[{"acknowledgement":"We thank N. Engelsen for comments on the manuscript. This work was supported by the Office of Naval Research, Vannevar Bush Faculty Fellowship, Department of Energy, and Defense Threat Reduction Agency. R.K. was partly supported by the AQT/INQNET program at Caltech.","quality_controlled":"1","publisher":"American Physical Society","oa":1,"isi":1,"year":"2020","day":"30","publication":"Physical Review A","doi":"10.1103/PhysRevA.102.012224","date_published":"2020-07-30T00:00:00Z","date_created":"2020-08-30T22:01:10Z","article_number":"012224","citation":{"short":"Y. Wu, R. Krishnakumar, J. Martínez-Rincón, B.K. Malia, O. Hosten, M.A. Kasevich, Physical Review A 102 (2020).","ieee":"Y. Wu, R. Krishnakumar, J. Martínez-Rincón, B. K. Malia, O. Hosten, and M. A. Kasevich, “Retrieval of cavity-generated atomic spin squeezing after free-space release,” Physical Review A, vol. 102, no. 1. American Physical Society, 2020.","ama":"Wu Y, Krishnakumar R, Martínez-Rincón J, Malia BK, Hosten O, Kasevich MA. Retrieval of cavity-generated atomic spin squeezing after free-space release. Physical Review A. 2020;102(1). doi:10.1103/PhysRevA.102.012224","apa":"Wu, Y., Krishnakumar, R., Martínez-Rincón, J., Malia, B. K., Hosten, O., & Kasevich, M. A. (2020). Retrieval of cavity-generated atomic spin squeezing after free-space release. Physical Review A. American Physical Society. https://doi.org/10.1103/PhysRevA.102.012224","mla":"Wu, Yunfan, et al. “Retrieval of Cavity-Generated Atomic Spin Squeezing after Free-Space Release.” Physical Review A, vol. 102, no. 1, 012224, American Physical Society, 2020, doi:10.1103/PhysRevA.102.012224.","ista":"Wu Y, Krishnakumar R, Martínez-Rincón J, Malia BK, Hosten O, Kasevich MA. 2020. Retrieval of cavity-generated atomic spin squeezing after free-space release. Physical Review A. 102(1), 012224.","chicago":"Wu, Yunfan, Rajiv Krishnakumar, Julián Martínez-Rincón, Benjamin K. Malia, Onur Hosten, and Mark A. Kasevich. “Retrieval of Cavity-Generated Atomic Spin Squeezing after Free-Space Release.” Physical Review A. American Physical Society, 2020. https://doi.org/10.1103/PhysRevA.102.012224."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Yunfan","full_name":"Wu, Yunfan","last_name":"Wu"},{"first_name":"Rajiv","full_name":"Krishnakumar, Rajiv","last_name":"Krishnakumar"},{"first_name":"Julián","last_name":"Martínez-Rincón","full_name":"Martínez-Rincón, Julián"},{"full_name":"Malia, Benjamin K.","last_name":"Malia","first_name":"Benjamin K."},{"id":"4C02D85E-F248-11E8-B48F-1D18A9856A87","first_name":"Onur","last_name":"Hosten","orcid":"0000-0002-2031-204X","full_name":"Hosten, Onur"},{"last_name":"Kasevich","full_name":"Kasevich, Mark A.","first_name":"Mark A."}],"article_processing_charge":"No","external_id":{"arxiv":["1912.08334"],"isi":["000555104200011"]},"title":"Retrieval of cavity-generated atomic spin squeezing after free-space release","abstract":[{"lang":"eng","text":"We demonstrate that releasing atoms into free space from an optical lattice does not deteriorate cavity-generated spin squeezing for metrological purposes. In this work, an ensemble of 500000 spin-squeezed atoms in a high-finesse optical cavity with near-uniform atom-cavity coupling is prepared, released into free space, recaptured in the cavity, and probed. Up to ∼10 dB of metrologically relevant squeezing is retrieved for 700μs free-fall times, and decaying levels of squeezing are realized for up to 3 ms free-fall times. The degradation of squeezing results from loss of atom-cavity coupling homogeneity between the initial squeezed state generation and final collective state readout. A theoretical model is developed to quantify this degradation and this model is experimentally validated."}],"oa_version":"Preprint","scopus_import":"1","main_file_link":[{"url":"https://arxiv.org/abs/1912.08334","open_access":"1"}],"month":"07","intvolume":" 102","publication_identifier":{"issn":["24699926"],"eissn":["24699934"]},"publication_status":"published","language":[{"iso":"eng"}],"issue":"1","volume":102,"_id":"8319","article_type":"original","type":"journal_article","status":"public","date_updated":"2024-02-28T13:11:28Z","department":[{"_id":"OnHo"}]},{"abstract":[{"lang":"eng","text":"Markov decision processes (MDPs) are the defacto framework for sequential decision making in the presence of stochastic uncertainty. A classical optimization criterion for MDPs is to maximize the expected discounted-sum payoff, which ignores low probability catastrophic events with highly negative impact on the system. On the other hand, risk-averse policies require the probability of undesirable events to be below a given threshold, but they do not account for optimization of the expected payoff. We consider MDPs with discounted-sum payoff with failure states which represent catastrophic outcomes. The objective of risk-constrained planning is to maximize the expected discounted-sum payoff among risk-averse policies that ensure the probability to encounter a failure state is below a desired threshold. Our main contribution is an efficient risk-constrained planning algorithm that combines UCT-like search with a predictor learned through interaction with the MDP (in the style of AlphaZero) and with a risk-constrained action selection via linear programming. We demonstrate the effectiveness of our approach with experiments on classical MDPs from the literature, including benchmarks with an order of 106 states."}],"oa_version":"Preprint","main_file_link":[{"url":"https://doi.org/10.48550/arXiv.2002.12086","open_access":"1"}],"intvolume":" 34","month":"04","publication_status":"published","publication_identifier":{"issn":["2374-3468"]},"language":[{"iso":"eng"}],"issue":"06","volume":34,"_id":"15055","conference":{"end_date":"2020-02-12","location":"New York, NY, United States","start_date":"2020-02-07","name":"AAAI: Conference on Artificial Intelligence"},"type":"journal_article","article_type":"original","keyword":["General Medicine"],"status":"public","date_updated":"2024-03-04T08:30:16Z","department":[{"_id":"KrCh"}],"acknowledgement":"Krishnendu Chatterjee is supported by the Austrian Science Fund (FWF) NFN Grant No. S11407-N23 (RiSE/SHiNE), and COST Action GAMENET. Tomas Brazdil is supported by the Grant Agency of Masaryk University grant no. MUNI/G/0739/2017 and by the Czech Science Foundation grant No. 18-11193S. Petr Novotny and Jirı Vahala are supported by the Czech Science Foundation grant No. GJ19-15134Y.","oa":1,"quality_controlled":"1","publisher":"Association for the Advancement of Artificial Intelligence","year":"2020","publication":"Proceedings of the 34th AAAI Conference on Artificial Intelligence","day":"03","page":"9794-9801","date_created":"2024-03-04T08:07:22Z","doi":"10.1609/aaai.v34i06.6531","date_published":"2020-04-03T00:00:00Z","project":[{"name":"Game Theory","grant_number":"S11407","_id":"25863FF4-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"citation":{"ista":"Brázdil T, Chatterjee K, Novotný P, Vahala J. 2020. Reinforcement learning of risk-constrained policies in Markov decision processes. Proceedings of the 34th AAAI Conference on Artificial Intelligence. 34(06), 9794–9801.","chicago":"Brázdil, Tomáš, Krishnendu Chatterjee, Petr Novotný, and Jiří Vahala. “Reinforcement Learning of Risk-Constrained Policies in Markov Decision Processes.” Proceedings of the 34th AAAI Conference on Artificial Intelligence. Association for the Advancement of Artificial Intelligence, 2020. https://doi.org/10.1609/aaai.v34i06.6531.","ama":"Brázdil T, Chatterjee K, Novotný P, Vahala J. Reinforcement learning of risk-constrained policies in Markov decision processes. Proceedings of the 34th AAAI Conference on Artificial Intelligence. 2020;34(06):9794-9801. doi:10.1609/aaai.v34i06.6531","apa":"Brázdil, T., Chatterjee, K., Novotný, P., & Vahala, J. (2020). Reinforcement learning of risk-constrained policies in Markov decision processes. Proceedings of the 34th AAAI Conference on Artificial Intelligence. New York, NY, United States: Association for the Advancement of Artificial Intelligence. https://doi.org/10.1609/aaai.v34i06.6531","short":"T. Brázdil, K. Chatterjee, P. Novotný, J. Vahala, Proceedings of the 34th AAAI Conference on Artificial Intelligence 34 (2020) 9794–9801.","ieee":"T. Brázdil, K. Chatterjee, P. Novotný, and J. Vahala, “Reinforcement learning of risk-constrained policies in Markov decision processes,” Proceedings of the 34th AAAI Conference on Artificial Intelligence, vol. 34, no. 06. Association for the Advancement of Artificial Intelligence, pp. 9794–9801, 2020.","mla":"Brázdil, Tomáš, et al. “Reinforcement Learning of Risk-Constrained Policies in Markov Decision Processes.” Proceedings of the 34th AAAI Conference on Artificial Intelligence, vol. 34, no. 06, Association for the Advancement of Artificial Intelligence, 2020, pp. 9794–801, doi:10.1609/aaai.v34i06.6531."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","external_id":{"arxiv":["2002.12086"]},"author":[{"full_name":"Brázdil, Tomáš","last_name":"Brázdil","first_name":"Tomáš"},{"last_name":"Chatterjee","orcid":"0000-0002-4561-241X","full_name":"Chatterjee, Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","first_name":"Krishnendu"},{"last_name":"Novotný","full_name":"Novotný, Petr","first_name":"Petr"},{"first_name":"Jiří","full_name":"Vahala, Jiří","last_name":"Vahala"}],"title":"Reinforcement learning of risk-constrained policies in Markov decision processes"},{"article_number":"aaw7824","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Park, Sangsoon, et al. “VRK-1 Extends Life Span by Activation of AMPK via Phosphorylation.” Science Advances, vol. 6, no. 27, aaw7824, American Association for the Advancement of Science, 2020, doi:10.1126/sciadv.aaw7824.","apa":"Park, S., Artan, M., Han, S. H., Park, H.-E. H., Jung, Y., Hwang, A. B., … Lee, S.-J. V. (2020). VRK-1 extends life span by activation of AMPK via phosphorylation. Science Advances. American Association for the Advancement of Science. https://doi.org/10.1126/sciadv.aaw7824","ama":"Park S, Artan M, Han SH, et al. VRK-1 extends life span by activation of AMPK via phosphorylation. Science Advances. 2020;6(27). doi:10.1126/sciadv.aaw7824","ieee":"S. Park et al., “VRK-1 extends life span by activation of AMPK via phosphorylation,” Science Advances, vol. 6, no. 27. American Association for the Advancement of Science, 2020.","short":"S. Park, M. Artan, S.H. Han, H.-E.H. Park, Y. Jung, A.B. Hwang, W.S. Shin, K.-T. Kim, S.-J.V. Lee, Science Advances 6 (2020).","chicago":"Park, Sangsoon, Murat Artan, Seung Hyun Han, Hae-Eun H. Park, Yoonji Jung, Ara B. Hwang, Won Sik Shin, Kyong-Tai Kim, and Seung-Jae V. Lee. “VRK-1 Extends Life Span by Activation of AMPK via Phosphorylation.” Science Advances. American Association for the Advancement of Science, 2020. https://doi.org/10.1126/sciadv.aaw7824.","ista":"Park S, Artan M, Han SH, Park H-EH, Jung Y, Hwang AB, Shin WS, Kim K-T, Lee S-JV. 2020. VRK-1 extends life span by activation of AMPK via phosphorylation. Science Advances. 6(27), aaw7824."},"title":"VRK-1 extends life span by activation of AMPK via phosphorylation","author":[{"first_name":"Sangsoon","full_name":"Park, Sangsoon","last_name":"Park"},{"id":"C407B586-6052-11E9-B3AE-7006E6697425","first_name":"Murat","last_name":"Artan","full_name":"Artan, Murat","orcid":"0000-0001-8945-6992"},{"full_name":"Han, Seung Hyun","last_name":"Han","first_name":"Seung Hyun"},{"first_name":"Hae-Eun H.","full_name":"Park, Hae-Eun H.","last_name":"Park"},{"last_name":"Jung","full_name":"Jung, Yoonji","first_name":"Yoonji"},{"full_name":"Hwang, Ara B.","last_name":"Hwang","first_name":"Ara B."},{"first_name":"Won Sik","last_name":"Shin","full_name":"Shin, Won Sik"},{"first_name":"Kyong-Tai","last_name":"Kim","full_name":"Kim, Kyong-Tai"},{"first_name":"Seung-Jae V.","full_name":"Lee, Seung-Jae V.","last_name":"Lee"}],"article_processing_charge":"No","acknowledgement":"This research was supported by grants NRF-2019R1A3B2067745 and NRF-2017R1A5A1015366 funded by the Korean Government (MSIT) through the National Research Foundation (NRF) of Korea to S.-J.V.L. and by grant Basic Science Research Program (No. 2019R1A2C2009440) funded by the Korean Government (MSIT) through the NRF of Korea to K.