[{"date_created":"2020-09-28T07:33:38Z","oa":1,"publisher":"Institute of Science and Technology Austria","file_date_updated":"2020-09-28T07:25:37Z","has_accepted_license":"1","publication_identifier":{"eissn":["2663-337X"]},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","OA_place":"publisher","abstract":[{"text":"This thesis concerns itself with the interactions of evolutionary and ecological forces and the consequences on genetic diversity and the ultimate survival of populations. It is important to understand what signals processes \r\nleave on the genome and what we can infer from such data, which is usually abundant but noisy. Furthermore, understanding how and when populations adapt or go extinct is important for practical purposes,  such as the genetic management of populations, as well as for theoretical questions, since local adaptation can be the first step toward speciation. \r\nIn Chapter 2, we introduce the method of maximum entropy to approximate the demographic changes of a population in a simple setting, namely the logistic growth model with immigration. We show that this method is not only a powerful \r\ntool in physics but can be gainfully applied in an ecological framework. We investigate how well it approximates the real \r\nbehavior of the system, and find that is does so, even in unexpected situations. Finally, we illustrate how it can model changing environments.\r\nIn Chapter 3, we analyze the co-evolution of allele frequencies and population sizes in an infinite island model.\r\nWe give conditions under which polygenic adaptation to a rare habitat is possible. The model we use is based on the diffusion approximation, considers eco-evolutionary feedback mechanisms (hard selection), and treats both \r\ndrift and environmental fluctuations explicitly. We also look at limiting scenarios, for which we derive analytical expressions. \r\nIn Chapter 4, we present a coalescent based simulation tool to obtain patterns of diversity in a spatially explicit subdivided population, in which the demographic history of each subpopulation can be specified. We compare \r\nthe results to existing predictions, and explore the relative importance of time and space under a variety of spatial arrangements and demographic histories, such as expansion and extinction. \r\nIn the last chapter, we give a brief outlook to further research. ","lang":"eng"}],"corr_author":"1","department":[{"_id":"NiBa"}],"author":[{"full_name":"Szep, Eniko","first_name":"Eniko","id":"485BB5A4-F248-11E8-B48F-1D18A9856A87","last_name":"Szep"}],"year":"2020","language":[{"iso":"eng"}],"ddc":["570"],"alternative_title":["ISTA Thesis"],"status":"public","article_processing_charge":"No","doi":"10.15479/AT:ISTA:8574","month":"09","_id":"8574","publication_status":"published","date_updated":"2026-04-08T07:21:44Z","supervisor":[{"full_name":"Barton, Nicholas H","orcid":"0000-0002-8548-5240","first_name":"Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton"}],"date_published":"2020-09-20T00:00:00Z","oa_version":"Published Version","title":"Local adaptation in metapopulations","type":"dissertation","degree_awarded":"PhD","page":"158","day":"20","citation":{"short":"E. Szep, Local Adaptation in Metapopulations, Institute of Science and Technology Austria, 2020.","apa":"Szep, E. (2020). <i>Local adaptation in metapopulations</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8574\">https://doi.org/10.15479/AT:ISTA:8574</a>","ieee":"E. Szep, “Local adaptation in metapopulations,” Institute of Science and Technology Austria, 2020.","ista":"Szep E. 2020. Local adaptation in metapopulations. Institute of Science and Technology Austria.","chicago":"Szep, Eniko. “Local Adaptation in Metapopulations.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8574\">https://doi.org/10.15479/AT:ISTA:8574</a>.","ama":"Szep E. Local adaptation in metapopulations. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8574\">10.15479/AT:ISTA:8574</a>","mla":"Szep, Eniko. <i>Local Adaptation in Metapopulations</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8574\">10.15479/AT:ISTA:8574</a>."},"file":[{"file_size":6354833,"date_created":"2020-09-28T07:25:35Z","file_name":"thesis_EnikoSzep_final.pdf","access_level":"open_access","creator":"dernst","success":1,"relation":"main_file","checksum":"20e71f015fbbd78fea708893ad634ed0","file_id":"8575","date_updated":"2020-09-28T07:25:35Z","content_type":"application/pdf"},{"creator":"dernst","file_id":"8576","relation":"source_file","checksum":"a8de2c14a1bb4e53c857787efbb289e1","file_size":23020401,"file_name":"thesisFiles_EnikoSzep.zip","access_level":"closed","date_created":"2020-09-28T07:25:37Z","content_type":"application/x-zip-compressed","date_updated":"2020-09-28T07:25:37Z"}]},{"project":[{"name":"Optimal Transport and Stochastic Dynamics","call_identifier":"H2020","grant_number":"716117","_id":"256E75B8-B435-11E9-9278-68D0E5697425"}],"has_accepted_license":"1","oa":1,"publisher":"Institute of Science and Technology Austria","date_created":"2020-04-02T06:40:23Z","file_date_updated":"2020-07-14T12:48:01Z","abstract":[{"lang":"eng","text":"This thesis is based on three main topics: In the first part, we study convergence of discrete gradient flow structures associated with regular finite-volume discretisations of Fokker-Planck equations. We show evolutionary I convergence of the discrete gradient flows to the L2-Wasserstein gradient flow corresponding to the solution of a Fokker-Planck\r\nequation in arbitrary dimension d >= 1. Along the argument, we prove Mosco- and I-convergence results for discrete energy functionals, which are of independent interest for convergence of equivalent gradient flow structures in Hilbert spaces.\r\nThe second part investigates L2-Wasserstein flows on metric graph. The starting point is a Benamou-Brenier formula for the L2-Wasserstein distance, which is proved via a regularisation scheme for solutions of the continuity equation, adapted to the peculiar geometric structure of metric graphs. Based on those results, we show that the L2-Wasserstein space over a metric graph admits a gradient flow which may be identified as a solution of a Fokker-Planck equation.\r\nIn the third part, we focus again on the discrete gradient flows, already encountered in the first part. We propose a variational structure which extends the gradient flow structure to Markov chains violating the detailed-balance conditions. Using this structure, we characterise contraction estimates for the discrete heat flow in terms of convexity of\r\ncorresponding path-dependent energy functionals. In addition, we use this approach to derive several functional inequalities for said functionals."}],"publication_identifier":{"issn":["2663-337X"]},"OA_place":"publisher","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","year":"2020","language":[{"iso":"eng"}],"author":[{"full_name":"Forkert, Dominik L","last_name":"Forkert","id":"35C79D68-F248-11E8-B48F-1D18A9856A87","first_name":"Dominik L"}],"corr_author":"1","department":[{"_id":"JaMa"}],"status":"public","alternative_title":["ISTA Thesis"],"ddc":["510"],"doi":"10.15479/AT:ISTA:7629","article_processing_charge":"No","ec_funded":1,"date_published":"2020-03-31T00:00:00Z","month":"03","supervisor":[{"full_name":"Maas, Jan","orcid":"0000-0002-0845-1338","first_name":"Jan","id":"4C5696CE-F248-11E8-B48F-1D18A9856A87","last_name":"Maas"}],"date_updated":"2026-04-08T07:22:00Z","publication_status":"published","_id":"7629","page":"154","degree_awarded":"PhD","title":"Gradient flows in spaces of probability measures for finite-volume schemes, metric graphs and non-reversible Markov chains","type":"dissertation","oa_version":"Published Version","citation":{"chicago":"Forkert, Dominik L. “Gradient Flows in Spaces of Probability Measures for Finite-Volume Schemes, Metric Graphs and Non-Reversible Markov Chains.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:7629\">https://doi.org/10.15479/AT:ISTA:7629</a>.","mla":"Forkert, Dominik L. <i>Gradient Flows in Spaces of Probability Measures for Finite-Volume Schemes, Metric Graphs and Non-Reversible Markov Chains</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7629\">10.15479/AT:ISTA:7629</a>.","ama":"Forkert DL. Gradient flows in spaces of probability measures for finite-volume schemes, metric graphs and non-reversible Markov chains. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7629\">10.15479/AT:ISTA:7629</a>","ista":"Forkert DL. 2020. Gradient flows in spaces of probability measures for finite-volume schemes, metric graphs and non-reversible Markov chains. Institute of Science and Technology Austria.","short":"D.L. Forkert, Gradient Flows in Spaces of Probability Measures for Finite-Volume Schemes, Metric Graphs and Non-Reversible Markov Chains, Institute of Science and Technology Austria, 2020.","apa":"Forkert, D. L. (2020). <i>Gradient flows in spaces of probability measures for finite-volume schemes, metric graphs and non-reversible Markov chains</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7629\">https://doi.org/10.15479/AT:ISTA:7629</a>","ieee":"D. L. Forkert, “Gradient flows in spaces of probability measures for finite-volume schemes, metric graphs and non-reversible Markov chains,” Institute of Science and Technology Austria, 2020."},"file":[{"file_size":3297129,"file_name":"Thesis_Forkert_PDFA.pdf","access_level":"open_access","date_created":"2020-04-14T10:47:59Z","creator":"dernst","file_id":"7657","relation":"main_file","checksum":"c814a1a6195269ca6fe48b0dca45ae8a","date_updated":"2020-07-14T12:48:01Z","content_type":"application/pdf"},{"file_id":"7658","checksum":"ceafb53f923d1b5bdf14b2b0f22e4a81","relation":"source_file","creator":"dernst","access_level":"closed","date_created":"2020-04-14T10:47:59Z","file_name":"Thesis_Forkert_source.zip","file_size":1063908,"content_type":"application/x-zip-compressed","date_updated":"2020-07-14T12:48:01Z"}],"day":"31"},{"file_date_updated":"2020-07-14T12:48:08Z","date_created":"2020-06-26T10:00:36Z","publisher":"Institute of Science and Technology Austria","oa":1,"has_accepted_license":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"related_material":{"record":[{"id":"6556","status":"public","relation":"dissertation_contains"},{"id":"7093","relation":"dissertation_contains","status":"public"}]},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","OA_place":"publisher","publication_identifier":{"isbn":["978-3-99078-006-0"],"issn":["2663-337X"]},"acknowledged_ssus":[{"_id":"E-Lib"},{"_id":"CampIT"}],"abstract":[{"lang":"eng","text":"Algorithms in computational 3-manifold topology typically take a triangulation as an input and return topological information about the underlying 3-manifold. However, extracting the desired information from a triangulation (e.g., evaluating an invariant) is often computationally very expensive. In recent years this complexity barrier has been successfully tackled in some cases by importing ideas from the theory of parameterized algorithms into the realm of 3-manifolds. Various computationally hard problems were shown to be efficiently solvable for input triangulations that are sufficiently “tree-like.”\r\nIn this thesis we focus on the key combinatorial parameter in the above context: we consider the treewidth of a compact, orientable 3-manifold, i.e., the smallest treewidth of the dual graph of any triangulation thereof. By building on the work of Scharlemann–Thompson and Scharlemann–Schultens–Saito on generalized Heegaard splittings, and on the work of Jaco–Rubinstein on layered triangulations, we establish quantitative relations between the treewidth and classical topological invariants of a 3-manifold. In particular, among other results, we show that the treewidth of a closed, orientable, irreducible, non-Haken 3-manifold is always within a constant factor of its Heegaard genus."}],"department":[{"_id":"UlWa"}],"corr_author":"1","author":[{"full_name":"Huszár, Kristóf","orcid":"0000-0002-5445-5057","first_name":"Kristóf","last_name":"Huszár","id":"33C26278-F248-11E8-B48F-1D18A9856A87"}],"language":[{"iso":"eng"}],"year":"2020","ddc":["514"],"alternative_title":["ISTA Thesis"],"status":"public","article_processing_charge":"No","doi":"10.15479/AT:ISTA:8032","_id":"8032","publication_status":"published","date_updated":"2026-04-08T07:21:28Z","supervisor":[{"first_name":"Uli","last_name":"Wagner","id":"36690CA2-F248-11E8-B48F-1D18A9856A87","full_name":"Wagner, Uli","orcid":"0000-0002-1494-0568"},{"last_name":"Spreer","first_name":"Jonathan","full_name":"Spreer, Jonathan"}],"month":"06","date_published":"2020-06-26T00:00:00Z","oa_version":"Published Version","title":"Combinatorial width parameters for 3-dimensional manifolds","type":"dissertation","degree_awarded":"PhD","page":"xviii+120","day":"26","file":[{"date_updated":"2020-07-14T12:48:08Z","content_type":"application/pdf","file_size":2637562,"access_level":"open_access","file_name":"Kristof_Huszar-Thesis.pdf","date_created":"2020-06-26T10:03:58Z","creator":"khuszar","file_id":"8034","checksum":"bd8be6e4f1addc863dfcc0fad29ee9c3","relation":"main_file"},{"date_updated":"2020-07-14T12:48:08Z","content_type":"application/x-zip-compressed","date_created":"2020-06-26T10:10:06Z","file_name":"Kristof_Huszar-Thesis-source.zip","access_level":"closed","file_size":7163491,"file_id":"8035","relation":"source_file","checksum":"d5f8456202b32f4a77552ef47a2837d1","creator":"khuszar"}],"citation":{"ama":"Huszár K. Combinatorial width parameters for 3-dimensional manifolds. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8032\">10.15479/AT:ISTA:8032</a>","mla":"Huszár, Kristóf. <i>Combinatorial Width Parameters for 3-Dimensional Manifolds</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8032\">10.15479/AT:ISTA:8032</a>.","chicago":"Huszár, Kristóf. “Combinatorial Width Parameters for 3-Dimensional Manifolds.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8032\">https://doi.org/10.15479/AT:ISTA:8032</a>.","ista":"Huszár K. 2020. Combinatorial width parameters for 3-dimensional manifolds. Institute of Science and Technology Austria.","ieee":"K. Huszár, “Combinatorial width parameters for 3-dimensional manifolds,” Institute of Science and Technology Austria, 2020.","short":"K. Huszár, Combinatorial Width Parameters for 3-Dimensional Manifolds, Institute of Science and Technology Austria, 2020.","apa":"Huszár, K. (2020). <i>Combinatorial width parameters for 3-dimensional manifolds</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8032\">https://doi.org/10.15479/AT:ISTA:8032</a>"}},{"author":[{"full_name":"Steiner, Julia","orcid":"0000-0003-0493-3775","first_name":"Julia","last_name":"Steiner","id":"3BB67EB0-F248-11E8-B48F-1D18A9856A87"}],"year":"2020","language":[{"iso":"eng"}],"department":[{"_id":"LeSa"}],"corr_author":"1","status":"public","alternative_title":["ISTA Thesis"],"ddc":["572"],"has_accepted_license":"1","project":[{"name":"Revealing the functional mechanism of Mrp antiporter, an ancestor of complex I","_id":"26169496-B435-11E9-9278-68D0E5697425","grant_number":"24741"}],"file_date_updated":"2021-09-16T12:40:56Z","date_created":"2020-09-09T14:27:01Z","publisher":"Institute of Science and Technology Austria","oa":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"EM-Fac"},{"_id":"ScienComp"}],"acknowledgement":"I acknowledge the scientific service units of the IST Austria for providing resources by the Life Science Facility, the Electron Microscopy Facility and the high-performance computer cluster. Special thanks to the cryo-EM specialists Valentin Hodirnau and Daniel Johann Gütl for spending many hours with me in front of the microscope and for supporting me to collect the data presented here. I also want to thank Professor Masahiro Ito for providing plasmid DNA\r\nencoding Mrp from Anoxybacillus flavithermus WK1. I am a recipient of a DOC Fellowship of the Austrian Academy of Sciences.","abstract":[{"text":"Mrp (Multi resistance and pH adaptation) are broadly distributed secondary active antiporters that catalyze the transport of monovalent ions such as sodium and potassium outside of the cell coupled to the inward translocation of protons. Mrp antiporters are unique in a way that they are composed of seven subunits (MrpABCDEFG) encoded in a single operon, whereas other antiporters catalyzing the same reaction are mostly encoded by a single gene. Mrp exchangers are crucial for intracellular pH homeostasis and Na+ efflux, essential mechanisms for H+ uptake under alkaline environments and for reduction of the intracellular concentration of toxic cations. Mrp displays no homology to any other monovalent Na+(K+)/H+ antiporters but Mrp subunits have primary sequence similarity to essential redox-driven proton pumps, such as respiratory complex I and membrane-bound hydrogenases. This similarity reinforces the hypothesis that these present day redox-driven proton pumps are descended from the Mrp antiporter. The Mrp structure serves as a model to understand the yet obscure coupling mechanism between ion or electron transfer and proton translocation in this large group of proteins. In the thesis, I am presenting the purification, biochemical analysis, cryo-EM analysis and molecular structure of the Mrp complex from Anoxybacillus flavithermus solved by cryo-EM at 3.0 Å resolution. Numerous conditions were screened to purify Mrp to high homogeneity and to obtain an appropriate distribution of single particles on cryo-EM grids covered with a continuous layer of ultrathin carbon. A preferred particle orientation problem was solved by performing a tilted data collection. The activity assays showed the specific pH-dependent\r\nprofile of secondary active antiporters. The molecular structure shows that Mrp is a dimer of seven-subunit protomers with 50 trans-membrane helices each. The dimer interface is built by many short and tilted transmembrane helices, probably causing a thinning of the bacterial membrane. The surface charge distribution shows an extraordinary asymmetry within each monomer, revealing presumable proton and sodium translocation pathways. The two largest\r\nand homologous Mrp subunits MrpA and MrpD probably translocate one proton each into the cell. The sodium ion is likely being translocated in the opposite direction within the small subunits along a ladder of charged and conserved residues. Based on the structure, we propose a mechanism were the antiport activity is accomplished via electrostatic interactions between the charged cations and key charged residues. The flexible key TM helices coordinate these\r\nelectrostatic interactions, while the membrane thinning between the monomers enables the translocation of sodium across the charged membrane. The entire family of redox-driven proton pumps is likely to perform their mechanism in a likewise manner.","lang":"eng"}],"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"8284"}]},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","OA_place":"publisher","publication_identifier":{"issn":["2663-337X"]},"title":"Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I","type":"dissertation","degree_awarded":"PhD","page":"191","oa_version":"None","file":[{"relation":"main_file","checksum":"2388d7e6e7a4d364c096fa89f305c3de","file_id":"8354","creator":"jsteiner","access_level":"open_access","file_name":"Thesis_Julia_Steiner_pdfA.pdf","date_created":"2020-09-09T14:22:35Z","file_size":117547589,"content_type":"application/pdf","date_updated":"2021-09-16T12:40:56Z"},{"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_updated":"2020-09-15T08:48:37Z","file_id":"8355","relation":"source_file","checksum":"ba112f957b7145462d0ab79044873ee9","creator":"jsteiner","access_level":"closed","file_name":"Thesis_Julia_Steiner.docx","date_created":"2020-09-09T14:23:25Z","file_size":223328668}],"citation":{"apa":"Steiner, J. (2020). <i>Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8353\">https://doi.org/10.15479/AT:ISTA:8353</a>","short":"J. Steiner, Biochemical and Structural Investigation of the Mrp Antiporter, an Ancestor of Complex I, Institute of Science and Technology Austria, 2020.","ieee":"J. Steiner, “Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I,” Institute of Science and Technology Austria, 2020.","chicago":"Steiner, Julia. “Biochemical and Structural Investigation of the Mrp Antiporter, an Ancestor of Complex I.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8353\">https://doi.org/10.15479/AT:ISTA:8353</a>.","ama":"Steiner J. Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8353\">10.15479/AT:ISTA:8353</a>","mla":"Steiner, Julia. <i>Biochemical and Structural Investigation of the Mrp Antiporter, an Ancestor of Complex I</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8353\">10.15479/AT:ISTA:8353</a>.","ista":"Steiner J. 2020. Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I. Institute of Science and Technology Austria."},"day":"09","doi":"10.15479/AT:ISTA:8353","article_processing_charge":"No","date_published":"2020-09-09T00:00:00Z","_id":"8353","supervisor":[{"first_name":"Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","last_name":"Sazanov","full_name":"Sazanov, Leonid A","orcid":"0000-0002-0977-7989"}],"date_updated":"2026-04-08T07:23:36Z","publication_status":"published","month":"09"},{"day":"03","citation":{"chicago":"Kragl, Bernhard. “Verifying Concurrent Programs: Refinement, Synchronization, Sequentialization.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8332\">https://doi.org/10.15479/AT:ISTA:8332</a>.","mla":"Kragl, Bernhard. <i>Verifying Concurrent Programs: Refinement, Synchronization, Sequentialization</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8332\">10.15479/AT:ISTA:8332</a>.","ama":"Kragl B. Verifying concurrent programs: Refinement, synchronization, sequentialization. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8332\">10.15479/AT:ISTA:8332</a>","ista":"Kragl B. 2020. Verifying concurrent programs: Refinement, synchronization, sequentialization. Institute of Science and Technology Austria.","short":"B. Kragl, Verifying Concurrent Programs: Refinement, Synchronization, Sequentialization, Institute of Science and Technology Austria, 2020.","apa":"Kragl, B. (2020). <i>Verifying concurrent programs: Refinement, synchronization, sequentialization</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8332\">https://doi.org/10.15479/AT:ISTA:8332</a>","ieee":"B. Kragl, “Verifying concurrent programs: Refinement, synchronization, sequentialization,” Institute of Science and Technology Austria, 2020."},"file":[{"content_type":"application/pdf","date_updated":"2020-09-04T12:17:47Z","checksum":"26fe261550f691280bda4c454bf015c7","relation":"main_file","file_id":"8333","creator":"bkragl","access_level":"open_access","date_created":"2020-09-04T12:17:47Z","file_name":"kragl-thesis.pdf","file_size":1348815},{"creator":"bkragl","checksum":"b9694ce092b7c55557122adba8337ebc","relation":"source_file","file_id":"8335","file_size":372312,"access_level":"closed","date_created":"2020-09-04T13:00:17Z","file_name":"kragl-thesis.zip","content_type":"application/zip","date_updated":"2020-09-04T13:00:17Z"}],"oa_version":"Published Version","degree_awarded":"PhD","page":"120","title":"Verifying concurrent programs: Refinement, synchronization, sequentialization","type":"dissertation","month":"09","supervisor":[{"first_name":"Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","last_name":"Henzinger","full_name":"Henzinger, Thomas A","orcid":"0000-0002-2985-7724"}],"publication_status":"published","date_updated":"2026-04-08T07:23:53Z","_id":"8332","date_published":"2020-09-03T00:00:00Z","article_processing_charge":"No","doi":"10.15479/AT:ISTA:8332","ddc":["000"],"alternative_title":["ISTA Thesis"],"status":"public","corr_author":"1","department":[{"_id":"ToHe"}],"language":[{"iso":"eng"}],"year":"2020","author":[{"full_name":"Kragl, Bernhard","orcid":"0000-0001-7745-9117","first_name":"Bernhard","id":"320FC952-F248-11E8-B48F-1D18A9856A87","last_name":"Kragl"}],"publication_identifier":{"issn":["2663-337X"]},"OA_place":"publisher","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","related_material":{"record":[{"id":"8012","status":"public","relation":"part_of_dissertation"},{"id":"8195","status":"public","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"133"},{"id":"160","relation":"part_of_dissertation","status":"public"}]},"abstract":[{"lang":"eng","text":"Designing and verifying concurrent programs is a notoriously challenging, time consuming, and error prone task, even for experts. This is due to the sheer number of possible interleavings of a concurrent program, all of which have to be tracked and accounted for in a formal proof. Inventing an inductive invariant that captures all interleavings of a low-level implementation is theoretically possible, but practically intractable. We develop a refinement-based verification framework that provides mechanisms to simplify proof construction by decomposing the verification task into smaller subtasks.\r\n\r\nIn a first line of work, we present a foundation for refinement reasoning over structured concurrent programs. We introduce layered concurrent programs as a compact notation to represent multi-layer refinement proofs. A layered concurrent program specifies a sequence of connected concurrent programs, from most concrete to most abstract, such that common parts of different programs are written exactly once. Each program in this sequence is expressed as structured concurrent program, i.e., a program over (potentially recursive) procedures, imperative control flow, gated atomic actions, structured parallelism, and asynchronous concurrency. This is in contrast to existing refinement-based verifiers, which represent concurrent systems as flat transition relations. We present a powerful refinement proof rule that decomposes refinement checking over structured programs into modular verification conditions. Refinement checking is supported by a new form of modular, parameterized invariants, called yield invariants, and a linear permission system to enhance local reasoning.