on Programming Languages and Systems. 40(3), 9.","chicago":"Chatterjee, Krishnendu, Rasmus Ibsen-Jensen, Amir Kafshdar Goharshady, and Andreas Pavlogiannis. “Algorithms for Algebraic Path Properties in Concurrent Systems of Constant Treewidth Components.” ACM Transactions on Programming Languages and Systems. Association for Computing Machinery (ACM), 2018. https://doi.org/10.1145/3210257.","ama":"Chatterjee K, Ibsen-Jensen R, Goharshady AK, Pavlogiannis A. Algorithms for algebraic path properties in concurrent systems of constant treewidth components. ACM Transactions on Programming Languages and Systems. 2018;40(3). doi:10.1145/3210257","short":"K. Chatterjee, R. Ibsen-Jensen, A.K. Goharshady, A. Pavlogiannis, ACM Transactions on Programming Languages and Systems 40 (2018).","ieee":"K. Chatterjee, R. Ibsen-Jensen, A. K. Goharshady, and A. Pavlogiannis, “Algorithms for algebraic path properties in concurrent systems of constant treewidth components,” ACM Transactions on Programming Languages and Systems, vol. 40, no. 3. Association for Computing Machinery (ACM), 2018."},"oa":1,"author":[{"orcid":"0000-0002-4561-241X","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","first_name":"Krishnendu","full_name":"Chatterjee, Krishnendu","last_name":"Chatterjee"},{"orcid":"0000-0003-4783-0389","first_name":"Rasmus","id":"3B699956-F248-11E8-B48F-1D18A9856A87","full_name":"Ibsen-Jensen, Rasmus","last_name":"Ibsen-Jensen"},{"first_name":"Amir Kafshdar","id":"391365CE-F248-11E8-B48F-1D18A9856A87","full_name":"Goharshady, Amir Kafshdar","orcid":"0000-0003-1702-6584","last_name":"Goharshady"},{"orcid":"0000-0002-8943-0722","first_name":"Andreas","id":"49704004-F248-11E8-B48F-1D18A9856A87","full_name":"Pavlogiannis, Andreas","last_name":"Pavlogiannis"}],"type":"journal_article","publisher":"Association for Computing Machinery (ACM)","arxiv":1,"language":[{"iso":"eng"}],"article_number":"9","intvolume":" 40","issue":"3","abstract":[{"lang":"eng","text":"We study algorithmic questions wrt algebraic path properties in concurrent systems, where the transitions of the system are labeled from a complete, closed semiring. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural problems that arise in program analysis. We consider that each component of the concurrent system is a graph with constant treewidth, a property satisfied by the controlflow graphs of most programs. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis. The study of multiple queries allows us to consider the tradeoff between the resource usage of the one-time preprocessing and for each individual query. The traditional approach constructs the product graph of all components and applies the best-known graph algorithm on the product. In this approach, even the answer to a single query requires the transitive closure (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time.\r\nOur main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time, each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results showing that the worst-case running time of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (i.e., improving the worst-case bound for the shortest path problem in general graphs). Preliminary experimental results show that our algorithms perform favorably on several benchmarks.\r\n"}],"doi":"10.1145/3210257","status":"public","publication_identifier":{"issn":["0164-0925"]},"publication_status":"published","day":"01","ec_funded":1,"isi":1,"month":"08","related_material":{"record":[{"status":"public","relation":"earlier_version","id":"1437"},{"status":"public","id":"5441","relation":"earlier_version"},{"status":"public","id":"5442","relation":"earlier_version"},{"status":"public","id":"8934","relation":"dissertation_contains"}]}},{"_id":"6010","scopus_import":"1","external_id":{"isi":["000440982000020"],"pmid":["30026198"]},"type":"journal_article","author":[{"full_name":"Garrido-Charad, Florencia","first_name":"Florencia","last_name":"Garrido-Charad"},{"last_name":"Vega Zuniga","id":"2E7C4E78-F248-11E8-B48F-1D18A9856A87","full_name":"Vega Zuniga, Tomas A","first_name":"Tomas A"},{"last_name":"Gutiérrez-Ibáñez","full_name":"Gutiérrez-Ibáñez, Cristián","first_name":"Cristián"},{"last_name":"Fernandez","full_name":"Fernandez, Pedro","first_name":"Pedro"},{"full_name":"López-Jury, Luciana","first_name":"Luciana","last_name":"López-Jury"},{"first_name":"Cristian","full_name":"González-Cabrera, Cristian","last_name":"González-Cabrera"},{"first_name":"Harvey J.","full_name":"Karten, Harvey J.","last_name":"Karten"},{"last_name":"Luksch","first_name":"Harald","full_name":"Luksch, Harald"},{"full_name":"Marín, Gonzalo J.","first_name":"Gonzalo J.","last_name":"Marín"}],"oa":1,"citation":{"ama":"Garrido-Charad F, Vega Zuniga TA, Gutiérrez-Ibáñez C, et al. “Shepherd’s crook” neurons drive and synchronize the enhancing and suppressive mechanisms of the midbrain stimulus selection network. Proceedings of the National Academy of Sciences. 2018;115(32):E7615-E7623. doi:10.1073/pnas.1804517115","short":"F. Garrido-Charad, T.A. Vega Zuniga, C. Gutiérrez-Ibáñez, P. Fernandez, L. López-Jury, C. González-Cabrera, H.J. Karten, H. Luksch, G.J. Marín, Proceedings of the National Academy of Sciences 115 (2018) E7615–E7623.","chicago":"Garrido-Charad, Florencia, Tomas A Vega Zuniga, Cristián Gutiérrez-Ibáñez, Pedro Fernandez, Luciana López-Jury, Cristian González-Cabrera, Harvey J. Karten, Harald Luksch, and Gonzalo J. Marín. ““Shepherd’s Crook” Neurons Drive and Synchronize the Enhancing and Suppressive Mechanisms of the Midbrain Stimulus Selection Network.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2018. https://doi.org/10.1073/pnas.1804517115.","ieee":"F. Garrido-Charad et al., ““Shepherd’s crook” neurons drive and synchronize the enhancing and suppressive mechanisms of the midbrain stimulus selection network,” Proceedings of the National Academy of Sciences, vol. 115, no. 32. National Academy of Sciences, pp. E7615–E7623, 2018.","ista":"Garrido-Charad F, Vega Zuniga TA, Gutiérrez-Ibáñez C, Fernandez P, López-Jury L, González-Cabrera C, Karten HJ, Luksch H, Marín GJ. 2018. “Shepherd’s crook” neurons drive and synchronize the enhancing and suppressive mechanisms of the midbrain stimulus selection network. Proceedings of the National Academy of Sciences. 115(32), E7615–E7623.","mla":"Garrido-Charad, Florencia, et al. ““Shepherd’s Crook” Neurons Drive and Synchronize the Enhancing and Suppressive Mechanisms of the Midbrain Stimulus Selection Network.” Proceedings of the National Academy of Sciences, vol. 115, no. 32, National Academy of Sciences, 2018, pp. E7615–23, doi:10.1073/pnas.1804517115.","apa":"Garrido-Charad, F., Vega Zuniga, T. A., Gutiérrez-Ibáñez, C., Fernandez, P., López-Jury, L., González-Cabrera, C., … Marín, G. J. (2018). “Shepherd’s crook” neurons drive and synchronize the enhancing and suppressive mechanisms of the midbrain stimulus selection network. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1804517115"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"MaJö"}],"oa_version":"Submitted Version","date_updated":"2023-09-19T14:35:36Z","quality_controlled":"1","title":"“Shepherd’s crook” neurons drive and synchronize the enhancing and suppressive mechanisms of the midbrain stimulus selection network","date_published":"2018-08-07T00:00:00Z","date_created":"2019-02-14T14:33:34Z","article_processing_charge":"No","volume":115,"publication":"Proceedings of the National Academy of Sciences","year":"2018","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pubmed/30026198"}],"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"pmid":1,"status":"public","doi":"10.1073/pnas.1804517115","abstract":[{"lang":"eng","text":"The optic tectum (TeO), or superior colliculus, is a multisensory midbrain center that organizes spatially orienting responses to relevant stimuli. To define the stimulus with the highest priority at each moment, a network of reciprocal connections between the TeO and the isthmi promotes competition between concurrent tectal inputs. In the avian midbrain, the neurons mediating enhancement and suppression of tectal inputs are located in separate isthmic nuclei, facilitating the analysis of the neural processes that mediate competition. A specific subset of radial neurons in the intermediate tectal layers relay retinal inputs to the isthmi, but at present it is unclear whether separate neurons innervate individual nuclei or a single neural type sends a common input to several of them. In this study, we used in vitro neural tracing and cell-filling experiments in chickens to show that single neurons innervate, via axon collaterals, the three nuclei that comprise the isthmotectal network. This demonstrates that the input signals representing the strength of the incoming stimuli are simultaneously relayed to the mechanisms promoting both enhancement and suppression of the input signals. By performing in vivo recordings in anesthetized chicks, we also show that this common input generates synchrony between both antagonistic mechanisms, demonstrating that activity enhancement and suppression are closely coordinated. From a computational point of view, these results suggest that these tectal neurons constitute integrative nodes that combine inputs from different sources to drive in parallel several concurrent neural processes, each performing complementary functions within the network through different firing patterns and connectivity."