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| 3. |
- 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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| 4. |
- Belotelov, V. I., et al.
(författare)
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Magnetophotonic intensity effects in hybrid metal-dielectric structures
- 2014
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 89:4, s. 045118-
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Tidskriftsartikel (refereegranskat)abstract
- The magneto-optical properties of a hybrid metal-dielectric structure consisting of a one-dimensional gold grating on top of a magnetic waveguide layer are studied experimentally and theoretically. It is demonstrated that a magnetic field applied in the longitudinal configuration (in the plane of the magnetic film and perpendicular to the slits in the gold grating) to the metal-dielectric structure modifies the field distribution of the optical modes and thus changes the mode excitation conditions. In the optical far field, this manifests in the alteration of the optical transmittance or reflectance when the structure becomes magnetized. This magneto-optical effect is shown to represent a novel class of effects related to the magnetic-field-induced modification of the Bloch modes of the periodic hybrid structure. That is why we define this effect as "longitudinal magnetophotonic intensity effect" (LMPIE). The LMPIE has two contributions, odd and even in magnetization. While the even LMPIE is maximal for the light polarized perpendicular to the grating slits (TM) and minimal for the orthogonal polarization (TE), the odd LMPIE takes maximum values at some intermediate polarization and vanishes for pure TM and TE polarizations. Two principal modes of the magnetic layer - TM and TE - acquire in the longitudinal magnetic field additional field components and thus turn into quasi-TM and quasi-TE modes, respectively. The largest LMPIE is observed for excitation of the antisymmetrical quasi-TE mode by TM-polarized light. The value of the LMPIE measured for the plasmonic structure with a magnetic film of Bi2Dy1Fe4Ga1O12 composition is about 1% for the even effect and 2% for the odd one. However, the plasmonic structure with a magnetic film with a higher concentration of bismuth (Bi2.97Er0.03Fe4Al0.5Ga0.5O12) gives significantly larger LMPIE: even LMPIE reaches 24% and odd LMPIE is 9%. Enhancement of the magneto-optical figure of merit (defined as the ratio of the specific Faraday angle of a magnetic film to its absorption coefficient) of the magnetic films potentially causes the even LMPIE to exceed 100% as is predicted by calculations. Thus, the nanostructured material described here may be considered as an ultrafast magnetophotonic light valve.
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- Belotelov, V. I., et al.
(författare)
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Plasmon-mediated magneto-optical transparency
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 2128-
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic field control of light is among the most intriguing methods for modulation of light intensity and polarization on sub-nanosecond timescales. The implementation in nanostructured hybrid materials provides a remarkable increase of magneto-optical effects. However, so far only the enhancement of already known effects has been demonstrated in such materials. Here we postulate a novel magneto-optical phenomenon that originates solely from suitably designed nanostructured metal-dielectric material, the so-called magneto-plasmonic crystal. In this material, an incident light excites coupled plasmonic oscillations and a waveguide mode. An in-plane magnetic field allows excitation of an orthogonally polarized waveguide mode that modifies optical spectrum of the magneto-plasmonic crystal and increases its transparency. The experimentally achieved light intensity modulation reaches 24%. As the effect can potentially exceed 100%, it may have great importance for applied nanophotonics. Further, the effect allows manipulating and exciting waveguide modes by a magnetic field and light of proper polarization.
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- Collins, P., et al.
(författare)
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The LHCb VELO upgrade
- 2011
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 636, s. S185-S193
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Tidskriftsartikel (refereegranskat)abstract
- The LHCb experiment at the LHC plans to massively increase its data taking capabilities by running at a higher luminosity with a fully upgraded detector around 2016. This scheme is independent of (but compatible with) the plans for the SLHC upgrades. The silicon detector will be upgraded to provide a 40 MHz readout and to be able to cope with the increased radiation environment. This paper describes the options currently under consideration. A highlight of the R&D so far undertaken is a beam test during summer 2009 using the Timepix chip to track charged particles. Preliminary results are presented, including a measurement of the resolution achieved by the 55 mu m pitch pixel array of better than 9.5 mu m for perpendicular tracks and 55 mu m for angled tracks.
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| 7. |
- Kalimo, Hannu, et al.