\r\n\r\nIn a second line of work, we present two new reduction-based program transformations that target asynchronous programs. These transformations reduce the number of interleavings that need to be considered, thus reducing the complexity of invariants. Synchronization simplifies the verification of asynchronous programs by introducing the fiction, for proof purposes, that asynchronous operations complete synchronously. Synchronization summarizes an asynchronous computation as immediate atomic effect. Inductive sequentialization establishes sequential reductions that captures every behavior of the original program up to reordering of coarse-grained commutative actions. A sequential reduction of a concurrent program is easy to reason about since it corresponds to a simple execution of the program in an idealized synchronous environment, where processes act in a fixed order and at the same speed.\r\n\r\nOur approach is implemented the CIVL verifier, which has been successfully used for the verification of several complex concurrent programs. In our methodology, the overall correctness of a program is established piecemeal by focusing on the invariant required for each refinement step separately. While the programmer does the creative work of specifying the chain of programs and the inductive invariant justifying each link in the chain, the tool automatically constructs the verification conditions underlying each refinement step."}],"oa":1,"publisher":"Institute of Science and Technology Austria","date_created":"2020-09-04T12:24:12Z","file_date_updated":"2020-09-04T13:00:17Z","has_accepted_license":"1"},{"abstract":[{"lang":"eng","text":"Multiple resistance and pH adaptation (Mrp) antiporters are multi-subunit Na+ (or K+)/H+ exchangers representing an ancestor of many essential redox-driven proton pumps, such as respiratory complex I. The mechanism of coupling between ion or electron transfer and proton translocation in this large protein family is unknown. Here, we present the structure of the Mrp complex from Anoxybacillus flavithermus solved by cryo-EM at 3.0 Å resolution. It is a dimer of seven-subunit protomers with 50 trans-membrane helices each. Surface charge distribution within each monomer is remarkably asymmetric, revealing probable proton and sodium translocation pathways. On the basis of the structure we propose a mechanism where the coupling between sodium and proton translocation is facilitated by a series of electrostatic interactions between a cation and key charged residues. This mechanism is likely to be applicable to the entire family of redox proton pumps, where electron transfer to substrates replaces cation movements."}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"acknowledgement":"This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Electron Microscopy Facility (EMF), the Life Science Facility (LSF) and the IST high-performance computing cluster. We thank Dr Victor-Valentin Hodirnau and Daniel Johann Gütl from IST Austria for assistance with collecting cryo-EM data. We thank Prof. Masahiro Ito (Graduate School of Life Sciences, Toyo University, Japan) for a kind provision of plasmid DNA encoding Mrp from A. flavithermus WK1. JS is a recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Science and Technology, Austria.","publication_identifier":{"eissn":["2050-084X"]},"volume":9,"related_material":{"record":[{"id":"8353","relation":"dissertation_contains","status":"public"}],"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/mystery-of-giant-proton-pump-solved/"}]},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","article_type":"original","project":[{"name":"Revealing the functional mechanism of Mrp antiporter, an ancestor of complex I","grant_number":"24741","_id":"26169496-B435-11E9-9278-68D0E5697425"}],"has_accepted_license":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"date_created":"2020-08-24T06:24:04Z","publisher":"eLife Sciences Publications","oa":1,"file_date_updated":"2020-08-24T13:31:53Z","status":"public","ddc":["570"],"author":[{"full_name":"Steiner, Julia","orcid":"0000-0003-0493-3775","first_name":"Julia","id":"3BB67EB0-F248-11E8-B48F-1D18A9856A87","last_name":"Steiner"},{"orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","first_name":"Leonid A"}],"language":[{"iso":"eng"}],"year":"2020","department":[{"_id":"LeSa"}],"date_published":"2020-07-31T00:00:00Z","intvolume":"         9","month":"07","quality_controlled":"1","_id":"8284","date_updated":"2026-04-08T07:23:36Z","publication_status":"published","doi":"10.7554/eLife.59407","article_number":"e59407","article_processing_charge":"No","citation":{"ista":"Steiner J, Sazanov LA. 2020. Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. eLife. 9, e59407.","chicago":"Steiner, Julia, and Leonid A Sazanov. “Structure and Mechanism of the Mrp Complex, an Ancient Cation/Proton Antiporter.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.59407\">https://doi.org/10.7554/eLife.59407</a>.","ama":"Steiner J, Sazanov LA. Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.59407\">10.7554/eLife.59407</a>","mla":"Steiner, Julia, and Leonid A. Sazanov. “Structure and Mechanism of the Mrp Complex, an Ancient Cation/Proton Antiporter.” <i>ELife</i>, vol. 9, e59407, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.59407\">10.7554/eLife.59407</a>.","apa":"Steiner, J., &#38; Sazanov, L. A. (2020). Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.59407\">https://doi.org/10.7554/eLife.59407</a>","short":"J. Steiner, L.A. Sazanov, ELife 9 (2020).","ieee":"J. Steiner and L. A. Sazanov, “Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020."},"isi":1,"file":[{"file_name":"2020_eLife_Steiner.pdf","access_level":"open_access","date_created":"2020-08-24T13:31:53Z","file_size":7320493,"file_id":"8289","relation":"main_file","checksum":"b3656d14d5ddbb9d26e3074eea2d0c15","creator":"cziletti","success":1,"date_updated":"2020-08-24T13:31:53Z","content_type":"application/pdf"}],"external_id":{"pmid":["32735215"],"isi":["000562123600001"]},"publication":"eLife","day":"31","scopus_import":"1","pmid":1,"type":"journal_article","title":"Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter","oa_version":"Published Version"},{"author":[{"first_name":"Katharina","id":"4D4AA390-F248-11E8-B48F-1D18A9856A87","last_name":"Ölsböck","full_name":"Ölsböck, Katharina","orcid":"0000-0002-4672-8297"}],"year":"2020","language":[{"iso":"eng"}],"department":[{"_id":"HeEd"},{"_id":"GradSch"}],"corr_author":"1","alternative_title":["ISTA Thesis"],"status":"public","ddc":["514"],"tmp":{"short":"CC BY-NC-SA (4.0)","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png"},"has_accepted_license":"1","file_date_updated":"2020-07-14T12:47:58Z","date_created":"2020-02-06T14:56:53Z","oa":1,"publisher":"Institute of Science and Technology Austria","abstract":[{"lang":"eng","text":"Many methods for the reconstruction of shapes from sets of points produce ordered simplicial complexes, which are collections of vertices, edges, triangles, and their higher-dimensional analogues, called simplices, in which every simplex gets assigned a real value measuring its size. This thesis studies ordered simplicial complexes, with a focus on their topology, which reflects the connectedness of the represented shapes and the presence of holes. We are interested both in understanding better the structure of these complexes, as well as in developing algorithms for applications.\r\n\r\nFor the Delaunay triangulation, the most popular measure for a simplex is the radius of the smallest empty circumsphere. Based on it, we revisit Alpha and Wrap complexes and experimentally determine their probabilistic properties for random data. Also, we prove the existence of tri-partitions, propose algorithms to open and close holes, and extend the concepts from Euclidean to Bregman geometries."}],"related_material":{"record":[{"id":"6608","relation":"part_of_dissertation","status":"public"}]},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","OA_place":"publisher","publication_identifier":{"issn":["2663-337X"]},"title":"The hole system of triangulated shapes","type":"dissertation","degree_awarded":"PhD","page":"155","oa_version":"Published Version","file":[{"date_updated":"2020-07-14T12:47:58Z","content_type":"application/pdf","file_size":76195184,"date_created":"2020-02-06T14:43:54Z","file_name":"thesis_ist-final_noack.pdf","access_level":"open_access","creator":"koelsboe","relation":"main_file","checksum":"1df9f8c530b443c0e63a3f2e4fde412e","file_id":"7461"},{"content_type":"application/x-zip-compressed","date_updated":"2020-07-14T12:47:58Z","description":"latex source files, figures","creator":"koelsboe","checksum":"7a52383c812b0be64d3826546509e5a4","relation":"source_file","file_id":"7462","file_size":122103715,"date_created":"2020-02-06T14:52:45Z","access_level":"closed","file_name":"latex-files.zip"}],"citation":{"ieee":"K. Ölsböck, “The hole system of triangulated shapes,” Institute of Science and Technology Austria, 2020.","apa":"Ölsböck, K. (2020). <i>The hole system of triangulated shapes</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7460\">https://doi.org/10.15479/AT:ISTA:7460</a>","short":"K. Ölsböck, The Hole System of Triangulated Shapes, Institute of Science and Technology Austria, 2020.","ista":"Ölsböck K. 2020. The hole system of triangulated shapes. Institute of Science and Technology Austria.","mla":"Ölsböck, Katharina. <i>The Hole System of Triangulated Shapes</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7460\">10.15479/AT:ISTA:7460</a>.","ama":"Ölsböck K. The hole system of triangulated shapes. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7460\">10.15479/AT:ISTA:7460</a>","chicago":"Ölsböck, Katharina. “The Hole System of Triangulated Shapes.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:7460\">https://doi.org/10.15479/AT:ISTA:7460</a>."},"day":"10","doi":"10.15479/AT:ISTA:7460","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","article_processing_charge":"No","date_published":"2020-02-10T00:00:00Z","_id":"7460","date_updated":"2026-04-08T07:23:21Z","supervisor":[{"id":"3FB178DA-F248-11E8-B48F-1D18A9856A87","last_name":"Edelsbrunner","first_name":"Herbert","orcid":"0000-0002-9823-6833","full_name":"Edelsbrunner, Herbert"}],"publication_status":"published","keyword":["shape reconstruction","hole manipulation","ordered complexes","Alpha complex","Wrap complex","computational topology","Bregman geometry"],"month":"02"},{"date_published":"2020-07-14T00:00:00Z","intvolume":"     12224","month":"07","quality_controlled":"1","_id":"8195","publication_status":"published","date_updated":"2026-04-08T07:23:52Z","doi":"10.1007/978-3-030-53288-8_14","article_processing_charge":"No","citation":{"mla":"Kragl, Bernhard, et al. “Refinement for Structured Concurrent Programs.” <i>Computer Aided Verification</i>, vol. 12224, Springer Nature, 2020, pp. 275–98, doi:<a href=\"https://doi.org/10.1007/978-3-030-53288-8_14\">10.1007/978-3-030-53288-8_14</a>.","ama":"Kragl B, Qadeer S, Henzinger TA. Refinement for structured concurrent programs. In: <i>Computer Aided Verification</i>. Vol 12224. Springer Nature; 2020:275-298. doi:<a href=\"https://doi.org/10.1007/978-3-030-53288-8_14\">10.1007/978-3-030-53288-8_14</a>","chicago":"Kragl, Bernhard, Shaz Qadeer, and Thomas A Henzinger. “Refinement for Structured Concurrent Programs.” In <i>Computer Aided Verification</i>, 12224:275–98. Springer Nature, 2020. <a href=\"https://doi.org/10.1007/978-3-030-53288-8_14\">https://doi.org/10.1007/978-3-030-53288-8_14</a>.","ista":"Kragl B, Qadeer S, Henzinger TA. 2020. Refinement for structured concurrent programs. Computer Aided Verification. , LNCS, vol. 12224, 275–298.","ieee":"B. Kragl, S. Qadeer, and T. A. Henzinger, “Refinement for structured concurrent programs,” in <i>Computer Aided Verification</i>, 2020, vol. 12224, pp. 275–298.","short":"B. Kragl, S. Qadeer, T.A. Henzinger, in:, Computer Aided Verification, Springer Nature, 2020, pp. 275–298.","apa":"Kragl, B., Qadeer, S., &#38; Henzinger, T. A. (2020). Refinement for structured concurrent programs. In <i>Computer Aided Verification</i> (Vol. 12224, pp. 275–298). Springer Nature. <a href=\"https://doi.org/10.1007/978-3-030-53288-8_14\">https://doi.org/10.1007/978-3-030-53288-8_14</a>"},"isi":1,"file":[{"date_updated":"2020-08-06T08:14:54Z","content_type":"application/pdf","file_size":804237,"file_name":"2020_LNCS_Kragl.pdf","date_created":"2020-08-06T08:14:54Z","access_level":"open_access","success":1,"creator":"dernst","file_id":"8201","relation":"main_file"}],"external_id":{"isi":["000695276000014"]},"day":"14","publication":"Computer Aided Verification","scopus_import":"1","title":"Refinement for structured concurrent programs","type":"conference","page":"275-298","oa_version":"Published Version","abstract":[{"lang":"eng","text":"This paper presents a foundation for refining concurrent programs with structured control flow. The verification problem is decomposed into subproblems that aid interactive program development, proof reuse, and automation. The formalization in this paper is the basis of a new design and implementation of the Civl verifier."