---
_id: '196'
abstract:
- lang: eng
text: 'The abelian sandpile serves as a model to study self-organized criticality,
a phenomenon occurring in biological, physical and social processes. The identity
of the abelian group is a fractal composed of self-similar patches, and its limit
is subject of extensive collaborative research. Here, we analyze the evolution
of the sandpile identity under harmonic fields of different orders. We show that
this evolution corresponds to periodic cycles through the abelian group characterized
by the smooth transformation and apparent conservation of the patches constituting
the identity. The dynamics induced by second and third order harmonics resemble
smooth stretchings, respectively translations, of the identity, while the ones
induced by fourth order harmonics resemble magnifications and rotations. Starting
with order three, the dynamics pass through extended regions of seemingly random
configurations which spontaneously reassemble into accentuated patterns. We show
that the space of harmonic functions projects to the extended analogue of the
sandpile group, thus providing a set of universal coordinates identifying configurations
between different domains. Since the original sandpile group is a subgroup of
the extended one, this directly implies that it admits a natural renormalization.
Furthermore, we show that the harmonic fields can be induced by simple Markov
processes, and that the corresponding stochastic dynamics show remarkable robustness
over hundreds of periods. Finally, we encode information into seemingly random
configurations, and decode this information with an algorithm requiring minimal
prior knowledge. Our results suggest that harmonic fields might split the sandpile
group into sub-sets showing different critical coefficients, and that it might
be possible to extend the fractal structure of the identity beyond the boundaries
of its domain. '
acknowledgement: "M.L. is grateful to the members of the C Guet and G Tkacik groups
for valuable comments and support. M.S. is grateful to Nikita Kalinin for inspiring
communications.\r\n"
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Mikhail
full_name: Shkolnikov, Mikhail
id: 35084A62-F248-11E8-B48F-1D18A9856A87
last_name: Shkolnikov
orcid: 0000-0002-4310-178X
citation:
ama: Lang M, Shkolnikov M. Harmonic dynamics of the Abelian sandpile. Proceedings
of the National Academy of Sciences. 2019;116(8):2821-2830. doi:10.1073/pnas.1812015116
apa: Lang, M., & Shkolnikov, M. (2019). Harmonic dynamics of the Abelian sandpile.
Proceedings of the National Academy of Sciences. National Academy of Sciences.
https://doi.org/10.1073/pnas.1812015116
chicago: Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian
Sandpile.” Proceedings of the National Academy of Sciences. National Academy
of Sciences, 2019. https://doi.org/10.1073/pnas.1812015116.
ieee: M. Lang and M. Shkolnikov, “Harmonic dynamics of the Abelian sandpile,” Proceedings
of the National Academy of Sciences, vol. 116, no. 8. National Academy of
Sciences, pp. 2821–2830, 2019.
ista: Lang M, Shkolnikov M. 2019. Harmonic dynamics of the Abelian sandpile. Proceedings
of the National Academy of Sciences. 116(8), 2821–2830.
mla: Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.”
Proceedings of the National Academy of Sciences, vol. 116, no. 8, National
Academy of Sciences, 2019, pp. 2821–30, doi:10.1073/pnas.1812015116.
short: M. Lang, M. Shkolnikov, Proceedings of the National Academy of Sciences 116
(2019) 2821–2830.
date_created: 2018-12-11T11:45:08Z
date_published: 2019-02-19T00:00:00Z
date_updated: 2023-09-11T14:09:34Z
day: '19'
department:
- _id: CaGu
- _id: GaTk
- _id: TaHa
doi: 10.1073/pnas.1812015116
external_id:
arxiv:
- '1806.10823'
isi:
- '000459074400013'
pmid:
- ' 30728300'
intvolume: ' 116'
isi: 1
issue: '8'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1073/pnas.1812015116
month: '02'
oa: 1
oa_version: Published Version
page: 2821-2830
pmid: 1
publication: Proceedings of the National Academy of Sciences
publication_identifier:
eissn:
- 1091-6490
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on IST Webpage
relation: press_release
url: https://ist.ac.at/en/news/famous-sandpile-model-shown-to-move-like-a-traveling-sand-dune/
scopus_import: '1'
status: public
title: Harmonic dynamics of the Abelian sandpile
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 116
year: '2019'
...
---
_id: '6465'
abstract:
- lang: eng
text: Tight control over protein degradation is a fundamental requirement for cells
to respond rapidly to various stimuli and adapt to a fluctuating environment.
Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons)
for the precise regulation of protein expression profiles in mammalian cells by
modulating target protein half-lives in a predictable manner. Using the well-established
tetracycline gene-regulation system as a model, we show that the dynamics of protein
expression can be tuned by fusing appropriate degron tags to gene regulators.
Next, we apply this degron library to tune a synthetic pulse-generating circuit
in mammalian cells. With this toolbox we establish a set of pulse generators with
tailored pulse lengths and magnitudes of protein expression. This methodology
will prove useful in the functional roles of essential proteins, fine-tuning of
gene-expression systems, and enabling a higher complexity in the design of synthetic
biological systems in mammalian cells.
article_number: '2013'
article_processing_charge: No
author:
- first_name: Hélène
full_name: Chassin, Hélène
last_name: Chassin
- first_name: Marius
full_name: Müller, Marius
last_name: Müller
- first_name: Marcel
full_name: Tigges, Marcel
last_name: Tigges
- first_name: Leo
full_name: Scheller, Leo
last_name: Scheller
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Martin
full_name: Fussenegger, Martin
last_name: Fussenegger
citation:
ama: Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. A modular
degron library for synthetic circuits in mammalian cells. Nature Communications.
2019;10(1). doi:10.1038/s41467-019-09974-5
apa: Chassin, H., Müller, M., Tigges, M., Scheller, L., Lang, M., & Fussenegger,
M. (2019). A modular degron library for synthetic circuits in mammalian cells.
Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-09974-5
chicago: Chassin, Hélène, Marius Müller, Marcel Tigges, Leo Scheller, Moritz Lang,
and Martin Fussenegger. “A Modular Degron Library for Synthetic Circuits in Mammalian
Cells.” Nature Communications. Springer Nature, 2019. https://doi.org/10.1038/s41467-019-09974-5.
ieee: H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, and M. Fussenegger,
“A modular degron library for synthetic circuits in mammalian cells,” Nature
Communications, vol. 10, no. 1. Springer Nature, 2019.
ista: Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. 2019. A
modular degron library for synthetic circuits in mammalian cells. Nature Communications.
10(1), 2013.
mla: Chassin, Hélène, et al. “A Modular Degron Library for Synthetic Circuits in
Mammalian Cells.” Nature Communications, vol. 10, no. 1, 2013, Springer
Nature, 2019, doi:10.1038/s41467-019-09974-5.
short: H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, M. Fussenegger, Nature
Communications 10 (2019).
date_created: 2019-05-19T21:59:14Z
date_published: 2019-05-01T00:00:00Z
date_updated: 2023-08-25T10:33:51Z
day: '01'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1038/s41467-019-09974-5
external_id:
isi:
- '000466338600006'
file:
- access_level: open_access
checksum: e214d3e4f8c81e35981583c4569b51b8
content_type: application/pdf
creator: dernst
date_created: 2019-05-20T07:33:54Z
date_updated: 2020-07-14T12:47:31Z
file_id: '6471'
file_name: 2019_NatureComm_Chassin.pdf
file_size: 1191827
relation: main_file
file_date_updated: 2020-07-14T12:47:31Z
has_accepted_license: '1'
intvolume: ' 10'
isi: 1
issue: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_identifier:
eissn:
- '20411723'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1038/s41467-023-36111-0
scopus_import: '1'
status: public
title: A modular degron library for synthetic circuits in mammalian cells
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2019'
...
---
_id: '305'
abstract:
- lang: eng
text: The hanging-drop network (HDN) is a technology platform based on a completely
open microfluidic network at the bottom of an inverted, surface-patterned substrate.
The platform is predominantly used for the formation, culturing, and interaction
of self-assembled spherical microtissues (spheroids) under precisely controlled
flow conditions. Here, we describe design, fabrication, and operation of microfluidic
hanging-drop networks.
acknowledgement: This work was financially supported by FP7 of the EU through the
project “Body on a chip,” ICT-FET-296257, and the ERC Advanced Grant “NeuroCMOS”
(contract 267351), as well as by an individual Ambizione Grant 142440 from the Swiss
National Science Foundation for Olivier Frey. The research leading to these results
also received funding from the People Programme (Marie Curie Actions) of the European
Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no.
