---
_id: '9226'
abstract:
- lang: eng
  text: 'Half a century after Lewis Wolpert''s seminal conceptual advance on how cellular
    fates distribute in space, we provide a brief historical perspective on how the
    concept of positional information emerged and influenced the field of developmental
    biology and beyond. We focus on a modern interpretation of this concept in terms
    of information theory, largely centered on its application to cell specification
    in the early Drosophila embryo. We argue that a true physical variable (position)
    is encoded in local concentrations of patterning molecules, that this mapping
    is stochastic, and that the processes by which positions and corresponding cell
    fates are determined based on these concentrations need to take such stochasticity
    into account. With this approach, we shift the focus from biological mechanisms,
    molecules, genes and pathways to quantitative systems-level questions: where does
    positional information reside, how it is transformed and accessed during development,
    and what fundamental limits it is subject to?'
acknowledgement: This work was supported in part by the National Science Foundation,
  through the Center for the Physics of Biological Function (PHY-1734030), by the
  National Institutes of Health (R01GM097275) and by the Fonds zur Förderung der wissenschaftlichen
  Forschung (FWF P28844). Deposited in PMC for release after 12 months.
article_number: dev176065
article_processing_charge: No
article_type: original
author:
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
- first_name: Thomas
  full_name: Gregor, Thomas
  last_name: Gregor
citation:
  ama: Tkačik G, Gregor T. The many bits of positional information. <i>Development</i>.
    2021;148(2). doi:<a href="https://doi.org/10.1242/dev.176065">10.1242/dev.176065</a>
  apa: Tkačik, G., &#38; Gregor, T. (2021). The many bits of positional information.
    <i>Development</i>. The Company of Biologists. <a href="https://doi.org/10.1242/dev.176065">https://doi.org/10.1242/dev.176065</a>
  chicago: Tkačik, Gašper, and Thomas Gregor. “The Many Bits of Positional Information.”
    <i>Development</i>. The Company of Biologists, 2021. <a href="https://doi.org/10.1242/dev.176065">https://doi.org/10.1242/dev.176065</a>.
  ieee: G. Tkačik and T. Gregor, “The many bits of positional information,” <i>Development</i>,
    vol. 148, no. 2. The Company of Biologists, 2021.
  ista: Tkačik G, Gregor T. 2021. The many bits of positional information. Development.
    148(2), dev176065.
  mla: Tkačik, Gašper, and Thomas Gregor. “The Many Bits of Positional Information.”
    <i>Development</i>, vol. 148, no. 2, dev176065, The Company of Biologists, 2021,
    doi:<a href="https://doi.org/10.1242/dev.176065">10.1242/dev.176065</a>.
  short: G. Tkačik, T. Gregor, Development 148 (2021).
date_created: 2021-03-07T23:01:25Z
date_published: 2021-02-01T00:00:00Z
date_updated: 2023-08-07T13:57:30Z
day: '01'
department:
- _id: GaTk
doi: 10.1242/dev.176065
external_id:
  isi:
  - '000613906000007'
  pmid:
  - '33526425'
intvolume: '       148'
isi: 1
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1242/dev.176065
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 254E9036-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P28844-B27
  name: Biophysics of information processing in gene regulation
publication: Development
publication_identifier:
  eissn:
  - 1477-9129
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: The many bits of positional information
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 148
year: '2021'
...
---
_id: '9283'
abstract:
- lang: eng
  text: Gene expression levels are influenced by multiple coexisting molecular mechanisms.
    Some of these interactions such as those of transcription factors and promoters
    have been studied extensively. However, predicting phenotypes of gene regulatory
    networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic
    GRN to study in Escherichia coli how network phenotypes depend on local genetic
    context, i.e. the genetic neighborhood of a transcription factor and its relative
    position. We show that one GRN with fixed topology can display not only quantitatively
    but also qualitatively different phenotypes, depending solely on the local genetic
    context of its components. Transcriptional read-through is the main molecular
    mechanism that places one transcriptional unit (TU) within two separate regulons
    without the need for complex regulatory sequences. We propose that relative order
    of individual TUs, with its potential for combinatorial complexity, plays an important
    role in shaping phenotypes of GRNs.
acknowledgement: "We thank J Bollback, L Hurst, M Lagator, C Nizak, O Rivoire, M Savageau,
  G Tkacik, and B Vicozo\r\nfor helpful discussions; A Dolinar and A Greshnova for
  technical assistance; T Bollenbach for supplying the strain JW0336; C Rusnac, and
  members of the Guet lab for comments. The research leading to these results has
  received funding from the People Programme (Marie Curie Actions) of the European
  Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n˚\r\n628377
  (ANS) and an Austrian Science Fund (FWF) grant n˚ I 3901-B32 (CCG)."
article_number: e65993
article_processing_charge: Yes
article_type: original
author:
- first_name: Anna A
  full_name: Nagy-Staron, Anna A
  id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87
  last_name: Nagy-Staron
  orcid: 0000-0002-1391-8377
- first_name: Kathrin
  full_name: Tomasek, Kathrin
  id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
  last_name: Tomasek
  orcid: 0000-0003-3768-877X
- first_name: Caroline
  full_name: Caruso Carter, Caroline
  last_name: Caruso Carter
- first_name: Elisabeth
  full_name: Sonnleitner, Elisabeth
  last_name: Sonnleitner
- first_name: Bor
  full_name: Kavcic, Bor
  id: 350F91D2-F248-11E8-B48F-1D18A9856A87
  last_name: Kavcic
  orcid: 0000-0001-6041-254X
- first_name: Tiago
  full_name: Paixão, Tiago
  last_name: Paixão
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
citation:
  ama: Nagy-Staron AA, Tomasek K, Caruso Carter C, et al. Local genetic context shapes
    the function of a gene regulatory network. <i>eLife</i>. 2021;10. doi:<a href="https://doi.org/10.7554/elife.65993">10.7554/elife.65993</a>
  apa: Nagy-Staron, A. A., Tomasek, K., Caruso Carter, C., Sonnleitner, E., Kavcic,
    B., Paixão, T., &#38; Guet, C. C. (2021). Local genetic context shapes the function
    of a gene regulatory network. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/elife.65993">https://doi.org/10.7554/elife.65993</a>
  chicago: Nagy-Staron, Anna A, Kathrin Tomasek, Caroline Caruso Carter, Elisabeth
    Sonnleitner, Bor Kavcic, Tiago Paixão, and Calin C Guet. “Local Genetic Context
    Shapes the Function of a Gene Regulatory Network.” <i>ELife</i>. eLife Sciences
    Publications, 2021. <a href="https://doi.org/10.7554/elife.65993">https://doi.org/10.7554/elife.65993</a>.
  ieee: A. A. Nagy-Staron <i>et al.</i>, “Local genetic context shapes the function
    of a gene regulatory network,” <i>eLife</i>, vol. 10. eLife Sciences Publications,
    2021.
  ista: Nagy-Staron AA, Tomasek K, Caruso Carter C, Sonnleitner E, Kavcic B, Paixão
    T, Guet CC. 2021. Local genetic context shapes the function of a gene regulatory
    network. eLife. 10, e65993.
  mla: Nagy-Staron, Anna A., et al. “Local Genetic Context Shapes the Function of
    a Gene Regulatory Network.” <i>ELife</i>, vol. 10, e65993, eLife Sciences Publications,
    2021, doi:<a href="https://doi.org/10.7554/elife.65993">10.7554/elife.65993</a>.
  short: A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic,
    T. Paixão, C.C. Guet, ELife 10 (2021).
date_created: 2021-03-23T10:11:46Z
date_published: 2021-03-08T00:00:00Z
date_updated: 2024-02-21T12:41:57Z
day: '08'
ddc:
- '570'
department:
- _id: GaTk
- _id: CaGu
doi: 10.7554/elife.65993
ec_funded: 1
external_id:
  isi:
  - '000631050900001'
file:
- access_level: open_access
  checksum: 3c2f44058c2dd45a5a1027f09d263f8e
  content_type: application/pdf
  creator: bkavcic
  date_created: 2021-03-23T10:12:58Z
  date_updated: 2021-03-23T10:12:58Z
  file_id: '9284'
  file_name: elife-65993-v2.pdf
  file_size: 1390469
  relation: main_file
  success: 1
file_date_updated: 2021-03-23T10:12:58Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
keyword:
- Genetics and Molecular Biology
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 2517526A-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '628377'
  name: 'The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic
    Networks to Genomic Studies'
- _id: 268BFA92-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03901
  name: 'CyberCircuits: Cybergenetic circuits to test composability of gene networks'
publication: eLife
publication_identifier:
  issn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
  record:
  - id: '8951'
    relation: research_data
    status: public
status: public
title: Local genetic context shapes the function of a gene regulatory network
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2021'
...
---
_id: '9362'
abstract:
- lang: eng
  text: A central goal in systems neuroscience is to understand the functions performed
    by neural circuits. Previous top-down models addressed this question by comparing
    the behaviour of an ideal model circuit, optimised to perform a given function,
    with neural recordings. However, this requires guessing in advance what function
    is being performed, which may not be possible for many neural systems. To address
    this, we propose an inverse reinforcement learning (RL) framework for inferring
    the function performed by a neural network from data. We assume that the responses
    of each neuron in a network are optimised so as to drive the network towards ‘rewarded’
    states, that are desirable for performing a given function. We then show how one
    can use inverse RL to infer the reward function optimised by the network from
    observing its responses. This inferred reward function can be used to predict
    how the neural network should adapt its dynamics to perform the same function
    when the external environment or network structure changes. This could lead to
    theoretical predictions about how neural network dynamics adapt to deal with cell
    death and/or varying sensory stimulus statistics.
acknowledgement: The authors would like to thank Ulisse Ferrari for useful discussions
  and feedback.
article_number: e0248940
article_processing_charge: No
article_type: original
author:
- first_name: Matthew J
  full_name: Chalk, Matthew J
  id: 2BAAC544-F248-11E8-B48F-1D18A9856A87
  last_name: Chalk
  orcid: 0000-0001-7782-4436
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
- first_name: Olivier
  full_name: Marre, Olivier
  last_name: Marre
citation:
  ama: Chalk MJ, Tkačik G, Marre O. Inferring the function performed by a recurrent
    neural network. <i>PLoS ONE</i>. 2021;16(4). doi:<a href="https://doi.org/10.1371/journal.pone.0248940">10.1371/journal.pone.0248940</a>
  apa: Chalk, M. J., Tkačik, G., &#38; Marre, O. (2021). Inferring the function performed
    by a recurrent neural network. <i>PLoS ONE</i>. Public Library of Science. <a
    href="https://doi.org/10.1371/journal.pone.0248940">https://doi.org/10.1371/journal.pone.0248940</a>
  chicago: Chalk, Matthew J, Gašper Tkačik, and Olivier Marre. “Inferring the Function
    Performed by a Recurrent Neural Network.” <i>PLoS ONE</i>. Public Library of Science,
    2021. <a href="https://doi.org/10.1371/journal.pone.0248940">https://doi.org/10.1371/journal.pone.0248940</a>.
  ieee: M. J. Chalk, G. Tkačik, and O. Marre, “Inferring the function performed by
    a recurrent neural network,” <i>PLoS ONE</i>, vol. 16, no. 4. Public Library of
    Science, 2021.
  ista: Chalk MJ, Tkačik G, Marre O. 2021. Inferring the function performed by a recurrent
    neural network. PLoS ONE. 16(4), e0248940.
  mla: Chalk, Matthew J., et al. “Inferring the Function Performed by a Recurrent
    Neural Network.” <i>PLoS ONE</i>, vol. 16, no. 4, e0248940, Public Library of
    Science, 2021, doi:<a href="https://doi.org/10.1371/journal.pone.0248940">10.1371/journal.pone.0248940</a>.
  short: M.J. Chalk, G. Tkačik, O. Marre, PLoS ONE 16 (2021).
date_created: 2021-05-02T22:01:28Z
date_published: 2021-04-15T00:00:00Z
date_updated: 2023-10-18T08:17:42Z
day: '15'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1371/journal.pone.0248940
external_id:
  isi:
  - '000641474900072'
  pmid:
  - '33857170'
file:
- access_level: open_access
  checksum: c52da133850307d2031f552d998f00e8
  content_type: application/pdf
  creator: kschuh
  date_created: 2021-05-04T13:22:19Z
  date_updated: 2021-05-04T13:22:19Z
  file_id: '9371'
  file_name: 2021_pone_Chalk.pdf
  file_size: 2768282
  relation: main_file
  success: 1
file_date_updated: 2021-05-04T13:22:19Z
has_accepted_license: '1'
intvolume: '        16'
isi: 1
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: PLoS ONE
publication_identifier:
  eissn:
  - '19326203'
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Inferring the function performed by a recurrent neural network
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: 16
year: '2021'
...