}],"issue":"32","month":"08","isi":1,"day":"07","publication_status":"published","publisher":"National Academy of Sciences","page":"E7615-E7623","intvolume":" 115","language":[{"iso":"eng"}]},{"conference":{"end_date":"2018-07-15","location":"Stockholm, Sweden","start_date":"2018-07-10","name":"ICML: International Conference on Machine Learning"},"quality_controlled":"1","project":[{"grant_number":"308036","name":"Lifelong Learning of Visual Scene Understanding","_id":"2532554C-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"title":"Data-dependent stability of stochastic gradient descent","date_published":"2018-02-01T00:00:00Z","date_created":"2019-02-14T14:51:57Z","publication":"Proceedings of the 35 th International Conference on Machine Learning","volume":80,"article_processing_charge":"No","year":"2018","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1703.01678"}],"_id":"6011","scopus_import":"1","external_id":{"isi":["000683379202095"],"arxiv":["1703.01678"]},"type":"conference","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Kuzborskij I, Lampert C. 2018. Data-dependent stability of stochastic gradient descent. Proceedings of the 35 th International Conference on Machine Learning. ICML: International Conference on Machine Learning vol. 80, 2815–2824.","apa":"Kuzborskij, I., & Lampert, C. (2018). Data-dependent stability of stochastic gradient descent. In Proceedings of the 35 th International Conference on Machine Learning (Vol. 80, pp. 2815–2824). Stockholm, Sweden: ML Research Press.","mla":"Kuzborskij, Ilja, and Christoph Lampert. “Data-Dependent Stability of Stochastic Gradient Descent.” Proceedings of the 35 Th International Conference on Machine Learning, vol. 80, ML Research Press, 2018, pp. 2815–24.","short":"I. Kuzborskij, C. Lampert, in:, Proceedings of the 35 Th International Conference on Machine Learning, ML Research Press, 2018, pp. 2815–2824.","ama":"Kuzborskij I, Lampert C. Data-dependent stability of stochastic gradient descent. In: Proceedings of the 35 Th International Conference on Machine Learning. Vol 80. ML Research Press; 2018:2815-2824.","chicago":"Kuzborskij, Ilja, and Christoph Lampert. “Data-Dependent Stability of Stochastic Gradient Descent.” In Proceedings of the 35 Th International Conference on Machine Learning, 80:2815–24. ML Research Press, 2018.","ieee":"I. Kuzborskij and C. Lampert, “Data-dependent stability of stochastic gradient descent,” in Proceedings of the 35 th International Conference on Machine Learning, Stockholm, Sweden, 2018, vol. 80, pp. 2815–2824."},"oa":1,"author":[{"last_name":"Kuzborskij","full_name":"Kuzborskij, Ilja","first_name":"Ilja"},{"id":"40C20FD2-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph","full_name":"Lampert, Christoph","orcid":"0000-0001-8622-7887","last_name":"Lampert"}],"date_updated":"2023-10-17T09:51:13Z","oa_version":"Preprint","department":[{"_id":"ChLa"}],"publisher":"ML Research Press","page":"2815-2824","intvolume":" 80","arxiv":1,"language":[{"iso":"eng"}],"status":"public","abstract":[{"lang":"eng","text":"We establish a data-dependent notion of algorithmic stability for Stochastic Gradient Descent (SGD), and employ it to develop novel generalization bounds. This is in contrast to previous distribution-free algorithmic stability results for SGD which depend on the worst-case constants. By virtue of the data-dependent argument, our bounds provide new insights into learning with SGD on convex and non-convex problems. In the convex case, we show that the bound on the generalization error depends on the risk at the initialization point. In the non-convex case, we prove that the expected curvature of the objective function around the initialization point has crucial influence on the generalization error. In both cases, our results suggest a simple data-driven strategy to stabilize SGD by pre-screening its initialization. As a corollary, our results allow us to show optimistic generalization bounds that exhibit fast convergence rates for SGD subject to a vanishing empirical risk and low noise of stochastic gradient. "}],"isi":1,"month":"02","day":"01","ec_funded":1,"publication_status":"published"},{"main_file_link":[{"url":"https://arxiv.org/abs/1806.07259","open_access":"1"}],"year":"2018","article_processing_charge":"No","volume":80,"publication":"Proceedings of the 35th International Conference on Machine Learning","date_created":"2019-02-14T15:21:07Z","date_published":"2018-02-01T00:00:00Z","title":"Learning equations for extrapolation and control","project":[{"name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"quality_controlled":"1","conference":{"end_date":"2018-07-15","location":"Stockholm, Sweden","start_date":"2018-07-10","name":"ICML: International Conference on Machine Learning"},"department":[{"_id":"ChLa"}],"oa_version":"Preprint","date_updated":"2023-10-17T09:50:53Z","oa":1,"author":[{"first_name":"Subham","full_name":"Sahoo, Subham","last_name":"Sahoo"},{"id":"40C20FD2-F248-11E8-B48F-1D18A9856A87","full_name":"Lampert, Christoph","first_name":"Christoph","orcid":"0000-0001-8622-7887","last_name":"Lampert"},{"full_name":"Martius, Georg S","first_name":"Georg S","id":"3A276B68-F248-11E8-B48F-1D18A9856A87","last_name":"Martius"}],"citation":{"chicago":"Sahoo, Subham, Christoph Lampert, and Georg S Martius. “Learning Equations for Extrapolation and Control.” In Proceedings of the 35th International Conference on Machine Learning, 80:4442–50. ML Research Press, 2018.","short":"S. Sahoo, C. Lampert, G.S. Martius, in:, Proceedings of the 35th International Conference on Machine Learning, ML Research Press, 2018, pp. 4442–4450.","ama":"Sahoo S, Lampert C, Martius GS. Learning equations for extrapolation and control. In: Proceedings of the 35th International Conference on Machine Learning. Vol 80. ML Research Press; 2018:4442-4450.","ieee":"S. Sahoo, C. Lampert, and G. S. Martius, “Learning equations for extrapolation and control,” in Proceedings of the 35th International Conference on Machine Learning, Stockholm, Sweden, 2018, vol. 80, pp. 4442–4450.","apa":"Sahoo, S., Lampert, C., & Martius, G. S. (2018). Learning equations for extrapolation and control. In Proceedings of the 35th International Conference on Machine Learning (Vol. 80, pp. 4442–4450). Stockholm, Sweden: ML Research Press.","mla":"Sahoo, Subham, et al. “Learning Equations for Extrapolation and Control.” Proceedings of the 35th International Conference on Machine Learning, vol. 80, ML Research Press, 2018, pp. 4442–50.","ista":"Sahoo S, Lampert C, Martius GS. 2018. Learning equations for extrapolation and control. Proceedings of the 35th International Conference on Machine Learning. ICML: International Conference on Machine Learning vol. 80, 4442–4450."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"conference","external_id":{"arxiv":["1806.07259"],"isi":["000683379204058"]},"scopus_import":"1","_id":"6012","language":[{"iso":"eng"}],"arxiv":1,"intvolume":" 80","page":"4442-4450","publisher":"ML Research Press","publication_status":"published","ec_funded":1,"day":"01","month":"02","related_material":{"link":[{"url":"https://ist.ac.at/en/news/first-machine-learning-method-capable-of-accurate-extrapolation/","relation":"press_release","description":"News on IST Homepage"}]},"isi":1,"abstract":[{"text":"We present an approach to identify concise equations from data using a shallow neural network approach. In contrast to ordinary black-box regression, this approach allows understanding functional relations and generalizing them from observed data to unseen parts of the parameter space. We show how to extend the class of learnable equations for a recently proposed equation learning network to include divisions, and we improve the learning and model selection strategy to be useful for challenging real-world data. For systems governed by analytical expressions, our method can in many cases identify the true underlying equation and extrapolate to unseen domains. We demonstrate its effectiveness by experiments on a cart-pendulum system, where only 2 random rollouts are required to learn the forward dynamics and successfully achieve the swing-up task.","lang":"eng"}],"status":"public"},{"main_file_link":[{"url":"https://arxiv.org/abs/1602.03124","open_access":"1"}],"year":"2018","article_processing_charge":"No","volume":15,"publication":"ACM Transactions on Algorithms","date_created":"2019-02-17T22:59:25Z","title":"Even delta-matroids and the complexity of planar boolean CSPs","date_published":"2018-12-01T00:00:00Z","project":[{"call_identifier":"FP7","_id":"25FBA906-B435-11E9-9278-68D0E5697425","grant_number":"616160","name":"Discrete Optimization in Computer Vision: Theory and Practice"}],"quality_controlled":"1","department":[{"_id":"VlKo"}],"date_updated":"2023-09-20T11:20:26Z","oa_version":"Preprint","oa":1,"author":[{"last_name":"Kazda","first_name":"Alexandr","full_name":"Kazda, Alexandr","id":"3B32BAA8-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Vladimir","id":"3D50B0BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kolmogorov, Vladimir","last_name":"Kolmogorov"},{"first_name":"Michal","id":"3CB3BC06-F248-11E8-B48F-1D18A9856A87","full_name":"Rolinek, Michal","last_name":"Rolinek"}],"citation":{"mla":"Kazda, Alexandr, et al. “Even Delta-Matroids and the Complexity of Planar Boolean CSPs.” ACM Transactions on Algorithms, vol. 15, no. 2, 22, ACM, 2018, doi:10.1145/3230649.","apa":"Kazda, A., Kolmogorov, V., & Rolinek, M. (2018). Even delta-matroids and the complexity of planar boolean CSPs. ACM Transactions on Algorithms. ACM. https://doi.org/10.1145/3230649","ista":"Kazda A, Kolmogorov V, Rolinek M. 2018. Even delta-matroids and the complexity of planar boolean CSPs. ACM Transactions on Algorithms. 15(2), 22.","chicago":"Kazda, Alexandr, Vladimir Kolmogorov, and Michal Rolinek. “Even Delta-Matroids and the Complexity of Planar Boolean CSPs.” ACM Transactions on Algorithms. ACM, 2018. https://doi.org/10.1145/3230649.","ama":"Kazda A, Kolmogorov V, Rolinek M. Even delta-matroids and the complexity of planar boolean CSPs. ACM Transactions on Algorithms. 2018;15(2). doi:10.1145/3230649","short":"A. Kazda, V. Kolmogorov, M. Rolinek, ACM Transactions on Algorithms 15 (2018).","ieee":"A. Kazda, V. Kolmogorov, and M. Rolinek, “Even delta-matroids and the complexity of planar boolean CSPs,” ACM Transactions on Algorithms, vol. 15, no. 2. ACM, 2018."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","type":"journal_article","external_id":{"isi":["000468036500007"],"arxiv":["1602.03124"]},"scopus_import":"1","_id":"6032","language":[{"iso":"eng"}],"arxiv":1,"intvolume":" 15","article_number":"22","article_type":"original","publisher":"ACM","publication_status":"published","ec_funded":1,"day":"01","month":"12","related_material":{"record":[{"status":"public","relation":"earlier_version","id":"1192"}]},"isi":1,"issue":"2","doi":"10.1145/3230649","abstract":[{"lang":"eng","text":"The main result of this article is a generalization of the classical blossom algorithm for finding perfect matchings. Our algorithm can efficiently solve Boolean CSPs where each variable appears in exactly two constraints (we call it edge CSP) and all constraints are even Δ-matroid relations (represented by lists of tuples). As a consequence of this, we settle the complexity classification of planar Boolean CSPs started by Dvorak and Kupec. Using a reduction to even Δ-matroids, we then extend the tractability result to larger classes of Δ-matroids that we call efficiently coverable. It properly includes classes that were known to be tractable before, namely, co-independent, compact, local, linear, and binary, with the following caveat:We represent Δ-matroids by lists of tuples, while the last two use a representation by matrices. Since an n ×n matrix can represent exponentially many tuples, our tractability result is not strictly stronger than the known algorithm for linear and binary Δ-matroids."