--- _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. date_created: 2020-07-23T09:51:28Z date_published: 2020-07-24T00:00:00Z date_updated: 2023-09-07T13:13:27Z 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: '7675' relation: part_of_dissertation status: public - id: '7569' relation: part_of_dissertation status: public - id: '7652' 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _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. date_created: 2020-02-06T14:56:53Z date_published: 2020-02-10T00:00:00Z date_updated: 2023-09-07T13:15:30Z 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _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 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. date_created: 2020-05-26T14:08:55Z date_published: 2020-05-25T00:00:00Z date_updated: 2023-09-07T13:15:55Z day: '25' ddc: - '000' degree_awarded: PhD department: - _id: KrPi doi: 10.15479/AT:ISTA:7896 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '7944' abstract: - lang: eng text: "This thesis considers two examples of reconfiguration problems: flipping edges in edge-labelled triangulations of planar point sets and swapping labelled tokens placed on vertices of a graph. In both cases the studied structures – all the triangulations of a given point set or all token placements on a given graph – can be thought of as vertices of the so-called reconfiguration graph, in which two vertices are adjacent if the corresponding structures differ by a single elementary operation – by a flip of a diagonal in a triangulation or by a swap of tokens on adjacent vertices, respectively. We study the reconfiguration of one instance of a structure into another via (shortest) paths in the reconfiguration graph.\r\n\r\nFor triangulations of point sets in which each edge has a unique label and a flip transfers the label from the removed edge to the new edge, we prove a polynomial-time testable condition, called the Orbit Theorem, that characterizes when two triangulations of the same point set lie in the same connected component of the reconfiguration graph. The condition was first conjectured by Bose, Lubiw, Pathak and Verdonschot. We additionally provide a polynomial time algorithm that computes a reconfiguring flip sequence, if it exists. Our proof of the Orbit Theorem uses topological properties of a certain high-dimensional cell complex that has the usual reconfiguration graph as its 1-skeleton.\r\n\r\nIn the context of token swapping on a tree graph, we make partial progress on the problem of finding shortest reconfiguration sequences. We disprove the so-called Happy Leaf Conjecture and demonstrate the importance of swapping tokens that are already placed at the correct vertices. We also prove that a generalization of the problem to weighted coloured token swapping is NP-hard on trees but solvable in polynomial time on paths and stars." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Zuzana full_name: Masárová, Zuzana id: 45CFE238-F248-11E8-B48F-1D18A9856A87 last_name: Masárová orcid: 0000-0002-6660-1322 citation: ama: Masárová Z. Reconfiguration problems. 2020. doi:10.15479/AT:ISTA:7944 apa: Masárová, Z. (2020). Reconfiguration problems. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7944 chicago: Masárová, Zuzana. “Reconfiguration Problems.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7944. ieee: Z. Masárová, “Reconfiguration problems,” Institute of Science and Technology Austria, 2020. ista: Masárová Z. 2020. Reconfiguration problems. Institute of Science and Technology Austria. mla: Masárová, Zuzana. Reconfiguration Problems. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7944. short: Z. Masárová, Reconfiguration Problems, Institute of Science and Technology Austria, 2020. date_created: 2020-06-08T00:49:46Z date_published: 2020-06-09T00:00:00Z date_updated: 2023-09-07T13:17:37Z day: '09' ddc: - '516' - '514' degree_awarded: PhD department: - _id: HeEd - _id: UlWa doi: 10.15479/AT:ISTA:7944 file: - access_level: open_access checksum: df688bc5a82b50baee0b99d25fc7b7f0 content_type: application/pdf creator: zmasarov date_created: 2020-06-08T00:34:00Z date_updated: 2020-07-14T12:48:05Z file_id: '7945' file_name: THESIS_Zuzka_Masarova.pdf file_size: 13661779 relation: main_file - access_level: closed checksum: 45341a35b8f5529c74010b7af43ac188 content_type: application/zip creator: zmasarov date_created: 2020-06-08T00:35:30Z date_updated: 2020-07-14T12:48:05Z file_id: '7946' file_name: THESIS_Zuzka_Masarova_SOURCE_FILES.zip file_size: 32184006 relation: source_file file_date_updated: 2020-07-14T12:48:05Z has_accepted_license: '1' keyword: - reconfiguration - reconfiguration graph - triangulations - flip - constrained triangulations - shellability - piecewise-linear balls - token swapping - trees - coloured weighted token swapping language: - iso: eng license: https://creativecommons.org/licenses/by-sa/4.0/ month: '06' oa: 1 oa_version: Published Version page: '160' publication_identifier: isbn: - 978-3-99078-005-3 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7950' relation: part_of_dissertation status: public - id: '5986' relation: part_of_dissertation status: public status: public supervisor: - first_name: Uli