[{"quality_controlled":"1","status":"public","conference":{"end_date":"2024-07-27","location":"Vienna, Austria","start_date":"2024-07-21","name":"ICML: International Conference on Machine Learning"},"abstract":[{"text":"It is known that sparsity can improve interpretability for deep neural networks. However, existing methods in the area either require networks that are pre-trained with sparsity constraints, or impose sparsity after the fact, altering the network’s general behavior. In this paper, we demonstrate, for the first time, that sparsity can instead be incorporated into the interpretation process itself, as a sample-specific preprocessing step. Unlike previous work, this approach, which we call SPADE, does not place constraints on the trained model and does not affect its behavior during inference on the sample. Given a trained model and a target sample, SPADE uses sample-targeted pruning to provide a \"trace\" of the network’s execution on the sample, reducing the network to the most important connections prior to computing an interpretation. We demonstrate that preprocessing with SPADE significantly increases the accuracy of image saliency maps across several interpretability methods. Additionally, SPADE improves the usefulness of neuron visualizations, aiding humans in reasoning about network behavior. Our code is available at https://github.com/IST-DASLab/SPADE.","lang":"eng"}],"main_file_link":[{"url":"https://doi.org/10.48550/arXiv.2310.04519","open_access":"1"}],"day":"01","oa":1,"publication":"Proceedings of the 41st International Conference on Machine Learning","arxiv":1,"publisher":"ML Research Press","alternative_title":["PMLR"],"scopus_import":"1","volume":235,"project":[{"_id":"9B9290DE-BA93-11EA-9121-9846C619BF3A","name":"Vienna Graduate School on Computational Optimization","grant_number":"W1260-N35"}],"oa_version":"Preprint","corr_author":"1","acknowledged_ssus":[{"_id":"ScienComp"}],"author":[{"first_name":"Arshia Soltani","last_name":"Moakhar","full_name":"Moakhar, Arshia Soltani"},{"orcid":"0000-0002-7778-3221","full_name":"Iofinova, Eugenia B","id":"f9a17499-f6e0-11ea-865d-fdf9a3f77117","first_name":"Eugenia B","last_name":"Iofinova"},{"last_name":"Frantar","id":"09a8f98d-ec99-11ea-ae11-c063a7b7fe5f","first_name":"Elias","full_name":"Frantar, Elias"},{"first_name":"Dan-Adrian","id":"4A899BFC-F248-11E8-B48F-1D18A9856A87","last_name":"Alistarh","orcid":"0000-0003-3650-940X","full_name":"Alistarh, Dan-Adrian"}],"month":"09","year":"2024","date_created":"2024-09-22T22:01:46Z","date_published":"2024-09-01T00:00:00Z","publication_status":"published","citation":{"ieee":"A. S. Moakhar, E. B. Iofinova, E. Frantar, and D.-A. Alistarh, “SPADE: Sparsity-guided debugging for deep neural networks,” in <i>Proceedings of the 41st International Conference on Machine Learning</i>, Vienna, Austria, 2024, vol. 235, pp. 45955–45987.","short":"A.S. Moakhar, E.B. Iofinova, E. Frantar, D.-A. Alistarh, in:, Proceedings of the 41st International Conference on Machine Learning, ML Research Press, 2024, pp. 45955–45987.","mla":"Moakhar, Arshia Soltani, et al. “SPADE: Sparsity-Guided Debugging for Deep Neural Networks.” <i>Proceedings of the 41st International Conference on Machine Learning</i>, vol. 235, ML Research Press, 2024, pp. 45955–87.","ista":"Moakhar AS, Iofinova EB, Frantar E, Alistarh D-A. 2024. SPADE: Sparsity-guided debugging for deep neural networks. Proceedings of the 41st International Conference on Machine Learning. ICML: International Conference on Machine Learning, PMLR, vol. 235, 45955–45987.","apa":"Moakhar, A. S., Iofinova, E. B., Frantar, E., &#38; Alistarh, D.-A. (2024). SPADE: Sparsity-guided debugging for deep neural networks. In <i>Proceedings of the 41st International Conference on Machine Learning</i> (Vol. 235, pp. 45955–45987). Vienna, Austria: ML Research Press.","chicago":"Moakhar, Arshia Soltani, Eugenia B Iofinova, Elias Frantar, and Dan-Adrian Alistarh. “SPADE: Sparsity-Guided Debugging for Deep Neural Networks.” In <i>Proceedings of the 41st International Conference on Machine Learning</i>, 235:45955–87. ML Research Press, 2024.","ama":"Moakhar AS, Iofinova EB, Frantar E, Alistarh D-A. SPADE: Sparsity-guided debugging for deep neural networks. In: <i>Proceedings of the 41st International Conference on Machine Learning</i>. Vol 235. ML Research Press; 2024:45955-45987."},"article_processing_charge":"No","language":[{"iso":"eng"}],"acknowledgement":"The authors would like to thank Stephen Casper and Tony Wang for their feedback on this work, and Eldar Kurtic for his advice on aspects of the project. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by Scientific Computing (SciComp). EI was supported in part by the FWF DK VGSCO, grant agreement number W1260-N35.","related_material":{"link":[{"url":"https://github.com/IST-DASLab/SPADE","relation":"software"}],"record":[{"id":"21854","status":"for_moderation","relation":"dissertation_contains"}]},"type":"conference","date_updated":"2026-05-15T11:12:30Z","intvolume":"       235","page":"45955-45987","_id":"18121","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"arxiv":["2310.04519"]},"department":[{"_id":"DaAl"}],"title":"SPADE: Sparsity-guided debugging for deep neural networks","publication_identifier":{"eissn":["2640-3498"]}},{"month":"07","author":[{"last_name":"Raices","first_name":"Julia","id":"3EE67F22-F248-11E8-B48F-1D18A9856A87","full_name":"Raices, Julia"}],"doi":"10.15479/at:ista:17206","acknowledged_ssus":[{"_id":"ScienComp"}],"oa_version":"Published Version","corr_author":"1","project":[{"name":"Prevalence and Influence of Sexual Antagonism on Genome Evolution","call_identifier":"H2020","_id":"250BDE62-B435-11E9-9278-68D0E5697425","grant_number":"715257"}],"alternative_title":["ISTA Thesis"],"publisher":"Institute of Science and Technology Austria","day":"05","oa":1,"abstract":[{"lang":"eng","text":"Males and females exhibit numerous differences, from the initial stages of sex determination to the\r\ndevelopment of secondary sexual characteristics. In Drosophila, these differences have been\r\nthoroughly studied. Extensive research has been performed to understand the role and molecular\r\nmode of action of central sex in determining switch genes, such as transformer (tra) and Sex-lethal\r\n(Sxl). Furthermore, studies have highlighted differential gene expression as an essential mechanism to\r\ncreate sexual dimorphism. An alternative path to sexual dimorphism that has been less explored is\r\nalternative splicing, the mechanism through which genes can produce multiple transcripts with\r\ndistinct properties and functions. The primary switch sex-determining gene Sxl is a good example of\r\nthe role of alternative splicing for sex-specific functions: the inclusion of a specific exon determines\r\nthe male or female form of the protein, which in turn switches on either the male or female\r\ndevelopmental pathway. The genes that act upstream of Sxl and determine which form is expressed -\r\nthe counter genes - have received less attention. This thesis addresses two critical questions about\r\nthe molecular encoding of sexes in the Drosophila melanogaster genome: First, the use of splice forms\r\nin male and female tissues in D. melanogaster is examined, inferring the molecular and evolutionary\r\nparameters shaping the diversity of the splicing landscape. Second, the behaviour of counter genes in\r\nDrosophila-related species is investigated, shedding light on potential changes leading to their\r\nincorporation into the sex-determination pathway.\r\nFor the alternative splicing analyses, long-read RNA sequencing of testes, ovaries, female and male\r\nmidguts, heads, and whole bodies was performed. A novel pipeline was developed to assign unique\r\ntranscript identifiers for each sequence of exons and introns in the read, enabling detailed\r\ncomparisons of splicing variants in each tissue/sex. Alternative splicing was found to be more\r\npervasive in females than males (22,201 exclusive splice forms in females versus 12,631 in males),\r\nespecially when comparing ovaries to other tissues. The ovaries alone displayed 15,299 exclusive\r\nsplice forms, suggesting most female exclusive splice forms originate there. Genome location and gene\r\nage were also correlated with the number of splice forms per gene. In particular, the X and 4th\r\nchromosomes (Muller elements A and F) showed more splice forms per gene than other\r\nchromosomes. Additionally, genes older than 63 million years exhibited more splice forms per gene\r\nthan younger genes. Our results suggest that alternative splicing is more prevalent than previously\r\nbelieved, with numerous female-exclusive forms, age, and location playing significant roles in shaping\r\nits prevalence.\r\nFor the counter genes analyses, we combined published gene expression, genomic, and gene\r\ninteraction data from various clades (Bactrocera jarvisi, B. oleae, Ceratitis capitata, Mus musculus,\r\nCaenorhabditis elegans, Homo sapiens, and D. melanogaster). The counter genes scute (sc), extra\r\nmacrochaetae (emc), groucho (gro), deadpan (dpn), daughterless (da), runt (run), Sxl, hermaphrodite\r\n(her), and tra maintain conserved Muller element locations between C. capitata and D. melanogaster,\r\nwhich are most of the counter genes identified in the C. capitata genome. Their expression patterns\r\nduring early embryogenesis in B. jarvisi and D. melanogaster are also similar for counter genes dpn,\r\ngro, da, and emc. However, Sxl and sc are also found to have more extreme expression ratios between\r\nthe species. Lastly, gene interactions within the counter genes are conserved, with da-sc and gro-dpn\r\ninteractions occurring in Drosophila, worms, humans, and mice. Interactions such as dpn-sc, dpn-da,\r\nda-emc, and gro-run are present in Drosophila, mice, and humans, suggesting these genes were\r\nrecruited by ancestral characteristics, primarily during embryogenesis. The conserved expression,\r\nlocation, and interactions of counter genes suggest serendipitous recruitment of such genes instead\r\nof a change in those characteristics as they were recruited for this function. "}],"status":"public","degree_awarded":"PhD","ddc":["570"],"OA_place":"publisher","ec_funded":1,"publication_identifier":{"issn":["2663-337X"]},"title":"Novel approaches to studying alternative splicing in Drosophila Melanogaster : Insights into sex-specific gene expression and the evolution of sex determination","has_accepted_license":"1","tmp":{"short":"CC BY-SA (4.0)","image":"/images/cc_by_sa.png","name":"Creative Commons Attribution-ShareAlike 4.0 International Public License (CC BY-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode"},"department":[{"_id":"BeVi"},{"_id":"GradSch"}],"file_date_updated":"2025-01-11T23:30:04Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","supervisor":[{"orcid":"0000-0002-4579-8306","full_name":"Vicoso, Beatriz","last_name":"Vicoso","id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87","first_name":"Beatriz"}],"file":[{"date_updated":"2025-01-11T23:30:04Z","checksum":"d5e9234bde8667b005a8cfe18bb467d3","date_created":"2024-07-11T07:18:01Z","file_id":"17223","access_level":"closed","creator":"cchlebak","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","file_size":13788479,"relation":"source_file","file_name":"ThesisRaices2024_postDefense.docx"},{"date_updated":"2025-01-11T23:30:04Z","embargo":"2025-01-11","checksum":"f5ed0139aa3e11ce58369f0915647c5c","date_created":"2024-07-11T07:22:32Z","file_id":"17224","creator":"cchlebak","access_level":"open_access","content_type":"application/pdf","file_size":5580296,"file_name":"ThesisRaices2024_nosignature.pdf","relation":"main_file"}],"_id":"17206","page":"82","license":"https://creativecommons.org/licenses/by-sa/4.0/","date_updated":"2026-04-07T13:03:22Z","type":"dissertation","language":[{"iso":"eng"}],"citation":{"ieee":"J. Raices, “Novel approaches to studying alternative splicing in Drosophila Melanogaster : Insights into sex-specific gene expression and the evolution of sex determination,” Institute of Science and Technology Austria, 2024.","short":"J. Raices, Novel Approaches to Studying Alternative Splicing in Drosophila Melanogaster : Insights into Sex-Specific Gene Expression and the Evolution of Sex Determination, Institute of Science and Technology Austria, 2024.","mla":"Raices, Julia. <i>Novel Approaches to Studying Alternative Splicing in Drosophila Melanogaster : Insights into Sex-Specific Gene Expression and the Evolution of Sex Determination</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:17206\">10.15479/at:ista:17206</a>.","ista":"Raices J. 2024. Novel approaches to studying alternative splicing in Drosophila Melanogaster : Insights into sex-specific gene expression and the evolution of sex determination. Institute of Science and Technology Austria.","apa":"Raices, J. (2024). <i>Novel approaches to studying alternative splicing in Drosophila Melanogaster : Insights into sex-specific gene expression and the evolution of sex determination</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:17206\">https://doi.org/10.15479/at:ista:17206</a>","ama":"Raices J. Novel approaches to studying alternative splicing in Drosophila Melanogaster : Insights into sex-specific gene expression and the evolution of sex determination. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:17206\">10.15479/at:ista:17206</a>","chicago":"Raices, Julia. “Novel Approaches to Studying Alternative Splicing in Drosophila Melanogaster : Insights into Sex-Specific Gene Expression and the Evolution of Sex Determination.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:17206\">https://doi.org/10.15479/at:ista:17206</a>."},"article_processing_charge":"No","publication_status":"published","date_published":"2024-07-05T00:00:00Z","year":"2024","date_created":"2024-07-05T14:15:29Z"},{"degree_awarded":"PhD","ddc":["570"],"ec_funded":1,"OA_place":"publisher","abstract":[{"text":"The Retroviridae family consists of two sub-families, the Orthoretrovirinae and the\r\nSpumaretrovirinae. The Orthoretroviruses contain important human pathogens, such as the\r\nhuman immunodeficiency virus 1 (HIV-1). They also harbor other retrovirus species which\r\nare regularly used as model systems to study the retroviral life cycle. The main structural\r\ncomponent of the retroviruses, is the Gag protein and its truncation derivatives occurring\r\nduring viral maturation. Orthoretroviral Gag assemblies have been extensively studied to\r\nunderstand the interactions that confer stability and morphology to viral particles.\r\nThe Spumaretrovirinae subfamily represent an early diverging branch of the Retroviridae.\r\nIts members, the Foamy viruses (FV), share most of the conventional features found in\r\nretroviruses. However, they also possess multiple characteristics that make them unique. In\r\nparticular, FV Gag does not get extensively cleaved as in orthoretroviruses. Hence, the Gag\r\narchitecture deviates from the canonical domain arrangement in FV. They also exhibit a\r\npeculiar particle morphology, having no apparent immature state and a seemingly\r\nicosahedral mature particle. Due to this, many fundamental questions on FV structural\r\nassembly mechanisms remain open. To answer these questions, was the main focus of this\r\nthesis.