[{"page":"291–295","abstract":[{"text":"Proton-translocating transhydrogenase (also known as nicotinamide nucleotide transhydrogenase (NNT)) is found in the plasma membranes of bacteria and the inner mitochondrial membranes of eukaryotes. NNT catalyses the transfer of a hydride between NADH and NADP+, coupled to the translocation of one proton across the membrane. Its main physiological function is the generation of NADPH, which is a substrate in anabolic reactions and a regulator of oxidative status; however, NNT may also fine-tune the Krebs cycle1,2. NNT deficiency causes familial glucocorticoid deficiency in humans and metabolic abnormalities in mice, similar to those observed in type II diabetes3,4. The catalytic mechanism of NNT has been proposed to involve a rotation of around 180° of the entire NADP(H)-binding domain that alternately participates in hydride transfer and proton-channel gating. However, owing to the lack of high-resolution structures of intact NNT, the details of this process remain unclear5,6. Here we present the cryo-electron microscopy structure of intact mammalian NNT in different conformational states. We show how the NADP(H)-binding domain opens the proton channel to the opposite sides of the membrane, and we provide structures of these two states. We also describe the catalytically important interfaces and linkers between the membrane and the soluble domains and their roles in nucleotide exchange. These structures enable us to propose a revised mechanism for a coupling process in NNT that is consistent with a large body of previous biochemical work. Our results are relevant to the development of currently unavailable NNT inhibitors, which may have therapeutic potential in ischaemia reperfusion injury, metabolic syndrome and some cancers7,8,9.","lang":"eng"}],"date_updated":"2024-03-25T23:30:08Z","oa_version":"Submitted Version","month":"09","type":"journal_article","volume":573,"date_created":"2019-09-04T06:21:41Z","file_date_updated":"2020-11-26T16:33:44Z","acknowledgement":" We thank R. Thompson, G. Effantin and V.-V. Hodirnau for their assistance with collecting NADP+, NADPH and apo datasets, respectively. Data processing was performed at the IST high-performance computing cluster.\r\nThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement no. 665385.","year":"2019","_id":"6848","publication_status":"published","oa":1,"has_accepted_license":"1","date_published":"2019-09-12T00:00:00Z","ddc":["572"],"acknowledged_ssus":[{"_id":"ScienComp"}],"external_id":{"pmid":["31462775"],"isi":["000485415400061"]},"status":"public","related_material":{"link":[{"url":"https://ist.ac.at/en/news/high-end-microscopy-reveals-structure-and-function-of-crucial-metabolic-enzyme/","description":"News on IST Website","relation":"press_release"}],"record":[{"relation":"dissertation_contains","id":"8340","status":"public"}]},"intvolume":"       573","citation":{"chicago":"Kampjut, Domen, and Leonid A Sazanov. “Structure and Mechanism of Mitochondrial Proton-Translocating Transhydrogenase.” <i>Nature</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1038/s41586-019-1519-2\">https://doi.org/10.1038/s41586-019-1519-2</a>.","ieee":"D. Kampjut and L. A. Sazanov, “Structure and mechanism of mitochondrial proton-translocating transhydrogenase,” <i>Nature</i>, vol. 573, no. 7773. Springer Nature, pp. 291–295, 2019.","short":"D. Kampjut, L.A. Sazanov, Nature 573 (2019) 291–295.","ama":"Kampjut D, Sazanov LA. Structure and mechanism of mitochondrial proton-translocating transhydrogenase. <i>Nature</i>. 2019;573(7773):291–295. doi:<a href=\"https://doi.org/10.1038/s41586-019-1519-2\">10.1038/s41586-019-1519-2</a>","apa":"Kampjut, D., &#38; Sazanov, L. A. (2019). Structure and mechanism of mitochondrial proton-translocating transhydrogenase. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-019-1519-2\">https://doi.org/10.1038/s41586-019-1519-2</a>","ista":"Kampjut D, Sazanov LA. 2019. Structure and mechanism of mitochondrial proton-translocating transhydrogenase. Nature. 573(7773), 291–295.","mla":"Kampjut, Domen, and Leonid A. Sazanov. “Structure and Mechanism of Mitochondrial Proton-Translocating Transhydrogenase.” <i>Nature</i>, vol. 573, no. 7773, Springer Nature, 2019, pp. 291–295, doi:<a href=\"https://doi.org/10.1038/s41586-019-1519-2\">10.1038/s41586-019-1519-2</a>."},"author":[{"last_name":"Kampjut","first_name":"Domen","id":"37233050-F248-11E8-B48F-1D18A9856A87","full_name":"Kampjut, Domen"},{"orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","full_name":"Sazanov, Leonid A","last_name":"Sazanov","first_name":"Leonid A"}],"day":"12","file":[{"date_created":"2020-11-26T16:33:44Z","access_level":"open_access","file_id":"8821","date_updated":"2020-11-26T16:33:44Z","checksum":"52728cda5210a3e9b74cc204e8aed3d5","file_size":3066206,"content_type":"application/pdf","relation":"main_file","creator":"lsazanov","file_name":"Manuscript_final_acc_withFigs_SI_opt_red.pdf","success":1}],"title":"Structure and mechanism of mitochondrial proton-translocating transhydrogenase","publisher":"Springer Nature","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"department":[{"_id":"LeSa"}],"publication":"Nature","scopus_import":"1","ec_funded":1,"article_processing_charge":"No","article_type":"letter_note","publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"doi":"10.1038/s41586-019-1519-2","quality_controlled":"1","project":[{"grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"isi":1,"language":[{"iso":"eng"}],"issue":"7773"},{"file_date_updated":"2021-02-10T23:30:09Z","date_created":"2019-09-06T06:54:16Z","oa_version":"Published Version","type":"dissertation","month":"09","date_updated":"2023-09-19T10:01:12Z","abstract":[{"text":"Brain function is mediated by complex dynamical interactions between excitatory and inhibitory cell types. The Cholecystokinin-expressing inhibitory cells (CCK-interneurons) are one of the least studied types, despite being suspected to play important roles in cognitive processes. We studied the network effects of optogenetic silencing of CCK-interneurons in the CA1 hippocampal area during exploration and sleep states. The cell firing pattern in response to light pulses allowed us to classify the recorded neurons in 5 classes, including disinhibited and non-responsive pyramidal cell and interneurons, and the inhibited interneurons corresponding to the CCK group. The light application, which inhibited the activity of CCK interneurons triggered wider changes in the firing dynamics of cells. We observed rate changes (i.e. remapping) of pyramidal cells during the exploration session in which the light was applied relative to the previous control session that was not restricted neither in time nor space to the light delivery. Also, the disinhibited pyramidal cells had higher increase in bursting than in single spike firing rate as a result of CCK silencing. In addition, the firing activity patterns during exploratory periods were more weakly reactivated in sleep for those periods in which CCK-interneuron were silenced than in the unaffected periods. Furthermore, light pulses during sleep disrupted the reactivation of recent waking patterns. Hence, silencing CCK neurons during exploration suppressed the reactivation of waking firing patterns in sleep and CCK interneuron activity was also required during sleep for the normal reactivation of waking patterns. These findings demonstrate the involvement of CCK cells in reactivation-related memory consolidation. An important part of our analysis was to test the relationship of the identified CCKinterneurons to brain oscillations. Our findings showed that these cells exhibited different oscillatory behaviour during anaesthesia and natural waking and sleep conditions. We showed that: 1) Contrary to the past studies performed under anaesthesia, the identified CCKinterneurons fired on the descending portion of the theta phase in waking exploration. 2) CCKinterneuron preferred phases around the trough of gamma oscillations. 3) Contrary to anaesthesia conditions, the average firing rate of the CCK-interneurons increased around the peak activity of the sharp-wave ripple (SWR) events in natural sleep, which is congruent with new reports about their functional connectivity. We also found that light driven CCK-interneuron silencing altered the dynamics on the CA1 network oscillatory activity: 1) Pyramidal cells negatively shifted their preferred theta phases when the light was applied, while interneurons responses were less consistent. 2) As a population, pyramidal cells negatively shifted their preferred activity during gamma oscillations, albeit we did not find gamma modulation differences related to the light application when pyramidal cells were subdivided into the disinhibited and unaffected groups. 3) During the peak of SWR events, all but the CCK-interneurons had a reduction in their relative firing rate change during the light application as compared to the change observed at SWR initiation. Finally, regarding to the place field activity of the recorded pyramidal neurons, we showed that the disinhibited pyramidal cells had reduced place field similarity, coherence and spatial information, but only during the light application. The mechanisms behind such observed behaviours might involve eCB signalling and plastic changes in CCK-interneuron synapses. In conclusion, the observed changes related to the light-mediated silencing of CCKinterneurons have unravelled characteristics of this interneuron subpopulation that might change the understanding not only of their particular network interactions, but also of the current theories about the emergence of certain cognitive processes such as place coding needed for navigation or hippocampus-dependent memory consolidation. ","lang":"eng"}],"page":"97","_id":"6849","year":"2019","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"M-Shop"}],"ddc":["570"],"date_published":"2019-09-09T00:00:00Z","supervisor":[{"full_name":"Csicsvari, Jozsef L","orcid":"0000-0002-5193-4036","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","last_name":"Csicsvari","first_name":"Jozsef L"}],"has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"apa":"Rangel Guerrero, D. K. (2019). <i>The role of CCK-interneurons in regulating hippocampal network dynamics</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6849\">https://doi.org/10.15479/AT:ISTA:6849</a>","ista":"Rangel Guerrero DK. 2019. The role of CCK-interneurons in regulating hippocampal network dynamics. Institute of Science and Technology Austria.","mla":"Rangel Guerrero, Dámaris K. <i>The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6849\">10.15479/AT:ISTA:6849</a>.","ama":"Rangel Guerrero DK. The role of CCK-interneurons in regulating hippocampal network dynamics. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6849\">10.15479/AT:ISTA:6849</a>","short":"D.K. Rangel Guerrero, The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics, Institute of Science and Technology Austria, 2019.","chicago":"Rangel Guerrero, Dámaris K. “The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6849\">https://doi.org/10.15479/AT:ISTA:6849</a>.","ieee":"D. K. Rangel Guerrero, “The role of CCK-interneurons in regulating hippocampal network dynamics,” Institute of Science and Technology Austria, 2019."