---
_id: '18121'
abstract:
- lang: eng
  text: It is known that sparsity can improve interpretability for deep neural networks.
    However, existing methods in the area either require networks that are pre-trained
    with sparsity constraints, or impose sparsity after the fact, altering the network’s
    general behavior. In this paper, we demonstrate, for the first time, that sparsity
    can instead be incorporated into the interpretation process itself, as a sample-specific
    preprocessing step. Unlike previous work, this approach, which we call SPADE,
    does not place constraints on the trained model and does not affect its behavior
    during inference on the sample. Given a trained model and a target sample, SPADE
    uses sample-targeted pruning to provide a "trace" of the network’s execution on
    the sample, reducing the network to the most important connections prior to computing
    an interpretation. We demonstrate that preprocessing with SPADE significantly
    increases the accuracy of image saliency maps across several interpretability
    methods. Additionally, SPADE improves the usefulness of neuron visualizations,
    aiding humans in reasoning about network behavior. Our code is available at https://github.com/IST-DASLab/SPADE.
acknowledged_ssus:
- _id: ScienComp
acknowledgement: The authors would like to thank Stephen Casper and Tony Wang for
  their feedback on this work, and Eldar Kurtic for his advice on aspects of the project.
  This research was supported by the Scientific Service Units (SSU) of IST Austria
  through resources provided by Scientific Computing (SciComp). EI was supported in
  part by the FWF DK VGSCO, grant agreement number W1260-N35.
alternative_title:
- PMLR
article_processing_charge: No
arxiv: 1
author:
- first_name: Arshia Soltani
  full_name: Moakhar, Arshia Soltani
  last_name: Moakhar
- first_name: Eugenia B
  full_name: Iofinova, Eugenia B
  id: f9a17499-f6e0-11ea-865d-fdf9a3f77117
  last_name: Iofinova
  orcid: 0000-0002-7778-3221
- first_name: Elias
  full_name: Frantar, Elias
  id: 09a8f98d-ec99-11ea-ae11-c063a7b7fe5f
  last_name: Frantar
- first_name: Dan-Adrian
  full_name: Alistarh, Dan-Adrian
  id: 4A899BFC-F248-11E8-B48F-1D18A9856A87
  last_name: Alistarh
  orcid: 0000-0003-3650-940X
citation:
  ama: 'Moakhar AS, Iofinova EB, Frantar E, Alistarh D-A. SPADE: Sparsity-guided debugging
    for deep neural networks. In: <i>Proceedings of the 41st International Conference
    on Machine Learning</i>. Vol 235. ML Research Press; 2024:45955-45987.'
  apa: 'Moakhar, A. S., Iofinova, E. B., Frantar, E., &#38; Alistarh, D.-A. (2024).
    SPADE: Sparsity-guided debugging for deep neural networks. In <i>Proceedings of
    the 41st International Conference on Machine Learning</i> (Vol. 235, pp. 45955–45987).
    Vienna, Austria: ML Research Press.'
  chicago: 'Moakhar, Arshia Soltani, Eugenia B Iofinova, Elias Frantar, and Dan-Adrian
    Alistarh. “SPADE: Sparsity-Guided Debugging for Deep Neural Networks.” In <i>Proceedings
    of the 41st International Conference on Machine Learning</i>, 235:45955–87. ML
    Research Press, 2024.'
  ieee: 'A. S. Moakhar, E. B. Iofinova, E. Frantar, and D.-A. Alistarh, “SPADE: Sparsity-guided
    debugging for deep neural networks,” in <i>Proceedings of the 41st International
    Conference on Machine Learning</i>, Vienna, Austria, 2024, vol. 235, pp. 45955–45987.'
  ista: 'Moakhar AS, Iofinova EB, Frantar E, Alistarh D-A. 2024. SPADE: Sparsity-guided
    debugging for deep neural networks. Proceedings of the 41st International Conference
    on Machine Learning. ICML: International Conference on Machine Learning, PMLR,
    vol. 235, 45955–45987.'
  mla: 'Moakhar, Arshia Soltani, et al. “SPADE: Sparsity-Guided Debugging for Deep
    Neural Networks.” <i>Proceedings of the 41st International Conference on Machine
    Learning</i>, vol. 235, ML Research Press, 2024, pp. 45955–87.'
  short: A.S. Moakhar, E.B. Iofinova, E. Frantar, D.-A. Alistarh, in:, Proceedings
    of the 41st International Conference on Machine Learning, ML Research Press, 2024,
    pp. 45955–45987.
conference:
  end_date: 2024-07-27
  location: Vienna, Austria
  name: 'ICML: International Conference on Machine Learning'
  start_date: 2024-07-21
corr_author: '1'
date_created: 2024-09-22T22:01:46Z
date_published: 2024-09-01T00:00:00Z
date_updated: 2026-05-15T11:12:30Z
day: '01'
department:
- _id: DaAl
external_id:
  arxiv:
  - '2310.04519'
intvolume: '       235'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.48550/arXiv.2310.04519
month: '09'
oa: 1
oa_version: Preprint
page: 45955-45987
project:
- _id: 9B9290DE-BA93-11EA-9121-9846C619BF3A
  grant_number: W1260-N35
  name: Vienna Graduate School on Computational Optimization
publication: Proceedings of the 41st International Conference on Machine Learning
publication_identifier:
  eissn:
  - 2640-3498
publication_status: published
publisher: ML Research Press
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/IST-DASLab/SPADE
  record:
  - id: '21854'
    relation: dissertation_contains
    status: for_moderation
scopus_import: '1'
status: public
title: 'SPADE: Sparsity-guided debugging for deep neural networks'
type: conference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 235
year: '2024'
...
---
OA_place: publisher
_id: '17206'
abstract:
- lang: eng
  text: "Males and females exhibit numerous differences, from the initial stages of
    sex determination to the\r\ndevelopment of secondary sexual characteristics. In
    Drosophila, these differences have been\r\nthoroughly studied. Extensive research
    has been performed to understand the role and molecular\r\nmode of action of central
    sex in determining switch genes, such as transformer (tra) and Sex-lethal\r\n(Sxl).
    Furthermore, studies have highlighted differential gene expression as an essential
    mechanism to\r\ncreate sexual dimorphism. An alternative path to sexual dimorphism
    that has been less explored is\r\nalternative splicing, the mechanism through
    which genes can produce multiple transcripts with\r\ndistinct properties and functions.
    The primary switch sex-determining gene Sxl is a good example of\r\nthe role of
    alternative splicing for sex-specific functions: the inclusion of a specific exon
    determines\r\nthe male or female form of the protein, which in turn switches on
    either the male or female\r\ndevelopmental pathway. The genes that act upstream
    of Sxl and determine which form is expressed -\r\nthe counter genes - have received
    less attention. This thesis addresses two critical questions about\r\nthe molecular
    encoding of sexes in the Drosophila melanogaster genome: First, the use of splice
    forms\r\nin male and female tissues in D. melanogaster is examined, inferring
    the molecular and evolutionary\r\nparameters shaping the diversity of the splicing
    landscape. Second, the behaviour of counter genes in\r\nDrosophila-related species
    is investigated, shedding light on potential changes leading to their\r\nincorporation
    into the sex-determination pathway.\r\nFor the alternative splicing analyses,
    long-read RNA sequencing of testes, ovaries, female and male\r\nmidguts, heads,
    and whole bodies was performed. A novel pipeline was developed to assign unique\r\ntranscript
    identifiers for each sequence of exons and introns in the read, enabling detailed\r\ncomparisons
    of splicing variants in each tissue/sex. Alternative splicing was found to be
    more\r\npervasive in females than males (22,201 exclusive splice forms in females
    versus 12,631 in males),\r\nespecially when comparing ovaries to other tissues.
    The ovaries alone displayed 15,299 exclusive\r\nsplice forms, suggesting most
    female exclusive splice forms originate there. Genome location and gene\r\nage
    were also correlated with the number of splice forms per gene. In particular,
    the X and 4th\r\nchromosomes (Muller elements A and F) showed more splice forms
    per gene than other\r\nchromosomes. Additionally, genes older than 63 million
    years exhibited more splice forms per gene\r\nthan younger genes. Our results
    suggest that alternative splicing is more prevalent than previously\r\nbelieved,
    with numerous female-exclusive forms, age, and location playing significant roles
    in shaping\r\nits prevalence.\r\nFor the counter genes analyses, we combined published
    gene expression, genomic, and gene\r\ninteraction data from various clades (Bactrocera
    jarvisi, B. oleae, Ceratitis capitata, Mus musculus,\r\nCaenorhabditis elegans,
    Homo sapiens, and D. melanogaster). The counter genes scute (sc), extra\r\nmacrochaetae
    (emc), groucho (gro), deadpan (dpn), daughterless (da), runt (run), Sxl, hermaphrodite\r\n(her),
    and tra maintain conserved Muller element locations between C. capitata and D.
    melanogaster,\r\nwhich are most of the counter genes identified in the C. capitata
    genome. Their expression patterns\r\nduring early embryogenesis in B. jarvisi
    and D. melanogaster are also similar for counter genes dpn,\r\ngro, da, and emc.
    However, Sxl and sc are also found to have more extreme expression ratios between\r\nthe
    species. Lastly, gene interactions within the counter genes are conserved, with
    da-sc and gro-dpn\r\ninteractions occurring in Drosophila, worms, humans, and
    mice. Interactions such as dpn-sc, dpn-da,\r\nda-emc, and gro-run are present
    in Drosophila, mice, and humans, suggesting these genes were\r\nrecruited by ancestral
    characteristics, primarily during embryogenesis. The conserved expression,\r\nlocation,
    and interactions of counter genes suggest serendipitous recruitment of such genes
    instead\r\nof a change in those characteristics as they were recruited for this
    function. "
acknowledged_ssus:
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Julia
  full_name: Raices, Julia
  id: 3EE67F22-F248-11E8-B48F-1D18A9856A87
  last_name: Raices
citation:
  ama: 'Raices J. Novel approaches to studying alternative splicing in Drosophila
    Melanogaster : Insights into sex-specific gene expression and the evolution of
    sex determination. 2024. doi:<a href="https://doi.org/10.15479/at:ista:17206">10.15479/at:ista:17206</a>'
  apa: 'Raices, J. (2024). <i>Novel approaches to studying alternative splicing in
    Drosophila Melanogaster : Insights into sex-specific gene expression and the evolution
    of sex determination</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:17206">https://doi.org/10.15479/at:ista:17206</a>'
  chicago: 'Raices, Julia. “Novel Approaches to Studying Alternative Splicing in Drosophila
    Melanogaster : Insights into Sex-Specific Gene Expression and the Evolution of
    Sex Determination.” Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:17206">https://doi.org/10.15479/at:ista:17206</a>.'
  ieee: 'J. Raices, “Novel approaches to studying alternative splicing in Drosophila
    Melanogaster : Insights into sex-specific gene expression and the evolution of
    sex determination,” Institute of Science and Technology Austria, 2024.'
  ista: 'Raices J. 2024. Novel approaches to studying alternative splicing in Drosophila
    Melanogaster : Insights into sex-specific gene expression and the evolution of
    sex determination. Institute of Science and Technology Austria.'
  mla: 'Raices, Julia. <i>Novel Approaches to Studying Alternative Splicing in Drosophila
    Melanogaster : Insights into Sex-Specific Gene Expression and the Evolution of
    Sex Determination</i>. Institute of Science and Technology Austria, 2024, doi:<a
    href="https://doi.org/10.15479/at:ista:17206">10.15479/at:ista:17206</a>.'
  short: 'J. Raices, Novel Approaches to Studying Alternative Splicing in Drosophila
    Melanogaster : Insights into Sex-Specific Gene Expression and the Evolution of
    Sex Determination, Institute of Science and Technology Austria, 2024.'
corr_author: '1'
date_created: 2024-07-05T14:15:29Z
date_published: 2024-07-05T00:00:00Z
date_updated: 2026-04-07T13:03:22Z
day: '05'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: BeVi
- _id: GradSch
doi: 10.15479/at:ista:17206
ec_funded: 1
file:
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  checksum: d5e9234bde8667b005a8cfe18bb467d3
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  date_created: 2024-07-11T07:18:01Z
  date_updated: 2025-01-11T23:30:04Z
  embargo_to: open_access
  file_id: '17223'
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  date_created: 2024-07-11T07:22:32Z
  date_updated: 2025-01-11T23:30:04Z
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file_date_updated: 2025-01-11T23:30:04Z
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-sa/4.0/
month: '07'
oa: 1
oa_version: Published Version
page: '82'
project:
- _id: 250BDE62-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715257'
  name: Prevalence and Influence of Sexual Antagonism on Genome Evolution
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Beatriz
  full_name: Vicoso, Beatriz
  id: 49E1C5C6-F248-11E8-B48F-1D18A9856A87
  last_name: Vicoso
  orcid: 0000-0002-4579-8306
title: 'Novel approaches to studying alternative splicing in Drosophila Melanogaster
  : Insights into sex-specific gene expression and the evolution of sex determination'
tmp:
  image: /images/cc_by_sa.png
  legal_code_url: https://creativecommons.org/licenses/by-sa/4.0/legalcode
  name: Creative Commons Attribution-ShareAlike 4.0 International Public License (CC
    BY-SA 4.0)
  short: CC BY-SA (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: publisher
_id: '18101'
abstract:
- lang: eng
  text: "The Retroviridae family consists of two sub-families, the Orthoretrovirinae
    and the\r\nSpumaretrovirinae. The Orthoretroviruses contain important human pathogens,
    such as the\r\nhuman immunodeficiency virus 1 (HIV-1). They also harbor other
    retrovirus species which\r\nare regularly used as model systems to study the retroviral
    life cycle. The main structural\r\ncomponent of the retroviruses, is the Gag protein
    and its truncation derivatives occurring\r\nduring viral maturation. Orthoretroviral
    Gag assemblies have been extensively studied to\r\nunderstand the interactions
    that confer stability and morphology to viral particles.\r\nThe Spumaretrovirinae
    subfamily represent an early diverging branch of the Retroviridae.\r\nIts members,
    the Foamy viruses (FV), share most of the conventional features found in\r\nretroviruses.