[291734]. We would like to thank Alexander Stettler, ETH Zurich for his expertise
and support in the cleanroom, and we acknowledge the Single Cell Unit of D-BSSE,
ETH Zurich for assistance in microscopy issues. M.L. is grateful to the members
of the Guet and Tkačik groups, IST Austria, for valuable comments and support.
alternative_title:
- MIMB
author:
- first_name: Patrick
full_name: Misun, Patrick
last_name: Misun
- first_name: Axel
full_name: Birchler, Axel
last_name: Birchler
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Andreas
full_name: Hierlemann, Andreas
last_name: Hierlemann
- first_name: Olivier
full_name: Frey, Olivier
last_name: Frey
citation:
ama: Misun P, Birchler A, Lang M, Hierlemann A, Frey O. Fabrication and operation
of microfluidic hanging drop networks. Methods in Molecular Biology. 2018;1771:183-202.
doi:10.1007/978-1-4939-7792-5_15
apa: Misun, P., Birchler, A., Lang, M., Hierlemann, A., & Frey, O. (2018). Fabrication
and operation of microfluidic hanging drop networks. Methods in Molecular Biology.
Springer. https://doi.org/10.1007/978-1-4939-7792-5_15
chicago: Misun, Patrick, Axel Birchler, Moritz Lang, Andreas Hierlemann, and Olivier
Frey. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods
in Molecular Biology. Springer, 2018. https://doi.org/10.1007/978-1-4939-7792-5_15.
ieee: P. Misun, A. Birchler, M. Lang, A. Hierlemann, and O. Frey, “Fabrication and
operation of microfluidic hanging drop networks,” Methods in Molecular Biology,
vol. 1771. Springer, pp. 183–202, 2018.
ista: Misun P, Birchler A, Lang M, Hierlemann A, Frey O. 2018. Fabrication and operation
of microfluidic hanging drop networks. Methods in Molecular Biology. 1771, 183–202.
mla: Misun, Patrick, et al. “Fabrication and Operation of Microfluidic Hanging Drop
Networks.” Methods in Molecular Biology, vol. 1771, Springer, 2018, pp.
183–202, doi:10.1007/978-1-4939-7792-5_15.
short: P. Misun, A. Birchler, M. Lang, A. Hierlemann, O. Frey, Methods in Molecular
Biology 1771 (2018) 183–202.
date_created: 2018-12-11T11:45:43Z
date_published: 2018-01-01T00:00:00Z
date_updated: 2021-01-12T07:40:42Z
day: '01'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1007/978-1-4939-7792-5_15
ec_funded: 1
intvolume: ' 1771'
language:
- iso: eng
month: '01'
oa_version: None
page: 183 - 202
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Methods in Molecular Biology
publication_status: published
publisher: Springer
publist_id: '7574'
quality_controlled: '1'
scopus_import: 1
status: public
title: Fabrication and operation of microfluidic hanging drop networks
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1771
year: '2018'
...
---
_id: '457'
abstract:
- lang: eng
text: Temperate bacteriophages integrate in bacterial genomes as prophages and represent
an important source of genetic variation for bacterial evolution, frequently transmitting
fitness-augmenting genes such as toxins responsible for virulence of major pathogens.
However, only a fraction of bacteriophage infections are lysogenic and lead to
prophage acquisition, whereas the majority are lytic and kill the infected bacteria.
Unless able to discriminate lytic from lysogenic infections, mechanisms of immunity
to bacteriophages are expected to act as a double-edged sword and increase the
odds of survival at the cost of depriving bacteria of potentially beneficial prophages.
We show that although restriction-modification systems as mechanisms of innate
immunity prevent both lytic and lysogenic infections indiscriminately in individual
bacteria, they increase the number of prophage-acquiring individuals at the population
level. We find that this counterintuitive result is a consequence of phage-host
population dynamics, in which restriction-modification systems delay infection
onset until bacteria reach densities at which the probability of lysogeny increases.
These results underscore the importance of population-level dynamics as a key
factor modulating costs and benefits of immunity to temperate bacteriophages
article_processing_charge: No
author:
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Dominik
full_name: Refardt, Dominik
last_name: Refardt
- first_name: Bruce
full_name: Levin, Bruce
last_name: Levin
- 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: Pleska M, Lang M, Refardt D, Levin B, Guet CC. Phage-host population dynamics
promotes prophage acquisition in bacteria with innate immunity. Nature Ecology
and Evolution. 2018;2(2):359-366. doi:10.1038/s41559-017-0424-z
apa: Pleska, M., Lang, M., Refardt, D., Levin, B., & Guet, C. C. (2018). Phage-host
population dynamics promotes prophage acquisition in bacteria with innate immunity.
