--- _id: '1823' abstract: - lang: eng text: Abstract Drug combinations are increasingly important in disease treatments, for combating drug resistance, and for elucidating fundamental relationships in cell physiology. When drugs are combined, their individual effects on cells may be amplified or weakened. Such drug interactions are crucial for treatment efficacy, but their underlying mechanisms remain largely unknown. To uncover the causes of drug interactions, we developed a systematic approach based on precise quantification of the individual and joint effects of antibiotics on growth of genome-wide Escherichia coli gene deletion strains. We found that drug interactions between antibiotics representing the main modes of action are highly robust to genetic perturbation. This robustness is encapsulated in a general principle of bacterial growth, which enables the quantitative prediction of mutant growth rates under drug combinations. Rare violations of this principle exposed recurring cellular functions controlling drug interactions. In particular, we found that polysaccharide and ATP synthesis control multiple drug interactions with previously unexplained mechanisms, and small molecule adjuvants targeting these functions synthetically reshape drug interactions in predictable ways. These results provide a new conceptual framework for the design of multidrug combinations and suggest that there are universal mechanisms at the heart of most drug interactions. Synopsis A general principle of bacterial growth enables the prediction of mutant growth rates under drug combinations. Rare violations of this principle expose cellular functions that control drug interactions and can be targeted by small molecules to alter drug interactions in predictable ways. Drug interactions between antibiotics are highly robust to genetic perturbations. A general principle of bacterial growth enables the prediction of mutant growth rates under drug combinations. Rare violations of this principle expose cellular functions that control drug interactions. Diverse drug interactions are controlled by recurring cellular functions, including LPS synthesis and ATP synthesis. A general principle of bacterial growth enables the prediction of mutant growth rates under drug combinations. Rare violations of this principle expose cellular functions that control drug interactions and can be targeted by small molecules to alter drug interactions in predictable ways. article_number: '807' author: - first_name: Guillaume full_name: Chevereau, Guillaume id: 424D78A0-F248-11E8-B48F-1D18A9856A87 last_name: Chevereau - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X citation: ama: Chevereau G, Bollenbach MT. Systematic discovery of drug interaction mechanisms. Molecular Systems Biology. 2015;11(4). doi:10.15252/msb.20156098 apa: Chevereau, G., & Bollenbach, M. T. (2015). Systematic discovery of drug interaction mechanisms. Molecular Systems Biology. Nature Publishing Group. https://doi.org/10.15252/msb.20156098 chicago: Chevereau, Guillaume, and Mark Tobias Bollenbach. “Systematic Discovery of Drug Interaction Mechanisms.” Molecular Systems Biology. Nature Publishing Group, 2015. https://doi.org/10.15252/msb.20156098. ieee: G. Chevereau and M. T. Bollenbach, “Systematic discovery of drug interaction mechanisms,” Molecular Systems Biology, vol. 11, no. 4. Nature Publishing Group, 2015. ista: Chevereau G, Bollenbach MT. 2015. Systematic discovery of drug interaction mechanisms. Molecular Systems Biology. 