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1.
  • 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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4.
  • Emerging Risk Factors, Collaboration, et al. (författare)
  • The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases
  • 2007
  • Ingår i: Eur J Epidemiol. - 0393-2990. ; 22:12, s. 839-69
  • Tidskriftsartikel (refereegranskat)abstract
    • Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
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5.
  • Ding, Li, et al. (författare)
  • Somatic mutations affect key pathways in lung adenocarcinoma
  • 2008
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
  • Tidskriftsartikel (refereegranskat)abstract
    • Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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6.
  • Ballantyne, C., et al. (författare)
  • Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA(2) and cardiovascular diseases
  • 2007
  • Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8275. ; 14:1, s. 41344-41344
  • Forskningsöversikt (refereegranskat)abstract
    • Background A large number of observational epidemiological studies have reported generally positive associations' between circulating mass and activity levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA(2) markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. Objectives By combination of data from individual participants from all relevant observational studies in a systematic,meta-analysis, with correction for regression dilution (using available data on serial measurements of Lp-PLA(2)), the Lp-PLA(2) Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA(2) with coronary heart disease (and, where data are sufficient with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA(2) and cardiovascular outcomes. Methods A central database is being established containing data on circulating Lp-PLA(2) values, sex and other potential confounding factors, age at baseline Lp-PLA(2) Measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA(2) will yield information on a total of about 15 000 cardiovascular disease endpoints.
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7.
  • Ballantyne, C., et al. (författare)
  • Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases
  • 2007
  • Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - : Oxford University Press (OUP). - 1741-8267 .- 1741-8275 .- 2047-4873. ; 14:1, s. 3-11
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: A large number of observational epidemiological studies have reported generally positive associations between circulating mass and activity levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA2 markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. OBJECTIVES: By combination of data from individual participants from all relevant observational studies in a systematic 'meta-analysis', with correction for regression dilution (using available data on serial measurements of Lp-PLA2), the Lp-PLA2 Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA2 with coronary heart disease (and, where data are sufficient, with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA2 and cardiovascular outcomes. METHODS: A central database is being established containing data on circulating Lp-PLA2 values, sex and other potential confounding factors, age at baseline Lp-PLA2 measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA2 will yield information on a total of about 15 000 cardiovascular disease endpoints.
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  • Fynbo, J. P. U., et al. (författare)
  • Low-resolution Spectroscopy of Gamma-ray Burst Optical Afterglows : Biases in the Swift Sample and Characterization of the Absorbers
  • 2009
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 185:2, s. 526-573
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a sample of 77 optical afterglows (OAs) of Swift detected gamma-ray bursts (GRBs) for which spectroscopic follow-up observations have been secured. Our first objective is to measure the redshifts of the bursts. For the majority (90%) of the afterglows, the redshifts have been determined from the spectra. We provide line lists and equivalent widths (EWs) for all detected lines redward of Lyα covered by the spectra. In addition to the GRB absorption systems, these lists include line strengths for a total of 33 intervening absorption systems. We discuss to what extent the current sample of Swift bursts with OA spectroscopy is a biased subsample of all Swift detected GRBs. For that purpose we define an X-ray-selected statistical sample of Swift bursts with optimal conditions for ground-based follow-up from the period 2005 March to 2008 September; 146 bursts fulfill our sample criteria. We derive the redshift distribution for the statistical (X-ray selected) sample and conclude that less than 18% of Swift bursts can be at z > 7. We compare the high-energy properties (e.g., γ-ray (15-350 keV) fluence and duration, X-ray flux, and excess absorption) for three subsamples of bursts in the statistical sample: (1) bursts with redshifts measured from OA spectroscopy; (2) bursts with detected optical and/or near-IR afterglow, but no afterglow-based redshift; and (3) bursts with no detection of the OA. The bursts in group (1) have slightly higher γ-ray fluences and higher X-ray fluxes and significantly less excess X-ray absorption than bursts in the other two groups. In addition, the fractions of dark bursts, defined as bursts with an optical to X-ray slope βOX < 0.5, is 14% in group (1), 38% in group (2), and >39% in group (3). For the full sample, the dark burst fraction is constrained to be in the range 25%-42%. From this we conclude that the sample of GRBs with OA spectroscopy is not representative for all Swift bursts, most likely due to a bias against the most dusty sight lines. This should be taken into account when determining, e.g., the redshift or metallicity distribution of GRBs and when using GRBs as a probe of star formation. Finally, we characterize GRB absorption systems as a class and compare them to QSO absorption systems, in particular the damped Lyα absorbers (DLAs). On average GRB absorbers are characterized by significantly stronger EWs for H I as well as for both low and high ionization metal lines than what is seen in intervening QSO absorbers. However, the distribution of line strengths is very broad and several GRB absorbers have lines with EWs well within the range spanned by QSO-DLAs. Based on the 33 z > 2 bursts in the sample, we place a 95% confidence upper limit of 7.5% on the mean escape fraction of ionizing photons from star-forming galaxies. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile, under programs 275.D-5022 (PI: Chincarini), 075.D-0270 (PI: Fynbo), 077.D-0661 (PI: Vreeswijk), 077.D-0805 (PI: Tagliaferri), 177.A-0591 (PI: Hjorth), 078.D-0416 (PI: Vreeswijk), 079.D-0429 (PI: Vreeswijk), 080.D-0526 (PI: Vreeswijk), 081.A-0135 (PI: Greiner), 281.D-5002 (PI: Della Valle), and 081.A-0856 (PI: Vreeswijk). Also based on observations made with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias. Some of the data obtained herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck foundation.
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  • Malesani, D., et al. (författare)
  • Early Spectroscopic Identification of SN 2008D
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 692:2, s. L84-L87
  • Tidskriftsartikel (refereegranskat)abstract
    • SN 2008D was discovered while following up an unusually bright X-ray transient (XT) in the nearby spiral galaxy NGC 2770. We present early optical spectra ( obtained 1.75 days after the XT) which allowed the first identification of the object as a supernova ( SN) at redshift z = 0.007. These spectra were acquired during the initial declining phase of the light curve, likely produced in the stellar envelope cooling after shock breakout, and rarely observed. They exhibit a rather flat spectral energy distribution with broad undulations, and a strong, W-shaped feature with minima at 3980 and 4190 angstrom ( rest frame). We also present extensive spectroscopy and photometry of the SN during the subsequent photospheric phase. Unlike SNe associated with gamma-ray bursts, SN 2008D displayed prominent He features and is therefore of Type Ib.
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  • Sollerman, J., et al. (författare)
  • Supernova 2006aj and the associated X-Ray Flash 060218
  • 2006
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 454, s. 503-509
  • Tidskriftsartikel (refereegranskat)abstract
    • We have studied the afterglow of the gamma-ray burst (GRB) of February 18, 2006. This is a nearby long GRB, with a very low peak energy, and is therefore classified as an X-ray Flash (XRF). XRF 060218 is clearly associated with a supernova - dubbed SN 2006aj. We present early spectra for SN 2006aj as well as optical lightcurves reaching out to 50 days past explosion. Our optical lightcurves define the rise times, the lightcurve shapes and the absolute magnitudes in the U, V and R bands, and we compare these data with data for other relevant supernovae. SN 2006aj evolved quite fast, somewhat similarly to SN 2002ap, but not as fast as SN 1994I. Our spectra show the evolution of the supernova over the peak, when the U-band portion of the spectrum rapidly fades due to extensive line blanketing. We compare to similar spectra of very energetic type Ic supernovae. Our first spectra are earlier than spectra for any other GRB-SN. The spectrum taken 12 days after burst in the rest frame is similar to somewhat later spectra of both SN 1998bw and SN 2003dh, implying a rapid early evolution. This is consistent with the fast lightcurve. From the narrow emission lines from the host galaxy we derive a redshift of z=0.0331±0.0007. This makes XRF 060218 the second closest gamma-ray burst detected. The flux of these emission lines indicate a high-excitation state, and a modest metallicity and star formation rate of the host galaxy.
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  • Tanvir, N. R., et al. (författare)
  • A γ-ray burst at a redshift of z~8.2
  • 2009
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 461, s. 1254-1257
  • Tidskriftsartikel (refereegranskat)abstract
    • Long-duration γ-ray bursts (GRBs) are thought to result from the explosions of certain massive stars, and some are bright enough that they should be observable out to redshifts of z>20 using current technology. Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-α emitting galaxy. Here we report that GRB090423 lies at a redshift of z~8.2, implying that massive stars were being produced and dying as GRBs ~630Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.
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  • Elíasdóttir, Á., et al. (författare)
  • Dust Extinction in High-z Galaxies with Gamma-Ray Burst Afterglow Spectroscopy : The 2175 Å Feature at z = 2.45
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 697, s. 1725-1740
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the clear detection of the 2175 Å dust absorption feature in the optical afterglow spectrum of the gamma-ray burst (GRB) GRB 070802 at a redshift of z = 2.45. This is the highest redshift for a detected 2175 Å dust bump to date, and it is the first clear detection of the 2175 Å bump in a GRB host galaxy, while several tens of optical afterglow spectra without the bump have been recorded in the past decade. The derived extinction curve gives AV = 0.8-1.5 depending on the assumed intrinsic slope. Of the three local extinction laws, a Large Magellanic Cloud (LMC) type extinction gives the best fit to the extinction curve of the host of GRB 070802. Besides the 2175 Å bump we find that the spectrum of GRB 070802 is characterized by unusually strong low-ionization metal lines and possibly a high metallicity for a GRB sightline ([Si/H] = -0.46 ± 0.38, [Zn/H] = -0.50 ± 0.68). In particular, the spectrum of GRB 070802 is unique for a GRB spectrum in that it shows clear C I absorption features, leading us to propose a correlation between the presence of the bump and C I. The gas-to-dust ratio for the host galaxy is found to be significantly lower than that of other GRB hosts with N(H I)/AV = (2.4 ± 1.0) × 1021 cm-2 mag-1, which lies between typical Milky Way and LMC values. Our results are in agreement with the tentative conclusion reached by Gordon et al. that the shape of the extinction curve, in particular the presence of the bump, is affected by the UV flux density in the environment of the dust. Based on observations collected under progs. ID 079.D-0429(B) and 177.D-0591(P,Q), using the FORS2 instrument installed at the Cassegrain focus of the Very Large Telescope (VLT), Unit 1 - Antu, operated by the European Southern Observatory (ESO) on Cerro Paranal, Chile.
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  • Messias, M. J, et al. (författare)
  • The Greenland Sea tracer experiment 1996–2002: Horizontal mixing and transport of Greenland Sea Intermediate Water
  • 2008
  • Ingår i: Progress In Oceanography. - : Elsevier BV. - 0079-6611. ; 78:1, s. 85-105
  • Tidskriftsartikel (refereegranskat)abstract
    • In summer 1996, a tracer release experiment using sulphur hexafluoride (SF6) was launched in the intermediate-depth waters of the central Greenland Sea (GS), to study the mixing and ventilation processes in the region and its role in the northern limb of the Atlantic overturning circulation. Here we describe the hydrographic context of the experiment, the methods adopted and the results from the monitoring of the horizontal tracer spread for the 1996–2002 period documented by 10 shipboard surveys. The tracer marked “Greenland Sea Arctic Intermediate Water” (GSAIW). This was redistributed in the gyre by variable winter convection penetrating only to mid-depths, reaching at most 1800 m depth during the strongest event observed in 2002. For the first 18 months, the tracer remained mainly in the Greenland Sea. Vigorous horizontal mixing within the Greenland Sea gyre and a tight circulation of the gyre interacting slowly with the other basins under strong topographic influences were identified. We use the tracer distributions to derive the horizontal shear at the scale of the Greenland Sea gyre, and rates of horizontal mixing at 10 and 300 km scales. Mixing rates at small scale are high, several times those observed at comparable depths at lower latitudes. Horizontal stirring at the sub-gyre scale is mediated by numerous and vigorous eddies. Evidence obtained during the tracer release suggests that these play an important role in mixing water masses to form the intermediate waters of the central Greenland Sea. By year two, the tracer had entered the surrounding current systems at intermediate depths and small concentrations were in proximity to the overflows into the North Atlantic. After 3 years, the tracer had spread over the Nordic Seas basins. Finally by year six, an intensive large survey provided an overall synoptic documentation of the spreading of the tagged GSAIW in the Nordic Seas. A circulation scheme of the tagged water originating from the centre of the GS is deduced from the horizontal spread of the tracer. We present this circulation and evaluate the transport budgets of the tracer between the GS and the surroundings basins. The overall residence time for the tagged GSAIW in the Greenland Sea was about 2.5 years. We infer an export of intermediate water of GSAIW from the GS of 1 to 1.85 Sv (1 Sv = 106 m3 s−1) for the period from September 1998 to June 2002 based on the evolution of the amount of tracer leaving the GS gyre. There is strong exchange between the Greenland Sea and Arctic Ocean via Fram Strait, but the contribution of the Greenland Sea to the Denmark Strait and Iceland Scotland overflows is modest, probably not exceeding 6% during the period under study.
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  • Schoerck, T, et al. (författare)
  • The stellar content of the Hamburg/ESO survey V. The metallicity distribution function of the Galactic halo
  • 2009
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 507:2, s. 817-832
  • Tidskriftsartikel (refereegranskat)abstract
    • We determine the metallicity distribution function (MDF) of the Galactic halo by means of a sample of 1638 metal-poor stars selected from the Hamburg/ESO objective-prism survey (HES). The sample was corrected for minor biases introduced by the strategy for spectroscopic follow-up observations of the metal-poor candidates, namely "best and brightest stars first". Comparison of the metallicities [Fe/H] of the stars determined from moderate-resolution (i.e., R similar to 2000) follow-up spectra with results derived from abundance analyses based on high-resolution spectra (i.e., R > 20 000) shows that the [Fe/H] estimates used for the determination of the halo MDF are accurate to within 0.3 dex, once highly C-rich stars are eliminated. We determined the selection function of the HES, which must be taken into account for a proper comparison between the HES MDF with MDFs of other stellar populations or those predicted by models of Galactic chemical evolution. The latter show a reasonable agreement with the overall shape of the HES MDF for [Fe/H] > -3.6, but only a model of Salvadori et al. (2007) with a critical metallicity for low-mass star formation of Z(cr) = 10(-3.4) Z(circle dot) reproduces the sharp drop at [Fe/H] similar to -3.6 present in the HES MDF. Although currently about ten stars at [Fe/H] < -3.6 are known, the evidence for the existence of a tail of the halo MDF extending to [Fe/H] similar to -5.5 is weak from the sample considered in this paper, because it only includes two stars [Fe/H] < -3.6. Therefore, a comparison with theoretical models has to await larger statistically complete and unbiased samples. A comparison of the MDF of Galactic globular clusters and of dSph satellites to the Galaxy shows qualitative agreement with the halo MDF, derived from the HES, once the selection function of the latter is included. However, statistical tests show that the differences between these are still highly significant.
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  • Casado, M. P., et al. (författare)
  • The ATLAS tau trigger
  • 2009
  • Ingår i: Nuclear physics B, Proceedings supplements. - : Elsevier BV. - 0920-5632 .- 1873-3832. ; 189, s. 291-298
  • Tidskriftsartikel (refereegranskat)abstract
    • The implementation of a trigger for hadronically decaying tau leptons at the Large Hadronic Collider (LHC) is challenging due to the high background rate, on the other hand it increases tremendously the discovery potential of ATLAS in searches for Standard Model (SM) or Supersymmetric (SUSY) Higgs or other more exotic final states. In this paper we describe the ATLAS tau trigger system, focusing on the early data taking period, and present results from studies based oil GEANT 4 simulated events, including trigger rates and the acceptance of tau leptons from SM processes. In order to cope with the rate and optimize the efficiency of important physics channels, the results of the current simulation studies indicate that ATLAS tau triggers should include either relatively high transverse momentum single tau signatures, or low transverse momentum tau signatures in combination with other signatures, such as missing transverse energy, leptons, or jets.
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  • Conte, Valeria, et al. (författare)
  • TrkB gene transfer does not alter hippocampal neuronal loss and cognitive deficits following traumatic brain injury in mice
  • 2008
  • Ingår i: Restorative Neurology and Neuroscience. - 0922-6028 .- 1878-3627. ; 26:1, s. 45-56
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The ability of brain-derived neurotrophic factor (BDNF) to attenuate secondary damage and influence behavioral outcome after experimental traumatic brain injury (TBI) remains controversial. Because TBI can result in decreased expression of the trkB receptor, thereby preventing BDNF from exerting potential neuroprotective effects, the contribution of both BDNF and its receptor trkB to hippocampal neuronal loss and cognitive dysfunction were evaluated. METHODS: Full-length trkB was overexpressed in the left hippocampus of adult C57Bl/6 mice using recombinant adeno-associated virus serotype 2/5 (rAAV 2/5). EGFP (enhanced green fluorescent protein) expression was present at two weeks after AAV-EGFP injection and remained sustained up to four weeks after the injection. At 2 weeks following gene transduction, mice were subjected to parasagittal controlled cortical impact (CCI) brain injury, followed by either BDNF or PBS infusion into the hippocampus. RESULTS: No differences were observed in learning ability at two weeks post-injury or in motor function from 48 hours to two weeks among treatment groups. The number of surviving pyramidal neurons in the CA2-CA3 region of the hippocampus was also not different among treatment groups. CONCLUSIONS: These data suggest that neither overexpression of trkB, BNDF infusion or their combination affects neuronal survival or behavioral outcome following experimental TBI in mice.
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  • Luheshi, Leila M, et al. (författare)
  • Systematic in vivo analysis of the intrinsic determinants of amyloid Beta pathogenicity.
  • 2007
  • Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1545-7885. ; 5:11, s. e290-
  • Tidskriftsartikel (refereegranskat)abstract
    • Protein aggregation into amyloid fibrils and protofibrillar aggregates is associated with a number of the most common neurodegenerative diseases. We have established, using a computational approach, that knowledge of the primary sequences of proteins is sufficient to predict their in vitro aggregation propensities. Here we demonstrate, using rational mutagenesis of the Abeta42 peptide based on such computational predictions of aggregation propensity, the existence of a strong correlation between the propensity of Abeta42 to form protofibrils and its effect on neuronal dysfunction and degeneration in a Drosophila model of Alzheimer disease. Our findings provide a quantitative description of the molecular basis for the pathogenicity of Abeta and link directly and systematically the intrinsic properties of biomolecules, predicted in silico and confirmed in vitro, to pathogenic events taking place in a living organism.
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  • Raval, Aparna, et al. (författare)
  • Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia
  • 2007
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 129:5, s. 879-890
  • Tidskriftsartikel (refereegranskat)abstract
    • The heritability of B cell chronic lymphocytic leukemia (CLL) is relatively high; however, no predisposing mutation has been convincingly identified. We show that loss or reduced expression of death-associated protein kinase 1 (DAPK1) underlies cases of heritable predisposition to CLL and the majority of sporadic CLL. Epigenetic silencing of DAPK1 by promoter methylation occurs in almost all sporadic CLL cases. Furthermore, we defined a disease haplotype, which segregates with the CLL phenotype in a large family. DAPK1 expression of the CLL allele is downregulated by 75% in germline cells due to increased HOXB7 binding. In the blood cells from affected family members, promoter methylation results in additional loss of DAPK1 expression. Thus, reduced expression of DAPK1 can result from germline predisposition, as well as epigenetic or somatic events causing or contributing to the CLL phenotype.
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  • Schmid-Fetzer, R., et al. (författare)
  • Assessment techniques, database design and software facilities for thermodynamics and diffusion
  • 2007
  • Ingår i: Calphad. - : Elsevier BV. - 0364-5916 .- 1873-2984. ; 31:1, s. 38-52
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this article is to give a set of recommendations to producers of assessed thermodynamic data, who may be involved in either the critical evaluation of limited chemical systems or the creation and dissemination of larger thermodynamic databases. Also, it is hoped that reviewers and editors of scientific publications in this field will find some of the information useful. Good practice in the assessment process is essential, particularly as datasets from many different sources may be combined together into a single database. With this in mind, we highlight some problems that can arise during the assessment process and we propose a quality assurance procedure. It is worth mentioning at this point, that the provision of reliable assessed thermodynamic data relies heavily on the availability of high quality experimental information. The different software packages for thermodynamics and diffusion are described here only briefly.
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30.
  • Watson, Andrew J., et al. (författare)
  • Tracking the Variable North Atlantic Sink for Atmospheric CO2
  • 2009
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326:5958, s. 1391-1393
  • Tidskriftsartikel (refereegranskat)abstract
    • The oceans are a major sink for atmospheric carbon dioxide (CO2). Historically, observations have been too sparse to allow accurate tracking of changes in rates of CO2 uptake over ocean basins, so little is known about how these vary. Here, we show observations indicating substantial variability in the CO2 uptake by the North Atlantic on time scales of a few years. Further, we use measurements from a coordinated network of instrumented commercial ships to define the annual flux into the North Atlantic, for the year 2005, to a precision of about 10%. This approach offers the prospect of accurately monitoring the changing ocean CO2 sink for those ocean basins that are well covered by shipping routes.
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31.
  • Xu, D., et al. (författare)
  • In Search of Progenitors for Supernovaless Gamma-Ray Bursts 060505 and 060614 : Re-examination of Their Afterglows
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 696:1, s. 971-979
  • Tidskriftsartikel (refereegranskat)abstract
    • GRB 060505 and GRB 060614 are nearby long-duration gamma-ray bursts (LGRBs) without accompanying supernovae (SNe) down to very strict limits. They thereby challenge the conventional LGRB-SN connection and naturally give rise to the question: are there other peculiar features in their afterglows which would help shed light on their progenitors? To answer this question, we combine new observational data with published data and investigate the multiband temporal and spectral properties of the two afterglows. We find that both afterglows can be well interpreted within the framework of the jetted standard external shock wave model, and that the afterglow parameters for both bursts fall well within the range observed for other LGRBs. Hence, from the properties of the afterglows there is nothing to suggest that these bursts should have another progenitor than other LGRBs. Recently, Swift-discovered GRB 080503 also has the spike + tail structure during its prompt γ-ray emission seemingly similar to GRB 060614. We analyze the prompt emission of this burst and find that this GRB is actually a hard-spike + hard-tail burst with a spectral lag of 0.8 ± 0.4 s during its tail emission. Thus, the properties of the prompt emission of GRB 060614 and GRB 080503 are clearly different, motivating further thinking of GRB classification (and even identification of faint core-collapse SNe). Finally, we note that, whereas the progenitor of the two SN-less bursts remains uncertain, the core-collapse origin for the SN-less bursts would be quite certain if a windlike environment can be observationally established, e.g., from an optical decay faster than the X-ray decay in the afterglow's slow cooling phase. Based on observations collected at the European Organization for Astronomical Research in the Southern Hemisphere, Chile, under programs 077.D-0661 and 177.A-0591.
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