1. |
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2. |
- Abolins, M., et al.
(författare)
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The ATLAS Data Acquisition and High Level Trigger system
- 2016
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the data acquisition and high level trigger system of the ATLAS experiment at the Large Hadron Collider at CERN, as deployed during Run 1. Data flow as well as control, configuration and monitoring aspects are addressed. An overview of the functionality of the system and of its performance is presented and design choices are discussed.
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3. |
- Abe, H., et al.
(författare)
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Gamma-ray observations of MAXI J1820+070 during the 2018 outburst
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 517:4, s. 4736-4751
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Tidskriftsartikel (refereegranskat)abstract
- MAXIJ1820+070 is a low-mass X-ray binary with a black hole (BH) as a compact object. This binary underwent an exceptionally bright X-ray outburst from 2018 March to October, showing evidence of a non-thermal particle population through its radio emission during this whole period. The combined results of 59.5 h of observations of the MAXI J1820+070 outburst with the H.E.S.S., MAGIC and VERITAS experiments at energies above 200 GeV are presented, together with Fermi-LAT data between 0.1 and 500 GeV, and multiwavelength observations from radio to X-rays. Gamma-ray emission is not detected from MAXI J1820+070, but the obtained upper limits and the multiwavelength data allow us to put meaningful constraints on the source properties under reasonable assumptions regarding the non-thermal particle population and the jet synchrotron spectrum. In particular, it is possible to show that, if a high-energy (HE) gamma-ray emitting region is present during the hard state of the source, its predicted flux should be at most a factor of 20 below the obtained Fermi-LAT upper limits, and closer to them for magnetic fields significantly below equipartition. During the state transitions, under the plausible assumption that electrons are accelerated up to similar to 500 GeV, the multiwavelength data and the gamma-ray upper limits lead consistently to the conclusion that a potential HE and very-HE gamma-ray emitting region should be located at a distance from the BH ranging between 10(11) and 10(13) cm. Similar outbursts from low-mass X-ray binaries might be detectable in the near future with upcoming instruments such as CTA.
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4. |
- Adams, C. B., et al.
(författare)
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Observation of the Gamma-Ray Binary HESS J0632+057 with the HESS, MAGIC, and VERITAS Telescopes
- 2021
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 923:2
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Tidskriftsartikel (refereegranskat)abstract
- The results of gamma-ray observations of the binary system HESS J0632 + 057 collected during 450 hr over 15 yr, between 2004 and 2019, are presented. Data taken with the atmospheric Cherenkov telescopes H.E.S.S., MAGIC, and VERITAS at energies above 350 GeV were used together with observations at X-ray energies obtained with Swift-XRT, Chandra, XMM-Newton, NuSTAR, and Suzaku. Some of these observations were accompanied by measurements of the H alpha emission line. A significant detection of the modulation of the very high-energy gamma-ray fluxes with a period of 316.7 +/- 4.4 days is reported, consistent with the period of 317.3 +/- 0.7 days obtained with a refined analysis of X-ray data. The analysis of data from four orbital cycles with dense observational coverage reveals short-timescale variability, with flux-decay timescales of less than 20 days at very high energies. Flux variations observed over a timescale of several years indicate orbit-to-orbit variability. The analysis confirms the previously reported correlation of X-ray and gamma-ray emission from the system at very high significance, but cannot find any correlation of optical H alpha parameters with fluxes at X-ray or gamma-ray energies in simultaneous observations. The key finding is that the emission of HESS J0632 + 057 in the X-ray and gamma-ray energy bands is highly variable on different timescales. The ratio of gamma-ray to X-ray flux shows the equality or even dominance of the gamma-ray energy range. This wealth of new data is interpreted taking into account the insufficient knowledge of the ephemeris of the system, and discussed in the context of results reported on other gamma-ray binary systems.
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5. |
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6. |
- Veres, P., et al.
(författare)
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Observation of inverse Compton emission from a long gamma-ray burst
- 2019
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 575:7783, s. 459-
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Tidskriftsartikel (refereegranskat)abstract
- Long-duration gamma-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectron volt-to-mega electronvoltband, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission(1,2). Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands(1-6). The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock(7-9). Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C(10,11). Here we report multifrequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 x 10(-6) to 10(12) electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.
