| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Abramowski, A., et al.
(författare)
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Simultaneous multi-wavelength campaign on PKS 2005-489 in a high state
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 533, s. A110-
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Tidskriftsartikel (refereegranskat)abstract
- The high-frequency peaked BL Lac object PKS 2005-489 was the target of a multi-wavelength campaign with simultaneous observations in the TeV gamma-ray (H.E.S.S.), GeV gamma-ray (Fermi/LAT), X-ray (RXTE, Swift), UV (Swift) and optical (ATOM, Swift) bands. This campaign was carried out during a high flux state in the synchrotron regime. The flux in the optical and X-ray bands reached the level of the historical maxima. The hard GeV spectrum observed with Fermi/LAT connects well to the very high energy (VHE, E > 100 GeV) spectrum measured with H.E.S.S. with a peak energy between similar to 5 and 500 GeV. Compared to observations with contemporaneous coverage in the VHE and X-ray bands in 2004, the X-ray flux was similar to 50 times higher during the 2009 campaign while the TeV gamma-ray flux shows marginal variation over the years. The spectral energy distribution during this multi-wavelength campaign was fit by a one zone synchrotron self-Compton model with a well determined cutoff in X-rays. The parameters of a one zone SSC model are inconsistent with variability time scales. The variability behaviour over years with the large changes in synchrotron emission and small changes in the inverse Compton emission does not warrant an interpretation within a one-zone SSC model despite an apparently satisfying fit to the broadband data in 2009.
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| 3. |
- 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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| 4. |
- 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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| 5. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 6. |
- Abramowski, A., et al.
(författare)
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Search for TeV Gamma-ray Emission from GRB 100621A, an extremely bright GRB in X-rays, with HESS
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 565, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- The long gamma-ray burst (GRB) 100621A, at the time the brightest X-ray transient ever detected by Swift-XRT in the 0.3-10 keV range, has been observed with the H.E.S.S. imaging air Cherenkov telescope array, sensitive to gamma radiation in the very-high-energy (VHE, >100 GeV) regime. Due to its relatively small redshift of z similar to 0.5, the favourable position in the southern sky and the relatively short follow-up time (<700 s after the satellite trigger) of the H.E.S.S. observations, this GRB could be within the sensitivity reach of the HESS. instrument. The analysis of the HESS. data shows no indication of emission and yields an integral flux upper limit above similar to 380 GeV of 4.2 x 10(-12) cm(-2) s(-1) s (95% confidence level), assuming a simple Band function extension model. A comparison to a spectral-temporal model, normalised to the prompt flux at sub-MeV energies, constraints the existence of a temporally extended and strong additional hard power law, as has been observed in the other bright X-ray GRB 130427A. A comparison between the HESS. upper limit and the contemporaneous energy output in X-rays constrains the ratio between the X-ray and VHE gamma-ray fluxes to be greater than 0.4. This value is an important quantity for modelling the afterglow and can constrain leptonic emission scenarios, where leptons are responsible for the X-ray emission and might produce VHE gamma rays.
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| 7. |
- Abramowski, A., et al.
(författare)
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Discovery of the Hard Spectrum VHE γ-Ray Source HESS J1641–463
- 2014
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 794:1, s. Article ID: L1-
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Tidskriftsartikel (refereegranskat)abstract
- This Letter reports the discovery of a remarkably hard spectrum source, HESS J1641-463, by the High Energy Stereoscopic System (H.E.S.S.) in the very high energy (VHE) domain. HESS J1641-463 remained unnoticed by the usual analysis techniques due to confusion with the bright nearby source HESS J1640-465. It emerged at a significance level of 8.5 standard deviations after restricting the analysis to events with energies above 4 TeV. It shows a moderate flux level of phi(E > 1TeV) = (3.64 +/- 0.44(stat)+/- 0.73(sys)) x 10(-13) cm(-2) s(-1), corresponding to 1.8% of the Crab Nebula flux above the same energy, and a hard spectrum with a photon index of Gamma = 2.07 +/- 0.11(stat)+/- 0.20(sys). It is a point-like source, although an extension up to a Gaussian width of sigma = 3 arcmin cannot be discounted due to uncertainties in the H.E.S.S. point-spread function. The VHE gamma-ray flux of HESS J1641-463 is found to be constant over the observed period when checking time binnings from the year-by-year to the 28 minute exposure timescales. HESS J1641-463 is positionally coincident with the radio supernova remnant SNR G338.5+0.1. No X-ray candidate stands out as a clear association; however, Chandra and XMM-Newton data reveal some potential weak counterparts. Various VHE gamma-ray production scenarios are discussed. If the emission from HESS J1641-463 is produced by cosmic ray protons colliding with the ambient gas, then their spectrum must extend close to 1 PeV. This object may represent a source population contributing significantly to the galactic cosmic ray flux around the knee.
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| 8. |
- Abramowski, A., et al.
(författare)
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Flux upper limits for 47 AGN observed with HESS in 2004-2011
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 564, s. A9-
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Tidskriftsartikel (refereegranskat)abstract
- Context. About 40% of the observation time of the High Energy Stereoscopic System (H.E.S.S.) is dedicated to studying active galactic nuclei (AGN), with the aim of increasing the sample of known extragalactic very-high-energy (VHE, E > 100 GeV) sources and constraining the physical processes at play in potential emitters. Aims. H.E.S.S. observations of AGN, spanning a period from April 2004 to December 2011, are investigated to constrain their gamma-ray fluxes. Only the 47 sources without significant excess detected at the position of the targets are presented. Methods. Upper limits on VHE fluxes of the targets were computed and a search for variability was performed on the nightly time scale. Results. For 41 objects, the flux upper limits we derived are the most constraining reported to date. These constraints at VHE are compared with the flux level expected from extrapolations of Fermi-LAT measurements in the two-year catalog of AGN. The H.E.S.S. upper limits are at least a factor of two lower than the extrapolated Fermi-LAT fluxes for 11 objects Taking into account the attenuation by the extragalactic background light reduces the tension for all but two of them, suggesting intrinsic curvature in the high-energy spectra of these two AGN. Conclusions. Compilation efforts led by current VHE instruments are of critical importance for target-selection strategies before the advent of the Cherenkov Telescope Array (CTA).
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| 9. |
- Abramowski, A., et al.
(författare)
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HESS J1640-465-an exceptionally luminous TeV gamma-ray supernova remnant
- 2014
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 439:3, s. 2828-2836
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Tidskriftsartikel (refereegranskat)abstract
- The results of follow-up observations of the TeV gamma-ray source HESS J1640-465 from 2004 to 2011 with the High Energy Stereoscopic System (HESS) are reported in this work. The spectrum is well described by an exponential cut-off power law with photon index Gamma = 2.11 +/- 0.09(stat) +/- 0.10(sys), and a cut-off energy of E-2 = 6.0(-1.2)(+2.0) TeV. The TeV emission is significantly extended and overlaps with the northwestern part of the shell of the SNR G338.3-0.0. The new HESS results, a re-analysis of archival XMM-Newton data and multiwavelength observations suggest that a significant part of the gamma-ray emission from HESS J1640-465 originates in the supernova remnant shell. In a hadronic scenario, as suggested by the smooth connection of the GeV and TeV spectra, the product of total proton energy and mean target density could be as high as W(p)n(H) similar to 4 x 10(52)(d/10kpc)(2) erg cm(-3).
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| 10. |
- Abramowski, A., et al.
(författare)
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HESS J1818-154, a new composite supernova remnant discovered in TeV gamma rays and X-rays
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 562, s. 562-
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Tidskriftsartikel (refereegranskat)abstract
- Composite supernova remnants (SNRs) constitute a small subclass of the remnants of massive stellar explosions where non-thermal radiation is observed from both the expanding shell-like shock front and from a pulsar wind nebula (PWN) located inside of the SNR. These systems represent a unique evolutionary phase of SNRs where observations in the radio, X-ray, and gamma-ray regimes allow the study of the co-evolution of both these energetic phenomena. In this article, we report results from observations of the shell-type SNR G15.4+0.1 performed with the High Energy Stereoscopic System (H. E. S. S.) and XMM-Newton. A compact TeV gamma-ray source, HESS J1818-154, located in the center and contained within the shell of G15.4+0.1 is detected by H. E. S. S. and featurs a spectrum best represented by a power-law model with a spectral index of -2.3 +/- 0.3(stat) +/- 0.2(sys) and an integral flux of F(>0.42 TeV) = (0.9 +/- 0.3(stat) +/- 0.2(sys)) x 10(-12) cm(-2) s(-1). Furthermore, a recent observation with XMM-Newton reveals extended X-ray emission strongly peaked in the center of G15.4+0.1. The X-ray source shows indications of an energy-dependent morphology featuring a compact core at energies above 4 keV and more extended emission that fills the entire region within the SNR at lower energies. Together, the X-ray and VHE gamma-ray emission provide strong evidence of a PWN located inside the shell of G15.4+0.1 and this SNR can therefore be classified as a composite based on these observations. The radio, X-ray, and gamma-ray emission from the PWN is compatible with a one-zone leptonic model that requires a low average magnetic field inside the emission region. An unambiguous counterpart to the putative pulsar, which is thought to power the PWN, has been detected neither in radio nor in X-ray observations of G15.4+0.1.
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