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Sökning: WFRF:(Mayer Miguel A)

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1.
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2.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • 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.
  • Acero, F., et al. (författare)
  • FERMI LARGE AREA TELESCOPE THIRD SOURCE CATALOG
  • 2015
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 218:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the third Fermi Large Area Telescope (LAT) source catalog (3FGL) of sources in the 100 MeV-300 GeV range. Based on the first 4 yr of science data from the Fermi Gamma-ray Space Telescope mission, it is the deepest yet in this energy range. Relative to the Second Fermi LAT catalog, the 3FGL catalog incorporates twice as much data, as well as a number of analysis improvements, including improved calibrations at the event reconstruction level, an updated model for Galactic diffuse.-ray emission, a refined procedure for source detection, and improved methods for associating LAT sources with potential counterparts at other wavelengths. The 3FGL catalog includes 3033 sources above 4 sigma significance, with source location regions, spectral properties, and monthly light curves for each. Of these, 78 are flagged as potentially being due to imperfections in the model for Galactic diffuse emission. Twenty-five sources are modeled explicitly as spatially extended, and overall 238 sources are considered as identified based on angular extent or correlated variability (periodic or otherwise) observed at other wavelengths. For 1010 sources we have not found plausible counterparts at other wavelengths. More than 1100 of the identified or associated sources are active galaxies of the blazar class; several other classes of non-blazar active galaxies are also represented in the 3FGL. Pulsars represent the largest Galactic source class. From source counts of Galactic sources we estimate that the contribution of unresolved sources to the Galactic diffuse emission is similar to 3% at 1 GeV.
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4.
  • Ackermann, M., et al. (författare)
  • 2FHL : THE SECOND CATALOG OF HARD FERMI-LAT SOURCES
  • 2016
  • Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 222:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a catalog of sources detected above 50 GeV by the Fermi-Large Area Telescope (LAT) in 80 months of data. The newly delivered Pass. 8 event-level analysis allows the detection and characterization of sources in the 50 GeV-2 TeV energy range. In this energy band, Fermi-LAT. has detected 360 sources, which constitute the second catalog of hard Fermi-LAT. sources (2FHL). The improved angular resolution enables the precise localization of point sources (similar to 1.' 7 radius at 68% C.L.) and the detection and characterization of spatially extended sources. We find that 86% of the sources can be associated with counterparts at other wavelengths, of which the majority (75%) are active galactic nuclei and the rest (11%) are Galactic sources. Only 25% of the 2FHL sources have been previously detected by Cherenkov telescopes, implying that the 2FHL provides a reservoir of candidates to be followed up at very high energies. This work closes the energy gap between the observations performed at GeV energies by Fermi-LAT. on orbit and the observations performed at higher energies by Cherenkov telescopes from the ground.
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5.
  • Ajello, M., et al. (författare)
  • FERMI-LAT OBSERVATIONS OF HIGH-ENERGY gamma-RAY EMISSION TOWARD THE GALACTIC CENTER
  • 2016
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 819:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The Fermi Large Area Telescope (LAT) has provided the most detailed view to date of the emission toward the Galactic center (GC) in high-energy gamma-rays. This paper describes the analysis of data taken during the first 62 months of the mission in the energy range 1-100 GeV from a 15 degrees x 15 degrees region about the direction of the GC. Specialized interstellar emission models (IEMs) are constructed to enable the separation of the.-ray emissions produced by cosmic ray particles interacting with the interstellar gas and radiation fields in the Milky Way into that from the inner similar to 1 kpc surrounding the GC, and that from the rest of the Galaxy. A catalog of point sources for the 15 degrees x 15 degrees region is self-consistently constructed using these IEMs: the First Fermi-LAT Inner Galaxy Point Source Catalog (1FIG). The spatial locations, fluxes, and spectral properties of the 1FIG sources are presented, and compared with gamma-ray point sources over the same region taken from existing catalogs. After subtracting the interstellar emission and point-source contributions a residual is found. If templates that peak toward the GC are used to model the positive residual the agreement with the data improves, but none of the additional templates tried account for all of its spatial structure. The spectrum of the positive residual modeled with these templates has a strong dependence on the choice of IEM.