},"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"5914"}]},"status":"public","alternative_title":["ISTA Thesis"],"degree_awarded":"PhD","title":"The role of CCK-interneurons in regulating hippocampal network dynamics","day":"09","file":[{"file_name":"Thesis_Damaris_Rangel_source.docx","creator":"drangel","embargo_to":"open_access","file_size":18253100,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","checksum":"244dc4f74dbfc94f414156092298831f","file_id":"6865","date_updated":"2021-02-10T23:30:09Z","access_level":"closed","date_created":"2019-09-09T13:09:45Z"},{"checksum":"59c73be40eeaa1c4db24067270151555","date_updated":"2020-09-11T22:30:04Z","file_id":"6866","access_level":"open_access","date_created":"2019-09-09T13:09:52Z","file_name":"Thesis_Damaris_Rangel_pdfa.pdf","creator":"drangel","relation":"main_file","embargo":"2020-09-10","content_type":"application/pdf","request_a_copy":0,"file_size":2160109}],"author":[{"first_name":"Dámaris K","last_name":"Rangel Guerrero","full_name":"Rangel Guerrero, Dámaris K","id":"4871BCE6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8602-4374"}],"article_processing_charge":"No","department":[{"_id":"JoCs"}],"publisher":"Institute of Science and Technology Austria","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","doi":"10.15479/AT:ISTA:6849","publication_identifier":{"issn":["2663-337X"],"isbn":["9783990780039"]},"language":[{"iso":"eng"}]},{"title":"Thinking about the evolution of complex traits in the era of genome-wide association studies","file":[{"file_id":"6862","date_updated":"2020-07-14T12:47:42Z","checksum":"23d3978cf4739a89ce2c3e779f9305ca","date_created":"2019-09-09T07:22:12Z","access_level":"open_access","file_name":"2019_AnnualReview_Sella.pdf","file_size":411491,"content_type":"application/pdf","relation":"main_file","creator":"dernst"}],"day":"05","author":[{"full_name":"Sella, Guy","last_name":"Sella","first_name":"Guy"},{"first_name":"Nicholas H","last_name":"Barton","orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","full_name":"Barton, Nicholas H"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"No","scopus_import":"1","publication":"Annual Review of Genomics and Human Genetics","department":[{"_id":"NiBa"}],"pmid":1,"publisher":"Annual Reviews","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","quality_controlled":"1","doi":"10.1146/annurev-genom-083115-022316","publication_identifier":{"eissn":["1545-293X"],"issn":["1527-8204"]},"language":[{"iso":"eng"}],"isi":1,"file_date_updated":"2020-07-14T12:47:42Z","date_created":"2019-09-07T14:28:29Z","volume":20,"type":"journal_article","month":"07","oa_version":"Published Version","abstract":[{"text":"Many traits of interest are highly heritable and genetically complex, meaning that much of the variation they exhibit arises from differences at numerous loci in the genome. Complex traits and their evolution have been studied for more than a century, but only in the last decade have genome-wide association studies (GWASs) in humans begun to reveal their genetic basis. Here, we bring these threads of research together to ask how findings from GWASs can further our understanding of the processes that give rise to heritable variation in complex traits and of the genetic basis of complex trait evolution in response to changing selection pressures (i.e., of polygenic adaptation). Conversely, we ask how evolutionary thinking helps us to interpret findings from GWASs and informs related efforts of practical importance.","lang":"eng"}],"date_updated":"2023-08-29T07:49:38Z","page":"461-493","_id":"6855","year":"2019","date_published":"2019-07-05T00:00:00Z","ddc":["576"],"has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"short":"G. Sella, N.H. Barton, Annual Review of Genomics and Human Genetics 20 (2019) 461–493.","ieee":"G. Sella and N. H. Barton, “Thinking about the evolution of complex traits in the era of genome-wide association studies,” <i>Annual Review of Genomics and Human Genetics</i>, vol. 20. Annual Reviews, pp. 461–493, 2019.","chicago":"Sella, Guy, and Nicholas H Barton. “Thinking about the Evolution of Complex Traits in the Era of Genome-Wide Association Studies.” <i>Annual Review of Genomics and Human Genetics</i>. Annual Reviews, 2019. <a href=\"https://doi.org/10.1146/annurev-genom-083115-022316\">https://doi.org/10.1146/annurev-genom-083115-022316</a>.","ista":"Sella G, Barton NH. 2019. Thinking about the evolution of complex traits in the era of genome-wide association studies. Annual Review of Genomics and Human Genetics. 20, 461–493.","mla":"Sella, Guy, and Nicholas H. Barton. “Thinking about the Evolution of Complex Traits in the Era of Genome-Wide Association Studies.” <i>Annual Review of Genomics and Human Genetics</i>, vol. 20, Annual Reviews, 2019, pp. 461–93, doi:<a href=\"https://doi.org/10.1146/annurev-genom-083115-022316\">10.1146/annurev-genom-083115-022316</a>.","apa":"Sella, G., &#38; Barton, N. H. (2019). Thinking about the evolution of complex traits in the era of genome-wide association studies. <i>Annual Review of Genomics and Human Genetics</i>. Annual Reviews. <a href=\"https://doi.org/10.1146/annurev-genom-083115-022316\">https://doi.org/10.1146/annurev-genom-083115-022316</a>","ama":"Sella G, Barton NH. Thinking about the evolution of complex traits in the era of genome-wide association studies. <i>Annual Review of Genomics and Human Genetics</i>. 2019;20:461-493. doi:<a href=\"https://doi.org/10.1146/annurev-genom-083115-022316\">10.1146/annurev-genom-083115-022316</a>"},"intvolume":"        20","external_id":{"pmid":["31283361"],"isi":["000485148400020"]},"status":"public"},{"volume":224,"file_date_updated":"2020-07-14T12:47:42Z","date_created":"2019-09-07T14:35:40Z","page":"1035-1047","oa_version":"Published Version","type":"journal_article","month":"11","abstract":[{"text":"Plant mating systems play a key role in structuring genetic variation both within and between species. In hybrid zones, the outcomes and dynamics of hybridization are usually interpreted as the balance between gene flow and selection against hybrids. Yet, mating systems can introduce selective forces that alter these expectations; with diverse outcomes for the level and direction of gene flow depending on variation in outcrossing and whether the mating systems of the species pair are the same or divergent. We present a survey of hybridization in 133 species pairs from 41 plant families and examine how patterns of hybridization vary with mating system. We examine if hybrid zone mode, level of gene flow, asymmetries in gene flow and the frequency of reproductive isolating barriers vary in relation to mating system/s of the species pair. We combine these results with a simulation model and examples from the literature to address two general themes: (i) the two‐way interaction between introgression and the evolution of reproductive systems, and (ii) how mating system can facilitate or restrict interspecific gene flow. We conclude that examining mating system with hybridization provides unique opportunities to understand divergence and the processes underlying reproductive isolation.","lang":"eng"}],"date_updated":"2023-10-18T08:47:08Z","_id":"6856","year":"2019","ddc":["570"],"date_published":"2019-11-01T00:00:00Z","oa":1,"publication_status":"published","has_accepted_license":"1","intvolume":"       224","citation":{"chicago":"Pickup, Melinda, Nicholas H Barton, Yaniv Brandvain, Christelle Fraisse, Sarah Yakimowski, Tanmay Dixit, Christian Lexer, Eva Cereghetti, and David Field. “Mating System Variation in Hybrid Zones: Facilitation, Barriers and Asymmetries to Gene Flow.” <i>New Phytologist</i>. Wiley, 2019. <a href=\"https://doi.org/10.1111/nph.16180\">https://doi.org/10.1111/nph.16180</a>.","ieee":"M. Pickup <i>et al.</i>, “Mating system variation in hybrid zones: Facilitation, barriers and asymmetries to gene flow,” <i>New Phytologist</i>, vol. 224, no. 3. Wiley, pp. 1035–1047, 2019.","short":"M. Pickup, N.H. Barton, Y. Brandvain, C. Fraisse, S. Yakimowski, T. Dixit, C. Lexer, E. Cereghetti, D. Field, New Phytologist 224 (2019) 1035–1047.","ama":"Pickup M, Barton NH, Brandvain Y, et al. Mating system variation in hybrid zones: Facilitation, barriers and asymmetries to gene flow. <i>New Phytologist</i>. 2019;224(3):1035-1047. doi:<a href=\"https://doi.org/10.1111/nph.16180\">10.1111/nph.16180</a>","apa":"Pickup, M., Barton, N. H., Brandvain, Y., Fraisse, C., Yakimowski, S., Dixit, T., … Field, D. (2019). Mating system variation in hybrid zones: Facilitation, barriers and asymmetries to gene flow. <i>New Phytologist</i>. Wiley. <a href=\"https://doi.org/10.1111/nph.16180\">https://doi.org/10.1111/nph.16180</a>","mla":"Pickup, Melinda, et al. “Mating System Variation in Hybrid Zones: Facilitation, Barriers and Asymmetries to Gene Flow.” <i>New Phytologist</i>, vol. 224, no. 3, Wiley, 2019, pp. 1035–47, doi:<a href=\"https://doi.org/10.1111/nph.16180\">10.1111/nph.16180</a>.","ista":"Pickup M, Barton NH, Brandvain Y, Fraisse C, Yakimowski S, Dixit T, Lexer C, Cereghetti E, Field D. 2019. Mating system variation in hybrid zones: Facilitation, barriers and asymmetries to gene flow. New Phytologist. 224(3), 1035–1047."},"external_id":{"pmid":["31505037"]},"status":"public","title":"Mating system variation in hybrid zones: Facilitation, barriers and asymmetries to gene flow","author":[{"first_name":"Melinda","last_name":"Pickup","full_name":"Pickup, Melinda","id":"2C78037E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6118-0541"},{"orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","full_name":"Barton, Nicholas H","first_name":"Nicholas H","last_name":"Barton"},{"full_name":"Brandvain, Yaniv","first_name":"Yaniv","last_name":"Brandvain"},{"last_name":"Fraisse","first_name":"Christelle","id":"32DF5794-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8441-5075","full_name":"Fraisse, Christelle"},{"full_name":"Yakimowski, Sarah","first_name":"Sarah","last_name":"Yakimowski"},{"full_name":"Dixit, Tanmay","first_name":"Tanmay","last_name":"Dixit"},{"last_name":"Lexer","first_name":"Christian","full_name":"Lexer, Christian"},{"id":"71AA91B4-05ED-11EA-8BEB-F5833E63BD63","full_name":"Cereghetti, Eva","last_name":"Cereghetti","first_name":"Eva"},{"first_name":"David","last_name":"Field","orcid":"0000-0002-4014-8478","id":"419049E2-F248-11E8-B48F-1D18A9856A87","full_name":"Field, David"}],"day":"01","file":[{"checksum":"21e4c95599bbcaf7c483b89954658672","file_id":"7011","date_updated":"2020-07-14T12:47:42Z","access_level":"open_access","date_created":"2019-11-13T08:15:05Z","file_name":"2019_NewPhytologist_Pickup.pdf","creator":"dernst","file_size":1511958,"content_type":"application/pdf","relation":"main_file"}],"publication":"New Phytologist","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"scopus_import":"1","ec_funded":1,"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Wiley","department":[{"_id":"NiBa"}],"pmid":1,"doi":"10.1111/nph.16180","quality_controlled":"1","publication_identifier":{"issn":["0028-646X"],"eissn":["1469-8137"]},"issue":"3","language":[{"iso":"eng"}],"project":[{"grant_number":"329960","name":"Mating system and the evolutionary dynamics of hybrid zones","call_identifier":"FP7","_id":"25B36484-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","_id":"2662AADE-B435-11E9-9278-68D0E5697425","name":"Sex chromosomes and species barriers","grant_number":"M02463"}]},{"title":"Gene Drives: Dynamics and regulatory matters – A report from the workshop “Evaluation of spatial and temporal control of Gene Drives”, 4 – 5 April 2019, Vienna","article_number":"1900151","day":"01","file":[{"creator":"dernst","relation":"main_file","content_type":"application/pdf","file_size":193248,"file_name":"2019_BioEssays_Giese.pdf","access_level":"open_access","date_created":"2019-10-11T06:59:26Z","checksum":"8cc7551bff70b2658f8d5630f228ee12","date_updated":"2020-07-14T12:47:42Z","file_id":"6939"}],"author":[{"first_name":"B","last_name":"Giese","full_name":"Giese, B"},{"last_name":"Friess","first_name":"J L","full_name":"Friess, J L"},{"last_name":"Schetelig","first_name":"M F ","full_name":"Schetelig, M F "},{"first_name":"Nicholas H","last_name":"Barton","full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Philip","last_name":"Messer","full_name":"Messer, Philip"},{"full_name":"Debarre, Florence","last_name":"Debarre","first_name":"Florence"},{"full_name":"Meimberg, H","first_name":"H","last_name":"Meimberg"},{"full_name":"Windbichler, N","last_name":"Windbichler","first_name":"N"},{"first_name":"C","last_name":"Boete","full_name":"Boete, C"}],"scopus_import":"1","article_processing_charge":"No","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication":"BioEssays","department":[{"_id":"NiBa"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Wiley","quality_controlled":"1","doi":"10.1002/bies.201900151","publication_identifier":{"eissn":["1521-1878"]},"language":[{"iso":"eng"}],"issue":"11","isi":1,"file_date_updated":"2020-07-14T12:47:42Z","date_created":"2019-09-07T14:40:03Z","volume":41,"date_updated":"2023-08-30T06:56:26Z","abstract":[{"text":"Gene Drives are regarded as future tools with a high potential for population control. Due to their inherent ability to overcome the rules of Mendelian inheritance, gene drives (GD) may spread genes rapidly through populations of sexually reproducing organisms. A release of organisms carrying a GD would constitute a paradigm shift in the handling of genetically modified organisms because gene drive organisms (GDO) are designed to drive their transgenes into wild populations and thereby increase the number of GDOs. The rapid development in this field and its focus on wild populations demand a prospective risk assessment with a focus on exposure related aspects. Presently, it is unclear how adequate risk management could be guaranteed to limit the spread of GDs in time and space, in order to avoid potential adverse effects in socio‐ecological systems.