}],"status":"public"},{"publisher":"Elsevier","page":"1267-1319","intvolume":" 35","language":[{"iso":"eng"}],"arxiv":1,"status":"public","doi":"10.1016/j.anihpc.2017.11.004","publist_id":"7199","abstract":[{"lang":"eng","text":"We establish the existence of a global solution for a new family of fluid-like equations, which are obtained in certain regimes in as the mean-field evolution of the supercurrent density in a (2D section of a) type-II superconductor with pinning and with imposed electric current. We also consider general vortex-sheet initial data, and investigate the uniqueness and regularity properties of the solution. For some choice of parameters, the equation under investigation coincides with the so-called lake equation from 2D shallow water fluid dynamics, and our analysis then leads to a new existence result for rough initial data."}],"issue":"5","isi":1,"month":"08","day":"01","acknowledgement":"The work of the author is supported by F.R.S.-FNRS ( Fonds de la Recherche Scientifique - FNRS ) through a Research Fellowship.\r\n\r\n","publication_status":"published","quality_controlled":"1","title":"Well-posedness for mean-field evolutions arising in superconductivity","date_published":"2018-08-01T00:00:00Z","date_created":"2018-12-11T11:47:27Z","publication":"Annales de l'Institut Henri Poincare (C) Non Linear Analysis","article_processing_charge":"No","volume":35,"year":"2018","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1607.00268"}],"_id":"606","scopus_import":"1","external_id":{"isi":["000437975500005"],"arxiv":["1607.00268"]},"type":"journal_article","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ieee":"M. Duerinckx and J. L. Fischer, “Well-posedness for mean-field evolutions arising in superconductivity,” Annales de l’Institut Henri Poincare (C) Non Linear Analysis, vol. 35, no. 5. Elsevier, pp. 1267–1319, 2018.","chicago":"Duerinckx, Mitia, and Julian L Fischer. “Well-Posedness for Mean-Field Evolutions Arising in Superconductivity.” Annales de l’Institut Henri Poincare (C) Non Linear Analysis. Elsevier, 2018. https://doi.org/10.1016/j.anihpc.2017.11.004.","short":"M. Duerinckx, J.L. Fischer, Annales de l’Institut Henri Poincare (C) Non Linear Analysis 35 (2018) 1267–1319.","ama":"Duerinckx M, Fischer JL. Well-posedness for mean-field evolutions arising in superconductivity. Annales de l’Institut Henri Poincare (C) Non Linear Analysis. 2018;35(5):1267-1319. doi:10.1016/j.anihpc.2017.11.004","apa":"Duerinckx, M., & Fischer, J. L. (2018). Well-posedness for mean-field evolutions arising in superconductivity. Annales de l’Institut Henri Poincare (C) Non Linear Analysis. Elsevier. https://doi.org/10.1016/j.anihpc.2017.11.004","mla":"Duerinckx, Mitia, and Julian L. Fischer. “Well-Posedness for Mean-Field Evolutions Arising in Superconductivity.” Annales de l’Institut Henri Poincare (C) Non Linear Analysis, vol. 35, no. 5, Elsevier, 2018, pp. 1267–319, doi:10.1016/j.anihpc.2017.11.004.","ista":"Duerinckx M, Fischer JL. 2018. Well-posedness for mean-field evolutions arising in superconductivity. Annales de l’Institut Henri Poincare (C) Non Linear Analysis. 35(5), 1267–1319."},"author":[{"first_name":"Mitia","full_name":"Duerinckx, Mitia","last_name":"Duerinckx"},{"last_name":"Fischer","first_name":"Julian L","full_name":"Fischer, Julian L","id":"2C12A0B0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0479-558X"}],"oa":1,"oa_version":"Submitted Version","date_updated":"2023-09-19T10:39:09Z","department":[{"_id":"JuFi"}]},{"quality_controlled":"1","title":"Well posedness and maximum entropy approximation for the dynamics of quantitative traits","date_published":"2018-08-01T00:00:00Z","date_created":"2018-12-11T11:47:28Z","volume":"376-377","article_processing_charge":"No","publication":"Physica D: Nonlinear Phenomena","year":"2018","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1704.08757"}],"_id":"607","scopus_import":"1","external_id":{"arxiv":["1704.08757"],"isi":["000437962900012"]},"type":"journal_article","author":[{"orcid":"0000-0002-7214-0171","first_name":"Katarina","full_name":"Bodova, Katarina","id":"2BA24EA0-F248-11E8-B48F-1D18A9856A87","last_name":"Bodova"},{"first_name":"Jan","full_name":"Haskovec, Jan","last_name":"Haskovec"},{"last_name":"Markowich","first_name":"Peter","full_name":"Markowich, Peter"}],"oa":1,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Bodova, Katarina, Jan Haskovec, and Peter Markowich. “Well Posedness and Maximum Entropy Approximation for the Dynamics of Quantitative Traits.” Physica D: Nonlinear Phenomena. Elsevier, 2018. https://doi.org/10.1016/j.physd.2017.10.015.","short":"K. Bodova, J. Haskovec, P. Markowich, Physica D: Nonlinear Phenomena 376–377 (2018) 108–120.","ama":"Bodova K, Haskovec J, Markowich P. Well posedness and maximum entropy approximation for the dynamics of quantitative traits. Physica D: Nonlinear Phenomena. 2018;376-377:108-120. doi:10.1016/j.physd.2017.10.015","ieee":"K. Bodova, J. Haskovec, and P. Markowich, “Well posedness and maximum entropy approximation for the dynamics of quantitative traits,” Physica D: Nonlinear Phenomena, vol. 376–377. Elsevier, pp. 108–120, 2018.","apa":"Bodova, K., Haskovec, J., & Markowich, P. (2018). Well posedness and maximum entropy approximation for the dynamics of quantitative traits. Physica D: Nonlinear Phenomena. Elsevier. https://doi.org/10.1016/j.physd.2017.10.015","mla":"Bodova, Katarina, et al. “Well Posedness and Maximum Entropy Approximation for the Dynamics of Quantitative Traits.” Physica D: Nonlinear Phenomena, vol. 376–377, Elsevier, 2018, pp. 108–20, doi:10.1016/j.physd.2017.10.015.","ista":"Bodova K, Haskovec J, Markowich P. 2018. Well posedness and maximum entropy approximation for the dynamics of quantitative traits. Physica D: Nonlinear Phenomena. 376–377, 108–120."},"department":[{"_id":"NiBa"},{"_id":"GaTk"}],"date_updated":"2023-09-19T10:38:34Z","oa_version":"Submitted Version","publisher":"Elsevier","page":"108-120","language":[{"iso":"eng"}],"arxiv":1,"status":"public","doi":"10.1016/j.physd.2017.10.015","abstract":[{"text":"We study the Fokker-Planck equation derived in the large system limit of the Markovian process describing the dynamics of quantitative traits. The Fokker-Planck equation is posed on a bounded domain and its transport and diffusion coefficients vanish on the domain's boundary. We first argue that, despite this degeneracy, the standard no-flux boundary condition is valid. We derive the weak formulation of the problem and prove the existence and uniqueness of its solutions by constructing the corresponding contraction semigroup on a suitable function space. Then, we prove that for the parameter regime with high enough mutation rate the problem exhibits a positive spectral gap, which implies exponential convergence to equilibrium.Next, we provide a simple derivation of the so-called Dynamic Maximum Entropy (DynMaxEnt) method for approximation of observables (moments) of the Fokker-Planck solution, which can be interpreted as a nonlinear Galerkin approximation. The limited applicability of the DynMaxEnt method inspires us to introduce its modified version that is valid for the whole range of admissible parameters. Finally, we present several numerical experiments to demonstrate the performance of both the original and modified DynMaxEnt methods. We observe that in the parameter regimes where both methods are valid, the modified one exhibits slightly better approximation properties compared to the original one.","lang":"eng"}],"publist_id":"7198","month":"08","isi":1,"day":"01","publication_status":"published","acknowledgement":"JH and PM are funded by KAUST baseline funds and grant no. 1000000193 .\r\nWe thank Nicholas Barton (IST Austria) for his useful comments and suggestions. \r\n\r\n"},{"quality_controlled":"1","date_published":"2018-02-15T00:00:00Z","title":"Synthesis from component libraries with costs","project":[{"name":"Quantitative Reactive Modeling","grant_number":"267989","call_identifier":"FP7","_id":"25EE3708-B435-11E9-9278-68D0E5697425"},{"name":"Rigorous Systems Engineering","grant_number":"S 11407_N23","_id":"25832EC2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"Z211","name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25F42A32-B435-11E9-9278-68D0E5697425"}],"volume":712,"article_processing_charge":"No","publication":"Theoretical Computer Science","main_file_link":[{"open_access":"1","url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.636.4529"}],"year":"2018","date_created":"2018-12-11T11:47:28Z","scopus_import":"1","external_id":{"isi":["000424959200003"]},"_id":"608","oa":1,"author":[{"last_name":"Avni","orcid":"0000-0001-5588-8287","id":"463C8BC2-F248-11E8-B48F-1D18A9856A87","first_name":"Guy","full_name":"Avni, Guy"},{"full_name":"Kupferman, Orna","first_name":"Orna","last_name":"Kupferman"}],"citation":{"ista":"Avni G, Kupferman O. 2018. Synthesis from component libraries with costs. Theoretical Computer Science. 712, 50–72.","apa":"Avni, G., & Kupferman, O. (2018). Synthesis from component libraries with costs. Theoretical Computer Science. Elsevier. https://doi.org/10.1016/j.tcs.2017.11.001","mla":"Avni, Guy, and Orna Kupferman. “Synthesis from Component Libraries with Costs.” Theoretical Computer Science, vol. 712, Elsevier, 2018, pp. 50–72, doi:10.1016/j.tcs.2017.11.001.","ama":"Avni G, Kupferman O. Synthesis from component libraries with costs. Theoretical Computer Science. 2018;712:50-72. doi:10.1016/j.tcs.2017.11.001","short":"G. Avni, O. Kupferman, Theoretical Computer Science 712 (2018) 50–72.","chicago":"Avni, Guy, and Orna Kupferman. “Synthesis from Component Libraries with Costs.” Theoretical Computer Science. Elsevier, 2018. https://doi.org/10.1016/j.tcs.2017.11.001.","ieee":"G. Avni and O. Kupferman, “Synthesis from component libraries with costs,” Theoretical Computer Science, vol. 712. Elsevier, pp. 50–72, 2018."