11(4), 807. mla: Chevereau, Guillaume, and Mark Tobias Bollenbach. “Systematic Discovery of Drug Interaction Mechanisms.” Molecular Systems Biology, vol. 11, no. 4, 807, Nature Publishing Group, 2015, doi:10.15252/msb.20156098. short: G. Chevereau, M.T. Bollenbach, Molecular Systems Biology 11 (2015). date_created: 2018-12-11T11:54:12Z date_published: 2015-04-01T00:00:00Z date_updated: 2021-01-12T06:53:26Z day: '01' ddc: - '570' department: - _id: ToBo doi: 10.15252/msb.20156098 ec_funded: 1 file: - access_level: open_access checksum: 4289b518fbe2166682fb1a1ef9b405f3 content_type: application/pdf creator: system date_created: 2018-12-12T10:14:34Z date_updated: 2020-07-14T12:45:17Z file_id: '5087' file_name: IST-2015-395-v1+1_807.full.pdf file_size: 1273573 relation: main_file file_date_updated: 2020-07-14T12:45:17Z has_accepted_license: '1' intvolume: ' 11' issue: '4' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '04' oa: 1 oa_version: Published Version project: - _id: 25E9AF9E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P27201-B22 name: Revealing the mechanisms underlying drug interactions - _id: 25EB3A80-B435-11E9-9278-68D0E5697425 grant_number: RGP0042/2013 name: Revealing the fundamental limits of cell growth - _id: 25E83C2C-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '303507' name: Optimality principles in responses to antibiotics publication: Molecular Systems Biology publication_status: published publisher: Nature Publishing Group publist_id: '5283' pubrep_id: '395' quality_controlled: '1' scopus_import: 1 status: public title: Systematic discovery of drug interaction mechanisms tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 11 year: '2015' ... --- _id: '1824' abstract: - lang: eng text: Condensation phenomena arise through a collective behaviour of particles. They are observed in both classical and quantum systems, ranging from the formation of traffic jams in mass transport models to the macroscopic occupation of the energetic ground state in ultra-cold bosonic gases (Bose-Einstein condensation). Recently, it has been shown that a driven and dissipative system of bosons may form multiple condensates. Which states become the condensates has, however, remained elusive thus far. The dynamics of this condensation are described by coupled birth-death processes, which also occur in evolutionary game theory. Here we apply concepts from evolutionary game theory to explain the formation of multiple condensates in such driven-dissipative bosonic systems. We show that the vanishing of relative entropy production determines their selection. The condensation proceeds exponentially fast, but the system never comes to rest. Instead, the occupation numbers of condensates may oscillate, as we demonstrate for a rock-paper-scissors game of condensates. article_number: '6977' author: - first_name: Johannes full_name: Knebel, Johannes last_name: Knebel - first_name: Markus full_name: Weber, Markus last_name: Weber - first_name: Torben H full_name: Krüger, Torben H id: 3020C786-F248-11E8-B48F-1D18A9856A87 last_name: Krüger orcid: 0000-0002-4821-3297 - first_name: Erwin full_name: Frey, Erwin last_name: Frey citation: ama: Knebel J, Weber M, Krüger TH, Frey E. Evolutionary games of condensates in coupled birth-death processes. Nature Communications. 2015;6. doi:10.1038/ncomms7977 apa: Knebel, J., Weber, M., Krüger, T. H., & Frey, E. (2015). Evolutionary games of condensates in coupled birth-death processes. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms7977 chicago: Knebel, Johannes, Markus Weber, Torben H Krüger, and Erwin Frey. “Evolutionary Games of Condensates in Coupled Birth-Death Processes.” Nature Communications. Nature Publishing Group, 2015. https://doi.org/10.1038/ncomms7977. ieee: J. Knebel, M. Weber, T. H. Krüger, and E. Frey, “Evolutionary games of condensates in coupled birth-death processes,” Nature Communications, vol. 6. Nature Publishing Group, 2015. ista: Knebel J, Weber M, Krüger TH, Frey E. 2015. Evolutionary games of condensates in coupled birth-death processes. Nature Communications. 