full_name: Wagner, Uli id: 36690CA2-F248-11E8-B48F-1D18A9856A87 last_name: Wagner orcid: 0000-0002-1494-0568 - first_name: Herbert full_name: Edelsbrunner, Herbert id: 3FB178DA-F248-11E8-B48F-1D18A9856A87 last_name: Edelsbrunner orcid: 0000-0002-9823-6833 title: Reconfiguration problems tmp: image: /images/cc_by_sa.png legal_code_url: https://creativecommons.org/licenses/by-sa/4.0/legalcode name: Creative Commons Attribution-ShareAlike 4.0 International Public License (CC BY-SA 4.0) short: CC BY-SA (4.0) type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _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. date_created: 2020-09-08T08:53:53Z date_published: 2020-09-08T00:00:00Z date_updated: 2023-09-07T13:17:06Z 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 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '8032' abstract: - lang: eng text: "Algorithms in computational 3-manifold topology typically take a triangulation as an input and return topological information about the underlying 3-manifold. However, extracting the desired information from a triangulation (e.g., evaluating an invariant) is often computationally very expensive. In recent years this complexity barrier has been successfully tackled in some cases by importing ideas from the theory of parameterized algorithms into the realm of 3-manifolds. Various computationally hard problems were shown to be efficiently solvable for input triangulations that are sufficiently “tree-like.”\r\nIn this thesis we focus on the key combinatorial parameter in the above context: we consider the treewidth of a compact, orientable 3-manifold, i.e., the smallest treewidth of the dual graph of any triangulation thereof. By building on the work of Scharlemann–Thompson and Scharlemann–Schultens–Saito on generalized Heegaard splittings, and on the work of Jaco–Rubinstein on layered triangulations, we establish quantitative relations between the treewidth and classical topological invariants of a 3-manifold. In particular, among other results, we show that the treewidth of a closed, orientable, irreducible, non-Haken 3-manifold is always within a constant factor of its Heegaard genus." acknowledged_ssus: - _id: E-Lib - _id: CampIT alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Kristóf full_name: Huszár, Kristóf id: 33C26278-F248-11E8-B48F-1D18A9856A87 last_name: Huszár orcid: 0000-0002-5445-5057 citation: ama: Huszár K. Combinatorial width parameters for 3-dimensional manifolds. 2020. doi:10.15479/AT:ISTA:8032 apa: Huszár, K. (2020). Combinatorial width parameters for 3-dimensional manifolds. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8032 chicago: Huszár, Kristóf. “Combinatorial Width Parameters for 3-Dimensional Manifolds.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8032. ieee: K. Huszár, “Combinatorial width parameters for 3-dimensional manifolds,” Institute of Science and Technology Austria, 2020. ista: Huszár K. 2020. Combinatorial width parameters for 3-dimensional manifolds. Institute of Science and Technology Austria. mla: Huszár, Kristóf. Combinatorial Width Parameters for 3-Dimensional Manifolds. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8032. short: K. Huszár, Combinatorial Width Parameters for 3-Dimensional Manifolds, Institute of Science and Technology Austria, 2020. date_created: 2020-06-26T10:00:36Z date_published: 2020-06-26T00:00:00Z date_updated: 2023-09-07T13:18:27Z day: '26' ddc: - '514' degree_awarded: PhD department: - _id: UlWa doi: 10.15479/AT:ISTA:8032 file: - access_level: open_access checksum: bd8be6e4f1addc863dfcc0fad29ee9c3 content_type: application/pdf creator: khuszar date_created: 2020-06-26T10:03:58Z date_updated: 2020-07-14T12:48:08Z file_id: '8034' file_name: Kristof_Huszar-Thesis.pdf file_size: 2637562 relation: main_file - access_level: closed checksum: d5f8456202b32f4a77552ef47a2837d1 content_type: application/x-zip-compressed creator: khuszar date_created: 2020-06-26T10:10:06Z date_updated: 2020-07-14T12:48:08Z file_id: '8035' file_name: Kristof_Huszar-Thesis-source.zip file_size: 7163491 relation: source_file file_date_updated: 2020-07-14T12:48:08Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: xviii+120 publication_identifier: isbn: - 978-3-99078-006-0 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6556' relation: dissertation_contains status: public - id: '7093' relation: dissertation_contains status: public status: public supervisor: - first_name: Uli full_name: Wagner, Uli id: 36690CA2-F248-11E8-B48F-1D18A9856A87 last_name: Wagner orcid: 0000-0002-1494-0568 - first_name: Jonathan full_name: Spreer, Jonathan last_name: Spreer title: Combinatorial width parameters for 3-dimensional manifolds 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _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. date_created: 2020-09-10T09:26:49Z date_published: 2020-09-10T00:00:00Z date_updated: 2023-09-07T13:18:51Z 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 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: '7572' relation: dissertation_contains status: public - id: '7197' 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: 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _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.' date_created: 