--- _id: '7902' abstract: - lang: eng text: "Mosaic genetic analysis has been widely used in different model organisms such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific fashion. More recently, and less easily conducted, mosaic genetic analysis in mice has also been enabled with the ambition to shed light on human gene function and disease. These genetic tools are of particular interest, but not restricted to, the study of the brain. Notably, the MADM technology offers a genetic approach in mice to visualize and concomitantly manipulate small subsets of genetically defined cells at a clonal level and single cell resolution. MADM-based analysis has already advanced the study of genetic mechanisms regulating brain development and is expected that further MADM-based analysis of genetic alterations will continue to reveal important insights on the fundamental principles of development and disease to potentially assist in the development of new therapies or treatments.\r\nIn summary, this work completed and characterized the necessary genome-wide genetic tools to perform MADM-based analysis at single cell level of the vast majority of mouse genes in virtually any cell type and provided a protocol to perform lineage tracing using the novel MADM resource. Importantly, this work also explored and revealed novel aspects of biologically relevant events in an in vivo context, such as the chromosome-specific bias of chromatid sister segregation pattern, the generation of cell-type diversity in the cerebral cortex and in the cerebellum and finally, the relevance of the interplay between the cell-autonomous gene function and cell-non-autonomous (community) effects in radial glial progenitor lineage progression.\r\nThis work provides a foundation and opens the door to further elucidating the molecular mechanisms underlying neuronal diversity and astrocyte generation." acknowledged_ssus: - _id: PreCl - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Ximena full_name: Contreras, Ximena id: 475990FE-F248-11E8-B48F-1D18A9856A87 last_name: Contreras citation: ama: Contreras X. Genetic dissection of neural development in health and disease at single cell resolution. 2020. doi:10.15479/AT:ISTA:7902 apa: Contreras, X. (2020). Genetic dissection of neural development in health and disease at single cell resolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7902 chicago: Contreras, Ximena. “Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7902. ieee: X. Contreras, “Genetic dissection of neural development in health and disease at single cell resolution,” Institute of Science and Technology Austria, 2020. ista: Contreras X. 2020. Genetic dissection of neural development in health and disease at single cell resolution. Institute of Science and Technology Austria. mla: Contreras, Ximena. Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7902. short: X. Contreras, Genetic Dissection of Neural Development in Health and Disease at Single Cell Resolution, Institute of Science and Technology Austria, 2020. date_created: 2020-05-29T08:27:32Z date_published: 2020-06-05T00:00:00Z date_updated: 2023-10-18T08:45:16Z day: '05' ddc: - '570' degree_awarded: PhD department: - _id: SiHi doi: 10.15479/AT:ISTA:7902 ec_funded: 1 file: - access_level: closed checksum: 43c172bf006c95b65992d473c7240d13 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: xcontreras date_created: 2020-06-05T08:18:08Z date_updated: 2021-06-07T22:30:03Z embargo_to: open_access file_id: '7927' file_name: PhDThesis_Contreras.docx file_size: 53134142 relation: source_file - access_level: open_access checksum: addfed9128271be05cae3608e03a6ec0 content_type: application/pdf creator: xcontreras date_created: 2020-06-05T08:18:07Z date_updated: 2021-06-07T22:30:03Z embargo: 2021-06-06 file_id: '7928' file_name: PhDThesis_Contreras.pdf file_size: 35117191 relation: main_file file_date_updated: 2021-06-07T22:30:03Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '214' project: - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6830' relation: dissertation_contains status: public - id: '28' relation: dissertation_contains status: public - id: '7815' relation: dissertation_contains status: public status: public supervisor: - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 title: Genetic dissection of neural development in health and disease at single cell resolution type: dissertation user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '8311' abstract: - lang: eng text: 'One of the core promises of blockchain technology is that of enabling trustworthy data dissemination in a trustless environment. What current blockchain systems deliver, however, is slow dissemination of public data, rendering blockchain technology unusable in settings where latency, transaction capacity, or data confidentiality are important. In this thesis we focus on providing solutions on two of the most pressing problems blockchain technology currently faces: scalability and data confidentiality. To address the scalability issue, we present OMNILEDGER, a novel scale-out distributed ledger that preserves long-term security under permissionless operation. It ensures security and correctness by using a bias-resistant public-randomness protocol for choosing large, statistically representative shards that process transactions, and by introducing an efficient cross-shard commit protocol that atomically handles transactions affecting multiple shards. To enable secure sharing of confidential data we present CALYPSO, the first fully decentralized, auditable access-control framework for secure blockchain-based data sharing which builds upon two abstractions. First, on-chain secrets enable collective management of (verifiably shared) secrets under a Byzantine adversary where an access-control blockchain enforces user-specific access rules and a secret-management cothority administers encrypted data. Second, skipchain-based identity and access management enables efficient administration of dynamic, sovereign identities and access policies and, in particular, permits clients to maintain long-term relationships with respect to evolving user identities thanks to the trust-delegating forward links of skipchains. In order to build OMNILEDGER and CALYPSO, we first build a set of tools for efficient decentralization, which are presented in Part II of this dissertation. These tools can be used in decentralized and distributed systems to achieve (1) scalable consensus (BYZCOIN), (2) bias- resistant distributed randomness creations (RANDHOUND), and (3) relationship-keeping between independently updating communication endpoints (SKIPCHAINIAC). Although we use this tools in the scope off this thesis, they can be (and already have been) used in a far wider scope.' article_processing_charge: No author: - first_name: Eleftherios full_name: Kokoris Kogias, Eleftherios id: f5983044-d7ef-11ea-ac6d-fd1430a26d30 last_name: Kokoris Kogias citation: ama: Kokoris Kogias E. Secure, confidential blockchains providing high throughput and low latency. 2019. doi:10.5075/epfl-thesis-7101 apa: Kokoris Kogias, E. (2019). Secure, confidential blockchains providing high throughput and low latency. École Polytechnique Fédérale de Lausanne. https://doi.org/10.5075/epfl-thesis-7101 chicago: Kokoris Kogias, Eleftherios. “Secure, Confidential Blockchains Providing High Throughput and Low Latency.” École Polytechnique Fédérale de Lausanne, 2019. https://doi.org/10.5075/epfl-thesis-7101. ieee: E. Kokoris Kogias, “Secure, confidential blockchains providing high throughput and low latency,” École Polytechnique Fédérale de Lausanne, 2019. ista: Kokoris Kogias E. 2019. Secure, confidential blockchains providing high throughput and low latency. École Polytechnique Fédérale de Lausanne. mla: Kokoris Kogias, Eleftherios. Secure, Confidential Blockchains Providing High Throughput and Low Latency. École Polytechnique Fédérale de Lausanne, 2019, doi:10.5075/epfl-thesis-7101. short: E. Kokoris Kogias, Secure, Confidential Blockchains Providing High Throughput and Low Latency, École Polytechnique Fédérale de Lausanne, 2019. date_created: 2020-08-27T11:22:24Z date_published: 2019-09-27T00:00:00Z date_updated: 2021-12-20T15:30:47Z day: '27' degree_awarded: PhD doi: 10.5075/epfl-thesis-7101 extern: '1' language: - iso: eng main_file_link: - open_access: '1' url: https://www.doi.org/10.5075/epfl-thesis-7101 month: '09' oa: 1 oa_version: Published Version page: '244' publication_status: published publisher: École Polytechnique Fédérale de Lausanne status: public supervisor: - first_name: Bryan Alexander full_name: Ford, Bryan Alexander last_name: Ford title: Secure, confidential blockchains providing high throughput and low latency type: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2019' ... --- _id: '6957' abstract: - lang: eng text: "In many shear flows like pipe flow, plane Couette flow, plane Poiseuille flow, etc. turbulence emerges subcritically. Here, when subjected to strong enough perturbations, the flow becomes turbulent in spite of the laminar base flow being linearly stable. The nature of this instability has puzzled the scientific community for decades. At onset, turbulence appears in localized patches and flows are spatio-temporally intermittent. In pipe flow the localized turbulent structures are referred to as puffs and in planar flows like plane Couette and channel flow, patches arise in the form of localized oblique bands. In this thesis, we study the onset of turbulence in channel flow in direct numerical simulations from a dynamical system theory perspective, as well as by performing experiments in a large aspect ratio channel.\r\n\r\nThe aim of the experimental work is to determine the critical Reynolds number where turbulence first becomes sustained. Recently, the onset of turbulence has been described in analogy to absorbing state phase transition (i.e. directed percolation). In particular, it has been shown that the critical point can be estimated from the competition between spreading and decay processes. Here, by performing experiments, we identify the mechanisms underlying turbulence proliferation in channel flow and find the critical Reynolds number, above which turbulence becomes sustained. Above the critical point, the continuous growth at the tip of the stripes outweighs the stochastic shedding of turbulent patches at the tail and the stripes expand. For growing stripes, the probability to decay decreases while the probability of stripe splitting increases. Consequently, and unlike for the puffs in pipe flow, neither of these two processes is time-independent i.e. memoryless. Coupling between stripe expansion and creation of new stripes via splitting leads to a significantly lower critical point ($Re_c=670+/-10$) than most earlier studies suggest. \r\n\r\nWhile the above approach sheds light on how turbulence first becomes sustained, it provides no insight into the origin of the stripes themselves. In the numerical part of the thesis we investigate how turbulent stripes form from invariant solutions of the Navier-Stokes equations. The origin of these turbulent stripes can be identified by applying concepts from the dynamical system theory. In doing so, we identify the exact coherent structures underlying stripes and their bifurcations and how they give rise to the turbulent attractor in phase space. We first report a family of localized nonlinear traveling wave solutions of the Navier-Stokes equations in channel flow. These solutions show structural similarities with turbulent stripes in experiments like obliqueness, quasi-streamwise streaks and vortices, etc. A parametric study of these traveling wave solution is performed, with parameters like Reynolds number, stripe tilt angle and domain size, including the stability of the solutions. These solutions emerge through saddle-node bifurcations and form a phase space skeleton for the turbulent stripes observed in the experiments. The lower branches of these TW solutions at different tilt angles undergo Hopf bifurcation and new solutions branches of relative periodic orbits emerge. These RPO solutions do not belong to the same family and therefore the routes to chaos for different angles are different. \r\n\r\nIn shear flows, turbulence at onset is transient in nature. \ Consequently,turbulence can not be tracked to lower Reynolds numbers, where the dynamics may simplify. Before this happens, turbulence becomes short-lived and laminarizes. In the last part of the thesis, we show that using numerical simulations we can continue turbulent stripes in channel flow past the 'relaminarization barrier' all the way to their origin. Here, turbulent stripe dynamics simplifies and the fluctuations are no longer stochastic and the stripe settles down to a relative periodic orbit. This relative periodic orbit originates from the aforementioned traveling wave solutions. Starting from the relative periodic orbit, a small increase in speed i.e. Reynolds number gives rise to chaos and the attractor dimension sharply increases in contrast to the classical transition scenario where the instabilities affect the flow globally and give rise to much more gradual route to turbulence." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Chaitanya S full_name: Paranjape, Chaitanya S id: 3D85B7C4-F248-11E8-B48F-1D18A9856A87 last_name: Paranjape citation: ama: Paranjape CS. Onset of turbulence in plane Poiseuille flow. 2019. doi:10.15479/AT:ISTA:6957 apa: Paranjape, C. S. (2019). Onset of turbulence in plane Poiseuille flow. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6957 chicago: Paranjape, Chaitanya S. “Onset of Turbulence in Plane Poiseuille Flow.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6957. ieee: C. S. Paranjape, “Onset of turbulence in plane Poiseuille flow,” Institute of Science and Technology Austria, 2019. ista: Paranjape CS. 2019. Onset of turbulence in plane Poiseuille flow. Institute of Science and Technology Austria. mla: Paranjape, Chaitanya S. Onset of Turbulence in Plane Poiseuille Flow. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6957. short: C.S. Paranjape, Onset of Turbulence in Plane Poiseuille Flow, Institute of Science and Technology Austria, 2019. date_created: 2019-10-22T12:08:43Z date_published: 2019-10-24T00:00:00Z date_updated: 2023-09-07T12:53:25Z day: '24' ddc: - '532' degree_awarded: PhD department: - _id: BjHo doi: 10.15479/AT:ISTA:6957 file: - access_level: closed checksum: 7ba298ba0ce7e1d11691af6b8eaf0a0a content_type: application/zip creator: cparanjape date_created: 2019-10-23T09:54:43Z date_updated: 2020-07-14T12:47:46Z file_id: '6962' file_name: Chaitanya_Paranjape_source_files_tex_figures.zip file_size: 45828099 relation: source_file - access_level: open_access checksum: 642697618314e31ac31392da7909c2d9 content_type: application/pdf creator: cparanjape date_created: 2019-10-23T10:37:09Z date_updated: 2020-07-14T12:47:46Z file_id: '6963' file_name: Chaitanya_Paranjape_Thesis.pdf file_size: 19504197 relation: main_file file_date_updated: 2020-07-14T12:47:46Z has_accepted_license: '1' keyword: - Instabilities - Turbulence - Nonlinear dynamics language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '138' publication_identifier: eissn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria status: public supervisor: - first_name: Björn full_name: Hof, Björn id: 3A374330-F248-11E8-B48F-1D18A9856A87 last_name: Hof orcid: 0000-0003-2057-2754 title: Onset of turbulence in plane Poiseuille flow type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '7186' abstract: - lang: eng text: "Tissue morphogenesis in developmental or physiological processes is regulated by molecular\r\nand mechanical signals. While the molecular signaling cascades are increasingly well\r\ndescribed, the mechanical signals affecting tissue shape changes have only recently been\r\nstudied in greater detail. To gain more insight into the mechanochemical and biophysical\r\nbasis of an epithelial spreading process (epiboly) in early zebrafish development, we studied\r\ncell-cell junction formation and actomyosin network dynamics at the boundary between\r\nsurface layer epithelial cells (EVL) and the yolk syncytial layer (YSL). During zebrafish epiboly,\r\nthe cell mass sitting on top of the yolk cell spreads to engulf the yolk cell by the end of\r\ngastrulation. It has been previously shown that an actomyosin ring residing within the YSL\r\npulls on the EVL tissue through a cable-constriction and a flow-friction motor, thereby\r\ndragging the tissue vegetal wards. Pulling forces are likely transmitted from the YSL\r\nactomyosin ring to EVL cells; however, the nature and formation of the junctional structure\r\nmediating this process has not been well described so far. Therefore, our main aim was to\r\ndetermine the nature, dynamics and potential function of the EVL-YSL junction during this\r\nepithelial tissue spreading. Specifically, we show that the EVL-YSL junction is a\r\nmechanosensitive structure, predominantly made of tight junction (TJ) proteins. The process\r\nof TJ mechanosensation depends on the retrograde flow of non-junctional, phase-separated\r\nZonula Occludens-1 (ZO-1) protein clusters towards the EVL-YSL boundary. Interestingly, we\r\ncould demonstrate that ZO-1 is present in a non-junctional pool on the surface of the yolk\r\ncell, and ZO-1 undergoes a phase separation process that likely renders the protein\r\nresponsive to flows. These flows are directed towards the junction and mediate proper\r\ntension-dependent recruitment of ZO-1. Upon reaching the EVL-YSL junction ZO-1 gets\r\nincorporated into the junctional pool mediated through its direct actin-binding domain.\r\nWhen the non-junctional pool and/or ZO-1 direct actin binding is absent, TJs fail in their\r\nproper mechanosensitive responses resulting in slower tissue spreading. We could further\r\ndemonstrate that depletion of ZO proteins within the YSL results in diminished actomyosin\r\nring formation. This suggests that a mechanochemical feedback loop is at work during\r\nzebrafish epiboly: ZO proteins help in proper actomyosin ring formation and actomyosin\r\ncontractility and flows positively influence ZO-1 junctional recruitment. Finally, such a\r\nmesoscale polarization process mediated through the flow of phase-separated protein\r\nclusters might have implications for other processes such as immunological synapse\r\nformation, C. elegans zygote polarization and wound healing." acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: EM-Fac - _id: SSU alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Cornelia full_name: Schwayer, Cornelia id: 3436488C-F248-11E8-B48F-1D18A9856A87 last_name: Schwayer orcid: 0000-0001-5130-2226 citation: ama: Schwayer C. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. 2019. doi:10.15479/AT:ISTA:7186 apa: Schwayer, C. (2019). Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7186 chicago: Schwayer, Cornelia. “Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:7186. ieee: C. Schwayer, “Mechanosensation of tight junctions depends on ZO-1 phase separation and flow,” Institute of Science and Technology Austria, 2019. ista: Schwayer C. 2019. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Institute of Science and Technology Austria. mla: Schwayer, Cornelia. Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:7186. short: C. Schwayer, Mechanosensation of Tight Junctions Depends on ZO-1 Phase Separation and Flow, Institute of Science and Technology Austria, 2019. date_created: 2019-12-16T14:26:14Z date_published: 2019-12-16T00:00:00Z date_updated: 2023-09-07T12:56:42Z day: '16' ddc: - '570' degree_awarded: PhD department: - _id: CaHe doi: 10.15479/AT:ISTA:7186 file: - access_level: closed checksum: 585583c1c875c5d9525703a539668a7c content_type: application/zip creator: cschwayer date_created: 2019-12-19T15:18:11Z date_updated: 2020-07-14T12:47:52Z file_id: '7194' file_name: DocumentSourceFiles.zip file_size: 19431292 relation: source_file - access_level: open_access checksum: 9b9b24351514948d27cec659e632e2cd content_type: application/pdf creator: cschwayer date_created: 2019-12-19T15:19:21Z date_updated: 2020-07-14T12:47:52Z file_id: '7195' file_name: Thesis_CS_final.pdf file_size: 19226428 relation: main_file file_date_updated: 2020-07-14T12:47:52Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '107' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '1096' relation: dissertation_contains status: public - id: '7001' relation: part_of_dissertation status: public status: public supervisor: - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 title: Mechanosensation of tight junctions depends on ZO-1 phase separation and flow type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6681' abstract: - lang: eng text: "The first part of the thesis considers the computational aspects of the homotopy groups πd(X) of a topological space X. It is well known that there is no algorithm to decide whether the fundamental group π1(X) of a given finite simplicial complex X is trivial. On the other hand, there are several algorithms that, given a finite simplicial complex X that is simply connected (i.e., with π1(X) trivial), compute the higher homotopy group πd(X) for any given d ≥ 2.\r\nHowever, these algorithms come with a caveat: They compute the isomorphism type of πd(X), d ≥ 2 as an abstract finitely generated abelian group given by generators and relations, but they work with very implicit representations of the elements of πd(X). We present an algorithm that, given a simply connected space X, computes πd(X) and represents its elements as simplicial maps from suitable triangulations of the d-sphere Sd to X. For fixed d, the algorithm runs in time exponential in size(X), the number of simplices of X. Moreover, we prove that this is optimal: For every fixed d ≥ 2,\r\nwe construct a family of simply connected spaces X such that for any simplicial map representing a generator of πd(X), the size of the triangulation of S d on which the map is defined, is exponential in size(X).\r\nIn the second part of the thesis, we prove that the following question is algorithmically undecidable for d < ⌊3(k+1)/2⌋, k ≥ 5 and (k, d) ̸= (5, 7), which covers essentially everything outside the meta-stable range: Given a finite simplicial complex K of dimension k, decide whether there exists a piecewise-linear (i.e., linear on an arbitrarily fine subdivision of K) embedding f : K ↪→ Rd of K into a d-dimensional Euclidean space." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Stephan Y full_name: Zhechev, Stephan Y id: 3AA52972-F248-11E8-B48F-1D18A9856A87 last_name: Zhechev citation: ama: Zhechev SY. Algorithmic aspects of homotopy theory and embeddability. 2019. doi:10.15479/AT:ISTA:6681 apa: Zhechev, S. Y. (2019). Algorithmic aspects of homotopy theory and embeddability. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6681 chicago: Zhechev, Stephan Y. “Algorithmic Aspects of Homotopy Theory and Embeddability.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6681. ieee: S. Y. Zhechev, “Algorithmic aspects of homotopy theory and embeddability,” Institute of Science and Technology Austria, 2019. ista: Zhechev SY. 2019. Algorithmic aspects of homotopy theory and embeddability. Institute of Science and Technology Austria. mla: Zhechev, Stephan Y. Algorithmic Aspects of Homotopy Theory and Embeddability. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6681. short: S.Y. Zhechev, Algorithmic Aspects of Homotopy Theory and Embeddability, Institute of Science and Technology Austria, 2019. date_created: 2019-07-26T11:14:34Z date_published: 2019-08-08T00:00:00Z date_updated: 2023-09-07T13:10:36Z day: '08' ddc: - '514' degree_awarded: PhD department: - _id: UlWa doi: 10.15479/AT:ISTA:6681 file: - access_level: open_access checksum: 3231e7cbfca3b5687366f84f0a57a0c0 content_type: application/pdf creator: szhechev date_created: 2019-08-07T13:02:50Z date_updated: 2020-07-14T12:47:37Z file_id: '6771' file_name: Stephan_Zhechev_thesis.pdf file_size: 1464227 relation: main_file - access_level: closed checksum: 85d65eb27b4377a9e332ee37a70f08b6 content_type: application/octet-stream creator: szhechev date_created: 2019-08-07T13:03:22Z date_updated: 2020-07-14T12:47:37Z file_id: '6772' file_name: Stephan_Zhechev_thesis.tex file_size: 303988 relation: source_file - access_level: closed checksum: 86b374d264ca2dd53e712728e253ee75 content_type: application/zip creator: szhechev date_created: 2019-08-07T13:03:34Z date_updated: 2020-07-14T12:47:37Z file_id: '6773' file_name: supplementary_material.zip file_size: 1087004 relation: supplementary_material file_date_updated: 2020-07-14T12:47:37Z has_accepted_license: '1' language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '08' oa: 1 oa_version: Published Version page: '104' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6774' 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: Algorithmic aspects of homotopy theory and embeddability 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: '2019' ... --- _id: '6894' abstract: - lang: eng text: "Hybrid automata combine finite automata and dynamical systems, and model the interaction of digital with physical systems. Formal analysis that can guarantee the safety of all behaviors or rigorously witness failures, while unsolvable in general, has been tackled algorithmically using, e.g., abstraction, bounded model-checking, assisted theorem proving.\r\nNevertheless, very few methods have addressed the time-unbounded reachability analysis of hybrid automata and, for current sound and automatic tools, scalability remains critical. We develop methods for the polyhedral abstraction of hybrid automata, which construct coarse overapproximations and tightens them incrementally, in a CEGAR fashion. We use template polyhedra, i.e., polyhedra whose facets are normal to a given set of directions.\r\nWhile, previously, directions were given by the user, we introduce (1) the first method\r\nfor computing template directions from spurious counterexamples, so as to generalize and\r\neliminate them. The method applies naturally to convex hybrid automata, i.e., hybrid\r\nautomata with (possibly non-linear) convex constraints on derivatives only, while for linear\r\nODE requires further abstraction. Specifically, we introduce (2) the conic abstractions,\r\nwhich, partitioning the state space into appropriate (possibly non-uniform) cones, divide\r\ncurvy trajectories into relatively straight sections, suitable for polyhedral abstractions.