| 1. |
- Vogel, Jacob W., et al.
(författare)
-
Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Zhou, XP, et al.
(författare)
-
Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
|
|
| 7. |
|
|
| 8. |
- Wang, Li-San, et al.
(författare)
-
Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
-
Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
-
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.
|
|
| 9. |
- Abellán, C., et al.
(författare)
-
Challenging Local Realism with Human Choices
- 2018
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 557, s. 212-216
-
Tidskriftsartikel (refereegranskat)abstract
- A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings. Although technology can satisfy the first two of these requirements, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests. Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology. The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons, single atoms, atomic ensembles and superconducting devices. Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bi-partite and tri-partite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties), the utilization of video-game methods for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Hillier, J. K., et al.
(författare)
-
Manual mapping of drumlins in synthetic landscapes to assess operator effectiveness
- 2015
-
Ingår i: Journal of Maps. - : Informa UK Limited. - 1744-5647. ; 11:5, s. 719-729
-
Tidskriftsartikel (refereegranskat)abstract
- Mapped topographic features are important for understanding processes that sculpt the Earth's surface. This paper presents maps that are the primary product of an exercise that brought together 27 researchers with an interest in landform mapping wherein the efficacy and causes of variation in mapping were tested using novel synthetic DEMs containing drumlins. The variation between interpreters (e.g. mapping philosophy, experience) and across the study region (e.g. woodland prevalence) opens these factors up to assessment. A priori known answers in the synthetics increase the number and strength of conclusions that may be drawn with respect to a traditional comparative study. Initial results suggest that overall detection rates are relatively low (34-40%), but reliability of mapping is higher (72-86%). The maps form a reference dataset.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Kim, Keunho J., et al.
(författare)
-
Small Region, Big Impact : Highly Anisotropic Lyman-continuum Escape from a Compact Starburst Region with Extreme Physical Properties
- 2023
-
Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 955:1
-
Tidskriftsartikel (refereegranskat)abstract
- Extreme, young stellar populations are considered to be the primary contributor to cosmic reionization. How the Lyman continuum (LyC) escapes these galaxies remains highly elusive, and it is challenging to observe this process in actual LyC emitters without resolving the relevant physical scales. We investigate the Sunburst Arc, a strongly lensed LyC emitter at z = 2.37 that reveals an exceptionally small-scale (tens of parsecs) region of high LyC escape. The small (<100 pc) LyC-leaking region has extreme properties: a very blue UV slope (β = −2.9 ± 0.1), a high ionization state ([O iii] λ5007/[O ii] λ3727 = 11 ± 3 and [O iii] λ5007/Hβ = 6.8 ± 0.4), strong oxygen emission (EW([O iii]) = 1095 ± 40 Å), and a high Lyα escape fraction (0.3 ± 0.03), none of which are found in nonleaking regions of the galaxy. The leaking region's UV slope is consistent with approximately "pure" stellar light that is minimally contaminated by the surrounding nebular continuum emission or extinguished by dust. These results suggest a highly anisotropic LyC escape process such that LyC is produced and escapes from a small, extreme starburst region where the stellar feedback from an ionizing star cluster creates one or more "pencil-beam" channels in the surrounding gas through which LyC can directly escape. Such anisotropic escape processes imply that random sight-line effects drive the significant scatters between measurements of galaxy properties and LyC escape fraction, and that strong lensing is a critical tool for resolving the processes that regulate the ionizing budget of galaxies for reionization.
|
|
| 18. |
- Krabbendam, Maarten, et al.
(författare)
-
Drag forces at the ice-sheet bed and resistance of hard-rock obstacles : the physics of glacial ripping
- 2023
-
Ingår i: Journal of Glaciology. - : Cambridge University Press (CUP). - 0022-1430 .- 1727-5652. ; 69:273, s. 103-119
-
Tidskriftsartikel (refereegranskat)abstract
- Glacial ripping involves glaciotectonic disintegration of rock hills and extensive removal of rock at the ice-sheet bed, triggered by hydraulic jacking caused by fluctuating water pressures. Evidence from eastern Sweden shows that glacial ripping caused significant subglacial erosion during the final deglaciation of the Fennoscandian ice sheet, distinct from abrasion and plucking (quarrying). Here we analyse the ice drag forces exerted onto rock obstacles at the base of an ice sheet, and the resisting forces of such rock obstacles: glaciotectonic disintegration requires that ice drag forces exceed the resisting forces of the rock obstacle. We consider rock obstacles of different sizes, shapes and fracture patterns, informed by natural examples from eastern Sweden. Our analysis shows that limited overpressure events, unfavourable fracture patterns, low-transmissivity fractures, slow ice and streamlined rock hamper rock hill disintegration. Conversely, under fast ice flow and fluctuating water pressures, disintegration is possible if the rock hill contains subhorizontal, transmissive fractures. Rock steps on previously smooth, abraded surfaces, caused by hydraulic jacking, also enhance drag forces and can cause disintegration of a rock hill. Glacial ripping is a physically plausible erosion mechanism, under realistic glaciological conditions prevalent near ice margins.
|
|
| 19. |
|
|
