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| 2. |
- 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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| 3. |
- Algaba, Juan-Carlos, et al.
(författare)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Forskningsöversikt (refereegranskat)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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| 4. |
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| 5. |
- Petroff, E., et al.
(författare)
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A polarized fast radio burst at low Galactic latitude
- 2017
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford Academic. - 0035-8711 .- 1365-2966. ; 469:4, s. 4465-4482
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Tidskriftsartikel (refereegranskat)abstract
- We report on the discovery of a new fast radio burst (FRB), FRB 150215, with the Parkes radio telescope on 2015 February 15. The burst was detected in real time with a dispersion measure (DM) of 1105.6 +/- 0.8 pc cm(-3), a pulse duration of 2.8(-0.5)(+1.2) ms, and a measured peak flux density assuming that the burst was at beam centre of 0.7(-0.1)(+0.2) Jy. The FRB originated at a Galactic longitude and latitude of 24.66 degrees, 5.28 degrees and 25 degrees away from the Galactic Center. The burst was found to be 43 +/- 5 per cent linearly polarized with a rotation measure (RM) in the range -9 < RM < 12 rad m(-2) (95 per cent confidence level), consistent with zero. The burst was followed up with 11 telescopes to search for radio, optical, X-ray, gamma-ray and neutrino emission. Neither transient nor variable emission was found to be associated with the burst and no repeat pulses have been observed in 17.25 h of observing. The sightline to the burst is close to the Galactic plane and the observed physical properties of FRB 150215 demonstrate the existence of sight lines of anomalously low RM for a given electron column density. The Galactic RM foreground may approach a null value due to magnetic field reversals along the line of sight, a decreased total electron column density from the Milky Way, or some combination of these effects. A lower Galactic DM contribution might explain why this burst was detectable whereas previous searches at low latitude have had lower detection rates than those out of the plane.
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| 6. |
- Shu, Xiang, et al.
(författare)
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Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
- 2019
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Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
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Tidskriftsartikel (refereegranskat)abstract
- Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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| 7. |
- Abdalla, H., et al.
(författare)
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Characterizing the γ-ray long-term variability of PKS2155 304 with HESS and Fermi-LAT
- 2017
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Ingår i: Astronomy and Astrophysics. - : The European Southern Observatory. - 0004-6361 .- 1432-0746. ; 598
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Tidskriftsartikel (refereegranskat)abstract
- Studying the temporal variability of BL Lac objects at the highest energies provides unique insights into the extreme physical processes occurring in relativistic jets and in the vicinity of super-massive black holes. To this end, the long-term variability of the BL Lac object PKS 2155-304 is analyzed in the high (HE, 100MeV < E < 300 GeV) and very high energy (VHE, E > 200 GeV) gamma-ray domain. Over the course of similar to 9 yr of H. E. S. S. observations the VHE light curve in the quiescent state is consistent with a log-normal behavior. The VHE variability in this state is well described by flicker noise (power-spectral-density index βVHE = 1 .10+ 0.10-0,13) on timescales larger than one day. An analysis of similar to 5.5 yr of HE Fermi-LAT data gives consistent results (βHE = 1 .20+ 0.21-0.23, on timescales larger than 10 days) compatible with the VHE findings. The HE and VHE power spectral densities show a scale invariance across the probed time ranges. A direct linear correlation between the VHE and HE fluxes could neither be excluded nor firmly established. These long-term-variability properties are discussed and compared to the red noise behavior (beta similar to 2) seen on shorter timescales during VHE-flaring states. The difference in power spectral noise behavior at VHE energies during quiescent and flaring states provides evidence that these states are influenced by different physical processes, while the compatibility of the HE and VHE long-term results is suggestive of a common physical link as it might be introduced by an underlying jet-disk connection.
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| 8. |
- Abdalla, H., et al.
