| 1. |
- Michel, M., et al.
(författare)
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Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function
- 2022
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Ingår i: Science. - Stockholm : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1471-1476
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed b,d-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging. © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
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| 2. |
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| 3. |
- Aartsen, M. G., et al.
(författare)
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Evidence for High-Energy Extraterrestrial Neutrinos at the IceCube Detector
- 2013
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 342:6161, s. 947-
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Tidskriftsartikel (refereegranskat)abstract
- We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds. Combined, both searches reject a purely atmospheric origin for the 28 events at the 4 sigma level. These 28 events, which include the highest energy neutrinos ever observed, have flavors, directions, and energies inconsistent with those expected from the atmospheric muon and neutrino backgrounds. These properties are, however, consistent with generic predictions for an additional component of extraterrestrial origin.
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| 4. |
- Aartsen, M. G., et al.
(författare)
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Neutrino emission from the direction of the blazar TXS 0506+056 prior to the IceCube-170922A alert
- 2018
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 361:6398, s. 147-151
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Tidskriftsartikel (refereegranskat)abstract
- A high-energy neutrino event detected by IceCube on 22 September 2017 was coincident in direction and time with a gamma-ray flare from the blazar TXS 0506+056. Prompted by this association, we investigated 9.5 years of IceCube neutrino observations to search for excess emission at the position of the blazar. We found an excess of high-energy neutrino events, with respect to atmospheric backgrounds, at that position between September 2014 and March 2015. Allowing for time-variable flux, this constitutes 3.5 sigma evidence for neutrino emission from the direction of TXS 0506+056, independent of and prior to the 2017 flaring episode. This suggests that blazars are identifiable sources of the high-energy astrophysical neutrino flux.
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| 5. |
- Abbadessa, G, et al.
(författare)
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Unsung hero Robert C. Gallo
- 2009
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 323:5911, s. 206-207
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Abbasi, R., et al.
(författare)
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Evidence for neutrino emission from the nearby active galaxy NGC 1068
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 378:6619, s. 538-
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Tidskriftsartikel (refereegranskat)abstract
- A supermassive black hole, obscured by cosmic dust, powers the nearby active galaxy NGC 1068. Neutrinos, which rarely interact with matter, could provide information on the galaxy's active core. We searched for neutrino emission from astrophysical objects using data recorded with the IceCube neutrino detector between 2011 and 2020. The positions of 110 known gamma-ray sources were individually searched for neutrino detections above atmospheric and cosmic backgrounds. We found that NGC 1068 has an excess of 79(-20)(+22) neutrinos at tera-electron volt energies, with a global significance of 4.2 sigma, which we interpret as associated with the active galaxy. The flux of high-energy neutrinos that we measured from NGC 1068 is more than an order of magnitude higher than the upper limit on emissions of tera-electron volt gamma rays from this source.
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| 7. |
- Abdalla, H., et al.
(författare)
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Revealing x-ray and gamma ray temporal and spectral similarities in the GRB 190829A afterglow
- 2021
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Ingår i: Science. - : American Association of Advancement in Science. - 0036-8075 .- 1095-9203. ; 372:6546, s. 1081-1085
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Tidskriftsartikel (refereegranskat)abstract
- Gamma-ray bursts (GRBs), which are bright flashes of gamma rays from extragalactic sources followed by fading afterglow emission, are associated with stellar core collapse events. We report the detection of very- high-energy (VHE) gamma rays from the afterglow of GRB 190829A, between 4 and 56 hours after the trigger, using the High Energy Stereoscopic System (H.E.S.S.). The low luminosity and redshift of GRB 190829A reduce both internal and external absorption, allowing determination of its intrinsic energy spectrum. Between energies of 0.18 and 3.3 tera-electron volts, this spectrum is described by a power law with photon index of 2.07 +/- 0.09, similar to the x-ray spectrum. The x-ray and VHE gamma- ray light curves also show similar decay profiles. These similar characteristics in the x-ray and gamma-ray bands challenge GRB afterglow emission scenarios.
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| 8. |
- Abdo, A. A., et al.
(författare)
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A Population of Gamma-Ray Millisecond Pulsars Seen with the Fermi Large Area Telescope
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5942, s. 848-852
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Tidskriftsartikel (refereegranskat)abstract
- Pulsars are born with subsecond spin periods and slow by electromagnetic braking for several tens of millions of years, when detectable radiation ceases. A second life can occur for neutron stars in binary systems. They can acquire mass and angular momentum from their companions, to be spun up to millisecond periods and begin radiating again. We searched Fermi Large Area Telescope data for pulsations from all known millisecond pulsars (MSPs) outside of globular clusters, using rotation parameters from radio telescopes. Strong gamma-ray pulsations were detected for eight MSPs. The gamma-ray pulse profiles and spectral properties resemble those of young gamma-ray pulsars. The basic emission mechanism seems to be the same for MSPs and young pulsars, with the emission originating in regions far from the neutron star surface.
