---
_id: '955'
abstract:
- lang: eng
  text: 'Gene expression is controlled by networks of regulatory proteins that interact
    specifically with external signals and DNA regulatory sequences. These interactions
    force the network components to co-evolve so as to continually maintain function.
    Yet, existing models of evolution mostly focus on isolated genetic elements. In
    contrast, we study the essential process by which regulatory networks grow: the
    duplication and subsequent specialization of network components. We synthesize
    a biophysical model of molecular interactions with the evolutionary framework
    to find the conditions and pathways by which new regulatory functions emerge.
    We show that specialization of new network components is usually slow, but can
    be drastically accelerated in the presence of regulatory crosstalk and mutations
    that promote promiscuous interactions between network components.'
article_number: '216'
article_processing_charge: Yes (in subscription journal)
author:
- first_name: Tamar
  full_name: Friedlander, Tamar
  id: 36A5845C-F248-11E8-B48F-1D18A9856A87
  last_name: Friedlander
- first_name: Roshan
  full_name: Prizak, Roshan
  id: 4456104E-F248-11E8-B48F-1D18A9856A87
  last_name: Prizak
- first_name: Nicholas H
  full_name: Barton, Nicholas H
  id: 4880FE40-F248-11E8-B48F-1D18A9856A87
  last_name: Barton
  orcid: 0000-0002-8548-5240
- first_name: Gasper
  full_name: Tkacik, Gasper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkacik
  orcid: 0000-0002-6699-1455
citation:
  ama: Friedlander T, Prizak R, Barton NH, Tkačik G. Evolution of new regulatory functions
    on biophysically realistic fitness landscapes. <i>Nature Communications</i>. 2017;8(1).
    doi:<a href="https://doi.org/10.1038/s41467-017-00238-8">10.1038/s41467-017-00238-8</a>
  apa: Friedlander, T., Prizak, R., Barton, N. H., &#38; Tkačik, G. (2017). Evolution
    of new regulatory functions on biophysically realistic fitness landscapes. <i>Nature
    Communications</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/s41467-017-00238-8">https://doi.org/10.1038/s41467-017-00238-8</a>
  chicago: Friedlander, Tamar, Roshan Prizak, Nicholas H Barton, and Gašper Tkačik.
    “Evolution of New Regulatory Functions on Biophysically Realistic Fitness Landscapes.”
    <i>Nature Communications</i>. Nature Publishing Group, 2017. <a href="https://doi.org/10.1038/s41467-017-00238-8">https://doi.org/10.1038/s41467-017-00238-8</a>.
  ieee: T. Friedlander, R. Prizak, N. H. Barton, and G. Tkačik, “Evolution of new
    regulatory functions on biophysically realistic fitness landscapes,” <i>Nature
    Communications</i>, vol. 8, no. 1. Nature Publishing Group, 2017.
  ista: Friedlander T, Prizak R, Barton NH, Tkačik G. 2017. Evolution of new regulatory
    functions on biophysically realistic fitness landscapes. Nature Communications.
    8(1), 216.
  mla: Friedlander, Tamar, et al. “Evolution of New Regulatory Functions on Biophysically
    Realistic Fitness Landscapes.” <i>Nature Communications</i>, vol. 8, no. 1, 216,
    Nature Publishing Group, 2017, doi:<a href="https://doi.org/10.1038/s41467-017-00238-8">10.1038/s41467-017-00238-8</a>.
  short: T. Friedlander, R. Prizak, N.H. Barton, G. Tkačik, Nature Communications
    8 (2017).
date_created: 2018-12-11T11:49:23Z
date_published: 2017-08-09T00:00:00Z
date_updated: 2025-05-28T11:42:50Z
day: '09'
ddc:
- '539'
- '576'
department:
- _id: GaTk
- _id: NiBa
doi: 10.1038/s41467-017-00238-8
ec_funded: 1
external_id:
  isi:
  - '000407198800005'
file:
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  checksum: 29a1b5db458048d3bd5c67e0e2a56818
  content_type: application/pdf
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  date_created: 2018-12-12T10:14:14Z
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  file_size: 998157
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file_date_updated: 2020-07-14T12:48:16Z
has_accepted_license: '1'
intvolume: '         8'
isi: 1
issue: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 25B07788-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '250152'
  name: Limits to selection in biology and in evolutionary computation
- _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:
  - '20411723'
publication_status: published
publisher: Nature Publishing Group
publist_id: '6459'
pubrep_id: '864'
quality_controlled: '1'
related_material:
  record:
  - id: '6071'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Evolution of new regulatory functions on biophysically realistic fitness landscapes
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: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 8
year: '2017'
...
