---
_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
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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
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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
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creator: szhechev
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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:
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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
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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
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- 2663-337X
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publisher: Institute of Science and Technology Austria
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- 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
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date_created: 2019-12-12T09:32:36Z
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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:
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- id: '6377'
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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:
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content_type: application/zip
creator: scepeda
date_created: 2019-05-23T11:18:16Z
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file_size: 23937464
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creator: scepeda
date_created: 2019-05-23T11:18:13Z
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file_name: CepedaThesis.pdf
file_size: 16646985
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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
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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:
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checksum: e60a72de35d270b31f1a23d50f224ec0
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creator: rprizak
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creator: rprizak
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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
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- _id: 258DCDE6-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '338804'
name: Random matrices, universality and disordered quantum systems
publication_identifier:
issn:
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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
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- 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:
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issn:
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status: public
status: public
supervisor:
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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
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ddc:
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- '006'
- '578'
- '592'
degree_awarded: PhD
department:
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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
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month: '02'
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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
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file_date_updated: 2020-11-07T23:30:03Z
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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
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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
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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:
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checksum: 34d0fe0f6e0af97b5937205a3e350423
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
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date_updated: 2020-07-14T12:47:50Z
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file_name: McKenzie PhD Thesis August 2018 - Corrected Final.docx
file_size: 5054633
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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'
...