-T.K. ","quality_controlled":"1","publisher":"American Association for the Advancement of Science","oa":1,"day":"01","publication":"Science Advances","has_accepted_license":"1","year":"2020","date_published":"2020-07-01T00:00:00Z","doi":"10.1126/sciadv.aaw7824","date_created":"2024-03-04T09:41:57Z","_id":"15057","status":"public","article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)"},"ddc":["570"],"date_updated":"2024-03-04T09:52:09Z","file_date_updated":"2024-03-04T09:46:41Z","department":[{"_id":"MaDe"}],"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Vaccinia virus–related kinase (VRK) is an evolutionarily conserved nuclear protein kinase. VRK-1, the single Caenorhabditis elegans VRK ortholog, functions in cell division and germline proliferation. However, the role of VRK-1 in postmitotic cells and adult life span remains unknown. Here, we show that VRK-1 increases organismal longevity by activating the cellular energy sensor, AMP-activated protein kinase (AMPK), via direct phosphorylation. We found that overexpression of vrk-1 in the soma of adult C. elegans increased life span and, conversely, inhibition of vrk-1 decreased life span. In addition, vrk-1 was required for longevity conferred by mutations that inhibit C. elegans mitochondrial respiration, which requires AMPK. VRK-1 directly phosphorylated and up-regulated AMPK in both C. elegans and cultured human cells. Thus, our data show that the somatic nuclear kinase, VRK-1, promotes longevity through AMPK activation, and this function appears to be conserved between C. elegans and humans."}],"month":"07","intvolume":" 6","file":[{"file_name":"2020_ScienceAdvances_Park.pdf","date_created":"2024-03-04T09:46:41Z","file_size":1864415,"date_updated":"2024-03-04T09:46:41Z","creator":"dernst","success":1,"file_id":"15058","checksum":"a37157cd0de709dce5fe03f4a31cd0b6","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2375-2548"]},"publication_status":"published","issue":"27","volume":6,"license":"https://creativecommons.org/licenses/by-nc/4.0/"},{"citation":{"chicago":"Pinotsis, Nikos, Karolina Zielinska, Mrigya Babuta, Joan L. Arolas, Julius Kostan, Muhammad Bashir Khan, Claudia Schreiner, et al. “Calcium Modulates the Domain Flexibility and Function of an α-Actinin Similar to the Ancestral α-Actinin.” Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences, 2020. https://doi.org/10.1073/pnas.1917269117.","ista":"Pinotsis N, Zielinska K, Babuta M, Arolas JL, Kostan J, Khan MB, Schreiner C, Testa Salmazo AP, Ciccarelli L, Puchinger M, Gkougkoulia EA, Ribeiro E de A, Marlovits TC, Bhattacharya A, Djinovic-Carugo K. 2020. Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin. Proceedings of the National Academy of Sciences. 117(36), 22101–22112.","mla":"Pinotsis, Nikos, et al. “Calcium Modulates the Domain Flexibility and Function of an α-Actinin Similar to the Ancestral α-Actinin.” Proceedings of the National Academy of Sciences, vol. 117, no. 36, Proceedings of the National Academy of Sciences, 2020, pp. 22101–12, doi:10.1073/pnas.1917269117.","short":"N. Pinotsis, K. Zielinska, M. Babuta, J.L. Arolas, J. Kostan, M.B. Khan, C. Schreiner, A.P. Testa Salmazo, L. Ciccarelli, M. Puchinger, E.A. Gkougkoulia, E. de A. Ribeiro, T.C. Marlovits, A. Bhattacharya, K. Djinovic-Carugo, Proceedings of the National Academy of Sciences 117 (2020) 22101–22112.","ieee":"N. Pinotsis et al., “Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin,” Proceedings of the National Academy of Sciences, vol. 117, no. 36. Proceedings of the National Academy of Sciences, pp. 22101–22112, 2020.","apa":"Pinotsis, N., Zielinska, K., Babuta, M., Arolas, J. L., Kostan, J., Khan, M. B., … Djinovic-Carugo, K. (2020). Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin. Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1917269117","ama":"Pinotsis N, Zielinska K, Babuta M, et al. Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin. Proceedings of the National Academy of Sciences. 2020;117(36):22101-22112. doi:10.1073/pnas.1917269117"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Pinotsis","full_name":"Pinotsis, Nikos","first_name":"Nikos"},{"first_name":"Karolina","full_name":"Zielinska, Karolina","last_name":"Zielinska"},{"first_name":"Mrigya","last_name":"Babuta","full_name":"Babuta, Mrigya"},{"first_name":"Joan L.","full_name":"Arolas, Joan L.","last_name":"Arolas"},{"last_name":"Kostan","full_name":"Kostan, Julius","first_name":"Julius"},{"first_name":"Muhammad Bashir","full_name":"Khan, Muhammad Bashir","last_name":"Khan"},{"last_name":"Schreiner","full_name":"Schreiner, Claudia","first_name":"Claudia"},{"last_name":"Testa Salmazo","full_name":"Testa Salmazo, Anita P","id":"41F1F098-F248-11E8-B48F-1D18A9856A87","first_name":"Anita P"},{"full_name":"Ciccarelli, Luciano","last_name":"Ciccarelli","first_name":"Luciano"},{"full_name":"Puchinger, Martin","last_name":"Puchinger","first_name":"Martin"},{"first_name":"Eirini A.","full_name":"Gkougkoulia, Eirini A.","last_name":"Gkougkoulia"},{"first_name":"Euripedes de Almeida","full_name":"Ribeiro, Euripedes de Almeida","last_name":"Ribeiro"},{"last_name":"Marlovits","full_name":"Marlovits, Thomas C.","first_name":"Thomas C."},{"full_name":"Bhattacharya, Alok","last_name":"Bhattacharya","first_name":"Alok"},{"first_name":"Kristina","full_name":"Djinovic-Carugo, Kristina","last_name":"Djinovic-Carugo"}],"article_processing_charge":"No","external_id":{"pmid":["32848067"]},"title":"Calcium modulates the domain flexibility and function of an α-actinin similar to the ancestral α-actinin","acknowledgement":"We thank the staff of the macromolecular crystallography (MX) and SAXS beamlines at the European Synchrotron Radiation facility, Diamond, and Swiss Light Source for excellent support, and the Life Sciences Facility of the Institute of Science and Technology Austria for usage of the rheometer. We thank Life Sciences editors for editing assistance. EM data were\r\nrecorded at the EM Facility of the Vienna BioCenter Core Facilities (Austria). Confocal microscopy was carried out at the Advanced Instrument Research Facility, Jawaharlal Nehru University. K.D.-C.’s research was supported by the Initial Training Network MUZIC (ITN-MUZIC) (N°238423), Austrian Science Fund (FWF) Projects I525, I1593, P22276, P19060, and W1221, Laura Bassi Centre of Optimized Structural Studies (N°253275), a Wellcome Trust Collaborative Award (201543/Z/16/Z), COST Action BM1405, Vienna Science and Technology Fund (WWTF) Chemical Biology Project LS17-008, and Christian Doppler Laboratory for High-Content Structural Biology and Biotechnology. K.Z., J.L.A., C.S., E.A.G., and A.S. were supported by the University of Vienna, J.K. by a Wellcome Trust Collaborative Award and by the Centre of Optimized Structural Studies, M.P. by FWF Project I1593, E.d.A.R. ITN-MUZIC, and FWF Projects I525 and I1593, and T.C.M. and L.C. by FWF Project I 2408-B22. E.A.G. acknowledges the PhD program Structure and Interaction of Biological Macromolecules. M.B. acknowledges the University Grant Commission, India, for a senior research fellowship. A.B. acknowledges a JC Bose Fellowship from the Science Engineering Research Council. ","quality_controlled":"1","publisher":"Proceedings of the National Academy of Sciences","oa":1,"year":"2020","day":"08","publication":"Proceedings of the National Academy of Sciences","page":"22101-22112","date_published":"2020-09-08T00:00:00Z","doi":"10.1073/pnas.1917269117","date_created":"2024-03-04T10:03:52Z","_id":"15061","type":"journal_article","article_type":"original","status":"public","date_updated":"2024-03-04T10:14:44Z","department":[{"_id":"CaBe"}],"acknowledged_ssus":[{"_id":"LifeSc"}],"abstract":[{"lang":"eng","text":"The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin–binding proteins, is fundamentally important in eukaryotes. α-Actinins are major F-actin bundlers that are inhibited by Ca2+ in nonmuscle cells. Here we report the mechanism of Ca2+-mediated regulation of Entamoeba histolytica α-actinin-2 (EhActn2) with features expected for the common ancestor of Entamoeba and higher eukaryotic α-actinins. Crystal structures of Ca2+-free and Ca2+-bound EhActn2 reveal a calmodulin-like domain (CaMD) uniquely inserted within the rod domain. Integrative studies reveal an exceptionally high affinity of the EhActn2 CaMD for Ca2+, binding of which can only be regulated in the presence of physiological concentrations of Mg2+. Ca2+ binding triggers an increase in protein multidomain rigidity, reducing conformational flexibility of F-actin–binding domains via interdomain cross-talk and consequently inhibiting F-actin bundling. In vivo studies uncover that EhActn2 plays an important role in phagocytic cup formation and might constitute a new drug target for amoebic dysentery."}],"pmid":1,"oa_version":"Published Version","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1073/pnas.191726911"}],"month":"09","intvolume":" 117","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"publication_status":"published","language":[{"iso":"eng"}],"issue":"36","volume":117},{"has_accepted_license":"1","year":"2020","day":"01","publication":"Journal of Applied and Computational Topology","page":"455-480","doi":"10.1007/s41468-020-00058-8","date_published":"2020-12-01T00:00:00Z","date_created":"2024-03-04T10:47:49Z","acknowledgement":"This research has been supported by the DFG Collaborative Research Center SFB/TRR 109 “Discretization in Geometry and Dynamics”, by Polish MNiSzW Grant No. 2621/7.PR/12/2013/2, by the Polish National Science Center under Maestro Grant No. 2014/14/A/ST1/00453 and Grant No. DEC-2013/09/N/ST6/02995. Open Access funding provided by Projekt DEAL.","publisher":"Springer Nature","quality_controlled":"1","oa":1,"citation":{"mla":"Bauer, U., et al. “Čech-Delaunay Gradient Flow and Homology Inference for Self-Maps.” Journal of Applied and Computational Topology, vol. 4, no. 4, Springer Nature, 2020, pp. 455–80, doi:10.1007/s41468-020-00058-8.","ama":"Bauer U, Edelsbrunner H, Jablonski G, Mrozek M. Čech-Delaunay gradient flow and homology inference for self-maps. Journal of Applied and Computational Topology. 2020;4(4):455-480. doi:10.1007/s41468-020-00058-8","apa":"Bauer, U., Edelsbrunner, H., Jablonski, G., & Mrozek, M. (2020). Čech-Delaunay gradient flow and homology inference for self-maps. Journal of Applied and Computational Topology. Springer Nature. https://doi.org/10.1007/s41468-020-00058-8","ieee":"U. Bauer, H. Edelsbrunner, G. Jablonski, and M. Mrozek, “Čech-Delaunay gradient flow and homology inference for self-maps,” Journal of Applied and Computational Topology, vol. 4, no. 4. Springer Nature, pp. 455–480, 2020.","short":"U. Bauer, H. Edelsbrunner, G. Jablonski, M. Mrozek, Journal of Applied and Computational Topology 4 (2020) 455–480.","chicago":"Bauer, U., Herbert Edelsbrunner, Grzegorz Jablonski, and M. Mrozek. “Čech-Delaunay Gradient Flow and Homology Inference for Self-Maps.” Journal of Applied and Computational Topology. Springer Nature, 2020. https://doi.org/10.1007/s41468-020-00058-8.","ista":"Bauer U, Edelsbrunner H, Jablonski G, Mrozek M. 2020. Čech-Delaunay gradient flow and homology inference for self-maps. Journal of Applied and Computational Topology. 4(4), 455–480."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"U.","full_name":"Bauer, U.","last_name":"Bauer"},{"last_name":"Edelsbrunner","full_name":"Edelsbrunner, Herbert","orcid":"0000-0002-9823-6833","first_name":"Herbert","id":"3FB178DA-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-3536-9866","full_name":"Jablonski, Grzegorz","last_name":"Jablonski","id":"4483EF78-F248-11E8-B48F-1D18A9856A87","first_name":"Grzegorz"},{"first_name":"M.","full_name":"Mrozek, M.","last_name":"Mrozek"}],"article_processing_charge":"Yes (via OA deal)","title":"Čech-Delaunay gradient flow and homology inference for self-maps","publication_identifier":{"issn":["2367-1726"],"eissn":["2367-1734"]},"publication_status":"published","file":[{"success":1,"checksum":"eed1168b6e66cd55272c19bb7fca8a1c","file_id":"15065","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2020_JourApplCompTopology_Bauer.pdf","date_created":"2024-03-04T10:52:42Z","creator":"dernst","file_size":851190,"date_updated":"2024-03-04T10:52:42Z"}],"language":[{"iso":"eng"}],"issue":"4","volume":4,"license":"https://creativecommons.org/licenses/by/4.0/","abstract":[{"text":"We call a continuous self-map that reveals itself through a discrete set of point-value pairs a sampled dynamical system. Capturing the available information with chain maps on Delaunay complexes, we use persistent homology to quantify the evidence of recurrent behavior. We establish a sampling theorem to recover the eigenspaces of the endomorphism on homology induced by the self-map. Using a combinatorial gradient flow arising from the discrete Morse theory for Čech and Delaunay complexes, we construct a chain map to transform the problem from the natural but expensive Čech complexes to the computationally efficient Delaunay triangulations. The fast chain map algorithm has applications beyond dynamical systems.","lang":"eng"}],"oa_version":"Published Version","scopus_import":"1","month":"12","intvolume":" 4","date_updated":"2024-03-04T10:54:04Z","ddc":["500"],"file_date_updated":"2024-03-04T10:52:42Z","department":[{"_id":"HeEd"}],"_id":"15064","type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public"},{"department":[{"_id":"LaEr"}],"date_updated":"2024-03-04T10:33:15Z","keyword":["General Medicine"],"status":"public","type":"journal_article","article_type":"original","_id":"15063","ec_funded":1,"issue":"1","volume":1,"language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"issn":["2690-1005","2690-0998"]},"intvolume":" 1","month":"11","main_file_link":[{"open_access":"1","url":"https://doi.org/10.48550/arXiv.1908.01653"}],"scopus_import":"1","oa_version":"Preprint","abstract":[{"lang":"eng","text":"We consider the least singular value of a large random matrix with real or complex i.i.d. Gaussian entries shifted by a constant z∈C. We prove an optimal lower tail estimate on this singular value in the critical regime where z is around the spectral edge, thus improving the classical bound of Sankar, Spielman and Teng (SIAM J. Matrix Anal. Appl. 28:2 (2006), 446–476) for the particular shift-perturbation in the edge regime. Lacking Brézin–Hikami formulas in the real case, we rely on the superbosonization formula (Comm. Math. Phys. 283:2 (2008), 343–395)."