1. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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2. |
- Abate, E., et al.
(författare)
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Combined performance tests before installation of the ATLAS Semiconductor and Transition Radiation Tracking Detectors
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS (A Toroidal LHC ApparatuS) Inner Detector provides charged particle tracking in the centre of the ATLAS experiment at the Large Hadron Collider (LHC). The Inner Detector consists of three subdetectors: the Pixel Detector, the Semiconductor Tracker (SCT), and the Transition Radiation Tracker (TRT). This paper summarizes the tests that were carried out at the final stage of SCT+TRT integration prior to their installation in ATLAS. The combined operation and performance of the SCT and TRT barrel and endcap detectors was investigated through a series of noise tests, and by recording the tracks of cosmic rays. This was a crucial test of hardware and software of the combined tracker detector systems. The results of noise and cross-talk tests on the SCT and TRT in their final assembled configuration, using final readout and supply hardware and software, are reported. The reconstruction and analysis of the recorded cosmic tracks allowed testing of the offline analysis chain and verification of basic tracker performance parameters, such as efficiency and spatial resolution, in combined operation before installation.
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3. |
- Abdesselam, A., et al.
(författare)
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Engineering for the ATLAS SemiConductor Tracker (SCT) end-cap
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS SemiConductor Tracker (SCT) is a silicon-strip tracking detector which forms part of the ATLAS inner detector. The SCT is designed to track charged particles produced in proton-proton collisions at the Large Hadron Collider (LHC) at CERN at an energy of 14 TeV. The tracker is made up of a central barrel and two identical end-caps. The barrel contains 2112 silicon modules, while each end-cap contains 988 modules. The overall tracking performance depends not only on the intrinsic measurement precision of the modules but also on the characteristics of the whole assembly, in particular, the stability and the total material budget. This paper describes the engineering design and construction of the SCT end-caps, which are required to support mechanically the silicon modules, supply services to them and provide a suitable environment within the inner detector. Critical engineering choices are highlighted and innovative solutions are presented - these will be of interest to other builders of large-scale tracking detectors. The SCT end-caps will be fully connected at the start of 2008. Further commissioning will continue, to be ready for proton-proton collision data in 2008.
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4. |
- Abdesselam, A., et al.
(författare)
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The ATLAS semiconductor tracker end-cap module
- 2007
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 575:3, s. 353-389
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Tidskriftsartikel (refereegranskat)abstract
- The challenges for the tracking detector systems at the LHC are unprecedented in terms of the number of channels, the required read-out speed and the expected radiation levels. The ATLAS Semiconductor Tracker. (SCT) end-caps have a total of about 3 million electronics channels each reading out every 25 ns into its own on-chip 3.3 mu s buffer. The highest anticipated dose after 10 years operation is 1.4x10(14) cm(-2) in units of 1 MeV neutron equivalent (assuming the damage factors scale with the non-ionising energy loss). The forward tracker has 1976 double-sided modules, mostly of area similar to 70 cm(2), each having 2 x 768 strips read out by six ASICs per side. The requirement to achieve an average perpendicular radiation length of 1.5% X-0, while coping with up to 7 W dissipation per module (after irradiation), leads to stringent constraints on the thermal design. The additional requirement of 1500e(-) equivalent noise charge (ENC) rising to only 1800e(-) ENC after irradiation, provides stringent design constraints on both the high-density Cu/Polyimide flex read-out circuit and the ABCD3TA read-out ASICs. Finally, the accuracy of module assembly must not compromise the 16 mu m (r phi) resolution perpendicular to the strip directions or 580 mu m radial resolution coming from the 40 mrad front-back stereo angle. A total of 2210 modules were built to the tight tolerances and specifications required for the SCT. This was 234 more than the 1976 required and represents a yield of 93%. The component flow was at times tight, but the module production rate of 40-50 per week was maintained despite this. The distributed production was not found to be a major logistical problem and it allowed additional flexibility to take advantage of where the effort was available, including any spare capacity, for building the end-cap modules. The collaboration that produced the ATLAS SCT end-cap modules kept in close contact at all times so that the effects of shortages or stoppages at different sites could be rapidly resolved.
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5. |
- Abdesselam, A., et al.
(författare)
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The barrel modules of the ATLAS semiconductor tracker
- 2006
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 568:2, s. 642-671
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the silicon microstrip modules in the barrel section of the SemiConductor Tracker (SCT) of the ATLAS experiment at the CERN Large Hadron Collider (LHC). The module requirements, components and assembly techniques are given, as well as first results of the module performance on the fully assembled barrels that make up the detector being installed in the ATLAS experiment.
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6. |
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7. |
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8. |
- Milling, S W F, et al.
(författare)
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Steady-state migrating intestinal dendritic cells induce potent inflammatory responses in naive CD4+ T cells.
