| 1. |
- 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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| 2. |
- Abolfathi, Bela, et al.
(författare)
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The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
- 2018
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Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
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Tidskriftsartikel (refereegranskat)abstract
- The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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| 3. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 4. |
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| 5. |
- Di Simplicio, Martina, et al.
(författare)
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An investigation of mental imagery in bipolar disorder : Exploring "the mind's eye"
- 2016
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Ingår i: Bipolar Disorders. - : WILEY-BLACKWELL. - 1398-5647 .- 1399-5618. ; 18:8, s. 669-683
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Mental imagery abnormalities occur across psychopathologies and are hypothesized to drive emotional difficulties in bipolar disorder (BD). A comprehensive assessment of mental imagery in BD is lacking. We aimed to test whether (i) mental imagery abnormalities (abnormalities in cognitive stages and subjective domains) occur in BD relative to non-clinical controls; and (ii) to determine the specificity of any abnormalities in BD relative to depression and anxiety disorders. Methods: Participants included 54 subjects in the BD group (depressed/euthymic; n=27 in each subgroup), subjects with unipolar depression (n=26), subjects with anxiety disorders (n=25), and non-clinical controls (n=27) matched for age, gender, ethnicity, education, and premorbid IQ. Experimental tasks assessed cognitive (non-emotional) measures of mental imagery (cognitive stages). Questionnaires, experimental tasks, and a phenomenological interview assessed subjective domains including spontaneous imagery use, interpretation bias, and emotional mental imagery. Results: (i) Compared to non-clinical controls, the BD combined group reported a greater impact of intrusive prospective imagery in daily life, more vivid and "real" negative images (prospective imagery task), and higher self-involvement (picture-word task). The BD combined group showed no clear abnormalities in cognitive stages of mental imagery. (ii) When depressed individuals with BD were compared to the depressed or anxious clinical control groups, no significant differences remained-across all groups, imagery differences were associated with affective lability and anxiety. Conclusions: Compared to non-clinical controls, BD is characterized by abnormalities in aspects of emotional mental imagery within the context of otherwise normal cognitive aspects. When matched for depression and anxiety, these abnormalities are not specific to BD-rather, imagery may reflect a transdiagnostic marker of emotional psychopathology.
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| 6. |
- Fomalont, E. B., et al.
(författare)
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THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
- 2015
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
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Tidskriftsartikel (refereegranskat)abstract
- A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
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| 7. |
- Morris, Simon, et al.
(författare)
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The ELT-MOS (MOSAIC) : towards the construction phase
- 2018
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Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY VII. - : SPIE-INT SOC OPTICAL ENGINEERING. - 9781510619586 ; 10702
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Konferensbidrag (refereegranskat)abstract
- When combined with the huge collecting area of the ELT, MOSAIC will be the most effective and flexible Multi-Object Spectrograph (MOS) facility in the world, having both a high multiplex and a multi-Integral Field Unit (Multi-IFU) capability. It will be the fastest way to spectroscopically follow-up the faintest sources, probing the reionisation epoch, as well as evaluating the evolution of the dwarf mass function over most of the age of the Universe. MOSAIC will be world-leading in generating an inventory of both the dark matter (from realistic rotation curves with MOAO fed NIR IFUs) and the cool to warm-hot gas phases in z=3.5 galactic haloes (with visible wavelenth IFUs). Galactic archaeology and the first massive black holes are additional targets for which MOSAIC will also be revolutionary. MOAO and accurate sky subtraction with fibres have now been demonstrated on sky, removing all low Technical Readiness Level (TRL) items from the instrument. A prompt implementation of MOSAIC is feasible, and indeed could increase the robustness and reduce risk on the ELT, since it does not require diffraction limited adaptive optics performance. Science programmes and survey strategies are currently being investigated by the Consortium, which is also hoping to welcome a few new partners in the next two years.
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| 8. |
- Nicholson, Anna M., et al.
(författare)
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Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium
- 2018
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Ingår i: Cell Stem Cell. - : CELL PRESS. - 1934-5909 .- 1875-9777. ; 22:6, s. 909-918.e8
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the means and timing by which mutations become fixed in the human colonic epithelium by visualizing somatic clones and mathematical inference. Fixation requires two sequential steps. First, one of approximately seven active stem cells residing within each colonic crypt has to be mutated. Second, the mutated stem cell has to replace neighbors to populate the entire crypt in a process that takes several years. Subsequent clonal expansion due to crypt fission is infrequent for neutral mutations (around 0.7% of all crypts undergo fission in a single year). Pro-oncogenic mutations subvert both stem cell replacement to accelerate fixation and clonal expansion by crypt fission to achieve high mutant allele frequencies with age. The benchmarking of these behaviors allows the advantage associated with different gene-specific mutations to be compared irrespective of the cellular mechanisms by which they are conferred.
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| 9. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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