[{"alternative_title":["ISTA Thesis"],"corr_author":"1","supervisor":[{"last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"}],"citation":{"ama":"Espinoza Martinez C. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. 2019. doi:10.15479/AT:ISTA:6363","short":"C. Espinoza Martinez, Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits, Institute of Science and Technology Austria, 2019.","chicago":"Espinoza Martinez, Claudia . “Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6363.","ista":"Espinoza Martinez C. 2019. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria.","apa":"Espinoza Martinez, C. (2019). Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6363","ieee":"C. Espinoza Martinez, “Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits,” Institute of Science and Technology Austria, 2019.","mla":"Espinoza Martinez, Claudia. Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6363."},"oa":1,"date_published":"2019-04-30T00:00:00Z","OA_place":"publisher","type":"dissertation","page":"140","publication_status":"published","degree_awarded":"PhD","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"21"}]},"_id":"6363","file_date_updated":"2021-02-11T11:17:15Z","file":[{"access_level":"open_access","checksum":"77c6c05cfe8b58c8abcf1b854375d084","date_created":"2019-05-07T16:00:39Z","relation":"main_file","file_name":"Espinozathesis_all2.pdf","date_updated":"2021-02-11T11:17:15Z","content_type":"application/pdf","file_id":"6389","embargo":"2020-05-09","file_size":13966891,"creator":"cespinoza"},{"creator":"cespinoza","file_size":11159900,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2020-07-14T12:47:28Z","file_id":"6390","embargo_to":"open_access","date_created":"2019-05-07T16:00:48Z","file_name":"Espinoza_Thesis.docx","relation":"source_file","access_level":"closed","checksum":"f6aa819f127691a2b0fc21c76eb09746"}],"date_updated":"2026-04-08T13:57:19Z","abstract":[{"lang":"eng","text":"Distinguishing between similar experiences is achieved by the brain in a process called pattern separation. In the hippocampus, pattern separation reduces the interference of memories and increases the storage capacity by decorrelating similar inputs patterns of neuronal activity into non-overlapping output firing patterns. Winners-take-all (WTA) mechanism is a theoretical model for pattern separation in which a \"winner\" cell suppresses the activity of the neighboring neurons through feedback inhibition. However, if the network properties of the dentate gyrus support WTA as a biologically conceivable model remains unknown. Here, we showed that the connectivity rules of PV+interneurons and their synaptic properties are optimizedfor efficient pattern separation. We found using multiple whole-cell in vitrorecordings that PV+interneurons mainly connect to granule cells (GC) through lateral inhibition, a form of feedback inhibition in which a GC inhibits other GCs but not itself through the activation of PV+interneurons. Thus, lateral inhibition between GC–PV+interneurons was ~10 times more abundant than recurrent connections. Furthermore, the GC–PV+interneuron connectivity was more spatially confined but less abundant than PV+interneurons–GC connectivity, leading to an asymmetrical distribution of excitatory and inhibitory connectivity. Our network model of the dentate gyrus with incorporated real connectivity rules efficiently decorrelates neuronal activity patterns using WTA as the primary mechanism. This process relied on lateral inhibition, fast-signaling properties of PV+interneurons and the asymmetrical distribution of excitatory and inhibitory connectivity. Finally, we found that silencing the activity of PV+interneurons in vivoleads to acute deficits in discrimination between similar environments, suggesting that PV+interneuron networks are necessary for behavioral relevant computations. Our results demonstrate that PV+interneurons possess unique connectivity and fast signaling properties that confer to the dentate gyrus network properties that allow the emergence of pattern separation. Thus, our results contribute to the knowledge of how specific forms of network organization underlie sophisticated types of information processing. \r\n"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_created":"2019-04-30T11:56:10Z","ddc":["570"],"day":"30","publication_identifier":{"isbn":["978-3-99078-000-8"],"issn":["2663-337X"]},"oa_version":"Published Version","article_processing_charge":"No","author":[{"orcid":"0000-0003-4710-2082","full_name":"Espinoza Martinez, Claudia ","id":"31FFEE2E-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia ","last_name":"Espinoza Martinez"}],"publisher":"Institute of Science and Technology Austria","year":"2019","doi":"10.15479/AT:ISTA:6363","department":[{"_id":"PeJo"}],"status":"public","month":"04","has_accepted_license":"1","title":"Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits","language":[{"iso":"eng"}]},{"alternative_title":["ISTA Thesis"],"citation":{"chicago":"Mckenzie, Catherine. “Design and Characterization of Methods and Biological Components to Realize Synthetic Neurotransmission.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/at:ista:7132.","apa":"Mckenzie, C. (2019). Design and characterization of methods and biological components to realize synthetic neurotransmission. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:7132","ieee":"C. Mckenzie, “Design and characterization of methods and biological components to realize synthetic neurotransmission,” Institute of Science and Technology Austria, 2019.","ista":"Mckenzie C. 2019. Design and characterization of methods and biological components to realize synthetic neurotransmission. Institute of Science and Technology Austria.","mla":"Mckenzie, Catherine. Design and Characterization of Methods and Biological Components to Realize Synthetic Neurotransmission. Institute of Science and Technology Austria, 2019, doi:10.15479/at:ista:7132.","ama":"Mckenzie C. Design and characterization of methods and biological components to realize synthetic neurotransmission. 2019. doi:10.15479/at:ista:7132","short":"C. Mckenzie, Design and Characterization of Methods and Biological Components to Realize Synthetic Neurotransmission, Institute of Science and Technology Austria, 2019."},"corr_author":"1","supervisor":[{"id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","first_name":"Harald L","orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L","last_name":"Janovjak"}],"publication_status":"published","date_published":"2019-06-27T00:00:00Z","oa":1,"page":"95","type":"dissertation","OA_place":"publisher","_id":"7132","file_date_updated":"2020-07-14T12:47:50Z","file":[{"creator":"dernst","file_size":5054633,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2020-07-14T12:47:50Z","file_id":"7133","date_created":"2019-11-27T09:06:10Z","file_name":"McKenzie PhD Thesis August 2018 - Corrected Final.docx","relation":"source_file","checksum":"34d0fe0f6e0af97b5937205a3e350423","access_level":"closed"},{"checksum":"140dfb5e3df7edca34f4b6fcc55d876f","access_level":"open_access","date_created":"2019-11-27T09:06:10Z","file_name":"McKenzie PhD Thesis August 2018 - Corrected Final.pdf","relation":"main_file","content_type":"application/pdf","date_updated":"2020-07-14T12:47:50Z","file_id":"7134","creator":"dernst","file_size":3231837}],"date_updated":"2026-08-19T22:30:42Z","degree_awarded":"PhD","related_material":{"record":[{"status":"public","id":"6266","relation":"old_edition"}]},"publication_identifier":{"issn":["2663-337X"]},"day":"27","oa_version":"Published Version","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","abstract":[{"lang":"eng","text":"A major challenge in neuroscience research is to dissect the circuits that orchestrate behavior in health and disease. Proteins from a wide range of non-mammalian species, such as microbial opsins, have been successfully transplanted to specific neuronal targets to override their natural communication patterns. The goal of our work is to manipulate synaptic communication in a manner that closely incorporates the functional intricacies of synapses by preserving temporal encoding (i.e. the firing pattern of the presynaptic neuron) and connectivity (i.e. target specific synapses rather than specific neurons). Our strategy to achieve this goal builds on the use of non-mammalian transplants to create a synthetic synapse. The mode of modulation comes from pre-synaptic uptake of a synthetic neurotransmitter (SN) into synaptic vesicles by means of a genetically targeted transporter selective for the SN. Upon natural vesicular release, exposure of the SN to the synaptic cleft will modify the post-synaptic potential through an orthogonal ligand gated ion channel. To achieve this goal we have functionally characterized a mixed cationic methionine-gated ion channel from Arabidopsis thaliana, designed a method to functionally characterize a synthetic transporter in isolated synaptic vesicles without the need for transgenic animals, identified and extracted multiple prokaryotic uptake systems that are substrate specific for methionine (Met), and established a primary/cell line co-culture system that would allow future combinatorial testing of this orthogonal transmitter-transporter-channel trifecta.\r\nSynthetic synapses will provide a unique opportunity to manipulate synaptic communication while maintaining the electrophysiological integrity of the pre-synaptic cell. In this way, information may be preserved that was generated in upstream circuits and that could be essential for concerted function and information processing."}],"ddc":["571","573"],"date_created":"2019-11-27T09:07:14Z","article_processing_charge":"No","author":[{"last_name":"Mckenzie","full_name":"Mckenzie, Catherine","first_name":"Catherine","id":"3EEDE19A-F248-11E8-B48F-1D18A9856A87"}],"publisher":"Institute of Science and Technology Austria","year":"2019","month":"06","title":"Design and characterization of methods and biological components to realize synthetic neurotransmission","language":[{"iso":"eng"}],"has_accepted_license":"1","department":[{"_id":"HaJa"}],"doi":"10.15479/at:ista:7132","status":"public"},{"status":"public","main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1910.05841"}],"doi":"10.48550/arXiv.1910.05841","department":[{"_id":"GeKa"}],"language":[{"iso":"eng"}],"title":"Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits","month":"10","year":"2019","project":[{"grant_number":"844511","_id":"26A151DA-B435-11E9-9278-68D0E5697425","name":"Majorana bound states in Ge/SiGe heterostructures","call_identifier":"H2020"},{"name":"Hole spin orbit qubits in Ge quantum wells","call_identifier":"FWF","grant_number":"P30207","_id":"2641CE5E-B435-11E9-9278-68D0E5697425"}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"NanoFab"}],"author":[{"last_name":"Hofmann","full_name":"Hofmann, Andrea C","id":"340F461A-F248-11E8-B48F-1D18A9856A87","first_name":"Andrea C"},{"full_name":"Jirovec, Daniel","orcid":"0000-0002-7197-4801","id":"4C473F58-F248-11E8-B48F-1D18A9856A87","first_name":"Daniel","last_name":"Jirovec"},{"last_name":"Borovkov","full_name":"Borovkov, Maxim","first_name":"Maxim"},{"last_name":"Prieto Gonzalez","first_name":"Ivan","id":"2A307FE2-F248-11E8-B48F-1D18A9856A87","full_name":"Prieto Gonzalez, Ivan","orcid":"0000-0002-7370-5357"},{"last_name":"Ballabio","first_name":"Andrea","full_name":"Ballabio, Andrea"},{"last_name":"Frigerio","full_name":"Frigerio, Jacopo","first_name":"Jacopo"},{"last_name":"Chrastina","full_name":"Chrastina, Daniel","first_name":"Daniel"},{"last_name":"Isella","first_name":"Giovanni","full_name":"Isella, Giovanni"},{"orcid":"0000-0001-8342-202X","full_name":"Katsaros, Georgios","id":"38DB5788-F248-11E8-B48F-1D18A9856A87","first_name":"Georgios","last_name":"Katsaros"}],"article_processing_charge":"No","date_created":"2021-10-01T12:14:51Z","external_id":{"arxiv":["1910.05841"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"We study double quantum dots in a Ge/SiGe heterostructure and test their maturity towards singlet-triplet ($S-T_0$) qubits. We demonstrate a large range of tunability, from two single quantum dots to a double quantum dot. We measure Pauli spin blockade and study the anisotropy of the $g$-factor. We use an adjacent quantum dot for sensing charge transitions in the double quantum dot at interest. In conclusion, Ge/SiGe possesses all ingredients necessary for building a singlet-triplet qubit.","lang":"eng"}],"oa_version":"Preprint","arxiv":1,"day":"13","acknowledgement":"We thank Matthias Brauns for helpful discussions and careful proofreading of the manuscript. This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 844511 and from the FWF project P30207. The research was supported by the Scientific Service Units of IST Austria through resources provided by the MIBA machine shop and the nanofabrication\r\nfacility.","related_material":{"record":[{"status":"public","id":"10058","relation":"dissertation_contains"}]},"ec_funded":1,"date_updated":"2026-08-19T22:30:44Z","_id":"10065","type":"preprint","date_published":"2019-10-13T00:00:00Z","oa":1,"publication":"arXiv","article_number":"1910.05841","publication_status":"draft","citation":{"mla":"Hofmann, Andrea C., et al. “Assessing the Potential of Ge/SiGe Quantum Dots as Hosts for Singlet-Triplet Qubits.” ArXiv, 1910.05841, doi:10.48550/arXiv.1910.05841.","ieee":"A. C. Hofmann et al., “Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits,” arXiv. .","apa":"Hofmann, A. C., Jirovec, D., Borovkov, M., Prieto Gonzalez, I., Ballabio, A., Frigerio, J., … Katsaros, G. (n.d.). Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits. arXiv. https://doi.org/10.48550/arXiv.1910.05841","ista":"Hofmann AC, Jirovec D, Borovkov M, Prieto Gonzalez I, Ballabio A, Frigerio J, Chrastina D, Isella G, Katsaros G. Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits. arXiv, 1910.05841.","chicago":"Hofmann, Andrea C, Daniel Jirovec, Maxim Borovkov, Ivan Prieto Gonzalez, Andrea Ballabio, Jacopo Frigerio, Daniel Chrastina, Giovanni Isella, and Georgios Katsaros. “Assessing the Potential of Ge/SiGe Quantum Dots as Hosts for Singlet-Triplet Qubits.” ArXiv, n.d. https://doi.org/10.48550/arXiv.1910.05841.","short":"A.C. Hofmann, D. Jirovec, M. Borovkov, I. Prieto Gonzalez, A. Ballabio, J. Frigerio, D. Chrastina, G. Isella, G. Katsaros, ArXiv (n.d.).","ama":"Hofmann AC, Jirovec D, Borovkov M, et al. Assessing the potential of Ge/SiGe quantum dots as hosts for singlet-triplet qubits. arXiv. doi:10.48550/arXiv.1910.05841"},"corr_author":"1"},{"issue":"13","author":[{"first_name":"Maciek","id":"45F536D2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6463-5257","full_name":"Adamowski, Maciek","last_name":"Adamowski"},{"id":"367EF8FA-F248-11E8-B48F-1D18A9856A87","first_name":"Lanxin","full_name":"Li, Lanxin","orcid":"0000-0002-5607-272X","last_name":"Li"},{"last_name":"Friml","orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří","first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"Yes","status":"public","doi":"10.3390/ijms20133337","department":[{"_id":"JiFr"}],"has_accepted_license":"1","title":"Reorientation of cortical microtubule arrays in the hypocotyl of arabidopsis thaliana is induced by the cell growth process and independent of auxin signaling","language":[{"iso":"eng"}],"month":"07","publisher":"MDPI","year":"2019","volume":20,"project":[{"call_identifier":"FP7","name":"Polarity and subcellular dynamics in plants","_id":"25716A02-B435-11E9-9278-68D0E5697425","grant_number":"282300"},{"call_identifier":"H2020","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"},{"name":"IST Austria Open Access Fund","_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854"}],"pmid":1,"type":"journal_article","oa":1,"date_published":"2019-07-07T00:00:00Z","publication":"International Journal of Molecular Sciences","article_number":"3337","publication_status":"published","corr_author":"1","citation":{"mla":"Adamowski, Maciek, et al. “Reorientation of Cortical Microtubule Arrays in the Hypocotyl of Arabidopsis Thaliana Is Induced by the Cell Growth Process and Independent of Auxin Signaling.” International Journal of Molecular Sciences, vol. 20, no. 13, 3337, MDPI, 2019, doi:10.3390/ijms20133337.","chicago":"Adamowski, Maciek, Lanxin Li, and Jiří Friml. “Reorientation of Cortical Microtubule Arrays in the Hypocotyl of Arabidopsis Thaliana Is Induced by the Cell Growth Process and Independent of Auxin Signaling.” International Journal of Molecular Sciences. MDPI, 2019. https://doi.org/10.3390/ijms20133337.","ieee":"M. Adamowski, L. Li, and J. Friml, “Reorientation of cortical microtubule arrays in the hypocotyl of arabidopsis thaliana is induced by the cell growth process and independent of auxin signaling,” International Journal of Molecular Sciences, vol. 20, no. 13. MDPI, 2019.","apa":"Adamowski, M., Li, L., & Friml, J. (2019). Reorientation of cortical microtubule arrays in the hypocotyl of arabidopsis thaliana is induced by the cell growth process and independent of auxin signaling. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms20133337","ista":"Adamowski M, Li L, Friml J. 2019. Reorientation of cortical microtubule arrays in the hypocotyl of arabidopsis thaliana is induced by the cell growth process and independent of auxin signaling. International Journal of Molecular Sciences. 20(13), 3337.","ama":"Adamowski M, Li L, Friml J. Reorientation of cortical microtubule arrays in the hypocotyl of arabidopsis thaliana is induced by the cell growth process and independent of auxin signaling. International Journal of Molecular Sciences. 2019;20(13). doi:10.3390/ijms20133337","short":"M. Adamowski, L. Li, J. Friml, International Journal of Molecular Sciences 20 (2019)."},"isi":1,"intvolume":" 20","quality_controlled":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"external_id":{"isi":["000477041100221"],"pmid":["31284661"]},"date_created":"2019-07-11T12:00:32Z","ddc":["580"],"abstract":[{"lang":"eng","text":"Cortical microtubule arrays in elongating epidermal cells in both the root and stem of plants have the propensity of dynamic reorientations that are correlated with the activation or inhibition of growth. Factors regulating plant growth, among them the hormone auxin, have been recognized as regulators of microtubule array orientations. Some previous work in the field has aimed at elucidating the causal relationship between cell growth, the signaling of auxin or other growth-regulating factors, and microtubule array reorientations, with various conclusions. Here, we revisit this problem of causality with a comprehensive set of experiments in Arabidopsis thaliana, using the now available pharmacological and genetic tools. We use isolated, auxin-depleted hypocotyls, an experimental system allowing for full control of both growth and auxin signaling. We demonstrate that reorientation of microtubules is not directly triggered by an auxin signal during growth activation. Instead, reorientation is triggered by the activation of the growth process itself and is auxin-independent in its nature. We discuss these findings in the context of previous relevant work, including that on the mechanical regulation of microtubule array orientation."}],"article_type":"original","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","day":"07","publication_identifier":{"eissn":["1422-0067"]},"related_material":{"record":[{"relation":"dissertation_contains","id":"10083","status":"public"}]},"ec_funded":1,"license":"https://creativecommons.org/licenses/by/4.0/","scopus_import":"1","date_updated":"2026-08-19T22:30:45Z","file_date_updated":"2020-07-14T12:47:34Z","file":[{"relation":"main_file","file_name":"2019_JournalMolecularScience_Adamowski.pdf","date_created":"2019-07-17T06:17:15Z","access_level":"open_access","checksum":"dd9d1cbb933a72ceb666c9667890ac51","creator":"dernst","file_size":3330291,"file_id":"6645","date_updated":"2020-07-14T12:47:34Z","content_type":"application/pdf"}],"_id":"6627"},{"date_updated":"2026-08-19T22:30:54Z","file_date_updated":"2020-11-26T16:33:44Z","file":[{"date_updated":"2020-11-26T16:33:44Z","success":1,"content_type":"application/pdf","file_id":"8821","creator":"lsazanov","file_size":3066206,"checksum":"52728cda5210a3e9b74cc204e8aed3d5","access_level":"open_access","date_created":"2020-11-26T16:33:44Z","file_name":"Manuscript_final_acc_withFigs_SI_opt_red.pdf","relation":"main_file"}],"_id":"6848","ec_funded":1,"related_material":{"record":[{"id":"8340","relation":"dissertation_contains","status":"public"}],"link":[{"relation":"press_release","description":"News on IST Website","url":"https://ist.ac.at/en/news/high-end-microscopy-reveals-structure-and-function-of-crucial-metabolic-enzyme/"}]},"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.","scopus_import":"1","oa_version":"Submitted Version","publication_identifier":{"eissn":["1476-4687"],"issn":["0028-0836"]},"day":"12","ddc":["572"],"date_created":"2019-09-04T06:21:41Z","external_id":{"isi":["000485415400061"],"pmid":["31462775"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_type":"letter_note","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"}],"quality_controlled":"1","isi":1,"citation":{"ama":"Kampjut D, Sazanov LA. Structure and mechanism of mitochondrial proton-translocating transhydrogenase. Nature. 2019;573(7773):291–295. doi:10.1038/s41586-019-1519-2","short":"D. Kampjut, L.A. Sazanov, Nature 573 (2019) 291–295.","mla":"Kampjut, Domen, and Leonid A. Sazanov. “Structure and Mechanism of Mitochondrial Proton-Translocating Transhydrogenase.” Nature, vol. 573, no. 7773, Springer Nature, 2019, pp. 291–295, doi:10.1038/s41586-019-1519-2.","chicago":"Kampjut, Domen, and Leonid A Sazanov. “Structure and Mechanism of Mitochondrial Proton-Translocating Transhydrogenase.” Nature. Springer Nature, 2019. https://doi.org/10.1038/s41586-019-1519-2.","ieee":"D. Kampjut and L. A. Sazanov, “Structure and mechanism of mitochondrial proton-translocating transhydrogenase,” Nature, vol. 573, no. 7773. Springer Nature, pp. 291–295, 2019.","apa":"Kampjut, D., & Sazanov, L. A. (2019). Structure and mechanism of mitochondrial proton-translocating transhydrogenase. Nature. Springer Nature. https://doi.org/10.1038/s41586-019-1519-2","ista":"Kampjut D, Sazanov LA. 2019. Structure and mechanism of mitochondrial proton-translocating transhydrogenase. Nature. 573(7773), 291–295."},"intvolume":" 573","publication":"Nature","publication_status":"published","page":"291–295","type":"journal_article","pmid":1,"date_published":"2019-09-12T00:00:00Z","oa":1,"volume":573,"project":[{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","call_identifier":"H2020"}],"publisher":"Springer Nature","year":"2019","title":"Structure and mechanism of mitochondrial proton-translocating transhydrogenase","language":[{"iso":"eng"}],"has_accepted_license":"1","month":"09","status":"public","doi":"10.1038/s41586-019-1519-2","department":[{"_id":"LeSa"}],"author":[{"full_name":"Kampjut, Domen","orcid":"0000-0002-6018-3422","first_name":"Domen","id":"37233050-F248-11E8-B48F-1D18A9856A87","last_name":"Kampjut"},{"last_name":"Sazanov","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A"}],"article_processing_charge":"No","issue":"7773","acknowledged_ssus":[{"_id":"ScienComp"}]},{"year":"2019","publisher":"ASPB","project":[{"call_identifier":"H2020","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425"}],"volume":180,"main_file_link":[{"url":"https://doi.org/10.1104/pp.19.00201","open_access":"1"}],"doi":"10.1104/pp.19.00201","department":[{"_id":"JiFr"}],"status":"public","month":"06","title":"Pinstatic acid promotes auxin transport by inhibiting PIN internalization","language":[{"iso":"eng"}],"issue":"2","article_processing_charge":"No","author":[{"first_name":"A","full_name":"Oochi, A","last_name":"Oochi"},{"last_name":"Hajny","full_name":"Hajny, Jakub","orcid":"0000-0003-2140-7195","first_name":"Jakub","id":"4800CC20-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Fukui","first_name":"K","full_name":"Fukui, K"},{"last_name":"Nakao","first_name":"Y","full_name":"Nakao, Y"},{"last_name":"Gallei","full_name":"Gallei, Michelle C","orcid":"0000-0003-1286-7368","first_name":"Michelle C","id":"35A03822-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Quareshy","full_name":"Quareshy, M","first_name":"M"},{"first_name":"K","full_name":"Takahashi, K","last_name":"Takahashi"},{"full_name":"Kinoshita, T","first_name":"T","last_name":"Kinoshita"},{"last_name":"Harborough","first_name":"SR","full_name":"Harborough, SR"},{"full_name":"Kepinski, S","first_name":"S","last_name":"Kepinski"},{"last_name":"Kasahara","first_name":"H","full_name":"Kasahara, H"},{"last_name":"Napier","full_name":"Napier, RM","first_name":"RM"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","first_name":"Jiří","full_name":"Friml, Jiří","orcid":"0000-0002-8302-7596","last_name":"Friml"},{"first_name":"KI","full_name":"Hayashi, KI","last_name":"Hayashi"}],"scopus_import":"1","acknowledgement":"We thank Dr. H. Fukaki (University of Kobe), Dr. R. Offringa (Leiden University), Dr. Jianwei Pan (Zhejiang Normal University), and Dr. M. Estelle (University of California at San Diego) for providing mutants and transgenic line seeds.