| 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. |
- Ackermann, M., et al.
(författare)
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Detection of the Characteristic Pion-Decay Signature in Supernova Remnants
- 2013
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 339:6121, s. 807-811
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Tidskriftsartikel (refereegranskat)abstract
- Cosmic rays are particles (mostly protons) accelerated to relativistic speeds. Despite wide agreement that supernova remnants (SNRs) are the sources of galactic cosmic rays, unequivocal evidence for the acceleration of protons in these objects is still lacking. When accelerated protons encounter interstellar material, they produce neutral pions, which in turn decay into gamma rays. This offers a compelling way to detect the acceleration sites of protons. The identification of pion-decay gamma rays has been difficult because high-energy electrons also produce gamma rays via bremsstrahlung and inverse Compton scattering. We detected the characteristic pion-decay feature in the gamma-ray spectra of two SNRs, IC 443 and W44, with the Fermi Large Area Telescope. This detection provides direct evidence that cosmic-ray protons are accelerated in SNRs.
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| 3. |
- Ackermann, M., et al.
(författare)
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Search for gamma-ray spectral lines with the Fermi Large Area Telescope and dark matter implications
- 2013
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:8, s. 082002-
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Tidskriftsartikel (refereegranskat)abstract
- Weakly interacting massive particles (WIMPs) are a theoretical class of particles that are excellent dark matter candidates. WIMP annihilation or decay may produce essentially monochromatic gamma rays detectable by the Fermi Large Area Telescope (LAT) against the astrophysical gamma-ray emission of the Galaxy. We have searched for spectral lines in the energy range 5-300 GeV using 3.7 years of data, reprocessed with updated instrument calibrations and an improved energy dispersion model compared to the previous Fermi-LAT Collaboration line searches. We searched in five regions selected to optimize sensitivity to different theoretically motivated dark matter density distributions. We did not find any globally significant lines in our a priori search regions and present 95% confidence limits for annihilation cross sections of self-conjugate WIMPs and decay lifetimes. Our most significant fit occurred at 133 GeV in our smallest search region and had a local significance of 3.3 standard deviations, which translates to a global significance of 1.5 standard deviations. We discuss potential systematic effects in this search, and examine the feature at 133 GeV in detail. We find that the use both of reprocessed data and of additional
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| 4. |
- Pletsch, H. J., et al.
(författare)
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Binary Millisecond Pulsar Discovery via Gamma-Ray Pulsations
- 2012
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 338:6112, s. 1314-1317
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Tidskriftsartikel (refereegranskat)abstract
- Millisecond pulsars, old neutron stars spun up by accreting matter from a companion star, can reach high rotation rates of hundreds of revolutions per second. Until now, all such "recycled" rotation-powered pulsars have been detected by their spin-modulated radio emission. In a computing-intensive blind search of gamma-ray data from the Fermi Large Area Telescope (with partial constraints from optical data), we detected a 2.5-millisecond pulsar, PSR J1311-3430. This unambiguously explains a formerly unidentified gamma-ray source that had been a decade-long enigma, confirming previous conjectures. The pulsar is in a circular orbit with an orbital period of only 93 minutes, the shortest of any spin-powered pulsar binary ever found.
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| 5. |
- Ackermann, M., et al.
(författare)
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Dark matter constraints from observations of 25 Milky Way satellite galaxies with the Fermi Large Area Telescope
- 2014
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:4
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Tidskriftsartikel (refereegranskat)abstract
- The dwarf spheroidal satellite galaxies of the Milky Way are some of the most dark-matter-dominated objects known. Due to their proximity, high dark matter content, and lack of astrophysical backgrounds, dwarf spheroidal galaxies are widely considered to be among the most promising targets for the indirect detection of dark matter via gamma rays. Here we report on.-ray observations of 25 Milky Way dwarf spheroidal satellite galaxies based on 4 years of Fermi Large Area Telescope (LAT) data. None of the dwarf galaxies are significantly detected in. rays, and we present.-ray flux upper limits between 500 MeV and 500 GeV. We determine the dark matter content of 18 dwarf spheroidal galaxies from stellar kinematic data and combine LAT observations of 15 dwarf galaxies to constrain the dark matter annihilation cross section. We set some of the tightest constraints to date on the annihilation of dark matter particles with masses between 2 GeV and 10 TeV into prototypical standard model channels. We find these results to be robust against systematic uncertainties in the LAT instrument performance, diffuse.-ray background modeling, and assumed dark matter density profile.
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| 6. |
- Ackermann, M., et al.
(författare)
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SEARCH FOR COSMIC-RAY-INDUCED GAMMA-RAY EMISSION IN GALAXY CLUSTERS
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 787:1
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Tidskriftsartikel (refereegranskat)abstract
- Current theories predict relativistic hadronic particle populations in clusters of galaxies in addition to the already observed relativistic leptons. In these scenarios hadronic interactions give rise to neutral pions which decay into gamma rays that are potentially observable with the Large Area Telescope (LAT) on board the Fermi space telescope. We present a joint likelihood analysis searching for spatially extended gamma-ray emission at the locations of 50 galaxy clusters in four years of Fermi-LAT data under the assumption of the universal cosmic-ray (CR) model proposed by Pinzke & Pfrommer. We find an excess at a significance of 2.7 sigma, which upon closer inspection, however, is correlated to individual excess emission toward three galaxy clusters: A400, A1367, and A3112. We discuss these cases in detail and conservatively attribute the emission to unmodeled background systems (for example, radio galaxies within the clusters). Through the combined analysis of 50 clusters, we exclude hadronic injection efficiencies in simple hadronic models above 21% and establish limits on the CR to thermal pressure ratio within the virial radius, R-200, to be below 1.25%-1.4% depending on the morphological classification. In addition, we derive new limits on the gamma-ray flux from individual clusters in our sample.
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