---
_id: '1823'
abstract:
- lang: eng
text: Abstract Drug combinations are increasingly important in disease treatments,
for combating drug resistance, and for elucidating fundamental relationships in
cell physiology. When drugs are combined, their individual effects on cells may
be amplified or weakened. Such drug interactions are crucial for treatment efficacy,
but their underlying mechanisms remain largely unknown. To uncover the causes
of drug interactions, we developed a systematic approach based on precise quantification
of the individual and joint effects of antibiotics on growth of genome-wide Escherichia
coli gene deletion strains. We found that drug interactions between antibiotics
representing the main modes of action are highly robust to genetic perturbation.
This robustness is encapsulated in a general principle of bacterial growth, which
enables the quantitative prediction of mutant growth rates under drug combinations.
Rare violations of this principle exposed recurring cellular functions controlling
drug interactions. In particular, we found that polysaccharide and ATP synthesis
control multiple drug interactions with previously unexplained mechanisms, and
small molecule adjuvants targeting these functions synthetically reshape drug
interactions in predictable ways. These results provide a new conceptual framework
for the design of multidrug combinations and suggest that there are universal
mechanisms at the heart of most drug interactions. Synopsis A general principle
of bacterial growth enables the prediction of mutant growth rates under drug combinations.
Rare violations of this principle expose cellular functions that control drug
interactions and can be targeted by small molecules to alter drug interactions
in predictable ways. Drug interactions between antibiotics are highly robust to
genetic perturbations. A general principle of bacterial growth enables the prediction
of mutant growth rates under drug combinations. Rare violations of this principle
expose cellular functions that control drug interactions. Diverse drug interactions
are controlled by recurring cellular functions, including LPS synthesis and ATP
synthesis. A general principle of bacterial growth enables the prediction of mutant
growth rates under drug combinations. Rare violations of this principle expose
cellular functions that control drug interactions and can be targeted by small
molecules to alter drug interactions in predictable ways.
article_number: '807'
author:
- first_name: Guillaume
full_name: Chevereau, Guillaume
id: 424D78A0-F248-11E8-B48F-1D18A9856A87
last_name: Chevereau
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Chevereau G, Bollenbach MT. Systematic discovery of drug interaction mechanisms.
Molecular Systems Biology. 2015;11(4). doi:10.15252/msb.20156098
apa: Chevereau, G., & Bollenbach, M. T. (2015). Systematic discovery of drug
interaction mechanisms. Molecular Systems Biology. Nature Publishing Group.
https://doi.org/10.15252/msb.20156098
chicago: Chevereau, Guillaume, and Mark Tobias Bollenbach. “Systematic Discovery
of Drug Interaction Mechanisms.” Molecular Systems Biology. Nature Publishing
Group, 2015. https://doi.org/10.15252/msb.20156098.
ieee: G. Chevereau and M. T. Bollenbach, “Systematic discovery of drug interaction
mechanisms,” Molecular Systems Biology, vol. 11, no. 4. Nature Publishing
Group, 2015.
ista: Chevereau G, Bollenbach MT. 2015. Systematic discovery of drug interaction
mechanisms. Molecular Systems Biology. 11(4), 807.
mla: Chevereau, Guillaume, and Mark Tobias Bollenbach. “Systematic Discovery of
Drug Interaction Mechanisms.” Molecular Systems Biology, vol. 11, no. 4,
807, Nature Publishing Group, 2015, doi:10.15252/msb.20156098.
short: G. Chevereau, M.T. Bollenbach, Molecular Systems Biology 11 (2015).
date_created: 2018-12-11T11:54:12Z
date_published: 2015-04-01T00:00:00Z
date_updated: 2021-01-12T06:53:26Z
day: '01'
ddc:
- '570'
department:
- _id: ToBo
doi: 10.15252/msb.20156098
ec_funded: 1
file:
- access_level: open_access
checksum: 4289b518fbe2166682fb1a1ef9b405f3
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:14:34Z
date_updated: 2020-07-14T12:45:17Z
file_id: '5087'
file_name: IST-2015-395-v1+1_807.full.pdf
file_size: 1273573
relation: main_file
file_date_updated: 2020-07-14T12:45:17Z
has_accepted_license: '1'
intvolume: ' 11'
issue: '4'
language:
- iso: eng
month: '04'
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: 25EB3A80-B435-11E9-9278-68D0E5697425
grant_number: RGP0042/2013
name: Revealing the fundamental limits of cell growth
- _id: 25E83C2C-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '303507'
name: Optimality principles in responses to antibiotics
publication: Molecular Systems Biology
publication_status: published
publisher: Nature Publishing Group
publist_id: '5283'
pubrep_id: '395'
quality_controlled: '1'
scopus_import: 1
status: public
title: Systematic discovery of drug interaction mechanisms
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: 11
year: '2015'
...