2020-09-04T12:24:12Z date_published: 2020-09-03T00:00:00Z date_updated: 2023-09-13T08:45:08Z 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: '133' relation: part_of_dissertation status: public - id: '8012' relation: part_of_dissertation status: public - id: '8195' relation: part_of_dissertation status: public - id: '160' 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _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. date_created: 2020-12-21T09:44:30Z date_published: 2020-12-21T00:00:00Z date_updated: 2023-09-20T11:30:58Z 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: '5886' relation: part_of_dissertation status: public - id: '8587' relation: part_of_dissertation status: public - id: '1120' 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _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. date_created: 2020-09-14T01:04:53Z date_published: 2020-09-14T00:00:00Z date_updated: 2023-09-22T09:49:31Z 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '7996' abstract: - lang: eng text: "Quantum computation enables the execution of algorithms that have exponential complexity. This might open the path towards the synthesis of new materials or medical drugs, optimization of transport or financial strategies etc., intractable on even the fastest classical computers. A quantum computer consists of interconnected two level quantum systems, called qubits, that satisfy DiVincezo’s criteria. Worldwide, there are ongoing efforts to find the qubit architecture which will unite quantum error correction compatible single and two qubit fidelities, long distance qubit to qubit coupling and \r\n calability. Superconducting qubits have gone the furthest in this race, demonstrating an algorithm running on 53 coupled qubits, but still the fidelities are not even close to those required for realizing a single logical qubit. emiconductor qubits offer extremely good characteristics, but they are currently investigated across different platforms. Uniting those good characteristics into a single platform might be a big step towards the quantum computer realization.\r\nHere we describe the implementation of a hole spin qubit hosted in a Ge hut wire double quantum dot. The high and tunable spin-orbit coupling together with a heavy hole state character is expected to allow fast spin manipulation and long coherence times. Furthermore large lever arms, for hut wire devices, should allow good coupling to superconducting resonators enabling efficient long distance spin to spin coupling and a sensitive gate reflectometry spin readout. The developed cryogenic setup (printed circuit board sample holders, filtering, high-frequency wiring) enabled us to perform low temperature spin dynamics experiments. Indeed, we measured the fastest single spin qubit Rabi frequencies reported so far, reaching 140 MHz, while the dephasing times of 130 ns oppose the long decoherence predictions. In order to further investigate this, a double quantum dot gate was connected directly to a lumped element\r\nresonator which enabled gate reflectometry readout. The vanishing inter-dot transition signal, for increasing external magnetic field, revealed the spin nature of the measured quantity." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Josip full_name: Kukucka, Josip id: 3F5D8856-F248-11E8-B48F-1D18A9856A87 last_name: Kukucka citation: ama: Kukucka J. Implementation of a hole spin qubit in Ge hut wires and dispersive spin sensing. 2020. doi:10.15479/AT:ISTA:7996 apa: Kukucka, J. (2020). Implementation of a hole spin qubit in Ge hut wires and dispersive spin sensing. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7996 chicago: Kukucka, Josip. “Implementation of a Hole Spin Qubit in Ge Hut Wires and Dispersive Spin Sensing.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7996. ieee: J. Kukucka, “Implementation of a hole spin qubit in Ge hut wires and dispersive spin sensing,” Institute of Science and Technology Austria, 2020. ista: Kukucka J. 2020. Implementation of a hole spin qubit in Ge hut wires and dispersive spin sensing. Institute of Science and Technology Austria. mla: Kukucka, Josip. Implementation of a Hole Spin Qubit in Ge Hut Wires and Dispersive Spin Sensing. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7996. short: J. Kukucka, Implementation of a Hole Spin Qubit in Ge Hut Wires and Dispersive Spin Sensing, Institute of Science and Technology Austria, 2020. date_created: 2020-06-22T09:22:23Z date_published: 2020-06-22T00:00:00Z date_updated: 2023-09-26T15:50:22Z day: '22' ddc: - '530' degree_awarded: PhD department: - _id: GeKa doi: 10.15479/AT:ISTA:7996 file: - access_level: closed checksum: 467e52feb3e361ce8cf5fe8d5c254ece content_type: application/x-zip-compressed creator: dernst date_created: 2020-06-22T09:22:04Z date_updated: 2020-07-14T12:48:07Z file_id: '7997' file_name: JK_thesis_latex_source_files.zip file_size: 392794743 relation: main_file - access_level: open_access checksum: 1de716bf110dbd77d383e479232bf496 content_type: application/pdf creator: dernst date_created: 2020-06-22T09:21:29Z date_updated: 2020-07-14T12:48:07Z file_id: '7998' file_name: PhD_thesis_JK_pdfa.pdf file_size: 