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- van Bragt, JJMH, et al.
(author)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Journal article (peer-reviewed)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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- Dedkov, Y S, et al.
(author)
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Correlations in the electronic structure of half-metallic ferromagnetic CrO2 films: An x-ray absorption and resonant photoemission spectroscopy study
- 2005
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In: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121. ; 72:6
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Journal article (peer-reviewed)abstract
- The electronic structure of high-quality CrO2(100) films was investigated by means of x-ray absorption and resonant photoemission spectroscopy at the 2p-3d excitation threshold. The obtained binding energy of the occupied Cr 3d states is in agreement with the results predicted within the local spin-density approximation using the dynamical mean-field theory [L. Craco , Phys. Rev. Lett. 90, 237203 (2003)]. The reported data support a model of CrO2 as a half-metallic ferromagnet with strong electron-correlation effects.
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| 18. |
- Wagner, J., et al.
(author)
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First 230? : GHz VLBI fringes on 3C 279 using the APEX Telescope (Research Note)
- 2015
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 581
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Journal article (peer-reviewed)abstract
- Aims. We report about a 230? GHz very long baseline interferometry (VLBI) fringe finder observation of blazar 3C 279 with the APEX telescope in Chile, the phased submillimeter array (SMA), and the SMT of the Arizona Radio Observatory (ARO). Methods. We installed VLBI equipment and measured the APEX station position to 1? cm accuracy (1σ). We then observed 3C 279 on 2012 May 7 in a 5? h 230? GHz VLBI track with baseline lengths of 2800? Mλ to 7200? Mλ and a finest fringe spacing of 28.6? μas. Results. Fringes were detected on all baselines with signal-to-noise ratios of 12 to 55 in 420? s. The correlated flux density on the longest baseline was ∼0.3? Jy beam-1, out of a total flux density of 19.8? Jy. Visibility data suggest an emission region ≤ 38? μas in size, and at least two components, possibly polarized. We find a lower limit of the brightness temperature of the inner jet region of about 1010? K. Lastly, we find an upper limit of 20% on the linear polarization fraction at a fringe spacing of ∼ 38? μas. Conclusions. With APEX the angular resolution of 230? GHz VLBI improves to 28.6? μas. This allows one to resolve the last-photon ring around the Galactic Center black hole event horizon, expected to be 40? μas in diameter, and probe radio jet launching at unprecedented resolution, down to a few gravitational radii in galaxies like M 87. To probe the structure in the inner parsecs of 3C 279 in detail, follow-up observations with APEX and five other mm-VLBI stations have been conducted (March 2013) and are being analyzed.
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| 19. |
- Burmann, Björn Marcus, 1979, et al.
(author)
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Regulation of alpha-synuclein by chaperones in mammalian cells
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 577:7788, s. 127-32
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Journal article (peer-reviewed)abstract
- Neurodegeneration in patients with Parkinson's disease is correlated with the occurrence of Lewy bodies-intracellular inclusions that contain aggregates of the intrinsically disordered protein alpha-synuclein(1). The aggregation propensity of alpha-synuclein in cells is modulated by specific factors that include post-translational modifications(2,3), Abelson-kinase-mediated phosphorylation(4,5) and interactions with intracellular machineries such as molecular chaperones, although the underlying mechanisms are unclear(6-8). Here we systematically characterize the interaction of molecular chaperones with alpha-synuclein in vitro as well as in cells at the atomic level. We find that six highly divergent molecular chaperones commonly recognize a canonical motif in alpha-synuclein, consisting of the N terminus and a segment around Tyr39, and hinder the aggregation of alpha-synuclein. NMR experiments(9) in cells show that the same transient interaction pattern is preserved inside living mammalian cells. Specific inhibition of the interactions between alpha-synuclein and the chaperone HSC70 and members of the HSP90 family, including HSP90 beta, results in transient membrane binding and triggers a remarkable re-localization of alpha-synuclein to the mitochondria and concomitant formation of aggregates. Phosphorylation of alpha-synuclein at Tyr39 directly impairs the interaction of alpha-synuclein with chaperones, thus providing a functional explanation for the role of Abelson kinase in Parkinson's disease. Our results establish a master regulatory mechanism of alpha-synuclein function and aggregation in mammalian cells, extending the functional repertoire of molecular chaperones and highlighting new perspectives for therapeutic interventions for Parkinson's disease.
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- Escala-Garcia, M, et al.
(author)
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Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis
- 2021
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 19787-
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Journal article (peer-reviewed)abstract
- Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.
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- Purrington, Kristen S., et al.
(author)
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Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer
- 2014
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:5, s. 1012-1019
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Journal article (peer-reviewed)abstract
- In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.
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| 24. |
- Aas, Wenche, et al.
(author)
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Trends in Air Pollution in Europe, 2000–2019
- 2024
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In: Aerosol and Air Quality Research. - 2071-1409 .- 1680-8584. ; 24:4
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Journal article (peer-reviewed)abstract
- This paper encompasses an assessment of air pollution trends in rural environments in Europe over the 2000–2019 period, benefiting from extensive long-term observational data from the EMEP monitoring network and EMEP MSC-W model computations. The trends in pollutant concentrations align with the decreasing emission patterns observed throughout Europe. Annual average concentrations of sulfur dioxide, particulate sulfate, and sulfur wet deposition have shown consistent declines of 3–4% annually since 2000. Similarly, oxidized nitrogen species have markedly decreased across Europe, with an annual reduction of 1.5–2% in nitrogen dioxide concentrations, total nitrate in the air, and oxidized nitrogen deposition. Notably, emission reductions and model predictions appear to slightly surpass the observed declines in sulfur and oxidized nitrogen, indicating a potential overestimation of reported emission reductions. Ammonia emissions have decreased less compared to other pollutants since 2000. Significant reductions in particulate ammonium have however, been achieved due to the impact of reductions in SOx and NOx emissions. For ground level ozone, both the observed and modelled peak levels in summer show declining trends, although the observed decline is smaller than modelled. There have been substantial annual reductions of 1.8% and 2.4% in the concentrations of PM10 and PM2.5, respectively. Elemental carbon has seen a reduction of approximately 4.5% per year since 2000. A similar reduction for organic carbon is only seen in winter when primary anthropogenic sources dominate. The observed improvements in European air quality emphasize the importance of comprehensive legislations to mitigate emissions.
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