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7. |
- Abdellaoui, G., et al.
(författare)
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Meteor studies in the framework of the JEM-EUSO program
- 2017
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Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 143, s. 245-255
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Tidskriftsartikel (refereegranskat)abstract
- We summarize the state of the art of a program of UV observations from space of meteor phenomena, a secondary objective of the JEM-EUSO international collaboration. Our preliminary analysis indicates that JEM-EUSO, taking advantage of its large FOV and good sensitivity, should be able to detect meteors down to absolute magnitude close to 7. This means that JEM-EUSO should be able to record a statistically significant flux of meteors, including both sporadic ones, and events produced by different meteor streams. Being unaffected by adverse weather conditions, JEM-EUSO can also be a very important facility for the detection of bright meteors and fireballs, as these events can be detected even in conditions of very high sky background. In the case of bright events, moreover, exhibiting some persistence of the meteor train, preliminary simulations show that it should be possible to exploit the motion of the ISS itself and derive at least a rough 3D reconstruction of the meteor trajectory. Moreover, the observing strategy developed to detect meteors may also be applied to the detection of nuclearites, exotic particles whose existence has been suggested by some theoretical investigations. Nuclearites are expected to move at higher velocities than meteoroids, and to exhibit a wider range of possible trajectories, including particles moving upward after crossing the Earth. Some pilot studies, including the approved Mini-EUSO mission, a precursor of JEM-EUSO, are currently operational or in preparation. We are doing simulations to assess the performance of Mini-EUSO for meteor studies, while a few meteor events have been already detected using the ground-based facility EUSO-TA.
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8. |
- Abdellaoui, G., et al.
(författare)
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First observations of speed of light tracks by a fluorescence detector looking down on the atmosphere
- 2018
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25(th) of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector.
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9. |
- Bruzzi, M, et al.
(författare)
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Radiation-hard semiconductor detectors for SuperLHC
- 2005
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 541:1-2, s. 189-201
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Tidskriftsartikel (refereegranskat)abstract
- An option of increasing the luminosity of the Large Hadron Collider (LHC) at CERN to 1035 cm-2 s-1 has been envisaged to extend the physics reach of the machine. An efficient tracking down to a few centimetres from the interaction point will be required to exploit the physics potential of the upgraded LHC. As a consequence, the semiconductor detectors close to the interaction region will receive severe doses of fast hadron irradiation and the inner tracker detectors will need to survive fast hadron fluences of up to above 1016cm-2. The CERN-RD50 project "Development of Radiation Hard Semiconductor Devices for Very High Luminosity Colliders" has been established in 2002 to explore detector materials and technologies that will allow to operate devices up to, or beyond, this limit. The strategies followed by RD50 to enhance the radiation tolerance include the development of new or defect engineered detector materials (SiC, GaN, Czochralski and epitaxial silicon, oxygen enriched Float Zone silicon), the improvement of present detector designs and the understanding of the microscopic defects causing the degradation of the irradiated detectors. The latest advancements within the RD50 collaboration on radiation hard semiconductor detectors will be reviewed and discussed in this work.
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10. |
- De Angelis, A., et al.
(författare)
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Science with e-ASTROGAM A space mission for MeV-GeV gamma-ray astrophysics
- 2018
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Ingår i: Journal of High Energy Astrophysics. - : Elsevier. - 2214-4048 .- 2214-4056. ; 19, s. 1-106
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Tidskriftsartikel (refereegranskat)abstract
- e-ASTROGAM ('enhanced ASTROGAM') is a breakthrough Observatory space mission, with a detector composed by a Silicon tracker, a calorimeter, and an anticoincidence system, dedicated to the study of the non-thermal Universe in the photon energy range from 0.3 MeV to 3 GeV - the lower energy limit can be pushed to energies as low as 150 keV for the tracker, and to 30 keV for calorimetric detection. The mission is based on an advanced space-proven detector technology, with unprecedented sensitivity, angular and energy resolution, combined with polarimetric capability. Thanks to its performance in the MeV-GeV domain, substantially improving its predecessors, e-ASTROGAM will open a new window on the non-thermal Universe, making pioneering observations of the most powerful Galactic and extragalactic sources, elucidating the nature of their relativistic outflows and their effects on the surroundings. With a line sensitivity in the MeV energy range one to two orders of magnitude better than previous generation instruments, e-ASTROGAM will determine the origin of key isotopes fundamental for the understanding of supernova explosion and the chemical evolution of our Galaxy. The mission will provide unique data of significant interest to a broad astronomical community, complementary to powerful observatories such as LIGO-Virgo-GEO600-KAGRA, SKA, ALMA, E-ELT, TMT, LSST, JWST, Athena, CTA, IceCube, KM3NeT, and LISA.
