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Sökning: WFRF:(Fox O. D.)

  • Resultat 1031-1040 av 1049
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1031.
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1032.
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1033.
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1034.
  • Voight, Benjamin F., et al. (författare)
  • Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:7, s. 579-589
  • Tidskriftsartikel (refereegranskat)abstract
    • By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
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1035.
  • Woollacott, I. O. C., et al. (författare)
  • Cerebrospinal fluid soluble TREM2 levels in frontotemporal dementia differ by genetic and pathological subgroup
  • 2018
  • Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Reliable biomarkers of frontotemporal dementia (FTD) are currently lacking. FTD may be associated with chronic immune dysfunction, microglial activation and raised inflammatory markers, particularly in progranulin (GRN) mutation carriers. Levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) are elevated in Alzheimer's disease (AD), but they have not been fully explored in FTD. Methods: We investigated whether cerebrospinal fluid (CSF) sTREM2 levels differ between FTD and controls, across different clinical and genetic subtypes of FTD, or between individuals with FTD due to AD versus non-AD pathology (based on CSF neurodegenerative biomarkers). We also assessed relationships between CSF sTREM2 and other CSF biomarkers (total tau [T-tau], tau phosphorylated at position threonine-181 [P-tau] and beta-amyloid 1-42 [A beta 42]) and age and disease duration. Biomarker levels were measured using immunoassays in 17 healthy controls and 64 patients with FTD (behavioural variant FTD, n = 20; primary progressive aphasia, n = 44). Ten of 64 had familial FTD, with mutations in GRN (n = 3), MAPT (n = 4), or C9orf72 (n = 3). Fifteen of 64 had neurodegenerative biomarkers consistent with AD pathology (11 of whom had logopenic variant PPA). Levels were compared using multivariable linear regressions. Results: CSF sTREM2 levels did not differ between FTD and controls or between clinical subgroups. However, GRN mutation carriers had higher levels than controls (mean ([SD] = 9.7 [2.9] vs. 6.8 [1.6] ng/ml; P= 0.028) and MAPT (3.9 [1.5] ng/ml; P= 0.003] or C9orf72 [4.6 [1.8] ng/ml; P=0.006) mutation carriers. Individuals with AD-like CSF had higher sTREM2 levels than those with non-AD-like CSF (9.0 [3.6] vs. 6.9 [3.0] ng/ml; P = 0.029). CSF sTREM2 levels were associated with T-tau levels in control and FTD groups and also with P-tau in those with FTD and AD-like CSF. CSF sTREM2 levels were influenced by both age and disease duration in FTD. Conclusions: Although CSF sTREM2 levels are not raised in FTD overall or in a particular clinical subtype of FTD, levels are raised in familial FTD associated with GRN mutations and in FTD syndromes due to AD pathology. Because CSF sTREM2 levels correlate with a marker of neuronal injury (T-tau), sTREM2 should be explored as a biomarker of disease intensity in future longitudinal studies of FTD.
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1036.
  • Alawode, D. O. T., et al. (författare)
  • Alzheimer's Disease Biomarkers Revisited From the Amyloid Cascade Hypothesis Standpoint
  • 2022
  • Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide. Amyloid beta (A beta) is one of the proteins which aggregate in AD, and its key role in the disease pathogenesis is highlighted in the amyloid cascade hypothesis, which states that the deposition of A beta in the brain parenchyma is a crucial initiating step in the future development of AD. The sensitivity of instruments used to measure proteins in blood and cerebrospinal fluid has significantly improved, such that A beta can now successfully be measured in plasma. However, due to the peripheral production of A beta, there is significant overlap between diagnostic groups. The presence of pathological A beta within the AD brain has several effects on the cells and surrounding tissue. Therefore, there is a possibility that using markers of tissue responses to A beta may reveal more information about A beta pathology and pathogenesis than looking at plasma A beta alone. In this manuscript, using the amyloid cascade hypothesis as a starting point, we will delve into how the effect of A beta on the surrounding tissue can be monitored using biomarkers. In particular, we will consider whether glial fibrillary acidic protein, triggering receptor expressed on myeloid cells 2, phosphorylated tau, and neurofilament light chain could be used to phenotype and quantify the tissue response against A beta pathology in AD.
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1037.
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1038.
  • Dhawan, Suhail, et al. (författare)
  • Magnification, dust, and time-delay constraints from the first resolved strongly lensed Type Ia supernova iPTF16geu
  • 2020
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 491:2, s. 2639-2654
  • Tidskriftsartikel (refereegranskat)abstract
    • We report lensing magnifications, extinction, and time-delay estimates for the first resolved, multiply imaged Type Ia supernova iPTF16geu, at z = 0.409, using Hubble Space Telescope (HST) observations in combination with supporting ground-based data. Multiband photometry of the resolved images provides unique information about the differential dimming due to dust in the lensing galaxy. Using HST and Keck AO reference images taken after the SN faded, we obtain a total lensing magnification for iPTF16geu of mu = 67.8(-2.9)(+2.6), accounting for extinction in the host and lensing galaxy. As expected from the symmetry of the system, we measure very short time-delays for the three fainter images with respect to the brightest one: -0.23 +/- 0.99,-1.43 +/- 0.74, and 1.36 +/- 1.07 d. Interestingly, we find large differences between the magnifications of the four supernova images, even after accounting for uncertainties in the extinction corrections: Delta m(1) = -3.88(-0.06)(+0.07), Delta m(2) = -2.99(-0.08)(+0.09), Delta m(3) = -2.19(-0.15)(+0.14), and Delta m(4) = -2.40(-0.12)(+0.14) mag, discrepant with model predictions suggesting similar image brightnesses. A possible explanation for the large differences is gravitational lensing by substructures, micro- or millilensing, in addition to the large-scale lens causing the image separations. We find that the inferred magnification is insensitive to the assumptions about the dust properties in the host and lens galaxy.
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1039.
  • Gasman, Danny, et al. (författare)
  • JWST MIRI/MRS in-flight absolute flux calibration and tailored fringe correction for unresolved sources
  • 2023
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 673
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The Medium Resolution Spectrometer (MRS) is one of the four observing modes of JWST/MIRI. Using JWST in-flight data of unresolved (point) sources, we can derive the MRS absolute spectral response function (ASRF) starting from raw data. Spectral fringing, caused by coherent reflections inside the detector arrays, plays a critical role in the derivation and interpretation of the MRS ASRF. The fringe corrections implemented in the current pipeline are not optimal for non-extended sources, and a high density of molecular features particularly inhibits an accurate correction. Aims. In this paper, we present an alternative way to calibrate the MIRI/MRS data. Firstly, we derive a fringe correction that accounts for the dependence of the fringe properties on the MIRI/MRS pupil illumination and detector pixel sampling of the point spread function. Secondly, we derive the MRS ASRF using an absolute flux calibrator observed across the full 5- 28 µm wavelength range of the MRS. Thirdly, we apply the new ASRF to the spectrum of a G dwarf and compare it with the output of the JWST/MIRI default data reduction pipeline. Finally, we examine the impact of the different fringe corrections on the detectability of molecular features in the G dwarf and K giant. Methods. The absolute flux calibrator HD 163466 (A-star) was used to derive tailored point source fringe flats at each of the default dither locations of the MRS. The fringe-corrected point source integrated spectrum of HD 163466 was used to derive the MRS ASRF using a theoretical model for the stellar continuum. A cross-correlation was run to quantify the uncertainty on the detection of CO, SiO, and OH in the K giant and CO in the G dwarf for different fringe corrections. Results. The point-source-tailored fringe correction and ASRF are found to perform at the same level as the current corrections, beating down the fringe contrast to the sub-percent level in the G dwarf in the longer wavelengths, whilst mitigating the alteration of real molecular features. The same tailored solutions can be applied to other MRS unresolved targets. Target acquisition is required to ensure the pointing is accurate enough to apply this method. A pointing repeatability issue in the MRS limits the effectiveness of the tailored fringe flats is at short wavelengths. Finally, resulting spectra require no scaling to make the sub-bands match, and a dichroic spectral leak at 12.2 µm is removed.
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1040.
  • Graham, M. L., et al. (författare)
  • Delayed Circumstellar Interaction for Type Ia SN 2015cp Revealed by an HST Ultraviolet Imaging Survey
  • 2019
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 871:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The nature and role of the binary companion of carbon-oxygen white dwarf stars that explode as Type Ia supernovae (SNe Ia) are not yet fully understood. Past detections of circumstellar material (CSM) that contain hydrogen for a small number of SN Ia progenitor systems suggest that at least some have a nondegenerate companion. In order to constrain the prevalence, location, and quantity of CSM in SN Ia systems, we performed a near-ultraviolet (NUV) survey with the Hubble Space Telescope (HST) to look for the high-energy signature of SN Ia ejecta interacting with the CSM. Our survey revealed that SN 2015cp, an SN 1991T-like overluminous SN Ia, was experiencing late-onset interaction between its ejecta and the surrounding CSM 664 days after its light-curve peak. We present ground-and space-based follow-up observations of SN. 2015cp that reveal optical emission lines of H and Ca, typical signatures of ejecta-CSM interaction. We show how SN. 2015cp was likely similar to the well-studied SN Ia-CSM event PTF11kx, making it the second case in which an unambiguously classified SN Ia was observed to interact with a distant shell of CSM that contains hydrogen (R-CSM greater than or similar to 10(16) cm). The remainder of our HST NUV images of SNe Ia were nondetections that we use to constrain the occurrence rate of observable late-onset CSM interaction. We apply theoretical models for the emission from ejecta-CSM interaction to our NUV nondetections and place upper limits on the mass and radial extent of CSM in SN Ia progenitor systems.
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