\r\nFinally, we introduce (3) space-time interpolation, which, combining interval arithmetic\r\nand template refinement, computes appropriate (possibly non-uniform) time partitioning\r\nand template directions along spurious trajectories, so as to eliminate them.\r\nWe obtain sound and automatic methods for the reachability analysis over dense\r\nand unbounded time of convex hybrid automata and hybrid automata with linear ODE.\r\nWe build prototype tools and compare—favorably—our methods against the respective\r\nstate-of-the-art tools, on several benchmarks." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Mirco full_name: Giacobbe, Mirco id: 3444EA5E-F248-11E8-B48F-1D18A9856A87 last_name: Giacobbe orcid: 0000-0001-8180-0904 citation: ama: Giacobbe M. Automatic time-unbounded reachability analysis of hybrid systems. 2019. doi:10.15479/AT:ISTA:6894 apa: Giacobbe, M. (2019). Automatic time-unbounded reachability analysis of hybrid systems. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6894 chicago: Giacobbe, Mirco. “Automatic Time-Unbounded Reachability Analysis of Hybrid Systems.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6894. ieee: M. Giacobbe, “Automatic time-unbounded reachability analysis of hybrid systems,” Institute of Science and Technology Austria, 2019. ista: Giacobbe M. 2019. Automatic time-unbounded reachability analysis of hybrid systems. Institute of Science and Technology Austria. mla: Giacobbe, Mirco. Automatic Time-Unbounded Reachability Analysis of Hybrid Systems. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6894. short: M. Giacobbe, Automatic Time-Unbounded Reachability Analysis of Hybrid Systems, Institute of Science and Technology Austria, 2019. date_created: 2019-09-22T14:08:44Z date_published: 2019-09-30T00:00:00Z date_updated: 2023-09-19T09:30:43Z day: '30' ddc: - '000' degree_awarded: PhD department: - _id: ToHe doi: 10.15479/AT:ISTA:6894 file: - access_level: open_access checksum: 773beaf4a85dc2acc2c12b578fbe1965 content_type: application/pdf creator: mgiacobbe date_created: 2019-09-27T14:15:05Z date_updated: 2020-07-14T12:47:43Z file_id: '6916' file_name: giacobbe_thesis.pdf file_size: 4100685 relation: main_file - access_level: closed checksum: 97f1c3da71feefd27e6e625d32b4c75b content_type: application/gzip creator: mgiacobbe date_created: 2019-09-27T14:22:04Z date_updated: 2020-07-14T12:47:43Z file_id: '6917' file_name: giacobbe_thesis_src.tar.gz file_size: 7959732 relation: source_file file_date_updated: 2020-07-14T12:47:43Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '132' publication_identifier: eissn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '631' relation: part_of_dissertation status: public - id: '647' relation: part_of_dissertation status: public - id: '140' 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: Automatic time-unbounded reachability analysis of hybrid systems 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: '2019' ... --- _id: '7172' abstract: - lang: eng text: "The development and growth of Arabidopsis thaliana is regulated by a combination of genetic programing and also by the environmental influences. An important role in these processes play the phytohormones and among them, auxin is crucial as it controls many important functions. It is transported through the whole plant body by creating local and temporal concentration maxima and minima, which have an impact on the cell status, tissue and organ identity. Auxin has the property to undergo a directional and finely regulated cell-to-cell transport, which is enabled by the transport proteins, localized on the plasma membrane. An important role in this process have the PIN auxin efflux proteins, which have an asymmetric/polar subcellular localization and determine the directionality of the auxin transport. During the last years, there were significant advances in understanding how the trafficking molecular machineries function, including studies on molecular interactions, function, subcellular localization and intracellular distribution. However, there is still a lack of detailed characterization on the steps of endocytosis, exocytosis, endocytic recycling and degradation. Due to this fact, I focused on the identification of novel trafficking factors and better characterization of the intracellular trafficking pathways. My PhD thesis consists of an introductory chapter, three experimental chapters, a chapter containing general discussion, conclusions and perspectives and also an appendix chapter with published collaborative papers.\r\nThe first chapter is separated in two different parts: I start by a general introduction to auxin biology and then I introduce the trafficking pathways in the model plant Arabidopsis thaliana. Then, I explain also the phosphorylation-signals for polar targeting and also the roles of the phytohormone strigolactone.\r\nThe second chapter includes the characterization of bar1/sacsin mutant, which was identified in a forward genetic screen for novel trafficking components in Arabidopsis thaliana, where by the implementation of an EMS-treated pPIN1::PIN1-GFP marker line and by using the established inhibitor of ARF-GEFs, Brefeldin A (BFA) as a tool to study trafficking processes, we identified a novel factor, which is mediating the adaptation of the plant cell to ARF-GEF inhibition. The mutation is in a previously uncharacterized gene, encoding a very big protein that we, based on its homologies, called SACSIN with domains suggesting roles as a molecular chaperon or as a component of the ubiquitin-proteasome system. Our physiology and imaging studies revealed that SACSIN is a crucial plant cell component of the adaptation to the ARF-GEF inhibition.\r\nThe third chapter includes six subchapters, where I focus on the role of the phytohormone strigolactone, which interferes with auxin feedback on PIN internalization. Strigolactone moderates the polar auxin transport by increasing the internalization of the PIN auxin efflux carriers, which reduces the canalization related growth responses. In addition, I also studied the role of phosphorylation in the strigolactone regulation of auxin feedback on PIN internalization. In this chapter I also present my results on the MAX2-dependence of strigolactone-mediated root growth inhibition and I also share my results on the auxin metabolomics profiling after application of GR24.\r\nIn the fourth chapter I studied the effect of two small molecules ES-9 and ES9-17, which were identified from a collection of small molecules with the property to impair the clathrin-mediated endocytosis.\r\nIn the fifth chapter, I discuss all my observations and experimental findings and suggest alternative hypothesis to interpret my results.\r\nIn the appendix there are three collaborative published projects. In the first, I participated in the characterization of the role of ES9 as a small molecule, which is inhibitor of clathrin- mediated endocytosis in different model organisms. In the second paper, I contributed to the characterization of another small molecule ES9-17, which is a non-protonophoric analog of ES9 and also impairs the clathrin-mediated endocytosis not only in plant cells, but also in mammalian HeLa cells. Last but not least, I also attach another paper, where I tried to establish the grafting method as a technique in our lab to study canalization related processes." acknowledged_ssus: - _id: LifeSc - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Mina K full_name: Vasileva, Mina K id: 3407EB18-F248-11E8-B48F-1D18A9856A87 last_name: Vasileva citation: ama: Vasileva MK. Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana. 2019. doi:10.15479/AT:ISTA:7172 apa: Vasileva, M. K. (2019). Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7172 chicago: Vasileva, Mina K. “Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis Thaliana.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:7172. ieee: M. K. Vasileva, “Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana,” Institute of Science and Technology Austria, 2019. ista: Vasileva MK. 2019. Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana. Institute of Science and Technology Austria. mla: Vasileva, Mina K. Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis Thaliana. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:7172. short: M.K. Vasileva, Molecular Mechanisms of Endomembrane Trafficking in Arabidopsis Thaliana, Institute of Science and Technology Austria, 2019. date_created: 2019-12-11T21:24:39Z date_published: 2019-12-12T00:00:00Z date_updated: 2023-09-19T10:39:33Z day: '12' ddc: - '570' degree_awarded: PhD department: - _id: JiFr doi: 10.15479/AT:ISTA:7172 file: - access_level: closed checksum: ef981c1a3b1d9da0edcbedcff4970d37 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: mvasilev date_created: 2019-12-12T09:32:36Z date_updated: 2020-07-14T12:47:51Z file_id: '7175' file_name: Thesis_Mina_final_upload_7.docx file_size: 20454014 relation: source_file - access_level: open_access checksum: 3882c4585e46c9cfb486e4225cad54ab content_type: application/pdf creator: mvasilev date_created: 2019-12-12T09:33:10Z date_updated: 2020-07-14T12:47:51Z file_id: '7176' file_name: Thesis_Mina_final_upload_7.pdf file_size: 11565025 relation: main_file file_date_updated: 2020-07-14T12:47:51Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '192' publication_identifier: eissn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '1346' relation: part_of_dissertation status: public - id: '6377' relation: part_of_dissertation status: public - id: '449' relation: part_of_dissertation status: public status: public supervisor: - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 title: Molecular mechanisms of endomembrane trafficking in Arabidopsis thaliana type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6473' abstract: - lang: eng text: "Single cells are constantly interacting with their environment and each other, more importantly, the accurate perception of environmental cues is crucial for growth, survival, and reproduction. This communication between cells and their environment can be formalized in mathematical terms and be quantified as the information flow between them, as prescribed by information theory. \r\nThe recent availability of real–time dynamical patterns of signaling molecules in single cells has allowed us to identify encoding about the identity of the environment in the time–series. However, efficient estimation of the information transmitted by these signals has been a data–analysis challenge due to the high dimensionality of the trajectories and the limited number of samples. In the first part of this thesis, we develop and evaluate decoding–based estimation methods to lower bound the mutual information and derive model–based precise information estimates for biological reaction networks governed by the chemical master equation. This is followed by applying the decoding-based methods to study the intracellular representation of extracellular changes in budding yeast, by observing the transient dynamics of nuclear translocation of 10 transcription factors in response to 3 stress conditions. Additionally, we apply these estimators to previously published data on ERK and Ca2+ signaling and yeast stress response. We argue that this single cell decoding-based measure of information provides an unbiased, quantitative and interpretable measure for the fidelity of biological signaling processes. \r\nFinally, in the last section, we deal with gene regulation which is primarily controlled by transcription factors (TFs) that bind to the DNA to activate gene expression. The possibility that non-cognate TFs activate transcription diminishes the accuracy of regulation with potentially disastrous effects for the cell. This ’crosstalk’ acts as a previously unexplored source of noise in biochemical networks and puts a strong constraint on their performance. To mitigate erroneous initiation we propose an out of equilibrium scheme that implements kinetic proofreading. We show that such architectures are favored over their equilibrium counterparts for complex organisms despite introducing noise in gene expression. " alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Sarah A full_name: Cepeda Humerez, Sarah A id: 3DEE19A4-F248-11E8-B48F-1D18A9856A87 last_name: Cepeda Humerez citation: ama: Cepeda Humerez SA. Estimating information flow in single cells. 2019. doi:10.15479/AT:ISTA:6473 apa: Cepeda Humerez, S. A. (2019). Estimating information flow in single cells. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6473 chicago: Cepeda Humerez, Sarah A. “Estimating Information Flow in Single Cells.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6473. ieee: S. A. Cepeda Humerez, “Estimating information flow in single cells,” Institute of Science and Technology Austria, 2019. ista: Cepeda Humerez SA. 2019. Estimating information flow in single cells. Institute of Science and Technology Austria. mla: Cepeda Humerez, Sarah A. Estimating Information Flow in Single Cells. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6473. short: S.A. Cepeda Humerez, Estimating Information Flow in Single Cells, Institute of Science and Technology Austria, 2019. date_created: 2019-05-21T00:11:23Z date_published: 2019-05-23T00:00:00Z date_updated: 2023-09-19T15:13:26Z day: '23' ddc: - '004' degree_awarded: PhD department: - _id: GaTk doi: 10.15479/AT:ISTA:6473 file: - access_level: closed checksum: 75f9184c1346e10a5de5f9cc7338309a content_type: application/zip creator: scepeda date_created: 2019-05-23T11:18:16Z date_updated: 2020-07-14T12:47:31Z file_id: '6480' file_name: Thesis_Cepeda.zip file_size: 23937464 relation: source_file - access_level: open_access checksum: afdc0633ddbd71d5b13550d7fb4f4454 content_type: application/pdf creator: scepeda date_created: 2019-05-23T11:18:13Z date_updated: 2020-07-14T12:47:31Z file_id: '6481' file_name: CepedaThesis.pdf file_size: 16646985 relation: main_file file_date_updated: 2020-07-14T12:47:31Z has_accepted_license: '1' keyword: - Information estimation - Time-series - data analysis language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '135' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '1576' relation: dissertation_contains status: public - id: '6900' relation: dissertation_contains status: public - id: '281' relation: dissertation_contains status: public - id: '2016' relation: dissertation_contains 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 title: Estimating information flow in single cells 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: '2019' ... --- _id: '6071' abstract: - lang: eng text: 'Transcription factors, by binding to specific sequences on the DNA, control the precise spatio-temporal expression of genes inside a cell. However, this specificity is limited, leading to frequent incorrect binding of transcription factors that might have deleterious consequences on the cell. By constructing a biophysical model of TF-DNA binding in the context of gene regulation, I will first explore how regulatory constraints can strongly shape the distribution of a population in sequence space. Then, by directly linking this to a picture of multiple types of transcription factors performing their functions simultaneously inside the cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions between transcription factors and binding sites that lead to erroneous regulatory states -- and understand the constraints this places on the design of regulatory systems. I will then develop a generic theoretical framework to investigate the coevolution of multiple transcription factors and multiple binding sites, in the context of a gene regulatory network that performs a certain function. As a particular tractable version of this problem, I will consider the evolution of two transcription factors when they transmit upstream signals to downstream target genes. Specifically, I will describe the evolutionary steady states and the evolutionary pathways involved, along with their timescales, of a system that initially undergoes a transcription factor duplication event. To connect this important theoretical model to the prominent biological event of transcription factor duplication giving rise to paralogous families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription factors, a major family in humans, and focus on the patterns of evolution that paralogs have undergone in their various protein domains in the recent past. ' alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Roshan full_name: Prizak, Roshan id: 4456104E-F248-11E8-B48F-1D18A9856A87 last_name: Prizak citation: ama: Prizak R. Coevolution of transcription factors and their binding sites in sequence space. 2019. doi:10.15479/at:ista:th6071 apa: Prizak, R. (2019). Coevolution of transcription factors and their binding sites in sequence space. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:th6071 chicago: Prizak, Roshan. “Coevolution of Transcription Factors and Their Binding Sites in Sequence Space.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/at:ista:th6071. ieee: R. Prizak, “Coevolution of transcription factors and their binding sites in sequence space,” Institute of Science and Technology Austria, 2019. ista: Prizak R. 2019. Coevolution of transcription factors and their binding sites in sequence space. Institute of Science and Technology Austria. mla: Prizak, Roshan. Coevolution of Transcription Factors and Their Binding Sites in Sequence Space. Institute of Science and Technology Austria, 2019, doi:10.15479/at:ista:th6071. short: R. Prizak, Coevolution of Transcription Factors and Their Binding Sites in Sequence Space, Institute of Science and Technology Austria, 2019. date_created: 2019-03-06T16:16:10Z date_published: 2019-03-11T00:00:00Z date_updated: 2023-09-22T10:00:48Z day: '11' ddc: - '576' degree_awarded: PhD department: - _id: GaTk - _id: NiBa doi: 10.15479/at:ista:th6071 file: - access_level: open_access checksum: e60a72de35d270b31f1a23d50f224ec0 content_type: application/pdf creator: rprizak date_created: 2019-03-06T16:05:07Z date_updated: 2020-07-14T12:47:18Z file_id: '6072' file_name: Thesis_final_PDFA_RoshanPrizak.pdf file_size: 20995465 relation: main_file - access_level: closed checksum: 67c2630333d05ebafef5f018863a8465 content_type: application/zip creator: rprizak date_created: 2019-03-06T16:09:39Z date_updated: 2020-07-14T12:47:18Z file_id: '6073' file_name: thesis_v2_merge.zip file_size: 85705272 relation: source_file title: Latex files file_date_updated: 2020-07-14T12:47:18Z has_accepted_license: '1' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: '189' project: - _id: 254E9036-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P28844-B27 name: Biophysics of information processing in gene regulation publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '1358' relation: part_of_dissertation status: public - id: '955' 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 title: Coevolution of transcription factors and their binding sites in sequence space type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6179' abstract: - lang: eng text: "In the first part of this thesis we consider large random matrices with arbitrary expectation and a general slowly decaying correlation among its entries. We prove universality of the local eigenvalue statistics and optimal local laws for the resolvent in the bulk and edge regime. The main novel tool is a systematic diagrammatic control of a multivariate cumulant expansion.\r\nIn the second part we consider Wigner-type matrices and show that at any cusp singularity of the limiting eigenvalue distribution the local eigenvalue statistics are uni- versal and form a Pearcey process. Since the density of states typically exhibits only square root or cubic root cusp singularities, our work complements previous results on the bulk and edge universality and it thus completes the resolution of the Wigner- Dyson-Mehta universality conjecture for the last remaining universality type. Our analysis holds not only for exact cusps, but approximate cusps as well, where an ex- tended Pearcey process emerges. As a main technical ingredient we prove an optimal local law at the cusp, and extend the fast relaxation to equilibrium of the Dyson Brow- nian motion to the cusp regime.\r\nIn the third and final part we explore the entrywise linear statistics of Wigner ma- trices and identify the fluctuations for a large class of test functions with little regularity. This enables us to study the rectangular Young diagram obtained from the interlacing eigenvalues of the random matrix and its minor, and we find that, despite having the same limit, the fluctuations differ from those of the algebraic Young tableaux equipped with the Plancharel measure." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Dominik J full_name: Schröder, Dominik J id: 408ED176-F248-11E8-B48F-1D18A9856A87 last_name: Schröder orcid: 0000-0002-2904-1856 citation: ama: 'Schröder DJ. From Dyson to Pearcey: Universal statistics in random matrix theory. 2019. doi:10.15479/AT:ISTA:th6179' apa: 'Schröder, D. J. (2019). From Dyson to Pearcey: Universal statistics in random matrix theory. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th6179' chicago: 'Schröder, Dominik J. “From Dyson to Pearcey: Universal Statistics in Random Matrix Theory.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:th6179.' ieee: 'D. J. Schröder, “From Dyson to Pearcey: Universal statistics in random matrix theory,” Institute of Science and Technology Austria, 2019.' ista: 'Schröder DJ. 2019. From Dyson to Pearcey: Universal statistics in random matrix theory. Institute of Science and Technology Austria.' mla: 'Schröder, Dominik J. From Dyson to Pearcey: Universal Statistics in Random Matrix Theory. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:th6179.' short: 'D.J. Schröder, From Dyson to Pearcey: Universal Statistics in Random Matrix Theory, Institute of Science and Technology Austria, 2019.' date_created: 2019-03-28T08:58:59Z date_published: 2019-03-18T00:00:00Z date_updated: 2024-02-22T14:34:33Z day: '18' ddc: - '515' - '519' degree_awarded: PhD department: - _id: LaEr doi: 10.15479/AT:ISTA:th6179 ec_funded: 1 file: - access_level: closed checksum: 6926f66f28079a81c4937e3764be00fc content_type: application/x-gzip creator: dernst date_created: 2019-03-28T08:53:52Z date_updated: 2020-07-14T12:47:21Z file_id: '6180' file_name: 2019_Schroeder_Thesis.tar.gz file_size: 7104482 relation: source_file - access_level: open_access checksum: 7d0ebb8d1207e89768cdd497a5bf80fb content_type: application/pdf creator: dernst date_created: 2019-03-28T08:53:52Z date_updated: 2020-07-14T12:47:21Z file_id: '6181' file_name: 2019_Schroeder_Thesis.pdf file_size: 4228794 relation: main_file file_date_updated: 2020-07-14T12:47:21Z has_accepted_license: '1' language: - iso: eng month: '03' oa: 1 oa_version: Published Version page: '375' project: - _id: 258DCDE6-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '338804' name: Random matrices, universality and disordered quantum systems publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '1144' relation: part_of_dissertation status: public - id: '6186' relation: part_of_dissertation status: public - id: '6185' relation: part_of_dissertation status: public - id: '6182' relation: part_of_dissertation status: public - id: '1012' relation: part_of_dissertation status: public - id: '6184' relation: part_of_dissertation status: public status: public supervisor: - first_name: László full_name: Erdös, László id: 4DBD5372-F248-11E8-B48F-1D18A9856A87 last_name: Erdös orcid: 0000-0001-5366-9603 title: 'From Dyson to Pearcey: Universal statistics in random matrix theory' type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6392' abstract: - lang: eng text: "The regulation of gene expression is one of the most fundamental processes in living systems. In recent years, thanks to advances in sequencing technology and automation, it has become possible to study gene expression quantitatively, genome-wide and in high-throughput. This leads to the possibility of exploring changes in gene expression in the context of many external perturbations and their combinations, and thus of characterising the basic principles governing gene regulation. In this thesis, I present quantitative experimental approaches to studying transcriptional and protein level changes in response to combinatorial drug treatment, as well as a theoretical data-driven approach to analysing thermodynamic principles guiding transcription of protein coding genes. \r\nIn the first part of this work, I present a novel methodological framework for quantifying gene expression changes in drug combinations, termed isogrowth profiling. External perturbations through small molecule drugs influence the growth rate of the cell, leading to wide-ranging changes in cellular physiology and gene expression. This confounds the gene expression changes specifically elicited by the particular drug. Combinatorial perturbations, owing to the increased stress they exert, influence the growth rate even more strongly and hence suffer the convolution problem to a greater extent when measuring gene expression changes. Isogrowth profiling is a way to experimentally abstract non-specific, growth rate related changes, by performing the measurement using varying ratios of two drugs at such concentrations that the overall inhibition rate is constant. Using a robotic setup for automated high-throughput re-dilution culture of Saccharomyces cerevisiae, the budding yeast, I investigate all pairwise interactions of four small molecule drugs through sequencing RNA along a growth isobole. Through principal component analysis, I demonstrate here that isogrowth profiling can uncover drug-specific as well as drug-interaction-specific gene expression changes. I show that drug-interaction-specific gene expression changes can be used for prediction of higher-order drug interactions. I propose a simplified generalised framework of isogrowth profiling, with few measurements needed for each drug pair, enabling the broad application of isogrowth profiling to high-throughput screening of inhibitors of cellular growth and beyond. Such high-throughput screenings of gene expression changes specific to pairwise drug interactions will be instrumental for predicting the higher-order interactions of the drugs.