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11. |
- Helbig, K. L., et al.
(författare)
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De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 103:5, s. 666-678
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Tidskriftsartikel (refereegranskat)abstract
- Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha(1)-subunit of the voltage-gated Ca(V)2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed Ca(V)2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.
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12. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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13. |
- Longo, F., et al.
(författare)
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Upper limits on the high-energy emission from gamma-ray bursts observed by AGILE-GRID
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 547, s. A95-
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Tidskriftsartikel (refereegranskat)abstract
- Context. The detection and the characterization of the highenergy emission component from individual gamma-ray bursts (GRBs) is one of the key science objectives of the currently operating gamma-ray satellite AGILE, launched in April 2007. In its first two years of operation AGILE detected three GRBs with photons of energy larger than 30 MeV. One more GRB was detected in AGILE third operation year, while operating in spinning mode. Aims. For the 64 other GRBs localized during the period July 2007 to October 2009 in the field of view of the AGILE Gamma-Ray Imaging Detector (GRID), but not detected by this instrument, we estimate the count and flux upper limits on the GRB high energy emission in the AGILE-GRID energy band (30 MeV-3 GeV). Methods. To calculate the count upper limits, we adopted a Bayesian approach. The flux upper limits are derived using several assumptions on the high-energy spectral behavior. For 28 GRBs with available prompt spectral information, a flux upper limit and the comparison with the expected flux estimated from spectral extrapolation of the Band spectrum to the 30 MeV-3 GeV band are provided. Moreover, upper limits on the flux under the assumption of an extra power law component dominating the 30 MeV-3 GeV band are calculated for all GRBs and considering four different values for the spectral photon index. Finally, we performed a likelihood upper limit on the possible delayed emission up to 1 h after the GRB. Results. The estimated flux upper limits range between 1 × 10 -4 and ∼2 × 10 -2 photons cm -2 s -1 and generally lie above the flux estimated from the extrapolation of the prompt emission in the 30 MeV-3 GeV band. A notable case is GRB 080721, where the AGILE-GRID upper limit suggests a steeper spectral index or the presence of a cut-off in the high energy part of the Band prompt spectrum. The four GRBs detected by AGILE-GRID show high-energy (30 MeV-3 GeV) to low-energy (1 keV-10 MeV) fluence ratios similar to those estimated in this paper for the 64 GRBs without GRID detection, favoring the possibility that AGILE-GRID detected only high-fluence, hard GRBs. From the flux upper limits derived in this work we put some constraint on high-energy radiation from the afterglow emission and from synchrotron self Compton emission in internal shocks.
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14. |
- Massetti, Matteo, et al.
(författare)
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Fully direct written organic micro-thermoelectric generators embedded in a plastic foil
- 2020
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Ingår i: Nano Energy. - : ELSEVIER. - 2211-2855 .- 2211-3282. ; 75
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Tidskriftsartikel (refereegranskat)abstract
- Organic materials have attracted great interest for thermoelectric applications due to their tuneable electronic properties, solution processability and earth-abundance, potentially enabling high-throughput realization of low-cost devices for low-power energy harvesting applications. So far, organic thermoelectricity has primarily focused on materials development, with less attention given to integrated generators. Yet, future applications will require the combination of efficient generators architectures and scalable manufacturing techniques to leverage the advantages of such promising materials. Here we report the realization of a monolithic organic micro-thermoelectric generator (mu-OTEG), using only direct writing methods, embedding the thermoelectric legs within a plastic substrate through a combination of direct laser writing and inkjet printing techniques. Employing PEDOT:PSS for the p-type legs and a doped fullerene derivative for the n-type ones, we demonstrate a mu-OTEG with power density of 30.5 nW/cm(2) under small thermal gradients, proving the concrete possibility of achieving power requirements of low-power, distributed sensing applications.
