409 research outputs found
On Electrical Equivalence of Aperture-Body and Transmission-Cavity Resonance Phenomena in Subwavelength Conducting Aperture Systems from an Equivalent Circuit Point of View
- Publication venue
- 'American Scientific Publishers'
- Publication date
- 29/12/2009
- Field of study
For a narrow slit structure backed by a conducting strip which is taken as a
representative example of an aperture-body resonance (ABR) problem, the
transmission resonance condition (i.e., condition for maximum power
transmission) and the transmission width (i.e., normalized maximum transmitted
power through the slit) are found to be the same as those for narrow slit
coupling problem in a thick conducting screen, which is designated as a
transmission-cavity resonance (TCR) problem. From a viewpoint of equivalent
circuit representation for the transmission resonance condition and the
funneling mechanism, the ABR and the TCR problems are thought to be essentially
of the same nature.Comment: 14 pages, 3 figure
Novel method of real-time PCR-based screening for common fetal trisomies
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/07/2021
- Field of study
Background
The non-invasive prenatal test (NIPT) is based on next generation sequencing (NGS) and is used for screening for fetal trisomy. However, it is time-consuming and technically difficult. Recently, peptide nucleic acid (PNA) probe-based real-time polymerase chain reaction (RT-PCR) was developed. This study aimed to examine the performance of the RT-PCR-based NIPT for screening of common fetal trisomies
Methods
From stored maternal plasma, RT-PCR was performed using Patio™ NIPT Detection Kit. In melting curve analysis, the height of melting peaks of target chromosome and reference chromosome was calculated as a peak ratio. The adjusted peak ratio of 8 markers with correction factors in each target chromosome was summated and calculated to z-score. The cut-off value for each target chromosome was established for classification (low risk vs. high risk for trisomy) whose performance was obtained in the validation phase.
Results
330 plasma samples from pregnant women with normal fetus and 22 trisomy cell-line samples were used to establish the optimal cut-off values for z-score of each target chromosome. In the validation phase, 1023 samples from pregnant women including 22 cases with fetal trisomy and 1001 cases of normal control were used. The RT-PCR-based NIPT showed 95.45% sensitivity [95% confidence interval (CI) 77.16–99.88%], 98.60% specificity (95% CI 97.66–99.23%), and 98.53% accuracy (95% CI 97.59–99.18%) for the identification of trisomy 21, 18, or 13. Of 1023 samples, fifteen cases were mismatched for classification [one case as a false negative (false negative rate: 4.5%) and 14 cases as false positives (false positive rate: 1.4%)].
Conclusion
The RT-PCR-based NIPT showed high sensitivity and specificity for the detection of common fetal trisomies and it could be a feasible alternative to NGS-based NIPT.This study was supported by the Technology Innovation Program (or Industrial Strategic Technology Development Program) (N0002392) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea). And this work was funded by grants (HI16C0628) from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the
Ministry of Health and Welfare, Republic of Korea. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
The Association of AMPK with ULK1 Regulates Autophagy
- Author
- A Matsuura
- AJ Meijer
- B Gan
- C Behrends
- CA Mercer
- CH Jung
- D Meley
- DB Shackelford
- DH Kim
- DM Gwinn
- E Vander Haar
- G Wang
- Gen Sheng Wu
- H Nakatogawa
- H Yamaguchi
- Hong-Gang Wang
- HR Samari
- HR Samari
- IG Ganley
- J Liang
- Jong Woo Lee
- K Inoki
- K Inoki
- M Buzzai
- M Komatsu
- M Tsukada
- N Hosokawa
- N Hosokawa
- N Mizushima
- N Mizushima
- N Okazaki
- QJ Wang
- R Viana
- RC Scott
- S Wullschleger
- SB Lee
- Sungman Park
- T Hara
- T Tomoda
- Y Kabeya
- Y Kamada
- Y Sancak
- Yoshinori Takahashi
- YY Chang
- Publication venue
- Public Library of Science
- Publication date
- 03/11/2010
- Field of study