---
_id: '1358'
abstract:
- lang: eng
  text: 'Gene regulation relies on the specificity of transcription factor (TF)–DNA
    interactions. Limited specificity may lead to crosstalk: a regulatory state in
    which a gene is either incorrectly activated due to noncognate TF–DNA interactions
    or remains erroneously inactive. As each TF can have numerous interactions with
    noncognate cis-regulatory elements, crosstalk is inherently a global problem,
    yet has previously not been studied as such. We construct a theoretical framework
    to analyse the effects of global crosstalk on gene regulation. We find that crosstalk
    presents a significant challenge for organisms with low-specificity TFs, such
    as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting
    at equilibrium, including variants of cooperativity and combinatorial regulation.
    Our results suggest that crosstalk imposes a previously unexplored global constraint
    on the functioning and evolution of regulatory networks, which is qualitatively
    distinct from the known constraints that act at the level of individual gene regulatory
    elements.'
article_number: '12307'
author:
- first_name: Tamar
  full_name: Friedlander, Tamar
  id: 36A5845C-F248-11E8-B48F-1D18A9856A87
  last_name: Friedlander
- first_name: Roshan
  full_name: Prizak, Roshan
  id: 4456104E-F248-11E8-B48F-1D18A9856A87
  last_name: Prizak
- 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: Nicholas H
  full_name: Barton, Nicholas H
  id: 4880FE40-F248-11E8-B48F-1D18A9856A87
  last_name: Barton
  orcid: 0000-0002-8548-5240
- first_name: Gasper
  full_name: Tkacik, Gasper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkacik
  orcid: 0000-0002-6699-1455
citation:
  ama: Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. Intrinsic limits to
    gene regulation by global crosstalk. <i>Nature Communications</i>. 2016;7. doi:<a
    href="https://doi.org/10.1038/ncomms12307">10.1038/ncomms12307</a>
  apa: Friedlander, T., Prizak, R., Guet, C. C., Barton, N. H., &#38; Tkačik, G. (2016).
    Intrinsic limits to gene regulation by global crosstalk. <i>Nature Communications</i>.
    Nature Publishing Group. <a href="https://doi.org/10.1038/ncomms12307">https://doi.org/10.1038/ncomms12307</a>
  chicago: Friedlander, Tamar, Roshan Prizak, Calin C Guet, Nicholas H Barton, and
    Gašper Tkačik. “Intrinsic Limits to Gene Regulation by Global Crosstalk.” <i>Nature
    Communications</i>. Nature Publishing Group, 2016. <a href="https://doi.org/10.1038/ncomms12307">https://doi.org/10.1038/ncomms12307</a>.
  ieee: T. Friedlander, R. Prizak, C. C. Guet, N. H. Barton, and G. Tkačik, “Intrinsic
    limits to gene regulation by global crosstalk,” <i>Nature Communications</i>,
    vol. 7. Nature Publishing Group, 2016.
  ista: Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. 2016. Intrinsic limits
    to gene regulation by global crosstalk. Nature Communications. 7, 12307.
  mla: Friedlander, Tamar, et al. “Intrinsic Limits to Gene Regulation by Global Crosstalk.”
    <i>Nature Communications</i>, vol. 7, 12307, Nature Publishing Group, 2016, doi:<a
    href="https://doi.org/10.1038/ncomms12307">10.1038/ncomms12307</a>.
  short: T. Friedlander, R. Prizak, C.C. Guet, N.H. Barton, G. Tkačik, Nature Communications
    7 (2016).