\r\n\r\nThe recent workshop on the “Evaluation of Spatial and Temporal Control of Gene Drives” hosted by the Institute of Safety/Security and Risk Sciences (ISR) in Vienna aimed at gaining some insight into the potential population dynamic behavior of GDs and appropriate measures of control. Scientists from France, Germany, England, and the USA discussed both topics in this meeting on April 4–5, 2019. This article summarizes results of the workshop.","lang":"eng"}],"oa_version":"Published Version","month":"11","type":"journal_article","_id":"6857","year":"2019","date_published":"2019-11-01T00:00:00Z","ddc":["570"],"has_accepted_license":"1","oa":1,"publication_status":"published","citation":{"mla":"Giese, B., et al. “Gene Drives: Dynamics and Regulatory Matters – A Report from the Workshop ‘Evaluation of Spatial and Temporal Control of Gene Drives’, 4 – 5 April 2019, Vienna.” <i>BioEssays</i>, vol. 41, no. 11, 1900151, Wiley, 2019, doi:<a href=\"https://doi.org/10.1002/bies.201900151\">10.1002/bies.201900151</a>.","ista":"Giese B, Friess JL, Schetelig MF, Barton NH, Messer P, Debarre F, Meimberg H, Windbichler N, Boete C. 2019. Gene Drives: Dynamics and regulatory matters – A report from the workshop “Evaluation of spatial and temporal control of Gene Drives”, 4 – 5 April 2019, Vienna. BioEssays. 41(11), 1900151.","apa":"Giese, B., Friess, J. L., Schetelig, M. F., Barton, N. H., Messer, P., Debarre, F., … Boete, C. (2019). Gene Drives: Dynamics and regulatory matters – A report from the workshop “Evaluation of spatial and temporal control of Gene Drives”, 4 – 5 April 2019, Vienna. <i>BioEssays</i>. Wiley. <a href=\"https://doi.org/10.1002/bies.201900151\">https://doi.org/10.1002/bies.201900151</a>","ama":"Giese B, Friess JL, Schetelig MF, et al. Gene Drives: Dynamics and regulatory matters – A report from the workshop “Evaluation of spatial and temporal control of Gene Drives”, 4 – 5 April 2019, Vienna. <i>BioEssays</i>. 2019;41(11). doi:<a href=\"https://doi.org/10.1002/bies.201900151\">10.1002/bies.201900151</a>","short":"B. Giese, J.L. Friess, M.F. Schetelig, N.H. Barton, P. Messer, F. Debarre, H. Meimberg, N. Windbichler, C. Boete, BioEssays 41 (2019).","ieee":"B. Giese <i>et al.</i>, “Gene Drives: Dynamics and regulatory matters – A report from the workshop ‘Evaluation of spatial and temporal control of Gene Drives’, 4 – 5 April 2019, Vienna,” <i>BioEssays</i>, vol. 41, no. 11. Wiley, 2019.","chicago":"Giese, B, J L Friess, M F  Schetelig, Nicholas H Barton, Philip Messer, Florence Debarre, H Meimberg, N Windbichler, and C Boete. “Gene Drives: Dynamics and Regulatory Matters – A Report from the Workshop ‘Evaluation of Spatial and Temporal Control of Gene Drives’, 4 – 5 April 2019, Vienna.” <i>BioEssays</i>. Wiley, 2019. <a href=\"https://doi.org/10.1002/bies.201900151\">https://doi.org/10.1002/bies.201900151</a>."},"intvolume":"        41","external_id":{"isi":["000489502000001"]},"status":"public"},{"quality_controlled":"1","doi":"10.1093/nsr/nwy113","publication_identifier":{"issn":["2095-5138"],"eissn":["2053-714X"]},"issue":"2","language":[{"iso":"eng"}],"isi":1,"title":"Is speciation driven by cycles of mixing and isolation?","file":[{"success":1,"file_name":"2019_NSR_Barton.pdf","creator":"dernst","content_type":"application/pdf","relation":"main_file","file_size":106463,"checksum":"571d60fa21a568607d1fd04e119da88c","date_updated":"2020-10-02T09:16:44Z","file_id":"8595","access_level":"open_access","date_created":"2020-10-02T09:16:44Z"}],"day":"01","author":[{"full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas H","last_name":"Barton"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"review","article_processing_charge":"No","scopus_import":"1","publication":"National Science Review","department":[{"_id":"NiBa"}],"publisher":"Oxford University Press","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_published":"2019-03-01T00:00:00Z","ddc":["570"],"has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"ieee":"N. H. Barton, “Is speciation driven by cycles of mixing and isolation?,” <i>National Science Review</i>, vol. 6, no. 2. Oxford University Press, pp. 291–292, 2019.","chicago":"Barton, Nicholas H. “Is Speciation Driven by Cycles of Mixing and Isolation?” <i>National Science Review</i>. Oxford University Press, 2019. <a href=\"https://doi.org/10.1093/nsr/nwy113\">https://doi.org/10.1093/nsr/nwy113</a>.","short":"N.H. Barton, National Science Review 6 (2019) 291–292.","ama":"Barton NH. Is speciation driven by cycles of mixing and isolation? <i>National Science Review</i>. 2019;6(2):291-292. doi:<a href=\"https://doi.org/10.1093/nsr/nwy113\">10.1093/nsr/nwy113</a>","ista":"Barton NH. 2019. Is speciation driven by cycles of mixing and isolation? National Science Review. 6(2), 291–292.","mla":"Barton, Nicholas H. “Is Speciation Driven by Cycles of Mixing and Isolation?” <i>National Science Review</i>, vol. 6, no. 2, Oxford University Press, 2019, pp. 291–92, doi:<a href=\"https://doi.org/10.1093/nsr/nwy113\">10.1093/nsr/nwy113</a>.","apa":"Barton, N. H. (2019). Is speciation driven by cycles of mixing and isolation? <i>National Science Review</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/nsr/nwy113\">https://doi.org/10.1093/nsr/nwy113</a>"},"intvolume":"         6","status":"public","external_id":{"isi":["000467957400025"]},"file_date_updated":"2020-10-02T09:16:44Z","date_created":"2019-09-07T14:43:02Z","volume":6,"month":"03","type":"journal_article","oa_version":"Published Version","date_updated":"2023-08-29T07:51:09Z","page":"291-292","_id":"6858","year":"2019"},{"year":"2019","_id":"6859","date_updated":"2023-08-29T07:52:02Z","abstract":[{"lang":"eng","text":"V (vacuolar)/A (archaeal)-type adenosine triphosphatases (ATPases), found in archaeaand eubacteria, couple ATP hydrolysis or synthesis to proton translocation across theplasma membrane using the rotary-catalysis mechanism. They belong to the V-typeATPase family, which differs from the mitochondrial/chloroplast F-type ATP synthasesin overall architecture. We solved cryo–electron microscopy structures of the intactThermus thermophilusV/A-ATPase, reconstituted into lipid nanodiscs, in three rotationalstates and two substates. These structures indicate substantial flexibility betweenV1and Voin a working enzyme, which results from mechanical competition between centralshaft rotation and resistance from the peripheral stalks. We also describedetails of adenosine diphosphate inhibition release, V1-Votorque transmission, andproton translocation, which are relevant for the entire V-type ATPase family."}],"month":"08","oa_version":"None","type":"journal_article","volume":365,"date_created":"2019-09-07T19:04:45Z","external_id":{"isi":["000482464000043"],"pmid":["31439765"]},"status":"public","related_material":{"link":[{"description":"News on IST Website","url":"https://ist.ac.at/en/news/structure-of-protein-nano-turbine-revealed/","relation":"press_release"}]},"intvolume":"       365","citation":{"ama":"Zhou L, Sazanov LA. Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase. <i>Science</i>. 2019;365(6455). doi:<a href=\"https://doi.org/10.1126/science.aaw9144\">10.1126/science.aaw9144</a>","ista":"Zhou L, Sazanov LA. 2019. Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase. Science. 365(6455), eaaw9144.","mla":"Zhou, Long, and Leonid A. Sazanov. “Structure and Conformational Plasticity of the Intact Thermus Thermophilus V/A-Type ATPase.” <i>Science</i>, vol. 365, no. 6455, eaaw9144, AAAS, 2019, doi:<a href=\"https://doi.org/10.1126/science.aaw9144\">10.1126/science.aaw9144</a>.","apa":"Zhou, L., &#38; Sazanov, L. A. (2019). Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase. <i>Science</i>. AAAS. <a href=\"https://doi.org/10.1126/science.aaw9144\">https://doi.org/10.1126/science.aaw9144</a>","ieee":"L. Zhou and L. A. Sazanov, “Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase,” <i>Science</i>, vol. 365, no. 6455. AAAS, 2019.","chicago":"Zhou, Long, and Leonid A Sazanov. “Structure and Conformational Plasticity of the Intact Thermus Thermophilus V/A-Type ATPase.” <i>Science</i>. AAAS, 2019. <a href=\"https://doi.org/10.1126/science.aaw9144\">https://doi.org/10.1126/science.aaw9144</a>.","short":"L. Zhou, L.A. Sazanov, Science 365 (2019)."},"publication_status":"published","date_published":"2019-08-23T00:00:00Z","acknowledged_ssus":[{"_id":"ScienComp"}],"publisher":"AAAS","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"department":[{"_id":"LeSa"}],"publication":"Science","article_processing_charge":"No","scopus_import":"1","author":[{"id":"3E751364-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1864-8951","full_name":"Zhou, Long","first_name":"Long","last_name":"Zhou"},{"orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","full_name":"Sazanov, Leonid A","last_name":"Sazanov","first_name":"Leonid A"}],"day":"23","title":"Structure and conformational plasticity of the intact Thermus thermophilus V/A-type ATPase","article_number":"eaaw9144","isi":1,"language":[{"iso":"eng"}],"issue":"6455","publication_identifier":{"issn":["0036-8075"],"eissn":["1095-9203"]},"doi":"10.1126/science.aaw9144","quality_controlled":"1"},{"_id":"6867","year":"2019","file_date_updated":"2020-07-14T12:47:42Z","date_created":"2019-09-15T22:00:42Z","volume":9,"date_updated":"2023-08-29T07:55:15Z","abstract":[{"lang":"eng","text":"A novel magnetic scratch method achieves repeatability, reproducibility and geometric control greater than pipette scratch assays and closely approximating the precision of cell exclusion assays while inducing the cell injury inherently necessary for wound healing assays. The magnetic scratch is affordable, easily implemented and standardisable and thus may contribute toward better comparability of data generated in different studies and laboratories."}],"type":"journal_article","oa_version":"Published Version","month":"09","citation":{"chicago":"Fenu, M., T. Bettermann, C. Vogl, Nasser Darwish-Miranda, J. Schramel, F. Jenner, and I. Ribitsch. “A Novel Magnet-Based Scratch Method for Standardisation of Wound-Healing Assays.” <i>Scientific Reports</i>. Springer Nature, 2019. <a href=\"https://doi.org/10.1038/s41598-019-48930-7\">https://doi.org/10.1038/s41598-019-48930-7</a>.","ieee":"M. Fenu <i>et al.</i>, “A novel magnet-based scratch method for standardisation of wound-healing assays,” <i>Scientific Reports</i>, vol. 9, no. 1. Springer Nature, 2019.","short":"M. Fenu, T. Bettermann, C. Vogl, N. Darwish-Miranda, J. Schramel, F. Jenner, I. Ribitsch, Scientific Reports 9 (2019).","ama":"Fenu M, Bettermann T, Vogl C, et al. A novel magnet-based scratch method for standardisation of wound-healing assays. <i>Scientific Reports</i>. 