| 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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DISCOVERY OF THE HARD SPECTRUM VHE gamma-RAY SOURCE HESS J1641-463
- 2014
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 794:1, s. 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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| 3. |
- 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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| 4. |
- Abramowski, A., et al.
(författare)
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Long-term monitoring of PKS2155-304 with ATOM and HESS:investigation of optical/gamma-ray correlations in different spectral states
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 571
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we report on the analysis of all the available optical and very high-energy gamma-ray (> 200 GeV) data for the BL Lac object PKS 2155-304, collected simultaneously with the ATOM and H.E.S.S. telescopes from 2007 until 2009. This study also includes X-ray (RXTE, Swift) and high-energy gamma-ray (Fermi-LAT) data. During the period analysed, the source was transitioning from its flaring to quiescent optical states, and was characterized by only moderate flux changes at different wavelengths on the timescales of days and months. A flattening of the optical continuum with an increasing optical flux can be noted in the collected dataset, but only occasionally and only at higher flux levels. We did not find any universal relation between the very high-energy gamma-ray and optical flux changes on the timescales from days and weeks up to several years. On the other hand, we noted that at higher flux levels the source can follow two distinct tracks in the optical flux-colour diagrams, which seem to be related to distinct gamma-ray states of the blazar. The obtained results therefore indicate a complex scaling between the optical and gamma-ray emission of PKS 2155 304, with different correlation patterns holding at different epochs, and a gamma-ray flux depending on the combination of an optical flux and colour rather than a flux alone.
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| 5. |
- Abramowski, A., et al.
(författare)
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Search for dark matter annihilation signatures in HESS observations of dwarf spheroidal galaxies
- 2014
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 90:11, s. 112012-
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Tidskriftsartikel (refereegranskat)abstract
- Dwarf spheroidal galaxies of the Local Group are close satellites of the Milky Way characterized by a large mass-to-light ratio and are not expected to be the site of nonthermal high-energy gamma-ray emission or intense star formation. Therefore they are among the most promising candidates for indirect dark matter searches. During the last years the High Energy Stereoscopic System (H.E.S.S.) of imaging atmospheric Cherenkov telescopes observed five of these dwarf galaxies for more than 140 hours in total, searching for TeV gamma-ray emission from annihilation of dark matter particles. The new results of the deep exposure of the Sagittarius dwarf spheroidal galaxy, the first observations of the Coma Berenices and Fornax dwarves and the reanalysis of two more dwarf spheroidal galaxies already published by the H.E.S.S. Collaboration, Carina and Sculptor, are presented. In the absence of a significant signal new constraints on the annihilation cross section applicable to weakly interacting massive particles (WIMPs) are derived by combining the observations of the five dwarf galaxies. The combined exclusion limit depends on the WIMP mass and the best constraint is reached at 1-2 TeV masses with a cross-section upper bound of similar to 3.9 x 10(-24) cm(3) s(-1) at a 95% confidence level.
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| 6. |
- Abramowski, A., et al.
(författare)
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Diffuse Galactic gamma-ray emission with HESS
- 2014
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 90:12, s. Article ID: 122007-
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse gamma-ray emission is the most prominent observable signature of celestial cosmic-ray interactions at high energies. While already being investigated at GeVenergies over several decades, assessments of diffuse gamma-ray emission at TeVenergies remain sparse. After completion of the systematic survey of the inner Galaxy, the H.E.S.S. experiment is in a prime position to observe large-scale diffuse emission at TeVenergies. Data of the H.E.S.S. Galactic Plane Survey are investigated in regions off known gamma-ray sources. Corresponding gamma-ray flux measurements were made over an extensive grid of celestial locations. Longitudinal and latitudinal profiles of the observed gamma-ray fluxes show characteristic excess emission not attributable to known gamma-ray sources. For the first time large-scale gamma-ray emission along the Galactic plane using imaging atmospheric Cherenkov telescopes has been observed. While the background subtraction technique limits the ability to recover modest variation on the scale of the H.E.S.S. field of view or larger, which is characteristic of the inverse Compton scatter-induced Galactic diffuse emission, contributions of neutral pion decay as well as emission from unresolved gamma-ray sources can be recovered in the observed signal to a large fraction. Calculations show that the minimum gamma-ray emission from pi(0) decay represents a significant contribution to the total signal. This detection is interpreted as a mix of diffuse Galactic gamma-ray emission and unresolved sources.
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| 7. |
- Blunden, Jessica, et al.
(författare)
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State of the Climate in 2012
- 2013
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
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Tidskriftsartikel (refereegranskat)abstract
- For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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| 8. |
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| 9. |
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| 10. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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