---
_id: '9439'
abstract:
- lang: eng
  text: The ability to adapt to changes in stimulus statistics is a hallmark of sensory
    systems. Here, we developed a theoretical framework that can account for the dynamics
    of adaptation from an information processing perspective. We use this framework
    to optimize and analyze adaptive sensory codes, and we show that codes optimized
    for stationary environments can suffer from prolonged periods of poor performance
    when the environment changes. To mitigate the adversarial effects of these environmental
    changes, sensory systems must navigate tradeoffs between the ability to accurately
    encode incoming stimuli and the ability to rapidly detect and adapt to changes
    in the distribution of these stimuli. We derive families of codes that balance
    these objectives, and we demonstrate their close match to experimentally observed
    neural dynamics during mean and variance adaptation. Our results provide a unifying
    perspective on adaptation across a range of sensory systems, environments, and
    sensory tasks.
acknowledgement: We thank D. Kastner and T. Münch for generously providing figures
  from their work. We also thank V. Jayaraman, M. Noorman, T. Ma, and K. Krishnamurthy
  for useful discussions and feedback on the manuscript. W.F.M. was funded by the
  European Union’s Horizon 2020 Research and Innovation Programme under Marie Skłodowska-Curie
  Grant Agreement No. 754411. A.M.H. was supported by the Howard Hughes Medical Institute.
article_processing_charge: No
article_type: original
author:
- first_name: Wiktor F
  full_name: Mlynarski, Wiktor F
  id: 358A453A-F248-11E8-B48F-1D18A9856A87
  last_name: Mlynarski
- first_name: Ann M.
  full_name: Hermundstad, Ann M.
  last_name: Hermundstad
citation:
  ama: Mlynarski WF, Hermundstad AM. Efficient and adaptive sensory codes. <i>Nature
    Neuroscience</i>. 2021;24:998-1009. doi:<a href="https://doi.org/10.1038/s41593-021-00846-0">10.1038/s41593-021-00846-0</a>
  apa: Mlynarski, W. F., &#38; Hermundstad, A. M. (2021). Efficient and adaptive sensory
    codes. <i>Nature Neuroscience</i>. Springer Nature. <a href="https://doi.org/10.1038/s41593-021-00846-0">https://doi.org/10.1038/s41593-021-00846-0</a>
  chicago: Mlynarski, Wiktor F, and Ann M. Hermundstad. “Efficient and Adaptive Sensory
    Codes.” <i>Nature Neuroscience</i>. Springer Nature, 2021. <a href="https://doi.org/10.1038/s41593-021-00846-0">https://doi.org/10.1038/s41593-021-00846-0</a>.
  ieee: W. F. Mlynarski and A. M. Hermundstad, “Efficient and adaptive sensory codes,”
    <i>Nature Neuroscience</i>, vol. 24. Springer Nature, pp. 998–1009, 2021.
  ista: Mlynarski WF, Hermundstad AM. 2021. Efficient and adaptive sensory codes.
    Nature Neuroscience. 24, 998–1009.
  mla: Mlynarski, Wiktor F., and Ann M. Hermundstad. “Efficient and Adaptive Sensory
    Codes.” <i>Nature Neuroscience</i>, vol. 24, Springer Nature, 2021, pp. 998–1009,
    doi:<a href="https://doi.org/10.1038/s41593-021-00846-0">10.1038/s41593-021-00846-0</a>.
  short: W.F. Mlynarski, A.M. Hermundstad, Nature Neuroscience 24 (2021) 998–1009.
date_created: 2021-05-30T22:01:24Z
date_published: 2021-05-20T00:00:00Z
date_updated: 2023-08-08T13:51:14Z
day: '20'
department:
- _id: GaTk
doi: 10.1038/s41593-021-00846-0
ec_funded: 1
external_id:
  isi:
  - '000652577300003'
intvolume: '        24'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: 'https://doi.org/10.1101/669200 '
month: '05'
oa: 1
oa_version: Preprint
page: 998-1009
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
publication: Nature Neuroscience
publication_identifier:
  eissn:
  - 1546-1726
  issn:
  - 1097-6256
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Efficient and adaptive sensory codes
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 24
year: '2021'
...
---
_id: '10077'
abstract:
- lang: eng
  text: Although much is known about how single neurons in the hippocampus represent
    an animal’s position, how cell-cell interactions contribute to spatial coding
    remains poorly understood. Using a novel statistical estimator and theoretical
    modeling, both developed in the framework of maximum entropy models, we reveal
    highly structured cell-to-cell interactions whose statistics depend on familiar
    vs. novel environment. In both conditions the circuit interactions optimize the
    encoding of spatial information, but for regimes that differ in the signal-to-noise
    ratio of their spatial inputs. Moreover, the topology of the interactions facilitates
    linear decodability, making the information easy to read out by downstream circuits.
    These findings suggest that the efficient coding hypothesis is not applicable
    only to individual neuron properties in the sensory periphery, but also to neural
    interactions in the central brain.
acknowledgement: We thank Peter Baracskay, Karola Kaefer and Hugo Malagon-Vina for
  the acquisition of the data. We thank Federico Stella for comments on an earlier
  version of the manuscript. MN was supported by European Union Horizon 2020 grant
  665385, JC was supported by European Research Council consolidator grant 281511,
  GT was supported by the Austrian Science Fund (FWF) grant P34015, CS was supported
  by an IST fellow grant, National Institute of Mental Health Award 1R01MH125571-01,
  by the National Science Foundation under NSF Award No. 1922658 and a Google faculty
  award.
article_processing_charge: No
author:
- first_name: Michele
  full_name: Nardin, Michele
  id: 30BD0376-F248-11E8-B48F-1D18A9856A87
  last_name: Nardin
  orcid: 0000-0001-8849-6570
- first_name: Jozsef L
  full_name: Csicsvari, Jozsef L
  id: 3FA14672-F248-11E8-B48F-1D18A9856A87
  last_name: Csicsvari
  orcid: 0000-0002-5193-4036
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
- first_name: Cristina
  full_name: Savin, Cristina
  id: 3933349E-F248-11E8-B48F-1D18A9856A87
  last_name: Savin
citation:
  ama: Nardin M, Csicsvari JL, Tkačik G, Savin C. The structure of hippocampal CA1
    interactions optimizes spatial coding across experience. <i>bioRxiv</i>. doi:<a
    href="https://doi.org/10.1101/2021.09.28.460602">10.1101/2021.09.28.460602</a>
  apa: Nardin, M., Csicsvari, J. L., Tkačik, G., &#38; Savin, C. (n.d.). The structure
    of hippocampal CA1 interactions optimizes spatial coding across experience. <i>bioRxiv</i>.
    Cold Spring Harbor Laboratory. <a href="https://doi.org/10.1101/2021.09.28.460602">https://doi.org/10.1101/2021.09.28.460602</a>
  chicago: Nardin, Michele, Jozsef L Csicsvari, Gašper Tkačik, and Cristina Savin.
    “The Structure of Hippocampal CA1 Interactions Optimizes Spatial Coding across
    Experience.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href="https://doi.org/10.1101/2021.09.28.460602">https://doi.org/10.1101/2021.09.28.460602</a>.
  ieee: M. Nardin, J. L. Csicsvari, G. Tkačik, and C. Savin, “The structure of hippocampal
    CA1 interactions optimizes spatial coding across experience,” <i>bioRxiv</i>.
    Cold Spring Harbor Laboratory.
  ista: Nardin M, Csicsvari JL, Tkačik G, Savin C. The structure of hippocampal CA1
    interactions optimizes spatial coding across experience. bioRxiv, <a href="https://doi.org/10.1101/2021.09.28.460602">10.1101/2021.09.28.460602</a>.
  mla: Nardin, Michele, et al. “The Structure of Hippocampal CA1 Interactions Optimizes
    Spatial Coding across Experience.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory,
    doi:<a href="https://doi.org/10.1101/2021.09.28.460602">10.1101/2021.09.28.460602</a>.
  short: M. Nardin, J.L. Csicsvari, G. Tkačik, C. Savin, BioRxiv (n.d.).
date_created: 2021-10-04T06:23:34Z
date_published: 2021-09-29T00:00:00Z
date_updated: 2024-03-25T23:30:09Z
day: '29'
department:
- _id: GradSch
- _id: JoCs
- _id: GaTk
doi: 10.1101/2021.09.28.460602
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.biorxiv.org/content/10.1101/2021.09.28.460602
month: '09'
oa: 1
oa_version: Preprint
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 257A4776-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '281511'
  name: Memory-related information processing in neuronal circuits of the hippocampus
    and entorhinal cortex
- _id: 626c45b5-2b32-11ec-9570-e509828c1ba6
  grant_number: P34015
  name: Efficient coding with biophysical realism
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
  record:
  - id: '11932'
    relation: dissertation_contains
    status: public
status: public
title: The structure of hippocampal CA1 interactions optimizes spatial coding across
  experience
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: preprint
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2021'
...
---
_id: '10535'
abstract:
- lang: eng
  text: Realistic models of biological processes typically involve interacting components
    on multiple scales, driven by changing environment and inherent stochasticity.
    Such models are often analytically and numerically intractable. We revisit a dynamic
    maximum entropy method that combines a static maximum entropy with a quasi-stationary
    approximation. This allows us to reduce stochastic non-equilibrium dynamics expressed
    by the Fokker-Planck equation to a simpler low-dimensional deterministic dynamics,
    without the need to track microscopic details. Although the method has been previously
    applied to a few (rather complicated) applications in population genetics, our
    main goal here is to explain and to better understand how the method works. We
    demonstrate the usefulness of the method for two widely studied stochastic problems,
    highlighting its accuracy in capturing important macroscopic quantities even in
    rapidly changing non-stationary conditions. For the Ornstein-Uhlenbeck process,
    the method recovers the exact dynamics whilst for a stochastic island model with
    migration from other habitats, the approximation retains high macroscopic accuracy
    under a wide range of scenarios in a dynamic environment.
acknowledged_ssus:
- _id: ScienComp
acknowledgement: "Computational resources for the study were provided by the Institute
  of Science and Technology, Austria.\r\nKB received funding from the Scientific Grant
  Agency of the Slovak Republic under the Grants Nos. 1/0755/19 and 1/0521/20."
article_number: e1009661
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Katarína
  full_name: Bod'ová, Katarína
  id: 2BA24EA0-F248-11E8-B48F-1D18A9856A87
  last_name: Bod'ová
  orcid: 0000-0002-7214-0171
- first_name: Eniko
  full_name: Szep, Eniko
  id: 485BB5A4-F248-11E8-B48F-1D18A9856A87
  last_name: Szep
- first_name: Nicholas H
  full_name: Barton, Nicholas H
  id: 4880FE40-F248-11E8-B48F-1D18A9856A87
  last_name: Barton
  orcid: 0000-0002-8548-5240
citation:
  ama: Bodova K, Szep E, Barton NH. Dynamic maximum entropy provides accurate approximation
    of structured population dynamics. <i>PLoS Computational Biology</i>. 2021;17(12).
    doi:<a href="https://doi.org/10.1371/journal.pcbi.1009661">10.1371/journal.pcbi.1009661</a>
  apa: Bodova, K., Szep, E., &#38; Barton, N. H. (2021). Dynamic maximum entropy provides
    accurate approximation of structured population dynamics. <i>PLoS Computational
    Biology</i>. Public Library of Science. <a href="https://doi.org/10.1371/journal.pcbi.1009661">https://doi.org/10.1371/journal.pcbi.1009661</a>
  chicago: Bodova, Katarina, Eniko Szep, and Nicholas H Barton. “Dynamic Maximum Entropy
    Provides Accurate Approximation of Structured Population Dynamics.” <i>PLoS Computational
    Biology</i>. Public Library of Science, 2021. <a href="https://doi.org/10.1371/journal.pcbi.1009661">https://doi.org/10.1371/journal.pcbi.1009661</a>.