\r\n\r\nIn the second part of this work, I extend isogrowth profiling to single-cell measurements of gene expression, characterising population heterogeneity in the budding yeast in response to combinatorial drug perturbation while controlling for non-specific growth rate effects. Through flow cytometry of strains with protein products fused to green fluorescent protein, I discover multiple proteins with bi-modally distributed expression levels in the population in response to drug treatment. I characterize more closely the effect of an ionic stressor, lithium chloride, and find that it inhibits the splicing of mRNA, most strongly affecting ribosomal protein transcripts and leading to a bi-stable behaviour of a small ribosomal subunit protein Rps22B. Time-lapse microscopy of a microfluidic culture system revealed that the induced Rps22B heterogeneity leads to preferential survival of Rps22B-low cells after long starvation, but to preferential proliferation of Rps22B-high cells after short starvation. Overall, this suggests that yeast cells might use splicing of ribosomal genes for bet-hedging in fluctuating environments. I give specific examples of how further exploration of cellular heterogeneity in yeast in response to external perturbation has the potential to reveal yet-undiscovered gene regulation circuitry.\r\n\r\nIn the last part of this thesis, a re-analysis of a published sequencing dataset of nascent elongating transcripts is used to characterise the thermodynamic constraints for RNA polymerase II (RNAP) elongation. Population-level data on RNAP position throughout the transcribed genome with single nucleotide resolution are used to infer the sequence specific thermodynamic determinants of RNAP pausing and backtracking. This analysis reveals that the basepairing strength of the eight nucleotide-long RNA:DNA duplex relative to the basepairing strength of the same sequence when in DNA:DNA duplex, and the change in this quantity during RNA polymerase movement, is the key determinant of RNAP pausing. This is true for RNAP pausing while elongating, but also of RNAP pausing while backtracking and of the backtracking length. The quantitative dependence of RNAP pausing on basepairing energetics is used to infer the increase in pausing due to transcriptional mismatches, leading to a hypothesis that pervasive RNA polymerase II pausing is due to basepairing energetics, as an evolutionary cost for increased RNA polymerase II fidelity.\r\n\r\nThis work advances our understanding of the general principles governing gene expression, with the goal of making computational predictions of single-cell gene expression responses to combinatorial perturbations based on the individual perturbations possible. This ability would substantially facilitate the design of drug combination treatments and, in the long term, lead to our increased ability to more generally design targeted manipulations to any biological system. " acknowledged_ssus: - _id: LifeSc - _id: M-Shop - _id: Bio alternative_title: - IST Austria Thesis author: - first_name: Martin full_name: Lukacisin, Martin id: 298FFE8C-F248-11E8-B48F-1D18A9856A87 last_name: Lukacisin orcid: 0000-0001-6549-4177 citation: ama: Lukacisin M. Quantitative investigation of gene expression principles through combinatorial drug perturbation and theory. 2019. doi:10.15479/AT:ISTA:6392 apa: Lukacisin, M. (2019). Quantitative investigation of gene expression principles through combinatorial drug perturbation and theory. IST Austria. https://doi.org/10.15479/AT:ISTA:6392 chicago: Lukacisin, Martin. “Quantitative Investigation of Gene Expression Principles through Combinatorial Drug Perturbation and Theory.” IST Austria, 2019. https://doi.org/10.15479/AT:ISTA:6392. ieee: M. Lukacisin, “Quantitative investigation of gene expression principles through combinatorial drug perturbation and theory,” IST Austria, 2019. ista: Lukacisin M. 2019. Quantitative investigation of gene expression principles through combinatorial drug perturbation and theory. IST Austria. mla: Lukacisin, Martin. Quantitative Investigation of Gene Expression Principles through Combinatorial Drug Perturbation and Theory. IST Austria, 2019, doi:10.15479/AT:ISTA:6392. short: M. Lukacisin, Quantitative Investigation of Gene Expression Principles through Combinatorial Drug Perturbation and Theory, IST Austria, 2019. date_created: 2019-05-09T19:53:00Z date_published: 2019-05-09T00:00:00Z date_updated: 2023-09-22T09:19:41Z day: '09' ddc: - '570' department: - _id: ToBo doi: 10.15479/AT:ISTA:6392 extern: '1' file: - access_level: closed checksum: 829bda074444857c7935171237bb7c0c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: mlukacisin date_created: 2019-05-10T13:51:49Z date_updated: 2020-07-14T12:47:29Z embargo_to: open_access file_id: '6409' file_name: Thesis_Draft_v3.4Final.docx file_size: 43740796 relation: hidden - access_level: open_access checksum: 56cb5e97f5f8fc41692401b53832d8e0 content_type: application/pdf creator: mlukacisin date_created: 2019-05-10T14:13:42Z date_updated: 2021-02-11T11:17:16Z embargo: 2020-04-17 file_id: '6410' file_name: Thesis_Draft_v3.4FinalA.pdf file_size: 35228388 relation: main_file file_date_updated: 2021-02-11T11:17:16Z has_accepted_license: '1' language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '103' publication_identifier: isbn: - 978-3-99078-001-5 issn: - 2663-337X publication_status: published publisher: IST Austria related_material: record: - id: '1029' relation: part_of_dissertation status: public status: public supervisor: - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X title: Quantitative investigation of gene expression principles through combinatorial drug perturbation and theory type: dissertation user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2019' ... --- _id: '6435' abstract: - lang: eng text: "Social insect colonies tend to have numerous members which function together like a single organism in such harmony that the term ``super-organism'' is often used. In this analogy the reproductive caste is analogous to the primordial germ\r\ncells of a metazoan, while the sterile worker caste corresponds to somatic cells. The worker castes, like tissues, are\r\nin charge of all functions of a living being, besides reproduction. The establishment of new super-organismal units\r\n(i.e. new colonies) is accomplished by the co-dependent castes. The term oftentimes goes beyond a metaphor. We invoke it when we speak about the metabolic rate, thermoregulation, nutrient regulation and gas exchange of a social insect colony. Furthermore, we assert that the super-organism has an immune system, and benefits from ``social immunity''.\r\n\r\nSocial immunity was first summoned by evolutionary biologists to resolve the apparent discrepancy between the expected high frequency of disease outbreak amongst numerous, closely related tightly-interacting hosts, living in stable and microbially-rich environments, against the exceptionally scarce epidemic accounts in natural populations. Social\r\nimmunity comprises a multi-layer assembly of behaviours which have evolved to effectively keep the pathogenic enemies of a colony at bay. The field of social immunity has drawn interest, as it becomes increasingly urgent to stop\r\nthe collapse of pollinator species and curb the growth of invasive pests. In the past decade, several mechanisms of\r\nsocial immune responses have been dissected, but many more questions remain open.\r\n\r\nI present my work in two experimental chapters. In the first, I use invasive garden ants (*Lasius neglectus*) to study how pathogen load and its distribution among nestmates affect the grooming response of the group. Any given group of ants will carry out the same total grooming work, but will direct their grooming effort towards individuals\r\ncarrying a relatively higher spore load. Contrary to expectation, the highest risk of transmission does not stem from grooming highly contaminated ants, but instead, we suggest that the grooming response likely minimizes spore loss to the environment, reducing contamination from inadvertent pickup from the substrate.\r\n\r\nThe second is a comparative developmental approach. I follow black garden ant queens (*Lasius niger*) and their colonies from mating flight, through hibernation for a year. Colonies which grow fast from the start, have a lower chance of survival through hibernation, and those which survive grow at a lower pace later. This is true for colonies of naive\r\nand challenged queens. Early pathogen exposure of the queens changes colony dynamics in an unexpected way: colonies from exposed queens are more likely to grow slowly and recover in numbers only after they survive hibernation.\r\n\r\nIn addition to the two experimental chapters, this thesis includes a co-authored published review on organisational\r\nimmunity, where we enlist the experimental evidence and theoretical framework on which this hypothesis is built,\r\nidentify the caveats and underline how the field is ripe to overcome them. In a final chapter, I describe my part in\r\ntwo collaborative efforts, one to develop an image-based tracker, and the second to develop a classifier for ant\r\nbehaviour." acknowledged_ssus: - _id: Bio - _id: ScienComp - _id: M-Shop - _id: LifeSc alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Barbara E full_name: Casillas Perez, Barbara E id: 351ED2AA-F248-11E8-B48F-1D18A9856A87 last_name: Casillas Perez citation: ama: Casillas Perez BE. Collective defenses of garden ants against a fungal pathogen. 2019. doi:10.15479/AT:ISTA:6435 apa: Casillas Perez, B. E. (2019). Collective defenses of garden ants against a fungal pathogen. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6435 chicago: Casillas Perez, Barbara E. “Collective Defenses of Garden Ants against a Fungal Pathogen.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6435. ieee: B. E. Casillas Perez, “Collective defenses of garden ants against a fungal pathogen,” Institute of Science and Technology Austria, 2019. ista: Casillas Perez BE. 2019. Collective defenses of garden ants against a fungal pathogen. Institute of Science and Technology Austria. mla: Casillas Perez, Barbara E. Collective Defenses of Garden Ants against a Fungal Pathogen. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6435. short: B.E. Casillas Perez, Collective Defenses of Garden Ants against a Fungal Pathogen, Institute of Science and Technology Austria, 2019. date_created: 2019-05-13T08:58:35Z date_published: 2019-05-07T00:00:00Z date_updated: 2023-09-07T12:57:04Z day: '07' ddc: - '570' - '006' - '578' - '592' degree_awarded: PhD department: - _id: SyCr doi: 10.15479/AT:ISTA:6435 ec_funded: 1 file: - access_level: open_access checksum: 6daf2d2086111aa8fd3fbc919a3e2833 content_type: application/pdf creator: casillas date_created: 2019-05-13T09:16:20Z date_updated: 2021-02-11T11:17:15Z embargo: 2020-05-08 file_id: '6438' file_name: tesisDoctoradoBC.pdf file_size: 3895187 relation: main_file - access_level: closed checksum: 3d221aaff7559a7060230a1ff610594f content_type: application/zip creator: casillas date_created: 2019-05-13T09:16:20Z date_updated: 2020-07-14T12:47:30Z embargo_to: open_access file_id: '6439' file_name: tesisDoctoradoBC.zip file_size: 7365118 relation: source_file file_date_updated: 2021-02-11T11:17:15Z has_accepted_license: '1' keyword: - Social Immunity - Sanitary care - Social Insects - Organisational Immunity - Colony development - Multi-target tracking language: - iso: eng month: '05' oa: 1 oa_version: Published Version page: '183' project: - _id: 2649B4DE-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '771402' name: Epidemics in ant societies on a chip publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '1999' relation: part_of_dissertation status: public status: public supervisor: - first_name: Sylvia M full_name: Cremer, Sylvia M id: 2F64EC8C-F248-11E8-B48F-1D18A9856A87 last_name: Cremer orcid: 0000-0002-2193-3868 title: Collective defenses of garden ants against a fungal pathogen type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6269' abstract: - lang: eng text: 'Clathrin-Mediated Endocytosis (CME) is an aspect of cellular trafficking that is constantly regulated for mediating developmental and physiological responses. The main aim of my thesis is to decipher the basic mechanisms of CME and post-endocytic trafficking in the whole multicellular organ systems of Arabidopsis. The first chapter of my thesis describes the search for new components involved in CME. Tandem affinity purification was conducted using CLC and its interacting partners were identified. Amongst the identified proteins were the Auxilin-likes1 and 2 (Axl1/2), putative uncoating factors, for which we made a full functional analysis. Over-expression of Axl1/2 causes extreme modifications in the dynamics of the machinery proteins and inhibition of endocytosis altogether. However the loss of function of the axl1/2 did not present any cellular or physiological phenotype, meaning Auxilin-likes do not form the major uncoating machinery. The second chapter of my thesis describes the establishment/utilisation of techniques to capture the dynamicity and the complexity of CME and post-endocytic trafficking. We have studied the development of endocytic pits at the PM – specifically, the mode of membrane remodeling during pit development and the role of actin in it, given plant cells possess high turgor pressure. Utilizing the improved z-resolution of TIRF and VAEM techniques, we