[{"doi":"10.1101/2020.04.18.047886","title":"A minimal biophysical model of combined antibiotic action","date_updated":"2024-03-25T23:30:05Z","publisher":"Cold Spring Harbor Laboratory","_id":"7673","publication":"bioRxiv","article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"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.","lang":"eng"}],"oa":1,"month":"04","status":"public","project":[{"grant_number":"P27201-B22","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","name":"Revealing the mechanisms underlying drug interactions","call_identifier":"FWF"},{"_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","call_identifier":"FWF","name":"Biophysics of information processing in gene regulation"}],"type":"preprint","date_published":"2020-04-18T00:00:00Z","citation":{"ista":"Kavcic B, Tkačik G, Bollenbach MT. 2020. A minimal biophysical model of combined antibiotic action. bioRxiv, <a href=\"https://doi.org/10.1101/2020.04.18.047886\">10.1101/2020.04.18.047886</a>.","apa":"Kavcic, B., Tkačik, G., &#38; Bollenbach, M. T. (2020). A minimal biophysical model of combined antibiotic action. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.04.18.047886\">https://doi.org/10.1101/2020.04.18.047886</a>","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,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory, 2020.","ama":"Kavcic B, Tkačik G, Bollenbach MT. A minimal biophysical model of combined antibiotic action. <i>bioRxiv</i>. 2020. doi:<a href=\"https://doi.org/10.1101/2020.04.18.047886\">10.1101/2020.04.18.047886</a>","mla":"Kavcic, Bor, et al. “A Minimal Biophysical Model of Combined Antibiotic Action.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, 2020, doi:<a href=\"https://doi.org/10.1101/2020.04.18.047886\">10.1101/2020.04.18.047886</a>.","chicago":"Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “A Minimal Biophysical Model of Combined Antibiotic Action.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, 2020. <a href=\"https://doi.org/10.1101/2020.04.18.047886\">https://doi.org/10.1101/2020.04.18.047886</a>."},"main_file_link":[{"url":"https://doi.org/10.1101/2020.04.18.047886 ","open_access":"1"}],"oa_version":"Preprint","related_material":{"record":[{"relation":"later_version","status":"public","id":"8997"},{"id":"8657","status":"public","relation":"dissertation_contains"}]},"language":[{"iso":"eng"}],"year":"2020","department":[{"_id":"GaTk"}],"author":[{"first_name":"Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","full_name":"Kavcic, Bor","orcid":"0000-0001-6041-254X","last_name":"Kavcic"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455"},{"first_name":"Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","full_name":"Bollenbach, Tobias","last_name":"Bollenbach","orcid":"0000-0003-4398-476X"}],"day":"18","publication_status":"published","date_created":"2020-04-22T08:27:56Z"},{"doi":"10.1101/2020.04.08.029405","publisher":"Cold Spring Harbor Laboratory","title":"Normative models of enhancer function","date_updated":"2023-09-07T13:13:26Z","_id":"7675","publication":"bioRxiv","article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene expression levels that is compatible with in vivo and in vitro bio-physical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In non-equilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal non-equilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in non-equilibrium models is in a tradeoff with gene expression noise, predicting bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space to a much smaller subspace that optimally realizes biological function prior to inference from data, our normative approach holds promise for mathematical models in systems biology."}],"oa":1,"month":"04","status":"public","project":[{"name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?","grant_number":"RGP0034/2018","_id":"2665AAFE-B435-11E9-9278-68D0E5697425"},{"_id":"267C84F4-B435-11E9-9278-68D0E5697425","name":"Biophysically realistic genotype-phenotype maps for regulatory networks"}],"type":"preprint","date_published":"2020-04-09T00:00:00Z","citation":{"ista":"Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv, <a href=\"https://doi.org/10.1101/2020.04.08.029405\">10.1101/2020.04.08.029405</a>.","apa":"Grah, R., Zoller, B., &#38; Tkačik, G. (2020). Normative models of enhancer function. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.04.08.029405\">https://doi.org/10.1101/2020.04.08.029405</a>","short":"R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020).","ieee":"R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory, 2020.","ama":"Grah R, Zoller B, Tkačik G. Normative models of enhancer function. <i>bioRxiv</i>. 2020. doi:<a href=\"https://doi.org/10.1101/2020.04.08.029405\">10.1101/2020.04.08.029405</a>","mla":"Grah, Rok, et al. “Normative Models of Enhancer Function.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, 2020, doi:<a href=\"https://doi.org/10.1101/2020.04.08.029405\">10.1101/2020.04.08.029405</a>.","chicago":"Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Normative Models of Enhancer Function.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, 2020. <a href=\"https://doi.org/10.1101/2020.04.08.029405\">https://doi.org/10.1101/2020.04.08.029405</a>."},"main_file_link":[{"url":"https://doi.org/10.1101/2020.04.08.029405 ","open_access":"1"}],"oa_version":"Preprint","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"8155"}]},"year":"2020","language":[{"iso":"eng"}],"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"author":[{"full_name":"Grah, Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","first_name":"Rok","orcid":"0000-0003-2539-3560","last_name":"Grah"},{"last_name":"Zoller","first_name":"Benjamin","full_name":"Zoller, Benjamin"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455"}],"day":"09","publication_status":"published","date_created":"2020-04-23T10:12:51Z"},{"has_accepted_license":"1","intvolume":"        40","citation":{"mla":"Lombardi, Fabrizio, et al. “Critical Dynamics and Coupling in Bursts of Cortical Rhythms Indicate Non-Homeostatic Mechanism for Sleep-Stage Transitions and Dual Role of VLPO Neurons in Both Sleep and Wake.” <i>Journal of Neuroscience</i>, vol. 40, no. 1, Society for Neuroscience, 2020, pp. 171–90, doi:<a href=\"https://doi.org/10.1523/jneurosci.1278-19.2019\">10.1523/jneurosci.1278-19.2019</a>.","ama":"Lombardi F, Gómez-Extremera M, Bernaola-Galván P, et al. Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake. <i>Journal of Neuroscience</i>. 2020;40(1):171-190. doi:<a href=\"https://doi.org/10.1523/jneurosci.1278-19.2019\">10.1523/jneurosci.1278-19.2019</a>","chicago":"Lombardi, Fabrizio, Manuel Gómez-Extremera, Pedro Bernaola-Galván, Ramalingam Vetrivelan, Clifford B. Saper, Thomas E. Scammell, and Plamen Ch. Ivanov. “Critical Dynamics and Coupling in Bursts of Cortical Rhythms Indicate Non-Homeostatic Mechanism for Sleep-Stage Transitions and Dual Role of VLPO Neurons in Both Sleep and Wake.” <i>Journal of Neuroscience</i>. Society for Neuroscience, 2020. <a href=\"https://doi.org/10.1523/jneurosci.1278-19.2019\">https://doi.org/10.1523/jneurosci.1278-19.2019</a>.","apa":"Lombardi, F., Gómez-Extremera, M., Bernaola-Galván, P., Vetrivelan, R., Saper, C. B., Scammell, T. E., &#38; Ivanov, P. C. (2020). Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake. <i>Journal of Neuroscience</i>. Society for Neuroscience. <a href=\"https://doi.org/10.1523/jneurosci.1278-19.2019\">https://doi.org/10.1523/jneurosci.1278-19.2019</a>","ista":"Lombardi F, Gómez-Extremera M, Bernaola-Galván P, Vetrivelan R, Saper CB, Scammell TE, Ivanov PC. 2020. Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake. Journal of Neuroscience. 40(1), 171–190.","ieee":"F. Lombardi <i>et al.</i>, “Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake,” <i>Journal of Neuroscience</i>, vol. 40, no. 1. Society for Neuroscience, pp. 171–190, 2020.","short":"F. Lombardi, M. Gómez-Extremera, P. Bernaola-Galván, R. Vetrivelan, C.B. Saper, T.E. Scammell, P.C. Ivanov, Journal of Neuroscience 40 (2020) 171–190."},"ec_funded":1,"status":"public","pmid":1,"abstract":[{"lang":"eng","text":"Origin and functions of intermittent transitions among sleep stages, including brief awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing sleep on scales of seconds and minutes results from intrinsic non-equilibrium critical dynamics. We investigate θ- and δ-wave dynamics in control rats and in rats where the sleep-promoting ventrolateral preoptic nucleus (VLPO) is lesioned (male Sprague-Dawley rats). We demonstrate that bursts in θ and δ cortical rhythms exhibit complex temporal organization, with long-range correlations and robust duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, features typical of non-equilibrium systems self-organizing at criticality. We show that such non-equilibrium behavior relates to anti-correlated coupling between θ- and δ-bursts, persists across a range of time scales, and is independent of the dominant physiologic state; indications of a basic principle in sleep regulation. Further, we find that VLPO lesions lead to a modulation of cortical dynamics resulting in altered dynamical parameters of θ- and δ-bursts and significant reduction in θ–δ coupling. Our empirical findings and model simulations demonstrate that θ–δ coupling is essential for the emerging non-equilibrium critical dynamics observed across the sleep–wake cycle, and indicate that VLPO neurons may have dual role for both sleep and arousal/brief wake activation. The uncovered critical behavior in sleep- and wake-related cortical rhythms indicates a mechanism essential for the micro-architecture of spontaneous sleep-stage and arousal transitions within a novel, non-homeostatic paradigm of sleep regulation."