  ieee: K. Bodova, E. Szep, and N. H. Barton, “Dynamic maximum entropy provides accurate
    approximation of structured population dynamics,” <i>PLoS Computational Biology</i>,
    vol. 17, no. 12. Public Library of Science, 2021.
  ista: Bodova K, Szep E, Barton NH. 2021. Dynamic maximum entropy provides accurate
    approximation of structured population dynamics. PLoS Computational Biology. 17(12),
    e1009661.
  mla: Bodova, Katarina, et al. “Dynamic Maximum Entropy Provides Accurate Approximation
    of Structured Population Dynamics.” <i>PLoS Computational Biology</i>, vol. 17,
    no. 12, e1009661, Public Library of Science, 2021, doi:<a href="https://doi.org/10.1371/journal.pcbi.1009661">10.1371/journal.pcbi.1009661</a>.
  short: K. Bodova, E. Szep, N.H. Barton, PLoS Computational Biology 17 (2021).
date_created: 2021-12-12T23:01:27Z
date_published: 2021-12-01T00:00:00Z
date_updated: 2022-08-01T10:48:04Z
day: '01'
ddc:
- '570'
department:
- _id: NiBa
- _id: GaTk
doi: 10.1371/journal.pcbi.1009661
external_id:
  arxiv:
  - '2102.03669'
  pmid:
  - '34851948'
file:
- access_level: open_access
  checksum: dcd185d4f7e0acee25edf1d6537f447e
  content_type: application/pdf
  creator: dernst
  date_created: 2022-05-16T08:53:11Z
  date_updated: 2022-05-16T08:53:11Z
  file_id: '11383'
  file_name: 2021_PLOsComBio_Bodova.pdf
  file_size: 2299486
  relation: main_file
  success: 1
file_date_updated: 2022-05-16T08:53:11Z
has_accepted_license: '1'
intvolume: '        17'
issue: '12'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
publication: PLoS Computational Biology
publication_identifier:
  eissn:
  - 1553-7358
  issn:
  - 1553-734X
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Dynamic maximum entropy provides accurate approximation of structured population
  dynamics
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: 17
year: '2021'
...
---
_id: '10579'
abstract:
- lang: eng
  text: 'We consider a totally asymmetric simple exclusion process (TASEP) consisting
    of particles on a lattice that require binding by a "token" to move. Using a combination
    of theory and simulations, we address the following questions: (i) How token binding
    kinetics affects the current-density relation; (ii) How the current-density relation
    depends on the scarcity of tokens; (iii) How tokens propagate the effects of the
    locally-imposed disorder (such a slow site) over the entire lattice; (iv) How
    a shared pool of tokens couples concurrent TASEPs running on multiple lattices;
    (v) How our results translate to TASEPs with open boundaries that exchange particles
    with the reservoir. Since real particle motion (including in systems that inspired
    the standard TASEP model, e.g., protein synthesis or movement of molecular motors)
    is often catalyzed, regulated, actuated, or otherwise mediated, the token-driven
    TASEP dynamics analyzed in this paper should allow for a better understanding
    of real systems and enable a closer match between TASEP theory and experimental
    observations.'
acknowledgement: B.K. thanks Stefano Elefante, Simon Rella, and Michal Hledík for
  their help with the usage of the cluster. B.K. additionally thanks Călin Guet and
  his group for help and advice. We thank M. Hennessey-Wesen for constructive comments
  on the manuscript. We thank Ankita Gupta (Indian Institute of Technology) for spotting
  a typographical error in Eq. (49) in the preprint version of this paper.
article_number: '2112.13558'
article_processing_charge: No
arxiv: 1
author:
- first_name: Bor
  full_name: Kavcic, Bor
  id: 350F91D2-F248-11E8-B48F-1D18A9856A87
  last_name: Kavcic
  orcid: 0000-0001-6041-254X
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
citation:
  ama: Kavcic B, Tkačik G. Token-driven totally asymmetric simple exclusion process.
    <i>arXiv</i>. doi:<a href="https://doi.org/10.48550/arXiv.2112.13558">10.48550/arXiv.2112.13558</a>
  apa: Kavcic, B., &#38; Tkačik, G. (n.d.). Token-driven totally asymmetric simple
    exclusion process. <i>arXiv</i>. <a href="https://doi.org/10.48550/arXiv.2112.13558">https://doi.org/10.48550/arXiv.2112.13558</a>
  chicago: Kavcic, Bor, and Gašper Tkačik. “Token-Driven Totally Asymmetric Simple
    Exclusion Process.” <i>ArXiv</i>, n.d. <a href="https://doi.org/10.48550/arXiv.2112.13558">https://doi.org/10.48550/arXiv.2112.13558</a>.
  ieee: B. Kavcic and G. Tkačik, “Token-driven totally asymmetric simple exclusion
    process,” <i>arXiv</i>. .
  ista: Kavcic B, Tkačik G. Token-driven totally asymmetric simple exclusion process.
    arXiv, 2112.13558.
  mla: Kavcic, Bor, and Gašper Tkačik. “Token-Driven Totally Asymmetric Simple Exclusion
    Process.” <i>ArXiv</i>, 2112.13558, doi:<a href="https://doi.org/10.48550/arXiv.2112.13558">10.48550/arXiv.2112.13558</a>.
  short: B. Kavcic, G. Tkačik, ArXiv (n.d.).
date_created: 2021-12-28T06:52:09Z
date_published: 2021-12-27T00:00:00Z
date_updated: 2023-05-03T10:54:05Z
day: '27'
ddc:
- '530'
department:
- _id: GaTk
doi: 10.48550/arXiv.2112.13558
external_id:
  arxiv:
  - '2112.13558'
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://arxiv.org/abs/2112.13558
month: '12'
oa: 1
oa_version: Preprint
publication: arXiv
publication_status: submitted
status: public
title: Token-driven totally asymmetric simple exclusion process
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2021'
...
---
_id: '9822'
abstract:
- lang: eng
  text: Attachment of adhesive molecules on cell culture surfaces to restrict cell
    adhesion to defined areas and shapes has been vital for the progress of in vitro
    research. In currently existing patterning methods, a combination of pattern properties
    such as stability, precision, specificity, high-throughput outcome, and spatiotemporal
    control is highly desirable but challenging to achieve. Here, we introduce a versatile
    and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent
    patterning step and a subsequent functionalization of the pattern via click chemistry.
    This two-step process is feasible on arbitrary surfaces and allows for generation
    of sustainable patterns and gradients. The method is validated in different biological
    systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining
    the growth and migration of cells to the designated areas. We then implement a
    sequential photopatterning approach by adding a second switchable patterning step,
    allowing for spatiotemporal control over two distinct surface patterns. As a proof
    of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis.
    Our results show that the spatiotemporal control provided by our “sequential photopatterning”
    system is essential for mimicking dynamic biological processes and that our innovative
    approach has great potential for further applications in cell science.
acknowledgement: We would like to thank Charlott Leu for the production of our chromium
  wafers, Louise Ritter for her contribution of the IF stainings in Figure 4, Shokoufeh
  Teymouri for her help with the Bioinert coated slides, and finally Prof. Dr. Joachim
  Rädler for his valuable scientific guidance.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Themistoklis
  full_name: Zisis, Themistoklis
  last_name: Zisis
- first_name: Jan
  full_name: Schwarz, Jan
  id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Miriam
  full_name: Balles, Miriam
  last_name: Balles
- first_name: Maibritt
  full_name: Kretschmer, Maibritt
  last_name: Kretschmer
- first_name: Maria
  full_name: Nemethova, Maria
  id: 34E27F1C-F248-11E8-B48F-1D18A9856A87
  last_name: Nemethova
- first_name: Remy P
  full_name: Chait, Remy P
  id: 3464AE84-F248-11E8-B48F-1D18A9856A87
  last_name: Chait
  orcid: 0000-0003-0876-3187
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Janina
  full_name: Lange, Janina
  last_name: Lange
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-4561-241X
- first_name: Stefan
  full_name: Zahler, Stefan
  last_name: Zahler
citation:
  ama: Zisis T, Schwarz J, Balles M, et al. Sequential and switchable patterning for
    studying cellular processes under spatiotemporal control. <i>ACS Applied Materials
    and Interfaces</i>. 2021;13(30):35545–35560. doi:<a href="https://doi.org/10.1021/acsami.1c09850">10.1021/acsami.1c09850</a>
  apa: Zisis, T., Schwarz, J., Balles, M., Kretschmer, M., Nemethova, M., Chait, R.
    P., … Zahler, S. (2021). Sequential and switchable patterning for studying cellular
    processes under spatiotemporal control. <i>ACS Applied Materials and Interfaces</i>.
    American Chemical Society. <a href="https://doi.org/10.1021/acsami.1c09850">https://doi.org/10.1021/acsami.1c09850</a>
  chicago: Zisis, Themistoklis, Jan Schwarz, Miriam Balles, Maibritt Kretschmer, Maria
    Nemethova, Remy P Chait, Robert Hauschild, et al. “Sequential and Switchable Patterning
    for Studying Cellular Processes under Spatiotemporal Control.” <i>ACS Applied
    Materials and Interfaces</i>. American Chemical Society, 2021. <a href="https://doi.org/10.1021/acsami.1c09850">https://doi.org/10.1021/acsami.1c09850</a>.
  ieee: T. Zisis <i>et al.</i>, “Sequential and switchable patterning for studying
    cellular processes under spatiotemporal control,” <i>ACS Applied Materials and
    Interfaces</i>, vol. 13, no. 30. American Chemical Society, pp. 35545–35560, 2021.
  ista: Zisis T, Schwarz J, Balles M, Kretschmer M, Nemethova M, Chait RP, Hauschild
    R, Lange J, Guet CC, Sixt MK, Zahler S. 2021. Sequential and switchable patterning
    for studying cellular processes under spatiotemporal control. ACS Applied Materials
    and Interfaces. 13(30), 35545–35560.
  mla: Zisis, Themistoklis, et al. “Sequential and Switchable Patterning for Studying
    Cellular Processes under Spatiotemporal Control.” <i>ACS Applied Materials and
    Interfaces</i>, vol. 13, no. 30, American Chemical Society, 2021, pp. 35545–35560,
    doi:<a href="https://doi.org/10.1021/acsami.1c09850">10.1021/acsami.1c09850</a>.
  short: T. Zisis, J. Schwarz, M. Balles, M. Kretschmer, M. Nemethova, R.P. Chait,
    R. Hauschild, J. Lange, C.C. Guet, M.K. Sixt, S. Zahler, ACS Applied Materials
    and Interfaces 13 (2021) 35545–35560.
date_created: 2021-08-08T22:01:28Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2023-08-10T14:22:48Z
day: '04'
ddc:
- '620'
- '570'
department:
- _id: MiSi
- _id: GaTk
- _id: Bio
- _id: CaGu
doi: 10.1021/acsami.1c09850
ec_funded: 1
external_id:
  isi:
  - '000683741400026'
  pmid:
  - '34283577'
file:
- access_level: open_access
  checksum: b043a91d9f9200e467b970b692687ed3
  content_type: application/pdf
  creator: asandaue
  date_created: 2021-08-09T09:44:03Z
  date_updated: 2021-08-09T09:44:03Z
  file_id: '9833'
  file_name: 2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf
  file_size: 7123293
  relation: main_file
  success: 1
file_date_updated: 2021-08-09T09:44:03Z
has_accepted_license: '1'
intvolume: '        13'
isi: 1
issue: '30'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 35545–35560
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '724373'
  name: Cellular navigation along spatial gradients
publication: ACS Applied Materials and Interfaces
publication_identifier:
  eissn:
  - '19448252'
  issn:
  - '19448244'
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Sequential and switchable patterning for studying cellular processes under
  spatiotemporal control
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2021'
...
---
_id: '9828'
abstract:
- lang: eng
  text: Amplitude demodulation is a classical operation used in signal processing.
    For a long time, its effective applications in practice have been limited to narrowband
    signals. In this work, we generalize amplitude demodulation to wideband signals.