Nature Ecology and Evolution. Springer Nature. https://doi.org/10.1038/s41559-017-0424-z
chicago: Pleska, Maros, Moritz Lang, Dominik Refardt, Bruce Levin, and Calin C Guet.
“Phage-Host Population Dynamics Promotes Prophage Acquisition in Bacteria with
Innate Immunity.” Nature Ecology and Evolution. Springer Nature, 2018.
https://doi.org/10.1038/s41559-017-0424-z.
ieee: M. Pleska, M. Lang, D. Refardt, B. Levin, and C. C. Guet, “Phage-host population
dynamics promotes prophage acquisition in bacteria with innate immunity,” Nature
Ecology and Evolution, vol. 2, no. 2. Springer Nature, pp. 359–366, 2018.
ista: Pleska M, Lang M, Refardt D, Levin B, Guet CC. 2018. Phage-host population
dynamics promotes prophage acquisition in bacteria with innate immunity. Nature
Ecology and Evolution. 2(2), 359–366.
mla: Pleska, Maros, et al. “Phage-Host Population Dynamics Promotes Prophage Acquisition
in Bacteria with Innate Immunity.” Nature Ecology and Evolution, vol. 2,
no. 2, Springer Nature, 2018, pp. 359–66, doi:10.1038/s41559-017-0424-z.
short: M. Pleska, M. Lang, D. Refardt, B. Levin, C.C. Guet, Nature Ecology and Evolution
2 (2018) 359–366.
date_created: 2018-12-11T11:46:35Z
date_published: 2018-02-01T00:00:00Z
date_updated: 2023-09-15T12:04:57Z
day: '01'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1038/s41559-017-0424-z
ec_funded: 1
external_id:
isi:
- '000426516400027'
intvolume: ' 2'
isi: 1
issue: '2'
language:
- iso: eng
month: '02'
oa_version: None
page: 359 - 366
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 251BCBEC-B435-11E9-9278-68D0E5697425
grant_number: RGY0079/2011
name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification
Systems (HFSP Young investigators' grant)
- _id: 251D65D8-B435-11E9-9278-68D0E5697425
grant_number: '24210'
name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems
at the Single-Cell Level (DOC Fellowship)
publication: Nature Ecology and Evolution
publication_status: published
publisher: Springer Nature
publist_id: '7364'
quality_controlled: '1'
related_material:
record:
- id: '202'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Phage-host population dynamics promotes prophage acquisition in bacteria with
innate immunity
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 2
year: '2018'
...
---
_id: '735'
abstract:
- lang: eng
text: Cell-cell contact formation constitutes an essential step in evolution, leading
to the differentiation of specialized cell types. However, remarkably little is
known about whether and how the interplay between contact formation and fate specification
affects development. Here, we identify a positive feedback loop between cell-cell
contact duration, morphogen signaling, and mesendoderm cell-fate specification
during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance
the competence of prechordal plate (ppl) progenitor cells to respond to Nodal
signaling, required for ppl cell-fate specification. We further show that Nodal
signaling promotes ppl cell-cell contact duration, generating a positive feedback
loop between ppl cell-cell contact duration and cell-fate specification. Finally,
by combining mathematical modeling and experimentation, we show that this feedback
determines whether anterior axial mesendoderm cells become ppl or, instead, turn
into endoderm. Thus, the interdependent activities of cell-cell signaling and
contact formation control fate diversification within the developing embryo.