6, 6977. mla: Knebel, Johannes, et al. “Evolutionary Games of Condensates in Coupled Birth-Death Processes.” Nature Communications, vol. 6, 6977, Nature Publishing Group, 2015, doi:10.1038/ncomms7977. short: J. Knebel, M. Weber, T.H. Krüger, E. Frey, Nature Communications 6 (2015). date_created: 2018-12-11T11:54:13Z date_published: 2015-04-24T00:00:00Z date_updated: 2021-01-12T06:53:26Z day: '24' ddc: - '530' department: - _id: LaEr doi: 10.1038/ncomms7977 file: - access_level: open_access checksum: c4cffb5c8b245e658a34eac71a03e7cc content_type: application/pdf creator: system date_created: 2018-12-12T10:16:54Z date_updated: 2020-07-14T12:45:17Z file_id: '5245' file_name: IST-2016-451-v1+1_ncomms7977.pdf file_size: 1151501 relation: main_file file_date_updated: 2020-07-14T12:45:17Z has_accepted_license: '1' intvolume: ' 6' language: - iso: eng month: '04' oa: 1 oa_version: Published Version publication: Nature Communications publication_status: published publisher: Nature Publishing Group publist_id: '5282' pubrep_id: '451' quality_controlled: '1' scopus_import: 1 status: public title: Evolutionary games of condensates in coupled birth-death processes tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 6 year: '2015' ... --- _id: '1831' abstract: - lang: eng text: This paper introduces a theme issue presenting the latest developments in research on the impacts of sociality on health and fitness. The articles that follow cover research on societies ranging from insects to humans. Variation in measures of fitness (i.e. survival and reproduction) has been linked to various aspects of sociality in humans and animals alike, and variability in individual health and condition has been recognized as a key mediator of these relationships. Viewed from a broad evolutionary perspective, the evolutionary transitions from a solitary lifestyle to group living have resulted in several new health-related costs and benefits of sociality. Social transmission of parasites within groups represents a major cost of group living, but some behavioural mechanisms, such as grooming, have evolved repeatedly to reduce this cost. Group living also has created novel costs in terms of altered susceptibility to infectious and non-infectious disease as a result of the unavoidable physiological consequences of social competition and integration, which are partly alleviated by social buffering in some vertebrates. Here, we define the relevant aspects of sociality, summarize their health-related costs and benefits, and discuss possible fitness measures in different study systems. Given the pervasive effects of social factors on health and fitness, we propose a synthesis of existing conceptual approaches in disease ecology, ecological immunology and behavioural neurosciences by adding sociality as a key factor, with the goal to generate a broader framework for organismal integration of health-related research. acknowledgement: We thank the German Research Foundation (DFG), the Ministry of Science and Culture of Lower-Saxony (MWK Hannover) and the German Primate Centre (DPZ) for their support of the 9. Göttinger Freilandtage in 2013, a conference at which most contributions to this issue were first presented, the referees of the contributions to this issue for their constructive comments, Meggan Craft for comments, and Helen Eaton for her support in producing this theme issue. article_number: '20140116' author: - first_name: Peter full_name: Kappeler, Peter last_name: Kappeler - first_name: Sylvia full_name: Cremer, Sylvia id: 2F64EC8C-F248-11E8-B48F-1D18A9856A87 last_name: Cremer orcid: 0000-0002-2193-3868 - first_name: Charles full_name: Nunn, Charles last_name: Nunn citation: ama: 'Kappeler P, Cremer S, Nunn C. Sociality and health: Impacts of sociality on disease susceptibility and transmission in animal and human societies. Philosophical Transactions of the Royal Society of London Series B, Biological Sciences. 2015;370(1669). doi:10.1098/rstb.2014.0116' apa: 'Kappeler, P., Cremer, S., & Nunn, C. (2015). Sociality and health: Impacts of sociality on disease susceptibility and transmission in animal and human societies. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. Royal Society. https://doi.org/10.1098/rstb.2014.0116' chicago: 'Kappeler, Peter, Sylvia Cremer, and Charles Nunn. “Sociality and Health: Impacts of Sociality on Disease Susceptibility and Transmission in Animal and Human Societies.” Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. Royal Society, 2015. https://doi.org/10.1098/rstb.2014.0116.' ieee: 'P. Kappeler, S. Cremer, and C. Nunn, “Sociality and health: Impacts of sociality on disease susceptibility and transmission in animal and human societies,” Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, vol. 370, no. 1669. Royal Society, 2015.' ista: 'Kappeler P, Cremer S, Nunn C. 2015. Sociality and health: Impacts of sociality on disease susceptibility and transmission in animal and human societies. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 370(1669), 20140116.' mla: 'Kappeler, Peter, et al. “Sociality and Health: Impacts of Sociality on Disease Susceptibility and Transmission in Animal and Human Societies.” Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, vol. 370, no. 1669, 20140116, Royal Society, 2015, doi:10.1098/rstb.2014.0116.' short: P. Kappeler, S. Cremer, C. Nunn, Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 370 (2015). date_created: 2018-12-11T11:54:15Z date_published: 2015-05-01T00:00:00Z date_updated: 2021-01-12T06:53:29Z day: '01' department: - _id: SyCr doi: 10.1098/rstb.2014.0116 external_id: pmid: - '25870402' intvolume: ' 370' issue: '1669' language: - iso: eng main_file_link: - open_access: '1' url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410382/ month: '05' oa: 1 oa_version: Submitted Version pmid: 1 publication: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences publication_status: published publisher: Royal Society publist_id: '5272' quality_controlled: '1' scopus_import: 1 status: public title: 'Sociality and health: Impacts of sociality on disease susceptibility and transmission in animal and human societies' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 370 year: '2015' ... --- _id: '1828' abstract: - lang: eng text: We construct a non-linear Markov process connected with a biological model of a bacterial genome recombination. The description of invariant measures of this process gives us the solution of one problem in elementary probability theory. article_processing_charge: No author: - first_name: Arseniy full_name: Akopyan, Arseniy id: 430D2C90-F248-11E8-B48F-1D18A9856A87 last_name: Akopyan orcid: 0000-0002-2548-617X - first_name: Sergey full_name: Pirogov, Sergey last_name: Pirogov - first_name: Aleksandr full_name: Rybko, Aleksandr last_name: Rybko citation: ama: Akopyan A, Pirogov S, Rybko A. Invariant measures of genetic recombination process. Journal of Statistical Physics. 2015;160(1):163-167. doi:10.1007/s10955-015-1238-5 apa: Akopyan, A., Pirogov, S., & Rybko, A. (2015). Invariant measures of genetic recombination process. Journal of Statistical Physics. Springer. https://doi.org/10.1007/s10955-015-1238-5 chicago: Akopyan, Arseniy, Sergey Pirogov, and Aleksandr Rybko. “Invariant Measures of Genetic Recombination Process.” Journal of Statistical Physics. Springer, 2015. https://doi.org/10.1007/s10955-015-1238-5. ieee: A. Akopyan, S. Pirogov, and A. Rybko, “Invariant measures of genetic recombination process,” Journal of Statistical Physics, vol. 160, no. 1. Springer, pp. 163–167, 2015. ista: Akopyan A, Pirogov S, Rybko A. 2015. Invariant measures of genetic recombination process. Journal of Statistical Physics. 160(1), 163–167. mla: Akopyan, Arseniy, et al. “Invariant Measures of Genetic Recombination Process.” Journal of Statistical Physics, vol. 160, no. 1, Springer, 2015, pp. 163–67, doi:10.1007/s10955-015-1238-5. short: A. Akopyan, S. Pirogov, A. Rybko, Journal of Statistical Physics 160 (2015) 163–167. date_created: 2018-12-11T11:54:14Z date_published: 2015-07-01T00:00:00Z date_updated: 2021-01-12T06:53:28Z day: '01' department: - _id: HeEd doi: 10.1007/s10955-015-1238-5 ec_funded: 1 intvolume: ' 160' issue: '1' language: - iso: eng main_file_link: - open_access: '1' url: arxiv.org/abs/1406.5313 month: '07' oa: 1 oa_version: Preprint page: 163 - 167 project: - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Journal of Statistical Physics publication_status: published publisher: Springer publist_id: '5276' quality_controlled: '1' scopus_import: 1 status: public title: Invariant measures of genetic recombination process type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 160 