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15. |
- Nava-Farias, Lorena, et al.
(författare)
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Applying laboratory methods for durability assessment of vitrified material to archaeological samples
- 2021
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Ingår i: npj Materials Degradation. - : Springer Nature. - 2397-2106. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Laboratory testing used to assess the long-term chemical durability of nuclear waste forms may not be applicable to disposal because the accelerated conditions may not represent disposal conditions. To address this, we examine the corrosion of vitrified archeological materials excavated from the near surface of a ~1500-year old Iron Age Swedish hillfort, Broborg, as an analog for the disposal of vitrified nuclear waste. We compare characterized site samples with corrosion characteristics generated by standard laboratory durability test methods including the product consistency test (PCT), the vapor hydration test (VHT), and the EPA Method 1313 test. Results show that the surficial layer of the Broborg samples resulting from VHT displays some similarities to the morphology of the surficial layer formed over longer timescales in the environment. This work provides improved understanding of long-term glass corrosion behavior in terms of the thickness, morphology, and chemistry of the surficial features that are formed.
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16. |
- Smol, T., et al.
(författare)
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MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype
- 2018
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Ingår i: Neurogenetics. - : SPRINGER. - 1364-6745 .- 1364-6753. ; 19:2, s. 93-103
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Tidskriftsartikel (refereegranskat)abstract
- Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Here we report 36 patients with MED13L molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15-17 and 25-31. We found that patients carrying missense mutations had more frequently epilepsy and showed a more severe phenotype. This study ascertains missense variations in MED13L as a cause for MED13L-related intellectual disability and improves the clinical delineation of the condition.
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17. |
- Bersano, A., et al.
(författare)
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Research Progresses in Understanding the Pathophysiology of Moyamoya Disease
- 2016
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1015-9770 .- 1421-9786. ; 41:3-4, s. 105-118
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Tidskriftsartikel (refereegranskat)abstract
- Background: The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is unclear whether these anomalies are the consequences of the disease or rather causal factors as well as these mechanisms remain insufficient to explain the pathophysiology of MMD. The presence of a family history in about 9-15% of Asian patients, the highly variable incidence rate between different ethnic and sex groups and the age of onset support the role of genetic factors in MMD pathogenesis. However, although some genetic loci have been associated with MMD, few of them have been replicated in independent series. Recently, RNF213 gene was shown to be strongly associated with MMD occurrence with a founder effect in East Asian patients. However, the mechanisms leading from RNF213 mutations to MMD clinical features are still unknown. Summary: The research on pathogenic mechanism of MMD is in its infancy. MMD is probably a complex and heterogeneous disorder, including different phenotypes and genotypes, in which more than a single factor is implicated. Key Message: Since the diagnosis of MMD is rapidly increasing worldwide, the development of more efficient stratifying risk systems, including both clinical but also biological drivers became imperative to improve our ability of predict prognosis and to develop mechanism-tailored interventions.
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20. |
- Ghirlanda, G., et al.
(författare)
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Compact radio emission indicates a structured jet was produced by a binary neutron star merger
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6430, s. 968-971
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Tidskriftsartikel (refereegranskat)abstract
- The binary neutron star merger event GW170817 was detected through both electromagnetic radiation and gravitational waves. Its afterglow emission may have been produced by either a narrow relativistic jet or an isotropic outflow. High-spatial-resolution measurements of the source size and displacement can discriminate between these scenarios. We present very-long-baseline interferometry observations, performed 207.4 days after the merger by using a global network of 32 radio telescopes. The apparent source size is constrained to be smaller than 2.5 milli-arc seconds at the 90% confidence level. This excludes the isotropic outflow scenario, which would have produced a larger apparent size, indicating that GW170817 produced a structured relativistic jet. Our rate calculations show that at least 10% of neutron star mergers produce such a jet.
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21. |
- Harris, Ted D., et al.