2019;9(1). doi:<a href=\"https://doi.org/10.1038/s41598-019-48930-7\">10.1038/s41598-019-48930-7</a>","apa":"Fenu, M., Bettermann, T., Vogl, C., Darwish-Miranda, N., Schramel, J., Jenner, F., &#38; Ribitsch, I. (2019). A novel magnet-based scratch method for standardisation of wound-healing assays. <i>Scientific Reports</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41598-019-48930-7\">https://doi.org/10.1038/s41598-019-48930-7</a>","ista":"Fenu M, Bettermann T, Vogl C, Darwish-Miranda N, Schramel J, Jenner F, Ribitsch I. 2019. A novel magnet-based scratch method for standardisation of wound-healing assays. Scientific Reports. 9(1), 12625.","mla":"Fenu, M., et al. “A Novel Magnet-Based Scratch Method for Standardisation of Wound-Healing Assays.” <i>Scientific Reports</i>, vol. 9, no. 1, 12625, Springer Nature, 2019, doi:<a href=\"https://doi.org/10.1038/s41598-019-48930-7\">10.1038/s41598-019-48930-7</a>."},"intvolume":"         9","external_id":{"pmid":["31477739"],"isi":["000483697800007"]},"status":"public","date_published":"2019-09-02T00:00:00Z","ddc":["570"],"has_accepted_license":"1","oa":1,"publication_status":"published","scopus_import":"1","article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication":"Scientific Reports","pmid":1,"department":[{"_id":"Bio"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Springer Nature","title":"A novel magnet-based scratch method for standardisation of wound-healing assays","article_number":"12625","day":"02","file":[{"access_level":"open_access","date_created":"2019-09-16T12:42:40Z","checksum":"9cfd986d4108e288cc72276ef047ab0c","date_updated":"2020-07-14T12:47:42Z","file_id":"6879","creator":"dernst","content_type":"application/pdf","relation":"main_file","file_size":3523795,"file_name":"2019_ScientificReports_Fenu.pdf"}],"author":[{"full_name":"Fenu, M.","first_name":"M.","last_name":"Fenu"},{"last_name":"Bettermann","first_name":"T.","full_name":"Bettermann, T."},{"first_name":"C.","last_name":"Vogl","full_name":"Vogl, C."},{"orcid":"0000-0002-8821-8236","id":"39CD9926-F248-11E8-B48F-1D18A9856A87","full_name":"Darwish-Miranda, Nasser","first_name":"Nasser","last_name":"Darwish-Miranda"},{"full_name":"Schramel, J.","first_name":"J.","last_name":"Schramel"},{"full_name":"Jenner, F.","last_name":"Jenner","first_name":"F."},{"full_name":"Ribitsch, I.","first_name":"I.","last_name":"Ribitsch"}],"language":[{"iso":"eng"}],"issue":"1","isi":1,"quality_controlled":"1","doi":"10.1038/s41598-019-48930-7","publication_identifier":{"eissn":["20452322"]}},{"publication":"eLife","scopus_import":"1","article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"RySh"}],"title":"HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons","article_number":"e42766","author":[{"full_name":"Byczkowicz, Niklas","first_name":"Niklas","last_name":"Byczkowicz"},{"first_name":"Abdelmoneim","last_name":"Eshra","full_name":"Eshra, Abdelmoneim"},{"id":"3786AB44-F248-11E8-B48F-1D18A9856A87","full_name":"Montanaro-Punzengruber, Jacqueline-Claire","last_name":"Montanaro-Punzengruber","first_name":"Jacqueline-Claire"},{"full_name":"Trevisiol, Andrea","first_name":"Andrea","last_name":"Trevisiol"},{"full_name":"Hirrlinger, Johannes","first_name":"Johannes","last_name":"Hirrlinger"},{"last_name":"Kole","first_name":"Maarten Hp","full_name":"Kole, Maarten Hp"},{"first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"last_name":"Hallermann","first_name":"Stefan","full_name":"Hallermann, Stefan"}],"file":[{"creator":"dernst","relation":"main_file","content_type":"application/pdf","file_size":4008137,"file_name":"2019_eLife_Byczkowicz.pdf","access_level":"open_access","date_created":"2019-09-16T13:14:33Z","checksum":"c350b7861ef0fb537cae8a3232aec016","date_updated":"2020-07-14T12:47:42Z","file_id":"6880"}],"day":"09","isi":1,"language":[{"iso":"eng"}],"doi":"10.7554/eLife.42766","quality_controlled":"1","publication_identifier":{"eissn":["2050084X"]},"_id":"6868","year":"2019","volume":8,"file_date_updated":"2020-07-14T12:47:42Z","date_created":"2019-09-15T22:00:43Z","abstract":[{"lang":"eng","text":"Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels control electrical rhythmicity and excitability in the heart and brain, but the function of HCN channels at the subcellular level in axons remains poorly understood. Here, we show that the action potential conduction velocity in both myelinated and unmyelinated central axons can be bidirectionally modulated by a HCN channel blocker, cyclic adenosine monophosphate (cAMP), and neuromodulators. Recordings from mouse cerebellar mossy fiber boutons show that HCN channels ensure reliable high-frequency firing and are strongly modulated by cAMP (EC50 40 mM; estimated endogenous cAMP concentration 13 mM). In addition, immunogold-electron microscopy revealed HCN2 as the dominating subunit in cerebellar mossy fibers. Computational modeling indicated that HCN2 channels control conduction velocity primarily by altering the resting membrane potential\r\nand are associated with significant metabolic costs. These results suggest that the cAMP-HCN pathway provides neuromodulators with an opportunity to finely tune energy consumption and temporal delays across axons in the brain."}],"date_updated":"2023-08-30T06:17:06Z","month":"09","type":"journal_article","oa_version":"Published Version","intvolume":"         8","citation":{"ama":"Byczkowicz N, Eshra A, Montanaro-Punzengruber J-C, et al. HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/eLife.42766\">10.7554/eLife.42766</a>","ista":"Byczkowicz N, Eshra A, Montanaro-Punzengruber J-C, Trevisiol A, Hirrlinger J, Kole MH, Shigemoto R, Hallermann S. 2019. HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons. eLife. 8, e42766.","mla":"Byczkowicz, Niklas, et al. “HCN Channel-Mediated Neuromodulation Can Control Action Potential Velocity and Fidelity in Central Axons.” <i>ELife</i>, vol. 8, e42766, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/eLife.42766\">10.7554/eLife.42766</a>.","apa":"Byczkowicz, N., Eshra, A., Montanaro-Punzengruber, J.-C., Trevisiol, A., Hirrlinger, J., Kole, M. H., … Hallermann, S. (2019). HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.42766\">https://doi.org/10.7554/eLife.42766</a>","ieee":"N. Byczkowicz <i>et al.</i>, “HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","chicago":"Byczkowicz, Niklas, Abdelmoneim Eshra, Jacqueline-Claire Montanaro-Punzengruber, Andrea Trevisiol, Johannes Hirrlinger, Maarten Hp Kole, Ryuichi Shigemoto, and Stefan Hallermann. “HCN Channel-Mediated Neuromodulation Can Control Action Potential Velocity and Fidelity in Central Axons.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/eLife.42766\">https://doi.org/10.7554/eLife.42766</a>.","short":"N. Byczkowicz, A. Eshra, J.-C. Montanaro-Punzengruber, A. Trevisiol, J. Hirrlinger, M.H. Kole, R. Shigemoto, S. Hallermann, ELife 8 (2019)."},"status":"public","external_id":{"isi":["000485663900001"]},"ddc":["570"],"date_published":"2019-09-09T00:00:00Z","oa":1,"publication_status":"published","has_accepted_license":"1"},{"year":"2019","_id":"6877","page":"51-53","date_updated":"2024-03-25T23:30:22Z","type":"journal_article","month":"09","oa_version":"None","volume":179,"date_created":"2019-09-15T22:00:46Z","status":"public","external_id":{"pmid":["31539498"],"isi":["000486618500011"]},"intvolume":"       179","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"6891"}]},"citation":{"mla":"Kopf, Aglaja, and Michael K. Sixt. “The Neural Crest Pitches in to Remove Apoptotic Debris.” <i>Cell</i>, vol. 179, no. 1, Elsevier, 2019, pp. 51–53, doi:<a href=\"https://doi.org/10.1016/j.cell.2019.08.047\">10.1016/j.cell.2019.08.047</a>.","ista":"Kopf A, Sixt MK. 2019. The neural crest pitches in to remove apoptotic debris. Cell. 179(1), 51–53.","apa":"Kopf, A., &#38; Sixt, M. K. (2019). The neural crest pitches in to remove apoptotic debris. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2019.08.047\">https://doi.org/10.1016/j.cell.2019.08.047</a>","ama":"Kopf A, Sixt MK. The neural crest pitches in to remove apoptotic debris. <i>Cell</i>. 2019;179(1):51-53. doi:<a href=\"https://doi.org/10.1016/j.cell.2019.08.047\">10.1016/j.cell.2019.08.047</a>","short":"A. Kopf, M.K. Sixt, Cell 179 (2019) 51–53.","ieee":"A. Kopf and M. K. Sixt, “The neural crest pitches in to remove apoptotic debris,” <i>Cell</i>, vol. 179, no. 1. Elsevier, pp. 51–53, 2019.","chicago":"Kopf, Aglaja, and Michael K Sixt. “The Neural Crest Pitches in to Remove Apoptotic Debris.” <i>Cell</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.cell.2019.08.047\">https://doi.org/10.1016/j.cell.2019.08.047</a>."},"publication_status":"published","date_published":"2019-09-19T00:00:00Z","publisher":"Elsevier","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"department":[{"_id":"MiSi"}],"publication":"Cell","scopus_import":"1","article_processing_charge":"No","article_type":"original","author":[{"full_name":"Kopf, Aglaja","orcid":"0000-0002-2187-6656","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","last_name":"Kopf","first_name":"Aglaja"},{"first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"day":"19","title":"The neural crest pitches in to remove apoptotic debris","isi":1,"language":[{"iso":"eng"}],"issue":"1","publication_identifier":{"issn":["0092-8674"],"eissn":["1097-4172"]},"doi":"10.1016/j.cell.2019.08.047","quality_controlled":"1"},{"quality_controlled":"1","doi":"10.4230/LIPICS.MFCS.2019.11","project":[{"name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"665385"},{"grant_number":"M02369","_id":"264B3912-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Formal Methods meets Algorithmic Game Theory"},{"grant_number":"Z211","name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25F42A32-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","_id":"25F2ACDE-B435-11E9-9278-68D0E5697425","name":"Rigorous Systems Engineering","grant_number":"S11402-N23"}],"language":[{"iso":"eng"}],"conference":{"start_date":"2019-08-26","name":"MFCS: nternational Symposium on Mathematical Foundations of Computer Science","location":"Aachen, Germany","end_date":"2019-08-30"},"file":[{"date_updated":"2020-07-14T12:47:42Z","file_id":"6913","checksum":"6346e116a4f4ed1414174d96d2c4fbd7","date_created":"2019-09-27T11:45:15Z","access_level":"open_access","file_name":"2019_LIPIcs_Avni.pdf","relation":"main_file","content_type":"application/pdf","file_size":554457,"creator":"kschuh"}],"day":"01","author":[{"orcid":"0000-0001-5588-8287","id":"463C8BC2-F248-11E8-B48F-1D18A9856A87","full_name":"Avni, Guy","first_name":"Guy","last_name":"Avni"},{"full_name":"Henzinger, Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724","first_name":"Thomas A","last_name":"Henzinger"},{"last_name":"Zikelic","first_name":"Dorde","id":"294AA7A6-F248-11E8-B48F-1D18A9856A87","full_name":"Zikelic, Dorde"}],"article_number":"11","title":"Bidding mechanisms in graph games","arxiv":1,"department":[{"_id":"ToHe"},{"_id":"KrCh"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"scopus_import":1,"has_accepted_license":"1","oa":1,"publication_status":"published","ddc":["004"],"date_published":"2019-08-01T00:00:00Z","status":"public","external_id":{"arxiv":["1905.03835"]},"alternative_title":["LIPIcs"],"citation":{"ista":"Avni G, Henzinger TA, Zikelic D. 2019. Bidding mechanisms in graph games. MFCS: nternational Symposium on Mathematical Foundations of Computer Science, LIPIcs, vol. 138, 11.","mla":"Avni, Guy, et al. <i>Bidding Mechanisms in Graph Games</i>. Vol. 138, 11, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019, doi:<a href=\"https://doi.org/10.4230/LIPICS.MFCS.2019.11\">10.4230/LIPICS.MFCS.2019.11</a>.","apa":"Avni, G., Henzinger, T. A., &#38; Zikelic, D. (2019). Bidding mechanisms in graph games (Vol. 138). Presented at the MFCS: nternational Symposium on Mathematical Foundations of Computer Science, Aachen, Germany: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. <a href=\"https://doi.org/10.4230/LIPICS.MFCS.2019.11\">https://doi.org/10.4230/LIPICS.MFCS.2019.11</a>","ama":"Avni G, Henzinger TA, Zikelic D. Bidding mechanisms in graph games. In: Vol 138. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2019. doi:<a href=\"https://doi.org/10.4230/LIPICS.MFCS.2019.11\">10.4230/LIPICS.MFCS.2019.11</a>","short":"G. Avni, T.A. Henzinger, D. Zikelic, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019.","ieee":"G. Avni, T. A. Henzinger, and D. Zikelic, “Bidding mechanisms in graph games,” presented at the MFCS: nternational Symposium on Mathematical Foundations of Computer Science, Aachen, Germany, 2019, vol. 138.","chicago":"Avni, Guy, Thomas A Henzinger, and Dorde Zikelic. “Bidding Mechanisms in Graph Games,” Vol. 138. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019. <a href=\"https://doi.org/10.4230/LIPICS.MFCS.2019.11\">https://doi.org/10.4230/LIPICS.MFCS.2019.11</a>."},"related_material":{"record":[{"id":"9239","status":"public","relation":"later_version"}]},"intvolume":"       138","month":"08","oa_version":"Published Version","type":"conference","date_updated":"2023-08-07T14:08:34Z","abstract":[{"text":"In two-player games on graphs, the players move a token through a graph to produce a finite or infinite path, which determines the qualitative winner or quantitative payoff of the game. We study bidding games in which the players bid for the right to move the token. Several bidding rules were studied previously. In Richman bidding, in each round, the players simultaneously submit bids, and the higher bidder moves the token and pays the other player. Poorman bidding is similar except that the winner of the bidding pays the \"bank\" rather than the other player. Taxman bidding spans the spectrum between Richman and poorman bidding. They are parameterized by a constant tau in [0,1]: portion tau of the winning bid is paid to the other player, and portion 1-tau to the bank. While finite-duration (reachability) taxman games have been studied before, we present, for the first time, results on infinite-duration taxman games. It was previously shown that both Richman and poorman infinite-duration games with qualitative objectives reduce to reachability games, and we show a similar result here. Our most interesting results concern quantitative taxman games, namely mean-payoff games, where poorman and Richman bidding differ significantly. A central quantity in these games is the ratio between the two players' initial budgets. While in poorman mean-payoff games, the optimal payoff of a player depends on the initial ratio, in Richman bidding, the payoff depends only on the structure of the game. In both games the optimal payoffs can be found using (different) probabilistic connections with random-turn games in which in each turn, instead of bidding, a coin is tossed to determine which player moves. While the value with Richman bidding equals the value of a random-turn game with an un-biased coin, with poorman bidding, the bias in the coin is the initial ratio of the budgets. We give a complete classification of mean-payoff taxman games that is based on a probabilistic connection: the value of a taxman bidding game with parameter tau and initial ratio r, equals the value of a random-turn game that uses a coin with bias F(tau, r) = (r+tau * (1-r))/(1+tau). Thus, we show that Richman bidding is the exception; namely, for every tau <1, the value of the game depends on the initial ratio. Our proof technique simplifies and unifies the previous proof techniques for both Richman and poorman bidding. ","lang":"eng"}],"date_created":"2019-09-18T08:04:26Z","file_date_updated":"2020-07-14T12:47:42Z","volume":138,"year":"2019","_id":"6884"},{"_id":"6885","year":"2019","file_date_updated":"2020-07-14T12:47:43Z","date_created":"2019-09-18T08:06:14Z","volume":140,"type":"conference","oa_version":"Published Version","month":"08","abstract":[{"lang":"eng","text":"A vector addition system with states (VASS) consists of a finite set of states and counters. A configuration is a state and a value for each counter; a transition changes the state and each counter is incremented, decremented, or left unchanged. While qualitative properties such as state and configuration reachability have been studied for VASS, we consider the long-run average cost of infinite computations of VASS. The cost of a configuration is for each state, a linear combination of the counter values. In the special case of uniform cost functions, the linear combination is the same for all states. The (regular) long-run emptiness problem is, given a VASS, a cost function, and a threshold value, if there is a (lasso-shaped) computation such that the long-run average value of the cost function does not exceed the threshold. For uniform cost functions, we show that the regular long-run emptiness problem is (a) decidable in polynomial time for integer-valued VASS, and (b) decidable but nonelementarily hard for natural-valued VASS (i.e., nonnegative counters). For general cost functions, we show that the problem is (c) NP-complete for integer-valued VASS, and (d) undecidable for natural-valued VASS. Our most interesting result is for (c) integer-valued VASS with general cost functions, where we establish a connection between the regular long-run emptiness problem and quadratic Diophantine inequalities. The general (nonregular) long-run emptiness problem is equally hard as the regular problem in all cases except (c), where it remains open. "}],"date_updated":"2021-01-12T08:09:27Z","citation":{"short":"K. Chatterjee, T.A. Henzinger, J. Otop, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019.","chicago":"Chatterjee, Krishnendu, Thomas A Henzinger, and Jan Otop. “Long-Run Average Behavior of Vector Addition Systems with States,” Vol. 140. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019. <a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.27\">https://doi.org/10.4230/LIPICS.CONCUR.2019.27</a>.","ieee":"K. Chatterjee, T. A. Henzinger, and J. Otop, “Long-run average behavior of vector addition systems with states,” presented at the CONCUR: International Conference on Concurrency Theory, Amsterdam, Netherlands, 2019, vol. 140.","apa":"Chatterjee, K., Henzinger, T. A., &#38; Otop, J. (2019). Long-run average behavior of vector addition systems with states (Vol. 140). Presented at the CONCUR: International Conference on Concurrency Theory, Amsterdam, Netherlands: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. <a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.27\">https://doi.org/10.4230/LIPICS.CONCUR.2019.27</a>","ista":"Chatterjee K, Henzinger TA, Otop J. 2019. Long-run average behavior of vector addition systems with states. CONCUR: International Conference on Concurrency Theory, LIPIcs, vol. 140, 27.","mla":"Chatterjee, Krishnendu, et al. <i>Long-Run Average Behavior of Vector Addition Systems with States</i>. Vol. 140, 27, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019, doi:<a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.27\">10.4230/LIPICS.CONCUR.2019.27</a>.","ama":"Chatterjee K, Henzinger TA, Otop J. Long-run average behavior of vector addition systems with states. In: Vol 140. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2019. doi:<a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.27\">10.4230/LIPICS.CONCUR.2019.27</a>"},"intvolume":"       140","status":"public","alternative_title":["LIPIcs"],"date_published":"2019-08-01T00:00:00Z","ddc":["000"],"has_accepted_license":"1","oa":1,"publication_status":"published","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"scopus_import":1,"department":[{"_id":"ToHe"},{"_id":"KrCh"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","article_number":"27","title":"Long-run average behavior of vector addition systems with states","file":[{"checksum":"4985e26e1572d1575d64d38acabd71d6","file_id":"6914","date_updated":"2020-07-14T12:47:43Z","access_level":"open_access","date_created":"2019-09-27T12:09:35Z","file_name":"2019_LIPIcs_Chatterjee.pdf","creator":"kschuh","file_size":538120,"content_type":"application/pdf","relation":"main_file"}],"day":"01","author":[{"first_name":"Krishnendu","last_name":"Chatterjee","full_name":"Chatterjee, Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4561-241X"},{"first_name":"Thomas A","last_name":"Henzinger","full_name":"Henzinger, Thomas A","orcid":"0000−0002−2985−7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Otop, Jan","last_name":"Otop","first_name":"Jan"}],"language":[{"iso":"eng"}],"conference":{"name":"CONCUR: International Conference on Concurrency Theory","location":"Amsterdam, Netherlands","start_date":"2019-08-27","end_date":"2019-08-30"},"project":[{"name":"Game Theory","_id":"25863FF4-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"S11407"},{"grant_number":"S11402-N23","call_identifier":"FWF","_id":"25F2ACDE-B435-11E9-9278-68D0E5697425","name":"Rigorous Systems Engineering"}],"quality_controlled":"1","doi":"10.4230/LIPICS.CONCUR.2019.27"},{"tmp":{"short":"CC BY (3.0)","name":"Creative Commons Attribution 3.0 Unported (CC BY 3.0)","legal_code_url":"https://creativecommons.org/licenses/by/3.0/legalcode","image":"/images/cc_by.png"},"scopus_import":"1","article_processing_charge":"No","department":[{"_id":"ToHe"}],"publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","article_number":"20","arxiv":1,"title":"Determinacy in discrete-bidding infinite-duration games","file":[{"file_name":"2019_LIPIcs_Aghajohari.pdf","creator":"kschuh","file_size":741425,"content_type":"application/pdf","relation":"main_file","checksum":"4df6d3575c506edb17215adada03cc8e","file_id":"6915","date_updated":"2020-07-14T12:47:43Z","access_level":"open_access","date_created":"2019-09-27T12:21:38Z"}],"license":"https://creativecommons.org/licenses/by/3.0/","day":"01","author":[{"full_name":"Aghajohari, Milad","last_name":"Aghajohari","first_name":"Milad"},{"orcid":"0000-0001-5588-8287","id":"463C8BC2-F248-11E8-B48F-1D18A9856A87","full_name":"Avni, Guy","last_name":"Avni","first_name":"Guy"},{"id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724","full_name":"Henzinger, Thomas A","last_name":"Henzinger","first_name":"Thomas A"}],"language":[{"iso":"eng"}],"conference":{"end_date":"2019-08-30","name":"CONCUR: International Conference on Concurrency Theory","location":"Amsterdam, Netherlands","start_date":"2019-08-27"},"project":[{"_id":"25F2ACDE-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Rigorous Systems Engineering","grant_number":"S11402-N23"},{"grant_number":"M02369","name":"Formal Methods meets Algorithmic Game Theory","_id":"264B3912-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"quality_controlled":"1","doi":"10.4230/LIPICS.CONCUR.2019.20","_id":"6886","year":"2019","date_created":"2019-09-18T08:06:58Z","file_date_updated":"2020-07-14T12:47:43Z","volume":140,"type":"conference","oa_version":"Published Version","month":"08","abstract":[{"lang":"eng","text":"In two-player games on graphs, the players move a token through a graph to produce an infinite path, which determines the winner of the game. Such games are central in formal methods since they model the interaction between a non-terminating system and its environment. In bidding games the players bid for the right to move the token: in each round, the players simultaneously submit bids, and the higher bidder moves the token and pays the other player. Bidding games are known to have a clean and elegant mathematical structure that relies on the ability of the players to submit arbitrarily small bids. Many applications, however, require a fixed granularity for the bids, which can represent, for example, the monetary value expressed in cents. We study, for the first time, the combination of discrete-bidding and infinite-duration games. Our most important result proves that these games form a large determined subclass of concurrent games, where determinacy is the strong property that there always exists exactly one player who can guarantee winning the game. In particular, we show that, in contrast to non-discrete bidding games, the mechanism with which tied bids are resolved plays an important role in discrete-bidding games. We study several natural tie-breaking mechanisms and show that, while some do not admit determinacy, most natural mechanisms imply determinacy for every pair of initial budgets. "}],"date_updated":"2022-01-26T08:27:10Z","citation":{"mla":"Aghajohari, Milad, et al. <i>Determinacy in Discrete-Bidding Infinite-Duration Games</i>. Vol. 140, 20, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019, doi:<a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.20\">10.4230/LIPICS.CONCUR.2019.20</a>.","ista":"Aghajohari M, Avni G, Henzinger TA. 2019. Determinacy in discrete-bidding infinite-duration games. CONCUR: International Conference on Concurrency Theory, LIPIcs, vol. 140, 20.","apa":"Aghajohari, M., Avni, G., &#38; Henzinger, T. A. (2019). Determinacy in discrete-bidding infinite-duration games (Vol. 140). Presented at the CONCUR: International Conference on Concurrency Theory, Amsterdam, Netherlands: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. <a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.20\">https://doi.org/10.4230/LIPICS.CONCUR.2019.20</a>","ama":"Aghajohari M, Avni G, Henzinger TA. Determinacy in discrete-bidding infinite-duration games. In: Vol 140. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2019. doi:<a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.20\">10.4230/LIPICS.CONCUR.2019.20</a>","short":"M. Aghajohari, G. Avni, T.A. Henzinger, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019.","ieee":"M. Aghajohari, G. Avni, and T. A. Henzinger, “Determinacy in discrete-bidding infinite-duration games,” presented at the CONCUR: International Conference on Concurrency Theory, Amsterdam, Netherlands, 2019, vol. 140.","chicago":"Aghajohari, Milad, Guy Avni, and Thomas A Henzinger. “Determinacy in Discrete-Bidding Infinite-Duration Games,” Vol. 140. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019. <a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.20\">https://doi.org/10.4230/LIPICS.CONCUR.2019.20</a>."},"intvolume":"       140","status":"public","external_id":{"arxiv":["1905.03588"]},"alternative_title":["LIPIcs"],"ddc":["000"],"date_published":"2019-08-01T00:00:00Z","has_accepted_license":"1","publication_status":"published","oa":1},{"intvolume":"       140","citation":{"apa":"Chatterjee, K., Dvorák, W., Henzinger, M. H., &#38; Svozil, A. (2019). Near-linear time algorithms for Streett objectives in graphs and MDPs. In <i>Leibniz International Proceedings in Informatics</i> (Vol. 140). Amsterdam, Netherlands: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. <a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.7\">https://doi.org/10.4230/LIPICS.CONCUR.2019.7</a>","mla":"Chatterjee, Krishnendu, et al. “Near-Linear Time Algorithms for Streett Objectives in Graphs and MDPs.” <i>Leibniz International Proceedings in Informatics</i>, vol. 140, 7, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019, doi:<a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.7\">10.4230/LIPICS.CONCUR.2019.7</a>.","ista":"Chatterjee K, Dvorák W, Henzinger MH, Svozil A. 2019. Near-linear time algorithms for Streett objectives in graphs and MDPs. Leibniz International Proceedings in Informatics. CONCUR: International Conference on Concurrency Theory, LIPIcs, vol. 140, 7.","ama":"Chatterjee K, Dvorák W, Henzinger MH, Svozil A. Near-linear time algorithms for Streett objectives in graphs and MDPs. In: <i>Leibniz International Proceedings in Informatics</i>. Vol 140. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2019. doi:<a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.7\">10.4230/LIPICS.CONCUR.2019.7</a>","short":"K. Chatterjee, W. Dvorák, M.H. Henzinger, A. Svozil, in:, Leibniz International Proceedings in Informatics, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019.","chicago":"Chatterjee, Krishnendu, Wolfgang Dvorák, Monika H Henzinger, and Alexander Svozil. “Near-Linear Time Algorithms for Streett Objectives in Graphs and MDPs.” In <i>Leibniz International Proceedings in Informatics</i>, Vol. 140. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019. <a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.7\">https://doi.org/10.4230/LIPICS.CONCUR.2019.7</a>.","ieee":"K. Chatterjee, W. Dvorák, M. H. Henzinger, and A. Svozil, “Near-linear time algorithms for Streett objectives in graphs and MDPs,” in <i>Leibniz International Proceedings in Informatics</i>, Amsterdam, Netherlands, 2019, vol. 140."},"alternative_title":["LIPIcs"],"status":"public","ddc":["000"],"date_published":"2019-08-01T00:00:00Z","oa":1,"publication_status":"published","has_accepted_license":"1","_id":"6887","year":"2019","volume":140,"file_date_updated":"2020-07-14T12:47:43Z","date_created":"2019-09-18T08:07:58Z","type":"conference","month":"08","oa_version":"Published Version","abstract":[{"text":"The fundamental model-checking problem, given as input a model and a specification, asks for the algorithmic verification of whether the model satisfies the specification. Two classical models for reactive systems are graphs and Markov decision processes (MDPs). A basic specification formalism in the verification of reactive systems is the strong fairness (aka Streett) objective, where given different types of requests and corresponding grants, the requirement is that for each type, if the request event happens infinitely often, then the corresponding grant event must also happen infinitely often. All omega-regular objectives can be expressed as Streett objectives and hence they are canonical in verification. Consider graphs/MDPs with n vertices, m edges, and a Streett objectives with k pairs, and let b denote the size of the description of the Streett objective for the sets of requests and grants. The current best-known algorithm for the problem requires time O(min(n^2, m sqrt{m log n}) + b log n). In this work we present randomized near-linear time algorithms, with expected running time O~(m + b), where the O~ notation hides poly-log factors. Our randomized algorithms are near-linear in the size of the input, and hence optimal up to poly-log factors. ","lang":"eng"}],"date_updated":"2022-08-12T10:54:34Z","conference":{"end_date":"2019-08-30","name":"CONCUR: International Conference on Concurrency Theory","location":"Amsterdam, Netherlands","start_date":"2019-08-27"},"language":[{"iso":"eng"}],"project":[{"grant_number":"S11407","name":"Game Theory","call_identifier":"FWF","_id":"25863FF4-B435-11E9-9278-68D0E5697425"},{"grant_number":"279307","name":"Quantitative Graph Games: Theory and Applications","_id":"2581B60A-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"doi":"10.4230/LIPICS.CONCUR.2019.7","quality_controlled":"1","publication":"Leibniz International Proceedings in Informatics","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"scopus_import":"1","article_processing_charge":"No","publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","department":[{"_id":"KrCh"}],"article_number":"7","title":"Near-linear time algorithms for Streett objectives in graphs and MDPs","author":[{"orcid":"0000-0002-4561-241X","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","full_name":"Chatterjee, Krishnendu","last_name":"Chatterjee","first_name":"Krishnendu"},{"full_name":"Dvorák, Wolfgang","first_name":"Wolfgang","last_name":"Dvorák"},{"first_name":"Monika H","last_name":"Henzinger","full_name":"Henzinger, Monika H","id":"540c9bbd-f2de-11ec-812d-d04a5be85630","orcid":"0000-0002-5008-6530"},{"first_name":"Alexander","last_name":"Svozil","full_name":"Svozil, Alexander"}],"day":"01","file":[{"access_level":"open_access","date_created":"2019-10-01T08:20:30Z","checksum":"e1f0e4061212454574f34a1368d018ec","date_updated":"2020-07-14T12:47:43Z","file_id":"6922","creator":"kschuh","relation":"main_file","content_type":"application/pdf","file_size":730112,"file_name":"2019_LIPIcs_Chatterjee.pdf"}]},{"project":[{"call_identifier":"FWF","_id":"25F42A32-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","grant_number":"Z211"}],"conference":{"start_date":"2019-05-20","name":"ICRA: International Conference on Robotics and Automation","location":"Montreal, QC, Canada","end_date":"2019-05-24"},"language":[{"iso":"eng"}],"publication_identifier":{"isbn":["9781538660270"]},"doi":"10.1109/icra.2019.8793840","quality_controlled":"1","user_id":"D865714E-FA4E-11E9-B85B-F5C5E5697425","publisher":"IEEE","department":[{"_id":"ToHe"}],"publication":"Proceedings - IEEE International Conference on Robotics and Automation","scopus_import":"1","article_processing_charge":"No","author":[{"id":"3DC22916-F248-11E8-B48F-1D18A9856A87","full_name":"Lechner, Mathias","first_name":"Mathias","last_name":"Lechner"},{"last_name":"Hasani","first_name":"Ramin","full_name":"Hasani, Ramin"},{"full_name":"Zimmer, Manuel","last_name":"Zimmer","first_name":"Manuel"},{"first_name":"Thomas A","last_name":"Henzinger","full_name":"Henzinger, Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","orcid":"0000−0002−2985−7724"},{"first_name":"Radu","last_name":"Grosu","full_name":"Grosu, Radu"}],"day":"01","file":[{"checksum":"f5545a6b60c3ffd01feb3613f81d03b6","file_id":"8636","date_updated":"2020-10-08T17:30:38Z","access_level":"open_access","date_created":"2020-10-08T17:30:38Z","file_name":"2019_ICRA_Lechner.pdf","success":1,"creator":"dernst","file_size":3265107,"relation":"main_file","content_type":"application/pdf"}],"article_number":"8793840","title":"Designing worm-inspired neural networks for interpretable robotic control","alternative_title":["ICRA"],"status":"public","citation":{"ama":"Lechner M, Hasani R, Zimmer M, Henzinger TA, Grosu R. Designing worm-inspired neural networks for interpretable robotic control. In: <i>Proceedings - IEEE International Conference on Robotics and Automation</i>. Vol 2019-May. IEEE; 2019. doi:<a href=\"https://doi.org/10.1109/icra.2019.8793840\">10.1109/icra.2019.8793840</a>","apa":"Lechner, M., Hasani, R., Zimmer, M., Henzinger, T. A., &#38; Grosu, R. (2019). Designing worm-inspired neural networks for interpretable robotic control. In <i>Proceedings - IEEE International Conference on Robotics and Automation</i> (Vol. 2019–May). Montreal, QC, Canada: IEEE. <a href=\"https://doi.org/10.1109/icra.2019.8793840\">https://doi.org/10.1109/icra.2019.8793840</a>","ista":"Lechner M, Hasani R, Zimmer M, Henzinger TA, Grosu R. 2019. Designing worm-inspired neural networks for interpretable robotic control. Proceedings - IEEE International Conference on Robotics and Automation. ICRA: International Conference on Robotics and Automation, ICRA, vol. 2019–May, 8793840.","mla":"Lechner, Mathias, et al. “Designing Worm-Inspired Neural Networks for Interpretable Robotic Control.” <i>Proceedings - IEEE International Conference on Robotics and Automation</i>, vol. 2019–May, 8793840, IEEE, 2019, doi:<a href=\"https://doi.org/10.1109/icra.2019.8793840\">10.1109/icra.2019.8793840</a>.","chicago":"Lechner, Mathias, Ramin Hasani, Manuel Zimmer, Thomas A Henzinger, and Radu Grosu. “Designing Worm-Inspired Neural Networks for Interpretable Robotic Control.” In <i>Proceedings - IEEE International Conference on Robotics and Automation</i>, Vol. 2019–May. IEEE, 2019. <a href=\"https://doi.org/10.1109/icra.2019.8793840\">https://doi.org/10.1109/icra.2019.8793840</a>.","ieee":"M. Lechner, R. Hasani, M. Zimmer, T. A. Henzinger, and R. Grosu, “Designing worm-inspired neural networks for interpretable robotic control,” in <i>Proceedings - IEEE International Conference on Robotics and Automation</i>, Montreal, QC, Canada, 2019, vol. 2019–May.","short":"M. Lechner, R. Hasani, M. Zimmer, T.A. Henzinger, R. Grosu, in:, Proceedings - IEEE International Conference on Robotics and Automation, IEEE, 2019."