date_created: 2018-12-11T11:51:34Z
date_published: 2016-08-04T00:00:00Z
date_updated: 2023-09-07T12:53:49Z
day: '04'
ddc:
- '576'
department:
- _id: GaTk
- _id: NiBa
- _id: CaGu
doi: 10.1038/ncomms12307
ec_funded: 1
file:
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  checksum: fe3f3a1526d180b29fe691ab11435b78
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  creator: system
  date_created: 2018-12-12T10:12:01Z
  date_updated: 2020-07-14T12:44:46Z
  file_id: '4919'
  file_name: IST-2016-627-v1+1_ncomms12307.pdf
  file_size: 861805
  relation: main_file
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  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:12:02Z
  date_updated: 2020-07-14T12:44:46Z
  file_id: '4920'
  file_name: IST-2016-627-v1+2_ncomms12307-s1.pdf
  file_size: 1084703
  relation: main_file
file_date_updated: 2020-07-14T12:44:46Z
has_accepted_license: '1'
intvolume: '         7'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 25B07788-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '250152'
  name: Limits to selection in biology and in evolutionary computation
- _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_status: published
publisher: Nature Publishing Group
publist_id: '5887'
pubrep_id: '627'
quality_controlled: '1'
related_material:
  record:
  - id: '6071'
    relation: dissertation_contains
    status: public
scopus_import: 1
status: public
title: Intrinsic limits to gene regulation by global crosstalk
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 7
year: '2016'
...
---
_id: '1827'
abstract:
- lang: eng
  text: Bow-tie or hourglass structure is a common architectural feature found in
    many biological systems. A bow-tie in a multi-layered structure occurs when intermediate
    layers have much fewer components than the input and output layers. Examples include
    metabolism where a handful of building blocks mediate between multiple input nutrients
    and multiple output biomass components, and signaling networks where information
    from numerous receptor types passes through a small set of signaling pathways
    to regulate multiple output genes. Little is known, however, about how bow-tie
    architectures evolve. Here, we address the evolution of bow-tie architectures
    using simulations of multi-layered systems evolving to fulfill a given input-output
    goal. We find that bow-ties spontaneously evolve when the information in the evolutionary
    goal can be compressed. Mathematically speaking, bow-ties evolve when the rank
    of the input-output matrix describing the evolutionary goal is deficient. The
    maximal compression possible (the rank of the goal) determines the size of the
    narrowest part of the network—that is the bow-tie. A further requirement is that
    a process is active to reduce the number of links in the network, such as product-rule
    mutations, otherwise a non-bow-tie solution is found in the evolutionary simulations.
    This offers a mechanism to understand a common architectural principle of biological
    systems, and a way to quantitate the effective rank of the goals under which they
    evolved.
article_processing_charge: No
author:
- first_name: Tamar
  full_name: Friedlander, Tamar
  id: 36A5845C-F248-11E8-B48F-1D18A9856A87
  last_name: Friedlander
- first_name: Avraham
  full_name: Mayo, Avraham
  last_name: Mayo
- first_name: Tsvi
  full_name: Tlusty, Tsvi
  last_name: Tlusty
- first_name: Uri
  full_name: Alon, Uri
  last_name: Alon
citation:
  ama: Friedlander T, Mayo A, Tlusty T, Alon U. Evolution of bow-tie architectures
    in biology. <i>PLoS Computational Biology</i>. 2015;11(3). doi:<a href="https://doi.org/10.1371/journal.pcbi.1004055">10.1371/journal.pcbi.1004055</a>
  apa: Friedlander, T., Mayo, A., Tlusty, T., &#38; Alon, U. (2015). Evolution of
    bow-tie architectures in biology. <i>PLoS Computational Biology</i>. Public Library
    of Science. <a href="https://doi.org/10.1371/journal.pcbi.1004055">https://doi.org/10.1371/journal.pcbi.1004055</a>
  chicago: Friedlander, Tamar, Avraham Mayo, Tsvi Tlusty, and Uri Alon. “Evolution
    of Bow-Tie Architectures in Biology.” <i>PLoS Computational Biology</i>. Public
    Library of Science, 2015. <a href="https://doi.org/10.1371/journal.pcbi.1004055">https://doi.org/10.1371/journal.pcbi.1004055</a>.
  ieee: T. Friedlander, A. Mayo, T. Tlusty, and U. Alon, “Evolution of bow-tie architectures
    in biology,” <i>PLoS Computational Biology</i>, vol. 11, no. 3. Public Library
    of Science, 2015.
  ista: Friedlander T, Mayo A, Tlusty T, Alon U. 2015. Evolution of bow-tie architectures
    in biology. PLoS Computational Biology. 11(3).
  mla: Friedlander, Tamar, et al. “Evolution of Bow-Tie Architectures in Biology.”
