---
_id: '862'
abstract:
- lang: eng
text: A long-standing controversy in evolutionary biology is whether or not evolving
lineages can cross valleys on the fitness landscape that correspond to low-fitness
genotypes, which can eventually enable them to reach isolated fitness peaks1-9.
Here we study the fitness landscapes traversed by switches between different AU
and GC Watson-Crick nucleotide pairs at complementary sites of mitochondrial transfer
RNA stem regions in 83 mammalian species. We find that such Watson-Crick switches
occur 30-40 times more slowly than pairs of neutral substitutions, and that alleles
corresponding to GU and AC non-Watson-Crick intermediate states segregate within
human populations at low frequencies, similar to those of non-synonymous alleles.
Substitutions leading to a Watson-Crick switch are strongly correlated, especially
in mitochondrial tRNAs encoded on the GT-nucleotide-rich strand of the mitochondrial
genome. Using these data we estimate that a typical Watson-Crick switch involves
crossing a fitness valley of a depth of about 10-3 or even about 10-2, with AC
intermediates being slightly more deleterious than GU intermediates. This compensatory
evolution must proceed through rare intermediate variants that never reach fixation.
The ubiquitous nature of compensatory evolution in mammalian mitochondrial tRNAs
and other molecules implies that simultaneous fixation of two alleles that are
individually deleterious may be a common phenomenon at the molecular level.
acknowledgement: We thank H. Innan, M. Laessig, R. Guigo, I. Povolotskaya, D. Ivankov
and M. Breen for thoughtful discussions and critical reading of the manuscript.
author:
- first_name: Margarita
full_name: Meer, Margarita V
last_name: Meer
- first_name: Alexey
full_name: Kondrashov, Alexey S
last_name: Kondrashov
- first_name: Yael
full_name: Artzy-Randrup, Yael
last_name: Artzy Randrup
- first_name: Fyodor
full_name: Fyodor Kondrashov
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
citation:
ama: Meer M, Kondrashov A, Artzy Randrup Y, Kondrashov F. Compensatory evolution
in mitochondrial tRNAs navigates valleys of low fitness. Nature. 2010;464(7286):279-282.
doi:10.1038/nature08691
apa: Meer, M., Kondrashov, A., Artzy Randrup, Y., & Kondrashov, F. (2010). Compensatory
evolution in mitochondrial tRNAs navigates valleys of low fitness. Nature.
Nature Publishing Group. https://doi.org/10.1038/nature08691
chicago: Meer, Margarita, Alexey Kondrashov, Yael Artzy Randrup, and Fyodor Kondrashov.
“Compensatory Evolution in Mitochondrial TRNAs Navigates Valleys of Low Fitness.”
Nature. Nature Publishing Group, 2010. https://doi.org/10.1038/nature08691.
ieee: M. Meer, A. Kondrashov, Y. Artzy Randrup, and F. Kondrashov, “Compensatory
evolution in mitochondrial tRNAs navigates valleys of low fitness,” Nature,
vol. 464, no. 7286. Nature Publishing Group, pp. 279–282, 2010.
ista: Meer M, Kondrashov A, Artzy Randrup Y, Kondrashov F. 2010. Compensatory evolution
in mitochondrial tRNAs navigates valleys of low fitness. Nature. 464(7286), 279–282.
mla: Meer, Margarita, et al. “Compensatory Evolution in Mitochondrial TRNAs Navigates
Valleys of Low Fitness.” Nature, vol. 464, no. 7286, Nature Publishing
Group, 2010, pp. 279–82, doi:10.1038/nature08691.
short: M. Meer, A. Kondrashov, Y. Artzy Randrup, F. Kondrashov, Nature 464 (2010)
279–282.
date_created: 2018-12-11T11:48:54Z
date_published: 2010-03-11T00:00:00Z
date_updated: 2021-01-12T08:20:20Z
day: '11'
doi: 10.1038/nature08691
extern: 1
intvolume: ' 464'
issue: '7286'
month: '03'
page: 279 - 282
publication: Nature
publication_status: published
publisher: Nature Publishing Group
publist_id: '6784'
quality_controlled: 0
status: public
title: Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness
type: journal_article
volume: 464
year: '2010'
...
---
_id: '872'
abstract:
- lang: eng
text: The rate of spontaneous mutation in natural populations is a fundamental parameter
for many evolutionary phenomena. Because the rate of mutation is generally low,
most of what is currently known about mutation has been obtained through indirect,
complex and imprecise methodological approaches. However, in the past few years
genome-wide sequencing of closely related individuals has made it possible to
estimate the rates of mutation directly at the level of the DNA, avoiding most
of the problems associated with using indirect methods. Here, we review the methods
used in the past with an emphasis on next generation sequencing, which may soon
make the accurate measurement of spontaneous mutation rates a matter of routine.
author:
- first_name: Fyodor
full_name: Fyodor Kondrashov
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
- first_name: Alexey
full_name: Kondrashov, Alexey S
last_name: Kondrashov
citation:
ama: Kondrashov F, Kondrashov A. Measurements of spontaneous rates of mutations
in the recent past and the near future. Philosophical Transactions of the Royal
Society of London Series B, Biological Sciences. 2010;365(1544):1169-1176.
doi:10.1098/rstb.2009.0286
apa: Kondrashov, F., & Kondrashov, A. (2010). Measurements of spontaneous rates
of mutations in the recent past and the near future. Philosophical Transactions
of the Royal Society of London. Series B, Biological Sciences. Royal Society,
The. https://doi.org/10.1098/rstb.2009.0286
chicago: Kondrashov, Fyodor, and Alexey Kondrashov. “Measurements of Spontaneous
Rates of Mutations in the Recent Past and the near Future.” Philosophical Transactions
of the Royal Society of London. Series B, Biological Sciences. Royal Society,
The, 2010. https://doi.org/10.1098/rstb.2009.0286.
ieee: F. Kondrashov and A. Kondrashov, “Measurements of spontaneous rates of mutations
in the recent past and the near future,” Philosophical Transactions of the
Royal Society of London. Series B, Biological Sciences, vol. 365, no. 1544.
Royal Society, The, pp. 1169–1176, 2010.
ista: Kondrashov F, Kondrashov A. 2010. Measurements of spontaneous rates of mutations
in the recent past and the near future. Philosophical Transactions of the Royal
Society of London. Series B, Biological Sciences. 365(1544), 1169–1176.
mla: Kondrashov, Fyodor, and Alexey Kondrashov. “Measurements of Spontaneous Rates
of Mutations in the Recent Past and the near Future.” Philosophical Transactions
of the Royal Society of London. Series B, Biological Sciences, vol. 365, no.
1544, Royal Society, The, 2010, pp. 1169–76, doi:10.1098/rstb.2009.0286.
short: F. Kondrashov, A. Kondrashov, Philosophical Transactions of the Royal Society
of London. Series B, Biological Sciences 365 (2010) 1169–1176.
date_created: 2018-12-11T11:48:57Z
date_published: 2010-04-27T00:00:00Z
date_updated: 2021-01-12T08:20:43Z
day: '27'
doi: 10.1098/rstb.2009.0286
extern: 1
intvolume: ' 365'
issue: '1544'
month: '04'
page: 1169 - 1176
publication: Philosophical Transactions of the Royal Society of London. Series B,
Biological Sciences
publication_status: published
publisher: Royal Society, The
publist_id: '6772'
quality_controlled: 0
status: public
title: Measurements of spontaneous rates of mutations in the recent past and the near
future
type: journal_article
volume: 365
year: '2010'
...
---
_id: '884'
abstract:
- lang: eng
text: 'Background: Divergence of two independently evolving sequences that originated
from a common ancestor can be described by two parameters, the asymptotic level
of divergence E and the rate r at which this level of divergence is approached.
Constant negative selection impedes allele replacements and, therefore, is routinely
assumed to decelerate sequence divergence. However, its impact on E and on r has
not been formally investigated.Results: Strong selection that favors only one
allele can make E arbitrarily small and r arbitrarily large. In contrast, in the
case of 4 possible alleles and equal mutation rates, the lowest value of r, attained
when two alleles confer equal fitnesses and the other two are strongly deleterious,
is only two times lower than its value under selective neutrality.Conclusions:
Constant selection can strongly constrain the level of sequence divergence, but
cannot reduce substantially the rate at which this level is approached. In particular,
under any constant selection the divergence of sequences that accumulated one
substitution per neutral site since their origin from the common ancestor must
already constitute at least one half of the asymptotic divergence at sites under
such selection.Reviewers: This article was reviewed by Drs. Nicolas Galtier, Sergei
Maslov, and Nick Grishin.'
author:
- first_name: Alexey
full_name: Kondrashov, Alexey S
last_name: Kondrashov
- first_name: Inna
full_name: Povolotskaya, Inna
last_name: Povolotskaya
- first_name: Dmitry
full_name: Ivankov, Dmitry N
last_name: Ivankov
- first_name: Fyodor
full_name: Fyodor Kondrashov
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
citation:
ama: Kondrashov A, Povolotskaya I, Ivankov D, Kondrashov F. Rate of sequence divergence
under constant selection. Biology Direct. 2010;5. doi:10.1186/1745-6150-5-5
apa: Kondrashov, A., Povolotskaya, I., Ivankov, D., & Kondrashov, F. (2010).