}],"acknowledgement":"Bernhard Kragl and Thomas A. Henzinger were supported by\r\nthe Austrian Science Fund (FWF) under grant Z211-N23 (Wittgenstein Award).","volume":12224,"publication_identifier":{"eissn":["1611-3349"],"isbn":["9783030532871"],"issn":["0302-9743"],"eisbn":["9783030532888"]},"related_material":{"record":[{"id":"8332","status":"public","relation":"dissertation_contains"}]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","project":[{"_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211","call_identifier":"FWF","name":"Formal methods for the design and analysis of complex systems"}],"has_accepted_license":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"date_created":"2020-08-03T11:45:35Z","publisher":"Springer Nature","oa":1,"file_date_updated":"2020-08-06T08:14:54Z","status":"public","alternative_title":["LNCS"],"ddc":["000"],"author":[{"first_name":"Bernhard","id":"320FC952-F248-11E8-B48F-1D18A9856A87","last_name":"Kragl","full_name":"Kragl, Bernhard","orcid":"0000-0001-7745-9117"},{"last_name":"Qadeer","first_name":"Shaz","full_name":"Qadeer, Shaz"},{"first_name":"Thomas A","last_name":"Henzinger","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","full_name":"Henzinger, Thomas A","orcid":"0000-0002-2985-7724"}],"language":[{"iso":"eng"}],"year":"2020","corr_author":"1","department":[{"_id":"ToHe"}]},{"department":[{"_id":"ToHe"}],"year":"2020","language":[{"iso":"eng"}],"author":[{"id":"320FC952-F248-11E8-B48F-1D18A9856A87","last_name":"Kragl","first_name":"Bernhard","orcid":"0000-0001-7745-9117","full_name":"Kragl, Bernhard"},{"full_name":"Enea, Constantin","last_name":"Enea","first_name":"Constantin"},{"first_name":"Thomas A","last_name":"Henzinger","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","full_name":"Henzinger, Thomas A","orcid":"0000-0002-2985-7724"},{"first_name":"Suha Orhun","last_name":"Mutluergil","full_name":"Mutluergil, Suha Orhun"},{"first_name":"Shaz","last_name":"Qadeer","full_name":"Qadeer, Shaz"}],"status":"public","conference":{"end_date":"2020-06-20","start_date":"2020-06-15","location":"London, United Kingdom","name":"PLDI: Programming Language Design and Implementation"},"oa":1,"publisher":"Association for Computing Machinery","date_created":"2020-06-25T11:40:16Z","project":[{"_id":"25F42A32-B435-11E9-9278-68D0E5697425","grant_number":"Z211","call_identifier":"FWF","name":"Formal methods for the design and analysis of complex systems"}],"publication_identifier":{"isbn":["9781450376136"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","related_material":{"record":[{"id":"8332","relation":"dissertation_contains","status":"public"}]},"abstract":[{"lang":"eng","text":"Asynchronous programs are notoriously difficult to reason about because they spawn computation tasks which take effect asynchronously in a nondeterministic way. Devising inductive invariants for such programs requires understanding and stating complex relationships between an unbounded number of computation tasks in arbitrarily long executions. In this paper, we introduce inductive sequentialization, a new proof rule that sidesteps this complexity via a sequential reduction, a sequential program that captures every behavior of the original program up to reordering of coarse-grained commutative actions. A sequential reduction of a concurrent program is easy to reason about since it corresponds to a simple execution of the program in an idealized synchronous environment, where processes act in a fixed order and at the same speed. We have implemented and integrated our proof rule in the CIVL verifier, allowing us to provably derive fine-grained implementations of asynchronous programs. We have successfully applied our proof rule to a diverse set of message-passing protocols, including leader election protocols, two-phase commit, and Paxos."}],"main_file_link":[{"url":"https://doi.org/10.1145/3385412.3385980","open_access":"1"}],"oa_version":"Published Version","scopus_import":"1","page":"227-242","type":"conference","title":"Inductive sequentialization of asynchronous programs","external_id":{"isi":["000614622300016"]},"day":"01","publication":"Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation","citation":{"ista":"Kragl B, Enea C, Henzinger TA, Mutluergil SO, Qadeer S. 2020. Inductive sequentialization of asynchronous programs. Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation. PLDI: Programming Language Design and Implementation, 227–242.","mla":"Kragl, Bernhard, et al. “Inductive Sequentialization of Asynchronous Programs.” <i>Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation</i>, Association for Computing Machinery, 2020, pp. 227–42, doi:<a href=\"https://doi.org/10.1145/3385412.3385980\">10.1145/3385412.3385980</a>.","ama":"Kragl B, Enea C, Henzinger TA, Mutluergil SO, Qadeer S. Inductive sequentialization of asynchronous programs. In: <i>Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation</i>. Association for Computing Machinery; 2020:227-242. doi:<a href=\"https://doi.org/10.1145/3385412.3385980\">10.1145/3385412.3385980</a>","chicago":"Kragl, Bernhard, Constantin Enea, Thomas A Henzinger, Suha Orhun Mutluergil, and Shaz Qadeer. “Inductive Sequentialization of Asynchronous Programs.” In <i>Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation</i>, 227–42. Association for Computing Machinery, 2020. <a href=\"https://doi.org/10.1145/3385412.3385980\">https://doi.org/10.1145/3385412.3385980</a>.","ieee":"B. Kragl, C. Enea, T. A. Henzinger, S. O. Mutluergil, and S. Qadeer, “Inductive sequentialization of asynchronous programs,” in <i>Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation</i>, London, United Kingdom, 2020, pp. 227–242.","short":"B. Kragl, C. Enea, T.A. Henzinger, S.O. Mutluergil, S. Qadeer, in:, Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation, Association for Computing Machinery, 2020, pp. 227–242.","apa":"Kragl, B., Enea, C., Henzinger, T. A., Mutluergil, S. O., &#38; Qadeer, S. (2020). Inductive sequentialization of asynchronous programs. In <i>Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation</i> (pp. 227–242). London, United Kingdom: Association for Computing Machinery. <a href=\"https://doi.org/10.1145/3385412.3385980\">https://doi.org/10.1145/3385412.3385980</a>"},"isi":1,"article_processing_charge":"No","doi":"10.1145/3385412.3385980","quality_controlled":"1","month":"06","publication_status":"published","date_updated":"2026-04-08T07:23:52Z","_id":"8012","date_published":"2020-06-01T00:00:00Z"},{"publication_identifier":{"issn":["2663-337X"]},"OA_place":"publisher","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"6677"}]},"abstract":[{"lang":"eng","text":"A search problem lies in the complexity class FNP if a solution to the given instance of the problem can be verified efficiently. The complexity class TFNP consists of all search problems in FNP that are total in the sense that a solution is guaranteed to exist. TFNP contains a host of interesting problems from fields such as algorithmic game theory, computational topology, number theory and combinatorics. Since TFNP is a semantic class, it is unlikely to have a complete problem. Instead, one studies its syntactic subclasses which are defined based on the combinatorial principle used to argue totality. Of particular interest is the subclass PPAD, which contains important problems\r\nlike computing Nash equilibrium for bimatrix games and computational counterparts of several fixed-point theorems as complete. In the thesis, we undertake the study of averagecase hardness of TFNP, and in particular its subclass PPAD.\r\nAlmost nothing was known about average-case hardness of PPAD before a series of recent results showed how to achieve it using a cryptographic primitive called program obfuscation.\r\nHowever, it is currently not known how to construct program obfuscation from standard cryptographic assumptions. Therefore, it is desirable to relax the assumption under which average-case hardness of PPAD can be shown. In the thesis we take a step in this direction. First, we show that assuming the (average-case) hardness of a numbertheoretic\r\nproblem related to factoring of integers, which we call Iterated-Squaring, PPAD is hard-on-average in the random-oracle model. Then we strengthen this result to show that the average-case hardness of PPAD reduces to the (adaptive) soundness of the Fiat-Shamir Transform, a well-known technique used to compile a public-coin interactive protocol into a non-interactive one. As a corollary, we obtain average-case hardness for PPAD in the random-oracle model assuming the worst-case hardness of #SAT. Moreover, the above results can all be strengthened to obtain average-case hardness for the class CLS ⊆ PPAD.\r\nOur main technical contribution is constructing incrementally-verifiable procedures for computing Iterated-Squaring and #SAT. By incrementally-verifiable, we mean that every intermediate state of the computation includes a proof of its correctness, and the proof can be updated and verified in polynomial time. Previous constructions of such procedures relied on strong, non-standard assumptions. Instead, we introduce a technique called recursive proof-merging to obtain the same from weaker assumptions. "}],"oa":1,"publisher":"Institute of Science and Technology Austria","date_created":"2020-05-26T14:08:55Z","file_date_updated":"2020-07-14T12:48:04Z","project":[{"name":"Provable Security for Physical Cryptography","call_identifier":"FP7","grant_number":"259668","_id":"258C570E-B435-11E9-9278-68D0E5697425"},{"name":"Teaching Old Crypto New Tricks","call_identifier":"H2020","grant_number":"682815","_id":"258AA5B2-B435-11E9-9278-68D0E5697425"}],"has_accepted_license":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"ddc":["000"],"alternative_title":["ISTA Thesis"],"status":"public","corr_author":"1","department":[{"_id":"KrPi"}],"year":"2020","language":[{"iso":"eng"}],"author":[{"full_name":"Kamath Hosdurg, Chethan","orcid":"0009-0006-6812-7317","first_name":"Chethan","id":"4BD3F30E-F248-11E8-B48F-1D18A9856A87","last_name":"Kamath Hosdurg"}],"month":"05","publication_status":"published","supervisor":[{"id":"3E04A7AA-F248-11E8-B48F-1D18A9856A87","last_name":"Pietrzak","first_name":"Krzysztof Z","orcid":"0000-0002-9139-1654","full_name":"Pietrzak, Krzysztof Z"}],"date_updated":"2026-04-08T07:24:42Z","_id":"7896","ec_funded":1,"date_published":"2020-05-25T00:00:00Z","article_processing_charge":"No","doi":"10.15479/AT:ISTA:7896","day":"25","citation":{"chicago":"Kamath Hosdurg, Chethan. “On the Average-Case Hardness of Total Search Problems.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:7896\">https://doi.org/10.15479/AT:ISTA:7896</a>.","mla":"Kamath Hosdurg, Chethan. <i>On the Average-Case Hardness of Total Search Problems</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7896\">10.15479/AT:ISTA:7896</a>.","ama":"Kamath Hosdurg C. On the average-case hardness of total search problems. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:7896\">10.15479/AT:ISTA:7896</a>","ista":"Kamath Hosdurg C. 2020. On the average-case hardness of total search problems. Institute of Science and Technology Austria.","apa":"Kamath Hosdurg, C. (2020). <i>On the average-case hardness of total search problems</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:7896\">https://doi.org/10.15479/AT:ISTA:7896</a>","short":"C. Kamath Hosdurg, On the Average-Case Hardness of Total Search Problems, Institute of Science and Technology Austria, 2020.","ieee":"C. Kamath Hosdurg, “On the average-case hardness of total search problems,” Institute of Science and Technology Austria, 2020."