\r\nThis work was supported by the Ministry of Education, Culture, Sports, Science, and Technology (Grant-in-Aid for Scientific Research no. JP25114518 to K.H.), the Biotechnology and Biological Sciences Research Council (award no. BB/L009366/1 to R.N. and S.K.), and the European Union’s Horizon2020 program (European Research Council grant agreement no. 742985 to J.F.).","related_material":{"record":[{"status":"public","id":"11626","relation":"dissertation_contains"},{"status":"public","id":"8822","relation":"dissertation_contains"}]},"ec_funded":1,"_id":"6260","date_updated":"2026-08-19T22:30:55Z","article_type":"original","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"Polar auxin transport plays a pivotal role in plant growth and development. PIN auxin efflux carriers regulate directional auxin movement by establishing local auxin maxima, minima, and gradients that drive multiple developmental processes and responses to environmental signals. Auxin has been proposed to modulate its own transport by regulating subcellular PIN trafficking via processes such as clathrin-mediated PIN endocytosis and constitutive recycling. Here, we further investigated the mechanisms by which auxin affects PIN trafficking by screening auxin analogs and identified pinstatic acid (PISA) as a positive modulator of polar auxin transport in Arabidopsis thaliana. PISA had an auxin-like effect on hypocotyl elongation and adventitious root formation via positive regulation of auxin transport. PISA did not activate SCFTIR1/AFB signaling and yet induced PIN accumulation at the cell surface by inhibiting PIN internalization from the plasma membrane. This work demonstrates PISA to be a promising chemical tool to dissect the regulatory mechanisms behind subcellular PIN trafficking and auxin transport."}],"ddc":["580"],"date_created":"2019-04-09T08:38:20Z","external_id":{"pmid":["30936248"],"isi":["000470086100045"]},"publication_identifier":{"eissn":["1532-2548"],"issn":["0032-0889"]},"day":"01","oa_version":"Published Version","intvolume":" 180","isi":1,"citation":{"ama":"Oochi A, Hajny J, Fukui K, et al. Pinstatic acid promotes auxin transport by inhibiting PIN internalization. Plant Physiology. 2019;180(2):1152-1165. doi:10.1104/pp.19.00201","short":"A. Oochi, J. Hajny, K. Fukui, Y. Nakao, M.C. Gallei, M. Quareshy, K. Takahashi, T. Kinoshita, S. Harborough, S. Kepinski, H. Kasahara, R. Napier, J. Friml, K. Hayashi, Plant Physiology 180 (2019) 1152–1165.","chicago":"Oochi, A, Jakub Hajny, K Fukui, Y Nakao, Michelle C Gallei, M Quareshy, K Takahashi, et al. “Pinstatic Acid Promotes Auxin Transport by Inhibiting PIN Internalization.” Plant Physiology. ASPB, 2019. https://doi.org/10.1104/pp.19.00201.","apa":"Oochi, A., Hajny, J., Fukui, K., Nakao, Y., Gallei, M. C., Quareshy, M., … Hayashi, K. (2019). Pinstatic acid promotes auxin transport by inhibiting PIN internalization. Plant Physiology. ASPB. https://doi.org/10.1104/pp.19.00201","ista":"Oochi A, Hajny J, Fukui K, Nakao Y, Gallei MC, Quareshy M, Takahashi K, Kinoshita T, Harborough S, Kepinski S, Kasahara H, Napier R, Friml J, Hayashi K. 2019. Pinstatic acid promotes auxin transport by inhibiting PIN internalization. Plant Physiology. 180(2), 1152–1165.","ieee":"A. Oochi et al., “Pinstatic acid promotes auxin transport by inhibiting PIN internalization,” Plant Physiology, vol. 180, no. 2. ASPB, pp. 1152–1165, 2019.","mla":"Oochi, A., et al. “Pinstatic Acid Promotes Auxin Transport by Inhibiting PIN Internalization.” Plant Physiology, vol. 180, no. 2, ASPB, 2019, pp. 1152–65, doi:10.1104/pp.19.00201."},"quality_controlled":"1","date_published":"2019-06-01T00:00:00Z","oa":1,"type":"journal_article","page":"1152-1165","pmid":1,"publication_status":"published","publication":"Plant Physiology"},{"publisher":"Institute of Science and Technology Austria","year":"2019","language":[{"iso":"eng"}],"title":"The role of CCK-interneurons in regulating hippocampal network dynamics","has_accepted_license":"1","month":"09","status":"public","doi":"10.15479/AT:ISTA:6849","department":[{"_id":"JoCs"}],"author":[{"id":"4871BCE6-F248-11E8-B48F-1D18A9856A87","first_name":"Dámaris K","orcid":"0000-0002-8602-4374","full_name":"Rangel Guerrero, Dámaris K","last_name":"Rangel Guerrero"}],"article_processing_charge":"No","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"M-Shop"}],"file":[{"creator":"drangel","file_size":18253100,"file_id":"6865","date_updated":"2021-02-10T23:30:09Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","file_name":"Thesis_Damaris_Rangel_source.docx","embargo_to":"open_access","date_created":"2019-09-09T13:09:45Z","checksum":"244dc4f74dbfc94f414156092298831f","access_level":"closed"},{"checksum":"59c73be40eeaa1c4db24067270151555","access_level":"open_access","date_created":"2019-09-09T13:09:52Z","file_name":"Thesis_Damaris_Rangel_pdfa.pdf","relation":"main_file","date_updated":"2020-09-11T22:30:04Z","request_a_copy":0,"content_type":"application/pdf","embargo":"2020-09-10","file_id":"6866","creator":"drangel","file_size":2160109}],"date_updated":"2026-04-08T13:56:53Z","file_date_updated":"2021-02-10T23:30:09Z","_id":"6849","degree_awarded":"PhD","related_material":{"record":[{"relation":"part_of_dissertation","id":"5914","status":"public"}]},"oa_version":"Published Version","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-003-9"]},"day":"09","ddc":["570"],"date_created":"2019-09-06T06:54:16Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","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"}],"citation":{"short":"D.K. Rangel Guerrero, The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics, Institute of Science and Technology Austria, 2019.","ama":"Rangel Guerrero DK. The role of CCK-interneurons in regulating hippocampal network dynamics. 2019. doi:10.15479/AT:ISTA:6849","mla":"Rangel Guerrero, Dámaris K. The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6849.","ista":"Rangel Guerrero DK. 2019. The role of CCK-interneurons in regulating hippocampal network dynamics. Institute of Science and Technology Austria.","apa":"Rangel Guerrero, D. K. (2019). The role of CCK-interneurons in regulating hippocampal network dynamics. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6849","ieee":"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. https://doi.org/10.15479/AT:ISTA:6849."},"supervisor":[{"last_name":"Csicsvari","full_name":"Csicsvari, Jozsef L","orcid":"0000-0002-5193-4036","first_name":"Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87"}],"corr_author":"1","alternative_title":["ISTA Thesis"],"publication_status":"published","page":"97","type":"dissertation","OA_place":"publisher","date_published":"2019-09-09T00:00:00Z","oa":1},{"date_created":"2019-08-09T09:54:20Z","external_id":{"arxiv":["1901.06087"]},"ddc":["000"],"abstract":[{"text":"In this work, we consider the almost-sure termination problem for probabilistic programs that asks whether a\r\ngiven probabilistic program terminates with probability 1. Scalable approaches for program analysis often\r\nrely on modularity as their theoretical basis. In non-probabilistic programs, the classical variant rule (V-rule)\r\nof Floyd-Hoare logic provides the foundation for modular analysis. Extension of this rule to almost-sure\r\ntermination of probabilistic programs is quite tricky, and a probabilistic variant was proposed in [16]. While the\r\nproposed probabilistic variant cautiously addresses the key issue of integrability, we show that the proposed\r\nmodular rule is still not sound for almost-sure termination of probabilistic programs.\r\nBesides establishing unsoundness of the previous rule, our contributions are as follows: First, we present a\r\nsound modular rule for almost-sure termination of probabilistic programs. Our approach is based on a novel\r\nnotion of descent supermartingales. Second, for algorithmic approaches, we consider descent supermartingales\r\nthat are linear and show that they can be synthesized in polynomial time. Finally, we present experimental\r\nresults on a variety of benchmarks and several natural examples that model various types of nested while\r\nloops in probabilistic programs and demonstrate that our approach is able to efficiently prove their almost-sure\r\ntermination property","lang":"eng"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","oa_version":"Published Version","arxiv":1,"day":"01","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"8934"}]},"ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc/4.0/","scopus_import":"1","file":[{"file_id":"6807","content_type":"application/pdf","date_updated":"2020-07-14T12:47:40Z","creator":"akafshda","file_size":1024643,"checksum":"3482d8ace6fb4991eb7810e3b70f1b9f","access_level":"open_access","file_name":"oopsla-2019.pdf","relation":"main_file","date_created":"2019-08-12T15:40:57Z"},{"file_id":"7821","date_updated":"2020-07-14T12:47:40Z","content_type":"application/pdf","file_size":538579,"creator":"dernst","access_level":"open_access","checksum":"4e5a6fb2b59a75222a4e8335a5a60eac","relation":"main_file","file_name":"2019_ACM_Huang.pdf","date_created":"2020-05-12T15:15:14Z"}],"file_date_updated":"2020-07-14T12:47:40Z","date_updated":"2026-08-19T22:30:58Z","_id":"6780","type":"conference","oa":1,"date_published":"2019-10-01T00:00:00Z","article_number":"129","publication":"Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications ","publication_status":"published","citation":{"ama":"Huang M, Fu H, Chatterjee K, Goharshady AK. Modular verification for almost-sure termination of probabilistic programs. In: Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications . Vol 3. ACM; 2019. doi:10.1145/3360555","short":"M. Huang, H. Fu, K. Chatterjee, A.K. Goharshady, in:, Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications , ACM, 2019.","chicago":"Huang, Mingzhang, Hongfei Fu, Krishnendu Chatterjee, and Amir Kafshdar Goharshady. “Modular Verification for Almost-Sure Termination of Probabilistic Programs.” In Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications , Vol. 3. ACM, 2019. https://doi.org/10.1145/3360555.","ieee":"M. Huang, H. Fu, K. Chatterjee, and A. K. Goharshady, “Modular verification for almost-sure termination of probabilistic programs,” in Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications , Athens, Greece, 2019, vol. 3.","apa":"Huang, M., Fu, H., Chatterjee, K., & Goharshady, A. K. (2019). Modular verification for almost-sure termination of probabilistic programs. In Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications (Vol. 3). Athens, Greece: ACM. https://doi.org/10.1145/3360555","ista":"Huang M, Fu H, Chatterjee K, Goharshady AK. 2019. Modular verification for almost-sure termination of probabilistic programs. Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications . OOPSLA: Object-oriented Programming, Systems, Languages and Applications vol. 3, 129.","mla":"Huang, Mingzhang, et al. “Modular Verification for Almost-Sure Termination of Probabilistic Programs.” Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications , vol. 3, 129, ACM, 2019, doi:10.1145/3360555."