article_processing_charge: No
author:
- first_name: Vanessa
full_name: Barone, Vanessa
id: 419EECCC-F248-11E8-B48F-1D18A9856A87
last_name: Barone
orcid: 0000-0003-2676-3367
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Gabriel
full_name: Krens, Gabriel
id: 2B819732-F248-11E8-B48F-1D18A9856A87
last_name: Krens
orcid: 0000-0003-4761-5996
- first_name: Saurabh
full_name: Pradhan, Saurabh
last_name: Pradhan
- first_name: Shayan
full_name: Shamipour, Shayan
id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
last_name: Shamipour
- first_name: Keisuke
full_name: Sako, Keisuke
id: 3BED66BE-F248-11E8-B48F-1D18A9856A87
last_name: Sako
orcid: 0000-0002-6453-8075
- first_name: Mateusz K
full_name: Sikora, Mateusz K
id: 2F74BCDE-F248-11E8-B48F-1D18A9856A87
last_name: Sikora
- 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: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
citation:
ama: Barone V, Lang M, Krens G, et al. An effective feedback loop between cell-cell
contact duration and morphogen signaling determines cell fate. Developmental
Cell. 2017;43(2):198-211. doi:10.1016/j.devcel.2017.09.014
apa: Barone, V., Lang, M., Krens, G., Pradhan, S., Shamipour, S., Sako, K., … Heisenberg,
C.-P. J. (2017). An effective feedback loop between cell-cell contact duration
and morphogen signaling determines cell fate. Developmental Cell. Cell
Press. https://doi.org/10.1016/j.devcel.2017.09.014
chicago: Barone, Vanessa, Moritz Lang, Gabriel Krens, Saurabh Pradhan, Shayan Shamipour,
Keisuke Sako, Mateusz K Sikora, Calin C Guet, and Carl-Philipp J Heisenberg. “An
Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling
Determines Cell Fate.” Developmental Cell. Cell Press, 2017. https://doi.org/10.1016/j.devcel.2017.09.014.
ieee: V. Barone et al., “An effective feedback loop between cell-cell contact
duration and morphogen signaling determines cell fate,” Developmental Cell,
vol. 43, no. 2. Cell Press, pp. 198–211, 2017.
ista: Barone V, Lang M, Krens G, Pradhan S, Shamipour S, Sako K, Sikora MK, Guet
CC, Heisenberg C-PJ. 2017. An effective feedback loop between cell-cell contact
duration and morphogen signaling determines cell fate. Developmental Cell. 43(2),
198–211.
mla: Barone, Vanessa, et al. “An Effective Feedback Loop between Cell-Cell Contact
Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell,
vol. 43, no. 2, Cell Press, 2017, pp. 198–211, doi:10.1016/j.devcel.2017.09.014.
short: V. Barone, M. Lang, G. Krens, S. Pradhan, S. Shamipour, K. Sako, M.K. Sikora,
C.C. Guet, C.-P.J. Heisenberg, Developmental Cell 43 (2017) 198–211.
date_created: 2018-12-11T11:48:13Z
date_published: 2017-10-23T00:00:00Z
date_updated: 2024-03-25T23:30:21Z
day: '23'
department:
- _id: CaHe
- _id: CaGu
- _id: GaTk
doi: 10.1016/j.devcel.2017.09.014
ec_funded: 1
external_id:
isi:
- '000413443700011'
intvolume: ' 43'
isi: 1
issue: '2'
language:
- iso: eng
month: '10'
oa_version: None
page: 198 - 211
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 252DD2A6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I2058
name: 'Cell segregation in gastrulation: the role of cell fate specification'
publication: Developmental Cell
publication_identifier:
issn:
- '15345807'
publication_status: published
publisher: Cell Press
publist_id: '6934'
quality_controlled: '1'
related_material:
record:
- id: '961'
relation: dissertation_contains
status: public
- id: '8350'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: An effective feedback loop between cell-cell contact duration and morphogen
signaling determines cell fate
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 43
year: '2017'
...
---
_id: '1007'
abstract:
- lang: eng
text: 'A nonlinear system possesses an invariance with respect to a set of transformations
if its output dynamics remain invariant when transforming the input, and adjusting
the initial condition accordingly. Most research has focused on invariances with
respect to time-independent pointwise transformations like translational-invariance
(u(t) -> u(t) + p, p in R) or scale-invariance (u(t) -> pu(t), p in R>0).
In this article, we introduce the concept of s0-invariances with respect to continuous
input transformations exponentially growing/decaying over time. We show that s0-invariant
systems not only encompass linear time-invariant (LTI) systems with transfer functions
having an irreducible zero at s0 in R, but also that the input/output relationship
of nonlinear s0-invariant systems possesses properties well known from their linear
counterparts. Furthermore, we extend the concept of s0-invariances to second-
and higher-order s0-invariances, corresponding to invariances with respect to
transformations of the time-derivatives of the input, and encompassing LTI systems
with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant
systems realize – under mild conditions – nth-order nonlinear differential operators:
when excited by an input of a characteristic functional form, the system’s output
converges to a constant value only depending on the nth (nonlinear) derivative
of the input.'
article_processing_charge: Yes (in subscription journal)
author:
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Eduardo
full_name: Sontag, Eduardo
last_name: Sontag
citation:
ama: Lang M, Sontag E. Zeros of nonlinear systems with input invariances. Automatica.
