647 research outputs found
A brain-sparing diphtheria toxin for chemical genetic ablation of peripheral cell lineages.
- Author
- Publication venue
- Nat Commun
- Publication date
- 01/01/2017
- Field of study
Conditional expression of diphtheria toxin receptor (DTR) is widely used for tissue-specific ablation of cells. However, diphtheria toxin (DT) crosses the blood-brain barrier, which limits its utility for ablating peripheral cells using Cre drivers that are also expressed in the central nervous system (CNS). Here we report the development of a brain-sparing DT, termed BRAINSPAReDT, for tissue-specific genetic ablation of cells outside the CNS. We prevent blood-brain barrier passage of DT through PEGylation, which polarizes the molecule and increases its size. We validate BRAINSPAReDT with regional genetic sympathectomy: BRAINSPAReDT ablates peripheral but not central catecholaminergic neurons, thus avoiding the Parkinson-like phenotype associated with full dopaminergic depletion. Regional sympathectomy compromises adipose tissue thermogenesis, and renders mice susceptible to obesity. We provide a proof of principle that BRAINSPAReDT can be used for Cre/DTR tissue-specific ablation outside the brain using CNS drivers, while consolidating the link between adiposity and the sympathetic nervous system
Circulating endothelial cell-derived extracellular vesicles mediate the acute phase response and sickness behaviour associated with CNS inflammation.
- Author
- B Moser
- BL Hart
- C Coupade de
- CI Timar
- CJ Smith
- CM Uhlar
- D Blond
- D Paul
- DC Wilcockson
- E Colombo
- F Dignat-George
- F Docagne
- G Katsuura
- G Raposo
- HR Anforth
- J Simak
- JB Pankoui Mfonkeu
- JG Wang
- JM Inal
- KA Hogquist
- L McCluskey
- M Bernardes-Silva
- MA McAteer
- MW Pfaffl
- N Kosaka
- N Sheikh
- PB Andersson
- R Yirmiya
- RJ Berckmans
- RJ Berckmans
- RM Deacon
- RN Walsh
- S Yamamoto
- SI Kasteren van
- SJ Campbell
- SJ Campbell
- SJ Campbell
- SJ Campbell
- SJ Campbell
- SJ Campbell
- SJ Campbell
- T Nozaki
- V Murta
- WM Clark
- Y Couch
- Y Jiang
- Z Yu
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2017
- Field of study
Brain injury elicits a systemic acute-phase response (APR), which is responsible for co-ordinating the peripheral immunological response to injury. To date, the mechanisms responsible for signalling the presence of injury or disease to selectively activate responses in distant organs were unclear. Circulating endogenous extracellular vesicles (EVs) are increased after brain injury and have the potential to carry targeted injury signals around the body. Here, we examined the potential of EVs, isolated from rats after focal inflammatory brain lesions using IL-1β, to activate a systemic APR in recipient naïve rats, as well as the behavioural consequences of EV transfer. Focal brain lesions increased EV release, and, following isolation and transfer, the EVs were sequestered by the liver where they initiated an APR. Transfer of blood-borne EVs from brain-injured animals was also enough to suppress exploratory behaviours in recipient naïve animals. EVs derived from brain endothelial cell cultures treated with IL-1β also activated an APR and altered behaviour in recipient animals. These experiments reveal that inflammation-induced circulating EVs derived from endothelial cells are able to initiate the APR to brain injury and are sufficient to generate the associated sickness behaviours, and are the first demonstration that EVs are capable of modifying behavioural responses
Compressed representation of a partially defined integer function over multiple arguments
- Author
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdelalim AA
- Abdullin S
- Abdulsalam A
- Acosta D
- Acosta MV
- Adair A
- Adam W
- Adams MR
- Adams T
- Adiguzel A
- Adler V
- Adzic P
- Agram J-L
- Aguilar-Benitez M
- Ahmad M
- Ahmad WH
- Ahuja S
- Akchurin N
- Akgun B
- Akgun U
- Akin IV
- Alagoz E
- Albajar C
- Albayrak EA
- Albergo S
- Albrow M
- Alcaraz Maestre J
- Alda Junior WL
- Alderweireldt S
- Alexander J
- Aliev T
- Alimena J
- Almeida N
- Alverson G
- Alves GA
- Amapane N
- Amsler C
- Anagnostou G
- Anastassov A
- Anderson J
- Andrea J
- Andreev V
- Andreev V
- Andreev Y
- Andrews W
- Androsov K
- Antonelli L