},"intvolume":" 3","tmp":{"image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode"},"conference":{"name":"OOPSLA: Object-oriented Programming, Systems, Languages and Applications","end_date":"2019-10-25","location":"Athens, Greece","start_date":"2019-10-23"},"quality_controlled":"1","status":"public","doi":"10.1145/3360555","department":[{"_id":"KrCh"}],"has_accepted_license":"1","title":"Modular verification for almost-sure termination of probabilistic programs","language":[{"iso":"eng"}],"month":"10","publisher":"ACM","year":"2019","volume":3,"project":[{"grant_number":"ICT15-003","_id":"25892FC0-B435-11E9-9278-68D0E5697425","name":"Efficient Algorithms for Computer Aided Verification"},{"_id":"25863FF4-B435-11E9-9278-68D0E5697425","grant_number":"S11407","name":"Game Theory","call_identifier":"FWF"},{"call_identifier":"FP7","name":"Quantitative Graph Games: Theory and Applications","grant_number":"279307","_id":"2581B60A-B435-11E9-9278-68D0E5697425"},{"_id":"267066CE-B435-11E9-9278-68D0E5697425","name":"Quantitative Analysis of Probabilistic Systems with a focus on Crypto-Currencies"},{"_id":"266EEEC0-B435-11E9-9278-68D0E5697425","name":"Quantitative Game-theoretic Analysis of Blockchain Applications and Smart Contracts"}],"author":[{"last_name":"Huang","full_name":"Huang, Mingzhang","first_name":"Mingzhang"},{"full_name":"Fu, Hongfei","first_name":"Hongfei","last_name":"Fu"},{"last_name":"Chatterjee","first_name":"Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","full_name":"Chatterjee, Krishnendu","orcid":"0000-0002-4561-241X"},{"last_name":"Goharshady","first_name":"Amir Kafshdar","id":"391365CE-F248-11E8-B48F-1D18A9856A87","full_name":"Goharshady, Amir Kafshdar","orcid":"0000-0003-1702-6584"}],"article_processing_charge":"No"},{"date_created":"2019-05-26T21:59:15Z","external_id":{"isi":["000474685800052"]},"ddc":["000"],"abstract":[{"text":"Smart contracts are programs that are stored and executed on the Blockchain and can receive, manage and transfer money (cryptocurrency units). Two important problems regarding smart contracts are formal analysis and compiler optimization. Formal analysis is extremely important, because smart contracts hold funds worth billions of dollars and their code is immutable after deployment. Hence, an undetected bug can cause significant financial losses. Compiler optimization is also crucial, because every action of a smart contract has to be executed by every node in the Blockchain network. Therefore, optimizations in compiling smart contracts can lead to significant savings in computation, time and energy.\r\n\r\nTwo classical approaches in program analysis and compiler optimization are intraprocedural and interprocedural analysis. In intraprocedural analysis, each function is analyzed separately, while interprocedural analysis considers the entire program. In both cases, the analyses are usually reduced to graph problems over the control flow graph (CFG) of the program. These graph problems are often computationally expensive. Hence, there has been ample research on exploiting structural properties of CFGs for efficient algorithms. One such well-studied property is the treewidth, which is a measure of tree-likeness of graphs. It is known that intraprocedural CFGs of structured programs have treewidth at most 6, whereas the interprocedural treewidth cannot be bounded. This result has been used as a basis for many efficient intraprocedural analyses.\r\n\r\nIn this paper, we explore the idea of exploiting the treewidth of smart contracts for formal analysis and compiler optimization. First, similar to classical programs, we show that the intraprocedural treewidth of structured Solidity and Vyper smart contracts is at most 9. Second, for global analysis, we prove that the interprocedural treewidth of structured smart contracts is bounded by 10 and, in sharp contrast with classical programs, treewidth-based algorithms can be easily applied for interprocedural analysis. Finally, we supplement our theoretical results with experiments using a tool we implemented for computing treewidth of smart contracts and show that the treewidth is much lower in practice. We use 36,764 real-world Ethereum smart contracts as benchmarks and find that they have an average treewidth of at most 3.35 for the intraprocedural case and 3.65 for the interprocedural case.\r\n","lang":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Submitted Version","day":"01","publication_identifier":{"isbn":["9781450359337"]},"related_material":{"record":[{"relation":"dissertation_contains","id":"8934","status":"public"}]},"scopus_import":"1","date_updated":"2026-08-19T22:30:58Z","file_date_updated":"2020-07-14T12:47:32Z","file":[{"file_id":"7827","content_type":"application/pdf","date_updated":"2020-07-14T12:47:32Z","file_size":6937138,"creator":"dernst","checksum":"dddc20f6d9881f23b8755eb720ec9d6f","access_level":"open_access","file_name":"2019_ACM_Chatterjee.pdf","relation":"main_file","date_created":"2020-05-14T09:50:11Z"}],"_id":"6490","page":"400-408","type":"conference","oa":1,"date_published":"2019-04-01T00:00:00Z","publication":"Proceedings of the 34th ACM Symposium on Applied Computing","publication_status":"published","corr_author":"1","isi":1,"citation":{"chicago":"Chatterjee, Krishnendu, Amir Kafshdar Goharshady, and Ehsan Kafshdar Goharshady. “The Treewidth of Smart Contracts.” In Proceedings of the 34th ACM Symposium on Applied Computing, Part F147772:400–408. ACM, 2019. https://doi.org/10.1145/3297280.3297322.","ieee":"K. Chatterjee, A. K. Goharshady, and E. K. Goharshady, “The treewidth of smart contracts,” in Proceedings of the 34th ACM Symposium on Applied Computing, Limassol, Cyprus, 2019, vol. Part F147772, pp. 400–408.","ista":"Chatterjee K, Goharshady AK, Goharshady EK. 2019. The treewidth of smart contracts. Proceedings of the 34th ACM Symposium on Applied Computing. SAC: Symposium on Applied Computing vol. Part F147772, 400–408.","apa":"Chatterjee, K., Goharshady, A. K., & Goharshady, E. K. (2019). The treewidth of smart contracts. In Proceedings of the 34th ACM Symposium on Applied Computing (Vol. Part F147772, pp. 400–408). Limassol, Cyprus: ACM. https://doi.org/10.1145/3297280.3297322","mla":"Chatterjee, Krishnendu, et al. “The Treewidth of Smart Contracts.” Proceedings of the 34th ACM Symposium on Applied Computing, vol. Part F147772, ACM, 2019, pp. 400–08, doi:10.1145/3297280.3297322.","ama":"Chatterjee K, Goharshady AK, Goharshady EK. The treewidth of smart contracts. In: Proceedings of the 34th ACM Symposium on Applied Computing. Vol Part F147772. ACM; 2019:400-408. doi:10.1145/3297280.3297322","short":"K. Chatterjee, A.K. Goharshady, E.K. Goharshady, in:, Proceedings of the 34th ACM Symposium on Applied Computing, ACM, 2019, pp. 400–408."},"quality_controlled":"1","conference":{"start_date":"2019-04-08","location":"Limassol, Cyprus","end_date":"2019-04-12","name":"SAC: Symposium on Applied Computing"},"status":"public","department":[{"_id":"KrCh"}],"doi":"10.1145/3297280.3297322","has_accepted_license":"1","title":"The treewidth of smart contracts","language":[{"iso":"eng"}],"month":"04","year":"2019","publisher":"ACM","volume":"Part F147772","pubrep_id":"1070","author":[{"last_name":"Chatterjee","orcid":"0000-0002-4561-241X","full_name":"Chatterjee, Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","first_name":"Krishnendu"},{"full_name":"Goharshady, Amir Kafshdar","orcid":"0000-0003-1702-6584","id":"391365CE-F248-11E8-B48F-1D18A9856A87","first_name":"Amir Kafshdar","last_name":"Goharshady"},{"first_name":"Ehsan Kafshdar","full_name":"Goharshady, Ehsan Kafshdar","last_name":"Goharshady"}],"article_processing_charge":"No"},{"type":"journal_article","oa":1,"date_published":"2019-11-01T00:00:00Z","article_number":"23","publication":"ACM Transactions on Programming Languages and Systems","publication_status":"published","isi":1,"citation":{"mla":"Chatterjee, Krishnendu, et al. “Faster Algorithms for Dynamic Algebraic Queries in Basic RSMs with Constant Treewidth.” ACM Transactions on Programming Languages and Systems, vol. 41, no. 4, 23, ACM, 2019, doi:10.1145/3363525.","chicago":"Chatterjee, Krishnendu, Amir Kafshdar Goharshady, Prateesh Goyal, Rasmus Ibsen-Jensen, and Andreas Pavlogiannis. “Faster Algorithms for Dynamic Algebraic Queries in Basic RSMs with Constant Treewidth.” ACM Transactions on Programming Languages and Systems. ACM, 2019. https://doi.org/10.1145/3363525.","apa":"Chatterjee, K., Goharshady, A. K., Goyal, P., Ibsen-Jensen, R., & Pavlogiannis, A. (2019). Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth. ACM Transactions on Programming Languages and Systems. ACM. https://doi.org/10.1145/3363525","ieee":"K. Chatterjee, A. K. Goharshady, P. Goyal, R. Ibsen-Jensen, and A. Pavlogiannis, “Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth,” ACM Transactions on Programming Languages and Systems, vol. 41, no. 4. ACM, 2019.","ista":"Chatterjee K, Goharshady AK, Goyal P, Ibsen-Jensen R, Pavlogiannis A. 2019. Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth. ACM Transactions on Programming Languages and Systems. 41(4), 23.","ama":"Chatterjee K, Goharshady AK, Goyal P, Ibsen-Jensen R, Pavlogiannis A. Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth. ACM Transactions on Programming Languages and Systems. 2019;41(4). doi:10.1145/3363525","short":"K. Chatterjee, A.K. Goharshady, P. Goyal, R. Ibsen-Jensen, A. Pavlogiannis, ACM Transactions on Programming Languages and Systems 41 (2019)."},"intvolume":" 41","quality_controlled":"1","date_created":"2019-12-09T08:33:33Z","external_id":{"isi":["000564108400004"]},"ddc":["000"],"abstract":[{"text":"Interprocedural analysis is at the heart of numerous applications in programming languages, such as alias analysis, constant propagation, and so on. Recursive state machines (RSMs) are standard models for interprocedural analysis. We consider a general framework with RSMs where the transitions are labeled from a semiring and path properties are algebraic with semiring operations. RSMs with algebraic path properties can model interprocedural dataflow analysis problems, the shortest path problem, the most probable path problem, and so on. The traditional algorithms for interprocedural analysis focus on path properties where the starting point is fixed as the entry point of a specific method. In this work, we consider possible multiple queries as required in many applications such as in alias analysis. The study of multiple queries allows us to bring in an important algorithmic distinction between the resource usage of the one-time preprocessing vs for each individual query. The second aspect we consider is that the control flow graphs for most programs have constant treewidth.\r\n\r\nOur main contributions are simple and implementable algorithms that support multiple queries for algebraic path properties for RSMs that have constant treewidth. Our theoretical results show that our algorithms have small additional one-time preprocessing but can answer subsequent queries significantly faster as compared to the current algorithmic solutions for interprocedural dataflow analysis. We have also implemented our algorithms and evaluated their performance for performing on-demand interprocedural dataflow analysis on various domains, such as for live variable analysis and reaching definitions, on a standard benchmark set. Our experimental results align with our theoretical statements and show that after a lightweight preprocessing, on-demand queries are answered much faster than the standard existing algorithmic approaches.