    We pose demodulation as a recovery problem of an oversampled corrupted signal
    and introduce special iterative schemes belonging to the family of alternating
    projection algorithms to solve it. Sensibly chosen structural assumptions on the
    demodulation outputs allow us to reveal the high inferential accuracy of the method
    over a rich set of relevant signals. This new approach surpasses current state-of-the-art
    demodulation techniques apt to wideband signals in computational efficiency by
    up to many orders of magnitude with no sacrifice in quality. Such performance
    opens the door for applications of the amplitude demodulation procedure in new
    contexts. In particular, the new method makes online and large-scale offline data
    processing feasible, including the calculation of modulator-carrier pairs in higher
    dimensions and poor sampling conditions, independent of the signal bandwidth.
    We illustrate the utility and specifics of applications of the new method in practice
    by using natural speech and synthetic signals.
acknowledgement: The author thanks his colleagues K. Huszár and G. Tkačik for valuable
  discussions and comments on the manuscript.
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Mantas
  full_name: Gabrielaitis, Mantas
  id: 4D5B0CBC-F248-11E8-B48F-1D18A9856A87
  last_name: Gabrielaitis
  orcid: 0000-0002-7758-2016
citation:
  ama: Gabrielaitis M. Fast and accurate amplitude demodulation of wideband signals.
    <i>IEEE Transactions on Signal Processing</i>. 2021;69:4039-4054. doi:<a href="https://doi.org/10.1109/TSP.2021.3087899">10.1109/TSP.2021.3087899</a>
  apa: Gabrielaitis, M. (2021). Fast and accurate amplitude demodulation of wideband
    signals. <i>IEEE Transactions on Signal Processing</i>. Institute of Electrical
    and Electronics Engineers. <a href="https://doi.org/10.1109/TSP.2021.3087899">https://doi.org/10.1109/TSP.2021.3087899</a>
  chicago: Gabrielaitis, Mantas. “Fast and Accurate Amplitude Demodulation of Wideband
    Signals.” <i>IEEE Transactions on Signal Processing</i>. Institute of Electrical
    and Electronics Engineers, 2021. <a href="https://doi.org/10.1109/TSP.2021.3087899">https://doi.org/10.1109/TSP.2021.3087899</a>.
  ieee: M. Gabrielaitis, “Fast and accurate amplitude demodulation of wideband signals,”
    <i>IEEE Transactions on Signal Processing</i>, vol. 69. Institute of Electrical
    and Electronics Engineers, pp. 4039–4054, 2021.
  ista: Gabrielaitis M. 2021. Fast and accurate amplitude demodulation of wideband
    signals. IEEE Transactions on Signal Processing. 69, 4039–4054.
  mla: Gabrielaitis, Mantas. “Fast and Accurate Amplitude Demodulation of Wideband
    Signals.” <i>IEEE Transactions on Signal Processing</i>, vol. 69, Institute of
    Electrical and Electronics Engineers, 2021, pp. 4039–54, doi:<a href="https://doi.org/10.1109/TSP.2021.3087899">10.1109/TSP.2021.3087899</a>.
  short: M. Gabrielaitis, IEEE Transactions on Signal Processing 69 (2021) 4039–4054.
date_created: 2021-08-08T22:01:31Z
date_published: 2021-06-09T00:00:00Z
date_updated: 2023-08-10T14:19:33Z
day: '09'
department:
- _id: GaTk
doi: 10.1109/TSP.2021.3087899
external_id:
  arxiv:
  - '2102.04832'
  isi:
  - '000682123900002'
intvolume: '        69'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://arxiv.org/abs/2102.04832
month: '06'
oa: 1
oa_version: Preprint
page: 4039 - 4054
publication: IEEE Transactions on Signal Processing
publication_identifier:
  eissn:
  - 1941-0476
  issn:
  - 1053-587X
publication_status: published
publisher: Institute of Electrical and Electronics Engineers
quality_controlled: '1'
scopus_import: '1'
status: public
title: Fast and accurate amplitude demodulation of wideband signals
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 69
year: '2021'
...
---
_id: '8084'
abstract:
- lang: eng
  text: Origin and functions of intermittent transitions among sleep stages, including
    brief awakenings and arousals, constitute a challenge to the current homeostatic
    framework for sleep regulation, focusing on factors modulating sleep over large
    time scales. Here we propose that the complex micro-architecture characterizing
    sleep on scales of seconds and minutes results from intrinsic non-equilibrium
    critical dynamics. We investigate θ- and δ-wave dynamics in control rats and in
    rats where the sleep-promoting ventrolateral preoptic nucleus (VLPO) is lesioned
    (male Sprague-Dawley rats). We demonstrate that bursts in θ and δ cortical rhythms
    exhibit complex temporal organization, with long-range correlations and robust
    duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts,
    quiescent phase) duration distributions, features typical of non-equilibrium systems
    self-organizing at criticality. We show that such non-equilibrium behavior relates
    to anti-correlated coupling between θ- and δ-bursts, persists across a range of
    time scales, and is independent of the dominant physiologic state; indications
    of a basic principle in sleep regulation. Further, we find that VLPO lesions lead
    to a modulation of cortical dynamics resulting in altered dynamical parameters
    of θ- and δ-bursts and significant reduction in θ–δ coupling. Our empirical findings
    and model simulations demonstrate that θ–δ coupling is essential for the emerging
    non-equilibrium critical dynamics observed across the sleep–wake cycle, and indicate
    that VLPO neurons may have dual role for both sleep and arousal/brief wake activation.
    The uncovered critical behavior in sleep- and wake-related cortical rhythms indicates
    a mechanism essential for the micro-architecture of spontaneous sleep-stage and
    arousal transitions within a novel, non-homeostatic paradigm of sleep regulation.
article_processing_charge: No
article_type: original
author:
- first_name: Fabrizio
  full_name: Lombardi, Fabrizio
  id: A057D288-3E88-11E9-986D-0CF4E5697425
  last_name: Lombardi
  orcid: 0000-0003-2623-5249
- first_name: Manuel
  full_name: Gómez-Extremera, Manuel
  last_name: Gómez-Extremera
- first_name: Pedro
  full_name: Bernaola-Galván, Pedro
  last_name: Bernaola-Galván
- first_name: Ramalingam
  full_name: Vetrivelan, Ramalingam
  last_name: Vetrivelan
- first_name: Clifford B.
  full_name: Saper, Clifford B.
  last_name: Saper
- first_name: Thomas E.
  full_name: Scammell, Thomas E.
  last_name: Scammell
- first_name: Plamen Ch.
  full_name: Ivanov, Plamen Ch.
  last_name: Ivanov
citation:
  ama: Lombardi F, Gómez-Extremera M, Bernaola-Galván P, et al. Critical dynamics
    and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism
    for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake.
    <i>Journal of Neuroscience</i>. 2020;40(1):171-190. doi:<a href="https://doi.org/10.1523/jneurosci.1278-19.2019">10.1523/jneurosci.1278-19.2019</a>
  apa: Lombardi, F., Gómez-Extremera, M., Bernaola-Galván, P., Vetrivelan, R., Saper,
    C. B., Scammell, T. E., &#38; Ivanov, P. C. (2020). Critical dynamics and coupling
    in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage
    transitions and dual role of VLPO neurons in both sleep and wake. <i>Journal of
    Neuroscience</i>. Society for Neuroscience. <a href="https://doi.org/10.1523/jneurosci.1278-19.2019">https://doi.org/10.1523/jneurosci.1278-19.2019</a>
  chicago: Lombardi, Fabrizio, Manuel Gómez-Extremera, Pedro Bernaola-Galván, Ramalingam
    Vetrivelan, Clifford B. Saper, Thomas E. Scammell, and Plamen Ch. Ivanov. “Critical
    Dynamics and Coupling in Bursts of Cortical Rhythms Indicate Non-Homeostatic Mechanism
    for Sleep-Stage Transitions and Dual Role of VLPO Neurons in Both Sleep and Wake.”
    <i>Journal of Neuroscience</i>. Society for Neuroscience, 2020. <a href="https://doi.org/10.1523/jneurosci.1278-19.2019">https://doi.org/10.1523/jneurosci.1278-19.2019</a>.
  ieee: F. Lombardi <i>et al.</i>, “Critical dynamics and coupling in bursts of cortical
    rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual
    role of VLPO neurons in both sleep and wake,” <i>Journal of Neuroscience</i>,
    vol. 40, no. 1. Society for Neuroscience, pp. 171–190, 2020.
  ista: Lombardi F, Gómez-Extremera M, Bernaola-Galván P, Vetrivelan R, Saper CB,
    Scammell TE, Ivanov PC. 2020. Critical dynamics and coupling in bursts of cortical
    rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual
    role of VLPO neurons in both sleep and wake. Journal of Neuroscience. 40(1), 171–190.
  mla: Lombardi, Fabrizio, et al. “Critical Dynamics and Coupling in Bursts of Cortical
    Rhythms Indicate Non-Homeostatic Mechanism for Sleep-Stage Transitions and Dual
    Role of VLPO Neurons in Both Sleep and Wake.” <i>Journal of Neuroscience</i>,
    vol. 40, no. 1, Society for Neuroscience, 2020, pp. 171–90, doi:<a href="https://doi.org/10.1523/jneurosci.1278-19.2019">10.1523/jneurosci.1278-19.2019</a>.
  short: F. Lombardi, M. Gómez-Extremera, P. Bernaola-Galván, R. Vetrivelan, C.B.
    Saper, T.E. Scammell, P.C. Ivanov, Journal of Neuroscience 40 (2020) 171–190.
date_created: 2020-07-05T15:24:51Z
date_published: 2020-01-02T00:00:00Z
date_updated: 2023-09-05T14:02:55Z
day: '02'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1523/jneurosci.1278-19.2019
ec_funded: 1
external_id:
  isi:
  - '000505167600016'
  pmid:
  - '31694962'
file:
- access_level: open_access
  content_type: application/pdf
  creator: dernst
  date_created: 2020-07-22T11:44:48Z
  date_updated: 2020-07-22T11:44:48Z
  file_id: '8150'
  file_name: 2020_JournNeuroscience_Lombardi.pdf
  file_size: 6646046
  relation: main_file
  success: 1
file_date_updated: 2020-07-22T11:44:48Z
has_accepted_license: '1'
intvolume: '        40'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 171-190
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
publication: Journal of Neuroscience
publication_identifier:
  eissn:
  - 1529-2401
  issn:
  - 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic
  mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep
  and wake
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 40
year: '2020'
...