\r\nMainly, it is not known how FV assemble their core in a virus particle and what are the\r\nimportant assembly interaction sites within said core. What is the minimum assembly\r\ncompetent domain of FV Gag? Is there a morphological change in the assembly type of FVGag lattices? If so, what is defining these morphological shifts? Finally, it would be\r\ninteresting to know what is the evolutionary relationship between FV and the rest of the\r\nretrotranscribing elements, from a structural point of view?\r\nTo answer these questions, membrane-enveloped mammalian cell-derived FV virus-like\r\nparticles (VLPs) were produced. Cryo-electron tomography (cryo-ET) analysis suggested\r\nthese FV VLPs do not form a canonical retroviral Gag lattice structure, which is in line with\r\nearlier observations. To further evaluate FV Gag assembly competence and morphology,\r\nthe first bacterial cell-derived in vitro VLP assembly system was designed and optimized.\r\nUsing this system with different truncation variants, the minimum assembly competent\r\ndomain of FV Gag was found to be the putative CA300-477 domain. Varying VLP\r\nmorphologies were also observed and strongly suggested residues upstream of CA300-477\r\nplay a role in morphology determination. Finally, a combined cryo-electron microscopy (cryoEM) and cryo-ET approach was taken to analyze tubular assemblies from the minimal\r\nassembly competent domain. This revealed an unexpectedly unique non-canonical\r\nassembly architecture. Three novel lattice stabilizing interfaces were described which\r\nproved to be as unique as the lattice arrangement. Comparison to a newly published FV CA\r\ncore structure revealed the CA-CA interactions in the atypical assembly do not recapitulate\r\nwhat is described for the FV core lattice. However, the new in vitro VLP assembly system\r\nobtained in this thesis also provides an exciting opportunity to study still unresolved FV\r\nassembly features in a potentially facilitated approach compared to conventional methods.\r\nIn summary, this work provided a deeper understanding of the basic FV Gag assembly unit,\r\nas well as presenting the first FV Gag-derived in vitro VLP assembly system. This system\r\nreveals a novel and unique assembly architecture among retroviral in vitro assemblies.","lang":"eng"}],"status":"public","alternative_title":["ISTA Thesis"],"publisher":"Institute of Science and Technology Austria","day":"26","oa":1,"month":"09","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"ScienComp"}],"author":[{"full_name":"Porley, Dario J","last_name":"Porley","id":"2FD6EA6C-F248-11E8-B48F-1D18A9856A87","first_name":"Dario J"}],"doi":"10.15479/at:ista:18101","oa_version":"Published Version","corr_author":"1","project":[{"grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_id":"9B9C98E0-BA93-11EA-9121-9846C619BF3A","name":"Structural characterization of spumavirus capsid assemblies to understand conserved Ortervirales assembly mechanisms","grant_number":"25762"}],"type":"dissertation","date_updated":"2026-04-07T13:21:01Z","publication_status":"published","citation":{"chicago":"Porley Esteves, Darío. “Structural Characterization of Spumavirus Capsid Assemblies.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:18101\">https://doi.org/10.15479/at:ista:18101</a>.","ama":"Porley Esteves D. Structural characterization of spumavirus capsid assemblies. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:18101\">10.15479/at:ista:18101</a>","apa":"Porley Esteves, D. (2024). <i>Structural characterization of spumavirus capsid assemblies</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:18101\">https://doi.org/10.15479/at:ista:18101</a>","ista":"Porley Esteves D. 2024. Structural characterization of spumavirus capsid assemblies. Institute of Science and Technology Austria.","mla":"Porley Esteves, Darío. <i>Structural Characterization of Spumavirus Capsid Assemblies</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:18101\">10.15479/at:ista:18101</a>.","ieee":"D. Porley Esteves, “Structural characterization of spumavirus capsid assemblies,” Institute of Science and Technology Austria, 2024.","short":"D. Porley Esteves, Structural Characterization of Spumavirus Capsid Assemblies, Institute of Science and Technology Austria, 2024."},"language":[{"iso":"eng"}],"article_processing_charge":"No","date_created":"2024-09-20T10:21:03Z","year":"2024","date_published":"2024-09-26T00:00:00Z","_id":"18101","page":"131","file_date_updated":"2025-03-25T23:30:03Z","department":[{"_id":"GradSch"},{"_id":"FlSc"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","supervisor":[{"orcid":"0000-0003-4790-8078","full_name":"Schur, Florian KM","last_name":"Schur","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","first_name":"Florian KM"}],"file":[{"date_updated":"2025-03-25T23:30:03Z","file_id":"18149","date_created":"2024-09-26T13:40:33Z","checksum":"3b8b0bacfe61112f3852744f3170e468","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","access_level":"closed","creator":"dporley","relation":"source_file","file_name":"PhD_thesis_DPorley_final_20240919.docx","file_size":14213128},{"date_updated":"2025-03-25T23:30:03Z","file_id":"18150","date_created":"2024-09-26T13:41:39Z","embargo":"2025-03-25","checksum":"6c3a652a8eede874118e11d66a63652f","content_type":"application/pdf","access_level":"open_access","creator":"dporley","relation":"main_file","file_name":"PhD_thesis_DPorley_final_20240926_pdfa1.pdf","file_size":18583031}],"publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-041-1"]},"title":"Structural characterization of spumavirus capsid assemblies","has_accepted_license":"1"},{"_id":"17465","page":"232","article_processing_charge":"No","language":[{"iso":"eng"}],"citation":{"short":"A. Shevchenko, High-Dimensional Limits in Artificial Neural Networks, Institute of Science and Technology Austria, 2024.","ieee":"A. Shevchenko, “High-dimensional limits in artificial neural networks,” Institute of Science and Technology Austria, 2024.","apa":"Shevchenko, A. (2024). <i>High-dimensional limits in artificial neural networks</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:17465\">https://doi.org/10.15479/at:ista:17465</a>","ama":"Shevchenko A. High-dimensional limits in artificial neural networks. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:17465\">10.15479/at:ista:17465</a>","chicago":"Shevchenko, Alexander. “High-Dimensional Limits in Artificial Neural Networks.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:17465\">https://doi.org/10.15479/at:ista:17465</a>.","mla":"Shevchenko, Alexander. <i>High-Dimensional Limits in Artificial Neural Networks</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:17465\">10.15479/at:ista:17465</a>.","ista":"Shevchenko A. 2024. High-dimensional limits in artificial neural networks. Institute of Science and Technology Austria."},"publication_status":"published","date_published":"2024-08-29T00:00:00Z","date_created":"2024-08-28T15:14:25Z","year":"2024","date_updated":"2025-04-25T10:32:06Z","type":"dissertation","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"11420"},{"id":"17469","relation":"part_of_dissertation","status":"public"},{"relation":"part_of_dissertation","status":"public","id":"14459"},{"id":"9198","relation":"part_of_dissertation","status":"public"}]},"title":"High-dimensional limits in artificial neural networks","has_accepted_license":"1","publication_identifier":{"issn":["2663-337X"]},"file":[{"access_level":"open_access","creator":"ashevche","content_type":"application/pdf","file_size":4468610,"relation":"main_file","file_name":"thesis_a2b.pdf","date_updated":"2024-10-05T22:30:05Z","embargo":"2024-10-04","date_created":"2024-09-02T09:23:32Z","checksum":"da6dd3166078934577f6af93d27000e2","file_id":"17482"},{"date_updated":"2024-10-05T22:30:05Z","checksum":"76a39ef252239560923cdda4ce0a31a4","date_created":"2024-09-02T09:23:46Z","file_id":"17483","creator":"ashevche","access_level":"closed","content_type":"application/zip","embargo_to":"open_access","file_size":15930999,"file_name":"Thesis Alex - ISTA.zip","relation":"source_file"}],"department":[{"_id":"GradSch"},{"_id":"DaAl"},{"_id":"MaMo"}],"file_date_updated":"2024-10-05T22:30:05Z","supervisor":[{"first_name":"Marco","id":"27EB676C-8706-11E9-9510-7717E6697425","last_name":"Mondelli","full_name":"Mondelli, Marco","orcid":"0000-0002-3242-7020"},{"first_name":"Dan-Adrian","id":"4A899BFC-F248-11E8-B48F-1D18A9856A87","last_name":"Alistarh","full_name":"Alistarh, Dan-Adrian","orcid":"0000-0003-3650-940X"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","status":"public","abstract":[{"text":"In the modern age of machine learning, artificial neural networks have become an integral part\r\nof many practical systems. One of the key ingredients of the success of the deep learning\r\napproach is recent computational advances which allowed the training of models with billions\r\nof parameters on large-scale data. Such over-parameterized and data-hungry regimes pose a\r\nchallenge for the theoretical analysis of modern models since “classical” statistical wisdom\r\nis no longer applicable. In this view, it is paramount to extend or develop new machinery\r\nthat will allow tackling the neural network analysis under new challenging asymptotic regimes,\r\nwhich is the focus of this thesis.\r\nLarge neural network systems are usually optimized via “local” search algorithms, such\r\nas stochastic gradient descent (SGD). However, given the high-dimensional nature of the\r\nparameter space, it is a priori not clear why such a crude “local” approach works so remarkably\r\nwell in practice. We take a step towards demystifying this phenomenon by showing that\r\nthe landscape of the SGD training dynamics exhibits a few beneficial properties for the\r\noptimization. First, we show that along the SGD trajectory an over-parameterized network\r\nis dropout stable. The emergence of dropout stability allows to conclude that the minima\r\nfound by SGD are connected via a continuous path of small loss. This in turn means that\r\nthe high-dimensional landscape of the neural network optimization problem is provably not so\r\nunfavourable to gradient-based training, due to mode connectivity. Next, we show that SGD\r\nfor an over-parameterized network tends to find solutions that are functionally more “simple”.\r\nThis in turn means that the SGD minima are more robust, since a less complicated solution\r\nwill less likely overfit the data. More formally, for a prototypical example of a wide two-layer\r\nReLU network on a 1d regression task we show that the SGD algorithm is implicitly selective in\r\nits choice of an interpolating solution. Namely, at convergence the neural network implements\r\na piece-wise linear function with the number of linear regions depending only on the amount\r\nof training data. This is in contrast to a “smooth”-like behaviour which one would expect\r\ngiven such a severe over-parameterization of the model.\r\nDiverging from the generic supervised setting of classification and regression problems, we\r\nanalyze an auto-encoder model that is commonly used for representation learning and data\r\ncompression. Despite the wide applicability of the auto-encoding paradigm, the theoretical\r\nunderstanding of their behaviour is limited even in the simplistic shallow case. The related\r\nwork is restricted to extreme asymptotic regimes in which the auto-encoder is either severely\r\nover-parameterized or under-parameterized. In contrast, we provide a tight characterization\r\nfor the 1-bit compression of Gaussian signals in the challenging proportional regime, i.e., the\r\ninput dimension and the size of the compressed representation obey the same asymptotics.\r\nWe also show that gradient-based methods are able to find a globally optimal solution and\r\nthat the predictions made for Gaussian data extrapolate beyond - to the case of compression\r\nof natural images. Next, we relax the Gaussian assumption and study more structured input\r\nsources. We show that the shallow model is sometimes agnostic to the structure of the data\r\nvii\r\nwhich results in a Gaussian-like behaviour. We prove that making the decoding component\r\nslightly less shallow is already enough to escape the “curse” of Gaussian performance.\r\n","lang":"eng"}],"OA_place":"repository","degree_awarded":"PhD","ddc":["519"],"oa_version":"Published Version","corr_author":"1","project":[{"_id":"059876FA-7A3F-11EA-A408-12923DDC885E","name":"Prix Lopez-Loretta 2019 - Marco Mondelli"},{"_id":"9B9290DE-BA93-11EA-9121-9846C619BF3A","name":"Vienna Graduate School on Computational Optimization","grant_number":"W1260-N35"}],"month":"08","author":[{"last_name":"Shevchenko","id":"F2B06EC2-C99E-11E9-89F0-752EE6697425","first_name":"Aleksandr","full_name":"Shevchenko, Aleksandr"}],"acknowledged_ssus":[{"_id":"ScienComp"}],"doi":"10.15479/at:ista:17465","day":"29","oa":1,"alternative_title":["ISTA Thesis"],"publisher":"Institute of Science and Technology Austria"},{"title":"Compression of structured data with autoencoders: Provable benefit of nonlinearities and depth","department":[{"_id":"DaAl"},{"_id":"MaMo"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"arxiv":["2402.05013"]},"_id":"17469","page":"24964-25015","type":"conference","date_updated":"2026-05-15T22:30:05Z","intvolume":"       235","acknowledgement":"Kevin Kogler, Alexander Shevchenko and Marco Mondelli are supported by the 2019 Lopez-Loreta Prize. Hamed\r\nHassani acknowledges the support by the NSF CIF award (1910056) and the NSF Institute for CORE Emerging Methods in Data Science (EnCORE).","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"17465"}]},"publication_status":"published","article_processing_charge":"No","language":[{"iso":"eng"}],"citation":{"ieee":"K. Kögler, A. Shevchenko, H. Hassani, and M. Mondelli, “Compression of structured data with autoencoders: Provable benefit of nonlinearities and depth,” in <i>Proceedings of the 41st International Conference on Machine Learning</i>, Vienna, Austria, 2024, vol. 235, pp. 24964–25015.","short":"K. Kögler, A. Shevchenko, H. Hassani, M. Mondelli, in:, Proceedings of the 41st International Conference on Machine Learning, ML Research Press, 2024, pp. 24964–25015.","mla":"Kögler, Kevin, et al. “Compression of Structured Data with Autoencoders: Provable Benefit of Nonlinearities and Depth.” <i>Proceedings of the 41st International Conference on Machine Learning</i>, vol. 235, ML Research Press, 2024, pp. 24964–5015.","ista":"Kögler K, Shevchenko A, Hassani H, Mondelli M. 2024. Compression of structured data with autoencoders: Provable benefit of nonlinearities and depth. Proceedings of the 41st International Conference on Machine Learning. ICML: International Conference on Machine Learning, PMLR, vol. 235, 24964–25015.","apa":"Kögler, K., Shevchenko, A., Hassani, H., &#38; Mondelli, M. (2024). Compression of structured data with autoencoders: Provable benefit of nonlinearities and depth. In <i>Proceedings of the 41st International Conference on Machine Learning</i> (Vol. 235, pp. 24964–25015). Vienna, Austria: ML Research Press.","chicago":"Kögler, Kevin, Alexander Shevchenko, Hamed Hassani, and Marco Mondelli. “Compression of Structured Data with Autoencoders: Provable Benefit of Nonlinearities and Depth.” In <i>Proceedings of the 41st International Conference on Machine Learning</i>, 235:24964–15. ML Research Press, 2024.","ama":"Kögler K, Shevchenko A, Hassani H, Mondelli M. Compression of structured data with autoencoders: Provable benefit of nonlinearities and depth. In: <i>Proceedings of the 41st International Conference on Machine Learning</i>. Vol 235. ML Research Press; 2024:24964-25015."