\r\n","lang":"eng"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","article_type":"original","oa_version":"Submitted Version","day":"01","publication_identifier":{"issn":["0164-0925"]},"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"8934"}]},"ec_funded":1,"scopus_import":"1","date_updated":"2026-08-19T22:30:58Z","file":[{"file_size":667357,"creator":"dernst","date_updated":"2020-10-08T12:58:10Z","content_type":"application/pdf","success":1,"file_id":"8632","date_created":"2020-10-08T12:58:10Z","file_name":"2019_ACMTransactions_Chatterjee.pdf","relation":"main_file","access_level":"open_access","checksum":"291cc86a07bd010d4815e177dac57b70"}],"file_date_updated":"2020-10-08T12:58:10Z","_id":"7158","issue":"4","author":[{"last_name":"Chatterjee","full_name":"Chatterjee, Krishnendu","orcid":"0000-0002-4561-241X","first_name":"Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-1702-6584","full_name":"Goharshady, Amir Kafshdar","id":"391365CE-F248-11E8-B48F-1D18A9856A87","first_name":"Amir Kafshdar","last_name":"Goharshady"},{"last_name":"Goyal","first_name":"Prateesh","full_name":"Goyal, Prateesh"},{"orcid":"0000-0003-4783-0389","full_name":"Ibsen-Jensen, Rasmus","id":"3B699956-F248-11E8-B48F-1D18A9856A87","first_name":"Rasmus","last_name":"Ibsen-Jensen"},{"id":"49704004-F248-11E8-B48F-1D18A9856A87","first_name":"Andreas","orcid":"0000-0002-8943-0722","full_name":"Pavlogiannis, Andreas","last_name":"Pavlogiannis"}],"article_processing_charge":"No","status":"public","department":[{"_id":"KrCh"}],"doi":"10.1145/3363525","has_accepted_license":"1","title":"Faster algorithms for dynamic algebraic queries in basic RSMs with constant treewidth","language":[{"iso":"eng"}],"month":"11","publisher":"ACM","year":"2019","volume":41,"project":[{"call_identifier":"FWF","name":"Modern Graph Algorithmic Techniques in Formal Verification","_id":"2584A770-B435-11E9-9278-68D0E5697425","grant_number":"P 23499-N23"},{"name":"Game Theory","call_identifier":"FWF","grant_number":"S11407","_id":"25863FF4-B435-11E9-9278-68D0E5697425"},{"name":"Quantitative Graph Games: Theory and Applications","call_identifier":"FP7","grant_number":"279307","_id":"2581B60A-B435-11E9-9278-68D0E5697425"}]},{"pubrep_id":"1069","article_processing_charge":"No","author":[{"last_name":"Chatterjee","orcid":"0000-0002-4561-241X","full_name":"Chatterjee, Krishnendu","first_name":"Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Goharshady, Amir Kafshdar","orcid":"0000-0003-1702-6584","first_name":"Amir Kafshdar","id":"391365CE-F248-11E8-B48F-1D18A9856A87","last_name":"Goharshady"},{"last_name":"Pourdamghani","full_name":"Pourdamghani, Arash","first_name":"Arash"}],"doi":"10.1145/3297280.3297319","department":[{"_id":"KrCh"}],"status":"public","month":"04","language":[{"iso":"eng"}],"title":"Hybrid Mining: Exploiting blockchain’s computational power for distributed problem solving","has_accepted_license":"1","year":"2019","publisher":"ACM","project":[{"_id":"2581B60A-B435-11E9-9278-68D0E5697425","grant_number":"279307","call_identifier":"FP7","name":"Quantitative Graph Games: Theory and Applications"},{"_id":"25892FC0-B435-11E9-9278-68D0E5697425","grant_number":"ICT15-003","name":"Efficient Algorithms for Computer Aided Verification"},{"name":"Rigorous Systems Engineering","call_identifier":"FWF","_id":"25832EC2-B435-11E9-9278-68D0E5697425","grant_number":"S 11407_N23"}],"volume":"Part F147772","date_published":"2019-04-01T00:00:00Z","oa":1,"type":"conference","page":"374-381","publication_status":"published","publication":"Proceedings of the 34th ACM Symposium on Applied Computing","isi":1,"citation":{"ieee":"K. Chatterjee, A. K. Goharshady, and A. Pourdamghani, “Hybrid Mining: Exploiting blockchain’s computational power for distributed problem solving,” in Proceedings of the 34th ACM Symposium on Applied Computing, Limassol, Cyprus, 2019, vol. Part F147772, pp. 374–381.","ista":"Chatterjee K, Goharshady AK, Pourdamghani A. 2019. Hybrid Mining: Exploiting blockchain’s computational power for distributed problem solving. Proceedings of the 34th ACM Symposium on Applied Computing. ACM Symposium on Applied Computing vol. Part F147772, 374–381.","apa":"Chatterjee, K., Goharshady, A. K., & Pourdamghani, A. (2019). Hybrid Mining: Exploiting blockchain’s computational power for distributed problem solving. In Proceedings of the 34th ACM Symposium on Applied Computing (Vol. Part F147772, pp. 374–381). Limassol, Cyprus: ACM. https://doi.org/10.1145/3297280.3297319","chicago":"Chatterjee, Krishnendu, Amir Kafshdar Goharshady, and Arash Pourdamghani. “Hybrid Mining: Exploiting Blockchain’s Computational Power for Distributed Problem Solving.” In Proceedings of the 34th ACM Symposium on Applied Computing, Part F147772:374–81. ACM, 2019. https://doi.org/10.1145/3297280.3297319.","mla":"Chatterjee, Krishnendu, et al. “Hybrid Mining: Exploiting Blockchain’s Computational Power for Distributed Problem Solving.” Proceedings of the 34th ACM Symposium on Applied Computing, vol. Part F147772, ACM, 2019, pp. 374–81, doi:10.1145/3297280.3297319.","short":"K. Chatterjee, A.K. Goharshady, A. Pourdamghani, in:, Proceedings of the 34th ACM Symposium on Applied Computing, ACM, 2019, pp. 374–381.","ama":"Chatterjee K, Goharshady AK, Pourdamghani A. Hybrid Mining: Exploiting blockchain’s computational power for distributed problem solving. In: Proceedings of the 34th ACM Symposium on Applied Computing. Vol Part F147772. ACM; 2019:374-381. doi:10.1145/3297280.3297319"},"conference":{"name":"ACM Symposium on Applied Computing","location":"Limassol, Cyprus","end_date":"2019-04-12","start_date":"2019-04-08"},"quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","abstract":[{"lang":"eng","text":"In today's cryptocurrencies, Hashcash proof of work is the most commonly-adopted approach to mining. In Hashcash, when a miner decides to add a block to the chain, she has to solve the difficult computational puzzle of inverting a hash function. While Hashcash has been successfully adopted in both Bitcoin and Ethereum, it has attracted significant and harsh criticism due to its massive waste of electricity, its carbon footprint and environmental effects, and the inherent lack of usefulness in inverting a hash function. Various other mining protocols have been suggested, including proof of stake, in which a miner's chance of adding the next block is proportional to her current balance. However, such protocols lead to a higher entry cost for new miners who might not still have any stake in the cryptocurrency, and can in the worst case lead to an oligopoly, where the rich have complete control over mining. In this paper, we propose Hybrid Mining: a new mining protocol that combines solving real-world useful problems with Hashcash. Our protocol allows new miners to join the network by taking part in Hashcash mining without having to own an initial stake. It also allows nodes of the network to submit hard computational problems whose solutions are of interest in the real world, e.g.~protein folding problems. Then, miners can choose to compete in solving these problems, in lieu of Hashcash, for adding a new block. Hence, Hybrid Mining incentivizes miners to solve useful problems, such as hard computational problems arising in biology, in a distributed manner. It also gives researchers in other areas an easy-to-use tool to outsource their hard computations to the blockchain network, which has enormous computational power, by paying a reward to the miner who solves the problem for them. Moreover, our protocol provides strong security guarantees and is at least as resilient to double spending as Bitcoin."}],"ddc":["004"],"external_id":{"isi":["000474685800049"]},"date_created":"2019-05-06T12:11:36Z","publication_identifier":{"isbn":["9781450359337"]},"day":"01","oa_version":"Submitted Version","scopus_import":"1","ec_funded":1,"related_material":{"record":[{"status":"public","id":"8934","relation":"dissertation_contains"}]},"_id":"6378","date_updated":"2026-08-19T22:30:58Z","file_date_updated":"2020-07-14T12:47:29Z","file":[{"date_created":"2019-05-06T12:09:27Z","relation":"main_file","file_name":"2019_ACM_Chatterjee.pdf","access_level":"open_access","checksum":"fbfbcd5a0c7a743862bfc3045539a614","creator":"dernst","file_size":1023934,"date_updated":"2020-07-14T12:47:29Z","content_type":"application/pdf","file_id":"6379"}]},{"date_published":"2019-06-08T00:00:00Z","oa":1,"page":"204-220","type":"conference","publication_status":"published","publication":"PLDI 2019: Proceedings of the 40th ACM SIGPLAN Conference on Programming Language Design and Implementation","citation":{"mla":"Wang, Peixin, et al. “Cost Analysis of Nondeterministic Probabilistic Programs.” PLDI 2019: Proceedings of the 40th ACM SIGPLAN Conference on Programming Language Design and Implementation, Association for Computing Machinery, 2019, pp. 204–20, doi:10.1145/3314221.3314581.","chicago":"Wang, Peixin, Hongfei Fu, Amir Kafshdar Goharshady, Krishnendu Chatterjee, Xudong Qin, and Wenjun Shi. “Cost Analysis of Nondeterministic Probabilistic Programs.” In PLDI 2019: Proceedings of the 40th ACM SIGPLAN Conference on Programming Language Design and Implementation, 204–20. Association for Computing Machinery, 2019. https://doi.org/10.1145/3314221.3314581.","apa":"Wang, P., Fu, H., Goharshady, A. K., Chatterjee, K., Qin, X., & Shi, W. (2019). Cost analysis of nondeterministic probabilistic programs. In PLDI 2019: Proceedings of the 40th ACM SIGPLAN Conference on Programming Language Design and Implementation (pp. 204–220). Phoenix, AZ, United States: Association for Computing Machinery. https://doi.org/10.1145/3314221.3314581","ieee":"P. Wang, H. Fu, A. K. Goharshady, K. Chatterjee, X. Qin, and W. Shi, “Cost analysis of nondeterministic probabilistic programs,” in PLDI 2019: Proceedings of the 40th ACM SIGPLAN Conference on Programming Language Design and Implementation, Phoenix, AZ, United States, 2019, pp. 204–220.","ista":"Wang P, Fu H, Goharshady AK, Chatterjee K, Qin X, Shi W. 2019. Cost analysis of nondeterministic probabilistic programs. PLDI 2019: Proceedings of the 40th ACM SIGPLAN Conference on Programming Language Design and Implementation. PLDI: Conference on Programming Language Design and Implementation, 204–220.","ama":"Wang P, Fu H, Goharshady AK, Chatterjee K, Qin X, Shi W. Cost analysis of nondeterministic probabilistic programs. In: PLDI 2019: Proceedings of the 40th ACM SIGPLAN Conference on Programming Language Design and Implementation. Association for Computing Machinery; 2019:204-220. doi:10.1145/3314221.3314581","short":"P. Wang, H. Fu, A.K. Goharshady, K. Chatterjee, X. Qin, W. Shi, in:, PLDI 2019: Proceedings of the 40th ACM SIGPLAN Conference on Programming Language Design and Implementation, Association for Computing Machinery, 2019, pp. 204–220."},"isi":1,"conference":{"name":"PLDI: Conference on Programming Language Design and Implementation","location":"Phoenix, AZ, United States","end_date":"2019-06-26","start_date":"2019-06-22"},"quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","abstract":[{"lang":"eng","text":"We consider the problem of expected cost analysis over nondeterministic probabilistic programs,\r\nwhich aims at automated methods for analyzing the resource-usage of such programs.\r\nPrevious approaches for this problem could only handle nonnegative bounded costs.\r\nHowever, in many scenarios, such as queuing networks or analysis of cryptocurrency protocols,\r\nboth positive and negative costs are necessary and the costs are unbounded as well.\r\n\r\nIn this work, we present a sound and efficient approach to obtain polynomial bounds on the\r\nexpected accumulated cost of nondeterministic probabilistic programs.\r\nOur approach can handle (a) general positive and negative costs with bounded updates in\r\nvariables; and (b) nonnegative costs with general updates to variables.\r\nWe show that several natural examples which could not be\r\nhandled by previous approaches are captured in our framework.\r\n\r\nMoreover, our approach leads to an efficient polynomial-time algorithm, while no\r\nprevious approach for cost analysis of probabilistic programs could guarantee polynomial runtime.\r\nFinally, we show the effectiveness of our approach using experimental results on a variety of programs for which we efficiently synthesize tight resource-usage bounds."