year: '2015' ... --- _id: '1836' abstract: - lang: eng text: In the standard framework for worst-case execution time (WCET) analysis of programs, the main data structure is a single instance of integer linear programming (ILP) that represents the whole program. The instance of this NP-hard problem must be solved to find an estimate forWCET, and it must be refined if the estimate is not tight.We propose a new framework for WCET analysis, based on abstract segment trees (ASTs) as the main data structure. The ASTs have two advantages. First, they allow computing WCET by solving a number of independent small ILP instances. Second, ASTs store more expressive constraints, thus enabling a more efficient and precise refinement procedure. In order to realize our framework algorithmically, we develop an algorithm for WCET estimation on ASTs, and we develop an interpolation-based counterexample-guided refinement scheme for ASTs. Furthermore, we extend our framework to obtain parametric estimates of WCET. We experimentally evaluate our approach on a set of examples from WCET benchmark suites and linear-algebra packages. We show that our analysis, with comparable effort, provides WCET estimates that in many cases significantly improve those computed by existing tools. alternative_title: - LNCS author: - first_name: Pavol full_name: Cerny, Pavol id: 4DCBEFFE-F248-11E8-B48F-1D18A9856A87 last_name: Cerny - first_name: Thomas A full_name: Henzinger, Thomas A id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000−0002−2985−7724 - first_name: Laura full_name: Kovács, Laura last_name: Kovács - first_name: Arjun full_name: Radhakrishna, Arjun id: 3B51CAC4-F248-11E8-B48F-1D18A9856A87 last_name: Radhakrishna - first_name: Jakob full_name: Zwirchmayr, Jakob last_name: Zwirchmayr citation: ama: Cerny P, Henzinger TA, Kovács L, Radhakrishna A, Zwirchmayr J. Segment abstraction for worst-case execution time analysis. 2015;9032:105-131. doi:10.1007/978-3-662-46669-8_5 apa: 'Cerny, P., Henzinger, T. A., Kovács, L., Radhakrishna, A., & Zwirchmayr, J. (2015). Segment abstraction for worst-case execution time analysis. Presented at the ESOP: European Symposium on Programming, London, United Kingdom: Springer. https://doi.org/10.1007/978-3-662-46669-8_5' chicago: Cerny, Pavol, Thomas A Henzinger, Laura Kovács, Arjun Radhakrishna, and Jakob Zwirchmayr. “Segment Abstraction for Worst-Case Execution Time Analysis.” Lecture Notes in Computer Science. Springer, 2015. https://doi.org/10.1007/978-3-662-46669-8_5. ieee: P. Cerny, T. A. Henzinger, L. Kovács, A. Radhakrishna, and J. Zwirchmayr, “Segment abstraction for worst-case execution time analysis,” vol. 9032. Springer, pp. 105–131, 2015. ista: Cerny P, Henzinger TA, Kovács L, Radhakrishna A, Zwirchmayr J. 2015. Segment abstraction for worst-case execution time analysis. 9032, 105–131. mla: Cerny, Pavol, et al. Segment Abstraction for Worst-Case Execution Time Analysis. Vol. 9032, Springer, 2015, pp. 105–31, doi:10.1007/978-3-662-46669-8_5. short: P. Cerny, T.A. Henzinger, L. Kovács, A. Radhakrishna, J. Zwirchmayr, 9032 (2015) 105–131. conference: end_date: 2015-04-18 location: London, United Kingdom name: 'ESOP: European Symposium on Programming' start_date: 2015-04-11 date_created: 2018-12-11T11:54:16Z date_published: 2015-04-01T00:00:00Z date_updated: 2020-08-11T10:09:32Z day: '01' department: - _id: ToHe doi: 10.1007/978-3-662-46669-8_5 ec_funded: 1 intvolume: ' 9032' language: - iso: eng month: '04' oa_version: None page: 105 - 131 project: - _id: 25EE3708-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '267989' name: Quantitative Reactive Modeling - _id: 25832EC2-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: S 11407_N23 name: Rigorous Systems Engineering publication_status: published publisher: Springer publist_id: '5266' quality_controlled: '1' scopus_import: 1 series_title: Lecture Notes in Computer Science status: public title: Segment abstraction for worst-case execution time analysis type: conference user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 9032 year: '2015' ...