},"file":[{"content_type":"application/pdf","date_updated":"2020-07-14T12:48:04Z","checksum":"b39e2e1c376f5819b823fb7077491c64","relation":"main_file","file_id":"7897","creator":"dernst","file_name":"2020_Thesis_Kamath.pdf","access_level":"open_access","date_created":"2020-05-26T14:08:13Z","file_size":1622742},{"date_updated":"2020-07-14T12:48:04Z","content_type":"application/x-zip-compressed","file_name":"Thesis_Kamath.zip","access_level":"closed","date_created":"2020-05-26T14:08:23Z","file_size":15301529,"relation":"source_file","checksum":"8b26ba729c1a85ac6bea775f5d73cdc7","file_id":"7898","creator":"dernst"}],"oa_version":"Published Version","degree_awarded":"PhD","page":"126","title":"On the average-case hardness of total search problems","type":"dissertation"},{"ddc":["580"],"alternative_title":["ISTA Thesis"],"status":"public","department":[{"_id":"JiFr"}],"corr_author":"1","author":[{"id":"31435098-F248-11E8-B48F-1D18A9856A87","last_name":"Han","first_name":"Huibin","full_name":"Han, Huibin"}],"language":[{"iso":"eng"}],"year":"2020","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","related_material":{"record":[{"id":"7643","status":"public","relation":"part_of_dissertation"}]},"OA_place":"publisher","publication_identifier":{"issn":["2663-337X"]},"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"acknowledgement":"I also want to thank the China Scholarship Council for supporting my study during the year from 2015 to 2019. I also want to thank IST facilities – the Bioimaging facility, the media kitchen, the plant facility and all of the campus services, for their support.","abstract":[{"lang":"eng","text":"The plant hormone auxin plays indispensable roles in plant growth and development. An essential level of regulation in auxin action is the directional auxin transport within cells. The establishment of auxin gradient in plant tissue has been attributed to local auxin biosynthesis and directional intercellular auxin transport, which both are controlled by various environmental and developmental signals. It is well established that asymmetric auxin distribution in cells is achieved by polarly localized PIN-FORMED (PIN) auxin efflux transporters. Despite the initial insights into cellular mechanisms of PIN polarization obtained from the last decades, the molecular mechanism and specific regulators mediating PIN polarization remains elusive. In this thesis, we aim to find novel players in PIN subcellular polarity regulation during Arabidopsis development. We first characterize the physiological effect of piperonylic acid (PA) on Arabidopsis hypocotyl gravitropic bending and PIN polarization. Secondly, we reveal the importance of SCFTIR1/AFB auxin signaling pathway in shoot gravitropism bending termination. In addition, we also explore the role of myosin XI complex, and actin cytoskeleton in auxin feedback regulation on PIN polarity. In Chapter 1, we give an overview of the current knowledge about PIN-mediated auxin fluxes in various plant tropic responses. In Chapter 2, we study the physiological effect of PA on shoot gravitropic bending. Our results show that PA treatment inhibits auxin-mediated PIN3 repolarization by interfering with PINOID and PIN3 phosphorylation status, ultimately leading to hyperbending hypocotyls. In Chapter 3, we provide evidence to show that the SCFTIR1/AFB nuclear auxin signaling pathway is crucial and required for auxin-mediated PIN3 repolarization and shoot gravitropic bending termination. In Chapter 4, we perform a phosphoproteomics approach and identify the motor protein Myosin XI and its binding protein, the MadB2 family, as an essential regulator of PIN polarity for auxin-canalization related developmental processes. In Chapter 5, we demonstrate the vital role of actin cytoskeleton in auxin feedback on PIN polarity by regulating PIN subcellular trafficking. Overall, the data presented in this PhD thesis brings novel insights into the PIN polar localization regulation that resulted in the (re)establishment of the polar auxin flow and gradient in response to environmental stimuli during plant development."}],"file_date_updated":"2021-10-01T13:33:02Z","date_created":"2020-09-30T14:50:51Z","publisher":"Institute of Science and Technology Austria","oa":1,"has_accepted_license":"1","day":"30","file":[{"date_updated":"2020-09-30T14:50:20Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_name":"2020_Han_Thesis.docx","access_level":"closed","date_created":"2020-09-30T14:50:20Z","file_size":49198118,"file_id":"8590","relation":"source_file","checksum":"c4bda1947d4c09c428ac9ce667b02327","creator":"dernst"},{"date_updated":"2021-10-01T13:33:02Z","content_type":"application/pdf","file_size":15513963,"access_level":"open_access","file_name":"2020_Han_Thesis.pdf","date_created":"2020-09-30T14:49:59Z","creator":"dernst","file_id":"8591","relation":"main_file","checksum":"3f4f5d1718c2230adf30639ecaf8a00b"}],"citation":{"ieee":"H. Han, “Novel insights into PIN polarity regulation during Arabidopsis development,” Institute of Science and Technology Austria, 2020.","apa":"Han, H. (2020). <i>Novel insights into PIN polarity regulation during Arabidopsis development</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8589\">https://doi.org/10.15479/AT:ISTA:8589</a>","short":"H. Han, Novel Insights into PIN Polarity Regulation during Arabidopsis Development, Institute of Science and Technology Austria, 2020.","ista":"Han H. 2020. Novel insights into PIN polarity regulation during Arabidopsis development. Institute of Science and Technology Austria.","mla":"Han, Huibin. <i>Novel Insights into PIN Polarity Regulation during Arabidopsis Development</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8589\">10.15479/AT:ISTA:8589</a>.","ama":"Han H. Novel insights into PIN polarity regulation during Arabidopsis development. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8589\">10.15479/AT:ISTA:8589</a>","chicago":"Han, Huibin. “Novel Insights into PIN Polarity Regulation during Arabidopsis Development.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8589\">https://doi.org/10.15479/AT:ISTA:8589</a>."},"oa_version":"Published Version","title":"Novel insights into PIN polarity regulation during Arabidopsis development","type":"dissertation","degree_awarded":"PhD","page":"164","_id":"8589","publication_status":"published","supervisor":[{"first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","last_name":"Friml","full_name":"Friml, Jiří","orcid":"0000-0002-8302-7596"}],"date_updated":"2026-04-08T07:24:28Z","month":"09","date_published":"2020-09-30T00:00:00Z","article_processing_charge":"No","doi":"10.15479/AT:ISTA:8589"},{"language":[{"iso":"eng"}],"year":"2020","author":[{"full_name":"Han, Huibin","first_name":"Huibin","id":"31435098-F248-11E8-B48F-1D18A9856A87","last_name":"Han"},{"full_name":"Rakusova, Hana","first_name":"Hana","id":"4CAAA450-78D2-11EA-8E57-B40A396E08BA","last_name":"Rakusova"},{"orcid":"0000-0001-7241-2328","full_name":"Verstraeten, Inge","id":"362BF7FE-F248-11E8-B48F-1D18A9856A87","last_name":"Verstraeten","first_name":"Inge"},{"first_name":"Yuzhou","last_name":"Zhang","id":"3B6137F2-F248-11E8-B48F-1D18A9856A87","full_name":"Zhang, Yuzhou","orcid":"0000-0003-2627-6956"},{"full_name":"Friml, Jiří","orcid":"0000-0002-8302-7596","first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","last_name":"Friml"}],"department":[{"_id":"JiFr"}],"corr_author":"1","status":"public","project":[{"name":"Tracing Evolution of Auxin Transport and Polarity in Plants","call_identifier":"H2020","grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425"},{"_id":"26538374-B435-11E9-9278-68D0E5697425","grant_number":"I03630","call_identifier":"FWF","name":"Molecular mechanisms of endocytic cargo recognition in plants"}],"oa":1,"publisher":"American Society of Plant Biologists","date_created":"2020-04-06T10:06:40Z","acknowledgement":"This work was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation Programme (ERC grant agreement number 742985), and the Austrian Science Fund (FWF, grant number I 3630-B25) to JF. HH is supported by the China Scholarship Council (CSC scholarship). ","issue":"5","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1104/pp.20.00212"}],"article_type":"letter_note","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"8589"}]},"volume":183,"publication_identifier":{"issn":["0032-0889"],"eissn":["1532-2548"]},"page":"37-40","title":"SCF TIR1/AFB auxin signaling for bending termination during shoot gravitropism","pmid":1,"type":"journal_article","scopus_import":"1","oa_version":"Published Version","isi":1,"citation":{"short":"H. Han, H. Rakusova, I. Verstraeten, Y. Zhang, J. Friml, Plant Physiology 183 (2020) 37–40.","apa":"Han, H., Rakusova, H., Verstraeten, I., Zhang, Y., &#38; Friml, J. (2020). SCF TIR1/AFB auxin signaling for bending termination during shoot gravitropism. <i>Plant Physiology</i>. American Society of Plant Biologists. <a href=\"https://doi.org/10.1104/pp.20.00212\">https://doi.org/10.1104/pp.20.00212</a>","ieee":"H. Han, H. Rakusova, I. Verstraeten, Y. Zhang, and J. Friml, “SCF TIR1/AFB auxin signaling for bending termination during shoot gravitropism,” <i>Plant Physiology</i>, vol. 183, no. 5. American Society of Plant Biologists, pp. 37–40, 2020.","ista":"Han H, Rakusova H, Verstraeten I, Zhang Y, Friml J. 2020. SCF TIR1/AFB auxin signaling for bending termination during shoot gravitropism. Plant Physiology. 183(5), 37–40.","chicago":"Han, Huibin, Hana Rakusova, Inge Verstraeten, Yuzhou Zhang, and Jiří Friml. “SCF TIR1/AFB Auxin Signaling for Bending Termination during Shoot Gravitropism.” <i>Plant Physiology</i>. American Society of Plant Biologists, 2020. <a href=\"https://doi.org/10.1104/pp.20.00212\">https://doi.org/10.1104/pp.20.00212</a>.","ama":"Han H, Rakusova H, Verstraeten I, Zhang Y, Friml J. SCF TIR1/AFB auxin signaling for bending termination during shoot gravitropism. <i>Plant Physiology</i>. 2020;183(5):37-40. doi:<a href=\"https://doi.org/10.1104/pp.20.00212\">10.1104/pp.20.00212</a>","mla":"Han, Huibin, et al. “SCF TIR1/AFB Auxin Signaling for Bending Termination during Shoot Gravitropism.” <i>Plant Physiology</i>, vol. 183, no. 5, American Society of Plant Biologists, 2020, pp. 37–40, doi:<a href=\"https://doi.org/10.1104/pp.20.00212\">10.1104/pp.20.00212</a>."},"publication":"Plant Physiology","day":"08","external_id":{"pmid":["32107280"],"isi":["000536641800018"]},"doi":"10.1104/pp.20.00212","article_processing_charge":"No","ec_funded":1,"date_published":"2020-05-08T00:00:00Z","publication_status":"published","date_updated":"2026-04-08T07:24:27Z","_id":"7643","quality_controlled":"1","intvolume":"       183","month":"05"},{"citation":{"ama":"Grah R, Friedlander T. The relation between crosstalk and gene regulation form revisited. <i>PLOS Computational Biology</i>. 2020;16(2). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007642\">10.1371/journal.pcbi.1007642</a>","mla":"Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene Regulation Form Revisited.” <i>PLOS Computational Biology</i>, vol. 16, no. 2, e1007642, Public Library of Science, 2020, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007642\">10.1371/journal.pcbi.1007642</a>.","chicago":"Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene Regulation Form Revisited.” <i>PLOS Computational Biology</i>. Public Library of Science, 2020. <a href=\"https://doi.org/10.1371/journal.pcbi.1007642\">https://doi.org/10.1371/journal.pcbi.1007642</a>.","ista":"Grah R, Friedlander T. 2020. The relation between crosstalk and gene regulation form revisited. PLOS Computational Biology. 16(2), e1007642.","ieee":"R. Grah and T. Friedlander, “The relation between crosstalk and gene regulation form revisited,” <i>PLOS Computational Biology</i>, vol. 16, no. 2. Public Library of Science, 2020.","apa":"Grah, R., &#38; Friedlander, T. (2020). The relation between crosstalk and gene regulation form revisited. <i>PLOS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007642\">https://doi.org/10.1371/journal.pcbi.1007642</a>","short":"R. Grah, T. Friedlander, PLOS Computational Biology 16 (2020)."},"file":[{"creator":"dernst","file_id":"7579","checksum":"5239dd134dc6e1c71fe7b3ce2953da37","relation":"main_file","file_size":2209325,"date_created":"2020-03-09T15:12:21Z","file_name":"2020_PlosCompBio_Grah.pdf","access_level":"open_access","content_type":"application/pdf","date_updated":"2020-07-14T12:48:00Z"}],"isi":1,"external_id":{"pmid":["32097416"],"isi":["000526725200019"]},"day":"25","publication":"PLOS Computational Biology","scopus_import":"1","title":"The relation between crosstalk and gene regulation form revisited","pmid":1,"type":"journal_article","oa_version":"Published Version","date_published":"2020-02-25T00:00:00Z","quality_controlled":"1","month":"02","intvolume":"        16","date_updated":"2026-04-08T07:25:08Z","publication_status":"published","_id":"7569","article_number":"e1007642","doi":"10.1371/journal.pcbi.1007642","article_processing_charge":"No","status":"public","ddc":["000","570"],"language":[{"iso":"eng"}],"year":"2020","author":[{"orcid":"0000-0003-2539-3560","full_name":"Grah, Rok","last_name":"Grah","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","first_name":"Rok"},{"full_name":"Friedlander, Tamar","last_name":"Friedlander","first_name":"Tamar"}],"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"abstract":[{"text":"Genes differ in the frequency at which they are expressed and in the form of regulation used to control their activity. In particular, positive or negative regulation can lead to activation of a gene in response to an external signal. Previous works proposed that the form of regulation of a gene correlates with its frequency of usage: positive regulation when the gene is frequently expressed and negative regulation when infrequently expressed. Such network design means that, in the absence of their regulators, the genes are found in their least required activity state, hence regulatory intervention is often necessary. Due to the multitude of genes and regulators, spurious binding and unbinding events, called “crosstalk”, could occur. To determine how the form of regulation affects the global crosstalk in the network, we used a mathematical model that includes multiple regulators and multiple target genes. We found that crosstalk depends non-monotonically on the availability of regulators. Our analysis showed that excess use of regulation entailed by the formerly suggested network design caused high crosstalk levels in a large part of the parameter space. We therefore considered the opposite ‘idle’ design, where the default unregulated state of genes is their frequently required activity state. We found, that ‘idle’ design minimized the use of regulation and thus minimized crosstalk. In addition, we estimated global crosstalk of S. cerevisiae using transcription factors binding data. We demonstrated that even partial network data could suffice to estimate its global crosstalk, suggesting its applicability to additional organisms. We found that S. cerevisiae estimated crosstalk is lower than that of a random network, suggesting that natural selection reduces crosstalk. In summary, our study highlights a new type of protein production cost which is typically overlooked: that of regulatory interference caused by the presence of excess regulators in the cell. It demonstrates the importance of whole-network descriptions, which could show effects missed by single-gene models.","lang":"eng"}],"issue":"2","publication_identifier":{"issn":["1553-7358"]},"volume":16,"article_type":"original","related_material":{"record":[{"relation":"research_data","status":"deleted","id":"9716"},{"relation":"research_data","status":"public","id":"9776"},{"relation":"research_data","status":"public","id":"9779"},{"id":"9777","relation":"research_data","status":"public"},{"id":"8155","status":"public","relation":"dissertation_contains"}]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"has_accepted_license":"1","oa":1,"publisher":"Public Library of Science","date_created":"2020-03-06T07:39:38Z","file_date_updated":"2020-07-14T12:48:00Z"},{"author":[{"id":"2A58201A-F248-11E8-B48F-1D18A9856A87","last_name":"Bezeljak","first_name":"Urban","orcid":"0000-0003-1365-5631","full_name":"Bezeljak, Urban"}],"language":[{"iso":"eng"}],"year":"2020","department":[{"_id":"MaLo"}],"corr_author":"1","status":"public","alternative_title":["ISTA Thesis"],"ddc":["570"],"has_accepted_license":"1","tmp":{"short":"CC BY-NC-SA (4.0)","name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png"},"file_date_updated":"2021-09-16T12:49:12Z","date_created":"2020-09-08T08:53:53Z","oa":1,"publisher":"Institute of Science and Technology Austria","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"NanoFab"}],"acknowledgement":"My thanks goes to the Loose lab members, BioImaging, Life Science and Nanofabrication Facilities and the wonderful international community at IST for sharing this experience with me.","abstract":[{"text":"One of the most striking hallmarks of the eukaryotic cell is the presence of intracellular vesicles and organelles. Each of these membrane-enclosed compartments has a distinct composition of lipids and proteins, which is essential for accurate membrane traffic and homeostasis. Interestingly, their biochemical identities are achieved with the help\r\nof small GTPases of the Rab family, which cycle between GDP- and GTP-bound forms on the selected membrane surface. While this activity switch is well understood for an individual protein, how Rab GTPases collectively transition between states to generate decisive signal propagation in space and time is unclear. In my PhD thesis, I present\r\nin vitro reconstitution experiments with theoretical modeling to systematically study a minimal Rab5 activation network from bottom-up. We find that positive feedback based on known molecular interactions gives rise to bistable GTPase activity switching on system’s scale. Furthermore, we determine that collective transition near the critical\r\npoint is intrinsically stochastic and provide evidence that the inactive Rab5 abundance on the membrane can shape the network response. Finally, we demonstrate that collective switching can spread on the lipid bilayer as a traveling activation wave, representing a possible emergent activity pattern in endosomal maturation. Together, our\r\nfindings reveal new insights into the self-organization properties of signaling networks away from chemical equilibrium. Our work highlights the importance of systematic characterization of biochemical systems in well-defined physiological conditions. This way, we were able to answer long-standing open questions in the field and close the gap between regulatory processes on a molecular scale and emergent responses on system’s level.","lang":"eng"}],"related_material":{"record":[{"id":"7580","status":"public","relation":"part_of_dissertation"}]},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","OA_place":"publisher","publication_identifier":{"issn":["2663-337X"]},"type":"dissertation","title":"In vitro reconstitution of a Rab activation switch","page":"215","degree_awarded":"PhD","oa_version":"Published Version","file":[{"file_size":65246782,"file_name":"2020_Urban_Bezeljak_Thesis_TeX.zip","access_level":"closed","date_created":"2020-09-08T09:00:29Z","creator":"dernst","relation":"source_file","checksum":"70871b335a595252a66c6bbf0824fb02","file_id":"8342","date_updated":"2021-09-16T12:49:12Z","content_type":"application/x-zip-compressed"},{"file_size":31259058,"access_level":"open_access","date_created":"2020-09-08T09:00:27Z","file_name":"2020_Urban_Bezeljak_Thesis.pdf","creator":"dernst","file_id":"8343","relation":"main_file","checksum":"59a62275088b00b7241e6ff4136434c7","date_updated":"2021-09-16T12:49:12Z","content_type":"application/pdf"}],"citation":{"short":"U. Bezeljak, In Vitro Reconstitution of a Rab Activation Switch, Institute of Science and Technology Austria, 2020.","apa":"Bezeljak, U. (2020). <i>In vitro reconstitution of a Rab activation switch</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8341\">https://doi.org/10.15479/AT:ISTA:8341</a>","ieee":"U. Bezeljak, “In vitro reconstitution of a Rab activation switch,” Institute of Science and Technology Austria, 2020.","ista":"Bezeljak U. 2020. In vitro reconstitution of a Rab activation switch. Institute of Science and Technology Austria.","chicago":"Bezeljak, Urban. “In Vitro Reconstitution of a Rab Activation Switch.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8341\">https://doi.org/10.15479/AT:ISTA:8341</a>.","mla":"Bezeljak, Urban. <i>In Vitro Reconstitution of a Rab Activation Switch</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8341\">10.15479/AT:ISTA:8341</a>.","ama":"Bezeljak U. In vitro reconstitution of a Rab activation switch. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8341\">10.15479/AT:ISTA:8341</a>"},"day":"08","doi":"10.15479/AT:ISTA:8341","article_processing_charge":"No","date_published":"2020-09-08T00:00:00Z","_id":"8341","date_updated":"2026-04-08T07:24:56Z","publication_status":"published","supervisor":[{"full_name":"Loose, Martin","orcid":"0000-0001-7309-9724","first_name":"Martin","last_name":"Loose","id":"462D4284-F248-11E8-B48F-1D18A9856A87"}],"month":"09"},{"type":"dissertation","title":"Gene regulation across scales – how biophysical constraints shape evolution","degree_awarded":"PhD","page":"310","oa_version":"Published Version","citation":{"apa":"Grah, R. (2020). <i>Gene regulation across scales – how biophysical constraints shape evolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8155\">https://doi.org/10.15479/AT:ISTA:8155</a>","short":"R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape Evolution, Institute of Science and Technology Austria, 2020.","ieee":"R. Grah, “Gene regulation across scales – how biophysical constraints shape evolution,” Institute of Science and Technology Austria, 2020.","ista":"Grah R. 2020. Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria.","chicago":"Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints Shape Evolution.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8155\">https://doi.org/10.15479/AT:ISTA:8155</a>.","ama":"Grah R. Gene regulation across scales – how biophysical constraints shape evolution. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8155\">10.15479/AT:ISTA:8155</a>","mla":"Grah, Rok. <i>Gene Regulation across Scales – How Biophysical Constraints Shape Evolution</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8155\">10.15479/AT:ISTA:8155</a>."},"file":[{"date_updated":"2020-07-27T12:00:07Z","content_type":"application/pdf","file_size":16638998,"access_level":"open_access","file_name":"Thesis_RokGrah_200727_convertedNew.pdf","date_created":"2020-07-27T12:00:07Z","creator":"rgrah","success":1,"relation":"main_file","file_id":"8176"},{"creator":"rgrah","relation":"main_file","file_id":"8177","file_size":347459978,"access_level":"closed","date_created":"2020-07-27T12:02:23Z","file_name":"Thesis_new.zip","content_type":"application/zip","date_updated":"2020-07-30T13:04:55Z"}],"day":"24","doi":"10.15479/AT:ISTA:8155","article_processing_charge":"No","date_published":"2020-07-24T00:00:00Z","month":"07","_id":"8155","supervisor":[{"last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","first_name":"Gašper","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper"}],"publication_status":"published","date_updated":"2026-04-08T07:25:09Z","author":[{"id":"483E70DE-F248-11E8-B48F-1D18A9856A87","last_name":"Grah","first_name":"Rok","orcid":"0000-0003-2539-3560","full_name":"Grah, Rok"}],"language":[{"iso":"eng"}],"year":"2020","corr_author":"1","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"alternative_title":["ISTA Thesis"],"status":"public","ddc":["530","570"],"project":[{"name":"Biophysically realistic genotype-phenotype maps for regulatory networks","_id":"267C84F4-B435-11E9-9278-68D0E5697425"}],"has_accepted_license":"1","date_created":"2020-07-23T09:51:28Z","publisher":"Institute of Science and Technology Austria","oa":1,"file_date_updated":"2020-07-30T13:04:55Z","abstract":[{"text":"In the thesis we focus on the interplay of the biophysics and evolution of gene regulation. We start by addressing how the type of prokaryotic gene regulation – activation and repression – affects spurious binding to DNA, also known as\r\ntranscriptional crosstalk. We propose that regulatory interference caused by excess regulatory proteins in the dense cellular medium – global crosstalk – could be a factor in determining which type of gene regulatory network is evolutionarily preferred. Next,we use a normative approach in eukaryotic gene regulation to describe minimal\r\nnon-equilibrium enhancer models that optimize so-called regulatory phenotypes. We find a class of models that differ from standard thermodynamic equilibrium models by a single parameter that notably increases the regulatory performance. Next chapter addresses the question of genotype-phenotype-fitness maps of higher dimensional phenotypes. We show that our biophysically realistic approach allows us to understand how the mechanisms of promoter function constrain genotypephenotype maps, and how they affect the evolutionary trajectories of promoters.\r\nIn the last chapter we ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using mathematical modeling, we show that amplifications can tune gene expression in many environments, including those where transcription factor-based schemes are\r\nhard to evolve or maintain. ","lang":"eng"}],"acknowledgement":"For the duration of his PhD, Rok was a recipient of a DOC fellowship of the Austrian Academy of Sciences.","publication_identifier":{"issn":["2663-337X"]},"related_material":{"record":[{"id":"7675","relation":"part_of_dissertation","status":"public"},{"status":"public","relation":"part_of_dissertation","id":"7569"},{"id":"7652","relation":"part_of_dissertation","status":"public"}]},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","OA_place":"publisher"},{"publisher":"National Academy of Sciences","oa":1,"date_created":"2020-03-12T05:32:26Z","project":[{"name":"Reconstitution of cell polarity and axis determination in a cell-free system","grant_number":"RGY0083/2016","_id":"2599F062-B435-11E9-9278-68D0E5697425"}],"volume":117,"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"article_type":"original","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","related_material":{"link":[{"description":"News on IST Homepage","url":"https://ist.ac.at/en/news/proteins-as-molecular-switches/","relation":"press_release"}],"record":[{"status":"public","relation":"dissertation_contains","id":"8341"}]},"main_file_link":[{"url":"https://doi.org/10.1101/776567","open_access":"1"}],"abstract":[{"text":"The eukaryotic endomembrane system is controlled by small GTPases of the Rab family, which are activated at defined times and locations in a switch-like manner. While this switch is well understood for an individual protein, how regulatory networks produce intracellular activity patterns is currently not known. Here, we combine in vitro reconstitution experiments with computational modeling to study a minimal Rab5 activation network. We find that the molecular interactions in this system give rise to a positive feedback and bistable collective switching of Rab5. Furthermore, we find that switching near the critical point is intrinsically stochastic and provide evidence that controlling the inactive population of Rab5 on the membrane can shape the network response. Notably, we demonstrate that collective switching can spread on the membrane surface as a traveling wave of Rab5 activation. Together, our findings reveal how biochemical signaling networks control vesicle trafficking pathways and how their nonequilibrium properties define the spatiotemporal organization of the cell.","lang":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"issue":"12","department":[{"_id":"MaLo"},{"_id":"CaBe"}],"year":"2020","language":[{"iso":"eng"}],"author":[{"first_name":"Urban","id":"2A58201A-F248-11E8-B48F-1D18A9856A87","last_name":"Bezeljak","full_name":"Bezeljak, Urban","orcid":"0000-0003-1365-5631"},{"first_name":"Hrushikesh","last_name":"Loya","full_name":"Loya, Hrushikesh"},{"first_name":"Beata M","id":"36FA4AFA-F248-11E8-B48F-1D18A9856A87","last_name":"Kaczmarek","full_name":"Kaczmarek, Beata M"},{"last_name":"Saunders","first_name":"Timothy E.","full_name":"Saunders, Timothy E."},{"full_name":"Loose, Martin","orcid":"0000-0001-7309-9724","first_name":"Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87","last_name":"Loose"}],"status":"public","article_processing_charge":"No","doi":"10.1073/pnas.1921027117","quality_controlled":"1","intvolume":"       117","month":"03","date_updated":"2026-04-08T07:24:55Z","publication_status":"published","_id":"7580","date_published":"2020-03-24T00:00:00Z","oa_version":"Preprint","scopus_import":"1","page":"6504-6549","type":"journal_article","title":"Stochastic activation and bistability in a Rab GTPase regulatory network","pmid":1,"external_id":{"isi":["000521821800040"],"pmid":["32161136"]},"publication":"Proceedings of the National Academy of Sciences of the United States of America","day":"24","citation":{"ama":"Bezeljak U, Loya H, Kaczmarek BM, Saunders TE, Loose M. Stochastic activation and bistability in a Rab GTPase regulatory network. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2020;117(12):6504-6549. doi:<a href=\"https://doi.org/10.1073/pnas.1921027117\">10.1073/pnas.1921027117</a>","mla":"Bezeljak, Urban, et al. “Stochastic Activation and Bistability in a Rab GTPase Regulatory Network.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 117, no. 12, National Academy of Sciences, 2020, pp. 6504–49, doi:<a href=\"https://doi.org/10.1073/pnas.1921027117\">10.1073/pnas.1921027117</a>.","chicago":"Bezeljak, Urban, Hrushikesh Loya, Beata M Kaczmarek, Timothy E. Saunders, and Martin Loose. “Stochastic Activation and Bistability in a Rab GTPase Regulatory Network.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2020. <a href=\"https://doi.org/10.1073/pnas.1921027117\">https://doi.org/10.1073/pnas.1921027117</a>.","ista":"Bezeljak U, Loya H, Kaczmarek BM, Saunders TE, Loose M. 2020. Stochastic activation and bistability in a Rab GTPase regulatory network. Proceedings of the National Academy of Sciences of the United States of America. 117(12), 6504–6549.","ieee":"U. Bezeljak, H. Loya, B. M. Kaczmarek, T. E. Saunders, and M. Loose, “Stochastic activation and bistability in a Rab GTPase regulatory network,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 117, no. 12. National Academy of Sciences, pp. 6504–6549, 2020.","short":"U. Bezeljak, H. Loya, B.M. Kaczmarek, T.E. Saunders, M. Loose, Proceedings of the National Academy of Sciences of the United States of America 117 (2020) 6504–6549.","apa":"Bezeljak, U., Loya, H., Kaczmarek, B. M., Saunders, T. E., &#38; Loose, M. (2020). Stochastic activation and bistability in a Rab GTPase regulatory network. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.1921027117\">https://doi.org/10.1073/pnas.1921027117</a>"},"isi":1},{"publication":"bioRxiv","day":"09","citation":{"ista":"Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv, <a href=\"https://doi.org/10.1101/2020.04.08.029405\">10.1101/2020.04.08.029405</a>.","mla":"Grah, Rok, et al. “Normative Models of Enhancer Function.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, 2020, doi:<a href=\"https://doi.org/10.1101/2020.04.08.029405\">10.1101/2020.04.08.029405</a>.","ama":"Grah R, Zoller B, Tkačik G. Normative models of enhancer function. <i>bioRxiv</i>. 2020. doi:<a href=\"https://doi.org/10.1101/2020.04.08.029405\">10.1101/2020.04.08.029405</a>","chicago":"Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Normative Models of Enhancer Function.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, 2020. <a href=\"https://doi.org/10.1101/2020.04.08.029405\">https://doi.org/10.1101/2020.04.08.029405</a>.","ieee":"R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory, 2020.","short":"R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020).","apa":"Grah, R., Zoller, B., &#38; Tkačik, G. (2020). Normative models of enhancer function. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.04.08.029405\">https://doi.org/10.1101/2020.04.08.029405</a>"},"status":"public","corr_author":"1","oa_version":"Preprint","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"title":"Normative models of enhancer function","author":[{"first_name":"Rok","last_name":"Grah","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","full_name":"Grah, Rok","orcid":"0000-0003-2539-3560"},{"full_name":"Zoller, Benjamin","first_name":"Benjamin","last_name":"Zoller"},{"orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"}],"type":"preprint","year":"2020","language":[{"iso":"eng"}],"month":"04","_id":"7675","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"8155"}]},"date_updated":"2026-04-08T07:25:08Z","publication_status":"published","date_published":"2020-04-09T00:00:00Z","main_file_link":[{"url":"https://doi.org/10.1101/2020.04.08.029405 ","open_access":"1"}],"abstract":[{"text":"In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene expression levels that is compatible with in vivo and in vitro bio-physical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In non-equilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal non-equilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in non-equilibrium models is in a tradeoff with gene expression noise, predicting bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space to a much smaller subspace that optimally realizes biological function prior to inference from data, our normative approach holds promise for mathematical models in systems biology.","lang":"eng"}],"date_created":"2020-04-23T10:12:51Z","oa":1,"publisher":"Cold Spring Harbor Laboratory","article_processing_charge":"No","doi":"10.1101/2020.04.08.029405","project":[{"_id":"2665AAFE-B435-11E9-9278-68D0E5697425","grant_number":"RGP0034/2018","name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?"},{"_id":"267C84F4-B435-11E9-9278-68D0E5697425","name":"Biophysically realistic genotype-phenotype maps for regulatory networks"}]},{"acknowledgement":"During the work on this thesis, I received substantial support from IST Austria’s scientific service units. A big thank you to Todor Asenov and other Miba Machine Shop team members for their help with fabrication of experimental prototypes. In addition, I would like to thank Scientific Computing team for the support with high performance computing.\r\nFinancial support was provided by the European Research Council (ERC) under grant agreement No 715767 - MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling, which I gratefully acknowledge.","acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"ScienComp"}],"abstract":[{"lang":"eng","text":"Fabrication of curved shells plays an important role in modern design, industry, and science. Among their remarkable properties are, for example, aesthetics of organic shapes, ability to evenly distribute loads, or efficient flow separation. They find applications across vast length scales ranging from sky-scraper architecture to microscopic devices. But, at\r\nthe same time, the design of curved shells and their manufacturing process pose a variety of challenges. In this thesis, they are addressed from several perspectives. In particular, this thesis presents approaches based on the transformation of initially flat sheets into the target curved surfaces. This involves problems of interactive design of shells with nontrivial mechanical constraints, inverse design of complex structural materials, and data-driven modeling of delicate and time-dependent physical properties. At the same time, two newly-developed self-morphing mechanisms targeting flat-to-curved transformation are presented.\r\nIn architecture, doubly curved surfaces can be realized as cold bent glass panelizations. Originally flat glass panels are bent into frames and remain stressed. This is a cost-efficient fabrication approach compared to hot bending, when glass panels are shaped plastically. However such constructions are prone to breaking during bending, and it is highly\r\nnontrivial to navigate the design space, keeping the panels fabricable and aesthetically pleasing at the same time. We introduce an interactive design system for cold bent glass façades, while previously even offline optimization for such scenarios has not been sufficiently developed. Our method is based on a deep learning approach providing quick\r\nand high precision estimation of glass panel shape and stress while handling the shape\r\nmultimodality.\r\nFabrication of smaller objects of scales below 1 m, can also greatly benefit from shaping originally flat sheets. In this respect, we designed new self-morphing shell mechanisms transforming from an initial flat state to a doubly curved state with high precision and detail. Our so-called CurveUps demonstrate the encodement of the geometric information\r\ninto the shell. Furthermore, we explored the frontiers of programmable materials and showed how temporal information can additionally be encoded into a flat shell. This allows prescribing deformation sequences for doubly curved surfaces and, thus, facilitates self-collision avoidance enabling complex shapes and functionalities otherwise impossible.\r\nBoth of these methods include inverse design tools keeping the user in the design loop."}],"OA_place":"publisher","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","related_material":{"record":[{"id":"8562","relation":"part_of_dissertation","status":"public"},{"relation":"research_data","status":"public","id":"8375"},{"status":"deleted","relation":"research_data","id":"7151"},{"id":"1001","status":"public","relation":"part_of_dissertation"},{"id":"7262","relation":"part_of_dissertation","status":"public"}]},"publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-010-7"]},"has_accepted_license":"1","project":[{"grant_number":"715767","_id":"24F9549A-B435-11E9-9278-68D0E5697425","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","call_identifier":"H2020"}],"file_date_updated":"2020-09-16T15:11:01Z","oa":1,"publisher":"Institute of Science and Technology Austria","date_created":"2020-09-10T16:19:55Z","alternative_title":["ISTA Thesis"],"status":"public","ddc":["000"],"language":[{"iso":"eng"}],"year":"2020","author":[{"full_name":"Guseinov, Ruslan","orcid":"0000-0001-9819-5077","first_name":"Ruslan","last_name":"Guseinov","id":"3AB45EE2-F248-11E8-B48F-1D18A9856A87"}],"department":[{"_id":"BeBi"}],"corr_author":"1","ec_funded":1,"date_published":"2020-09-21T00:00:00Z","date_updated":"2026-04-08T07:25:22Z","publication_status":"published","supervisor":[{"first_name":"Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87","last_name":"Bickel","full_name":"Bickel, Bernd","orcid":"0000-0001-6511-9385"}],"_id":"8366","month":"09","keyword":["computer-aided design","shape modeling","self-morphing","mechanical engineering"],"doi":"10.15479/AT:ISTA:8366","article_processing_charge":"No","file":[{"content_type":"application/pdf","date_updated":"2020-09-10T16:11:49Z","creator":"rguseino","success":1,"file_id":"8367","checksum":"f8da89553da36037296b0a80f14ebf50","relation":"main_file","file_size":70950442,"file_name":"thesis_rguseinov.pdf","access_level":"open_access","date_created":"2020-09-10T16:11:49Z"},{"creator":"rguseino","file_id":"8374","checksum":"e8fd944c960c20e0e27e6548af69121d","relation":"source_file","file_size":76207597,"file_name":"thesis_source.zip","access_level":"closed","date_created":"2020-09-11T09:39:48Z","content_type":"application/x-zip-compressed","date_updated":"2020-09-16T15:11:01Z"}],"citation":{"short":"R. Guseinov, Computational Design of Curved Thin Shells: From Glass Façades to Programmable Matter, Institute of Science and Technology Austria, 2020.","apa":"Guseinov, R. (2020). <i>Computational design of curved thin shells: From glass façades to programmable matter</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8366\">https://doi.org/10.15479/AT:ISTA:8366</a>","ieee":"R. Guseinov, “Computational design of curved thin shells: From glass façades to programmable matter,” Institute of Science and Technology Austria, 2020.","ista":"Guseinov R. 2020. Computational design of curved thin shells: From glass façades to programmable matter. Institute of Science and Technology Austria.","chicago":"Guseinov, Ruslan. “Computational Design of Curved Thin Shells: From Glass Façades to Programmable Matter.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8366\">https://doi.org/10.15479/AT:ISTA:8366</a>.","ama":"Guseinov R. Computational design of curved thin shells: From glass façades to programmable matter. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8366\">10.15479/AT:ISTA:8366</a>","mla":"Guseinov, Ruslan. <i>Computational Design of Curved Thin Shells: From Glass Façades to Programmable Matter</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8366\">10.15479/AT:ISTA:8366</a>."},"day":"21","degree_awarded":"PhD","page":"118","type":"dissertation","title":"Computational design of curved thin shells: From glass façades to programmable matter","oa_version":"Published Version"},{"has_accepted_license":"1","project":[{"grant_number":"715767","_id":"24F9549A-B435-11E9-9278-68D0E5697425","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","call_identifier":"H2020"}],"file_date_updated":"2023-05-23T20:54:43Z","publisher":"Association for Computing Machinery","oa":1,"date_created":"2020-09-23T11:30:02Z","acknowledgement":"We thank IST Austria’s Scientific Computing team for their support, Corinna Datsiou and Sophie Pennetier for their expert input on the practical applications of cold bent glass, and Zaha Hadid Architects and Waagner Biro for providing the architectural datasets. Photo of Fondation Louis Vuitton by Francisco Anzola / CC BY 2.0 / cropped.\r\nPhoto of Opus by Danica O. Kus. This project has received funding from the European Union’s\r\nHorizon 2020 research and innovation program under grant agreement No 675789 - Algebraic Representations in Computer-Aided Design for complEx Shapes (ARCADES), from the European Research Council (ERC) under grant agreement No 715767 - MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling, and SFB-Transregio “Discretization in Geometry and Dynamics” through grant I 2978 of the Austrian Science Fund (FWF). F. Rist and K. Gavriil have been partially supported by KAUST baseline funding.","arxiv":1,"acknowledged_ssus":[{"_id":"ScienComp"}],"issue":"6","abstract":[{"text":"Cold bent glass is a promising and cost-efficient method for realizing doubly curved glass facades. They are produced by attaching planar glass sheets to curved frames and require keeping the occurring stress within safe limits.\r\nHowever, it is very challenging to navigate the design space of cold bent glass panels due to the fragility of the material, which impedes the form-finding for practically feasible and aesthetically pleasing cold bent glass facades. We propose an interactive, data-driven approach for designing cold bent glass facades that can be seamlessly integrated into a typical architectural design pipeline. Our method allows non-expert users to interactively edit a parametric surface while providing real-time feedback on the deformed shape and maximum stress of cold bent glass panels. Designs are automatically refined to minimize several fairness criteria while maximal stresses are kept within glass limits. We achieve interactive frame rates by using a differentiable Mixture Density Network trained from more than a million simulations. Given a curved boundary, our regression model is capable of handling multistable\r\nconfigurations and accurately predicting the equilibrium shape of the panel and its corresponding maximal stress. We show predictions are highly accurate and validate our results with a physical realization of a cold bent glass surface.","lang":"eng"}],"article_type":"original","related_material":{"record":[{"status":"public","relation":"research_data","id":"8761"},{"status":"public","relation":"dissertation_contains","id":"8366"}],"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/bend-dont-break/","description":"News on IST Homepage"}]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication_identifier":{"eissn":["1557-7368"],"issn":["0730-0301"]},"volume":39,"language":[{"iso":"eng"}],"year":"2020","author":[{"first_name":"Konstantinos","last_name":"Gavriil","full_name":"Gavriil, Konstantinos"},{"orcid":"0000-0001-9819-5077","full_name":"Guseinov, Ruslan","last_name":"Guseinov","id":"3AB45EE2-F248-11E8-B48F-1D18A9856A87","first_name":"Ruslan"},{"full_name":"Perez Rodriguez, Jesus","first_name":"Jesus","id":"2DC83906-F248-11E8-B48F-1D18A9856A87","last_name":"Perez Rodriguez"},{"first_name":"Davide","last_name":"Pellis","full_name":"Pellis, Davide"},{"full_name":"Henderson, Paul M","orcid":"0000-0002-5198-7445","first_name":"Paul M","last_name":"Henderson","id":"13C09E74-18D9-11E9-8878-32CFE5697425"},{"last_name":"Rist","first_name":"Florian","full_name":"Rist, Florian"},{"last_name":"Pottmann","first_name":"Helmut","full_name":"Pottmann, Helmut"},{"id":"49876194-F248-11E8-B48F-1D18A9856A87","last_name":"Bickel","first_name":"Bernd","orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd"}],"department":[{"_id":"BeBi"}],"corr_author":"1","status":"public","ddc":["000"],"article_number":"208","doi":"10.1145/3414685.3417843","article_processing_charge":"No","ec_funded":1,"date_published":"2020-11-26T00:00:00Z","publication_status":"published","date_updated":"2026-04-08T07:25:22Z","_id":"8562","quality_controlled":"1","intvolume":"        39","month":"11","title":"Computational design of cold bent glass façades","type":"journal_article","scopus_import":"1","oa_version":"Submitted Version","file":[{"file_id":"13084","checksum":"c7f67717ad74e670b7daeae732abe151","relation":"main_file","creator":"bbickel","success":1,"access_level":"open_access","date_created":"2023-05-23T20:54:43Z","file_name":"coldglass.pdf","file_size":28964641,"content_type":"application/pdf","date_updated":"2023-05-23T20:54:43Z"}],"isi":1,"citation":{"short":"K. Gavriil, R. Guseinov, J. Perez Rodriguez, D. Pellis, P.M. Henderson, F. Rist, H. Pottmann, B. Bickel, ACM Transactions on Graphics 39 (2020).","apa":"Gavriil, K., Guseinov, R., Perez Rodriguez, J., Pellis, D., Henderson, P. M., Rist, F., … Bickel, B. (2020). Computational design of cold bent glass façades. <i>ACM Transactions on Graphics</i>. Association for Computing Machinery. <a href=\"https://doi.org/10.1145/3414685.3417843\">https://doi.org/10.1145/3414685.3417843</a>","ieee":"K. Gavriil <i>et al.</i>, “Computational design of cold bent glass façades,” <i>ACM Transactions on Graphics</i>, vol. 39, no. 6. Association for Computing Machinery, 2020.","chicago":"Gavriil, Konstantinos, Ruslan Guseinov, Jesus Perez Rodriguez, Davide Pellis, Paul M Henderson, Florian Rist, Helmut Pottmann, and Bernd Bickel. “Computational Design of Cold Bent Glass Façades.” <i>ACM Transactions on Graphics</i>. Association for Computing Machinery, 2020. <a href=\"https://doi.org/10.1145/3414685.3417843\">https://doi.org/10.1145/3414685.3417843</a>.","mla":"Gavriil, Konstantinos, et al. “Computational Design of Cold Bent Glass Façades.” <i>ACM Transactions on Graphics</i>, vol. 39, no. 6, 208, Association for Computing Machinery, 2020, doi:<a href=\"https://doi.org/10.1145/3414685.3417843\">10.1145/3414685.3417843</a>.","ama":"Gavriil K, Guseinov R, Perez Rodriguez J, et al. Computational design of cold bent glass façades. <i>ACM Transactions on Graphics</i>. 2020;39(6). doi:<a href=\"https://doi.org/10.1145/3414685.3417843\">10.1145/3414685.3417843</a>","ista":"Gavriil K, Guseinov R, Perez Rodriguez J, Pellis D, Henderson PM, Rist F, Pottmann H, Bickel B. 2020. Computational design of cold bent glass façades. ACM Transactions on Graphics. 39(6), 208."},"publication":"ACM Transactions on Graphics","day":"26","external_id":{"arxiv":["2009.03667"],"isi":["000595589100048"]}},{"author":[{"first_name":"Ruslan","last_name":"Guseinov","id":"3AB45EE2-F248-11E8-B48F-1D18A9856A87","full_name":"Guseinov, Ruslan","orcid":"0000-0001-9819-5077"},{"full_name":"McMahan, Connor","first_name":"Connor","last_name":"McMahan"},{"id":"2DC83906-F248-11E8-B48F-1D18A9856A87","last_name":"Perez Rodriguez","first_name":"Jesus","full_name":"Perez Rodriguez, Jesus"},{"last_name":"Daraio","first_name":"Chiara","full_name":"Daraio, Chiara"},{"first_name":"Bernd","last_name":"Bickel","id":"49876194-F248-11E8-B48F-1D18A9856A87","full_name":"Bickel, Bernd","orcid":"0000-0001-6511-9385"}],"language":[{"iso":"eng"}],"year":"2020","corr_author":"1","department":[{"_id":"BeBi"}],"status":"public","ddc":["000"],"project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships"},{"_id":"24F9549A-B435-11E9-9278-68D0E5697425","grant_number":"715767","call_identifier":"H2020","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling"}],"has_accepted_license":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"date_created":"2020-01-13T16:54:26Z","publisher":"Springer Nature","oa":1,"file_date_updated":"2020-07-14T12:47:55Z","abstract":[{"text":"Advances in shape-morphing materials, such as hydrogels, shape-memory polymers and light-responsive polymers have enabled prescribing self-directed deformations of initially flat geometries. However, most proposed solutions evolve towards a target geometry without considering time-dependent actuation paths. To achieve more complex geometries and avoid self-collisions, it is critical to encode a spatial and temporal shape evolution within the initially flat shell. Recent realizations of time-dependent morphing are limited to the actuation of few, discrete hinges and cannot form doubly curved surfaces. Here, we demonstrate a method for encoding temporal shape evolution in architected shells that assume complex shapes and doubly curved geometries. The shells are non-periodic tessellations of pre-stressed contractile unit cells that soften in water at rates prescribed locally by mesostructure geometry. The ensuing midplane contraction is coupled to the formation of encoded curvatures. We propose an inverse design tool based on a data-driven model for unit cells’ temporal responses.","lang":"eng"}],"publication_identifier":{"issn":["2041-1723"]},"volume":11,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","related_material":{"link":[{"url":"https://ist.ac.at/en/news/geometry-meets-time/","description":"News on IST Homepage","relation":"press_release"}],"record":[{"id":"7154","status":"public","relation":"research_data"},{"id":"8366","status":"public","relation":"dissertation_contains"}]},"article_type":"original","scopus_import":"1","pmid":1,"type":"journal_article","title":"Programming temporal morphing of self-actuated shells","oa_version":"Published Version","citation":{"chicago":"Guseinov, Ruslan, Connor McMahan, Jesus Perez Rodriguez, Chiara Daraio, and Bernd Bickel. “Programming Temporal Morphing of Self-Actuated Shells.” <i>Nature Communications</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41467-019-14015-2\">https://doi.org/10.1038/s41467-019-14015-2</a>.","mla":"Guseinov, Ruslan, et al. “Programming Temporal Morphing of Self-Actuated Shells.” <i>Nature Communications</i>, vol. 11, 237, Springer Nature, 2020, doi:<a href=\"https://doi.org/10.1038/s41467-019-14015-2\">10.1038/s41467-019-14015-2</a>.","ama":"Guseinov R, McMahan C, Perez Rodriguez J, Daraio C, Bickel B. Programming temporal morphing of self-actuated shells. <i>Nature Communications</i>. 2020;11. doi:<a href=\"https://doi.org/10.1038/s41467-019-14015-2\">10.1038/s41467-019-14015-2</a>","ista":"Guseinov R, McMahan C, Perez Rodriguez J, Daraio C, Bickel B. 2020. Programming temporal morphing of self-actuated shells. Nature Communications. 11, 237.","apa":"Guseinov, R., McMahan, C., Perez Rodriguez, J., Daraio, C., &#38; Bickel, B. (2020). Programming temporal morphing of self-actuated shells. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-019-14015-2\">https://doi.org/10.1038/s41467-019-14015-2</a>","short":"R. Guseinov, C. McMahan, J. Perez Rodriguez, C. Daraio, B. Bickel, Nature Communications 11 (2020).","ieee":"R. Guseinov, C. McMahan, J. Perez Rodriguez, C. Daraio, and B. Bickel, “Programming temporal morphing of self-actuated shells,” <i>Nature Communications</i>, vol. 11. Springer Nature, 2020."},"isi":1,"file":[{"content_type":"application/pdf","date_updated":"2020-07-14T12:47:55Z","file_id":"7336","checksum":"7db23fef2f4cda712f17f1004116ddff","relation":"main_file","creator":"rguseino","access_level":"open_access","date_created":"2020-01-15T14:35:34Z","file_name":"2020_NatureComm_Guseinov.pdf","file_size":1315270}],"external_id":{"pmid":["31932589"],"isi":["000511916800015"]},"day":"13","publication":"Nature Communications","doi":"10.1038/s41467-019-14015-2","article_number":"237","article_processing_charge":"No","date_published":"2020-01-13T00:00:00Z","ec_funded":1,"intvolume":"        11","month":"01","keyword":["Design","Synthesis and processing","Mechanical engineering","Polymers"],"quality_controlled":"1","_id":"7262","date_updated":"2026-04-08T07:25:22Z","publication_status":"published"}]