Autophagy is a highly orchestrated intracellular bulk degradation process that is activated by various environmental stresses. The serine/threonine kinase ULK1, like its yeast homologue Atg1, is a key initiator of autophagy that is negatively regulated by the mTOR kinase. However, the molecular mechanism that controls the inhibitory effect of mTOR on ULK1-mediated autophagy is not fully understood. Here we identified AMPK, a central energy sensor, as a new ULK1-binding partner. We found that AMPK binds to the PS domain of ULK1 and this interaction is required for ULK1-mediated autophagy. Interestingly, activation of AMPK by AICAR induces 14-3-3 binding to the AMPK-ULK1-mTORC1 complex, which coincides with raptor Ser792 phosphorylation and mTOR inactivation. Consistently, AICAR induces autophagy in TSC2-deficient cells expressing wild-type raptor but not the mutant raptor that lacks the AMPK phosphorylation sites (Ser722 and Ser792). Taken together, these results suggest that AMPK association with ULK1 plays an important role in autophagy induction, at least in part, by phosphorylation of raptor to lift the inhibitory effect of mTOR on the ULK1 autophagic complex
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector
- Author
- Aad G
- Abbott B
- Abbott DC
- Abeling K
- Abhayasinghe DK
- Abidi SH
- AbouZeid OS
- Abraham NL
- Abramowicz H
- Abreu H
- Abud AA
- Abulaiti Y
- Acharya BS
- Achkar B
- Adachi S
- Adam L
- Adamczyk L
- Adamek L
- Adelman J
- Adersberger M
- Adiguzel A
- Adorni S
- Adye T
- Affolder AA
- Afik Y
- Agapopoulou C
- Agaras MN
- Aggarwal A
- Agheorghiesei C
- Aguilar-Saavedra JA
- Ahmadov F
- Ahmed WS
- Ai X
- Aielli G
- Akatsuka S
- Akesson TPA
- Akilli E
- Akimov A
- Al Khoury K
- Alberghi GL
- Albert J
- Alderweireldt S
- Aleksa M
- Aleksandrov IN
- Alexa C
- Alexopoulos T
- Alfonsi A
- Alfonsi F
- Alhroob M
- Ali B
- Aliev M
- Alimonti G
- Allaire C
- Allbrooke BMM
- Allen BW
- Allport PP
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- Alshehri AA
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- Alviggi MG
- Amaral Coutinho Y
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- Amor Dos Santos SP
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- Zhemchugov A
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- Zwalinski L
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2015
- Field of study
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV
- Author
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- Yildizb HD
- Yilmaz M
- Yoosootiniya R
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- Zajacova Z
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- Zarzhitsky P
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- Zenonos Z
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- Zhemchugov A
- Zheng S
- Zhong J
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- Zhu CG
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- Zhuravlov V
- Zieminska D
- Zimmermann R
- Zimmermann S
- Zimmermann S
- Zinonos Z
- Ziolkowski M
- Zitoun R
- Zivkovic L
- Zmouchko VV
- Zobernig G
- Zoccoli A
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- Zsenei A
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- Zwalinski L
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/03/2013
- Field of study
The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration
Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector
- Author
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- Abdallah J
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- Abdesselam A
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- Zhemchugov A
- Zheng S
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- Zhuravlov V
- Zieminska D
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- Ziolkowski M
- Zitoun R
- Zivkovic L
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- zur Nedden M
- Zutshi V
- Zwalinski L
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 31/12/2010
- Field of study
The inclusive and dijet production cross-sections have been measured for jets
containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass
energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The
measurements use data corresponding to an integrated luminosity of 34 pb^-1.