Rate of sequence divergence under constant selection. Biology Direct. BioMed
Central. https://doi.org/10.1186/1745-6150-5-5
chicago: Kondrashov, Alexey, Inna Povolotskaya, Dmitry Ivankov, and Fyodor Kondrashov.
“Rate of Sequence Divergence under Constant Selection.” Biology Direct.
BioMed Central, 2010. https://doi.org/10.1186/1745-6150-5-5.
ieee: A. Kondrashov, I. Povolotskaya, D. Ivankov, and F. Kondrashov, “Rate of sequence
divergence under constant selection,” Biology Direct, vol. 5. BioMed Central,
2010.
ista: Kondrashov A, Povolotskaya I, Ivankov D, Kondrashov F. 2010. Rate of sequence
divergence under constant selection. Biology Direct. 5.
mla: Kondrashov, Alexey, et al. “Rate of Sequence Divergence under Constant Selection.”
Biology Direct, vol. 5, BioMed Central, 2010, doi:10.1186/1745-6150-5-5.
short: A. Kondrashov, I. Povolotskaya, D. Ivankov, F. Kondrashov, Biology Direct
5 (2010).
date_created: 2018-12-11T11:49:00Z
date_published: 2010-01-21T00:00:00Z
date_updated: 2021-01-12T08:21:15Z
day: '21'
doi: 10.1186/1745-6150-5-5
extern: 1
intvolume: ' 5'
license: https://creativecommons.org/licenses/by/4.0/
month: '01'
publication: Biology Direct
publication_status: published
publisher: BioMed Central
publist_id: '6762'
quality_controlled: 0
status: public
title: Rate of sequence divergence under constant selection
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
volume: 5
year: '2010'
...
---
_id: '89'
abstract:
- lang: eng
text: We demonstrate the operation of a device that can produce chitosan nanoparticles
in a tunable size range from 50-300 nm with small size dispersion. A piezoelectric
oscillator operated at megahertz frequencies is used to aerosolize a solution
containing dissolved chitosan. The solvent is then evaporated from the aerosolized
droplets in a heat pipe, leaving monodisperse nanoparticles to be collected. The
nanoparticle size is controlled both by the concentration of the dissolved polymer
and by the size of the aerosol droplets that are created. Our device can be used
with any polymer or polymer/therapeutic combination that can be prepared in a
homogeneous solution and vaporized.
acknowledgement: This work was supported by the National Science Foundation under
Grants PHY-0456898 and PHY-0757989, and acknowledgment is made to the Donors of
the Petroleum Research Fund administered by the American Chemical Society for partial
support of this research.
author:
- first_name: Ian
full_name: Wright, Ian
last_name: Wright
- first_name: Andrew P
full_name: Higginbotham, Andrew P
id: 4AD6785A-F248-11E8-B48F-1D18A9856A87
last_name: Higginbotham
orcid: 0000-0003-2607-2363
- first_name: Shenda
full_name: Baker, Shenda
last_name: Baker
- first_name: Tom
full_name: Donnelly, Tom
last_name: Donnelly
citation:
ama: Wright I, Higginbotham AP, Baker S, Donnelly T. Generation of nanoparticles
of controlled size using ultrasonic piezoelectric oscillators in solution. ACS
Applied Materials and Interfaces. 2010;2(8):2360-2364. doi:10.1021/am100375w
apa: Wright, I., Higginbotham, A. P., Baker, S., & Donnelly, T. (2010). Generation
of nanoparticles of controlled size using ultrasonic piezoelectric oscillators
in solution. ACS Applied Materials and Interfaces. American Chemical Society.
https://doi.org/10.1021/am100375w
chicago: Wright, Ian, Andrew P Higginbotham, Shenda Baker, and Tom Donnelly. “Generation
of Nanoparticles of Controlled Size Using Ultrasonic Piezoelectric Oscillators
in Solution.” ACS Applied Materials and Interfaces. American Chemical Society,
2010. https://doi.org/10.1021/am100375w.
ieee: I. Wright, A. P. Higginbotham, S. Baker, and T. Donnelly, “Generation of nanoparticles
of controlled size using ultrasonic piezoelectric oscillators in solution,” ACS
Applied Materials and Interfaces, vol. 2, no. 8. American Chemical Society,
pp. 2360–2364, 2010.
ista: Wright I, Higginbotham AP, Baker S, Donnelly T. 2010. Generation of nanoparticles
of controlled size using ultrasonic piezoelectric oscillators in solution. ACS
Applied Materials and Interfaces. 2(8), 2360–2364.
mla: Wright, Ian, et al. “Generation of Nanoparticles of Controlled Size Using Ultrasonic
Piezoelectric Oscillators in Solution.” ACS Applied Materials and Interfaces,
vol. 2, no. 8, American Chemical Society, 2010, pp. 2360–64, doi:10.1021/am100375w.
short: I. Wright, A.P. Higginbotham, S. Baker, T. Donnelly, ACS Applied Materials
and Interfaces 2 (2010) 2360–2364.
date_created: 2018-12-11T11:44:34Z
date_published: 2010-07-20T00:00:00Z
date_updated: 2021-01-12T08:21:17Z
day: '20'
doi: 10.1021/am100375w
extern: '1'
external_id:
pmid:
- ' 20735108'
intvolume: ' 2'
issue: '8'
language:
- iso: eng
month: '07'
oa_version: None
page: 2360 - 2364
pmid: 1
publication: ACS Applied Materials and Interfaces
publication_status: published
publisher: American Chemical Society
publist_id: '7965'
quality_controlled: '1'
status: public
title: Generation of nanoparticles of controlled size using ultrasonic piezoelectric
oscillators in solution
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 2
year: '2010'
...
---
_id: '891'
abstract:
- lang: eng
text: Gene duplications and their subsequent divergence play an important part in
the evolution of novel gene functions. Several models for the emergence, maintenance
and evolution of gene copies have been proposed. However, a clear consensus on
how gene duplications are fixed and maintained in genomes is lacking. Here, we
present a comprehensive classification of the models that are relevant to all
stages of the evolution of gene duplications. Each model predicts a unique combination
of evolutionary dynamics and functional properties. Setting out these predictions
is an important step towards identifying the main mechanisms that are involved
in the evolution of gene duplications.
acknowledgement: |
We thank M. Lynch for insightful comments on the manuscript.
author:
- first_name: Hideki
full_name: Innan, Hideki
last_name: Innan
- first_name: Fyodor
full_name: Fyodor Kondrashov
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
citation:
ama: 'Innan H, Kondrashov F. The evolution of gene duplications: Classifying and
distinguishing between models. Nature Reviews Genetics. 2010;11(2):97-108.
doi:10.1038/nrg2689'
apa: 'Innan, H., & Kondrashov, F. (2010). The evolution of gene duplications:
Classifying and distinguishing between models. Nature Reviews Genetics.
Nature Publishing Group. https://doi.org/10.1038/nrg2689'
chicago: 'Innan, Hideki, and Fyodor Kondrashov. “The Evolution of Gene Duplications:
Classifying and Distinguishing between Models.” Nature Reviews Genetics.
Nature Publishing Group, 2010. https://doi.org/10.1038/nrg2689.'
ieee: 'H. Innan and F. Kondrashov, “The evolution of gene duplications: Classifying
and distinguishing between models,” Nature Reviews Genetics, vol. 11, no.
2. Nature Publishing Group, pp. 97–108, 2010.'
ista: 'Innan H, Kondrashov F. 2010. The evolution of gene duplications: Classifying
and distinguishing between models. Nature Reviews Genetics. 11(2), 97–108.'
mla: 'Innan, Hideki, and Fyodor Kondrashov. “The Evolution of Gene Duplications:
Classifying and Distinguishing between Models.” Nature Reviews Genetics,
vol. 11, no. 2, Nature Publishing Group, 2010, pp. 97–108, doi:10.1038/nrg2689.'
short: H. Innan, F. Kondrashov, Nature Reviews Genetics 11 (2010) 97–108.
date_created: 2018-12-11T11:49:03Z
date_published: 2010-02-01T00:00:00Z
date_updated: 2021-01-12T08:21:19Z
day: '01'
doi: 10.1038/nrg2689
extern: 1
intvolume: ' 11'
issue: '2'
month: '02'
page: 97 - 108
publication: Nature Reviews Genetics
publication_status: published
publisher: Nature Publishing Group
publist_id: '6755'
quality_controlled: 0
status: public
title: 'The evolution of gene duplications: Classifying and distinguishing between
models'
type: journal_article
volume: 11
year: '2010'
...
---
_id: '901'
abstract:
- lang: eng
text: 'Background: Surveying deleterious variation in human populations is crucial
for our understanding, diagnosis and potential treatment of human genetic pathologies.