- Antunovic Z
- Apanasevich L
- Apollinari G
- Appelt E
- Apresyan A
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- Arcidiacono R
- Arenton MW
- Arfaei H
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- Arneodo M
- Arora S
- Asavapibhop B
- Asawatangtrakuldee C
- Asghar MI
- Asin I
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- Assran Y
- Ata M
- Attikis A
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- Autermann C
- Auzinger G
- Avdeeva E
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- Avetisyan A
- Avila C
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- Publication venue
- Publication date
- 01/01/2013
- Field of study
In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
- Author
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdullin S
- Acosta D
- Acosta JG
- Acosta MV
- Adair A
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- Anastassov A
- Anderson J
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- Andrews W
- Anghel IM
- Anjos TS
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- Apollinari G
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- Autermann C
- Auzinger G
- Avdeeva E
- Avery P
- Avetisyan A
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- Azhgirey I
- Aziz T
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- Yetkin T
- Yi K
- Yildirim E
- Yilmaz Y
- Yohay R
- Yoo HD
- Yoo J
- Yoon AS
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- Yumiceva F
- Yun JC
- Zabel J
- Zabi A
- Zablocki J
- Zaganidis N
- Zakaria M
- Zalewski P
- Zanetti M
- Zang J
- Zang SL
- Zarubin A
- Zatserklyaniy A
- Zeinali M
- Zeise M
- Zeuner WD
- Zeyrek M
- Zhang J
- Zhang Z
- Zheng Y
- Zhokin A
- Zhu B
- Zhu RY
- Zhukov V
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- Zoeller MH
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- Zumerle G
- Zuranski A
- Publication venue
- 'IOP Publishing'
- Publication date
- 01/01/2012
- Field of study
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
- Author
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdullin S
- Acosta D
- Acosta JG
- Acosta MV
- Adair A
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- Adam W
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- Adiguzel A
- Adler V
- Adzic P
- Agostino L
- Agram JL
- Aguilar-Benitez M
- Aguilo E
- Ahmad M
- Ahmad WH
- Ahuja S
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- Akin IV
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- Amsler C
- Anagnostou G
- Anastassov A
- Anderson J
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- Andrea J
- Andreev V
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- Andreev Y
- Andrews W
- Anghel IM
- Anjos TS
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- Antunes JR
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- Yilmaz Y
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- Yun JC
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- Zalewski P
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- Zang J
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- Publication venue
- 'IOP Publishing'
- Publication date
- 01/01/2012
- Field of study
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV
- Author
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- Abbiendi G
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- Yi K
- Yildirim E
- Yilmaz Y
- Yohay R
- Yoo HD
- Yoo J
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- Yumiceva F
- Yun JC
- Zabel J
- Zabi A
- Zablocki J
- Zaganidis N
- Zakaria M
- Zalewski P
- Zanetti M
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- Zarubin A
- Zatserklyaniy A
- Zeinali M
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- Zumerle G
- Zuranski A
- Publication venue
- 'American Physical Society (APS)'
- Publication date
- 01/01/2012
- Field of study
The azimuthal anisotropy of charged particles in PbPb collisions at
nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS
detector at the LHC over an extended transverse momentum (pt) range up to
approximately 60 GeV. The data cover both the low-pt region associated with
hydrodynamic flow phenomena and the high-pt region where the anisotropies may
reflect the path-length dependence of parton energy loss in the created medium.