    However, they also possess multiple characteristics that make them unique. In\r\nparticular,
    FV Gag does not get extensively cleaved as in orthoretroviruses. Hence, the Gag\r\narchitecture
    deviates from the canonical domain arrangement in FV. They also exhibit a\r\npeculiar
    particle morphology, having no apparent immature state and a seemingly\r\nicosahedral
    mature particle. Due to this, many fundamental questions on FV structural\r\nassembly
    mechanisms remain open. To answer these questions, was the main focus of this\r\nthesis.\r\nMainly,
    it is not known how FV assemble their core in a virus particle and what are the\r\nimportant
    assembly interaction sites within said core. What is the minimum assembly\r\ncompetent
    domain of FV Gag? Is there a morphological change in the assembly type of FVGag
    lattices? If so, what is defining these morphological shifts? Finally, it would
    be\r\ninteresting to know what is the evolutionary relationship between FV and
    the rest of the\r\nretrotranscribing elements, from a structural point of view?\r\nTo
    answer these questions, membrane-enveloped mammalian cell-derived FV virus-like\r\nparticles
    (VLPs) were produced. Cryo-electron tomography (cryo-ET) analysis suggested\r\nthese
    FV VLPs do not form a canonical retroviral Gag lattice structure, which is in
    line with\r\nearlier observations. To further evaluate FV Gag assembly competence
    and morphology,\r\nthe first bacterial cell-derived in vitro VLP assembly system
    was designed and optimized.\r\nUsing this system with different truncation variants,
    the minimum assembly competent\r\ndomain of FV Gag was found to be the putative
    CA300-477 domain. Varying VLP\r\nmorphologies were also observed and strongly
    suggested residues upstream of CA300-477\r\nplay a role in morphology determination.
    Finally, a combined cryo-electron microscopy (cryoEM) and cryo-ET approach was
    taken to analyze tubular assemblies from the minimal\r\nassembly competent domain.
    This revealed an unexpectedly unique non-canonical\r\nassembly architecture. Three
    novel lattice stabilizing interfaces were described which\r\nproved to be as unique
    as the lattice arrangement. Comparison to a newly published FV CA\r\ncore structure
    revealed the CA-CA interactions in the atypical assembly do not recapitulate\r\nwhat
    is described for the FV core lattice. However, the new in vitro VLP assembly system\r\nobtained
    in this thesis also provides an exciting opportunity to study still unresolved
    FV\r\nassembly features in a potentially facilitated approach compared to conventional
    methods.\r\nIn summary, this work provided a deeper understanding of the basic
    FV Gag assembly unit,\r\nas well as presenting the first FV Gag-derived in vitro
    VLP assembly system. This system\r\nreveals a novel and unique assembly architecture
    among retroviral in vitro assemblies."
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Dario J
  full_name: Porley, Dario J
  id: 2FD6EA6C-F248-11E8-B48F-1D18A9856A87
  last_name: Porley
citation:
  ama: Porley Esteves D. Structural characterization of spumavirus capsid assemblies.
    2024. doi:<a href="https://doi.org/10.15479/at:ista:18101">10.15479/at:ista:18101</a>
  apa: Porley Esteves, D. (2024). <i>Structural characterization of spumavirus capsid
    assemblies</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:18101">https://doi.org/10.15479/at:ista:18101</a>
  chicago: Porley Esteves, Darío. “Structural Characterization of Spumavirus Capsid
    Assemblies.” Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:18101">https://doi.org/10.15479/at:ista:18101</a>.
  ieee: D. Porley Esteves, “Structural characterization of spumavirus capsid assemblies,”
    Institute of Science and Technology Austria, 2024.
  ista: Porley Esteves D. 2024. Structural characterization of spumavirus capsid assemblies.
    Institute of Science and Technology Austria.
  mla: Porley Esteves, Darío. <i>Structural Characterization of Spumavirus Capsid
    Assemblies</i>. Institute of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:18101">10.15479/at:ista:18101</a>.
  short: D. Porley Esteves, Structural Characterization of Spumavirus Capsid Assemblies,
    Institute of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-09-20T10:21:03Z
date_published: 2024-09-26T00:00:00Z
date_updated: 2026-04-07T13:21:01Z
day: '26'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: FlSc
doi: 10.15479/at:ista:18101
ec_funded: 1
file:
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  date_created: 2024-09-26T13:40:33Z
  date_updated: 2025-03-25T23:30:03Z
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file_date_updated: 2025-03-25T23:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '131'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 9B9C98E0-BA93-11EA-9121-9846C619BF3A
  grant_number: '25762'
  name: Structural characterization of spumavirus capsid assemblies to understand
    conserved Ortervirales assembly mechanisms
publication_identifier:
  isbn:
  - 978-3-99078-041-1
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Florian KM
  full_name: Schur, Florian KM
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
title: Structural characterization of spumavirus capsid assemblies
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: repository
_id: '17465'
abstract:
- lang: eng
  text: "In the modern age of machine learning, artificial neural networks have become
    an integral part\r\nof many practical systems. One of the key ingredients of the
    success of the deep learning\r\napproach is recent computational advances which
    allowed the training of models with billions\r\nof parameters on large-scale data.
    Such over-parameterized and data-hungry regimes pose a\r\nchallenge for the theoretical
    analysis of modern models since “classical” statistical wisdom\r\nis no longer
    applicable. In this view, it is paramount to extend or develop new machinery\r\nthat
    will allow tackling the neural network analysis under new challenging asymptotic
    regimes,\r\nwhich is the focus of this thesis.\r\nLarge neural network systems
    are usually optimized via “local” search algorithms, such\r\nas stochastic gradient
    descent (SGD). However, given the high-dimensional nature of the\r\nparameter
    space, it is a priori not clear why such a crude “local” approach works so remarkably\r\nwell
    in practice. We take a step towards demystifying this phenomenon by showing that\r\nthe
    landscape of the SGD training dynamics exhibits a few beneficial properties for
    the\r\noptimization. First, we show that along the SGD trajectory an over-parameterized
    network\r\nis dropout stable. The emergence of dropout stability allows to conclude
    that the minima\r\nfound by SGD are connected via a continuous path of small loss.
    This in turn means that\r\nthe high-dimensional landscape of the neural network
    optimization problem is provably not so\r\nunfavourable to gradient-based training,
    due to mode connectivity. Next, we show that SGD\r\nfor an over-parameterized
    network tends to find solutions that are functionally more “simple”.\r\nThis in
    turn means that the SGD minima are more robust, since a less complicated solution\r\nwill
    less likely overfit the data. More formally, for a prototypical example of a wide
    two-layer\r\nReLU network on a 1d regression task we show that the SGD algorithm
    is implicitly selective in\r\nits choice of an interpolating solution. Namely,
    at convergence the neural network implements\r\na piece-wise linear function with
    the number of linear regions depending only on the amount\r\nof training data.
    This is in contrast to a “smooth”-like behaviour which one would expect\r\ngiven
    such a severe over-parameterization of the model.\r\nDiverging from the generic
    supervised setting of classification and regression problems, we\r\nanalyze an
    auto-encoder model that is commonly used for representation learning and data\r\ncompression.
    Despite the wide applicability of the auto-encoding paradigm, the theoretical\r\nunderstanding
    of their behaviour is limited even in the simplistic shallow case. The related\r\nwork
    is restricted to extreme asymptotic regimes in which the auto-encoder is either
    severely\r\nover-parameterized or under-parameterized. In contrast, we provide
    a tight characterization\r\nfor the 1-bit compression of Gaussian signals in the
    challenging proportional regime, i.e., the\r\ninput dimension and the size of
    the compressed representation obey the same asymptotics.\r\nWe also show that
    gradient-based methods are able to find a globally optimal solution and\r\nthat
    the predictions made for Gaussian data extrapolate beyond - to the case of compression\r\nof
    natural images. Next, we relax the Gaussian assumption and study more structured
    input\r\nsources. We show that the shallow model is sometimes agnostic to the
    structure of the data\r\nvii\r\nwhich results in a Gaussian-like behaviour. We
    prove that making the decoding component\r\nslightly less shallow is already enough
    to escape the “curse” of Gaussian performance.\r\n"
acknowledged_ssus:
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Aleksandr
  full_name: Shevchenko, Aleksandr
  id: F2B06EC2-C99E-11E9-89F0-752EE6697425
  last_name: Shevchenko
citation:
  ama: Shevchenko A. High-dimensional limits in artificial neural networks. 2024.
    doi:<a href="https://doi.org/10.15479/at:ista:17465">10.15479/at:ista:17465</a>
  apa: Shevchenko, A. (2024). <i>High-dimensional limits in artificial neural networks</i>.
    Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:17465">https://doi.org/10.15479/at:ista:17465</a>
  chicago: Shevchenko, Alexander. “High-Dimensional Limits in Artificial Neural Networks.”
    Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:17465">https://doi.org/10.15479/at:ista:17465</a>.
  ieee: A. Shevchenko, “High-dimensional limits in artificial neural networks,” Institute
    of Science and Technology Austria, 2024.
  ista: Shevchenko A. 2024. High-dimensional limits in artificial neural networks.
    Institute of Science and Technology Austria.
  mla: Shevchenko, Alexander. <i>High-Dimensional Limits in Artificial Neural Networks</i>.
    Institute of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:17465">10.15479/at:ista:17465</a>.
  short: A. Shevchenko, High-Dimensional Limits in Artificial Neural Networks, Institute
    of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-08-28T15:14:25Z
date_published: 2024-08-29T00:00:00Z
date_updated: 2025-04-25T10:32:06Z
day: '29'
ddc:
- '519'
degree_awarded: PhD
department:
- _id: GradSch
- _id: DaAl
- _id: MaMo
doi: 10.15479/at:ista:17465
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file_date_updated: 2024-10-05T22:30:05Z
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '232'
project:
- _id: 059876FA-7A3F-11EA-A408-12923DDC885E
  name: Prix Lopez-Loretta 2019 - Marco Mondelli
- _id: 9B9290DE-BA93-11EA-9121-9846C619BF3A
  grant_number: W1260-N35
  name: Vienna Graduate School on Computational Optimization
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '11420'
    relation: part_of_dissertation
    status: public
  - id: '17469'
    relation: part_of_dissertation
    status: public
  - id: '14459'
    relation: part_of_dissertation
    status: public
  - id: '9198'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Marco
  full_name: Mondelli, Marco
  id: 27EB676C-8706-11E9-9510-7717E6697425
  last_name: Mondelli
  orcid: 0000-0002-3242-7020
- first_name: Dan-Adrian
  full_name: Alistarh, Dan-Adrian
  id: 4A899BFC-F248-11E8-B48F-1D18A9856A87
  last_name: Alistarh
  orcid: 0000-0003-3650-940X
title: High-dimensional limits in artificial neural networks
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2024'
...
---
_id: '17469'
abstract:
- lang: eng
  text: 'Autoencoders are a prominent model in many empirical branches of machine
    learning and lossy data compression. However, basic theoretical questions remain
    unanswered even in a shallow two-layer setting. In particular, to what degree
    does a shallow autoencoder capture the structure of the underlying data distribution?
    For the prototypical case of the 1-bit compression of sparse Gaussian data, we
    prove that gradient descent converges to a solution that completely disregards
    the sparse structure of the input. Namely, the performance of the algorithm is
    the same as if it was compressing a Gaussian source - with no sparsity. For general
    data distributions, we give evidence of a phase transition phenomenon in the shape
    of the gradient descent minimizer, as a function of the data sparsity: below the
    critical sparsity level, the minimizer is a rotation taken uniformly at random
    (just like in the compression of non-sparse data); above the critical sparsity,
    the minimizer is the identity (up to a permutation). Finally, by exploiting a
    connection with approximate message passing algorithms, we show how to improve
    upon Gaussian performance for the compression of sparse data: adding a denoising
    function to a shallow architecture already reduces the loss provably, and a suitable
    multi-layer decoder leads to a further improvement. We validate our findings on
    image datasets, such as CIFAR-10 and MNIST.'
acknowledgement: "Kevin Kogler, Alexander Shevchenko and Marco Mondelli are supported
  by the 2019 Lopez-Loreta Prize. Hamed\r\nHassani acknowledges the support by the
  NSF CIF award (1910056) and the NSF Institute for CORE Emerging Methods in Data
  Science (EnCORE)."
alternative_title:
- PMLR
article_processing_charge: No
arxiv: 1
author:
- first_name: Kevin
  full_name: Kögler, Kevin
  id: 94ec913c-dc85-11ea-9058-e5051ab2428b
  last_name: Kögler
- first_name: Aleksandr
  full_name: Shevchenko, Aleksandr
  id: F2B06EC2-C99E-11E9-89F0-752EE6697425
  last_name: Shevchenko
- first_name: Hamed
  full_name: Hassani, Hamed
  last_name: Hassani
- first_name: Marco
  full_name: Mondelli, Marco
  id: 27EB676C-8706-11E9-9510-7717E6697425
  last_name: Mondelli
  orcid: 0000-0002-3242-7020
citation:
  ama: 'Kögler K, Shevchenko A, Hassani H, Mondelli M. Compression of structured data
    with autoencoders: Provable benefit of nonlinearities and depth. In: <i>Proceedings
    of the 41st International Conference on Machine Learning</i>. Vol 235. ML Research
    Press; 2024:24964-25015.'
  apa: 'Kögler, K., Shevchenko, A., Hassani, H., &#38; Mondelli, M. (2024). Compression
    of structured data with autoencoders: Provable benefit of nonlinearities and depth.
    In <i>Proceedings of the 41st International Conference on Machine Learning</i>
    (Vol. 235, pp. 24964–25015). Vienna, Austria: ML Research Press.'
  chicago: 'Kögler, Kevin, Alexander Shevchenko, Hamed Hassani, and Marco Mondelli.