}],"ddc":["000"],"external_id":{"isi":["000523190300014"],"arxiv":["1902.04659"]},"date_created":"2019-03-25T10:13:25Z","day":"08","arxiv":1,"oa_version":"Submitted Version","scopus_import":"1","related_material":{"record":[{"relation":"earlier_version","id":"5457","status":"public"},{"status":"public","relation":"dissertation_contains","id":"8934"}]},"ec_funded":1,"_id":"6175","file_date_updated":"2020-07-14T12:47:20Z","date_updated":"2026-08-19T22:30:58Z","file":[{"content_type":"application/pdf","date_updated":"2020-07-14T12:47:20Z","file_id":"6176","creator":"akafshda","file_size":4051066,"checksum":"703a5e9b8c8587f2a44085ffd9a4db64","access_level":"open_access","date_created":"2019-03-25T10:11:22Z","file_name":"paper.pdf","relation":"main_file"}],"article_processing_charge":"No","author":[{"full_name":"Wang, Peixin","first_name":"Peixin","last_name":"Wang"},{"last_name":"Fu","first_name":"Hongfei","id":"3AAD03D6-F248-11E8-B48F-1D18A9856A87","full_name":"Fu, Hongfei"},{"last_name":"Goharshady","orcid":"0000-0003-1702-6584","full_name":"Goharshady, Amir Kafshdar","id":"391365CE-F248-11E8-B48F-1D18A9856A87","first_name":"Amir Kafshdar"},{"orcid":"0000-0002-4561-241X","full_name":"Chatterjee, Krishnendu","first_name":"Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","last_name":"Chatterjee"},{"last_name":"Qin","full_name":"Qin, Xudong","first_name":"Xudong"},{"full_name":"Shi, Wenjun","first_name":"Wenjun","last_name":"Shi"}],"department":[{"_id":"KrCh"}],"doi":"10.1145/3314221.3314581","status":"public","month":"06","title":"Cost analysis of nondeterministic probabilistic programs","language":[{"iso":"eng"}],"keyword":["Program Cost Analysis","Program Termination","Probabilistic Programs","Martingales"],"has_accepted_license":"1","publisher":"Association for Computing Machinery","year":"2019","project":[{"name":"Efficient Algorithms for Computer Aided Verification","grant_number":"ICT15-003","_id":"25892FC0-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"Game Theory","_id":"25863FF4-B435-11E9-9278-68D0E5697425","grant_number":"S11407"},{"_id":"25832EC2-B435-11E9-9278-68D0E5697425","grant_number":"S 11407_N23","call_identifier":"FWF","name":"Rigorous Systems Engineering"},{"call_identifier":"FP7","name":"Quantitative Graph Games: Theory and Applications","grant_number":"279307","_id":"2581B60A-B435-11E9-9278-68D0E5697425"},{"name":"Quantitative Game-theoretic Analysis of Blockchain Applications and Smart Contracts","_id":"266EEEC0-B435-11E9-9278-68D0E5697425"}]},{"main_file_link":[{"url":"https://arxiv.org/abs/1705.00317","open_access":"1"}],"doi":"10.1145/3339984","department":[{"_id":"KrCh"}],"status":"public","month":"10","language":[{"iso":"eng"}],"title":"Non-polynomial worst-case analysis of recursive programs","year":"2019","publisher":"ACM","project":[{"name":"Efficient Algorithms for Computer Aided Verification","_id":"25892FC0-B435-11E9-9278-68D0E5697425","grant_number":"ICT15-003"},{"name":"Rigorous Systems Engineering","call_identifier":"FWF","_id":"25832EC2-B435-11E9-9278-68D0E5697425","grant_number":"S 11407_N23"},{"grant_number":"279307","_id":"2581B60A-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Quantitative Graph Games: Theory and Applications"},{"_id":"267066CE-B435-11E9-9278-68D0E5697425","name":"Quantitative Analysis of Probabilistic Systems with a focus on Crypto-Currencies"},{"_id":"266EEEC0-B435-11E9-9278-68D0E5697425","name":"Quantitative Game-theoretic Analysis of Blockchain Applications and Smart Contracts"}],"volume":41,"issue":"4","article_processing_charge":"No","author":[{"last_name":"Chatterjee","first_name":"Krishnendu","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","full_name":"Chatterjee, Krishnendu","orcid":"0000-0002-4561-241X"},{"first_name":"Hongfei","full_name":"Fu, Hongfei","last_name":"Fu"},{"full_name":"Goharshady, Amir Kafshdar","orcid":"0000-0003-1702-6584","id":"391365CE-F248-11E8-B48F-1D18A9856A87","first_name":"Amir Kafshdar","last_name":"Goharshady"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_type":"original","abstract":[{"text":"We study the problem of developing efficient approaches for proving\r\nworst-case bounds of non-deterministic recursive programs. Ranking functions\r\nare sound and complete for proving termination and worst-case bounds of\r\nnonrecursive programs. First, we apply ranking functions to recursion,\r\nresulting in measure functions. We show that measure functions provide a sound\r\nand complete approach to prove worst-case bounds of non-deterministic recursive\r\nprograms. Our second contribution is the synthesis of measure functions in\r\nnonpolynomial forms. We show that non-polynomial measure functions with\r\nlogarithm and exponentiation can be synthesized through abstraction of\r\nlogarithmic or exponentiation terms, Farkas' Lemma, and Handelman's Theorem\r\nusing linear programming. While previous methods obtain worst-case polynomial\r\nbounds, our approach can synthesize bounds of the form $\\mathcal{O}(n\\log n)$\r\nas well as $\\mathcal{O}(n^r)$ where $r$ is not an integer. We present\r\nexperimental results to demonstrate that our approach can obtain efficiently\r\nworst-case bounds of classical recursive algorithms such as (i) Merge-Sort, the\r\ndivide-and-conquer algorithm for the Closest-Pair problem, where we obtain\r\n$\\mathcal{O}(n \\log n)$ worst-case bound, and (ii) Karatsuba's algorithm for\r\npolynomial multiplication and Strassen's algorithm for matrix multiplication,\r\nwhere we obtain $\\mathcal{O}(n^r)$ bound such that $r$ is not an integer and\r\nclose to the best-known bounds for the respective algorithms.","lang":"eng"}],"date_created":"2019-11-13T08:33:43Z","external_id":{"arxiv":["1705.00317"],"isi":["000564108400001"]},"day":"01","oa_version":"Preprint","arxiv":1,"scopus_import":"1","related_material":{"record":[{"status":"public","relation":"earlier_version","id":"639"},{"status":"public","relation":"dissertation_contains","id":"8934"}]},"ec_funded":1,"_id":"7014","date_updated":"2026-08-19T22:30:58Z","date_published":"2019-10-01T00:00:00Z","oa":1,"type":"journal_article","publication_status":"published","publication":"ACM Transactions on Programming Languages and Systems","article_number":"20","intvolume":" 41","citation":{"ista":"Chatterjee K, Fu H, Goharshady AK. 2019. Non-polynomial worst-case analysis of recursive programs. ACM Transactions on Programming Languages and Systems. 41(4), 20.","ieee":"K. Chatterjee, H. Fu, and A. K. Goharshady, “Non-polynomial worst-case analysis of recursive programs,” ACM Transactions on Programming Languages and Systems, vol. 41, no. 4. ACM, 2019.","apa":"Chatterjee, K., Fu, H., & Goharshady, A. K. (2019). Non-polynomial worst-case analysis of recursive programs. ACM Transactions on Programming Languages and Systems. ACM. https://doi.org/10.1145/3339984","chicago":"Chatterjee, Krishnendu, Hongfei Fu, and Amir Kafshdar Goharshady. “Non-Polynomial Worst-Case Analysis of Recursive Programs.” ACM Transactions on Programming Languages and Systems. ACM, 2019. https://doi.org/10.1145/3339984.","mla":"Chatterjee, Krishnendu, et al. “Non-Polynomial Worst-Case Analysis of Recursive Programs.” ACM Transactions on Programming Languages and Systems, vol. 41, no. 4, 20, ACM, 2019, doi:10.1145/3339984.","short":"K. Chatterjee, H. Fu, A.K. Goharshady, ACM Transactions on Programming Languages and Systems 41 (2019).","ama":"Chatterjee K, Fu H, Goharshady AK. Non-polynomial worst-case analysis of recursive programs. ACM Transactions on Programming Languages and Systems. 2019;41(4). doi:10.1145/3339984"},"isi":1,"quality_controlled":"1"},{"oa_version":"Published Version","publication_identifier":{"issn":["2475-1421"]},"day":"01","date_created":"2019-05-06T12:18:17Z","ddc":["004"],"abstract":[{"lang":"eng","text":"There is a huge gap between the speeds of modern caches and main memories, and therefore cache misses account for a considerable loss of efficiency in programs. The predominant technique to address this issue has been Data Packing: data elements that are frequently accessed within time proximity are packed into the same cache block, thereby minimizing accesses to the main memory. We consider the algorithmic problem of Data Packing on a two-level memory system. Given a reference sequence R of accesses to data elements, the task is to partition the elements into cache blocks such that the number of cache misses on R is minimized. The problem is notoriously difficult: it is NP-hard even when the cache has size 1, and is hard to approximate for any cache size larger than 4. Therefore, all existing techniques for Data Packing are based on heuristics and lack theoretical guarantees. In this work, we present the first positive theoretical results for Data Packing, along with new and stronger negative results. We consider the problem under the lens of the underlying access hypergraphs, which are hypergraphs of affinities between the data elements, where the order of an access hypergraph corresponds to the size of the affinity group. We study the problem parameterized by the treewidth of access hypergraphs, which is a standard notion in graph theory to measure the closeness of a graph to a tree. Our main results are as follows: We show there is a number q* depending on the cache parameters such that (a) if the access hypergraph of order q* has constant treewidth, then there is a linear-time algorithm for Data Packing; (b)the Data Packing problem remains NP-hard even if the access hypergraph of order q*-1 has constant treewidth. Thus, we establish a fine-grained dichotomy depending on a single parameter, namely, the highest order among access hypegraphs that have constant treewidth; and establish the optimal value q* of this parameter. Finally, we present an experimental evaluation of a prototype implementation of our algorithm. Our results demonstrate that, in practice, access hypergraphs of many commonly-used algorithms have small treewidth. We compare our approach with several state-of-the-art heuristic-based algorithms and show that our algorithm leads to significantly fewer cache-misses. "}],"article_type":"original","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2026-08-19T22:30:58Z","file_date_updated":"2020-07-14T12:47:29Z","file":[{"relation":"main_file","file_name":"2019_ACM_POPL_Chatterjee.pdf","date_created":"2019-05-06T12:23:11Z","checksum":"c157752f96877b36685ad7063ada4524","access_level":"open_access","file_size":1294962,"creator":"dernst","file_id":"6381","content_type":"application/pdf","date_updated":"2020-07-14T12:47:29Z"}],"_id":"6380","acknowledgement":"The research was partially supported by Vienna Science and Technology Fund (WWTF) Project ICT15-003, Austrian Science Fund (FWF) NFN Grant No S11407-N23 (RiSE/SHiNE), ERC\r\nStarting Grant (279307: Graph Games), and the IBM PhD Fellowship program.","related_material":{"record":[{"id":"8934","relation":"dissertation_contains","status":"public"}]},"ec_funded":1,"scopus_import":"1","article_number":"53","publication":"Proceedings of the ACM on Programming Languages","publication_status":"published","OA_place":"publisher","type":"journal_article","oa":1,"date_published":"2019-01-01T00:00:00Z","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"quality_controlled":"1","citation":{"short":"K. Chatterjee, A.K. Goharshady, N. Okati, A. Pavlogiannis, Proceedings of the ACM on Programming Languages 3 (2019).","ama":"Chatterjee K, Goharshady AK, Okati N, Pavlogiannis A. Efficient parameterized algorithms for data packing. Proceedings of the ACM on Programming Languages. 2019;3(POPL). doi:10.1145/3290366","apa":"Chatterjee, K., Goharshady, A. K., Okati, N., & Pavlogiannis, A. (2019). Efficient parameterized algorithms for data packing. Proceedings of the ACM on Programming Languages. ACM. https://doi.org/10.1145/3290366","ista":"Chatterjee K, Goharshady AK, Okati N, Pavlogiannis A. 2019. Efficient parameterized algorithms for data packing. Proceedings of the ACM on Programming Languages. 3(POPL), 53.","ieee":"K. Chatterjee, A. K. Goharshady, N. Okati, and A. Pavlogiannis, “Efficient parameterized algorithms for data packing,” Proceedings of the ACM on Programming Languages, vol. 3, no. POPL. ACM, 2019.","chicago":"Chatterjee, Krishnendu, Amir Kafshdar Goharshady, Nastaran Okati, and Andreas Pavlogiannis. “Efficient Parameterized Algorithms for Data Packing.” Proceedings of the ACM on Programming Languages. ACM, 2019. https://doi.org/10.1145/3290366.","mla":"Chatterjee, Krishnendu, et al. “Efficient Parameterized Algorithms for Data Packing.” Proceedings of the ACM on Programming Languages, vol. 3, no. POPL, 53, ACM, 2019, doi:10.1145/3290366."