The b-jets are identified using either a lifetime-based method, where secondary
decay vertices of b-hadrons in jets are reconstructed using information from
the tracking detectors, or a muon-based method where the presence of a muon is
used to identify semileptonic decays of b-hadrons inside jets. The inclusive
b-jet cross-section is measured as a function of transverse momentum in the
range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet
cross-section is measured as a function of the dijet invariant mass in the
range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets
and the angular variable chi in two dijet mass regions. The results are
compared with next-to-leading-order QCD predictions. Good agreement is observed
between the measured cross-sections and the predictions obtained using POWHEG +
Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet
cross-section. However, it does not reproduce the measured inclusive
cross-section well, particularly for central b-jets with large transverse
momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final
version published in European Physical Journal
Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector
- Author
- Aad G
- Abajyan T
- Abbott B
- Abdallah J
- Khalek SA
- Abdelalim AA
- Abdinov O
- Aben R
- Abi B
- Abolins M
- AbouZeid OS
- Abramowicz H
- Abreu H
- Acharya BS
- Adamczyk L
- Adams DL
- Addy TN
- Adelman J
- Adomeit S
- Adragna P
- Adye T
- Aefsky S
- Aguilar-Saavedra JA
- Agustoni M
- Aharrouche M
- Ahlen SP
- Ahles F
- Ahmad A
- Ahsan M
- Aielli G
- Akesson TPA
- Akimoto G
- Akimov AV
- Alam MS
- Alam MA
- Albert J
- Albrand S
- Aleksa M
- Aleksandrov IN
- Alessandria F
- Alexa C
- Alexander G
- Alexandre G
- Alexopoulos T
- Alhroob M
- Aliev M
- Alimonti G
- Alison J
- Allbrooke BMM
- Allport PP
- Allwood-Spiers SE
- Almond J
- Aloisio A
- Alon R
- Alonso A
- Alonso F
- Altheimer A
- Gonzalez BA
- Alviggi MG
- Amako K
- Amelung C
- Ammosov VV
- Amor Dos Santos SP
- Amorim A
- Amram N
- Anastopoulos C
- Ancu LS
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- Anderson KJ
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- Antonaki A
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- Aoki M
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- de Renstrom PAB
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- Wicek F
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- Wickens FJ
- Wiedenmann W
- Wielers M
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- Wiglesworth C
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- Winkelmann S
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- Wolter MW
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- Wosiek BK
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- Woudstra MJ
- Wozniak KW
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- Yamaguchi H
- Yamamoto A
- Yamamoto K
- Yamamoto S
- Yamamura T
- Yamanaka T
- Yamazaki T
- Yamazaki Y
- Yan Z
- Yang H
- Yang UK
- Yang Y
- Yang Z
- Yanush S
- Yao L
- Yao Y
- Yasu Y
- Smit GVY
- Ye J
- Ye S
- Yilmaz M
- Yoosoofmiya R
- Yorita K
- Yoshida R
- Yoshihara K
- Young C
- Young CJ
- Youssef S
- Yu D
- Yu DR
- Yu J
- Yu J
- Yuan L
- Yurkewicz A
- Zabinski B
- Zaidan R
- Zaitsev AM
- Zajacova Z
- Zanello L
- Zanzi D
- Zaytsev A
- Zeitnitz C
- Zeman M
- Zemla A
- Zendler C
- Zenin O
- Zenis T
- Zinonos Z
- Zerwas D
- della Porta GZ
- Zhang D
- Zhang H
- Zhang J
- Zhang X
- Zhang Z
- Zhao L
- Zhao Z
- Zhemchugov A
- Zhong J
- Zhou B
- Zhou N
- Zhou Y
- Zhu CG
- Zhu H
- Zhu J
- Zhu Y
- Zhuang X
- Zhuravlov V
- Zibell A
- Zieminska D
- Zimin NI
- Zimmermann R
- Zimmermann S
- Zimmermann S
- Ziolkowski M
- Zitoun R
- Zivkovic L
- Zmouchko VV
- Zobernig G
- Zoccoli A
- zur Nedden M
- Zutshi V
- Zwalinski L
- Collaboration ATLAS
- Publication venue
- Springer Verlag
- Publication date
- 01/01/2008
- Field of study
A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of s=7TeV proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40
Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector
- Author
- Aad G
- Abajyan T
- Abbott B
- Abdallah J
- Abdelalim AA
- Abdinov O
- Aben R
- Abi B
- Abolins M
- AbouZeid OS
- Abramowicz H
- Abreu H
- Acharya BS
- Adamczyk L
- Adams DL
- Addy TN
- Adelman J
- Adomeit S
- Adragna P
- Adye T
- Aefsky S
- Aguilar-Saavedra JA
- Agustoni M
- Aharrouche M
- Ahlen SP
- Ahles R
- Ahmad A
- Ahsan M
- Aielli G
- Akesson TPA
- Akimoto G
- Akimov AV
- Alam MA
- Alam MS
- Albert J
- Albrand S
- Aleksa M
- Aleksandrov IN
- Alessandria F
- Alexa C
- Alexander G
- Alexandre G
- Alexopoulos T
- Alhroob M
- Aliev M
- Alimonti G
- Alison J
- Allbrooke BMM
- Allport PP
- Allwood-Spiers SE
- Almenar CC
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- Castanheira MTD