captured the time-lapse of the endocytic events at the plasma membrane; and using particle detection software, we quantitatively analysed all the endocytic trajectories in an unbiased way to obtain the endocytic rate of the system. This together with the direct analysis of cargo internalisation from the PM provided an estimate on the endocytic potential of the cell. We also developed a methodology for ultrastructural analysis of different populations of Clathrin-Coated Structures (CCSs) in both PM and endomembranes in unroofed protoplasts. Structural analysis, together with the intensity profile of CCSs at the PM show that the mode of CCP development at the PM follows ‘Constant curvature model’; meaning that clathrin polymerisation energy is a major contributing factor of membrane remodeling. In addition, other analyses clearly show that actin is not required for membrane remodeling during invagination or any other step of CCP development, despite the prevalent high turgor pressure. However, actin is essential in orchestrating the post-endocytic trafficking of CCVs facilitating the EE formation. We also observed that the uncoating process post-endocytosis is not immediate; an alternative mechanism of uncoating – Sequential multi-step process – functions in the cell. Finally we also looked at one of the important physiological stimuli modulating the process – hormone, auxin. auxin has been known to influence CME before. We have made a detailed study on the concentration-time based effect of auxin on the machinery proteins, CCP development, and the specificity of cargoes endocytosed. To this end, we saw no general effect of auxin on CME at earlier time points. However, very low concentration of IAA, such as 50nM, accelerates endocytosis of specifically PIN2 through CME. Such a tight regulatory control with high specificity to PIN2 could be essential in modulating its polarity. ' acknowledged_ssus: - _id: Bio - _id: EM-Fac alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Madhumitha full_name: Narasimhan, Madhumitha id: 44BF24D0-F248-11E8-B48F-1D18A9856A87 last_name: Narasimhan orcid: 0000-0002-8600-0671 citation: ama: Narasimhan M. Clathrin-Mediated endocytosis, post-endocytic trafficking and their regulatory controls in plants . 2019. doi:10.15479/at:ista:th1075 apa: Narasimhan, M. (2019). Clathrin-Mediated endocytosis, post-endocytic trafficking and their regulatory controls in plants . Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:th1075 chicago: Narasimhan, Madhumitha. “Clathrin-Mediated Endocytosis, Post-Endocytic Trafficking and Their Regulatory Controls in Plants .” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/at:ista:th1075. ieee: M. Narasimhan, “Clathrin-Mediated endocytosis, post-endocytic trafficking and their regulatory controls in plants ,” Institute of Science and Technology Austria, 2019. ista: Narasimhan M. 2019. Clathrin-Mediated endocytosis, post-endocytic trafficking and their regulatory controls in plants . Institute of Science and Technology Austria. mla: Narasimhan, Madhumitha. Clathrin-Mediated Endocytosis, Post-Endocytic Trafficking and Their Regulatory Controls in Plants . Institute of Science and Technology Austria, 2019, doi:10.15479/at:ista:th1075. short: M. Narasimhan, Clathrin-Mediated Endocytosis, Post-Endocytic Trafficking and Their Regulatory Controls in Plants , Institute of Science and Technology Austria, 2019. date_created: 2019-04-09T14:37:06Z date_published: 2019-02-04T00:00:00Z date_updated: 2023-09-08T11:43:03Z day: '04' ddc: - '575' degree_awarded: PhD department: - _id: JiFr doi: 10.15479/at:ista:th1075 file: - access_level: open_access checksum: c958f27dd752712886e7e2638b847a3c content_type: video/x-msvideo creator: dernst date_created: 2019-04-09T14:35:18Z date_updated: 2021-02-11T23:30:15Z embargo: 2020-02-11 file_id: '6270' file_name: Supplementary_movie_1.avi file_size: 5402078 relation: main_file - access_level: open_access checksum: 8786fdc29c62987c0aad3c866a4d3691 content_type: video/x-msvideo creator: dernst date_created: 2019-04-09T14:35:18Z date_updated: 2021-02-11T23:30:15Z embargo: 2020-02-11 file_id: '6271' file_name: 3.7_supplementary_movie_10.avi file_size: 5927736 relation: main_file - access_level: open_access checksum: 25f784c5159d6f4d966b2f9b371ebaf6 content_type: video/x-msvideo creator: dernst date_created: 2019-04-09T14:35:18Z date_updated: 2021-02-11T23:30:15Z embargo: 2020-02-11 file_id: '6272' file_name: 3.7_supplementary_movie_9.avi file_size: 9570210 relation: main_file - 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access_level: open_access checksum: 4fcdaa3a6c645514a3b3205f0f69dc76 content_type: application/pdf creator: dernst date_created: 2019-04-09T14:35:33Z date_updated: 2021-02-11T11:17:15Z embargo: 2020-02-11 file_id: '6285' file_name: 2019_Thesis_Narasimhan.pdf file_size: 10553937 relation: main_file - access_level: closed checksum: 268f0b6bad21d5f0d671e5d4b88104a7 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: dernst date_created: 2019-04-09T14:35:36Z date_updated: 2020-07-14T12:47:26Z embargo_to: open_access file_id: '6286' file_name: 2019_Thesis_Narasimhan_source.docx file_size: 135291990 relation: source_file file_date_updated: 2021-02-11T23:30:15Z has_accepted_license: '1' language: - iso: eng month: '02' oa: 1 oa_version: Published Version page: '138' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '412' relation: part_of_dissertation status: public status: public supervisor: - first_name: Jiří full_name: Friml, Jiří id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 title: 'Clathrin-Mediated endocytosis, post-endocytic trafficking and their regulatory controls in plants ' 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: '2019' ... --- _id: '6947' abstract: - lang: eng text: Lymph nodes are es s ential organs of the immune s ys tem where adaptive immune responses originate, and consist of various leukocyte populations and a stromal backbone. Fibroblastic reticular cells (FRCs) are the main stromal cells and form a sponge-like extracellular matrix network, called conduits , which they thems elves enwrap and contract. Lymph, containing s oluble antigens , arrive in lymph nodes via afferent lymphatic vessels that connect to the s ubcaps ular s inus and conduit network. According to the current paradigm, the conduit network dis tributes afferent lymph through lymph nodes and thus provides acces s for immune cells to lymph-borne antigens. An elas tic caps ule s urrounds the organ and confines the immune cells and FRC network. Lymph nodes are completely packed with lymphocytes and lymphocyte numbers directly dictates the size of the organ. Although lymphocytes cons tantly enter and leave the lymph node, its s ize remains remarkedly s table under homeostatic conditions. It is only partly known how the cellularity and s ize of the lymph node is regulated and how the lymph node is able to swell in inflammation. The role of the FRC network in lymph node s welling and trans fer of fluids are inves tigated in this thes is. Furthermore, we s tudied what trafficking routes are us ed by cancer cells in lymph nodes to form distal metastases.We examined the role of a mechanical feedback in regulation of lymph node swelling. Using parallel plate compression and UV-las er cutting experiments we dis s ected the mechanical force dynamics of the whole lymph node, and individually for FRCs and the caps ule. Physical forces generated by packed lymphocytes directly affect the tens ion on the FRC network and capsule, which increases its resistance to swelling. This implies a feedback mechanism between tis s ue pres s ure and ability of lymphocytes to enter the organ. Following inflammation, the lymph node swells ∼10 fold in two weeks . Yet, what is the role for tens ion on the FRC network and caps ule, and how are lymphocytes able to enter in conditions that resist swelling remain open ques tions . We s how that tens ion on the FRC network is important to limit the swelling rate of the organ so that the FRC network can grow in a coordinated fashion. This is illustrated by interfering with FRC contractility, which leads to faster swelling rates and a dis organized FRC network in the inflamed lymph node. Growth of the FRC network in turn is expected to releas e tens ion on thes e s tructures and lowers the res is tance to swelling, thereby allowing more lymphocytes to enter the organ and drive more swelling. Halt of swelling coincides with a thickening of the caps ule, which forms a thick res is tant band around the organ and lowers tens ion on the FRC network to form a new force equilibrium.The FRC and conduit network are further believed to be a privileged s ite of s oluble information within the lymph node, although many details remain uns olved. We s how by 3D ultra-recons truction that FRCs and antigen pres enting cells cover the s urface of conduit s ys tem for more than 99% and we dis cus s the implications for s oluble information exchangeat the conduit level.Finally, there is an ongoing debate in the cancer field whether and how cancer cells in lymph nodes s eed dis tal metas tas es . We s how that cancer cells infus ed into the lymph node can utilize trafficking routes of immune cells and rapidly migrate to blood vessels. Once in the blood circulation, these cells are able to form metastases in distal tissues. acknowledged_ssus: - _id: Bio - _id: PreCl - _id: EM-Fac alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Frank P full_name: Assen, Frank P id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87 last_name: Assen orcid: 0000-0003-3470-6119 citation: ama: 'Assen FP. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. 2019. doi:10.15479/AT:ISTA:6947' apa: 'Assen, F. P. (2019). Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6947' chicago: 'Assen, Frank P. “Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6947.' ieee: 'F. P. Assen, “Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking,” Institute of Science and Technology Austria, 2019.' ista: 'Assen FP. 2019. Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking. Institute of Science and Technology Austria.' mla: 'Assen, Frank P. Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6947.' short: 'F.P. Assen, Lymph Node Mechanics: Deciphering the Interplay between Stroma Contractility, Morphology and Lymphocyte Trafficking, Institute of Science and Technology Austria, 2019.' date_created: 2019-10-14T16:54:52Z date_published: 2019-10-09T00:00:00Z date_updated: 2023-09-13T08:50:57Z day: '9' ddc: - '570' degree_awarded: PhD department: - _id: MiSi doi: 10.15479/AT:ISTA:6947 file: - access_level: closed checksum: 53a739752a500f84d0f8ec953cbbd0b6 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: fassen date_created: 2019-11-06T12:30:02Z date_updated: 2020-11-07T23:30:03Z embargo_to: open_access file_id: '6990' file_name: PhDthesis_FrankAssen_revised2.docx file_size: 214172667 relation: source_file - access_level: open_access checksum: 8c156b65d9347bb599623a4b09f15d15 content_type: application/pdf creator: fassen date_created: 2019-11-06T12:30:57Z date_updated: 2020-11-07T23:30:03Z embargo: 2020-11-06 file_id: '6991' file_name: PhDthesis_FrankAssen_revised2.pdf file_size: 83637532 relation: main_file file_date_updated: 2020-11-07T23:30:03Z has_accepted_license: '1' language: - iso: eng month: '10' oa: 1 oa_version: Published Version page: '142' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '664' relation: part_of_dissertation status: public - id: '402' relation: part_of_dissertation status: public status: public supervisor: - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 title: 'Lymph node mechanics: Deciphering the interplay between stroma contractility, morphology and lymphocyte trafficking' type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6849' abstract: - lang: eng text: 'Brain function is mediated by complex dynamical interactions between excitatory and inhibitory cell types. The Cholecystokinin-expressing inhibitory cells (CCK-interneurons) are one of the least studied types, despite being suspected to play important roles in cognitive processes. We studied the network effects of optogenetic silencing of CCK-interneurons in the CA1 hippocampal area during exploration and sleep states. The cell firing pattern in response to light pulses allowed us to classify the recorded neurons in 5 classes, including disinhibited and non-responsive pyramidal cell and interneurons, and the inhibited interneurons corresponding to the CCK group. The light application, which inhibited the activity of CCK interneurons triggered wider changes in the firing dynamics of cells. We observed rate changes (i.e. remapping) of pyramidal cells during the exploration session in which the light was applied relative to the previous control session that was not restricted neither in time nor space to the light delivery. Also, the disinhibited pyramidal cells had higher increase in bursting than in single spike firing rate as a result of CCK silencing. In addition, the firing activity patterns during exploratory periods were more weakly reactivated in sleep for those periods in which CCK-interneuron were silenced than in the unaffected periods. Furthermore, light pulses during sleep disrupted the reactivation of recent waking patterns. Hence, silencing CCK neurons during exploration suppressed the reactivation of waking firing patterns in sleep and CCK interneuron activity was also required during sleep for the normal reactivation of waking patterns. These findings demonstrate the involvement of CCK cells in reactivation-related memory consolidation. An important part of our analysis was to test the relationship of the identified CCKinterneurons to brain oscillations. Our findings showed that these cells exhibited different oscillatory behaviour during anaesthesia and natural waking and sleep conditions. We showed that: 1) Contrary to the past studies performed under anaesthesia, the identified CCKinterneurons fired on the descending portion of the theta phase in waking exploration. 