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6.
  • Ackermann, M., et al. (författare)
  • Updated search for spectral lines from Galactic dark matter interactions with pass 8 data from the Fermi Large Area Telescope
  • 2015
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 91:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Dark matter in the Milky Way may annihilate directly into. rays, producing a monoenergetic spectral line. Therefore, detecting such a signature would be strong evidence for dark matter annihilation or decay. We search for spectral lines in the Fermi Large Area Telescope observations of the Milky Way halo in the energy range 200 MeV-500 GeV using analysis methods from our most recent line searches. The main improvements relative to previous works are our use of 5.8 years of data reprocessed with the Pass 8 event-level analysis and the additional data resulting from the modified observing strategy designed to increase exposure of the Galactic center region. We search in five sky regions selected to optimize sensitivity to different theoretically motivated dark matter scenarios and find no significant detections. In addition to presenting the results from our search for lines, we also investigate the previously reported tentative detection of a line at 133 GeV using the new Pass 8 data.
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7.
  • Acero, F., et al. (författare)
  • DEVELOPMENT OF THE MODEL OF GALACTIC INTERSTELLAR EMISSION FOR STANDARD POINT-SOURCE ANALYSIS OF FERMI LARGE AREA TELESCOPE DATA
  • 2016
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 223:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Most of the celestial. rays detected by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope originate from the interstellar medium when energetic cosmic rays interact with interstellar nucleons and photons. Conventional point-source and extended-source studies rely on the modeling of this diffuse emission for accurate characterization. Here, we describe the development of the Galactic Interstellar Emission Model (GIEM), which is the standard adopted by the LAT Collaboration and is publicly available. This model is based on a linear combination of maps for interstellar gas column density in Galactocentric annuli and for the inverse-Compton emission produced in the Galaxy. In the GIEM, we also include large-scale structures like Loop. I and the Fermi bubbles. The measured gas emissivity spectra confirm that the cosmic-ray proton density decreases with Galactocentric distance beyond 5 kpc from the Galactic Center. The measurements also suggest a softening of the proton spectrum with Galactocentric distance. We observe that the Fermi bubbles have boundaries with a shape similar to a catenary at latitudes below 20 degrees and we observe an enhanced emission toward their base extending in the north and south Galactic directions and located within similar to 4 degrees of the Galactic Center.
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8.
  • Ackermann, M., et al. (författare)
  • Resolving the Extragalactic gamma-Ray Background above 50 GeV with the Fermi Large Area Telescope
  • 2016
  • Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 116:15
  • Tidskriftsartikel (refereegranskat)abstract
    • The Fermi Large Area Telescope (LAT) Collaboration has recently released a catalog of 360 sources detected above 50 GeV (2FHL). This catalog was obtained using 80 months of data re-processed with Pass 8, the newest event-level analysis, which significantly improves the acceptance and angular resolution of the instrument. Most of the 2FHL sources at high Galactic latitude are blazars. Using detailed Monte Carlo simulations, we measure, for the first time, the source count distribution, dN= dS, of extragalactic.-ray sources at E > 50 GeV and find that it is compatible with a Euclidean distribution down to the lowest measured source flux in the 2FHL (8 x 10(-12) ph cm(-2) s(-1)). We employ a one-point photon fluctuation analysis to constrain the behavior of dN= dS below the source detection threshold. Overall, the source count distribution is constrained over three decades in flux and found compatible with a broken power law with a break flux, Sb, in the range [8 x 10-12; 1.5 x 10-11] ph cm(-2) s(-1) and power-law indices below and above the break of a 2. [1.60; 1.75] and a 1 +/- 2.49 +/- 0.12, respectively. Integration of dN= dS shows that point sources account for at least 86_16 -14 % of the total extragalactic gamma-ray background. The simple form of the derived source count distribution is consistent with a single population (i. e., blazars) dominating the source counts to the minimum flux explored by this analysis. We estimate the density of sources detectable in blind surveys that will be performed in the coming years by the Cherenkov Telescope Array.
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9.