    “Compression of Structured Data with Autoencoders: Provable Benefit of Nonlinearities
    and Depth.” In <i>Proceedings of the 41st International Conference on Machine
    Learning</i>, 235:24964–15. ML Research Press, 2024.'
  ieee: 'K. Kögler, A. Shevchenko, H. Hassani, and M. Mondelli, “Compression of structured
    data with autoencoders: Provable benefit of nonlinearities and depth,” in <i>Proceedings
    of the 41st International Conference on Machine Learning</i>, Vienna, Austria,
    2024, vol. 235, pp. 24964–25015.'
  ista: 'Kögler K, Shevchenko A, Hassani H, Mondelli M. 2024. Compression of structured
    data with autoencoders: Provable benefit of nonlinearities and depth. Proceedings
    of the 41st International Conference on Machine Learning. ICML: International
    Conference on Machine Learning, PMLR, vol. 235, 24964–25015.'
  mla: 'Kögler, Kevin, et al. “Compression of Structured Data with Autoencoders: Provable
    Benefit of Nonlinearities and Depth.” <i>Proceedings of the 41st International
    Conference on Machine Learning</i>, vol. 235, ML Research Press, 2024, pp. 24964–5015.'
  short: K. Kögler, A. Shevchenko, H. Hassani, M. Mondelli, in:, Proceedings of the
    41st International Conference on Machine Learning, ML Research Press, 2024, pp.
    24964–25015.
conference:
  end_date: 2024-07-27
  location: Vienna, Austria
  name: 'ICML: International Conference on Machine Learning'
  start_date: 2024-07-21
corr_author: '1'
date_created: 2024-08-29T11:47:57Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2026-05-15T22:30:05Z
day: '01'
department:
- _id: DaAl
- _id: MaMo
external_id:
  arxiv:
  - '2402.05013'
intvolume: '       235'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://proceedings.mlr.press/v235/kogler24a.html
month: '07'
oa: 1
oa_version: Published Version
page: 24964-25015
project:
- _id: 059876FA-7A3F-11EA-A408-12923DDC885E
  name: Prix Lopez-Loretta 2019 - Marco Mondelli
publication: Proceedings of the 41st International Conference on Machine Learning
publication_status: published
publisher: ML Research Press
quality_controlled: '1'
related_material:
  record:
  - id: '17465'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: 'Compression of structured data with autoencoders: Provable benefit of nonlinearities
  and depth'
type: conference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 235
year: '2024'
...
---
OA_place: publisher
_id: '17119'
abstract:
- lang: eng
  text: "Genomes are shaped by natural selection at the level of the organism, as
    genomic variants that\r\nhave a beneficial effect on the viability or fecundity
    of their carriers are on average expected\r\nto be passed on to more offspring
    than less beneficial alleles. However, selection also favors\r\ngenomic variants
    that drive their own transmission to the next generation above the mendelian\r\nexpectation
    of 50 percent in heterozygotes, even if these self-promoting variants are less\r\nbeneficial
    to the organism than other variants at the same locus. Such variants, called meiotic\r\ndrivers,
    are found in diverse taxa, and often impose fitness costs on their host organisms.
    As\r\nmeiotic drivers often require multiple genes and sequences for transmission
    ratio distortion,\r\nthey are often found in regions of low recombination, such
    as inversions, which prevent their\r\nrecombination with the non-driving homologous
    regions. Reduced recombination rates are\r\nexpected to lead to the accumulation
    of deleterious mutations, which may affect hundreds\r\nof genes trapped in the
    inversions of meiotic drivers. Although the observed fitness costs of\r\nself-promoting
    haplotypes are thought to possibly reflect sequence degeneration, no study has\r\nsystematically
    investigated the level of degeneration on a meiotic driver. Further, the low\r\nrates
    of recombination between driving and non-driving haplotypes have limited the power
    of\r\ntraditional genetic studies in uncovering the gene content of meiotic drivers,
    and made the\r\nthe identification of the genes causing transmission ratio distortion
    difficult.\r\nAfter an introduction to meiotic drivers in Chapter 1, this thesis
    presents three studies that\r\nmake use of next generation sequencing data to
    characterize the sequence and expression\r\nevolution of genes on the t-haplotype,
    a large and ancient meiotic driver in house mice that is\r\ntransmitted to up
    to 100% of the offspring in males heterozygous for it. Chapter 2 presents\r\na
    comprehensive assessment of the t-haplotype’s sequence evolution, which shows
    signs of\r\nsequence degeneration counteracted by occasional recombination with
    the non-driving homolog\r\nover large parts of the meiotic driver, proposing an
    explanation for its long-term survival.\r\nChapter 3 investigates the sequence
    and expression evolution of genes on the t-haplotype,\r\nand finds widespread
    expression and copy number changes and signs of less efficient purifying\r\nselection
    compared to the genes on the non-driving homolog. Further, this chapter finds\r\ncandidates
    for involvment in drive: two positively selected genes on the t-haplotype, and\r\nthe
    discovery of a t-specific gene duplicate, which was gained from another chromosome,\r\nand
    which acquired novel sequence and testis-specific expression on the t-haplotype.
    Finally,\r\nChapter 4 provides unprecedented insights into the gene expression
    landscape in testes of\r\nt-carrier mice, using single nucleus sequencing. Cell-resolved
    RNA-sequencing allows the\r\ncomparison of expression in spermatids carrying or
    not carrying the t-haplotype as well as the\r\ntiming of t-haplotype-induced expression
    changes along spermatogenesis. This study shows\r\nthe timing of previously found
    drive-associated genes, and uncovers novel candidate genes and\r\nbiological processes
    that may underlie the complex biology of transmission ratio distortion of\r\nthe
    t-haplotype. Chapter 5 synthesizes the findings of the three studies, and discusses
    them in\r\nthe context of the current state of meiotic drive research."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Réka K
  full_name: Kelemen, Réka K
  id: 48D3F8DE-F248-11E8-B48F-1D18A9856A87
  last_name: Kelemen
  orcid: 0000-0002-8489-9281
citation:
  ama: Kelemen RK. Characterizing the sequence and expression evolution of the t-haplotype,
    a model meiotic driver. 2024. doi:<a href="https://doi.org/10.15479/at:ista:17119">10.15479/at:ista:17119</a>
  apa: Kelemen, R. K. (2024). <i>Characterizing the sequence and expression evolution
    of the t-haplotype, a model meiotic driver</i>. Institute of Science and Technology
    Austria. <a href="https://doi.org/10.15479/at:ista:17119">https://doi.org/10.15479/at:ista:17119</a>
  chicago: Kelemen, Réka K. “Characterizing the Sequence and Expression Evolution
    of the T-Haplotype, a Model Meiotic Driver.” Institute of Science and Technology
    Austria, 2024. <a href="https://doi.org/10.15479/at:ista:17119">https://doi.org/10.15479/at:ista:17119</a>.
  ieee: R. K. Kelemen, “Characterizing the sequence and expression evolution of the
    t-haplotype, a model meiotic driver,” Institute of Science and Technology Austria,
    2024.
  ista: Kelemen RK. 2024. Characterizing the sequence and expression evolution of
    the t-haplotype, a model meiotic driver. Institute of Science and Technology Austria.
  mla: Kelemen, Réka K. <i>Characterizing the Sequence and Expression Evolution of
    the T-Haplotype, a Model Meiotic Driver</i>. Institute of Science and Technology
    Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:17119">10.15479/at:ista:17119</a>.
  short: R.K. Kelemen, Characterizing the Sequence and Expression Evolution of the
    T-Haplotype, a Model Meiotic Driver, Institute of Science and Technology Austria,
    2024.
corr_author: '1'
date_created: 2024-06-07T16:14:13Z
date_published: 2024-06-20T00:00:00Z
date_updated: 2026-04-07T13:21:37Z
day: '20'
ddc:
- '576'
degree_awarded: PhD
department:
- _id: GradSch
- _id: BeVi
doi: 10.15479/at:ista:17119
ec_funded: 1
file:
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  date_updated: 2025-01-10T23:30:10Z
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  file_name: thesis.zip
  file_size: 180557931
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  date_created: 2024-07-10T08:00:20Z
  date_updated: 2025-01-10T23:30:10Z
  embargo: 2025-01-10
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  file_size: 19405484
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file_date_updated: 2025-01-10T23:30:10Z
has_accepted_license: '1'
keyword:
- meiotic driver
- neofunctionalization
- single nucleus sequencing
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '06'
oa: 1
oa_version: Published Version
page: '105'
project:
- _id: 250BDE62-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715257'
  name: Prevalence and Influence of Sexual Antagonism on Genome Evolution
- _id: 34ae1506-11ca-11ed-8bc3-c14f4c474396
  grant_number: F8810
  name: The highjacking of meiosis for asexual reproduction
publication_identifier:
  isbn:
  - 978-3-99078-039-8
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '542'
    relation: part_of_dissertation
    status: public
  - id: '10767'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Beatriz
  full_name: Vicoso, Beatriz
  id: 49E1C5C6-F248-11E8-B48F-1D18A9856A87
  last_name: Vicoso
  orcid: 0000-0002-4579-8306
title: Characterizing the sequence and expression evolution of the t-haplotype, a
  model meiotic driver
tmp:
  image: /images/cc_by_nc_sa.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
    BY-NC-SA 4.0)
  short: CC BY-NC-SA (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: publisher
_id: '18477'
abstract:
- lang: eng
  text: "ADAR1 is broadly expressed across various tissues and is vital in regulating
    pathways\r\nassociated with innate immune responses. ADAR1 marks double-stranded
    RNA as \"self\"\r\nthrough its A-to-I editing activity, effectively repressing
    autoimmunity and maintaining\r\nimmune tolerance. This editing process has been
    detected at millions of sites across the\r\nhuman genome. However, the mechanism
    underlying ADAR1's substrate selectivity\r\nproperties remains largely unclear,
    with much of the current knowledge derived from\r\ncomparisons to its more extensively
    studied homolog, ADAR2. By studying ADAR1 in complex\r\nwith its RNA substrates
    and applying a combination of biochemical techniques and structural\r\nstudies
    using CryoEM, we aim to gain a more comprehensive understanding of the substrate\r\nselectivity
    characteristics of ADAR1.\r\nIn this thesis, the purification protocol for ADAR1
    was successfully optimized, resulting in the\r\nfirst report in the literature
    to achieve high protein purity and activity. This advancement\r\nenabled the investigation
    of complex formation between ADAR1 and various RNA substrates,\r\nleading to the
    identification of optimal conditions for preparing the cryoEM sample. However,\r\ndespite
    comprehensive optimization of the cryo-EM conditions, the resulting data lacked
    the\r\ndesired quality, highlighting the need for similar rigorous optimization
    of the RNA substrates\r\nto facilitate structural studies of the ADAR1-RNA complex.
    The study was complemented by\r\nAlphaFold predictions, which provided some insights
    into this mechanism.\r\nMoreover, during this project I established a collaboration
    with a research group focused on\r\nstudying ADAR homologs. Notably ADAR homologs
    were identified in bivalve species, and it\r\nwas further demonstrated that ADAR
    and its A-to-I editing activity are upregulated in Pacific\r\noysters during infections
    with Ostreid herpesvirus-1—a highly infectious virus that leads to\r\nsignificant
    losses in oyster populations globally. I successfully purified oyster ADAR and\r\nprepared
    in vitro edited RNA for nanopore sequencing—a direct sequencing technology\r\ncapable
    of detecting modified nucleotides without the need for reverse transcription.
    The\r\ncollaborators initiated optimization of this nanopore-based approach. However,
    current\r\ntechnological limitations still constrain the reliable detection of
    modified nucleotides.\r\nThe project also examined the impact of RNA editing on
    RNA binding and filament formation\r\nby MDA5, a key cytosolic dsRNA sensor that
    triggers an interferon response. A primary target\r\nof ADAR1's editing activity
    is RNA derived from repetitive elements present in the genome,\r\nparticularly
    Alu elements forming double-stranded RNA. When unedited, these RNA\r\nsequences
    are recognized by MDA5. However, the mechanisms by which MDA5 interacts with\r\nAlu
    RNAs, as well as the role of A-to-I editing in influencing this binding, are still
    not well\r\nunderstood.\r\nThe interaction between MDA5 and Alu elements, was
    successfully established. This was\r\nachieved through the testing of different
    RNA variants and the evaluation of filament\r\nformation using binding techniques
    and electron microscopy imaging. This groundwork has\r\nset the conditions for
    further evaluation using CryoEM. Furthermore, the effects of A-to-I\r\nediting
    on the binding properties of MDA5 with Alu RNA were investigated. Given the recent\r\nresearch
    that has provided new insights into MDA5's interaction with dsRNA, it is essential
    to\r\nrevise the experimental setup to integrate these findings before moving
    forward with the\r\nCryoEM sample analysis."
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Beata M
  full_name: Kaczmarek, Beata M
  id: 36FA4AFA-F248-11E8-B48F-1D18A9856A87
  last_name: Kaczmarek
citation:
  ama: Kaczmarek BM. Biochemical and structural insights into ADAR1 RNA editing. 2024.
    doi:<a href="https://doi.org/10.15479/at:ista:18477">10.15479/at:ista:18477</a>
  apa: Kaczmarek, B. M. (2024). <i>Biochemical and structural insights into ADAR1
    RNA editing</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:18477">https://doi.org/10.15479/at:ista:18477</a>
  chicago: Kaczmarek, Beata M. “Biochemical and Structural Insights into ADAR1 RNA
    Editing.” Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:18477">https://doi.org/10.15479/at:ista:18477</a>.
  ieee: B. M. Kaczmarek, “Biochemical and structural insights into ADAR1 RNA editing,”
    Institute of Science and Technology Austria, 2024.
  ista: Kaczmarek BM. 2024. Biochemical and structural insights into ADAR1 RNA editing.
    Institute of Science and Technology Austria.
  mla: Kaczmarek, Beata M. <i>Biochemical and Structural Insights into ADAR1 RNA Editing</i>.
    Institute of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:18477">10.15479/at:ista:18477</a>.
  short: B.M. Kaczmarek, Biochemical and Structural Insights into ADAR1 RNA Editing,
    Institute of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-10-27T07:35:13Z
date_published: 2024-10-29T00:00:00Z
date_updated: 2026-04-07T13:23:59Z
day: '29'
ddc:
- '572'
degree_awarded: PhD
department:
- _id: GradSch
- _id: CaBe
doi: 10.15479/at:ista:18477
file:
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file_date_updated: 2025-10-29T23:30:02Z
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '10'
oa: 1
oa_version: Published Version
page: '124'
publication_identifier:
  isbn:
  - 978-3-99078-045-9
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Carrie A
  full_name: Bernecky, Carrie A
  id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87
  last_name: Bernecky
  orcid: 0000-0003-0893-7036
title: Biochemical and structural insights into ADAR1 RNA editing
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: publisher
_id: '17319'
abstract:
- lang: eng
  text: "This thesis comprises two distinct projects, each offering unique insights
    into fundamental\r\ncellular processes. While distinct in their focus, these different
    perspectives have a common\r\ntheme: chemiosmotic theory and utilisation of the
    proton gradient for driving the essential\r\nprocesses like auxin efflux and ATP
    synthesis, effectively bridging the membrane protein\r\nstructure and function
    from the realms of plant biology and cellular bioenergetics.\r\nThe first project
    of this thesis centres on the characterisation of PIN proteins, a class of\r\ntransmembrane
    transporters pivotal in the regulation of auxin transport and distribution in\r\nplants.