},"date_created":"2024-08-29T11:47:57Z","year":"2024","date_published":"2024-07-01T00:00:00Z","month":"07","author":[{"first_name":"Kevin","id":"94ec913c-dc85-11ea-9058-e5051ab2428b","last_name":"Kögler","full_name":"Kögler, Kevin"},{"last_name":"Shevchenko","first_name":"Aleksandr","id":"F2B06EC2-C99E-11E9-89F0-752EE6697425","full_name":"Shevchenko, Aleksandr"},{"full_name":"Hassani, Hamed","last_name":"Hassani","first_name":"Hamed"},{"id":"27EB676C-8706-11E9-9510-7717E6697425","first_name":"Marco","last_name":"Mondelli","orcid":"0000-0002-3242-7020","full_name":"Mondelli, Marco"}],"corr_author":"1","oa_version":"Published Version","volume":235,"scopus_import":"1","project":[{"name":"Prix Lopez-Loretta 2019 - Marco Mondelli","_id":"059876FA-7A3F-11EA-A408-12923DDC885E"}],"alternative_title":["PMLR"],"publisher":"ML Research Press","arxiv":1,"day":"01","oa":1,"publication":"Proceedings of the 41st International Conference on Machine Learning","abstract":[{"text":"Autoencoders are a prominent model in many empirical branches of machine learning and lossy data compression. However, basic theoretical questions remain unanswered even in a shallow two-layer setting. In particular, to what degree does a shallow autoencoder capture the structure of the underlying data distribution? For the prototypical case of the 1-bit compression of sparse Gaussian data, we prove that gradient descent converges to a solution that completely disregards the sparse structure of the input. Namely, the performance of the algorithm is the same as if it was compressing a Gaussian source - with no sparsity. For general data distributions, we give evidence of a phase transition phenomenon in the shape of the gradient descent minimizer, as a function of the data sparsity: below the critical sparsity level, the minimizer is a rotation taken uniformly at random (just like in the compression of non-sparse data); above the critical sparsity, the minimizer is the identity (up to a permutation). Finally, by exploiting a connection with approximate message passing algorithms, we show how to improve upon Gaussian performance for the compression of sparse data: adding a denoising function to a shallow architecture already reduces the loss provably, and a suitable multi-layer decoder leads to a further improvement. We validate our findings on image datasets, such as CIFAR-10 and MNIST.","lang":"eng"}],"main_file_link":[{"open_access":"1","url":"https://proceedings.mlr.press/v235/kogler24a.html"}],"status":"public","conference":{"start_date":"2024-07-21","name":"ICML: International Conference on Machine Learning","location":"Vienna, Austria","end_date":"2024-07-27"},"quality_controlled":"1"},{"project":[{"grant_number":"715257","call_identifier":"H2020","_id":"250BDE62-B435-11E9-9278-68D0E5697425","name":"Prevalence and Influence of Sexual Antagonism on Genome Evolution"},{"grant_number":"F8810","_id":"34ae1506-11ca-11ed-8bc3-c14f4c474396","name":"The highjacking of meiosis for asexual reproduction"}],"corr_author":"1","oa_version":"Published Version","author":[{"id":"48D3F8DE-F248-11E8-B48F-1D18A9856A87","first_name":"Réka K","last_name":"Kelemen","orcid":"0000-0002-8489-9281","full_name":"Kelemen, Réka K"}],"doi":"10.15479/at:ista:17119","month":"06","oa":1,"day":"20","publisher":"Institute of Science and Technology Austria","alternative_title":["ISTA Thesis"],"status":"public","keyword":["meiotic driver","neofunctionalization","single nucleus sequencing"],"abstract":[{"lang":"eng","text":"Genomes are shaped by natural selection at the level of the organism, as genomic variants that\r\nhave a beneficial effect on the viability or fecundity of their carriers are on average expected\r\nto be passed on to more offspring than less beneficial alleles. However, selection also favors\r\ngenomic variants that drive their own transmission to the next generation above the mendelian\r\nexpectation of 50 percent in heterozygotes, even if these self-promoting variants are less\r\nbeneficial to the organism than other variants at the same locus. Such variants, called meiotic\r\ndrivers, are found in diverse taxa, and often impose fitness costs on their host organisms. As\r\nmeiotic drivers often require multiple genes and sequences for transmission ratio distortion,\r\nthey are often found in regions of low recombination, such as inversions, which prevent their\r\nrecombination with the non-driving homologous regions. Reduced recombination rates are\r\nexpected to lead to the accumulation of deleterious mutations, which may affect hundreds\r\nof genes trapped in the inversions of meiotic drivers. Although the observed fitness costs of\r\nself-promoting haplotypes are thought to possibly reflect sequence degeneration, no study has\r\nsystematically investigated the level of degeneration on a meiotic driver. Further, the low\r\nrates of recombination between driving and non-driving haplotypes have limited the power of\r\ntraditional genetic studies in uncovering the gene content of meiotic drivers, and made the\r\nthe identification of the genes causing transmission ratio distortion difficult.\r\nAfter an introduction to meiotic drivers in Chapter 1, this thesis presents three studies that\r\nmake use of next generation sequencing data to characterize the sequence and expression\r\nevolution of genes on the t-haplotype, a large and ancient meiotic driver in house mice that is\r\ntransmitted to up to 100% of the offspring in males heterozygous for it. Chapter 2 presents\r\na comprehensive assessment of the t-haplotype’s sequence evolution, which shows signs of\r\nsequence degeneration counteracted by occasional recombination with the non-driving homolog\r\nover large parts of the meiotic driver, proposing an explanation for its long-term survival.\r\nChapter 3 investigates the sequence and expression evolution of genes on the t-haplotype,\r\nand finds widespread expression and copy number changes and signs of less efficient purifying\r\nselection compared to the genes on the non-driving homolog. Further, this chapter finds\r\ncandidates for involvment in drive: two positively selected genes on the t-haplotype, and\r\nthe discovery of a t-specific gene duplicate, which was gained from another chromosome,\r\nand which acquired novel sequence and testis-specific expression on the t-haplotype. Finally,\r\nChapter 4 provides unprecedented insights into the gene expression landscape in testes of\r\nt-carrier mice, using single nucleus sequencing. Cell-resolved RNA-sequencing allows the\r\ncomparison of expression in spermatids carrying or not carrying the t-haplotype as well as the\r\ntiming of t-haplotype-induced expression changes along spermatogenesis. This study shows\r\nthe timing of previously found drive-associated genes, and uncovers novel candidate genes and\r\nbiological processes that may underlie the complex biology of transmission ratio distortion of\r\nthe t-haplotype. Chapter 5 synthesizes the findings of the three studies, and discusses them in\r\nthe context of the current state of meiotic drive research."}],"OA_place":"publisher","ec_funded":1,"ddc":["576"],"degree_awarded":"PhD","has_accepted_license":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"title":"Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-039-8"]},"file":[{"relation":"source_file","file_name":"thesis.zip","file_size":180557931,"content_type":"application/zip","embargo_to":"open_access","access_level":"closed","creator":"rkelemen","file_id":"17121","date_created":"2024-06-07T16:09:17Z","checksum":"fab59146e3b3dc2e5d214576984a2a63","date_updated":"2025-01-10T23:30:10Z"},{"relation":"main_file","file_name":"thesis_to_archive.pdf","file_size":19405484,"content_type":"application/pdf","access_level":"open_access","creator":"rkelemen","file_id":"17213","checksum":"91cc4c25a792239e8a7688e8aec7c62a","date_created":"2024-07-10T08:00:20Z","embargo":"2025-01-10","date_updated":"2025-01-10T23:30:10Z"}],"supervisor":[{"orcid":"0000-0002-4579-8306","full_name":"Vicoso, Beatriz","last_name":"Vicoso","id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87","first_name":"Beatriz"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","department":[{"_id":"GradSch"},{"_id":"BeVi"}],"file_date_updated":"2025-01-10T23:30:10Z","page":"105","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","_id":"17119","date_published":"2024-06-20T00:00:00Z","date_created":"2024-06-07T16:14:13Z","year":"2024","citation":{"mla":"Kelemen, Réka K. <i>Characterizing the Sequence and Expression Evolution of the T-Haplotype, a Model Meiotic Driver</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:17119\">10.15479/at:ista:17119</a>.","ista":"Kelemen RK. 2024. Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver. Institute of Science and Technology Austria.","apa":"Kelemen, R. K. (2024). <i>Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:17119\">https://doi.org/10.15479/at:ista:17119</a>","chicago":"Kelemen, Réka K. “Characterizing the Sequence and Expression Evolution of the T-Haplotype, a Model Meiotic Driver.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:17119\">https://doi.org/10.15479/at:ista:17119</a>.","ama":"Kelemen RK. Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:17119\">10.15479/at:ista:17119</a>","short":"R.K. Kelemen, Characterizing the Sequence and Expression Evolution of the T-Haplotype, a Model Meiotic Driver, Institute of Science and Technology Austria, 2024.","ieee":"R. K. Kelemen, “Characterizing the sequence and expression evolution of the t-haplotype, a model meiotic driver,” Institute of Science and Technology Austria, 2024."},"language":[{"iso":"eng"}],"article_processing_charge":"No","publication_status":"published","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"542"},{"id":"10767","relation":"part_of_dissertation","status":"public"}]},"date_updated":"2026-04-07T13:21:37Z","type":"dissertation"},{"alternative_title":["ISTA Thesis"],"publisher":"Institute of Science and Technology Austria","day":"29","oa":1,"month":"10","author":[{"full_name":"Kaczmarek, Beata M","id":"36FA4AFA-F248-11E8-B48F-1D18A9856A87","first_name":"Beata M","last_name":"Kaczmarek"}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"doi":"10.15479/at:ista:18477","corr_author":"1","oa_version":"Published Version","degree_awarded":"PhD","ddc":["572"],"OA_place":"publisher","abstract":[{"lang":"eng","text":"ADAR1 is broadly expressed across various tissues and is vital in regulating pathways\r\nassociated with innate immune responses. ADAR1 marks double-stranded RNA as \"self\"\r\nthrough its A-to-I editing activity, effectively repressing autoimmunity and maintaining\r\nimmune tolerance. This editing process has been detected at millions of sites across the\r\nhuman genome. However, the mechanism underlying ADAR1's substrate selectivity\r\nproperties remains largely unclear, with much of the current knowledge derived from\r\ncomparisons to its more extensively studied homolog, ADAR2. By studying ADAR1 in complex\r\nwith its RNA substrates and applying a combination of biochemical techniques and structural\r\nstudies using CryoEM, we aim to gain a more comprehensive understanding of the substrate\r\nselectivity characteristics of ADAR1.\r\nIn this thesis, the purification protocol for ADAR1 was successfully optimized, resulting in the\r\nfirst report in the literature to achieve high protein purity and activity. This advancement\r\nenabled the investigation of complex formation between ADAR1 and various RNA substrates,\r\nleading to the identification of optimal conditions for preparing the cryoEM sample. However,\r\ndespite comprehensive optimization of the cryo-EM conditions, the resulting data lacked the\r\ndesired quality, highlighting the need for similar rigorous optimization of the RNA substrates\r\nto facilitate structural studies of the ADAR1-RNA complex. The study was complemented by\r\nAlphaFold predictions, which provided some insights into this mechanism.\r\nMoreover, during this project I established a collaboration with a research group focused on\r\nstudying ADAR homologs. Notably ADAR homologs were identified in bivalve species, and it\r\nwas further demonstrated that ADAR and its A-to-I editing activity are upregulated in Pacific\r\noysters during infections with Ostreid herpesvirus-1—a highly infectious virus that leads to\r\nsignificant losses in oyster populations globally. I successfully purified oyster ADAR and\r\nprepared in vitro edited RNA for nanopore sequencing—a direct sequencing technology\r\ncapable of detecting modified nucleotides without the need for reverse transcription. The\r\ncollaborators initiated optimization of this nanopore-based approach. However, current\r\ntechnological limitations still constrain the reliable detection of modified nucleotides.\r\nThe project also examined the impact of RNA editing on RNA binding and filament formation\r\nby MDA5, a key cytosolic dsRNA sensor that triggers an interferon response. A primary target\r\nof ADAR1's editing activity is RNA derived from repetitive elements present in the genome,\r\nparticularly Alu elements forming double-stranded RNA. When unedited, these RNA\r\nsequences are recognized by MDA5. However, the mechanisms by which MDA5 interacts with\r\nAlu RNAs, as well as the role of A-to-I editing in influencing this binding, are still not well\r\nunderstood.\r\nThe interaction between MDA5 and Alu elements, was successfully established. This was\r\nachieved through the testing of different RNA variants and the evaluation of filament\r\nformation using binding techniques and electron microscopy imaging. This groundwork has\r\nset the conditions for further evaluation using CryoEM. Furthermore, the effects of A-to-I\r\nediting on the binding properties of MDA5 with Alu RNA were investigated. Given the recent\r\nresearch that has provided new insights into MDA5's interaction with dsRNA, it is essential to\r\nrevise the experimental setup to integrate these findings before moving forward with the\r\nCryoEM sample analysis."}],"status":"public","file_date_updated":"2025-10-29T23:30:02Z","department":[{"_id":"GradSch"},{"_id":"CaBe"}],"supervisor":[{"id":"2CB9DFE2-F248-11E8-B48F-1D18A9856A87","first_name":"Carrie A","last_name":"Bernecky","orcid":"0000-0003-0893-7036","full_name":"Bernecky, Carrie A"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","file":[{"relation":"source_file","file_name":"20241029_PhD_thesis_BKaczmarek.docx","file_size":23136626,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","access_level":"closed","creator":"bkaczmar","file_id":"18485","checksum":"2053294ea4d770c495e4cc501e2a218b","date_created":"2024-10-29T11:56:36Z","date_updated":"2025-10-29T23:30:02Z"},{"file_size":11707360,"file_name":"20241029_PhD_thesis_BKaczmarek.pdf","relation":"main_file","creator":"bkaczmar","access_level":"open_access","content_type":"application/pdf","date_created":"2024-10-29T11:56:44Z","embargo":"2025-10-29","checksum":"8ce857a4cd44b776791eaf180ac9dbb3","file_id":"18486","date_updated":"2025-10-29T23:30:02Z"}],"publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-045-9"]},"title":"Biochemical and structural insights into ADAR1 RNA editing","has_accepted_license":"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"},"date_updated":"2026-04-07T13:23:59Z","type":"dissertation","language":[{"iso":"eng"}],"article_processing_charge":"No","citation":{"short":"B.M. Kaczmarek, Biochemical and Structural Insights into ADAR1 RNA Editing, Institute of Science and Technology Austria, 2024.","ieee":"B. M. Kaczmarek, “Biochemical and structural insights into ADAR1 RNA editing,” Institute of Science and Technology Austria, 2024.","apa":"Kaczmarek, B. M. (2024). <i>Biochemical and structural insights into ADAR1 RNA editing</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:18477\">https://doi.org/10.15479/at:ista:18477</a>","ama":"Kaczmarek BM. Biochemical and structural insights into ADAR1 RNA editing. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:18477\">10.15479/at:ista:18477</a>","chicago":"Kaczmarek, Beata M. “Biochemical and Structural Insights into ADAR1 RNA Editing.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:18477\">https://doi.org/10.15479/at:ista:18477</a>.","mla":"Kaczmarek, Beata M. <i>Biochemical and Structural Insights into ADAR1 RNA Editing</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:18477\">10.15479/at:ista:18477</a>.","ista":"Kaczmarek BM. 2024. Biochemical and structural insights into ADAR1 RNA editing. Institute of Science and Technology Austria."},"publication_status":"published","date_published":"2024-10-29T00:00:00Z","year":"2024","date_created":"2024-10-27T07:35:13Z","_id":"18477","page":"124"},{"date_updated":"2026-04-07T13:20:44Z","type":"dissertation","date_published":"2024-07-26T00:00:00Z","date_created":"2024-07-26T09:05:55Z","year":"2024","article_processing_charge":"No","language":[{"iso":"eng"}],"citation":{"mla":"Lukic, Kristina. <i>Membrane Proteins in Plant Physiology and Bioenergetics : Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the Novel Inhibitor Yaku’amide B</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:17319\">10.15479/at:ista:17319</a>.","ista":"Lukic K. 2024. Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku’amide B. Institute of Science and Technology Austria.","apa":"Lukic, K. (2024). <i>Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku’amide B</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:17319\">https://doi.org/10.15479/at:ista:17319</a>","ama":"Lukic K. Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku’amide B. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:17319\">10.15479/at:ista:17319</a>","chicago":"Lukic, Kristina. “Membrane Proteins in Plant Physiology and Bioenergetics : Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the Novel Inhibitor Yaku’amide B.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:17319\">https://doi.org/10.15479/at:ista:17319</a>.","short":"K. Lukic, Membrane Proteins in Plant Physiology and Bioenergetics : Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the Novel Inhibitor Yaku’amide B, Institute of Science and Technology Austria, 2024.","ieee":"K. Lukic, “Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku’amide B,” Institute of Science and Technology Austria, 2024."},"publication_status":"published","page":"224","_id":"17319","supervisor":[{"id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A","last_name":"Sazanov","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","department":[{"_id":"LeSa"},{"_id":"GradSch"}],"file_date_updated":"2025-01-26T23:30:04Z","file":[{"content_type":"application/pdf","access_level":"open_access","creator":"cchlebak","relation":"main_file","file_name":"Thesis_Kristina_Lukic.pdf","file_size":24639084,"date_updated":"2025-01-26T23:30:04Z","file_id":"17320","checksum":"95517e697ea6a87e267e649cad560989","embargo":"2025-01-26","date_created":"2024-07-26T13:14:24Z"},{"date_updated":"2025-01-26T23:30:04Z","file_id":"17321","checksum":"74325746a9a05078fb9935dbf2aef752","date_created":"2024-07-26T13:14:50Z","embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","access_level":"closed","creator":"cchlebak","relation":"source_file","file_name":"Thesis_Kristina_Lukic.docx","file_size":96334272}],"publication_identifier":{"issn":["2663-337X"]},"has_accepted_license":"1","title":"Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku'amide B","ddc":["580"],"degree_awarded":"PhD","OA_place":"publisher","abstract":[{"lang":"eng","text":"This thesis comprises two distinct projects, each offering unique insights into fundamental\r\ncellular processes. While distinct in their focus, these different perspectives have a common\r\ntheme: chemiosmotic theory and utilisation of the proton gradient for driving the essential\r\nprocesses like auxin efflux and ATP synthesis, effectively bridging the membrane protein\r\nstructure and function from the realms of plant biology and cellular bioenergetics.\r\nThe first project of this thesis centres on the characterisation of PIN proteins, a class of\r\ntransmembrane transporters pivotal in the regulation of auxin transport and distribution in\r\nplants. PINs form a conserved and phylogenetically abundant group of transporters present in\r\nland plants and certain algae. Despite their great importance, they were one of the few elusive\r\nproteins essential for plant development not to be structurally and mechanistically\r\ncharacterised since their discovery almost 30 years ago. This work aimed to uncover the\r\nstructural and functional dynamics of the PIN protein-mediated auxin transport using an array\r\nof experimental techniques, including protein purification, biochemical assays and structural\r\nanalysis. Through an exhaustive screening process that took several years and included testing\r\ndifferent PIN homologues, expression systems, constructs, and purification conditions, we\r\ndeveloped a robust protocol for isolating the pure, stable, and monodisperse PIN8 protein.\r\nMoreover, utilising biophysical methods and buffer screening, we demonstrated that PIN8\r\nexhibits detergent and pH-dependent stability, with mild detergents and lower pH (5.0 and 6.0)\r\nbeing optimal for the stability of the protein. Using SEC-MALS and crosslinking, we\r\ndetermined that PIN8 forms dimers, which was confirmed by our structural studies. We\r\nobtained a cryo-EM map of PIN8 at pH 6.0, and, compared to recently published structures,\r\nour map implies major pH-dependent conformational changes and possibly utilisation of the\r\nproton gradient in the transport mechanism.\r\nThe subject of the second project was F1Fo-ATP synthase, an enzyme complex fundamental\r\nto cellular energy metabolism. Through an approach integrating biochemical assays and\r\nstructural analysis, this research aimed to unveil the molecular mechanism of inhibition of ATP\r\nsynthase by yaku´amide, a bioactive compound with potential therapeutic implications. Using\r\nsubmitochondrial particles and purified F1Fo-ATP synthase, we demonstrated that, contrary to\r\npublished data, yaku´amide inhibits both ATP hydrolysis and ATP synthesis reactions.\r\nMoreover, we found that yaku´amide inhibitory activity is proton motive force (pmf)\r\ndependent, with lower inhibition in a more coupled system. Utilising cryo-EM, we obtained\r\nmaps and models for the three main rotational states of murine ATP synthase (State 1 at 3.0 Å,\r\n8\r\nState 2 at 3.1 Å, and State 3 at 3.2 Å, overall). We observed several new features in our maps;\r\nhowever, we cannot definitively determine the exact mechanism of yaku amide’s inhibition on\r\nthe protein due to either resolution limits or suboptimal binding of the inhibitor."}],"status":"public","publisher":"Institute of Science and Technology Austria","alternative_title":["ISTA Thesis"],"day":"26","oa":1,"author":[{"first_name":"Kristina","id":"2B04DB84-F248-11E8-B48F-1D18A9856A87","last_name":"Lukic","full_name":"Lukic, Kristina","orcid":"0000-0003-1581-881X"}],"doi":"10.15479/at:ista:17319","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"month":"07","corr_author":"1","oa_version":"Published Version"},{"page":"1061-1071","_id":"15323","date_published":"2024-07-01T00:00:00Z","year":"2024","date_created":"2024-04-14T22:01:03Z","language":[{"iso":"eng"}],"article_processing_charge":"No","citation":{"mla":"Vercellino, Irene, and Leonid A. Sazanov. “SCAF1 Drives the Compositional Diversity of Mammalian Respirasomes.” <i>Nature Structural and Molecular Biology</i>, vol. 31, Springer Nature, 2024, pp. 1061–71, doi:<a href=\"https://doi.org/10.1038/s41594-024-01255-0\">10.1038/s41594-024-01255-0</a>.","ista":"Vercellino I, Sazanov LA. 2024. SCAF1 drives the compositional diversity of mammalian respirasomes. Nature Structural and Molecular Biology. 31, 1061–1071.","apa":"Vercellino, I., &#38; Sazanov, L. A. (2024). SCAF1 drives the compositional diversity of mammalian respirasomes. <i>Nature Structural and Molecular Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41594-024-01255-0\">https://doi.org/10.1038/s41594-024-01255-0</a>","ama":"Vercellino I, Sazanov LA. SCAF1 drives the compositional diversity of mammalian respirasomes. <i>Nature Structural and Molecular Biology</i>. 2024;31:1061-1071. doi:<a href=\"https://doi.org/10.1038/s41594-024-01255-0\">10.1038/s41594-024-01255-0</a>","chicago":"Vercellino, Irene, and Leonid A Sazanov. “SCAF1 Drives the Compositional Diversity of Mammalian Respirasomes.” <i>Nature Structural and Molecular Biology</i>. Springer Nature, 2024. <a href=\"https://doi.org/10.1038/s41594-024-01255-0\">https://doi.org/10.1038/s41594-024-01255-0</a>.","ieee":"I. Vercellino and L. A. Sazanov, “SCAF1 drives the compositional diversity of mammalian respirasomes,” <i>Nature Structural and Molecular Biology</i>, vol. 31. Springer Nature, pp. 1061–1071, 2024.","short":"I. Vercellino, L.A. Sazanov, Nature Structural and Molecular Biology 31 (2024) 1061–1071."},"publication_status":"published","related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41594-025-01721-3"}]},"acknowledgement":"Supercomplexes of the respiratory chain are established constituents of the oxidative phosphorylation system, but their role in mammalian metabolism has been hotly debated. Although recent studies have shown that different tissues/organs are equipped with specific sets of supercomplexes, depending on their metabolic needs, the notion that supercomplexes have a role in the regulation of metabolism has been challenged. However, irrespective of the mechanistic conclusions, the composition of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse) tissues contain three defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes, of which only one contains the supercomplex-associated factor SCAF1, whose involvement in respirasome formation has long been contended. Our structures confirm that the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated to a different respirasome (the CS-respirasome), containing a second copy of CIV. We also identify an alternative respirasome (A-respirasome), with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis for their specific role in different metabolic conditions.","isi":1,"date_updated":"2025-11-24T08:35:04Z","intvolume":"        31","type":"journal_article","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"},"has_accepted_license":"1","title":"SCAF1 drives the compositional diversity of mammalian respirasomes","publication_identifier":{"issn":["1545-9993"],"eissn":["1545-9985"]},"file":[{"date_updated":"2025-01-01T23:30:03Z","checksum":"21f05d188762acd7f49a97f3d09c8d9f","embargo":"2025-01-01","date_created":"2024-05-14T11:57:56Z","file_id":"15392","creator":"lsazanov","access_level":"open_access","content_type":"application/pdf","file_size":24424729,"file_name":"megacomplex_submit_NSMB_withFigures.pdf","relation":"main_file"}],"external_id":{"pmid":["38575788"],"isi":["001196897300001"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"LeSa"}],"file_date_updated":"2025-01-01T23:30:03Z","status":"public","abstract":[{"text":"Supercomplexes of the respiratory chain are established constituents of the oxidative phosphorylation system, but their role in mammalian metabolism has been hotly debated. Although recent studies have shown that different tissues/organs are equipped with specific sets of supercomplexes, depending on their metabolic needs, the notion that supercomplexes have a role in the regulation of metabolism has been challenged. However, irrespective of the mechanistic conclusions, the composition of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse) tissues contain three defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes, of which only one contains the supercomplex-associated factor SCAF1, whose involvement in respirasome formation has long been contended. Our structures confirm that the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated to a different respirasome (the CS-respirasome), containing a second copy of CIV. We also identify an alternative respirasome (A-respirasome), with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis for their specific role in different metabolic conditions.","lang":"eng"}],"ec_funded":1,"ddc":["572"],"quality_controlled":"1","project":[{"grant_number":"101020697","call_identifier":"H2020","_id":"627abdeb-2b32-11ec-9570-ec31a97243d3","name":"Structure and mechanism of respiratory chain molecular machines"}],"pmid":1,"scopus_import":"1","article_type":"original","volume":31,"oa_version":"Submitted Version","corr_author":"1","doi":"10.1038/s41594-024-01255-0","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"ScienComp"}],"author":[{"id":"3ED6AF16-F248-11E8-B48F-1D18A9856A87","first_name":"Irene","last_name":"Vercellino","full_name":"Vercellino, Irene","orcid":"0000-0001-5618-3449"},{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","last_name":"Sazanov","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989"}],"month":"07","publication":"Nature Structural and Molecular Biology","oa":1,"day":"01","publisher":"Springer Nature"},{"day":"31","oa":1,"publisher":"Institute of Science and Technology Austria","alternative_title":["ISTA Thesis"],"corr_author":"1","oa_version":"Published Version","doi":"10.15479/at:ista:17346","author":[{"full_name":"Bollmann, Lars","id":"47AD3038-F248-11E8-B48F-1D18A9856A87","first_name":"Lars","last_name":"Bollmann"}],"month":"07","OA_place":"publisher","ddc":["573"],"degree_awarded":"PhD","status":"public","keyword":["Memory","Hippocampus","Consolidation"],"abstract":[{"text":"Acquiring, retaining, and retrieving information over a wide range of timescales are crucial\r\nfunctions of the brain. The successful processing of memories affects many aspects of our\r\nlives and enables us and many other organisms to operate in a complex environment and\r\nto interact with it. In this context, the hippocampus and functionally connected brain\r\nareas, such as the prefrontal cortex, are central and have been subject to intensive research\r\nin the past decades. Storage of memories is believed to rely on distributed neural activity\r\nwithin these neural circuits. Additionally, neural memory traces of recent experience are\r\nreinstated during periods of rest or sleep. These reactivations are thought to play an\r\noutstanding role in the consolidation of memories and potentially facilitate the transfer of\r\ninformation from the hippocampus to cortical areas for long-term storage and integration\r\ninto existing knowledge.\r\nHowever, there is growing evidence that memory-related neural representations in the\r\nhippocampus are not as stable as initially thought and that they change even in the\r\nabsence of learning. It has been suggested that these changes reflect the accumulation of\r\nexperience, but the influence of interspersed consolidation periods has not been considered.