A number of recent genome-wide analyses focused on the prevalence of segregating
deleterious alleles in the nuclear genome. However, such studies have not been
conducted for the mitochondrial genome.Results: We present a systematic survey
of polymorphisms in the human mitochondrial genome, including those predicted
to be deleterious and those that correspond to known pathogenic mutations. Analyzing
4458 completely sequenced mitochondrial genomes we characterize the genetic diversity
of different types of single nucleotide polymorphisms (SNPs) in African (L haplotypes)
and non-African (M and N haplotypes) populations. We find that the overall level
of polymorphism is higher in the mitochondrial compared to the nuclear genome,
although the mitochondrial genome appears to be under stronger selection as indicated
by proportionally fewer nonsynonymous than synonymous substitutions. The African
mitochondrial genomes show higher heterozygosity, a greater number of polymorphic
sites and higher frequencies of polymorphisms for synonymous, benign and damaging
polymorphism than non-African genomes. However, African genomes carry significantly
fewer SNPs that have been previously characterized as pathogenic compared to non-African
genomes.Conclusions: Finding SNPs classified as pathogenic to be the only category
of polymorphisms that are more abundant in non-African genomes is best explained
by a systematic ascertainment bias that favours the discovery of pathogenic polymorphisms
segregating in non-African populations. This further suggests that, contrary to
the common disease-common variant hypothesis, pathogenic mutations are largely
population-specific and different SNPs may be associated with the same disease
in different populations. Therefore, to obtain a comprehensive picture of the
deleterious variability in the human population, as well as to improve the diagnostics
of individuals carrying African mitochondrial haplotypes, it is necessary to survey
different populations independently.Reviewers: This article was reviewed by Dr
Mikhail Gelfand, Dr Vasily Ramensky (nominated by Dr Eugene Koonin) and Dr David
Rand (nominated by Dr Laurence Hurst).'
acknowledgement: We thank Ivan Adzhubei and Shamil Sunyaev for extensive assistance
with PolyPhen 2 and insightful discussion. We thank the Spanish Ministry of Science
and Innovation, Plan Nacional Program grant BFU2009-09271 for funding.
author:
- first_name: Michael
full_name: Breen, Michael S
last_name: Breen
- first_name: Fyodor
full_name: Fyodor Kondrashov
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
citation:
ama: Breen M, Kondrashov F. Mitochondrial pathogenic mutations are population-specific.
Biology Direct. 2010;5. doi:10.1186/1745-6150-5-68
apa: Breen, M., & Kondrashov, F. (2010). Mitochondrial pathogenic mutations
are population-specific. Biology Direct. BioMed Central. https://doi.org/10.1186/1745-6150-5-68
chicago: Breen, Michael, and Fyodor Kondrashov. “Mitochondrial Pathogenic Mutations
Are Population-Specific.” Biology Direct. BioMed Central, 2010. https://doi.org/10.1186/1745-6150-5-68.
ieee: M. Breen and F. Kondrashov, “Mitochondrial pathogenic mutations are population-specific,”
Biology Direct, vol. 5. BioMed Central, 2010.
ista: Breen M, Kondrashov F. 2010. Mitochondrial pathogenic mutations are population-specific.
Biology Direct. 5.
mla: Breen, Michael, and Fyodor Kondrashov. “Mitochondrial Pathogenic Mutations
Are Population-Specific.” Biology Direct, vol. 5, BioMed Central, 2010,
doi:10.1186/1745-6150-5-68.
short: M. Breen, F. Kondrashov, Biology Direct 5 (2010).
date_created: 2018-12-11T11:49:06Z
date_published: 2010-12-31T00:00:00Z
date_updated: 2021-01-12T08:21:46Z
day: '31'
doi: 10.1186/1745-6150-5-68
extern: 1
intvolume: ' 5'
month: '12'
publication: Biology Direct
publication_status: published
publisher: BioMed Central
publist_id: '6749'
quality_controlled: 0
status: public
title: Mitochondrial pathogenic mutations are population-specific
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
volume: 5
year: '2010'
...
---
_id: '920'
abstract:
- lang: eng
text: Most eukaryotic cells sense and respond to the mechanical properties of their
surroundings. This can strongly influence their collective behavior in embryonic
development, tissue function, and wound healing. We use a deformable substrate
to measure collective behavior in cell motion due to substrate mediated cell-cell
interactions. We quantify spatial and temporal correlations in migration velocity
and substrate deformation, and show that cooperative cell-driven patterns of substrate
deformation mediate long-distance mechanical coupling between cells and control
collective cell migration.
acknowledgement: "This work was supported by the NSF (DMR-0602684) and the Harvard
MRSEC (DMR-0820484).\r\nWe would like to thank Dr. James Butler for helpful conversations."
article_processing_charge: No
author:
- first_name: Thomas
full_name: Angelini, Thomas
last_name: Angelini
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Xavier
full_name: Trepat, Xavier
last_name: Trepat
- first_name: Jeffrey
full_name: Fredberg, Jeffrey
last_name: Fredberg
- first_name: David
full_name: Weitz, David
last_name: Weitz
citation:
ama: Angelini T, Hannezo EB, Trepat X, Fredberg J, Weitz D. Cell migration driven
by cooperative substrate deformation patterns. Physical Review Letters.
2010;104(16). doi:10.1103/PhysRevLett.104.168104
apa: Angelini, T., Hannezo, E. B., Trepat, X., Fredberg, J., & Weitz, D. (2010).
Cell migration driven by cooperative substrate deformation patterns. Physical
Review Letters. American Physical Society. https://doi.org/10.1103/PhysRevLett.104.168104
chicago: Angelini, Thomas, Edouard B Hannezo, Xavier Trepat, Jeffrey Fredberg, and
David Weitz. “Cell Migration Driven by Cooperative Substrate Deformation Patterns.”
Physical Review Letters. American Physical Society, 2010. https://doi.org/10.1103/PhysRevLett.104.168104.
ieee: T. Angelini, E. B. Hannezo, X. Trepat, J. Fredberg, and D. Weitz, “Cell migration
driven by cooperative substrate deformation patterns,” Physical Review Letters,
vol. 104, no. 16. American Physical Society, 2010.
ista: Angelini T, Hannezo EB, Trepat X, Fredberg J, Weitz D. 2010. Cell migration
driven by cooperative substrate deformation patterns. Physical Review Letters.
104(16).
mla: Angelini, Thomas, et al. “Cell Migration Driven by Cooperative Substrate Deformation
Patterns.” Physical Review Letters, vol. 104, no. 16, American Physical
Society, 2010, doi:10.1103/PhysRevLett.104.168104.
short: T. Angelini, E.B. Hannezo, X. Trepat, J. Fredberg, D. Weitz, Physical Review
Letters 104 (2010).
date_created: 2018-12-11T11:49:12Z
date_published: 2010-04-23T00:00:00Z
date_updated: 2021-01-12T08:21:55Z
day: '23'
doi: 10.1103/PhysRevLett.104.168104
extern: '1'
intvolume: ' 104'
issue: '16'
language:
- iso: eng
month: '04'
oa_version: None
publication: Physical Review Letters
publication_status: published
publisher: American Physical Society
publist_id: '6523'
status: public
title: Cell migration driven by cooperative substrate deformation patterns
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 104
year: '2010'
...
---
_id: '9764'
article_processing_charge: No
author:
- first_name: Ulises
full_name: Rosas, Ulises
last_name: Rosas
- 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: Lucy
full_name: Copsey, Lucy
last_name: Copsey
- first_name: Pierre
full_name: Barbier De Reuille, Pierre
last_name: Barbier De Reuille
- first_name: Enrico
full_name: Coen, Enrico
last_name: Coen
citation:
ama: Rosas U, Barton NH, Copsey L, Barbier De Reuille P, Coen E. Heterosis and the
drift load. 2010. doi:10.1371/journal.pbio.1000429.s003
apa: Rosas, U., Barton, N. H., Copsey, L., Barbier De Reuille, P., & Coen, E.
(2010). Heterosis and the drift load. Public Library of Science. https://doi.org/10.1371/journal.pbio.1000429.s003
chicago: Rosas, Ulises, Nicholas H Barton, Lucy Copsey, Pierre Barbier De Reuille,
and Enrico Coen. “Heterosis and the Drift Load.” Public Library of Science, 2010.
https://doi.org/10.1371/journal.pbio.1000429.s003.
ieee: U. Rosas, N. H. Barton, L. Copsey, P. Barbier De Reuille, and E. Coen, “Heterosis
and the drift load.” Public Library of Science, 2010.
ista: Rosas U, Barton NH, Copsey L, Barbier De Reuille P, Coen E. 2010. Heterosis
and the drift load, Public Library of Science, 10.1371/journal.pbio.1000429.s003.
mla: Rosas, Ulises, et al. Heterosis and the Drift Load. Public Library of
Science, 2010, doi:10.1371/journal.pbio.1000429.s003.
short: U. Rosas, N.H. Barton, L. Copsey, P. Barbier De Reuille, E. Coen, (2010).
date_created: 2021-08-02T09:45:39Z
date_published: 2010-07-20T00:00:00Z
date_updated: 2025-09-30T09:42:52Z
day: '20'
department:
- _id: NiBa
doi: 10.1371/journal.pbio.1000429.s003
month: '07'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '3779'
relation: used_in_publication
status: public
status: public
title: Heterosis and the drift load
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2010'
...
---
_id: '474'
abstract:
- lang: eng
text: 'Classical models of gene flow fail in three ways: they cannot explain large-scale
patterns; they predict much more genetic diversity than is observed; and they
assume that loosely linked genetic loci evolve independently. We propose a new
model that deals with these problems. Extinction events kill some fraction of
individuals in a region. These are replaced by offspring from a small number of
parents, drawn from the preexisting population. This model of evolution forwards
in time corresponds to a backwards model, in which ancestral lineages jump to
a new location if they are hit by an event, and may coalesce with other lineages
that are hit by the same event. We derive an expression for the identity in allelic
state, and show that, over scales much larger than the largest event, this converges
to the classical value derived by Wright and Malécot. However, rare events that
cover large areas cause low genetic diversity, large-scale patterns, and correlations
in ancestry between unlinked loci.'
acknowledgement: This work has made use of the resources provided by the Edinburgh
Compute and Data Facility (ECDF). The ECDF is partially supported by the eDIKT initiative.
NHB is supported in part by EPSRC Grant EP/E066070/1; JK is supported by EPSRC Grant
EP/E066070/1; and AME is supported in part by EPSRC Grant EP/E065945/1.
article_processing_charge: No
author:
- 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: Jerome
full_name: Kelleher, Jerome
last_name: Kelleher
- first_name: Alison
full_name: Etheridge, Alison
last_name: Etheridge
citation:
ama: 'Barton NH, Kelleher J, Etheridge A. A new model for extinction and recolonization
in two dimensions: Quantifying phylogeography. Evolution. 2010;64(9):2701-2715.
doi:10.1111/j.1558-5646.2010.01019.x'
apa: 'Barton, N. H., Kelleher, J., & Etheridge, A. (2010). A new model for extinction
and recolonization in two dimensions: Quantifying phylogeography. Evolution.
Wiley-Blackwell. https://doi.org/10.1111/j.1558-5646.2010.01019.x'
chicago: 'Barton, Nicholas H, Jerome Kelleher, and Alison Etheridge. “A New Model
for Extinction and Recolonization in Two Dimensions: Quantifying Phylogeography.”
Evolution. Wiley-Blackwell, 2010. https://doi.org/10.1111/j.1558-5646.2010.01019.x.'
ieee: 'N. H. Barton, J. Kelleher, and A. Etheridge, “A new model for extinction
and recolonization in two dimensions: Quantifying phylogeography,” Evolution,
vol. 64, no. 9. Wiley-Blackwell, pp. 2701–2715, 2010.'
ista: 'Barton NH, Kelleher J, Etheridge A. 2010. A new model for extinction and
recolonization in two dimensions: Quantifying phylogeography. Evolution. 64(9),
2701–2715.'
mla: 'Barton, Nicholas H., et al. “A New Model for Extinction and Recolonization
in Two Dimensions: Quantifying Phylogeography.” Evolution, vol. 64, no.
9, Wiley-Blackwell, 2010, pp. 2701–15, doi:10.1111/j.1558-5646.2010.01019.x.'
short: N.H. Barton, J. Kelleher, A. Etheridge, Evolution 64 (2010) 2701–2715.
corr_author: '1'
date_created: 2018-12-11T11:46:40Z
date_published: 2010-09-01T00:00:00Z
date_updated: 2025-09-30T09:50:22Z
day: '01'
department:
- _id: NiBa
doi: 10.1111/j.1558-5646.2010.01019.x
external_id:
isi:
- '000281636400017'
intvolume: ' 64'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa_version: None
page: 2701 - 2715
publication: Evolution
publication_status: published
publisher: Wiley-Blackwell
publist_id: '2780'
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'A new model for extinction and recolonization in two dimensions: Quantifying
phylogeography'
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 64
year: '2010'
...
---
_id: '488'
abstract:
- lang: eng
text: 'Streaming string transducers [1] define (partial) functions from input strings
to output strings. A streaming string transducer makes a single pass through the
input string and uses a finite set of variables that range over strings from the
output alphabet. At every step, the transducer processes an input symbol, and
updates all the variables in parallel using assignments whose right-hand-sides
are concatenations of output symbols and variables with the restriction that a
variable can be used at most once in a right-hand-side expression. It has been
shown that streaming string transducers operating on strings over infinite data
domains are of interest in algorithmic verification of list-processing programs,
as they lead to PSPACE decision procedures for checking pre/post conditions and
for checking semantic equivalence, for a well-defined class of heap-manipulating
programs. In order to understand the theoretical expressiveness of streaming transducers,
we focus on streaming transducers processing strings over finite alphabets, given
the existence of a robust and well-studied class of "regular" transductions
for this case. Such regular transductions can be defined either by two-way deterministic
finite-state transducers, or using a logical MSO-based characterization. Our main
result is that the expressiveness of streaming string transducers coincides exactly
with this class of regular transductions. '
alternative_title:
- LIPIcs
article_processing_charge: No
author:
- first_name: Rajeev
full_name: Alur, Rajeev
last_name: Alur
- first_name: Pavol
full_name: Cerny, Pavol
id: 4DCBEFFE-F248-11E8-B48F-1D18A9856A87
last_name: Cerny
citation:
ama: 'Alur R, Cerny P. Expressiveness of streaming string transducers. In: Vol 8.
Schloss Dagstuhl - Leibniz-Zentrum für Informatik; 2010:1-12. doi:10.4230/LIPIcs.FSTTCS.2010.1'
apa: 'Alur, R., & Cerny, P. (2010). Expressiveness of streaming string transducers
(Vol. 8, pp. 1–12). Presented at the FSTTCS: Foundations of Software Technology
and Theoretical Computer Science, Chennai, India: Schloss Dagstuhl - Leibniz-Zentrum
für Informatik. https://doi.org/10.4230/LIPIcs.FSTTCS.2010.1'
chicago: Alur, Rajeev, and Pavol Cerny. “Expressiveness of Streaming String Transducers,”
8:1–12. Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2010. https://doi.org/10.4230/LIPIcs.FSTTCS.2010.1.
ieee: 'R. Alur and P. Cerny, “Expressiveness of streaming string transducers,” presented
at the FSTTCS: Foundations of Software Technology and Theoretical Computer Science,
Chennai, India, 2010, vol. 8, pp. 1–12.'
ista: 'Alur R, Cerny P. 2010. Expressiveness of streaming string transducers. FSTTCS:
Foundations of Software Technology and Theoretical Computer Science, LIPIcs, vol.
8, 1–12.'
mla: Alur, Rajeev, and Pavol Cerny. Expressiveness of Streaming String Transducers.
Vol. 8, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, 2010, pp. 1–12, doi:10.4230/LIPIcs.FSTTCS.2010.1.
short: R. Alur, P. Cerny, in:, Schloss Dagstuhl - Leibniz-Zentrum für Informatik,
2010, pp. 1–12.
conference:
end_date: 2010-12-18
location: Chennai, India
name: 'FSTTCS: Foundations of Software Technology and Theoretical Computer Science'
start_date: 2010-12-15
corr_author: '1'
date_created: 2018-12-11T11:46:45Z
date_published: 2010-01-01T00:00:00Z
date_updated: 2025-09-30T09:49:32Z
day: '01'
ddc:
- '005'
department:
- _id: ToHe
doi: 10.4230/LIPIcs.FSTTCS.2010.1
external_id:
isi:
- '000310361000001'
file:
- access_level: open_access
checksum: 5845be5aa19791830f7407d8853f2df0
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:08:29Z
date_updated: 2020-07-14T12:46:35Z
file_id: '4690'
file_name: IST-2018-948-v1+1_2011_Cerny_Expressiveness_of.pdf
file_size: 492344
relation: main_file
file_date_updated: 2020-07-14T12:46:35Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '01'
oa: 1
oa_version: Published Version
page: 1 - 12
publication_status: published
publisher: Schloss Dagstuhl - Leibniz-Zentrum für Informatik
publist_id: '7331'
pubrep_id: '948'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Expressiveness of streaming string transducers
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: conference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 8
year: '2010'
...
---
_id: '489'
abstract:
- lang: eng
text: 'Graph games of infinite length are a natural model for open reactive processes:
one player represents the controller, trying to ensure a given specification,
and the other represents a hostile environment. The evolution of the system depends
on the decisions of both players, supplemented by chance. In this work, we focus
on the notion of randomised strategy. More specifically, we show that three natural
definitions may lead to very different results: in the most general cases, an
almost-surely winning situation may become almost-surely losing if the player
is only allowed to use a weaker notion of strategy. In more reasonable settings,
translations exist, but they require infinite memory, even in simple cases. Finally,
some traditional problems becomes undecidable for the strongest type of strategies.'
alternative_title:
- EPTCS
article_processing_charge: No
arxiv: 1
author:
- first_name: Julien
full_name: Cristau, Julien
last_name: Cristau
- first_name: Claire
full_name: David, Claire
last_name: David
- first_name: Florian
full_name: Horn, Florian
id: 37327ACE-F248-11E8-B48F-1D18A9856A87
last_name: Horn
citation:
ama: 'Cristau J, David C, Horn F. How do we remember the past in randomised strategies?
In: Proceedings of GandALF 2010. Vol 25. Open Publishing Association; 2010:30-39.
doi:10.4204/EPTCS.25.7'
apa: 'Cristau, J., David, C., & Horn, F. (2010). How do we remember the past
in randomised strategies? In Proceedings of GandALF 2010 (Vol. 25, pp.
30–39). Minori, Amalfi Coast, Italy: Open Publishing Association. https://doi.org/10.4204/EPTCS.25.7'
chicago: Cristau, Julien, Claire David, and Florian Horn. “How Do We Remember the
Past in Randomised Strategies?” In Proceedings of GandALF 2010, 25:30–39.