---
_id: '1824'
abstract:
- lang: eng
text: Condensation phenomena arise through a collective behaviour of particles.
They are observed in both classical and quantum systems, ranging from the formation
of traffic jams in mass transport models to the macroscopic occupation of the
energetic ground state in ultra-cold bosonic gases (Bose-Einstein condensation).
Recently, it has been shown that a driven and dissipative system of bosons may
form multiple condensates. Which states become the condensates has, however, remained
elusive thus far. The dynamics of this condensation are described by coupled birth-death
processes, which also occur in evolutionary game theory. Here we apply concepts
from evolutionary game theory to explain the formation of multiple condensates
in such driven-dissipative bosonic systems. We show that the vanishing of relative
entropy production determines their selection. The condensation proceeds exponentially
fast, but the system never comes to rest. Instead, the occupation numbers of condensates
may oscillate, as we demonstrate for a rock-paper-scissors game of condensates.
article_number: '6977'
author:
- first_name: Johannes
full_name: Knebel, Johannes
last_name: Knebel
- first_name: Markus
full_name: Weber, Markus
last_name: Weber
- first_name: Torben H
full_name: Krüger, Torben H
id: 3020C786-F248-11E8-B48F-1D18A9856A87
last_name: Krüger
orcid: 0000-0002-4821-3297
- first_name: Erwin
full_name: Frey, Erwin
last_name: Frey
citation:
ama: Knebel J, Weber M, Krüger TH, Frey E. Evolutionary games of condensates in
coupled birth-death processes. Nature Communications. 2015;6. doi:10.1038/ncomms7977
apa: Knebel, J., Weber, M., Krüger, T. H., & Frey, E. (2015). Evolutionary games
of condensates in coupled birth-death processes. Nature Communications.
Nature Publishing Group. https://doi.org/10.1038/ncomms7977
chicago: Knebel, Johannes, Markus Weber, Torben H Krüger, and Erwin Frey. “Evolutionary
Games of Condensates in Coupled Birth-Death Processes.” Nature Communications.
Nature Publishing Group, 2015. https://doi.org/10.1038/ncomms7977.
ieee: J. Knebel, M. Weber, T. H. Krüger, and E. Frey, “Evolutionary games of condensates
in coupled birth-death processes,” Nature Communications, vol. 6. Nature
Publishing Group, 2015.
ista: Knebel J, Weber M, Krüger TH, Frey E. 2015. Evolutionary games of condensates
in coupled birth-death processes. Nature Communications. 6, 6977.
mla: Knebel, Johannes, et al. “Evolutionary Games of Condensates in Coupled Birth-Death
Processes.” Nature Communications, vol. 6, 6977, Nature Publishing Group,
2015, doi:10.1038/ncomms7977.
short: J. Knebel, M. Weber, T.H. Krüger, E. Frey, Nature Communications 6 (2015).
date_created: 2018-12-11T11:54:13Z
date_published: 2015-04-24T00:00:00Z
date_updated: 2021-01-12T06:53:26Z
day: '24'
ddc:
- '530'
department:
- _id: LaEr
doi: 10.1038/ncomms7977
file:
- access_level: open_access
checksum: c4cffb5c8b245e658a34eac71a03e7cc
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:16:54Z
date_updated: 2020-07-14T12:45:17Z
file_id: '5245'
file_name: IST-2016-451-v1+1_ncomms7977.pdf
file_size: 1151501
relation: main_file
file_date_updated: 2020-07-14T12:45:17Z
has_accepted_license: '1'
intvolume: ' 6'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_status: published
publisher: Nature Publishing Group
publist_id: '5282'
pubrep_id: '451'
quality_controlled: '1'
scopus_import: 1
status: public
title: Evolutionary games of condensates in coupled birth-death processes
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: 6
year: '2015'
...