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| 9. |
- Abdo, A. A., et al.
(författare)
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Detection of 16 Gamma-Ray Pulsars Through Blind Frequency Searches Using the Fermi LAT
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5942, s. 840-844
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Tidskriftsartikel (refereegranskat)abstract
- Pulsars are rapidly rotating, highly magnetized neutron stars emitting radiation across the electromagnetic spectrum. Although there are more than 1800 known radio pulsars, until recently only seven were observed to pulse in gamma rays, and these were all discovered at other wavelengths. The Fermi Large Area Telescope (LAT) makes it possible to pinpoint neutron stars through their gamma-ray pulsations. We report the detection of 16 gamma-ray pulsars in blind frequency searches using the LAT. Most of these pulsars are coincident with previously unidentified gamma-ray sources, and many are associated with supernova remnants. Direct detection of gamma-ray pulsars enables studies of emission mechanisms, population statistics, and the energetics of pulsar wind nebulae and supernova remnants.
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| 10. |
- Abdo, A. A., et al.
(författare)
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Detection of High-Energy Gamma-Ray Emission from the Globular Cluster 47 Tucanae with Fermi
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5942, s. 845-848
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Tidskriftsartikel (refereegranskat)abstract
- We report the detection of gamma-ray emissions above 200 megaelectron volts at a significance level of 17 sigma from the globular cluster 47 Tucanae, using data obtained with the Large Area Telescope onboard the Fermi Gamma-ray Space Telescope. Globular clusters are expected to emit gamma rays because of the large populations of millisecond pulsars that they contain. The spectral shape of 47 Tucanae is consistent with gamma-ray emission from a population of millisecond pulsars. The observed gamma-ray luminosity implies an upper limit of 60 millisecond pulsars present in 47 Tucanae.
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| 11. |
- Abdo, A. A., et al.
(författare)
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Fermi Gamma-Ray Imaging of a Radio Galaxy
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 328:5979, s. 725-729
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Tidskriftsartikel (refereegranskat)abstract
- The Fermi Gamma-ray Space Telescope has detected the gamma-ray glow emanating from the giant radio lobes of the radio galaxy Centaurus A. The resolved gamma-ray image shows the lobes clearly separated from the central active source. In contrast to all other active galaxies detected so far in high-energy gamma-rays, the lobe flux constitutes a considerable portion (greater than one-half) of the total source emission. The gamma-ray emission from the lobes is interpreted as inverse Compton-scattered relic radiation from the cosmic microwave background, with additional contribution at higher energies from the infrared-to-optical extragalactic background light. These measurements provide gamma-ray constraints on the magnetic field and particle energy content in radio galaxy lobes, as well as a promising method to probe the cosmic relic photon fields.
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| 12. |
- Abdo, A. A., et al.
(författare)
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Fermi Observations of High-Energy Gamma-Ray Emission from GRB 080916C
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 323:5922, s. 1688-1693
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Tidskriftsartikel (refereegranskat)abstract
- Gamma-ray bursts (GRBs) are highly energetic explosions signaling the death of massive stars in distant galaxies. The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gamma-ray energy. In September 2008, Fermi observed the exceptionally luminous GRB 080916C, with the largest apparent energy release yet measured. The high-energy gamma rays are observed to start later and persist longer than the lower energy photons. A simple spectral form fits the entire GRB spectrum, providing strong constraints on emission models. The known distance of the burst enables placing lower limits on the bulk Lorentz factor of the outflow and on the quantum gravity mass.
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| 13. |
- 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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| 14. |
- Abdo, A. A., et al.
(författare)
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Gamma-Ray Emission from the Shell of Supernova Remnant W44 Revealed by the Fermi LAT
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5969, s. 1103-1106
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Tidskriftsartikel (refereegranskat)abstract
- Recent observations of supernova remnants (SNRs) hint that they accelerate cosmic rays to energies close to similar to 10(15) electron volts. However, the nature of the particles that produce the emission remains ambiguous. We report observations of SNR W44 with the Fermi Large Area Telescope at energies between 2 x 10(8) electron volts and 3 x 10(11) electron volts. The detection of a source with a morphology corresponding to the SNR shell implies that the emission is produced by particles accelerated there. The gamma-ray spectrum is well modeled with emission from protons and nuclei. Its steepening above similar to 10(9) electron volts provides a probe with which to study how particle acceleration responds to environmental effects such as shock propagation in dense clouds and how accelerated particles are released into interstellar space.