Open Publishing Association, 2010. https://doi.org/10.4204/EPTCS.25.7.
ieee: J. Cristau, C. David, and F. Horn, “How do we remember the past in randomised
strategies?,” in Proceedings of GandALF 2010, Minori, Amalfi Coast, Italy,
2010, vol. 25, pp. 30–39.
ista: 'Cristau J, David C, Horn F. 2010. How do we remember the past in randomised
strategies? Proceedings of GandALF 2010. GandALF: Games, Automata, Logic, and
Formal Verification, EPTCS, vol. 25, 30–39.'
mla: Cristau, Julien, et al. “How Do We Remember the Past in Randomised Strategies?”
Proceedings of GandALF 2010, vol. 25, Open Publishing Association, 2010,
pp. 30–39, doi:10.4204/EPTCS.25.7.
short: J. Cristau, C. David, F. Horn, in:, Proceedings of GandALF 2010, Open Publishing
Association, 2010, pp. 30–39.
conference:
end_date: 2010-06-18
location: Minori, Amalfi Coast, Italy
name: 'GandALF: Games, Automata, Logic, and Formal Verification'
start_date: 2010-06-17
corr_author: '1'
date_created: 2018-12-11T11:46:45Z
date_published: 2010-06-09T00:00:00Z
date_updated: 2025-06-11T08:14:27Z
day: '09'
department:
- _id: KrCh
doi: 10.4204/EPTCS.25.7
external_id:
arxiv:
- '1006.1404'
intvolume: ' 25'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1006.1404
month: '06'
oa: 1
oa_version: Published Version
page: 30 - 39
publication: Proceedings of GandALF 2010
publication_status: published
publisher: Open Publishing Association
publist_id: '7332'
quality_controlled: '1'
scopus_import: '1'
status: public
title: How do we remember the past in randomised strategies?
type: conference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 25
year: '2010'
...
---
_id: '533'
abstract:
- lang: eng
text: Any programming error that can be revealed before compiling a program saves
precious time for the programmer. While integrated development environments already
do a good job by detecting, e.g., data-flow abnormalities, current static analysis
tools suffer from false positives ("noise") or require strong user interaction.
We propose to avoid this deficiency by defining a new class of errors. A program
fragment is doomed if its execution will inevitably fail, regardless of which
state it is started in. We use a formal verification method to identify such errors
fully automatically and, most significantly, without producing noise. We report
on experiments with a prototype tool.
article_processing_charge: No
author:
- first_name: Jochen
full_name: Hoenicke, Jochen
last_name: Hoenicke
- first_name: Kari
full_name: Leino, Kari
last_name: Leino
- first_name: Andreas
full_name: Podelski, Andreas
last_name: Podelski
- first_name: Martin
full_name: Schäf, Martin
last_name: Schäf
- first_name: Thomas
full_name: Wies, Thomas
id: 447BFB88-F248-11E8-B48F-1D18A9856A87
last_name: Wies
citation:
ama: Hoenicke J, Leino K, Podelski A, Schäf M, Wies T. Doomed program points. Formal
Methods in System Design. 2010;37(2-3):171-199. doi:10.1007/s10703-010-0102-0
apa: Hoenicke, J., Leino, K., Podelski, A., Schäf, M., & Wies, T. (2010). Doomed
program points. Formal Methods in System Design. Springer. https://doi.org/10.1007/s10703-010-0102-0
chicago: Hoenicke, Jochen, Kari Leino, Andreas Podelski, Martin Schäf, and Thomas
Wies. “Doomed Program Points.” Formal Methods in System Design. Springer,
2010. https://doi.org/10.1007/s10703-010-0102-0.
ieee: J. Hoenicke, K. Leino, A. Podelski, M. Schäf, and T. Wies, “Doomed program
points,” Formal Methods in System Design, vol. 37, no. 2–3. Springer, pp.
171–199, 2010.
ista: Hoenicke J, Leino K, Podelski A, Schäf M, Wies T. 2010. Doomed program points.
Formal Methods in System Design. 37(2–3), 171–199.
mla: Hoenicke, Jochen, et al. “Doomed Program Points.” Formal Methods in System
Design, vol. 37, no. 2–3, Springer, 2010, pp. 171–99, doi:10.1007/s10703-010-0102-0.
short: J. Hoenicke, K. Leino, A. Podelski, M. Schäf, T. Wies, Formal Methods in
System Design 37 (2010) 171–199.
corr_author: '1'
date_created: 2018-12-11T11:47:01Z
date_published: 2010-12-01T00:00:00Z
date_updated: 2025-09-30T09:48:58Z
day: '01'
department:
- _id: ToHe
doi: 10.1007/s10703-010-0102-0
external_id:
isi:
- '000286631700004'
intvolume: ' 37'
isi: 1
issue: 2-3
language:
- iso: eng
month: '12'
oa_version: None
page: 171 - 199
publication: Formal Methods in System Design
publication_status: published
publisher: Springer
publist_id: '7284'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Doomed program points
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 37
year: '2010'
...
---
_id: '5388'
abstract:
- lang: eng
text: "We present an algorithmic method for the synthesis of concurrent programs
that are optimal with respect to quantitative performance measures. The input
consists of a sequential sketch, that is, a program that does not contain synchronization
constructs, and of a parametric performance model that assigns costs to actions
such as locking, context switching, and idling. The quantitative synthesis problem
is to automatically introduce synchronization constructs into the sequential sketch
so that both correctness is guaranteed and worst-case (or average-case) performance
is optimized. Correctness is formalized as race freedom or linearizability.\r\n\r\nWe
show that for worst-case performance, the problem can be modeled\r\nas a 2-player
graph game with quantitative (limit-average) objectives, and\r\nfor average-case
performance, as a 2 1/2 -player graph game (with probabilistic transitions). In
both cases, the optimal correct program is derived from an optimal strategy in
the corresponding quantitative game. We prove that the respective game problems
are computationally expensive (NP-complete), and present several techniques that
overcome the theoretical difficulty in cases of concurrent programs of practical
interest.\r\n\r\nWe have implemented a prototype tool and used it for the automatic
syn- thesis of programs that access a concurrent list. For certain parameter val-
ues, our method automatically synthesizes various classical synchronization schemes
for implementing a concurrent list, such as fine-grained locking or a lazy algorithm.
For other parameter values, a new, hybrid synchronization style is synthesized,
which uses both the lazy approach and coarse-grained locks (instead of standard
fine-grained locks). The trade-off occurs because while fine-grained locking tends
to decrease the cost that is due to waiting for locks, it increases cache size
requirements."
alternative_title:
- IST Austria Technical Report
author:
- first_name: Krishnendu
full_name: Chatterjee, Krishnendu
id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87
last_name: Chatterjee
orcid: 0000-0002-4561-241X
- 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: Arjun
full_name: Radhakrishna, Arjun
id: 3B51CAC4-F248-11E8-B48F-1D18A9856A87
last_name: Radhakrishna
- first_name: Rohit
full_name: Singh, Rohit
last_name: Singh
citation:
ama: Chatterjee K, Cerny P, Henzinger TA, Radhakrishna A, Singh R. Quantitative
Synthesis for Concurrent Programs. IST Austria; 2010. doi:10.15479/AT:IST-2010-0004
apa: Chatterjee, K., Cerny, P., Henzinger, T. A., Radhakrishna, A., & Singh,
R. (2010). Quantitative synthesis for concurrent programs. IST Austria.
https://doi.org/10.15479/AT:IST-2010-0004
chicago: Chatterjee, Krishnendu, Pavol Cerny, Thomas A Henzinger, Arjun Radhakrishna,
and Rohit Singh. Quantitative Synthesis for Concurrent Programs. IST Austria,
2010. https://doi.org/10.15479/AT:IST-2010-0004.
ieee: K. Chatterjee, P. Cerny, T. A. Henzinger, A. Radhakrishna, and R. Singh, Quantitative
synthesis for concurrent programs. IST Austria, 2010.
ista: Chatterjee K, Cerny P, Henzinger TA, Radhakrishna A, Singh R. 2010. Quantitative
synthesis for concurrent programs, IST Austria, 17p.
mla: Chatterjee, Krishnendu, et al. Quantitative Synthesis for Concurrent Programs.
IST Austria, 2010, doi:10.15479/AT:IST-2010-0004.
short: K. Chatterjee, P. Cerny, T.A. Henzinger, A. Radhakrishna, R. Singh, Quantitative
Synthesis for Concurrent Programs, IST Austria, 2010.
date_created: 2018-12-12T11:39:03Z
date_published: 2010-10-07T00:00:00Z
date_updated: 2025-04-15T08:12:00Z
day: '07'
ddc:
- '000'
- '005'
department:
- _id: KrCh
- _id: ToHe
doi: 10.15479/AT:IST-2010-0004
file:
- access_level: open_access
checksum: da38782d2388a6fa32109d10bb9bad67
content_type: application/pdf
creator: system
date_created: 2018-12-12T11:53:53Z
date_updated: 2020-07-14T12:46:42Z
file_id: '5515'
file_name: IST-2010-0004_IST-2010-0004.pdf
file_size: 429101
relation: main_file
file_date_updated: 2020-07-14T12:46:42Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '17'
publication_identifier:
issn:
- 2664-1690
publication_status: published
publisher: IST Austria
pubrep_id: '24'
related_material:
record:
- id: '3366'
relation: later_version
status: public
status: public
title: Quantitative synthesis for concurrent programs
type: technical_report
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2010'
...