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"ToHe"}],"oa_version":"Published Version","date_updated":"2023-09-19T10:00:21Z","type":"journal_article","publisher":"Elsevier","language":[{"iso":"eng"}],"article_type":"original","page":"50 - 72","intvolume":" 712","doi":"10.1016/j.tcs.2017.11.001","abstract":[{"text":"Synthesis is the automated construction of a system from its specification. In real life, hardware and software systems are rarely constructed from scratch. Rather, a system is typically constructed from a library of components. Lustig and Vardi formalized this intuition and studied LTL synthesis from component libraries. In real life, designers seek optimal systems. In this paper we add optimality considerations to the setting. We distinguish between quality considerations (for example, size - the smaller a system is, the better it is), and pricing (for example, the payment to the company who manufactured the component). We study the problem of designing systems with minimal quality-cost and price. A key point is that while the quality cost is individual - the choices of a designer are independent of choices made by other designers that use the same library, pricing gives rise to a resource-allocation game - designers that use the same component share its price, with the share being proportional to the number of uses (a component can be used several times in a design). We study both closed and open settings, and in both we solve the problem of finding an optimal design. In a setting with multiple designers, we also study the game-theoretic problems of the induced resource-allocation game.","lang":"eng"}],"publist_id":"7197","status":"public","ec_funded":1,"day":"15","publication_status":"published","month":"02","isi":1},{"type":"book_chapter","month":"05","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Bondarenko A, Mellit A, Prymak A, Radchenko D, Viazovska M. 2018.There is no strongly regular graph with parameters (460; 153; 32; 60). In: Contemporary Computational Mathematics. , 131–134.","apa":"Bondarenko, A., Mellit, A., Prymak, A., Radchenko, D., & Viazovska, M. (2018). There is no strongly regular graph with parameters (460; 153; 32; 60). In Contemporary Computational Mathematics (pp. 131–134). Springer. https://doi.org/10.1007/978-3-319-72456-0_7","mla":"Bondarenko, Andriy, et al. “There Is No Strongly Regular Graph with Parameters (460; 153; 32; 60).” Contemporary Computational Mathematics, Springer, 2018, pp. 131–34, doi:10.1007/978-3-319-72456-0_7.","ieee":"A. Bondarenko, A. Mellit, A. Prymak, D. Radchenko, and M. Viazovska, “There is no strongly regular graph with parameters (460; 153; 32; 60),” in Contemporary Computational Mathematics, Springer, 2018, pp. 131–134.","ama":"Bondarenko A, Mellit A, Prymak A, Radchenko D, Viazovska M. There is no strongly regular graph with parameters (460; 153; 32; 60). In: Contemporary Computational Mathematics. Springer; 2018:131-134. doi:10.1007/978-3-319-72456-0_7","short":"A. Bondarenko, A. Mellit, A. Prymak, D. Radchenko, M. Viazovska, in:, Contemporary Computational Mathematics, Springer, 2018, pp. 131–134.","chicago":"Bondarenko, Andriy, Anton Mellit, Andriy Prymak, Danylo Radchenko, and Maryna Viazovska. “There Is No Strongly Regular Graph with Parameters (460; 153; 32; 60).” In Contemporary Computational Mathematics, 131–34. Springer, 2018. https://doi.org/10.1007/978-3-319-72456-0_7."},"day":"23","extern":"1","author":[{"last_name":"Bondarenko","first_name":"Andriy","full_name":"Bondarenko, Andriy"},{"last_name":"Mellit","id":"388D3134-F248-11E8-B48F-1D18A9856A87","first_name":"Anton","full_name":"Mellit, Anton"},{"last_name":"Prymak","full_name":"Prymak, Andriy","first_name":"Andriy"},{"first_name":"Danylo","full_name":"Radchenko, Danylo","last_name":"Radchenko"},{"first_name":"Maryna","full_name":"Viazovska, Maryna","last_name":"Viazovska"}],"oa":1,"oa_version":"Preprint","publication_status":"published","date_updated":"2021-01-12T08:06:06Z","department":[{"_id":"TaHa"}],"status":"public","_id":"61","doi":"10.1007/978-3-319-72456-0_7","publist_id":"7993","abstract":[{"lang":"eng","text":"We prove that there is no strongly regular graph (SRG) with parameters (460; 153; 32; 60). The proof is based on a recent lower bound on the number of 4-cliques in a SRG and some applications of Euclidean representation of SRGs. "}],"external_id":{"arxiv":["1509.06286"]},"page":"131 - 134","date_created":"2018-12-11T11:44:25Z","publication":"Contemporary Computational Mathematics","arxiv":1,"language":[{"iso":"eng"}],"article_processing_charge":"No","main_file_link":[{"url":"https://arxiv.org/abs/1509.06286","open_access":"1"}],"year":"2018","publisher":"Springer","quality_controlled":"1","date_published":"2018-05-23T00:00:00Z","title":"There is no strongly regular graph with parameters (460; 153; 32; 60)"},{"publisher":"National Academy of Sciences","intvolume":" 115","page":"E6890-E6899","language":[{"iso":"eng"}],"status":"public","pmid":1,"publication_identifier":{"issn":["0027-8424","1091-6490"]},"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","issue":"29","doi":"10.1073/pnas.1714610115","abstract":[{"text":"Neuropeptides are ubiquitous modulators of behavior and physiology. They are packaged in specialized secretory organelles called dense core vesicles (DCVs) that are released upon neural stimulation. Unlike synaptic vesicles, which can be recycled and refilled close to release sites, DCVs must be replenished by de novo synthesis in the cell body. Here, we dissect DCV cell biology in vivo in a Caenorhabditis elegans sensory neuron whose tonic activity we can control using a natural stimulus. We express fluorescently tagged neuropeptides in the neuron and define parameters that describe their subcellular distribution. We measure these parameters at high and low neural activity in 187 mutants defective in proteins implicated in membrane traffic, neuroendocrine secretion, and neuronal or synaptic activity. Using unsupervised hierarchical clustering methods, we analyze these data and identify 62 groups of genes with similar mutant phenotypes. We explore the function of a subset of these groups. We recapitulate many previous findings, validating our paradigm. We uncover a large battery of proteins involved in recycling DCV membrane proteins, something hitherto poorly explored. We show that the unfolded protein response promotes DCV production, which may contribute to intertissue communication of stress. We also find evidence that different mechanisms of priming and exocytosis may operate at high and low neural activity. Our work provides a defined framework to study DCV biology at different neural activity levels.","lang":"eng"}],"month":"07","publication_status":"published","extern":"1","day":"17","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"title":"Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron","date_published":"2018-07-17T00:00:00Z","quality_controlled":"1","date_created":"2019-03-19T12:41:33Z","ddc":["570"],"year":"2018","volume":115,"publication":"Proceedings of the National Academy of Sciences","_id":"6109","external_id":{"pmid":["29959203"]},"file_date_updated":"2020-07-14T12:47:19Z","type":"journal_article","file":[{"creator":"kschuh","checksum":"5e81665377441cdd8d99ab952c534319","relation":"main_file","content_type":"application/pdf","date_updated":"2020-07-14T12:47:19Z","file_size":1567765,"file_name":"2018_PNAS_Laurent.pdf","file_id":"6110","date_created":"2019-03-19T13:01:58Z","access_level":"open_access"}],"date_updated":"2021-01-12T08:06:09Z","oa_version":"Published Version","author":[{"full_name":"Laurent, Patrick","first_name":"Patrick","last_name":"Laurent"},{"last_name":"Ch’ng","first_name":"QueeLim","full_name":"Ch’ng, QueeLim"},{"last_name":"Jospin","first_name":"Maëlle","full_name":"Jospin, Maëlle"},{"first_name":"Changchun","full_name":"Chen, Changchun","last_name":"Chen"},{"last_name":"Lorenzo","full_name":"Lorenzo, Ramiro","first_name":"Ramiro"},{"orcid":"0000-0001-8347-0443","first_name":"Mario","full_name":"de Bono, Mario","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","last_name":"de Bono"}],"oa":1,"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ama":"Laurent P, Ch’ng Q, Jospin M, Chen C, Lorenzo R, de Bono M. Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron. Proceedings of the National Academy of Sciences. 2018;115(29):E6890-E6899. doi:10.1073/pnas.1714610115","short":"P. Laurent, Q. Ch’ng, M. Jospin, C. Chen, R. Lorenzo, M. de Bono, Proceedings of the National Academy of Sciences 115 (2018) E6890–E6899.","chicago":"Laurent, Patrick, QueeLim Ch’ng, Maëlle Jospin, Changchun Chen, Ramiro Lorenzo, and Mario de Bono. “Genetic Dissection of Neuropeptide Cell Biology at High and Low Activity in a Defined Sensory Neuron.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2018. https://doi.org/10.1073/pnas.1714610115.","ieee":"P. Laurent, Q. Ch’ng, M. Jospin, C. Chen, R. Lorenzo, and M. de Bono, “Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron,” Proceedings of the National Academy of Sciences, vol. 115, no. 29. National Academy of Sciences, pp. E6890–E6899, 2018.","ista":"Laurent P, Ch’ng Q, Jospin M, Chen C, Lorenzo R, de Bono M. 2018. Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron. Proceedings of the National Academy of Sciences. 115(29), E6890–E6899.","mla":"Laurent, Patrick, et al. “Genetic Dissection of Neuropeptide Cell Biology at High and Low Activity in a Defined Sensory Neuron.” Proceedings of the National Academy of Sciences, vol. 115, no. 29, National Academy of Sciences, 2018, pp. E6890–99, doi:10.1073/pnas.1714610115.","apa":"Laurent, P., Ch’ng, Q., Jospin, M., Chen, C., Lorenzo, R., & de Bono, M. (2018). Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1714610115"},"has_accepted_license":"1"},{"external_id":{"pmid":["29879119"]},"file_date_updated":"2020-07-14T12:47:19Z","_id":"6111","date_updated":"2021-01-12T08:06:11Z","oa_version":"Published Version","file":[{"access_level":"open_access","file_id":"6112","date_created":"2019-03-19T13:18:01Z","file_name":"2018_PLOS_McLachlan.pdf","date_updated":"2020-07-14T12:47:19Z","content_type":"application/pdf","file_size":13011506,"checksum":"622036b945365dbc575bea2768aa9bc8","relation":"main_file","creator":"kschuh"}],"citation":{"short":"I.G. McLachlan, I. Beets, M. de Bono, M.G. Heiman, PLOS Genetics 14 (2018).","ama":"McLachlan IG, Beets I, de Bono M, Heiman MG. A neuronal MAP kinase constrains growth of a Caenorhabditis elegans sensory dendrite throughout the life of the organism. PLOS Genetics. 