- Castillo IS
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- Cavasinni V
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- Chalupkova I
- Chan K
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- Chapman JD
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- Charlton DG
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- Cheatham S
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- Chekulaev SV
- Chelkov GA
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- Sundermann JE
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- Tan KG
- Tanaka J
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- Tanasijczuk AJ
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- Therhaag JJ
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- Thomas JP
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- Thompson EN
- Thompson PD
- Thompson PD
- Thomsen LA
- Thomson E
- Thomson M
- Thong WM
- Thun RP
- Tian F
- Tibbetts MJ
- Tic T
- Tikhomirov VO
- Tikhonov YA
- Timoshenko S
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- Todorova-Nova S
- Toggerson B
- Tojo J
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- Tricoli A
- Trigger IM
- Trincaz-Duvoid S
- Tripiana MF
- Triplett N
- Trischuk W
- Trocme B
- Troncon C
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- Trzebinski M
- Trzupek A
- Tsarouchas C
- Tseng JC-L
- Tsiakiris M
- Tsiareshka P
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- Tsipolitis G
- Tsiskaridze S
- Tsiskaridze V
- Tskhadadze EG
- Tsukerman II
- Tsulaia V
- Tsung J-W
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- Tua A
- Tudorache A
- Tudorache V
- Tuggle JM
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- Turra R
- Tuts PM
- Tykhonov A
- Tylmad M
- Tyndel M
- Tzanakos G
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- Uhlenbrock M
- Uhrmacher M
- Ukegawa F
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- Unno Y
- Urbaniec D
- Urquijo P
- Usai G
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- Valentinetti S
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- van Gemmeren P
- van Huysduynen LH
- van Vulpen I
- Vanadia M
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- Varnes EW
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- Volpi M
- Volpini G
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- Voss TT
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- Vuillermet R
- Vukotic I
- Wagner P
- Wagner W
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- Whiteson D
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- Wiglesworth C
- Wiik-Fuchs LAM
- Wijeratne PA
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- Wilkens HG
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- Williams HH
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- Willocoq S
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- Wilson MG
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- Winkelmann S
- Winklmeier F
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- Wu Y
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- Xella S
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- Xu D
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- Yabsley B
- Yacoob S
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- Yamada M
- Yamaguchi H
- Yamamoto A
- Yamamoto K
- Yamamoto S
- Yamamura T
- Yamanaka T
- Yamazaki T
- Yamazaki Y
- Yan Z
- Yang H
- Yang UK
- Yang Y
- Yang Z
- Yanush S
- Yao L
- Yao Y
- Yasu Y
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- Yildiz HD
- Yilmaz M
- Yoosoofmiya R
- Yorita K
- Yoshida R
- Yoshihara K
- Young C
- Young CJ
- Youssef S
- Yu D
- Yu DR
- Yu J
- Yu J
- Yuan L
- Yurkewicz A
- Zabinski B
- Zaidan R
- Zaitsev AM
- Zajacova Z
- Zanello L
- Zanzi D
- Zaytsev A
- Zeitnitz C
- Zeman M
- Zemla A
- Zendler C
- Zenin O
- Zenis T
- Zerwas D
- Zhang D
- Zhang H
- Zhang J
- Zhang X
- Zhang Z
- Zhao L
- Zhao Z
- Zhemchugov A
- Zhong J
- Zhou B
- Zhou N
- Zhou Y
- Zhu CG
- Zhu H
- Zhu J
- Zhu Y
- Zhuang X
- Zhuravlov V
- Zibell A
- Zieminska D
- Zimin NI
- Zimmermann R
- Zimmermann S
- Zimmermann S
- Zinonos Z
- Ziolkowski M
- Zitoun R
- Zivkovic L
- Zmouchko VV
- Zobernig G
- Zoccoli A
- zur Nedden M
- Zutshi V
- Zwalinski L
- Publication venue
- Springer
- Publication date
- 01/01/2012
- Field of study
The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Z′ gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/γ bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the μ + μ −channel. A Z ′ boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Z′ Models
Automatic quantification of microvessel density in urinary bladder carcinoma
- Author
- A Arakawa
- AHS Lee
- AJ Dickinson
- AS-Y Leong
- BH Bochner
- BM Wagner
- C Busch