---
_id: '8097'
abstract:
- lang: eng
  text: 'Antibiotics that interfere with translation, when combined, interact in diverse
    and difficult-to-predict ways. Here, we explain these interactions by "translation
    bottlenecks": points in the translation cycle where antibiotics block ribosomal
    progression. To elucidate the underlying mechanisms of drug interactions between
    translation inhibitors, we generate translation bottlenecks genetically using
    inducible control of translation factors that regulate well-defined translation
    cycle steps. These perturbations accurately mimic antibiotic action and drug interactions,
    supporting that the interplay of different translation bottlenecks causes these
    interactions. We further show that growth laws, combined with drug uptake and
    binding kinetics, enable the direct prediction of a large fraction of observed
    interactions, yet fail to predict suppression. However, varying two translation
    bottlenecks simultaneously supports that dense traffic of ribosomes and competition
    for translation factors account for the previously unexplained suppression. These
    results highlight the importance of "continuous epistasis" in bacterial physiology.'
acknowledged_ssus:
- _id: LifeSc
article_processing_charge: No
author:
- first_name: Bor
  full_name: Kavcic, Bor
  id: 350F91D2-F248-11E8-B48F-1D18A9856A87
  last_name: Kavcic
  orcid: 0000-0001-6041-254X
citation:
  ama: Kavcic B. Analysis scripts and research data for the paper “Mechanisms of drug
    interactions between translation-inhibiting antibiotics.” 2020. doi:<a href="https://doi.org/10.15479/AT:ISTA:8097">10.15479/AT:ISTA:8097</a>
  apa: Kavcic, B. (2020). Analysis scripts and research data for the paper “Mechanisms
    of drug interactions between translation-inhibiting antibiotics.” Institute of
    Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:8097">https://doi.org/10.15479/AT:ISTA:8097</a>
  chicago: Kavcic, Bor. “Analysis Scripts and Research Data for the Paper ‘Mechanisms
    of Drug Interactions between Translation-Inhibiting Antibiotics.’” Institute of
    Science and Technology Austria, 2020. <a href="https://doi.org/10.15479/AT:ISTA:8097">https://doi.org/10.15479/AT:ISTA:8097</a>.
  ieee: B. Kavcic, “Analysis scripts and research data for the paper ‘Mechanisms of
    drug interactions between translation-inhibiting antibiotics.’” Institute of Science
    and Technology Austria, 2020.
  ista: Kavcic B. 2020. Analysis scripts and research data for the paper ‘Mechanisms
    of drug interactions between translation-inhibiting antibiotics’, Institute of
    Science and Technology Austria, <a href="https://doi.org/10.15479/AT:ISTA:8097">10.15479/AT:ISTA:8097</a>.
  mla: Kavcic, Bor. <i>Analysis Scripts and Research Data for the Paper “Mechanisms
    of Drug Interactions between Translation-Inhibiting Antibiotics.”</i> Institute
    of Science and Technology Austria, 2020, doi:<a href="https://doi.org/10.15479/AT:ISTA:8097">10.15479/AT:ISTA:8097</a>.
  short: B. Kavcic, (2020).
contributor:
- contributor_type: research_group
  first_name: Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
- contributor_type: research_group
  first_name: Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
date_created: 2020-07-06T20:40:19Z
date_published: 2020-07-15T00:00:00Z
date_updated: 2024-02-21T12:40:51Z
day: '15'
department:
- _id: GaTk
doi: 10.15479/AT:ISTA:8097
file:
- access_level: open_access
  checksum: 5c321dbbb6d4b3c85da786fd3ebbdc98
  content_type: application/zip
  creator: bkavcic
  date_created: 2020-07-06T20:38:27Z
  date_updated: 2020-07-14T12:48:09Z
  file_id: '8098'
  file_name: natComm_2020_scripts.zip
  file_size: 255770756
  relation: main_file
file_date_updated: 2020-07-14T12:48:09Z
has_accepted_license: '1'
keyword:
- Escherichia coli
- antibiotic combinations
- translation
- growth laws
- drug interactions
- bacterial physiology
- translation inhibitors
month: '07'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
status: public
title: Analysis scripts and research data for the paper "Mechanisms of drug interactions
  between translation-inhibiting antibiotics"
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: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8105'
abstract:
- lang: eng
  text: Physical and biological systems often exhibit intermittent dynamics with bursts
    or avalanches (active states) characterized by power-law size and duration distributions.
    These emergent features are typical of systems at the critical point of continuous
    phase transitions, and have led to the hypothesis that such systems may self-organize
    at criticality, i.e. without any fine tuning of parameters. Since the introduction
    of the Bak-Tang-Wiesenfeld (BTW) model, the paradigm of self-organized criticality
    (SOC) has been very fruitful for the analysis of emergent collective behaviors
    in a number of systems, including the brain. Although considerable effort has
    been devoted in identifying and modeling scaling features of burst and avalanche
    statistics, dynamical aspects related to the temporal organization of bursts remain
    often poorly understood or controversial. Of crucial importance to understand
    the mechanisms responsible for emergent behaviors is the relationship between
    active and quiet periods, and the nature of the correlations. Here we investigate
    the dynamics of active (θ-bursts) and quiet states (δ-bursts) in brain activity
    during the sleep-wake cycle. We show the duality of power-law (θ, active phase)
    and exponential-like (δ, quiescent phase) duration distributions, typical of SOC,
    jointly emerge with power-law temporal correlations and anti-correlated coupling
    between active and quiet states. Importantly, we demonstrate that such temporal
    organization shares important similarities with earthquake dynamics, and propose
    that specific power-law correlations and coupling between active and quiet states
    are distinctive characteristics of a class of systems with self-organization at
    criticality.
article_number: '00005'
article_processing_charge: No
article_type: original
author:
- first_name: Fabrizio
  full_name: Lombardi, Fabrizio
  id: A057D288-3E88-11E9-986D-0CF4E5697425
  last_name: Lombardi
  orcid: 0000-0003-2623-5249
- first_name: Jilin W.J.L.
  full_name: Wang, Jilin W.J.L.
  last_name: Wang
- first_name: Xiyun
  full_name: Zhang, Xiyun
  last_name: Zhang
- first_name: Plamen Ch
  full_name: Ivanov, Plamen Ch
  last_name: Ivanov
citation:
  ama: Lombardi F, Wang JWJL, Zhang X, Ivanov PC. Power-law correlations and coupling
    of active and quiet states underlie a class of complex systems with self-organization
    at criticality. <i>EPJ Web of Conferences</i>. 2020;230. doi:<a href="https://doi.org/10.1051/epjconf/202023000005">10.1051/epjconf/202023000005</a>
  apa: Lombardi, F., Wang, J. W. J. L., Zhang, X., &#38; Ivanov, P. C. (2020). Power-law
    correlations and coupling of active and quiet states underlie a class of complex
    systems with self-organization at criticality. <i>EPJ Web of Conferences</i>.
    EDP Sciences. <a href="https://doi.org/10.1051/epjconf/202023000005">https://doi.org/10.1051/epjconf/202023000005</a>
  chicago: Lombardi, Fabrizio, Jilin W.J.L. Wang, Xiyun Zhang, and Plamen Ch Ivanov.
    “Power-Law Correlations and Coupling of Active and Quiet States Underlie a Class
    of Complex Systems with Self-Organization at Criticality.” <i>EPJ Web of Conferences</i>.
    EDP Sciences, 2020. <a href="https://doi.org/10.1051/epjconf/202023000005">https://doi.org/10.1051/epjconf/202023000005</a>.
  ieee: F. Lombardi, J. W. J. L. Wang, X. Zhang, and P. C. Ivanov, “Power-law correlations
    and coupling of active and quiet states underlie a class of complex systems with
    self-organization at criticality,” <i>EPJ Web of Conferences</i>, vol. 230. EDP
    Sciences, 2020.
  ista: Lombardi F, Wang JWJL, Zhang X, Ivanov PC. 2020. Power-law correlations and
    coupling of active and quiet states underlie a class of complex systems with self-organization
    at criticality. EPJ Web of Conferences. 230, 00005.
  mla: Lombardi, Fabrizio, et al. “Power-Law Correlations and Coupling of Active and
    Quiet States Underlie a Class of Complex Systems with Self-Organization at Criticality.”
    <i>EPJ Web of Conferences</i>, vol. 230, 00005, EDP Sciences, 2020, doi:<a href="https://doi.org/10.1051/epjconf/202023000005">10.1051/epjconf/202023000005</a>.
  short: F. Lombardi, J.W.J.L. Wang, X. Zhang, P.C. Ivanov, EPJ Web of Conferences
    230 (2020).
date_created: 2020-07-12T16:20:33Z
date_published: 2020-03-11T00:00:00Z
date_updated: 2021-01-12T08:16:55Z
day: '11'
ddc:
- '530'
department:
- _id: GaTk
doi: 10.1051/epjconf/202023000005
file:
- access_level: open_access
  content_type: application/pdf
  creator: dernst
  date_created: 2020-07-22T06:17:11Z
  date_updated: 2020-07-22T06:17:11Z
  file_id: '8144'
  file_name: 2020_EPJWebConf_Lombardi.pdf
  file_size: 2197543
  relation: main_file
  success: 1
file_date_updated: 2020-07-22T06:17:11Z
has_accepted_license: '1'
intvolume: '       230'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
publication: EPJ Web of Conferences
publication_identifier:
  issn:
  - 2100-014X
publication_status: published
publisher: EDP Sciences
quality_controlled: '1'
status: public
title: Power-law correlations and coupling of active and quiet states underlie a class
  of complex systems with self-organization at criticality
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: 230
year: '2020'
...
---
_id: '8155'
abstract:
- lang: eng
  text: "In the thesis we focus on the interplay of the biophysics and evolution of
    gene regulation. We start by addressing how the type of prokaryotic gene regulation
    – activation and repression – affects spurious binding to DNA, also known as\r\ntranscriptional
    crosstalk. We propose that regulatory interference caused by excess regulatory
    proteins in the dense cellular medium – global crosstalk – could be a factor in
    determining which type of gene regulatory network is evolutionarily preferred.
    Next,we use a normative approach in eukaryotic gene regulation to describe minimal\r\nnon-equilibrium
    enhancer models that optimize so-called regulatory phenotypes. We find a class
    of models that differ from standard thermodynamic equilibrium models by a single
    parameter that notably increases the regulatory performance. Next chapter addresses
    the question of genotype-phenotype-fitness maps of higher dimensional phenotypes.
    We show that our biophysically realistic approach allows us to understand how
    the mechanisms of promoter function constrain genotypephenotype maps, and how
    they affect the evolutionary trajectories of promoters.\r\nIn the last chapter
    we ask whether the intrinsic instability of gene duplication and amplification
    provides a generic alternative to canonical gene regulation. Using mathematical
    modeling, we show that amplifications can tune gene expression in many environments,
    including those where transcription factor-based schemes are\r\nhard to evolve
    or maintain. "
acknowledgement: For the duration of his PhD, Rok was a recipient of a DOC fellowship
  of the Austrian Academy of Sciences.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Rok
  full_name: Grah, Rok
  id: 483E70DE-F248-11E8-B48F-1D18A9856A87
  last_name: Grah
  orcid: 0000-0003-2539-3560
citation:
  ama: Grah R. Gene regulation across scales – how biophysical constraints shape evolution.
    2020. doi:<a href="https://doi.org/10.15479/AT:ISTA:8155">10.15479/AT:ISTA:8155</a>
  apa: Grah, R. (2020). <i>Gene regulation across scales – how biophysical constraints
    shape evolution</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:8155">https://doi.org/10.15479/AT:ISTA:8155</a>
  chicago: Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints
    Shape Evolution.” Institute of Science and Technology Austria, 2020. <a href="https://doi.org/10.15479/AT:ISTA:8155">https://doi.org/10.15479/AT:ISTA:8155</a>.
  ieee: R. Grah, “Gene regulation across scales – how biophysical constraints shape
    evolution,” Institute of Science and Technology Austria, 2020.
  ista: Grah R. 2020. Gene regulation across scales – how biophysical constraints
    shape evolution. Institute of Science and Technology Austria.
  mla: Grah, Rok. <i>Gene Regulation across Scales – How Biophysical Constraints Shape
    Evolution</i>. Institute of Science and Technology Austria, 2020, doi:<a href="https://doi.org/10.15479/AT:ISTA:8155">10.15479/AT:ISTA:8155</a>.
  short: R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape
    Evolution, Institute of Science and Technology Austria, 2020.
date_created: 2020-07-23T09:51:28Z
date_published: 2020-07-24T00:00:00Z
date_updated: 2023-09-07T13:13:27Z
day: '24'
ddc:
- '530'
- '570'
degree_awarded: PhD
department:
- _id: CaGu
- _id: GaTk
doi: 10.15479/AT:ISTA:8155
file:
- access_level: open_access
  content_type: application/pdf
  creator: rgrah
  date_created: 2020-07-27T12:00:07Z
  date_updated: 2020-07-27T12:00:07Z
  file_id: '8176'
  file_name: Thesis_RokGrah_200727_convertedNew.pdf
  file_size: 16638998
  relation: main_file
  success: 1
- access_level: closed
  content_type: application/zip
  creator: rgrah
  date_created: 2020-07-27T12:02:23Z
  date_updated: 2020-07-30T13:04:55Z
  file_id: '8177'
  file_name: Thesis_new.zip
  file_size: 347459978
  relation: main_file
file_date_updated: 2020-07-30T13:04:55Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: '310'
project:
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
  name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '7675'
    relation: part_of_dissertation
    status: public
  - id: '7569'
    relation: part_of_dissertation
    status: public
  - id: '7652'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Calin C
  full_name: Guet, Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
title: Gene regulation across scales – how biophysical constraints shape evolution
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '8250'
abstract:
- lang: eng
  text: 'Antibiotics that interfere with translation, when combined, interact in diverse
    and difficult-to-predict ways. Here, we explain these interactions by “translation
    bottlenecks”: points in the translation cycle where antibiotics block ribosomal
    progression. To elucidate the underlying mechanisms of drug interactions between
    translation inhibitors, we generate translation bottlenecks genetically using
    inducible control of translation factors that regulate well-defined translation
    cycle steps. These perturbations accurately mimic antibiotic action and drug interactions,
    supporting that the interplay of different translation bottlenecks causes these
    interactions. We further show that growth laws, combined with drug uptake and
    binding kinetics, enable the direct prediction of a large fraction of observed
    interactions, yet fail to predict suppression. However, varying two translation
    bottlenecks simultaneously supports that dense traffic of ribosomes and competition
    for translation factors account for the previously unexplained suppression. These
    results highlight the importance of “continuous epistasis” in bacterial physiology.'
acknowledgement: "We thank M. Hennessey-Wesen, I. Tomanek, K. Jain, A. Staron, K.