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| 15. |
- Abdo, A. A., et al.
(författare)
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Gamma-Ray Flares from the Crab Nebula
- 2011
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 331:6018, s. 739-742
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Tidskriftsartikel (refereegranskat)abstract
- A young and energetic pulsar powers the well-known Crab Nebula. Here, we describe two separate gamma-ray (photon energy greater than 100 mega-electron volts) flares from this source detected by the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. The first flare occurred in February 2009 and lasted approximately 16 days. The second flare was detected in September 2010 and lasted approximately 4 days. During these outbursts, the gamma-ray flux from the nebula increased by factors of four and six, respectively. The brevity of the flares implies that the gamma rays were emitted via synchrotron radiation from peta-electron-volt (10(15) electron volts) electrons in a region smaller than 1.4 x 10(-2) parsecs. These are the highest-energy particles that can be associated with a discrete astronomical source, and they pose challenges to particle acceleration theory.
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| 16. |
- Abdo, A. A., et al.
(författare)
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The Fermi Gamma-Ray Space Telescope Discovers the Pulsar in the Young Galactic Supernova Remnant CTA 1
- 2008
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 322:5905, s. 1218-1221
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Tidskriftsartikel (refereegranskat)abstract
- Energetic young pulsars and expanding blast waves [ supernova remnants (SNRs)] are the most visible remains after massive stars, ending their lives, explode in core-collapse supernovae. The Fermi Gamma- Ray Space Telescope has unveiled a radio quiet pulsar located near the center of the compact synchrotron nebula inside the supernova remnant CTA 1. The pulsar, discovered through its gamma- ray pulsations, has a period of 316.86 milliseconds and a period derivative of 3.614 x 10(-13) seconds per second. Its characteristic age of 10(4) years is comparable to that estimated for the SNR. We speculate that most unidentified Galactic gamma- ray sources associated with star- forming regions and SNRs are such young pulsars.
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| 17. |
- Abdollahi, S., et al.
(författare)
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A gamma-ray determination of the Universe's star formation history
- 2018
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 362:6418, s. 1031-1034
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Tidskriftsartikel (refereegranskat)abstract
- The light emitted by all galaxies over the history of the Universe produces the extragalactic background light (EBL) at ultraviolet, optical, and infrared wavelengths. The EBL is a source of opacity for gamma rays via photon-photon interactions, leaving an imprint in the spectra of distant gamma-ray sources. We measured this attenuation using 739 active galaxies and one gamma-ray burst detected by the Fermi Large Area Telescope. This allowed us to reconstruct the evolution of the EBL and determine the star formation history of the Universe over 90% of cosmic time. Our star formation history is consistent with independent measurements from galaxy surveys, peaking at redshift z similar to 2. Upper limits of the EBL at the epoch of reionization suggest a turnover in the abundance of faint galaxies at z similar to 6.
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| 18. |
- Abi-Rached, Laurent, et al.
(författare)
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The Shaping of Modern Human Immune Systems by Multiregional Admixture with Archaic Humans
- 2011
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 334:6052, s. 89-94
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Tidskriftsartikel (refereegranskat)abstract
- Whole genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic human leukocyte antigen (HLA) class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian populations. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly shaped modern human immune systems.
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| 19. |
- Abila, R., et al.
(författare)
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Oil extraction imperils Africa’s Great Lakes
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6312, s. 561-562
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- As the world's demands for hydrocarbons increase (1), remote areas previously made inaccessible by technological limitations are now being prospected for oil and gas deposits. Virtually unnoticed by the public, such activities are ongoing in the East African Great Lakes region, threatening these ecosystems famed for their hyper-diverse biota, including the unique adaptive radiations of cichlid fishes (2). Countries in the region see exploitation of hydrocarbon reserves as a vital economic opportunity. In the Lake Albert region of Uganda, for example, the government foresees a $3.6 billion oil profit per year starting in 2018—a sum almost as high as the country's current annual budget (3). However, oil extraction in the East African Great Lakes region poses grave risks to the environment and local communities.
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| 20. |
- Abramowski, A., et al.
