224 research outputs found
Elevated vitreous body glial fibrillary acidic protein in retinal diseases
- Author
- A Bringmann
- A Bringmann
- A Petzold
- A Petzold
- A Petzold
- A Petzold
- Anselm Gerhard Maria JĂźnemann
- Axel Petzold
- CJ GuĂŠrin
- CJ GuĂŠrin
- Cord Huchzermeyer
- D Mitry
- DG Charteris
- DH Anderson
- E Aken Van
- Eberhart Zrenner
- Friedrich E. Kruse
- GP Lewis
- GP Lewis
- GP Lewis
- GP Lewis
- GP Lewis
- GP Lewis
- H Funatsu
- J Yu
- Konrad Rejdak
- LF Eng
- LF Eng
- LI Los
- M Francke
- M Okada
- M Okada
- NE Byer
- PA Erickson
- PA Erickson
- PA Erickson
- PA Erickson
- PA Erickson
- Pawel Grieb
- RG Schumann
- Robert Rejdak
- Ryszard Maciejewski
- S-C Bu
- SA Reeves
- SF Geller
- SK Fisher
- SK Fisher
- T Ekegren
- TM Nork
- WH Ross
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
TIRAP, an Adaptor Protein for TLR2/4, Transduces a Signal from RAGE Phosphorylated upon Ligand Binding
- Author
- A Taguchi
- Akira Motoyama
- AM Schmidt
- AM Schmidt
- BI Hudson
- C Fages
- C Gebhardt
- CH Yeh
- Dhyan Chandra
- E Leclerc
- E Leclerc
- E Leclerc
- GP Sims
- H Ohnishi
- Hitoshi Murata
- HM Lander
- JH Youn
- JR van Beijnum
- K Ishihara
- K Loser
- Ken Kataoka
- Ken-ichi Yamamoto
- L Lin
- L Lin
- LA O'Neill
- M Fukata
- M Jagannathan
- M Neeper
- M Sakaguchi
- Masakiyo Sakaguchi
- Nam-ho Huh
- NJ Gay
- O Hori
- RR Schumann
- S Akashi-Takamura
- S Ghavami
- SF Yan
- SK Drexler
- T Kawai
- T Nukui
- T Vogl
- Tomoyuki Ono
- Toshihiko Hibino
- YJ Zhou
- Yoshihiko Sakaguchi
- YV Fedorov
- Publication venue
- Public Library of Science
- Publication date
- 01/01/2011
- Field of study
The receptor for advanced glycation end products (RAGE) is thought to be involved in the pathogenesis of a broad range of inflammatory, degenerative and hyperproliferative diseases. It binds to diverse ligands and activates multiple intracellular signaling pathways. Despite these pivotal functions, molecular events just downstream of ligand-activated RAGE have been surprisingly unknown. Here we show that the cytoplasmic domain of RAGE is phosphorylated at Ser391 by PKCÎś upon binding of ligands. TIRAP and MyD88, which are known to be adaptor proteins for Toll-like receptor-2 and -4 (TLR2/4), bound to the phosphorylated RAGE and transduced a signal to downstream molecules. Blocking of the function of TIRAP and MyD88 largely abrogated intracellular signaling from ligand-activated RAGE. Our findings indicate that functional interaction between RAGE and TLRs coordinately regulates inflammation, immune response and other cellular functions
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
- Author
- Abadjiev K
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdullin S
- Abelev B
- Acosta D
- Acosta JG
- Acosta MV
- Actis O
- Adam N
- Adam W
- Adams MR
- Adams T
- Adiguzel A
- Adler V
- Adolphi R
- Adzic P
- Afaq MA
- Agostino L
- Agram JL
- Aguilar-Benitez M
- Ahmad M
- Ahmad WH
- Ahmed I
- Ahmed W
- Ahuja S
- Aisa D
- Aisa S
- Akchurin N
- Akgun B
- Akgun U
- Akimenko S
- Akin IV
- Alagoz E
- Alampi G
- Albajar C
- Albayrak EA
- Alberdi J
- Albergo S
- Albert E
- Albrow M
- Alexander J
- Alidra M
- Aliev T
- Allfrey P
- Almeida N
- Altenhofer G
- Altsybeev I
- Alver B
- Alverson G
- Alves GA
- Amaglobeli N
- Amapane N