(författare)
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What makes a cyanobacterial bloom disappear? : A review of the abiotic and biotic cyanobacterial bloom loss factors
- 2024
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Ingår i: Harmful Algae. - : Elsevier. - 1568-9883 .- 1878-1470. ; 133
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Forskningsöversikt (refereegranskat)abstract
- Cyanobacterial blooms present substantial challenges to managers and threaten ecological and public health. Although the majority of cyanobacterial bloom research and management focuses on factors that control bloom initiation, duration, toxicity, and geographical extent, relatively little research focuses on the role of loss processes in blooms and how these processes are regulated. Here, we define a loss process in terms of population dynamics as any process that removes cells from a population, thereby decelerating or reducing the development and extent of blooms. We review abiotic (e.g., hydraulic flushing and oxidative stress/UV light) and biotic factors (e.g., allelopathic compounds, infections, grazing, and resting cells/programmed cell death) known to govern bloom loss. We found that the dominant loss processes depend on several system specific factors including cyanobacterial genera -specific traits, in situ physicochemical conditions, and the microbial, phytoplankton, and consumer community composition. We also address loss processes in the context of bloom management and discuss perspectives and challenges in predicting how a changing climate may directly and indirectly affect loss processes on blooms. A deeper understanding of bloom loss processes and their underlying mechanisms may help to mitigate the negative consequences of cyanobacterial blooms and improve current management strategies.
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24. |
- Matthews, Bethany E., et al.
(författare)
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Micro- and Nanoscale Surface Analysis of Late Iron Age Glass from Broborg, a Vitrified Swedish Hillfort
- 2023
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Ingår i: Microscopy and Microanalysis. - : Oxford University Press. - 1431-9276 .- 1435-8115. ; 29:1, s. 50-68
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Tidskriftsartikel (refereegranskat)abstract
- Archaeological glasses with prolonged exposure to biogeochemical processes in the environment can be used to understand glass alteration, which is important for the safe disposal of vitrified nuclear waste. Samples of mafic and felsic glasses with different chemistries, formed from melting amphibolitic and granitoid rocks, were obtained from Broborg, a Swedish Iron Age hillfort. Glasses were excavated from the top of the hillfort wall and from the wall interior. A detailed microscopic, spectroscopic, and diffraction study of surficial textures and chemistries were conducted on these glasses. Felsic glass chemistry was uniform, with a smooth surface showing limited chemical alteration (<150 nm), irrespective of the position in the wall. Mafic glass was heterogeneous, with pyroxene, spinel, feldspar, and quartz crystals in the glassy matrix. Mafic glass surfaces in contact with topsoil were rougher than those within the wall and had carbon-rich material consistent with microbial colonization. Limited evidence for chemical or physical alteration of mafic glass was found; the thin melt film that coated all exposed surfaces remained intact, despite exposure to hydraulically unsaturated conditions, topsoil, and associated microbiome for over 1,500 years. This supports the assumption that aluminosilicate nuclear waste glasses will have a high chemical durability in near-surface disposal facilities.
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29. |
- Rådestad, E., et al.
(författare)
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Characterization of infiltrating lymphocytes in human benign and malignant prostate tissue
- 2017
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Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 8:36, s. 60257-60269
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Tidskriftsartikel (refereegranskat)abstract
- Immune checkpoint blockade has shown promising results in numerous cancer types. However, in prostate cancer (PC), absent or limited responses have been reported. To investigate further, we compared the phenotype of infiltrating T-cells isolated from prostate tissue from patients with PC (n = 5), benign prostatic hyperplasia (BPH) (n = 27), BPH with concurrent PC (n = 4) and controls (n = 7). The majority of T-cells were CD8+ and had a CCR7-CD45RO+ effector memory phenotype. However, the yield of T-cells isolated from PC lesions was on average 20-fold higher than that obtained from control prostates. Furthermore, there were differences between the prostate conditions regarding the percentage of T-cells expressing several activation markers and co-inhibitory receptors. In conclusion, many prostateinfiltrating T-cells express co-inhibitory receptors PD-1 and LAG-3, regardless of prostate condition. Despite the observed increase in counts and percentages of PD- 1+ T-cells in PC, the concomitant demonstration of high percentage of PD-1+ T-cells in control prostates suggests that PD-1 may play a role in controlling the homeostasis of the prostate rather than in contributing to PC-associated immune-suppression. Thus, PD-1 may not be a good candidate for checkpoint blockade in PC and these data are relevant for evaluation of clinical trials and in designing future immunotherapeutic approaches of PC.
