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Sökning: WFRF:(La Spada Albert R)

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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)
  • FERMI-LAT OBSERVATIONS OF THE LIGO EVENT GW150914
  • 2016
  • Ingår i: Astrophysical Journal Letters. - : Institute of Physics Publishing (IOPP). - 2041-8205 .- 2041-8213. ; 823:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The Fermi Large Area Telescope (LAT) has an instantaneous field of view (FoV) covering similar to 1/5 of the sky and it completes a survey of the entire sky in high-energy gamma-rays every 3 hr. It enables searches for transient phenomena over timescales from milliseconds to years. Among these phenomena could be electromagnetic counterparts to gravitational wave (GW) sources. In this paper, we present a detailed study of the LAT observations relevant to Laser Interferometer Gravitational-wave Observatory (LIGO) event GW150914, which is the first direct detection of gravitational waves and has been interpreted as being due to the coalescence of two stellar-mass black holes. The localization region for GW150914 was outside the LAT FoV at the time of the GW signal. However, as part of routine survey observations, the LAT observed the entire LIGO localization region within similar to 70 minutes of the trigger and thus enabled a comprehensive search for a.-ray counterpart to GW150914. The study of the LAT data presented here did not find any potential counterparts to GW150914, but it did provide limits on the presence of a transient counterpart above 100 MeV on timescales of hours to days over the entire GW150914 localization region.
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5.
  • 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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6.
  • Ackermann, M., et al. (författare)
  • The Fermi Galactic Center GeV Excess and Implications for Dark Matter
  • 2017
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing. - 0004-637X .- 1538-4357. ; 840:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The region around the Galactic Center (GC) is now well established to be brighter at energies of a few GeV than what is expected from conventional models of diffuse gamma-ray emission and catalogs of known gamma-ray sources. We study the GeV excess using 6.5 yr of data from the Fermi Large Area Telescope. We characterize the uncertainty of the GC excess spectrum and morphology due to uncertainties in cosmic-ray source distributions and propagation, uncertainties in the distribution of interstellar gas in the Milky Way, and uncertainties due to a potential contribution from the Fermi bubbles. We also evaluate uncertainties in the excess properties due to resolved point sources of gamma rays. The GC is of particular interest, as it would be expected to have the brightest signal from annihilation of weakly interacting massive dark matter (DM) particles. However, control regions along the Galactic plane, where a DM signal is not expected, show excesses of similar amplitude relative to the local background. Based on the magnitude of the systematic uncertainties, we conservatively report upper limits for the annihilation cross-section as a function of particle mass and annihilation channel.
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7.
  • Abdollahi, S., et al. (författare)
  • The Second Catalog of Flaring Gamma-Ray Sources from the Fermi All-sky Variability Analysis
  • 2017
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 846:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the second catalog of flaring gamma-ray sources (2FAV) detected with the Fermi All-sky Variability Analysis (FAVA), a tool that blindly searches for transients over the entire sky observed by the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. With respect to the first FAVA catalog, this catalog benefits from a larger data set, the latest LAT data release (Pass 8), as well as from an improved analysis that includes likelihood techniques for a more precise localization of the transients. Applying this analysis to the first 7.4 years of Fermi observations, and in two separate energy bands 0.1-0.8 GeV and 0.8-300 GeV, a total of 4547 flares were detected with significance greater than 6s (before trials), on the timescale of one week. Through spatial clustering of these flares, 518 variable gamma-ray sources were identified. Based on positional coincidence, likely counterparts have been found for 441 sources, mostly among the blazar class of active galactic nuclei. For 77 2FAV sources, no likely gamma-ray counterpart has been found. For each source in the catalog, we provide the time, location, and spectrum of each flaring episode. Studying the spectra of the flares, we observe a harder-when-brighter behavior for flares associated with blazars, with the exception of BL Lac flares detected in the low-energy band. The photon indexes of the flares are never significantly smaller than 1.5. For a leptonic model, and under the assumption of isotropy, this limit suggests that the spectrum of freshly accelerated electrons is never harder than p similar to 2.
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8.
  • Ackermann, M., et al. (författare)
  • Observations of M31 and M33 with the Fermi Large Area Telescope : A Galactic Center Excess in Andromeda?
  • 2017
  • Ingår i: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 836:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Fermi Large Area Telescope (LAT) has opened the way for comparative studies of cosmic rays (CRs) and high-energy objects in the Milky Way (MW) and in other, external, star-forming galaxies. Using 2 yr of observations with the Fermi LAT, Local Group galaxy M31 was detected as a marginally extended gamma-ray source, while only an upper limit has been derived for the other nearby galaxy M33. We revisited the gamma-ray emission in the direction of M31 and M33 using more than 7 yr of LAT Pass 8 data in the energy range 0.1-100 GeV, presenting detailed morphological and spectral analyses. M33 remains undetected, and we computed an upper limit of 2.0 x 10(-12) erg cm(-2) s(-1) on the 0.1-100 GeV energy flux (95% confidence level). This revised upper limit remains consistent with the observed correlation between gamma-ray luminosity and star formation rate tracers and implies an average CR density in M33 that is at most half of that of the MW. M31 is detected with a significance of nearly 10 sigma. Its spectrum is consistent with a power law with photon index Gamma = 2.4 +/- 0.1(stat) (vertical bar) (syst) and a 0.1-100 GeV energy flux of (5.6 +/- 0.6(stat vertical bar syst)) x 10(-12) erg cm(-1) s(-1). M31 is detected to be extended with a 4 sigma significance. The spatial distribution of the emission is consistent with a uniform-brightness disk with a radius of 0 degrees.4 and no offset from the center of the galaxy, but nonuniform intensity distributions cannot be excluded. The flux from M31 appears confined to the inner regions of the galaxy and does not fill the disk of the galaxy or extend far from it. The gamma-ray signal is not correlated with regions rich in gas or star formation activity, which suggests that the emission is not interstellar in origin, unless the energetic particles radiating in gamma rays do not originate in recent star formation. Alternative and nonexclusive interpretations are that the emission results from a population of millisecond pulsars dispersed in the bulge and disk of M31 by disrupted globular clusters or from the decay or annihilation of dark matter particles, similar to what has been proposed to account for the so-called Galactic center excess found in Fermi-LAT observations of the MW.
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