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Träfflista för sökning "WFRF:(Coyle P) "

Sökning: WFRF:(Coyle P)

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1.
  • Schael, S., et al. (författare)
  • Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
  • 2013
  • Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
  • Forskningsöversikt (refereegranskat)abstract
    • Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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2.
  • Schael, S, et al. (författare)
  • Precision electroweak measurements on the Z resonance
  • 2006
  • Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
  • 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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3.
  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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4.
  • 2021
  • swepub:Mat__t
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5.
  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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6.
  • 2017
  • Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
  • Tidskriftsartikel (refereegranskat)
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7.
  • Adrian-Martinez, S., et al. (författare)
  • A first search for coincident gravitational waves and high energy neutrinos using LIGO, Virgo and ANTARES data from 2007
  • 2013
  • Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :6
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.
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8.
  • Petroff, E., et al. (författare)
  • A polarized fast radio burst at low Galactic latitude
  • 2017
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford Academic. - 0035-8711 .- 1365-2966. ; 469:4, s. 4465-4482
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the discovery of a new fast radio burst (FRB), FRB 150215, with the Parkes radio telescope on 2015 February 15. The burst was detected in real time with a dispersion measure (DM) of 1105.6 +/- 0.8 pc cm(-3), a pulse duration of 2.8(-0.5)(+1.2) ms, and a measured peak flux density assuming that the burst was at beam centre of 0.7(-0.1)(+0.2) Jy. The FRB originated at a Galactic longitude and latitude of 24.66 degrees, 5.28 degrees and 25 degrees away from the Galactic Center. The burst was found to be 43 +/- 5 per cent linearly polarized with a rotation measure (RM) in the range -9 < RM < 12 rad m(-2) (95 per cent confidence level), consistent with zero. The burst was followed up with 11 telescopes to search for radio, optical, X-ray, gamma-ray and neutrino emission. Neither transient nor variable emission was found to be associated with the burst and no repeat pulses have been observed in 17.25 h of observing. The sightline to the burst is close to the Galactic plane and the observed physical properties of FRB 150215 demonstrate the existence of sight lines of anomalously low RM for a given electron column density. The Galactic RM foreground may approach a null value due to magnetic field reversals along the line of sight, a decreased total electron column density from the Milky Way, or some combination of these effects. A lower Galactic DM contribution might explain why this burst was detectable whereas previous searches at low latitude have had lower detection rates than those out of the plane.
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9.
  • Ageron, M., et al. (författare)
  • ANTARES : The first undersea neutrino telescope
  • 2011
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 656:1, s. 11-38
  • Tidskriftsartikel (refereegranskat)abstract
    • The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational Neutrino Telescope in the Mediterranean Sea. The main purpose of the detector is to perform neutrino astronomy and the apparatus also offers facilities for marine and Earth sciences. This paper describes the design, the construction and the installation of the telescope in the deep sea, offshore from Toulon in France. An illustration of the detector performance is given. (C) 2011 Elsevier B.V. All rights reserved.
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10.
  • Aguilar, J A, et al. (författare)
  • Study of large hemispherical photomultiplier tubes for the ANTARES neutrino telescope
  • 2005
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 555:1-2, s. 132-141
  • Tidskriftsartikel (refereegranskat)abstract
    • The ANTARES neutrino telescope, to be immersed depth in the Mediterranean Sea, will consist of a three-dimensional matrix of 900 large area photomultiplier tubes housed in pressure-resistant glass spheres. The selection of the optimal photomultiplier was a critical step for the project and required an intensive phase of tests and developments carried out in close collaboration with the main manufacturers worldwide. This paper provides an overview of the tests performed by the collaboration and describes in detail the features of the photomultiplier tube chosen for ANTARES. (c) 2005 Elsevier B.V. All rights reserved.
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11.