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35. |
- Glinos, Dafni A., et al.
(författare)
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Transcriptome variation in human tissues revealed by long-read sequencing
- 2022
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 608:7922, s. 353-359
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Tidskriftsartikel (refereegranskat)abstract
- Regulation of transcript structure generates transcript diversity and plays an important role in human disease(1-7). The advent oflong-read sequencing technologies offers the opportunity to study the role of genetic variation in transcript structure(8-)(16). In this Article, we present a large human long-read RNA-seq dataset using the Oxford Nanopore Technologies platform from 88 samples from Genotype-Tissue Expression (GTEx) tissues and cell lines, complementing the GTEx resource. We identified just over 70,000 novel transcripts for annotated genes, and validated the protein expression of 10% of novel transcripts. We developed a new computational package, LORALS, to analyse the genetic effects of rare and common variants on the transcriptome by allele-specific analysis of long reads. We characterized allele-specific expression and transcript structure events, providing new insights into the specific transcript alterations caused by common and rare genetic variants and highlighting the resolution gained from long-read data. We were able to perturb the transcript structure upon knockdown of PTBP1, an RNA binding protein that mediates splicing, thereby finding genetic regulatory effects that are modified by the cellular environment. Finally, we used this dataset to enhance variant interpretation and study rare variants leading to aberrant splicing patterns.
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37. |
- Jansson, Johan, et al.
(författare)
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Adaptive simulation of unsteady flow past the submerged part of a floating wind turbine platform
- 2015
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Ingår i: MARINE 2015 - Computational Methods in Marine Engineering VI. - : International Center for Numerical Methods in Engineering (CIMNE). - 9788494392863 ; , s. 35-46
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Konferensbidrag (refereegranskat)abstract
- Offshore floating platforms for wind turbines represent challenging concepts for designers trying to combine an optimal compromise between cost effectiveness and performance. Modelling of the hydrodynamic behaviour of the structure is still the subject of wide debate in the technical communities. The assessment of the hydrodynamics of the support structure is not an easy task as the floaters consist of an assembly of columns, braces and pontoons, commonly also with heave plates: Each of these components corresponds to a different hydrodynamic model and it further interacts with the other elements. This results in very complex non-linear modeling, which makes it necessary to resort to computational fluid dynamics (CFD) methods for the evaluation of the combined hydrodynamics. In the framework of the collaboration between the Basque Centre for Applied Mathematics (BCAM) and Tecnalia R&I, the interaction of the sea flow with a semisubmersible floating offshore wind platform have been calculated by using the open source solver Unicorn in the FEniCS-HPC framework when subject to a steady inflow. The prototype of the platform consists in a semi-submersible 4-columns column stabilized platform - NAUTILUS Floating Solutions concept-; columns are connected by a rigid ring pontoon provided with heave damping plates at the bottom. The novelty of the approach in FEniCS-HPC hinges upon an implicit formulation for the turbulence, a cheap free slip model of the boundary layer and goal-oriented mesh adaptivity [8, 6, 9, 20, 1]. We find that the results are consistent with experimental results for cylinders at high Reynolds number.
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38. |
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39. |
- Khounlotham, Manirath, et al.