2017;81C:46-55. doi:10.1016/j.automatica.2017.03.030
apa: Lang, M., & Sontag, E. (2017). Zeros of nonlinear systems with input invariances.
Automatica. International Federation of Automatic Control. https://doi.org/10.1016/j.automatica.2017.03.030
chicago: Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input
Invariances.” Automatica. International Federation of Automatic Control,
2017. https://doi.org/10.1016/j.automatica.2017.03.030.
ieee: M. Lang and E. Sontag, “Zeros of nonlinear systems with input invariances,”
Automatica, vol. 81C. International Federation of Automatic Control, pp.
46–55, 2017.
ista: Lang M, Sontag E. 2017. Zeros of nonlinear systems with input invariances.
Automatica. 81C, 46–55.
mla: Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.”
Automatica, vol. 81C, International Federation of Automatic Control, 2017,
pp. 46–55, doi:10.1016/j.automatica.2017.03.030.
short: M. Lang, E. Sontag, Automatica 81C (2017) 46–55.
date_created: 2018-12-11T11:49:39Z
date_published: 2017-06-01T00:00:00Z
date_updated: 2023-10-17T08:51:18Z
day: '01'
ddc:
- '000'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1016/j.automatica.2017.03.030
ec_funded: 1
external_id:
isi:
- '000403513900006'
file:
- access_level: open_access
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:11:29Z
date_updated: 2018-12-12T10:11:29Z
file_id: '4884'
file_name: IST-2017-813-v1+1_ZerosOfNonlinearSystems.pdf
file_size: 1401954
relation: main_file
file_date_updated: 2018-12-12T10:11:29Z
has_accepted_license: '1'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 46 - 55
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Automatica
publication_identifier:
issn:
- 0005-1098
publication_status: published
publisher: International Federation of Automatic Control
publist_id: '6391'
pubrep_id: '813'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Zeros of nonlinear systems with input invariances
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: 81C
year: '2017'
...
---
_id: '1170'
abstract:
- lang: eng
text: The increasing complexity of dynamic models in systems and synthetic biology
poses computational challenges especially for the identification of model parameters.
While modularization of the corresponding optimization problems could help reduce
the “curse of dimensionality,” abundant feedback and crosstalk mechanisms prohibit
a simple decomposition of most biomolecular networks into subnetworks, or modules.
Drawing on ideas from network modularization and multiple-shooting optimization,
we present here a modular parameter identification approach that explicitly allows
for such interdependencies. Interfaces between our modules are given by the experimentally
measured molecular species. This definition allows deriving good (initial) estimates
for the inter-module communication directly from the experimental data. Given
these estimates, the states and parameter sensitivities of different modules can
be integrated independently. To achieve consistency between modules, we iteratively
adjust the estimates for inter-module communication while optimizing the parameters.
After convergence to an optimal parameter set---but not during earlier iterations---the
intermodule communication as well as the individual modules\' state dynamics agree
with the dynamics of the nonmodularized network. Our modular parameter identification
approach allows for easy parallelization; it can reduce the computational complexity
for larger networks and decrease the probability to converge to suboptimal local
minima. We demonstrate the algorithm\'s performance in parameter estimation for
two biomolecular networks, a synthetic genetic oscillator and a mammalian signaling
pathway.
author:
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Jörg
full_name: Stelling, Jörg
last_name: Stelling
citation:
ama: Lang M, Stelling J. Modular parameter identification of biomolecular networks.
SIAM Journal on Scientific Computing. 2016;38(6):B988-B1008. doi:10.1137/15M103306X
apa: Lang, M., & Stelling, J. (2016). Modular parameter identification of biomolecular
networks. SIAM Journal on Scientific Computing. Society for Industrial
and Applied Mathematics . https://doi.org/10.1137/15M103306X
chicago: Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular
Networks.” SIAM Journal on Scientific Computing. Society for Industrial
and Applied Mathematics , 2016. https://doi.org/10.1137/15M103306X.
ieee: M. Lang and J. Stelling, “Modular parameter identification of biomolecular
networks,” SIAM Journal on Scientific Computing, vol. 38, no. 6. Society
for Industrial and Applied Mathematics , pp. B988–B1008, 2016.
ista: Lang M, Stelling J. 2016. Modular parameter identification of biomolecular
networks. SIAM Journal on Scientific Computing. 38(6), B988–B1008.
mla: Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular
Networks.” SIAM Journal on Scientific Computing, vol. 38, no. 6, Society
for Industrial and Applied Mathematics , 2016, pp. B988–1008, doi:10.1137/15M103306X.