\r\nPrevious studies have analyzed consolidation periods by detecting activity that strongly\r\nresembled neural activity during the acquisition of memory. Besides being often limited\r\nto only non-rapid eye movement (NREM) sleep, the used approaches were not capable of\r\ntracking changes in neural representations over extended temporal periods. More fluid\r\nrepresentations do not only challenge our understanding of how information is stored, but\r\nthey also affect the transfer of information between brain areas during the consolidation\r\nprocess.\r\nFor this thesis, I investigated the evolution of memory-related activity during sleep\r\nperiods expected to be involved in consolidation in the hippocampus and between the\r\nhippocampus and prefrontal cortex. I found that reactivated activity in the hippocampus\r\ngradually transformed during prolonged periods of sleep and inactivity. In the beginning,\r\nneural activity strongly resembled acquisition activity, whereas, with the progression of\r\ntime, it became more similar to the subsequent recall activity. NREM periods drove\r\nthis process, while rapid-eye movement (REM) periods showed a resetting effect. This\r\nreactivation drift was due to firing rate changes of a subset of cells and mirrored the\r\nrepresentational changes from the acquisition to the recall. A stable subset of cells\r\nwithstood the drift and maintained their activity. Therefore, my results indicate that\r\nmemory-related representations undergo spontaneous modifications during consolidation\r\nperiods and that these changes are predictive of representational drift.\r\nFurthermore, I found that the amount of change in the neural activity during subsequent\r\nsleep periods was biased by prior behavioral performance. Observed changes in the\r\nhippocampus and the prefrontal cortex were synchronized and increased after poor\r\nperformance, highlighting a potential role in the exchange of information. Low-variance\r\nvii\r\nperiods with distinct, more stable activity from a subset of cells significantly contributed\r\nto the heightened synchrony between both areas. Hence, interleaved phases of more stable\r\nneural activity could facilitate the information transfer between brain areas.\r\nIn conclusion, my investigations underline the fluidity of memory-related representations\r\nand assign a prominent role to sleep reactivation periods in their evolution. In addition, I\r\nidentified a potential mechanism of stable activity phases that might facilitate the synchronization across hippocampal-prefrontal activity despite ongoing changes. Reconciling\r\nand integrating findings from both spontaneous and behaviorally-related representational\r\nchanges in functionally related brain areas will help to broaden our understanding of how\r\nknowledge is stored, maintained, updated, and transferred between brain areas.","lang":"eng"}],"file":[{"relation":"main_file","file_name":"PhD_Thesis_Lars_Bollmann.pdf","file_size":12920169,"content_type":"application/pdf","access_level":"open_access","creator":"lbollman","file_id":"17359","checksum":"12c76297cc27449da80c60d79127770d","date_created":"2024-07-31T18:37:19Z","embargo":"2025-01-31","date_updated":"2025-01-31T23:30:03Z"},{"embargo_to":"open_access","content_type":"application/zip","access_level":"closed","creator":"lbollman","relation":"source_file","file_name":"Latex_source.zip","file_size":27568807,"date_updated":"2025-01-31T23:30:03Z","file_id":"17360","checksum":"19a0265079dec8038830ad6e35c5106e","date_created":"2024-07-31T18:38:39Z"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","supervisor":[{"full_name":"Csicsvari, Jozsef L","orcid":"0000-0002-5193-4036","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","first_name":"Jozsef L","last_name":"Csicsvari"}],"file_date_updated":"2025-01-31T23:30:03Z","department":[{"_id":"GradSch"},{"_id":"JoCs"}],"has_accepted_license":"1","title":"Stability and change in the memory system during rest","publication_identifier":{"issn":["2663-337X"]},"date_created":"2024-07-29T15:08:42Z","year":"2024","date_published":"2024-07-31T00:00:00Z","publication_status":"published","article_processing_charge":"No","citation":{"short":"L. Bollmann, Stability and Change in the Memory System during Rest, Institute of Science and Technology Austria, 2024.","ieee":"L. Bollmann, “Stability and change in the memory system during rest,” Institute of Science and Technology Austria, 2024.","ista":"Bollmann L. 2024. Stability and change in the memory system during rest. Institute of Science and Technology Austria.","mla":"Bollmann, Lars. <i>Stability and Change in the Memory System during Rest</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:17346\">10.15479/at:ista:17346</a>.","ama":"Bollmann L. Stability and change in the memory system during rest. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:17346\">10.15479/at:ista:17346</a>","chicago":"Bollmann, Lars. “Stability and Change in the Memory System during Rest.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:17346\">https://doi.org/10.15479/at:ista:17346</a>.","apa":"Bollmann, L. (2024). <i>Stability and change in the memory system during rest</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:17346\">https://doi.org/10.15479/at:ista:17346</a>"},"language":[{"iso":"eng"}],"type":"dissertation","date_updated":"2026-04-07T13:21:20Z","page":"103","_id":"17346"},{"OA_place":"publisher","degree_awarded":"MS","ddc":["570"],"status":"public","abstract":[{"text":"Epilepsy affects about 50 to 65 million people globally. It summarizes a spectrum of neurological\r\ndisorders that have in common a hyperactivity of the neuronal network resulting in seizures. A common\r\nassumption is that an imbalance between neuronal excitation and inhibition is a key mechanism in\r\nseizure generation and epileptogeneisis. In at least one-third of the patients, current therapies have\r\nproven unsuccessful in treating seizure progression. One potential reason could be that the therapies\r\nonly focus on neurons. Recent studies suggest that neuronal hyperactivity causes a microglial\r\nresponse, which reinstates brain homeostasis. Additionally, interactions between microglia and neurons\r\nhave been shown to inhibit neuronal firing and dampen seizure activity. However, the exact relationship\r\nbetween microglia and seizure progression in epilepsy is yet to be elucidated. A main bottleneck is that\r\nseveral studies investigate microglia dynamics in ex vivo slice models, which can severely affect the\r\nmicroglia dynamics due to their rapid response to environmental changes. On the other hand, in vivo\r\nstudies focus mostly on behavior characterization of the epileptic seizure phenotype and their long-term\r\nconsequences on microglia activity leaving out the direct consequences of acute seizure activity on\r\nmicroglia dynamics.\r\nHere, we perform a pilot study to combine electroencephalography (EEG) and in vivo live imaging to\r\ndirectly monitor and correlate the onset of seizure activity with microglia response. To induce seizures,\r\nwe take advantage of the kainic acid (KA) model, which represents similar neuropathological and\r\nelectroencephalographic features seen in human patients with temporal lobe epilepsy (TLE). After\r\nconfirmation of induction of the seizure and microglia activity in the hippocampus as a focal point, we\r\ninvestigated whether these changes also reached the primary visual cortex (V1) as a secondary\r\ngeneralized seizure activity. Indeed, we found that microglia changed their morphology at high doses\r\nof KA in the V1. Next, we optimized each of the two methodological components: for the EEG recording,\r\nour initial attempts under the microscope suffered from extensive electrical noise, which overlaid the\r\nactual signal. Thus, we built a customized Faraday-cage and confirmed that the signal-to-noise ratio\r\nwas sufficiently reduced to be able to record brain oscillatory activity. For the in vivo live imaging of\r\nmicroglia, we had to optimize the imaging parameters, so that we would be able to detect microglial\r\nprocesses in a sufficient resolution to track their process changes. Finally, we combined both\r\nmethodologies with the KA model. We confirmed that KA induced seizure activity and found first\r\nindication that those correlate with microglia volume changes.\r\nOverall, we have developed a first methodological approach, which allows the analysis of the acute\r\neffects of seizure onset on microglia. Future studies will have to continue to optimize the drift during\r\nimaging recording and the post-image analysis. ","lang":"eng"}],"oa":1,"day":"02","alternative_title":["ISTA Master's Thesis"],"publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","corr_author":"1","month":"05","author":[{"full_name":"Murmann, Julie Stefanie","first_name":"Julie Stefanie","id":"1d390868-f128-11eb-9611-a0ca5f7833b5","last_name":"Murmann"}],"doi":"10.15479/at:ista:15352","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"publication_status":"published","article_processing_charge":"No","language":[{"iso":"eng"}],"citation":{"short":"J.S. Murmann, Investigating Acute Microglia Response to Seizure Activity in Vivo: Combining 2-Photon Imaging and EEG Recording, Institute of Science and Technology Austria, 2024.","ieee":"J. S. Murmann, “Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording,” Institute of Science and Technology Austria, 2024.","mla":"Murmann, Julie Stefanie. <i>Investigating Acute Microglia Response to Seizure Activity in Vivo: Combining 2-Photon Imaging and EEG Recording</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:15352\">10.15479/at:ista:15352</a>.","ista":"Murmann JS. 2024. Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording. Institute of Science and Technology Austria.","apa":"Murmann, J. S. (2024). <i>Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:15352\">https://doi.org/10.15479/at:ista:15352</a>","ama":"Murmann JS. Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:15352\">10.15479/at:ista:15352</a>","chicago":"Murmann, Julie Stefanie. “Investigating Acute Microglia Response to Seizure Activity in Vivo: Combining 2-Photon Imaging and EEG Recording.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:15352\">https://doi.org/10.15479/at:ista:15352</a>."},"year":"2024","date_created":"2024-05-02T08:31:38Z","date_published":"2024-05-02T00:00:00Z","type":"dissertation","date_updated":"2026-04-07T13:05:00Z","_id":"15352","page":"54","file":[{"date_updated":"2025-05-02T22:30:04Z","checksum":"095817a6c944954ac3f277e547031a33","embargo":"2025-05-02","date_created":"2024-05-02T12:26:13Z","file_id":"15354","creator":"cchlebak","access_level":"open_access","content_type":"application/pdf","file_size":5936142,"file_name":"Murmann_Thesis_final_2024_2.pdf","relation":"main_file"},{"access_level":"closed","creator":"cchlebak","embargo_to":"open_access","content_type":"application/x-zip-compressed","file_size":20645510,"relation":"source_file","file_name":"Murmann_Thesis_final_2024.zip","date_updated":"2025-05-02T22:30:04Z","checksum":"43b632255372973a437ac87739cfd4db","date_created":"2024-05-02T12:37:56Z","file_id":"15355"}],"file_date_updated":"2025-05-02T22:30:04Z","department":[{"_id":"SaSi"},{"_id":"GradSch"}],"supervisor":[{"last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","title":"Investigating acute microglia response to seizure activity in vivo: Combining 2-Photon imaging and EEG recording","has_accepted_license":"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"},"publication_identifier":{"issn":["2791-4585"]}},{"oa_version":"Published Version","corr_author":"1","project":[{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program"}],"month":"01","author":[{"orcid":"0009-0004-2973-278X","full_name":"Chiossi, Heloisa","first_name":"Heloisa","id":"2BBA502C-F248-11E8-B48F-1D18A9856A87","last_name":"Chiossi"}],"doi":"10.15479/at:ista:14821","oa":1,"day":"19","alternative_title":["ISTA Thesis"],"publisher":"Institute of Science and Technology Austria","status":"public","abstract":[{"lang":"eng","text":"The hippocampus is central to memory formation, storage and retrieval over many\r\ntimescales. Neurons in this brain area are highly selective to spatial position as well as to many\r\nother variables of the environment. It is believed that the selectivity patterns of hippocampal\r\nneurons reflect the structure of tasks an animal performs. However, especially at timescales\r\nlonger than a few minutes or hours it is not fully known how these representations evolve, nor\r\nhow they map to behaviour in the process. In this thesis, I monitored the evolution of\r\nhippocampal representations in a novel spatial-associative memory task for rats. Reward\r\nlocations were associated with global sensory cues (i.e. context); animals had to remember the\r\nassociations and dig for food in those locations only. I used in vivo electrophysiology to record\r\nthe activity of the hippocampus dorsal CA1 neurons during the learning period of a few days.\r\nI report here a novel and simple method to classify behaviour performance to account\r\nfor individual variability in learning speed and spurious performance unrelated to true task rule\r\nlearning. Using this classification I was then able to investigate neural responses on different\r\nstages of learning matched across animals. On the first day of learning, I observed a fast\r\nformation of single-cell selectivity to task variables which remained stable over days. I also\r\nobserved that reward tuning was not a single process but dependent on task-related cognitive\r\nload. At the population level, a linear decoding approach revealed a hierarchy in the\r\nrepresentation of task variables that changed with learning. In the high-dimensional space of\r\npopulation activity, the representation of contexts was specific to each position in the maze, and\r\ncould thus be better decoded if the position was known. The decoding of position did not improve\r\nwith knowledge of other variables. As learning progressed, the hippocampal code underwent a\r\nreorganisation of high-variance directions in population activity, identified by principal\r\ncomponent analysis. I found that dominant dimensions started carrying increasing amounts of\r\ninformation about task context specifically at those positions where it mattered for task\r\nperformance. When I contrasted this with variables less relevant to task performance (e.g.\r\nmovement direction), I did not observe differences in decoding quality over positions nor a\r\nreduction of dimensionality with learning.\r\nOverall, the largest changes in CA1 neural response with task learning happened in a\r\nmatter of a few trials; over days, changes undetectable in single-cell statistics were responsible\r\nfor re-structuring the hierarchy of neural representations at the population level; these changes\r\nwere task-specific and reflected different stages of learning. This indicates that complex task\r\nlearning may involve different magnitudes of response modulation in CA1, which happen at\r\nspecific time scales linked to behaviour."