| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
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| 3. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 4. |
- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 5. |
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| 6. |
- Aartsen, M. G., et al.
(författare)
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Observation of High-Energy Astrophysical Neutrinos in Three Years of IceCube Data
- 2014
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 113:10, s. 101101-
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Tidskriftsartikel (refereegranskat)abstract
- A search for high-energy neutrinos interacting within the IceCube detector between 2010 and 2012 provided the first evidence for a high-energy neutrino flux of extraterrestrial origin. Results from an analysis using the same methods with a third year (2012-2013) of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm(-2) s(-1) sr(-1) per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7 sigma. The data are consistent with expectations for equal fluxes of all three neutrino flavors and with isotropic arrival directions, suggesting either numerous or spatially extended sources. The three-year data set, with a live time of 988 days, contains a total of 37 neutrino candidate events with deposited energies ranging from 30 to 2000 TeV. The 2000-TeV event is the highest-energy neutrino interaction ever observed.
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| 7. |
- Aartsen, M. G., et al.
(författare)
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SEARCH FOR TIME-INDEPENDENT NEUTRINO EMISSION FROM ASTROPHYSICAL SOURCES WITH 3 yr OF IceCube DATASearch for time-independent neutrino emission from astrophysical sources with 3 yr of icecube data
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 779:2, s. 132-
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a search for neutrino point sources using the IceCube data collected between 2008 April and 2011 May with three partially completed configurations of the detector: the 40-, 59-, and 79-string configurations. The live-time of this data set is 1040 days. An unbinned maximum likelihood ratio test was used to search for an excess of neutrinos above the atmospheric background at any given direction in the sky. By adding two more years of data with improved event selection and reconstruction techniques, the sensitivity was improved by a factor of 3.5 or more with respect to the previously published results obtained with the 40-string configuration of IceCube. We performed an all-sky survey and a dedicated search using a catalog of a priori selected objects observed by other telescopes. In both searches, the data are compatible with the background-only hypothesis. In the absence of evidence for a signal, we set upper limits on the flux of muon neutrinos. For an E-2 neutrino spectrum, the observed limits are (0.9-5) x 10(-12) TeV-1 cm(-2) s(-1) for energies between 1 TeV and 1 PeV in the northern sky and (0.9-23.2) x 10(-12) TeV-1 cm(-2) s(-1) for energies between 10(2) TeV and 10(2) PeV in the southern sky. We also report upper limits for neutrino emission from groups of sources that were selected according to theoretical models or observational parameters and analyzed with a stacking approach. Some of the limits presented already reach the level necessary to quantitatively test current models of neutrino emission.
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| 8. |
- Aartsen, M. G., et al.
(författare)
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SEARCHES FOR EXTENDED AND POINT-LIKE NEUTRINO SOURCES WITH FOUR YEARS OF ICECUBE DATA
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 796:2, s. 109-
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Tidskriftsartikel (refereegranskat)abstract
- We present results on searches for point-like sources of neutrinos using four years of IceCube data, including the first year of data from the completed 86 string detector. The total livetime of the combined data set is 1373 days. For an E-2 spectrum, the observed 90% C. L. flux upper limits are similar to 10(-12) TeV-1 cm(-2) s(-1) for energies between 1 TeV and 1 PeV in the northern sky and similar to 10(-11) TeV-1 cm(-2) s(-1) for energies between 100 TeV and 100 PeV in the southern sky. This represents a 40% improvement compared to previous publications, resulting from both the additional year of data and the introduction of improved reconstructions. In addition, we present the first results from an all-sky search for extended sources of neutrinos. We update the results of searches for neutrino emission from stacked catalogs of sources and test five new catalogs; two of Galactic supernova remnants and three of active galactic nuclei. In all cases, the data are compatible with the background-only hypothesis, and upper limits on the flux of muon neutrinos are reported for the sources considered.
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| 9. |
- Aartsen, M. G., et al.
(författare)
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Energy reconstruction methods in the IceCube neutrino telescope
- 2014
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Ingår i: Journal of Instrumentation. - 1748-0221 .- 1748-0221. ; 9, s. P03009-
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Tidskriftsartikel (refereegranskat)abstract
- Accurate measurement of neutrino energies is essential to many of the scientific goals of large-volume neutrino telescopes. The fundamental observable in such detectors is the Cherenkov light produced by the transit through a medium of charged particles created in neutrino interactions. The amount of light emitted is proportional to the deposited energy, which is approximately equal to the neutrino energy for v(e) and v(mu) charged-current interactions and can be used to set a lower bound on neutrino energies and to measure neutrino spectra statistically in other channels. Here we describe methods and performance of reconstructing charged-particle energies and topologies from the observed Cherenkov light yield, including techniques to measure the energies of uncontained muon tracks, achieving average uncertainties in electromagnetic-equivalent deposited energy of similar to 15% above 10 TeV.
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| 10. |
- Aartsen, M. G., et al.
(författare)
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IceCube search for dark matter annihilation in nearby galaxies and galaxy clusters
- 2013
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:12
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a first search for self-annihilating dark matter in nearby galaxies and galaxy clusters using a sample of high-energy neutrinos acquired in 339.8 days of live time during 2009/10 with the IceCube neutrino observatory in its 59-string configuration. The targets of interest include the Virgo and Coma galaxy clusters, the Andromeda galaxy, and several dwarf galaxies. We obtain upper limits on the cross section as a function of the weakly interacting massive particle mass between 300 GeV and 100 TeV for the annihilation into b (b) over bar, W+(W) over bar (-), tau(+)tau(-), mu(+)mu(-) , and nu(nu) over bar. A limit derived for the Virgo cluster, when assuming a large effect from subhalos, challenges the weakly interacting massive particle interpretation of a recently observed GeV positron excess in cosmic rays.
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