---
_id: '5389'
abstract:
- lang: eng
text: Boolean notions of correctness are formalized by preorders on systems. Quantitative
measures of correctness can be formalized by real-valued distance functions between
systems, where the distance between implementation and specification provides
a measure of “fit” or “desirability.” We extend the simulation preorder to the
quantitative setting, by making each player of a simulation game pay a certain
price for her choices. We use the resulting games with quantitative objectives
to define three different simulation distances. The correctness distance measures
how much the specification must be changed in order to be satisfied by the implementation.
The coverage distance measures how much the im- plementation restricts the degrees
of freedom offered by the specification. The robustness distance measures how
much a system can deviate from the implementation description without violating
the specification. We consider these distances for safety as well as liveness
specifications. The distances can be computed in polynomial time for safety specifications,
and for liveness specifications given by weak fairness constraints. We show that
the distance functions satisfy the triangle inequality, that the distance between
two systems does not increase under parallel composition with a third system,
and that the distance between two systems can be bounded from above and below
by distances between abstractions of the two systems. These properties suggest
that our simulation distances provide an appropriate basis for a quantitative
theory of discrete systems. We also demonstrate how the robustness distance can
be used to measure how many transmission errors are tolerated by error correcting
codes.
alternative_title:
- IST Austria Technical Report
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: Arjun
full_name: Radhakrishna, Arjun
id: 3B51CAC4-F248-11E8-B48F-1D18A9856A87
last_name: Radhakrishna
citation:
ama: Cerny P, Henzinger TA, Radhakrishna A. Simulation Distances. IST Austria;
2010. doi:10.15479/AT:IST-2010-0003
apa: Cerny, P., Henzinger, T. A., & Radhakrishna, A. (2010). Simulation distances.
IST Austria. https://doi.org/10.15479/AT:IST-2010-0003
chicago: Cerny, Pavol, Thomas A Henzinger, and Arjun Radhakrishna. Simulation
Distances. IST Austria, 2010. https://doi.org/10.15479/AT:IST-2010-0003.
ieee: P. Cerny, T. A. Henzinger, and A. Radhakrishna, Simulation distances.
IST Austria, 2010.
ista: Cerny P, Henzinger TA, Radhakrishna A. 2010. Simulation distances, IST Austria,
24p.
mla: Cerny, Pavol, et al. Simulation Distances. IST Austria, 2010, doi:10.15479/AT:IST-2010-0003.
short: P. Cerny, T.A. Henzinger, A. Radhakrishna, Simulation Distances, IST Austria,
2010.
date_created: 2018-12-12T11:39:03Z
date_published: 2010-06-04T00:00:00Z
date_updated: 2025-09-30T07:46:05Z
day: '04'
ddc:
- '005'
department:
- _id: ToHe
doi: 10.15479/AT:IST-2010-0003
file:
- access_level: open_access
checksum: 284ded99764e32a583a8ea83fcea254b
content_type: application/pdf
creator: system
date_created: 2018-12-12T11:54:25Z
date_updated: 2020-07-14T12:46:42Z
file_id: '5547'
file_name: IST-2010-0003_IST-2010-0003.pdf
file_size: 367246
relation: main_file
file_date_updated: 2020-07-14T12:46:42Z
has_accepted_license: '1'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '24'
publication_identifier:
issn:
- 2664-1690
publication_status: published
publisher: IST Austria
pubrep_id: '25'
related_material:
record:
- id: '4393'
relation: later_version
status: public
- id: '3249'
relation: later_version
status: public
status: public
title: Simulation distances
type: technical_report
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2010'
...
---
_id: '5390'
abstract:
- lang: eng
text: The class of ω regular languages provide a robust specification language in
verification. Every ω-regular condition can be decomposed into a safety part and
a liveness part. The liveness part ensures that something good happens “eventually.”
Two main strengths of the classical, infinite-limit formulation of liveness are
robustness (independence from the granularity of transitions) and simplicity (abstraction
of complicated time bounds). However, the classical liveness formulation suffers
from the drawback that the time until something good happens may be unbounded.
A stronger formulation of liveness, so-called finitary liveness, overcomes this
drawback, while still retaining robustness and simplicity. Finitary liveness requires
that there exists an unknown, fixed bound b such that something good happens within
b transitions. In this work we consider the finitary parity and Streett (fairness)
conditions. We present the topological, automata-theoretic and logical characterization
of finitary languages defined by finitary parity and Streett conditions. We (a)
show that the finitary parity and Streett languages are Σ2-complete; (b) present
a complete characterization of the expressive power of various classes of automata
with finitary and infinitary conditions (in particular we show that non-deterministic
finitary parity and Streett automata cannot be determinized to deterministic finitary
parity or Streett automata); and (c) show that the languages defined by non-deterministic
finitary parity automata exactly characterize the star-free fragment of ωB-regular
languages.
alternative_title:
- IST Austria Technical Report
author:
- first_name: Krishnendu
full_name: Chatterjee, Krishnendu
id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87
last_name: Chatterjee
orcid: 0000-0002-4561-241X
- first_name: Nathanaël
full_name: Fijalkow, Nathanaël
last_name: Fijalkow
citation:
ama: Chatterjee K, Fijalkow N. Topological, Automata-Theoretic and Logical Characterization
of Finitary Languages. IST Austria; 2010. doi:10.15479/AT:IST-2010-0002
apa: Chatterjee, K., & Fijalkow, N. (2010). Topological, automata-theoretic
and logical characterization of finitary languages. IST Austria. https://doi.org/10.15479/AT:IST-2010-0002
chicago: Chatterjee, Krishnendu, and Nathanaël Fijalkow. Topological, Automata-Theoretic
and Logical Characterization of Finitary Languages. IST Austria, 2010. https://doi.org/10.15479/AT:IST-2010-0002.
ieee: K. Chatterjee and N. Fijalkow, Topological, automata-theoretic and logical
characterization of finitary languages. IST Austria, 2010.
ista: Chatterjee K, Fijalkow N. 2010. Topological, automata-theoretic and logical
characterization of finitary languages, IST Austria, 21p.
mla: Chatterjee, Krishnendu, and Nathanaël Fijalkow. Topological, Automata-Theoretic
and Logical Characterization of Finitary Languages. IST Austria, 2010, doi:10.15479/AT:IST-2010-0002.
short: K. Chatterjee, N. Fijalkow, Topological, Automata-Theoretic and Logical Characterization
of Finitary Languages, IST Austria, 2010.
date_created: 2018-12-12T11:39:03Z
date_published: 2010-06-04T00:00:00Z
date_updated: 2020-07-14T23:04:41Z
day: '04'
ddc:
- '000'
department:
- _id: KrCh
doi: 10.15479/AT:IST-2010-0002
file:
- access_level: open_access
checksum: 283d3604d76dd4d5161585d4c8625fbe
content_type: application/pdf
creator: system
date_created: 2018-12-12T11:54:10Z
date_updated: 2020-07-14T12:46:43Z
file_id: '5532'
file_name: IST-2010-0002_IST-2010-0002.pdf
file_size: 395662
relation: main_file
file_date_updated: 2020-07-14T12:46:43Z
has_accepted_license: '1'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '21'
publication_identifier:
issn:
- 2664-1690
publication_status: published
publisher: IST Austria
pubrep_id: '26'
status: public
title: Topological, automata-theoretic and logical characterization of finitary languages
type: technical_report
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2010'
...
---
_id: '5391'
abstract:
- lang: eng
text: Concurrent data structures with fine-grained synchronization are notoriously
difficult to implement correctly. The difficulty of reasoning about these implementations
does not stem from the number of variables or the program size, but rather from
the large number of possible interleavings. These implementations are therefore
prime candidates for model checking. We introduce an algorithm for verifying linearizability
of singly-linked heap-based concurrent data structures. We consider a model consisting
of an unbounded heap where each node consists an element from an unbounded data
domain, with a restricted set of operations for testing and updating pointers
and data elements. Our main result is that linearizability is decidable for programs
that invoke a fixed number of methods, possibly in parallel. This decidable fragment
covers many of the common implementation techniques — fine-grained locking, lazy
synchronization, and lock-free synchronization. We also show how the technique
can be used to verify optimistic implementations with the help of programmer annotations.
We developed a verification tool CoLT and evaluated it on a representative sample
of Java implementations of the concurrent set data structure. The tool verified
linearizability of a number of implementations, found a known error in a lock-free
imple- mentation and proved that the corrected version is linearizable.
alternative_title:
- IST Austria Technical Report
author:
- first_name: Pavol
full_name: Cerny, Pavol
id: 4DCBEFFE-F248-11E8-B48F-1D18A9856A87
last_name: Cerny
- first_name: Arjun
full_name: Radhakrishna, Arjun
id: 3B51CAC4-F248-11E8-B48F-1D18A9856A87
last_name: Radhakrishna
- first_name: Damien
full_name: Zufferey, Damien
id: 4397AC76-F248-11E8-B48F-1D18A9856A87
last_name: Zufferey
orcid: 0000-0002-3197-8736
- first_name: Swarat
full_name: Chaudhuri, Swarat
last_name: Chaudhuri
- first_name: Rajeev
full_name: Alur, Rajeev
last_name: Alur
citation:
ama: Cerny P, Radhakrishna A, Zufferey D, Chaudhuri S, Alur R. Model Checking
of Linearizability of Concurrent List Implementations. IST Austria; 2010.
doi:10.15479/AT:IST-2010-0001
apa: Cerny, P., Radhakrishna, A., Zufferey, D., Chaudhuri, S., & Alur, R. (2010).