}],"ec_funded":1,"OA_place":"publisher","degree_awarded":"PhD","ddc":["570"],"title":"Adaptive hierarchical representations in the hippocampus","has_accepted_license":"1","publication_identifier":{"issn":["2663-337X"]},"file":[{"access_level":"closed","creator":"hchiossi","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","file_size":8656268,"relation":"source_file","file_name":"PhD_Thesis_190124.docx","date_updated":"2025-01-19T23:30:04Z","checksum":"d3fa3de1abd5af5204c13e9d55375615","date_created":"2024-01-19T11:04:05Z","file_id":"14838"},{"date_updated":"2025-01-19T23:30:04Z","file_id":"14839","checksum":"13adc8dcfb5b6b18107f89f0a98fa8bd","date_created":"2024-01-19T11:03:59Z","embargo":"2025-01-19","content_type":"application/pdf","access_level":"open_access","creator":"hchiossi","relation":"main_file","file_name":"PhD_Thesis_190124.pdf","file_size":6567275}],"file_date_updated":"2025-01-19T23:30:04Z","department":[{"_id":"GradSch"},{"_id":"JoCs"}],"supervisor":[{"last_name":"Csicsvari","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","first_name":"Jozsef L","orcid":"0000-0002-5193-4036","full_name":"Csicsvari, Jozsef L"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","_id":"14821","page":"89","publication_status":"published","language":[{"iso":"eng"}],"article_processing_charge":"No","citation":{"short":"H.S.C. Chiossi, Adaptive Hierarchical Representations in the Hippocampus, Institute of Science and Technology Austria, 2024.","ieee":"H. S. C. Chiossi, “Adaptive hierarchical representations in the hippocampus,” Institute of Science and Technology Austria, 2024.","apa":"Chiossi, H. S. C. (2024). <i>Adaptive hierarchical representations in the hippocampus</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:14821\">https://doi.org/10.15479/at:ista:14821</a>","ama":"Chiossi HSC. Adaptive hierarchical representations in the hippocampus. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:14821\">10.15479/at:ista:14821</a>","chicago":"Chiossi, Heloisa S. C. “Adaptive Hierarchical Representations in the Hippocampus.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:14821\">https://doi.org/10.15479/at:ista:14821</a>.","mla":"Chiossi, Heloisa S. C. <i>Adaptive Hierarchical Representations in the Hippocampus</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:14821\">10.15479/at:ista:14821</a>.","ista":"Chiossi HSC. 2024. Adaptive hierarchical representations in the hippocampus. Institute of Science and Technology Austria."},"date_created":"2024-01-16T14:25:21Z","year":"2024","date_published":"2024-01-19T00:00:00Z","type":"dissertation","date_updated":"2026-04-07T13:21:56Z"},{"status":"public","abstract":[{"lang":"eng","text":"We prove discrete-to-continuum convergence for dynamical optimal transport on  Zd\r\n -periodic graphs with cost functional having linear growth at infinity. This result provides an answer to a problem left open by Gladbach, Kopfer, Maas, and Portinale (Calc Var Partial Differential Equations 62(5), 2023), where the convergence behaviour of discrete boundary-value dynamical transport problems is proved under the stronger assumption of superlinear growth. Our result extends the known literature to some important classes of examples, such as scaling limits of  1 -Wasserstein transport problems. Similarly to what happens in the quadratic case, the geometry of the graph plays a crucial role in the structure of the limit cost function, as we discuss in the final part of this work, which includes some visual representations."}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1017/S0956792524000810"}],"OA_place":"publisher","quality_controlled":"1","oa_version":"Published Version","scopus_import":"1","article_type":"original","project":[{"grant_number":"F6504","_id":"fc31cba2-9c52-11eb-aca3-ff467d239cd2","name":"Taming Complexity in Partial Differential Systems"}],"month":"12","author":[{"full_name":"Portinale, Lorenzo","last_name":"Portinale","first_name":"Lorenzo","id":"30AD2CBC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Quattrocchi, Filippo","orcid":"0009-0000-9773-1931","last_name":"Quattrocchi","first_name":"Filippo","id":"3ebd6ba8-edfb-11eb-afb5-91a9745ba308"}],"doi":"10.1017/s0956792524000810","day":"20","oa":1,"publication":"European Journal of Applied Mathematics","publisher":"Cambridge University Press","_id":"18706","page":"1-29","DOAJ_listed":"1","publication_status":"epub_ahead","OA_type":"gold","citation":{"ieee":"L. Portinale and F. Quattrocchi, “Discrete-to-continuum limits of optimal transport with linear growth on periodic graphs,” <i>European Journal of Applied Mathematics</i>. Cambridge University Press, pp. 1–29, 2024.","short":"L. Portinale, F. Quattrocchi, European Journal of Applied Mathematics (2024) 1–29.","ista":"Portinale L, Quattrocchi F. 2024. Discrete-to-continuum limits of optimal transport with linear growth on periodic graphs. European Journal of Applied Mathematics., 1–29.","mla":"Portinale, Lorenzo, and Filippo Quattrocchi. “Discrete-to-Continuum Limits of Optimal Transport with Linear Growth on Periodic Graphs.” <i>European Journal of Applied Mathematics</i>, Cambridge University Press, 2024, pp. 1–29, doi:<a href=\"https://doi.org/10.1017/s0956792524000810\">10.1017/s0956792524000810</a>.","chicago":"Portinale, Lorenzo, and Filippo Quattrocchi. “Discrete-to-Continuum Limits of Optimal Transport with Linear Growth on Periodic Graphs.” <i>European Journal of Applied Mathematics</i>. Cambridge University Press, 2024. <a href=\"https://doi.org/10.1017/s0956792524000810\">https://doi.org/10.1017/s0956792524000810</a>.","ama":"Portinale L, Quattrocchi F. Discrete-to-continuum limits of optimal transport with linear growth on periodic graphs. <i>European Journal of Applied Mathematics</i>. 2024:1-29. doi:<a href=\"https://doi.org/10.1017/s0956792524000810\">10.1017/s0956792524000810</a>","apa":"Portinale, L., &#38; Quattrocchi, F. (2024). Discrete-to-continuum limits of optimal transport with linear growth on periodic graphs. <i>European Journal of Applied Mathematics</i>. Cambridge University Press. <a href=\"https://doi.org/10.1017/s0956792524000810\">https://doi.org/10.1017/s0956792524000810</a>"},"language":[{"iso":"eng"}],"article_processing_charge":"Yes","year":"2024","date_created":"2024-12-23T11:03:59Z","date_published":"2024-12-20T00:00:00Z","type":"journal_article","date_updated":"2026-05-15T22:30:21Z","isi":1,"acknowledgement":"L.P. gratefully acknowledges fundings from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – GZ 2047/1, Projekt-ID 390685813. F.Q. gratefully acknowledges support from the Austrian Science Fund (FWF) project 10.55776/F65.","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"20563"}]},"title":"Discrete-to-continuum limits of optimal transport with linear growth on periodic graphs","publication_identifier":{"eissn":["1469-4425"],"issn":["0956-7925"]},"department":[{"_id":"GradSch"},{"_id":"JaMa"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","external_id":{"isi":["001381435800001"]}},{"oa_version":"Preprint","corr_author":"1","project":[{"name":"Taming Complexity in Partial Differential Systems","_id":"260482E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"F06504"}],"month":"04","doi":"10.48550/arXiv.2403.07803","author":[{"full_name":"Quattrocchi, Filippo","orcid":"0009-0000-9773-1931","first_name":"Filippo","id":"3ebd6ba8-edfb-11eb-afb5-91a9745ba308","last_name":"Quattrocchi"}],"arxiv":1,"publication":"arXiv","oa":1,"day":"09","keyword":["gradient flows","Jordan–Kinderlehrer–Otto scheme","curves of maximal slope","optimal transport","Dirichlet boundary conditions","Fokker–Planck equation"],"status":"public","main_file_link":[{"url":"https://doi.org/10.48550/arXiv.2403.07803","open_access":"1"}],"abstract":[{"text":"We prove the convergence of a modified Jordan--Kinderlehrer--Otto scheme to a solution to the Fokker--Planck equation in $\\Omega \\Subset \\mathbb{R}^d$ with general, positive and temporally constant, Dirichlet boundary conditions. We work under mild assumptions on the domain, the drift, and the initial datum.   In the special case where $\\Omega$ is an interval in $\\mathbb{R}^1$, we prove that such a solution is a gradient flow -- curve of maximal slope -- within a suitable space of measures, endowed with a modified Wasserstein distance.\r\nOur discrete scheme and modified distance draw inspiration from contributions by A. Figalli and N. Gigli [J. Math. Pures Appl. 94, (2010), pp. 107--130], and J. Morales [J. Math. Pures Appl. 112, (2018), pp. 41--88] on an optimal-transport approach to evolution equations with Dirichlet boundary conditions. Similarly to these works, we allow the mass to flow from/to the boundary $\\partial \\Omega$ throughout the evolution. However, our leading idea is to also keep track of the mass at the boundary by working with measures defined on the whole closure $\\overline \\Omega$. The driving functional is a modification of the classical relative entropy that also makes use of the information at the boundary. As an intermediate result, when $\\Omega$ is an interval in $\\mathbb{R}^1$, we find a formula for the descending slope of this geodesically nonconvex functional. ","lang":"eng"}],"article_number":"2403.07803","OA_place":"repository","title":"Variational structures for the Fokker-Planck equation with general Dirichlet boundary conditions","department":[{"_id":"GradSch"},{"_id":"JaMa"}],"external_id":{"arxiv":["2403.07803"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"20571","article_processing_charge":"No","citation":{"short":"F. Quattrocchi, ArXiv (n.d.).","ieee":"F. Quattrocchi, “Variational structures for the Fokker-Planck equation with general Dirichlet boundary conditions,” <i>arXiv</i>. .","ista":"Quattrocchi F. Variational structures for the Fokker-Planck equation with general Dirichlet boundary conditions. arXiv, 2403.07803.","mla":"Quattrocchi, Filippo. “Variational Structures for the Fokker-Planck Equation with General Dirichlet Boundary Conditions.” <i>ArXiv</i>, 2403.07803, doi:<a href=\"https://doi.org/10.48550/arXiv.2403.07803\">10.48550/arXiv.2403.07803</a>.","chicago":"Quattrocchi, Filippo. “Variational Structures for the Fokker-Planck Equation with General Dirichlet Boundary Conditions.” <i>ArXiv</i>, n.d. <a href=\"https://doi.org/10.48550/arXiv.2403.07803\">https://doi.org/10.48550/arXiv.2403.07803</a>.","ama":"Quattrocchi F. Variational structures for the Fokker-Planck equation with general Dirichlet boundary conditions. <i>arXiv</i>. doi:<a href=\"https://doi.org/10.48550/arXiv.2403.07803\">10.48550/arXiv.2403.07803</a>","apa":"Quattrocchi, F. (n.d.). Variational structures for the Fokker-Planck equation with general Dirichlet boundary conditions. <i>arXiv</i>. <a href=\"https://doi.org/10.48550/arXiv.2403.07803\">https://doi.org/10.48550/arXiv.2403.07803</a>"},"OA_type":"green","language":[{"iso":"eng"}],"publication_status":"draft","date_published":"2024-04-09T00:00:00Z","date_created":"2025-10-28T13:12:56Z","year":"2024","date_updated":"2026-05-15T22:30:21Z","type":"preprint","related_material":{"record":[{"status":"public","relation":"later_version","id":"20865"},{"status":"public","relation":"dissertation_contains","id":"20563"}]},"acknowledgement":"The author would like to thank Jan Maas for suggesting this project and for many helpful\r\ncomments, Antonio Agresti, Lorenzo Dello Schiavo and Julian Fischer for several fruitful discussions, and Oliver Tse for pointing out the reference [15]. He also gratefully acknowledges support from the Austrian Science Fund (FWF) project 10.55776/F65.\r\n"},{"title":"Asymptotics for optimal empirical quantization of measures","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"arxiv":["2408.12924"]},"department":[{"_id":"GradSch"},{"_id":"JaMa"}],"_id":"20570","acknowledgement":"The author is thankful to Nicolas Clozeau, Lorenzo Dello Schiavo, Jan Maas, Dejan Slepčev,\r\nand Dario Trevisan for many fruitful discussions and comments. The author gratefully acknowledges support from the Austrian Science Fund (FWF) project 10.55776/F65.","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"20563"}]},"type":"preprint","date_updated":"2026-05-15T22:30:21Z","date_created":"2025-10-28T13:12:22Z","year":"2024","date_published":"2024-08-23T00:00:00Z","publication_status":"draft","article_processing_charge":"No","language":[{"iso":"eng"}],"citation":{"ista":"Quattrocchi F. Asymptotics for optimal empirical quantization of measures. arXiv, 2408.12924.","mla":"Quattrocchi, Filippo. “Asymptotics for Optimal Empirical Quantization of Measures.” <i>ArXiv</i>, 2408.12924, doi:<a href=\"https://doi.org/10.48550/arXiv.2408.12924\">10.48550/arXiv.2408.12924</a>.","ama":"Quattrocchi F. Asymptotics for optimal empirical quantization of measures. <i>arXiv</i>. doi:<a href=\"https://doi.org/10.48550/arXiv.2408.12924\">10.48550/arXiv.2408.12924</a>","chicago":"Quattrocchi, Filippo. “Asymptotics for Optimal Empirical Quantization of Measures.” <i>ArXiv</i>, n.d. <a href=\"https://doi.org/10.48550/arXiv.2408.12924\">https://doi.org/10.48550/arXiv.2408.12924</a>.","apa":"Quattrocchi, F. (n.d.). Asymptotics for optimal empirical quantization of measures. <i>arXiv</i>. <a href=\"https://doi.org/10.48550/arXiv.2408.12924\">https://doi.org/10.48550/arXiv.2408.12924</a>","ieee":"F. Quattrocchi, “Asymptotics for optimal empirical quantization of measures,” <i>arXiv</i>. .","short":"F. Quattrocchi, ArXiv (n.d.)."},"OA_type":"green","author":[{"full_name":"Quattrocchi, Filippo","orcid":"0009-0000-9773-1931","last_name":"Quattrocchi","first_name":"Filippo","id":"3ebd6ba8-edfb-11eb-afb5-91a9745ba308"}],"doi":"10.48550/arXiv.2408.12924","month":"08","project":[{"grant_number":"F06504","name":"Taming Complexity in Partial Differential Systems","_id":"260482E2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"corr_author":"1","oa_version":"Preprint","oa":1,"day":"23","publication":"arXiv","arxiv":1,"article_number":"2408.12924","abstract":[{"lang":"eng","text":"We investigate the minimal error in approximating a general probability\r\nmeasure $\\mu$ on $\\mathbb{R}^d$ by the uniform measure on a finite set with\r\nprescribed cardinality $n$. The error is measured in the $p$-Wasserstein\r\ndistance. In particular, when $1\\le p<d$, we establish asymptotic upper and\r\nlower bounds as $n \\to \\infty$ on the rescaled minimal error that have the\r\nsame, explicit dependency on $\\mu$.\r\n  In some instances, we prove that the rescaled minimal error has a limit.\r\nThese include general measures in dimension $d = 2$ with $1 \\le p < 2$, and\r\nuniform measures in arbitrary dimension with $1 \\le p < d$. For some uniform\r\nmeasures, we prove the limit existence for $p \\ge d$ as well.\r\n  For a class of compactly supported measures with H\\\"older densities, we\r\ndetermine the convergence speed of the minimal error for every $p \\ge 1$.\r\n  Furthermore, we establish a new Pierce-type (i.e., nonasymptotic) upper\r\nestimate of the minimal error when $1 \\le p < d$.\r\n  In the initial sections, we survey the state of the art and draw connections\r\nwith similar problems, such as classical and random quantization."