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| 10. |
- Egron, E., et al.
(författare)
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Single-dish and VLBI observations of Cygnus X-3 during the 2016 giant flare episode
- 2017
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 471:3, s. 2703-2714
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Tidskriftsartikel (refereegranskat)abstract
- In 2016 September, the microquasar Cygnus X-3 underwent a giant radio flare, which was monitored for 6 d with the Medicina Radio Astronomical Station and the Sardinia Radio Telescope. Long observations were performed in order to follow the evolution of the flare on an hourly scale, covering six frequency ranges from 1.5 to 25.6 GHz. The radio emission reached a maximum of 13.2 +/- 0.7 Jy at 7.2 GHz and 10 +/- 1 Jy at 18.6 GHz. Rapid flux variations were observed at high radio frequencies at the peak of the flare, together with rapid evolution of the spectral index: a steepened from 0.3 to 0.6 (with S-nu alpha nu(-alpha)) within 5 h. This is the first time that such fast variations are observed, giving support to the evolution from optically thick to optically thin plasmons in expansion moving outward from the core. Based on the Italian network (Noto, Medicina and SRT) and extended to the European antennas (Torun, Yebes, Onsala), very long baseline interferometry (VLBI) observations were triggered at 22 GHz on five different occasions, four times prior to the giant flare, and once during its decay phase. Flux variations of 2 h duration were recorded during the first session. They correspond to a mini-flare that occurred close to the core 10 d before the onset of the giant flare. From the latest VLBI observation we infer that 4 d after the flare peak the jet emission was extended over 30 mas.
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| 11. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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- Daranciang, Dan, et al.
(författare)
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Ultrafast Photovoltaic Response in Ferroelectric Nanolayers
- 2012
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Ingår i: Physical Review Letters. - 1079-7114. ; 108:8
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Tidskriftsartikel (refereegranskat)abstract
- We show that light drives large-amplitude structural changes in thin films of the prototypical ferroelectric PbTiO3 via direct coupling to its intrinsic photovoltaic response. Using time-resolved x-ray scattering to visualize atomic displacements on femtosecond time scales, photoinduced changes in the unit-cell tetragonality are observed. These are driven by the motion of photogenerated free charges within the ferroelectric and can be simply explained by a model including both shift and screening currents, associated with the displacement of electrons first antiparallel to and then parallel to the ferroelectric polarization direction.
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| 16. |
- Kalaria, Raj, et al.
(författare)
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The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.
- 2024
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.
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| 17. |
- Kovacs, Gabor G., et al.
(författare)
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Aging-related tau astrogliopathy (ARTAG) : harmonized evaluation strategy
- 2016
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 131:1, s. 87-102
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Tidskriftsartikel (refereegranskat)abstract
- Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.
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| 18. |
- Rich, Rebecca L., et al.
(författare)
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A global benchmark study using affinity-based biosensors
- 2009
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
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Tidskriftsartikel (refereegranskat)abstract
- To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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| 19. |
- Uitterlinden, André G, et al.
(författare)
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The association between common vitamin D receptor gene variations and osteoporosis : a participant-level meta-analysis
- 2006
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Ingår i: Annals of Internal Medicine. - 0003-4819. ; 145:4, s. 255-264
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear.OBJECTIVE: To evaluate the relation between VDR polymorphisms, BMD, and fractures.DESIGN: Prospective multicenter large-scale association study.SETTING: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams.PARTICIPANTS: 26,242 participants (18,405 women).MEASUREMENTS: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures.RESULTS: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model).LIMITATIONS: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis.CONCLUSIONS: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures.
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| 20. |
- Kovacs, Gabor G., et al.
(författare)
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Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG)
- 2017
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Ingår i: Journal of Neuropathology and Experimental Neurology. - : Oxford University Press (OUP). - 0022-3069 .- 1554-6578. ; 76:7, s. 605-619
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Tidskriftsartikel (refereegranskat)abstract
- Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was > 60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (> 90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.
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| 21. |
- Quétel, C. R., et al.