- Ambroglini F
- Amsler C
- Anagnostou G
- Ananthan B
- Anastassov A
- Andelin D
- Anderson M
- Andrea J
- Andreev V
- Andreev Y
- Anghel IM
- Anguelov T
- Anh T. Vu
- Anisimov A
- Antillon E
- Antipov P
- Antonelli L
- Anttila E
- Antunes JR
- Antunovic Z
- Apanasevich L
- Apollinari G
- Apresyan A
- Arce P
- Arcidiacono R
- Arenton MW
- Arfaei H
- Argiro S
- Arisaka K
- Arneodo M
- Arnold B
- Arora S
- Artamonov A
- Asaadi J
- Asghar MI
- Ashby S
- Askew A
- Atac M
- Atramentov O
- Auffray E
- Aurisano A
- Autermann C
- Avery P
- Avetisyan A
- Avila C
- Awan MIM
- Ayan AS
- Ayhan A
- Azhgirey I
- Aziz T
- Azzi P
- Azzurri P
- Baarmand MM
- Babb J
- Babucci E
- Baccaro S
- Bacchetta N
- Bacchi W
- Bachtis M
- Baden D
- Badgett W
- Baechler J
- Baer H
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- Baffioni S
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- Bailleux D
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- Bakhshiansohi H
- Bakirci MN
- Bakken JA
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- Ballin J
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- Wilson M. G.
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- Wingerter-Seez I.
- Wingham M
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- Xie S
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- Zachariadou A
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- Zeuner WD
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- Ziebarth EB
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- Publication venue
- 'IOP Publishing'
- Publication date
- 01/01/2009
- Field of study
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
In Vitro Neutralisation of Rotavirus Infection by Two Broadly Specific Recombinant Monovalent Llama-Derived Antibody Fragments
- Author
- A Servin
- AC Linhares
- AF Salim
- Alexandra W. C. Einerhand
- AM Ledeboer
- B Corthesy
- Danielle Wolvers
- DF Gualtero
- E Salazar-Lindo
- Farah Aladin
- GE Armah
- GP Davidson
- H Khoury
- HB Greenberg
- I Ogilvie
- I Schwartz-Cornil
- J Matthijnssens
- J Matthijnssens
- J Taylor
- Janneke Bouma
- JB Pesavento
- JE Tate
- Jim Gray
- JM van der Vaart
- JW Burns
- K Holmstrom
- K Ursu
- Karol Sestak
- Kate Bellamy
- L Garaicoechea
- Leon G. J. Frenken
- LG Frenken
- M Estes
- M Iturriza-GĂłmara
- Miren Iturriza-GĂłmara
- MK Estes
- N Pant
- N Santos
- Pim Hermans
- RF Ramig
- RH van der Linden
- S Guandalini
- SA Madhi
- SA Sarker
- SA Sarker
- Sandra Bezemer
- T Schumann
- UD Parashar
- Publication venue
- Public Library of Science
- Publication date
- 05/03/2012
- Field of study
Rotavirus is the main cause of viral gastroenteritis in young children. Therefore, the development of inexpensive antiviral products for the prevention and/or treatment of rotavirus disease remains a priority. Previously we have shown that a recombinant monovalent antibody fragment (referred to as Anti-Rotavirus Proteins or ARP1) derived from a heavy chain antibody of a llama immunised with rotavirus was able to neutralise rotavirus infection in a mouse model system. In the present work we investigated the specificity and neutralising activity of two llama antibody fragments, ARP1 and ARP3, against 13 cell culture adapted rotavirus strains of diverse genotypes. In