short: M. Lang, J. Stelling, SIAM Journal on Scientific Computing 38 (2016) B988–B1008.
date_created: 2018-12-11T11:50:31Z
date_published: 2016-11-15T00:00:00Z
date_updated: 2021-01-12T06:48:49Z
day: '15'
ddc:
- '003'
- '518'
- '570'
- '621'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1137/15M103306X
file:
- access_level: local
checksum: 781bc3ffd30b2dd65b7727c5a285fc78
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:14:41Z
date_updated: 2020-07-14T12:44:37Z
file_id: '5095'
file_name: IST-2017-811-v1+1_modular_parameter_identification.pdf
file_size: 871964
relation: main_file
file_date_updated: 2020-07-14T12:44:37Z
has_accepted_license: '1'
intvolume: ' 38'
issue: '6'
language:
- iso: eng
month: '11'
oa_version: Submitted Version
page: B988 - B1008
publication: SIAM Journal on Scientific Computing
publication_status: published
publisher: 'Society for Industrial and Applied Mathematics '
publist_id: '6186'
pubrep_id: '811'
quality_controlled: '1'
scopus_import: 1
status: public
title: Modular parameter identification of biomolecular networks
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 38
year: '2016'
...
---
_id: '1320'
abstract:
- lang: eng
text: 'In recent years, several biomolecular systems have been shown to be scale-invariant
(SI), i.e. to show the same output dynamics when exposed to geometrically scaled
input signals (u → pu, p > 0) after pre-adaptation to accordingly scaled constant
inputs. In this article, we show that SI systems-as well as systems invariant
with respect to other input transformations-can realize nonlinear differential
operators: when excited by inputs obeying functional forms characteristic for
a given class of invariant systems, the systems'' outputs converge to constant
values directly quantifying the speed of the input.'
acknowledgement: 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° [291734]. Work supported
in part by grants AFOSR FA9550-14-1-0060 and NIH 1R01GM100473.
article_number: '7526722'
author:
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Eduardo
full_name: Sontag, Eduardo
last_name: Sontag
citation:
ama: 'Lang M, Sontag E. Scale-invariant systems realize nonlinear differential operators.
In: Vol 2016-July. IEEE; 2016. doi:10.1109/ACC.2016.7526722'
apa: 'Lang, M., & Sontag, E. (2016). Scale-invariant systems realize nonlinear
differential operators (Vol. 2016–July). Presented at the ACC: American Control
Conference, Boston, MA, USA: IEEE. https://doi.org/10.1109/ACC.2016.7526722'
chicago: Lang, Moritz, and Eduardo Sontag. “Scale-Invariant Systems Realize Nonlinear
Differential Operators,” Vol. 2016–July. IEEE, 2016. https://doi.org/10.1109/ACC.2016.7526722.
ieee: 'M. Lang and E. Sontag, “Scale-invariant systems realize nonlinear differential
operators,” presented at the ACC: American Control Conference, Boston, MA, USA,
2016, vol. 2016–July.'
ista: 'Lang M, Sontag E. 2016. Scale-invariant systems realize nonlinear differential
operators. ACC: American Control Conference vol. 2016–July, 7526722.'
mla: Lang, Moritz, and Eduardo Sontag. Scale-Invariant Systems Realize Nonlinear
Differential Operators. Vol. 2016–July, 7526722, IEEE, 2016, doi:10.1109/ACC.2016.7526722.
short: M. Lang, E. Sontag, in:, IEEE, 2016.
conference:
end_date: 2016-07-08
location: Boston, MA, USA
name: 'ACC: American Control Conference'
start_date: 2016-07-06
date_created: 2018-12-11T11:51:21Z
date_published: 2016-07-28T00:00:00Z
date_updated: 2021-01-12T06:49:51Z
day: '28'
ddc:
- '003'
- '621'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1109/ACC.2016.7526722
ec_funded: 1
file:
- access_level: local
checksum: 7219432b43defc62a0d45f48d4ce6a19
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:16:17Z
date_updated: 2020-07-14T12:44:43Z
file_id: '5203'
file_name: IST-2017-810-v1+1_root.pdf
file_size: 539166
relation: main_file
file_date_updated: 2020-07-14T12:44:43Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa_version: Preprint
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication_status: published
publisher: IEEE
publist_id: '5950'
pubrep_id: '810'
quality_controlled: '1'
scopus_import: 1
status: public
title: Scale-invariant systems realize nonlinear differential operators
type: conference
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 2016-July
year: '2016'
...