}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.48550/arXiv.2408.12924"}],"status":"public","keyword":["optimal empirical quantization","vector quantization","Wasserstein distance","semidiscrete optimal transport","Zador’s Theorem","Pierce’s Lemma"],"OA_place":"repository"},{"title":"Strong charge-photon coupling in Germanium enabled by granular aluminium superinductors","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"},"has_accepted_license":"1","publication_identifier":{"issn":["2663-337X"]},"file":[{"file_id":"18130","checksum":"dc15958f6400b5bdaa28bf58fc7a4056","date_created":"2024-09-23T17:15:09Z","date_updated":"2025-05-23T22:30:09Z","relation":"source_file","file_name":"janik_thesis.zip","file_size":156207943,"embargo_to":"open_access","content_type":"application/x-zip-compressed","access_level":"closed","creator":"mjanik"},{"date_updated":"2025-05-23T22:30:09Z","date_created":"2024-09-23T17:15:30Z","embargo":"2025-05-23","checksum":"74737aee285dc1f491643327350efe9c","file_id":"18131","access_level":"open_access","creator":"mjanik","content_type":"application/pdf","file_size":96195684,"relation":"main_file","file_name":"janik_thesis_pdfa.pdf"}],"file_date_updated":"2025-05-23T22:30:09Z","department":[{"_id":"GradSch"},{"_id":"GeKa"}],"supervisor":[{"last_name":"Katsaros","first_name":"Georgios","id":"38DB5788-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8342-202X","full_name":"Katsaros, Georgios"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","_id":"18129","page":"164","publication_status":"published","citation":{"chicago":"Janik, Marian. “Strong Charge-Photon Coupling in Germanium Enabled by Granular Aluminium Superinductors.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:18129\">https://doi.org/10.15479/at:ista:18129</a>.","ama":"Janik M. Strong charge-photon coupling in Germanium enabled by granular aluminium superinductors. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:18129\">10.15479/at:ista:18129</a>","apa":"Janik, M. (2024). <i>Strong charge-photon coupling in Germanium enabled by granular aluminium superinductors</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:18129\">https://doi.org/10.15479/at:ista:18129</a>","ista":"Janik M. 2024. Strong charge-photon coupling in Germanium enabled by granular aluminium superinductors. Institute of Science and Technology Austria.","mla":"Janik, Marian. <i>Strong Charge-Photon Coupling in Germanium Enabled by Granular Aluminium Superinductors</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:18129\">10.15479/at:ista:18129</a>.","ieee":"M. Janik, “Strong charge-photon coupling in Germanium enabled by granular aluminium superinductors,” Institute of Science and Technology Austria, 2024.","short":"M. Janik, Strong Charge-Photon Coupling in Germanium Enabled by Granular Aluminium Superinductors, Institute of Science and Technology Austria, 2024."},"article_processing_charge":"No","language":[{"iso":"eng"}],"year":"2024","date_created":"2024-09-23T17:25:43Z","date_published":"2024-09-24T00:00:00Z","type":"dissertation","date_updated":"2026-04-07T13:23:25Z","related_material":{"record":[{"id":"18144","relation":"part_of_dissertation","status":"public"}]},"corr_author":"1","oa_version":"Published Version","project":[{"name":"High impedance circuit quantum electrodynamics with hole spins","_id":"c0977eea-5a5b-11eb-8a69-a862db0cf4d1","grant_number":"I05060"},{"grant_number":"P36507","_id":"bd8bd29e-d553-11ed-ba76-f0070d4b237a","name":"Merging spin and superconducting qubits in planar Ge"},{"name":"Towards scalable hut wire quantum devices","_id":"237B3DA4-32DE-11EA-91FC-C7463DDC885E","call_identifier":"FWF","grant_number":"P32235"},{"grant_number":"101069515","_id":"34c0acea-11ca-11ed-8bc3-8775e10fd452","name":"Integrated Germanium Quantum Technology"},{"_id":"eb9b30ac-77a9-11ec-83b8-871f581d53d2","name":"Protected states of quantum matter"}],"month":"09","author":[{"orcid":"0009-0003-9037-8831","full_name":"Janik, Marian","id":"396A1950-F248-11E8-B48F-1D18A9856A87","first_name":"Marian","last_name":"Janik"}],"doi":"10.15479/at:ista:18129","acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"NanoFab"}],"oa":1,"day":"24","alternative_title":["ISTA Thesis"],"publisher":"Institute of Science and Technology Austria","status":"public","abstract":[{"lang":"eng","text":"State-of-the-art quantum computers, with roughly a thousand qubits, face a crucial technological challenge of scaling up. Spins confined in quantum dots (QDs) are a promising candidate\r\nfor qubits due to their long coherence, tunability, control, and readout. However, their natural\r\ncoupling is the short-ranged (∼ 100 nm) exchange interaction, limited to nearest neighbours.\r\nLong-ranged (∼ 1 mm) qubit interactions mediated by a photon could be engineered through a\r\ncoherent spin-photon coupling. Achieving a strong coupling to a photon is inherently challenging in QDs due to the small dipole moment of the confined charge. However, the potential of\r\nhigh-impedance resonators to compensate for this has gained significant attention in the past\r\ndecade. Nevertheless, previous QD circuit quantum electrodynamics implementations have not\r\nexceeded the impedance of ∼ 3.8 kΩ, leaving opportunities for significant improvement. The\r\nlarge kinetic inductance of granular aluminium (grAl) could provide an order-of-magnitude\r\nenhancement. However, fully exploiting the potential of disordered or granular superconductors\r\nis challenging as their impedances close to the superconductor-to-insulator transition are\r\ndifficult to control reproducibly. We report on the realization of a wireless ohmmeter which\r\nallows in situ resistance measurements during film deposition and, therefore, indirect control\r\nof the kinetic inductance of grAl films. This allows us to reproducibly fabricate resonators\r\nwith characteristic impedance exceeding the resistance quantum, even reaching 22.3 kW, due\r\nto the large sheet kinetic inductance of up to 3 nH □−1\r\n. By integrating an 8 kW resonator\r\nwith a germanium double QD, we demonstrate a strong charge-photon coupling with the\r\nhighest rate reported, 566 MHz. The demonstrated method and grAl properties make these\r\nresonators suitable for boosting the spin-photon coupling strength, a crucial requirement for\r\nfast, high-fidelity, long-distance two-qubit gates.\r\n"}],"OA_place":"publisher","degree_awarded":"PhD","ddc":["539"]},{"publication_identifier":{"issn":["2791-4585"]},"title":"Bayesian linear regression for analyzing general omics data with time-to-event phenotypes","has_accepted_license":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"department":[{"_id":"GradSch"},{"_id":"MaRo"}],"file_date_updated":"2025-02-14T23:30:03Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","supervisor":[{"orcid":"0000-0001-8982-8813","full_name":"Robinson, Matthew Richard","last_name":"Robinson","id":"E5D42276-F5DA-11E9-8E24-6303E6697425","first_name":"Matthew Richard"}],"file":[{"file_name":"Masters_thesis_AriadnaVillanueva.pdf","relation":"main_file","file_size":13052436,"content_type":"application/pdf","creator":"avillanu","access_level":"open_access","file_id":"17433","date_created":"2024-08-14T11:51:24Z","embargo":"2025-02-14","checksum":"0c2daa174609f0c00919dccc5701d375","date_updated":"2025-02-14T23:30:03Z"},{"relation":"source_file","file_name":"Masters thesis-AriadnaVillanueva.zip","file_size":45642547,"content_type":"application/zip","embargo_to":"open_access","access_level":"closed","creator":"avillanu","file_id":"17434","checksum":"e9ed4465dfa539ac4c3a8d4d0b6271a1","date_created":"2024-08-14T11:51:57Z","date_updated":"2025-02-14T23:30:03Z"}],"_id":"17368","page":"60","type":"dissertation","date_updated":"2026-04-07T13:03:41Z","publication_status":"published","citation":{"ieee":"A. Villanueva Marijuan, “Bayesian linear regression for analyzing general omics data with time-to-event phenotypes,” Institute of Science and Technology Austria, 2024.","short":"A. Villanueva Marijuan, Bayesian Linear Regression for Analyzing General Omics Data with Time-to-Event Phenotypes, Institute of Science and Technology Austria, 2024.","mla":"Villanueva Marijuan, Ariadna. <i>Bayesian Linear Regression for Analyzing General Omics Data with Time-to-Event Phenotypes</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:17368\">10.15479/at:ista:17368</a>.","ista":"Villanueva Marijuan A. 2024. Bayesian linear regression for analyzing general omics data with time-to-event phenotypes. Institute of Science and Technology Austria.","apa":"Villanueva Marijuan, A. (2024). <i>Bayesian linear regression for analyzing general omics data with time-to-event phenotypes</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:17368\">https://doi.org/10.15479/at:ista:17368</a>","ama":"Villanueva Marijuan A. Bayesian linear regression for analyzing general omics data with time-to-event phenotypes. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:17368\">10.15479/at:ista:17368</a>","chicago":"Villanueva Marijuan, Ariadna. “Bayesian Linear Regression for Analyzing General Omics Data with Time-to-Event Phenotypes.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:17368\">https://doi.org/10.15479/at:ista:17368</a>."},"language":[{"iso":"eng"}],"article_processing_charge":"No","date_created":"2024-08-02T10:52:40Z","year":"2024","date_published":"2024-08-13T00:00:00Z","month":"08","author":[{"full_name":"Villanueva Marijuan, Ariadna","id":"e0ae4864-133f-11ed-8f02-adaa8dd27540","first_name":"Ariadna","last_name":"Villanueva Marijuan"}],"doi":"10.15479/at:ista:17368","corr_author":"1","oa_version":"Published Version","alternative_title":["ISTA Master's Thesis"],"publisher":"Institute of Science and Technology Austria","oa":1,"day":"13","abstract":[{"text":"Recent advancements in molecular diagnostic techniques have enabled the collection of\r\nmultiple types of omics data from patients, including genomics, epigenomics, proteomics,\r\nand transcriptomics. However, we lack effective methods for integrating all these different\r\ndata types and combining them with clinical outcomes to study the molecular mechanisms\r\nthat govern pathological phenotypes. We present multi-omics BayesW, a penalized Bayesian\r\nregression method that can handle general omics data for survival analysis of time-to-event\r\nphenotypes. Our method can: (1) accommodate incomplete data by allowing censored\r\nindividuals, (2) use continuous time-to-event data to test associations of markers with a\r\nphenotype and (3) estimate effects jointly while allowing for independent groups of biological\r\nmarkers. Extensive simulations using planted signals on real data demonstrate that our model\r\naccurately retrieves the true parameters of the model while controlling for false discoveries\r\nand maintaining the expected prediction accuracy. We address data correlations by estimating\r\nthe effects jointly, even between omic groups, while also estimating the individual variance\r\nexplained by each group. We apply our model to two datasets. Using 18,000 individuals from\r\nthe Generation Scotland study we model the association of time at onset of Type 2 Diabetes,\r\nStroke, Ischemic Disease, and Osteoarthritis from baseline study entry, with 831,724 CpG\r\nmethylation probes. We find that large proportions of variation in disease onset times can\r\nbe attributed to methylation as measured in whole blood at baseline in individuals without\r\ndisease symptoms. We then apply our model to The Cancer Genome Atlas (TCGA) pan-cancer\r\ndataset, in which we use 5 types of omics: copy number variation, epigenetics, somatic\r\nmutations, miRNA, and gene expression. For cancer survival age-at-onset we find that, when\r\nfitting the 5 groups together, almost all variation attributable to \"omics\" data is explained by\r\nDNA methylation. When considering progression times, both methylation and gene expression\r\nexplain a large part of the variance. We found 2 genes that are significantly associated (95%\r\nposterior inclusion probability) with cancer survival time, conditional on all other genome-wide\r\nomics data variation. Owing to the vast variability of mechanisms characterizing different\r\ncancers, there are likely few specific genes with a strong signal in a pan-cancer setting. Taken\r\ntogether, we showed the applicability of our multi-omics BayesW model to a wide-range of\r\nbiological questions in multi-omics data.\r\n","lang":"eng"}],"keyword":["Epigenetics","Multi-omics","Bayesian regression"],"status":"public","degree_awarded":"MS","ddc":["610"],"OA_place":"publisher"},{"_id":"18144","related_material":{"record":[{"relation":"research_data","status":"public","id":"18886"},{"id":"19401","status":"public","relation":"later_version"},{"id":"18129","relation":"dissertation_contains","status":"public"}]},"acknowledgement":"We acknowledge Franco De Palma, Mahya Khorramshahi, Fabian Oppliger, Thomas Reisinger, Pasquale Scarlino and Xiao Xue for helpful discussions. This research was supported by the Scientific Service Units of ISTA through resources provided by the MIBA Machine Shop and the Nanofabrication facility. This research and related results were made possible with the support of the NOMIS Foundation, the HORIZON-RIA 101069515 project, the FWF Projects with DOI:10.55776/P32235, DOI:10.55776/I5060 and DOI:10.55776/P36507. IMP acknowledges funding from the Deutsche Forschungsgemeinschaft (DFG – German Research Foundation) under project number 450396347 (GeHoldeQED). ICN2 acknowledges funding from Generalitat de Catalunya 2021SGR00457. We acknowledge support from CSIC Interdisciplinary Thematic Platform (PTI+) on Quantum Technologies (PTI-QTEP+). This research work has been funded by the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC’s\r\nQuantum Technologies Platform (QTEP). ICN2 is supported by the Severo Ochoa program from Spanish MCIN/AEI (Grant No.: CEX2021-001214-S) and is funded by the CERCA Programme/Generalitat de Catalunya. Part of the present work has been performed in the framework of Universitat Autònoma de Barcelona Materials Science PhD program. AGM has received funding from Grant RYC2021-033479-I funded by MCIN/AEI/10.13039/501100011033 and by European Union NextGenerationEU/PRTR. M.B. acknowledges support from SUR Generalitat de Catalunya and the EU Social Fund; project ref. 2020 FI 00103. The authors\r\nacknowledge the use of instrumentation and the technical advice provided by the Joint Electron Microscopy Center at ALBA (JEMCA). ICN2 acknowledges funding from Grant IU16-014206 (METCAM-FIB) funded by the European Union through the European Regional Development\r\nFund (ERDF), with the support of the Ministry of Research and Universities, Generalitat de Catalunya. ICN2 is a founding member of e-DREAM [60].","date_updated":"2026-05-15T22:30:24Z","type":"preprint","date_published":"2024-07-03T00:00:00Z","year":"2024","date_created":"2024-09-26T09:50:43Z","article_processing_charge":"No","language":[{"iso":"eng"}],"citation":{"apa":"Janik, M., Roux, K. E. R., Borja Espinosa, C. N., Sagi, O., Baghdadi, A., Adletzberger, T., … Katsaros, G. (n.d.). Strong charge-photon coupling in planar germanium enabled by granular  aluminium superinductors. <i>arXiv</i>. <a href=\"https://doi.org/10.48550/arXiv.2407.03079\">https://doi.org/10.48550/arXiv.2407.03079</a>","chicago":"Janik, Marian, Kevin Etienne Robert Roux, Carla N Borja Espinosa, Oliver Sagi, Abdulhamid Baghdadi, Thomas Adletzberger, Stefano Calcaterra, et al. “Strong Charge-Photon Coupling in Planar Germanium Enabled by Granular  Aluminium Superinductors.” <i>ArXiv</i>, n.d. <a href=\"https://doi.org/10.48550/arXiv.2407.03079\">https://doi.org/10.48550/arXiv.2407.03079</a>.","ama":"Janik M, Roux KER, Borja Espinosa CN, et al. Strong charge-photon coupling in planar germanium enabled by granular  aluminium superinductors. <i>arXiv</i>. doi:<a href=\"https://doi.org/10.48550/arXiv.2407.03079\">10.48550/arXiv.2407.03079</a>","mla":"Janik, Marian, et al. “Strong Charge-Photon Coupling in Planar Germanium Enabled by Granular  Aluminium Superinductors.” <i>ArXiv</i>, 2407.03079, doi:<a href=\"https://doi.org/10.48550/arXiv.2407.03079\">10.48550/arXiv.2407.03079</a>.","ista":"Janik M, Roux KER, Borja Espinosa CN, Sagi O, Baghdadi A, Adletzberger T, Calcaterra S, Botifoll M, Manjón AG, Arbiol J, Chrastina D, Isella G, Pop IM, Katsaros G. Strong charge-photon coupling in planar germanium enabled by granular  aluminium superinductors. arXiv, 2407.03079.","ieee":"M. Janik <i>et al.