  • Ackermann, M., et al. (författare)
  • Deep view of the Large Magellanic Cloud with six years of Fermi-LAT observations
  • 2016
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 586
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The nearby Large Magellanic Cloud (LMC) provides a rare opportunity of a spatially resolved view of an external star-forming galaxy in gamma-rays. The LMC was detected at 0.1-100 GeV as an extended source with CGRO/EGRET and using early observations with the Fermi-LAT. The emission was found to correlate with massive star-forming regions and to be particularly bright towards 30 Doradus. Aims. Studies of the origin and transport of cosmic rays (CRs) in the Milky Way are frequently hampered by line-of-sight confusion and poor distance determination. The LMC offers a complementary way to address these questions by revealing whether and how the gamma-ray emission is connected to specific objects, populations of objects, and structures in the galaxy. Methods. We revisited the gamma-ray emission from the LMC using about 73 months of Fermi-LAT P7REP data in the 0.2-100 GeV range. We developed a complete spatial and spectral model of the LMC emission, for which we tested several approaches: a simple geometrical description, template-fitting, and a physically driven model for CR-induced interstellar emission. Results. In addition to identifying PSR J0540-6919 through its pulsations, we find two hard sources positionally coincident with plerion N 157B and supernova remnant N 132D, which were also detected at TeV energies with H.E.S.S. We detect an additional soft source that is currently unidentified. Extended emission dominates the total flux from the LMC. It consists of an extended component of about the size of the galaxy and additional emission from three to four regions with degree-scale sizes. If it is interpreted as CRs interacting with interstellar gas, the large-scale emission implies a large-scale population of similar to 1-100 GeV CRs with a density of similar to 30% of the local Galactic value. On top of that, the three to four small-scale emission regions would correspond to enhancements of the CR density by factors 2 to 6 or higher, possibly more energetic and younger populations of CRs compared to the large-scale population. An alternative explanation is that this is emission from an unresolved population of at least two dozen objects, such as pulsars and their nebulae or supernova remnants. This small-scale extended emission has a spatial distribution that does not clearly correlate with known components of the LMC, except for a possible relation to cavities and supergiant shells. Conclusions. The Fermi-LAT GeV observations allowed us to detect individual sources in the LMC. Three of the newly discovered sources are associated with rare and extreme objects. The 30 Doradus region is prominent in GeV gamma-rays because PSR J0540-6919 and N 157B are strong emitters. The extended emission from the galaxy has an unexpected spatial distribution, and observations at higher energies and in radio may help to clarify its origin.
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10.
  • Ackermann, M., et al. (författare)
  • Search for extended gamma-ray emission from the Virgo Galaxy Cluster with Fermi-LAT
  • 2015
  • Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 812:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Galaxy clusters are one of the prime sites to search for dark matter (DM) annihilation signals. Depending on the substructure of the DM halo of a galaxy cluster and the cross sections for DM annihilation channels, these signals might be detectable by the latest generation of gamma-ray telescopes. Here we use three years of Fermi-Large Area Telescope data, which are the most suitable for searching for very extended emission in the vicinity of the nearby Virgo galaxy cluster. Our analysis reveals statistically significant extended emission which can be well characterized by a uniformly emitting disk profile with a radius of 3 degrees that moreover is offset from the cluster center. We demonstrate that the significance of this extended emission strongly depends on the adopted interstellar emission model (IEM) and is most likely an artifact of our incomplete description of the IEM in this region. We also search for and find new point source candidates in the region. We then derive conservative upper limits on the velocity-averaged DM pair annihilation cross section from Virgo. We take into account the potential gamma-ray flux enhancement due to DM sub-halos and its complex morphology as a merging cluster. For DM annihilating into b (b) over bar, assuming a conservative sub-halo model setup, we find limits that are between 1 and 1.5 orders of magnitude above the expectation from the thermal cross section for m(DM) <= 100 GeV. In a more optimistic scenario, we exclude similar to 3 x 10(-26)cm(3)s(-1) for m(DM)less than or similar to 40 GeV for the same channel. Finally, we derive upper limits on the gamma-ray-flux produced by hadronic cosmic-ray interactions in the inter cluster medium. We find that the volume-averaged cosmic-ray-to-thermal pressure ratio is less than similar to 6%.
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