---
_id: '1008'
abstract:
- lang: eng
text: Feedback loops in biological networks, among others, enable differentiation
and cell cycle progression, and increase robustness in signal transduction. In
natural networks, feedback loops are often complex and intertwined, making it
challenging to identify which loops are mainly responsible for an observed behavior.
However, minimal synthetic replicas could allow for such identification. Here,
we engineered a synthetic permease-inducer-repressor system in Saccharomyces cerevisiae
to analyze if a transport-mediated positive feedback loop could be a core mechanism
for the switch-like behavior in the regulation of metabolic gene networks such
as the S. cerevisiae GAL system or the Escherichia coli lac operon. We characterized
the synthetic circuit using deterministic and stochastic mathematical models.
Similar to its natural counterparts, our synthetic system shows bistable and hysteretic
behavior, and the inducer concentration range for bistability as well as the switching
rates between the two stable states depend on the repressor concentration. Our
results indicate that a generic permease–inducer–repressor circuit with a single
feedback loop is sufficient to explain the experimentally observed bistable behavior
of the natural systems. We anticipate that the approach of reimplementing natural
systems with orthogonal parts to identify crucial network components is applicable
to other natural systems such as signaling pathways.
acknowledgement: We thank Julio Polaina (Instituto de Agroqu ı ́ mica y Tecnolog ı
́ a de Alimentos, C.S.I.C., Paterna, Spain) for the gift of plasmid pMR4, Gregor
W. Schmidt for provision of and support with the micro fl uidic device, Markus Du
̈ rr for the cell tracking R script, and Lukas Widmer for the script for MEIGO using
“ parfor ” in MATLAB. We acknowledge the members of the Stelling group for discussions,
comments, and support.
author:
- first_name: Robert
full_name: Gnügge, Robert
last_name: Gnügge
- first_name: Lekshmi
full_name: Dharmarajan, Lekshmi
last_name: Dharmarajan
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Jörg
full_name: Stelling, Jörg
last_name: Stelling
citation:
ama: Gnügge R, Dharmarajan L, Lang M, Stelling J. An orthogonal permease–inducer–repressor
feedback loop shows bistability. ACS Synthetic Biology. 2016;5(10):1098-1107.
doi:10.1021/acssynbio.6b00013
apa: Gnügge, R., Dharmarajan, L., Lang, M., & Stelling, J. (2016). An orthogonal
permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology.
American Chemical Society. https://doi.org/10.1021/acssynbio.6b00013
chicago: Gnügge, Robert, Lekshmi Dharmarajan, Moritz Lang, and Jörg Stelling. “An
Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS
Synthetic Biology. American Chemical Society, 2016. https://doi.org/10.1021/acssynbio.6b00013.
ieee: R. Gnügge, L. Dharmarajan, M. Lang, and J. Stelling, “An orthogonal permease–inducer–repressor
feedback loop shows bistability,” ACS Synthetic Biology, vol. 5, no. 10.
American Chemical Society, pp. 1098–1107, 2016.
ista: Gnügge R, Dharmarajan L, Lang M, Stelling J. 2016. An orthogonal permease–inducer–repressor
feedback loop shows bistability. ACS Synthetic Biology. 5(10), 1098–1107.
mla: Gnügge, Robert, et al. “An Orthogonal Permease–Inducer–Repressor Feedback Loop
Shows Bistability.” ACS Synthetic Biology, vol. 5, no. 10, American Chemical
Society, 2016, pp. 1098–107, doi:10.1021/acssynbio.6b00013.
short: R. Gnügge, L. Dharmarajan, M. Lang, J. Stelling, ACS Synthetic Biology 5
(2016) 1098–1107.
date_created: 2018-12-11T11:49:40Z
date_published: 2016-05-05T00:00:00Z
date_updated: 2021-01-12T06:47:37Z
day: '05'
department:
- _id: CaGu
doi: 10.1021/acssynbio.6b00013
intvolume: ' 5'
issue: '10'
language:
- iso: eng
month: '05'
oa_version: None
page: 1098 - 1107
publication: ACS Synthetic Biology
publication_status: published
publisher: American Chemical Society
publist_id: '6390'
quality_controlled: '1'
status: public
title: An orthogonal permease–inducer–repressor feedback loop shows bistability
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2016'
...