    PINs form a conserved and phylogenetically abundant group of transporters present
    in\r\nland plants and certain algae. Despite their great importance, they were
    one of the few elusive\r\nproteins essential for plant development not to be structurally
    and mechanistically\r\ncharacterised since their discovery almost 30 years ago.
    This work aimed to uncover the\r\nstructural and functional dynamics of the PIN
    protein-mediated auxin transport using an array\r\nof experimental techniques,
    including protein purification, biochemical assays and structural\r\nanalysis.
    Through an exhaustive screening process that took several years and included testing\r\ndifferent
    PIN homologues, expression systems, constructs, and purification conditions, we\r\ndeveloped
    a robust protocol for isolating the pure, stable, and monodisperse PIN8 protein.\r\nMoreover,
    utilising biophysical methods and buffer screening, we demonstrated that PIN8\r\nexhibits
    detergent and pH-dependent stability, with mild detergents and lower pH (5.0 and
    6.0)\r\nbeing optimal for the stability of the protein. Using SEC-MALS and crosslinking,
    we\r\ndetermined that PIN8 forms dimers, which was confirmed by our structural
    studies. We\r\nobtained a cryo-EM map of PIN8 at pH 6.0, and, compared to recently
    published structures,\r\nour map implies major pH-dependent conformational changes
    and possibly utilisation of the\r\nproton gradient in the transport mechanism.\r\nThe
    subject of the second project was F1Fo-ATP synthase, an enzyme complex fundamental\r\nto
    cellular energy metabolism. Through an approach integrating biochemical assays
    and\r\nstructural analysis, this research aimed to unveil the molecular mechanism
    of inhibition of ATP\r\nsynthase by yaku´amide, a bioactive compound with potential
    therapeutic implications. Using\r\nsubmitochondrial particles and purified F1Fo-ATP
    synthase, we demonstrated that, contrary to\r\npublished data, yaku´amide inhibits
    both ATP hydrolysis and ATP synthesis reactions.\r\nMoreover, we found that yaku´amide
    inhibitory activity is proton motive force (pmf)\r\ndependent, with lower inhibition
    in a more coupled system. Utilising cryo-EM, we obtained\r\nmaps and models for
    the three main rotational states of murine ATP synthase (State 1 at 3.0 Å,\r\n8\r\nState
    2 at 3.1 Å, and State 3 at 3.2 Å, overall). We observed several new features in
    our maps;\r\nhowever, we cannot definitively determine the exact mechanism of
    yaku amide’s inhibition on\r\nthe protein due to either resolution limits or suboptimal
    binding of the inhibitor."
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Kristina
  full_name: Lukic, Kristina
  id: 2B04DB84-F248-11E8-B48F-1D18A9856A87
  last_name: Lukic
  orcid: 0000-0003-1581-881X
citation:
  ama: 'Lukic K. Membrane proteins in plant physiology and bioenergetics : Investigating
    auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor
    Yaku’amide B. 2024. doi:<a href="https://doi.org/10.15479/at:ista:17319">10.15479/at:ista:17319</a>'
  apa: 'Lukic, K. (2024). <i>Membrane proteins in plant physiology and bioenergetics :
    Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the
    novel inhibitor Yaku’amide B</i>. Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/at:ista:17319">https://doi.org/10.15479/at:ista:17319</a>'
  chicago: 'Lukic, Kristina. “Membrane Proteins in Plant Physiology and Bioenergetics :
    Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the
    Novel Inhibitor Yaku’amide B.” Institute of Science and Technology Austria, 2024.
    <a href="https://doi.org/10.15479/at:ista:17319">https://doi.org/10.15479/at:ista:17319</a>.'
  ieee: 'K. Lukic, “Membrane proteins in plant physiology and bioenergetics : Investigating
    auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor
    Yaku’amide B,” Institute of Science and Technology Austria, 2024.'
  ista: 'Lukic K. 2024. Membrane proteins in plant physiology and bioenergetics :
    Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the
    novel inhibitor Yaku’amide B. Institute of Science and Technology Austria.'
  mla: 'Lukic, Kristina. <i>Membrane Proteins in Plant Physiology and Bioenergetics :
    Investigating Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the
    Novel Inhibitor Yaku’amide B</i>. Institute of Science and Technology Austria,
    2024, doi:<a href="https://doi.org/10.15479/at:ista:17319">10.15479/at:ista:17319</a>.'
  short: 'K. Lukic, Membrane Proteins in Plant Physiology and Bioenergetics : Investigating
    Auxin Efflux Transporter PIN8 and ATP Synthase Inhibition by the Novel Inhibitor
    Yaku’amide B, Institute of Science and Technology Austria, 2024.'
corr_author: '1'
date_created: 2024-07-26T09:05:55Z
date_published: 2024-07-26T00:00:00Z
date_updated: 2026-04-07T13:20:44Z
day: '26'
ddc:
- '580'
degree_awarded: PhD
department:
- _id: LeSa
- _id: GradSch
doi: 10.15479/at:ista:17319
file:
- access_level: open_access
  checksum: 95517e697ea6a87e267e649cad560989
  content_type: application/pdf
  creator: cchlebak
  date_created: 2024-07-26T13:14:24Z
  date_updated: 2025-01-26T23:30:04Z
  embargo: 2025-01-26
  file_id: '17320'
  file_name: Thesis_Kristina_Lukic.pdf
  file_size: 24639084
  relation: main_file
- access_level: closed
  checksum: 74325746a9a05078fb9935dbf2aef752
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: cchlebak
  date_created: 2024-07-26T13:14:50Z
  date_updated: 2025-01-26T23:30:04Z
  embargo_to: open_access
  file_id: '17321'
  file_name: Thesis_Kristina_Lukic.docx
  file_size: 96334272
  relation: source_file
file_date_updated: 2025-01-26T23:30:04Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: '224'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Leonid A
  full_name: Sazanov, Leonid A
  id: 338D39FE-F248-11E8-B48F-1D18A9856A87
  last_name: Sazanov
  orcid: 0000-0002-0977-7989
title: 'Membrane proteins in plant physiology and bioenergetics : Investigating auxin
  efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku''amide
  B'
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
_id: '15323'
abstract:
- lang: eng
  text: Supercomplexes of the respiratory chain are established constituents of the
    oxidative phosphorylation system, but their role in mammalian metabolism has been
    hotly debated. Although recent studies have shown that different tissues/organs
    are equipped with specific sets of supercomplexes, depending on their metabolic
    needs, the notion that supercomplexes have a role in the regulation of metabolism
    has been challenged. However, irrespective of the mechanistic conclusions, the
    composition of various high molecular weight supercomplexes remains uncertain.
    Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse)
    tissues contain three defined types of ‘respirasome’, supercomplexes made of CI,
    CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes,
    of which only one contains the supercomplex-associated factor SCAF1, whose involvement
    in respirasome formation has long been contended. Our structures confirm that
    the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1,
    which is instead associated to a different respirasome (the CS-respirasome), containing
    a second copy of CIV. We also identify an alternative respirasome (A-respirasome),
    with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization
    of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis
    for their specific role in different metabolic conditions.
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
- _id: PreCl
- _id: ScienComp
acknowledgement: Supercomplexes of the respiratory chain are established constituents
  of the oxidative phosphorylation system, but their role in mammalian metabolism
  has been hotly debated. Although recent studies have shown that different tissues/organs
  are equipped with specific sets of supercomplexes, depending on their metabolic
  needs, the notion that supercomplexes have a role in the regulation of metabolism
  has been challenged. However, irrespective of the mechanistic conclusions, the composition
  of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic
  electron microscopy, we demonstrate that mammalian (mouse) tissues contain three
  defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry
  and position of CIV differs in the three respirasomes, of which only one contains
  the supercomplex-associated factor SCAF1, whose involvement in respirasome formation
  has long been contended. Our structures confirm that the ‘canonical’ respirasome
  (the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated
  to a different respirasome (the CS-respirasome), containing a second copy of CIV.
  We also identify an alternative respirasome (A-respirasome), with CIV bound to the
  ‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial
  supercomplexes allows us to hypothesize a mechanistic basis for their specific role
  in different metabolic conditions.
article_processing_charge: No
article_type: original
author:
- first_name: Irene
  full_name: Vercellino, Irene
  id: 3ED6AF16-F248-11E8-B48F-1D18A9856A87
  last_name: Vercellino
  orcid: 0000-0001-5618-3449
- first_name: Leonid A
  full_name: Sazanov, Leonid A
  id: 338D39FE-F248-11E8-B48F-1D18A9856A87
  last_name: Sazanov
  orcid: 0000-0002-0977-7989
citation:
  ama: Vercellino I, Sazanov LA. SCAF1 drives the compositional diversity of mammalian
    respirasomes. <i>Nature Structural and Molecular Biology</i>. 2024;31:1061-1071.
    doi:<a href="https://doi.org/10.1038/s41594-024-01255-0">10.1038/s41594-024-01255-0</a>
  apa: Vercellino, I., &#38; Sazanov, L. A. (2024). SCAF1 drives the compositional
    diversity of mammalian respirasomes. <i>Nature Structural and Molecular Biology</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41594-024-01255-0">https://doi.org/10.1038/s41594-024-01255-0</a>
  chicago: Vercellino, Irene, and Leonid A Sazanov. “SCAF1 Drives the Compositional
    Diversity of Mammalian Respirasomes.” <i>Nature Structural and Molecular Biology</i>.
    Springer Nature, 2024. <a href="https://doi.org/10.1038/s41594-024-01255-0">https://doi.org/10.1038/s41594-024-01255-0</a>.
  ieee: I. Vercellino and L. A. Sazanov, “SCAF1 drives the compositional diversity
    of mammalian respirasomes,” <i>Nature Structural and Molecular Biology</i>, vol.
    31. Springer Nature, pp. 1061–1071, 2024.
  ista: Vercellino I, Sazanov LA. 2024. SCAF1 drives the compositional diversity of
    mammalian respirasomes. Nature Structural and Molecular Biology. 31, 1061–1071.
  mla: Vercellino, Irene, and Leonid A. Sazanov. “SCAF1 Drives the Compositional Diversity
    of Mammalian Respirasomes.” <i>Nature Structural and Molecular Biology</i>, vol.
    31, Springer Nature, 2024, pp. 1061–71, doi:<a href="https://doi.org/10.1038/s41594-024-01255-0">10.1038/s41594-024-01255-0</a>.
  short: I. Vercellino, L.A. Sazanov, Nature Structural and Molecular Biology 31 (2024)
    1061–1071.
corr_author: '1'
date_created: 2024-04-14T22:01:03Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2025-11-24T08:35:04Z
day: '01'
ddc:
- '572'
department:
- _id: LeSa
doi: 10.1038/s41594-024-01255-0
ec_funded: 1
external_id:
  isi:
  - '001196897300001'
  pmid:
  - '38575788'
file:
- access_level: open_access
  checksum: 21f05d188762acd7f49a97f3d09c8d9f
  content_type: application/pdf
  creator: lsazanov
  date_created: 2024-05-14T11:57:56Z
  date_updated: 2025-01-01T23:30:03Z
  embargo: 2025-01-01
  file_id: '15392'
  file_name: megacomplex_submit_NSMB_withFigures.pdf
  file_size: 24424729
  relation: main_file
file_date_updated: 2025-01-01T23:30:03Z
has_accepted_license: '1'
intvolume: '        31'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Submitted Version
page: 1061-1071
pmid: 1
project:
- _id: 627abdeb-2b32-11ec-9570-ec31a97243d3
  call_identifier: H2020
  grant_number: '101020697'
  name: Structure and mechanism of respiratory chain molecular machines
publication: Nature Structural and Molecular Biology
publication_identifier:
  eissn:
  - 1545-9985
  issn:
  - 1545-9993
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: erratum
    url: https://doi.org/10.1038/s41594-025-01721-3
scopus_import: '1'
status: public
title: SCAF1 drives the compositional diversity of mammalian respirasomes
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: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 31
year: '2024'
...
---
OA_place: publisher
_id: '17346'
abstract:
- lang: eng
  text: "Acquiring, retaining, and retrieving information over a wide range of timescales
    are crucial\r\nfunctions of the brain. The successful processing of memories affects
    many aspects of our\r\nlives and enables us and many other organisms to operate
    in a complex environment and\r\nto interact with it. In this context, the hippocampus
    and functionally connected brain\r\nareas, such as the prefrontal cortex, are
    central and have been subject to intensive research\r\nin the past decades. Storage
    of memories is believed to rely on distributed neural activity\r\nwithin these
    neural circuits. Additionally, neural memory traces of recent experience are\r\nreinstated
    during periods of rest or sleep. These reactivations are thought to play an\r\noutstanding
    role in the consolidation of memories and potentially facilitate the transfer
    of\r\ninformation from the hippocampus to cortical areas for long-term storage
    and integration\r\ninto existing knowledge.\r\nHowever, there is growing evidence
    that memory-related neural representations in the\r\nhippocampus are not as stable
    as initially thought and that they change even in the\r\nabsence of learning.
    It has been suggested that these changes reflect the accumulation of\r\nexperience,
    but the influence of interspersed consolidation periods has not been considered.\r\nPrevious
    studies have analyzed consolidation periods by detecting activity that strongly\r\nresembled
    neural activity during the acquisition of memory. Besides being often limited\r\nto
    only non-rapid eye movement (NREM) sleep, the used approaches were not capable
    of\r\ntracking changes in neural representations over extended temporal periods.