(författare)
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Methylmercury in tuna: demonstrating measurement capabilities and evaluating comparability of results worldwide from the CCQM P-39 comparison
- 2005
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Ingår i: Journal of Analytical Atomic Spectrometry. - : Royal Society of Chemistry (RSC). - 0267-9477 .- 1364-5544. ; 20, s. 1058-66
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Tidskriftsartikel (refereegranskat)abstract
- Six metrology institutes (NMIs) representing at the Comité International des Poids et Mesures (CIPM) 4 Member States of the Metre Convention and 2 international organisations, and 8 expert laboratories selected outside CIPM have compared their capabilities to quantitatively measure methylmercury (MeHg) in a prepared tuna material containing approximately 4.3 mg kg–1 Hg. This comparison was the object of the CIPM–Comité Consultatif pour la Quantité de Matière (CCQM) Pilot Study 39, organised by the Institute for Reference Materials and Measurements (IRMM), from the European Commission—Joint Research Centre. Beside the test material itself, a bottle of the BCR-464 tuna Certified Reference Material (CRM) and an ampoule of IRMM-670, a 202Hg isotope enriched MeHg candidate isotopic CRM, were distributed to all participants, who were free to apply the measurement strategy of their choice. Four, including 1 NMI, relied on external calibration or the method of standard additions, whereas the other 10 implemented an isotope dilution mass spectrometry (IDMS) approach and chose to use the IRMM-670 for their measurements. Alkaline digestion at room temperature (with manual shaking) or high temperature (under sonication, oven or hot plate conditions) was employed by most participants, with hydrochloric acid leaching the second most popular choice. Alkylation (4 phenylations, 4 ethylations and 3 propylations) in the aqueous phase was preferred by a large majority over butylation by the Grignard reaction. All participants were requested to estimate the uncertainty associated with their results and 9 out of 14 stated relative combined uncertainties below 6%(k= 2). Despite this apparent consensus, the perception of which factor caused the largest contribution to this estimation differed among participants because of the differences in the analytical methodologies deployed but also because of wide differences of the concepts of uncertainty estimation. The mixture mode(MM) median, calculated also from the measurement uncertainties stated by the participants, was 1.967 ± 0.204 × 10–5 mol kg–1(95% confidence). Twelve of the results were re-grouped within a range of less than 0.3 × 10–5 mol kg–1(MM median = 1.967 ± 0.162 × 10–5 mol kg–1, 95% confidence): they nearly all (1 exception) overlapped with each other within k= 2 stated uncertainties. For the other 2 results the uncertainty seemed to have been particularly underestimated as they lay, respectively, at more than 20% above and less than –40% below the overall average. The relative standard deviation of the results of 9 laboratories out of the 10 that applied IDMS was about 2.6%. It can be assumed from the degree of equivalence shown by 12 out of 14 study participants that, at present, laboratories worldwide are potentially able to supply accurate results for MeHg in fish-type matrices (containing about 2 × 10–5 mol kg–1) within ±10% uncertainty. This encouraging outcome permitted scheduling of a follow-up CCQM-K43 key comparison for a lower MeHg content level in salmon tissues.
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| 22. |
- Rosenberg, G. A., et al.
(författare)
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Consensus statement for diagnosis of subcortical small vessel disease
- 2016
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 36:1, s. 6-25
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Tidskriftsartikel (refereegranskat)abstract
- Vascular cognitive impairment (VCI) is the diagnostic term used to describe a heterogeneous group of sporadic and hereditary diseases of the large and small blood vessels. Subcortical small vessel disease (SVD) leads to lacunar infarcts and progressive damage to the white matter. Patients with progressive damage to the white matter, referred to as Binswanger's disease (BD), constitute a spectrum from pure vascular disease to a mixture with neurodegenerative changes. Binswanger's disease patients are a relatively homogeneous subgroup with hypoxic hypoperfusion, lacunar infarcts, and inflammation that act synergistically to disrupt the blood-brain barrier (BBB) and break down myelin. Identification of this subgroup can be facilitated by multimodal disease markers obtained from clinical, cerebrospinal fluid, neuropsychological, and imaging studies. This consensus statement identifies a potential set of biomarkers based on underlying pathologic changes that could facilitate diagnosis and aid patient selection for future collaborative treatment trials.
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| 24. |
- Connors, R. M. T., et al.
(författare)
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Combining timing characteristics with physical broad-band spectral modelling of black hole X-ray binary GX 339-4
- 2019
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 485:3, s. 3696-3714
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Tidskriftsartikel (refereegranskat)abstract
- GX 339-4 is a black hole X-ray binary that is a key focus of accretion studies, since it goes into outburst roughly every 2-3 yr. Tracking of its radio, infrared (IR), and X-ray flux during multiple outbursts reveals tight broad-band correlations. The radio emission originates in a compact, self-absorbed jet; however, the origin of the X-ray emission is still debated: jet base or corona? We fit 20 quasi-simultaneous radio, IR, optical, and X-ray observations of GX 339-4 covering three separate outbursts in 2005, 2007, 2010-2011, with a composite corona+jet model, where inverse Compton emission from both regions contributes to the X-ray emission. Using a recently proposed identifier of the X-ray variability properties known as power-spectral hue, we attempt to explain both the spectral and evolving timing characteristics, with the model. We find the X-ray spectra are best fit by inverse Compton scattering in a dominant hot corona (kT(e) similar to hundreds of keV). However, radio and IR-optical constraints imply a non-negligible contribution from inverse Compton scattering off hotter electrons (kT(e) >= 511 keV) in the base of the jets, ranging from a few up to similar to 50 per cent of the integrated 3-100 keV flux. We also find that the physical properties of the jet show interesting correlations with the shape of the broad-band X-ray variability of the source, posing intriguing suggestions for the connection between the jet and corona.
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