    <i>PLoS Computational Biology</i>, vol. 11, no. 3, Public Library of Science,
    2015, doi:<a href="https://doi.org/10.1371/journal.pcbi.1004055">10.1371/journal.pcbi.1004055</a>.
  short: T. Friedlander, A. Mayo, T. Tlusty, U. Alon, PLoS Computational Biology 11
    (2015).
date_created: 2018-12-11T11:54:14Z
date_published: 2015-03-23T00:00:00Z
date_updated: 2023-02-23T14:07:51Z
day: '23'
ddc:
- '576'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1004055
ec_funded: 1
file:
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  checksum: b8aa66f450ff8de393014b87ec7d2efb
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  creator: system
  date_created: 2018-12-12T10:15:39Z
  date_updated: 2020-07-14T12:45:17Z
  file_id: '5161'
  file_name: IST-2016-452-v1+1_journal.pcbi.1004055.pdf
  file_size: 1811647
  relation: main_file
file_date_updated: 2020-07-14T12:45:17Z
has_accepted_license: '1'
intvolume: '        11'
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
publication: PLoS Computational Biology
publication_status: published
publisher: Public Library of Science
publist_id: '5278'
pubrep_id: '452'
quality_controlled: '1'
related_material:
  record:
  - id: '9718'
    relation: research_data
    status: public
  - id: '9773'
    relation: research_data
    status: public
scopus_import: 1
status: public
title: Evolution of bow-tie architectures in biology
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 11
year: '2015'
...
---
_id: '9718'
article_processing_charge: No
author:
- first_name: Tamar
  full_name: Friedlander, Tamar
  id: 36A5845C-F248-11E8-B48F-1D18A9856A87
  last_name: Friedlander
- first_name: Avraham E.
  full_name: Mayo, Avraham E.
  last_name: Mayo
- first_name: Tsvi
  full_name: Tlusty, Tsvi
  last_name: Tlusty
- first_name: Uri
  full_name: Alon, Uri
  last_name: Alon
citation:
  ama: Friedlander T, Mayo AE, Tlusty T, Alon U. Supporting information text. 2015.
    doi:<a href="https://doi.org/10.1371/journal.pcbi.1004055.s001">10.1371/journal.pcbi.1004055.s001</a>
  apa: Friedlander, T., Mayo, A. E., Tlusty, T., &#38; Alon, U. (2015). Supporting
    information text. Public Library of Science. <a href="https://doi.org/10.1371/journal.pcbi.1004055.s001">https://doi.org/10.1371/journal.pcbi.1004055.s001</a>
  chicago: Friedlander, Tamar, Avraham E. Mayo, Tsvi Tlusty, and Uri Alon. “Supporting
    Information Text.” Public Library of Science, 2015. <a href="https://doi.org/10.1371/journal.pcbi.1004055.s001">https://doi.org/10.1371/journal.pcbi.1004055.s001</a>.
  ieee: T. Friedlander, A. E. Mayo, T. Tlusty, and U. Alon, “Supporting information
    text.” Public Library of Science, 2015.
  ista: Friedlander T, Mayo AE, Tlusty T, Alon U. 2015. Supporting information text,
    Public Library of Science, <a href="https://doi.org/10.1371/journal.pcbi.1004055.s001">10.1371/journal.pcbi.1004055.s001</a>.
  mla: Friedlander, Tamar, et al. <i>Supporting Information Text</i>. Public Library
    of Science, 2015, doi:<a href="https://doi.org/10.1371/journal.pcbi.1004055.s001">10.1371/journal.pcbi.1004055.s001</a>.
  short: T. Friedlander, A.E. Mayo, T. Tlusty, U. Alon, (2015).
date_created: 2021-07-26T08:35:23Z
date_published: 2015-03-23T00:00:00Z
date_updated: 2023-02-23T10:16:13Z
day: '23'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1004055.s001
month: '03'
oa_version: Published Version
publisher: Public Library of Science
related_material:
  record:
  - id: '1827'
    relation: used_in_publication
    status: public
status: public
title: Supporting information text
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2015'
...