  • Aguilar, J A, et al. (författare)
  • Transmission of light in deep sea water at the site of the ANTARES neutrino telescope
  • 2005
  • Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 23:1, s. 131-155
  • Tidskriftsartikel (refereegranskat)abstract
    • The ANTARES neutrino telescope is a large photomultiplier array designed to detect neutrino-induced upward-going muons by their Cherenkov radiation. Understanding the absorption and scattering of light in the deep Mediterranean is fundamental to optimising the design and performance of the detector. This paper presents measurements of blue and UV light transmission at the ANTARES site taken between 1997 and 2000. The derived values for the scattering length and the angular distribution of particulate scattering were found to be highly correlated, and results are therefore presented in terms of an absorption length;,ab, and an effective scattering length lambda(sct)(eff). The values for blue (UV) light are found to be lambda(abs) similar or equal to 60(26) m, lambda(sct)(eff similar or equal to) 265(122) m, with significant (similar to15%) time variability. Finally, the results of ANTARES simulations showing the effect of these water properties on the anticipated performance of the detector are presented. (C) 2004 Elsevier B.V. All rights reserved.
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12.
  • Ageron, M., et al. (författare)
  • Studies of a full-scale mechanical prototype line for the ANTARES neutrino telescope and tests of a prototype instrument for deep-sea acoustic measurements
  • 2007
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 581:3, s. 695-708
  • Tidskriftsartikel (refereegranskat)abstract
    • full-scale mechanical prototype line was deployed to a depth of 2500 m to test the leak tightness of the electronics containers and the pressure-resistant properties of an electromechanical cable under evaluation for use in the ANTARES deep-sea neutrino telescope. During a month-long immersion study, line parameter data were taken using miniature autonomous data loggers and shore-based optical time domain reflectometry. Details of the mechanical prototype line, the electromechanical cable and data acquisition are presented. Data taken during the immersion study revealed deficiencies in the pressure resistance of the electromechanical cable terminations at the entry points to the electronics containers. The improvements to the termination, which have been integrated into subsequent detection lines, are discussed. The line also allowed deep-sea acoustic measurements with a prototype hydrophone system. The technical setup of this system is described, and the first results of the data analysis are presented. (c) 2007 Elsevier B.V. All rights reserved.
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13.
  • Ageron, M., et al. (författare)
  • The ANTARES optical beacon system
  • 2007
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 578:3, s. 498-509
  • Tidskriftsartikel (refereegranskat)abstract
    • ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three-dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular, when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented. (C) 2007 Elsevier B.V. All rights reserved.
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14.
  • Aguilar, J. A., et al. (författare)
  • First results of the instrumentation line for the deep-sea ANTARES neutrino telescope
  • 2006
  • Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 26:4-5, s. 314-324
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2005, the ANTARES Collaboration deployed and operated at a depth of 2500 m a so-called Mini Instrumentation Line equipped with Optical Modules (MILOM) at the ANTARES site. The various data acquired during the continuous operation from April to December 2005 of the MILOM confirm the satisfactory performance of the Optical Modules, their front-end electronics and readout system. as well as the calibration devices of the detector. The in situ measurement of the Optical Module time response yields a resolution better than 0.5 ns. The performance of the acoustic positioning system, which enables the spatial reconstruction of the ANTARES detector with a precision of about 10 cm, is verified. These results demonstrate that with the full ANTARES neutrino telescope the design angular resolution of better than 0.3 degrees can be realistically achieved.
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15.
  • Aguilar, J. A., et al. (författare)
  • The data acquisition system for the ANTARES neutrino telescope
  • 2007
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 570:1, s. 107-116
  • Tidskriftsartikel (refereegranskat)abstract
    • The ANTARES neutrino telescope is being constructed in the Mediterranean Sea. It consists of a large three-dimensional array of photo-multiplier tubes. The data acquisition system of the detector takes care of the digitisation of the photo-multiplier tube signals, data transport, data filtering, and data storage. The detector is operated using a control program interfaced with all elements. The design and the implementation of the data acquisition system are described. (c) 2006 Elsevier B.V. All rights reserved.
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16.
  • Adrian-Martinez, S., et al. (författare)
  • The First Combined Search For Neutrino Point-Sources In The Southern Hemisphere With The Antares And Icecube Neutrino Telescopes
  • 2016
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 823:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of searches for point-like sources of neutrinos based on the first combined analysis of data from both the ANTARES and IceCube neutrino telescopes. The combination of both detectors, which differ in size and location, forms a window in the southern sky where the sensitivity to point sources improves by up to a factor of 2 compared with individual analyses. Using data recorded by ANTARES from 2007 to 2012, and by IceCube from 2008 to 2011, we search for sources of neutrino emission both across the southern sky and from a preselected list of candidate objects. No significant excess over background has been found in these searches, and flux upper limits for the candidate sources are presented for E-2.5 and E-2 power-law spectra with different energy cut-offs.
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17.
  • Ageron, M., et al. (författare)
  • Performance of the first ANTARES detector line
  • 2009
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 31:4, s. 277-283
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we report on the data recorded with the first Antares detector line. The line was deployed on the 14th of February 2006 and was connected to the readout 2 weeks later. Environmental data for one and a half years of running are shown. Measurements of atmospheric muons from data taken from selected runs during the first 6 months of operation are presented. Performance figures in terms of time residuals and angular resolution are given. Finally the angular distribution of atmospheric muons is presented and from this the depth profile of the muon intensity is derived. (C) 2009 Elsevier B.V. All rights reserved.
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19.
  • Fowler, D., et al. (författare)
  • Atmospheric composition change : Ecosystems-Atmosphere interactions
  • 2009
  • Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 43:33, s. 5193-5267
  • Forskningsöversikt (refereegranskat)abstract
    • Ecosystems and the atmosphere: This review describes the state of understanding the processes involved in the exchange of trace gases and aerosols between the earth's surface and the atmosphere. The gases covered include NO, NO2, HONO, HNO3, NH3, SO2, DMS, Biogenic VOC, O-3, CH4, N2O and particles in the size range 1 nm-10 mu m including organic and inorganic chemical species. The main focus of the review is on the exchange between terrestrial ecosystems, both managed and natural and the atmosphere, although some new developments in ocean-atmosphere exchange are included. The material presented is biased towards the last decade, but includes earlier work, where more recent developments are limited or absent. New methodologies and instrumentation have enabled, if not driven technical advances in measurement. These developments have advanced the process understanding and upscaling of fluxes, especially for particles, VOC and NH3. Examples of these applications include mass spectrometric methods, such as Aerosol Mass Spectrometry (AMS) adapted for field measurement of atmosphere-surface fluxes using micrometeorological methods for chemically resolved aerosols. Also briefly described are some advances in theory and techniques in micrometeorology. For some of the compounds there have been paradigm shifts in approach and application of both techniques and assessment. These include flux measurements over marine surfaces and urban areas using micrometeorological methods and the up-scaling of flux measurements using aircraft and satellite remote sensing. The application of a flux-based approach in assessment of O-3 effects on vegetation at regional scales is an important policy linked development secured through improved quantification of fluxes. The coupling of monitoring, modelling and intensive flux measurement at a continental scale within the NitroEurope network represents a quantum development in the application of research teams to address the underpinning science of reactive nitrogen in the cycling between ecosystems and the atmosphere in Europe. Some important developments of the science have been applied to assist in addressing policy questions, which have been the main driver of the research agenda, while other developments in understanding have not been applied to their wider field especially in chemistry-transport models through deficiencies in obtaining appropriate data to enable application or inertia within the modelling community. The paper identifies applications, gaps and research questions that have remained intractable at least since 2000 within the specialized sections of the paper, and where possible these have been focussed on research questions for the coming decade. 
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21.
  • Muehlenbein, MP, et al. (författare)
  • Traveller exposures to animals: a GeoSentinel analysis
  • 2020
  • Ingår i: Journal of travel medicine. - : Oxford University Press (OUP). - 1708-8305 .- 1195-1982. ; 27:7
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundHuman coexistence with other animals can result in both intentional and unintentional contact with a variety of mammalian and non-mammalian species. International travellers are at risk for such encounters; travellers risk injury, infection and possibly death from domestic and wild animal bites, scratches, licks and other exposures. The aim of the present analysis was to understand the diversity and distribution of animal-related exposures among international travellers.MethodsData from January 2007 through December 2018 from the GeoSentinel Surveillance Network were reviewed. Records were included if the exposure was non-migration travel with a diagnosis of an animal (dog, cat, monkey, snake or other) bite or other exposure (non-bite); records were excluded if the region of exposure was not ascertainable or if another, unrelated acute diagnosis was reported.ResultsA total of 6470 animal exposures (bite or non-bite) were included. The majority (71%) occurred in Asia. Travellers to 167 countries had at least one report of an animal bite or non-bite exposure. The majority (76%) involved dogs, monkeys and cats, although a wide range of wild and domestic species were involved. Almost two-thirds (62.6%) of 4395 travellers with information available did not report a pretravel consultation with a healthcare provider.ConclusionsMinimizing bites and other animal exposures requires education (particularly during pretravel consultations) and behavioral modification. These should be supplemented by the use of pre-exposure rabies vaccination for travellers to high-risk countries (especially to those with limited access to rabies immunoglobulin), as well as encouragement of timely (in-country) post-exposure prophylaxis for rabies and Macacine alphaherpesvirus 1 (herpesvirus B) when warranted.
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22.
  • Hanstock, Helen, 1989-, et al. (författare)
  • Tear Fluid SIgA as a Noninvasive Biomarker of Mucosal Immunity and Common Cold Risk
  • 2016
  • Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 48:3, s. 569-577
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Research has not convincingly demonstrated the utility of saliva secretory Immunoglobulin-A (SIgA) as a biomarker of upper-respiratory-tract-infection (URTI) risk and disagreement exists about the influence of heavy exercise ('open-window-theory') and dehydration on saliva SIgA. Prompted by the search for viable alternatives, we compared the utility of tear and saliva SIgA to predict URTI prospectively (study-one) and assessed the influence of exercise (study-two) and dehydration (study-three) using a repeated-measures-crossover design.Methods: In study-one, forty subjects were recruited during the common-cold season. Subjects provided tear and saliva samples weekly and recorded upper-respiratory-symptoms (URS) daily for 3-weeks. RT-PCR confirmed common-cold pathogens in 9 of 11 subjects reporting URS (82%). Predictive utility of tear and saliva SIgA was explored by comparing healthy samples with those collected the week pre-URS. In study-two, thirteen subjects performed a 2-hour run at 65% VO2peak. In study-three, thirteen subjects performed exercise-heat-stress to 3% body-mass-loss followed by overnight fluid restriction.Results: Tear SIgA concentration and secretion rate were 48% and 51% lower respectively during URTI and 34% and 46% lower the week pre-URS (P<0.05) but saliva SIgA remained unchanged. URS risk the following week increased 9-fold (95% CI: 1.7 to 48) when tear SIgA secretion rate <5.5 μg[BULLET OPERATOR]min and 6-fold (95% CI: 1.2 to 29) when tear SIgA secretion rate decreased >30%. Tear SIgA secretion rate >5.5 μg[BULLET OPERATOR]min or no decrease >30% predicted subjects free of URS in >80% of cases. Tear SIgA concentration decreased post-exercise (-57%: P<0.05) in line with the 'open-window-theory' but was unaffected by dehydration. Saliva flow rate decreased and saliva SIgA concentration increased post-exercise and during dehydration (P<0.05).Conclusion: Tear SIgA has utility as a non-invasive biomarker of mucosal immunity and common-cold risk.
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23.
  • Zhao, Chaoyang, et al. (författare)
  • A massive expansion of effector genes underlies gall-formation in the wheat pest Mayetiola destructor
  • 2015
  • Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 25:5, s. 613-620
  • Tidskriftsartikel (refereegranskat)abstract
    • Gall-forming arthropods are highly specialized herbivores that, in combination with their hosts, produce extended phenotypes with unique morphologies [1]. Many are economically important, and others have improved our understanding of ecology and adaptive radiation [2]. However, the mechanisms that these arthropods use to induce plant galls are poorly understood. We sequenced the genome of the Hessian fly (Mayetiola destructor; Diptera: Cecidomyiidae), a plant parasitic gall midge and a pest of wheat (Triticum spp.), with the aim of identifying genic modifications that contribute to its plant-parasitic lifestyle. Among several adaptive modifications, we discovered an expansive reservoir of potential effector proteins. Nearly 5% of the 20,163 predicted gene models matched putative effector gene transcripts present in the M. destructor larval salivary gland. Another 466 putative effectors were discovered among the genes that have no sequence similarities in other organisms. The largest known arthropod gene family (family SSGP-71) was also discovered within the effector reservoir. SSGP-71 proteins lack sequence homologies to other proteins, but their structures resemble both ubiquitin E3 ligases in plants and E3-ligase-mimicking effectors in plant pathogenic bacteria. SSGP-71 proteins and wheat Skp proteins interact in vivo. Mutations in different SSGP-71 genes avoid the effector-triggered immunity that is directed by the wheat resistance genes H6 and H9. Results point to effectors as the agents responsible for arthropod-induced plant gall formation.
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24.
  • Al-Garawi, A., et al. (författare)
  • Influenza A facilitates sensitization to house dust mite in infant mice leading to an asthma phenotype in adulthood
  • 2011
  • Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 4:6, s. 682-694
  • Tidskriftsartikel (refereegranskat)abstract
    • The origins of allergic asthma, particularly in infancy, remain obscure. Respiratory viral infections and allergen sensitization in early life have been associated with asthma in young children. However, a causal link has not been established. We investigated whether an influenza A infection in early life alters immune responses to house dust mite (HDM) and promotes an asthmatic phenotype later in life. Neonatal (8-day-old) mice were infected with influenza virus and 7 days later, exposed to HDM for 3 weeks. Unlike adults, neonatal mice exposed to HDM exhibited negligible immune responsiveness to HDM, but not to influenza A. HDM responsiveness in adults was associated with distinct Ly6c(+) CD11b(+) inflammatory dendritic cell and CD8 alpha(+) plasmacytoid (pDC) populations that were absent in HDM-exposed infant mice, suggesting an important role in HDM-mediated inflammation. Remarkably, HDM hyporesponsiveness was overcome when exposure occurred concurrently with an acute influenza infection; young mice now displayed robust allergen-specific immunity, allergic inflammation, and lung remodeling. Remodeling persisted into early adulthood, even after prolonged discontinuation of allergen exposure and was associated with marked impairment of lung function. Our data demonstrate that allergen exposure coincident with acute viral infection in early life subverts constitutive allergen hyporesponsiveness and imprints an asthmatic phenotype in adulthood.
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25.
  • Engebretson, Mark J., et al. (författare)
  • Interhemispheric Comparisons of Large Nighttime Magnetic Perturbation Events Relevant to GICs
  • 2020
  • Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 125:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Nearly all studies of impulsive magnetic perturbation events (MPEs) with large magnetic field variability (dB/dt) that can produce dangerous geomagnetically induced currents (GICs) have used data from the Northern Hemisphere. Here we present details of four large‐amplitude MPE events (|ΔBx| > 900 nT and |dB/dt| > 10 nT/s in at least one component) observed between 2015 and 2018 in conjugate high‐latitude regions (65–80° corrected geomagnetic latitude), using magnetometer data from (1) Pangnirtung and Iqaluit in eastern Arctic Canada and the magnetically conjugate South Pole Station in Antarctica and (2) the Greenland West Coast Chain and two magnetically conjugate chains in Antarctica, AAL‐PIP and BAS LPM. From one to three different isolated MPEs localized in corrected geomagnetic latitude were observed during three premidnight events; many were simultaneous within 3 min in both hemispheres. Their conjugate latitudinal amplitude profiles, however, matched qualitatively at best. During an extended postmidnight interval, which we associate with an interval of omega bands, multiple highly localized MPEs occurred independently in time at each station in both hemispheres. These nighttime MPEs occurred under a wide range of geomagnetic conditions, but common to each was a negative interplanetary magnetic field Bz that exhibited at least a modest increase at or near the time of the event. A comparison of perturbation amplitudes to modeled ionospheric conductances in conjugate hemispheres clearly favored a current generator model over a voltage generator model for three of the four events; neither model provided a good fit for the premidnight event that occurred near vernal equinox.
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27.
  • Kappos, Ludwig, et al. (författare)
  • Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
  • 2018
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
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28.
  • Kearley, Jennifer, et al. (författare)
  • IL-9 Governs Allergen-induced Mast Cell Numbers in the Lung and Chronic Remodeling of the Airways
  • 2011
  • Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 183:7, s. 865-875
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: IL-9 is a pleiotropic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma. Objectives: The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier studies focused on the role of IL-9 in acute inflammatory models; here we have investigated the effects of IL-9 blockade during chronic allergic inflammation. Methods: Mice were exposed to either prolonged ovalbumin or house dust mite allergen challenge to induce chronic inflammation and airway remodeling. Measurements and Main Results: We found that IL-9 governs allergen-induced mast cell (MC) numbers in the lung and has pronounced effects on chronic allergic inflammation. Anti-IL-9 antibody-treated mice were protected from airway remodeling with a concomitant reduction in mature MC numbers and activation, in addition to decreased expression of the profibrotic mediators transforming growth factor-beta 1, vascular endothelial growth factor, and fibroblast growth factor-2 in the lung. Airway remodeling was associated with impaired lung function in the peripheral airways and this was reversed by IL-9 neutralization. In human asthmatic lung tissue, we identified MCs as the main IL-9 receptor expressing population and found them to be sources of vascular endothelial growth factor and fibroblast growth factor-2. Conclusions: Our data suggest an important role for an IL-9-MC axis in the pathology associated with chronic asthma and demonstrate that an impact on this axis could lead to a reduction in chronic inflammation and improved lung function in patients with asthma.
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29.
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31.
  • Shrewsbury, Vanessa A, et al. (författare)
  • Update of the best practice dietetic management of overweight and obese children and adolescents: a systematic review protocol
  • 2018
  • Ingår i: The JBI Database of Systematic Reviews and Implementation Reports. - 2202-4433. ; 16:7, s. 1495-1502
  • Tidskriftsartikel (refereegranskat)abstract
    • REVIEW QUESTION/OBJECTIVE: To update an existing systematic review series of randomized controlled trials (RCT) that include a dietary intervention for the management of overweight or obesity in children or adolescents. Specifically, the review questions are: In randomized controlled trials of interventions which include a dietary intervention for the management of overweight or obesity in children or adolescents.
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32.
  • Svendsen, P, et al. (författare)
  • Tracking of proinflammatory collagen-specific T cells in early and late collagen-induced arthritis in humanized mice
  • 2004
  • Ingår i: Journal of Immunology. - 1550-6606. ; 173:11, s. 7037-7045
  • Tidskriftsartikel (refereegranskat)abstract
    • Rheumatoid arthritis is a chronic inflammatory disease associated with certain HLA-DR4 subtypes. The target autoantigen(s) is unknown, but type II collagen (CII) is a candidate, with a single immunodominant DR4-restricted 261-273 T cell epitope (CII(261273)). In the present study, we have prepared HLA-DR4:CII(261-273) tetramers and analyzed peripheral blood, lymph node, and synovial fluid cells from DR4-transgenic mice with early and late collagen-induced arthritis to draw a fuller picture of the role of CII-reactive Th cells in disease development. Their frequencies increased similar to20-fold in blood 1-2 wk postimmunization, and even more in acutely arthritic joints. Our data strongly suggest that CII-specific Th cells are necessary, but not sufficient for collagen-induced arthritis. The CII-specific Th cells displayed an activated proinflammatory Th1 phenotype, and their expansion correlated with onset and severity of arthritis and also with anti-CII Ab levels. Surprisingly, shortly after the first clinical signs of arthritis, activated HLA-DR4:CII tetramer(+) cells became undetectable in the synovial fluid and rare in the blood, but persisted in lymph nodes. Consequently, future human studies should focus on patients with early arthritis, and on their synovial cells, to re-evaluate the occurrence and pathogenic importance of CII-specific or other Th cells in rheumatoid arthritis.
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