---
_id: '1831'
abstract:
- lang: eng
text: This paper introduces a theme issue presenting the latest developments in
research on the impacts of sociality on health and fitness. The articles that
follow cover research on societies ranging from insects to humans. Variation in
measures of fitness (i.e. survival and reproduction) has been linked to various
aspects of sociality in humans and animals alike, and variability in individual
health and condition has been recognized as a key mediator of these relationships.
Viewed from a broad evolutionary perspective, the evolutionary transitions from
a solitary lifestyle to group living have resulted in several new health-related
costs and benefits of sociality. Social transmission of parasites within groups
represents a major cost of group living, but some behavioural mechanisms, such
as grooming, have evolved repeatedly to reduce this cost. Group living also has
created novel costs in terms of altered susceptibility to infectious and non-infectious
disease as a result of the unavoidable physiological consequences of social competition
and integration, which are partly alleviated by social buffering in some vertebrates.
Here, we define the relevant aspects of sociality, summarize their health-related
costs and benefits, and discuss possible fitness measures in different study systems.
Given the pervasive effects of social factors on health and fitness, we propose
a synthesis of existing conceptual approaches in disease ecology, ecological immunology
and behavioural neurosciences by adding sociality as a key factor, with the goal
to generate a broader framework for organismal integration of health-related research.
acknowledgement: We thank the German Research Foundation (DFG), the Ministry of Science
and Culture of Lower-Saxony (MWK Hannover) and the German Primate Centre (DPZ) for
their support of the 9. Göttinger Freilandtage in 2013, a conference at which most
contributions to this issue were first presented, the referees of the contributions
to this issue for their constructive comments, Meggan Craft for comments, and Helen
Eaton for her support in producing this theme issue.
article_number: '20140116'
author:
- first_name: Peter
full_name: Kappeler, Peter
last_name: Kappeler
- first_name: Sylvia
full_name: Cremer, Sylvia
id: 2F64EC8C-F248-11E8-B48F-1D18A9856A87
last_name: Cremer
orcid: 0000-0002-2193-3868
- first_name: Charles
full_name: Nunn, Charles
last_name: Nunn
citation:
ama: 'Kappeler P, Cremer S, Nunn C. Sociality and health: Impacts of sociality on
disease susceptibility and transmission in animal and human societies. Philosophical
Transactions of the Royal Society of London Series B, Biological Sciences.
2015;370(1669). doi:10.1098/rstb.2014.0116'
apa: 'Kappeler, P., Cremer, S., & Nunn, C. (2015). Sociality and health: Impacts
of sociality on disease susceptibility and transmission in animal and human societies.
Philosophical Transactions of the Royal Society of London. Series B, Biological
Sciences. Royal Society. https://doi.org/10.1098/rstb.2014.0116'
chicago: 'Kappeler, Peter, Sylvia Cremer, and Charles Nunn. “Sociality and Health:
Impacts of Sociality on Disease Susceptibility and Transmission in Animal and
Human Societies.” Philosophical Transactions of the Royal Society of London.
Series B, Biological Sciences. Royal Society, 2015. https://doi.org/10.1098/rstb.2014.0116.'
ieee: 'P. Kappeler, S. Cremer, and C. Nunn, “Sociality and health: Impacts of sociality
on disease susceptibility and transmission in animal and human societies,” Philosophical
Transactions of the Royal Society of London. Series B, Biological Sciences,
vol. 370, no. 1669. Royal Society, 2015.'
ista: 'Kappeler P, Cremer S, Nunn C. 2015. Sociality and health: Impacts of sociality
on disease susceptibility and transmission in animal and human societies. Philosophical
Transactions of the Royal Society of London. Series B, Biological Sciences. 370(1669),
20140116.'
mla: 'Kappeler, Peter, et al. “Sociality and Health: Impacts of Sociality on Disease
Susceptibility and Transmission in Animal and Human Societies.” Philosophical
Transactions of the Royal Society of London. Series B, Biological Sciences,
vol. 370, no. 1669, 20140116, Royal Society, 2015, doi:10.1098/rstb.2014.0116.'