</i>, “Strong charge-photon coupling in planar germanium enabled by granular  aluminium superinductors,” <i>arXiv</i>. .","short":"M. Janik, K.E.R. Roux, C.N. Borja Espinosa, O. Sagi, A. Baghdadi, T. Adletzberger, S. Calcaterra, M. Botifoll, A.G. Manjón, J. Arbiol, D. Chrastina, G. Isella, I.M. Pop, G. Katsaros, ArXiv (n.d.)."},"publication_status":"draft","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"},"title":"Strong charge-photon coupling in planar germanium enabled by granular  aluminium superinductors","external_id":{"arxiv":["2407.03079"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"GeKa"},{"_id":"GradSch"},{"_id":"JoFi"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.48550/arXiv.2407.03079"}],"article_number":"2407.03079","abstract":[{"text":"High kinetic inductance superconductors are gaining increasing interest for\r\nthe realisation of qubits, amplifiers and detectors. Moreover, thanks to their\r\nhigh impedance, quantum buses made of such materials enable large zero-point\r\nfluctuations of the voltage, boosting the coupling rates to spin and charge\r\nqubits. However, fully exploiting the potential of disordered or granular\r\nsuperconductors is challenging, as their inductance and, therefore, impedance\r\nat high values are difficult to control. Here we have integrated a granular\r\naluminium resonator, having a characteristic impedance exceeding the resistance\r\nquantum, with a germanium double quantum dot and demonstrate strong\r\ncharge-photon coupling with a rate of $g_\\text{c}/2\\pi= (566 \\pm 2)$ MHz. This\r\nwas achieved due to the realisation of a wireless ohmmeter, which allows\r\n\\emph{in situ} measurements during film deposition and, therefore, control of\r\nthe kinetic inductance of granular aluminium films. Reproducible fabrication of\r\ncircuits with impedances (inductances) exceeding 13 k$\\Omega$ (1 nH per square)\r\nis now possible. This broadly applicable method opens the path for novel qubits\r\nand high-fidelity, long-distance two-qubit gates.","lang":"eng"}],"status":"public","OA_place":"repository","doi":"10.48550/arXiv.2407.03079","author":[{"orcid":"0009-0003-9037-8831","full_name":"Janik, Marian","id":"396A1950-F248-11E8-B48F-1D18A9856A87","first_name":"Marian","last_name":"Janik"},{"last_name":"Roux","first_name":"Kevin Etienne Robert","id":"53f93ea2-803f-11ed-ab7e-b283135794ef","full_name":"Roux, Kevin Etienne Robert"},{"full_name":"Borja Espinosa, Carla N","last_name":"Borja Espinosa","id":"18777c01-896a-11ed-bdf8-e4851dc07d16","first_name":"Carla N"},{"full_name":"Sagi, Oliver","last_name":"Sagi","first_name":"Oliver","id":"71616374-A8E9-11E9-A7CA-09ECE5697425"},{"full_name":"Baghdadi, Abdulhamid","last_name":"Baghdadi","first_name":"Abdulhamid","id":"160D87FA-96B5-11E9-BF77-7626E6697425"},{"full_name":"Adletzberger, Thomas","first_name":"Thomas","id":"38756BB2-F248-11E8-B48F-1D18A9856A87","last_name":"Adletzberger"},{"full_name":"Calcaterra, Stefano","last_name":"Calcaterra","first_name":"Stefano"},{"first_name":"Marc","last_name":"Botifoll","full_name":"Botifoll, Marc"},{"full_name":"Manjón, Alba Garzón","first_name":"Alba Garzón","last_name":"Manjón"},{"full_name":"Arbiol, Jordi","first_name":"Jordi","last_name":"Arbiol"},{"full_name":"Chrastina, Daniel","last_name":"Chrastina","first_name":"Daniel"},{"last_name":"Isella","first_name":"Giovanni","full_name":"Isella, Giovanni"},{"last_name":"Pop","first_name":"Ioan M.","full_name":"Pop, Ioan M."},{"last_name":"Katsaros","id":"38DB5788-F248-11E8-B48F-1D18A9856A87","first_name":"Georgios","orcid":"0000-0001-8342-202X","full_name":"Katsaros, Georgios"}],"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"NanoFab"}],"month":"07","project":[{"grant_number":"101069515","name":"Integrated Germanium Quantum Technology","_id":"34c0acea-11ca-11ed-8bc3-8775e10fd452"},{"name":"Towards scalable hut wire quantum devices","_id":"237B3DA4-32DE-11EA-91FC-C7463DDC885E","call_identifier":"FWF","grant_number":"P32235"},{"grant_number":"P36507","_id":"bd8bd29e-d553-11ed-ba76-f0070d4b237a","name":"Merging spin and superconducting qubits in planar Ge"},{"grant_number":"I05060","name":"High impedance circuit quantum electrodynamics with hole spins","_id":"c0977eea-5a5b-11eb-8a69-a862db0cf4d1"}],"corr_author":"1","oa_version":"Preprint","publication":"arXiv","day":"03","oa":1,"arxiv":1},{"OA_place":"publisher","ec_funded":1,"ddc":["570"],"quality_controlled":"1","status":"public","abstract":[{"lang":"eng","text":"The coupling between Ca2+ channels and release sensors is a key factor defining the signaling properties of a synapse. However, the coupling nanotopography at many synapses remains unknown, and it is unclear how it changes during development. To address these questions, we examined coupling at the cerebellar inhibitory basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission by paired recording and intracellular pipette perfusion revealed that the effects of exogenous Ca2+ chelators decreased during development, despite constant reliance of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked vesicles were only clustered at later developmental stages. Modeling suggested a developmental transformation from a more random to a more clustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic transmission."}],"publication":"Neuron","oa":1,"day":"06","publisher":"Elsevier","pmid":1,"project":[{"name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692"},{"grant_number":"Z00312","name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits"},{"_id":"26B66A3E-B435-11E9-9278-68D0E5697425","name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse","grant_number":"25383"}],"article_type":"original","volume":112,"scopus_import":"1","corr_author":"1","oa_version":"Published Version","author":[{"last_name":"Chen","id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","first_name":"JingJing","full_name":"Chen, JingJing"},{"last_name":"Kaufmann","first_name":"Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter"},{"full_name":"Chen, Chong","last_name":"Chen","first_name":"Chong","id":"3DFD581A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Arai, Itaru","first_name":"Itaru","id":"32A73F6C-F248-11E8-B48F-1D18A9856A87","last_name":"Arai"},{"orcid":"0000-0003-2344-1039","full_name":"Kim, Olena","last_name":"Kim","id":"3F8ABDDA-F248-11E8-B48F-1D18A9856A87","first_name":"Olena"},{"orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto"},{"orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"doi":"10.1016/j.neuron.2023.12.002","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"M-Shop"}],"month":"03","date_published":"2024-03-06T00:00:00Z","date_created":"2024-01-21T23:00:56Z","year":"2024","OA_type":"hybrid","language":[{"iso":"eng"}],"article_processing_charge":"Yes (via OA deal)","citation":{"apa":"Chen, J., Kaufmann, W., Chen, C., Arai,  itaru, Kim, O., Shigemoto, R., &#38; Jonas, P. M. (2024). Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. <i>Neuron</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/10.1016/j.neuron.2023.12.002</a>","ama":"Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. <i>Neuron</i>. 2024;112(5):755-771.e9. doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>","chicago":"Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">https://doi.org/10.1016/j.neuron.2023.12.002</a>.","mla":"Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>, vol. 112, no. 5, Elsevier, 2024, p. 755–771.e9, doi:<a href=\"https://doi.org/10.1016/j.neuron.2023.12.002\">10.1016/j.neuron.2023.12.002</a>.","ista":"Chen J, Kaufmann W, Chen C, Arai  itaru, Kim O, Shigemoto R, Jonas PM. 2024. Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse. Neuron. 112(5), 755–771.e9.","ieee":"J. Chen <i>et al.</i>, “Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse,” <i>Neuron</i>, vol. 112, no. 5. Elsevier, p. 755–771.e9, 2024.","short":"J. Chen, W. Kaufmann, C. Chen,  itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas, Neuron 112 (2024) 755–771.e9."},"publication_status":"published","related_material":{"record":[{"id":"15101","status":"public","relation":"dissertation_contains"}],"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/synapses-brought-to-the-point/","description":"News on ISTA Website"}]},"acknowledgement":"We thank Drs. David DiGregorio and Erwin Neher for critically reading an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions, Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan for advice on numerical solution of partial differential equations, Maria Reva for help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility, and Machine Shop). The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of the Austrian Academy of Sciences to J.-J.C.","isi":1,"date_updated":"2026-05-15T22:30:26Z","intvolume":"       112","type":"journal_article","page":"755-771.e9","_id":"14843","PlanS_conform":"1","issue":"5","file":[{"relation":"main_file","file_name":"2024_Neuron_Chen.pdf","file_size":8192355,"content_type":"application/pdf","access_level":"open_access","creator":"dernst","file_id":"19614","success":1,"checksum":"30098b4f0209556ddfb3540a23d07ca5","date_created":"2025-04-23T14:02:08Z","date_updated":"2025-04-23T14:02:08Z"}],"external_id":{"isi":["001202925700001"],"pmid":["38215739"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2025-04-23T14:02:08Z","department":[{"_id":"PeJo"},{"_id":"EM-Fac"},{"_id":"RySh"}],"has_accepted_license":"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"},"title":"Developmental transformation of Ca2+ channel-vesicle nanotopography at a central GABAergic synapse","publication_identifier":{"eissn":["1097-4199"],"issn":["0896-6273"]}},{"ddc":["570"],"degree_awarded":"PhD","ec_funded":1,"OA_place":"publisher","abstract":[{"lang":"eng","text":"The coupling between presynaptic Ca2+ channels and release sensors is a key factor that\r\ndetermines speed and efficacy of synapse transmission. At some excitatory synapses,\r\nchannel–sensor coupling becomes tighter during development, and tightening is often\r\nassociated with a switch in the reliance on different Ca2+ channel subtypes. However, the\r\ncoupling topography at many synapses remains unknown, and it is unclear how it changes\r\nduring development. To address this question, we analyzed the coupling configuration at the\r\ncerebellar basket cell (BC) to Purkinje cell (PC) synapse at different developmental stages,\r\ncombining biophysical analysis, structural analysis, and modeling.\r\nQuantal analysis of BC–PC indicated that release probability decreased, while the\r\nnumber of functional sites increased during development. Although transmitter release\r\npersistently relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects\r\nof the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased\r\nduring development, indicative of tightening of source-sensor coupling. Furthermore,\r\npresynaptic action potentials became shorter during development, suggesting reduced\r\nefficacy of Ca2+ channel activation.\r\nStructural analysis by freeze-fracture replica labeling (FRL) and transmission electron\r\nmicroscopy (EM) indicated that presynaptic P/Q-type Ca2+ channels formed nanoclusters\r\nthroughout development, whereas docked vesicles were only clustered at later\r\ndevelopmental stages. The number of functional release sites correlated better with the AZ\r\nnumber early in development, but match better with the Ca2+ channel cluster number at later\r\nstages.\r\nModeling suggested a developmental transformation from a more random to a more\r\nclustered coupling nanotopography. Thus, presynaptic signaling developmentally approaches\r\na point-to-point configuration, optimizing speed, reliability, and energy efficiency of synaptic\r\ntransmission."}],"status":"public","publisher":"Institute of Science and Technology Austria","alternative_title":["ISTA Thesis"],"oa":1,"day":"11","author":[{"id":"2C4E65C8-F248-11E8-B48F-1D18A9856A87","first_name":"JingJing","last_name":"Chen","full_name":"Chen, JingJing"}],"doi":"10.15479/at:ista:15101","acknowledged_ssus":[{"_id":"EM-Fac"}],"month":"03","project":[{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"name":"Synaptic communication in neuronal microcircuits","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"grant_number":"P36232","_id":"bd88be38-d553-11ed-ba76-81d5a70a6ef5","name":"Mechanisms of GABA release in hippocampal circuits"},{"grant_number":"25383","_id":"26B66A3E-B435-11E9-9278-68D0E5697425","name":"Development of nanodomain coupling between Ca2+ channels and release sensors at a central inhibitory synapse"}],"corr_author":"1","oa_version":"Published Version","related_material":{"record":[{"id":"14843","relation":"part_of_dissertation","status":"public"}]},"type":"dissertation","date_updated":"2026-04-07T13:24:22Z","date_created":"2024-03-11T10:09:54Z","year":"2024","date_published":"2024-03-11T00:00:00Z","publication_status":"published","article_processing_charge":"No","language":[{"iso":"eng"}],"citation":{"apa":"Chen, J. (2024). <i>Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:15101\">https://doi.org/10.15479/at:ista:15101</a>","chicago":"Chen, JingJing. “Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse.” Institute of Science and Technology Austria, 2024. <a href=\"https://doi.org/10.15479/at:ista:15101\">https://doi.org/10.15479/at:ista:15101</a>.","ama":"Chen J. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. 2024. doi:<a href=\"https://doi.org/10.15479/at:ista:15101\">10.15479/at:ista:15101</a>","mla":"Chen, JingJing. <i>Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse</i>. Institute of Science and Technology Austria, 2024, doi:<a href=\"https://doi.org/10.15479/at:ista:15101\">10.15479/at:ista:15101</a>.","ista":"Chen J. 2024. Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse. Institute of Science and Technology Austria.","short":"J. Chen, Developmental Transformation of Nanodomain Coupling between Ca2+ Channels and Release Sensors at a Central GABAergic Synapse, Institute of Science and Technology Austria, 2024.","ieee":"J. Chen, “Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse,” Institute of Science and Technology Austria, 2024."},"page":"84","_id":"15101","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","supervisor":[{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"file_date_updated":"2024-04-02T22:30:03Z","department":[{"_id":"GradSch"},{"_id":"PeJo"}],"file":[{"date_updated":"2024-04-02T22:30:03Z","date_created":"2024-03-11T14:10:58Z","checksum":"db4947474ffa271e66c254b6fe876a55","file_id":"15104","access_level":"closed","creator":"jchen","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","file_size":11271363,"relation":"source_file","file_name":"Thesis_Jingjing CHEN.docx"},{"file_size":16627311,"relation":"main_file","file_name":"Thesis_Jingjing CHEN_merged.pdf","access_level":"open_access","creator":"jchen","content_type":"application/pdf","checksum":"a5eeae8b5702cd540f5d03469bc33dde","embargo":"2024-04-01","date_created":"2024-03-11T14:11:06Z","file_id":"15105","date_updated":"2024-04-02T22:30:03Z"}],"publication_identifier":{"issn":["2663-337X"]},"has_accepted_license":"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"},"title":"Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse"}]