| 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. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 3. |
- Abdo, A. A., et al.
(författare)
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FERMI LARGE AREA TELESCOPE FIRST SOURCE CATALOG
- 2010
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 188:2, s. 405-436
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Tidskriftsartikel (refereegranskat)abstract
- We present a catalog of high-energy gamma-ray sources detected by the Large Area Telescope (LAT), the primary science instrument on the Fermi Gamma-ray Space Telescope (Fermi), during the first 11 months of the science phase of the mission, which began on 2008 August 4. The First Fermi-LAT catalog (1FGL) contains 1451 sources detected and characterized in the 100 MeV to 100 GeV range. Source detection was based on the average flux over the 11 month period, and the threshold likelihood Test Statistic is 25, corresponding to a significance of just over 4 sigma. The 1FGL catalog includes source location regions, defined in terms of elliptical fits to the 95% confidence regions and power-law spectral fits as well as flux measurements in five energy bands for each source. In addition, monthly light curves are provided. Using a protocol defined before launch we have tested for several populations of gamma-ray sources among the sources in the catalog. For individual LAT-detected sources we provide firm identifications or plausible associations with sources in other astronomical catalogs. Identifications are based on correlated variability with counterparts at other wavelengths, or on spin or orbital periodicity. For the catalogs and association criteria that we have selected, 630 of the sources are unassociated. Care was taken to characterize the sensitivity of the results to the model of interstellar diffuse gamma-ray emission used to model the bright foreground, with the result that 161 sources at low Galactic latitudes and toward bright local interstellar clouds are flagged as having properties that are strongly dependent on the model or as potentially being due to incorrectly modeled structure in the Galactic diffuse emission.
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| 4. |
- Abdo, A. A., et al.
(författare)
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Fermi-large area telescope observations of the exceptional gamma-ray outbursts of 3C 273 in 2009 September
- 2010
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Ingår i: ASTROPHYSICAL JOURNAL LETTERS. - 2041-8205. ; 714:1, s. L73-L78
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Tidskriftsartikel (refereegranskat)abstract
- We present the light curves and spectral data of two exceptionally luminous gamma-ray outbursts observed by the Large Area Telescope experiment on board the Fermi Gamma-ray Space Telescope from 3C 273 in 2009 September. During these flares, having a duration of a few days, the source reached its highest gamma-ray flux ever measured. This allowed us to study, in some details, their spectral and temporal structures. The rise and the decay are asymmetric on timescales of 6 hr, and the spectral index was significantly harder during the flares than during the preceding 11 months. We also found that short, very intense flares put out the same time-integrated energy as long, less intense flares like that observed in 2009 August.
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| 5. |
- Abdo, A. A., et al.
(författare)
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Fermi Observations of γ-Ray Emission from the Moon
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 758:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on the detection of high-energy gamma-ray emission from the Moon during the first 24 months of observations by the Fermi Large Area Telescope (LAT). This emission comes from particle cascades produced by cosmic-ray (CR) nuclei and electrons interacting with the lunar surface. The differential spectrum of the Moon is soft and can be described as a log-parabolic function with an effective cutoff at 2-3 GeV, while the average integral flux measured with the LAT from the beginning of observations in 2008 August to the end of 2010 August is F(> 100 MeV) = (1.04 +/- 0.01 [statistical error] +/- 0.1 [systematic error]) x 10(-6) cm(-2) s(-1). This flux is about a factor 2-3 higher than that observed between 1991 and 1994 by the EGRET experiment on boardthe Compton Gamma Ray Observatory, F(> 100 MeV) approximate to 5 x 10(-7) cm-2 s-1, when solar activity was relatively high. The higher gamma-ray flux measured by Fermi is consistent with the deep solar minimum conditions during the first 24 months of the mission, which reduced effects of heliospheric modulation, and thus increased the heliospheric flux of Galactic CRs. A detailed comparison of the light curve with McMurdo Neutron Monitor rates suggests a correlation of the trends. The Moon and the Sun are so far the only known bright emitters of gamma-rays with fast celestial motion. Their paths across thesky are projected onto the Galactic center and high Galactic latitudes as well as onto other areas crowded with high-energy gamma-ray sources. Analysis ofthe lunar and solar emission may thus be important for studies of weak and transient sources near the ecliptic.
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| 6. |
- Abdo, A. A., et al.
(författare)
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Gamma-ray emission concurrent with the nova in the symbiotic binary V407 cygni
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 329:5993, s. 817-821
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Tidskriftsartikel (refereegranskat)abstract
- Novae are thermonuclear explosions on a white dwarf surface fueled by mass accreted from a companion star. Current physical models posit that shocked expanding gas from the nova shell can produce x-ray emission, but emission at higher energies has not been widely expected. Here, we report the Fermi Large Area Telescope detection of variable γ-ray emission (0.1 to 10 billion electron volts) from the recently detected optical nova of the symbiotic star V407 Cygni. We propose that the material of the nova shell interacts with the dense ambient medium of the red giant primary and that particles can be accelerated effectively to produce π0 decay γ-rays from proton-proton interactions. Emission involving inverse Compton scattering of the red giant radiation is also considered and is not ruled out.
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| 7. |
- Abdo, A. A., et al.