},"intvolume":" 3","has_accepted_license":"1","language":[{"iso":"eng"}],"title":"Efficient parameterized algorithms for data packing","month":"01","status":"public","doi":"10.1145/3290366","department":[{"_id":"KrCh"}],"volume":3,"project":[{"grant_number":"ICT15-003","_id":"25892FC0-B435-11E9-9278-68D0E5697425","name":"Efficient Algorithms for Computer Aided Verification"},{"grant_number":"S 11407_N23","_id":"25832EC2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Rigorous Systems Engineering"},{"name":"Quantitative Graph Games: Theory and Applications","call_identifier":"FP7","_id":"2581B60A-B435-11E9-9278-68D0E5697425","grant_number":"279307"}],"year":"2019","publisher":"ACM","OA_type":"hybrid","pubrep_id":"1056","author":[{"last_name":"Chatterjee","full_name":"Chatterjee, Krishnendu","orcid":"0000-0002-4561-241X","id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","first_name":"Krishnendu"},{"full_name":"Goharshady, Amir Kafshdar","orcid":"0000-0003-1702-6584","first_name":"Amir Kafshdar","id":"391365CE-F248-11E8-B48F-1D18A9856A87","last_name":"Goharshady"},{"first_name":"Nastaran","full_name":"Okati, Nastaran","last_name":"Okati"},{"last_name":"Pavlogiannis","first_name":"Andreas","id":"49704004-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8943-0722","full_name":"Pavlogiannis, Andreas"}],"article_processing_charge":"Yes (in subscription journal)","issue":"POPL"},{"article_processing_charge":"No","author":[{"id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","first_name":"Krishnendu","orcid":"0000-0002-4561-241X","full_name":"Chatterjee, Krishnendu","last_name":"Chatterjee"},{"id":"391365CE-F248-11E8-B48F-1D18A9856A87","first_name":"Amir Kafshdar","full_name":"Goharshady, Amir Kafshdar","orcid":"0000-0003-1702-6584","last_name":"Goharshady"},{"last_name":"Pourdamghani","full_name":"Pourdamghani, Arash","first_name":"Arash"}],"year":"2019","publisher":"IEEE","project":[{"_id":"25892FC0-B435-11E9-9278-68D0E5697425","grant_number":"ICT15-003","name":"Efficient Algorithms for Computer Aided Verification"},{"name":"Rigorous Systems Engineering","call_identifier":"FWF","_id":"25832EC2-B435-11E9-9278-68D0E5697425","grant_number":"S 11407_N23"},{"_id":"2581B60A-B435-11E9-9278-68D0E5697425","grant_number":"279307","name":"Quantitative Graph Games: Theory and Applications","call_identifier":"FP7"},{"name":"Quantitative Game-theoretic Analysis of Blockchain Applications and Smart Contracts","_id":"266EEEC0-B435-11E9-9278-68D0E5697425"},{"name":"Quantitative Analysis of Probabilistic Systems with a focus on Crypto-Currencies","_id":"267066CE-B435-11E9-9278-68D0E5697425"}],"main_file_link":[{"open_access":"1","url":"https://arxiv.org/abs/1902.07986"}],"doi":"10.1109/BLOC.2019.8751326","department":[{"_id":"KrCh"}],"status":"public","month":"05","language":[{"iso":"eng"}],"title":"Probabilistic smart contracts: Secure randomness on the blockchain","isi":1,"citation":{"apa":"Chatterjee, K., Goharshady, A. K., & Pourdamghani, A. (2019). Probabilistic smart contracts: Secure randomness on the blockchain. In IEEE International Conference on Blockchain and Cryptocurrency. Seoul, Korea: IEEE. https://doi.org/10.1109/BLOC.2019.8751326","ieee":"K. Chatterjee, A. K. Goharshady, and A. Pourdamghani, “Probabilistic smart contracts: Secure randomness on the blockchain,” in IEEE International Conference on Blockchain and Cryptocurrency, Seoul, Korea, 2019.","ista":"Chatterjee K, Goharshady AK, Pourdamghani A. 2019. Probabilistic smart contracts: Secure randomness on the blockchain. IEEE International Conference on Blockchain and Cryptocurrency. IEEE International Conference on Blockchain and Cryptocurrency, 8751326.","chicago":"Chatterjee, Krishnendu, Amir Kafshdar Goharshady, and Arash Pourdamghani. “Probabilistic Smart Contracts: Secure Randomness on the Blockchain.” In IEEE International Conference on Blockchain and Cryptocurrency. IEEE, 2019. https://doi.org/10.1109/BLOC.2019.8751326.","mla":"Chatterjee, Krishnendu, et al. “Probabilistic Smart Contracts: Secure Randomness on the Blockchain.” IEEE International Conference on Blockchain and Cryptocurrency, 8751326, IEEE, 2019, doi:10.1109/BLOC.2019.8751326.","short":"K. Chatterjee, A.K. Goharshady, A. Pourdamghani, in:, IEEE International Conference on Blockchain and Cryptocurrency, IEEE, 2019.","ama":"Chatterjee K, Goharshady AK, Pourdamghani A. Probabilistic smart contracts: Secure randomness on the blockchain. In: IEEE International Conference on Blockchain and Cryptocurrency. IEEE; 2019. doi:10.1109/BLOC.2019.8751326"},"conference":{"name":"IEEE International Conference on Blockchain and Cryptocurrency","start_date":"2019-05-14","end_date":"2019-05-17","location":"Seoul, Korea"},"quality_controlled":"1","date_published":"2019-05-01T00:00:00Z","oa":1,"type":"conference","publication_status":"published","article_number":"8751326","publication":"IEEE International Conference on Blockchain and Cryptocurrency","scopus_import":"1","ec_funded":1,"related_material":{"record":[{"id":"8934","relation":"dissertation_contains","status":"public"}]},"_id":"6056","date_updated":"2026-08-19T22:30:59Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","abstract":[{"lang":"eng","text":"In today's programmable blockchains, smart contracts are limited to being deterministic and non-probabilistic. This lack of randomness is a consequential limitation, given that a wide variety of real-world financial contracts, such as casino games and lotteries, depend entirely on randomness. As a result, several ad-hoc random number generation approaches have been developed to be used in smart contracts. These include ideas such as using an oracle or relying on the block hash. However, these approaches are manipulatable, i.e. their output can be tampered with by parties who might not be neutral, such as the owner of the oracle or the miners.We propose a novel game-theoretic approach for generating provably unmanipulatable pseudorandom numbers on the blockchain. Our approach allows smart contracts to access a trustworthy source of randomness that does not rely on potentially compromised miners or oracles, hence enabling the creation of a new generation of smart contracts that are not limited to being non-probabilistic and can be drawn from the much more general class of probabilistic programs."}],"date_created":"2019-02-26T09:03:15Z","external_id":{"arxiv":["1902.07986"],"isi":["000491257000076"]},"day":"01","oa_version":"Preprint","arxiv":1},{"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"article_processing_charge":"No","author":[{"last_name":"Assen","orcid":"0000-0003-3470-6119","full_name":"Assen, Frank P","first_name":"Frank P","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87"}],"month":"10","has_accepted_license":"1","title":"Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking","language":[{"iso":"eng"}],"doi":"10.15479/AT:ISTA:6947","department":[{"_id":"MiSi"}],"status":"public","publisher":"Institute of Science and Technology Austria","year":"2019","publication_status":"published","oa":1,"date_published":"2019-10-09T00:00:00Z","OA_place":"publisher","type":"dissertation","page":"142","alternative_title":["ISTA Thesis"],"supervisor":[{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","last_name":"Sixt"}],"corr_author":"1","citation":{"ama":"Assen FP. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. 2019. doi:10.15479/AT:ISTA:6947","short":"F.P. Assen, Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking, Institute of Science and Technology Austria, 2019.","chicago":"Assen, Frank P. “Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6947.","ieee":"F. P. Assen, “Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking,” Institute of Science and Technology Austria, 2019.","ista":"Assen FP. 2019. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. Institute of Science and Technology Austria.","apa":"Assen, F. P. (2019). Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6947","mla":"Assen, Frank P. Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6947."},"day":"09","publication_identifier":{"issn":["2663-337X"]},"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Lymph nodes are es s ential organs of the immune s ys tem where adaptive immune responses originate, and consist of various leukocyte populations and a stromal backbone. Fibroblastic reticular cells (FRCs) are the main stromal cells and form a sponge-like extracellular matrix network, called conduits , which they thems elves enwrap and contract. Lymph, containing s oluble antigens , arrive in lymph nodes via afferent lymphatic vessels that connect to the s ubcaps ular s inus and conduit network. According to the current paradigm, the conduit network dis tributes afferent lymph through lymph nodes and thus provides acces s for immune cells to lymph-borne antigens. An elas tic caps ule s urrounds the organ and confines the immune cells and FRC network. Lymph nodes are completely packed with lymphocytes and lymphocyte numbers directly dictates the size of the organ. Although lymphocytes cons tantly enter and leave the lymph node, its s ize remains remarkedly s table under homeostatic conditions. It is only partly known how the cellularity and s ize of the lymph node is regulated and how the lymph node is able to swell in inflammation. The role of the FRC network in lymph node s welling and trans fer of fluids are inves tigated in this thes is. Furthermore, we s tudied what trafficking routes are us ed by cancer cells in lymph nodes to form distal metastases.We examined the role of a mechanical feedback in regulation of lymph node swelling. Using parallel plate compression and UV-las er cutting experiments we dis s ected the mechanical force dynamics of the whole lymph node, and individually for FRCs and the caps ule. Physical forces generated by packed lymphocytes directly affect the tens ion on the FRC network and capsule, which increases its resistance to swelling. This implies a feedback mechanism between tis s ue pres s ure and ability of lymphocytes to enter the organ. Following inflammation, the lymph node swells ∼10 fold in two weeks . Yet, what is the role for tens ion on the FRC network and caps ule, and how are lymphocytes able to enter in conditions that resist swelling remain open ques tions . We s how that tens ion on the FRC network is important to limit the swelling rate of the organ so that the FRC network can grow in a coordinated fashion. This is illustrated by interfering with FRC contractility, which leads to faster swelling rates and a dis organized FRC network in the inflamed lymph node. Growth of the FRC network in turn is expected to releas e tens ion on thes e s tructures and lowers the res is tance to swelling, thereby allowing more lymphocytes to enter the organ and drive more swelling. Halt of swelling coincides with a thickening of the caps ule, which forms a thick res is tant band around the organ and lowers tens ion on the FRC network to form a new force equilibrium.The FRC and conduit network are further believed to be a privileged s ite of s oluble information within the lymph node, although many details remain uns olved. We s how by 3D ultra-recons truction that FRCs and antigen pres enting cells cover the s urface of conduit s ys tem for more than 99% and we dis cus s the implications for s oluble information exchangeat the conduit level.Finally, there is an ongoing debate in the cancer field whether and how cancer cells in lymph nodes s eed dis tal metas tas es . We s how that cancer cells infus ed into the lymph node can utilize trafficking routes of immune cells and rapidly migrate to blood vessels. Once in the blood circulation, these cells are able to form metastases in distal tissues."