- CJ Fisher
- CK Hawke
- CN Penfold
- CP Dinney
- E Bengtsson
- EA Philp
- GD Grossfeld
- GW Chodak
- HA Lambkin
- HC Hollingsworth
- HK Choi
- IG Duarte
- J Folkman
- J Folkman
- JM Morgan
- JS de Jong
- K Nakanishi
- K Wester
- L Martin
- LE Wold
- M Barbareschi
- M Barbareschi
- MA Green
- N McDermott
- N Weidner
- N Weidner
- N Weidner
- N Weidner
- P Ranefall
- P Ranefall
- P Ranefall
- P-U Malmström
- PB Vermeulen
- PD Kohlberger
- PU Malmstrom
- PU Malmstrom
- SB Fox
- SB Fox
- T Jarkrans
- TM Jaeger
- Publication venue
- Nature Publishing Group
- Publication date
- Field of study
Seventy-three TUR-T biopsies from bladder carcinoma were evaluated regarding microvessel density, defined as microvessel number (nMVD) and cross-section endothelial cell area (aMVD). A semi-automatic and a newly developed, automatic image analysis technique were applied in immunostainings, performed according to an optimized staining protocol. In 12 cases a comparison of biopsy material and the corresponding cystectomy specimen were tested, showing a good correlation in 11 of 12 cases (92%). The techniques proved reproducible for both nMVD and aMVD quantifications related to total tumour area. However, the automatic method was dependent on high immunostaining quality. Simultaneous, semi-automatic quantification of microvessels, stroma and epithelial fraction resulted in a decreased reproducibility. Quantification in ten images, selected in a descending order of MVD by subjective visual judgement, showed a poor observer capacity to estimate and rank MVD. Based on our results we propose quantification of MVD related to one tissue compartment. When staining quality is of high standard, automatic quantification is applicable, which facilitates quantification of multiple areas and thus, should minimize selection variability. © 1999 Cancer Research Campaig
The role of interfacial lipids in stabilizing membrane protein oligomers
- Author
- A Anderluh
- A Arkhipov
- A Konijnenberg
- A Laganowsky
- A Laganowsky
- A Yamashita
- Andrew J. Baldwin
- B Brügger
- B Hess
- BK Tan
- C Lee
- C Pliotas
- Carol V. Robinson
- CL Piscitelli
- D Drew
- David Drew
- DH de Jong
- E Jefferys
- E Krissinel
- E Reading
- ED Levy
- F Kilic
- G Bussi
- H Hernández
- H Ilgü
- H Wu
- HF Sturt
- HJC Berendsen
- IG Tironi
- J Cox
- J Gault
- J Zhen
- JA Coleman
- JM Duarte
- JN Savas
- Jonathan T. S. Hopper
- Joseph A. C. Donlan
- JP Whitelegge
- JT Hopper
- K Herz
- Kallol Gupta
- M Audet
- M Coincon
- M Landreh
- Michael Landreh
- MJ Abraham
- MT Marty
- N Michaud-Agrawal
- NP Barrera
- NP Barrera
- Phillip J. Stansfeld
- PJ Stansfeld
- PJ Stansfeld
- PL Yeagle
- Povilas Uzdavinys
- R Sounier
- S Dorsch
- S Pall
- SB Hansen
- SC Wang
- TTLC-blot Taki
- W Huang
- Weston B. Struwe
- Y Gao
- Y Xu
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2017
- Field of study
Oligomerization of membrane proteins in response to lipid binding has a critical role in many cell-signalling pathways1 but is often difficult to define2 or predict3. Here we report the development of a mass spectrometry platform to determine simultaneously the presence of interfacial lipids and oligomeric stability and to uncover how lipids act as key regulators of membrane-protein association. Evaluation of oligomeric strength for a dataset of 125 α-helical oligomeric membrane proteins reveals an absence of interfacial lipids in the mass spectra of 12 membrane proteins with high oligomeric stability. For the bacterial homologue of the eukaryotic biogenic transporters (LeuT4, one of the proteins with the lowest oligomeric stability), we found a precise cohort of lipids within the dimer interface. Delipidation, mutation of lipid-binding sites or expression in cardiolipin-deficient Escherichia coli abrogated dimer formation. Molecular dynamics simulation revealed that cardiolipin acts as a bidentate ligand, bridging across subunits. Subsequently, we show that for the Vibrio splendidus sugar transporter SemiSWEET5, another protein with low oligomeric stability, cardiolipin shifts the equilibrium from monomer to functional dimer. We hypothesized that lipids are essential for dimerization of the Na+/H+ antiporter NhaA from E. coli, which has the lowest oligomeric strength, but not for the substantially more stable homologous Thermus thermophilus protein NapA. We found that lipid binding is obligatory for dimerization of NhaA, whereas NapA has adapted to form an interface that is stable without lipids. Overall, by correlating interfacial strength with the presence of interfacial lipids, we provide a rationale for understanding the role of lipids in both transient and stable interactions within a range of α-helical membrane proteins, including G-protein-coupled receptors
- …