    More fluid\r\nrepresentations do not only challenge our understanding of how information
    is stored, but\r\nthey also affect the transfer of information between brain areas
    during the consolidation\r\nprocess.\r\nFor this thesis, I investigated the evolution
    of memory-related activity during sleep\r\nperiods expected to be involved in
    consolidation in the hippocampus and between the\r\nhippocampus and prefrontal
    cortex. I found that reactivated activity in the hippocampus\r\ngradually transformed
    during prolonged periods of sleep and inactivity. In the beginning,\r\nneural
    activity strongly resembled acquisition activity, whereas, with the progression
    of\r\ntime, it became more similar to the subsequent recall activity. NREM periods
    drove\r\nthis process, while rapid-eye movement (REM) periods showed a resetting
    effect. This\r\nreactivation drift was due to firing rate changes of a subset
    of cells and mirrored the\r\nrepresentational changes from the acquisition to
    the recall. A stable subset of cells\r\nwithstood the drift and maintained their
    activity. Therefore, my results indicate that\r\nmemory-related representations
    undergo spontaneous modifications during consolidation\r\nperiods and that these
    changes are predictive of representational drift.\r\nFurthermore, I found that
    the amount of change in the neural activity during subsequent\r\nsleep periods
    was biased by prior behavioral performance. Observed changes in the\r\nhippocampus
    and the prefrontal cortex were synchronized and increased after poor\r\nperformance,
    highlighting a potential role in the exchange of information. Low-variance\r\nvii\r\nperiods
    with distinct, more stable activity from a subset of cells significantly contributed\r\nto
    the heightened synchrony between both areas. Hence, interleaved phases of more
    stable\r\nneural activity could facilitate the information transfer between brain
    areas.\r\nIn conclusion, my investigations underline the fluidity of memory-related
    representations\r\nand assign a prominent role to sleep reactivation periods in
    their evolution. In addition, I\r\nidentified a potential mechanism of stable
    activity phases that might facilitate the synchronization across hippocampal-prefrontal
    activity despite ongoing changes. Reconciling\r\nand integrating findings from
    both spontaneous and behaviorally-related representational\r\nchanges in functionally
    related brain areas will help to broaden our understanding of how\r\nknowledge
    is stored, maintained, updated, and transferred between brain areas."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Lars
  full_name: Bollmann, Lars
  id: 47AD3038-F248-11E8-B48F-1D18A9856A87
  last_name: Bollmann
citation:
  ama: Bollmann L. Stability and change in the memory system during rest. 2024. doi:<a
    href="https://doi.org/10.15479/at:ista:17346">10.15479/at:ista:17346</a>
  apa: Bollmann, L. (2024). <i>Stability and change in the memory system during rest</i>.
    Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:17346">https://doi.org/10.15479/at:ista:17346</a>
  chicago: Bollmann, Lars. “Stability and Change in the Memory System during Rest.”
    Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:17346">https://doi.org/10.15479/at:ista:17346</a>.
  ieee: L. Bollmann, “Stability and change in the memory system during rest,” Institute
    of Science and Technology Austria, 2024.
  ista: Bollmann L. 2024. Stability and change in the memory system during rest. Institute
    of Science and Technology Austria.
  mla: Bollmann, Lars. <i>Stability and Change in the Memory System during Rest</i>.
    Institute of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:17346">10.15479/at:ista:17346</a>.
  short: L. Bollmann, Stability and Change in the Memory System during Rest, Institute
    of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-07-29T15:08:42Z
date_published: 2024-07-31T00:00:00Z
date_updated: 2026-04-07T13:21:20Z
day: '31'
ddc:
- '573'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JoCs
doi: 10.15479/at:ista:17346
file:
- access_level: open_access
  checksum: 12c76297cc27449da80c60d79127770d
  content_type: application/pdf
  creator: lbollman
  date_created: 2024-07-31T18:37:19Z
  date_updated: 2025-01-31T23:30:03Z
  embargo: 2025-01-31
  file_id: '17359'
  file_name: PhD_Thesis_Lars_Bollmann.pdf
  file_size: 12920169
  relation: main_file
- access_level: closed
  checksum: 19a0265079dec8038830ad6e35c5106e
  content_type: application/zip
  creator: lbollman
  date_created: 2024-07-31T18:38:39Z
  date_updated: 2025-01-31T23:30:03Z
  embargo_to: open_access
  file_id: '17360'
  file_name: Latex_source.zip
  file_size: 27568807
  relation: source_file
file_date_updated: 2025-01-31T23:30:03Z
has_accepted_license: '1'
keyword:
- Memory
- Hippocampus
- Consolidation
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: '103'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
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: Stability and change in the memory system during rest
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: publisher
_id: '15352'
abstract:
- lang: eng
  text: "Epilepsy affects about 50 to 65 million people globally. It summarizes a
    spectrum of neurological\r\ndisorders that have in common a hyperactivity of the
    neuronal network resulting in seizures. A common\r\nassumption is that an imbalance
    between neuronal excitation and inhibition is a key mechanism in\r\nseizure generation
    and epileptogeneisis. In at least one-third of the patients, current therapies
    have\r\nproven unsuccessful in treating seizure progression. One potential reason
    could be that the therapies\r\nonly focus on neurons. Recent studies suggest that
    neuronal hyperactivity causes a microglial\r\nresponse, which reinstates brain
    homeostasis. Additionally, interactions between microglia and neurons\r\nhave
    been shown to inhibit neuronal firing and dampen seizure activity. However, the
    exact relationship\r\nbetween microglia and seizure progression in epilepsy is
    yet to be elucidated. A main bottleneck is that\r\nseveral studies investigate
    microglia dynamics in ex vivo slice models, which can severely affect the\r\nmicroglia
    dynamics due to their rapid response to environmental changes. On the other hand,
    in vivo\r\nstudies focus mostly on behavior characterization of the epileptic
    seizure phenotype and their long-term\r\nconsequences on microglia activity leaving
    out the direct consequences of acute seizure activity on\r\nmicroglia dynamics.\r\nHere,
    we perform a pilot study to combine electroencephalography (EEG) and in vivo live
    imaging to\r\ndirectly monitor and correlate the onset of seizure activity with
    microglia response. To induce seizures,\r\nwe take advantage of the kainic acid
    (KA) model, which represents similar neuropathological and\r\nelectroencephalographic
    features seen in human patients with temporal lobe epilepsy (TLE). After\r\nconfirmation
    of induction of the seizure and microglia activity in the hippocampus as a focal
    point, we\r\ninvestigated whether these changes also reached the primary visual
    cortex (V1) as a secondary\r\ngeneralized seizure activity. Indeed, we found that
    microglia changed their morphology at high doses\r\nof KA in the V1. Next, we
    optimized each of the two methodological components: for the EEG recording,\r\nour
    initial attempts under the microscope suffered from extensive electrical noise,
    which overlaid the\r\nactual signal. Thus, we built a customized Faraday-cage
    and confirmed that the signal-to-noise ratio\r\nwas sufficiently reduced to be
    able to record brain oscillatory activity. For the in vivo live imaging of\r\nmicroglia,
    we had to optimize the imaging parameters, so that we would be able to detect
    microglial\r\nprocesses in a sufficient resolution to track their process changes.
    Finally, we combined both\r\nmethodologies with the KA model. We confirmed that
    KA induced seizure activity and found first\r\nindication that those correlate
    with microglia volume changes.\r\nOverall, we have developed a first methodological
    approach, which allows the analysis of the acute\r\neffects of seizure onset on
    microglia. Future studies will have to continue to optimize the drift during\r\nimaging
    recording and the post-image analysis. "
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
alternative_title:
- ISTA Master's Thesis
article_processing_charge: No
author:
- first_name: Julie Stefanie
  full_name: Murmann, Julie Stefanie
  id: 1d390868-f128-11eb-9611-a0ca5f7833b5
  last_name: Murmann
citation:
  ama: 'Murmann JS. Investigating acute microglia response to seizure activity in
    vivo: Combining 2-Photon imaging and EEG recording. 2024. doi:<a href="https://doi.org/10.15479/at:ista:15352">10.15479/at:ista:15352</a>'
  apa: 'Murmann, J. S. (2024). <i>Investigating acute microglia response to seizure
    activity in vivo: Combining 2-Photon imaging and EEG recording</i>. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:15352">https://doi.org/10.15479/at:ista:15352</a>'
  chicago: 'Murmann, Julie Stefanie. “Investigating Acute Microglia Response to Seizure
    Activity in Vivo: Combining 2-Photon Imaging and EEG Recording.” Institute of
    Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:15352">https://doi.org/10.15479/at:ista:15352</a>.'
  ieee: 'J. S. Murmann, “Investigating acute microglia response to seizure activity
    in vivo: Combining 2-Photon imaging and EEG recording,” Institute of Science and
    Technology Austria, 2024.'
  ista: 'Murmann JS. 2024. Investigating acute microglia response to seizure activity
    in vivo: Combining 2-Photon imaging and EEG recording. Institute of Science and
    Technology Austria.'
  mla: 'Murmann, Julie Stefanie. <i>Investigating Acute Microglia Response to Seizure
    Activity in Vivo: Combining 2-Photon Imaging and EEG Recording</i>. Institute
    of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:15352">10.15479/at:ista:15352</a>.'
  short: 'J.S. Murmann, Investigating Acute Microglia Response to Seizure Activity
    in Vivo: Combining 2-Photon Imaging and EEG Recording, Institute of Science and
    Technology Austria, 2024.'
corr_author: '1'
date_created: 2024-05-02T08:31:38Z
date_published: 2024-05-02T00:00:00Z
date_updated: 2026-04-07T13:05:00Z
day: '02'
ddc:
- '570'
degree_awarded: MS
department:
- _id: SaSi
- _id: GradSch
doi: 10.15479/at:ista:15352
file:
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  creator: cchlebak
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  date_updated: 2025-05-02T22:30:04Z
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file_date_updated: 2025-05-02T22:30:04Z
has_accepted_license: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '54'
publication_identifier:
  issn:
  - 2791-4585
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
title: 'Investigating acute microglia response to seizure activity in vivo: Combining
  2-Photon imaging and EEG recording'
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: publisher
_id: '14821'
abstract:
- lang: eng
  text: "The hippocampus is central to memory formation, storage and retrieval over
    many\r\ntimescales. Neurons in this brain area are highly selective to spatial
    position as well as to many\r\nother variables of the environment. It is believed
    that the selectivity patterns of hippocampal\r\nneurons reflect the structure
    of tasks an animal performs. However, especially at timescales\r\nlonger than
    a few minutes or hours it is not fully known how these representations evolve,
    nor\r\nhow they map to behaviour in the process. In this thesis, I monitored the
    evolution of\r\nhippocampal representations in a novel spatial-associative memory
    task for rats. Reward\r\nlocations were associated with global sensory cues (i.e.
    context); animals had to remember the\r\nassociations and dig for food in those
    locations only. I used in vivo electrophysiology to record\r\nthe activity of
    the hippocampus dorsal CA1 neurons during the learning period of a few days.\r\nI
    report here a novel and simple method to classify behaviour performance to account\r\nfor
    individual variability in learning speed and spurious performance unrelated to
    true task rule\r\nlearning. Using this classification I was then able to investigate
    neural responses on different\r\nstages of learning matched across animals. On
    the first day of learning, I observed a fast\r\nformation of single-cell selectivity
    to task variables which remained stable over days. I also\r\nobserved that reward
    tuning was not a single process but dependent on task-related cognitive\r\nload.
    At the population level, a linear decoding approach revealed a hierarchy in the\r\nrepresentation
    of task variables that changed with learning. In the high-dimensional space of\r\npopulation
    activity, the representation of contexts was specific to each position in the
    maze, and\r\ncould thus be better decoded if the position was known. The decoding
    of position did not improve\r\nwith knowledge of other variables. As learning
    progressed, the hippocampal code underwent a\r\nreorganisation of high-variance
    directions in population activity, identified by principal\r\ncomponent analysis.
    I found that dominant dimensions started carrying increasing amounts of\r\ninformation
    about task context specifically at those positions where it mattered for task\r\nperformance.
    When I contrasted this with variables less relevant to task performance (e.g.\r\nmovement
    direction), I did not observe differences in decoding quality over positions nor
    a\r\nreduction of dimensionality with learning.\r\nOverall, the largest changes
    in CA1 neural response with task learning happened in a\r\nmatter of a few trials;
    over days, changes undetectable in single-cell statistics were responsible\r\nfor
    re-structuring the hierarchy of neural representations at the population level;
    these changes\r\nwere task-specific and reflected different stages of learning.
    This indicates that complex task\r\nlearning may involve different magnitudes
    of response modulation in CA1, which happen at\r\nspecific time scales linked
    to behaviour."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Heloisa
  full_name: Chiossi, Heloisa
  id: 2BBA502C-F248-11E8-B48F-1D18A9856A87
  last_name: Chiossi
  orcid: 0009-0004-2973-278X
citation:
  ama: Chiossi HSC. Adaptive hierarchical representations in the hippocampus. 2024.
    doi:<a href="https://doi.org/10.15479/at:ista:14821">10.15479/at:ista:14821</a>
  apa: Chiossi, H. S. C. (2024). <i>Adaptive hierarchical representations in the hippocampus</i>.
    Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:14821">https://doi.org/10.15479/at:ista:14821</a>
  chicago: Chiossi, Heloisa S. C. “Adaptive Hierarchical Representations in the Hippocampus.”
    Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:14821">https://doi.org/10.15479/at:ista:14821</a>.
  ieee: H. S. C. Chiossi, “Adaptive hierarchical representations in the hippocampus,”
    Institute of Science and Technology Austria, 2024.
  ista: Chiossi HSC. 2024. Adaptive hierarchical representations in the hippocampus.
    Institute of Science and Technology Austria.
  mla: Chiossi, Heloisa S. C. <i>Adaptive Hierarchical Representations in the Hippocampus</i>.