(författare)
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The exceptionally powerful TeV gamma-ray emitters in the Large Magellanic Cloud
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6220, s. 406-412
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Tidskriftsartikel (refereegranskat)abstract
- The Large Magellanic Cloud, a satellite galaxy of the Milky Way, has been observed with the High Energy Stereoscopic System (H.E.S.S.) above an energy of 100 billion electron volts for a deep exposure of 210 hours. Three sources of different types were detected: the pulsar wind nebula of the most energetic pulsar known, N 157B; the radio-loud supernova remnant N 132D; and the largest nonthermal x-ray shell, the superbubble 30 Dor C. The unique object SN 1987A is, unexpectedly, not detected, which constrains the theoretical framework of particle acceleration in very young supernova remnants. These detections reveal the most energetic tip of a g-ray source population in an external galaxy and provide via 30 Dor C the unambiguous detection of g-ray emission from a superbubble.
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| 21. |
- Abramson, Alex, et al.
(författare)
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An ingestible self-orienting system for oral delivery of macromolecules
- 2019
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Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 363:6427, s. 611-
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Tidskriftsartikel (refereegranskat)abstract
- Biomacromolecules have transformed our capacity to effectively treat diseases; however, their rapid degradation and poor absorption in the gastrointestinal (GI) tract generally limit their administration to parenteral routes. An oral biologic delivery system must aid in both localization and permeation to achieve systemic drug uptake. Inspired by the leopard tortoise's ability to passively reorient, we developed an ingestible self-orienting millimeter-scale applicator (SOMA) that autonomously positions itself to engage with GI tissue. It then deploys milliposts fabricated from active pharmaceutical ingredients directly through the gastric mucosa while avoiding perforation. We conducted in vivo studies in rats and swine that support the applicator's safety and, using insulin as a model drug, demonstrated that the SOMA delivers active pharmaceutical ingredient plasma levels comparable to those achieved with subcutaneous millipost administration.
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| 22. |
- Acciari, V. A., et al.
(författare)
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Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
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Tidskriftsartikel (refereegranskat)abstract
- The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.
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| 23. |
- Acero, F., et al.
(författare)
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Detection of Gamma Rays from a Starburst Galaxy
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326:5956, s. 1080-1082
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Tidskriftsartikel (refereegranskat)abstract
- Starburst galaxies exhibit in their central regions a highly increased rate of supernovae, the remnants of which are thought to accelerate energetic cosmic rays up to energies of similar to 10(15) electron volts. We report the detection of gamma rays-tracers of such cosmic rays-from the starburst galaxy NGC 253 using the High Energy Stereoscopic System (H. E. S. S.) array of imaging atmospheric Cherenkov telescopes. The gamma-ray flux above 220 billion electron volts is F = (5.5 +/- 1.0(stat) +/- 2.8(sys)) x 10(-13) cm(-2) s(-1), implying a cosmic-ray density about three orders of magnitude larger than that in the center of the Milky Way. The fraction of cosmic-ray energy channeled into gamma rays in this starburst environment is five times as large as that in our Galaxy.
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| 24. |
- Ackermann, M., et al.
(författare)
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A Cocoon of Freshly Accelerated Cosmic Rays Detected by Fermi in the Cygnus Superbubble
- 2011
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 334:6059, s. 1103-1107
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Tidskriftsartikel (refereegranskat)abstract
- The origin of Galactic cosmic rays is a century-long puzzle. Indirect evidence points to their acceleration by supernova shockwaves, but we know little of their escape from the shock and their evolution through the turbulent medium surrounding massive stars. Gamma rays can probe their spreading through theambient gas and radiation fields. The Fermi Large Area Telescope (LAT) has observed the star-forming region of Cygnus X. The 1- to 100-gigaelectronvolt images reveal a 50-parsec-wide cocoon of freshly accelerated cosmic rays that flood the cavities carved by the stellar winds and ionization fronts from young stellar clusters. It provides an example to study the youth of cosmic rays in a superbubble environment before they merge into the older Galactic population.
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| 25. |
- Ackermann, M., et al.
(författare)
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An extremely bright gamma-ray pulsar in the Large Magellanic Cloud : An extremely bright gamma-ray pulsar in the Large Magellanic Cloud
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 350:6262, s. 801-805
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Tidskriftsartikel (refereegranskat)abstract
- Pulsars are rapidly spinning, highly magnetized neutron stars, created in the gravitational collapse of massive stars. We report the detection of pulsed giga-electron volt gamma rays from the young pulsar PSR J0540-6919 in the Large Magellanic Cloud, a satellite galaxy of the Milky Way. This is the first gamma-ray pulsar detected in another galaxy. It has the most luminous pulsed gamma-ray emission yet observed, exceeding the Crab pulsar's by a factor of 20. PSR J0540-6919 presents an extreme test case for understanding the structure and evolution of neutron star magnetospheres.
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