short: P. Kappeler, S. Cremer, C. Nunn, Philosophical Transactions of the Royal
Society of London. Series B, Biological Sciences 370 (2015).
date_created: 2018-12-11T11:54:15Z
date_published: 2015-05-01T00:00:00Z
date_updated: 2021-01-12T06:53:29Z
day: '01'
department:
- _id: SyCr
doi: 10.1098/rstb.2014.0116
external_id:
pmid:
- '25870402'
intvolume: ' 370'
issue: '1669'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410382/
month: '05'
oa: 1
oa_version: Submitted Version
pmid: 1
publication: Philosophical Transactions of the Royal Society of London. Series B,
Biological Sciences
publication_status: published
publisher: Royal Society
publist_id: '5272'
quality_controlled: '1'
scopus_import: 1
status: public
title: 'Sociality and health: Impacts of sociality on disease susceptibility and transmission
in animal and human societies'
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 370
year: '2015'
...
---
_id: '1828'
abstract:
- lang: eng
text: We construct a non-linear Markov process connected with a biological model
of a bacterial genome recombination. The description of invariant measures of
this process gives us the solution of one problem in elementary probability theory.
article_processing_charge: No
author:
- first_name: Arseniy
full_name: Akopyan, Arseniy
id: 430D2C90-F248-11E8-B48F-1D18A9856A87
last_name: Akopyan
orcid: 0000-0002-2548-617X
- first_name: Sergey
full_name: Pirogov, Sergey
last_name: Pirogov
- first_name: Aleksandr
full_name: Rybko, Aleksandr
last_name: Rybko
citation:
ama: Akopyan A, Pirogov S, Rybko A. Invariant measures of genetic recombination
process. Journal of Statistical Physics. 2015;160(1):163-167. doi:10.1007/s10955-015-1238-5
apa: Akopyan, A., Pirogov, S., & Rybko, A. (2015). Invariant measures of genetic
recombination process. Journal of Statistical Physics. Springer. https://doi.org/10.1007/s10955-015-1238-5
chicago: Akopyan, Arseniy, Sergey Pirogov, and Aleksandr Rybko. “Invariant Measures
of Genetic Recombination Process.” Journal of Statistical Physics. Springer,
2015. https://doi.org/10.1007/s10955-015-1238-5.
ieee: A. Akopyan, S. Pirogov, and A. Rybko, “Invariant measures of genetic recombination
process,” Journal of Statistical Physics, vol. 160, no. 1. Springer, pp.
163–167, 2015.
ista: Akopyan A, Pirogov S, Rybko A. 2015. Invariant measures of genetic recombination
process. Journal of Statistical Physics. 160(1), 163–167.
mla: Akopyan, Arseniy, et al. “Invariant Measures of Genetic Recombination Process.”
Journal of Statistical Physics, vol. 160, no. 1, Springer, 2015, pp. 163–67,
doi:10.1007/s10955-015-1238-5.
short: A. Akopyan, S. Pirogov, A. Rybko, Journal of Statistical Physics 160 (2015)
163–167.
date_created: 2018-12-11T11:54:14Z
date_published: 2015-07-01T00:00:00Z
date_updated: 2021-01-12T06:53:28Z
day: '01'
department:
- _id: HeEd
doi: 10.1007/s10955-015-1238-5
ec_funded: 1
intvolume: ' 160'
issue: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: arxiv.org/abs/1406.5313
month: '07'
oa: 1
oa_version: Preprint
page: 163 - 167
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Journal of Statistical Physics
publication_status: published
publisher: Springer
publist_id: '5276'
quality_controlled: '1'
scopus_import: 1
status: public
title: Invariant measures of genetic recombination process
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 160
year: '2015'
...
---
_id: '1836'
abstract:
- lang: eng
text: In the standard framework for worst-case execution time (WCET) analysis of
programs, the main data structure is a single instance of integer linear programming
(ILP) that represents the whole program. The instance of this NP-hard problem
must be solved to find an estimate forWCET, and it must be refined if the estimate
is not tight.We propose a new framework for WCET analysis, based on abstract segment
trees (ASTs) as the main data structure. The ASTs have two advantages. First,
they allow computing WCET by solving a number of independent small ILP instances.