- 2009
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Ingår i: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 2:2, s. 156-65
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Tidskriftsartikel (refereegranskat)abstract
- Steady-state dendritic cells (DCs) migrating in the lymph from the intestine induce tolerance to harmless intestinal antigens, preventing inflammatory responses. To determine if such DCs are inherently tolerogenic we collected intestinal lymph DCs (L-DCs) by cannulation of the thoracic duct of rats after mesenteric lymphadenectomy, and examined their capacity to activate naive CD4+ lymphocytes in an allogeneic mixed leucocyte reaction. L-DCs stimulated strong proliferative responses, induced secretion of inflammatory cytokines including interferon-gamma, and induced FoxP3-positive lymphocytes to divide. To determine if the activated CD4+ T cells had been tolerized, they were rested and restimulated with irradiated splenocytes. The restimulated CD4+ T cells again proliferated and secreted inflammatory cytokines. These data demonstrate that the DCs, which migrate from the intestine in the steady state, are paradoxically able to induce strong inflammatory responses from naive T cells, despite their role in the maintenance of oral tolerance.
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9. |
- Sanger, G J, et al.
(författare)
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GSK962040 : a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility
- 2009
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:6, s. 657-664, e30-31
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent clinical need for a safe, efficacious stimulant of gastric emptying; current therapies include erythromycin (an antibiotic with additional properties which preclude chronic use) and metoclopramide (a 5-hydroxytryptamine type 4 receptor agonist and an antagonist at brain D2 receptors, associated with movement disorders). To move away from the complex motilide structure of erythromycin, a small molecule motilin receptor agonist, GSK962040, was identified and characterized. The compound was evaluated using recombinant human receptors, rabbit and human isolated stomach preparations known to respond to motilin and in vivo, by measuring its ability to increase defecation in conscious rabbits. At the human motilin receptor, the pEC50 (the negative logarithm to base 10 of the EC50 value, the concentration of agonist that produces 50% of the maximal response) values for GSK962040 and erythromycin as agonists were, respectively, 7.9 and 7.3; GSK962040 had no significant activity at a range of other receptors (including ghrelin), ion channels and enzymes. In rabbit gastric antrum, GSK962040 300 nmol L−1–10 μmol L−1 caused a prolonged facilitation of the amplitude of cholinergically mediated contractions, to a maximum of 248 ± 47% at 3 μmol L−1. In human-isolated stomach, GSK962040 10 μmol L−1, erythromycin 10 μmol L−1 and [Nle13]-motilin 100 nmol L−1, each caused muscle contraction of similar amplitude. In conscious rabbits, intravenous doses of 5 mg kg−1 GSK962040 or 10 mg kg−1 erythromycin significantly increased faecal output over a 2-h period. Together, these data show that GSK962040, a non-motilide structure, selectively activates the motilin receptor. Simplification of the structural requirements to activate this receptor greatly facilitates the design of potentially new medicines for gastroparesis.
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10. |
- Yrlid, Ulf, 1971, et al.
(författare)
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A distinct subset of intestinal dendritic cells responds selectively to oral TLR7/8 stimulation.
- 2006
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Ingår i: European journal of immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 36:10, s. 2639-48
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Tidskriftsartikel (refereegranskat)abstract
- The intestinal innate immune system continually interacts with commensal bacteria, thus oral vaccines should induce extra/alternative activation of DC, potentially through TLR. To examine this we collected intestinal lymph DC (iL-DC) under steady-state conditions and after feeding resiquimod (R-848), a synthetic TLR7/8 ligand, which we showed induces complete emptying of gut DC into lymph. iL-DC are heterogeneous with subset-specific functions. In this study we determined the kinetics of iL-DC subset release, activation and cytokine secretion induced by R-848. We show that L-DC comprise three distinct subsets (CD172ahigh, CD172aint and CD172alow) present with similar frequencies in intestinal but not hepatic lymph. No iL-DC express TLR7 mRNA, and only CD172a+ iL-DC express TLR8. However, after oral R-848 administration, output of all three subsets increases dramatically. CD172ahigh DC release precedes that of CD172alow DC, and the increased frequency of CD25high iL-DC is restricted to the two CD172a+ subsets. After feeding R-848 only CD172ahigh iL-DC secrete IL-6 and IL-12p40. However, CD172aint and CD172ahigh DC secrete similar but markedly lower amounts when stimulated in vitro. These results highlight the importance of in vivo approaches to assess adjuvant effects on DC and give novel insights into the subset-specific effects of an oral TLR ligand on intestinal DC.
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11. |
- Yrlid, Ulf, 1971, et al.
(författare)
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Plasmacytoid dendritic cells do not migrate in intestinal or hepatic lymph.
