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| 5. |
- 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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| 6. |
- Alcorn, J, et al.
(författare)
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Basic instrumentation for Hall A at Jefferson Lab
- 2004
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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. ; 522:3, s. 294-346
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Tidskriftsartikel (refereegranskat)abstract
- The instrumentation in Hall A at the Thomas Jefferson National Accelerator Facility was designed to study electro-and photo-induced reactions at very high luminosity and good momentum and angular resolution for at least one of the reaction products. The central components of Hall A are two identical high resolution spectrometers, which allow the vertical drift chambers in the focal plane to provide a momentum resolution of better than 2 x 10(-4). A variety of Cherenkov counters, scintillators and lead-glass calorimeters provide excellent particle identification. The facility has been operated successfully at a luminosity well in excess of 10(38) CM-2 s(-1). The research program is aimed at a variety of subjects, including nucleon structure functions, nucleon form factors and properties of the nuclear medium. (C) 2003 Elsevier B.V. All rights reserved.
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| 7. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 8. |
- Zhu, L Y, et al.
(författare)
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Cross section measurements of charged pion photoproduction in hydrogen and deuterium from 1.1 to 5.5 GeV
- 2005
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 71:4
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Tidskriftsartikel (refereegranskat)abstract
- The differential cross sections for the gamma n ->pi(-)p and the gamma p ->pi(+)n processes were measured at Jefferson Lab. The photon energies ranged from 1.1 to 5.5 GeV, corresponding to center-of-mass energies from 1.7 to 3.4 GeV. The pion center-of-mass angles varied from 50(degrees) to 110(degrees). The pi(-) and pi(+) photoproduction data both exhibit a global scaling behavior at high energies and high transverse momenta, consistent with the constituent counting rule prediction and the existing pi(+) data. The data suggest possible substructure of the scaling behavior, which might be oscillations around the scaling value. The data show an enhancement in the scaled cross section at center-of-mass energy near 2.2 GeV. The differential cross section ratios [d sigma/dt(gamma n ->pi(-)p)/d sigma/dt(gamma p ->pi(+)n)] at high energies and high transverse momenta can be described by calculations based on one-hard-gluon-exchange diagrams.
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| 9. |
- Dutta, D, et al.
(författare)
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Nuclear transparency with the gamma n ->pi(-)p process in He-4
- 2003
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 68:2: 021001
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Tidskriftsartikel (refereegranskat)abstract
- We have measured the nuclear transparency of the fundamental process gamman-->pi(-)p in He-4. These measurements were performed at Jefferson Lab in the photon energy range of 1.6-4.5 GeV and at theta(cm)(pi)=70degrees and 90degrees. These measurements are the first of their kind in the study of nuclear transparency in photoreactions. They also provide a benchmark test of Glauber calculations based on traditional models of nuclear physics. The transparency results suggest deviations from the traditional nuclear physics picture. The momentum transfer dependence of the measured nuclear transparency is consistent with Glauber calculations that include the quantum chromodynamics phenomenon of color transparency.
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| 11. |
- Zhu, LY, et al.
(författare)
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Cross-section measurement of charged-pion photoproduction from hydrogen and deuterium
- 2003
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Ingår i: Physical Review Letters. - 1079-7114. ; 91:2: 022003
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Tidskriftsartikel (refereegranskat)abstract
- We have measured the differential cross section for the gamman-->pi(-)p and gammap-->pi(+)n reactions at theta(c.m.)=90degrees in the photon energy range from 1.1 to 5.5 GeV at Jefferson Lab (JLab). The data at E(gamma)greater than or similar to3.3 GeV exhibit a global scaling behavior for both pi(-) and pi(+) photoproduction, consistent with the constituent counting rule and the existing pi(+) photoproduction data. Possible oscillations around the scaling value are suggested by these new data. The data show enhancement in the scaled cross section at a center-of-mass energy near 2.2 GeV. The cross section ratio of exclusive pi(-) to pi(+) photoproduction at high energy is consistent with the prediction based on one-hard-gluon-exchange diagrams.
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| 12. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 13. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 14. |
- Lambert, J-C, et al.
(författare)
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Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease
- 2013
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 18:4, s. 461-470
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Tidskriftsartikel (refereegranskat)abstract
- Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n = 2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 x 10(-10)). We finally searched for association between SNPs within the FRMD4A locus and A beta plasma concentrations in three independent non-demented populations (n = 2579). We reported that polymorphisms were associated with plasma A beta 42/A beta 40 ratio (best signal, P=5.4 x 10(-7)). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.
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| 15. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 19. |
- Matthia, D., et al.
(författare)
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Temporal and spatial evolution of the solar energetic particle event on 20 January 2005 and resulting radiation doses in aviation
- 2009
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 114:8, s. A08104 (art no)-
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Tidskriftsartikel (refereegranskat)abstract
- The solar energetic particle event on 20 January 2005 was one of the largest ground level events ever observed. Neutron monitor stations in the Antarctic recorded count rate increases of several thousand percent caused by secondary energetic particles, and it took more than 36 h to return to background level. Such huge increases in high energetic solar cosmic radiation on the ground are obviously accompanied by considerable changes in the radiation environment at aviation altitudes. Measurements of 28 neutron monitor stations were used in this work to numerically approximate the primary solar proton spectra during the first 12 h of the event by minimizing the differences between measurements and the results of Monte-Carlo calculated count rate increases. The primary spectrum of solar energetic protons was approximated by a power law in rigidity and a linear angular distribution. The incoming direction of the solar energetic particles was determined and compared to the interplanetary magnetic field direction during the event. The effects on the radiation exposure at altitudes of about 12 km during that time were estimated to range from none at low latitudes up to almost 2 mSv/h for a very short time in the Antarctic region and about 0.1 mSv/h at high latitudes on the Northern Hemisphere. After 12 h, dose rates were still increased by 50% at latitudes above 60 degrees whereas no increases at all occurred at latitudes below 40 degrees during the whole event.
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| 20. |
- Matthiä, Daniel, et al.
(författare)
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The Ground Level Event 70 on December 13th, 2006 and Related Effective Doses at Aviation Altitudes
- 2009
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Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 136:4, s. 304-310
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Tidskriftsartikel (refereegranskat)abstract
- The 70th ground level event in the records of the Neutron Monitor network occurred on 13 December 2006 reaching a maximum count rate increase at the Oulu station of more than 90% during the 5 min interval 3.05-3.10 UTC. Thereafter, count rates gradually decreased registering increases of a few per cent above the galactic cosmic ray background after a few hours. The primary proton spectrum during the first 6 h after the onset of the event is characterised in this work by fitting the energy and angular distribution by a power law in rigidity and a linear dependence in the pitch angle using a minimisation technique. The results were obtained by analysing the data from 28 Neutron Monitor stations. At very high northern and southern latitudes, the effective dose rates were estimated to reach values of 25-30 mu Sv h(-1) at atmospheric depth of 200 g cm(-2) during the maximum of the event. The increase in effective dose during north atlantic and polar flights was estimated to be in the order of 20 %.
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- Waligórski, M P R, et al.
(författare)
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Cellular parameters for track structure modeling of radiation hazard in space.
- 2004
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Ingår i: Adv Space Res. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 34:6, s. 1378-82
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Tidskriftsartikel (refereegranskat)abstract
- Based on irradiation with 45 MeV/u N and B ions and with Co-60 c rays, cellular parameters of Katz’s track structure modelhave been fitted for the survival of V79-379A Chinese hamster lung fibroblasts. Cellular parameters representing neoplastictransformations in C3H10T/1/2 cells after their irradiation with heavy ion beams, taken from earlier work, were also used to modelthe radiation hazard in deep space, following the system for evaluating, summing and reporting occupational exposures proposed in1967 by a subcommittee of NCRP. We have performed model calculations of the number of transformations in surviving cells, aftera given fluence of heavy charged particles of initial energy 500 MeV/u, penetrating thick layers of cells. We take the product of celltransformation and survival probabilities, calculated along the path lengths of charged particles using cellular survival and transformationparameters, to represent a quantity proportional to the ‘‘radiation risk factor’’ discussed in the NCRP document. The‘‘synergistic’’ effect of simultaneous charged particle transfers is accounted for by the ‘‘track overlap’’ mode inherent in the model ofKatz.
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