--- _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' ...