---
_id: '9773'
article_processing_charge: No
author:
- first_name: Tamar
  full_name: Friedlander, Tamar
  id: 36A5845C-F248-11E8-B48F-1D18A9856A87
  last_name: Friedlander
- first_name: Avraham E.
  full_name: Mayo, Avraham E.
  last_name: Mayo
- first_name: Tsvi
  full_name: Tlusty, Tsvi
  last_name: Tlusty
- first_name: Uri
  full_name: Alon, Uri
  last_name: Alon
citation:
  ama: Friedlander T, Mayo AE, Tlusty T, Alon U. Evolutionary simulation code. 2015.
    doi:<a href="https://doi.org/10.1371/journal.pcbi.1004055.s002">10.1371/journal.pcbi.1004055.s002</a>
  apa: Friedlander, T., Mayo, A. E., Tlusty, T., &#38; Alon, U. (2015). Evolutionary
    simulation code. Public Library of Science. <a href="https://doi.org/10.1371/journal.pcbi.1004055.s002">https://doi.org/10.1371/journal.pcbi.1004055.s002</a>
  chicago: Friedlander, Tamar, Avraham E. Mayo, Tsvi Tlusty, and Uri Alon. “Evolutionary
    Simulation Code.” Public Library of Science, 2015. <a href="https://doi.org/10.1371/journal.pcbi.1004055.s002">https://doi.org/10.1371/journal.pcbi.1004055.s002</a>.
  ieee: T. Friedlander, A. E. Mayo, T. Tlusty, and U. Alon, “Evolutionary simulation
    code.” Public Library of Science, 2015.
  ista: Friedlander T, Mayo AE, Tlusty T, Alon U. 2015. Evolutionary simulation code,
    Public Library of Science, <a href="https://doi.org/10.1371/journal.pcbi.1004055.s002">10.1371/journal.pcbi.1004055.s002</a>.
  mla: Friedlander, Tamar, et al. <i>Evolutionary Simulation Code</i>. Public Library
    of Science, 2015, doi:<a href="https://doi.org/10.1371/journal.pcbi.1004055.s002">10.1371/journal.pcbi.1004055.s002</a>.
  short: T. Friedlander, A.E. Mayo, T. Tlusty, U. Alon, (2015).
date_created: 2021-08-05T12:58:07Z
date_published: 2015-03-23T00:00:00Z
date_updated: 2023-02-23T10:16:13Z
day: '23'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1004055.s002
month: '03'
oa_version: Published Version
publisher: Public Library of Science
related_material:
  record:
  - id: '1827'
    relation: used_in_publication
    status: public
status: public
title: Evolutionary simulation code
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2015'
...
---
_id: '1815'
abstract:
- lang: eng
  text: Many membrane channels and receptors exhibit adaptive, or desensitized, response
    to a strong sustained input stimulus, often supported by protein activity-dependent
    inactivation. Adaptive response is thought to be related to various cellular functions
    such as homeostasis and enlargement of dynamic range by background compensation.
    Here we study the quantitative relation between adaptive response and background
    compensation within a modeling framework. We show that any particular type of
    adaptive response is neither sufficient nor necessary for adaptive enlargement
    of dynamic range. In particular a precise adaptive response, where system activity
    is maintained at a constant level at steady state, does not ensure a large dynamic
    range neither in input signal nor in system output. A general mechanism for input
    dynamic range enlargement can come about from the activity-dependent modulation
    of protein responsiveness by multiple biochemical modification, regardless of
    the type of adaptive response it induces. Therefore hierarchical biochemical processes
    such as methylation and phosphorylation are natural candidates to induce this
    property in signaling systems.
author:
- first_name: Tamar
  full_name: Tamar Friedlander
  id: 36A5845C-F248-11E8-B48F-1D18A9856A87
  last_name: Friedlander
- first_name: Naama
  full_name: Brenner, Naama
  last_name: Brenner
citation:
  ama: Friedlander T, Brenner N. Adaptive response and enlargement of dynamic range.
    <i>Mathematical Biosciences and Engineering</i>. 2011;8(2):515-526. doi:<a href="https://doi.org/10.3934/mbe.2011.8.515">10.3934/mbe.2011.8.515</a>
  apa: Friedlander, T., &#38; Brenner, N. (2011). Adaptive response and enlargement
    of dynamic range. <i>Mathematical Biosciences and Engineering</i>. Arizona State
    University. <a href="https://doi.org/10.3934/mbe.2011.8.515">https://doi.org/10.3934/mbe.2011.8.515</a>
  chicago: Friedlander, Tamar, and Naama Brenner. “Adaptive Response and Enlargement
    of Dynamic Range.” <i>Mathematical Biosciences and Engineering</i>. Arizona State
    University, 2011. <a href="https://doi.org/10.3934/mbe.2011.8.515">https://doi.org/10.3934/mbe.2011.8.515</a>.