(författare)
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The Arctic AβPP mutation leads to Alzheimer's disease pathology with highly variable topographic deposition of differentially truncated Aβ
- 2013
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Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 1:1, s. 60-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Arctic mutation (p.E693G/p.E22G)fs within the β-amyloid (Aβ) region of the β-amyloid precursor protein gene causes an autosomal dominant disease with clinical picture of typical Alzheimer's disease. Here we report the special character of Arctic AD neuropathology in four deceased patients.RESULTS: Aβ deposition in the brains was wide-spread (Thal phase 5) and profuse. Virtually all parenchymal deposits were composed of non-fibrillar, Congo red negative Aβ aggregates. Congo red only stained angiopathic vessels. Mass spectrometric analyses showed that Aβ deposits contained variably truncated and modified wild type and mutated Aβ species. In three of four Arctic AD brains, most cerebral cortical plaques appeared targetoid with centres containing C-terminally (beyond aa 40) and variably N-terminally truncated Aβ surrounded by coronas immunopositive for Aβx-42. In the fourth patient plaque centres contained almost no Aβ making the plaques ring-shaped. The architectural pattern of plaques also varied between different anatomic regions. Tau pathology corresponded to Braak stage VI, and appeared mainly as delicate neuropil threads (NT) enriched within Aβ plaques. Dystrophic neurites were scarce, while neurofibrillary tangles were relatively common. Neuronal perikarya within the Aβ plaques appeared relatively intact.CONCLUSIONS: In Arctic AD brain differentially truncated abundant Aβ is deposited in plaques of variable numbers and shapes in different regions of the brain (including exceptional targetoid plaques in neocortex). The extracellular non-fibrillar Aβ does not seem to cause overt damage to adjacent neurons or to induce formation of neurofibrillary tangles, supporting the view that intracellular Aβ oligomers are more neurotoxic than extracellular Aβ deposits. However, the enrichment of NTs within plaques suggests some degree of intra-plaque axonal damage including accumulation of hp-tau, which may impair axoplasmic transport, and thereby contribute to synaptic loss. Finally, similarly as the cotton wool plaques in AD resulting from exon 9 deletion in the presenilin-1 gene, the Arctic plaques induced only modest glial and inflammatory tissue reaction.
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- Comadran, J., et al.
(författare)
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Natural variation in a homolog of Antirrhinum CENTRORADIALIS contributed to spring growth habit and environmental adaptation in cultivated barley
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:12, s. 1388-1392
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Tidskriftsartikel (refereegranskat)abstract
- As early farming spread from the Fertile Crescent in the Near East around 10,000 years before the present(1), domesticated crops encountered considerable ecological and environmental change. Spring-sown crops that flowered without the need for an extended period of cold to promote flowering and day length insensitive crops able to exploit the longer, cooler days of higher latitudes emerged and became established. To investigate the genetic consequences of adaptation to these new environments, we identified signatures of divergent selection in the highly differentiated modern-day spring and winter barleys. In one genetically divergent region, we identify a natural variant of the barley homolog of Antirrhinum CENTRORADIALIS(2) (HvCEN) as a contributor to successful environmental adaptation. The distribution of HvCEN alleles in a large collection of wild and landrace accessions indicates that this involved selection and enrichment of preexisting genetic variants rather than the acquisition of mutations after domestication.
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| 9. |
- Graafsma, Heinz, et al.
(författare)
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PERCIVAL soft X-ray imager
- 2013
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Ingår i: IEEE Nuclear Science Symposium Conference Record. - : IEEE conference proceedings. - 9781479905348 ; , s. Art. no. 6829506-
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Konferensbidrag (refereegranskat)abstract
- Our goal is to provide the scientific community with a large (10cm × 10cm) pixellated detector featuring a large dynamic range (1-105 photons), good spatial resolution (27μm), good Quantum Efficiency (QE) in the low energy range (250eV-1keV), variable readout speed (up to 120 frames/s), i.e. with characteristics compatible with user needs at today's of low-energy Free Electron Lasers (FEL) and synchrotron sources. © 2013 IEEE.
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| 10. |
- Wunderer, C. B., et al.
(författare)
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The PERCIVAL soft X-ray imager
- 2014
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Ingår i: Journal of Instrumentation. - 1748-0221 .- 1748-0221. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- With the increased brilliance of state-of-the-art Synchrotron radiation sources and the advent of Free Electron Lasers enabling revolutionary science with EUV to X-ray photons comes an urgent need for suitable photon imaging detectors. Requirements include high frame rates, very large dynamic range, single-photon counting capability with low probability of false positives, and (multi)-megapixels. PERCIVAL (''Pixelated Energy Resolving CMOS Imager, Versatile and Large'') is currently being developed by a collaboration of DESY, RAL, Elettra and DLS to address this need for the soft X-ray regime. PERCIVAL is a monolithic active pixel sensor (MAPS), i.e. based on CMOS technology. It will be back-thinned to access its primary energy range of 250 eV to 1 keV with target efficiencies above 90%. According to its preliminary specifications, the roughly 10 × 10 cm2, 3520 × 3710 pixel monolithic sensor will operate at frame rates up to 120 Hz (commensurate with most FELs) and use multiple gains within its 27 μm pixels to measure (e.g. at 500 eV) 1 to ∼ 105 simultaneously-arriving photons. Currently, small-scale front-illuminated prototype systems (160 × 210 pixels) are undergoing detailed testing with visible-light as well as X-ray photons. © 2014 IOP Publishing Ltd and Sissa Medialab srl.
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