(författare)
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Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis
- 2012
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Ingår i: Immunity. - Cambridge, United States : Cell Press. - 1074-7613 .- 1097-4180. ; 37:3, s. 563-573
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Tidskriftsartikel (refereegranskat)abstract
- Mice lacking junctional adhesion molecule A (JAM-A, encoded by F11r) exhibit enhanced intestinal epithelial permeability, bacterial translocation, and elevated colonic lymphocyte numbers, yet do not develop colitis. To investigate the contribution of adaptive immune compensation in response to increased intestinal epithelial permeability, we examined the susceptibility of F11r(-/-)Rag1(-/-) mice to acute colitis. Although negligible contributions of adaptive immunity in F11r(+/+)Rag1(-/-) mice were observed, F11r(-/-)Rag1(-/-) mice exhibited increased microflora-dependent colitis. Elimination of T cell subsets and cytokine analyses revealed a protective role for TGF-beta-producing CD4(+) T cells in F11r(-/-) mice. Additionally, loss of JAM-A resulted in elevated mucosal and serum IgA that was dependent upon CD4(+) T cells and TGF-beta. Absence of IgA in F11r(+/+)Igha(-/-) mice did not affect disease, whereas F11r(-/-)Igha(-/-) mice displayed markedly increased susceptibility to acute injury-induced colitis. These data establish a role for adaptive immune-mediated protection from acute colitis under conditions of intestinal epithelial barrier compromise.
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40. |
- Koch, Stefan, et al.
(författare)
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The Wnt antagonist Dkk1 regulates intestinal epithelial homeostasis and wound repair
- 2011
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Ingår i: Gastroenterology. - Maryland Heights, United States : W.B. Saunders Co.. - 0016-5085 .- 1528-0012. ; 141:1, s. 259-268
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Tidskriftsartikel (refereegranskat)abstract
- Background & AimsDkk1 is a secreted antagonist of the Wnt/β-catenin signaling pathway. It is induced by inflammatory cytokines during colitis and exacerbates tissue damage by promoting apoptosis of epithelial cells. However, little is known about the physiologic role of Dkk1 in normal intestinal homeostasis and during wound repair following mucosal injury. We investigated whether inhibition of Dkk1 affects the morphology and function of the adult intestine.MethodsWe used doubleridge mice (Dkk1d/d), which have reduced expression of Dkk1, and an inhibitory Dkk1 antibody to modulate Wnt/β-catenin signaling in the intestine. Intestinal inflammation was induced with dextran sulfate sodium (DSS), followed by a recovery period in which mice were given regular drinking water. Animals were killed before, during, or after DSS administration; epithelial homeostasis and the activity of major signaling pathways were investigated by morphometric analysis, bromo-2′-deoxyuridine incorporation, and immunostaining.ResultsReduced expression of Dkk1 increased proliferation of epithelial cells and lengthened crypts in the large intestine, which was associated with increased transcriptional activity of β-catenin. Crypt extension was particularly striking when Dkk1 was inhibited during acute colitis. Dkk1d/dmice recovered significantly faster from intestinal inflammation but exhibited crypt architectural irregularities and epithelial hyperproliferation compared with wild-type mice. Survival signaling pathways were concurrently up-regulated in Dkk1d/d mice, including the AKT/β-catenin, ERK/Elk-1, and c-Jun pathways.ConclusionsDkk1, an antagonist of Wnt/β-catenin signaling, regulates intestinal epithelial homeostasis under physiologic conditions and during inflammation. Depletion of Dkk1 induces a strong proliferative response that promotes wound repair after colitis.
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41. |
- Melandri, A., et al.
(författare)
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The high-redshift gamma-ray burst GRB 140515A A comprehensive X-ray and optical study
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 581
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Tidskriftsartikel (refereegranskat)abstract
- High-redshift eamma-ray bursts (GRBs) offer several advantages When studying the distant Universe, providing unique information about the structure and properties of the galaxies in which they exploded. Spectroscopic identification with large ground-based telescopes has improved our knowledge of this kind of distant events. We present the multi-wavelength analysis of the high-z S'wift GRB GRB 1.40515A (z = 6.327). The best estimate of the neutral hydrogen fraction of the intergalactic medium towards the burst is X-HI <= 0.002. The spectral absorption lines detected for this event are the weakest lines ever observed in GRB afterglows, suggesting that GRB 140515A exploded in a very low-density environment. Its circtun-burst medium is characterised by an average extinction (A(V) similar to 0.1) that seems to be typical of z >= 6 events. The observed multi-band light curves are explained either with a very hard injected spectrum (p = 1.7) or with a multi-component emission (p = 2.1). In the second case a long-lasting central engine activity is needed in order to explain the late time X-ray emission. The possible origin of GRB 140515A in a Pop III (or in a Pop II star with a local environment enriched by Pop III) massive star is unlikely.