  ieee: T. Friedlander and N. Brenner, “Adaptive response and enlargement of dynamic
    range,” <i>Mathematical Biosciences and Engineering</i>, vol. 8, no. 2. Arizona
    State University, pp. 515–526, 2011.
  ista: Friedlander T, Brenner N. 2011. Adaptive response and enlargement of dynamic
    range. Mathematical Biosciences and Engineering. 8(2), 515–526.
  mla: Friedlander, Tamar, and Naama Brenner. “Adaptive Response and Enlargement of
    Dynamic Range.” <i>Mathematical Biosciences and Engineering</i>, vol. 8, no. 2,
    Arizona State University, 2011, pp. 515–26, doi:<a href="https://doi.org/10.3934/mbe.2011.8.515">10.3934/mbe.2011.8.515</a>.
  short: T. Friedlander, N. Brenner, Mathematical Biosciences and Engineering 8 (2011)
    515–526.
date_created: 2018-12-11T11:54:10Z
date_published: 2011-04-02T00:00:00Z
date_updated: 2021-01-12T06:53:23Z
day: '02'
doi: 10.3934/mbe.2011.8.515
extern: 1
intvolume: '         8'
issue: '2'
main_file_link:
- open_access: '1'
  url: http://arxiv.org/abs/1003.2791
month: '04'
oa: 1
page: 515 - 526
publication: Mathematical Biosciences and Engineering
publication_status: published
publisher: Arizona State University
publist_id: '5291'
quality_controlled: 0
status: public
title: Adaptive response and enlargement of dynamic range
type: journal_article
volume: 8
year: '2011'
...
---
_id: '1825'
abstract:
- lang: eng
  text: 'Many membrane channels and receptors exhibit adaptive, or desensitized, response
    to a strong sustained input stimulus. A key mechanism that underlies this response
    is the slow, activity-dependent removal of responding molecules to a pool which
    is unavailable to respond immediately to the input. This mechanism is implemented
    in different ways in various biological systems and has traditionally been studied
    separately for each. Here we highlight the common aspects of this principle, shared
    by many biological systems, and suggest a unifying theoretical framework. We study
    theoretically a class of models which describes the general mechanism and allows
    us to distinguish its universal from system-specific features. We show that under
    general conditions, regardless of the details of kinetics, molecule availability
    encodes an averaging over past activity and feeds back multiplicatively on the
    system output. The kinetics of recovery from unavailability determines the effective
    memory kernel inside the feedback branch, giving rise to a variety of system-specific
    forms of adaptive response—precise or input-dependent, exponential or power-law—as
    special cases of the same model. '
author:
- first_name: Tamar
  full_name: Tamar Friedlander
  id: 36A5845C-F248-11E8-B48F-1D18A9856A87
  last_name: Friedlander
- first_name: Naama
  full_name: Brenner, Naama
  last_name: Brenner
citation:
  ama: Friedlander T, Brenner N. Adaptive response by state-dependent inactivation.
    <i>PNAS</i>. 2009;106(52):22558-22563. doi:<a href="https://doi.org/10.1073/pnas.0902146106
    ">10.1073/pnas.0902146106 </a>
  apa: Friedlander, T., &#38; Brenner, N. (2009). Adaptive response by state-dependent
    inactivation. <i>PNAS</i>. National Academy of Sciences. <a href="https://doi.org/10.1073/pnas.0902146106
    ">https://doi.org/10.1073/pnas.0902146106 </a>
  chicago: Friedlander, Tamar, and Naama Brenner. “Adaptive Response by State-Dependent
    Inactivation.” <i>PNAS</i>. National Academy of Sciences, 2009. <a href="https://doi.org/10.1073/pnas.0902146106
    ">https://doi.org/10.1073/pnas.0902146106 </a>.
  ieee: T. Friedlander and N. Brenner, “Adaptive response by state-dependent inactivation,”
    <i>PNAS</i>, vol. 106, no. 52. National Academy of Sciences, pp. 22558–22563,
    2009.
  ista: Friedlander T, Brenner N. 2009. Adaptive response by state-dependent inactivation.