Model checking of linearizability of concurrent list implementations. IST
Austria. https://doi.org/10.15479/AT:IST-2010-0001
chicago: Cerny, Pavol, Arjun Radhakrishna, Damien Zufferey, Swarat Chaudhuri, and
Rajeev Alur. Model Checking of Linearizability of Concurrent List Implementations.
IST Austria, 2010. https://doi.org/10.15479/AT:IST-2010-0001.
ieee: P. Cerny, A. Radhakrishna, D. Zufferey, S. Chaudhuri, and R. Alur, Model
checking of linearizability of concurrent list implementations. IST Austria,
2010.
ista: Cerny P, Radhakrishna A, Zufferey D, Chaudhuri S, Alur R. 2010. Model checking
of linearizability of concurrent list implementations, IST Austria, 27p.
mla: Cerny, Pavol, et al. Model Checking of Linearizability of Concurrent List
Implementations. IST Austria, 2010, doi:10.15479/AT:IST-2010-0001.
short: P. Cerny, A. Radhakrishna, D. Zufferey, S. Chaudhuri, R. Alur, Model Checking
of Linearizability of Concurrent List Implementations, IST Austria, 2010.
date_created: 2018-12-12T11:39:04Z
date_published: 2010-04-19T00:00:00Z
date_updated: 2024-10-21T06:03:05Z
day: '19'
ddc:
- '004'
department:
- _id: ToHe
doi: 10.15479/AT:IST-2010-0001
file:
- access_level: open_access
checksum: 986645caad7dd85a6a091488f6c646dc
content_type: application/pdf
creator: system
date_created: 2018-12-12T11:53:44Z
date_updated: 2020-07-14T12:46:43Z
file_id: '5505'
file_name: IST-2010-0001_IST-2010-0001.pdf
file_size: 372286
relation: main_file
file_date_updated: 2020-07-14T12:46:43Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: '27'
publication_identifier:
issn:
- 2664-1690
publication_status: published
publisher: IST Austria
pubrep_id: '27'
related_material:
record:
- id: '4390'
relation: later_version
status: public
status: public
title: Model checking of linearizability of concurrent list implementations
type: technical_report
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2010'
...
---
_id: '5940'
article_processing_charge: No
author:
- first_name: Gabriel
full_name: Juhás, Gabriel
last_name: Juhás
- first_name: Igor
full_name: Kazlov, Igor
id: 4A997E50-F248-11E8-B48F-1D18A9856A87
last_name: Kazlov
- first_name: Ana
full_name: Juhásová, Ana
last_name: Juhásová
citation:
ama: 'Juhás G, Kazlov I, Juhásová A. Instance Deadlock: A Mystery behind Frozen
Programs. In: Applications and Theory of Petri Nets. Berlin, Heidelberg:
Springer Berlin Heidelberg; 2010:1-17. doi:10.1007/978-3-642-13675-7_1'
apa: 'Juhás, G., Kazlov, I., & Juhásová, A. (2010). Instance Deadlock: A Mystery
behind Frozen Programs. In Applications and Theory of Petri Nets (pp. 1–17).
Berlin, Heidelberg: Springer Berlin Heidelberg. https://doi.org/10.1007/978-3-642-13675-7_1'
chicago: 'Juhás, Gabriel, Igor Kazlov, and Ana Juhásová. “Instance Deadlock: A Mystery
behind Frozen Programs.” In Applications and Theory of Petri Nets, 1–17.
Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. https://doi.org/10.1007/978-3-642-13675-7_1.'
ieee: 'G. Juhás, I. Kazlov, and A. Juhásová, “Instance Deadlock: A Mystery behind
Frozen Programs,” in Applications and Theory of Petri Nets, Berlin, Heidelberg:
Springer Berlin Heidelberg, 2010, pp. 1–17.'
ista: 'Juhás G, Kazlov I, Juhásová A. 2010.Instance Deadlock: A Mystery behind Frozen
Programs. In: Applications and Theory of Petri Nets. , 1–17.'
mla: 'Juhás, Gabriel, et al. “Instance Deadlock: A Mystery behind Frozen Programs.”
Applications and Theory of Petri Nets, Springer Berlin Heidelberg, 2010,
pp. 1–17, doi:10.1007/978-3-642-13675-7_1.'
short: G. Juhás, I. Kazlov, A. Juhásová, in:, Applications and Theory of Petri Nets,
Springer Berlin Heidelberg, Berlin, Heidelberg, 2010, pp. 1–17.
date_created: 2019-02-08T09:33:41Z
date_published: 2010-01-01T00:00:00Z
date_updated: 2022-04-01T13:45:24Z
doi: 10.1007/978-3-642-13675-7_1
extern: '1'
language:
- iso: eng
oa_version: None
page: 1-17
place: Berlin, Heidelberg
publication: Applications and Theory of Petri Nets
publication_identifier:
isbn:
- '9783642136740'
- '9783642136757'
issn:
- 0302-9743
- 1611-3349
publication_status: published
publisher: Springer Berlin Heidelberg
status: public
title: 'Instance Deadlock: A Mystery behind Frozen Programs'
type: book_chapter
user_id: 4A997E50-F248-11E8-B48F-1D18A9856A87
year: '2010'
...
---
_id: '598'
abstract:
- lang: eng
text: It is not well understood how the human Mediator complex, transcription factor
IIH and RNA polymerase II (Pol II) work together with activators to initiate transcription.
Activator binding alters Mediator structure, yet the functional consequences of
such structural shifts remain unknown. The p53 C terminus and its activation domain
interact with different Mediator subunits, and we find that each interaction differentially
affects Mediator structure; strikingly, distinct p53-Mediator structures differentially
affect Pol II activity. Only the p53 activation domain induces the formation of
a large pocket domain at the Mediator-Pol II interaction site, and this correlates
with activation of stalled Pol II to a productively elongating state. Moreover,
we define a Mediator requirement for TFIIH-dependent Pol II C-terminal domain
phosphorylation and identify substantial differences in Pol II C-terminal domain
processing that correspond to distinct p53-Mediator structural states. Our results
define a fundamental mechanism by which p53 activates transcription and suggest
that Mediator structural shifts trigger activation of stalled Pol II complexes.
article_processing_charge: No
author:
- first_name: Krista
full_name: Meyer, Krista
last_name: Meyer
- first_name: Shih
full_name: Lin, Shih
last_name: Lin
- first_name: Carrie A
full_name: Bernecky, Carrie A
id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87
last_name: Bernecky
orcid: 0000-0003-0893-7036
- first_name: Yuefeng
full_name: Gao, Yuefeng
last_name: Gao
- first_name: Dylan
full_name: Taatjes, Dylan
last_name: Taatjes
citation:
ama: Meyer K, Lin S, Bernecky C, Gao Y, Taatjes D. P53 activates transcription by
directing structural shifts in Mediator. Nature Structural and Molecular Biology.
2010;17(6):753-760. doi:10.1038/nsmb.1816
apa: Meyer, K., Lin, S., Bernecky, C., Gao, Y., & Taatjes, D. (2010). P53 activates
transcription by directing structural shifts in Mediator. Nature Structural
and Molecular Biology. Nature Publishing Group. https://doi.org/10.1038/nsmb.1816
chicago: Meyer, Krista, Shih Lin, Carrie Bernecky, Yuefeng Gao, and Dylan Taatjes.
“P53 Activates Transcription by Directing Structural Shifts in Mediator.” Nature
Structural and Molecular Biology. Nature Publishing Group, 2010. https://doi.org/10.1038/nsmb.1816.
ieee: K. Meyer, S. Lin, C. Bernecky, Y. Gao, and D. Taatjes, “P53 activates transcription
by directing structural shifts in Mediator,” Nature Structural and Molecular
Biology, vol. 17, no. 6. Nature Publishing Group, pp. 753–760, 2010.
ista: Meyer K, Lin S, Bernecky C, Gao Y, Taatjes D. 2010. P53 activates transcription
by directing structural shifts in Mediator. Nature Structural and Molecular Biology.
17(6), 753–760.
mla: Meyer, Krista, et al. “P53 Activates Transcription by Directing Structural
Shifts in Mediator.” Nature Structural and Molecular Biology, vol. 17,
no. 6, Nature Publishing Group, 2010, pp. 753–60, doi:10.1038/nsmb.1816.
short: K. Meyer, S. Lin, C. Bernecky, Y. Gao, D. Taatjes, Nature Structural and
Molecular Biology 17 (2010) 753–760.
date_created: 2018-12-11T11:47:24Z
date_published: 2010-06-01T00:00:00Z
date_updated: 2021-01-12T08:05:28Z
day: '01'
doi: 10.1038/nsmb.1816
extern: '1'
intvolume: ' 17'
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2932482/
month: '06'
oa: 1
oa_version: None
page: 753 - 760
publication: Nature Structural and Molecular Biology
publication_status: published
publisher: Nature Publishing Group
publist_id: '7210'
status: public
title: P53 activates transcription by directing structural shifts in Mediator
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 17
year: '2010'
...
---
_id: '6142'
abstract:
- lang: eng
text: Defining the mutational landscape when individuals of a species grow separately
and diverge over many generations can provide insights into trait evolution. A
specific example of this involves studying changes associated with domestication
where different lines of the same wild stock have been cultivated independently
in different standard environments. Whole genome sequence comparison of such lines
permits estimation of mutation rates, inference of genes' ancestral states and
ancestry of existing strains, and correction of sequencing errors in genome databases.