    Institute of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:14821">10.15479/at:ista:14821</a>.
  short: H.S.C. Chiossi, Adaptive Hierarchical Representations in the Hippocampus,
    Institute of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-01-16T14:25:21Z
date_published: 2024-01-19T00:00:00Z
date_updated: 2026-04-07T13:21:56Z
day: '19'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: JoCs
doi: 10.15479/at:ista:14821
ec_funded: 1
file:
- access_level: closed
  checksum: d3fa3de1abd5af5204c13e9d55375615
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  creator: hchiossi
  date_created: 2024-01-19T11:04:05Z
  date_updated: 2025-01-19T23:30:04Z
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  file_size: 8656268
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  content_type: application/pdf
  creator: hchiossi
  date_created: 2024-01-19T11:03:59Z
  date_updated: 2025-01-19T23:30:04Z
  embargo: 2025-01-19
  file_id: '14839'
  file_name: PhD_Thesis_190124.pdf
  file_size: 6567275
  relation: main_file
file_date_updated: 2025-01-19T23:30:04Z
has_accepted_license: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: '89'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
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: Adaptive hierarchical representations in the hippocampus
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '18706'
abstract:
- lang: eng
  text: "We prove discrete-to-continuum convergence for dynamical optimal transport
    on  Zd\r\n -periodic graphs with cost functional having linear growth at infinity.
    This result provides an answer to a problem left open by Gladbach, Kopfer, Maas,
    and Portinale (Calc Var Partial Differential Equations 62(5), 2023), where the
    convergence behaviour of discrete boundary-value dynamical transport problems
    is proved under the stronger assumption of superlinear growth. Our result extends
    the known literature to some important classes of examples, such as scaling limits
    of  1 -Wasserstein transport problems. Similarly to what happens in the quadratic
    case, the geometry of the graph plays a crucial role in the structure of the limit
    cost function, as we discuss in the final part of this work, which includes some
    visual representations."
acknowledgement: L.P. gratefully acknowledges fundings from the Deutsche Forschungsgemeinschaft
  (DFG, German Research Foundation) under Germany’s Excellence Strategy – GZ 2047/1,
  Projekt-ID 390685813. F.Q. gratefully acknowledges support from the Austrian Science
  Fund (FWF) project 10.55776/F65.
article_processing_charge: Yes
article_type: original
author:
- first_name: Lorenzo
  full_name: Portinale, Lorenzo
  id: 30AD2CBC-F248-11E8-B48F-1D18A9856A87
  last_name: Portinale
- first_name: Filippo
  full_name: Quattrocchi, Filippo
  id: 3ebd6ba8-edfb-11eb-afb5-91a9745ba308
  last_name: Quattrocchi
  orcid: 0009-0000-9773-1931
citation:
  ama: Portinale L, Quattrocchi F. Discrete-to-continuum limits of optimal transport
    with linear growth on periodic graphs. <i>European Journal of Applied Mathematics</i>.
    2024:1-29. doi:<a href="https://doi.org/10.1017/s0956792524000810">10.1017/s0956792524000810</a>
  apa: Portinale, L., &#38; Quattrocchi, F. (2024). Discrete-to-continuum limits of
    optimal transport with linear growth on periodic graphs. <i>European Journal of
    Applied Mathematics</i>. Cambridge University Press. <a href="https://doi.org/10.1017/s0956792524000810">https://doi.org/10.1017/s0956792524000810</a>
  chicago: Portinale, Lorenzo, and Filippo Quattrocchi. “Discrete-to-Continuum Limits
    of Optimal Transport with Linear Growth on Periodic Graphs.” <i>European Journal
    of Applied Mathematics</i>. Cambridge University Press, 2024. <a href="https://doi.org/10.1017/s0956792524000810">https://doi.org/10.1017/s0956792524000810</a>.
  ieee: L. Portinale and F. Quattrocchi, “Discrete-to-continuum limits of optimal
    transport with linear growth on periodic graphs,” <i>European Journal of Applied
    Mathematics</i>. Cambridge University Press, pp. 1–29, 2024.
  ista: Portinale L, Quattrocchi F. 2024. Discrete-to-continuum limits of optimal
    transport with linear growth on periodic graphs. European Journal of Applied Mathematics.,
    1–29.
  mla: Portinale, Lorenzo, and Filippo Quattrocchi. “Discrete-to-Continuum Limits
    of Optimal Transport with Linear Growth on Periodic Graphs.” <i>European Journal
    of Applied Mathematics</i>, Cambridge University Press, 2024, pp. 1–29, doi:<a
    href="https://doi.org/10.1017/s0956792524000810">10.1017/s0956792524000810</a>.
  short: L. Portinale, F. Quattrocchi, European Journal of Applied Mathematics (2024)
    1–29.
date_created: 2024-12-23T11:03:59Z
date_published: 2024-12-20T00:00:00Z
date_updated: 2026-05-15T22:30:21Z
day: '20'
department:
- _id: GradSch
- _id: JaMa
doi: 10.1017/s0956792524000810
external_id:
  isi:
  - '001381435800001'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1017/S0956792524000810
month: '12'
oa: 1
oa_version: Published Version
page: 1-29
project:
- _id: fc31cba2-9c52-11eb-aca3-ff467d239cd2
  grant_number: F6504
  name: Taming Complexity in Partial Differential Systems
publication: European Journal of Applied Mathematics
publication_identifier:
  eissn:
  - 1469-4425
  issn:
  - 0956-7925
publication_status: epub_ahead
publisher: Cambridge University Press
quality_controlled: '1'
related_material:
  record:
  - id: '20563'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Discrete-to-continuum limits of optimal transport with linear growth on periodic
  graphs
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
OA_place: repository
OA_type: green
_id: '20571'
abstract:
- lang: eng
  text: "We prove the convergence of a modified Jordan--Kinderlehrer--Otto scheme
    to a solution to the Fokker--Planck equation in $\\Omega \\Subset \\mathbb{R}^d$
    with general, positive and temporally constant, Dirichlet boundary conditions.
    We work under mild assumptions on the domain, the drift, and the initial datum.
    \  In the special case where $\\Omega$ is an interval in $\\mathbb{R}^1$, we prove
    that such a solution is a gradient flow -- curve of maximal slope -- within a
    suitable space of measures, endowed with a modified Wasserstein distance.\r\nOur
    discrete scheme and modified distance draw inspiration from contributions by A.
    Figalli and N. Gigli [J. Math. Pures Appl. 94, (2010), pp. 107--130], and J. Morales
    [J. Math. Pures Appl. 112, (2018), pp. 41--88] on an optimal-transport approach
    to evolution equations with Dirichlet boundary conditions. Similarly to these
    works, we allow the mass to flow from/to the boundary $\\partial \\Omega$ throughout
    the evolution. However, our leading idea is to also keep track of the mass at
    the boundary by working with measures defined on the whole closure $\\overline
    \\Omega$. The driving functional is a modification of the classical relative entropy
    that also makes use of the information at the boundary. As an intermediate result,
    when $\\Omega$ is an interval in $\\mathbb{R}^1$, we find a formula for the descending
    slope of this geodesically nonconvex functional. "
acknowledgement: "The author would like to thank Jan Maas for suggesting this project
  and for many helpful\r\ncomments, Antonio Agresti, Lorenzo Dello Schiavo and Julian
  Fischer for several fruitful discussions, and Oliver Tse for pointing out the reference
  [15]. He also gratefully acknowledges support from the Austrian Science Fund (FWF)
  project 10.55776/F65.\r\n"
article_number: '2403.07803'
article_processing_charge: No
arxiv: 1
author:
- first_name: Filippo
  full_name: Quattrocchi, Filippo
  id: 3ebd6ba8-edfb-11eb-afb5-91a9745ba308
  last_name: Quattrocchi
  orcid: 0009-0000-9773-1931
citation:
  ama: Quattrocchi F. Variational structures for the Fokker-Planck equation with general
    Dirichlet boundary conditions. <i>arXiv</i>. doi:<a href="https://doi.org/10.48550/arXiv.2403.07803">10.48550/arXiv.2403.07803</a>
  apa: Quattrocchi, F. (n.d.). Variational structures for the Fokker-Planck equation
    with general Dirichlet boundary conditions. <i>arXiv</i>. <a href="https://doi.org/10.48550/arXiv.2403.07803">https://doi.org/10.48550/arXiv.2403.07803</a>
  chicago: Quattrocchi, Filippo. “Variational Structures for the Fokker-Planck Equation
    with General Dirichlet Boundary Conditions.” <i>ArXiv</i>, n.d. <a href="https://doi.org/10.48550/arXiv.2403.07803">https://doi.org/10.48550/arXiv.2403.07803</a>.
  ieee: F. Quattrocchi, “Variational structures for the Fokker-Planck equation with
    general Dirichlet boundary conditions,” <i>arXiv</i>. .
  ista: Quattrocchi F. Variational structures for the Fokker-Planck equation with
    general Dirichlet boundary conditions. arXiv, 2403.07803.
  mla: Quattrocchi, Filippo. “Variational Structures for the Fokker-Planck Equation
    with General Dirichlet Boundary Conditions.” <i>ArXiv</i>, 2403.07803, doi:<a
    href="https://doi.org/10.48550/arXiv.2403.07803">10.48550/arXiv.2403.07803</a>.
  short: F. Quattrocchi, ArXiv (n.d.).
corr_author: '1'
date_created: 2025-10-28T13:12:56Z
date_published: 2024-04-09T00:00:00Z
date_updated: 2026-05-15T22:30:21Z
day: '09'
department:
- _id: GradSch
- _id: JaMa
doi: 10.48550/arXiv.2403.07803
external_id:
  arxiv:
  - '2403.07803'
keyword:
- gradient flows
- Jordan–Kinderlehrer–Otto scheme
- curves of maximal slope
- optimal transport
- Dirichlet boundary conditions
- Fokker–Planck equation
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.48550/arXiv.2403.07803
month: '04'
oa: 1
oa_version: Preprint
project:
- _id: 260482E2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: F06504
  name: Taming Complexity in Partial Differential Systems
publication: arXiv
publication_status: draft
related_material:
  record:
  - id: '20865'
    relation: later_version
    status: public
  - id: '20563'
    relation: dissertation_contains
    status: public
status: public
title: Variational structures for the Fokker-Planck equation with general Dirichlet
  boundary conditions
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
OA_place: repository
OA_type: green
_id: '20570'
abstract:
- lang: eng
  text: "We investigate the minimal error in approximating a general probability\r\nmeasure
    $\\mu$ on $\\mathbb{R}^d$ by the uniform measure on a finite set with\r\nprescribed
    cardinality $n$. The error is measured in the $p$-Wasserstein\r\ndistance. In
    particular, when $1\\le p<d$, we establish asymptotic upper and\r\nlower bounds
    as $n \\to \\infty$ on the rescaled minimal error that have the\r\nsame, explicit
    dependency on $\\mu$.\r\n  In some instances, we prove that the rescaled minimal
    error has a limit.\r\nThese include general measures in dimension $d = 2$ with
    $1 \\le p < 2$, and\r\nuniform measures in arbitrary dimension with $1 \\le p
    < d$. For some uniform\r\nmeasures, we prove the limit existence for $p \\ge d$
    as well.\r\n  For a class of compactly supported measures with H\\\"older densities,
    we\r\ndetermine the convergence speed of the minimal error for every $p \\ge 1$.\r\n
    \ Furthermore, we establish a new Pierce-type (i.e., nonasymptotic) upper\r\nestimate
    of the minimal error when $1 \\le p < d$.\r\n  In the initial sections, we survey
    the state of the art and draw connections\r\nwith similar problems, such as classical
    and random quantization."
acknowledgement: "The author is thankful to Nicolas Clozeau, Lorenzo Dello Schiavo,
  Jan Maas, Dejan Slepčev,\r\nand Dario Trevisan for many fruitful discussions and
  comments. The author gratefully acknowledges support from the Austrian Science Fund
  (FWF) project 10.55776/F65."
article_number: '2408.12924'
article_processing_charge: No
arxiv: 1
author:
- first_name: Filippo
  full_name: Quattrocchi, Filippo
  id: 3ebd6ba8-edfb-11eb-afb5-91a9745ba308
  last_name: Quattrocchi
  orcid: 0009-0000-9773-1931
citation:
  ama: Quattrocchi F. Asymptotics for optimal empirical quantization of measures.
    <i>arXiv</i>. doi:<a href="https://doi.org/10.48550/arXiv.2408.12924">10.48550/arXiv.2408.12924</a>
  apa: Quattrocchi, F. (n.d.). Asymptotics for optimal empirical quantization of measures.
    <i>arXiv</i>. <a href="https://doi.org/10.48550/arXiv.2408.12924">https://doi.org/10.48550/arXiv.2408.12924</a>
  chicago: Quattrocchi, Filippo. “Asymptotics for Optimal Empirical Quantization of
    Measures.” <i>ArXiv</i>, n.d. <a href="https://doi.org/10.48550/arXiv.2408.12924">https://doi.org/10.48550/arXiv.2408.12924</a>.
  ieee: F. Quattrocchi, “Asymptotics for optimal empirical quantization of measures,”
    <i>arXiv</i>. .
  ista: Quattrocchi F. Asymptotics for optimal empirical quantization of measures.
    arXiv, 2408.12924.
  mla: Quattrocchi, Filippo. “Asymptotics for Optimal Empirical Quantization of Measures.”