(författare)
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Extended VHE gamma-ray emission towards SGR1806-20, LBV 1806-20, and stellar cluster Cl*1806-20
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
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Tidskriftsartikel (refereegranskat)abstract
- Using the High Energy Spectroscopic System (H.E.S.S.) telescopes we have discovered a steady and extended very high-energy (VHE) gamma-ray source towards the luminous blue variable candidate LBV 1806-20, massive stellar cluster Cl* 1806-20, and magnetar SGR 1806-20. The new VHE source, HESS J1808-204, was detected at a statistical significance of >6 sigma (post-trial) with a photon flux normalisation (2.9 +/- 0.4(stat) +/- 0.5(sys)) x 10(-13) ph cm(-2) s(-1) TeV-1 at 1 TeV and a power-law photon index of 2.3 +/- 0.2(stat) +/- 0.3(sys). The luminosity of this source (0.2 to 10 TeV; scaled to distance d = 8 : 7 kpc) is L-VHE similar to 1.6 x 10(34)(d = 8.7 kpc)(2) erg s(-1). The VHE gamma-ray emission is extended and is well fit by a single Gaussian with statistical standard deviation of 0.095 degrees +/- 0.015 degrees. This extension is similar to that of the synchrotron radio nebula G10.0-0.3, which is thought to be powered by LBV 1806-20. The VHE gamma-ray luminosity could be provided by the stellar wind luminosity of LBV 1806-20 by itself and/or the massive star members of Cl* 1806-20. Alternatively, magnetic dissipation (e.g. via reconnection) from SGR 1806-20 can potentially account for the VHE luminosity. The origin and hadronic and/or leptonic nature of the accelerated particles responsible for HESS J1808-204 is not yet clear. If associated with SGR 1806 20, the potentially young age of the magnetar (650 yr) can be used to infer the transport limits of these particles to match the VHE source size. This discovery provides new interest in the potential for high-energy particle acceleration from magnetars, massive stars, and/or stellar clusters.
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| 9. |
- Abdalla, H., et al.
(författare)
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First limits on the very-high energy gamma-ray afterglow emission of a fast radio burst HESS observations of FRB 150418
- 2017
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Ingår i: Astronomy and Astrophysics. - : The European Southern Observatory (ESO). - 0004-6361 .- 1432-0746. ; 597
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Following the detection of the fast radio burst FRB150418 by the SUPERB project at the Parkes radio telescope, we aim to search for very-high energy gamma-ray afterglow emission. Methods. Follow-up observations in the very-high energy gamma-ray domain were obtained with the H.E.S.S. imaging atmospheric Cherenkov telescope system within 14.5 h of the radio burst. Results. The obtained 1.4 h of gamma-ray observations are presented and discussed. At the 99% C.L. we obtained an integral upper limit on the gamma-ray flux of Phi(gamma)(E > 350 GeV) < 1.33 x 10(-8) m(-2) s(-1). Differential flux upper limits as function of the photon energy were derived and used to constrain the intrinsic high-energy afterglow emission of FRB 150418. Conclusions. No hints for high-energy afterglow emission of FRB 150418 were found. Taking absorption on the extragalactic background light into account and assuming a distance of z = 0 : 492 based on radio and optical counterpart studies and consistent with the FRB dispersion, we constrain the gamma-ray luminosity at 1 TeV to L < 5 : 1 x 10(47) erg/s at 99% C.L.
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| 10. |
- Abdalla, H., et al.
(författare)
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HESS Limits on Linelike Dark Matter Signatures in the 100 GeV to 2 TeV Energy Range Close to the Galactic Center
- 2016
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 117:15
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Tidskriftsartikel (refereegranskat)abstract
- A search for dark matter linelike signals iss performed in the vicinity of the Galactic Center by the H.E.S.S. experiment on observational data taken in 2014. An unbinned likelihood analysis iss developed to improve the sensitivity to linelike signals. The upgraded analysis along with newer data extend the energy coverage of the previous measurement down to 100 GeV. The 18 h of data collected with the H.E.S.S. array allow one to rule out at 95% C.L. the presence of a 130 GeV line (at l = -1.5 degrees, b = 0 degrees and for a dark matter profile centered at this location) previously reported in Fermi-LAT data. This new analysis overlaps significantly in energy with previous Fermi-LAT and H.E.S.S. results. No significant excess associated with dark matter annihilations was found in the energy range of 100 GeV to 2 TeV and upper limits on the gamma-ray flux and the velocity weighted annihilation cross section are derived adopting an Einasto dark matter halo profile. Expected limits for present and future large statistics H.E.S.S. observations are also given.
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