}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"8084","title":"Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake","publication_identifier":{"eissn":["1529-2401"],"issn":["0270-6474"]},"issue":"1","file_date_updated":"2020-07-22T11:44:48Z","isi":1,"scopus_import":"1","oa_version":"Published Version","external_id":{"isi":["000505167600016"],"pmid":["31694962"]},"article_type":"original","volume":40,"type":"journal_article","date_published":"2020-01-02T00:00:00Z","project":[{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425"}],"month":"01","oa":1,"file":[{"date_updated":"2020-07-22T11:44:48Z","file_size":6646046,"access_level":"open_access","file_name":"2020_JournNeuroscience_Lombardi.pdf","success":1,"relation":"main_file","creator":"dernst","content_type":"application/pdf","file_id":"8150","date_created":"2020-07-22T11:44:48Z"}],"quality_controlled":"1","article_processing_charge":"No","publication":"Journal of Neuroscience","date_updated":"2023-09-05T14:02:55Z","doi":"10.1523/jneurosci.1278-19.2019","publisher":"Society for Neuroscience","date_created":"2020-07-05T15:24:51Z","publication_status":"published","day":"02","author":[{"full_name":"Lombardi, Fabrizio","id":"A057D288-3E88-11E9-986D-0CF4E5697425","first_name":"Fabrizio","orcid":"0000-0003-2623-5249","last_name":"Lombardi"},{"last_name":"Gómez-Extremera","first_name":"Manuel","full_name":"Gómez-Extremera, Manuel"},{"last_name":"Bernaola-Galván","full_name":"Bernaola-Galván, Pedro","first_name":"Pedro"},{"last_name":"Vetrivelan","full_name":"Vetrivelan, Ramalingam","first_name":"Ramalingam"},{"first_name":"Clifford B.","full_name":"Saper, Clifford B.","last_name":"Saper"},{"full_name":"Scammell, Thomas E.","first_name":"Thomas E.","last_name":"Scammell"},{"last_name":"Ivanov","full_name":"Ivanov, Plamen Ch.","first_name":"Plamen Ch."}],"page":"171-190","department":[{"_id":"GaTk"}],"year":"2020","ddc":["570"],"language":[{"iso":"eng"}]},{"month":"07","file":[{"content_type":"application/zip","file_id":"8098","date_created":"2020-07-06T20:38:27Z","creator":"bkavcic","relation":"main_file","file_name":"natComm_2020_scripts.zip","access_level":"open_access","checksum":"5c321dbbb6d4b3c85da786fd3ebbdc98","date_updated":"2020-07-14T12:48:09Z","file_size":255770756}],"oa":1,"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"}],"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"8097","doi":"10.15479/AT:ISTA:8097","title":"Analysis scripts and research data for the paper \"Mechanisms of drug interactions between translation-inhibiting antibiotics\"","date_updated":"2024-02-21T12:40:51Z","publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","contributor":[{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","contributor_type":"research_group","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"contributor_type":"research_group","last_name":"Bollenbach","first_name":"Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87"}],"has_accepted_license":"1","citation":{"ama":"Kavcic B. Analysis scripts and research data for the paper “Mechanisms of drug interactions between translation-inhibiting antibiotics.” 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8097\">10.15479/AT:ISTA:8097</a>","mla":"Kavcic, Bor. <i>Analysis Scripts and Research Data for the Paper “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.”</i> Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8097\">10.15479/AT:ISTA:8097</a>.","chicago":"Kavcic, Bor. “Analysis Scripts and Research Data for the Paper ‘Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.’” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8097\">https://doi.org/10.15479/AT:ISTA:8097</a>.","ista":"Kavcic B. 2020. Analysis scripts and research data for the paper ‘Mechanisms of drug interactions between translation-inhibiting antibiotics’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:8097\">10.15479/AT:ISTA:8097</a>.","apa":"Kavcic, B. (2020). Analysis scripts and research data for the paper “Mechanisms of drug interactions between translation-inhibiting antibiotics.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8097\">https://doi.org/10.15479/AT:ISTA:8097</a>","ieee":"B. Kavcic, “Analysis scripts and research data for the paper ‘Mechanisms of drug interactions between translation-inhibiting antibiotics.’” Institute of Science and Technology Austria, 2020.","short":"B. Kavcic, (2020)."},"date_published":"2020-07-15T00:00:00Z","type":"research_data","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"department":[{"_id":"GaTk"}],"file_date_updated":"2020-07-14T12:48:09Z","year":"2020","acknowledged_ssus":[{"_id":"LifeSc"}],"date_created":"2020-07-06T20:40:19Z","day":"15","keyword":["Escherichia coli","antibiotic combinations","translation","growth laws","drug interactions","bacterial physiology","translation inhibitors"],"author":[{"first_name":"Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","full_name":"Kavcic, Bor","last_name":"Kavcic","orcid":"0000-0001-6041-254X"}]},{"month":"03","quality_controlled":"1","oa":1,"file":[{"date_updated":"2020-07-22T06:17:11Z","file_size":2197543,"file_name":"2020_EPJWebConf_Lombardi.pdf","access_level":"open_access","success":1,"creator":"dernst","relation":"main_file","content_type":"application/pdf","file_id":"8144","date_created":"2020-07-22T06:17:11Z"}],"article_number":"00005","article_processing_charge":"No","date_updated":"2021-01-12T08:16:55Z","doi":"10.1051/epjconf/202023000005","publisher":"EDP Sciences","publication":"EPJ Web of Conferences","oa_version":"Published Version","article_type":"original","date_published":"2020-03-11T00:00:00Z","type":"journal_article","volume":230,"department":[{"_id":"GaTk"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"ddc":["530"],"language":[{"iso":"eng"}],"year":"2020","date_created":"2020-07-12T16:20:33Z","day":"11","publication_status":"published","author":[{"last_name":"Lombardi","orcid":"0000-0003-2623-5249","full_name":"Lombardi, Fabrizio","id":"A057D288-3E88-11E9-986D-0CF4E5697425","first_name":"Fabrizio"},{"full_name":"Wang, Jilin W.J.L.","first_name":"Jilin W.J.L.","last_name":"Wang"},{"last_name":"Zhang","full_name":"Zhang, Xiyun","first_name":"Xiyun"},{"first_name":"Plamen Ch","full_name":"Ivanov, Plamen Ch","last_name":"Ivanov"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"Physical and biological systems often exhibit intermittent dynamics with bursts or avalanches (active states) characterized by power-law size and duration distributions. These emergent features are typical of systems at the critical point of continuous phase transitions, and have led to the hypothesis that such systems may self-organize at criticality, i.e. without any fine tuning of parameters. Since the introduction of the Bak-Tang-Wiesenfeld (BTW) model, the paradigm of self-organized criticality (SOC) has been very fruitful for the analysis of emergent collective behaviors in a number of systems, including the brain. Although considerable effort has been devoted in identifying and modeling scaling features of burst and avalanche statistics, dynamical aspects related to the temporal organization of bursts remain often poorly understood or controversial. Of crucial importance to understand the mechanisms responsible for emergent behaviors is the relationship between active and quiet periods, and the nature of the correlations. Here we investigate the dynamics of active (θ-bursts) and quiet states (δ-bursts) in brain activity during the sleep-wake cycle. We show the duality of power-law (θ, active phase) and exponential-like (δ, quiescent phase) duration distributions, typical of SOC, jointly emerge with power-law temporal correlations and anti-correlated coupling between active and quiet states. Importantly, we demonstrate that such temporal organization shares important similarities with earthquake dynamics, and propose that specific power-law correlations and coupling between active and quiet states are distinctive characteristics of a class of systems with self-organization at criticality.","lang":"eng"}],"title":"Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality","_id":"8105","intvolume":"       230","citation":{"ama":"Lombardi F, Wang JWJL, Zhang X, Ivanov PC. Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality. <i>EPJ Web of Conferences</i>. 2020;230. doi:<a href=\"https://doi.org/10.1051/epjconf/202023000005\">10.1051/epjconf/202023000005</a>","mla":"Lombardi, Fabrizio, et al. “Power-Law Correlations and Coupling of Active and Quiet States Underlie a Class of Complex Systems with Self-Organization at Criticality.” <i>EPJ Web of Conferences</i>, vol. 230, 00005, EDP Sciences, 2020, doi:<a href=\"https://doi.org/10.1051/epjconf/202023000005\">10.1051/epjconf/202023000005</a>.","chicago":"Lombardi, Fabrizio, Jilin W.J.L. Wang, Xiyun Zhang, and Plamen Ch Ivanov. “Power-Law Correlations and Coupling of Active and Quiet States Underlie a Class of Complex Systems with Self-Organization at Criticality.” <i>EPJ Web of Conferences</i>. EDP Sciences, 2020. <a href=\"https://doi.org/10.1051/epjconf/202023000005\">https://doi.org/10.1051/epjconf/202023000005</a>.","ista":"Lombardi F, Wang JWJL, Zhang X, Ivanov PC. 2020. Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality. EPJ Web of Conferences. 230, 00005.","apa":"Lombardi, F., Wang, J. W. J. L., Zhang, X., &#38; Ivanov, P. C. (2020). Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality. <i>EPJ Web of Conferences</i>. EDP Sciences. <a href=\"https://doi.org/10.1051/epjconf/202023000005\">https://doi.org/10.1051/epjconf/202023000005</a>","short":"F. Lombardi, J.W.J.L. Wang, X. Zhang, P.C. Ivanov, EPJ Web of Conferences 230 (2020).","ieee":"F. Lombardi, J. W. J. L. Wang, X. Zhang, and P. C. Ivanov, “Power-law correlations and coupling of active and quiet states underlie a class of complex systems with self-organization at criticality,” <i>EPJ Web of Conferences</i>, vol. 230. EDP Sciences, 2020."},"has_accepted_license":"1","status":"public","file_date_updated":"2020-07-22T06:17:11Z","publication_identifier":{"issn":["2100-014X"]}},{"file":[{"success":1,"file_name":"Thesis_RokGrah_200727_convertedNew.pdf","access_level":"open_access","file_size":16638998,"date_updated":"2020-07-27T12:00:07Z","date_created":"2020-07-27T12:00:07Z","file_id":"8176","content_type":"application/pdf","creator":"rgrah","relation":"main_file"},{"date_updated":"2020-07-30T13:04:55Z","file_size":347459978,"access_level":"closed","file_name":"Thesis_new.zip","creator":"rgrah","relation":"main_file","content_type":"application/zip","date_created":"2020-07-27T12:02:23Z","file_id":"8177"}],"oa":1,"month":"07","date_updated":"2023-09-07T13:13:27Z","doi":"10.15479/AT:ISTA:8155","publisher":"Institute of Science and Technology Austria","article_processing_charge":"No","oa_version":"Published Version","type":"dissertation","project":[{"name":"Biophysically realistic genotype-phenotype maps for regulatory networks","_id":"267C84F4-B435-11E9-9278-68D0E5697425"}],"date_published":"2020-07-24T00:00:00Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"supervisor":[{"last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"},{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik"}],"ddc":["530","570"],"year":"2020","language":[{"iso":"eng"}],"related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"7675"},{"relation":"part_of_dissertation","status":"public","id":"7569"},{"id":"7652","status":"public","relation":"part_of_dissertation"}]},"publication_status":"published","day":"24","degree_awarded":"PhD","date_created":"2020-07-23T09:51:28Z","page":"310","alternative_title":["ISTA Thesis"],"author":[{"last_name":"Grah","orcid":"0000-0003-2539-3560","first_name":"Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","full_name":"Grah, Rok"}],"acknowledgement":"For the duration of his PhD, Rok was a recipient of a DOC fellowship of the Austrian Academy of Sciences.","_id":"8155","title":"Gene regulation across scales – how biophysical constraints shape evolution","abstract":[{"lang":"eng","text":"In the thesis we focus on the interplay of the biophysics and evolution of gene regulation. We start by addressing how the type of prokaryotic gene regulation – activation and repression – affects spurious binding to DNA, also known as\r\ntranscriptional crosstalk. We propose that regulatory interference caused by excess regulatory proteins in the dense cellular medium – global crosstalk – could be a factor in determining which type of gene regulatory network is evolutionarily preferred. Next,we use a normative approach in eukaryotic gene regulation to describe minimal\r\nnon-equilibrium enhancer models that optimize so-called regulatory phenotypes. We find a class of models that differ from standard thermodynamic equilibrium models by a single parameter that notably increases the regulatory performance. Next chapter addresses the question of genotype-phenotype-fitness maps of higher dimensional phenotypes. We show that our biophysically realistic approach allows us to understand how the mechanisms of promoter function constrain genotypephenotype maps, and how they affect the evolutionary trajectories of promoters.\r\nIn the last chapter we ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using mathematical modeling, we show that amplifications can tune gene expression in many environments, including those where transcription factor-based schemes are\r\nhard to evolve or maintain. "}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","has_accepted_license":"1","citation":{"short":"R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape Evolution, Institute of Science and Technology Austria, 2020.","ieee":"R. Grah, “Gene regulation across scales – how biophysical constraints shape evolution,” Institute of Science and Technology Austria, 2020.","ista":"Grah R. 2020. Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria.","apa":"Grah, R. (2020). <i>Gene regulation across scales – how biophysical constraints shape evolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8155\">https://doi.org/10.15479/AT:ISTA:8155</a>","chicago":"Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints Shape Evolution.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8155\">https://doi.org/10.15479/AT:ISTA:8155</a>.","ama":"Grah R. Gene regulation across scales – how biophysical constraints shape evolution. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8155\">10.15479/AT:ISTA:8155</a>","mla":"Grah, Rok. <i>Gene Regulation across Scales – How Biophysical Constraints Shape Evolution</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8155\">10.15479/AT:ISTA:8155</a>."},"status":"public","file_date_updated":"2020-07-30T13:04:55Z","publication_identifier":{"issn":["2663-337X"]}},{"department":[{"_id":"GaTk"}],"related_material":{"record":[{"id":"7569","status":"public","relation":"used_in_publication"}]},"year":"2020","day":"25","date_created":"2021-08-06T07:15:04Z","author":[{"last_name":"Grah","orcid":"0000-0003-2539-3560","first_name":"Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","full_name":"Grah, Rok"},{"first_name":"Tamar","full_name":"Friedlander, Tamar","last_name":"Friedlander"}],"month":"02","date_updated":"2023-08-18T06:47:47Z","doi":"10.1371/journal.pcbi.1007642.s001","title":"Supporting information","publisher":"Public Library of Science","_id":"9776","article_processing_charge":"No","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","citation":{"mla":"Grah, Rok, and Tamar Friedlander. <i>Supporting Information</i>. Public Library of Science, 2020, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s001\">10.1371/journal.pcbi.1007642.s001</a>.","ama":"Grah R, Friedlander T. Supporting information. 2020. doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s001\">10.1371/journal.pcbi.1007642.s001</a>","chicago":"Grah, Rok, and Tamar Friedlander. “Supporting Information.” Public Library of Science, 2020. <a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s001\">https://doi.org/10.1371/journal.pcbi.1007642.s001</a>.","apa":"Grah, R., &#38; Friedlander, T. (2020). Supporting information. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s001\">https://doi.org/10.1371/journal.pcbi.1007642.s001</a>","ista":"Grah R, Friedlander T. 2020. Supporting information, Public Library of Science, <a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s001\">10.1371/journal.pcbi.1007642.s001</a>.","ieee":"R. Grah and T. Friedlander, “Supporting information.” Public Library of Science, 2020.","short":"R. Grah, T. Friedlander, (2020)."},"oa_version":"Published Version","status":"public","type":"research_data_reference","date_published":"2020-02-25T00:00:00Z"},{"oa":1,"month":"02","doi":"10.1371/journal.pcbi.1007642.s002","title":"Maximizing crosstalk","publisher":"Public Library of Science","date_updated":"2023-09-12T11:02:25Z","_id":"9777","article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Grah, Rok, and Tamar Friedlander. <i>Maximizing Crosstalk</i>. Public Library of Science, 2020, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s002\">10.1371/journal.pcbi.1007642.s002</a>.","ama":"Grah R, Friedlander T. Maximizing crosstalk. 2020. doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s002\">10.1371/journal.pcbi.1007642.s002</a>","chicago":"Grah, Rok, and Tamar Friedlander. “Maximizing Crosstalk.” Public Library of Science, 2020. <a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s002\">https://doi.org/10.1371/journal.pcbi.1007642.s002</a>.","apa":"Grah, R., &#38; Friedlander, T. (2020). Maximizing crosstalk. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s002\">https://doi.org/10.1371/journal.pcbi.1007642.s002</a>","ista":"Grah R, Friedlander T. 2020. Maximizing crosstalk, Public Library of Science, <a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s002\">10.1371/journal.pcbi.1007642.s002</a>.","ieee":"R. Grah and T. Friedlander, “Maximizing crosstalk.” Public Library of Science, 2020.","short":"R. Grah, T. Friedlander, (2020)."},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1371/journal.pcbi.1007642.s002"}],"oa_version":"None","status":"public","type":"research_data_reference","date_published":"2020-02-25T00:00:00Z","department":[{"_id":"GaTk"}],"related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"7569"}]},"year":"2020","day":"25","date_created":"2021-08-06T07:21:51Z","author":[{"last_name":"Grah","orcid":"0000-0003-2539-3560","full_name":"Grah, Rok","first_name":"Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Tamar","full_name":"Friedlander, Tamar","last_name":"Friedlander"}]},{"oa_version":"Published Version","citation":{"chicago":"Grah, Rok, and Tamar Friedlander. “Distribution of Crosstalk Values.” Public Library of Science, 2020. <a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s003\">https://doi.org/10.1371/journal.pcbi.1007642.s003</a>.","mla":"Grah, Rok, and Tamar Friedlander. <i>Distribution of Crosstalk Values</i>. Public Library of Science, 2020, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s003\">10.1371/journal.pcbi.1007642.s003</a>.","ama":"Grah R, Friedlander T. Distribution of crosstalk values. 