    <i>ArXiv</i>, 2408.12924, doi:<a href="https://doi.org/10.48550/arXiv.2408.12924">10.48550/arXiv.2408.12924</a>.
  short: F. Quattrocchi, ArXiv (n.d.).
corr_author: '1'
date_created: 2025-10-28T13:12:22Z
date_published: 2024-08-23T00:00:00Z
date_updated: 2026-05-15T22:30:21Z
day: '23'
department:
- _id: GradSch
- _id: JaMa
doi: 10.48550/arXiv.2408.12924
external_id:
  arxiv:
  - '2408.12924'
keyword:
- optimal empirical quantization
- vector quantization
- Wasserstein distance
- semidiscrete optimal transport
- Zador’s Theorem
- Pierce’s Lemma
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.48550/arXiv.2408.12924
month: '08'
oa: 1
oa_version: Preprint
project:
- _id: 260482E2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: F06504
  name: Taming Complexity in Partial Differential Systems
publication: arXiv
publication_status: draft
related_material:
  record:
  - id: '20563'
    relation: dissertation_contains
    status: public
status: public
title: Asymptotics for optimal empirical quantization of measures
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
OA_place: publisher
_id: '18129'
abstract:
- lang: eng
  text: "State-of-the-art quantum computers, with roughly a thousand qubits, face
    a crucial technological challenge of scaling up. Spins confined in quantum dots
    (QDs) are a promising candidate\r\nfor qubits due to their long coherence, tunability,
    control, and readout. However, their natural\r\ncoupling is the short-ranged (∼
    100 nm) exchange interaction, limited to nearest neighbours.\r\nLong-ranged (∼
    1 mm) qubit interactions mediated by a photon could be engineered through a\r\ncoherent
    spin-photon coupling. Achieving a strong coupling to a photon is inherently challenging
    in QDs due to the small dipole moment of the confined charge. However, the potential
    of\r\nhigh-impedance resonators to compensate for this has gained significant
    attention in the past\r\ndecade. Nevertheless, previous QD circuit quantum electrodynamics
    implementations have not\r\nexceeded the impedance of ∼ 3.8 kΩ, leaving opportunities
    for significant improvement. The\r\nlarge kinetic inductance of granular aluminium
    (grAl) could provide an order-of-magnitude\r\nenhancement. However, fully exploiting
    the potential of disordered or granular superconductors\r\nis challenging as their
    impedances close to the superconductor-to-insulator transition are\r\ndifficult
    to control reproducibly. We report on the realization of a wireless ohmmeter which\r\nallows
    in situ resistance measurements during film deposition and, therefore, indirect
    control\r\nof the kinetic inductance of grAl films. This allows us to reproducibly
    fabricate resonators\r\nwith characteristic impedance exceeding the resistance
    quantum, even reaching 22.3 kW, due\r\nto the large sheet kinetic inductance of
    up to 3 nH □−1\r\n. By integrating an 8 kW resonator\r\nwith a germanium double
    QD, we demonstrate a strong charge-photon coupling with the\r\nhighest rate reported,
    566 MHz. The demonstrated method and grAl properties make these\r\nresonators
    suitable for boosting the spin-photon coupling strength, a crucial requirement
    for\r\nfast, high-fidelity, long-distance two-qubit gates.\r\n"
acknowledged_ssus:
- _id: M-Shop
- _id: NanoFab
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Marian
  full_name: Janik, Marian
  id: 396A1950-F248-11E8-B48F-1D18A9856A87
  last_name: Janik
  orcid: 0009-0003-9037-8831
citation:
  ama: Janik M. Strong charge-photon coupling in Germanium enabled by granular aluminium
    superinductors. 2024. doi:<a href="https://doi.org/10.15479/at:ista:18129">10.15479/at:ista:18129</a>
  apa: Janik, M. (2024). <i>Strong charge-photon coupling in Germanium enabled by
    granular aluminium superinductors</i>. Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/at:ista:18129">https://doi.org/10.15479/at:ista:18129</a>
  chicago: Janik, Marian. “Strong Charge-Photon Coupling in Germanium Enabled by Granular
    Aluminium Superinductors.” Institute of Science and Technology Austria, 2024.
    <a href="https://doi.org/10.15479/at:ista:18129">https://doi.org/10.15479/at:ista:18129</a>.
  ieee: M. Janik, “Strong charge-photon coupling in Germanium enabled by granular
    aluminium superinductors,” Institute of Science and Technology Austria, 2024.
  ista: Janik M. 2024. Strong charge-photon coupling in Germanium enabled by granular
    aluminium superinductors. Institute of Science and Technology Austria.
  mla: Janik, Marian. <i>Strong Charge-Photon Coupling in Germanium Enabled by Granular
    Aluminium Superinductors</i>. Institute of Science and Technology Austria, 2024,
    doi:<a href="https://doi.org/10.15479/at:ista:18129">10.15479/at:ista:18129</a>.
  short: M. Janik, Strong Charge-Photon Coupling in Germanium Enabled by Granular
    Aluminium Superinductors, Institute of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-09-23T17:25:43Z
date_published: 2024-09-24T00:00:00Z
date_updated: 2026-04-07T13:23:25Z
day: '24'
ddc:
- '539'
degree_awarded: PhD
department:
- _id: GradSch
- _id: GeKa
doi: 10.15479/at:ista:18129
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has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '164'
project:
- _id: c0977eea-5a5b-11eb-8a69-a862db0cf4d1
  grant_number: I05060
  name: High impedance circuit quantum electrodynamics with hole spins
- _id: bd8bd29e-d553-11ed-ba76-f0070d4b237a
  grant_number: P36507
  name: Merging spin and superconducting qubits in planar Ge
- _id: 237B3DA4-32DE-11EA-91FC-C7463DDC885E
  call_identifier: FWF
  grant_number: P32235
  name: Towards scalable hut wire quantum devices
- _id: 34c0acea-11ca-11ed-8bc3-8775e10fd452
  grant_number: '101069515'
  name: Integrated Germanium Quantum Technology
- _id: eb9b30ac-77a9-11ec-83b8-871f581d53d2
  name: Protected states of quantum matter
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
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  - id: '18144'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Georgios
  full_name: Katsaros, Georgios
  id: 38DB5788-F248-11E8-B48F-1D18A9856A87
  last_name: Katsaros
  orcid: 0000-0001-8342-202X
title: Strong charge-photon coupling in Germanium enabled by granular aluminium superinductors
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: publisher
_id: '17368'
abstract:
- lang: eng
  text: "Recent advancements in molecular diagnostic techniques have enabled the collection
    of\r\nmultiple types of omics data from patients, including genomics, epigenomics,
    proteomics,\r\nand transcriptomics. However, we lack effective methods for integrating
    all these different\r\ndata types and combining them with clinical outcomes to
    study the molecular mechanisms\r\nthat govern pathological phenotypes. We present
    multi-omics BayesW, a penalized Bayesian\r\nregression method that can handle
    general omics data for survival analysis of time-to-event\r\nphenotypes. Our method
    can: (1) accommodate incomplete data by allowing censored\r\nindividuals, (2)
    use continuous time-to-event data to test associations of markers with a\r\nphenotype
    and (3) estimate effects jointly while allowing for independent groups of biological\r\nmarkers.
    Extensive simulations using planted signals on real data demonstrate that our
    model\r\naccurately retrieves the true parameters of the model while controlling
    for false discoveries\r\nand maintaining the expected prediction accuracy. We
    address data correlations by estimating\r\nthe effects jointly, even between omic
    groups, while also estimating the individual variance\r\nexplained by each group.
    We apply our model to two datasets. Using 18,000 individuals from\r\nthe Generation
    Scotland study we model the association of time at onset of Type 2 Diabetes,\r\nStroke,
    Ischemic Disease, and Osteoarthritis from baseline study entry, with 831,724 CpG\r\nmethylation
    probes. We find that large proportions of variation in disease onset times can\r\nbe
    attributed to methylation as measured in whole blood at baseline in individuals
    without\r\ndisease symptoms. We then apply our model to The Cancer Genome Atlas
    (TCGA) pan-cancer\r\ndataset, in which we use 5 types of omics: copy number variation,
    epigenetics, somatic\r\nmutations, miRNA, and gene expression. For cancer survival
    age-at-onset we find that, when\r\nfitting the 5 groups together, almost all variation
    attributable to \"omics\" data is explained by\r\nDNA methylation. When considering
    progression times, both methylation and gene expression\r\nexplain a large part
    of the variance. We found 2 genes that are significantly associated (95%\r\nposterior
    inclusion probability) with cancer survival time, conditional on all other genome-wide\r\nomics
    data variation. Owing to the vast variability of mechanisms characterizing different\r\ncancers,
    there are likely few specific genes with a strong signal in a pan-cancer setting.
    Taken\r\ntogether, we showed the applicability of our multi-omics BayesW model
    to a wide-range of\r\nbiological questions in multi-omics data.\r\n"
alternative_title:
- ISTA Master's Thesis
article_processing_charge: No
author:
- first_name: Ariadna
  full_name: Villanueva Marijuan, Ariadna
  id: e0ae4864-133f-11ed-8f02-adaa8dd27540
  last_name: Villanueva Marijuan
citation:
  ama: Villanueva Marijuan A. Bayesian linear regression for analyzing general omics
    data with time-to-event phenotypes. 2024. doi:<a href="https://doi.org/10.15479/at:ista:17368">10.15479/at:ista:17368</a>
  apa: Villanueva Marijuan, A. (2024). <i>Bayesian linear regression for analyzing
    general omics data with time-to-event phenotypes</i>. Institute of Science and
    Technology Austria. <a href="https://doi.org/10.15479/at:ista:17368">https://doi.org/10.15479/at:ista:17368</a>
  chicago: Villanueva Marijuan, Ariadna. “Bayesian Linear Regression for Analyzing
    General Omics Data with Time-to-Event Phenotypes.” Institute of Science and Technology
    Austria, 2024. <a href="https://doi.org/10.15479/at:ista:17368">https://doi.org/10.15479/at:ista:17368</a>.
  ieee: A. Villanueva Marijuan, “Bayesian linear regression for analyzing general
    omics data with time-to-event phenotypes,” Institute of Science and Technology
    Austria, 2024.
  ista: Villanueva Marijuan A. 2024. Bayesian linear regression for analyzing general
    omics data with time-to-event phenotypes. Institute of Science and Technology
    Austria.
  mla: Villanueva Marijuan, Ariadna. <i>Bayesian Linear Regression for Analyzing General
    Omics Data with Time-to-Event Phenotypes</i>. Institute of Science and Technology
    Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:17368">10.15479/at:ista:17368</a>.
  short: A. Villanueva Marijuan, Bayesian Linear Regression for Analyzing General
    Omics Data with Time-to-Event Phenotypes, Institute of Science and Technology
    Austria, 2024.
corr_author: '1'
date_created: 2024-08-02T10:52:40Z
date_published: 2024-08-13T00:00:00Z
date_updated: 2026-04-07T13:03:41Z
day: '13'
ddc:
- '610'
degree_awarded: MS
department:
- _id: GradSch
- _id: MaRo
doi: 10.15479/at:ista:17368
file:
- access_level: open_access
  checksum: 0c2daa174609f0c00919dccc5701d375
  content_type: application/pdf
  creator: avillanu
  date_created: 2024-08-14T11:51:24Z
  date_updated: 2025-02-14T23:30:03Z
  embargo: 2025-02-14
  file_id: '17433'
  file_name: Masters_thesis_AriadnaVillanueva.pdf
  file_size: 13052436
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  date_updated: 2025-02-14T23:30:03Z
  embargo_to: open_access
  file_id: '17434'
  file_name: Masters thesis-AriadnaVillanueva.zip
  file_size: 45642547
  relation: source_file
file_date_updated: 2025-02-14T23:30:03Z
has_accepted_license: '1'
keyword:
- Epigenetics
- Multi-omics
- Bayesian regression
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '60'
publication_identifier:
  issn:
  - 2791-4585
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Matthew Richard
  full_name: Robinson, Matthew Richard
  id: E5D42276-F5DA-11E9-8E24-6303E6697425
  last_name: Robinson
  orcid: 0000-0001-8982-8813
title: Bayesian linear regression for analyzing general omics data with time-to-event
  phenotypes
tmp:
  image: /images/cc_by_nc_sa.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
    BY-NC-SA 4.0)
  short: CC BY-NC-SA (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...
---
OA_place: repository
_id: '18144'
abstract:
- lang: eng
  text: "High kinetic inductance superconductors are gaining increasing interest for\r\nthe
    realisation of qubits, amplifiers and detectors. Moreover, thanks to their\r\nhigh
    impedance, quantum buses made of such materials enable large zero-point\r\nfluctuations
    of the voltage, boosting the coupling rates to spin and charge\r\nqubits. However,
    fully exploiting the potential of disordered or granular\r\nsuperconductors is
    challenging, as their inductance and, therefore, impedance\r\nat high values are
    difficult to control. Here we have integrated a granular\r\naluminium resonator,
    having a characteristic impedance exceeding the resistance\r\nquantum, with a
    germanium double quantum dot and demonstrate strong\r\ncharge-photon coupling
    with a rate of $g_\\text{c}/2\\pi= (566 \\pm 2)$ MHz. This\r\nwas achieved due
    to the realisation of a wireless ohmmeter, which allows\r\n\\emph{in situ} measurements
    during film deposition and, therefore, control of\r\nthe kinetic inductance of
    granular aluminium films. Reproducible fabrication of\r\ncircuits with impedances
    (inductances) exceeding 13 k$\\Omega$ (1 nH per square)\r\nis now possible. This
    broadly applicable method opens the path for novel qubits\r\nand high-fidelity,
    long-distance two-qubit gates."
acknowledged_ssus:
- _id: M-Shop
- _id: NanoFab
acknowledgement: "We acknowledge Franco De Palma, Mahya Khorramshahi, Fabian Oppliger,
  Thomas Reisinger, Pasquale Scarlino and Xiao Xue for helpful discussions. This research
  was supported by the Scientific Service Units of ISTA through resources provided
  by the MIBA Machine Shop and the Nanofabrication facility. This research and related
  results were made possible with the support of the NOMIS Foundation, the HORIZON-RIA
  101069515 project, the FWF Projects with DOI:10.55776/P32235, DOI:10.55776/I5060
  and DOI:10.55776/P36507. IMP acknowledges funding from the Deutsche Forschungsgemeinschaft
  (DFG – German Research Foundation) under project number 450396347 (GeHoldeQED).
  ICN2 acknowledges funding from Generalitat de Catalunya 2021SGR00457. We acknowledge
  support from CSIC Interdisciplinary Thematic Platform (PTI+) on Quantum Technologies
  (PTI-QTEP+). This research work has been funded by the European Commission – NextGenerationEU
  (Regulation EU 2020/2094), through CSIC’s\r\nQuantum Technologies Platform (QTEP).
  ICN2 is supported by the Severo Ochoa program from Spanish MCIN/AEI (Grant No.:
  CEX2021-001214-S) and is funded by the CERCA Programme/Generalitat de Catalunya.
  Part of the present work has been performed in the framework of Universitat Autònoma
  de Barcelona Materials Science PhD program. AGM has received funding from Grant
  RYC2021-033479-I funded by MCIN/AEI/10.13039/501100011033 and by European Union
  NextGenerationEU/PRTR. M.B. acknowledges support from SUR Generalitat de Catalunya
  and the EU Social Fund; project ref. 2020 FI 00103. The authors\r\nacknowledge the
  use of instrumentation and the technical advice provided by the Joint Electron Microscopy
  Center at ALBA (JEMCA). ICN2 acknowledges funding from Grant IU16-014206 (METCAM-FIB)
  funded by the European Union through the European Regional Development\r\nFund (ERDF),
  with the support of the Ministry of Research and Universities, Generalitat de Catalunya.