The anisotropy parameter (v2) of the particles is extracted by correlating
charged tracks with respect to the event-plane reconstructed by using the
energy deposited in forward-angle calorimeters. For the six bins of collision
centrality studied, spanning the range of 0-60% most-central events, the
observed v2 values are found to first increase with pt, reaching a maximum
around pt = 3 GeV, and then to gradually decrease to almost zero, with the
decline persisting up to at least pt = 40 GeV over the full centrality range
measured.Comment: Replaced with published version. Added journal reference and DO
Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy
- Author
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdullin S
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- Cremaldi LM
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- Cumalat JP
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- Cushman P
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- Custodio A
- Cutajar M
- Cutts D
- Cwiok M
- Czellar S
- D'Agnolo RT
- D'Alessandro R
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- D'Enterria D
- D'Hondt J
- Da Costa EM
- Dabrowski A
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- Dahmes B
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- Dallavalle GM
- Damgov J
- Damiao DD
- Dammann D
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- Yilmaz Y
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- Zielinski M
- Zito G
- Zou W
- Zucchetta A
- Zumerle G
- Zuranski A
- Publication venue
- 'American Physical Society (APS)'
- Publication date
- 01/01/2012
- Field of study
A search for new physics is performed in events with two same-sign isolated
leptons, hadronic jets, and missing transverse energy in the final state. The
analysis is based on a data sample corresponding to an integrated luminosity of
4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of
7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of
140 increase in integrated luminosity over previously published results. The
observed yields agree with the standard model predictions and thus no evidence
for new physics is found. The observations are used to set upper limits on
possible new physics contributions and to constrain supersymmetric models. To
facilitate the interpretation of the data in a broader range of new physics
scenarios, information on the event selection, detector response, and
efficiencies is provided.Comment: Published in Physical Review Letter
Search for anomalous t t-bar production in the highly-boosted all-hadronic final state
- Author
- A. A. Ocampo Rios
- A. Abdulsalam
- A. Adair
- A. Adiguzel
- A. Anastassov
- A. Apresyan
- A. Askew
- A. Attikis
- A. Avetisyan
- A. B. Meyer
- A. Baden
- A. Barker
- A. Bean
- A. Belyaev
- A. Belyaev
- A. Benaglia
- A. Beretvas
- A. Bethani
- A. Bhatti
- A. Bocci
- A. Bodek
- A. Bonato
- A. Bornheim
- A. Branca
- A. Brinkerhoff
- A. Burgmeier
- A. C. Benvenuti
- A. C. Marini
- A. C. Mignerey
- A. Cakir
- A. Calderon
- A. Campbell
- A. Castro
- A. Chatterjee
- A. Cimmino
- A. Colaleo
- A. CustĂłdio
- A. David
- A. De Benedetti
- A. De Cosa
- A. De Roeck
- A. Deisher
- A. Delgado Peris
- A. Dermenev
- A. Dierlamm
- A. Dimitrov
- A. Dominguez
- A. Drozdetskiy
- A. Elliott-Peisert
- A. Ellithi Kamel
- A. Ershov
- A. Everett
- A. F. Barfuss
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- A. Falkiewicz
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- A. Ferapontov
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- Y. Eshaq
- Y. F. Liu
- Y. Fu
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- Y. Gotra
- Y. Guo
- Y. H. Chang
- Y. H. Chang
- Y. Hsiung
- Y. Iiyama
- Y. Ivanov
- Y. J. Lei
- Y. J. Lu
- Y. K. Choi
- Y. Kim
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- Y. Kuessel
- Y. Lu
- Y. M. Tzeng
- Y. Ma
- Y. Mao
- Y. Maravin
- Y. Musienko
- Y. Onel
- Y. Pakhotin
- Y. Roh
- Y. S. Chung
- Y. Sirois
- Y. Tschudi
- Y. Tu
- Y. W. Chang
- Y. Weng
- Y. Yang
- Y. Yilmaz
- Y. Zheng
- Y.-J. Lee
- YL Dokshitzer
- Yu. Andreev
- Z. Antunovic
- Z. C. Yang
- Z. Chen
- Z. Hatherell
- Z. Hu
- Z. J. Guo
- Z. K. Liu
- Z. L. Trocsanyi
- Z. Szillasi
- Z. Tsamalaidze
- Z. Wang
- Z. Zhang
- Zero J. Kim
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2012
- Field of study
A search is presented for a massive particle, generically referred to as a
Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are
sufficiently massive to produce highly Lorentz-boosted top quarks, which yield
collimated decay products that are partially or fully merged into single jets.