Second, ASTs store more expressive constraints, thus enabling a more efficient
and precise refinement procedure. In order to realize our framework algorithmically,
we develop an algorithm for WCET estimation on ASTs, and we develop an interpolation-based
counterexample-guided refinement scheme for ASTs. Furthermore, we extend our framework
to obtain parametric estimates of WCET. We experimentally evaluate our approach
on a set of examples from WCET benchmark suites and linear-algebra packages. We
show that our analysis, with comparable effort, provides WCET estimates that in
many cases significantly improve those computed by existing tools.
alternative_title:
- LNCS
author:
- first_name: Pavol
full_name: Cerny, Pavol
id: 4DCBEFFE-F248-11E8-B48F-1D18A9856A87
last_name: Cerny
- first_name: Thomas A
full_name: Henzinger, Thomas A
id: 40876CD8-F248-11E8-B48F-1D18A9856A87
last_name: Henzinger
orcid: 0000−0002−2985−7724
- first_name: Laura
full_name: Kovács, Laura
last_name: Kovács
- first_name: Arjun
full_name: Radhakrishna, Arjun
id: 3B51CAC4-F248-11E8-B48F-1D18A9856A87
last_name: Radhakrishna
- first_name: Jakob
full_name: Zwirchmayr, Jakob
last_name: Zwirchmayr
citation:
ama: Cerny P, Henzinger TA, Kovács L, Radhakrishna A, Zwirchmayr J. Segment abstraction
for worst-case execution time analysis. 2015;9032:105-131. doi:10.1007/978-3-662-46669-8_5
apa: 'Cerny, P., Henzinger, T. A., Kovács, L., Radhakrishna, A., & Zwirchmayr,
J. (2015). Segment abstraction for worst-case execution time analysis. Presented
at the ESOP: European Symposium on Programming, London, United Kingdom: Springer.
https://doi.org/10.1007/978-3-662-46669-8_5'
chicago: Cerny, Pavol, Thomas A Henzinger, Laura Kovács, Arjun Radhakrishna, and
Jakob Zwirchmayr. “Segment Abstraction for Worst-Case Execution Time Analysis.”
Lecture Notes in Computer Science. Springer, 2015. https://doi.org/10.1007/978-3-662-46669-8_5.
ieee: P. Cerny, T. A. Henzinger, L. Kovács, A. Radhakrishna, and J. Zwirchmayr,
“Segment abstraction for worst-case execution time analysis,” vol. 9032. Springer,
pp. 105–131, 2015.
ista: Cerny P, Henzinger TA, Kovács L, Radhakrishna A, Zwirchmayr J. 2015. Segment
abstraction for worst-case execution time analysis. 9032, 105–131.
mla: Cerny, Pavol, et al. Segment Abstraction for Worst-Case Execution Time Analysis.
Vol. 9032, Springer, 2015, pp. 105–31, doi:10.1007/978-3-662-46669-8_5.
short: P. Cerny, T.A. Henzinger, L. Kovács, A. Radhakrishna, J. Zwirchmayr, 9032
(2015) 105–131.
conference:
end_date: 2015-04-18
location: London, United Kingdom
name: 'ESOP: European Symposium on Programming'
start_date: 2015-04-11
date_created: 2018-12-11T11:54:16Z
date_published: 2015-04-01T00:00:00Z
date_updated: 2020-08-11T10:09:32Z
day: '01'
department:
- _id: ToHe
doi: 10.1007/978-3-662-46669-8_5
ec_funded: 1
intvolume: ' 9032'
language:
- iso: eng
month: '04'
oa_version: None
page: 105 - 131
project:
- _id: 25EE3708-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '267989'
name: Quantitative Reactive Modeling
- _id: 25832EC2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: S 11407_N23
name: Rigorous Systems Engineering
publication_status: published
publisher: Springer
publist_id: '5266'
quality_controlled: '1'
scopus_import: 1
series_title: Lecture Notes in Computer Science
status: public
title: Segment abstraction for worst-case execution time analysis
type: conference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9032
year: '2015'
...