2020. doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s003\">10.1371/journal.pcbi.1007642.s003</a>","ieee":"R. Grah and T. Friedlander, “Distribution of crosstalk values.” Public Library of Science, 2020.","short":"R. Grah, T. Friedlander, (2020).","apa":"Grah, R., &#38; Friedlander, T. (2020). Distribution of crosstalk values. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s003\">https://doi.org/10.1371/journal.pcbi.1007642.s003</a>","ista":"Grah R, Friedlander T. 2020. Distribution of crosstalk values, Public Library of Science, <a href=\"https://doi.org/10.1371/journal.pcbi.1007642.s003\">10.1371/journal.pcbi.1007642.s003</a>."},"type":"research_data_reference","date_published":"2020-02-25T00:00:00Z","status":"public","month":"02","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","article_processing_charge":"No","publisher":"Public Library of Science","title":"Distribution of crosstalk values","doi":"10.1371/journal.pcbi.1007642.s003","date_updated":"2023-08-18T06:47:47Z","_id":"9779","date_created":"2021-08-06T07:24:37Z","day":"25","author":[{"orcid":"0000-0003-2539-3560","last_name":"Grah","first_name":"Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","full_name":"Grah, Rok"},{"last_name":"Friedlander","full_name":"Friedlander, Tamar","first_name":"Tamar"}],"department":[{"_id":"GaTk"}],"related_material":{"record":[{"relation":"research_data","status":"public","id":"7569"}]},"year":"2020"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"department":[{"_id":"GaTk"}],"ddc":["570","000"],"year":"2019","language":[{"iso":"eng"}],"day":"01","publication_status":"published","date_created":"2019-11-25T08:20:47Z","author":[{"last_name":"Wang","first_name":"Jilin W. J. L.","full_name":"Wang, Jilin W. J. L."},{"orcid":"0000-0003-2623-5249","last_name":"Lombardi","id":"A057D288-3E88-11E9-986D-0CF4E5697425","first_name":"Fabrizio","full_name":"Lombardi, Fabrizio"},{"last_name":"Zhang","full_name":"Zhang, Xiyun","first_name":"Xiyun"},{"last_name":"Anaclet","first_name":"Christelle","full_name":"Anaclet, Christelle"},{"full_name":"Ivanov, Plamen Ch.","first_name":"Plamen Ch.","last_name":"Ivanov"}],"oa":1,"file":[{"file_size":3982516,"date_updated":"2020-07-14T12:47:49Z","checksum":"2a096a9c6dcc6eaa94077b2603bc6c12","access_level":"open_access","file_name":"2019_PLOSComBio_Wang.pdf","creator":"dernst","relation":"main_file","date_created":"2019-11-25T08:24:01Z","file_id":"7104","content_type":"application/pdf"}],"quality_controlled":"1","article_number":"e1007268","month":"11","date_updated":"2023-10-17T12:30:07Z","doi":"10.1371/journal.pcbi.1007268","publisher":"Public Library of Science","publication":"PLoS Computational Biology","article_processing_charge":"No","article_type":"original","oa_version":"Published Version","external_id":{"isi":["000500976100014"],"pmid":["31725712"]},"type":"journal_article","project":[{"grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships"}],"date_published":"2019-11-01T00:00:00Z","volume":15,"file_date_updated":"2020-07-14T12:47:49Z","scopus_import":"1","isi":1,"publication_identifier":{"issn":["1553-7358"]},"issue":"11","pmid":1,"title":"Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture","_id":"7103","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"Origin and functions of intermittent transitions among sleep stages, including short awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing the sleep-wake cycle results from an underlying non-equilibrium critical dynamics, bridging collective behaviors across spatio-temporal scales. We investigate θ and δ wave dynamics in control rats and in rats with lesions of sleep-promoting neurons in the parafacial zone. We demonstrate that intermittent bursts in θ and δ rhythms exhibit a complex temporal organization, with long-range power-law correlations and a robust duality of power law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, typical features of non-equilibrium systems self-organizing at criticality. Crucially, such temporal organization relates to anti-correlated coupling between θ- and δ-bursts, and is independent of the dominant physiologic state and lesions, a solid indication of a basic principle in sleep dynamics."}],"citation":{"mla":"Wang, Jilin W. J. L., et al. “Non-Equilibrium Critical Dynamics of Bursts in θ and δ Rhythms as Fundamental Characteristic of Sleep and Wake Micro-Architecture.” <i>PLoS Computational Biology</i>, vol. 15, no. 11, e1007268, Public Library of Science, 2019, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007268\">10.1371/journal.pcbi.1007268</a>.","ama":"Wang JWJL, Lombardi F, Zhang X, Anaclet C, Ivanov PC. Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture. <i>PLoS Computational Biology</i>. 2019;15(11). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007268\">10.1371/journal.pcbi.1007268</a>","chicago":"Wang, Jilin W. J. L., Fabrizio Lombardi, Xiyun Zhang, Christelle Anaclet, and Plamen Ch. Ivanov. “Non-Equilibrium Critical Dynamics of Bursts in θ and δ Rhythms as Fundamental Characteristic of Sleep and Wake Micro-Architecture.” <i>PLoS Computational Biology</i>. Public Library of Science, 2019. <a href=\"https://doi.org/10.1371/journal.pcbi.1007268\">https://doi.org/10.1371/journal.pcbi.1007268</a>.","apa":"Wang, J. W. J. L., Lombardi, F., Zhang, X., Anaclet, C., &#38; Ivanov, P. C. (2019). Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture. <i>PLoS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007268\">https://doi.org/10.1371/journal.pcbi.1007268</a>","ista":"Wang JWJL, Lombardi F, Zhang X, Anaclet C, Ivanov PC. 2019. Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture. PLoS Computational Biology. 15(11), e1007268.","ieee":"J. W. J. L. Wang, F. Lombardi, X. Zhang, C. Anaclet, and P. C. Ivanov, “Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture,” <i>PLoS Computational Biology</i>, vol. 15, no. 11. Public Library of Science, 2019.","short":"J.W.J.L. Wang, F. Lombardi, X. Zhang, C. Anaclet, P.C. Ivanov, PLoS Computational Biology 15 (2019)."},"intvolume":"        15","has_accepted_license":"1","status":"public","ec_funded":1},{"oa_version":"Preprint","article_type":"original","external_id":{"arxiv":["1708.09364"],"isi":["000458109300009"]},"date_published":"2019-02-07T00:00:00Z","type":"journal_article","volume":150,"oa":1,"quality_controlled":"1","article_number":"054108","month":"02","doi":"10.1063/1.5064867","publisher":"AIP Publishing","date_updated":"2023-09-06T14:59:28Z","publication":"The Journal of Chemical Physics","article_processing_charge":"No","day":"07","publication_status":"published","date_created":"2020-01-30T10:34:36Z","arxiv":1,"author":[{"last_name":"Sokolowski","orcid":"0000-0002-1287-3779","full_name":"Sokolowski, Thomas R","id":"3E999752-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas R"},{"full_name":"Paijmans, Joris","first_name":"Joris","last_name":"Paijmans"},{"last_name":"Bossen","first_name":"Laurens","full_name":"Bossen, Laurens"},{"first_name":"Thomas","full_name":"Miedema, Thomas","last_name":"Miedema"},{"full_name":"Wehrens, Martijn","first_name":"Martijn","last_name":"Wehrens"},{"first_name":"Nils B.","full_name":"Becker, Nils B.","last_name":"Becker"},{"full_name":"Kaizu, Kazunari","first_name":"Kazunari","last_name":"Kaizu"},{"full_name":"Takahashi, Koichi","first_name":"Koichi","last_name":"Takahashi"},{"first_name":"Marileen","full_name":"Dogterom, Marileen","last_name":"Dogterom"},{"last_name":"ten Wolde","first_name":"Pieter Rein","full_name":"ten Wolde, Pieter Rein"}],"department":[{"_id":"GaTk"}],"year":"2019","language":[{"iso":"eng"}],"citation":{"ieee":"T. R. Sokolowski <i>et al.</i>, “eGFRD in all dimensions,” <i>The Journal of Chemical Physics</i>, vol. 150, no. 5. AIP Publishing, 2019.","short":"T.R. Sokolowski, J. Paijmans, L. Bossen, T. Miedema, M. Wehrens, N.B. Becker, K. Kaizu, K. Takahashi, M. Dogterom, P.R. ten Wolde, The Journal of Chemical Physics 150 (2019).","ista":"Sokolowski TR, Paijmans J, Bossen L, Miedema T, Wehrens M, Becker NB, Kaizu K, Takahashi K, Dogterom M, ten Wolde PR. 2019. eGFRD in all dimensions. The Journal of Chemical Physics. 150(5), 054108.","apa":"Sokolowski, T. R., Paijmans, J., Bossen, L., Miedema, T., Wehrens, M., Becker, N. B., … ten Wolde, P. R. (2019). eGFRD in all dimensions. <i>The Journal of Chemical Physics</i>. AIP Publishing. <a href=\"https://doi.org/10.1063/1.5064867\">https://doi.org/10.1063/1.5064867</a>","chicago":"Sokolowski, Thomas R, Joris Paijmans, Laurens Bossen, Thomas Miedema, Martijn Wehrens, Nils B. Becker, Kazunari Kaizu, Koichi Takahashi, Marileen Dogterom, and Pieter Rein ten Wolde. “EGFRD in All Dimensions.” <i>The Journal of Chemical Physics</i>. AIP Publishing, 2019. <a href=\"https://doi.org/10.1063/1.5064867\">https://doi.org/10.1063/1.5064867</a>.","ama":"Sokolowski TR, Paijmans J, Bossen L, et al. eGFRD in all dimensions. <i>The Journal of Chemical Physics</i>. 2019;150(5). doi:<a href=\"https://doi.org/10.1063/1.5064867\">10.1063/1.5064867</a>","mla":"Sokolowski, Thomas R., et al. “EGFRD in All Dimensions.” <i>The Journal of Chemical Physics</i>, vol. 150, no. 5, 054108, AIP Publishing, 2019, doi:<a href=\"https://doi.org/10.1063/1.5064867\">10.1063/1.5064867</a>."},"intvolume":"       150","main_file_link":[{"url":"https://arxiv.org/abs/1708.09364","open_access":"1"}],"status":"public","title":"eGFRD in all dimensions","_id":"7422","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","abstract":[{"text":"Biochemical reactions often occur at low copy numbers but at once in crowded and diverse environments. Space and stochasticity therefore play an essential role in biochemical networks. Spatial-stochastic simulations have become a prominent tool for understanding how stochasticity at the microscopic level influences the macroscopic behavior of such systems. While particle-based models guarantee the level of detail necessary to accurately describe the microscopic dynamics at very low copy numbers, the algorithms used to simulate them typically imply trade-offs between computational efficiency and biochemical accuracy. eGFRD (enhanced Green’s Function Reaction Dynamics) is an exact algorithm that evades such trade-offs by partitioning the N-particle system into M ≤ N analytically tractable one- and two-particle systems; the analytical solutions (Green’s functions) then are used to implement an event-driven particle-based scheme that allows particles to make large jumps in time and space while retaining access to their state variables at arbitrary simulation times. Here we present “eGFRD2,” a new eGFRD version that implements the principle of eGFRD in all dimensions, thus enabling efficient particle-based simulation of biochemical reaction-diffusion processes in the 3D cytoplasm, on 2D planes representing membranes, and on 1D elongated cylinders representative of, e.g., cytoskeletal tracks or DNA; in 1D, it also incorporates convective motion used to model active transport. We find that, for low particle densities, eGFRD2 is up to 6 orders of magnitude faster than conventional Brownian dynamics. We exemplify the capabilities of eGFRD2 by simulating an idealized model of Pom1 gradient formation, which involves 3D diffusion, active transport on microtubules, and autophosphorylation on the membrane, confirming recent experimental and theoretical results on this system to hold under genuinely stochastic conditions.","lang":"eng"}],"publication_identifier":{"eissn":["1089-7690"],"issn":["0021-9606"]},"issue":"5","isi":1},{"author":[{"full_name":"Bialek, William","first_name":"William","last_name":"Bialek"},{"first_name":"Thomas","full_name":"Gregor, Thomas","last_name":"Gregor"},{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455"}],"page":"5","date_created":"2020-02-28T10:57:08Z","arxiv":1,"day":"18","publication_status":"submitted","language":[{"iso":"eng"}],"year":"2019","department":[{"_id":"GaTk"}],"date_published":"2019-12-18T00:00:00Z","type":"preprint","project":[{"_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","call_identifier":"FWF","name":"Biophysics of information processing in gene regulation"}],"status":"public","oa_version":"Preprint","external_id":{"arxiv":["1912.08579"]},"citation":{"short":"W. Bialek, T. Gregor, G. Tkačik, ArXiv:1912.08579 (n.d.).","ieee":"W. Bialek, T. Gregor, and G. Tkačik, “Action at a distance in transcriptional regulation,” <i>arXiv:1912.08579</i>. ArXiv.","apa":"Bialek, W., Gregor, T., &#38; Tkačik, G. (n.d.). Action at a distance in transcriptional regulation. <i>arXiv:1912.08579</i>. ArXiv.","ista":"Bialek W, Gregor T, Tkačik G. Action at a distance in transcriptional regulation. arXiv:1912.08579, .","chicago":"Bialek, William, Thomas Gregor, and Gašper Tkačik. “Action at a Distance in Transcriptional Regulation.” <i>ArXiv:1912.08579</i>. ArXiv, n.d.","mla":"Bialek, William, et al. “Action at a Distance in Transcriptional Regulation.” <i>ArXiv:1912.08579</i>, ArXiv.","ama":"Bialek W, Gregor T, Tkačik G. Action at a distance in transcriptional regulation. <i>arXiv:191208579</i>."},"main_file_link":[{"url":"https://arxiv.org/abs/1912.08579","open_access":"1"}],"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"There is increasing evidence that protein binding to specific sites along DNA can activate the reading out of genetic information without coming into direct physical contact with the gene. There also is evidence that these distant but interacting sites are embedded in a liquid droplet of proteins which condenses out of the surrounding solution. We argue that droplet-mediated interactions can account for crucial features of gene regulation only if the droplet is poised at a non-generic point in its phase diagram. We explore a minimal model that embodies this idea, show that this model has a natural mechanism for self-tuning, and suggest direct experimental tests. "}],"title":"Action at a distance in transcriptional regulation","publisher":"ArXiv","date_updated":"2021-01-12T08:14:09Z","_id":"7552","publication":"arXiv:1912.08579","month":"12","oa":1},{"isi":1,"scopus_import":"1","publication_identifier":{"isbn":["9781538669006"]},"abstract":[{"text":"We derive a tight lower bound on equivocation (conditional entropy), or equivalently a tight upper bound on mutual information between a signal variable and channel outputs. The bound is in terms of the joint distribution of the signals and maximum a posteriori decodes (most probable signals given channel output). As part of our derivation, we describe the key properties of the distribution of signals, channel outputs and decodes, that minimizes equivocation and maximizes mutual information. This work addresses a problem in data analysis, where mutual information between signals and decodes is sometimes used to lower bound the mutual information between signals and channel outputs. Our result provides a corresponding upper bound.","lang":"eng"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"7606","title":"A tight upper bound on mutual information","ec_funded":1,"status":"public","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1812.01475"}],"citation":{"ama":"Hledik M, Sokolowski TR, Tkačik G. A tight upper bound on mutual information. In: <i>IEEE Information Theory Workshop, ITW 2019</i>. IEEE; 2019. doi:<a href=\"https://doi.org/10.1109/ITW44776.2019.8989292\">10.1109/ITW44776.2019.8989292</a>","mla":"Hledik, Michal, et al. “A Tight Upper Bound on Mutual Information.” <i>IEEE Information Theory Workshop, ITW 2019</i>, 8989292, IEEE, 2019, doi:<a href=\"https://doi.org/10.1109/ITW44776.2019.8989292\">10.1109/ITW44776.2019.8989292</a>.","chicago":"Hledik, Michal, Thomas R Sokolowski, and Gašper Tkačik. “A Tight Upper Bound on Mutual Information.” In <i>IEEE Information Theory Workshop, ITW 2019</i>. IEEE, 2019. <a href=\"https://doi.org/10.1109/ITW44776.2019.8989292\">https://doi.org/10.1109/ITW44776.2019.8989292</a>.","ista":"Hledik M, Sokolowski TR, Tkačik G. 2019. A tight upper bound on mutual information. IEEE Information Theory Workshop, ITW 2019. Information Theory Workshop, 8989292.","apa":"Hledik, M., Sokolowski, T. R., &#38; Tkačik, G. (2019). A tight upper bound on mutual information. In <i>IEEE Information Theory Workshop, ITW 2019</i>. Visby, Sweden: IEEE. <a href=\"https://doi.org/10.1109/ITW44776.2019.8989292\">https://doi.org/10.1109/ITW44776.2019.8989292</a>","ieee":"M. Hledik, T. R. Sokolowski, and G. Tkačik, “A tight upper bound on mutual information,” in <i>IEEE Information Theory Workshop, ITW 2019</i>, Visby, Sweden, 2019.","short":"M. Hledik, T.R. Sokolowski, G. Tkačik, in:, IEEE Information Theory Workshop, ITW 2019, IEEE, 2019."},"year":"2019","language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"15020"}]},"department":[{"_id":"GaTk"}],"author":[{"full_name":"Hledik, Michal","id":"4171253A-F248-11E8-B48F-1D18A9856A87","first_name":"Michal","last_name":"Hledik"},{"orcid":"0000-0002-1287-3779","last_name":"Sokolowski","first_name":"Thomas R","id":"3E999752-F248-11E8-B48F-1D18A9856A87","full_name":"Sokolowski, Thomas R"},{"orcid":"0000-0002-6699-1455","last_name":"Tkačik","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"}],"conference":{"start_date":"2019-08-25","name":"Information Theory Workshop","location":"Visby, Sweden","end_date":"2019-08-28"},"arxiv":1,"date_created":"2020-03-22T23:00:47Z","publication_status":"published","day":"01","article_processing_charge":"No","publication":"IEEE Information Theory Workshop, ITW 2019","doi":"10.1109/ITW44776.2019.8989292","date_updated":"2025-06-30T13:21:05Z","publisher":"IEEE","month":"08","article_number":"8989292","oa":1,"quality_controlled":"1","project":[{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","call_identifier":"H2020"}],"type":"conference","date_published":"2019-08-01T00:00:00Z","external_id":{"arxiv":["1812.01475"],"isi":["000540384500015"]},"oa_version":"Preprint"},{"citation":{"apa":"Lang, M., &#38; Shkolnikov, M. (2019). Harmonic dynamics of the Abelian sandpile. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.1812015116\">https://doi.org/10.1073/pnas.1812015116</a>","ista":"Lang M, Shkolnikov M. 2019. Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. 116(8), 2821–2830.","ieee":"M. Lang and M. Shkolnikov, “Harmonic dynamics of the Abelian sandpile,” <i>Proceedings of the National Academy of Sciences</i>, vol. 116, no. 8. National Academy of Sciences, pp. 2821–2830, 2019.","short":"M. Lang, M. Shkolnikov, Proceedings of the National Academy of Sciences 116 (2019) 2821–2830.","mla":"Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” <i>Proceedings of the National Academy of Sciences</i>, vol. 116, no. 8, National Academy of Sciences, 2019, pp. 2821–30, doi:<a href=\"https://doi.org/10.1073/pnas.1812015116\">10.1073/pnas.1812015116</a>.","ama":"Lang M, Shkolnikov M. Harmonic dynamics of the Abelian sandpile. <i>Proceedings of the National Academy of Sciences</i>. 2019;116(8):2821-2830. doi:<a href=\"https://doi.org/10.1073/pnas.1812015116\">10.1073/pnas.1812015116</a>","chicago":"Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2019. <a href=\"https://doi.org/10.1073/pnas.1812015116\">https://doi.org/10.1073/pnas.1812015116</a>."},"intvolume":"       116","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1073/pnas.1812015116"}],"status":"public","acknowledgement":"M.L. is grateful to the members of the C Guet and G Tkacik groups for valuable comments and support. M.S. is grateful to Nikita Kalinin for inspiring communications.\r\n","pmid":1,"title":"Harmonic dynamics of the Abelian sandpile","_id":"196","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","abstract":[{"text":"The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. ","lang":"eng"}],"publication_identifier":{"eissn":["1091-6490"]},"issue":"8","scopus_import":"1","isi":1,"article_type":"original","oa_version":"Published Version","external_id":{"pmid":[" 30728300"],"arxiv":["1806.10823"],"isi":["000459074400013"]},"type":"journal_article","date_published":"2019-02-19T00:00:00Z","volume":116,"oa":1,"quality_controlled":"1","month":"02","doi":"10.1073/pnas.1812015116","date_updated":"2023-09-11T14:09:34Z","publisher":"National Academy of Sciences","publication":"Proceedings of the National Academy of Sciences","article_processing_charge":"No","day":"19","publication_status":"published","date_created":"2018-12-11T11:45:08Z","arxiv":1,"page":"2821-2830","author":[{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz","full_name":"Lang, Moritz","last_name":"Lang"},{"first_name":"Mikhail","id":"35084A62-F248-11E8-B48F-1D18A9856A87","full_name":"Shkolnikov, Mikhail","orcid":"0000-0002-4310-178X","last_name":"Shkolnikov"}],"department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"TaHa"}],"related_material":{"link":[{"url":"https://ist.ac.at/en/news/famous-sandpile-model-shown-to-move-like-a-traveling-sand-dune/","relation":"press_release","description":"News on IST Webpage"}]},"language":[{"iso":"eng"}],"year":"2019"},{"has_accepted_license":"1","intvolume":"        15","citation":{"short":"B. Kavcic, A. Sakashita, H. Noguchi, P. Ziherl, Soft Matter 15 (2019) 602–614.","ieee":"B. Kavcic, A. Sakashita, H. Noguchi, and P. Ziherl, “Limiting shapes of confined lipid vesicles,” <i>Soft Matter</i>, vol. 15, no. 4. Royal Society of Chemistry, pp. 602–614, 2019.","ista":"Kavcic B, Sakashita A, Noguchi H, Ziherl P. 2019. Limiting shapes of confined lipid vesicles. Soft Matter. 15(4), 602–614.","apa":"Kavcic, B., Sakashita, A., Noguchi, H., &#38; Ziherl, P. (2019). Limiting shapes of confined lipid vesicles. <i>Soft Matter</i>. Royal Society of Chemistry. <a href=\"https://doi.org/10.1039/c8sm01956h\">https://doi.org/10.1039/c8sm01956h</a>","chicago":"Kavcic, Bor, A. Sakashita, H. Noguchi, and P. Ziherl. “Limiting Shapes of Confined Lipid Vesicles.” <i>Soft Matter</i>. Royal Society of Chemistry, 2019. <a href=\"https://doi.org/10.1039/c8sm01956h\">https://doi.org/10.1039/c8sm01956h</a>.","ama":"Kavcic B, Sakashita A, Noguchi H, Ziherl P. Limiting shapes of confined lipid vesicles. <i>Soft Matter</i>. 2019;15(4):602-614. doi:<a href=\"https://doi.org/10.1039/c8sm01956h\">10.1039/c8sm01956h</a>","mla":"Kavcic, Bor, et al. “Limiting Shapes of Confined Lipid Vesicles.” <i>Soft Matter</i>, vol. 15, no. 4, Royal Society of Chemistry, 2019, pp. 602–14, doi:<a href=\"https://doi.org/10.1039/c8sm01956h\">10.1039/c8sm01956h</a>."},"status":"public","pmid":1,"_id":"5817","title":"Limiting shapes of confined lipid vesicles","abstract":[{"text":"We theoretically study the shapes of lipid vesicles confined to a spherical cavity, elaborating a framework based on the so-called limiting shapes constructed from geometrically simple structural elements such as double-membrane walls and edges. Partly inspired by numerical results, the proposed non-compartmentalized and compartmentalized limiting shapes are arranged in the bilayer-couple phase diagram which is then compared to its free-vesicle counterpart. We also compute the area-difference-elasticity phase diagram of the limiting shapes and we use it to interpret shape transitions experimentally observed in vesicles confined within another vesicle. The limiting-shape framework may be generalized to theoretically investigate the structure of certain cell organelles such as the mitochondrion.","lang":"eng"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publication_identifier":{"issn":["1744-683X"],"eissn":["1744-6848"]},"issue":"4","file_date_updated":"2020-10-09T11:00:05Z","isi":1,"scopus_import":"1","oa_version":"Submitted Version","external_id":{"pmid":["30629082"],"isi":["000457329700003"]},"article_type":"original","volume":15,"date_published":"2019-01-10T00:00:00Z","type":"journal_article","oa":1,"file":[{"creator":"bkavcic","relation":"main_file","file_id":"8641","date_created":"2020-10-09T11:00:05Z","content_type":"application/pdf","file_size":5370762,"date_updated":"2020-10-09T11:00:05Z","checksum":"614c337d6424ccd3d48d1b1f9513510d","access_level":"open_access","file_name":"lmt_sftmtr_V8.pdf","success":1}],"quality_controlled":"1","month":"01","publication":"Soft Matter","date_updated":"2023-09-13T08:47:16Z","doi":"10.1039/c8sm01956h","publisher":"Royal Society of Chemistry","article_processing_charge":"No","publication_status":"published","day":"10","license":"https://creativecommons.org/licenses/by-nc-nd/3.0/","date_created":"2019-01-11T07:37:47Z","page":"602-614","author":[{"last_name":"Kavcic","orcid":"0000-0001-6041-254X","full_name":"Kavcic, Bor","first_name":"Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sakashita","first_name":"A.","full_name":"Sakashita, A."},{"full_name":"Noguchi, H.","first_name":"H.","last_name":"Noguchi"},{"full_name":"Ziherl, P.","first_name":"P.","last_name":"Ziherl"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0)","short":"CC BY-NC-ND (3.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/3.0/legalcode"},"department":[{"_id":"GaTk"}],"ddc":["530"],"year":"2019","language":[{"iso":"eng"}]},{"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","abstract":[{"text":"In developing organisms, spatially prescribed cell identities are thought to be determined by the expression levels of multiple genes. Quantitative tests of this idea, however, require a theoretical framework capable of exposing the rules and precision of cell specification over developmental time. We use the gap gene network in the early fly embryo as an example to show how expression levels of the four gap genes can be jointly decoded into an optimal specification of position with 1% accuracy. The decoder correctly predicts, with no free parameters, the dynamics of pair-rule expression patterns at different developmental time points and in various mutant backgrounds. Precise cellular identities are thus available at the earliest stages of development, contrasting the prevailing view of positional information being slowly refined across successive layers of the patterning network. Our results suggest that developmental enhancers closely approximate a mathematically optimal decoding strategy.","lang":"eng"}],"title":"Optimal decoding of cellular identities in a genetic network","_id":"5945","pmid":1,"status":"public","citation":{"ieee":"M. D. Petkova, G. Tkačik, W. Bialek, E. F. Wieschaus, and T. Gregor, “Optimal decoding of cellular identities in a genetic network,” <i>Cell</i>, vol. 176, no. 4. Cell Press, p. 844–855.e15, 2019.","short":"M.D. Petkova, G. Tkačik, W. Bialek, E.F. Wieschaus, T. Gregor, Cell 176 (2019) 844–855.e15.","ista":"Petkova MD, Tkačik G, Bialek W, Wieschaus EF, Gregor T. 2019. Optimal decoding of cellular identities in a genetic network. Cell. 176(4), 844–855.e15.","apa":"Petkova, M. D., Tkačik, G., Bialek, W., Wieschaus, E. F., &#38; Gregor, T. (2019). Optimal decoding of cellular identities in a genetic network. <i>Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cell.2019.01.007\">https://doi.org/10.1016/j.cell.2019.01.007</a>","chicago":"Petkova, Mariela D., Gašper Tkačik, William Bialek, Eric F. Wieschaus, and Thomas Gregor. “Optimal Decoding of Cellular Identities in a Genetic Network.” <i>Cell</i>. Cell Press, 2019. <a href=\"https://doi.org/10.1016/j.cell.2019.01.007\">https://doi.org/10.1016/j.cell.2019.01.007</a>.","ama":"Petkova MD, Tkačik G, Bialek W, Wieschaus EF, Gregor T. Optimal decoding of cellular identities in a genetic network. <i>Cell</i>. 2019;176(4):844-855.e15. doi:<a href=\"https://doi.org/10.1016/j.cell.2019.01.007\">10.1016/j.cell.2019.01.007</a>","mla":"Petkova, Mariela D., et al. “Optimal Decoding of Cellular Identities in a Genetic Network.” <i>Cell</i>, vol. 176, no. 4, Cell Press, 2019, p. 844–855.e15, doi:<a href=\"https://doi.org/10.1016/j.cell.2019.01.007\">10.1016/j.cell.2019.01.007</a>."},"intvolume":"       176","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.cell.2019.01.007"}],"scopus_import":"1","isi":1,"issue":"4","article_processing_charge":"No","doi":"10.1016/j.cell.2019.01.007","publisher":"Cell Press","date_updated":"2023-08-24T14:42:47Z","publication":"Cell","month":"02","quality_controlled":"1","oa":1,"project":[{"grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425","name":"Biophysics of information processing in gene regulation","call_identifier":"FWF"}],"type":"journal_article","date_published":"2019-02-07T00:00:00Z","volume":176,"external_id":{"pmid":["30712870"],"isi":["000457969200015"]},"oa_version":"Published Version","article_type":"original","related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/cells-find-their-identity-using-a-mathematically-optimal-strategy/"}]},"language":[{"iso":"eng"}],"year":"2019","department":[{"_id":"GaTk"}],"author":[{"first_name":"Mariela D.","full_name":"Petkova, Mariela D.","last_name":"Petkova"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gasper","full_name":"Tkacik, Gasper","orcid":"0000-0002-6699-1455","last_name":"Tkacik"},{"first_name":"William","full_name":"Bialek, William","last_name":"Bialek"},{"last_name":"Wieschaus","first_name":"Eric F.","full_name":"Wieschaus, Eric F."},{"last_name":"Gregor","first_name":"Thomas","full_name":"Gregor, Thomas"}],"page":"844-855.e15","date_created":"2019-02-10T22:59:16Z","day":"07","publication_status":"published"},{"author":[{"last_name":"Mitosch","id":"39B66846-F248-11E8-B48F-1D18A9856A87","first_name":"Karin","full_name":"Mitosch, Karin"},{"last_name":"Rieckh","first_name":"Georg","id":"34DA8BD6-F248-11E8-B48F-1D18A9856A87","full_name":"Rieckh, Georg"},{"first_name":"Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","full_name":"Bollenbach, Mark Tobias","last_name":"Bollenbach","orcid":"0000-0003-4398-476X"}],"day":"14","publication_status":"published","date_created":"2019-02-24T22:59:18Z","acknowledged_ssus":[{"_id":"Bio"}],"year":"2019","language":[{"iso":"eng"}],"department":[{"_id":"GaTk"}],"date_published":"2019-02-14T00:00:00Z","project":[{"call_identifier":"FWF","name":"Revealing the mechanisms underlying drug interactions","grant_number":"P27201-B22","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425"},{"grant_number":"RGP0042/2013","_id":"25EB3A80-B435-11E9-9278-68D0E5697425","name":"Revealing the fundamental limits of cell growth"}],"type":"journal_article","volume":15,"external_id":{"pmid":["30765425"],"isi":["000459628300003"]},"oa_version":"Submitted Version","doi":"10.15252/msb.20188470","date_updated":"2023-08-24T14:49:53Z","publisher":"Embo Press","publication":"Molecular systems biology","article_processing_charge":"No","oa":1,"quality_controlled":"1","article_number":"e8470","month":"02","issue":"2","scopus_import":"1","isi":1,"status":"public","citation":{"short":"K. Mitosch, G. Rieckh, M.T. Bollenbach, Molecular Systems Biology 15 (2019).","ieee":"K. Mitosch, G. Rieckh, and M. T. Bollenbach, “Temporal order and precision of complex stress responses in individual bacteria,” <i>Molecular systems biology</i>, vol. 15, no. 2. Embo Press, 2019.","apa":"Mitosch, K., Rieckh, G., &#38; Bollenbach, M. T. (2019). Temporal order and precision of complex stress responses in individual bacteria. <i>Molecular Systems Biology</i>. Embo Press. <a href=\"https://doi.org/10.15252/msb.20188470\">https://doi.org/10.15252/msb.20188470</a>","ista":"Mitosch K, Rieckh G, Bollenbach MT. 2019. Temporal order and precision of complex stress responses in individual bacteria. Molecular systems biology. 15(2), e8470.","chicago":"Mitosch, Karin, Georg Rieckh, and Mark Tobias Bollenbach. “Temporal Order and Precision of Complex Stress Responses in Individual Bacteria.” <i>Molecular Systems Biology</i>. Embo Press, 2019. <a href=\"https://doi.org/10.15252/msb.20188470\">https://doi.org/10.15252/msb.20188470</a>.","mla":"Mitosch, Karin, et al. “Temporal Order and Precision of Complex Stress Responses in Individual Bacteria.” <i>Molecular Systems Biology</i>, vol. 15, no. 2, e8470, Embo Press, 2019, doi:<a href=\"https://doi.org/10.15252/msb.20188470\">10.15252/msb.20188470</a>.","ama":"Mitosch K, Rieckh G, Bollenbach MT. Temporal order and precision of complex stress responses in individual bacteria. <i>Molecular systems biology</i>. 2019;15(2). doi:<a href=\"https://doi.org/10.15252/msb.20188470\">10.15252/msb.20188470</a>"},"intvolume":"        15","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pubmed/30765425"}],"title":"Temporal order and precision of complex stress responses in individual bacteria","_id":"6046","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","abstract":[{"lang":"eng","text":"Sudden stress often triggers diverse, temporally structured gene expression responses in microbes, but it is largely unknown how variable in time such responses are and if genes respond in the same temporal order in every single cell. Here, we quantified timing variability of individual promoters responding to sublethal antibiotic stress using fluorescent reporters, microfluidics, and time‐lapse microscopy. We identified lower and upper bounds that put definite constraints on timing variability, which varies strongly among promoters and conditions. Timing variability can be interpreted using results from statistical kinetics, which enable us to estimate the number of rate‐limiting molecular steps underlying different responses. We found that just a few critical steps control some responses while others rely on dozens of steps. To probe connections between different stress responses, we then tracked the temporal order and response time correlations of promoter pairs in individual cells. Our results support that, when bacteria are exposed to the antibiotic nitrofurantoin, the ensuing oxidative stress and SOS responses are part of the same causal chain of molecular events. In contrast, under trimethoprim, the acid stress response and the SOS response are part of different chains of events running in parallel. Our approach reveals fundamental constraints on gene expression timing and provides new insights into the molecular events that underlie the timing of stress responses."}],"pmid":1},{"volume":52,"project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"type":"journal_article","date_published":"2019-01-07T00:00:00Z","oa_version":"Published Version","external_id":{"isi":["000455379500001"]},"article_processing_charge":"Yes (in subscription journal)","publication":"Journal of Physics A: Mathematical and Theoretical","doi":"10.1088/1751-8121/aaf2dd","publisher":"IOP Publishing","date_updated":"2023-08-24T14:49:23Z","month":"01","article_number":"045002","oa":1,"file":[{"date_updated":"2020-07-14T12:47:17Z","file_size":1804557,"file_name":"2019_IOP_DeMartino.pdf","access_level":"open_access","checksum":"1112304ad363a6d8afaeccece36473cf","relation":"main_file","creator":"kschuh","content_type":"application/pdf","date_created":"2019-04-19T12:18:57Z","file_id":"6344"}],"quality_controlled":"1","author":[{"id":"3FF5848A-F248-11E8-B48F-1D18A9856A87","first_name":"Daniele","full_name":"De Martino, Daniele","last_name":"De Martino","orcid":"0000-0002-5214-4706"}],"date_created":"2019-02-24T22:59:19Z","publication_status":"published","day":"07","language":[{"iso":"eng"}],"year":"2019","ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"department":[{"_id":"GaTk"}],"ec_funded":1,"status":"public","has_accepted_license":"1","citation":{"chicago":"De Martino, Daniele. “Feedback-Induced Self-Oscillations in Large Interacting Systems Subjected to Phase Transitions.” <i>Journal of Physics A: Mathematical and Theoretical</i>. IOP Publishing, 2019. <a href=\"https://doi.org/10.1088/1751-8121/aaf2dd\">https://doi.org/10.1088/1751-8121/aaf2dd</a>.","ama":"De Martino D. Feedback-induced self-oscillations in large interacting systems subjected to phase transitions. <i>Journal of Physics A: Mathematical and Theoretical</i>. 2019;52(4). doi:<a href=\"https://doi.org/10.1088/1751-8121/aaf2dd\">10.1088/1751-8121/aaf2dd</a>","mla":"De Martino, Daniele. “Feedback-Induced Self-Oscillations in Large Interacting Systems Subjected to Phase Transitions.” <i>Journal of Physics A: Mathematical and Theoretical</i>, vol. 52, no. 4, 045002, IOP Publishing, 2019, doi:<a href=\"https://doi.org/10.1088/1751-8121/aaf2dd\">10.1088/1751-8121/aaf2dd</a>.","short":"D. De Martino, Journal of Physics A: Mathematical and Theoretical 52 (2019).","ieee":"D. De Martino, “Feedback-induced self-oscillations in large interacting systems subjected to phase transitions,” <i>Journal of Physics A: Mathematical and Theoretical</i>, vol. 52, no. 4. IOP Publishing, 2019.","ista":"De Martino D. 2019. Feedback-induced self-oscillations in large interacting systems subjected to phase transitions. Journal of Physics A: Mathematical and Theoretical. 52(4), 045002.","apa":"De Martino, D. (2019). Feedback-induced self-oscillations in large interacting systems subjected to phase transitions. <i>Journal of Physics A: Mathematical and Theoretical</i>. IOP Publishing. <a href=\"https://doi.org/10.1088/1751-8121/aaf2dd\">https://doi.org/10.1088/1751-8121/aaf2dd</a>"},"intvolume":"        52","abstract":[{"text":"In this article it is shown that large systems with many interacting units endowing multiple phases display self-oscillations in the presence of linear feedback between the control and order parameters, where an Andronov–Hopf bifurcation takes over the phase transition. This is simply illustrated through the mean field Landau theory whose feedback dynamics turn out to be described by the Van der Pol equation and it is then validated for the fully connected Ising model following heat bath dynamics. Despite its simplicity, this theory accounts potentially for a rich range of phenomena: here it is applied to describe in a stylized way (i) excess demand-price cycles due to strong herding in a simple agent-based market model; (ii) congestion waves in queuing networks triggered by user feedback to delays in overloaded conditions; and (iii) metabolic network oscillations resulting from cell growth control in a bistable phenotypic landscape.","lang":"eng"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"6049","title":"Feedback-induced self-oscillations in large interacting systems subjected to phase transitions","issue":"4","isi":1,"scopus_import":"1","file_date_updated":"2020-07-14T12:47:17Z"},{"ddc":["576"],"year":"2019","language":[{"iso":"eng"}],"related_material":{"record":[{"id":"1358","status":"public","relation":"part_of_dissertation"},{"status":"public","relation":"part_of_dissertation","id":"955"}]},"supervisor":[{"orcid":"0000-0002-6699-1455","last_name":"Tkačik","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper"}],"department":[{"_id":"GaTk"},{"_id":"NiBa"}],"author":[{"full_name":"Prizak, Roshan","first_name":"Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87","last_name":"Prizak"}],"page":"189","alternative_title":["ISTA Thesis"],"degree_awarded":"PhD","date_created":"2019-03-06T16:16:10Z","publication_status":"published","day":"11","article_processing_charge":"No","doi":"10.15479/at:ista:th6071","publisher":"Institute of Science and Technology Austria","date_updated":"2025-05-28T11:57:05Z","month":"03","oa":1,"file":[{"checksum":"e60a72de35d270b31f1a23d50f224ec0","file_name":"Thesis_final_PDFA_RoshanPrizak.pdf","access_level":"open_access","file_size":20995465,"date_updated":"2020-07-14T12:47:18Z","date_created":"2019-03-06T16:05:07Z","file_id":"6072","content_type":"application/pdf","relation":"main_file","creator":"rprizak"},{"relation":"source_file","creator":"rprizak","date_created":"2019-03-06T16:09:39Z","file_id":"6073","content_type":"application/zip","file_size":85705272,"title":"Latex files","date_updated":"2020-07-14T12:47:18Z","checksum":"67c2630333d05ebafef5f018863a8465","file_name":"thesis_v2_merge.zip","access_level":"closed"}],"type":"dissertation","date_published":"2019-03-11T00:00:00Z","project":[{"name":"Biophysics of information processing in gene regulation","call_identifier":"FWF","grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425"}],"oa_version":"Published Version","file_date_updated":"2020-07-14T12:47:18Z","publication_identifier":{"issn":["2663-337X"]},"abstract":[{"lang":"eng","text":"Transcription factors, by binding to specific sequences on the DNA, control the precise spatio-temporal expression of genes inside a cell. However, this specificity is limited, leading to frequent incorrect binding of transcription factors that might have deleterious consequences on the cell. By constructing a biophysical model of TF-DNA binding in the context of gene regulation, I will first explore how regulatory constraints can strongly shape the distribution of a population in sequence space. Then, by directly linking this to a picture of multiple types of transcription factors performing their functions simultaneously inside the cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions between transcription factors and binding sites that lead to erroneous regulatory states -- and understand the constraints this places on the design of regulatory systems. I will then develop a generic theoretical framework to investigate the coevolution of multiple transcription factors and multiple binding sites, in the context of a gene regulatory network that performs a certain function. As a particular tractable version of this problem, I will consider the evolution of two transcription factors when they transmit upstream signals to downstream target genes. Specifically, I will describe the evolutionary steady states and the evolutionary pathways involved, along with their timescales, of a system that initially undergoes a transcription factor duplication event. To connect this important theoretical model to the prominent biological event of transcription factor duplication giving rise to paralogous families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription factors, a major family in humans, and focus on the patterns of evolution that paralogs have undergone in their various protein domains in the recent past. "}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"6071","title":"Coevolution of transcription factors and their binding sites in sequence space","status":"public","has_accepted_license":"1","citation":{"chicago":"Prizak, Roshan. “Coevolution of Transcription Factors and Their Binding Sites in Sequence Space.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/at:ista:th6071\">https://doi.org/10.15479/at:ista:th6071</a>.","mla":"Prizak, Roshan. <i>Coevolution of Transcription Factors and Their Binding Sites in Sequence Space</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/at:ista:th6071\">10.15479/at:ista:th6071</a>.","ama":"Prizak R. Coevolution of transcription factors and their binding sites in sequence space. 2019. doi:<a href=\"https://doi.org/10.15479/at:ista:th6071\">10.15479/at:ista:th6071</a>","short":"R. Prizak, Coevolution of Transcription Factors and Their Binding Sites in Sequence Space, Institute of Science and Technology Austria, 2019.","ieee":"R. Prizak, “Coevolution of transcription factors and their binding sites in sequence space,” Institute of Science and Technology Austria, 2019.","apa":"Prizak, R. (2019). <i>Coevolution of transcription factors and their binding sites in sequence space</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:th6071\">https://doi.org/10.15479/at:ista:th6071</a>","ista":"Prizak R. 2019. Coevolution of transcription factors and their binding sites in sequence space. Institute of Science and Technology Austria."}},{"title":"Receptor crosstalk improves concentration sensing of multiple ligands","_id":"6090","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"Cells need to reliably sense external ligand concentrations to achieve various biological functions such as chemotaxis or signaling. The molecular recognition of ligands by surface receptors is degenerate in many systems, leading to crosstalk between ligand-receptor pairs. Crosstalk is often thought of as a deviation from optimal specific recognition, as the binding of noncognate ligands can interfere with the detection of the receptor's cognate ligand, possibly leading to a false triggering of a downstream signaling pathway. Here we quantify the optimal precision of sensing the concentrations of multiple ligands by a collection of promiscuous receptors. We demonstrate that crosstalk can improve precision in concentration sensing and discrimination tasks. To achieve superior precision, the additional information about ligand concentrations contained in short binding events of the noncognate ligand should be exploited. We present a proofreading scheme to realize an approximate estimation of multiple ligand concentrations that reaches a precision close to the derived optimal bounds. Our results help rationalize the observed ubiquity of receptor crosstalk in molecular sensing.","lang":"eng"}],"status":"public","intvolume":"        99","citation":{"ieee":"M. Carballo-Pacheco <i>et al.</i>, “Receptor crosstalk improves concentration sensing of multiple ligands,” <i>Physical Review E</i>, vol. 99, no. 2. American Physical Society, 2019.","short":"M. Carballo-Pacheco, J. Desponds, T. Gavrilchenko, A. Mayer, R. Prizak, G. Reddy, I. Nemenman, T. Mora, Physical Review E 99 (2019).","apa":"Carballo-Pacheco, M., Desponds, J., Gavrilchenko, T., Mayer, A., Prizak, R., Reddy, G., … Mora, T. (2019). Receptor crosstalk improves concentration sensing of multiple ligands. <i>Physical Review E</i>. American Physical Society. <a href=\"https://doi.org/10.1103/PhysRevE.99.022423\">https://doi.org/10.1103/PhysRevE.99.022423</a>","ista":"Carballo-Pacheco M, Desponds J, Gavrilchenko T, Mayer A, Prizak R, Reddy G, Nemenman I, Mora T. 2019. Receptor crosstalk improves concentration sensing of multiple ligands. Physical Review E. 99(2), 022423.","chicago":"Carballo-Pacheco, Martín, Jonathan Desponds, Tatyana Gavrilchenko, Andreas Mayer, Roshan Prizak, Gautam Reddy, Ilya Nemenman, and Thierry Mora. “Receptor Crosstalk Improves Concentration Sensing of Multiple Ligands.” <i>Physical Review E</i>. American Physical Society, 2019. <a href=\"https://doi.org/10.1103/PhysRevE.99.022423\">https://doi.org/10.1103/PhysRevE.99.022423</a>.","mla":"Carballo-Pacheco, Martín, et al. “Receptor Crosstalk Improves Concentration Sensing of Multiple Ligands.” <i>Physical Review E</i>, vol. 99, no. 2, 022423, American Physical Society, 2019, doi:<a href=\"https://doi.org/10.1103/PhysRevE.99.022423\">10.1103/PhysRevE.99.022423</a>.","ama":"Carballo-Pacheco M, Desponds J, Gavrilchenko T, et al. Receptor crosstalk improves concentration sensing of multiple ligands. <i>Physical Review E</i>. 2019;99(2). doi:<a href=\"https://doi.org/10.1103/PhysRevE.99.022423\">10.1103/PhysRevE.99.022423</a>"},"main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/448118v1.abstract"}],"scopus_import":"1","isi":1,"issue":"2","publisher":"American Physical Society","doi":"10.1103/PhysRevE.99.022423","date_updated":"2024-02-28T13:12:06Z","publication":"Physical Review E","article_processing_charge":"No","oa":1,"quality_controlled":"1","article_number":"022423","month":"02","type":"journal_article","date_published":"2019-02-26T00:00:00Z","volume":99,"oa_version":"Preprint","external_id":{"isi":["000459916500007"]},"language":[{"iso":"eng"}],"year":"2019","department":[{"_id":"NiBa"},{"_id":"GaTk"}],"author":[{"last_name":"Carballo-Pacheco","full_name":"Carballo-Pacheco, Martín","first_name":"Martín"},{"last_name":"Desponds","full_name":"Desponds, Jonathan","first_name":"Jonathan"},{"first_name":"Tatyana","full_name":"Gavrilchenko, Tatyana","last_name":"Gavrilchenko"},{"first_name":"Andreas","full_name":"Mayer, Andreas","last_name":"Mayer"},{"first_name":"Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87","full_name":"Prizak, Roshan","last_name":"Prizak"},{"last_name":"Reddy","full_name":"Reddy, Gautam","first_name":"Gautam"},{"first_name":"Ilya","full_name":"Nemenman, Ilya","last_name":"Nemenman"},{"first_name":"Thierry","full_name":"Mora, Thierry","last_name":"Mora"}],"day":"26","publication_status":"published","date_created":"2019-03-10T22:59:20Z"}]