}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_created":"2019-10-14T16:54:52Z","ddc":["570"],"_id":"6947","file_date_updated":"2020-11-07T23:30:03Z","file":[{"file_id":"6990","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2020-11-07T23:30:03Z","file_size":214172667,"creator":"fassen","checksum":"53a739752a500f84d0f8ec953cbbd0b6","access_level":"closed","relation":"source_file","file_name":"PhDthesis_FrankAssen_revised2.docx","date_created":"2019-11-06T12:30:02Z","embargo_to":"open_access"},{"file_size":83637532,"creator":"fassen","date_updated":"2020-11-07T23:30:03Z","content_type":"application/pdf","embargo":"2020-11-06","file_id":"6991","date_created":"2019-11-06T12:30:57Z","file_name":"PhDthesis_FrankAssen_revised2.pdf","relation":"main_file","checksum":"8c156b65d9347bb599623a4b09f15d15","access_level":"open_access"}],"date_updated":"2026-06-18T18:47:59Z","degree_awarded":"PhD","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"664"},{"id":"402","relation":"part_of_dissertation","status":"public"}]}},{"article_processing_charge":"No","author":[{"last_name":"Käfer","full_name":"Käfer, Karola","id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87","first_name":"Karola"}],"doi":"10.15479/AT:ISTA:6825","department":[{"_id":"JoCs"},{"_id":"GradSch"}],"status":"public","month":"08","has_accepted_license":"1","language":[{"iso":"eng"}],"title":"The hippocampus and medial prefrontal cortex during flexible behavior","year":"2019","publisher":"Institute of Science and Technology Austria","oa":1,"date_published":"2019-08-24T00:00:00Z","OA_place":"publisher","type":"dissertation","page":"89","publication_status":"published","alternative_title":["ISTA Thesis"],"corr_author":"1","supervisor":[{"orcid":"0000-0002-5193-4036","full_name":"Csicsvari, Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","first_name":"Jozsef L","last_name":"Csicsvari"}],"citation":{"ama":"Käfer K. The hippocampus and medial prefrontal cortex during flexible behavior. 2019. doi:10.15479/AT:ISTA:6825","short":"K. Käfer, The Hippocampus and Medial Prefrontal Cortex during Flexible Behavior, Institute of Science and Technology Austria, 2019.","chicago":"Käfer, Karola. “The Hippocampus and Medial Prefrontal Cortex during Flexible Behavior.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6825.","apa":"Käfer, K. (2019). The hippocampus and medial prefrontal cortex during flexible behavior. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6825","ieee":"K. Käfer, “The hippocampus and medial prefrontal cortex during flexible behavior,” Institute of Science and Technology Austria, 2019.","ista":"Käfer K. 2019. The hippocampus and medial prefrontal cortex during flexible behavior. Institute of Science and Technology Austria.","mla":"Käfer, Karola. The Hippocampus and Medial Prefrontal Cortex during Flexible Behavior. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6825."},"abstract":[{"lang":"eng","text":"The solving of complex tasks requires the functions of more than one brain area and their interaction. Whilst spatial navigation and memory is dependent on the hippocampus, flexible behavior relies on the medial prefrontal cortex (mPFC). To further examine the roles of the hippocampus and mPFC, we recorded their neural activity during a task that depends on both of these brain regions.\r\nWith tetrodes, we recorded the extracellular activity of dorsal hippocampal CA1 (HPC) and mPFC neurons in Long-Evans rats performing a rule-switching task on the plus-maze. The plus-maze task had a spatial component since it required navigation along one of the two start arms and at the maze center a choice between one of the two goal arms. Which goal contained a reward depended on the rule currently in place. After an uncued rule change the animal had to abandon the old strategy and switch to the new rule, testing cognitive flexibility. Investigating the coordination of activity between the HPC and mPFC allows determination during which task stages their interaction is required. Additionally, comparing neural activity patterns in these two brain regions allows delineation of the specialized functions of the HPC and mPFC in this task. We analyzed neural activity in the HPC and mPFC in terms of oscillatory interactions, rule coding and replay.\r\nWe found that theta coherence between the HPC and mPFC is increased at the center and goals of the maze, both when the rule was stable or has changed. Similar results were found for locking of HPC and mPFC neurons to HPC theta oscillations. However, no differences in HPC-mPFC theta coordination were observed between the spatially- and cue-guided rule. Phase locking of HPC and mPFC neurons to HPC gamma oscillations was not modulated by\r\nmaze position or rule type. We found that the HPC coded for the two different rules with cofiring relationships between\r\ncell pairs. However, we could not find conclusive evidence for rule coding in the mPFC. Spatially-selective firing in the mPFC generalized between the two start and two goal arms. With Bayesian positional decoding, we found that the mPFC reactivated non-local positions during awake immobility periods. Replay of these non-local positions could represent entire behavioral trajectories resembling trajectory replay of the HPC. Furthermore, mPFC\r\ntrajectory-replay at the goal positively correlated with rule-switching performance. \r\nFinally, HPC and mPFC trajectory replay occurred independently of each other. These results show that the mPFC can replay ordered patterns of activity during awake immobility, possibly underlying its role in flexible behavior. "}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_created":"2019-08-21T15:00:57Z","ddc":["570"],"publication_identifier":{"issn":["2663-337X"]},"day":"24","oa_version":"Published Version","related_material":{"record":[{"relation":"part_of_dissertation","id":"5949","status":"public"}]},"degree_awarded":"PhD","_id":"6825","date_updated":"2026-04-08T13:56:14Z","file":[{"access_level":"open_access","checksum":"2664420e332a33338568f4f3bfc59287","date_created":"2019-09-03T08:07:13Z","relation":"main_file","file_name":"Thesis_Kaefer_PDFA.pdf","content_type":"application/pdf","date_updated":"2020-09-06T22:30:03Z","request_a_copy":0,"file_id":"6846","embargo":"2020-09-05","creator":"kkaefer","file_size":3205202},{"access_level":"closed","checksum":"9a154eab6f07aa590a3d2651dc0d926a","relation":"source_file","file_name":"Thesis_Kaefer.zip","embargo_to":"open_access","date_created":"2019-09-03T08:07:17Z","file_id":"6847","date_updated":"2024-04-10T22:30:48Z","content_type":"application/zip","creator":"kkaefer","file_size":2506835}],"file_date_updated":"2024-04-10T22:30:48Z"},{"_id":"5949","file_date_updated":"2020-07-14T12:47:13Z","file":[{"file_id":"5950","date_updated":"2020-07-14T12:47:13Z","content_type":"application/pdf","file_size":2132893,"creator":"dernst","checksum":"5e8de271ca04aef92a5de42d6aac4404","access_level":"open_access","file_name":"2019_Hippocampus_Kaefer.pdf","relation":"main_file","date_created":"2019-02-11T10:42:51Z"}],"date_updated":"2026-08-19T22:31:00Z","scopus_import":"1","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"6825"}]},"ec_funded":1,"day":"01","oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_type":"original","abstract":[{"text":"Aberrant proteostasis of protein aggregation may lead to behavior disorders including chronic mental illnesses (CMI). Furthermore, the neuronal activity alterations that underlie CMI are not well understood. We recorded the local field potential and single-unit activity of the hippocampal CA1 region in vivo in rats transgenically overexpressing the Disrupted-in-Schizophrenia 1 (DISC1) gene (tgDISC1), modeling sporadic CMI. These tgDISC1 rats have previously been shown to exhibit DISC1 protein aggregation, disturbances in the dopaminergic system and attention-related deficits. Recordings were performed during exploration of familiar and novel open field environments and during sleep, allowing investigation of neuronal abnormalities in unconstrained behavior. Compared to controls, tgDISC1 place cells exhibited smaller place fields and decreased speed-modulation of their firing rates, demonstrating altered spatial coding and deficits in encoding location-independent sensory inputs. Oscillation analyses showed that tgDISC1 pyramidal neurons had higher theta phase locking strength during novelty, limiting their phase coding ability. However, their mean theta phases were more variable at the population level, reducing oscillatory network synchronization. Finally, tgDISC1 pyramidal neurons showed a lack of novelty-induced shift in their preferred theta and gamma firing phases, indicating deficits in coding of novel environments with oscillatory firing. By combining single cell and neuronal population analyses, we link DISC1 protein pathology with abnormal hippocampal neural coding and network synchrony, and thereby gain a more comprehensive understanding of CMI mechanisms.","lang":"eng"}],"ddc":["570"],"external_id":{"isi":["000480635400003"]},"date_created":"2019-02-10T22:59:18Z","quality_controlled":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"intvolume":" 29","isi":1,"citation":{"ama":"Käfer K, Malagon-Vina H, Dickerson D, et al. Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization. Hippocampus. 2019;29(9):802-816. doi:10.1002/hipo.23076","short":"K. Käfer, H. Malagon-Vina, D. Dickerson, J. O’Neill, S.V. Trossbach, C. Korth, J.L. Csicsvari, Hippocampus 29 (2019) 802–816.","mla":"Käfer, Karola, et al. “Disrupted-in-Schizophrenia 1 Overexpression Disrupts Hippocampal Coding and Oscillatory Synchronization.” Hippocampus, vol. 29, no. 9, Wiley, 2019, pp. 802–16, doi:10.1002/hipo.23076.","chicago":"Käfer, Karola, Hugo Malagon-Vina, Desiree Dickerson, Joseph O’Neill, Svenja V. Trossbach, Carsten Korth, and Jozsef L Csicsvari. “Disrupted-in-Schizophrenia 1 Overexpression Disrupts Hippocampal Coding and Oscillatory Synchronization.” Hippocampus. Wiley, 2019. https://doi.org/10.1002/hipo.23076.","apa":"Käfer, K., Malagon-Vina, H., Dickerson, D., O’Neill, J., Trossbach, S. V., Korth, C., & Csicsvari, J. L. (2019). Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization. Hippocampus. Wiley. https://doi.org/10.1002/hipo.23076","ista":"Käfer K, Malagon-Vina H, Dickerson D, O’Neill J, Trossbach SV, Korth C, Csicsvari JL. 2019. Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization. Hippocampus. 29(9), 802–816.","ieee":"K. Käfer et al., “Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization,” Hippocampus, vol. 29, no. 9. Wiley, pp. 802–816, 2019."},"publication_status":"published","publication":"Hippocampus","date_published":"2019-09-01T00:00:00Z","oa":1,"type":"journal_article","page":"802-816","project":[{"call_identifier":"FP7","name":"inter-and intracellular signalling in schizophrenia","_id":"257BBB4C-B435-11E9-9278-68D0E5697425","grant_number":"607616"}],"volume":29,"year":"2019","publisher":"Wiley","month":"09","title":"Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization","language":[{"iso":"eng"}],"has_accepted_license":"1","department":[{"_id":"JoCs"}],"doi":"10.1002/hipo.23076","status":"public","article_processing_charge":"Yes (via OA deal)","author":[{"last_name":"Käfer","id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87","first_name":"Karola","full_name":"Käfer, Karola"},{"full_name":"Malagon-Vina, Hugo","first_name":"Hugo","last_name":"Malagon-Vina"},{"id":"444EB89E-F248-11E8-B48F-1D18A9856A87","first_name":"Desiree","full_name":"Dickerson, Desiree","last_name":"Dickerson"},{"last_name":"O'Neill","full_name":"O'Neill, Joseph","first_name":"Joseph"},{"first_name":"Svenja V.","full_name":"Trossbach, Svenja V.","last_name":"Trossbach"},{"first_name":"Carsten","full_name":"Korth, Carsten","last_name":"Korth"},{"orcid":"0000-0002-5193-4036","full_name":"Csicsvari, Jozsef L","first_name":"Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","last_name":"Csicsvari"}],"issue":"9"},{"article_processing_charge":"No","author":[{"last_name":"Ivanov","full_name":"Ivanov, Valeriy","first_name":"Valeriy"},{"last_name":"Fatichi","full_name":"Fatichi, Simone","id":"cf8e546b-a9b0-11f0-a43b-aa89ed1b56d6","first_name":"Simone"},{"full_name":"Daly, Edoardo","first_name":"Edoardo","last_name":"Daly"}],"citation":{"ama":"Ivanov V, Fatichi S, Daly E. 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Oxford University Press, 2019."},"publication_status":"published","publication":"Oxford Bibliographies in Environmental Science","date_published":"2019-08-28T00:00:00Z","type":"journal_article","OA_type":"closed access","_id":"22587","date_updated":"2026-08-20T06:50:13Z","scopus_import":"1","das_tickbox":"1","year":"2019","publisher":"Oxford University Press","extern":"1","month":"08","day":"28","publication_identifier":{"eisbn":["9780197858356"]},"language":[{"iso":"eng"}],"oa_version":"None","title":"Ecohydrology","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_type":"original","doi":"10.1093/obo/9780199363445-0120","date_created":"2026-07-27T12:30:25Z","status":"public"}]