},"publication_status":"published","oa":1,"has_accepted_license":"1","ddc":["000"],"date_published":"2019-05-01T00:00:00Z","year":"2019","_id":"6888","type":"conference","oa_version":"Submitted Version","month":"05","date_updated":"2021-01-12T08:09:28Z","abstract":[{"lang":"eng","text":"In this paper, we design novel liquid time-constant recurrent neural networks for robotic control, inspired by the brain of the nematode, C. elegans. In the worm's nervous system, neurons communicate through nonlinear time-varying synaptic links established amongst them by their particular wiring structure. This property enables neurons to express liquid time-constants dynamics and therefore allows the network to originate complex behaviors with a small number of neurons. We identify neuron-pair communication motifs as design operators and use them to configure compact neuronal network structures to govern sequential robotic tasks. The networks are systematically designed to map the environmental observations to motor actions, by their hierarchical topology from sensory neurons, through recurrently-wired interneurons, to motor neurons. The networks are then parametrized in a supervised-learning scheme by a search-based algorithm. We demonstrate that obtained networks realize interpretable dynamics. We evaluate their performance in controlling mobile and arm robots, and compare their attributes to other artificial neural network-based control agents. Finally, we experimentally show their superior resilience to environmental noise, compared to the existing machine learning-based methods."}],"volume":"2019-May","file_date_updated":"2020-10-08T17:30:38Z","date_created":"2019-09-18T08:09:51Z"},{"_id":"6889","year":"2019","volume":140,"file_date_updated":"2020-07-14T12:47:43Z","date_created":"2019-09-18T08:11:43Z","type":"conference","month":"08","oa_version":"Published Version","abstract":[{"text":"We study Markov decision processes and turn-based stochastic games with parity conditions. There are three qualitative winning criteria, namely, sure winning, which requires all paths to satisfy the condition, almost-sure winning, which requires the condition to be satisfied with probability 1, and limit-sure winning, which requires the condition to be satisfied with probability arbitrarily close to 1. We study the combination of two of these criteria for parity conditions, e.g., there are two parity conditions one of which must be won surely, and the other almost-surely. The problem has been studied recently by Berthon et al. for MDPs with combination of sure and almost-sure winning, under infinite-memory strategies, and the problem has been established to be in NP cap co-NP. Even in MDPs there is a difference between finite-memory and infinite-memory strategies. Our main results for combination of sure and almost-sure winning are as follows: (a) we show that for MDPs with finite-memory strategies the problem is in NP cap co-NP; (b) we show that for turn-based stochastic games the problem is co-NP-complete, both for finite-memory and infinite-memory strategies; and (c) we present algorithmic results for the finite-memory case, both for MDPs and turn-based stochastic games, by reduction to non-stochastic parity games. In addition we show that all the above complexity results also carry over to combination of sure and limit-sure winning, and results for all other combinations can be derived from existing results in the literature. Thus we present a complete picture for the study of combinations of two qualitative winning criteria for parity conditions in MDPs and turn-based stochastic games. ","lang":"eng"}],"date_updated":"2021-01-12T08:09:28Z","intvolume":"       140","citation":{"ama":"Chatterjee K, Piterman N. Combinations of Qualitative Winning for Stochastic Parity Games. In: Vol 140. Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2019. doi:<a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.6\">10.4230/LIPICS.CONCUR.2019.6</a>","apa":"Chatterjee, K., &#38; Piterman, N. (2019). Combinations of Qualitative Winning for Stochastic Parity Games (Vol. 140). Presented at the CONCUR: International Conference on Concurrency Theory, Amsterdam, Netherlands: Schloss Dagstuhl - Leibniz-Zentrum für Informatik. <a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.6\">https://doi.org/10.4230/LIPICS.CONCUR.2019.6</a>","ista":"Chatterjee K, Piterman N. 2019. Combinations of Qualitative Winning for Stochastic Parity Games. CONCUR: International Conference on Concurrency Theory, LIPIcs, vol. 140, 6.","mla":"Chatterjee, Krishnendu, and Nir Piterman. <i>Combinations of Qualitative Winning for Stochastic Parity Games</i>. Vol. 140, 6, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019, doi:<a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.6\">10.4230/LIPICS.CONCUR.2019.6</a>.","chicago":"Chatterjee, Krishnendu, and Nir Piterman. “Combinations of Qualitative Winning for Stochastic Parity Games,” Vol. 140. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019. <a href=\"https://doi.org/10.4230/LIPICS.CONCUR.2019.6\">https://doi.org/10.4230/LIPICS.CONCUR.2019.6</a>.","ieee":"K. Chatterjee and N. Piterman, “Combinations of Qualitative Winning for Stochastic Parity Games,” presented at the CONCUR: International Conference on Concurrency Theory, Amsterdam, Netherlands, 2019, vol. 140.","short":"K. Chatterjee, N. Piterman, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2019."},"alternative_title":["LIPIcs"],"status":"public","ddc":["000"],"date_published":"2019-08-01T00:00:00Z","publication_status":"published","oa":1,"has_accepted_license":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"scopus_import":1,"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publisher":"Schloss Dagstuhl - Leibniz-Zentrum für Informatik","department":[{"_id":"KrCh"}],"article_number":"6","title":"Combinations of Qualitative Winning for Stochastic Parity Games","author":[{"full_name":"Chatterjee, Krishnendu","orcid":"0000-0002-4561-241X","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","last_name":"Chatterjee","first_name":"Krishnendu"},{"first_name":"Nir","last_name":"Piterman","full_name":"Piterman, Nir"}],"file":[{"date_created":"2019-10-01T08:49:45Z","access_level":"open_access","file_id":"6923","date_updated":"2020-07-14T12:47:43Z","checksum":"7b2ecfd4d9d02360308c0ca986fc10a7","file_size":509163,"relation":"main_file","content_type":"application/pdf","creator":"kschuh","file_name":"2019_LIPIcs_Chatterjee.pdf"}],"day":"01","conference":{"start_date":"2019-08-27","location":"Amsterdam, Netherlands","name":"CONCUR: International Conference on Concurrency Theory","end_date":"2019-08-30"},"language":[{"iso":"eng"}],"project":[{"_id":"25863FF4-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Game Theory","grant_number":"S11407"},{"name":"Efficient Algorithms for Computer Aided Verification","_id":"25892FC0-B435-11E9-9278-68D0E5697425","grant_number":"ICT15-003"}],"doi":"10.4230/LIPICS.CONCUR.2019.6","quality_controlled":"1"},{"date_published":"2019-08-27T00:00:00Z","publication_status":"published","intvolume":"       105","citation":{"ama":"Obr M, Schur FK. Structural analysis of pleomorphic and asymmetric viruses using cryo-electron tomography and subtomogram averaging. In: Rey FA, ed. <i>Complementary Strategies to Study Virus Structure and Function</i>. Vol 105. Advances in Virus Research. Elsevier; 2019:117-159. doi:<a href=\"https://doi.org/10.1016/bs.aivir.2019.07.008\">10.1016/bs.aivir.2019.07.008</a>","ista":"Obr M, Schur FK. 2019.Structural analysis of pleomorphic and asymmetric viruses using cryo-electron tomography and subtomogram averaging. In: Complementary Strategies to Study Virus Structure and Function. vol. 105, 117–159.","mla":"Obr, Martin, and Florian KM Schur. “Structural Analysis of Pleomorphic and Asymmetric Viruses Using Cryo-Electron Tomography and Subtomogram Averaging.” <i>Complementary Strategies to Study Virus Structure and Function</i>, edited by Félix A. Rey, vol. 105, Elsevier, 2019, pp. 117–59, doi:<a href=\"https://doi.org/10.1016/bs.aivir.2019.07.008\">10.1016/bs.aivir.2019.07.008</a>.","apa":"Obr, M., &#38; Schur, F. K. (2019). Structural analysis of pleomorphic and asymmetric viruses using cryo-electron tomography and subtomogram averaging. In F. A. Rey (Ed.), <i>Complementary Strategies to Study Virus Structure and Function</i> (Vol. 105, pp. 117–159). Elsevier. <a href=\"https://doi.org/10.1016/bs.aivir.2019.07.008\">https://doi.org/10.1016/bs.aivir.2019.07.008</a>","ieee":"M. Obr and F. K. Schur, “Structural analysis of pleomorphic and asymmetric viruses using cryo-electron tomography and subtomogram averaging,” in <i>Complementary Strategies to Study Virus Structure and Function</i>, vol. 105, F. A. Rey, Ed. Elsevier, 2019, pp. 117–159.","chicago":"Obr, Martin, and Florian KM Schur. “Structural Analysis of Pleomorphic and Asymmetric Viruses Using Cryo-Electron Tomography and Subtomogram Averaging.” In <i>Complementary Strategies to Study Virus Structure and Function</i>, edited by Félix A. Rey, 105:117–59. Advances in Virus Research. Elsevier, 2019. <a href=\"https://doi.org/10.1016/bs.aivir.2019.07.008\">https://doi.org/10.1016/bs.aivir.2019.07.008</a>.","short":"M. Obr, F.K. Schur, in:, F.A. Rey (Ed.), Complementary Strategies to Study Virus Structure and Function, Elsevier, 2019, pp. 117–159."},"editor":[{"full_name":"Rey, Félix A.","first_name":"Félix A.","last_name":"Rey"}],"status":"public","external_id":{"isi":["000501594500006"],"pmid":["    31522703"]},"volume":105,"date_created":"2019-09-18T08:15:37Z","page":"117-159","date_updated":"2023-08-30T06:56:00Z","abstract":[{"text":"Describing the protein interactions that form pleomorphic and asymmetric viruses represents a considerable challenge to most structural biology techniques, including X-ray crystallography and single particle cryo-electron microscopy. Obtaining a detailed understanding of these interactions is nevertheless important, considering the number of relevant human pathogens that do not follow strict icosahedral or helical symmetry. Cryo-electron tomography and subtomogram averaging methods provide structural insights into complex biological environments and are well suited to go beyond structures of perfectly symmetric viruses. This chapter discusses recent developments showing that cryo-ET and subtomogram averaging can provide high-resolution insights into hitherto unknown structural features of pleomorphic and asymmetric virus particles. It also describes how these methods have significantly added to our understanding of retrovirus capsid assemblies in immature and mature viruses. Additional examples of irregular viruses and their associated proteins, whose structures have been studied via cryo-ET and subtomogram averaging, further support the versatility of these methods.","lang":"eng"}],"type":"book_chapter","month":"08","oa_version":"None","_id":"6890","year":"2019","doi":"10.1016/bs.aivir.2019.07.008","quality_controlled":"1","publication_identifier":{"issn":["0065-3527"],"isbn":["9780128184561"]},"isi":1,"series_title":"Advances in Virus Research","language":[{"iso":"eng"}],"title":"Structural analysis of pleomorphic and asymmetric viruses using cryo-electron tomography and subtomogram averaging","author":[{"full_name":"Obr, Martin","orcid":"0000-0003-1756-6564","id":"4741CA5A-F248-11E8-B48F-1D18A9856A87","last_name":"Obr","first_name":"Martin"},{"id":"48AD8942-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4790-8078","full_name":"Schur, Florian KM","last_name":"Schur","first_name":"Florian KM"}],"day":"27","publication":"Complementary Strategies to Study Virus Structure and Function","scopus_import":"1","article_processing_charge":"No","publisher":"Elsevier","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"department":[{"_id":"FlSc"}]},{"degree_awarded":"PhD","title":"The implication of cytoskeletal dynamics on leukocyte migration","day":"24","file":[{"date_updated":"2020-10-17T22:30:03Z","file_id":"6950","checksum":"00d100d6468e31e583051e0a006b640c","date_created":"2019-10-15T05:28:42Z","access_level":"closed","file_name":"Kopf_PhD_Thesis.docx","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":74735267,"creator":"akopf","embargo_to":"open_access"},{"date_updated":"2020-10-17T22:30:03Z","file_id":"6951","checksum":"5d1baa899993ae6ca81aebebe1797000","date_created":"2019-10-15T05:28:47Z","access_level":"open_access","file_name":"Kopf_PhD_Thesis1.pdf","content_type":"application/pdf","embargo":"2020-10-16","relation":"main_file","file_size":52787224,"creator":"akopf"}],"author":[{"id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2187-6656","full_name":"Kopf, Aglaja","first_name":"Aglaja","last_name":"Kopf"}],"article_processing_charge":"No","department":[{"_id":"MiSi"}],"publisher":"Institute of Science and Technology Austria","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","doi":"10.15479/AT:ISTA:6891","publication_identifier":{"eissn":["2663-337X"],"isbn":["978-3-99078-002-2"]},"language":[{"iso":"eng"}],"keyword":["cell biology","immunology","leukocyte","migration","microfluidics"],"project":[{"grant_number":"W01250-B20","name":"Nano-Analytics of Cellular Systems","call_identifier":"FWF","_id":"265E2996-B435-11E9-9278-68D0E5697425"}],"date_created":"2019-09-19T08:19:44Z","file_date_updated":"2020-10-17T22:30:03Z","oa_version":"Published Version","type":"dissertation","month":"07","abstract":[{"text":"While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance. \r\nCells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients. \r\nNevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner. \r\nTherefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments. \r\nThe results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate. \r\nThus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration. \r\nThereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance.\r\n","lang":"eng"}],"date_updated":"2023-10-18T08:49:17Z","page":"171","_id":"6891","year":"2019","date_published":"2019-07-24T00:00:00Z","ddc":["570"],"supervisor":[{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","first_name":"Michael K","last_name":"Sixt"}],"has_accepted_license":"1","oa":1,"publication_status":"published","citation":{"mla":"Kopf, Aglaja. <i>The Implication of Cytoskeletal Dynamics on Leukocyte Migration</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6891\">10.15479/AT:ISTA:6891</a>.","ista":"Kopf A. 2019. The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria.","apa":"Kopf, A. (2019). <i>The implication of cytoskeletal dynamics on leukocyte migration</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6891\">https://doi.org/10.15479/AT:ISTA:6891</a>","ama":"Kopf A. The implication of cytoskeletal dynamics on leukocyte migration. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6891\">10.15479/AT:ISTA:6891</a>","short":"A. Kopf, The Implication of Cytoskeletal Dynamics on Leukocyte Migration, Institute of Science and Technology Austria, 2019.","ieee":"A. Kopf, “The implication of cytoskeletal dynamics on leukocyte migration,” Institute of Science and Technology Austria, 2019.","chicago":"Kopf, Aglaja. “The Implication of Cytoskeletal Dynamics on Leukocyte Migration.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6891\">https://doi.org/10.15479/AT:ISTA:6891</a>."},"related_material":{"link":[{"url":"https://ist.ac.at/en/news/feeling-like-a-cell/","relation":"press_release"}],"record":[{"relation":"part_of_dissertation","id":"6328","status":"public"},{"relation":"part_of_dissertation","id":"15","status":"public"},{"relation":"part_of_dissertation","id":"6877","status":"public"}]},"status":"public","alternative_title":["ISTA Thesis"]},{"alternative_title":["ISTA Thesis"],"status":"public","related_material":{"record":[{"id":"631","status":"public","relation":"part_of_dissertation"},{"status":"public","id":"647","relation":"part_of_dissertation"},{"status":"public","id":"140","relation":"part_of_dissertation"}]},"citation":{"ieee":"M. Giacobbe, “Automatic time-unbounded reachability analysis of hybrid systems,” Institute of Science and Technology Austria, 2019.","chicago":"Giacobbe, Mirco. “Automatic Time-Unbounded Reachability Analysis of Hybrid Systems.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6894\">https://doi.org/10.15479/AT:ISTA:6894</a>.","short":"M. Giacobbe, Automatic Time-Unbounded Reachability Analysis of Hybrid Systems, Institute of Science and Technology Austria, 2019.","ama":"Giacobbe M. Automatic time-unbounded reachability analysis of hybrid systems. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6894\">10.15479/AT:ISTA:6894</a>","ista":"Giacobbe M. 2019. Automatic time-unbounded reachability analysis of hybrid systems. Institute of Science and Technology Austria.","mla":"Giacobbe, Mirco. <i>Automatic Time-Unbounded Reachability Analysis of Hybrid Systems</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6894\">10.15479/AT:ISTA:6894</a>.","apa":"Giacobbe, M. (2019). <i>Automatic time-unbounded reachability analysis of hybrid systems</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6894\">https://doi.org/10.15479/AT:ISTA:6894</a>"},"publication_status":"published","oa":1,"has_accepted_license":"1","supervisor":[{"orcid":"0000−0002−2985−7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","full_name":"Henzinger, Thomas A","first_name":"Thomas A","last_name":"Henzinger"}],"ddc":["000"],"date_published":"2019-09-30T00:00:00Z","year":"2019","_id":"6894","page":"132","date_updated":"2023-09-19T09:30:43Z","abstract":[{"text":"Hybrid automata combine finite automata and dynamical systems, and model the interaction of digital with physical systems. Formal analysis that can guarantee the safety of all behaviors or rigorously witness failures, while unsolvable in general, has been tackled algorithmically using, e.g., abstraction, bounded model-checking, assisted theorem proving.\r\nNevertheless, very few methods have addressed the time-unbounded reachability analysis of hybrid automata and, for current sound and automatic tools, scalability remains critical. We develop methods for the polyhedral abstraction of hybrid automata, which construct coarse overapproximations and tightens them incrementally, in a CEGAR fashion. We use template polyhedra, i.e., polyhedra whose facets are normal to a given set of directions.\r\nWhile, previously, directions were given by the user, we introduce (1) the first method\r\nfor computing template directions from spurious counterexamples, so as to generalize and\r\neliminate them. The method applies naturally to convex hybrid automata, i.e., hybrid\r\nautomata with (possibly non-linear) convex constraints on derivatives only, while for linear\r\nODE requires further abstraction. Specifically, we introduce (2) the conic abstractions,\r\nwhich, partitioning the state space into appropriate (possibly non-uniform) cones, divide\r\ncurvy trajectories into relatively straight sections, suitable for polyhedral abstractions.\r\nFinally, we introduce (3) space-time interpolation, which, combining interval arithmetic\r\nand template refinement, computes appropriate (possibly non-uniform) time partitioning\r\nand template directions along spurious trajectories, so as to eliminate them.\r\nWe obtain sound and automatic methods for the reachability analysis over dense\r\nand unbounded time of convex hybrid automata and hybrid automata with linear ODE.\r\nWe build prototype tools and compare—favorably—our methods against the respective\r\nstate-of-the-art tools, on several benchmarks.","lang":"eng"}],"type":"dissertation","oa_version":"Published Version","month":"09","date_created":"2019-09-22T14:08:44Z","file_date_updated":"2020-07-14T12:47:43Z","language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2663-337X"]},"doi":"10.15479/AT:ISTA:6894","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publisher":"Institute of Science and Technology Austria","department":[{"_id":"ToHe"}],"article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"author":[{"orcid":"0000-0001-8180-0904","id":"3444EA5E-F248-11E8-B48F-1D18A9856A87","full_name":"Giacobbe, Mirco","first_name":"Mirco","last_name":"Giacobbe"}],"file":[{"date_created":"2019-09-27T14:15:05Z","access_level":"open_access","date_updated":"2020-07-14T12:47:43Z","file_id":"6916","checksum":"773beaf4a85dc2acc2c12b578fbe1965","content_type":"application/pdf","relation":"main_file","file_size":4100685,"creator":"mgiacobbe","file_name":"giacobbe_thesis.pdf"},{"checksum":"97f1c3da71feefd27e6e625d32b4c75b","date_updated":"2020-07-14T12:47:43Z","file_id":"6917","access_level":"closed","date_created":"2019-09-27T14:22:04Z","file_name":"giacobbe_thesis_src.tar.gz","creator":"mgiacobbe","relation":"source_file","content_type":"application/gzip","file_size":7959732}],"day":"30","title":"Automatic time-unbounded reachability analysis of hybrid systems","degree_awarded":"PhD"},{"publisher":"Elsevier","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"GaNo"}],"pmid":1,"publication":"Brain Research","article_type":"original","article_processing_charge":"No","scopus_import":"1","author":[{"last_name":"Oliveira","first_name":"Bárbara","full_name":"Oliveira, Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Yahya, Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","last_name":"Yahya","first_name":"Aysan Çerağ"},{"first_name":"Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"day":"01","article_number":"146458","title":"Modeling cell-cell interactions in the brain using cerebral organoids","isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["18726240"],"issn":["00068993"]},"doi":"10.1016/j.brainres.2019.146458","quality_controlled":"1","year":"2019","_id":"6896","month":"12","type":"journal_article","oa_version":"None","date_updated":"2023-08-30T06:19:49Z","abstract":[{"lang":"eng","text":"Until recently, a great amount of brain studies have been conducted in human post mortem tissues, cell lines and model organisms. These researches provided useful insights regarding cell-cell interactions occurring in the brain. However, such approaches suffer from technical limitations and inaccurate modeling of the tissue 3D cytoarchitecture. Importantly, they might lack a human genetic background essential for disease modeling. With the development of protocols to generate human cerebral organoids, we are now closer to reproducing the early stages of human brain development in vitro. As a result, more relevant cell-cell interaction studies can be conducted.\r\n\r\nIn this review, we discuss the advantages of 3D cultures over 2D in modulating brain cell-cell interactions during physiological and pathological development, as well as the progress made in developing organoids in which neurons, macroglia, microglia and vascularization are present. Finally, we debate the limitations of those models and possible future directions."}],"volume":1724,"date_created":"2019-09-22T22:00:35Z","status":"public","external_id":{"isi":["000491646600033"],"pmid":["31521639"]},"intvolume":"      1724","citation":{"mla":"Oliveira, Bárbara, et al. “Modeling Cell-Cell Interactions in the Brain Using Cerebral Organoids.” <i>Brain Research</i>, vol. 1724, 146458, Elsevier, 2019, doi:<a href=\"https://doi.org/10.1016/j.brainres.2019.146458\">10.1016/j.brainres.2019.146458</a>.","ista":"Oliveira B, Yahya AÇ, Novarino G. 2019. Modeling cell-cell interactions in the brain using cerebral organoids. Brain Research. 1724, 146458.","apa":"Oliveira, B., Yahya, A. Ç., &#38; Novarino, G. (2019). Modeling cell-cell interactions in the brain using cerebral organoids. <i>Brain Research</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.brainres.2019.146458\">https://doi.org/10.1016/j.brainres.2019.146458</a>","ama":"Oliveira B, Yahya AÇ, Novarino G. Modeling cell-cell interactions in the brain using cerebral organoids. <i>Brain Research</i>. 2019;1724. doi:<a href=\"https://doi.org/10.1016/j.brainres.2019.146458\">10.1016/j.brainres.2019.146458</a>","short":"B. Oliveira, A.Ç. Yahya, G. Novarino, Brain Research 1724 (2019).","ieee":"B. Oliveira, A. Ç. Yahya, and G. Novarino, “Modeling cell-cell interactions in the brain using cerebral organoids,” <i>Brain Research</i>, vol. 1724. Elsevier, 2019.","chicago":"Oliveira, Bárbara, Aysan Çerağ Yahya, and Gaia Novarino. “Modeling Cell-Cell Interactions in the Brain Using Cerebral Organoids.” <i>Brain Research</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.brainres.2019.146458\">https://doi.org/10.1016/j.brainres.2019.146458</a>."},"publication_status":"published","date_published":"2019-12-01T00:00:00Z"}]