  Tomasek, M. Scott,\r\nK.C. Huang, and Z. Gitai for reading the manuscript and constructive
  comments. B.K. is\r\nindebted to C. Guet for additional guidance and generous support,
  which rendered this\r\nwork possible. B.K. thanks all members of Guet group for
  many helpful discussions and\r\nsharing of resources. B.K. additionally acknowledges
  the tremendous support from A.\r\nAngermayr and K. Mitosch with experimental work.
  We further thank E. Brown for\r\nhelpful comments regarding lamotrigine, and A.
  Buskirk for valuable suggestions\r\nregarding the ribosome footprint size. This
  work was supported in part by Austrian\r\nScience Fund (FWF) standalone grants P
  27201-B22 (to T.B.) and P 28844 (to G.T.),\r\nHFSP program Grant RGP0042/2013 (to
  T.B.), German Research Foundation (DFG)\r\nstandalone grant BO 3502/2-1 (to T.B.),
  and German Research Foundation (DFG)\r\nCollaborative Research Centre (SFB) 1310
  (to T.B.). Open access funding provided by\r\nProjekt DEAL."
article_number: '4013'
article_processing_charge: No
article_type: original
author:
- first_name: Bor
  full_name: Kavcic, Bor
  id: 350F91D2-F248-11E8-B48F-1D18A9856A87
  last_name: Kavcic
  orcid: 0000-0001-6041-254X
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
- first_name: Tobias
  full_name: Bollenbach, Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
citation:
  ama: Kavcic B, Tkačik G, Bollenbach MT. Mechanisms of drug interactions between
    translation-inhibiting antibiotics. <i>Nature Communications</i>. 2020;11. doi:<a
    href="https://doi.org/10.1038/s41467-020-17734-z">10.1038/s41467-020-17734-z</a>
  apa: Kavcic, B., Tkačik, G., &#38; Bollenbach, M. T. (2020). Mechanisms of drug
    interactions between translation-inhibiting antibiotics. <i>Nature Communications</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41467-020-17734-z">https://doi.org/10.1038/s41467-020-17734-z</a>
  chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of
    Drug Interactions between Translation-Inhibiting Antibiotics.” <i>Nature Communications</i>.
    Springer Nature, 2020. <a href="https://doi.org/10.1038/s41467-020-17734-z">https://doi.org/10.1038/s41467-020-17734-z</a>.
  ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions
    between translation-inhibiting antibiotics,” <i>Nature Communications</i>, vol.
    11. Springer Nature, 2020.
  ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between
    translation-inhibiting antibiotics. Nature Communications. 11, 4013.
  mla: Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting
    Antibiotics.” <i>Nature Communications</i>, vol. 11, 4013, Springer Nature, 2020,
    doi:<a href="https://doi.org/10.1038/s41467-020-17734-z">10.1038/s41467-020-17734-z</a>.
  short: B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020).
date_created: 2020-08-12T09:13:50Z
date_published: 2020-08-11T00:00:00Z
date_updated: 2024-03-25T23:30:05Z
day: '11'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1038/s41467-020-17734-z
external_id:
  isi:
  - '000562769300008'
file:
- access_level: open_access
  checksum: 986bebb308850a55850028d3d2b5b664
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  creator: dernst
  date_created: 2020-08-17T07:36:57Z
  date_updated: 2020-08-17T07:36:57Z
  file_id: '8275'
  file_name: 2020_NatureComm_Kavcic.pdf
  file_size: 1965672
  relation: main_file
  success: 1
file_date_updated: 2020-08-17T07:36:57Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P27201-B22
  name: Revealing the mechanisms underlying drug interactions
- _id: 254E9036-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P28844-B27
  name: Biophysics of information processing in gene regulation
publication: Nature Communications
publication_identifier:
  issn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  record:
  - id: '8657'
    relation: dissertation_contains
    status: public
status: public
title: Mechanisms of drug interactions between translation-inhibiting antibiotics
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2020'
...
---
_id: '8657'
abstract:
- lang: eng
  text: "Synthesis of proteins – translation – is a fundamental process of life. Quantitative
    studies anchor translation into the context of bacterial physiology and reveal
    several mathematical relationships, called “growth laws,” which capture physiological
    feedbacks between protein synthesis and cell growth. Growth laws describe the
    dependency of the ribosome abundance as a function of growth rate, which can change
    depending on the growth conditions. Perturbations of translation reveal that bacteria
    employ a compensatory strategy in which the reduced translation capability results
    in increased expression of the translation machinery.\r\nPerturbations of translation
    are achieved in various ways; clinically interesting is the application of translation-targeting
    antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology
    are often poorly understood. Bacterial responses to two or more simultaneously
    applied antibiotics are even more puzzling. The combined antibiotic effect determines
    the type of drug interaction, which ranges from synergy (the effect is stronger
    than expected) to antagonism (the effect is weaker) and suppression (one of the
    drugs loses its potency).\r\nIn the first part of this work, we systematically
    measure the pairwise interaction network for translation inhibitors that interfere
    with different steps in translation. We find that the interactions are surprisingly
    diverse and tend to be more antagonistic. To explore the underlying mechanisms,
    we begin with a minimal biophysical model of combined antibiotic action. We base
    this model on the kinetics of antibiotic uptake and binding together with the
    physiological response described by the growth laws. The biophysical model explains
    some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn
    the second part of this work, we hypothesize that elusive suppressive drug interactions
    result from the interplay between ribosomes halted in different stages of translation.
    To elucidate this putative mechanism of drug interactions between translation
    inhibitors, we generate translation bottlenecks genetically using in- ducible
    control of translation factors that regulate well-defined translation cycle steps.
    These perturbations accurately mimic antibiotic action and drug interactions,
    supporting that the interplay of different translation bottlenecks partially causes
    these interactions.\r\nWe extend this approach by varying two translation bottlenecks
    simultaneously. This approach reveals the suppression of translocation inhibition
    by inhibited translation. We rationalize this effect by modeling dense traffic
    of ribosomes that move on transcripts in a translation factor-mediated manner.
    This model predicts a dissolution of traffic jams caused by inhibited translocation
    when the density of ribosome traffic is reduced by lowered initiation. We base
    this model on the growth laws and quantitative relationships between different
    translation and growth parameters.\r\nIn the final part of this work, we describe
    a set of tools aimed at quantification of physiological and translation parameters.
    We further develop a simple model that directly connects the abundance of a translation
    factor with the growth rate, which allows us to extract physiological parameters
    describing initiation. We demonstrate the development of tools for measuring translation
    rate.\r\nThis thesis showcases how a combination of high-throughput growth rate
    mea- surements, genetics, and modeling can reveal mechanisms of drug interactions.
    Furthermore, by a gradual transition from combinations of antibiotics to precise
    genetic interventions, we demonstrated the equivalency between genetic and chemi-
    cal perturbations of translation. These findings tile the path for quantitative
    studies of antibiotic combinations and illustrate future approaches towards the
    quantitative description of translation."
acknowledged_ssus:
- _id: LifeSc
- _id: M-Shop
acknowledgement: I thank Life Science Facilities for their continuous support with
  providing top-notch laboratory materials, keeping the devices humming, and coordinating
  the repairs and building of custom-designed laboratory equipment with the MIBA Machine
  shop.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Bor
  full_name: Kavcic, Bor
  id: 350F91D2-F248-11E8-B48F-1D18A9856A87
  last_name: Kavcic
  orcid: 0000-0001-6041-254X
citation:
  ama: 'Kavcic B. Perturbations of protein synthesis: from antibiotics to genetics
    and physiology. 2020. doi:<a href="https://doi.org/10.15479/AT:ISTA:8657">10.15479/AT:ISTA:8657</a>'
  apa: 'Kavcic, B. (2020). <i>Perturbations of protein synthesis: from antibiotics
    to genetics and physiology</i>. Institute of Science and Technology Austria. <a
    href="https://doi.org/10.15479/AT:ISTA:8657">https://doi.org/10.15479/AT:ISTA:8657</a>'
  chicago: 'Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to
    Genetics and Physiology.” Institute of Science and Technology Austria, 2020. <a
    href="https://doi.org/10.15479/AT:ISTA:8657">https://doi.org/10.15479/AT:ISTA:8657</a>.'
  ieee: 'B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics
    and physiology,” Institute of Science and Technology Austria, 2020.'
  ista: 'Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics
    and physiology. Institute of Science and Technology Austria.'
  mla: 'Kavcic, Bor. <i>Perturbations of Protein Synthesis: From Antibiotics to Genetics
    and Physiology</i>. Institute of Science and Technology Austria, 2020, doi:<a
    href="https://doi.org/10.15479/AT:ISTA:8657">10.15479/AT:ISTA:8657</a>.'
  short: 'B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics
    and Physiology, Institute of Science and Technology Austria, 2020.'
date_created: 2020-10-13T16:46:14Z
date_published: 2020-10-14T00:00:00Z
date_updated: 2023-09-07T13:20:48Z
day: '14'
ddc:
- '571'
- '530'
- '570'
degree_awarded: PhD
department:
- _id: GaTk
doi: 10.15479/AT:ISTA:8657
file:
- access_level: open_access
  checksum: d708ecd62b6fcc3bc1feb483b8dbe9eb
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  creator: bkavcic
  date_created: 2020-10-15T06:41:20Z
  date_updated: 2021-10-07T22:30:03Z
  embargo: 2021-10-06
  file_id: '8663'
  file_name: kavcicB_thesis202009.pdf
  file_size: 52636162
  relation: main_file
- access_level: closed
  checksum: bb35f2352a04db19164da609f00501f3
  content_type: application/zip
  creator: bkavcic
  date_created: 2020-10-15T06:41:53Z
  date_updated: 2021-10-07T22:30:03Z
  embargo_to: open_access
  file_id: '8664'
  file_name: 2020b.zip
  file_size: 321681247
  relation: source_file
file_date_updated: 2021-10-07T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '271'
publication_identifier:
  isbn:
  - 978-3-99078-011-4
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '7673'
    relation: part_of_dissertation
    status: public
  - id: '8250'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
- first_name: Mark Tobias
  full_name: Bollenbach, Mark Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
title: 'Perturbations of protein synthesis: from antibiotics to genetics and physiology'
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '8698'
abstract:
- lang: eng
  text: The brain represents and reasons probabilistically about complex stimuli and
    motor actions using a noisy, spike-based neural code. A key building block for
    such neural computations, as well as the basis for supervised and unsupervised
    learning, is the ability to estimate the surprise or likelihood of incoming high-dimensional
    neural activity patterns. Despite progress in statistical modeling of neural responses
    and deep learning, current approaches either do not scale to large neural populations
    or cannot be implemented using biologically realistic mechanisms. Inspired by
    the sparse and random connectivity of real neuronal circuits, we present a model
    for neural codes that accurately estimates the likelihood of individual spiking
    patterns and has a straightforward, scalable, efficient, learnable, and realistic
    neural implementation. This model’s performance on simultaneously recorded spiking
    activity of >100 neurons in the monkey visual and prefrontal cortices is comparable
    with or better than that of state-of-the-art models. Importantly, the model can
    be learned using a small number of samples and using a local learning rule that
    utilizes noise intrinsic to neural circuits. Slower, structural changes in random
    connectivity, consistent with rewiring and pruning processes, further improve
    the efficiency and sparseness of the resulting neural representations. Our results
    merge insights from neuroanatomy, machine learning, and theoretical neuroscience
    to suggest random sparse connectivity as a key design principle for neuronal computation.
acknowledgement: We thank Udi Karpas, Roy Harpaz, Tal Tamir, Adam Haber, and Amir
  Bar for discussions and suggestions; and especially Oren Forkosh and Walter Senn
  for invaluable discussions of the learning rule. This work was supported by European
  Research Council Grant 311238 (to E.S.) and Israel Science Foundation Grant 1629/12
  (to E.S.); as well as research support from Martin Kushner Schnur and Mr. and Mrs.