    PNAS. 106(52), 22558–22563.
  mla: Friedlander, Tamar, and Naama Brenner. “Adaptive Response by State-Dependent
    Inactivation.” <i>PNAS</i>, vol. 106, no. 52, National Academy of Sciences, 2009,
    pp. 22558–63, doi:<a href="https://doi.org/10.1073/pnas.0902146106 ">10.1073/pnas.0902146106
    </a>.
  short: T. Friedlander, N. Brenner, PNAS 106 (2009) 22558–22563.
date_created: 2018-12-11T11:54:13Z
date_published: 2009-12-01T00:00:00Z
date_updated: 2021-01-12T06:53:26Z
day: '01'
doi: '10.1073/pnas.0902146106 '
extern: 1
intvolume: '       106'
issue: '52'
main_file_link:
- open_access: '1'
  url: http://www.pnas.org/content/106/52/22558.full.pdf
month: '12'
oa: 1
page: 22558 - 22563
publication: PNAS
publication_status: published
publisher: National Academy of Sciences
publist_id: '5281'
quality_controlled: 0
status: public
title: Adaptive response by state-dependent inactivation
type: journal_article
volume: 106
year: '2009'
...
---
_id: '1826'
abstract:
- lang: eng
  text: Proliferating cell populations at steady-state growth often exhibit broad
    protein distributions with exponential tails. The sources of this variation and
    its universality are of much theoretical interest. Here we address the problem
    by asymptotic analysis of the population balance equation. We show that the steady-state
    distribution tail is determined by a combination of protein production and cell
    division and is insensitive to other model details. Under general conditions this
    tail is exponential with a dependence on parameters consistent with experiment.
    We discuss the conditions for this effect to be dominant over other sources of
    variation and the relation to experiments.
author:
- first_name: Tamar
  full_name: Tamar Friedlander
  id: 36A5845C-F248-11E8-B48F-1D18A9856A87
  last_name: Friedlander
- first_name: Naama
  full_name: Brenner, Naama
  last_name: Brenner
citation:
  ama: Friedlander T, Brenner N. Cellular properties and population asymptotics in
    the population balance equation. <i>Physical Review Letters</i>. 2008;101(1).
    doi:<a href="https://doi.org/10.1103/PhysRevLett.101.018104">10.1103/PhysRevLett.101.018104</a>
  apa: Friedlander, T., &#38; Brenner, N. (2008). Cellular properties and population
    asymptotics in the population balance equation. <i>Physical Review Letters</i>.
    American Physical Society. <a href="https://doi.org/10.1103/PhysRevLett.101.018104">https://doi.org/10.1103/PhysRevLett.101.018104</a>
  chicago: Friedlander, Tamar, and Naama Brenner. “Cellular Properties and Population
    Asymptotics in the Population Balance Equation.” <i>Physical Review Letters</i>.
    American Physical Society, 2008. <a href="https://doi.org/10.1103/PhysRevLett.101.018104">https://doi.org/10.1103/PhysRevLett.101.018104</a>.
  ieee: T. Friedlander and N. Brenner, “Cellular properties and population asymptotics
    in the population balance equation,” <i>Physical Review Letters</i>, vol. 101,
    no. 1. American Physical Society, 2008.
  ista: Friedlander T, Brenner N. 2008. Cellular properties and population asymptotics
    in the population balance equation. Physical Review Letters. 101(1).
  mla: Friedlander, Tamar, and Naama Brenner. “Cellular Properties and Population
    Asymptotics in the Population Balance Equation.” <i>Physical Review Letters</i>,
    vol. 101, no. 1, American Physical Society, 2008, doi:<a href="https://doi.org/10.1103/PhysRevLett.101.018104">10.1103/PhysRevLett.101.018104</a>.
  short: T. Friedlander, N. Brenner, Physical Review Letters 101 (2008).
date_created: 2018-12-11T11:54:13Z
date_published: 2008-07-01T00:00:00Z
date_updated: 2021-01-12T06:53:27Z
day: '01'
doi: 10.1103/PhysRevLett.101.018104
extern: 1
intvolume: '       101'
issue: '1'
main_file_link:
- open_access: '0'
  url: http://arxiv.org/abs/0804.4804
month: '07'
publication: Physical Review Letters
publication_status: published
publisher: American Physical Society
publist_id: '5280'
quality_controlled: 0
status: public
title: Cellular properties and population asymptotics in the population balance equation
type: journal_article
volume: 101
year: '2008'
...