28453247 relation: main_file file_date_updated: 2020-07-14T12:48:07Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '178' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '1328' relation: part_of_dissertation status: public - id: '7541' relation: part_of_dissertation status: public - id: '77' relation: part_of_dissertation status: public - id: '23' relation: part_of_dissertation status: public - id: '840' relation: part_of_dissertation status: public status: public supervisor: - first_name: Georgios full_name: Katsaros, Georgios id: 38DB5788-F248-11E8-B48F-1D18A9856A87 last_name: Katsaros orcid: 0000-0001-8342-202X title: Implementation of a hole spin qubit in Ge hut wires and dispersive spin sensing type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _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. date_created: 2020-09-14T13:42:09Z date_published: 2020-09-14T00:00:00Z date_updated: 2023-10-16T10:04:02Z 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: '7937' relation: part_of_dissertation status: public - id: '8193' relation: part_of_dissertation status: public - id: '8092' relation: part_of_dissertation status: public - id: '911' 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '7196' abstract: - lang: eng text: 'In this thesis we study certain mathematical aspects of evolution. The two primary forces that drive an evolutionary process are mutation and selection. Mutation generates new variants in a population. Selection chooses among the variants depending on the reproductive rates of individuals. Evolutionary processes are intrinsically random – a new mutation that is initially present in the population at low frequency can go extinct, even if it confers a reproductive advantage. The overall rate of evolution is largely determined by two quantities: the probability that an invading advantageous mutation spreads through the population (called fixation probability) and the time until it does so (called fixation time). Both those quantities crucially depend not only on the strength of the invading mutation but also on the population structure. In this thesis, we aim to understand how the underlying population structure affects the overall rate of evolution. Specifically, we study population structures that increase the fixation probability of advantageous mutants (called amplifiers of selection). Broadly speaking, our results are of three different types: We present various strong amplifiers, we identify regimes under which only limited amplification is feasible, and we propose population structures that provide different tradeoffs between high fixation probability and short fixation time.' alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Josef full_name: Tkadlec, Josef id: 3F24CCC8-F248-11E8-B48F-1D18A9856A87 last_name: Tkadlec orcid: 0000-0002-1097-9684 citation: ama: Tkadlec J. A role of graphs in evolutionary processes. 2020. doi:10.15479/AT:ISTA:7196 apa: Tkadlec, J. (2020). A role of graphs in evolutionary processes. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7196 chicago: Tkadlec, Josef. “A Role of Graphs in Evolutionary Processes.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7196. ieee: J. Tkadlec, “A role of graphs in evolutionary processes,” Institute of Science and Technology Austria, 2020. ista: Tkadlec J. 2020. A role of graphs in evolutionary processes. Institute of Science and Technology Austria. mla: Tkadlec, Josef. A Role of Graphs in Evolutionary Processes. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7196. short: J. Tkadlec, A Role of Graphs in Evolutionary Processes, Institute of Science and Technology Austria, 2020. date_created: 2019-12-20T12:26:36Z date_published: 2020-01-12T00:00:00Z date_updated: 2023-10-17T12:29:46Z day: '12' ddc: - '519' degree_awarded: PhD department: - _id: KrCh - _id: GradSch doi: 10.15479/AT:ISTA:7196 file: - access_level: closed checksum: 451f8e64b0eb26bf297644ac72bfcbe9 content_type: application/zip creator: jtkadlec date_created: 2020-01-12T11:49:49Z date_updated: 2020-07-14T12:47:52Z file_id: '7255' file_name: thesis.zip file_size: 21100497 relation: source_file - access_level: open_access checksum: d8c44cbc4f939c49a8efc9d4b8bb3985 content_type: application/pdf creator: dernst date_created: 2020-01-28T07:32:42Z date_updated: 2020-07-14T12:47:52Z file_id: '7367' file_name: 2020_Tkadlec_Thesis.pdf file_size: 11670983 relation: main_file file_date_updated: 2020-07-14T12:47:52Z has_accepted_license: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: '144' publication_identifier: eissn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7210' relation: dissertation_contains status: public - id: '5751' relation: dissertation_contains status: public - id: '7212' relation: dissertation_contains status: public status: public supervisor: - first_name: Krishnendu full_name: Chatterjee, Krishnendu id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87 last_name: Chatterjee orcid: 0000-0002-4561-241X title: A role of graphs in evolutionary processes type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '8156' abstract: - lang: eng text: 'We present solutions to several problems originating from geometry and discrete mathematics: existence of equipartitions, maps without Tverberg multiple points, and inscribing quadrilaterals. Equivariant obstruction theory is the natural topological approach to these type of questions. However, for the specific problems we consider it had yielded only partial or no results. We get our results by complementing equivariant obstruction theory with other techniques from topology and geometry.' alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Sergey full_name: Avvakumov, Sergey id: 3827DAC8-F248-11E8-B48F-1D18A9856A87 last_name: Avvakumov citation: ama: Avvakumov S. Topological methods in geometry and discrete mathematics. 2020. doi:10.15479/AT:ISTA:8156 apa: Avvakumov, S. (2020). Topological methods in geometry and discrete mathematics. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8156 chicago: Avvakumov, Sergey. “Topological Methods in Geometry and Discrete Mathematics.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8156. ieee: S. Avvakumov, “Topological methods in geometry and discrete mathematics,” Institute of Science and Technology Austria, 2020. ista: Avvakumov S. 2020. Topological methods in geometry and discrete mathematics. Institute of Science and Technology Austria. mla: Avvakumov, Sergey. Topological Methods in Geometry and Discrete Mathematics. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8156. short: S. Avvakumov, Topological Methods in Geometry and Discrete Mathematics, Institute of Science and Technology Austria, 2020. date_created: 2020-07-23T09:51:29Z date_published: 2020-07-24T00:00:00Z date_updated: 2023-12-18T10:51:01Z day: '24' ddc: - '514' degree_awarded: PhD department: - _id: UlWa doi: 10.15479/AT:ISTA:8156 file: - access_level: closed content_type: application/zip creator: savvakum date_created: 2020-07-27T12:44:51Z date_updated: 2020-07-27T12:44:51Z file_id: '8178' file_name: source.zip file_size: 1061740 relation: source_file - access_level: open_access content_type: application/pdf creator: savvakum date_created: 2020-07-27T12:46:53Z date_updated: 2020-07-27T12:46:53Z file_id: '8179' file_name: thesis_pdfa.pdf file_size: 1336501 relation: main_file success: 1 file_date_updated: 2020-07-27T12:46:53Z has_accepted_license: '1' language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '119' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '8182' relation: part_of_dissertation status: public - id: '8183' relation: part_of_dissertation status: public - id: '8185' relation: part_of_dissertation status: public - id: '8184' relation: part_of_dissertation status: public - id: '6355' relation: part_of_dissertation status: public - id: '75' relation: part_of_dissertation status: public status: public supervisor: - first_name: Uli full_name: Wagner, Uli id: 36690CA2-F248-11E8-B48F-1D18A9856A87 last_name: Wagner orcid: 0000-0002-1494-0568 title: Topological methods in geometry and discrete mathematics type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _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.' date_created: 2020-09-10T16:19:55Z date_published: 2020-09-21T00:00:00Z date_updated: 2024-02-21T12:44:29Z 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: '7151' relation: research_data status: deleted - id: '7262' relation: part_of_dissertation status: public - id: '8562' relation: part_of_dissertation status: public - id: '1001' relation: part_of_dissertation status: public - id: '8375' relation: research_data 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _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. date_created: 2020-02-26T10:56:37Z date_published: 2020-02-28T00:00:00Z date_updated: 2023-09-07T13:20:03Z 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '8657' abstract: - lang: eng text: "Synthesis of proteins – translation – is a fundamental process of life. Quantitative studies anchor translation into the context of bacterial physiology and reveal several mathematical relationships, called “growth laws,” which capture physiological feedbacks between protein synthesis and cell growth. Growth laws describe the dependency of the ribosome abundance as a function of growth rate, which can change depending on the growth conditions. Perturbations of translation reveal that bacteria employ a compensatory strategy in which the reduced translation capability results in increased expression of the translation machinery.\r\nPerturbations of translation are achieved in various ways; clinically interesting is the application of translation-targeting antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology are often poorly understood. Bacterial responses to two or more simultaneously applied antibiotics are even more puzzling. The combined antibiotic effect determines the type of drug interaction, which ranges from synergy (the effect is stronger than expected) to antagonism (the effect is weaker) and suppression (one of the drugs loses its potency).\r\nIn the first part of this work, we systematically measure the pairwise interaction network for translation inhibitors that interfere with different steps in translation. We find that the interactions are surprisingly diverse and tend to be more antagonistic. To explore the underlying mechanisms, we begin with a minimal biophysical model of combined antibiotic action. We base this model on the kinetics of antibiotic uptake and binding together with the physiological response described by the growth laws. The biophysical model explains some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn the second part of this work, we hypothesize that elusive suppressive drug interactions result from the interplay between ribosomes halted in different stages of translation. To elucidate this putative mechanism of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using in- ducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks partially causes these interactions.\r\nWe extend this approach by varying two translation bottlenecks simultaneously. This approach reveals the suppression of translocation inhibition by inhibited translation. We rationalize this effect by modeling dense traffic of ribosomes that move on transcripts in a translation factor-mediated manner. This model predicts a dissolution of traffic jams caused by inhibited translocation when the density of ribosome traffic is reduced by lowered initiation. We base this model on the growth laws and quantitative relationships between different translation and growth parameters.\r\nIn the final part of this work, we describe a set of tools aimed at quantification of physiological and translation parameters. We further develop a simple model that directly connects the abundance of a translation factor with the growth rate, which allows us to extract physiological parameters describing initiation. We demonstrate the development of tools for measuring translation rate.\r\nThis thesis showcases how a combination of high-throughput growth rate mea- surements, genetics, and modeling can reveal mechanisms of drug interactions. Furthermore, by a gradual transition from combinations of antibiotics to precise genetic interventions, we demonstrated the equivalency between genetic and chemi- cal perturbations of translation. These findings tile the path for quantitative studies of antibiotic combinations and illustrate future approaches towards the quantitative description of translation." acknowledged_ssus: - _id: LifeSc - _id: M-Shop acknowledgement: I thank Life Science Facilities for their continuous support with providing top-notch laboratory materials, keeping the devices humming, and coordinating the repairs and building of custom-designed laboratory equipment with the MIBA Machine shop. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Bor full_name: Kavcic, Bor id: 350F91D2-F248-11E8-B48F-1D18A9856A87 last_name: Kavcic orcid: 0000-0001-6041-254X citation: ama: 'Kavcic B. Perturbations of protein synthesis: from antibiotics to genetics and physiology. 2020. doi:10.15479/AT:ISTA:8657' apa: 'Kavcic, B. (2020). Perturbations of protein synthesis: from antibiotics to genetics and physiology. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8657' chicago: 'Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8657.' ieee: 'B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics and physiology,” Institute of Science and Technology Austria, 2020.' ista: 'Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics and physiology. Institute of Science and Technology Austria.' mla: 'Kavcic, Bor. Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8657.' short: 'B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology, Institute of Science and Technology Austria, 2020.' date_created: 2020-10-13T16:46:14Z date_published: 2020-10-14T00:00:00Z date_updated: 2023-09-07T13:20:48Z day: '14' ddc: - '571' - '530' - '570' degree_awarded: PhD department: - _id: GaTk doi: 10.15479/AT:ISTA:8657 file: - access_level: open_access checksum: d708ecd62b6fcc3bc1feb483b8dbe9eb content_type: application/pdf creator: bkavcic date_created: 2020-10-15T06:41:20Z date_updated: 2021-10-07T22:30:03Z embargo: 2021-10-06 file_id: '8663' file_name: kavcicB_thesis202009.pdf file_size: 52636162 relation: main_file - access_level: closed checksum: bb35f2352a04db19164da609f00501f3 content_type: application/zip creator: bkavcic date_created: 2020-10-15T06:41:53Z date_updated: 2021-10-07T22:30:03Z embargo_to: open_access file_id: '8664' file_name: 2020b.zip file_size: 321681247 relation: source_file file_date_updated: 2021-10-07T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '271' publication_identifier: isbn: - 978-3-99078-011-4 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7673' relation: part_of_dissertation status: public - id: '8250' relation: part_of_dissertation status: public status: public supervisor: - first_name: Gašper full_name: Tkačik, Gašper id: 3D494DCA-F248-11E8-B48F-1D18A9856A87 last_name: Tkačik orcid: 0000-0002-6699-1455 - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X title: 'Perturbations of protein synthesis: from antibiotics to genetics and physiology' type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '7680' abstract: - lang: eng text: "Proteins and their complex dynamic interactions regulate cellular mechanisms from sensing and transducing extracellular signals, to mediating genetic responses, and sustaining or changing cell morphology. To manipulate these protein-protein interactions (PPIs) that govern the behavior and fate of cells, synthetically constructed, genetically encoded tools provide the means to precisely target proteins of interest (POIs), and control their subcellular localization and activity in vitro and in vivo. Ideal synthetic tools react to an orthogonal cue, i.e. a trigger that does not activate any other endogenous process, thereby allowing manipulation of the POI alone.\r\nIn optogenetics, naturally occurring photosensory domain from plants, algae and bacteria are re-purposed and genetically fused to POIs. Illumination with light of a specific wavelength triggers a conformational change that can mediate PPIs, such as dimerization or oligomerization. By using light as a trigger, these tools can be activated with high spatial and temporal precision, on subcellular and millisecond scales. Chemogenetic tools consist of protein domains that recognize and bind small molecules. By genetic fusion to POIs, these domains can mediate PPIs upon addition of their specific ligands, which are often synthetically designed to provide highly specific interactions and exhibit good bioavailability.\r\nMost optogenetic tools to mediate PPIs are based on well-studied photoreceptors responding to red, blue or near-UV light, leaving a striking gap in the green band of the visible light spectrum. Among both optogenetic and chemogenetic tools, there is an abundance of methods to induce PPIs, but tools to disrupt them require UV illumination, rely on covalent linkage and subsequent enzymatic cleavage or initially result in protein clustering of unknown stoichiometry.\r\nThis work describes how the recently structurally and photochemically characterized green-light responsive cobalamin-binding domains (CBDs) from bacterial transcription factors were re-purposed to function as a green-light responsive optogenetic tool. In contrast to previously engineered optogenetic tools, CBDs do not induce PPI, but rather confer a PPI already upon expression, which can be rapidly disrupted by illumination. This was employed to mimic inhibition of constitutive activity of a growth factor receptor, and successfully implement for cell signalling in mammalian cells and in vivo to rescue development in zebrafish. This work further describes the development and application of a chemically induced de-dimerizer (CDD) based on a recently identified and structurally described bacterial oxyreductase. CDD forms a dimer upon expression in absence of its cofactor, the flavin derivative F420. Safety and of domain expression and ligand exposure are demonstrated in vitro and in vivo in zebrafish. The system is further applied to inhibit cell signalling output from a chimeric receptor upon F420 treatment.\r\nCBDs and CDD expand the repertoire of synthetic tools by providing novel mechanisms of mediating PPIs, and by recognizing previously not utilized cues. In the future, they can readily be combined with existing synthetic tools to functionally manipulate PPIs in vitro and in vivo." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Stephanie full_name: Kainrath, Stephanie id: 32CFBA64-F248-11E8-B48F-1D18A9856A87 last_name: Kainrath citation: ama: Kainrath S. Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. 2020. doi:10.15479/AT:ISTA:7680 apa: Kainrath, S. (2020). Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7680 chicago: Kainrath, Stephanie. “Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7680. ieee: S. Kainrath, “Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals,” Institute of Science and Technology Austria, 2020. ista: Kainrath S. 2020. Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. Institute of Science and Technology Austria. mla: Kainrath, Stephanie. Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7680. short: S. Kainrath, Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals, Institute of Science and Technology Austria, 2020. date_created: 2020-04-24T16:00:51Z date_published: 2020-04-24T00:00:00Z date_updated: 2023-09-22T09:20:10Z day: '24' ddc: - '570' degree_awarded: PhD department: - _id: CaGu doi: 10.15479/AT:ISTA:7680 file: - access_level: open_access checksum: fb9a4468eb27be92690728e35c823796 content_type: application/pdf creator: stgingl date_created: 2020-04-28T11:19:21Z date_updated: 2021-10-31T23:30:05Z embargo: 2021-10-30 file_id: '7692' file_name: Thesis_without-signatures_PDFA.pdf file_size: 3268017 relation: main_file - access_level: closed checksum: f6c80ca97104a631a328cb79a2c53493 content_type: application/octet-stream creator: stgingl date_created: 2020-04-28T11:19:24Z date_updated: 2021-10-31T23:30:05Z embargo_to: open_access file_id: '7693' file_name: Thesis_without signatures.docx file_size: 5167703 relation: source_file file_date_updated: 2021-10-31T23:30:05Z has_accepted_license: '1' language: - iso: eng month: '04' oa: 1 oa_version: None page: '98' publication_identifier: eissn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '1028' relation: dissertation_contains status: public status: public supervisor: - first_name: Harald L full_name: Janovjak, Harald L id: 33BA6C30-F248-11E8-B48F-1D18A9856A87 last_name: Janovjak orcid: 0000-0002-8023-9315 title: Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '8620' abstract: - lang: eng text: "The development of the human brain occurs through a tightly regulated series of dynamic and adaptive processes during prenatal and postnatal life. A disruption of this strictly orchestrated series of events can lead to a number of neurodevelopmental conditions, including Autism Spectrum Disorders (ASDs). ASDs are a very common, etiologically and phenotypically heterogeneous group of disorders sharing the core symptoms of social interaction and communication deficits and restrictive and repetitive interests and behaviors. They are estimated to affect one in 59 individuals in the U.S. and, over the last three decades, mutations in more than a hundred genetic loci have been convincingly linked to ASD pathogenesis. Yet, for the vast majority of these ASD-risk genes their role during brain development and precise molecular function still remain elusive.\r\nDe novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin 3 (CUL3) lead to ASD. In the study described here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 heterozygous knockout mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3+/-, Cul3+/fl Emx1-Cre and Cul3fl/fl Emx1-Cre mutant brains display cortical lamination abnormalities due to defective migration of post-mitotic excitatory neurons, as well as reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal cortical organization, Cul3 heterozygous deletion is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level we show that Cul3 regulates cytoskeletal and adhesion protein abundance in the mouse embryonic cortex. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neural cells results in atypical organization of the actin mesh at the cell leading edge. Of note, heterozygous deletion of Cul3 in adult mice does not induce the majority of the behavioral defects observed in constitutive Cul3 haploinsufficient animals, pointing to a critical time-window for Cul3 deficiency.\r\nIn conclusion, our data indicate that Cul3 plays a critical role in the regulation of cytoskeletal proteins and neuronal migration. ASD-associated defects and behavioral abnormalities are primarily due to dosage sensitive Cul3 functions at early brain developmental stages." acknowledged_ssus: - _id: Bio - _id: PreCl acknowledgement: I would like to especially thank Armel Nicolas from the Proteomics and Christoph Sommer from the Bioimaging Facilities for the data analysis, and to thank the team of the Preclinical Facility, especially Sabina Deixler, Angela Schlerka, Anita Lepold, Mihalea Mihai and Michael Schun for taking care of the mouse line maintenance and their great support. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell citation: ama: Morandell J. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. 2020. doi:10.15479/AT:ISTA:8620 apa: Morandell, J. (2020). Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8620 chicago: Morandell, Jasmin. “Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8620. ieee: J. Morandell, “Illuminating the role of Cul3 in autism spectrum disorder pathogenesis,” Institute of Science and Technology Austria, 2020. ista: Morandell J. 2020. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria. mla: Morandell, Jasmin. Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8620. short: J. Morandell, Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis, Institute of Science and Technology Austria, 2020. date_created: 2020-10-07T14:53:13Z date_published: 2020-10-12T00:00:00Z date_updated: 2023-09-07T13:22:14Z day: '12' ddc: - '610' degree_awarded: PhD department: - _id: GaNo doi: 10.15479/AT:ISTA:8620 file: - access_level: open_access checksum: 7ee83e42de3e5ce2fedb44dff472f75f content_type: application/pdf creator: jmorande date_created: 2020-10-07T14:41:49Z date_updated: 2021-10-16T22:30:04Z embargo: 2021-10-15 file_id: '8621' file_name: Jasmin_Morandell_Thesis-2020_final.pdf file_size: 16155786 relation: main_file - access_level: closed checksum: 5e0464af453734210ce7aab7b4a92e3a content_type: application/x-zip-compressed creator: jmorande date_created: 2020-10-07T14:45:07Z date_updated: 2021-10-16T22:30:04Z embargo_to: open_access file_id: '8622' file_name: Jasmin_Morandell_Thesis-2020_final.zip file_size: 24344152 relation: source_file file_date_updated: 2021-10-16T22:30:04Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '138' project: - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 05A0D778-7A3F-11EA-A408-12923DDC885E grant_number: F07807 name: Neural stem cells in autism and epilepsy publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '7800' relation: part_of_dissertation status: public - id: '8131' relation: part_of_dissertation status: public status: public supervisor: - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 title: Illuminating the role of Cul3 in autism spectrum disorder pathogenesis type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _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 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. date_created: 2020-09-07T18:42:23Z date_published: 2020-09-09T00:00:00Z date_updated: 2023-09-07T13:26:17Z 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: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ...