| 1. |
- Abramowski, A., et al.
(författare)
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The 2010 very high energy gamma-RAY flare and 10 years of multi-wavelength observations of M 87
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2, s. 151-
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Tidskriftsartikel (refereegranskat)abstract
- The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3-6) x 10(9) M-circle dot) provides a unique opportunity to investigate the origin of very high energy (VHE; E > 100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of tau(rise)(d) = (1.69 +/- 0.30) days and tau(decay)(d) = (0.611 +/- 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (similar to day), peak fluxes (Phi(>0.35 TeV) similar or equal to (1-3) x 10(-11) photons cm(-2) s(-1)), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken similar to 3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core (flux increased by factor similar to 2; variability timescale <2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE gamma-ray emission from M 87 are reviewed in the light of the new data.
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| 2. |
- Aliu, E., et al.
(författare)
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Long-term TeV and X-ray Observations of the Gamma-ray Binary HESS J0632+057
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 780:2
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Tidskriftsartikel (refereegranskat)abstract
- HESS J0632+057 is the only gamma-ray binary known so far whose position in the sky allows observations with ground-based observatories in both thenorthern and southern hemispheres. Here we report on long-term observations of HESS J0632+057 conducted with the Very Energetic Radiation Imaging Telescope Array System and High Energy Stereoscopic System Cherenkov telescopes and the X-ray satellite Swift, spanning a time range from 2004 to 2012 and covering most of the system's orbit. The very-high-energy (VHE) emission is found to be variable and is correlated with that at X-ray energies. An orbital period of 315(-4)(+6) days is derived from the X-ray data set, which is compatible with previous results, P = (321 +/- 5) days. The VHE light curve shows a distinct maximum at orbital phases close to 0.3, or about 100 days after periastron passage, which coincides with the periodic enhancement of the X-rayemission. Furthermore, the analysis of the TeV data shows for the first time a statistically significant (> 6.5 sigma) detection at orbital phases 0.6-0.9. Theobtained gamma-ray and X-ray light curves and the correlation of the source emission at these two energy bands are discussed in the context of the recent ephemeris obtained for the system. Our results are compared to those reported for other gamma-ray binaries.
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| 3. |
- Acciari, V. A., et al.
(författare)
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Discovery of very high energy gamma rays from PKS 1424+240 and multiwavelength constraints on ITS redshift
- 2010
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Ingår i: ASTROPHYSICAL JOURNAL LETTERS. - 2041-8205. ; 708:2, s. L100-L106
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Tidskriftsartikel (refereegranskat)abstract
- We report the first detection of very high energy(83) (VHE) gamma-ray emission above 140 GeV from PKS 1424+240, a BL Lac object with an unknown redshift. The photon spectrum above 140 GeV measured by VERITAS is well described by a power law with a photon index of 3.8 +/- 0.5(stat) +/- 0.3(syst) and a flux normalization at 200 GeV of (5.1 +/- 0.9(stat) +/- 0.5(syst)) x 10(-11) TeV-1 cm(-2) s(-1), where stat and syst denote the statistical and systematical uncertainties, respectively. The VHE flux is steady over the observation period between MJD 54881 and 55003 (from 2009 February 19 to June 21). Flux variability is also not observed in contemporaneous high-energy observations with the Fermi Large Area Telescope. Contemporaneous X-ray and optical data were also obtained from the Swift XRT and MDM observatory, respectively. The broadband spectral energy distribution is well described by a one-zone synchrotron self-Compton model favoring a redshift of less than 0.1. Using the photon index measured with Fermi in combination with recent extragalactic background light absorption models it can be concluded from the VERITAS data that the redshift of PKS 1424+240 is less than 0.66.
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| 4. |
- Acciari, V. A., et al.
(författare)
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THE DISCOVERY OF gamma-RAY EMISSION FROM THE BLAZAR RGB J0710+591
- 2010
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Ingår i: ASTROPHYSICAL JOURNAL LETTERS. - 2041-8205. ; 715:1, s. L49-L55
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Tidskriftsartikel (refereegranskat)abstract
- The high-frequency-peaked BL Lacertae object RGB J0710+591 was observed in the very high-energy (VHE; E > 100 GeV) wave band by the VERITAS array of atmospheric Cherenkov telescopes. The observations, taken between 2008 December and 2009 March and totaling 22.1 hr, yield the discovery of VHE gamma rays from the source. RGB J0710+591 is detected at a statistical significance of 5.5 standard deviations (5.5 sigma) above the background, corresponding to an integral flux of (3.9 +/- 0.8) x 10(-12) cm(-2) s(-1) (3% of the Crab Nebula's flux) above 300 GeV. The observed spectrum can be fit by a power law from 0.31 to 4.6 TeV with a photon spectral index of 2.69 +/- 0.26(stat) +/- 0.20(sys). These data are complemented by contemporaneous multiwavelength data from the Fermi Large Area Telescope, the Swift X-ray Telescope, the Swift Ultra-Violet and Optical Telescope, and the Michigan-Dartmouth-MIT observatory. Modeling the broadband spectral energy distribution (SED) with an equilibrium synchrotron self-Compton model yields a good statistical fit to the data. The addition of an external-Compton component to the model does not improve the fit nor brings the system closer to equipartition. The combined Fermi and VERITAS data constrain the properties of the high-energy emission component of the source over 4 orders of magnitude and give measurements of the rising and falling sections of the SED.
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| 5. |
- Tanvir, N. R., et al.
(författare)
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A γ-ray burst at a redshift of z~8.2
- 2009
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 461, s. 1254-1257
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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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| 6. |
- Aliu, E., et al.
(författare)
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Discovery of TeV Gamma-Ray Emission toward Supernova Remnant SNR G78.2+2.1
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 770:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of an unidentified, extended source of very-high-energy gamma-ray emission, VER J2019+407, within the radio shell of the supernova remnant SNR G78.2+2.1, using 21.4 hr of data taken by the VERITAS gamma-ray observatory in 2009. These data confirm the preliminary indications of gamma-ray emission previously seen in a two-year (2007-2009) blind survey of the Cygnus region by VERITAS. VER J2019+407, which is detected at a post-trials significance of 7.5 standard deviations in the 2009 data, is localized to the northwestern rim of the remnant in a region of enhanced radio and X-ray emission. It has an intrinsic extent of and its spectrum is well-characterized by a differential power law (dN/dE = N 0 × (E/TeV)–Γ) with a photon index of Γ = 2.37 ± 0.14stat ± 0.20sys and a flux normalization of N 0 = 1.5 ± 0.2stat ± 0.4sys × 10–12 photon TeV–1 cm–2 s–1. This yields an integral flux of 5.2 ± 0.8stat ± 1.4sys × 10–12 photon cm–2 s–1above 320 GeV, corresponding to 3.7% of the Crab Nebula flux. We consider the relationship of the TeV gamma-ray emission with the GeV gamma-ray emission seen from SNR G78.2+2.1 as well as that seen from a nearby cocoon of freshly accelerated cosmic rays. Multiple scenarios are considered as possible origins for the TeV gamma-ray emission, including hadronic particle acceleration at the SNR shock.
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| 7. |
- Aliu, E., et al.
(författare)
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VERITAS Observations of the Nova in V407 Cygni
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 754:1
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Tidskriftsartikel (refereegranskat)abstract
- We report on very high energy (E > 100 GeV) gamma-ray observations of V407 Cygni, a symbiotic binary that underwent a nova outburst producing 0.1-10 GeV gamma rays during 2010 March 10-26. Observations were made with the Very Energetic Radiation Imaging Telescope Array System during 2010 March 19-26 at relatively large zenith angles due to the position of V407 Cyg. An improved reconstruction technique for large zenith angle observations is presented and used to analyze the data. We do not detect V407 Cygni and place a differential upper limit on the flux at 1.6 TeV of 2.3 × 10–12 erg cm–2 s–1 (at the 95% confidence level). When considered jointly with data from Fermi-LAT, this result places limits on the acceleration of very high energy particles in the nova.
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| 8. |
- Acciari, V. A., et al.
(författare)
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VERITAS Observations of Gamma-Ray Bursts Detected by Swift
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 743:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of 16 Swift-triggered Gamma-ray burst (GRB) follow-up observations taken with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) telescope array from 2007 January to 2009 June. The median energy threshold and response time of these observations were 260 GeV and 320 s, respectively. Observations had an average duration of 90 minutes. Each burst is analyzed independently in two modes: over the whole duration of the observations and again over a shorter timescale determined by the maximum VERITAS sensitivity to a burst with a t –1.5 time profile. This temporal model is characteristic of GRB afterglows with high-energy, long-lived emission that have been detected by the Large Area Telescope on board the Fermi satellite. No significant very high energy (VHE) gamma-ray emission was detected and upper limits above the VERITAS threshold energy are calculated. The VERITAS upper limits are corrected for gamma-ray extinction by the extragalactic background light and interpreted in the context of the keV emission detected by Swift. For some bursts the VHE emission must have less power than the keV emission, placing constraints on inverse Compton models of VHE emission.
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| 9. |
- Aliu, E., et al.
(författare)
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Observations of the Unidentified Gamma-Ray Source TeV J2032+4130 by VERITAS
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 783
-
Tidskriftsartikel (refereegranskat)abstract
- TeV J2032+4130 was the first unidentified source discovered at very high energies (VHEs; E > 100 GeV), with no obvious counterpart in any other wavelength. It is also the first extended source to be observed in VHE gamma rays. Following its discovery, intensive observational campaigns have been carried out in all wavelengths in order to understand the nature of the object, which have met with limited success. We report here on a deep observation of TeV J2032+4130 based on 48.2 hr of data taken from 2009 to 2012 by the Very Energetic Radiation Imaging Telescope Array System experiment. The source is detected at 8.7 standard deviations (σ) and is found to be extended and asymmetric with a width of 9.'5 ± 1.'2 along the major axis and 4.'0 ± 0.'5 along the minor axis. The spectrum is well described by a differential power law with an index of 2.10 ± 0.14stat ± 0.21sys and a normalization of (9.5 ± 1.6stat ± 2.2sys) × 10–13 TeV–1 cm–2 s–1 at 1 TeV. We interpret these results in the context of multiwavelength scenarios which particularly favor the pulsar wind nebula interpretation.
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| 10. |
- Collaboration, V E R I T A S, et al.
(författare)
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Detection of Pulsed Gamma Rays Above 100 GeV from the Crab Pulsar
- 2011
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 334:6052, s. 69-72
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Tidskriftsartikel (refereegranskat)abstract
- We report the detection of pulsed gamma rays from the Crab pulsar at energies above 100 giga–electron volts (GeV) with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) array of atmospheric Cherenkov telescopes. The detection cannot be explained on the basis of current pulsar models. The photon spectrum of pulsed emission between 100 mega–electron volts and 400 GeV is described by a broken power law that is statistically preferred over a power law with an exponential cutoff. It is unlikely that the observation can be explained by invoking curvature radiation as the origin of the observed gamma rays above 100 GeV. Our findings require that these gamma rays be produced more than 10 stellar radii from the neutron star.
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| 11. |
- Aliu, E., et al.
(författare)
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VERITAS Observations of Day-scale Flaring of M 87 in 2010 April
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2
-
Tidskriftsartikel (refereegranskat)abstract
- VERITAS has been monitoring the very-high-energy (VHE; > 100 GeV) gamma-ray activity of the radio galaxy M 87 since 2007. During 2008, flaring activity on a timescale of a few days was observed with a peak flux of (0.70 ± 0.16) × 10–11 cm–2 s–1 at energies above 350 GeV. In 2010 April, VERITAS detected a flare from M 87 with peak flux of (2.71 ± 0.68) × 10–11 cm–2 s–1 forE > 350 GeV. The source was observed for six consecutive nights during the flare, resulting in a total of 21 hr of good-quality data. The most rapid flux variation occurred on the trailing edge of the flare with an exponential flux decay time of 0.90+0.22 –0.15 days. The shortest detected exponential rise time is three times as long, at 2.87+1.65 –0.99 days. The quality of the data sample is such that spectral analysis can be performed for three periods: rising flux, peak flux, and falling flux. The spectra obtained are consistent with power-law forms. The spectral index at the peak of the flare is equal to 2.19 ± 0.07. There is some indication that the spectrum is softer in the falling phase of the flare than the peak phase, with a confidence level corresponding to 3.6 standard deviations. We discuss the implications of these results for the acceleration and cooling rates of VHE electrons in M 87 and the constraints they provide on the physical size of the emitting region.
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| 12. |
- Archambault, S., et al.
(författare)
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VERITAS Observations of the Microquasar Cygnus X-3
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 779:2
-
Tidskriftsartikel (refereegranskat)abstract
- We report results from TeV gamma-ray observations of the microquasar Cygnus X-3. The observations were made with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) over a time period from 2007 June 11 to 2011 November 28. VERITAS is most sensitive to gamma rays at energies between 85 GeV and 30 TeV. The effective exposure time amounts to a total of about 44 hr, with the observations covering six distinct radio/X-ray states of the object. No significant TeV gamma-ray emission was detected in any of the states, nor with all observations combined. The lack of a positive signal, especially in the states where GeV gamma rays were detected, places constraints on TeV gamma-ray production in Cygnus X-3. We discuss the implications of the results.
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| 13. |
- Acciari, V. A., et al.
(författare)
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VERITAS Observations of the TeV Binary LS I +61\deg 303 During 2008-2010
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 738:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of observations of the TeV binary LS I +61° 303 with the VERITAS telescope array between 2008 and 2010, at energies above 300 GeV. In the past, both ground-based gamma-ray telescopes VERITAS and MAGIC have reported detections of TeV emission near the apastron phases of the binary orbit. The observations presented here show no strong evidence for TeV emission during these orbital phases; however, during observations taken in late 2010, significant emission was detected from the source close to the phase of superior conjunction (much closer to periastron passage) at a 5.6 standard deviation (5.6σ) post-trials significance. In total, between 2008 October and 2010 December a total exposure of 64.5 hr was accumulated with VERITAS on LS I +61° 303, resulting in an excess at the 3.3σ significance level for constant emission over the entire integrated data set. The flux upper limits derived for emission during the previously reliably active TeV phases (i.e., close to apastron) are less than 5% of the Crab Nebula flux in the same energy range. This result stands in apparent contrast to previous observations by both MAGIC and VERITAS which detected the source during these phases at 10% of the Crab Nebula flux. During the two year span of observations, a large amount of X-ray data were also accrued on LS I +61° 303 by theSwift X-ray Telescope and the Rossi X-ray Timing Explorer Proportional Counter Array. We find no evidence for a correlation between emission in the X-ray and TeV regimes during 20 directly overlapping observations. We also comment on data obtained contemporaneously by the Fermi Large Area Telescope.
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| 14. |
- Aliu, E., et al.
(författare)
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A Three-year Multi-wavelength Study of the Very-high-energy γ-Ray Blazar 1ES 0229+200
- 2014
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 782:1
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Tidskriftsartikel (refereegranskat)abstract
- The high-frequency-peaked BL Lacertae object 1ES 0229+200 is a relatively distant (z = 0.1396), hard-spectrum (Γ ~ 2.5), very-high-energy (VHE; E > 100 GeV) emitting γ-ray blazar. VHE measurements of this active galactic nucleus have been used to place constraints on the intensity of the extragalactic background light and the intergalactic magnetic field (IGMF). A multi-wavelength study of this object centered around VHE observations by Very Energetic Radiation Imaging Telescope Array System (VERITAS) is presented. This study obtained, over a period of three years, an 11.7 standard deviation detection and an average integral flux F(E > 300 GeV) = (23.3 ± 2.8stat ± 5.8sys) × 10–9 photons m–2 s–1, or 1.7% of the Crab Nebula's flux (assuming the Crab Nebula spectrum measured by H.E.S.S). Supporting observations from Swift and RXTE are analyzed. TheSwift observations are combined with previously published Fermi observations and the VHE measurements to produce an overall spectral energy distribution which is then modeled assuming one-zone synchrotron-self-Compton emission. The χ2probability of the TeV flux being constant is 1.6%. This, when considered in combination with measured variability in the X-ray band, and the demonstrated variability of many TeV blazars, suggests that the use of blazars such as 1ES 0229+200 for IGMF studies may not be straightforward and challenges models that attribute hard TeV spectra to secondary γ-ray production along the line of sight.
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| 15. |
- Aliu, E., et al.
(författare)
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Discovery of TeV Gamma-Ray Emission from CTA 1 by VERITAS
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 764:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of TeV gamma-ray emission coincident with the shell-type radio supernova remnant (SNR) CTA 1 using the VERITAS gamma-ray observatory. The source, VER J0006+729, was detected as a 6.5 standard deviation excess over background and shows an extended morphology, approximated by a two-dimensional Gaussian of semimajor (semiminor) axis 030 (024) and a centroid 5' from the Fermi gamma-ray pulsar PSR J0007+7303 and its X-ray pulsar wind nebula (PWN). The photon spectrum is well described by a power-law dN/dE = N 0(E/3 TeV)–Γ, with a differential spectral index of Γ = 2.2 ± 0.2stat ± 0.3sys, and normalization N 0 = (9.1 ± 1.3stat ± 1.7sys) × 10–14 cm–2 s–1 TeV–1. The integral flux, F γ = 4.0 ×10–12 erg cm–2 s–1 above 1 TeV, corresponds to 0.2% of the pulsar spin-down power at 1.4 kpc. The energetics, colocation with the SNR, and the relatively small extent of the TeV emission strongly argue for the PWN origin of the TeV photons. We consider the origin of the TeV emission in CTA 1.
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| 16. |
- Aliu, E., et al.
(författare)
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Multiwavelength Observations of the Previously Unidentified Blazar RX J0648.7+1516
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 742:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on the VERITAS discovery of very high energy (VHE) gamma-ray emission above 200 GeV from the high-frequency-peaked BL Lac (HBL) object RX J0648.7+1516 (GB J0648+1516), associated with 1FGL J0648.8+1516. The photon spectrum above 200 GeV is fitted by a power law dN/dE = F 0(E/E 0)–Γ with a photon index Γ of 4.4 ± 0.8stat ± 0.3syst and a flux normalization F 0 of (2.3 ± 0.5stat ± 1.2sys) × 10–11 TeV–1 cm–2 s–1 with E 0 = 300 GeV. No VHE variability is detected during VERITAS observations of RX J0648.7+1516 between 2010 March 4 and April 15. Following the VHE discovery, the optical identification and spectroscopic redshift were obtained using the Shane 3 m Telescope at the Lick Observatory, showing the unidentified object to be a BL Lac type with a redshift of z = 0.179. Broadband multiwavelength observations contemporaneous with the VERITAS exposure period can be used to subclassify the blazar as an HBL object, including data from the MDM observatory, Swift-UVOT, and X-Ray Telescope, and continuous monitoring at photon energies above 1 GeV from the FermiLarge Area Telescope (LAT). We find that in the absence of undetected, high-energy rapid variability, the one-zone synchrotron self-Compton (SSC) model overproduces the high-energy gamma-ray emission measured by the Fermi-LAT over 2.3 years. The spectral energy distribution can be parameterized satisfactorily with an external-Compton or lepto-hadronic model, which have two and six additional free parameters, respectively, compared to the one-zone SSC model.
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| 17. |
- Aliu, E., et al.
(författare)
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Multiwavelength Observations and Modeling of 1ES 1959+650 in a Low Flux State
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 775:1
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Tidskriftsartikel (refereegranskat)abstract
- We report on the VERITAS observations of the high-frequency peaked BL Lac object 1ES 1959+650 in the period 2007-2011. This source is detected at TeV energies by VERITAS at 16.4 standard deviation (σ) significance in 7.6 hr of observation in a low flux state. A multiwavelength spectral energy distribution (SED) is constructed from contemporaneous data from VERITAS,Fermi-LAT, RXTE PCA, and Swift UVOT. Swift XRT data is not included in the SED due to a lack of simultaneous observations with VERITAS. In contrast to the orphan γ-ray flare exhibited by this source in 2002, the X-ray flux of the source is found to vary by an order of magnitude, while other energy regimes exhibit less variable emission. A quasi-equilibrium synchrotron self-Compton model with an additional external radiation field is used to describe three SEDs corresponding to the lowest, highest, and average X-ray states. The variation in the X-ray spectrum is modeled by changing the electron injection spectral index, with minor adjustments of the kinetic luminosity in electrons. This scenario produces small-scale flux variability of the order of 2 in the high energy (E > 1 MeV) and very high energy (E > 100 GeV) γ-ray regimes, which is corroborated by the Fermi-LAT, VERITAS, and Whipple 10 m telescope light curves.
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| 18. |
- Aliu, E., et al.
(författare)
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Search for a Correlation between Very-high-energy Gamma Rays and Giant Radio Pulses in the Crab Pulsar
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 760:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a joint observational campaign between the Green Bank radio telescope and the VERITAS gamma-ray telescope, which searched for a correlation between the emission of very-high-energy (VHE) gamma rays (E γ > 150 GeV) and giant radio pulses (GRPs) from the Crab pulsar at 8.9 GHz. A total of 15,366 GRPs were recorded during 11.6 hr of simultaneous observations, which were made across four nights in 2008 December and in 2009 November and December. We searched for an enhancement of the pulsed gamma-ray emission within time windows placed around the arrival time of the GRP events. In total, eight different time windows with durations ranging from 0.033 ms to 72 s were positioned at three different locations relative to the GRP to search for enhanced gamma-ray emission which lagged, led, or was concurrent with, the GRP event. Furthermore, we performed separate searches on main pulse GRPs and interpulse GRPs and on the most energetic GRPs in our data sample. No significant enhancement of pulsed VHE emission was found in any of the preformed searches. We set upper limits of 5-10 times the average VHE flux of the Crab pulsar on the flux simultaneous with interpulse GRPs on single-rotation-period timescales. On ~8 s timescales around interpulse GRPs, we set an upper limit of 2-3 times the average VHE flux. Within the framework of recent models for pulsed VHE emission from the Crab pulsar, the expected VHE-GRP emission correlations are below the derived limits.
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| 19. |
- Aliu, E., et al.
(författare)
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VERITAS Observations of Six Bright, Hard-spectrum Fermi-LAT Blazars
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 759:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on VERITAS very high energy (VHE; E ≥ 100 GeV) observations of six blazars selected from the Fermi Large Area Telescope First Source Catalog (1FGL). The gamma-ray emission from 1FGL sources was extrapolated up to the VHE band, taking gamma-ray absorption by the extragalactic background light into account. This allowed the selection of six bright, hard-spectrum blazars that were good candidate TeV emitters. Spectroscopic redshift measurements were attempted with the Keck Telescope for the targets without Sloan Digital Sky Survey spectroscopic data. No VHE emission is detected during the observations of the six sources described here. Corresponding TeV upper limits are presented, along with contemporaneousFermi observations and non-concurrent Swift UVOT and X-Ray Telescope data. The blazar broadband spectral energy distributions (SEDs) are assembled and modeled with a single-zone synchrotron self-Compton model. The SED built for each of the six blazars shows a synchrotron peak bordering between the intermediate- and high-spectrum-peak classifications, with four of the six resulting in particle-dominated emission regions.
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| 20. |
- Acciari, V. A., et al.
(författare)
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Gamma-Ray Observations of the Be/Pulsar Binary 1A 0535+262 During a Giant X-Ray Outburst
- 2011
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 733:2
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Tidskriftsartikel (refereegranskat)abstract
- Giant X-ray outbursts, with luminosities of about 1037 erg s–1, are observed roughly every five years from the nearby Be/pulsar binary 1A 0535+262. In this article, we present observations of the source with VERITAS at very high energies (VHEs;E >100 GeV) triggered by the X-ray outburst in 2009 December. The observations started shortly after the onset of the outburst and provided comprehensive coverage of the episode, as well as the 111 day binary orbit. No VHE emission is evident at any time. We also examined data from the contemporaneous observations of 1A 0535+262 with the Fermi/Large Area Telescope at high-energy photons (E > 0.1 GeV) and failed to detect the source at GeV energies. The X-ray continua measured with theSwift/X-Ray Telescope and the RXTE/PCA can be well described by the combination of blackbody and Comptonized emission from thermal electrons. Therefore, the gamma-ray and X-ray observations suggest the absence of a significant population of non-thermal particles in the system. This distinguishes 1A 0535+262 from those Be X-ray binaries (such as PSR B1259-63 and LS I +61°303) that have been detected at GeV-TeV energies. We discuss the implications of the results on theoretical models.
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| 21. |
- Waszak, S. M., et al.
(författare)
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Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort
- 2018
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Ingår i: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 19:6, s. 785-798
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Tidskriftsartikel (refereegranskat)abstract
- Background Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 4069) and 5-year overall survival was 65% (95% CI 5281); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. Interpretation Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. Copyright (c) 2018 The Author(s). Published by Elsevier Ltd.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Mikkelsen, Tarjei S, et al.
(författare)
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Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7141, s. 167-177
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Tidskriftsartikel (refereegranskat)abstract
- We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Bakajin, O., et al.
(författare)
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Separation of 100-kilobase DNA molecules in 10 seconds
- 2001
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 73:24, s. 6053-6056
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Tidskriftsartikel (refereegranskat)abstract
- Long double-stranded DNA molecules were separated in microfabricated hexagonal arrays in less than 1 min, several orders of magnitude faster than by using conventional technology. DNA samples were first concentrated at the entrance to the array in a thin band by entropic focusing. They were then separated by pulsed field electrophoresis. T4 (168.9 kbp) and λ (48.5 kbp) DNAs could be resolved into two clearly separated bands in ∼10 s in these experiments. This corresponds to a mass resolution of 6% in 11 min in a 1-cm-long array.
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| 32. |
- Ghosh, KK, et al.
(författare)
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An In Vivo Study of a Rat Fluid-Percussion-Induced Traumatic Brain Injury Model with [11C]PBR28 and [18F]flumazenil PET Imaging
- 2021
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:2
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [11C]PBR28 and [18F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [11C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [18F]flumazenil is a radioligand for GABAA-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [11C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [18F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [11C]PBR28 and [18F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment.
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| 33. |
- Gómez-Ramírez, P, et al.
(författare)
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An overview of existing raptor contaminant monitoring activities in Europe
- 2014
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Ingår i: Environment International. - : Elsevier. - 0160-4120. ; 67, s. 12-21
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Tidskriftsartikel (refereegranskat)abstract
- Biomonitoring using raptors as sentinels can provide early warning of the potential impacts of contaminants on humans and the environment and also a means of tracking the success of associated mitigation measures. Examples include detection of heavy metal-induced immune system impairment, PCB-induced altered reproductive impacts, and toxicity associated with lead in shot game. Authorisation of such releases and implementation of mitigation is now increasingly delivered through EU-wide directives but there is little established pan-European monitoring to quantify outcomes. We investigated the potential for EU-wide coordinated contaminant monitoring using raptors as sentinels. We did this using a questionnaire to ascertain the current scale of national activity across 44 European countries. According to this survey, there have been 52 different contaminant monitoring schemes with raptors over the last 50 years. There were active schemes in 15 (predominantly western European) countries and 23 schemes have been running for >20 years; most monitoring was conducted for >5 years. Legacy persistent organic compounds (specifically organochlorine insecticides and PCBs), and metals/metalloids were monitored in most of the 15 countries. Fungicides, flame retardants and anticoagulant rodenticides were also relatively frequently monitored (each in at least 6 countries). Common buzzard (Buteo buteo), common kestrel (Falco tinnunculus), golden eagle (Aquila chrysaetos), white-tailed sea eagle (Haliaeetus albicilla), peregrine falcon (Falco peregrinus), tawny owl (Strix aluco) and barn owl (Tyto alba) were most commonly monitored (each in 6–10 countries). Feathers and eggs were most widely analysed although many schemes also analysed body tissues. Our study reveals an existing capability across multiple European countries for contaminant monitoring using raptors. However, coordination between existing schemes and expansion of monitoring into Eastern Europe is needed. This would enable assessment of the appropriateness of the EU-regulation of substances that are hazardous to humans and the environment, the effectiveness of EU level mitigation policies, and identify pan-European spatial and temporal trends in current and emerging contaminants of concern.
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| 34. |
- Lind, U., et al.
(författare)
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Valine 571 functions as a regional organizer in programming the glucocorticoid receptor for differential binding of glucocorticoids and mineralocorticoids
- 1999
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Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 274:26, s. 18515-18523
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Tidskriftsartikel (refereegranskat)abstract
- The glucocorticoid receptor (GR) interacts specifically with glucocorticoids, whereas its closest relative, the mineralocorticoid receptor (MR), interacts with both glucocorticoids and mineralocorticoids, such as aldosterone. To investigate the mechanism underlying the glucocorticoid/mineralocorticoid specificity of the GR, we used a yeast model system to screen for GR ligand-binding domain mutants, substituted with MR residues in the segment 565-574, that can be efficiently activated by aldosterone. In all such increased activity mutants, valine 571 was replaced by methionine, even though most mutants also contained substitutions of other residues with their MR counterparts. Further analysis in yeast and COS-7 cells has revealed that the identity of residue 571 determines the behavior of other MR substituted residues in the 565-574 segment. Generally, MR substitutions in this region are only consistent with aldosterone binding if residue 571 is also replaced with methionine (MR conformation). If residue 571 is valine (GR conformation), most other MR substitution mutants drastically reduce interaction with both mineralocorticoid and glucocorticoid hormones. Based on these functional data, we hypothesize that residue 571 functions as a regional organizer involved in discriminating between glucocorticoid and mineralocorticoid hormones. We have used a molecular model of the GR ligand-binding domain in an attempt to interpret our functional data in structural terms.
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| 35. |
- Moon, Woosok, et al.
(författare)
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Physical length scales of wind-blown snow redistribution and accumulation on relatively smooth Arctic first-year sea ice
- 2019
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 14:10
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Tidskriftsartikel (refereegranskat)abstract
- Snow thickness measurements over relatively smooth Arctic first-year sea ice, obtained near Cambridge Bay in the Canadian Arctic (2014, 2016 and 2017) and near Elson Lagoon in the Alaskan Arctic (2003 and 2006), are analyzed to quantify physical length-scales and their relevant scaling behaviors. We use the multi-fractal temporally weighted detrended fluctuation analysis method to detect two major physical length-scales from the two independent study locations. Our results suggest that physical processes underlying the formation of snow dunes are consistent and that the wind is the main process shaping the snow thickness variability and redistribution. One scale, around 10 m, appears to be related to the formation of the snow 'dunes', while the other scale, between 30 and 100 m, is likely associated with the various interactions of the snow dunes such as merging, calving and lateral linking. Results imply that snow on level sea ice shows self-organized characteristics.
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| 36. |
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| 37. |
- Albert, James S., et al.
(författare)
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Scientists' warning to humanity on the freshwater biodiversity crisis
- 2021
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 50, s. 85-94
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Tidskriftsartikel (refereegranskat)abstract
- Freshwater ecosystems provide irreplaceable services for both nature and society. The quality and quantity of freshwater affect biogeochemical processes and ecological dynamics that determine biodiversity, ecosystem productivity, and human health and welfare at local, regional and global scales. Freshwater ecosystems and their associated riparian habitats are amongst the most biologically diverse on Earth, and have inestimable economic, health, cultural, scientific and educational values. Yet human impacts to lakes, rivers, streams, wetlands and groundwater are dramatically reducing biodiversity and robbing critical natural resources and services from current and future generations. Freshwater biodiversity is declining rapidly on every continent and in every major river basin on Earth, and this degradation is occurring more rapidly than in terrestrial ecosystems. Currently, about one third of all global freshwater discharges pass through human agricultural, industrial or urban infrastructure. About one fifth of the Earth's arable land is now already equipped for irrigation, including all the most productive lands, and this proportion is projected to surpass one third by midcentury to feed the rapidly expanding populations of humans and commensal species, especially poultry and ruminant livestock. Less than one fifth of the world's preindustrial freshwater wetlands remain, and this proportion is projected to decline to under one tenth by midcentury, with imminent threats from water transfer megaprojects in Brazil and India, and coastal wetland drainage megaprojects in China. The Living Planet Index for freshwater vertebrate populations has declined to just one third that of 1970, and is projected to sink below one fifth by midcentury. A linear model of global economic expansion yields the chilling prediction that human utilization of critical freshwater resources will approach one half of the Earth's total capacity by midcentury. Although the magnitude and growth of the human freshwater footprint are greater than is generally understood by policy makers, the news media, or the general public, slowing and reversing dramatic losses of freshwater species and ecosystems is still possible. We recommend a set of urgent policy actions that promote clean water, conserve watershed services, and restore freshwater ecosystems and their vital services. Effective management of freshwater resources and ecosystems must be ranked amongst humanity's highest priorities.
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| 38. |
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| 39. |
- Benyi, E., et al.
(författare)
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Risks of Malignant and Non-Malignant Tumours in Tall Women Treated with High-Dose Oestrogen during Adolescence
- 2014
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 82:2, s. 89-96
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: High-dose oestrogen treatment has been used to reduce growth in tall adolescent girls. The long-term safety with regard to cancer has not been clarified. Our aim was to study if this growth reduction therapy affects cancer risk later in life. Methods: A cohort study of 369 (172 treated, 197 untreated) Swedish women who in 1973-1993 were assessed for tall adolescent stature was designed. Data were collected from university hospital records, patient questionnaires, and the Swedish Cancer Register. Results: Risks are presented as odds ratios (ORs) with 95% confidence intervals comparing treated to untreated subjects. In treated subjects, the overall OR for having a tumour (malignant or nonmalignant) was 1.7 (0.8-3.8). The ORs were 2.3 (0.4-12.8) for breast tumours, 0.8 (0.2-2.6) for gynaecological tumours, and 6.1 (1.04-infinity) for melanoma. When limiting to malignant tumours, the crude ORs were of similar magnitude. Conclusion: The OR for any melanoma was higher in treated than in untreated women, suggesting an increased risk of melanoma associated with high-dose oestrogen treatment during adolescence. Although the risk estimates were increased for overall tumours, breast tumours, malignant gynaecological tumours, and malignant melanoma, these associations were not statistically significant. Our results need to be verified in a larger cohort.
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| 40. |
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| 41. |
- Carlstedt-Duke, J
(författare)
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Glucocorticoid Receptor beta: View II
- 1999
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Ingår i: Trends in endocrinology and metabolism: TEM. - : Elsevier BV. - 1879-3061 .- 1043-2760. ; 10:8, s. 339-342
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Tidskriftsartikel (refereegranskat)
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| 42. |
- Duke, T, et al.
(författare)
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World Health Organization and knowledge translation in maternal, newborn, child and adolescent health and nutrition
- 2022
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Ingår i: Archives of disease in childhood. - : BMJ. - 1468-2044 .- 0003-9888. ; 107:7, s. 644-649
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Tidskriftsartikel (refereegranskat)abstract
- The World Health Organization (WHO) has a mandate to promote maternal and child health and welfare through support to governments in the form of technical assistance, standards, epidemiological and statistical services, promoting teaching and training of healthcare professionals and providing direct aid in emergencies. The Strategic and Technical Advisory Group of Experts (STAGE) for maternal, newborn, child and adolescent health and nutrition (MNCAHN) was established in 2020 to advise the Director-General of WHO on issues relating to MNCAHN. STAGE comprises individuals from multiple low-income and middle-income and high-income countries, has representatives from many professional disciplines and with diverse experience and interests.Progress in MNCAHN requires improvements in quality of services, equity of access and the evolution of services as technical guidance, community needs and epidemiology changes. Knowledge translation of WHO guidance and other guidelines is an important part of this. Countries need effective and responsive structures for adaptation and implementation of evidence-based interventions, strategies to improve guideline uptake, education and training and mechanisms to monitor quality and safety. This paper summarises STAGE’s recommendations on how to improve knowledge translation in MNCAHN. They include support for national and regional technical advisory groups and subnational committees that coordinate maternal and child health; support for national plans for MNCAHN and their implementation and monitoring; the production of a small number of consolidated MNCAHN guidelines to promote integrated and holistic care; education and quality improvement strategies to support guidelines uptake; monitoring of gaps in knowledge translation and operational research in MNCAHN.
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| 43. |
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| 44. |
- Graham, HR, et al.
(författare)
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Cost-effectiveness and sustainability of improved hospital oxygen systems in Nigeria
- 2022
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Improving hospital oxygen systems can improve quality of care and reduce mortality for children, but we lack data on cost-effectiveness or sustainability. This study evaluated medium-term sustainability and cost-effectiveness of the Nigeria Oxygen Implementation programme.MethodsProspective follow-up of a stepped-wedge trial involving 12 secondary-level hospitals. Cross-sectional facility assessment, clinical audit (January–March 2021), summary admission data (January 2018–December 2020), programme cost data. Intervention: pulse oximetry introduction followed by solar-powered oxygen system installation with clinical and technical training and support. Primary outcomes: (i) proportion of children screened with pulse oximetry; (ii) proportion of hypoxaemic (SpO2 <90%) children who received oxygen. Comparison across three time periods: preintervention (2014–2015), intervention (2016–2017) and follow-up (2018–2020) using mixed-effects logistic regression. Calculated cost-effectiveness of the intervention on child pneumonia mortality using programme costs, recorded deaths and estimated counterfactual deaths using effectiveness estimates from our effectiveness study. Reported cost-effectiveness over the original 2-year intervention period (2016–2017) and extrapolated over 5 years (2016–2020).ResultsPulse oximetry coverage for neonates and children remained high during follow-up (83% and 81%) compared with full oxygen system period (94% and 92%) and preintervention (3.9% and 2.9%). Oxygen coverage for hypoxaemic neonates/children was similarly high (94%/88%) compared with full oxygen system period (90%/82%). Functional oxygen sources were present in 11/12 (92%) paediatric areas and all (8/8) neonatal areas; three-quarters (15/20) of wards had a functional oximeter. Of 32 concentrators deployed, 23/32 (72%) passed technical testing and usage was high (median 10 797 hours). Estimated 5-year cost-effectiveness US$86 per patient treated, $2694–4382 per life saved and $82–125 per disability-adjusted life year-averted. We identified practical issues for hospitals and Ministries of Health wishing to adapt and scale up pulse oximetry and oxygen.ConclusionHospital-level improvements to oxygen and pulse oximetry systems in Nigerian hospitals have been sustained over the medium-term and are a highly cost-effective child pneumonia intervention.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Kunz, S, et al.
(författare)
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Identification of a novel glucocorticoid receptor mutation in budesonide-resistant human bronchial epithelial cells
- 2003
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Ingår i: Molecular endocrinology (Baltimore, Md.). - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 17:12, s. 2566-2582
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Tidskriftsartikel (refereegranskat)abstract
- We developed a molecular genetic model to investigate glucocorticoid receptor (GR) signaling in human bronchial epithelial cells in response to the therapeutic steroid budesonide. Based on a genetic selection scheme using the human Chago K1 cell line and integrated copies of a glucocorticoid-responsive herpes simplex virus thymidine kinase gene and a green fluorescent protein gene, we isolated five Chago K1 variants that grew in media containing budesonide and ganciclovir. Three spontaneous budesonide-resistant subclones were found to express low levels of GR, whereas two mutants isolated from ethylmethane sulfonate-treated cultures contained normal levels of GR protein. Analysis of the GR coding sequence in the budesonide-resistant subclone Ch-BdE5 identified a novel Val to Met mutation at amino acid position 575 (GRV575M) which caused an 80% decrease in transcriptional regulatory functions with only a minimal effect on ligand binding activity. Homology modeling of the GR structure in this region of the hormone binding domain and molecular dynamic simulations suggested that the GRV575M mutation would have a decreased affinity for the LXXLL motif of p160 coactivators. To test this prediction, we performed transactivation and glutathione-S-transferase pull-down assays using the p160 coactivator glucocorticoid interacting protein 1 (GRIP1)/transcriptional intermediary factor 2 and found that GRV575M transcriptional activity was not enhanced by GRIP1 in transfected cells nor was it able to bind GRIP1 in vitro. Identification of the novel GRV575M variant in human bronchial epithelial cells using a molecular genetic selection scheme suggests that functional assays performed in relevant cell types could identify subtle defects in GR signaling that contribute to reduced steroid sensitivities in vivo.
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| 50. |
- Lind, U, et al.
(författare)
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Functional probing of the human glucocorticoid receptor steroid-interacting surface by site-directed mutagenesis - Gln-642 plays an important role in steroid recognition and binding
- 2000
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 275:25, s. 19041-19049
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate which amino acids in the glucocorticoid receptor ligand-binding domain might be involved in determining steroid binding specificity by interaction with the D-ring of glucocorticoids, we have performed site-directed mutagenesis of the four amino acids Met-560, Met-639, Gln-642, and Thr-739 based on their proximity to the steroid in a model structure. Mutations of these residues affected steroid binding affinity, specificity, and/or steroid-dependent transactivation. The results indicate that these residues are located in close proximity to the ligand and appear to play a role in steroid recognition and/or transactivating sensitivity, possibly by changes in the steroid-dependent conformational change of this region, resulting in the formation of the AF-2 site. Mutation of Gln-642 resulted in a marked decrease in affinity for steroids containing a 17 alpha-OH group. This effect was alleviated by the presence of a 16 alpha-CH3 group to a varying degree. Thr-739 appears to form a hydrogen bond with the 21-OH group of the steroid, as well as possibly forming hydrophobic interactions with the steroid, Met-EGO and Met-639 appear to form hydrophobic interactions with the D-ring of the steroid, although the nature of these interactions cannot be characterized in more detail at this point.
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