The analysis uses new methods to analyze jet substructure, providing
suppression of the non-top multijet backgrounds. The analysis is based on a
data sample of proton-proton collisions at a center-of-mass energy of 7 TeV,
corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits
in the range of 1 pb are set on the product of the production cross section and
branching fraction for a topcolor Z' modeled for several widths, as well as for
a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any
enhancement in t t-bar production beyond expectations of the standard model for
t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version
includes a minor typo correction that will be submitted as an erratu
Measurement of jet fragmentation into charged particles in pp and PbPb collisions at sqrt(s[NN]) = 2.76 TeV
- Author
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- Zuranski A
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2012
- Field of study
Jet fragmentation in pp and PbPb collisions at a centre-of-mass energy of
2.76 TeV per nucleon pair was studied using data collected with the CMS
detector at the LHC. Fragmentation functions are constructed using
charged-particle tracks with transverse momenta pt > 4 GeV for dijet events
with a leading jet of pt > 100 GeV. The fragmentation functions in PbPb events
are compared to those in pp data as a function of collision centrality, as well
as dijet-pt imbalance. Special emphasis is placed on the most central PbPb
events including dijets with unbalanced momentum, indicative of energy loss of
the hard scattered parent partons. The fragmentation patterns for both the
leading and subleading jets in PbPb collisions agree with those seen in pp data
at 2.76 TeV. The results provide evidence that, despite the large parton energy
loss observed in PbPb collisions, the partition of the remaining momentum
within the jet cone into high-pt particles is not strongly modified in
comparison to that observed for jets in vacuum.Comment: Submitted to the Journal of High Energy Physic
Site-selective protein-modification chemistry for basic biology and drug development.
- Author
- A Perols
- A Sachdeva
- AJ Keefe
- B Fierz
- B-Q Shen
- BM Zeglis
- C Chatterjee
- C Goodman
- CD Spicer
- CT Walsh
- D Schumacher
- DP Nguyen
- E Arbely
- EM Pelegri-O'Day
- EM Sletten
- F Casadio
- F Li
- F Tian
- Filipa P. da Cruz
- G Pasut
- GJL Bernardes
- Gonçalo J. L. Bernardes
- H Cho
- H Neumann
- HF Gaertner
- HP Hemantha
- J Li
- J Li
- J Madrzak
- J Xie
- J-M Kee
- JI MacDonald
- JL Seitchik
- JM Chalker
- JM Chalker
- JM Chalker
- JM Gilmore
- JR Junutula
- JY Axup
- K Lang
- K Lang
- K Wang
- KJ Hamblett
- KP Chooi
- L Davis
- LN Tumey
- M Rashidian
- M Steiner
- M Yang
- MD Simon
- N Stephanopoulos
- N Toda
- Nikolaus Krall
- NS Beckley
- Omar Boutureira
- P Agarwal
- P Dawson
- P Wang
- PM Drake
- PMSD Cal
- R Huang
- R Rossin
- R Serwa
- RM Versteegen
- RP Lyon
- RVJ Chari
- RVJ Chari
- S Arur
- S Tyagi
- S Virdee
- S Virdee
- S Zheng
- SI van Kasteren
- SNS Alconcel
- T Burckstummer
- T Schneider
- TS Elliott
- TW Muir
- W Liu
- Publication venue
- Nat Chem
- Publication date
- 30/11/2015
- Field of study
Nature has produced intricate machinery to covalently diversify the structure of proteins after their synthesis in the ribosome. In an attempt to mimic nature, chemists have developed a large set of reactions that enable post-expression modification of proteins at pre-determined sites. These reactions are now used to selectively install particular modifications on proteins for many biological and therapeutic applications. For example, they provide an opportunity to install post-translational modifications on proteins to determine their exact biological roles. Labelling of proteins in live cells with fluorescent dyes allows protein uptake and intracellular trafficking to be tracked and also enables physiological parameters to be measured optically. Through the conjugation of potent cytotoxicants to antibodies, novel anti-cancer drugs with improved efficacy and reduced side effects may be obtained. In this Perspective, we highlight the most exciting current and future applications of chemical site-selective protein modification and consider which hurdles still need to be overcome for more widespread use.We thank FCT Portugal (FCT Investigator to G.J.L.B.), the EU (Marie-Curie CIG to G.J.L.B. and Marie-Curie IEF to O.B.) and the EPSRC for funding. G.J.L.B. is a Royal Society University Research Fellow.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nchem.239
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