2018;14(6). doi:10.1371/journal.pgen.1007435","chicago":"McLachlan, Ian G., Isabel Beets, Mario de Bono, and Maxwell G. Heiman. “A Neuronal MAP Kinase Constrains Growth of a Caenorhabditis Elegans Sensory Dendrite throughout the Life of the Organism.” PLOS Genetics. Public Library of Science, 2018. https://doi.org/10.1371/journal.pgen.1007435.","ieee":"I. G. McLachlan, I. Beets, M. de Bono, and M. G. Heiman, “A neuronal MAP kinase constrains growth of a Caenorhabditis elegans sensory dendrite throughout the life of the organism,” PLOS Genetics, vol. 14, no. 6. Public Library of Science, 2018.","ista":"McLachlan IG, Beets I, de Bono M, Heiman MG. 2018. A neuronal MAP kinase constrains growth of a Caenorhabditis elegans sensory dendrite throughout the life of the organism. PLOS Genetics. 14(6), e1007435.","apa":"McLachlan, I. G., Beets, I., de Bono, M., & Heiman, M. G. (2018). A neuronal MAP kinase constrains growth of a Caenorhabditis elegans sensory dendrite throughout the life of the organism. PLOS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1007435","mla":"McLachlan, Ian G., et al. “A Neuronal MAP Kinase Constrains Growth of a Caenorhabditis Elegans Sensory Dendrite throughout the Life of the Organism.” PLOS Genetics, vol. 14, no. 6, e1007435, Public Library of Science, 2018, doi:10.1371/journal.pgen.1007435."},"has_accepted_license":"1","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa":1,"author":[{"last_name":"McLachlan","full_name":"McLachlan, Ian G.","first_name":"Ian G."},{"full_name":"Beets, Isabel","first_name":"Isabel","last_name":"Beets"},{"last_name":"de Bono","full_name":"de Bono, Mario","first_name":"Mario","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8347-0443"},{"first_name":"Maxwell G.","full_name":"Heiman, Maxwell G.","last_name":"Heiman"}],"type":"journal_article","title":"A neuronal MAP kinase constrains growth of a Caenorhabditis elegans sensory dendrite throughout the life of the organism","date_published":"2018-06-07T00:00:00Z","quality_controlled":"1","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"year":"2018","publication":"PLOS Genetics","volume":14,"ddc":["570"],"date_created":"2019-03-19T13:09:28Z","issue":"6","doi":"10.1371/journal.pgen.1007435","abstract":[{"text":"Neurons develop elaborate morphologies that provide a model for understanding cellular architecture. By studying C. elegans sensory dendrites, we previously identified genes that act to promote the extension of ciliated sensory dendrites during embryogenesis. Interestingly, the nonciliated dendrite of the oxygen-sensing neuron URX is not affected by these genes, suggesting it develops through a distinct mechanism. Here, we use a visual forward genetic screen to identify mutants that affect URX dendrite morphogenesis. We find that disruption of the MAP kinase MAPK-15 or the βH-spectrin SMA-1 causes a phenotype opposite to what we had seen before: dendrites extend normally during embryogenesis but begin to overgrow as the animals reach adulthood, ultimately extending up to 150% of their normal length. SMA-1 is broadly expressed and acts non-cell-autonomously, while MAPK-15 is expressed in many sensory neurons including URX and acts cell-autonomously. MAPK-15 acts at the time of overgrowth, localizes at the dendrite ending, and requires its kinase activity, suggesting it acts locally in time and space to constrain dendrite growth. Finally, we find that the oxygen-sensing guanylate cyclase GCY-35, which normally localizes at the dendrite ending, is localized throughout the overgrown region, and that overgrowth can be suppressed by overexpressing GCY-35 or by genetically mimicking elevated cGMP signaling. These results suggest that overgrowth may correspond to expansion of a sensory compartment at the dendrite ending, reminiscent of the remodeling of sensory cilia or dendritic spines. Thus, in contrast to established pathways that promote dendrite growth during early development, our results reveal a distinct mechanism that constrains dendrite growth throughout the life of the animal, possibly by controlling the size of a sensory compartment at the dendrite ending.","lang":"eng"}],"pmid":1,"status":"public","publication_identifier":{"issn":["1553-7404"]},"publication_status":"published","day":"07","extern":"1","month":"06","publisher":"Public Library of Science","language":[{"iso":"eng"}],"article_number":"e1007435","intvolume":" 14"},{"external_id":{"isi":["000428419500030"]},"file_date_updated":"2020-07-14T12:47:20Z","scopus_import":"1","_id":"612","date_updated":"2024-03-25T23:30:16Z","oa_version":"Published Version","file":[{"date_created":"2018-12-12T10:15:36Z","file_id":"5157","access_level":"open_access","file_size":5542926,"date_updated":"2020-07-14T12:47:20Z","content_type":"application/pdf","file_name":"IST-2018-1013-v1+1_2018_Kleindienst_Differential.pdf","creator":"system","relation":"main_file","checksum":"a55b3103476ecb5f4f983d8801807e8b"}],"department":[{"_id":"RySh"}],"has_accepted_license":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Luján, Rafael, et al. “Differential Association of GABAB Receptors with Their Effector Ion Channels in Purkinje Cells.” Brain Structure and Function, vol. 223, no. 3, Springer, 2018, pp. 1565–87, doi:10.1007/s00429-017-1568-y.","apa":"Luján, R., Aguado, C., Ciruela, F., Cózar, J., Kleindienst, D., De La Ossa, L., … Fukazawa, Y. (2018). Differential association of GABAB receptors with their effector ion channels in Purkinje cells. Brain Structure and Function. Springer. https://doi.org/10.1007/s00429-017-1568-y","ista":"Luján R, Aguado C, Ciruela F, Cózar J, Kleindienst D, De La Ossa L, Bettler B, Wickman K, Watanabe M, Shigemoto R, Fukazawa Y. 2018. Differential association of GABAB receptors with their effector ion channels in Purkinje cells. Brain Structure and Function. 223(3), 1565–1587.","chicago":"Luján, Rafael, Carolina Aguado, Francisco Ciruela, Javier Cózar, David Kleindienst, Luis De La Ossa, Bernhard Bettler, et al. “Differential Association of GABAB Receptors with Their Effector Ion Channels in Purkinje Cells.” Brain Structure and Function. Springer, 2018. https://doi.org/10.1007/s00429-017-1568-y.","ama":"Luján R, Aguado C, Ciruela F, et al. Differential association of GABAB receptors with their effector ion channels in Purkinje cells. Brain Structure and Function. 2018;223(3):1565-1587. doi:10.1007/s00429-017-1568-y","short":"R. Luján, C. Aguado, F. Ciruela, J. Cózar, D. Kleindienst, L. De La Ossa, B. Bettler, K. Wickman, M. Watanabe, R. Shigemoto, Y. Fukazawa, Brain Structure and Function 223 (2018) 1565–1587.","ieee":"R. Luján et al., “Differential association of GABAB receptors with their effector ion channels in Purkinje cells,” Brain Structure and Function, vol. 223, no. 3. Springer, pp. 1565–1587, 2018."},"oa":1,"author":[{"last_name":"Luján","first_name":"Rafael","full_name":"Luján, Rafael"},{"last_name":"Aguado","full_name":"Aguado, Carolina","first_name":"Carolina"},{"last_name":"Ciruela","full_name":"Ciruela, Francisco","first_name":"Francisco"},{"full_name":"Cózar, Javier","first_name":"Javier","last_name":"Cózar"},{"last_name":"Kleindienst","full_name":"Kleindienst, David","first_name":"David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Luis","full_name":"De La Ossa, Luis","last_name":"De La Ossa"},{"full_name":"Bettler, Bernhard","first_name":"Bernhard","last_name":"Bettler"},{"last_name":"Wickman","first_name":"Kevin","full_name":"Wickman, Kevin"},{"last_name":"Watanabe","first_name":"Masahiko","full_name":"Watanabe, Masahiko"},{"orcid":"0000-0001-8761-9444","first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto"},{"last_name":"Fukazawa","first_name":"Yugo","full_name":"Fukazawa, Yugo"}],"pubrep_id":"1013","type":"journal_article","project":[{"grant_number":"720270","name":"Human Brain Project Specific Grant Agreement 1 (HBP SGA 1)","call_identifier":"H2020","_id":"25CBA828-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"}],"date_published":"2018-04-01T00:00:00Z","title":"Differential association of GABAB receptors with their effector ion channels in Purkinje cells","quality_controlled":"1","tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"year":"2018","publication":"Brain Structure and Function","article_processing_charge":"No","volume":223,"ddc":["571"],"date_created":"2018-12-11T11:47:29Z","issue":"3","doi":"10.1007/s00429-017-1568-y","publist_id":"7192","abstract":[{"lang":"eng","text":"Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically through the modulation of different effector signalling pathways. Here, we analysed the distribution of GABAB receptors using highly sensitive SDS-digested freeze-fracture replica labelling in mouse cerebellar Purkinje cells. Immunoreactivity for GABAB1 was observed on presynaptic and, more abundantly, on postsynaptic compartments, showing both scattered and clustered distribution patterns. Quantitative analysis of immunoparticles revealed a somato-dendritic gradient, with the density of immunoparticles increasing 26-fold from somata to dendritic spines. To understand the spatial relationship of GABAB receptors with two key effector ion channels, the G protein-gated inwardly rectifying K+ (GIRK/Kir3) channel and the voltage-dependent Ca2+ channel, biochemical and immunohistochemical approaches were performed. Co-immunoprecipitation analysis demonstrated that GABAB receptors co-assembled with GIRK and CaV2.1 channels in the cerebellum. Using double-labelling immunoelectron microscopic techniques, co-clustering between GABAB1 and GIRK2 was detected in dendritic spines, whereas they were mainly segregated in the dendritic shafts. In contrast, co-clustering of GABAB1 and CaV2.1 was detected in dendritic shafts but not spines. Presynaptically, although no significant co-clustering of GABAB1 and GIRK2 or CaV2.1 channels was detected, inter-cluster distance for GABAB1 and GIRK2 was significantly smaller in the active zone than in the dendritic shafts, and that for GABAB1 and CaV2.1 was significantly smaller in the active zone than in the dendritic shafts and spines. Thus, GABAB receptors are associated with GIRK and CaV2.1 channels in different subcellular compartments. These data provide a better framework for understanding the different roles played by GABAB receptors and their effector ion channels in the cerebellar network."}],"status":"public","publication_status":"published","day":"01","ec_funded":1,"isi":1,"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"9562"}]},"month":"04","publisher":"Springer","language":[{"iso":"eng"}],"intvolume":" 223","page":"1565 - 1587","article_type":"original"},{"publist_id":"7188","abstract":[{"lang":"eng","text":"Social insects protect their colonies from infectious disease through collective defences that result in social immunity. In ants, workers first try to prevent infection of colony members. Here, we show that if this fails and a pathogen establishes an infection, ants employ an efficient multicomponent behaviour − "destructive disinfection" − to prevent further spread of disease through the colony. Ants specifically target infected pupae during the pathogen's non-contagious incubation period, relying on chemical 'sickness cues' emitted by pupae. They then remove the pupal cocoon, perforate its cuticle and administer antimicrobial poison, which enters the body and prevents pathogen replication from the inside out. Like the immune system of a body that specifically targets and eliminates infected cells, this social immunity measure sacrifices infected brood to stop the pathogen completing its lifecycle, thus protecting the rest of the colony. Hence, the same principles of disease defence apply at different levels of biological organisation."}],"doi":"10.7554/eLife.32073","status":"public","ec_funded":1,"day":"09","publication_status":"published","month":"01","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"819"}]},"isi":1,"publisher":"eLife Sciences Publications","language":[{"iso":"eng"}],"intvolume":" 7","article_number":"e32073","scopus_import":"1","file_date_updated":"2020-07-14T12:47:20Z","external_id":{"isi":["000419601300001"]},"_id":"616","author":[{"id":"3C7F4840-F248-11E8-B48F-1D18A9856A87","first_name":"Christopher","full_name":"Pull, Christopher","orcid":"0000-0003-1122-3982","last_name":"Pull"},{"full_name":"Ugelvig, Line V","id":"3DC97C8E-F248-11E8-B48F-1D18A9856A87","first_name":"Line V","orcid":"0000-0003-1832-8883","last_name":"Ugelvig"},{"first_name":"Florian","id":"39523C54-F248-11E8-B48F-1D18A9856A87","full_name":"Wiesenhofer, Florian","last_name":"Wiesenhofer"},{"last_name":"Grasse","first_name":"Anna V","id":"406F989C-F248-11E8-B48F-1D18A9856A87","full_name":"Grasse, Anna V"},{"full_name":"Tragust, Simon","id":"35A7A418-F248-11E8-B48F-1D18A9856A87","first_name":"Simon","last_name":"Tragust"},{"last_name":"Schmitt","first_name":"Thomas","full_name":"Schmitt, Thomas"},{"full_name":"Brown, Mark","first_name":"Mark","last_name":"Brown"},{"last_name":"Cremer","orcid":"0000-0002-2193-3868","id":"2F64EC8C-F248-11E8-B48F-1D18A9856A87","first_name":"Sylvia","full_name":"Cremer, Sylvia"}],"oa":1,"has_accepted_license":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ieee":"C. Pull et al., “Destructive disinfection of infected brood prevents systemic disease spread in ant colonies,” eLife, vol. 7. eLife Sciences Publications, 2018.","ama":"Pull C, Ugelvig LV, Wiesenhofer F, et al. Destructive disinfection of infected brood prevents systemic disease spread in ant colonies. eLife. 2018;7. doi:10.7554/eLife.32073","short":"C. Pull, L.V. Ugelvig, F. Wiesenhofer, A.V. Grasse, S. Tragust, T. Schmitt, M. Brown, S. Cremer, ELife 7 (2018).","chicago":"Pull, Christopher, Line V Ugelvig, Florian Wiesenhofer, Anna V Grasse, Simon Tragust, Thomas Schmitt, Mark Brown, and Sylvia Cremer. “Destructive Disinfection of Infected Brood Prevents Systemic Disease Spread in Ant Colonies.” ELife. eLife Sciences Publications, 2018. https://doi.org/10.7554/eLife.32073.","ista":"Pull C, Ugelvig LV, Wiesenhofer F, Grasse AV, Tragust S, Schmitt T, Brown M, Cremer S. 2018. Destructive disinfection of infected brood prevents systemic disease spread in ant colonies. eLife. 7, e32073.","apa":"Pull, C., Ugelvig, L. V., Wiesenhofer, F., Grasse, A. V., Tragust, S., Schmitt, T., … Cremer, S. (2018). Destructive disinfection of infected brood prevents systemic disease spread in ant colonies. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.32073","mla":"Pull, Christopher, et al. “Destructive Disinfection of Infected Brood Prevents Systemic Disease Spread in Ant Colonies.” ELife, vol. 7, e32073, eLife Sciences Publications, 2018, doi:10.7554/eLife.32073."},"department":[{"_id":"SyCr"}],"file":[{"creator":"system","checksum":"540f941e8d3530a9441e4affd94f07d7","relation":"main_file","date_updated":"2020-07-14T12:47:20Z","content_type":"application/pdf","file_size":1435585,"file_name":"IST-2018-978-v1+1_elife-32073-v1.pdf","file_id":"4832","date_created":"2018-12-12T10:10:43Z","access_level":"open_access"}],"date_updated":"2023-09-11T12:54:26Z","oa_version":"Published Version","type":"journal_article","pubrep_id":"978","quality_controlled":"1","title":"Destructive disinfection of infected brood prevents systemic disease spread in ant colonies","date_published":"2018-01-09T00:00:00Z","project":[{"grant_number":"243071","name":"Social Vaccination in Ant Colonies: from Individual Mechanisms to Society Effects","call_identifier":"FP7","_id":"25DC711C-B435-11E9-9278-68D0E5697425"},{"_id":"25DDF0F0-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"302004","name":"Pathogen Detectors Collective disease defence and pathogen detection abilities in ant societies: a chemo-neuro-immunological approach"}],"tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_processing_charge":"Yes","volume":7,"publication":"eLife","year":"2018","date_created":"2018-12-11T11:47:31Z","ddc":["570","590"]},{"type":"journal_article","oa":1,"author":[{"orcid":"0000-0002-8696-6978","id":"29D0B332-F248-11E8-B48F-1D18A9856A87","full_name":"Kutzer, Megan","first_name":"Megan","last_name":"Kutzer"},{"first_name":"Joachim","full_name":"Kurtz, Joachim","last_name":"Kurtz"},{"last_name":"Armitage","full_name":"Armitage, Sophie","first_name":"Sophie"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Kutzer M, Kurtz J, Armitage S. 2018. Genotype and diet affect resistance, survival, and fecundity but not fecundity tolerance. Journal of Evolutionary Biology. 31(1), 159–171.","apa":"Kutzer, M., Kurtz, J., & Armitage, S. (2018). Genotype and diet affect resistance, survival, and fecundity but not fecundity tolerance. Journal of Evolutionary Biology. Wiley. https://doi.org/10.1111/jeb.13211","mla":"Kutzer, Megan, et al. “Genotype and Diet Affect Resistance, Survival, and Fecundity but Not Fecundity Tolerance.” Journal of Evolutionary Biology, vol. 31, no. 1, Wiley, 2018, pp. 159–71, doi:10.1111/jeb.13211.","ieee":"M. Kutzer, J. Kurtz, and S. Armitage, “Genotype and diet affect resistance, survival, and fecundity but not fecundity tolerance,” Journal of Evolutionary Biology, vol. 31, no. 1. Wiley, pp. 159–171, 2018.","short":"M. Kutzer, J. Kurtz, S. Armitage, Journal of Evolutionary Biology 31 (2018) 159–171.","ama":"Kutzer M, Kurtz J, Armitage S. Genotype and diet affect resistance, survival, and fecundity but not fecundity tolerance. Journal of Evolutionary Biology. 2018;31(1):159-171. doi:10.1111/jeb.13211","chicago":"Kutzer, Megan, Joachim Kurtz, and Sophie Armitage. “Genotype and Diet Affect Resistance, Survival, and Fecundity but Not Fecundity Tolerance.” Journal of Evolutionary Biology. Wiley, 2018. https://doi.org/10.1111/jeb.13211."},"department":[{"_id":"SyCr"}],"oa_version":"Published Version","date_updated":"2023-09-11T14:06:04Z","_id":"617","scopus_import":"1","external_id":{"pmid":["29150962"],"isi":["000419307000014"]},"date_created":"2018-12-11T11:47:31Z","volume":31,"article_processing_charge":"No","publication":"Journal of Evolutionary Biology","main_file_link":[{"url":"https://doi.org/10.1111/jeb.13211","open_access":"1"}],"year":"2018","quality_controlled":"1","title":"Genotype and diet affect resistance, survival, and fecundity but not fecundity tolerance","date_published":"2018-01-01T00:00:00Z","month":"01","isi":1,"day":"01","acknowledgement":"We would like to thank Susann Wicke for performing the genome-wide SNP/indel analyses, as well as Veronica Alves, Kevin Ferro, Momir Futo, Barbara Hasert, Dafne Maximo, Nora Schulz, Marlene Sroka, and Barth Wieczorek for technical help. We thank Brian Lazzaro for the L. lactis strain and Bruno Lemaitre for the Pseudomonas entomophila strain. We would like to thank two anonymous reviewers for their helpful comments. We are grateful to the Deutsche Forschungsgemeinschaft (DFG) priority programme 1399 ‘Host parasite coevolution’ for funding this project (AR 872/1-1). ","publication_status":"published","publication_identifier":{"issn":["1010-061X"],"eissn":["1420-9101"]},"status":"public","pmid":1,"abstract":[{"lang":"eng","text":"Insects are exposed to a variety of potential pathogens in their environment, many of which can severely impact fitness and health. Consequently, hosts have evolved resistance and tolerance strategies to suppress or cope with infections. Hosts utilizing resistance improve fitness by clearing or reducing pathogen loads, and hosts utilizing tolerance reduce harmful fitness effects per pathogen load. To understand variation in, and selective pressures on, resistance and tolerance, we asked to what degree they are shaped by host genetic background, whether plasticity in these responses depends upon dietary environment, and whether there are interactions between these two factors. Females from ten wild-type Drosophila melanogaster genotypes were kept on high- or low-protein (yeast) diets and infected with one of two opportunistic bacterial pathogens, Lactococcus lactis or Pseudomonas entomophila. We measured host resistance as the inverse of bacterial load in the early infection phase. The relationship (slope) between fly fecundity and individual-level bacteria load provided our fecundity tolerance measure. Genotype and dietary yeast determined host fecundity and strongly affected survival after infection with pathogenic P. entomophila. There was considerable genetic variation in host resistance, a commonly found phenomenon resulting from for example varying resistance costs or frequency-dependent selection. Despite this variation and the reproductive cost of higher P. entomophila loads, fecundity tolerance did not vary across genotypes. The absence of genetic variation in tolerance may suggest that at this early infection stage, fecundity tolerance is fixed or that any evolved tolerance mechanisms are not expressed under these infection conditions."}],"doi":"10.1111/jeb.13211","publist_id":"7187","issue":"1","article_type":"original","page":"159 - 171","intvolume":" 31","language":[{"iso":"eng"}],"publisher":"Wiley"},{"_id":"6183","status":"public","external_id":{"arxiv":["1804.07752"]},"abstract":[{"lang":"eng","text":"We study the unique solution $m$ of the Dyson equation \\[ -m(z)^{-1} = z - a\r\n+ S[m(z)] \\] on a von Neumann algebra $\\mathcal{A}$ with the constraint\r\n$\\mathrm{Im}\\,m\\geq 0$. Here, $z$ lies in the complex upper half-plane, $a$ is\r\na self-adjoint element of $\\mathcal{A}$ and $S$ is a positivity-preserving\r\nlinear operator on $\\mathcal{A}$. We show that $m$ is the Stieltjes transform\r\nof a compactly supported $\\mathcal{A}$-valued measure on $\\mathbb{R}$. Under\r\nsuitable assumptions, we establish that this measure has a uniformly\r\n$1/3$-H\\\"{o}lder continuous density with respect to the Lebesgue measure, which\r\nis supported on finitely many intervals, called bands. In fact, the density is\r\nanalytic inside the bands with a square-root growth at the edges and internal\r\ncubic root cusps whenever the gap between two bands vanishes. The shape of\r\nthese singularities is universal and no other singularity may occur. We give a\r\nprecise asymptotic description of $m$ near the singular points. These\r\nasymptotics generalize the analysis at the regular edges given in the companion\r\npaper on the Tracy-Widom universality for the edge eigenvalue statistics for\r\ncorrelated random matrices [arXiv:1804.07744] and they play a key role in the\r\nproof of the Pearcey universality at the cusp for Wigner-type matrices\r\n[arXiv:1809.03971,arXiv:1811.04055]. We also extend the finite dimensional band\r\nmass formula from [arXiv:1804.07744] to the von Neumann algebra setting by\r\nshowing that the spectral mass of the bands is topologically rigid under\r\ndeformations and we conclude that these masses are quantized in some important\r\ncases."}],"month":"04","related_material":{"record":[{"relation":"dissertation_contains","id":"149","status":"public"},{"status":"public","relation":"later_version","id":"14694"}]},"type":"preprint","department":[{"_id":"LaEr"}],"oa_version":"Preprint","date_updated":"2023-12-18T10:46:08Z","publication_status":"submitted","oa":1,"author":[{"first_name":"Johannes","id":"36D3D8B6-F248-11E8-B48F-1D18A9856A87","full_name":"Alt, Johannes","last_name":"Alt"},{"first_name":"László","id":"4DBD5372-F248-11E8-B48F-1D18A9856A87","full_name":"Erdös, László","orcid":"0000-0001-5366-9603","last_name":"Erdös"},{"orcid":"0000-0002-4821-3297","id":"3020C786-F248-11E8-B48F-1D18A9856A87","full_name":"Krüger, Torben H","first_name":"Torben H","last_name":"Krüger"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ama":"Alt J, Erdös L, Krüger TH. The Dyson equation with linear self-energy: Spectral bands, edges and cusps. arXiv.","short":"J. Alt, L. Erdös, T.H. Krüger, ArXiv (n.d.).","chicago":"Alt, Johannes, László Erdös, and Torben H Krüger. “The Dyson Equation with Linear Self-Energy: Spectral Bands, Edges and Cusps.” ArXiv, n.d.","ieee":"J. Alt, L. Erdös, and T. H. Krüger, “The Dyson equation with linear self-energy: Spectral bands, edges and cusps,” arXiv. .","ista":"Alt J, Erdös L, Krüger TH. The Dyson equation with linear self-energy: Spectral bands, edges and cusps. arXiv, 1804.07752.","apa":"Alt, J., Erdös, L., & Krüger, T. H. (n.d.). The Dyson equation with linear self-energy: Spectral bands, edges and cusps. arXiv.","mla":"Alt, Johannes, et al. “The Dyson Equation with Linear Self-Energy: Spectral Bands, Edges and Cusps.” ArXiv, 1804.07752."},"day":"20","title":"The Dyson equation with linear self-energy: Spectral bands, edges and cusps","date_published":"2018-04-20T00:00:00Z","date_created":"2019-03-28T09:20:06Z","article_number":"1804.07752","main_file_link":[{"url":"https://arxiv.org/abs/1804.07752","open_access":"1"}],"year":"2018","article_processing_charge":"No","arxiv":1,"language":[{"iso":"eng"}],"publication":"arXiv"},{"isi":1,"month":"09","related_material":{"link":[{"relation":"erratum","url":"http://doi.org/10.1038/s41598-018-36220-7"}]},"acknowledgement":"Equipment was generously donated by the NVIDIA Corporation, and made available by the National Science Foundation (NSF) through grant #CNS-1629914. This research used resources of the Argonne Leadership Computing Facility, which is a DOE Office of Science User Facility supported under Contract DE-AC02-06CH11357.","publication_status":"published","day":"24","status":"public","issue":"1","publist_id":"7992","doi":"10.1038/s41598-018-32628-3","abstract":[{"text":"Imaging is a dominant strategy for data collection in neuroscience, yielding stacks of images that often scale to gigabytes of data for a single experiment. Machine learning algorithms from computer vision can serve as a pair of virtual eyes that tirelessly processes these images, automatically detecting and identifying microstructures. Unlike learning methods, our Flexible Learning-free Reconstruction of Imaged Neural volumes (FLoRIN) pipeline exploits structure-specific contextual clues and requires no training. This approach generalizes across different modalities, including serially-sectioned scanning electron microscopy (sSEM) of genetically labeled and contrast enhanced processes, spectral confocal reflectance (SCoRe) microscopy, and high-energy synchrotron X-ray microtomography (μCT) of large tissue volumes. We deploy the FLoRIN pipeline on newly published and novel mouse datasets, demonstrating the high biological fidelity of the pipeline’s reconstructions. FLoRIN reconstructions are of sufficient quality for preliminary biological study, for example examining the distribution and morphology of cells or extracting single axons from functional data. Compared to existing supervised learning methods, FLoRIN is one to two orders of magnitude faster and produces high-quality reconstructions that are tolerant to noise and artifacts, as is shown qualitatively and quantitatively.","lang":"eng"}],"article_number":"14247","intvolume":" 8","article_type":"original","language":[{"iso":"eng"}],"publisher":"Nature Publishing Group","type":"journal_article","oa_version":"Published Version","date_updated":"2023-09-11T14:02:55Z","file":[{"file_size":4141645,"content_type":"application/pdf","date_updated":"2020-07-14T12:47:24Z","file_name":"2018_ScientificReports_Shahbazi.pdf","date_created":"2018-12-17T12:22:24Z","file_id":"5699","access_level":"open_access","creator":"dernst","relation":"main_file","checksum":"1a14ae0666b82fbaa04bef110e3f6bf2"}],"department":[{"_id":"MaJö"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","has_accepted_license":"1","citation":{"apa":"Shabazi, A., Kinnison, J., Vescovi, R., Du, M., Hill, R., Jösch, M. A., … Scheirer, W. (2018). Flexible learning-free segmentation and reconstruction of neural volumes. Scientific Reports. Nature Publishing Group. https://doi.org/10.1038/s41598-018-32628-3","mla":"Shabazi, Ali, et al. “Flexible Learning-Free Segmentation and Reconstruction of Neural Volumes.” Scientific Reports, vol. 8, no. 1, 14247, Nature Publishing Group, 2018, doi:10.1038/s41598-018-32628-3.","ista":"Shabazi A, Kinnison J, Vescovi R, Du M, Hill R, Jösch MA, Takeno M, Zeng H, Da Costa N, Grutzendler J, Kasthuri N, Scheirer W. 2018. Flexible learning-free segmentation and reconstruction of neural volumes. Scientific Reports. 8(1), 14247.","ieee":"A. Shabazi et al., “Flexible learning-free segmentation and reconstruction of neural volumes,” Scientific Reports, vol. 8, no. 1. Nature Publishing Group, 2018.","chicago":"Shabazi, Ali, Jeffery Kinnison, Rafael Vescovi, Ming Du, Robert Hill, Maximilian A Jösch, Marc Takeno, et al. “Flexible Learning-Free Segmentation and Reconstruction of Neural Volumes.” Scientific Reports. Nature Publishing Group, 2018. https://doi.org/10.1038/s41598-018-32628-3.","ama":"Shabazi A, Kinnison J, Vescovi R, et al. Flexible learning-free segmentation and reconstruction of neural volumes. Scientific Reports. 2018;8(1). doi:10.1038/s41598-018-32628-3","short":"A. Shabazi, J. Kinnison, R. Vescovi, M. Du, R. Hill, M.A. Jösch, M. Takeno, H. Zeng, N. Da Costa, J. Grutzendler, N. Kasthuri, W. Scheirer, Scientific Reports 8 (2018)."},"oa":1,"author":[{"last_name":"Shabazi","full_name":"Shabazi, Ali","first_name":"Ali"},{"full_name":"Kinnison, Jeffery","first_name":"Jeffery","last_name":"Kinnison"},{"first_name":"Rafael","full_name":"Vescovi, Rafael","last_name":"Vescovi"},{"full_name":"Du, Ming","first_name":"Ming","last_name":"Du"},{"last_name":"Hill","first_name":"Robert","full_name":"Hill, Robert"},{"last_name":"Jösch","orcid":"0000-0002-3937-1330","first_name":"Maximilian A","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","full_name":"Jösch, Maximilian A"},{"full_name":"Takeno, Marc","first_name":"Marc","last_name":"Takeno"},{"last_name":"Zeng","first_name":"Hongkui","full_name":"Zeng, Hongkui"},{"last_name":"Da Costa","first_name":"Nuno","full_name":"Da Costa, Nuno"},{"first_name":"Jaime","full_name":"Grutzendler, Jaime","last_name":"Grutzendler"},{"last_name":"Kasthuri","full_name":"Kasthuri, Narayanan","first_name":"Narayanan"},{"last_name":"Scheirer","full_name":"Scheirer, Walter","first_name":"Walter"}],"_id":"62","external_id":{"isi":["000445336600015"]},"file_date_updated":"2020-07-14T12:47:24Z","scopus_import":"1","ddc":["570"],"date_created":"2018-12-11T11:44:25Z","year":"2018","publication":"Scientific Reports","article_processing_charge":"No","volume":8,"tmp":{"image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"title":"Flexible learning-free segmentation and reconstruction of neural volumes","date_published":"2018-09-24T00:00:00Z","quality_controlled":"1"},{"publisher":"Company of Biologists","language":[{"iso":"eng"}],"intvolume":" 131","article_number":"jcs207696","abstract":[{"text":"Clathrin-mediated endocytosis requires the coordinated assembly of various endocytic proteins and lipids at the plasma membrane. Accumulating evidence demonstrates a crucial role for phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) in endocytosis, but specific roles for PtdIns(4)P other than as the biosynthetic precursor of PtdIns(4,5)P2 have not been clarified. In this study we investigated the role of PtdIns(4)P or PtdIns(4,5)P2 in receptor-mediated endocytosis through the construction of temperature-sensitive (ts) mutants for the PI 4-kinases Stt4p and Pik1p and the PtdIns(4) 5-kinase Mss4p. Quantitative analyses of endocytosis revealed that both the stt4(ts)pik1(ts) and mss4(ts) mutants have a severe defect in endocytic internalization. Live-cell imaging of endocytic protein dynamics in stt4(ts)pik1(ts) and mss4(ts) mutants revealed that PtdIns(4)P is required for the recruitment of the alpha-factor receptor Ste2p to clathrin-coated pits whereas PtdIns(4,5)P2 is required for membrane internalization. We also found that the localization to endocytic sites of the ENTH/ANTH domain-bearing clathrin adaptors, Ent1p/Ent2p and Yap1801p/Yap1802p, is significantly impaired in the stt4(ts)pik1(ts) mutant, but not in the mss4(ts) mutant. These results suggest distinct roles in successive steps for PtdIns(4)P and PtdIns(4,5)P2 during receptor-mediated endocytosis.","lang":"eng"}],"publist_id":"7184","doi":"10.1242/jcs.207696","issue":"1","pmid":1,"status":"public","day":"04","publication_status":"published","month":"01","isi":1,"quality_controlled":"1","date_published":"2018-01-04T00:00:00Z","title":"Distinct roles for plasma membrane PtdIns 4 P and PtdIns 4 5 P2 during yeast receptor mediated endocytosis","volume":131,"article_processing_charge":"No","publication":"Journal of Cell Science","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pubmed/29192062"}],"year":"2018","date_created":"2018-12-11T11:47:32Z","scopus_import":"1","external_id":{"isi":["000424786900012"],"pmid":["29192062"]},"_id":"620","author":[{"last_name":"Yamamoto","first_name":"Wataru","full_name":"Yamamoto, Wataru"},{"full_name":"Wada, Suguru","first_name":"Suguru","last_name":"Wada"},{"full_name":"Nagano, Makoto","first_name":"Makoto","last_name":"Nagano"},{"last_name":"Aoshima","full_name":"Aoshima, Kaito","first_name":"Kaito"},{"last_name":"Siekhaus","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","full_name":"Siekhaus, Daria E","first_name":"Daria E","orcid":"0000-0001-8323-8353"},{"full_name":"Toshima, Junko","first_name":"Junko","last_name":"Toshima"},{"first_name":"Jiro","full_name":"Toshima, Jiro","last_name":"Toshima"}],"oa":1,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Yamamoto W, Wada S, Nagano M, Aoshima K, Siekhaus DE, Toshima J, Toshima J. 2018. Distinct roles for plasma membrane PtdIns 4 P and PtdIns 4 5 P2 during yeast receptor mediated endocytosis. Journal of Cell Science. 131(1), jcs207696.","mla":"Yamamoto, Wataru, et al. “Distinct Roles for Plasma Membrane PtdIns 4 P and PtdIns 4 5 P2 during Yeast Receptor Mediated Endocytosis.” Journal of Cell Science, vol. 131, no. 1, jcs207696, Company of Biologists, 2018, doi:10.1242/jcs.207696.","apa":"Yamamoto, W., Wada, S., Nagano, M., Aoshima, K., Siekhaus, D. E., Toshima, J., & Toshima, J. (2018). Distinct roles for plasma membrane PtdIns 4 P and PtdIns 4 5 P2 during yeast receptor mediated endocytosis. Journal of Cell Science. Company of Biologists. https://doi.org/10.1242/jcs.207696","ieee":"W. Yamamoto et al., “Distinct roles for plasma membrane PtdIns 4 P and PtdIns 4 5 P2 during yeast receptor mediated endocytosis,” Journal of Cell Science, vol. 131, no. 1. Company of Biologists, 2018.","short":"W. Yamamoto, S. Wada, M. Nagano, K. Aoshima, D.E. Siekhaus, J. Toshima, J. Toshima, Journal of Cell Science 131 (2018).","ama":"Yamamoto W, Wada S, Nagano M, et al. Distinct roles for plasma membrane PtdIns 4 P and PtdIns 4 5 P2 during yeast receptor mediated endocytosis. Journal of Cell Science. 2018;131(1). doi:10.1242/jcs.207696","chicago":"Yamamoto, Wataru, Suguru Wada, Makoto Nagano, Kaito Aoshima, Daria E Siekhaus, Junko Toshima, and Jiro Toshima. “Distinct Roles for Plasma Membrane PtdIns 4 P and PtdIns 4 5 P2 during Yeast Receptor Mediated Endocytosis.” Journal of Cell Science. Company of Biologists, 2018. https://doi.org/10.1242/jcs.207696."},"department":[{"_id":"DaSi"}],"date_updated":"2023-09-11T12:57:13Z","oa_version":"Published Version","type":"journal_article"},{"title":"Genetic determinants of antibiotic resistance evolution","date_published":"2018-12-28T00:00:00Z","date_created":"2019-04-09T13:57:15Z","ddc":["570","576","579"],"article_processing_charge":"No","year":"2018","_id":"6263","file_date_updated":"2021-02-11T11:17:17Z","type":"dissertation","author":[{"id":"4342E402-F248-11E8-B48F-1D18A9856A87","first_name":"Marta","full_name":"Lukacisinova, Marta","orcid":"0000-0002-2519-8004","last_name":"Lukacisinova"}],"oa":1,"has_accepted_license":"1","citation":{"short":"M. Lukacisinova, Genetic Determinants of Antibiotic Resistance Evolution, Institute of Science and Technology Austria, 2018.","ama":"Lukacisinova M. Genetic determinants of antibiotic resistance evolution. 2018. doi:10.15479/AT:ISTA:th1072","chicago":"Lukacisinova, Marta. “Genetic Determinants of Antibiotic Resistance Evolution.” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th1072.","ieee":"M. Lukacisinova, “Genetic determinants of antibiotic resistance evolution,” Institute of Science and Technology Austria, 2018.","ista":"Lukacisinova M. 2018. Genetic determinants of antibiotic resistance evolution. Institute of Science and Technology Austria.","apa":"Lukacisinova, M. (2018). Genetic determinants of antibiotic resistance evolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th1072","mla":"Lukacisinova, Marta. Genetic Determinants of Antibiotic Resistance Evolution. Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th1072."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"ToBo"}],"file":[{"checksum":"fc60585c9eaad868ac007004ef130908","relation":"main_file","creator":"dernst","embargo":"2020-01-25","file_name":"2018_Thesis_Lukacisinova.pdf","content_type":"application/pdf","date_updated":"2021-02-11T11:17:17Z","file_size":5656866,"access_level":"open_access","file_id":"6264","date_created":"2019-04-09T13:49:24Z"},{"file_size":5168054,"date_updated":"2020-07-14T12:47:25Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"2018_Thesis_Lukacisinova_source.docx","embargo_to":"open_access","date_created":"2019-04-09T13:49:23Z","file_id":"6265","access_level":"closed","creator":"dernst","relation":"source_file","checksum":"264057ec0a92ab348cc83b41f021ba92"}],"date_updated":"2023-09-22T09:20:37Z","oa_version":"Published Version","publisher":"Institute of Science and Technology Austria","supervisor":[{"last_name":"Bollenbach","full_name":"Bollenbach, Tobias","first_name":"Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X"}],"page":"91","language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"status":"public","degree_awarded":"PhD","doi":"10.15479/AT:ISTA:th1072","abstract":[{"text":"Antibiotic resistance can emerge spontaneously through genomic mutation and render treatment ineffective. To counteract this process, in addition to the discovery and description of resistance mechanisms,a deeper understanding of resistanceevolvabilityand its determinantsis needed. To address this challenge, this thesisuncoversnew genetic determinants of resistance evolvability using a customized robotic setup, exploressystematic ways in which resistance evolution is perturbed due to dose-responsecharacteristics of drugs and mutation rate differences,and mathematically investigates the evolutionary fate of one specific type of evolvability modifier -a stress-induced mutagenesis allele.We find severalgenes which strongly inhibit or potentiate resistance evolution. In order to identify them, we first developedan automated high-throughput feedback-controlled protocol whichkeeps the population size and selection pressure approximately constant for hundreds of cultures by dynamically re-diluting the cultures and adjusting the antibiotic concentration. We implementedthis protocol on a customized liquid handling robot and propagated 100 different gene deletion strains of Escherichia coliin triplicate for over 100 generations in tetracycline and in chloramphenicol, and comparedtheir adaptation rates.We find a diminishing returns pattern, where initially sensitive strains adapted more compared to less sensitive ones. Our data uncover that deletions of certain genes which do not affect mutation rate,including efflux pump components, a chaperone and severalstructural and regulatory genes can strongly and reproducibly alterresistance evolution. Sequencing analysis of evolved populations indicates that epistasis with resistance mutations is the most likelyexplanation. This work could inspire treatment strategies in which targeted inhibitors of evolvability mechanisms will be given alongside antibiotics to slow down resistance evolution and extend theefficacy of antibiotics.We implemented astochasticpopulation genetics model, toverifyways in which general properties, namely, dose-response characteristics of drugs and mutation rates, influence evolutionary dynamics. In particular, under the exposure to antibiotics with shallow dose-response curves,bacteria have narrower distributions of fitness effects of new mutations. We show that in silicothis also leads to slower resistance evolution. We see and confirm with experiments that increased mutation rates, apart from speeding up evolution, also leadto high reproducibility of phenotypic adaptation in a context of continually strong selection pressure.Knowledge of these patterns can aid in predicting the dynamics of antibiotic resistance evolutionand adapting treatment schemes accordingly.Focusing on a previously described type of evolvability modifier –a stress-induced mutagenesis allele –we find conditions under which it can persist in a population under periodic selectionakin to clinical treatment. We set up a deterministic infinite populationcontinuous time model tracking the frequencies of a mutator and resistance allele and evaluate various treatment schemes in how well they maintain a stress-induced mutator allele. In particular,a high diversity of stresses is crucial for the persistence of the mutator allele. This leads to a general trade-off where exactly those diversifying treatment schemes which are likely to decrease levels of resistance could lead to stronger selection of highly evolvable genotypes.In the long run, this work will lead to a deeper understanding of the genetic and cellular mechanisms involved in antibiotic resistance evolution and could inspire new strategies for slowing down its rate. ","lang":"eng"}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"LifeSc"}],"related_material":{"record":[{"status":"public","id":"1619","relation":"part_of_dissertation"},{"status":"public","id":"696","relation":"part_of_dissertation"},{"status":"public","relation":"part_of_dissertation","id":"1027"}]},"month":"12","alternative_title":["ISTA Thesis"],"day":"28","publication_status":"published"}]