}],"title":"Optimal lower bound on the least singular value of the shifted Ginibre ensemble","external_id":{"arxiv":["1908.01653"]},"article_processing_charge":"No","author":[{"full_name":"Cipolloni, Giorgio","orcid":"0000-0002-4901-7992","last_name":"Cipolloni","first_name":"Giorgio","id":"42198EFA-F248-11E8-B48F-1D18A9856A87"},{"id":"4DBD5372-F248-11E8-B48F-1D18A9856A87","first_name":"László","full_name":"Erdös, László","orcid":"0000-0001-5366-9603","last_name":"Erdös"},{"last_name":"Schröder","orcid":"0000-0002-2904-1856","full_name":"Schröder, Dominik J","id":"408ED176-F248-11E8-B48F-1D18A9856A87","first_name":"Dominik J"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Cipolloni, Giorgio, et al. “Optimal Lower Bound on the Least Singular Value of the Shifted Ginibre Ensemble.” Probability and Mathematical Physics, vol. 1, no. 1, Mathematical Sciences Publishers, 2020, pp. 101–46, doi:10.2140/pmp.2020.1.101.","short":"G. Cipolloni, L. Erdös, D.J. Schröder, Probability and Mathematical Physics 1 (2020) 101–146.","ieee":"G. Cipolloni, L. Erdös, and D. J. Schröder, “Optimal lower bound on the least singular value of the shifted Ginibre ensemble,” Probability and Mathematical Physics, vol. 1, no. 1. Mathematical Sciences Publishers, pp. 101–146, 2020.","apa":"Cipolloni, G., Erdös, L., & Schröder, D. J. (2020). Optimal lower bound on the least singular value of the shifted Ginibre ensemble. Probability and Mathematical Physics. Mathematical Sciences Publishers. https://doi.org/10.2140/pmp.2020.1.101","ama":"Cipolloni G, Erdös L, Schröder DJ. Optimal lower bound on the least singular value of the shifted Ginibre ensemble. Probability and Mathematical Physics. 2020;1(1):101-146. doi:10.2140/pmp.2020.1.101","chicago":"Cipolloni, Giorgio, László Erdös, and Dominik J Schröder. “Optimal Lower Bound on the Least Singular Value of the Shifted Ginibre Ensemble.” Probability and Mathematical Physics. Mathematical Sciences Publishers, 2020. https://doi.org/10.2140/pmp.2020.1.101.","ista":"Cipolloni G, Erdös L, Schröder DJ. 2020. Optimal lower bound on the least singular value of the shifted Ginibre ensemble. Probability and Mathematical Physics. 1(1), 101–146."},"project":[{"_id":"258DCDE6-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Random matrices, universality and disordered quantum systems","grant_number":"338804"},{"name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"date_created":"2024-03-04T10:27:57Z","date_published":"2020-11-16T00:00:00Z","doi":"10.2140/pmp.2020.1.101","page":"101-146","publication":"Probability and Mathematical Physics","day":"16","year":"2020","oa":1,"publisher":"Mathematical Sciences Publishers","quality_controlled":"1","acknowledgement":"Partially supported by ERC Advanced Grant No. 338804. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreement No. 66538"},{"oa":1,"publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","quality_controlled":"1","date_created":"2024-03-05T07:09:12Z","date_published":"2020-10-07T00:00:00Z","doi":"10.4230/LIPIcs.DISC.2020.40","publication":"34th International Symposium on Distributed Computing","day":"07","year":"2020","has_accepted_license":"1","article_number":"40","title":"Brief announcement: Efficient load-balancing through distributed token dropping","external_id":{"arxiv":["2005.07761"]},"article_processing_charge":"No","author":[{"first_name":"Sebastian","last_name":"Brandt","full_name":"Brandt, Sebastian"},{"first_name":"Barbara","last_name":"Keller","full_name":"Keller, Barbara"},{"first_name":"Joel","id":"334EFD2E-F248-11E8-B48F-1D18A9856A87","last_name":"Rybicki","orcid":"0000-0002-6432-6646","full_name":"Rybicki, Joel"},{"full_name":"Suomela, Jukka","last_name":"Suomela","first_name":"Jukka"},{"last_name":"Uitto","full_name":"Uitto, Jara","first_name":"Jara"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Brandt, Sebastian, Barbara Keller, Joel Rybicki, Jukka Suomela, and Jara Uitto. “Brief Announcement: Efficient Load-Balancing through Distributed Token Dropping.” In 34th International Symposium on Distributed Computing, Vol. 179. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2020. https://doi.org/10.4230/LIPIcs.DISC.2020.40.","ista":"Brandt S, Keller B, Rybicki J, Suomela J, Uitto J. 2020. Brief announcement: Efficient load-balancing through distributed token dropping. 34th International Symposium on Distributed Computing. DISC: Symposium on Distributed Computing, LIPIcs, vol. 179, 40.","mla":"Brandt, Sebastian, et al. “Brief Announcement: Efficient Load-Balancing through Distributed Token Dropping.” 34th International Symposium on Distributed Computing, vol. 179, 40, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2020, doi:10.4230/LIPIcs.DISC.2020.40.","short":"S. Brandt, B. Keller, J. Rybicki, J. Suomela, J. Uitto, in:, 34th International Symposium on Distributed Computing, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2020.","ieee":"S. Brandt, B. Keller, J. Rybicki, J. Suomela, and J. Uitto, “Brief announcement: Efficient load-balancing through distributed token dropping,” in 34th International Symposium on Distributed Computing, Virtual, 2020, vol. 179.","ama":"Brandt S, Keller B, Rybicki J, Suomela J, Uitto J. Brief announcement: Efficient load-balancing through distributed token dropping. In: 34th International Symposium on Distributed Computing. Vol 179. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2020. doi:10.4230/LIPIcs.DISC.2020.40","apa":"Brandt, S., Keller, B., Rybicki, J., Suomela, J., & Uitto, J. (2020). Brief announcement: Efficient load-balancing through distributed token dropping. In 34th International Symposium on Distributed Computing (Vol. 179). Virtual: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. https://doi.org/10.4230/LIPIcs.DISC.2020.40"},"intvolume":" 179","month":"10","alternative_title":["LIPIcs"],"scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","text":"We introduce a new graph problem, the token dropping game, and we show how to solve it efficiently in a distributed setting. We use the token dropping game as a tool to design an efficient distributed algorithm for the stable orientation problem, which is a special case of the more general locally optimal semi-matching problem. The prior work by Czygrinow et al. (DISC 2012) finds a locally optimal semi-matching in O(Δ⁵) rounds in graphs of maximum degree Δ, which directly implies an algorithm with the same runtime for stable orientations. We improve the runtime to O(Δ⁴) for stable orientations and prove a lower bound of Ω(Δ) rounds."}],"license":"https://creativecommons.org/licenses/by/3.0/","volume":179,"related_material":{"record":[{"relation":"later_version","status":"public","id":"9678"}]},"language":[{"iso":"eng"}],"file":[{"checksum":"23e2d9321aef53092dc1e24a8ab82d72","file_id":"15075","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2024-03-05T07:08:27Z","file_name":"2020_LIPIcs_Brandt.pdf","date_updated":"2024-03-05T07:08:27Z","file_size":303529,"creator":"dernst"}],"publication_status":"published","status":"public","conference":{"location":"Virtual","end_date":"2020-10-16","start_date":"2020-10-12","name":"DISC: Symposium on Distributed Computing"},"tmp":{"short":"CC BY (3.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/3.0/legalcode","name":"Creative Commons Attribution 3.0 Unported (CC BY 3.0)"},"type":"conference","_id":"15074","file_date_updated":"2024-03-05T07:08:27Z","department":[{"_id":"DaAl"}],"ddc":["000"],"date_updated":"2024-03-05T07:13:13Z"},{"month":"06","intvolume":" 168","alternative_title":["LIPIcs"],"scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","text":"We consider the following dynamic load-balancing process: given an underlying graph G with n nodes, in each step t≥ 0, one unit of load is created, and placed at a randomly chosen graph node. In the same step, the chosen node picks a random neighbor, and the two nodes balance their loads by averaging them. We are interested in the expected gap between the minimum and maximum loads at nodes as the process progresses, and its dependence on n and on the graph structure. Variants of the above graphical balanced allocation process have been studied previously by Peres, Talwar, and Wieder [Peres et al., 2015], and by Sauerwald and Sun [Sauerwald and Sun, 2015]. These authors left as open the question of characterizing the gap in the case of cycle graphs in the dynamic case, where weights are created during the algorithm’s execution. For this case, the only known upper bound is of 𝒪(n log n), following from a majorization argument due to [Peres et al., 2015], which analyzes a related graphical allocation process. In this paper, we provide an upper bound of 𝒪 (√n log n) on the expected gap of the above process for cycles of length n. We introduce a new potential analysis technique, which enables us to bound the difference in load between k-hop neighbors on the cycle, for any k ≤ n/2. We complement this with a \"gap covering\" argument, which bounds the maximum value of the gap by bounding its value across all possible subsets of a certain structure, and recursively bounding the gaps within each subset. We provide analytical and experimental evidence that our upper bound on the gap is tight up to a logarithmic factor."}],"related_material":{"record":[{"status":"public","id":"8286","relation":"later_version"}]},"volume":168,"ec_funded":1,"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"e5eb16199f4ccfd77a321977eb3f026f","file_id":"15078","success":1,"date_updated":"2024-03-05T07:25:15Z","file_size":782987,"creator":"dernst","date_created":"2024-03-05T07:25:15Z","file_name":"2020_LIPIcs_Alistarh.pdf"}],"language":[{"iso":"eng"}],"publication_status":"published","status":"public","type":"conference","conference":{"start_date":"2020-07-08","end_date":"2020-07-11","location":"Saarbrücken, Germany, Virtual","name":"ICALP: International Colloquium on Automata, Languages, and Programming"},"tmp":{"short":"CC BY (3.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/3.0/legalcode","name":"Creative Commons Attribution 3.0 Unported (CC BY 3.0)"},"_id":"15077","department":[{"_id":"DaAl"}],"file_date_updated":"2024-03-05T07:25:15Z","ddc":["000"],"date_updated":"2024-03-05T07:35:53Z","publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","quality_controlled":"1","oa":1,"acknowledgement":"The authors sincerely thank Thomas Sauerwald and George Giakkoupis for insightful discussions, and Mohsen Ghaffari, Yuval Peres, and Udi Wieder for feedback on earlier\r\nversions of this draft. We also thank the ICALP anonymous reviewers for their very useful comments.\r\nFunding: European Research Council funding award PR1042ERC01","date_published":"2020-06-29T00:00:00Z","doi":"10.4230/LIPIcs.ICALP.2020.7","date_created":"2024-03-05T07:25:37Z","day":"29","publication":"47th International Colloquium on Automata, Languages, and Programming","has_accepted_license":"1","year":"2020","project":[{"grant_number":"805223","name":"Elastic Coordination for Scalable Machine Learning","call_identifier":"H2020","_id":"268A44D6-B435-11E9-9278-68D0E5697425"}],"article_number":"7","title":"Dynamic averaging load balancing on cycles","author":[{"first_name":"Dan-Adrian","id":"4A899BFC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3650-940X","full_name":"Alistarh, Dan-Adrian","last_name":"Alistarh"},{"last_name":"Nadiradze","orcid":"0000-0001-5634-0731","full_name":"Nadiradze, Giorgi","id":"3279A00C-F248-11E8-B48F-1D18A9856A87","first_name":"Giorgi"},{"id":"bcc145fd-e77f-11ea-ae8b-80d661dbff67","first_name":"Amirmojtaba","full_name":"Sabour, Amirmojtaba","last_name":"Sabour"}],"article_processing_charge":"No","external_id":{"arxiv":["2003.09297"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Alistarh, Dan-Adrian, Giorgi Nadiradze, and Amirmojtaba Sabour. “Dynamic Averaging Load Balancing on Cycles.” In 47th International Colloquium on Automata, Languages, and Programming, Vol. 168. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2020. https://doi.org/10.4230/LIPIcs.ICALP.2020.7.","ista":"Alistarh D-A, Nadiradze G, Sabour A. 2020. Dynamic averaging load balancing on cycles. 47th International Colloquium on Automata, Languages, and Programming. ICALP: International Colloquium on Automata, Languages, and Programming, LIPIcs, vol. 168, 7.","mla":"Alistarh, Dan-Adrian, et al. “Dynamic Averaging Load Balancing on Cycles.” 