addition, immunocapture electron microscopy (IEM) was performed to determine binding of ARP1 to clinical isolates and cell culture adapted strains. ARP1 and ARP3 were able to neutralise a broad variety of rotavirus serotypes/genotypes in vitro, and in addition, IEM showed specific binding to a variety of cell adapted strains as well as strains from clinical specimens. These results indicated that these molecules could potentially be used as immunoprophylactic and/or immunotherapeutic products for the prevention and/or treatment of infection of a broad range of clinically relevant rotavirus strains
Combination Therapy Is Superior to Sequential Monotherapy for the Initial Treatment of Hypertension:A Double-Blind Randomized Controlled Trial
- Author
- Balakrishnan K
- Brown MJ
- Brown R
- Burton TJ
- Cannon J
- Caulfield M
- Collier D
- Coughlan C
- Cruickshank JK
- Enobakhare E
- Findlay E
- Ford I
- Gardiner-Hill CJ
- Helmy J
- Hobbs L
- Hobbs R
- Hood S
- Iles R
- Kean S
- Kwok S
- Lacy P
- MacDonald TM
- MacIntyre IM
- Mackay J
- Mackenzie IS
- Maniero C
- Markandu N
- Martin U
- McCallum L
- McCann GP
- McG Thom SA
- McGinnis AR
- McInnes G
- McInnes GT
- Melville V
- Morant S
- Muir S
- Myint KS
- Nazir S
- Padmanabhan S
- Palmer J
- Papworth R
- Quinn U
- Rutkowski K
- Salsbury J
- Saxena M
- Schumann A
- Sever P
- Simon R
- Soran H
- Stanley AG
- Webb A
- Webb DJ
- White C
- Williams B
- Wilson R
- Zak A
- Publication venue
- 'Ovid Technologies (Wolters Kluwer Health)'
- Publication date
- 01/01/2017
- Field of study
Background: Guidelines for hypertension vary in their preference for initial combination therapy or initial monotherapy, stratified by patient profile; therefore, we compared the efficacy and tolerability of these approaches.
Methods and Results: We performed a 1âyear, doubleâblind, randomized controlled trial in 605 untreated patients aged 18 to 79 years with systolic blood pressure (BP) âĽ150 mm Hg or diastolic BP âĽ95 mm Hg. In phase 1 (weeks 0â16), patients were randomly assigned to initial monotherapy (losartan 50â100 mg or hydrochlorothiazide 12.5â25 mg crossing over at 8 weeks), or initial combination (losartan 50â100 mg plus hydrochlorothiazide 12.5â25 mg). In phase 2 (weeks 17â32), all patients received losartan 100 mg and hydrochlorothiazide 12.5 to 25 mg. In phase 3 (weeks 33â52), amlodipine with or without doxazosin could be added to achieve target BP. Hierarchical primary outcomes were the difference from baseline in home systolic BP, averaged over phases 1 and 2 and, if significant, at 32 weeks. Secondary outcomes included adverse events, and difference in home systolic BP responses between tertiles of plasma renin. Home systolic BP after initial monotherapy fell 4.9 mm Hg (range: 3.7â6.0 mm Hg) less over 32 weeks (P<0.001) than after initial combination but caught up at 32 weeks (difference 1.2 mm Hg [range: â0.4 to 2.8 mm Hg], P=0.13). In phase 1, home systolic BP response to each monotherapy differed substantially between renin tertiles, whereas response to combination therapy was uniform and at least 5 mm Hg more than to monotherapy. There were no differences in withdrawals due to adverse events.
Conclusions: Initial combination therapy can be recommended for patients with BP >150/95 mm Hg.
Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00994617
Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNÎł-like response
- Author
- Thomas Harwardt
- Simone Lukas
- Marion Zenger
- Tobias Reitberger
- Daniela Danzer
- Theresa Ăbner
- Diane C. Munday
- Michael Nevels
- Christina Paulus
- Robert F. Kalejta
- S Abroun
- JJ O'Shea
- D Guschin
- SJ Rodig
- NC Reich
- H Yu
- F Schaper
- B Carow
- Y Yin
- JR Teijaro
- N Au-Yeung
- I Najjar
- B Saha
- G Regis
- AP Costa-Pereira
- HH Ho
- A Stephanou
- P Kumari
- RE Randall
- C Richardson
- T Knoblach
- VH Wood
- R Renne
- M Chatterjee-Kishore
- JE McLaren
- WJ Liu
- WY Chen
- J McLaren
- SV Kuchipudi
- JM Reitsma
- CA King
- D Daigle
- T Du
- ER Hill
- S Koganti
- E Slinger
- M Boeckh
- P Griffiths
- Y Cohen
- E Mocarski
- C Paulus
- M Scherer
- L Amsler
- M Trilling
- VT Le-Trilling
- EE Marshall
- JH Ahn
- JM Gawn
- RF Greaves
- ES Mocarski
- L Torres
- C Paulus
- S Krauss
- YH Huh
- M Scherer
- S MĂźller
- ML Spengler
- M Nevels
- J Reinhardt
- RL Lafemina
- GW Wilkinson
- K MĂźcke
- YE Kim
- J Jaworska
- JL Meier
- A Kaptein
- J Renneson
- RT Taylor
- EP Browne
- G Chan
- M Mezger
- DN Streblow
- J Dumortier
- MC Cheeran
- P Caposio
- SP Gravel
- K Lee
- K Koh
- E Beurel
- M Shu
- DJ Dauer
- M Snyder
- Q Lepiller
- Y Xu
- RD Everett
- Y Lu
- GP Hayhurst
- AD Yurochko
- MJ Margolis
- Q Tang
- M Reeves
- JH Ahn
- M Nevels
- E Zalckvar
- B Raghavan
- B Strobl
- PC Heinrich
- N Stahl
- U Hemmann
- C Gerhartz
- Y Qing
- D Kamimura
- HA Bluyssen
- GR Gariano
- T Li
- F Dag
- JK Holzki
- MB Reeves
- C SĂśderberg-Naucler
- XF Liu
- CA Biron
- M Trilling
- D Hargett
- E Poole
- MS Smith
- E Poole
- RD Everett
- BK Tischer
- H Zhu
- S Hambleton
- FL Graham
- C Sinzger
- M Umashankar
- UK Laemmli
- A Colson
- K Mahboubi
- RP Donnelly
- BJ Grube
- RR Schumann
- MK Steiner
- T Mohri
- JH Lee
- G Hoermann
- SK Singh
- SA Robertson
- A Gazel
- A Ito
- A Okaya
- L Zhang
- A Dreuw
- S Porter
- H Wang
- FM Rogerson
- RI Nurieva
- M Ciofani
- Y Ikeda
- F Blanchard
- SL Turner
- E Larrea
- SR Walker
- BJ Van Lenten
- S Sawa
- P Chakrabarty
- MA Nowell
- EJ Kim
- JA van Roon
- TG Boulton
- CT Sherman
- OA Timofeeva
- Z Ni
- BJ Jenkins
- PA Croonquist
- H Zhu
- M Saito
- JE Jung
- F Xiao
- D Zhang
- D Maritano
- M Ichiba
- KN Khan
- T Wuestefeld
- TK Sengupta
- M Tomida
- AF Voronova
- L Williams
- O Kim
- C Bovolenta
- M Zemskova
- F Zhang
- JX Zhang
- Publication venue
- Publication date
- 01/07/2016
- Field of study
MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNÎł. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNÎł-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNÎł-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe
Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa
- Author
- Abramovic L
- Adams HHH
- Adan R
- Agartz I
- Alfredsson L
- Alhusaini S
- Almasy L
- Ames D
- Andersson M
- Ando T
- Andreassen O
- Andreassen OA
- Anttila V
- Arepalli S
- Arias-Vasquez A
- Aribisala BS
- Armstrong NJ
- Aschauer H
- Ashbrook DG
- Assareh AA
- Athanasiu L
- Baker J
- Barrett J
- Bastin ME
- Batury V-L
- Becker JT
- Bencko V
- Bergen A
- Bernard M
- Berrettini W
- Birgegard A
- Bis JC
- Blangero J
- Bohlken MM
- Boks MP
- Boni C
- Boomsma DI
- Bralten J
- Brandt H
- Breen G
- Brodaty H
- Brouwer RM
- Brown AA
- Brunner HG
- Buckner RL
- Buitelaar JK
- Bulayeva KB
- Bulik CM
- Bulik CM
- Bulik-Sullivan B
- Burghardt R
- Cahn W
- Calhoun VD
- Cannon DM
- Carlberg L
- Carless MA
- Cassina M
- Cavalleri GL
- Chakravarty MM
- Chauhan G
- Chen Q
- Cheung J
- Ching CRK
- Cichon CCS
- Cichon S
- Clementi M
- Cohen-Woods S
- Coleman J
- Cone R
- Cookson MR
- Corvin A
- Courtet P
- Crawford S
- Crespo-Facorro B
- Crow S
- Crowley J
- Cuellar-Partida G
- Curran JE
- Czisch M
- Dale AM
- Danner U
- Davies GE
- Davis O
- de Geus EJC
- de Zubicaray GI
- de Zwaan M
- Deary IJ
- Dedoussis G
- Degortes D
- Delanty N
- Den Braber A
- Depondt C
- DeSocio J
- Desrivieres S
- Dick D