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42. |
- Nava, Porfirio, et al.
(författare)
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IFN gamma-induced suppression of beta-catenin signaling : evidence for roles of Akt and 14.3.3 zeta
- 2014
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Ingår i: Molecular Biology of the Cell. - Bethesda, United States : American Society for Cell Biology. - 1059-1524 .- 1939-4586. ; 25:19, s. 2894-2904
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Tidskriftsartikel (refereegranskat)abstract
- The proinflammatory cytokine interferon gamma (IFNgamma ) influences intestinal epithelial cell (IEC) homeostasis in a biphasic manner by acutely stimulating proliferation that is followed by sustained inhibition of proliferation despite continued mucosal injury. beta-Catenin activation has been classically associated with increased IEC proliferation. However, we observed that IFNgamma inhibits IEC proliferation despite sustained activation of Akt/beta-catenin signaling. Here we show that inhibition of Akt/beta-catenin-mediated cell proliferation by IFNgamma is associated with the formation of a protein complex containing phosphorylated beta-catenin 552 (pbeta-cat552) and 14.3.3zeta. Akt1 served as a bimodal switch that promotes or inhibits beta-catenin transactivation in response to IFNgamma stimulation. IFNgamma initially promotes beta-catenin transactivation through Akt-dependent C-terminal phosphorylation of beta-catenin to promote its association with 14.3.3zeta. Augmented beta-catenin transactivation leads to increased Akt1 protein levels, and active Akt1 accumulates in the nucleus, where it phosphorylates 14.3.3zeta to translocate 14.3.3zeta/beta-catenin from the nucleus, thereby inhibiting beta-catenin transactivation and IEC proliferation. These results outline a dual function of Akt1 that suppresses IEC proliferation during intestinal inflammation.
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43. |
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44. |
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45. |
- Setter, Nava, et al.
(författare)
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Ferroelectric thin films: Review of materials, properties, and applications
- 2006
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 100:5, s. 051606-1-46-
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Tidskriftsartikel (refereegranskat)abstract
- An overview of the state of art in ferroelectric thin films is presented. First, we review applications: microsystems' applications, applications in high frequency electronics, and memories based on ferroelectric materials. The second section deals with materials, structure (domains, in particular), and size effects. Properties of thin films that are important for applications are then addressed: polarization reversal and properties related to the reliability of ferroelectric memories, piezoelectric nonlinearity of ferroelectric films which is relevant to microsystems' applications, and permittivity and loss in ferroelectric films-important in all applications and essential in high frequency devices. In the context of properties we also discuss nanoscale probing of ferroelectrics. Finally, we comment on two important emerging topics: multiferroic materials and ferroelectric one-dimensional nanostructures. (c) 2006 American Institute of Physics.
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48. |
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49. |
- Solders, M., et al.
(författare)
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MAIT cells accumulate in placental intervillous space and display a highly cytotoxic phenotype upon bacterial stimulation
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- During pregnancy, the maternal immune system must tolerate the developing foetus, and yet retain a potent antimicrobial response to prevent infections. Mucosal associated invariant T (MAIT) cells recognize microbial-derived vitamin B metabolites presented on the MR1 molecule, but their presence and function at the foetal-maternal interface is not known. We here isolated mononuclear cells from paired samples of peripheral blood (PB), intervillous blood (IVB), and decidua parietalis (DP) following uncomplicated term pregnancies. Interestingly, MAIT cells were highly enriched in IVB compared to PB and DP. The activation status of IVB MAIT cells was similar to that of PB MAIT cells, except for a lower expression of PD-1. Both IVB MAIT cells and conventional T cells were more dominated by an effector memory phenotype compared to PB MAIT cells and T cells. IVB MAIT cells also responded more vigorously with expression of IFN-gamma, granzyme B, and perforin in response to Escherichia coli stimulation compared to PB. MR1 was not expressed in syncytiotrophoblasts, but in placental villous and decidual macrophages. These data indicate that maternal MAIT cells accumulate in the intervillous space of the placenta and that they are highly armed to quickly respond if bacteria are encountered at the foetal-maternal interface.
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50. |
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