2) CCKinterneuron preferred phases around the trough of gamma oscillations. 3) Contrary to anaesthesia conditions, the average firing rate of the CCK-interneurons increased around the peak activity of the sharp-wave ripple (SWR) events in natural sleep, which is congruent with new reports about their functional connectivity. We also found that light driven CCK-interneuron silencing altered the dynamics on the CA1 network oscillatory activity: 1) Pyramidal cells negatively shifted their preferred theta phases when the light was applied, while interneurons responses were less consistent. 2) As a population, pyramidal cells negatively shifted their preferred activity during gamma oscillations, albeit we did not find gamma modulation differences related to the light application when pyramidal cells were subdivided into the disinhibited and unaffected groups. 3) During the peak of SWR events, all but the CCK-interneurons had a reduction in their relative firing rate change during the light application as compared to the change observed at SWR initiation. Finally, regarding to the place field activity of the recorded pyramidal neurons, we showed that the disinhibited pyramidal cells had reduced place field similarity, coherence and spatial information, but only during the light application. The mechanisms behind such observed behaviours might involve eCB signalling and plastic changes in CCK-interneuron synapses. In conclusion, the observed changes related to the light-mediated silencing of CCKinterneurons have unravelled characteristics of this interneuron subpopulation that might change the understanding not only of their particular network interactions, but also of the current theories about the emergence of certain cognitive processes such as place coding needed for navigation or hippocampus-dependent memory consolidation. ' acknowledged_ssus: - _id: Bio - _id: PreCl - _id: M-Shop alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Dámaris K full_name: Rangel Guerrero, Dámaris K id: 4871BCE6-F248-11E8-B48F-1D18A9856A87 last_name: Rangel Guerrero orcid: 0000-0002-8602-4374 citation: ama: Rangel Guerrero DK. The role of CCK-interneurons in regulating hippocampal network dynamics. 2019. doi:10.15479/AT:ISTA:6849 apa: Rangel Guerrero, D. K. (2019). The role of CCK-interneurons in regulating hippocampal network dynamics. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6849 chicago: Rangel Guerrero, Dámaris K. “The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6849. ieee: D. K. Rangel Guerrero, “The role of CCK-interneurons in regulating hippocampal network dynamics,” Institute of Science and Technology Austria, 2019. ista: Rangel Guerrero DK. 2019. The role of CCK-interneurons in regulating hippocampal network dynamics. Institute of Science and Technology Austria. mla: Rangel Guerrero, Dámaris K. The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6849. short: D.K. Rangel Guerrero, The Role of CCK-Interneurons in Regulating Hippocampal Network Dynamics, Institute of Science and Technology Austria, 2019. date_created: 2019-09-06T06:54:16Z date_published: 2019-09-09T00:00:00Z date_updated: 2023-09-19T10:01:12Z day: '09' ddc: - '570' degree_awarded: PhD department: - _id: JoCs doi: 10.15479/AT:ISTA:6849 file: - access_level: closed checksum: 244dc4f74dbfc94f414156092298831f content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: drangel date_created: 2019-09-09T13:09:45Z date_updated: 2021-02-10T23:30:09Z embargo_to: open_access file_id: '6865' file_name: Thesis_Damaris_Rangel_source.docx file_size: 18253100 relation: source_file - access_level: open_access checksum: 59c73be40eeaa1c4db24067270151555 content_type: application/pdf creator: drangel date_created: 2019-09-09T13:09:52Z date_updated: 2020-09-11T22:30:04Z embargo: 2020-09-10 file_id: '6866' file_name: Thesis_Damaris_Rangel_pdfa.pdf file_size: 2160109 relation: main_file request_a_copy: 0 file_date_updated: 2021-02-10T23:30:09Z has_accepted_license: '1' language: - iso: eng month: '09' oa: 1 oa_version: Published Version page: '97' publication_identifier: isbn: - '9783990780039' issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '5914' relation: part_of_dissertation status: public status: public supervisor: - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 title: The role of CCK-interneurons in regulating hippocampal network dynamics type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '7132' abstract: - lang: eng text: "A major challenge in neuroscience research is to dissect the circuits that orchestrate behavior in health and disease. Proteins from a wide range of non-mammalian species, such as microbial opsins, have been successfully transplanted to specific neuronal targets to override their natural communication patterns. The goal of our work is to manipulate synaptic communication in a manner that closely incorporates the functional intricacies of synapses by preserving temporal encoding (i.e. the firing pattern of the presynaptic neuron) and connectivity (i.e. target specific synapses rather than specific neurons). Our strategy to achieve this goal builds on the use of non-mammalian transplants to create a synthetic synapse. The mode of modulation comes from pre-synaptic uptake of a synthetic neurotransmitter (SN) into synaptic vesicles by means of a genetically targeted transporter selective for the SN. Upon natural vesicular release, exposure of the SN to the synaptic cleft will modify the post-synaptic potential through an orthogonal ligand gated ion channel. To achieve this goal we have functionally characterized a mixed cationic methionine-gated ion channel from Arabidopsis thaliana, designed a method to functionally characterize a synthetic transporter in isolated synaptic vesicles without the need for transgenic animals, identified and extracted multiple prokaryotic uptake systems that are substrate specific for methionine (Met), and established a primary/cell line co-culture system that would allow future combinatorial testing of this orthogonal transmitter-transporter-channel trifecta.\r\nSynthetic synapses will provide a unique opportunity to manipulate synaptic communication while maintaining the electrophysiological integrity of the pre-synaptic cell. In this way, information may be preserved that was generated in upstream circuits and that could be essential for concerted function and information processing." alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Catherine full_name: Mckenzie, Catherine id: 3EEDE19A-F248-11E8-B48F-1D18A9856A87 last_name: Mckenzie citation: ama: Mckenzie C. Design and characterization of methods and biological components to realize synthetic neurotransmission. 2019. doi:10.15479/at:ista:7132 apa: Mckenzie, C. (2019). Design and characterization of methods and biological components to realize synthetic neurotransmission. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:7132 chicago: Mckenzie, Catherine. “Design and Characterization of Methods and Biological Components to Realize Synthetic Neurotransmission.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/at:ista:7132. ieee: C. Mckenzie, “Design and characterization of methods and biological components to realize synthetic neurotransmission,” Institute of Science and Technology Austria, 2019. ista: Mckenzie C. 2019. Design and characterization of methods and biological components to realize synthetic neurotransmission. Institute of Science and Technology Austria. mla: Mckenzie, Catherine. Design and Characterization of Methods and Biological Components to Realize Synthetic Neurotransmission. Institute of Science and Technology Austria, 2019, doi:10.15479/at:ista:7132. short: C. Mckenzie, Design and Characterization of Methods and Biological Components to Realize Synthetic Neurotransmission, Institute of Science and Technology Austria, 2019. date_created: 2019-11-27T09:07:14Z date_published: 2019-06-27T00:00:00Z date_updated: 2024-03-27T23:30:21Z day: '27' ddc: - '571' - '573' degree_awarded: PhD department: - _id: HaJa doi: 10.15479/at:ista:7132 file: - access_level: closed checksum: 34d0fe0f6e0af97b5937205a3e350423 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: dernst date_created: 2019-11-27T09:06:10Z date_updated: 2020-07-14T12:47:50Z file_id: '7133' file_name: McKenzie PhD Thesis August 2018 - Corrected Final.docx file_size: 5054633 relation: source_file - access_level: open_access checksum: 140dfb5e3df7edca34f4b6fcc55d876f content_type: application/pdf creator: dernst date_created: 2019-11-27T09:06:10Z date_updated: 2020-07-14T12:47:50Z file_id: '7134' file_name: McKenzie PhD Thesis August 2018 - Corrected Final.pdf file_size: 3231837 relation: main_file file_date_updated: 2020-07-14T12:47:50Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '95' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6266' relation: old_edition 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: Design and characterization of methods and biological components to realize synthetic neurotransmission type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6825' abstract: - lang: eng text: "The solving of complex tasks requires the functions of more than one brain area and their interaction. Whilst spatial navigation and memory is dependent on the hippocampus, flexible behavior relies on the medial prefrontal cortex (mPFC). To further examine the roles of the hippocampus and mPFC, we recorded their neural activity during a task that depends on both of these brain regions.\r\nWith tetrodes, we recorded the extracellular activity of dorsal hippocampal CA1 (HPC) and mPFC neurons in Long-Evans rats performing a rule-switching task on the plus-maze. The plus-maze task had a spatial component since it required navigation along one of the two start arms and at the maze center a choice between one of the two goal arms. Which goal contained a reward depended on the rule currently in place. After an uncued rule change the animal had to abandon the old strategy and switch to the new rule, testing cognitive flexibility. Investigating the coordination of activity between the HPC and mPFC allows determination during which task stages their interaction is required. Additionally, comparing neural activity patterns in these two brain regions allows delineation of the specialized functions of the HPC and mPFC in this task. We analyzed neural activity in the HPC and mPFC in terms of oscillatory interactions, rule coding and replay.\r\nWe found that theta coherence between the HPC and mPFC is increased at the center and goals of the maze, both when the rule was stable or has changed. Similar results were found for locking of HPC and mPFC neurons to HPC theta oscillations. However, no differences in HPC-mPFC theta coordination were observed between the spatially- and cue-guided rule. Phase locking of HPC and mPFC neurons to HPC gamma oscillations was not modulated by\r\nmaze position or rule type. We found that the HPC coded for the two different rules with cofiring relationships between\r\ncell pairs. However, we could not find conclusive evidence for rule coding in the mPFC. Spatially-selective firing in the mPFC generalized between the two start and two goal arms. With Bayesian positional decoding, we found that the mPFC reactivated non-local positions during awake immobility periods. Replay of these non-local positions could represent entire behavioral trajectories resembling trajectory replay of the HPC. Furthermore, mPFC\r\ntrajectory-replay at the goal positively correlated with rule-switching performance. \r\nFinally, HPC and mPFC trajectory replay occurred independently of each other. These results show that the mPFC can replay ordered patterns of activity during awake immobility, possibly underlying its role in flexible behavior. " alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Karola full_name: Käfer, Karola id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87 last_name: Käfer citation: ama: Käfer K. The hippocampus and medial prefrontal cortex during flexible behavior. 2019. doi:10.15479/AT:ISTA:6825 apa: Käfer, K. (2019). The hippocampus and medial prefrontal cortex during flexible behavior. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6825 chicago: Käfer, Karola. “The Hippocampus and Medial Prefrontal Cortex during Flexible Behavior.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6825. ieee: K. Käfer, “The hippocampus and medial prefrontal cortex during flexible behavior,” Institute of Science and Technology Austria, 2019. ista: Käfer K. 2019. The hippocampus and medial prefrontal cortex during flexible behavior. Institute of Science and Technology Austria. mla: Käfer, Karola. The Hippocampus and Medial Prefrontal Cortex during Flexible Behavior. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6825. short: K. Käfer, The Hippocampus and Medial Prefrontal Cortex during Flexible Behavior, Institute of Science and Technology Austria, 2019. date_created: 2019-08-21T15:00:57Z date_published: 2019-08-24T00:00:00Z date_updated: 2023-09-07T13:01:42Z day: '24' ddc: - '570' degree_awarded: PhD department: - _id: JoCs doi: 10.15479/AT:ISTA:6825 file: - access_level: open_access checksum: 2664420e332a33338568f4f3bfc59287 content_type: application/pdf creator: kkaefer date_created: 2019-09-03T08:07:13Z date_updated: 2020-09-06T22:30:03Z embargo: 2020-09-05 file_id: '6846' file_name: Thesis_Kaefer_PDFA.pdf file_size: 3205202 relation: main_file request_a_copy: 0 - access_level: closed checksum: 9a154eab6f07aa590a3d2651dc0d926a content_type: application/zip creator: kkaefer date_created: 2019-09-03T08:07:17Z date_updated: 2020-09-15T22:30:05Z embargo_to: open_access file_id: '6847' file_name: Thesis_Kaefer.zip file_size: 2506835 relation: main_file file_date_updated: 2020-09-15T22:30:05Z has_accepted_license: '1' language: - iso: eng month: '08' oa: 1 oa_version: Published Version page: '89' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '5949' relation: part_of_dissertation status: public status: public supervisor: - first_name: Jozsef L full_name: Csicsvari, Jozsef L id: 3FA14672-F248-11E8-B48F-1D18A9856A87 last_name: Csicsvari orcid: 0000-0002-5193-4036 title: The hippocampus and medial prefrontal cortex during flexible behavior type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6546' abstract: - lang: eng text: "Invasive migration plays a crucial role not only during development and homeostasis but also in pathological states, such as tumor metastasis. Drosophila macrophage migration into the extended germband is an interesting system to study invasive migration. It carries similarities to immune cell transmigration and cancer cell invasion, therefore studying this process could also bring new understanding of invasion in higher organisms. In our work, we uncover a highly conserved member of the major facilitator family that plays a role in tissue invasion through regulation of glycosylation on a subgroup of proteins and/or by aiding the precise timing of DN-Cadherin downregulation. \r\n\r\nAberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify \r\na key conserved regulator that orchestrates O-glycosylation on a protein subset to activate \r\na program governing migration steps important for both development and cancer metastasis. \r\n" acknowledged_ssus: - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Katarina full_name: Valosková, Katarina id: 46F146FC-F248-11E8-B48F-1D18A9856A87 last_name: Valosková citation: ama: Valosková K. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. 2019. doi:10.15479/AT:ISTA:6546 apa: Valosková, K. (2019). The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6546 chicago: Valosková, Katarina. “The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6546. ieee: K. Valosková, “The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration,” Institute of Science and Technology Austria, 2019. ista: Valosková K. 2019. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria. mla: Valosková, Katarina. The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6546. short: K. Valosková, The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration, Institute of Science and Technology Austria, 2019. date_created: 2019-06-07T12:49:19Z date_published: 2019-06-07T00:00:00Z date_updated: 2023-09-19T10:15:54Z day: '07' ddc: - '570' degree_awarded: PhD department: - _id: DaSi doi: 10.15479/AT:ISTA:6546 file: - access_level: closed checksum: 68949c2d96210b45b981a23e9c9cd93c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: khribikova date_created: 2019-06-07T13:00:04Z date_updated: 2020-07-14T12:47:33Z embargo_to: open_access file_id: '6549' file_name: Katarina Valoskova_PhD thesis_final version.docx file_size: 14110626 relation: source_file - access_level: open_access checksum: 555329cd76e196c96f5278c480ee2e6e content_type: application/pdf creator: khribikova date_created: 2019-06-07T13:00:08Z date_updated: 2021-02-11T11:17:14Z embargo: 2020-06-07 file_id: '6550' file_name: Katarina Valoskova_PhD thesis_final version.pdf file_size: 10054156 relation: main_file file_date_updated: 2021-02-11T11:17:14Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '141' project: - _id: 253CDE40-B435-11E9-9278-68D0E5697425 grant_number: '24283' name: Examination of the role of a MFS transporter in the migration of Drosophila immune cells publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6187' relation: part_of_dissertation status: public - id: '544' relation: part_of_dissertation status: public status: public supervisor: - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 title: The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6363' abstract: - lang: eng text: "Distinguishing between similar experiences is achieved by the brain \ in a process called pattern separation. In the hippocampus, pattern \ separation reduces the interference of memories and increases the storage capacity by decorrelating similar inputs patterns of neuronal activity into \ non-overlapping output firing patterns. Winners-take-all (WTA) mechanism \ is a theoretical model for pattern separation in which a \"winner\" \ cell suppresses the activity of the neighboring neurons through feedback inhibition. However, if the network properties of the dentate gyrus support WTA as a biologically conceivable model remains unknown. Here, we showed that the connectivity rules of PV+interneurons and their synaptic properties are optimizedfor efficient pattern separation. We found using multiple whole-cell in vitrorecordings that PV+interneurons mainly connect to granule cells (GC) through lateral inhibition, a form of feedback inhibition in which a GC inhibits other GCs but not \ itself through the activation of PV+interneurons. Thus, lateral inhibition between GC–PV+interneurons was ~10 times more abundant than recurrent connections. Furthermore, the GC–PV+interneuron connectivity was more spatially confined \ but less abundant than PV+interneurons–GC connectivity, leading to an \ asymmetrical distribution of excitatory and inhibitory connectivity. Our network model of the dentate gyrus with incorporated real connectivity rules efficiently decorrelates neuronal activity patterns using WTA as the primary mechanism. \ This process relied on lateral inhibition, fast-signaling properties of \ PV+interneurons and the asymmetrical distribution of excitatory and inhibitory connectivity. Finally, we found that silencing the activity of PV+interneurons in vivoleads to acute deficits in discrimination between similar environments, suggesting that PV+interneuron networks are necessary for behavioral relevant computations. Our results demonstrate that PV+interneurons possess unique connectivity and fast signaling properties that confer to the dentate \ gyrus network properties that allow the emergence of pattern separation. Thus, our results contribute to the knowledge of how specific forms of network organization underlie sophisticated types of information processing. \r\n" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: 'Claudia ' full_name: 'Espinoza Martinez, Claudia ' id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87 last_name: Espinoza Martinez orcid: 0000-0003-4710-2082 citation: ama: Espinoza Martinez C. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. 2019. doi:10.15479/AT:ISTA:6363 apa: Espinoza Martinez, C. (2019). Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6363 chicago: Espinoza Martinez, Claudia . “Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6363. ieee: C. Espinoza Martinez, “Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits,” Institute of Science and Technology Austria, 2019. ista: Espinoza Martinez C. 2019. Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits. Institute of Science and Technology Austria. mla: Espinoza Martinez, Claudia. Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6363. short: C. Espinoza Martinez, Parvalbumin+ Interneurons Enable Efficient Pattern Separation in Hippocampal Microcircuits, Institute of Science and Technology Austria, 2019. date_created: 2019-04-30T11:56:10Z date_published: 2019-04-30T00:00:00Z date_updated: 2023-09-15T12:03:48Z day: '30' ddc: - '570' degree_awarded: PhD department: - _id: PeJo doi: 10.15479/AT:ISTA:6363 file: - access_level: open_access checksum: 77c6c05cfe8b58c8abcf1b854375d084 content_type: application/pdf creator: cespinoza date_created: 2019-05-07T16:00:39Z date_updated: 2021-02-11T11:17:15Z embargo: 2020-05-09 file_id: '6389' file_name: Espinozathesis_all2.pdf file_size: 13966891 relation: main_file - access_level: closed checksum: f6aa819f127691a2b0fc21c76eb09746 content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: cespinoza date_created: 2019-05-07T16:00:48Z date_updated: 2020-07-14T12:47:28Z embargo_to: open_access file_id: '6390' file_name: Espinoza_Thesis.docx file_size: 11159900 relation: source_file file_date_updated: 2021-02-11T11:17:15Z has_accepted_license: '1' language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: '140' publication_identifier: isbn: - 978-3-99078-000-8 issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '21' relation: part_of_dissertation status: public status: public supervisor: - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 title: Parvalbumin+ interneurons enable efficient pattern separation in hippocampal microcircuits type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ... --- _id: '6891' abstract: - lang: eng text: "While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance. \r\nCells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients. \r\nNevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner. \r\nTherefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments. \r\nThe results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate. \r\nThus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration. \r\nThereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance.\r\n" alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Aglaja full_name: Kopf, Aglaja id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87 last_name: Kopf orcid: 0000-0002-2187-6656 citation: ama: Kopf A. The implication of cytoskeletal dynamics on leukocyte migration. 2019. doi:10.15479/AT:ISTA:6891 apa: Kopf, A. (2019). The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6891 chicago: Kopf, Aglaja. “The Implication of Cytoskeletal Dynamics on Leukocyte Migration.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6891. ieee: A. Kopf, “The implication of cytoskeletal dynamics on leukocyte migration,” Institute of Science and Technology Austria, 2019. ista: Kopf A. 2019. The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria. mla: Kopf, Aglaja. The Implication of Cytoskeletal Dynamics on Leukocyte Migration. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6891. short: A. Kopf, The Implication of Cytoskeletal Dynamics on Leukocyte Migration, Institute of Science and Technology Austria, 2019. date_created: 2019-09-19T08:19:44Z date_published: 2019-07-24T00:00:00Z date_updated: 2023-10-18T08:49:17Z day: '24' ddc: - '570' degree_awarded: PhD department: - _id: MiSi doi: 10.15479/AT:ISTA:6891 file: - access_level: closed checksum: 00d100d6468e31e583051e0a006b640c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: akopf date_created: 2019-10-15T05:28:42Z date_updated: 2020-10-17T22:30:03Z embargo_to: open_access file_id: '6950' file_name: Kopf_PhD_Thesis.docx file_size: 74735267 relation: source_file - access_level: open_access checksum: 5d1baa899993ae6ca81aebebe1797000 content_type: application/pdf creator: akopf date_created: 2019-10-15T05:28:47Z date_updated: 2020-10-17T22:30:03Z embargo: 2020-10-16 file_id: '6951' file_name: Kopf_PhD_Thesis1.pdf file_size: 52787224 relation: main_file file_date_updated: 2020-10-17T22:30:03Z has_accepted_license: '1' keyword: - cell biology - immunology - leukocyte - migration - microfluidics language: - iso: eng month: '07' oa: 1 oa_version: Published Version page: '171' project: - _id: 265E2996-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W01250-B20 name: Nano-Analytics of Cellular Systems publication_identifier: eissn: - 2663-337X isbn: - 978-3-99078-002-2 publication_status: published publisher: Institute of Science and Technology Austria related_material: link: - relation: press_release url: https://ist.ac.at/en/news/feeling-like-a-cell/ record: - id: '6328' relation: part_of_dissertation status: public - id: '15' relation: part_of_dissertation status: public - id: '6877' relation: part_of_dissertation status: public status: public supervisor: - first_name: Michael K full_name: Sixt, Michael K id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87 last_name: Sixt orcid: 0000-0002-6620-9179 title: The implication of cytoskeletal dynamics on leukocyte migration type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ...