--- OA_place: publisher _id: '8332' 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." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Bernhard full_name: Kragl, Bernhard id: 320FC952-F248-11E8-B48F-1D18A9856A87 last_name: Kragl orcid: 0000-0001-7745-9117 citation: ama: 'Kragl B. Verifying concurrent programs: Refinement, synchronization, sequentialization. 2020. doi:10.15479/AT:ISTA:8332' apa: 'Kragl, B. (2020). Verifying concurrent programs: Refinement, synchronization, sequentialization. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8332' chicago: 'Kragl, Bernhard. “Verifying Concurrent Programs: Refinement, Synchronization, Sequentialization.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8332.' ieee: 'B. Kragl, “Verifying concurrent programs: Refinement, synchronization, sequentialization,” Institute of Science and Technology Austria, 2020.' ista: 'Kragl B. 2020. Verifying concurrent programs: Refinement, synchronization, sequentialization. Institute of Science and Technology Austria.' mla: 'Kragl, Bernhard. Verifying Concurrent Programs: Refinement, Synchronization, Sequentialization. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8332.' short: 'B. Kragl, Verifying Concurrent Programs: Refinement, Synchronization, Sequentialization, Institute of Science and Technology Austria, 2020.' corr_author: '1' date_created: 2020-09-04T12:24:12Z date_published: 2020-09-03T00:00:00Z date_updated: 2026-06-18T19:29:42Z day: '03' ddc: - '000' degree_awarded: PhD department: - _id: ToHe doi: 10.15479/AT:ISTA:8332 file: - access_level: open_access checksum: 26fe261550f691280bda4c454bf015c7 content_type: application/pdf creator: bkragl date_created: 2020-09-04T12:17:47Z date_updated: 2020-09-04T12:17:47Z file_id: '8333' file_name: kragl-thesis.pdf file_size: 1348815 relation: main_file - access_level: closed checksum: b9694ce092b7c55557122adba8337ebc content_type: application/zip creator: bkragl date_created: 2020-09-04T13:00:17Z date_updated: 2020-09-04T13:00:17Z file_id: '8335' file_name: kragl-thesis.zip file_size: 372312 relation: source_file file_date_updated: 2020-09-04T13:00:17Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '120' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '8195' relation: part_of_dissertation status: public - id: '133' relation: part_of_dissertation status: public - id: '160' relation: part_of_dissertation status: public - id: '8012' relation: part_of_dissertation status: public status: public supervisor: - first_name: Thomas A full_name: Henzinger, Thomas A id: 40876CD8-F248-11E8-B48F-1D18A9856A87 last_name: Henzinger orcid: 0000-0002-2985-7724 title: 'Verifying concurrent programs: Refinement, synchronization, sequentialization' type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '8341' abstract: - lang: eng 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." 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. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Urban full_name: Bezeljak, Urban id: 2A58201A-F248-11E8-B48F-1D18A9856A87 last_name: Bezeljak orcid: 0000-0003-1365-5631 citation: ama: Bezeljak U. In vitro reconstitution of a Rab activation switch. 2020. doi:10.15479/AT:ISTA:8341 apa: Bezeljak, U. (2020). In vitro reconstitution of a Rab activation switch. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8341 chicago: Bezeljak, Urban. “In Vitro Reconstitution of a Rab Activation Switch.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8341. 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. mla: Bezeljak, Urban. In Vitro Reconstitution of a Rab Activation Switch. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8341. short: U. Bezeljak, In Vitro Reconstitution of a Rab Activation Switch, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-09-08T08:53:53Z date_published: 2020-09-08T00:00:00Z date_updated: 2026-04-08T07:24:56Z day: '08' ddc: - '570' degree_awarded: PhD department: - _id: MaLo doi: 10.15479/AT:ISTA:8341 file: - access_level: closed checksum: 70871b335a595252a66c6bbf0824fb02 content_type: application/x-zip-compressed creator: dernst date_created: 2020-09-08T09:00:29Z date_updated: 2021-09-16T12:49:12Z file_id: '8342' file_name: 2020_Urban_Bezeljak_Thesis_TeX.zip file_size: 65246782 relation: source_file - access_level: open_access checksum: 59a62275088b00b7241e6ff4136434c7 content_type: application/pdf creator: dernst date_created: 2020-09-08T09:00:27Z date_updated: 2021-09-16T12:49:12Z file_id: '8343' file_name: 2020_Urban_Bezeljak_Thesis.pdf file_size: 31259058 relation: main_file file_date_updated: 2021-09-16T12:49:12Z has_accepted_license: '1' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-sa/4.0/ month: '09' oa: 1 oa_version: Published Version page: '215' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7580' relation: part_of_dissertation status: public status: public supervisor: - first_name: Martin full_name: Loose, Martin id: 462D4284-F248-11E8-B48F-1D18A9856A87 last_name: Loose orcid: 0000-0001-7309-9724 title: In vitro reconstitution of a Rab activation switch tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '8353' abstract: - lang: eng 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." 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." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Julia full_name: Steiner, Julia id: 3BB67EB0-F248-11E8-B48F-1D18A9856A87 last_name: Steiner orcid: 0000-0003-0493-3775 citation: ama: Steiner J. Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I. 2020. doi:10.15479/AT:ISTA:8353 apa: Steiner, J. (2020). Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8353 chicago: Steiner, Julia. “Biochemical and Structural Investigation of the Mrp Antiporter, an Ancestor of Complex I.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8353. ieee: J. Steiner, “Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I,” Institute of Science and Technology Austria, 2020. ista: Steiner J. 2020. Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I. Institute of Science and Technology Austria. mla: Steiner, Julia. Biochemical and Structural Investigation of the Mrp Antiporter, an Ancestor of Complex I. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8353. short: J. Steiner, Biochemical and Structural Investigation of the Mrp Antiporter, an Ancestor of Complex I, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-09-09T14:27:01Z date_published: 2020-09-09T00:00:00Z date_updated: 2026-04-08T07:23:36Z day: '09' ddc: - '572' degree_awarded: PhD department: - _id: LeSa doi: 10.15479/AT:ISTA:8353 file: - access_level: open_access checksum: 2388d7e6e7a4d364c096fa89f305c3de content_type: application/pdf creator: jsteiner date_created: 2020-09-09T14:22:35Z date_updated: 2021-09-16T12:40:56Z file_id: '8354' file_name: Thesis_Julia_Steiner_pdfA.pdf file_size: 117547589 relation: main_file - access_level: closed checksum: ba112f957b7145462d0ab79044873ee9 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: jsteiner date_created: 2020-09-09T14:23:25Z date_updated: 2020-09-15T08:48:37Z file_id: '8355' file_name: Thesis_Julia_Steiner.docx file_size: 223328668 relation: source_file file_date_updated: 2021-09-16T12:40:56Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: None page: '191' project: - _id: 26169496-B435-11E9-9278-68D0E5697425 grant_number: '24741' name: Revealing the functional mechanism of Mrp antiporter, an ancestor of complex I publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '8284' relation: part_of_dissertation status: public status: public supervisor: - first_name: Leonid A full_name: Sazanov, Leonid A id: 338D39FE-F248-11E8-B48F-1D18A9856A87 last_name: Sazanov orcid: 0000-0002-0977-7989 title: Biochemical and structural investigation of the Mrp antiporter, an ancestor of complex I type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '8358' abstract: - lang: eng text: "During bacterial cell division, the tubulin-homolog FtsZ forms a ring-like structure at the center of the cell. This so-called Z-ring acts as a scaffold recruiting several division-related proteins to mid-cell and plays a key role in distributing proteins at the division site, a feature driven by the treadmilling motion of FtsZ filaments around the septum. What regulates the architecture, dynamics and stability of the Z-ring is still poorly understood, but FtsZ-associated proteins (Zaps) are known to play an important role. \r\nAdvances in fluorescence microscopy and in vitro reconstitution experiments have helped to shed light into some of the dynamic properties of these complex systems, but methods that allow to collect and analyze large quantitative data sets of the underlying polymer dynamics are still missing.\r\nHere, using an in vitro reconstitution approach, we studied how different Zaps affect FtsZ filament dynamics and organization into large-scale patterns, giving special emphasis to the role of the well-conserved protein ZapA. For this purpose, we use high-resolution fluorescence microscopy combined with novel image analysis workfows to study pattern organization and polymerization dynamics of active filaments. We quantified the influence of Zaps on FtsZ on three diferent spatial scales: the large-scale organization of the membrane-bound filament network, the underlying\r\npolymerization dynamics and the behavior of single molecules.\r\nWe found that ZapA cooperatively increases the spatial order of the filament network, binds only transiently to FtsZ filaments and has no effect on filament length and treadmilling velocity. Our data provides a model for how FtsZ-associated proteins can increase the precision and stability of the bacterial cell division machinery in a\r\nswitch-like manner, without compromising filament dynamics. Furthermore, we believe that our automated quantitative methods can be used to analyze a large variety of dynamic cytoskeletal systems, using standard time-lapse\r\nmovies of homogeneously labeled proteins obtained from experiments in vitro or even inside the living cell.\r\n" acknowledged_ssus: - _id: Bio acknowledgement: I should also express my gratitude to the bioimaging facility at IST Austria, for their assistance with the TIRF setup over the years, and especially to Christoph Sommer, who gave me a lot of input when I was starting to dive into programming. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Paulo R full_name: Dos Santos Caldas, Paulo R id: 38FCDB4C-F248-11E8-B48F-1D18A9856A87 last_name: Dos Santos Caldas orcid: 0000-0001-6730-4461 citation: ama: Dos Santos Caldas PR. Organization and dynamics of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinkers. 2020. doi:10.15479/AT:ISTA:8358 apa: Dos Santos Caldas, P. R. (2020). Organization and dynamics of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinkers. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8358 chicago: Dos Santos Caldas, Paulo R. “Organization and Dynamics of Treadmilling Filaments in Cytoskeletal Networks of FtsZ and Its Crosslinkers.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8358. ieee: P. R. Dos Santos Caldas, “Organization and dynamics of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinkers,” Institute of Science and Technology Austria, 2020. ista: Dos Santos Caldas PR. 2020. Organization and dynamics of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinkers. Institute of Science and Technology Austria. mla: Dos Santos Caldas, Paulo R. Organization and Dynamics of Treadmilling Filaments in Cytoskeletal Networks of FtsZ and Its Crosslinkers. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8358. short: P.R. Dos Santos Caldas, Organization and Dynamics of Treadmilling Filaments in Cytoskeletal Networks of FtsZ and Its Crosslinkers, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-09-10T09:26:49Z date_published: 2020-09-10T00:00:00Z date_updated: 2026-04-08T07:26:30Z day: '10' ddc: - '572' degree_awarded: PhD department: - _id: MaLo doi: 10.15479/AT:ISTA:8358 file: - access_level: open_access checksum: 882f93fe9c351962120e2669b84bf088 content_type: application/pdf creator: pcaldas date_created: 2020-09-10T12:11:29Z date_updated: 2020-09-10T12:11:29Z file_id: '8364' file_name: phd_thesis_pcaldas.pdf file_size: 141602462 relation: main_file success: 1 - access_level: closed checksum: 70cc9e399c4e41e6e6ac445ae55e8558 content_type: application/x-zip-compressed creator: pcaldas date_created: 2020-09-10T12:18:17Z date_updated: 2020-09-11T07:48:10Z file_id: '8365' file_name: phd_thesis_latex_pcaldas.zip file_size: 450437458 relation: source_file file_date_updated: 2020-09-11T07:48:10Z has_accepted_license: '1' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '09' oa: 1 oa_version: Published Version page: '135' publication_identifier: isbn: - 978-3-99078-009-1 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7197' relation: part_of_dissertation status: public - id: '7572' relation: dissertation_contains status: public status: public supervisor: - first_name: Martin full_name: Loose, Martin id: 462D4284-F248-11E8-B48F-1D18A9856A87 last_name: Loose orcid: 0000-0001-7309-9724 title: Organization and dynamics of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinkers tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '8366' 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." acknowledged_ssus: - _id: M-Shop - _id: ScienComp 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." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Ruslan full_name: Guseinov, Ruslan id: 3AB45EE2-F248-11E8-B48F-1D18A9856A87 last_name: Guseinov orcid: 0000-0001-9819-5077 citation: ama: 'Guseinov R. Computational design of curved thin shells: From glass façades to programmable matter. 2020. doi:10.15479/AT:ISTA:8366' apa: 'Guseinov, R. (2020). Computational design of curved thin shells: From glass façades to programmable matter. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8366' chicago: 'Guseinov, Ruslan. “Computational Design of Curved Thin Shells: From Glass Façades to Programmable Matter.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8366.' 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.' mla: 'Guseinov, Ruslan. Computational Design of Curved Thin Shells: From Glass Façades to Programmable Matter. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8366.' short: 'R. Guseinov, Computational Design of Curved Thin Shells: From Glass Façades to Programmable Matter, Institute of Science and Technology Austria, 2020.' corr_author: '1' date_created: 2020-09-10T16:19:55Z date_published: 2020-09-21T00:00:00Z date_updated: 2026-04-08T07:25:22Z day: '21' ddc: - '000' degree_awarded: PhD department: - _id: BeBi doi: 10.15479/AT:ISTA:8366 ec_funded: 1 file: - access_level: open_access checksum: f8da89553da36037296b0a80f14ebf50 content_type: application/pdf creator: rguseino date_created: 2020-09-10T16:11:49Z date_updated: 2020-09-10T16:11:49Z file_id: '8367' file_name: thesis_rguseinov.pdf file_size: 70950442 relation: main_file success: 1 - access_level: closed checksum: e8fd944c960c20e0e27e6548af69121d content_type: application/x-zip-compressed creator: rguseino date_created: 2020-09-11T09:39:48Z date_updated: 2020-09-16T15:11:01Z file_id: '8374' file_name: thesis_source.zip file_size: 76207597 relation: source_file file_date_updated: 2020-09-16T15:11:01Z has_accepted_license: '1' keyword: - computer-aided design - shape modeling - self-morphing - mechanical engineering language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '118' project: - _id: 24F9549A-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715767' name: 'MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling' publication_identifier: isbn: - 978-3-99078-010-7 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '8562' relation: part_of_dissertation status: public - id: '8375' relation: research_data status: public - id: '7151' relation: research_data status: deleted - id: '1001' relation: part_of_dissertation status: public - id: '7262' relation: part_of_dissertation status: public status: public supervisor: - first_name: Bernd full_name: Bickel, Bernd id: 49876194-F248-11E8-B48F-1D18A9856A87 last_name: Bickel orcid: 0000-0001-6511-9385 title: 'Computational design of curved thin shells: From glass façades to programmable matter' type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '8386' abstract: - lang: eng text: "Form versus function is a long-standing debate in various design-related fields, such as architecture as well as graphic and industrial design. A good design that balances form and function often requires considerable human effort and collaboration among experts from different professional fields. Computational design tools provide a new paradigm for designing functional objects. In computational design, form and function are represented as mathematical\r\nquantities, with the help of numerical and combinatorial algorithms, they can assist even novice users in designing versatile models that exhibit their desired functionality. This thesis presents three disparate research studies on the computational design of functional objects: The appearance of 3d print—we optimize the volumetric material distribution for faithfully replicating colored surface texture in 3d printing; the dynamic motion of mechanical structures—\r\nour design system helps the novice user to retarget various mechanical templates with different functionality to complex 3d shapes; and a more abstract functionality, multistability—our algorithm automatically generates models that exhibit multiple stable target poses. For each of these cases, our computational design tools not only ensure the functionality of the results but also permit the user aesthetic freedom over the form. Moreover, fabrication constraints\r\nwere taken into account, which allow for the immediate creation of physical realization via 3D printing or laser cutting." acknowledged_ssus: - _id: SSU acknowledgement: The research in this thesis has received funding from the European Union’s Horizon 2020 research and innovation programme, under the Marie Skłodowska-Curie grant agreement No 642841 (DISTRO) and the European Research Council grant agreement No 715767 (MATERIALIZABLE). All the research projects in this thesis were also supported by Scientific Service Units (SSUs) at IST Austria. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Ran full_name: Zhang, Ran id: 4DDBCEB0-F248-11E8-B48F-1D18A9856A87 last_name: Zhang orcid: 0000-0002-3808-281X citation: ama: Zhang R. Structure-aware computational design and its application to 3D printable volume scattering, mechanism, and multistability. 2020. doi:10.15479/AT:ISTA:8386 apa: Zhang, R. (2020). Structure-aware computational design and its application to 3D printable volume scattering, mechanism, and multistability. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8386 chicago: Zhang, Ran. “Structure-Aware Computational Design and Its Application to 3D Printable Volume Scattering, Mechanism, and Multistability.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8386. ieee: R. Zhang, “Structure-aware computational design and its application to 3D printable volume scattering, mechanism, and multistability,” Institute of Science and Technology Austria, 2020. ista: Zhang R. 2020. Structure-aware computational design and its application to 3D printable volume scattering, mechanism, and multistability. Institute of Science and Technology Austria. mla: Zhang, Ran. Structure-Aware Computational Design and Its Application to 3D Printable Volume Scattering, Mechanism, and Multistability. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8386. short: R. Zhang, Structure-Aware Computational Design and Its Application to 3D Printable Volume Scattering, Mechanism, and Multistability, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-09-14T01:04:53Z date_published: 2020-09-14T00:00:00Z date_updated: 2026-04-16T10:06:31Z day: '14' ddc: - '003' degree_awarded: PhD department: - _id: BeBi doi: 10.15479/AT:ISTA:8386 ec_funded: 1 file: - access_level: closed checksum: edcf578b6e1c9b0dd81ff72d319b66ba content_type: application/x-zip-compressed creator: rzhang date_created: 2020-09-14T01:02:59Z date_updated: 2020-09-14T12:18:43Z file_id: '8388' file_name: Thesis_Ran.zip file_size: 1245800191 relation: source_file - access_level: open_access checksum: 817e20c33be9247f906925517c56a40d content_type: application/pdf creator: rzhang date_created: 2020-09-15T12:51:53Z date_updated: 2020-09-15T12:51:53Z file_id: '8396' file_name: PhD_thesis_Ran Zhang_20200915.pdf file_size: 161385316 relation: main_file success: 1 file_date_updated: 2020-09-15T12:51:53Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '148' project: - _id: 2508E324-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '642841' name: Distributed 3D Object Design - _id: 24F9549A-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715767' name: 'MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '486' relation: part_of_dissertation status: public - id: '1002' relation: part_of_dissertation status: public status: public supervisor: - first_name: Bernd full_name: Bickel, Bernd id: 49876194-F248-11E8-B48F-1D18A9856A87 last_name: Bickel orcid: 0000-0001-6511-9385 title: Structure-aware computational design and its application to 3D printable volume scattering, mechanism, and multistability type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '8390' abstract: - lang: eng text: "Deep neural networks have established a new standard for data-dependent feature extraction pipelines in the Computer Vision literature. Despite their remarkable performance in the standard supervised learning scenario, i.e. when models are trained with labeled data and tested on samples that follow a similar distribution, neural networks have been shown to struggle with more advanced generalization abilities, such as transferring knowledge across visually different domains, or generalizing to new unseen combinations of known concepts. In this thesis we argue that, in contrast to the usual black-box behavior of neural networks, leveraging more structured internal representations is a promising direction\r\nfor tackling such problems. In particular, we focus on two forms of structure. First, we tackle modularity: We show that (i) compositional architectures are a natural tool for modeling reasoning tasks, in that they efficiently capture their combinatorial nature, which is key for generalizing beyond the compositions seen during training. We investigate how to to learn such models, both formally and experimentally, for the task of abstract visual reasoning. Then, we show that (ii) in some settings, modularity allows us to efficiently break down complex tasks into smaller, easier, modules, thereby improving computational efficiency; We study this behavior in the context of generative models for colorization, as well as for small objects detection. Secondly, we investigate the inherently layered structure of representations learned by neural networks, and analyze its role in the context of transfer learning and domain adaptation across visually\r\ndissimilar domains. " acknowledged_ssus: - _id: CampIT - _id: ScienComp acknowledgement: Last but not least, I would like to acknowledge the support of the IST IT and scientific computing team for helping provide a great work environment. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Amélie full_name: Royer, Amélie id: 3811D890-F248-11E8-B48F-1D18A9856A87 last_name: Royer orcid: 0000-0002-8407-0705 citation: ama: Royer A. Leveraging structure in Computer Vision tasks for flexible Deep Learning models. 2020. doi:10.15479/AT:ISTA:8390 apa: Royer, A. (2020). Leveraging structure in Computer Vision tasks for flexible Deep Learning models. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8390 chicago: Royer, Amélie. “Leveraging Structure in Computer Vision Tasks for Flexible Deep Learning Models.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8390. ieee: A. Royer, “Leveraging structure in Computer Vision tasks for flexible Deep Learning models,” Institute of Science and Technology Austria, 2020. ista: Royer A. 2020. Leveraging structure in Computer Vision tasks for flexible Deep Learning models. Institute of Science and Technology Austria. mla: Royer, Amélie. Leveraging Structure in Computer Vision Tasks for Flexible Deep Learning Models. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8390. short: A. Royer, Leveraging Structure in Computer Vision Tasks for Flexible Deep Learning Models, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-09-14T13:42:09Z date_published: 2020-09-14T00:00:00Z date_updated: 2026-04-08T07:26:44Z day: '14' ddc: - '000' degree_awarded: PhD department: - _id: ChLa doi: 10.15479/AT:ISTA:8390 file: - access_level: open_access checksum: c914d2f88846032f3d8507734861b6ee content_type: application/pdf creator: dernst date_created: 2020-09-14T13:39:14Z date_updated: 2020-09-14T13:39:14Z file_id: '8391' file_name: 2020_Thesis_Royer.pdf file_size: 30224591 relation: main_file success: 1 - access_level: closed checksum: ae98fb35d912cff84a89035ae5794d3c content_type: application/x-zip-compressed creator: dernst date_created: 2020-09-14T13:39:17Z date_updated: 2020-09-14T13:39:17Z file_id: '8392' file_name: thesis_sources.zip file_size: 74227627 relation: main_file file_date_updated: 2020-09-14T13:39:17Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '197' publication_identifier: isbn: - 978-3-99078-007-7 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7936' relation: part_of_dissertation status: public - id: '8092' relation: part_of_dissertation status: public - id: '911' relation: part_of_dissertation status: public - id: '8193' relation: part_of_dissertation status: public - id: '7937' relation: part_of_dissertation status: public status: public supervisor: - first_name: Christoph full_name: Lampert, Christoph id: 40C20FD2-F248-11E8-B48F-1D18A9856A87 last_name: Lampert orcid: 0000-0001-8622-7887 title: Leveraging structure in Computer Vision tasks for flexible Deep Learning models tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '7460' 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." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Katharina full_name: Ölsböck, Katharina id: 4D4AA390-F248-11E8-B48F-1D18A9856A87 last_name: Ölsböck orcid: 0000-0002-4672-8297 citation: ama: Ölsböck K. The hole system of triangulated shapes. 2020. doi:10.15479/AT:ISTA:7460 apa: Ölsböck, K. (2020). The hole system of triangulated shapes. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7460 chicago: Ölsböck, Katharina. “The Hole System of Triangulated Shapes.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7460. ieee: 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. The Hole System of Triangulated Shapes. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7460. short: K. Ölsböck, The Hole System of Triangulated Shapes, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-02-06T14:56:53Z date_published: 2020-02-10T00:00:00Z date_updated: 2026-04-08T07:23:21Z day: '10' ddc: - '514' degree_awarded: PhD department: - _id: HeEd - _id: GradSch doi: 10.15479/AT:ISTA:7460 file: - access_level: open_access checksum: 1df9f8c530b443c0e63a3f2e4fde412e content_type: application/pdf creator: koelsboe date_created: 2020-02-06T14:43:54Z date_updated: 2020-07-14T12:47:58Z file_id: '7461' file_name: thesis_ist-final_noack.pdf file_size: 76195184 relation: main_file - access_level: closed checksum: 7a52383c812b0be64d3826546509e5a4 content_type: application/x-zip-compressed creator: koelsboe date_created: 2020-02-06T14:52:45Z date_updated: 2020-07-14T12:47:58Z description: latex source files, figures file_id: '7462' file_name: latex-files.zip file_size: 122103715 relation: source_file file_date_updated: 2020-07-14T12:47:58Z has_accepted_license: '1' keyword: - shape reconstruction - hole manipulation - ordered complexes - Alpha complex - Wrap complex - computational topology - Bregman geometry language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: '155' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6608' relation: part_of_dissertation status: public status: public supervisor: - first_name: Herbert full_name: Edelsbrunner, Herbert id: 3FB178DA-F248-11E8-B48F-1D18A9856A87 last_name: Edelsbrunner orcid: 0000-0002-9823-6833 title: The hole system of triangulated shapes tmp: image: /images/cc_by_nc_sa.png legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) short: CC BY-NC-SA (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '7514' abstract: - lang: eng text: "We study the interacting homogeneous Bose gas in two spatial dimensions in the thermodynamic limit at fixed density. We shall be concerned with some mathematical aspects of this complicated problem in many-body quantum mechanics. More specifically, we consider the dilute limit where the scattering length of the interaction potential, which is a measure for the effective range of the potential, is small compared to the average distance between the particles. We are interested in a setting with positive (i.e., non-zero) temperature. After giving a survey of the relevant literature in the field, we provide some facts and examples to set expectations for the two-dimensional system. The crucial difference to the three-dimensional system is that there is no Bose–Einstein condensate at positive temperature due to the Hohenberg–Mermin–Wagner theorem. However, it turns out that an asymptotic formula for the free energy holds similarly to the three-dimensional case.\r\nWe motivate this formula by considering a toy model with δ interaction potential. By restricting this model Hamiltonian to certain trial states with a quasi-condensate we obtain an upper bound for the free energy that still has the quasi-condensate fraction as a free parameter. When minimizing over the quasi-condensate fraction, we obtain the Berezinskii–Kosterlitz–Thouless critical temperature for superfluidity, which plays an important role in our rigorous contribution. The mathematically rigorous result that we prove concerns the specific free energy in the dilute limit. We give upper and lower bounds on the free energy in terms of the free energy of the non-interacting system and a correction term coming from the interaction. Both bounds match and thus we obtain the leading term of an asymptotic approximation in the dilute limit, provided the thermal wavelength of the particles is of the same order (or larger) than the average distance between the particles. The remarkable feature of this result is its generality: the correction term depends on the interaction potential only through its scattering length and it holds for all nonnegative interaction potentials with finite scattering length that are measurable. In particular, this allows to model an interaction of hard disks." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Simon full_name: Mayer, Simon id: 30C4630A-F248-11E8-B48F-1D18A9856A87 last_name: Mayer citation: ama: Mayer S. The free energy of a dilute two-dimensional Bose gas. 2020. doi:10.15479/AT:ISTA:7514 apa: Mayer, S. (2020). The free energy of a dilute two-dimensional Bose gas. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7514 chicago: Mayer, Simon. “The Free Energy of a Dilute Two-Dimensional Bose Gas.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7514. ieee: S. Mayer, “The free energy of a dilute two-dimensional Bose gas,” Institute of Science and Technology Austria, 2020. ista: Mayer S. 2020. The free energy of a dilute two-dimensional Bose gas. Institute of Science and Technology Austria. mla: Mayer, Simon. The Free Energy of a Dilute Two-Dimensional Bose Gas. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7514. short: S. Mayer, The Free Energy of a Dilute Two-Dimensional Bose Gas, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-02-24T09:17:27Z date_published: 2020-02-24T00:00:00Z date_updated: 2026-04-08T07:25:40Z day: '24' ddc: - '510' degree_awarded: PhD department: - _id: RoSe - _id: GradSch doi: 10.15479/AT:ISTA:7514 ec_funded: 1 file: - access_level: open_access checksum: b4de7579ddc1dbdd44ff3f17c48395f6 content_type: application/pdf creator: dernst date_created: 2020-02-24T09:15:06Z date_updated: 2020-07-14T12:47:59Z file_id: '7515' file_name: thesis.pdf file_size: 1563429 relation: main_file - access_level: closed checksum: ad7425867b52d7d9e72296e87bc9cb67 content_type: application/x-zip-compressed creator: dernst date_created: 2020-02-24T09:15:16Z date_updated: 2020-07-14T12:47:59Z file_id: '7516' file_name: thesis_source.zip file_size: 2028038 relation: source_file file_date_updated: 2020-07-14T12:47:59Z has_accepted_license: '1' language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: '148' project: - _id: 25C6DC12-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '694227' name: Analysis of quantum many-body systems publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7524' relation: part_of_dissertation status: public status: public supervisor: - first_name: Robert full_name: Seiringer, Robert id: 4AFD0470-F248-11E8-B48F-1D18A9856A87 last_name: Seiringer orcid: 0000-0002-6781-0521 title: The free energy of a dilute two-dimensional Bose gas tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '8155' abstract: - lang: eng text: "In the thesis we focus on the interplay of the biophysics and evolution of gene regulation. We start by addressing how the type of prokaryotic gene regulation – activation and repression – affects spurious binding to DNA, also known as\r\ntranscriptional crosstalk. We propose that regulatory interference caused by excess regulatory proteins in the dense cellular medium – global crosstalk – could be a factor in determining which type of gene regulatory network is evolutionarily preferred. Next,we use a normative approach in eukaryotic gene regulation to describe minimal\r\nnon-equilibrium enhancer models that optimize so-called regulatory phenotypes. We find a class of models that differ from standard thermodynamic equilibrium models by a single parameter that notably increases the regulatory performance. Next chapter addresses the question of genotype-phenotype-fitness maps of higher dimensional phenotypes. We show that our biophysically realistic approach allows us to understand how the mechanisms of promoter function constrain genotypephenotype maps, and how they affect the evolutionary trajectories of promoters.\r\nIn the last chapter we ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using mathematical modeling, we show that amplifications can tune gene expression in many environments, including those where transcription factor-based schemes are\r\nhard to evolve or maintain. " acknowledgement: For the duration of his PhD, Rok was a recipient of a DOC fellowship of the Austrian Academy of Sciences. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Rok full_name: Grah, Rok id: 483E70DE-F248-11E8-B48F-1D18A9856A87 last_name: Grah orcid: 0000-0003-2539-3560 citation: ama: Grah R. Gene regulation across scales – how biophysical constraints shape evolution. 2020. doi:10.15479/AT:ISTA:8155 apa: Grah, R. (2020). Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8155 chicago: Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints Shape Evolution.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8155. 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. mla: Grah, Rok. Gene Regulation across Scales – How Biophysical Constraints Shape Evolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8155. short: R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape Evolution, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-07-23T09:51:28Z date_published: 2020-07-24T00:00:00Z date_updated: 2026-07-06T12:43:42Z day: '24' ddc: - '530' - '570' degree_awarded: PhD department: - _id: CaGu - _id: GaTk doi: 10.15479/AT:ISTA:8155 file: - access_level: open_access content_type: application/pdf creator: rgrah date_created: 2020-07-27T12:00:07Z date_updated: 2020-07-27T12:00:07Z file_id: '8176' file_name: Thesis_RokGrah_200727_convertedNew.pdf file_size: 16638998 relation: main_file success: 1 - access_level: closed content_type: application/zip creator: rgrah date_created: 2020-07-27T12:02:23Z date_updated: 2020-07-30T13:04:55Z file_id: '8177' file_name: Thesis_new.zip file_size: 347459978 relation: main_file file_date_updated: 2020-07-30T13:04:55Z has_accepted_license: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '310' project: - _id: 267C84F4-B435-11E9-9278-68D0E5697425 name: Biophysically realistic genotype-phenotype maps for regulatory networks publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7569' relation: part_of_dissertation status: public - id: '7652' relation: part_of_dissertation status: public - id: '7675' relation: part_of_dissertation status: public status: public supervisor: - first_name: Calin C full_name: Guet, Calin C id: 47F8433E-F248-11E8-B48F-1D18A9856A87 last_name: Guet orcid: 0000-0001-6220-2052 - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 title: Gene regulation across scales – how biophysical constraints shape evolution type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '8958' abstract: - lang: eng text: "The oft-quoted dictum by Arthur Schawlow: ``A diatomic molecule has one atom too many'' has been disavowed. Inspired by the possibility to experimentally manipulate and enhance chemical reactivity in helium nanodroplets, we investigate the rotation of coupled cold molecules in the presence of a many-body environment.\r\nIn this thesis, we introduce new variational approaches to quantum impurities and apply them to the Fröhlich polaron - a quasiparticle formed out of an electron (or other point-like impurity) in a polar medium, and to the angulon - a quasiparticle formed out of a rotating molecule in a bosonic bath.\r\nWith this theoretical toolbox, we reveal the self-localization transition for the angulon quasiparticle. We show that, unlike for polarons, self-localization of angulons occurs at finite impurity-bath coupling already at the mean-field level. The transition is accompanied by the spherical-symmetry breaking of the angulon ground state and a discontinuity in the first derivative of the ground-state energy. Moreover, the type of symmetry breaking is dictated by the symmetry of the microscopic impurity-bath interaction, which leads to a number of distinct self-localized states. \r\nFor the system containing multiple impurities, by analogy with the bipolaron, we introduce the biangulon quasiparticle describing two rotating molecules that align with respect to each other due to the effective attractive interaction mediated by the excitations of the bath. We study this system from the strong-coupling regime to the weak molecule-bath interaction regime. We show that the molecules tend to have a strong alignment in the ground state, the biangulon shows shifted angulon instabilities and an additional spectral instability, where resonant angular momentum transfer between the molecules and the bath takes place. Finally, we introduce a diagonalization scheme that allows us to describe the transition from two separated angulons to a biangulon as a function of the distance between the two molecules." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Xiang full_name: Li, Xiang id: 4B7E523C-F248-11E8-B48F-1D18A9856A87 last_name: Li citation: ama: Li X. Rotation of coupled cold molecules in the presence of a many-body environment. 2020. doi:10.15479/AT:ISTA:8958 apa: Li, X. (2020). Rotation of coupled cold molecules in the presence of a many-body environment. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8958 chicago: Li, Xiang. “Rotation of Coupled Cold Molecules in the Presence of a Many-Body Environment.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8958. ieee: X. Li, “Rotation of coupled cold molecules in the presence of a many-body environment,” Institute of Science and Technology Austria, 2020. ista: Li X. 2020. Rotation of coupled cold molecules in the presence of a many-body environment. Institute of Science and Technology Austria. mla: Li, Xiang. Rotation of Coupled Cold Molecules in the Presence of a Many-Body Environment. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8958. short: X. Li, Rotation of Coupled Cold Molecules in the Presence of a Many-Body Environment, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-12-21T09:44:30Z date_published: 2020-12-21T00:00:00Z date_updated: 2026-07-07T05:31:09Z day: '21' ddc: - '539' degree_awarded: PhD department: - _id: MiLe doi: 10.15479/AT:ISTA:8958 ec_funded: 1 file: - access_level: open_access checksum: 3994c54a1241451d561db1d4f43bad30 content_type: application/pdf creator: xli date_created: 2020-12-22T10:55:56Z date_updated: 2020-12-22T10:55:56Z file_id: '8967' file_name: THESIS_Xiang_Li.pdf file_size: 3622305 relation: main_file success: 1 - access_level: closed checksum: 0954ecfc5554c05615c14de803341f00 content_type: application/x-zip-compressed creator: xli date_created: 2020-12-22T10:56:03Z date_updated: 2020-12-30T07:18:03Z file_id: '8968' file_name: THESIS_Xiang_Li.zip file_size: 4018859 relation: source_file file_date_updated: 2020-12-30T07:18:03Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '125' project: - _id: 26031614-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29902 name: Quantum rotations in the presence of a many-body environment - _id: 2688CF98-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '801770' name: 'Angulon: physics and applications of a new quasiparticle' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '8587' relation: part_of_dissertation status: public - id: '1120' relation: part_of_dissertation status: public - id: '5886' relation: part_of_dissertation status: public status: public supervisor: - first_name: Mikhail full_name: Lemeshko, Mikhail id: 37CB05FA-F248-11E8-B48F-1D18A9856A87 last_name: Lemeshko orcid: 0000-0002-6990-7802 title: Rotation of coupled cold molecules in the presence of a many-body environment type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '8589' 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. 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. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Huibin full_name: Han, Huibin id: 31435098-F248-11E8-B48F-1D18A9856A87 last_name: Han citation: ama: Han H. Novel insights into PIN polarity regulation during Arabidopsis development. 2020. doi:10.15479/AT:ISTA:8589 apa: Han, H. (2020). Novel insights into PIN polarity regulation during Arabidopsis development. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8589 chicago: Han, Huibin. “Novel Insights into PIN Polarity Regulation during Arabidopsis Development.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8589. ieee: 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. Novel Insights into PIN Polarity Regulation during Arabidopsis Development. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8589. short: H. Han, Novel Insights into PIN Polarity Regulation during Arabidopsis Development, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-09-30T14:50:51Z date_published: 2020-09-30T00:00:00Z date_updated: 2026-07-28T12:51:58Z day: '30' ddc: - '580' degree_awarded: PhD department: - _id: JiFr doi: 10.15479/AT:ISTA:8589 file: - access_level: closed checksum: c4bda1947d4c09c428ac9ce667b02327 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: dernst date_created: 2020-09-30T14:50:20Z date_updated: 2020-09-30T14:50:20Z file_id: '8590' file_name: 2020_Han_Thesis.docx file_size: 49198118 relation: source_file - access_level: open_access checksum: 3f4f5d1718c2230adf30639ecaf8a00b content_type: application/pdf creator: dernst date_created: 2020-09-30T14:49:59Z date_updated: 2021-10-01T13:33:02Z file_id: '8591' file_name: 2020_Han_Thesis.pdf file_size: 15513963 relation: main_file file_date_updated: 2021-10-01T13:33:02Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '164' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7643' relation: part_of_dissertation status: public status: public supervisor: - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 title: Novel insights into PIN polarity regulation during Arabidopsis development type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '7896' 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. " alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Chethan full_name: Kamath Hosdurg, Chethan id: 4BD3F30E-F248-11E8-B48F-1D18A9856A87 last_name: Kamath Hosdurg orcid: 0009-0006-6812-7317 citation: ama: Kamath Hosdurg C. On the average-case hardness of total search problems. 2020. doi:10.15479/AT:ISTA:7896 apa: Kamath Hosdurg, C. (2020). On the average-case hardness of total search problems. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7896 chicago: Kamath Hosdurg, Chethan. “On the Average-Case Hardness of Total Search Problems.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7896. ieee: C. Kamath Hosdurg, “On the average-case hardness of total search problems,” Institute of Science and Technology Austria, 2020. ista: Kamath Hosdurg C. 2020. On the average-case hardness of total search problems. Institute of Science and Technology Austria. mla: Kamath Hosdurg, Chethan. On the Average-Case Hardness of Total Search Problems. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7896. short: C. Kamath Hosdurg, On the Average-Case Hardness of Total Search Problems, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-05-26T14:08:55Z date_published: 2020-05-25T00:00:00Z date_updated: 2026-07-30T13:43:53Z day: '25' ddc: - '000' degree_awarded: PhD department: - _id: KrPi - _id: GradSch doi: 10.15479/AT:ISTA:7896 doi_confirm: '1' ec_funded: 1 file: - access_level: open_access checksum: b39e2e1c376f5819b823fb7077491c64 content_type: application/pdf creator: dernst date_created: 2020-05-26T14:08:13Z date_updated: 2020-07-14T12:48:04Z file_id: '7897' file_name: 2020_Thesis_Kamath.pdf file_size: 1622742 relation: main_file - access_level: closed checksum: 8b26ba729c1a85ac6bea775f5d73cdc7 content_type: application/x-zip-compressed creator: dernst date_created: 2020-05-26T14:08:23Z date_updated: 2020-07-14T12:48:04Z file_id: '7898' file_name: Thesis_Kamath.zip file_size: 15301529 relation: source_file file_date_updated: 2020-07-14T12:48:04Z has_accepted_license: '1' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '126' project: - _id: 258C570E-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '259668' name: Provable Security for Physical Cryptography - _id: 258AA5B2-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '682815' name: Teaching Old Crypto New Tricks publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6677' relation: part_of_dissertation status: public status: public supervisor: - first_name: Krzysztof Z full_name: Pietrzak, Krzysztof Z id: 3E04A7AA-F248-11E8-B48F-1D18A9856A87 last_name: Pietrzak orcid: 0000-0002-9139-1654 title: On the average-case hardness of total search problems tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2020' ... --- OA_place: publisher _id: '7902' abstract: - lang: eng text: "Mosaic genetic analysis has been widely used in different model organisms such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific fashion. More recently, and less easily conducted, mosaic genetic analysis in mice has also been enabled with the ambition to shed light on human gene function and disease. These genetic tools are of particular interest, but not restricted to, the study of the brain. Notably, the MADM technology offers a genetic approach in mice to visualize and concomitantly manipulate small subsets of genetically defined cells at a clonal level and single cell resolution. MADM-based analysis has already advanced the study of genetic mechanisms regulating brain development and is expected that further MADM-based analysis of genetic alterations will continue to reveal important insights on the fundamental principles of development and disease to potentially assist in the development of new therapies or treatments.\r\nIn summary, this work completed and characterized the necessary genome-wide genetic tools to perform MADM-based analysis at single cell level of the vast majority of mouse genes in virtually any cell type and provided a protocol to perform lineage tracing using the novel MADM resource. Importantly, this work also explored and revealed novel aspects of biologically relevant events in an in vivo context, such as the chromosome-specific bias of chromatid sister segregation pattern, the generation of cell-type diversity in the cerebral cortex and in the cerebellum and finally, the relevance of the interplay between the cell-autonomous gene function and cell-non-autonomous (community) effects in radial glial progenitor lineage progression.\r\nThis work provides a foundation and opens the door to further elucidating the molecular mechanisms underlying neuronal diversity and astrocyte generation." acknowledged_ssus: - _id: PreCl - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras citation: ama: Contreras X. Genetic dissection of neural development in health and disease at single cell resolution. 2020. doi:10.15479/AT:ISTA:7902 apa: Contreras, X. (2020). Genetic dissection of neural development in health and disease at single cell resolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7902 chicago: Contreras, Ximena. “Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7902. ieee: X. Contreras, “Genetic dissection of neural development in health and disease at single cell resolution,” Institute of Science and Technology Austria, 2020. ista: Contreras X. 2020. Genetic dissection of neural development in health and disease at single cell resolution. Institute of Science and Technology Austria. mla: Contreras, Ximena. Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7902. short: X. Contreras, Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-05-29T08:27:32Z date_published: 2020-06-05T00:00:00Z date_updated: 2026-06-18T19:12:39Z day: '05' ddc: - '570' degree_awarded: PhD department: - _id: SiHi doi: 10.15479/AT:ISTA:7902 ec_funded: 1 file: - access_level: closed checksum: 43c172bf006c95b65992d473c7240d13 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: xcontreras date_created: 2020-06-05T08:18:08Z date_updated: 2021-06-07T22:30:03Z embargo_to: open_access file_id: '7927' file_name: PhDThesis_Contreras.docx file_size: 53134142 relation: source_file - access_level: open_access checksum: addfed9128271be05cae3608e03a6ec0 content_type: application/pdf creator: xcontreras date_created: 2020-06-05T08:18:07Z date_updated: 2021-06-07T22:30:03Z embargo: 2021-06-06 file_id: '7928' file_name: PhDThesis_Contreras.pdf file_size: 35117191 relation: main_file file_date_updated: 2021-06-07T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '214' project: - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '28' relation: dissertation_contains status: public - id: '7815' relation: dissertation_contains status: public - id: '6830' relation: dissertation_contains status: public status: public supervisor: - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 title: Genetic dissection of neural development in health and disease at single cell resolution type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- _id: '8350' abstract: - lang: eng text: "Cytoplasm is a gel-like crowded environment composed of tens of thousands of macromolecules, organelles, cytoskeletal networks and cytosol. The structure of the cytoplasm is thought to be highly organized and heterogeneous due to the crowding of its constituents and their effective compartmentalization. In such an environment, the diffusive dynamics of the molecules is very restricted, an effect that is further amplified by clustering and anchoring of molecules. Despite the jammed nature of the cytoplasm at the microscopic scale, large-scale reorganization of cytoplasm is essential for important cellular functions, such as nuclear positioning and cell division. How such mesoscale reorganization of the cytoplasm is achieved, especially for very large cells such as oocytes or syncytial tissues that can span hundreds of micrometers in size, has only begun to be understood.\r\nIn this thesis, I focus on the recent advances in elucidating the molecular, cellular and biophysical principles underlying cytoplasmic organization across different scales, structures and species. First, I outline which of these principles have been identified by reductionist approaches, such as in vitro reconstitution assays, where boundary conditions and components can be modulated at ease. I then describe how the theoretical and experimental framework established in these reduced systems have been applied to their more complex in vivo counterparts, in particular oocytes and embryonic syncytial structures, and discuss how such complex biological systems can initiate symmetry breaking and establish patterning.\r\nSpecifically, I examine an example of large-scale reorganizations taking place in zebrafish embryos, where extensive cytoplasmic streaming leads to the segregation of cytoplasm from yolk granules along the animal-vegetal axis of the embryo. Using biophysical experimentation and theory, I investigate the forces underlying this process, to show that this process does not rely on cortical actin reorganization, as previously thought, but instead on a cell-cycle-dependent bulk actin polymerization wave traveling from the animal to the vegetal pole of the embryo. This wave functions in segregation by both pulling cytoplasm animally and pushing yolk granules vegetally. Cytoplasm pulling is mediated by bulk actin network flows exerting friction forces on the cytoplasm, while yolk granule pushing is achieved by a mechanism closely resembling actin comet formation on yolk granules. This study defines a novel role of bulk actin polymerization waves in embryo polarization via cytoplasmic segregation. Lastly, I describe the cytoplasmic reorganizations taking place during zebrafish oocyte maturation, where the initial segregation of the cytoplasm and yolk granules occurs. Here, I demonstrate a previously uncharacterized wave of microtubule aster formation, traveling the oocyte along the animal-vegetal axis. Further research is required to determine the role of such microtubule structures in cytoplasmic reorganizations therein.\r\nCollectively, these studies provide further evidence for the coupling between cell cytoskeleton and cell cycle machinery, which can underlie a core self-organizing mechanism for orchestrating large-scale reorganizations in a cell-cycle-tunable manner, where the modulations of the force-generating machinery and cytoplasmic mechanics can be harbored to fulfill cellular functions." acknowledged_ssus: - _id: PreCl - _id: Bio - _id: EM-Fac acknowledgement: "I would have had no fish and hence no results without our wonderful fish facility crew, Verena Mayer, Eva Schlegl, Andreas Mlak and Matthias Nowak. Special thanks to Verena for being always happy to help and dealing with our chaotic schedules in the lab. Danke auch, Verena, für deine Geduld, mit mir auf Deutsch zu sprechen. Das hat mir sehr geholfen.\r\nSpecial thanks to the Bioimaging and EM facilities at IST Austria for supporting us every day. Very special thanks would go to Robert Hauschild for his continuous support on data analysis and also to Jack Merrin for designing and building microfabricated chambers for the project and for the various discussions on making zebrafish extracts." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Shayan full_name: Shamipour, Shayan id: 40B34FE2-F248-11E8-B48F-1D18A9856A87 last_name: Shamipour citation: ama: Shamipour S. Bulk actin dynamics drive phase segregation in zebrafish oocytes . 2020. doi:10.15479/AT:ISTA:8350 apa: Shamipour, S. (2020). Bulk actin dynamics drive phase segregation in zebrafish oocytes . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8350 chicago: Shamipour, Shayan. “Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes .” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8350. ieee: S. Shamipour, “Bulk actin dynamics drive phase segregation in zebrafish oocytes ,” Institute of Science and Technology Austria, 2020. ista: Shamipour S. 2020. Bulk actin dynamics drive phase segregation in zebrafish oocytes . Institute of Science and Technology Austria. mla: Shamipour, Shayan. Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes . Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8350. short: S. Shamipour, Bulk Actin Dynamics Drive Phase Segregation in Zebrafish Oocytes , Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-09-09T11:12:10Z date_published: 2020-09-09T00:00:00Z date_updated: 2025-09-11T07:08:52Z day: '09' ddc: - '570' degree_awarded: PhD department: - _id: BjHo - _id: CaHe doi: 10.15479/AT:ISTA:8350 file: - access_level: closed checksum: 6e47871c74f85008b9876112eb3fcfa1 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: sshamip date_created: 2020-09-09T11:06:27Z date_updated: 2021-09-11T22:30:05Z embargo_to: open_access file_id: '8351' file_name: Shayan-Thesis-Final.docx file_size: 65194814 relation: source_file - access_level: open_access checksum: 1b44c57f04d7e8a6fe41b1c9c55a52a3 content_type: application/pdf creator: sshamip date_created: 2020-09-09T11:06:13Z date_updated: 2021-09-11T22:30:05Z embargo: 2021-09-10 file_id: '8352' file_name: Shayan-Thesis-Final.pdf file_size: 23729605 relation: main_file file_date_updated: 2021-09-11T22:30:05Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: None page: '107' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7001' relation: part_of_dissertation status: public - id: '6508' relation: part_of_dissertation status: public - id: '735' relation: part_of_dissertation status: public - id: '661' relation: part_of_dissertation status: public status: public supervisor: - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 - first_name: Björn full_name: Hof, Björn id: 3A374330-F248-11E8-B48F-1D18A9856A87 last_name: Hof orcid: 0000-0003-2057-2754 title: 'Bulk actin dynamics drive phase segregation in zebrafish oocytes ' type: dissertation user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- OA_place: publisher _id: '8983' abstract: - lang: eng text: Metabolic adaptation is a critical feature of migrating cells. It tunes the metabolic programs of migrating cells to allow them to efficiently exert their crucial roles in development, inflammatory responses and tumor metastasis. Cell migration through physically challenging contexts requires energy. However, how the metabolic reprogramming that underlies in vivo cell invasion is controlled is still unanswered. In my PhD project, I identify a novel conserved metabolic shift in Drosophila melanogaster immune cells that by modulating their bioenergetic potential controls developmentally programmed tissue invasion. We show that this regulation requires a novel conserved nuclear protein, named Atossa. Atossa enhances the transcription of a set of proteins, including an RNA helicase Porthos and two metabolic enzymes, each of which increases the tissue invasion of leading Drosophila macrophages and can rescue the atossa mutant phenotype. Porthos selectively regulates the translational efficiency of a subset of mRNAs containing a 5’-UTR cis-regulatory TOP-like sequence. These 5’TOPL mRNA targets encode mitochondrial-related proteins, including subunits of mitochondrial oxidative phosphorylation (OXPHOS) components III and V and other metabolic-related proteins. Porthos powers up mitochondrial OXPHOS to engender a sufficient ATP supply, which is required for tissue invasion of leading macrophages. Atossa’s two vertebrate orthologs rescue the invasion defect. In my PhD project, I elucidate that Atossa displays a conserved developmental metabolic control to modulate metabolic capacities and the cellular energy state, through altered transcription and translation, to aid the tissue infiltration of leading cells into energy demanding barriers. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: E-Lib - _id: CampIT acknowledgement: Also, I would like to express my appreciation and thanks to the Bioimaging facility, LSF, GSO, library, and IT people at IST Austria. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Shamsi full_name: Emtenani, Shamsi id: 49D32318-F248-11E8-B48F-1D18A9856A87 last_name: Emtenani orcid: 0000-0001-6981-6938 citation: ama: Emtenani S. Metabolic regulation of Drosophila macrophage tissue invasion. 2020. doi:10.15479/AT:ISTA:8983 apa: Emtenani, S. (2020). Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8983 chicago: Emtenani, Shamsi. “Metabolic Regulation of Drosophila Macrophage Tissue Invasion.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8983. ieee: S. Emtenani, “Metabolic regulation of Drosophila macrophage tissue invasion,” Institute of Science and Technology Austria, 2020. ista: Emtenani S. 2020. Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria. mla: Emtenani, Shamsi. Metabolic Regulation of Drosophila Macrophage Tissue Invasion. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8983. short: S. Emtenani, Metabolic Regulation of Drosophila Macrophage Tissue Invasion, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-12-30T15:41:26Z date_published: 2020-12-30T00:00:00Z date_updated: 2026-04-08T07:28:54Z day: '30' ddc: - '570' degree_awarded: PhD department: - _id: DaSi doi: 10.15479/AT:ISTA:8983 file: - access_level: open_access checksum: ec2797ab7a6f253b35df0572b36d1b43 content_type: application/pdf creator: semtenan date_created: 2020-12-30T15:34:01Z date_updated: 2021-12-31T23:30:04Z embargo: 2021-12-30 file_id: '8984' file_name: Thesis_Shamsi_Emtenani_pdfA.pdf file_size: 10848175 relation: main_file - access_level: closed checksum: cc30e6608a9815414024cf548dff3b3a content_type: application/pdf creator: semtenan date_created: 2020-12-30T15:37:36Z date_updated: 2021-12-31T23:30:04Z embargo_to: open_access file_id: '8985' file_name: Thesis_Shamsi_Emtenani_source file.pdf file_size: 10073648 relation: source_file file_date_updated: 2021-12-31T23:30:04Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '141' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '8557' relation: part_of_dissertation status: public - id: '6187' relation: part_of_dissertation status: public status: public supervisor: - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 title: Metabolic regulation of Drosophila macrophage tissue invasion type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '7258' abstract: - lang: eng text: Many flows encountered in nature and applications are characterized by a chaotic motion known as turbulence. Turbulent flows generate intense friction with pipe walls and are responsible for considerable amounts of energy losses at world scale. The nature of turbulent friction and techniques aimed at reducing it have been subject of extensive research over the last century, but no definite answer has been found yet. In this thesis we show that in pipes at moderate turbulent Reynolds numbers friction is better described by the power law first introduced by Blasius and not by the Prandtl–von Kármán formula. At higher Reynolds numbers, large scale motions gradually become more important in the flow and can be related to the change in scaling of friction. Next, we present a series of new techniques that can relaminarize turbulence by suppressing a key mechanism that regenerates it at walls, the lift–up effect. In addition, we investigate the process of turbulence decay in several experiments and discuss the drag reduction potential. Finally, we examine the behavior of friction under pulsating conditions inspired by the human heart cycle and we show that under such circumstances turbulent friction can be reduced to produce energy savings. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Davide full_name: Scarselli, Davide id: 40315C30-F248-11E8-B48F-1D18A9856A87 last_name: Scarselli orcid: 0000-0001-5227-4271 citation: ama: Scarselli D. New approaches to reduce friction in turbulent pipe flow. 2020. doi:10.15479/AT:ISTA:7258 apa: Scarselli, D. (2020). New approaches to reduce friction in turbulent pipe flow. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7258 chicago: Scarselli, Davide. “New Approaches to Reduce Friction in Turbulent Pipe Flow.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7258. ieee: D. Scarselli, “New approaches to reduce friction in turbulent pipe flow,” Institute of Science and Technology Austria, 2020. ista: Scarselli D. 2020. New approaches to reduce friction in turbulent pipe flow. Institute of Science and Technology Austria. mla: Scarselli, Davide. New Approaches to Reduce Friction in Turbulent Pipe Flow. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7258. short: D. Scarselli, New Approaches to Reduce Friction in Turbulent Pipe Flow, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-01-12T16:07:26Z date_published: 2020-01-13T00:00:00Z date_updated: 2026-04-08T07:28:22Z day: '13' ddc: - '532' degree_awarded: PhD department: - _id: BjHo doi: 10.15479/AT:ISTA:7258 ec_funded: 1 file: - access_level: closed checksum: 4df1ab24e9896635106adde5a54615bf content_type: application/zip creator: dscarsel date_created: 2020-01-12T15:57:14Z date_updated: 2021-01-13T23:30:05Z embargo_to: open_access file_id: '7259' file_name: 2020_Scarselli_Thesis.zip file_size: 26640830 relation: source_file - access_level: open_access checksum: 48659ab98e3414293c7a721385c2fd1c content_type: application/pdf creator: dscarsel date_created: 2020-01-12T15:56:14Z date_updated: 2021-01-13T23:30:05Z embargo: 2021-01-12 file_id: '7260' file_name: 2020_Scarselli_Thesis.pdf file_size: 8515844 relation: main_file file_date_updated: 2021-01-13T23:30:05Z has_accepted_license: '1' language: - iso: eng month: '01' oa: 1 oa_version: None page: '174' project: - _id: 25152F3A-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '306589' name: Decoding the complexity of turbulence at its origin - _id: 25104D44-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '737549' name: Eliminating turbulence in oil pipelines - _id: 25136C54-B435-11E9-9278-68D0E5697425 grant_number: HO 4393/1-2 name: Experimental studies of the turbulence transition and transport processes in turbulent Taylor-Couette currents publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '422' relation: part_of_dissertation status: public - id: '461' relation: part_of_dissertation status: public - id: '6228' relation: part_of_dissertation status: public - id: '6486' relation: part_of_dissertation status: public status: public supervisor: - first_name: Björn full_name: Hof, Björn id: 3A374330-F248-11E8-B48F-1D18A9856A87 last_name: Hof orcid: 0000-0003-2057-2754 title: New approaches to reduce friction in turbulent pipe flow type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '8340' abstract: - lang: eng text: Mitochondria are sites of oxidative phosphorylation in eukaryotic cells. Oxidative phosphorylation operates by a chemiosmotic mechanism made possible by redox-driven proton pumping machines which establish a proton motive force across the inner mitochondrial membrane. This electrochemical proton gradient is used to drive ATP synthesis, which powers the majority of cellular processes such as protein synthesis, locomotion and signalling. In this thesis I investigate the structures and molecular mechanisms of two inner mitochondrial proton pumping enzymes, respiratory complex I and transhydrogenase. I present the first high-resolution structure of the full transhydrogenase from any species, and a significantly improved structure of complex I. Improving the resolution from 3.3 Å available previously to up to 2.3 Å in this thesis allowed us to model bound water molecules, crucial in the proton pumping mechanism. For both enzymes, up to five cryo-EM datasets with different substrates and inhibitors bound were solved to delineate the catalytic cycle and understand the proton pumping mechanism. In transhydrogenase, the proton channel is gated by reversible detachment of the NADP(H)-binding domain which opens the proton channel to the opposite sites of the membrane. In complex I, the proton channels are gated by reversible protonation of key glutamate and lysine residues and breaking of the water wire connecting the proton pumps with the quinone reduction site. The tight coupling between the redox and the proton pumping reactions in transhydrogenase is achieved by controlling the NADP(H) exchange which can only happen when the NADP(H)-binding domain interacts with the membrane domain. In complex I, coupling is achieved by cycling of the whole complex between the closed state, in which quinone can get reduced, and the open state, in which NADH can induce quinol ejection from the binding pocket. On the basis of these results I propose detailed mechanisms for catalytic cycles of transhydrogenase and complex I that are consistent with a large amount of previous work. In both enzymes, conformational and electrostatic mechanisms contribute to the overall catalytic process. Results presented here could be used for better understanding of the human pathologies arising from deficiencies of complex I or transhydrogenase and could be used to develop novel therapies. acknowledged_ssus: - _id: EM-Fac acknowledgement: 'I acknowledge the support of IST facilities, especially the Electron Miscroscopy facility for providing training and resources. Special thanks also go to cryo-EM specialists who helped me to collect the data present here: Dr Valentin Hodirnau (IST Austria), Dr Tom Heuser (IMBA, Vienna), Dr Rebecca Thompson (Uni. of Leeds) and Dr Jirka Nováček (CEITEC). This work has been supported by iNEXT, project number 653706, funded by the Horizon 2020 programme of the European Union. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665385.' alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Domen full_name: Kampjut, Domen id: 37233050-F248-11E8-B48F-1D18A9856A87 last_name: Kampjut orcid: 0000-0002-6018-3422 citation: ama: Kampjut D. Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes. 2020. doi:10.15479/AT:ISTA:8340 apa: Kampjut, D. (2020). Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8340 chicago: Kampjut, Domen. “Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping Enzymes.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8340. ieee: D. Kampjut, “Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes,” Institute of Science and Technology Austria, 2020. ista: Kampjut D. 2020. Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes. Institute of Science and Technology Austria. mla: Kampjut, Domen. Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping Enzymes. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8340. short: D. Kampjut, Molecular Mechanisms of Mitochondrial Redox-Coupled Proton Pumping Enzymes, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-09-07T18:42:23Z date_published: 2020-09-09T00:00:00Z date_updated: 2026-04-08T07:43:58Z day: '09' ddc: - '572' degree_awarded: PhD department: - _id: LeSa doi: 10.15479/AT:ISTA:8340 ec_funded: 1 file: - access_level: closed checksum: dd270baf82121eb4472ad19d77bf227c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: dkampjut date_created: 2020-09-08T13:32:06Z date_updated: 2021-09-11T22:30:04Z embargo_to: open_access file_id: '8345' file_name: ThesisFull20200908.docx file_size: 166146359 relation: source_file - access_level: open_access checksum: 82fce6f95ffa47ecc4ebca67ea2cc38c content_type: application/pdf creator: dernst date_created: 2020-09-14T15:02:20Z date_updated: 2021-09-11T22:30:04Z embargo: 2021-09-10 file_id: '8393' file_name: 2020_Thesis_Kampjut.pdf file_size: 13873769 relation: main_file file_date_updated: 2021-09-11T22:30:04Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: None page: '242' project: - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication_identifier: isbn: - 978-3-99078-008-4 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6848' relation: part_of_dissertation status: public status: public supervisor: - first_name: Leonid A full_name: Sazanov, Leonid A id: 338D39FE-F248-11E8-B48F-1D18A9856A87 last_name: Sazanov orcid: 0000-0002-0977-7989 title: Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '7525' abstract: - lang: eng text: "The medial habenula (MHb) is an evolutionary conserved epithalamic structure important for the modulation of emotional memory. It is involved in regulation of anxiety, compulsive behavior, addiction (nicotinic and opioid), sexual and feeding behavior. MHb receives inputs from septal regions and projects exclusively to the interpeduncular nucleus (IPN). Distinct sub-regions of the septum project to different subnuclei of MHb: the bed nucleus of anterior commissure projects to dorsal MHb and the triangular septum projects to ventral MHb. Furthermore, the dorsal and ventral MHb project to the lateral and rostral/central IPN, respectively. Importantly, these projections have unique features of prominent co-release of different neurotransmitters and requirement of a peculiar type of calcium channel for release. In general, synaptic neurotransmission requires an activity-dependent influx of Ca2+ into the presynaptic terminal through voltage-gated calcium channels. The calcium channel family most commonly involved in neurotransmitter release comprises three members, P/Q-, N- and R-type with Cav2.1, Cav2.2 and Cav2.3 subunits, respectively. In contrast to most CNS synapses that mainly express Cav2.1 and/or Cav2.2, MHb terminals in the IPN exclusively express Cav2.3. In other parts of the brain, such as the hippocampus, Cav2.3 is mostly located to postsynaptic elements. This unusual presynaptic location of Cav2.3 in the MHb-IPN pathway implies unique mechanisms of glutamate release in this pathway. One potential example of such uniqueness is the facilitation of release by GABAB receptor (GBR) activation. Presynaptic GBRs usually inhibit the release of neurotransmitters by inhibiting presynaptic calcium channels. MHb shows the highest expression levels of GBR in the brain. GBRs comprise two subunits, GABAB1 (GB1) and GABAB2 (GB2), and are associated with auxiliary subunits, called potassium channel tetramerization domain containing proteins (KCTD) 8, 12, 12b and 16. Among these four subunits, KCTD12b is exclusively expressed in ventral MHb, and KCTD8 shows the strongest expression in the whole MHb among other brain regions, indicating that KCTD8 and KCTD12b may be involved in the unique mechanisms of neurotransmitter release mediated by Cav2.3 and regulated by GBRs in this pathway. \r\nIn the present study, we first verified that neurotransmission in both dorsal and ventral MHb-IPN pathways is mainly mediated by Cav2.3 using a selective blocker of R-type channels, SNX-482. We next found that baclofen, a GBR agonist, has facilitatory effects on release from ventral MHb terminal in rostral IPN, whereas it has inhibitory effects on release from dorsal MHb terminals in lateral IPN, indicating that KCTD12b expressed exclusively in ventral MHb may have a role in the facilitatory effects of GBR activation. In a heterologous expression system using HEK cells, we found that KCTD8 and KCTD12b but not KCTD12 directly bind with Cav2.3. Pre-embedding immunogold electron microscopy data show that Cav2.3 and KCTD12b are distributed most densely in presynaptic active zone in IPN with KCTD12b being present only in rostral/central but not lateral IPN, whereas GABAB, KCTD8 and KCTD12 are distributed most densely in perisynaptic sites with KCTD12 present more frequently in postsynaptic elements and only in rostral/central IPN. In freeze-fracture replica labelling, Cav2.3, KCTD8 and KCTD12b are co-localized with each other in the same active zone indicating that they may form complexes regulating vesicle release in rostral IPN. \r\nOn electrophysiological studies of wild type (WT) mice, we found that paired-pulse ratio in rostral IPN of KCTD12b knock-out (KO) mice is lower than those of WT and KCTD8 KO mice. Consistent with this finding, in mean variance analysis, release probability in rostral IPN of KCTD12b KO mice is higher than that of WT and KCTD8 KO mice. Although paired-pulse ratios are not different between WT and KCTD8 KO mice, the mean variance analysis revealed significantly lower release probability in rostral IPN of KCTD8 KO than WT mice. These results demonstrate bidirectional regulation of Cav2.3-mediated release by KCTD8 and KCTD12b without GBR activation in rostral IPN. Finally, we examined the baclofen effects in rostral IPN of KCTD8 and KCTD12b KO mice, and found the facilitation of release remained in both KO mice, indicating that the peculiar effects of the GBR activation in this pathway do not depend on the selective expression of these KCTD subunits in ventral MHb. However, we found that presynaptic potentiation of evoked EPSC amplitude by baclofen falls to baseline after washout faster in KCTD12b KO mice than WT, KCTD8 KO and KCTD8/12b double KO mice. This result indicates that KCTD12b is involved in sustained potentiation of vesicle release by GBR activation, whereas KCTD8 is involved in its termination in the absence of KCTD12b. Consistent with these functional findings, replica labelling revealed an increase in density of KCTD8, but not Cav2.3 or GBR at active zone in rostral IPN of KCTD12b KO mice compared with that of WT mice, suggesting that increased association of KCTD8 with Cav2.3 facilitates the release probability and termination of the GBR effect in the absence of KCTD12b.\r\nIn summary, our study provided new insights into the physiological roles of presynaptic Cav2.3, GBRs and their auxiliary subunits KCTDs at an evolutionary conserved neuronal circuit. Future studies will be required to identify the exact molecular mechanism underlying the GBR-mediated presynaptic potentiation on ventral MHb terminals. It remains to be determined whether the prominent presence of presynaptic KCTDs at active zone could exert similar neuromodulatory functions in different pathways of the brain.\r\n" acknowledged_ssus: - _id: EM-Fac alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Pradeep full_name: Bhandari, Pradeep id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87 last_name: Bhandari orcid: 0000-0003-0863-4481 citation: ama: Bhandari P. Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. 2020. doi:10.15479/AT:ISTA:7525 apa: Bhandari, P. (2020). Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7525 chicago: Bhandari, Pradeep. “Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7525. ieee: P. Bhandari, “Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway,” Institute of Science and Technology Austria, 2020. ista: Bhandari P. 2020. Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway. Institute of Science and Technology Austria. mla: Bhandari, Pradeep. Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7525. short: P. Bhandari, Localization and Functional Role of Cav2.3 in the Medial Habenula to Interpeduncular Nucleus Pathway, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-02-26T10:56:37Z date_published: 2020-02-28T00:00:00Z date_updated: 2026-04-08T07:27:27Z day: '28' ddc: - '570' degree_awarded: PhD department: - _id: RySh doi: 10.15479/AT:ISTA:7525 file: - access_level: open_access checksum: 4589234fdb12b4ad72273b311723a7b4 content_type: application/pdf creator: pbhandari date_created: 2020-02-28T08:37:53Z date_updated: 2021-03-01T23:30:04Z embargo: 2021-02-28 file_id: '7538' file_name: Pradeep Bhandari Thesis.pdf file_size: 9646346 relation: main_file title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway - access_level: closed checksum: aa79490553ca0a5c9b6fbcd152e93928 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: pbhandari date_created: 2020-02-28T08:47:14Z date_updated: 2021-03-01T23:30:04Z embargo_to: open_access file_id: '7539' file_name: Pradeep Bhandari Thesis.docx file_size: 35252164 relation: source_file title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway file_date_updated: 2021-03-01T23:30:04Z has_accepted_license: '1' keyword: - Cav2.3 - medial habenula (MHb) - interpeduncular nucleus (IPN) language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: '79' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 title: Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ... --- OA_place: publisher _id: '8822' abstract: - lang: eng text: "Self-organization is a hallmark of plant development manifested e.g. by intricate leaf vein patterns, flexible formation of vasculature during organogenesis or its regeneration following wounding. Spontaneously arising channels transporting the phytohormone auxin, created by coordinated polar localizations of PIN-FORMED 1 (PIN1) auxin exporter, provide positional cues for these as well as other plant patterning processes. To find regulators acting downstream of auxin and the TIR1/AFB auxin signaling pathway essential for PIN1 coordinated polarization during auxin canalization, we performed microarray experiments. Besides the known components of general PIN polarity maintenance, such as PID and PIP5K kinases, we identified and characterized a new regulator of auxin canalization, the transcription factor WRKY DNA-BINDING PROTEIN 23 (WRKY23).\r\nNext, we designed a subsequent microarray experiment to further uncover other molecular players, downstream of auxin-TIR1/AFB-WRKY23 involved in the regulation of auxin-mediated PIN repolarization. We identified a novel and crucial part of the molecular machinery underlying auxin canalization. The auxin-regulated malectin-type receptor-like kinase CAMEL and the associated leucine-rich repeat receptor-like kinase CANAR target and directly phosphorylate PIN auxin transporters. camel and canar mutants are impaired in PIN1 subcellular trafficking and auxin-mediated repolarization leading to defects in auxin transport, ultimately to leaf venation and vasculature regeneration defects. Our results describe the CAMEL-CANAR receptor complex, which is required for auxin feed-back on its own transport and thus for coordinated tissue polarization during auxin canalization." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Jakub full_name: Hajny, Jakub id: 4800CC20-F248-11E8-B48F-1D18A9856A87 last_name: Hajny orcid: 0000-0003-2140-7195 citation: ama: Hajny J. Identification and characterization of the molecular machinery of auxin-dependent canalization during vasculature formation and regeneration. 2020. doi:10.15479/AT:ISTA:8822 apa: Hajny, J. (2020). Identification and characterization of the molecular machinery of auxin-dependent canalization during vasculature formation and regeneration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8822 chicago: Hajny, Jakub. “Identification and Characterization of the Molecular Machinery of Auxin-Dependent Canalization during Vasculature Formation and Regeneration.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8822. ieee: J. Hajny, “Identification and characterization of the molecular machinery of auxin-dependent canalization during vasculature formation and regeneration,” Institute of Science and Technology Austria, 2020. ista: Hajny J. 2020. Identification and characterization of the molecular machinery of auxin-dependent canalization during vasculature formation and regeneration. Institute of Science and Technology Austria. mla: Hajny, Jakub. Identification and Characterization of the Molecular Machinery of Auxin-Dependent Canalization during Vasculature Formation and Regeneration. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8822. short: J. Hajny, Identification and Characterization of the Molecular Machinery of Auxin-Dependent Canalization during Vasculature Formation and Regeneration, Institute of Science and Technology Austria, 2020. corr_author: '1' date_created: 2020-12-01T12:38:18Z date_published: 2020-12-01T00:00:00Z date_updated: 2026-06-18T19:02:05Z day: '01' ddc: - '580' degree_awarded: PhD department: - _id: JiFr doi: 10.15479/AT:ISTA:8822 file: - access_level: closed checksum: 210a9675af5e4c78b0b56d920ac82866 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: jhajny date_created: 2020-12-04T07:27:52Z date_updated: 2021-07-16T22:30:03Z embargo_to: open_access file_id: '8919' file_name: Jakub Hajný IST Austria final_JH.docx file_size: 91279806 relation: source_file - access_level: open_access checksum: 1781385b4aa73eba89cc76c6172f71d2 content_type: application/pdf creator: jhajny date_created: 2020-12-09T15:04:41Z date_updated: 2021-12-08T23:30:03Z embargo: 2021-12-07 file_id: '8933' file_name: Jakub Hajný IST Austria final_JH-merged without Science.pdf file_size: 68707697 relation: main_file file_date_updated: 2021-12-08T23:30:03Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '249' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '449' relation: part_of_dissertation status: public - id: '7500' relation: part_of_dissertation status: public - id: '7427' relation: part_of_dissertation status: public - id: '191' relation: part_of_dissertation status: public - id: '6260' relation: part_of_dissertation status: public status: public supervisor: - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 title: Identification and characterization of the molecular machinery of auxin-dependent canalization during vasculature formation and regeneration type: dissertation user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd year: '2020' ...