- Dikeos D
- Dillman A
- Dina C
- Ding B
- Djurovic S
- Dmitrzak-Weglarz M
- Docampo E
- Donohoe G
- Drevets WC
- Duggirala R
- Duncan L
- Dyer TD
- Ebling M
- Egberts K
- Ehrlich S
- Ehrlich S
- Ehrlich S
- Erk S
- Escaramis G
- Esko T
- Espeseth T
- Espeseth T
- Estivill X
- Favaro A
- Fedko IO
- Fernandez G
- Fernandez-Aranda F
- Ferrucci L
- Fichter M
- Finan C
- Fischer K
- Fischl B
- Fisher SE
- Floyd J
- Focker M
- Foretova L
- Foroud TM
- Forzan M
- Fox C
- Fox PT
- Francks C
- Franke B
- Franklin C
- Fukunaga M
- Gallinger VGS
- Gambaro G
- Gaspar H
- Gibbs JR
- Giddaluru S
- Giegling I
- Glahn DC
- Goldman AL
- Goldstein J
- Gollub RL
- Gonidakis F
- Goring HHH
- Gorwood P
- Grabe HJ
- Gratacos M
- Green RC
- Greve D
- Grimm O
- Gruber O
- Guadalupe T
- Gudnason V
- Guelfi S
- Guillaume S
- Guo Y
- Hager R
- Hakobjan MMH
- Hakonarson H
- Halmi K
- Hansell NK
- Hardy J
- Harrison R
- Hartberg CB
- Hartman CA
- Hashimoto R
- Hass J
- Hatzikotoulas K
- Haukvik UK
- Hauser J
- Hebebrand J
- Hegenscheid K
- Heinz A
- Heister AJGAM
- Helder S
- Hendriks J
- Herms S
- Hernandez DG
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- Publication venue
- 'Springer Fachmedien Wiesbaden GmbH'
- Publication date
- 01/07/2019
- Field of study
In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, nâ=â13,170) and genetic risk for AN (PGC-ED consortium, nâ=â14,477). Genetic correlations ranged from ââ0.10 to 0.23 (all pâ>â0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted pâ=â0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDRâ=â0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDRâ=â0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN
Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV
- Author
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- Publication venue
- Publication date
- 01/01/2016
- Field of study
Peer reviewe
CMS Data Processing Workflows during an Extended Cosmic Ray Run
- Author
- Abadjiev K
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdullin S
- Abelev B
- Acosta D
- Acosta JG
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- Zachariadou A
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- Zeuner WD
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- Zhang J
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- Zheng Y
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- Zhukov V
- Zhukova V
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- Publication venue
- INSTITUTE OF PHYSICS PUBLISHING
- Publication date
- 01/01/2009
- Field of study
Peer reviewe
Aligning the CMS Muon Chambers with the Muon Alignment System during an Extended Cosmic Ray Run
- Author
- Abadjiev K
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdullin S
- Abelev B
- Acosta D
- Acosta JG
- Acosta MV
- Actis O
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- Adam W
- Adams MR
- Adams T
- Adiguzel A
- Adler V
- Adolphi R
- Adzic P
- Afaq MA
- Agostino L
- Agram JL
- Aguilar Benitez M
- Ahmad M
- Ahmad WH
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- Ahmed W
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- Akgun B
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- Akin IV
- Alagoz E
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- Alberdi J
- Albergo S
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- Alexander J
- Alidra M
- Aliev T
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- Altenhofer G
- Altsybeev I
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- Alverson G
- Alves GA
- Amaglobeli N
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- Ambroglini F
- Amsler C
- Anagnostou G
- Ananthan B
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- Andelin D
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- Andreev Y
- Anghel IM
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- Asghar MI
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- Publication venue
- Publication date
- 01/01/2009
- Field of study
Peer reviewe
- âŚ