(författare)
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The first catalog of active galactic nuclei detected by the Fermi large area telescope
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 715:1, s. 429-457
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Tidskriftsartikel (refereegranskat)abstract
- We present the first catalog of active galactic nuclei (AGNs) detected by the Large Area Telescope (LAT), corresponding to 11 months of data collected in scientific operation mode. The First LAT AGN Catalog (1LAC) includes 671 gamma-ray sources located at high Galactic latitudes (|b| > 10 degrees) that are detected with a test statistic greater than 25 and associated statistically with AGNs. Some LAT sources are associated with multiple AGNs, and consequently, the catalog includes 709 AGNs, comprising 300 BL Lacertae objects, 296 flat-spectrum radio quasars, 41 AGNs of other types, and 72 AGNs of unknown type. We also classify the blazars based on their spectral energy distributions as archival radio, optical, and X-ray data permit. In addition to the formal 1LAC sample, we provide AGN associations for 51 low-latitude LAT sources and AGN "affiliations" (unquantified counterpart candidates) for 104 high-latitude LAT sources without AGN associations. The overlap of the 1LAC with existing gamma-ray AGN catalogs (LBAS, EGRET, AGILE, Swift, INTEGRAL, TeVCat) is briefly discussed. Various properties-such as gamma-ray fluxes and photon power-law spectral indices, redshifts, gamma-ray luminosities, variability, and archival radio luminosities-and their correlations are presented and discussed for the different blazar classes. We compare the 1LAC results with predictions regarding the gamma-ray AGN populations, and we comment on the power of the sample to address the question of the blazar sequence.
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| 8. |
- Abdo, A. A., et al.
(författare)
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The second Fermi large area telescope catalog of gamma-ray pulsars
- 2013
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 208:2, s. 17-
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Tidskriftsartikel (refereegranskat)abstract
- This catalog summarizes 117 high-confidence ≥0.1 GeV gamma-ray pulsar detections using three years of data acquired by the Large Area Telescope (LAT) on the Fermi satellite. Half are neutron stars discovered using LAT data through periodicity searches in gamma-ray and radio data around LAT unassociated source positions. The 117 pulsars are evenly divided into three groups: millisecond pulsars, young radio-loud pulsars, and young radio-quiet pulsars. We characterize the pulse profiles and energy spectra and derive luminosities when distance information exists. Spectral analysis of the off-peak phase intervals indicates probable pulsar wind nebula emission for four pulsars, and off-peak magnetospheric emission for several young and millisecond pulsars. We compare the gamma-ray properties with those in the radio, optical, and X-ray bands. We provide flux limits for pulsars with no observed gamma-ray emission, highlighting a small number of gamma-faint, radio-loud pulsars. The large, varied gamma-ray pulsar sample constrains emission models. Fermi's selection biases complement those of radio surveys, enhancing comparisons with predicted population distributions.
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| 9. |
- Acero, F., et al.
(författare)
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Constraints on the galactic population of TeV pulsar wind nebulae using fermi large area telescope observations
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 773:1, s. 77-
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Tidskriftsartikel (refereegranskat)abstract
- Pulsar wind nebulae (PWNe) have been established as the most populous class of TeV gamma-ray emitters. Since launch, the Fermi Large Area Telescope (LAT) has identified five high-energy (100 MeV < E < 100 GeV) gamma-ray sources as PWNe and detected a large number of PWN candidates, all powered by young and energetic pulsars. The wealth of multi-wavelength data available and the new results provided by Fermi-LAT give us an opportunity to find new PWNe and to explore the radiative processes taking place in known ones. The TeV gamma-ray unidentified (UNID) sources are the best candidates for finding new PWNe. Using 45 months of Fermi-LAT data for energies above 10 GeV, an analysis was performed near the position of 58 TeV PWNe and UNIDs within 5. of the Galactic plane to establish new constraints on PWN properties and find new clues on the nature of UNIDs. Of the 58 sources, 30 were detected, and this work provides their gamma-ray fluxes for energies above 10 GeV. The spectral energy distributions and upper limits, in the multi-wavelength context, also provide new information on the source nature and can help distinguish between emission scenarios, i.e., between classification as a pulsar candidate or as a PWN candidate. Six new GeV PWN candidates are described in detail and compared with existing models. A population study of GeV PWN candidates as a function of the pulsar/PWN system characteristics is presented.
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| 10. |
- Ackermann, M., et al.
(författare)
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A STATISTICAL APPROACH TO RECOGNIZING SOURCE CLASSES FOR UNASSOCIATED SOURCES IN THE FIRST FERMI-LAT CATALOG
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 753:1, s. 83-
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Tidskriftsartikel (refereegranskat)abstract
- The Fermi Large Area Telescope (LAT) First Source Catalog (1FGL) provided spatial, spectral, and temporal properties for a large number of gamma-ray sources using a uniform analysis method. After correlating with the most-complete catalogs of source types known to emit gamma rays, 630 of these sources are unassociated (i.e., have no obvious counterparts at other wavelengths). Here, we employ two statistical analyses of the primary gamma-ray characteristics for these unassociated sources in an effort to correlate their gamma-ray properties with the active galactic nucleus (AGN) and pulsar populations in 1FGL. Based on the correlation results, we classify 221 AGN-like and 134 pulsar-like sources in the 1FGL unassociated sources. The results of these source classifications appear to match the expected source distributions, especially at high Galactic latitudes. While useful for planning future multiwavelength follow-up observations, these analyses use limited inputs, and their predictions should not be considered equivalent to probable source classes for these sources. We discuss multiwavelength results and catalog cross-correlations to date, and provide new source associations for 229 Fermi-LAT sources that had no association listed in the 1FGL catalog. By validating the source classifications against these new associations, we find that the new association matches the predicted source class in similar to 80% of the sources.
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