- 2006
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - 0022-1767. ; 177:9, s. 6115-21
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Tidskriftsartikel (refereegranskat)abstract
- Plasmacytoid dendritic cells (pDCs) recognize pathogen-associated molecules, particularly viral, and represent an important mechanism in innate defense. They may however, also have roles in steady-state tolerogenic responses at mucosal sites. pDCs can be isolated from blood, mucosa, and lymph nodes (LNs). Although pDCs can express peripherally derived Ags in LNs and at mucosal sites, it is not clear whether pDCs actually migrate from the periphery in lymph or whether LN pDCs acquire Ags by other mechanisms. To determine whether pDCs migrate in lymph, intestine or liver-draining LNs were removed and thoracic duct leukocytes (TDLs) were collected. TDLs expressing MHC-II and CD45R, but not TCRalphabeta or CD45RA, were then analyzed. These enriched TDLs neither transcribe type I IFNs nor secrete inflammatory cytokines in response to viral stimuli in vitro or after a TLR7/8 stimulus in vivo. In addition, these TDLs do not express CD5, CD90, CD200, or Siglec-H, but do express Ig, and therefore represent B cells, despite their lack of CD45RA expression. Intestinal and hepatic lymph are hence devoid of bona fide pDCs under both steady-state conditions and after TLR7/8 stimulation. This shows that any role for pDCs in Ag-specific T cell activation or tolerance must differ from the roles of classical dendritic cells, because it cannot result from peripheral Ag capture, followed by migration of pDCs via lymph to the LN.
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12. |
- Yrlid, Ulf, 1971, et al.
(författare)
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Regulation of intestinal dendritic cell migration and activation by plasmacytoid dendritic cells, TNF-alpha and type 1 IFNs after feeding a TLR7/8 ligand.
- 2006
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - 0022-1767. ; 176:9, s. 5205-12
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) migrating via lymph are the primary influence regulating naive T cell differentiation, be it active immunity or tolerance. How DCs achieve this regulation in vivo is poorly understood. Intestinal DCs are in direct contact with harmless or pathogenic luminal contents, but may also be influenced by signals from epithelial cells, macrophages, or other resident or immigrant cells. To understand the role of TLR7 and TLR8 in regulating intestinal DC function, we fed a TLR7/8 ligand (resiquimod (R-848)) to rats and mice and examined DC in pseudoafferent lymph (rat) and mesenteric lymph nodes (MLNs). Oral R-848 induced a 20- to 30-fold increase in DC output from the intestine within 10 h due to a virtually total release of lamina propria DCs. This resulted in an accumulation of DCs in the MLNs that in mice was completely TNF-alpha dependent. Surprisingly, intestinal lymph DCs (iL-DCs) released by R-848 did not up-regulate CD86, but did up-regulate CD25. In contrast, MLN-DCs from R-848-stimulated rats and mice expressed high levels of CD86. This DC activation in MLNs was dependent on type 1 IFNs. The major source of these rapidly released cytokines is plasmacytoid DCs (pDCs) and not classical DCs, because depletion of pDCs significantly reduces the R-848-stimulated increase in serum cytokine levels as well as the accumulation and activation of DCs in MLNs. These experiments show that TLR-mediated regulation of iL-DC functions in vivo is complex and does not depend only on direct iL-DC stimulation, but can be regulated by pDCs.
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13. |
- Yrlid, Ulf, 1971, et al.
(författare)
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Relationships between distinct blood monocyte subsets and migrating intestinal lymph dendritic cells in vivo under steady-state conditions.
- 2006
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - 0022-1767. ; 176:7, s. 4155-62
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Tidskriftsartikel (refereegranskat)abstract
- The origins of dendritic cells (DCs) are poorly understood. In inflammation, DCs can arise from blood monocytes (M(O)s), but their steady-state origin may differ, as shown for Langerhans cells. Two main subsets of M(O)s, defined by expression of different chemokine receptors, CCR2 and CX(3)CR1, have been described in mice and humans. Recent studies have identified the inflammatory function of CCR2(high)CX(3)CR1(low) M(O)s but have not defined unambiguously the origin and fate of CCR2(low)CX(3)CR1(high) cells. In this study, we show that rat M(O)s can also be divided into CCR2(high)CX(3)CR1(low)(CD43(low)) and CCR2(low)CX(3)CR1(high)(CD43(high)) subsets with distinct migratory properties in vivo. Using whole body perfusion to obtain M(O)s, including the marginating pool, we show by adoptive transfer that CD43(low) M(O)s can differentiate into CD43(high) M(O)s in blood without cell division. By adoptive transfer of blood M(O)s followed by collection of pseudoafferent lymph, we show for the first time that a small proportion of intestinal lymph DCs are derived from CCR2(low)CX(3)CR1(high)(CD43(high)) blood M(O)s in vivo under steady-state conditions. This study confirms one of the possible origins of CCR2(low)CX(3)CR1(high) blood M(O)s and indicate that they may contribute to migratory intestinal DCs in vivo in the absence of inflammatory stimuli.
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