  Lawrence Feis (E.S.); National Institute of Mental Health Grant R01MH109180 (to
  R.K.); a Pew Scholarship in Biomedical Sciences (to R.K.); Simons Collaboration
  on the Global Brain Grant 542997 (to R.K. and E.S.); and a CRCNS (Collaborative
  Research in Computational Neuroscience) grant (to R.K. and E.S.).
article_processing_charge: No
article_type: original
author:
- first_name: Ori
  full_name: Maoz, Ori
  last_name: Maoz
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
- first_name: Mohamad Saleh
  full_name: Esteki, Mohamad Saleh
  last_name: Esteki
- first_name: Roozbeh
  full_name: Kiani, Roozbeh
  last_name: Kiani
- first_name: Elad
  full_name: Schneidman, Elad
  last_name: Schneidman
citation:
  ama: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. Learning probabilistic
    neural representations with randomly connected circuits. <i>Proceedings of the
    National Academy of Sciences of the United States of America</i>. 2020;117(40):25066-25073.
    doi:<a href="https://doi.org/10.1073/pnas.1912804117">10.1073/pnas.1912804117</a>
  apa: Maoz, O., Tkačik, G., Esteki, M. S., Kiani, R., &#38; Schneidman, E. (2020).
    Learning probabilistic neural representations with randomly connected circuits.
    <i>Proceedings of the National Academy of Sciences of the United States of America</i>.
    National Academy of Sciences. <a href="https://doi.org/10.1073/pnas.1912804117">https://doi.org/10.1073/pnas.1912804117</a>
  chicago: Maoz, Ori, Gašper Tkačik, Mohamad Saleh Esteki, Roozbeh Kiani, and Elad
    Schneidman. “Learning Probabilistic Neural Representations with Randomly Connected
    Circuits.” <i>Proceedings of the National Academy of Sciences of the United States
    of America</i>. National Academy of Sciences, 2020. <a href="https://doi.org/10.1073/pnas.1912804117">https://doi.org/10.1073/pnas.1912804117</a>.
  ieee: O. Maoz, G. Tkačik, M. S. Esteki, R. Kiani, and E. Schneidman, “Learning probabilistic
    neural representations with randomly connected circuits,” <i>Proceedings of the
    National Academy of Sciences of the United States of America</i>, vol. 117, no.
    40. National Academy of Sciences, pp. 25066–25073, 2020.
  ista: Maoz O, Tkačik G, Esteki MS, Kiani R, Schneidman E. 2020. Learning probabilistic
    neural representations with randomly connected circuits. Proceedings of the National
    Academy of Sciences of the United States of America. 117(40), 25066–25073.
  mla: Maoz, Ori, et al. “Learning Probabilistic Neural Representations with Randomly
    Connected Circuits.” <i>Proceedings of the National Academy of Sciences of the
    United States of America</i>, vol. 117, no. 40, National Academy of Sciences,
    2020, pp. 25066–73, doi:<a href="https://doi.org/10.1073/pnas.1912804117">10.1073/pnas.1912804117</a>.
  short: O. Maoz, G. Tkačik, M.S. Esteki, R. Kiani, E. Schneidman, Proceedings of
    the National Academy of Sciences of the United States of America 117 (2020) 25066–25073.
date_created: 2020-10-25T23:01:16Z
date_published: 2020-10-06T00:00:00Z
date_updated: 2023-08-22T12:11:23Z
day: '06'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1073/pnas.1912804117
external_id:
  isi:
  - '000579045200012'
  pmid:
  - '32948691'
file:
- access_level: open_access
  checksum: c6a24fdecf3f28faf447078e7a274a88
  content_type: application/pdf
  creator: cziletti
  date_created: 2020-10-27T14:57:50Z
  date_updated: 2020-10-27T14:57:50Z
  file_id: '8713'
  file_name: 2020_PNAS_Maoz.pdf
  file_size: 1755359
  relation: main_file
  success: 1
file_date_updated: 2020-10-27T14:57:50Z
has_accepted_license: '1'
intvolume: '       117'
isi: 1
issue: '40'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: 25066-25073
pmid: 1
publication: Proceedings of the National Academy of Sciences of the United States
  of America
publication_identifier:
  eissn:
  - '10916490'
  issn:
  - '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
scopus_import: '1'
status: public
title: Learning probabilistic neural representations with randomly connected circuits
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 117
year: '2020'
...
---
_id: '8930'
abstract:
- lang: eng
  text: Phenomenological relations such as Ohm’s or Fourier’s law have a venerable
    history in physics but are still scarce in biology. This situation restrains predictive
    theory. Here, we build on bacterial “growth laws,” which capture physiological
    feedback between translation and cell growth, to construct a minimal biophysical
    model for the combined action of ribosome-targeting antibiotics. Our model predicts
    drug interactions like antagonism or synergy solely from responses to individual
    drugs. We provide analytical results for limiting cases, which agree well with
    numerical results. We systematically refine the model by including direct physical
    interactions of different antibiotics on the ribosome. In a limiting case, our
    model provides a mechanistic underpinning for recent predictions of higher-order
    interactions that were derived using entropy maximization. We further refine the
    model to include the effects of antibiotics that mimic starvation and the presence
    of resistance genes. We describe the impact of a starvation-mimicking antibiotic
    on drug interactions analytically and verify it experimentally. Our extended model
    suggests a change in the type of drug interaction that depends on the strength
    of resistance, which challenges established rescaling paradigms. We experimentally
    show that the presence of unregulated resistance genes can lead to altered drug
    interaction, which agrees with the prediction of the model. While minimal, the
    model is readily adaptable and opens the door to predicting interactions of second
    and higher-order in a broad range of biological systems.
article_processing_charge: No
author:
- first_name: Bor
  full_name: Kavcic, Bor
  id: 350F91D2-F248-11E8-B48F-1D18A9856A87
  last_name: Kavcic
  orcid: 0000-0001-6041-254X
citation:
  ama: Kavcic B. Analysis scripts and research data for the paper “Minimal biophysical
    model of combined antibiotic action.” 2020. doi:<a href="https://doi.org/10.15479/AT:ISTA:8930">10.15479/AT:ISTA:8930</a>
  apa: Kavcic, B. (2020). Analysis scripts and research data for the paper “Minimal
    biophysical model of combined antibiotic action.” Institute of Science and Technology
    Austria. <a href="https://doi.org/10.15479/AT:ISTA:8930">https://doi.org/10.15479/AT:ISTA:8930</a>
  chicago: Kavcic, Bor. “Analysis Scripts and Research Data for the Paper ‘Minimal
    Biophysical Model of Combined Antibiotic Action.’” Institute of Science and Technology
    Austria, 2020. <a href="https://doi.org/10.15479/AT:ISTA:8930">https://doi.org/10.15479/AT:ISTA:8930</a>.
  ieee: B. Kavcic, “Analysis scripts and research data for the paper ‘Minimal biophysical
    model of combined antibiotic action.’” Institute of Science and Technology Austria,
    2020.
  ista: Kavcic B. 2020. Analysis scripts and research data for the paper ‘Minimal
    biophysical model of combined antibiotic action’, Institute of Science and Technology
    Austria, <a href="https://doi.org/10.15479/AT:ISTA:8930">10.15479/AT:ISTA:8930</a>.
  mla: Kavcic, Bor. <i>Analysis Scripts and Research Data for the Paper “Minimal Biophysical
    Model of Combined Antibiotic Action.”</i> Institute of Science and Technology
    Austria, 2020, doi:<a href="https://doi.org/10.15479/AT:ISTA:8930">10.15479/AT:ISTA:8930</a>.
  short: B. Kavcic, (2020).
contributor:
- contributor_type: supervisor
  first_name: Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
- contributor_type: supervisor
  first_name: Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
date_created: 2020-12-09T15:04:02Z
date_published: 2020-12-10T00:00:00Z
date_updated: 2024-02-21T12:41:42Z
day: '10'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.15479/AT:ISTA:8930
file:
- access_level: open_access
  checksum: 60a818edeffaa7da1ebf5f8fbea9ba18
  content_type: application/zip
  creator: bkavcic
  date_created: 2020-12-09T15:00:19Z
  date_updated: 2020-12-09T15:00:19Z
  file_id: '8932'
  file_name: PLoSCompBiol2020_datarep.zip
  file_size: 315494370
  relation: main_file
  success: 1
file_date_updated: 2020-12-09T15:00:19Z
has_accepted_license: '1'
keyword:
- Escherichia coli
- antibiotic combinations
- translation
- growth laws
- drug interactions
- bacterial physiology
- translation inhibitors
month: '12'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '8997'
    relation: used_in_publication
    status: public
status: public
title: Analysis scripts and research data for the paper "Minimal biophysical model
  of combined antibiotic action"
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: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8955'
abstract:
- lang: eng
  text: Skeletal muscle activity is continuously modulated across physiologic states
    to provide coordination, flexibility and responsiveness to body tasks and external
    inputs. Despite the central role the muscular system plays in facilitating vital
    body functions, the network of brain-muscle interactions required to control hundreds
    of muscles and synchronize their activation in relation to distinct physiologic
    states has not been investigated. Recent approaches have focused on general associations
    between individual brain rhythms and muscle activation during movement tasks.
    However, the specific forms of coupling, the functional network of cortico-muscular
    coordination, and how network structure and dynamics are modulated by autonomic
    regulation across physiologic states remains unknown. To identify and quantify
    the cortico-muscular interaction network and uncover basic features of neuro-autonomic
    control of muscle function, we investigate the coupling between synchronous bursts
    in cortical rhythms and peripheral muscle activation during sleep and wake. Utilizing
    the concept of time delay stability and a novel network physiology approach, we
    find that the brain-muscle network exhibits complex dynamic patterns of communication
    involving multiple brain rhythms across cortical locations and different electromyographic
    frequency bands. Moreover, our results show that during each physiologic state
    the cortico-muscular network is characterized by a specific profile of network
    links strength, where particular brain rhythms play role of main mediators of
    interaction and control. Further, we discover a hierarchical reorganization in
    network structure across physiologic states, with high connectivity and network
    link strength during wake, intermediate during REM and light sleep, and low during
    deep sleep, a sleep-stage stratification that demonstrates a unique association
    between physiologic states and cortico-muscular network structure. The reported
    empirical observations are consistent across individual subjects, indicating universal
    behavior in network structure and dynamics, and high sensitivity of cortico-muscular
    control to changes in autonomic regulation, even at low levels of physical activity
    and muscle tone during sleep. Our findings demonstrate previously unrecognized
    basic principles of brain-muscle network communication and control, and provide
    new perspectives on the regulatory mechanisms of brain dynamics and locomotor
    activation, with potential clinical implications for neurodegenerative, movement
    and sleep disorders, and for developing efficient treatment strategies.
acknowledgement: We acknowledge support from the W. M. Keck Foundation, National Institutes
  of Health (NIH Grant 1R01-HL098437), the US-Israel Binational Science Foundation
  (BSF Grant 2012219), and the Office of Naval Research (ONR Grant 000141010078).
  FL acknowledges support also from the European Union's Horizon 2020 research and
  innovation program under the Marie Sklodowska-Curie Grant Agreement No. 754411.
article_number: '558070'
article_processing_charge: No
article_type: original
author:
- first_name: Rossella
  full_name: Rizzo, Rossella
  last_name: Rizzo
- first_name: Xiyun
  full_name: Zhang, Xiyun
  last_name: Zhang
- first_name: Jilin W.J.L.
  full_name: Wang, Jilin W.J.L.
  last_name: Wang
- first_name: Fabrizio
  full_name: Lombardi, Fabrizio
  id: A057D288-3E88-11E9-986D-0CF4E5697425
  last_name: Lombardi
  orcid: 0000-0003-2623-5249
- first_name: Plamen Ch
  full_name: Ivanov, Plamen Ch
  last_name: Ivanov
citation:
  ama: Rizzo R, Zhang X, Wang JWJL, Lombardi F, Ivanov PC. Network physiology of cortico–muscular
    interactions. <i>Frontiers in Physiology</i>. 2020;11. doi:<a href="https://doi.org/10.3389/fphys.2020.558070">10.3389/fphys.2020.558070</a>
  apa: Rizzo, R., Zhang, X., Wang, J. W. J. L., Lombardi, F., &#38; Ivanov, P. C.
    (2020). Network physiology of cortico–muscular interactions. <i>Frontiers in Physiology</i>.
    Frontiers. <a href="https://doi.org/10.3389/fphys.2020.558070">https://doi.org/10.3389/fphys.2020.558070</a>
  chicago: Rizzo, Rossella, Xiyun Zhang, Jilin W.J.L. Wang, Fabrizio Lombardi, and
    Plamen Ch Ivanov. “Network Physiology of Cortico–Muscular Interactions.” <i>Frontiers
    in Physiology</i>. Frontiers, 2020. <a href="https://doi.org/10.3389/fphys.2020.558070">https://doi.org/10.3389/fphys.2020.558070</a>.
  ieee: R. Rizzo, X. Zhang, J. W. J. L. Wang, F. Lombardi, and P. C. Ivanov, “Network
    physiology of cortico–muscular interactions,” <i>Frontiers in Physiology</i>,
    vol. 11. Frontiers, 2020.
  ista: Rizzo R, Zhang X, Wang JWJL, Lombardi F, Ivanov PC. 2020. Network physiology
    of cortico–muscular interactions. Frontiers in Physiology. 11, 558070.
  mla: Rizzo, Rossella, et al. “Network Physiology of Cortico–Muscular Interactions.”
    <i>Frontiers in Physiology</i>, vol. 11, 558070, Frontiers, 2020, doi:<a href="https://doi.org/10.3389/fphys.2020.558070">10.3389/fphys.2020.558070</a>.
  short: R. Rizzo, X. Zhang, J.W.J.L. Wang, F. Lombardi, P.C. Ivanov, Frontiers in
    Physiology 11 (2020).
date_created: 2020-12-20T23:01:18Z
date_published: 2020-11-26T00:00:00Z
date_updated: 2023-08-24T11:00:45Z
day: '26'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.3389/fphys.2020.558070
ec_funded: 1
external_id:
  isi:
  - '000596849400001'
  pmid:
  - '33324233'
file:
- access_level: open_access
  checksum: ef9515b28c5619b7126c0f347958bcb3
  content_type: application/pdf
  creator: dernst
  date_created: 2020-12-21T10:37:50Z
  date_updated: 2020-12-21T10:37:50Z
  file_id: '8961'
  file_name: 2020_Frontiers_Rizzo.pdf
  file_size: 13380030
  relation: main_file
  success: 1
file_date_updated: 2020-12-21T10:37:50Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
publication: Frontiers in Physiology
publication_identifier:
  eissn:
  - 1664042X
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: Network physiology of cortico–muscular interactions
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2020'
...
---
_id: '9000'
abstract:
- lang: eng
  text: 'In prokaryotes, thermodynamic models of gene regulation provide a highly
    quantitative mapping from promoter sequences to gene-expression levels that is
    compatible with in vivo and in vitro biophysical measurements. Such concordance
    has not been achieved for models of enhancer function in eukaryotes. In equilibrium
    models, it is difficult to reconcile the reported short transcription factor (TF)
    residence times on the DNA with the high specificity of regulation. In nonequilibrium
    models, progress is difficult due to an explosion in the number of parameters.
    Here, we navigate this complexity by looking for minimal nonequilibrium enhancer
    models that yield desired regulatory phenotypes: low TF residence time, high specificity,
    and tunable cooperativity. We find that a single extra parameter, interpretable
    as the “linking rate,” by which bound TFs interact with Mediator components, enables
    our models to escape equilibrium bounds and access optimal regulatory phenotypes,
    while remaining consistent with the reported phenomenology and simple enough to
    be inferred from upcoming experiments. We further find that high specificity in
    nonequilibrium models is in a trade-off with gene-expression noise, predicting
    bursty dynamics—an experimentally observed hallmark of eukaryotic transcription.
    By drastically reducing the vast parameter space of nonequilibrium enhancer models
    to a much smaller subspace that optimally realizes biological function, we deliver
    a rich class of models that could be tractably inferred from data in the near
    future.'
acknowledgement: G.T. was supported by Human Frontiers Science Program Grant RGP0034/2018.
  R.G. was supported by the Austrian Academy of Sciences DOC Fellowship. R.G. thanks
  S. Avvakumov for helpful discussions.
article_processing_charge: No
article_type: original
author:
- first_name: Rok
  full_name: Grah, Rok
  id: 483E70DE-F248-11E8-B48F-1D18A9856A87
  last_name: Grah
  orcid: 0000-0003-2539-3560
- first_name: Benjamin
  full_name: Zoller, Benjamin
  last_name: Zoller
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
citation:
  ama: Grah R, Zoller B, Tkačik G. Nonequilibrium models of optimal enhancer function.
    <i>PNAS</i>. 2020;117(50):31614-31622. doi:<a href="https://doi.org/10.1073/pnas.2006731117">10.1073/pnas.2006731117</a>
  apa: Grah, R., Zoller, B., &#38; Tkačik, G. (2020). Nonequilibrium models of optimal
    enhancer function. <i>PNAS</i>. National Academy of Sciences. <a href="https://doi.org/10.1073/pnas.2006731117">https://doi.org/10.1073/pnas.2006731117</a>
  chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Nonequilibrium Models of
    Optimal Enhancer Function.” <i>PNAS</i>. National Academy of Sciences, 2020. <a
    href="https://doi.org/10.1073/pnas.2006731117">https://doi.org/10.1073/pnas.2006731117</a>.
  ieee: R. Grah, B. Zoller, and G. Tkačik, “Nonequilibrium models of optimal enhancer
    function,” <i>PNAS</i>, vol. 117, no. 50. National Academy of Sciences, pp. 31614–31622,
    2020.
  ista: Grah R, Zoller B, Tkačik G. 2020. Nonequilibrium models of optimal enhancer
    function. PNAS. 117(50), 31614–31622.
  mla: Grah, Rok, et al. “Nonequilibrium Models of Optimal Enhancer Function.” <i>PNAS</i>,
    vol. 117, no. 50, National Academy of Sciences, 2020, pp. 31614–22, doi:<a href="https://doi.org/10.1073/pnas.2006731117">10.1073/pnas.2006731117</a>.
  short: R. Grah, B. Zoller, G. Tkačik, PNAS 117 (2020) 31614–31622.
date_created: 2021-01-10T23:01:17Z
date_published: 2020-12-15T00:00:00Z
date_updated: 2023-08-24T11:10:22Z
day: '15'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1073/pnas.2006731117
external_id:
  isi:
  - '000600608300015'
  pmid:
  - '33268497'
file:
- access_level: open_access
  checksum: 69039cd402a571983aa6cb4815ffa863
  content_type: application/pdf
  creator: dernst
  date_created: 2021-01-11T08:37:31Z
  date_updated: 2021-01-11T08:37:31Z
  file_id: '9004'
  file_name: 2020_PNAS_Grah.pdf
  file_size: 1199247
  relation: main_file
  success: 1
file_date_updated: 2021-01-11T08:37:31Z
has_accepted_license: '1'
intvolume: '       117'
isi: 1
issue: '50'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 31614-31622
pmid: 1
project:
- _id: 2665AAFE-B435-11E9-9278-68D0E5697425
  grant_number: RGP0034/2018
  name: Can evolution minimize spurious signaling crosstalk to reach optimal performance?
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
  name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication: PNAS
publication_identifier:
  eissn:
  - '10916490'
  issn:
  - '00278424'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/new-compact-model-for-gene-regulation-in-higher-organisms/
scopus_import: '1'
status: public
title: Nonequilibrium models of optimal enhancer function
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 117
year: '2020'
...
---
_id: '7383'
abstract:
- lang: eng
  text: Organisms cope with change by employing transcriptional regulators. However,
    when faced with rare environments, the evolution of transcriptional regulators
    and their promoters may be too slow. We ask whether the intrinsic instability
    of gene duplication and amplification provides a generic alternative to canonical
    gene regulation. By real-time monitoring of gene copy number mutations in E. coli,
    we show that gene duplications and amplifications enable adaptation to fluctuating
    environments by rapidly generating copy number, and hence expression level, polymorphism.
    This ‘amplification-mediated gene expression tuning’ occurs on timescales similar
    to canonical gene regulation and can deal with rapid environmental changes. Mathematical
    modeling shows that amplifications also tune gene expression in stochastic environments
    where transcription factor-based schemes are hard to evolve or maintain. The fleeting
    nature of gene amplifications gives rise to a generic population-level mechanism
    that relies on genetic heterogeneity to rapidly tune expression of any gene, without
    leaving any genomic signature.
article_processing_charge: No
author:
- first_name: Rok
  full_name: Grah, Rok
  id: 483E70DE-F248-11E8-B48F-1D18A9856A87
  last_name: Grah
  orcid: 0000-0003-2539-3560
citation:
  ama: 'Grah R. Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level
    Gene Expression regulation. 2020. doi:<a href="https://doi.org/10.15479/AT:ISTA:7383">10.15479/AT:ISTA:7383</a>'
  apa: 'Grah, R. (2020). Matlab scripts for the Paper: Gene Amplification as a Form
    of Population-Level Gene Expression regulation. Institute of Science and Technology
    Austria. <a href="https://doi.org/10.15479/AT:ISTA:7383">https://doi.org/10.15479/AT:ISTA:7383</a>'
  chicago: 'Grah, Rok. “Matlab Scripts for the Paper: Gene Amplification as a Form
    of Population-Level Gene Expression Regulation.” Institute of Science and Technology
    Austria, 2020. <a href="https://doi.org/10.15479/AT:ISTA:7383">https://doi.org/10.15479/AT:ISTA:7383</a>.'
  ieee: 'R. Grah, “Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level
    Gene Expression regulation.” Institute of Science and Technology Austria, 2020.'
  ista: 'Grah R. 2020. Matlab scripts for the Paper: Gene Amplification as a Form
    of Population-Level Gene Expression regulation, Institute of Science and Technology
    Austria, <a href="https://doi.org/10.15479/AT:ISTA:7383">10.15479/AT:ISTA:7383</a>.'
  mla: 'Grah, Rok. <i>Matlab Scripts for the Paper: Gene Amplification as a Form of
    Population-Level Gene Expression Regulation</i>. Institute of Science and Technology
    Austria, 2020, doi:<a href="https://doi.org/10.15479/AT:ISTA:7383">10.15479/AT:ISTA:7383</a>.'
  short: R. Grah, (2020).
contributor:
- contributor_type: project_leader
  first_name: Calin C
  id: 47F8433E-F248-11E8-B48F-1D18A9856A87
  last_name: Guet
  orcid: 0000-0001-6220-2052
date_created: 2020-01-28T10:41:49Z
date_published: 2020-01-28T00:00:00Z
date_updated: 2024-02-21T12:42:31Z
day: '28'
department:
- _id: CaGu
- _id: GaTk
doi: 10.15479/AT:ISTA:7383
file:
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  checksum: 9d292cf5207b3829225f44c044cdb3fd
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  date_updated: 2020-07-14T12:47:57Z
  file_id: '7384'
  file_name: Scripts.zip
  file_size: 73363365
  relation: main_file
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  date_created: 2020-01-28T10:39:30Z
  date_updated: 2020-07-14T12:47:57Z
  file_id: '7385'
  file_name: READ_ME_MAIN.txt
  file_size: 962
  relation: main_file
file_date_updated: 2020-07-14T12:47:57Z
has_accepted_license: '1'
keyword:
- Matlab scripts
- analysis of microfluidics
- mathematical model
month: '01'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '7652'
    relation: used_in_publication
    status: public
status: public
title: 'Matlab scripts for the Paper: Gene Amplification as a Form of Population-Level
  Gene Expression regulation'
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