  ICN2 is a founding member of e-DREAM [60]."
article_number: '2407.03079'
article_processing_charge: No
arxiv: 1
author:
- first_name: Marian
  full_name: Janik, Marian
  id: 396A1950-F248-11E8-B48F-1D18A9856A87
  last_name: Janik
  orcid: 0009-0003-9037-8831
- first_name: Kevin Etienne Robert
  full_name: Roux, Kevin Etienne Robert
  id: 53f93ea2-803f-11ed-ab7e-b283135794ef
  last_name: Roux
- first_name: Carla N
  full_name: Borja Espinosa, Carla N
  id: 18777c01-896a-11ed-bdf8-e4851dc07d16
  last_name: Borja Espinosa
- first_name: Oliver
  full_name: Sagi, Oliver
  id: 71616374-A8E9-11E9-A7CA-09ECE5697425
  last_name: Sagi
- first_name: Abdulhamid
  full_name: Baghdadi, Abdulhamid
  id: 160D87FA-96B5-11E9-BF77-7626E6697425
  last_name: Baghdadi
- first_name: Thomas
  full_name: Adletzberger, Thomas
  id: 38756BB2-F248-11E8-B48F-1D18A9856A87
  last_name: Adletzberger
- first_name: Stefano
  full_name: Calcaterra, Stefano
  last_name: Calcaterra
- first_name: Marc
  full_name: Botifoll, Marc
  last_name: Botifoll
- first_name: Alba Garzón
  full_name: Manjón, Alba Garzón
  last_name: Manjón
- first_name: Jordi
  full_name: Arbiol, Jordi
  last_name: Arbiol
- first_name: Daniel
  full_name: Chrastina, Daniel
  last_name: Chrastina
- first_name: Giovanni
  full_name: Isella, Giovanni
  last_name: Isella
- first_name: Ioan M.
  full_name: Pop, Ioan M.
  last_name: Pop
- first_name: Georgios
  full_name: Katsaros, Georgios
  id: 38DB5788-F248-11E8-B48F-1D18A9856A87
  last_name: Katsaros
  orcid: 0000-0001-8342-202X
citation:
  ama: Janik M, Roux KER, Borja Espinosa CN, et al. Strong charge-photon coupling
    in planar germanium enabled by granular  aluminium superinductors. <i>arXiv</i>.
    doi:<a href="https://doi.org/10.48550/arXiv.2407.03079">10.48550/arXiv.2407.03079</a>
  apa: Janik, M., Roux, K. E. R., Borja Espinosa, C. N., Sagi, O., Baghdadi, A., Adletzberger,
    T., … Katsaros, G. (n.d.). Strong charge-photon coupling in planar germanium enabled
    by granular  aluminium superinductors. <i>arXiv</i>. <a href="https://doi.org/10.48550/arXiv.2407.03079">https://doi.org/10.48550/arXiv.2407.03079</a>
  chicago: Janik, Marian, Kevin Etienne Robert Roux, Carla N Borja Espinosa, Oliver
    Sagi, Abdulhamid Baghdadi, Thomas Adletzberger, Stefano Calcaterra, et al. “Strong
    Charge-Photon Coupling in Planar Germanium Enabled by Granular  Aluminium Superinductors.”
    <i>ArXiv</i>, n.d. <a href="https://doi.org/10.48550/arXiv.2407.03079">https://doi.org/10.48550/arXiv.2407.03079</a>.
  ieee: M. Janik <i>et al.</i>, “Strong charge-photon coupling in planar germanium
    enabled by granular  aluminium superinductors,” <i>arXiv</i>. .
  ista: Janik M, Roux KER, Borja Espinosa CN, Sagi O, Baghdadi A, Adletzberger T,
    Calcaterra S, Botifoll M, Manjón AG, Arbiol J, Chrastina D, Isella G, Pop IM,
    Katsaros G. Strong charge-photon coupling in planar germanium enabled by granular 
    aluminium superinductors. arXiv, 2407.03079.
  mla: Janik, Marian, et al. “Strong Charge-Photon Coupling in Planar Germanium Enabled
    by Granular  Aluminium Superinductors.” <i>ArXiv</i>, 2407.03079, doi:<a href="https://doi.org/10.48550/arXiv.2407.03079">10.48550/arXiv.2407.03079</a>.
  short: M. Janik, K.E.R. Roux, C.N. Borja Espinosa, O. Sagi, A. Baghdadi, T. Adletzberger,
    S. Calcaterra, M. Botifoll, A.G. Manjón, J. Arbiol, D. Chrastina, G. Isella, I.M.
    Pop, G. Katsaros, ArXiv (n.d.).
corr_author: '1'
date_created: 2024-09-26T09:50:43Z
date_published: 2024-07-03T00:00:00Z
date_updated: 2026-05-15T22:30:24Z
day: '03'
department:
- _id: GeKa
- _id: GradSch
- _id: JoFi
doi: 10.48550/arXiv.2407.03079
external_id:
  arxiv:
  - '2407.03079'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.48550/arXiv.2407.03079
month: '07'
oa: 1
oa_version: Preprint
project:
- _id: 34c0acea-11ca-11ed-8bc3-8775e10fd452
  grant_number: '101069515'
  name: Integrated Germanium Quantum Technology
- _id: 237B3DA4-32DE-11EA-91FC-C7463DDC885E
  call_identifier: FWF
  grant_number: P32235
  name: Towards scalable hut wire quantum devices
- _id: bd8bd29e-d553-11ed-ba76-f0070d4b237a
  grant_number: P36507
  name: Merging spin and superconducting qubits in planar Ge
- _id: c0977eea-5a5b-11eb-8a69-a862db0cf4d1
  grant_number: I05060
  name: High impedance circuit quantum electrodynamics with hole spins
publication: arXiv
publication_status: draft
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    status: public
status: public
title: Strong charge-photon coupling in planar germanium enabled by granular  aluminium
  superinductors
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: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '14843'
abstract:
- lang: eng
  text: The coupling between Ca2+ channels and release sensors is a key factor defining
    the signaling properties of a synapse. However, the coupling nanotopography at
    many synapses remains unknown, and it is unclear how it changes during development.
    To address these questions, we examined coupling at the cerebellar inhibitory
    basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission
    by paired recording and intracellular pipette perfusion revealed that the effects
    of exogenous Ca2+ chelators decreased during development, despite constant reliance
    of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica
    labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic
    P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked
    vesicles were only clustered at later developmental stages. Modeling suggested
    a developmental transformation from a more random to a more clustered coupling
    nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point
    configuration, optimizing speed, reliability, and energy efficiency of synaptic
    transmission.
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
- _id: M-Shop
acknowledgement: We thank Drs. David DiGregorio and Erwin Neher for critically reading
  an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions,
  Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan
  for advice on numerical solution of partial differential equations, Maria Reva for
  help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and
  Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina
  Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria
  Kralli-Beller for manuscript editing. This research was supported by the Scientific
  Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility,
  and Machine Shop). The project received funding from the European Research Council
  (ERC) under the European Union’s Horizon 2020 research and innovation program (grant
  agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung
  (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of
  the Austrian Academy of Sciences to J.-J.C.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: JingJing
  full_name: Chen, JingJing
  id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87
  last_name: Chen
- first_name: Walter
  full_name: Kaufmann, Walter
  id: 3F99E422-F248-11E8-B48F-1D18A9856A87
  last_name: Kaufmann
  orcid: 0000-0001-9735-5315
- first_name: Chong
  full_name: Chen, Chong
  id: 3DFD581A-F248-11E8-B48F-1D18A9856A87
  last_name: Chen
- first_name: Itaru
  full_name: Arai, Itaru
  id: 32A73F6C-F248-11E8-B48F-1D18A9856A87
  last_name: Arai
- first_name: Olena
  full_name: Kim, Olena
  id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
  last_name: Kim
  orcid: 0000-0003-2344-1039
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle
    nanotopography at a central GABAergic synapse. <i>Neuron</i>. 2024;112(5):755-771.e9.
    doi:<a href="https://doi.org/10.1016/j.neuron.2023.12.002">10.1016/j.neuron.2023.12.002</a>
  apa: Chen, J., Kaufmann, W., Chen, C., Arai,  itaru, Kim, O., Shigemoto, R., &#38;
    Jonas, P. M. (2024). Developmental transformation of Ca2+ channel-vesicle nanotopography
    at a central GABAergic synapse. <i>Neuron</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuron.2023.12.002">https://doi.org/10.1016/j.neuron.2023.12.002</a>
  chicago: Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi
    Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle
    Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>. Elsevier, 2024.
    <a href="https://doi.org/10.1016/j.neuron.2023.12.002">https://doi.org/10.1016/j.neuron.2023.12.002</a>.
  ieee: J. Chen <i>et al.</i>, “Developmental transformation of Ca2+ channel-vesicle
    nanotopography at a central GABAergic synapse,” <i>Neuron</i>, vol. 112, no. 5.
    Elsevier, p. 755–771.e9, 2024.
  ista: Chen J, Kaufmann W, Chen C, Arai  itaru, Kim O, Shigemoto R, Jonas PM. 2024.
    Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
    GABAergic synapse. Neuron. 112(5), 755–771.e9.
  mla: Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle
    Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>, vol. 112, no. 5,
    Elsevier, 2024, p. 755–771.e9, doi:<a href="https://doi.org/10.1016/j.neuron.2023.12.002">10.1016/j.neuron.2023.12.002</a>.
  short: J. Chen, W. Kaufmann, C. Chen,  itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas,
    Neuron 112 (2024) 755–771.e9.
corr_author: '1'
date_created: 2024-01-21T23:00:56Z
date_published: 2024-03-06T00:00:00Z
date_updated: 2026-05-15T22:30:26Z
day: '06'
ddc:
- '570'
department:
- _id: PeJo
- _id: EM-Fac
- _id: RySh
doi: 10.1016/j.neuron.2023.12.002
ec_funded: 1
external_id:
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  - '001202925700001'
  pmid:
  - '38215739'
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  name: Mechanisms of GABA release in hippocampal circuits
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  name: Development of nanodomain coupling between Ca2+ channels and release sensors
    at a central inhibitory synapse
publication: Neuron
publication_identifier:
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publication_status: published
publisher: Elsevier
quality_controlled: '1'
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status: public
title: Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
  GABAergic synapse
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: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
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...
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abstract:
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  text: "The coupling between presynaptic Ca2+ channels and release sensors is a key
    factor that\r\ndetermines speed and efficacy of synapse transmission. At some
    excitatory synapses,\r\nchannel–sensor coupling becomes tighter during development,
    and tightening is often\r\nassociated with a switch in the reliance on different
    Ca2+ channel subtypes. However, the\r\ncoupling topography at many synapses remains
    unknown, and it is unclear how it changes\r\nduring development. To address this
    question, we analyzed the coupling configuration at the\r\ncerebellar basket cell
    (BC) to Purkinje cell (PC) synapse at different developmental stages,\r\ncombining
    biophysical analysis, structural analysis, and modeling.\r\nQuantal analysis of
    BC–PC indicated that release probability decreased, while the\r\nnumber of functional
    sites increased during development. Although transmitter release\r\npersistently
    relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects\r\nof
    the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased\r\nduring
    development, indicative of tightening of source-sensor coupling. Furthermore,\r\npresynaptic
    action potentials became shorter during development, suggesting reduced\r\nefficacy
    of Ca2+ channel activation.\r\nStructural analysis by freeze-fracture replica
    labeling (FRL) and transmission electron\r\nmicroscopy (EM) indicated that presynaptic
    P/Q-type Ca2+ channels formed nanoclusters\r\nthroughout development, whereas
    docked vesicles were only clustered at later\r\ndevelopmental stages. The number
    of functional release sites correlated better with the AZ\r\nnumber early in development,
    but match better with the Ca2+ channel cluster number at later\r\nstages.\r\nModeling
    suggested a developmental transformation from a more random to a more\r\nclustered
    coupling nanotopography. Thus, presynaptic signaling developmentally approaches\r\na
    point-to-point configuration, optimizing speed, reliability, and energy efficiency
    of synaptic\r\ntransmission."
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
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author:
- first_name: JingJing
  full_name: Chen, JingJing
  id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87
  last_name: Chen
citation:
  ama: Chen J. Developmental transformation of nanodomain coupling between Ca2+ channels
    and release sensors at a central GABAergic synapse. 2024. doi:<a href="https://doi.org/10.15479/at:ista:15101">10.15479/at:ista:15101</a>
  apa: Chen, J. (2024). <i>Developmental transformation of nanodomain coupling between
    Ca2+ channels and release sensors at a central GABAergic synapse</i>. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:15101">https://doi.org/10.15479/at:ista:15101</a>
  chicago: Chen, JingJing. “Developmental Transformation of Nanodomain Coupling between
    Ca2+ Channels and Release Sensors at a Central GABAergic Synapse.” Institute of
    Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:15101">https://doi.org/10.15479/at:ista:15101</a>.
  ieee: J. Chen, “Developmental transformation of nanodomain coupling between Ca2+
    channels and release sensors at a central GABAergic synapse,” Institute of Science
    and Technology Austria, 2024.
  ista: Chen J. 2024. Developmental transformation of nanodomain coupling between
    Ca2+ channels and release sensors at a central GABAergic synapse. Institute of
    Science and Technology Austria.
  mla: Chen, JingJing. <i>Developmental Transformation of Nanodomain Coupling between
    Ca2+ Channels and Release Sensors at a Central GABAergic Synapse</i>. Institute
    of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:15101">10.15479/at:ista:15101</a>.
  short: J. Chen, Developmental Transformation of Nanodomain Coupling between Ca2+
    Channels and Release Sensors at a Central GABAergic Synapse, Institute of Science
    and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-03-11T10:09:54Z
date_published: 2024-03-11T00:00:00Z
date_updated: 2026-04-07T13:24:22Z
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degree_awarded: PhD
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- _id: PeJo
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  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
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  name: Mechanisms of GABA release in hippocampal circuits
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  name: Development of nanodomain coupling between Ca2+ channels and release sensors
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status: public
supervisor:
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  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
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  orcid: 0000-0001-5001-4804
title: Developmental transformation of nanodomain coupling between Ca2+ channels and
  release sensors at a central GABAergic synapse
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
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  short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
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...