47th International Colloquium on Automata, Languages, and Programming, vol. 168, 7, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2020, doi:10.4230/LIPIcs.ICALP.2020.7.","apa":"Alistarh, D.-A., Nadiradze, G., & Sabour, A. (2020). Dynamic averaging load balancing on cycles. In 47th International Colloquium on Automata, Languages, and Programming (Vol. 168). Saarbrücken, Germany, Virtual: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. https://doi.org/10.4230/LIPIcs.ICALP.2020.7","ama":"Alistarh D-A, Nadiradze G, Sabour A. Dynamic averaging load balancing on cycles. In: 47th International Colloquium on Automata, Languages, and Programming. Vol 168. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2020. doi:10.4230/LIPIcs.ICALP.2020.7","ieee":"D.-A. Alistarh, G. Nadiradze, and A. Sabour, “Dynamic averaging load balancing on cycles,” in 47th International Colloquium on Automata, Languages, and Programming, Saarbrücken, Germany, Virtual, 2020, vol. 168.","short":"D.-A. Alistarh, G. Nadiradze, A. Sabour, in:, 47th International Colloquium on Automata, Languages, and Programming, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2020."}},{"abstract":[{"text":"Two plane drawings of geometric graphs on the same set of points are called disjoint compatible if their union is plane and they do not have an edge in common. For a given set S of 2n points two plane drawings of perfect matchings M1 and M2 (which do not need to be disjoint nor compatible) are disjoint tree-compatible if there exists a plane drawing of a spanning tree T on S which is disjoint compatible to both M1 and M2.\r\nWe show that the graph of all disjoint tree-compatible perfect geometric matchings on 2n points in convex position is connected if and only if 2n ≥ 10. Moreover, in that case the diameter\r\nof this graph is either 4 or 5, independent of n.","lang":"eng"}],"oa_version":"Published Version","acknowledgement":"Research on this work was initiated at the 6th Austrian-Japanese-Mexican-Spanish Workshop on Discrete Geometry and continued during the 16th European Geometric Graph-Week, both held near Strobl, Austria. We are grateful to the participants for the inspiring atmosphere. We especially thank Alexander Pilz for bringing this class of problems to our attention and Birgit Vogtenhuber for inspiring discussions. D.P. is partially supported by the FWF grant I 3340-N35 (Collaborative DACH project Arrangements and Drawings). The research stay of P.P. at IST Austria is funded by the project CZ.02.2.69/0.0/0.0/17_050/0008466 Improvement of internationalization in the field of research and development at Charles University, through the support of quality projects MSCA-IF. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 734922.","quality_controlled":"1","oa":1,"main_file_link":[{"url":"https://www1.pub.informatik.uni-wuerzburg.de/eurocg2020/data/uploads/papers/eurocg20_paper_56.pdf","open_access":"1"}],"month":"04","publication_status":"published","year":"2020","day":"01","publication":"36th European Workshop on Computational Geometry","language":[{"iso":"eng"}],"date_published":"2020-04-01T00:00:00Z","date_created":"2024-03-05T08:57:17Z","_id":"15082","article_number":"56","type":"conference","conference":{"name":"EuroCG: European Workshop on Computational Geometry","location":"Würzburg, Germany, Virtual","end_date":"2020-03-18","start_date":"2020-03-16"},"status":"public","citation":{"chicago":"Aichholzer, Oswin, Julia Obmann, Pavel Patak, Daniel Perz, and Josef Tkadlec. “Disjoint Tree-Compatible Plane Perfect Matchings.” In 36th European Workshop on Computational Geometry, 2020.","ista":"Aichholzer O, Obmann J, Patak P, Perz D, Tkadlec J. 2020. Disjoint tree-compatible plane perfect matchings. 36th European Workshop on Computational Geometry. EuroCG: European Workshop on Computational Geometry, 56.","mla":"Aichholzer, Oswin, et al. “Disjoint Tree-Compatible Plane Perfect Matchings.” 36th European Workshop on Computational Geometry, 56, 2020.","ama":"Aichholzer O, Obmann J, Patak P, Perz D, Tkadlec J. Disjoint tree-compatible plane perfect matchings. In: 36th European Workshop on Computational Geometry. ; 2020.","apa":"Aichholzer, O., Obmann, J., Patak, P., Perz, D., & Tkadlec, J. (2020). Disjoint tree-compatible plane perfect matchings. In 36th European Workshop on Computational Geometry. Würzburg, Germany, Virtual.","short":"O. Aichholzer, J. Obmann, P. Patak, D. Perz, J. Tkadlec, in:, 36th European Workshop on Computational Geometry, 2020.","ieee":"O. Aichholzer, J. Obmann, P. Patak, D. Perz, and J. Tkadlec, “Disjoint tree-compatible plane perfect matchings,” in 36th European Workshop on Computational Geometry, Würzburg, Germany, Virtual, 2020."},"date_updated":"2024-03-05T09:00:07Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Aichholzer","full_name":"Aichholzer, Oswin","first_name":"Oswin"},{"full_name":"Obmann, Julia","last_name":"Obmann","first_name":"Julia"},{"id":"B593B804-1035-11EA-B4F1-947645A5BB83","first_name":"Pavel","full_name":"Patak, Pavel","last_name":"Patak"},{"last_name":"Perz","full_name":"Perz, Daniel","first_name":"Daniel"},{"first_name":"Josef","id":"3F24CCC8-F248-11E8-B48F-1D18A9856A87","last_name":"Tkadlec","full_name":"Tkadlec, Josef","orcid":"0000-0002-1097-9684"}],"article_processing_charge":"No","department":[{"_id":"KrCh"},{"_id":"UlWa"}],"title":"Disjoint tree-compatible plane perfect matchings"},{"_id":"6748","article_type":"original","type":"journal_article","status":"public","date_updated":"2024-03-06T08:28:50Z","department":[{"_id":"MaMo"}],"abstract":[{"lang":"eng","text":"Fitting a function by using linear combinations of a large number N of `simple' components is one of the most fruitful ideas in statistical learning. This idea lies at the core of a variety of methods, from two-layer neural networks to kernel regression, to boosting. In general, the resulting risk minimization problem is non-convex and is solved by gradient descent or its variants. Unfortunately, little is known about global convergence properties of these approaches.\r\nHere we consider the problem of learning a concave function f on a compact convex domain Ω⊆ℝd, using linear combinations of `bump-like' components (neurons). The parameters to be fitted are the centers of N bumps, and the resulting empirical risk minimization problem is highly non-convex. We prove that, in the limit in which the number of neurons diverges, the evolution of gradient descent converges to a Wasserstein gradient flow in the space of probability distributions over Ω. Further, when the bump width δ tends to 0, this gradient flow has a limit which is a viscous porous medium equation. Remarkably, the cost function optimized by this gradient flow exhibits a special property known as displacement convexity, which implies exponential convergence rates for N→∞, δ→0. Surprisingly, this asymptotic theory appears to capture well the behavior for moderate values of δ,N. Explaining this phenomenon, and understanding the dependence on δ,N in a quantitative manner remains an outstanding challenge."}],"oa_version":"Preprint","main_file_link":[{"url":"https://arxiv.org/abs/1901.01375","open_access":"1"}],"intvolume":" 48","month":"12","publication_status":"published","publication_identifier":{"issn":["1932-6157"],"eissn":["1941-7330"]},"language":[{"iso":"eng"}],"issue":"6","volume":48,"citation":{"mla":"Javanmard, Adel, et al. “Analysis of a Two-Layer Neural Network via Displacement Convexity.” Annals of Statistics, vol. 48, no. 6, Institute of Mathematical Statistics, 2020, pp. 3619–42, doi:10.1214/20-AOS1945.","short":"A. Javanmard, M. Mondelli, A. Montanari, Annals of Statistics 48 (2020) 3619–3642.","ieee":"A. Javanmard, M. Mondelli, and A. Montanari, “Analysis of a two-layer neural network via displacement convexity,” Annals of Statistics, vol. 48, no. 6. Institute of Mathematical Statistics, pp. 3619–3642, 2020.","ama":"Javanmard A, Mondelli M, Montanari A. Analysis of a two-layer neural network via displacement convexity. Annals of Statistics. 2020;48(6):3619-3642. doi:10.1214/20-AOS1945","apa":"Javanmard, A., Mondelli, M., & Montanari, A. (2020). Analysis of a two-layer neural network via displacement convexity. Annals of Statistics. Institute of Mathematical Statistics. https://doi.org/10.1214/20-AOS1945","chicago":"Javanmard, Adel, Marco Mondelli, and Andrea Montanari. “Analysis of a Two-Layer Neural Network via Displacement Convexity.” Annals of Statistics. Institute of Mathematical Statistics, 2020. https://doi.org/10.1214/20-AOS1945.","ista":"Javanmard A, Mondelli M, Montanari A. 2020. Analysis of a two-layer neural network via displacement convexity. Annals of Statistics. 48(6), 3619–3642."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"arxiv":["1901.01375"],"isi":["000598369200021"]},"article_processing_charge":"No","author":[{"last_name":"Javanmard","full_name":"Javanmard, Adel","first_name":"Adel"},{"id":"27EB676C-8706-11E9-9510-7717E6697425","first_name":"Marco","orcid":"0000-0002-3242-7020","full_name":"Mondelli, Marco","last_name":"Mondelli"},{"full_name":"Montanari, Andrea","last_name":"Montanari","first_name":"Andrea"}],"title":"Analysis of a two-layer neural network via displacement convexity","oa":1,"quality_controlled":"1","publisher":"Institute of Mathematical Statistics","year":"2020","isi":1,"publication":"Annals of Statistics","day":"11","page":"3619-3642","date_created":"2019-07-31T09:39:42Z","date_published":"2020-12-11T00:00:00Z","doi":"10.1214/20-AOS1945"},{"oa":1,"publisher":"The Royal Society","quality_controlled":"1","acknowledgement":"V.K. thanks the German National Academic Foundation (Studienstiftung des deutschen Volkes) for financial\r\nsupport. J.F.D. is grateful for financial support by the Stordalen Foundation via the Planetary Boundary Research\r\nNetwork (PB.net), the Earth League’s EarthDoc program and the European Research Council Advanced Grant\r\nproject ERA (Earth Resilience in the Anthropocene). We are thankful for support by the Leibniz Association\r\n(project DominoES).\r\nAcknowledgements. This work has been performed in the context of the copan collaboration and the FutureLab on Earth\r\nResilience in the Anthropocene at the Potsdam Institute for Climate Impact Research. Furthermore, we acknowledge\r\ndiscussions with and helpful comments by N. Wunderling, J. Heitzig and M. Wiedermann.","date_created":"2020-11-08T23:01:25Z","date_published":"2020-06-01T00:00:00Z","doi":"10.1098/rsos.200599","publication":"Royal Society Open Science","day":"01","year":"2020","has_accepted_license":"1","isi":1,"article_number":"200599","title":"Emergence of cascading dynamics in interacting tipping elements of ecology and climate: Cascading dynamics in tipping elements","article_processing_charge":"No","external_id":{"arxiv":["1910.12042"],"isi":["000545625200001"]},"author":[{"first_name":"Ann Kristin","full_name":"Klose, Ann Kristin","last_name":"Klose"},{"orcid":"0000-0002-6963-0129","full_name":"Karle, Volker","last_name":"Karle","id":"D7C012AE-D7ED-11E9-95E8-1EC5E5697425","first_name":"Volker"},{"first_name":"Ricarda","full_name":"Winkelmann, Ricarda","last_name":"Winkelmann"},{"first_name":"Jonathan F.","last_name":"Donges","full_name":"Donges, Jonathan F."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"short":"A.K. Klose, V. Karle, R. Winkelmann, J.F. Donges, Royal Society Open Science 7 (2020).","ieee":"A. K. Klose, V. Karle, R. Winkelmann, and J. F. Donges, “Emergence of cascading dynamics in interacting tipping elements of ecology and climate: Cascading dynamics in tipping elements,” Royal Society Open Science, vol. 7, no. 6. The Royal Society, 2020.","apa":"Klose, A. K., Karle, V., Winkelmann, R., & Donges, J. F. (2020). Emergence of cascading dynamics in interacting tipping elements of ecology and climate: Cascading dynamics in tipping elements. Royal Society Open Science. The Royal Society. https://doi.org/10.1098/rsos.200599","ama":"Klose AK, Karle V, Winkelmann R, Donges JF. Emergence of cascading dynamics in interacting tipping elements of ecology and climate: Cascading dynamics in tipping elements. Royal Society Open Science. 2020;7(6). doi:10.1098/rsos.200599","mla":"Klose, Ann Kristin, et al. “Emergence of Cascading Dynamics in Interacting Tipping Elements of Ecology and Climate: Cascading Dynamics in Tipping Elements.” Royal Society Open Science, vol. 7, no. 6, 200599, The Royal Society, 2020, doi:10.1098/rsos.200599.","ista":"Klose AK, Karle V, Winkelmann R, Donges JF. 2020. Emergence of cascading dynamics in interacting tipping elements of ecology and climate: Cascading dynamics in tipping elements. Royal Society Open Science. 7(6), 200599.","chicago":"Klose, Ann Kristin, Volker Karle, Ricarda Winkelmann, and Jonathan F. Donges. “Emergence of Cascading Dynamics in Interacting Tipping Elements of Ecology and Climate: Cascading Dynamics in Tipping Elements.” Royal Society Open Science. The Royal Society, 2020. https://doi.org/10.1098/rsos.200599."},"intvolume":" 7","month":"06","scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","text":"In ecology, climate and other fields, (sub)systems have been identified that can transition into a qualitatively different state when a critical threshold or tipping point in a driving process is crossed. An understanding of those tipping elements is of great interest given the increasing influence of humans on the biophysical Earth system. Complex interactions exist between tipping elements, e.g. physical mechanisms connect subsystems of the climate system. Based on earlier work on such coupled nonlinear systems, we systematically assessed the qualitative long-term behaviour of interacting tipping elements. We developed an understanding of the consequences of interactions\r\non the tipping behaviour allowing for tipping cascades to emerge under certain conditions. The (narrative) application of\r\nthese qualitative results to real-world examples of interacting tipping elements indicates that tipping cascades with profound consequences may occur: the interacting Greenland ice sheet and thermohaline ocean circulation might tip before the tipping points of the isolated subsystems are crossed. The eutrophication of the first lake in a lake chain might propagate through the following lakes without a crossing of their individual critical nutrient input levels. The possibility of emerging cascading tipping dynamics calls for the development of a unified theory of interacting tipping elements and the quantitative analysis of interacting real-world tipping elements."}],"issue":"6","volume":7,"language":[{"iso":"eng"}],"file":[{"file_name":"2020_RoyalSocOpenScience_Klose.pdf","date_created":"2020-11-09T09:07:11Z","file_size":1611485,"date_updated":"2020-11-09T09:07:11Z","creator":"dernst","success":1,"file_id":"8748","checksum":"5505c445de373bfd836eb4d3b48b1f37","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"publication_status":"published","publication_identifier":{"eissn":["20545703"]},"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","_id":"8741","department":[{"_id":"MiLe"}],"file_date_updated":"2020-11-09T09:07:11Z","ddc":["530","550"],"date_updated":"2024-03-12T12:31:30Z"},{"_id":"7687","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","status":"public","date_updated":"2024-03-12T10:12:33Z","ddc":["020"],"file_date_updated":"2024-03-12T10:12:33Z","department":[{"_id":"E-Lib"}],"abstract":[{"lang":"eng","text":"A working group, which was established within the Network of Repository Managers (RepManNet), has dealt with common certifications for repositories. In addition, current requirements of the research funding agencies FWF and EU were also taken into account. The Core Trust Seal was examined in more detail. For this purpose, a questionnaire was sent to those organizations that are already certified with CTS in Austria. The answers were summarized and evaluated anonymously. It is recommended to go for a repository certification. Moreover, the development of a DINI certificate in Austria is strongly suggested."},{"text":" Eine Arbeitsgruppe, die im Rahmen des Netzwerks für RepositorienmanagerInnen (RepManNet) entstanden ist, hat sich mit gängigen Zertifizierungen für Repositorien beschäftigt. Weiters wurden aktuelle Vorgaben der Forschungsförderer FWF und EU herangezogen. Das Core Trust Seal wurde genauer betrachtet. Hierfür wurden jenen Organisationen, die in Österreich bereits mit CTS zertifiziert sind, ein Fragebogen übermittelt. Die Antworten wurden anonymisiert zusammengefasst und ausgewertet. Plädiert wird für eine Zertifizierung von Repositorien und die Entwicklung einer DINI-Zertifizierung in Österreich.","lang":"ger"}],"oa_version":"Published Version","scopus_import":"1","intvolume":" 73","month":"04","publication_status":"published","publication_identifier":{"issn":["1022-2588"]},"language":[{"iso":"ger"}],"file":[{"date_created":"2020-06-17T10:50:13Z","file_name":"2020_VOEB_Ernst.pdf","creator":"dernst","date_updated":"2024-03-12T10:12:33Z","file_size":579291,"file_id":"7970","checksum":"fee784f15a489deb7def6ccf8c5bf8c3","access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"issue":"1","volume":73,"citation":{"chicago":"Ernst, Doris, Gertraud Novotny, and Eva Maria Schönher. “(Core Trust) Seal your repository!” Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare. Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare, 2020. https://doi.org/10.31263/voebm.v73i1.3491.","ista":"Ernst D, Novotny G, Schönher EM. 2020. (Core Trust) Seal your repository! Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare. 73(1), 46–59.","mla":"Ernst, Doris, et al. “(Core Trust) Seal your repository!” Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare, vol. 73, no. 1, Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare, 2020, pp. 46–59, doi:10.31263/voebm.v73i1.3491.","ama":"Ernst D, Novotny G, Schönher EM. (Core Trust) Seal your repository! Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare. 2020;73(1):46-59. doi:10.31263/voebm.v73i1.3491","apa":"Ernst, D., Novotny, G., & Schönher, E. M. (2020). (Core Trust) Seal your repository! Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare. Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare. https://doi.org/10.31263/voebm.v73i1.3491","ieee":"D. Ernst, G. Novotny, and E. M. Schönher, “(Core Trust) Seal your repository!,” Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare, vol. 73, no. 1. Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare, pp. 46–59, 2020.","short":"D. Ernst, G. Novotny, E.M. Schönher, Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare 73 (2020) 46–59."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","author":[{"first_name":"Doris","id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","last_name":"Ernst","full_name":"Ernst, Doris","orcid":"0000-0002-2354-0195"},{"last_name":"Novotny","full_name":"Novotny, Gertraud","first_name":"Gertraud"},{"first_name":"Eva Maria","full_name":"Schönher, Eva Maria","last_name":"Schönher"}],"title":"(Core Trust) Seal your repository!","oa":1,"publisher":"Vereinigung Osterreichischer Bibliothekarinnen und Bibliothekare","year":"2020","has_accepted_license":"1","popular_science":"1","publication":"Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare","day":"28","page":"46-59","date_created":"2020-04-28T08:37:38Z","date_published":"2020-04-28T00:00:00Z","doi":"10.31263/voebm.v73i1.3491"},{"oa":1,"quality_controlled":"1","publisher":"MDPI","acknowledgement":"The work was supported by of Russian Foundation of Basic Research: grant № 19-04-00831 for Viktoria Shcherbakova and Olga Troshina, grant № 18-34-00334 for Viktoriia Oshurkova and Vladimir Trubitsyn. \r\nWe thank Dr Natalia Suzina (IBPM RAS, Federal Research Center Pushchino Center for\r\nBiological Research RAS) for the help with the microscopic studies, respectively; Dr. Margarita Meyer (Division of Genetics, Department of Medicine, BWH and HMS, USA) and Dr Fedor Kondrashov (IST, Austria) for their help in obtaining the genomic sequence of strain JL01. ","date_created":"2024-03-04T11:41:31Z","doi":"10.3390/ecm2020-07116","date_published":"2020-11-02T00:00:00Z","publication":"Proceedings of 1st International Electronic Conference on Microbiology","day":"02","year":"2020","has_accepted_license":"1","title":"Characterization of methanosarcina mazei JL01 isolated from holocene arctic permafrost and study of the archaeon cooperation with bacterium Sphaerochaeta associata GLS2T","article_processing_charge":"Yes","author":[{"first_name":"Viktoriia","full_name":"Oshurkova, Viktoriia","last_name":"Oshurkova"},{"full_name":"Troshina, Olga","last_name":"Troshina","first_name":"Olga"},{"last_name":"Trubitsyn","full_name":"Trubitsyn, Vladimir","first_name":"Vladimir"},{"first_name":"Yana","full_name":"Ryzhmanova, Yana","last_name":"Ryzhmanova"},{"id":"C4558D3C-6102-11E9-A62E-F418E6697425","first_name":"Olga","orcid":"0000-0003-1006-6639","full_name":"Bochkareva, Olga","last_name":"Bochkareva"},{"first_name":"Viktoria","last_name":"Shcherbakova","full_name":"Shcherbakova, Viktoria"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Oshurkova V, Troshina O, Trubitsyn V, Ryzhmanova Y, Bochkareva O, Shcherbakova V. 2020. Characterization of methanosarcina mazei JL01 isolated from holocene arctic permafrost and study of the archaeon cooperation with bacterium Sphaerochaeta associata GLS2T. Proceedings of 1st International Electronic Conference on Microbiology. ECM: Electronic Conference on Microbiology.","chicago":"Oshurkova, Viktoriia, Olga Troshina, Vladimir Trubitsyn, Yana Ryzhmanova, Olga Bochkareva, and Viktoria Shcherbakova. “Characterization of Methanosarcina Mazei JL01 Isolated from Holocene Arctic Permafrost and Study of the Archaeon Cooperation with Bacterium Sphaerochaeta Associata GLS2T.” In Proceedings of 1st International Electronic Conference on Microbiology. MDPI, 2020. https://doi.org/10.3390/ecm2020-07116.","short":"V. Oshurkova, O. Troshina, V. Trubitsyn, Y. Ryzhmanova, O. Bochkareva, V. Shcherbakova, in:, Proceedings of 1st International Electronic Conference on Microbiology, MDPI, 2020.","ieee":"V. Oshurkova, O. Troshina, V. Trubitsyn, Y. Ryzhmanova, O. Bochkareva, and V. Shcherbakova, “Characterization of methanosarcina mazei JL01 isolated from holocene arctic permafrost and study of the archaeon cooperation with bacterium Sphaerochaeta associata GLS2T,” in Proceedings of 1st International Electronic Conference on Microbiology, Virtual, 2020.","apa":"Oshurkova, V., Troshina, O., Trubitsyn, V., Ryzhmanova, Y., Bochkareva, O., & Shcherbakova, V. (2020). Characterization of methanosarcina mazei JL01 isolated from holocene arctic permafrost and study of the archaeon cooperation with bacterium Sphaerochaeta associata GLS2T. In Proceedings of 1st International Electronic Conference on Microbiology. Virtual: MDPI. https://doi.org/10.3390/ecm2020-07116","ama":"Oshurkova V, Troshina O, Trubitsyn V, Ryzhmanova Y, Bochkareva O, Shcherbakova V. Characterization of methanosarcina mazei JL01 isolated from holocene arctic permafrost and study of the archaeon cooperation with bacterium Sphaerochaeta associata GLS2T. In: Proceedings of 1st International Electronic Conference on Microbiology. MDPI; 2020. doi:10.3390/ecm2020-07116","mla":"Oshurkova, Viktoriia, et al. “Characterization of Methanosarcina Mazei JL01 Isolated from Holocene Arctic Permafrost and Study of the Archaeon Cooperation with Bacterium Sphaerochaeta Associata GLS2T.” Proceedings of 1st International Electronic Conference on Microbiology, MDPI, 2020, doi:10.3390/ecm2020-07116."},"month":"11","oa_version":"Published Version","abstract":[{"lang":"eng","text":"A mesophilic methanogenic culture, designated JL01, was isolated from Holocene permafrost in the Russian Arctic [1]. After long-term extensive cultivation at 15°C it turned out to be a tied binary culture of archaeal (JL01) and bacterial (Sphaerochaeta associata GLS2) strains.\r\nStrain JL01 was a strict anaerobe and grew on methanol, acetate and methylamines as energy and carbon sources. Cells were irregular coccoid, non-motile, non-spore-forming, and Gram-stainpositive. Optimum conditions for growth were 24-28 oC, pH 6.8–7.3 and 0.075-0.1 M NaCl.\r\nPhylogenetic tree reconstructions based on 16S rRNA and concatenated alignment of broadly\r\nconserved protein-coding genes revealed its close relation to Methanosarcina mazei S-6\r\nT (similarity 99.5%). The comparison of whole genomic sequences (ANI) of the isolate and the type strain of M.mazei was 98.5%, which is higher than the values recommended for new species. Thus strain JL01 (=VKM B-2370=JCM 31898) represents the first M. mazei isolated from permanently subzero Arcticsediments. The long-term co-cultivation of JL01 with S. associata GLS2T showed the methane production without any additional carbon and energy sources. Genome analysis of S. associata GLS2T revealed putative genes involved in methanochondroithin catabolism."}],"language":[{"iso":"eng"}],"file":[{"file_name":"2020_ECM_Oshurkova.pdf","date_created":"2024-03-20T08:05:46Z","creator":"dernst","file_size":595543,"date_updated":"2024-03-20T08:05:46Z","success":1,"file_id":"15127","checksum":"d1914af7811a21a4b2744eb51b5834e3","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"publication_status":"published","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"conference":{"start_date":"2020-11-02","end_date":"2020-11-30","location":"Virtual","name":"ECM: Electronic Conference on Microbiology"},"type":"conference","_id":"15071","file_date_updated":"2024-03-20T08:05:46Z","department":[{"_id":"FyKo"}],"ddc":["570"],"date_updated":"2024-03-20T08:06:22Z"},{"publisher":"eLife Sciences Publications","quality_controlled":"1","oa":1,"doi":"10.7554/elife.55275","date_published":"2020-02-26T00:00:00Z","date_created":"2024-03-21T07:55:12Z","day":"26","publication":"eLife","year":"2020","article_number":"55275","title":"Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing","author":[{"first_name":"Jennifer L","full_name":"Fribourgh, Jennifer L","last_name":"Fribourgh"},{"first_name":"Ashutosh","full_name":"Srivastava, Ashutosh","last_name":"Srivastava"},{"first_name":"Colby R","last_name":"Sandate","full_name":"Sandate, Colby R"},{"id":"6437c950-2a03-11ee-914d-d6476dd7b75c","first_name":"Alicia Kathleen","full_name":"Michael, Alicia Kathleen","last_name":"Michael"},{"first_name":"Peter L","full_name":"Hsu, Peter L","last_name":"Hsu"},{"first_name":"Christin","full_name":"Rakers, Christin","last_name":"Rakers"},{"full_name":"Nguyen, Leslee T","last_name":"Nguyen","first_name":"Leslee T"},{"first_name":"Megan R","last_name":"Torgrimson","full_name":"Torgrimson, Megan R"},{"first_name":"Gian Carlo G","full_name":"Parico, Gian Carlo G","last_name":"Parico"},{"full_name":"Tripathi, Sarvind","last_name":"Tripathi","first_name":"Sarvind"},{"first_name":"Ning","full_name":"Zheng, Ning","last_name":"Zheng"},{"last_name":"Lander","full_name":"Lander, Gabriel C","first_name":"Gabriel C"},{"first_name":"Tsuyoshi","last_name":"Hirota","full_name":"Hirota, Tsuyoshi"},{"first_name":"Florence","full_name":"Tama, Florence","last_name":"Tama"},{"first_name":"Carrie L","full_name":"Partch, Carrie L","last_name":"Partch"}],"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Fribourgh JL, Srivastava A, Sandate CR, Michael AK, Hsu PL, Rakers C, Nguyen LT, Torgrimson MR, Parico GCG, Tripathi S, Zheng N, Lander GC, Hirota T, Tama F, Partch CL. 2020. Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. eLife. 9, 55275.","chicago":"Fribourgh, Jennifer L, Ashutosh Srivastava, Colby R Sandate, Alicia K. Michael, Peter L Hsu, Christin Rakers, Leslee T Nguyen, et al. “Dynamics at the Serine Loop Underlie Differential Affinity of Cryptochromes for CLOCK:BMAL1 to Control Circadian Timing.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/elife.55275.","apa":"Fribourgh, J. L., Srivastava, A., Sandate, C. R., Michael, A. K., Hsu, P. L., Rakers, C., … Partch, C. L. (2020). Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.55275","ama":"Fribourgh JL, Srivastava A, Sandate CR, et al. Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. eLife. 2020;9. doi:10.7554/elife.55275","ieee":"J. L. Fribourgh et al., “Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing,” eLife, vol. 9. eLife Sciences Publications, 2020.","short":"J.L. Fribourgh, A. Srivastava, C.R. Sandate, A.K. Michael, P.L. Hsu, C. Rakers, L.T. Nguyen, M.R. Torgrimson, G.C.G. Parico, S. Tripathi, N. Zheng, G.C. Lander, T. Hirota, F. Tama, C.L. Partch, ELife 9 (2020).","mla":"Fribourgh, Jennifer L., et al. “Dynamics at the Serine Loop Underlie Differential Affinity of Cryptochromes for CLOCK:BMAL1 to Control Circadian Timing.” ELife, vol. 9, 55275, eLife Sciences Publications, 2020, doi:10.7554/elife.55275."},"month":"02","intvolume":" 9","scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.7554/eLife.55275"}],"oa_version":"Published Version","abstract":[{"text":"Mammalian circadian rhythms are generated by a transcription-based feedback loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2), which ultimately interact with CLOCK:BMAL1 to close the feedback loop with ~24 hr periodicity. Here we pinpoint a key difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Both cryptochromes bind the BMAL1 transactivation domain similarly to sequester it from coactivators and repress CLOCK:BMAL1 activity. However, we find that CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We discovered a dynamic serine-rich loop adjacent to the secondary pocket in the photolyase homology region (PHR) domain that regulates differential binding of cryptochromes to the PAS domain core of CLOCK:BMAL1. Notably, binding of the co-repressor PER2 remodels the serine loop of CRY2, making it more CRY1-like and enhancing its affinity for CLOCK:BMAL1.","lang":"eng"}],"volume":9,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2050-084X"]},"publication_status":"published","status":"public","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"article_type":"original","type":"journal_article","_id":"15153","extern":"1","date_updated":"2024-03-25T12:25:02Z"},{"_id":"7525","type":"dissertation","keyword":["Cav2.3","medial habenula (MHb)","interpeduncular nucleus (IPN)"],"status":"public","date_updated":"2023-09-07T13:20:03Z","supervisor":[{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444"}],"ddc":["570"],"department":[{"_id":"RySh"}],"file_date_updated":"2021-03-01T23:30:04Z","acknowledged_ssus":[{"_id":"EM-Fac"}],"abstract":[{"lang":"eng","text":"The medial habenula (MHb) is an evolutionary conserved epithalamic structure important for the modulation of emotional memory. It is involved in regulation of anxiety, compulsive behavior, addiction (nicotinic and opioid), sexual and feeding behavior. MHb receives inputs from septal regions and projects exclusively to the interpeduncular nucleus (IPN). Distinct sub-regions of the septum project to different subnuclei of MHb: the bed nucleus of anterior commissure projects to dorsal MHb and the triangular septum projects to ventral MHb. Furthermore, the dorsal and ventral MHb project to the lateral and rostral/central IPN, respectively. Importantly, these projections have unique features of prominent co-release of different neurotransmitters and requirement of a peculiar type of calcium channel for release. In general, synaptic neurotransmission requires an activity-dependent influx of Ca2+ into the presynaptic terminal through voltage-gated calcium channels. The calcium channel family most commonly involved in neurotransmitter release comprises three members, P/Q-, N- and R-type with Cav2.1, Cav2.2 and Cav2.3 subunits, respectively. In contrast to most CNS synapses that mainly express Cav2.1 and/or Cav2.2, MHb terminals in the IPN exclusively express Cav2.3. In other parts of the brain, such as the hippocampus, Cav2.3 is mostly located to postsynaptic elements. This unusual presynaptic location of Cav2.3 in the MHb-IPN pathway implies unique mechanisms of glutamate release in this pathway. One potential example of such uniqueness is the facilitation of release by GABAB receptor (GBR) activation. Presynaptic GBRs usually inhibit the release of neurotransmitters by inhibiting presynaptic calcium channels. MHb shows the highest expression levels of GBR in the brain. GBRs comprise two subunits, GABAB1 (GB1) and GABAB2 (GB2), and are associated with auxiliary subunits, called potassium channel tetramerization domain containing proteins (KCTD) 8, 12, 12b and 16. Among these four subunits, KCTD12b is exclusively expressed in ventral MHb, and KCTD8 shows the strongest expression in the whole MHb among other brain regions, indicating that KCTD8 and KCTD12b may be involved in the unique mechanisms of neurotransmitter release mediated by Cav2.3 and regulated by GBRs in this pathway. \r\nIn the present study, we first verified that neurotransmission in both dorsal and ventral MHb-IPN pathways is mainly mediated by Cav2.3 using a selective blocker of R-type channels, SNX-482. We next found that baclofen, a GBR agonist, has facilitatory effects on release from ventral MHb terminal in rostral IPN, whereas it has inhibitory effects on release from dorsal MHb terminals in lateral IPN, indicating that KCTD12b expressed exclusively in ventral MHb may have a role in the facilitatory effects of GBR activation. In a heterologous expression system using HEK cells, we found that KCTD8 and KCTD12b but not KCTD12 directly bind with Cav2.3. Pre-embedding immunogold electron microscopy data show that Cav2.3 and KCTD12b are distributed most densely in presynaptic active zone in IPN with KCTD12b being present only in rostral/central but not lateral IPN, whereas GABAB, KCTD8 and KCTD12 are distributed most densely in perisynaptic sites with KCTD12 present more frequently in postsynaptic elements and only in rostral/central IPN. In freeze-fracture replica labelling, Cav2.3, KCTD8 and KCTD12b are co-localized with each other in the same active zone indicating that they may form complexes regulating vesicle release in rostral IPN. \r\nOn electrophysiological studies of wild type (WT) mice, we found that paired-pulse ratio in rostral IPN of KCTD12b knock-out (KO) mice is lower than those of WT and KCTD8 KO mice. Consistent with this finding, in mean variance analysis, release probability in rostral IPN of KCTD12b KO mice is higher than that of WT and KCTD8 KO mice. Although paired-pulse ratios are not different between WT and KCTD8 KO mice, the mean variance analysis revealed significantly lower release probability in rostral IPN of KCTD8 KO than WT mice. These results demonstrate bidirectional regulation of Cav2.3-mediated release by KCTD8 and KCTD12b without GBR activation in rostral IPN. Finally, we examined the baclofen effects in rostral IPN of KCTD8 and KCTD12b KO mice, and found the facilitation of release remained in both KO mice, indicating that the peculiar effects of the GBR activation in this pathway do not depend on the selective expression of these KCTD subunits in ventral MHb. However, we found that presynaptic potentiation of evoked EPSC amplitude by baclofen falls to baseline after washout faster in KCTD12b KO mice than WT, KCTD8 KO and KCTD8/12b double KO mice. This result indicates that KCTD12b is involved in sustained potentiation of vesicle release by GBR activation, whereas KCTD8 is involved in its termination in the absence of KCTD12b. Consistent with these functional findings, replica labelling revealed an increase in density of KCTD8, but not Cav2.3 or GBR at active zone in rostral IPN of KCTD12b KO mice compared with that of WT mice, suggesting that increased association of KCTD8 with Cav2.3 facilitates the release probability and termination of the GBR effect in the absence of KCTD12b.\r\nIn summary, our study provided new insights into the physiological roles of presynaptic Cav2.3, GBRs and their auxiliary subunits KCTDs at an evolutionary conserved neuronal circuit. Future studies will be required to identify the exact molecular mechanism underlying the GBR-mediated presynaptic potentiation on ventral MHb terminals. It remains to be determined whether the prominent presence of presynaptic KCTDs at active zone could exert similar neuromodulatory functions in different pathways of the brain.\r\n"}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"month":"02","degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"]},"language":[{"iso":"eng"}],"file":[{"date_updated":"2021-03-01T23:30:04Z","file_size":9646346,"creator":"pbhandari","date_created":"2020-02-28T08:37:53Z","title":"Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway","file_name":"Pradeep Bhandari Thesis.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"4589234fdb12b4ad72273b311723a7b4","file_id":"7538","embargo":"2021-02-28"},{"relation":"source_file","access_level":"closed","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"7539","checksum":"aa79490553ca0a5c9b6fbcd152e93928","creator":"pbhandari","file_size":35252164,"date_updated":"2021-03-01T23:30:04Z","file_name":"Pradeep Bhandari Thesis.docx","date_created":"2020-02-28T08:47:14Z","title":"Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway"}],"citation":{"chicago":"Bhandari, Pradeep. “Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7525.","ista":"Bhandari P. 2020. Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. Institute of Science and Technology Austria.","mla":"Bhandari, Pradeep. Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7525.","apa":"Bhandari, P. (2020). Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7525","ama":"Bhandari P. Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. 2020. doi:10.15479/AT:ISTA:7525","ieee":"P. Bhandari, “Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway,” Institute of Science and Technology Austria, 2020.","short":"P. Bhandari, Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway, Institute of Science and Technology Austria, 2020."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_processing_charge":"No","author":[{"id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","first_name":"Pradeep","full_name":"Bhandari, Pradeep","orcid":"0000-0003-0863-4481","last_name":"Bhandari"}],"title":"Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway","oa":1,"publisher":"Institute of Science and Technology Austria","year":"2020","has_accepted_license":"1","day":"28","page":"79","date_created":"2020-02-26T10:56:37Z","doi":"10.15479/AT:ISTA:7525","date_published":"2020-02-28T00:00:00Z"},{"publication_identifier":{"issn":["1047-8477"]},"publication_status":"published","file":[{"file_name":"2020_JourStrucBiology_Faessler.pdf","date_created":"2020-12-10T14:01:10Z","file_size":7076870,"date_updated":"2020-12-10T14:01:10Z","creator":"dernst","success":1,"checksum":"c48cbf594e84fc2f91966ffaafc0918c","file_id":"8937","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"language":[{"iso":"eng"}],"issue":"3","volume":212,"related_material":{"record":[{"id":"14592","status":"public","relation":"used_in_publication"},{"id":"12491","status":"public","relation":"dissertation_contains"}]},"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"abstract":[{"text":"Cryo-electron microscopy (cryo-EM) of cellular specimens provides insights into biological processes and structures within a native context. However, a major challenge still lies in the efficient and reproducible preparation of adherent cells for subsequent cryo-EM analysis. This is due to the sensitivity of many cellular specimens to the varying seeding and culturing conditions required for EM experiments, the often limited amount of cellular material and also the fragility of EM grids and their substrate. Here, we present low-cost and reusable 3D printed grid holders, designed to improve specimen preparation when culturing challenging cellular samples directly on grids. The described grid holders increase cell culture reproducibility and throughput, and reduce the resources required for cell culturing. We show that grid holders can be integrated into various cryo-EM workflows, including micro-patterning approaches to control cell seeding on grids, and for generating samples for cryo-focused ion beam milling and cryo-electron tomography experiments. Their adaptable design allows for the generation of specialized grid holders customized to a large variety of applications.","lang":"eng"}],"oa_version":"Published Version","scopus_import":"1","month":"12","intvolume":" 212","date_updated":"2024-03-27T23:30:05Z","ddc":["570"],"department":[{"_id":"FlSc"}],"file_date_updated":"2020-12-10T14:01:10Z","_id":"8586","type":"journal_article","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","keyword":["electron microscopy","cryo-EM","EM sample preparation","3D printing","cell culture"],"isi":1,"has_accepted_license":"1","year":"2020","day":"01","publication":"Journal of Structural Biology","doi":"10.1016/j.jsb.2020.107633","date_published":"2020-12-01T00:00:00Z","date_created":"2020-09-29T13:24:06Z","acknowledgement":"This work was supported by the Austrian Science Fund (FWF, P33367) to FKMS. BZ acknowledges support by the Niederösterreich Fond. This research was also supported by the Scientific Service Units (SSU) of IST Austria through resources provided by Scientific Computing (SciComp), the Life Science Facility (LSF), the BioImaging Facility (BIF) and the Electron Microscopy Facility (EMF). We thank Georgi Dimchev (IST Austria) and Sonja Jacob (Vienna Biocenter Core Facilities) for testing our grid holders in different experimental setups and Daniel Gütl and the Kondrashov group (IST Austria) for granting us repeated access to their 3D printers. We also thank Jonna Alanko and the Sixt lab (IST Austria) for providing us HeLa cells, primary BL6 mouse tail fibroblasts, NIH 3T3 fibroblasts and human telomerase immortalised foreskin fibroblasts for our experiments. We are thankful to Ori Avinoam and William Wan for helpful comments on the manuscript and also thank Dorotea Fracchiolla (Art&Science) for illustrating the graphical abstract.","quality_controlled":"1","publisher":"Elsevier","oa":1,"citation":{"chicago":"Fäßler, Florian, Bettina Zens, Robert Hauschild, and Florian KM Schur. “3D Printed Cell Culture Grid Holders for Improved Cellular Specimen Preparation in Cryo-Electron Microscopy.” Journal of Structural Biology. Elsevier, 2020. https://doi.org/10.1016/j.jsb.2020.107633.","ista":"Fäßler F, Zens B, Hauschild R, Schur FK. 2020. 3D printed cell culture grid holders for improved cellular specimen preparation in cryo-electron microscopy. Journal of Structural Biology. 212(3), 107633.","mla":"Fäßler, Florian, et al. “3D Printed Cell Culture Grid Holders for Improved Cellular Specimen Preparation in Cryo-Electron Microscopy.” Journal of Structural Biology, vol. 212, no. 3, 107633, Elsevier, 2020, doi:10.1016/j.jsb.2020.107633.","apa":"Fäßler, F., Zens, B., Hauschild, R., & Schur, F. K. (2020). 3D printed cell culture grid holders for improved cellular specimen preparation in cryo-electron microscopy. Journal of Structural Biology. Elsevier. https://doi.org/10.1016/j.jsb.2020.107633","ama":"Fäßler F, Zens B, Hauschild R, Schur FK. 3D printed cell culture grid holders for improved cellular specimen preparation in cryo-electron microscopy. Journal of Structural Biology. 2020;212(3). doi:10.1016/j.jsb.2020.107633","short":"F. Fäßler, B. Zens, R. Hauschild, F.K. Schur, Journal of Structural Biology 212 (2020).","ieee":"F. Fäßler, B. Zens, R. Hauschild, and F. K. Schur, “3D printed cell culture grid holders for improved cellular specimen preparation in cryo-electron microscopy,” Journal of Structural Biology, vol. 212, no. 3. Elsevier, 2020."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"first_name":"Florian","id":"404F5528-F248-11E8-B48F-1D18A9856A87","full_name":"Fäßler, Florian","orcid":"0000-0001-7149-769X","last_name":"Fäßler"},{"id":"45FD126C-F248-11E8-B48F-1D18A9856A87","first_name":"Bettina","last_name":"Zens","orcid":"0000-0002-9561-1239","full_name":"Zens, Bettina"},{"full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert"},{"last_name":"Schur","orcid":"0000-0003-4790-8078","full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","first_name":"Florian KM"}],"article_processing_charge":"Yes (via OA deal)","external_id":{"isi":["000600997800008"]},"title":"3D printed cell culture grid holders for improved cellular specimen preparation in cryo-electron microscopy","article_number":"107633","project":[{"name":"Structure and isoform diversity of the Arp2/3 complex","grant_number":"P33367","_id":"9B954C5C-BA93-11EA-9121-9846C619BF3A"},{"name":"NÖ-Fonds Preis für die Jungforscherin des Jahres am IST Austria","_id":"059B463C-7A3F-11EA-A408-12923DDC885E"}]},{"publisher":"Institute of Science and Technology Austria","oa":1,"acknowledgement":"I thank Life Science Facilities for their continuous support with providing top-notch laboratory materials, keeping the devices humming, and coordinating the repairs and building of custom-designed laboratory equipment with the MIBA Machine shop.","doi":"10.15479/AT:ISTA:8657","date_published":"2020-10-14T00:00:00Z","date_created":"2020-10-13T16:46:14Z","page":"271","day":"14","has_accepted_license":"1","year":"2020","title":"Perturbations of protein synthesis: from antibiotics to genetics and physiology","author":[{"id":"350F91D2-F248-11E8-B48F-1D18A9856A87","first_name":"Bor","last_name":"Kavcic","full_name":"Kavcic, Bor","orcid":"0000-0001-6041-254X"}],"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8657.","ista":"Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics and physiology. Institute of Science and Technology Austria.","mla":"Kavcic, Bor. Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8657.","ama":"Kavcic B. Perturbations of protein synthesis: from antibiotics to genetics and physiology. 2020. doi:10.15479/AT:ISTA:8657","apa":"Kavcic, B. (2020). Perturbations of protein synthesis: from antibiotics to genetics and physiology. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8657","ieee":"B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics and physiology,” Institute of Science and Technology Austria, 2020.","short":"B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology, Institute of Science and Technology Austria, 2020."},"month":"10","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"M-Shop"}],"abstract":[{"text":"Synthesis of proteins – translation – is a fundamental process of life. Quantitative studies anchor translation into the context of bacterial physiology and reveal several mathematical relationships, called “growth laws,” which capture physiological feedbacks between protein synthesis and cell growth. Growth laws describe the dependency of the ribosome abundance as a function of growth rate, which can change depending on the growth conditions. Perturbations of translation reveal that bacteria employ a compensatory strategy in which the reduced translation capability results in increased expression of the translation machinery.\r\nPerturbations of translation are achieved in various ways; clinically interesting is the application of translation-targeting antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology are often poorly understood. Bacterial responses to two or more simultaneously applied antibiotics are even more puzzling. The combined antibiotic effect determines the type of drug interaction, which ranges from synergy (the effect is stronger than expected) to antagonism (the effect is weaker) and suppression (one of the drugs loses its potency).\r\nIn the first part of this work, we systematically measure the pairwise interaction network for translation inhibitors that interfere with different steps in translation. We find that the interactions are surprisingly diverse and tend to be more antagonistic. To explore the underlying mechanisms, we begin with a minimal biophysical model of combined antibiotic action. We base this model on the kinetics of antibiotic uptake and binding together with the physiological response described by the growth laws. The biophysical model explains some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn the second part of this work, we hypothesize that elusive suppressive drug interactions result from the interplay between ribosomes halted in different stages of translation. To elucidate this putative mechanism of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using in- ducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks partially causes these interactions.\r\nWe extend this approach by varying two translation bottlenecks simultaneously. This approach reveals the suppression of translocation inhibition by inhibited translation. We rationalize this effect by modeling dense traffic of ribosomes that move on transcripts in a translation factor-mediated manner. This model predicts a dissolution of traffic jams caused by inhibited translocation when the density of ribosome traffic is reduced by lowered initiation. We base this model on the growth laws and quantitative relationships between different translation and growth parameters.\r\nIn the final part of this work, we describe a set of tools aimed at quantification of physiological and translation parameters. We further develop a simple model that directly connects the abundance of a translation factor with the growth rate, which allows us to extract physiological parameters describing initiation. We demonstrate the development of tools for measuring translation rate.\r\nThis thesis showcases how a combination of high-throughput growth rate mea- surements, genetics, and modeling can reveal mechanisms of drug interactions. Furthermore, by a gradual transition from combinations of antibiotics to precise genetic interventions, we demonstrated the equivalency between genetic and chemi- cal perturbations of translation. These findings tile the path for quantitative studies of antibiotic combinations and illustrate future approaches towards the quantitative description of translation.","lang":"eng"}],"related_material":{"record":[{"status":"public","id":"7673","relation":"part_of_dissertation"},{"status":"public","id":"8250","relation":"part_of_dissertation"}]},"file":[{"date_updated":"2021-10-07T22:30:03Z","file_size":52636162,"creator":"bkavcic","date_created":"2020-10-15T06:41:20Z","file_name":"kavcicB_thesis202009.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"d708ecd62b6fcc3bc1feb483b8dbe9eb","file_id":"8663","embargo":"2021-10-06"},{"content_type":"application/zip","embargo_to":"open_access","access_level":"closed","relation":"source_file","file_id":"8664","checksum":"bb35f2352a04db19164da609f00501f3","date_updated":"2021-10-07T22:30:03Z","file_size":321681247,"creator":"bkavcic","date_created":"2020-10-15T06:41:53Z","file_name":"2020b.zip"}],"language":[{"iso":"eng"}],"publication_identifier":{"isbn":["978-3-99078-011-4"],"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","status":"public","type":"dissertation","_id":"8657","file_date_updated":"2021-10-07T22:30:03Z","department":[{"_id":"GaTk"}],"ddc":["571","530","570"],"supervisor":[{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","last_name":"Tkačik"},{"first_name":"Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","last_name":"Bollenbach","orcid":"0000-0003-4398-476X","full_name":"Bollenbach, Mark Tobias"}],"date_updated":"2023-09-07T13:20:48Z"},{"acknowledgement":"This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement No. 692692 and Marie Sklodowska-Curie 708497) and from Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27 Wittgenstein award and DK W1205-B09). We thank Johann Danzl and Ryuichi Shigemoto for critically reading the manuscript; Walter Kaufmann, Daniel Gutl, and Vanessa Zheden for extensive EM training, advice, and experimental assistance; Benjamin Suter for substantial help with light stimulation, ImageJ plugins for analysis, and manuscript editing; Florian Marr and Christina Altmutter for technical support; Eleftheria Kralli-Beller for manuscript editing; Julia König and Paul Wurzinger (Leica Microsystems) for helpful technical discussions; and Taija Makinen for providing the Prox1-CreERT2 mouse line.","oa":1,"quality_controlled":"1","publisher":"Elsevier","year":"2020","has_accepted_license":"1","isi":1,"publication":"Neuron","day":"18","page":"992-1006","date_created":"2020-02-10T15:59:45Z","date_published":"2020-03-18T00:00:00Z","doi":"10.1016/j.neuron.2019.12.022","project":[{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"call_identifier":"H2020","_id":"25BAF7B2-B435-11E9-9278-68D0E5697425","name":"Presynaptic calcium channels distribution and impact on coupling at the hippocampal mossy fiber synapse","grant_number":"708497"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize","grant_number":"Z00312"},{"call_identifier":"FWF","_id":"25C3DBB6-B435-11E9-9278-68D0E5697425","name":"Zellkommunikation in Gesundheit und Krankheit","grant_number":"W01205"}],"citation":{"ieee":"C. Borges Merjane, O. Kim, and P. M. Jonas, “Functional electron microscopy (‘Flash and Freeze’) of identified cortical synapses in acute brain slices,” Neuron, vol. 105. Elsevier, pp. 992–1006, 2020.","short":"C. Borges Merjane, O. Kim, P.M. Jonas, Neuron 105 (2020) 992–1006.","apa":"Borges Merjane, C., Kim, O., & Jonas, P. M. (2020). Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2019.12.022","ama":"Borges Merjane C, Kim O, Jonas PM. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 2020;105:992-1006. doi:10.1016/j.neuron.2019.12.022","mla":"Borges Merjane, Carolina, et al. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron, vol. 105, Elsevier, 2020, pp. 992–1006, doi:10.1016/j.neuron.2019.12.022.","ista":"Borges Merjane C, Kim O, Jonas PM. 2020. Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices. Neuron. 105, 992–1006.","chicago":"Borges Merjane, Carolina, Olena Kim, and Peter M Jonas. “Functional Electron Microscopy (‘Flash and Freeze’) of Identified Cortical Synapses in Acute Brain Slices.” Neuron. Elsevier, 2020. https://doi.org/10.1016/j.neuron.2019.12.022."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","external_id":{"pmid":["31928842"],"isi":["000520854700008"]},"author":[{"first_name":"Carolina","id":"4305C450-F248-11E8-B48F-1D18A9856A87","last_name":"Borges Merjane","full_name":"Borges Merjane, Carolina","orcid":"0000-0003-0005-401X"},{"id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","first_name":"Olena","last_name":"Kim","full_name":"Kim, Olena"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"}],"title":"Functional electron microscopy (“Flash and Freeze”) of identified cortical synapses in acute brain slices","abstract":[{"text":"How structural and functional properties of synapses relate to each other is a fundamental question in neuroscience. Electrophysiology has elucidated mechanisms of synaptic transmission, and electron microscopy (EM) has provided insight into morphological properties of synapses. Here we describe an enhanced method for functional EM (“flash and freeze”), combining optogenetic stimulation with high-pressure freezing. We demonstrate that the improved method can be applied to intact networks in acute brain slices and organotypic slice cultures from mice. As a proof of concept, we probed vesicle pool changes during synaptic transmission at the hippocampal mossy fiber-CA3 pyramidal neuron synapse. Our findings show overlap of the docked vesicle pool and the functionally defined readily releasable pool and provide evidence of fast endocytosis at this synapse. Functional EM with acute slices and slice cultures has the potential to reveal the structural and functional mechanisms of transmission in intact, genetically perturbed, and disease-affected synapses.","lang":"eng"}],"oa_version":"Published Version","pmid":1,"scopus_import":"1","intvolume":" 105","month":"03","publication_status":"published","publication_identifier":{"issn":["0896-6273"]},"language":[{"iso":"eng"}],"file":[{"checksum":"3582664addf26859e86ac5bec3e01416","file_id":"8778","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2020-11-20T08:58:53Z","file_name":"2020_Neuron_BorgesMerjane.pdf","date_updated":"2020-11-20T08:58:53Z","file_size":9712957,"creator":"dernst"}],"ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","volume":105,"related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/flash-and-freeze-reveals-dynamics-of-nerve-connections/"}],"record":[{"status":"public","id":"11196","relation":"dissertation_contains"}]},"_id":"7473","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"type":"journal_article","article_type":"original","status":"public","date_updated":"2024-03-27T23:30:07Z","ddc":["570"],"department":[{"_id":"PeJo"}],"file_date_updated":"2020-11-20T08:58:53Z"},{"title":"Mechanisms of drug interactions between translation-inhibiting antibiotics","article_processing_charge":"No","external_id":{"isi":["000562769300008"]},"author":[{"full_name":"Kavcic, Bor","orcid":"0000-0001-6041-254X","last_name":"Kavcic","first_name":"Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","full_name":"Bollenbach, Tobias","orcid":"0000-0003-4398-476X","last_name":"Bollenbach"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"mla":"Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications, vol. 11, 4013, Springer Nature, 2020, doi:10.1038/s41467-020-17734-z.","ieee":"B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions between translation-inhibiting antibiotics,” Nature Communications, vol. 11. Springer Nature, 2020.","short":"B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020).","apa":"Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-020-17734-z","ama":"Kavcic B, Tkačik G, Bollenbach MT. Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. 2020;11. doi:10.1038/s41467-020-17734-z","chicago":"Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications. Springer Nature, 2020. https://doi.org/10.1038/s41467-020-17734-z.","ista":"Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. 11, 4013."},"project":[{"call_identifier":"FWF","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","name":"Revealing the mechanisms underlying drug interactions","grant_number":"P27201-B22"},{"_id":"254E9036-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27"}],"article_number":"4013","date_created":"2020-08-12T09:13:50Z","doi":"10.1038/s41467-020-17734-z","date_published":"2020-08-11T00:00:00Z","publication":"Nature Communications","day":"11","year":"2020","isi":1,"has_accepted_license":"1","oa":1,"publisher":"Springer Nature","quality_controlled":"1","acknowledgement":"We thank M. Hennessey-Wesen, I. Tomanek, K. Jain, A. Staron, K. Tomasek, M. Scott,\r\nK.C. Huang, and Z. Gitai for reading the manuscript and constructive comments. B.K. is\r\nindebted to C. Guet for additional guidance and generous support, which rendered this\r\nwork possible. B.K. thanks all members of Guet group for many helpful discussions and\r\nsharing of resources. B.K. additionally acknowledges the tremendous support from A.\r\nAngermayr and K. Mitosch with experimental work. We further thank E. Brown for\r\nhelpful comments regarding lamotrigine, and A. Buskirk for valuable suggestions\r\nregarding the ribosome footprint size. This work was supported in part by Austrian\r\nScience Fund (FWF) standalone grants P 27201-B22 (to T.B.) and P 28844 (to G.T.),\r\nHFSP program Grant RGP0042/2013 (to T.B.), German Research Foundation (DFG)\r\nstandalone grant BO 3502/2-1 (to T.B.), and German Research Foundation (DFG)\r\nCollaborative Research Centre (SFB) 1310 (to T.B.). Open access funding provided by\r\nProjekt DEAL.","file_date_updated":"2020-08-17T07:36:57Z","department":[{"_id":"GaTk"}],"ddc":["570"],"date_updated":"2024-03-27T23:30:08Z","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","_id":"8250","related_material":{"record":[{"id":"8657","status":"public","relation":"dissertation_contains"}]},"volume":11,"language":[{"iso":"eng"}],"file":[{"success":1,"checksum":"986bebb308850a55850028d3d2b5b664","file_id":"8275","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2020_NatureComm_Kavcic.pdf","date_created":"2020-08-17T07:36:57Z","file_size":1965672,"date_updated":"2020-08-17T07:36:57Z","creator":"dernst"}],"publication_status":"published","publication_identifier":{"issn":["2041-1723"]},"intvolume":" 11","month":"08","oa_version":"Published Version","abstract":[{"text":"Antibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by “translation bottlenecks”: points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further show that growth laws, combined with drug uptake and binding kinetics, enable the direct prediction of a large fraction of observed interactions, yet fail to predict suppression. However, varying two translation bottlenecks simultaneously supports that dense traffic of ribosomes and competition for translation factors account for the previously unexplained suppression. These results highlight the importance of “continuous epistasis” in bacterial physiology.","lang":"eng"}]},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2024-03-27T23:30:08Z","citation":{"ama":"Kavcic B, Tkačik G, Bollenbach MT. A minimal biophysical model of combined antibiotic action. bioRxiv. 2020. doi:10.1101/2020.04.18.047886","apa":"Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). A minimal biophysical model of combined antibiotic action. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.18.047886","short":"B. Kavcic, G. Tkačik, M.T. Bollenbach, BioRxiv (2020).","ieee":"B. Kavcic, G. Tkačik, and M. T. Bollenbach, “A minimal biophysical model of combined antibiotic action,” bioRxiv. Cold Spring Harbor Laboratory, 2020.","mla":"Kavcic, Bor, et al. “A Minimal Biophysical Model of Combined Antibiotic Action.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.18.047886.","ista":"Kavcic B, Tkačik G, Bollenbach MT. 2020. A minimal biophysical model of combined antibiotic action. bioRxiv, 10.1101/2020.04.18.047886.","chicago":"Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “A Minimal Biophysical Model of Combined Antibiotic Action.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.18.047886."},"title":"A minimal biophysical model of combined antibiotic action","department":[{"_id":"GaTk"}],"author":[{"first_name":"Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","last_name":"Kavcic","full_name":"Kavcic, Bor","orcid":"0000-0001-6041-254X"},{"last_name":"Tkačik","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"},{"first_name":"Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X","full_name":"Bollenbach, Tobias","last_name":"Bollenbach"}],"article_processing_charge":"No","_id":"7673","status":"public","project":[{"_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Revealing the mechanisms underlying drug interactions","grant_number":"P27201-B22"},{"name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27","call_identifier":"FWF","_id":"254E9036-B435-11E9-9278-68D0E5697425"}],"type":"preprint","day":"18","publication":"bioRxiv","language":[{"iso":"eng"}],"publication_status":"published","year":"2020","related_material":{"record":[{"relation":"later_version","status":"public","id":"8997"},{"relation":"dissertation_contains","id":"8657","status":"public"}]},"date_published":"2020-04-18T00:00:00Z","doi":"10.1101/2020.04.18.047886","date_created":"2020-04-22T08:27:56Z","oa_version":"Preprint","abstract":[{"lang":"eng","text":"Combining drugs can improve the efficacy of treatments. However, predicting the effect of drug combinations is still challenging. The combined potency of drugs determines the drug interaction, which is classified as synergistic, additive, antagonistic, or suppressive. While probabilistic, non-mechanistic models exist, there is currently no biophysical model that can predict antibiotic interactions. Here, we present a physiologically relevant model of the combined action of antibiotics that inhibit protein synthesis by targeting the ribosome. This model captures the kinetics of antibiotic binding and transport, and uses bacterial growth laws to predict growth in the presence of antibiotic combinations. We find that this biophysical model can produce all drug interaction types except suppression. We show analytically that antibiotics which cannot bind to the ribosome simultaneously generally act as substitutes for one another, leading to additive drug interactions. Previously proposed null expectations for higher-order drug interactions follow as a limiting case of our model. We further extend the model to include the effects of direct physical or allosteric interactions between individual drugs on the ribosome. Notably, such direct interactions profoundly change the combined drug effect, depending on the kinetic parameters of the drugs used. The model makes additional predictions for the effects of resistance genes on drug interactions and for interactions between ribosome-targeting antibiotics and antibiotics with other targets. These findings enhance our understanding of the interplay between drug action and cell physiology and are a key step toward a general framework for predicting drug interactions."}],"month":"04","publisher":"Cold Spring Harbor Laboratory","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.04.18.047886 "}],"oa":1}]