Here we study domestication of the C. elegans Bristol strain as a model, and report
the genome sequence of LSJ1 (Bristol), a sibling of the standard C. elegans reference
wild type N2 (Bristol). The LSJ1 and N2 lines were cultivated separately from
shortly after the Bristol strain was isolated until methods to freeze C. elegans
were developed. We find that during this time the two strains have accumulated
1208 genetic differences. We describe phenotypic variation between N2 and LSJ1
in the rate at which embryos develop, the rate of production of eggs, the maturity
of eggs at laying, and feeding behavior, all the result of post-isolation changes.
We infer the ancestral alleles in the original Bristol isolate and highlight 2038
likely sequencing errors in the original N2 reference genome sequence. Many of
these changes modify genome annotation. Our study provides a starting point to
further investigate genotype-phenotype association and offers insights into the
process of selection as a result of laboratory domestication.
article_number: e13922
author:
- first_name: Katherine P.
full_name: Weber, Katherine P.
last_name: Weber
- first_name: Subhajyoti
full_name: De, Subhajyoti
last_name: De
- first_name: Iwanka
full_name: Kozarewa, Iwanka
last_name: Kozarewa
- first_name: Daniel J.
full_name: Turner, Daniel J.
last_name: Turner
- first_name: M. Madan
full_name: Babu, M. Madan
last_name: Babu
- first_name: Mario
full_name: de Bono, Mario
id: 4E3FF80E-F248-11E8-B48F-1D18A9856A87
last_name: de Bono
orcid: 0000-0001-8347-0443
citation:
ama: Weber KP, De S, Kozarewa I, Turner DJ, Babu MM, de Bono M. Whole genome sequencing
highlights genetic changes associated with laboratory domestication of C. elegans.
PLoS ONE. 2010;5(11). doi:10.1371/journal.pone.0013922
apa: Weber, K. P., De, S., Kozarewa, I., Turner, D. J., Babu, M. M., & de Bono,
M. (2010). Whole genome sequencing highlights genetic changes associated with
laboratory domestication of C. elegans. PLoS ONE. Public Library of Science.
https://doi.org/10.1371/journal.pone.0013922
chicago: Weber, Katherine P., Subhajyoti De, Iwanka Kozarewa, Daniel J. Turner,
M. Madan Babu, and Mario de Bono. “Whole Genome Sequencing Highlights Genetic
Changes Associated with Laboratory Domestication of C. Elegans.” PLoS ONE.
Public Library of Science, 2010. https://doi.org/10.1371/journal.pone.0013922.
ieee: K. P. Weber, S. De, I. Kozarewa, D. J. Turner, M. M. Babu, and M. de Bono,
“Whole genome sequencing highlights genetic changes associated with laboratory
domestication of C. elegans,” PLoS ONE, vol. 5, no. 11. Public Library
of Science, 2010.
ista: Weber KP, De S, Kozarewa I, Turner DJ, Babu MM, de Bono M. 2010. Whole genome
sequencing highlights genetic changes associated with laboratory domestication
of C. elegans. PLoS ONE. 5(11), e13922.
mla: Weber, Katherine P., et al. “Whole Genome Sequencing Highlights Genetic Changes
Associated with Laboratory Domestication of C. Elegans.” PLoS ONE, vol.
5, no. 11, e13922, Public Library of Science, 2010, doi:10.1371/journal.pone.0013922.
short: K.P. Weber, S. De, I. Kozarewa, D.J. Turner, M.M. Babu, M. de Bono, PLoS
ONE 5 (2010).
date_created: 2019-03-20T15:20:30Z
date_published: 2010-11-11T00:00:00Z
date_updated: 2021-01-12T08:06:20Z
day: '11'
ddc:
- '570'
doi: 10.1371/journal.pone.0013922
extern: '1'
external_id:
pmid:
- '21085631'
file:
- access_level: open_access
checksum: a01e6bbe15f044c0c79a26d7d881953e
content_type: application/pdf
creator: kschuh
date_created: 2019-03-20T15:22:48Z
date_updated: 2020-07-14T12:47:20Z
file_id: '6143'
file_name: 2010_PLOS_Weber.PDF
file_size: 578059
relation: main_file
file_date_updated: 2020-07-14T12:47:20Z
has_accepted_license: '1'
intvolume: ' 5'
issue: '11'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
publication: PLoS ONE
publication_identifier:
issn:
- 1932-6203
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
status: public
title: Whole genome sequencing highlights genetic changes associated with laboratory
domestication of C. elegans
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: 5
year: '2010'
...
---
_id: '6198'
abstract:
- lang: eng
text: 'Stroke is a major public health problem leading to high rates of death and
disability in adults. Excessive stimulation of N-methyl-D-aspartate receptors
(NMDARs) and the resulting neuronal nitric oxide synthase (nNOS) activation are
crucial for neuronal injury after stroke insult. However, directly inhibiting
NMDARs or nNOS can cause severe side effects because they have key physiological
functions in the CNS. Here we show that cerebral ischemia induces the interaction
of nNOS with postsynaptic density protein-95 (PSD-95). Disrupting nNOS-PSD-95
interaction via overexpressing the N-terminal amino acid residues 1-133 of nNOS
(nNOS-N(1-133)) prevented glutamate-induced excitotoxicity and cerebral ischemic
damage. Given the mechanism of nNOS-PSD-95 interaction, we developed a series
of compounds and discovered a small-molecular inhibitor of the nNOS-PSD-95 interaction,
ZL006. This drug blocked the ischemia-induced nNOS-PSD-95 association selectively,
had potent neuroprotective activity in vitro and ameliorated focal cerebral ischemic
damage in mice and rats subjected to middle cerebral artery occlusion (MCAO) and
reperfusion. Moreover, it readily crossed the blood-brain barrier, did not inhibit
NMDAR function, catalytic activity of nNOS or spatial memory, and had no effect
on aggressive behaviors. Thus, this new drug may serve as a treatment for stroke,
perhaps without major side effects. '
author:
- first_name: L
full_name: Zhou, L
last_name: Zhou
- first_name: F
full_name: Li, F
last_name: Li
- first_name: Haibing
full_name: Xu, Haibing
id: 310349D0-F248-11E8-B48F-1D18A9856A87
last_name: Xu
- first_name: CX
full_name: Luo, CX
last_name: Luo
- first_name: HY
full_name: Wu, HY
last_name: Wu
- first_name: MM
full_name: Zhu, MM
last_name: Zhu
- first_name: W
full_name: Lu, W
last_name: Lu
- first_name: X
full_name: Ji, X
last_name: Ji
- first_name: QG
full_name: Zhou, QG
last_name: Zhou
- first_name: DY
full_name: Zhu, DY
last_name: Zhu
citation:
ama: Zhou L, Li F, Xu H, et al. Treatment of cerebral ischemia by disrupting ischemia-induced
interaction of nNOS with PSD-95. Nature Medicine. 2010;16(12):1439-1443.
doi:10.1038/nm.2245
apa: Zhou, L., Li, F., Xu, H., Luo, C., Wu, H., Zhu, M., … Zhu, D. (2010). Treatment
of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95.
Nature Medicine. Nature Publishing Group. https://doi.org/10.1038/nm.2245
chicago: Zhou, L, F Li, Haibing Xu, CX Luo, HY Wu, MM Zhu, W Lu, X Ji, QG Zhou,
and DY Zhu. “Treatment of Cerebral Ischemia by Disrupting Ischemia-Induced Interaction
of NNOS with PSD-95.” Nature Medicine. Nature Publishing Group, 2010. https://doi.org/10.1038/nm.2245.
ieee: L. Zhou et al., “Treatment of cerebral ischemia by disrupting ischemia-induced
interaction of nNOS with PSD-95,” Nature Medicine, vol. 16, no. 12. Nature
Publishing Group, pp. 1439–1443, 2010.
ista: Zhou L, Li F, Xu H, Luo C, Wu H, Zhu M, Lu W, Ji X, Zhou Q, Zhu D. 2010. Treatment
of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95.
Nature Medicine. 16(12), 1439–1443.
mla: Zhou, L., et al. “Treatment of Cerebral Ischemia by Disrupting Ischemia-Induced
Interaction of NNOS with PSD-95.” Nature Medicine, vol. 16, no. 12, Nature
Publishing Group, 2010, pp. 1439–43, doi:10.1038/nm.2245.
short: L. Zhou, F. Li, H. Xu, C. Luo, H. Wu, M. Zhu, W. Lu, X. Ji, Q. Zhou, D. Zhu,
Nature Medicine 16 (2010) 1439–1443.
date_created: 2019-04-04T14:55:32Z
date_published: 2010-11-21T00:00:00Z
date_updated: 2021-01-12T08:06:43Z
day: '21'
doi: 10.1038/nm.2245
extern: '1'
external_id:
pmid:
- '21102461'
intvolume: ' 16'
issue: '12'
language:
- iso: eng
month: '11'
oa_version: None
page: 1439-1443
pmid: 1
publication: Nature Medicine
publication_identifier:
issn:
- 1078-8956
- 1546-170x
publication_status: published
publisher: Nature Publishing Group
quality_controlled: '1'
status: public
title: Treatment of cerebral ischemia by disrupting ischemia-induced interaction of
nNOS with PSD-95
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2010'
...