| 1. |
- Bajema, Ingeborg M., et al.
(författare)
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The European Vasculitis Society 2016 Meeting Report
- 2017
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 2:6, s. 1018-1031
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Tidskriftsartikel (refereegranskat)abstract
- The 2016 European Vasculitis Society (EUVAS) meeting, held in Leiden, the Netherlands, was centered around phenotypic subtyping in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). There were parallel meetings of the EUVAS petals, which here report on disease assessment; database; and long-term follow-up, registries, genetics, histology, biomarker studies, and clinical trials. Studies currently conducted will improve our ability to discriminate between different forms of vasculitis. In a project that involves the 10-year follow-up of AAV patients, we are working on retrieving data on patient and renal survival, relapse rate, the cumulative incidence of malignancies, and comorbidities. Across Europe, several vasculitis registries were developed covering over 10,000 registered patients. In the near future, these registries will facilitate clinical research in AAV on a scale hitherto unknown. Current studies on the genetic background of AAV will explore the potential prognostic significance of genetic markers and further refine genetic associations with distinct disease subsets. The histopathological classification of ANCA-associated glomerulonephritis is currently evaluated in light of data coming out of a large international validation study. In our continuous search for biomarkers to predict clinical outcome, promising new markers are important subjects of current research. Over the last 2 decades, a host of clinical trials have provided evidence for refinement of therapeutic regimens. We give an overview of clinical trials currently under development, and consider refractory vasculitis in detail. The goal of EUVAS is to stimulate ongoing research in clinical, serological, and histological management and techniques for patients with systemic vasculitis, with an outlook on the applicability for clinical trials.
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| 2. |
- Basu, Neil, et al.
(författare)
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EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis
- 2010
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Ingår i: Annals of the Rheumatic Diseases. - London, UK : BMJ. - 1468-2060 .- 0003-4967. ; 69:10, s. 1744-1750
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The systemic vasculitides are multiorgan diseases where early diagnosis and treatment can significantly improve outcomes. Robust nomenclature reduces diagnostic delay. However, key aspects of current nomenclature are widely perceived to be out of date, these include disease definitions, classification and diagnostic criteria. Therefore, the aim of the present work was to identify deficiencies and provide contemporary points to consider for the development of future definitions and criteria in systemic vasculitis. Methods The expert panel identified areas of concern within existing definitions/criteria. Consequently, a systematic literature review was undertaken looking to address these deficiencies and produce 'points to consider' in accordance with standardised European League Against Rheumatism (EULAR) operating procedures. In the absence of evidence, expert consensus was used. Results There was unanimous consensus for re-evaluating existing definitions and developing new criteria. A total of 17 points to consider were proposed, covering 6 main areas: biopsy, laboratory testing, diagnostic radiology, nosology, definitions and research agenda. Suggestions to improve and expand current definitions were described including the incorporation of anti-neutrophil cytoplasm antibody and aetiological factors, where known. The importance of biopsy in diagnosis and exclusion of mimics was highlighted, while equally emphasising its problems. Thus, the role of alternative diagnostic tools such as MRI, ultrasound and surrogate markers were also discussed. Finally, structures to develop future criteria were considered. Conclusions Limitations in current classification criteria and definitions for vasculitis have been identified and suggestions provided for improvement. Additionally it is proposed that, in combination with the updated evidence, these should form the basis of future attempts to develop and validate revised criteria and definitions of vasculitis.
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| 3. |
- Cam, Morgane, et al.
(författare)
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Induction of Amyloid-β42 Production by Fipronil and Other Pyrazole Insecticides.
- 2018
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 62:4, s. 1663-1681
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Tidskriftsartikel (refereegranskat)abstract
- Generation of amyloid-β peptides (Aβs) by proteolytic cleavage of the amyloid-β protein precursor (AβPP), especially increased production of Aβ42/Aβ43 over Aβ40, and their aggregation as oligomers and plaques, represent a characteristic feature of Alzheimer's disease (AD). In familial AD (FAD), altered Aβ production originates from specific mutations ofAβPP or presenilins 1/2 (PS1/PS2), the catalytic subunits of γ-secretase. In sporadic AD, the origin of altered production of Aβs remains unknown. We hypothesize that the 'human chemical exposome' contains products able to favor the production of Aβ42/Aβ43 over Aβ40 and shorter Aβs. To detect such products, we screened a library of 3500+compounds in a cell-based assay for enhanced Aβ42/Aβ43 production. Nine pyrazole insecticides were found to induce a β- and γ-secretase-dependent, 3-10-fold increase in the production of extracellular Aβ42 in various cell lines and neurons differentiated from induced pluripotent stem cells derived from healthy and FAD patients. Immunoprecipitation/mass spectrometry analyses showed increased production of Aβs cleaved at positions 42/43, and reduced production of peptides cleaved at positions 38 and shorter. Strongly supporting a direct effect on γ-secretase activity, pyrazoles shifted the cleavage pattern of another γ-secretase substrate, alcadeinα, and shifted the cleavage of AβPP by highly purified γ-secretase toward Aβ42/Aβ43. Focusing on fipronil, we showed that some of its metabolites, in particular the persistent fipronil sulfone, also favor the production of Aβ42/Aβ43 in both cell-based and cell-free systems. Fipronil administered orally to mice and rats is known to be metabolized rapidly, mostly to fipronil sulfone, which stably accumulates in adipose tissue and brain. In conclusion, several widely used pyrazole insecticides enhance the production of toxic, aggregation prone Aβ42/Aβ43 peptides, suggesting the possible existence of environmental "Alzheimerogens" which may contribute to the initiation and propagation of the amyloidogenic process in sporadic AD.
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| 4. |
- Galletti, L., et al.
(författare)
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Influence of topological edge states on the properties of Al/Bi2Se3/Al hybrid Josephson devices
- 2014
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Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 89:13
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Tidskriftsartikel (refereegranskat)abstract
- In superconductor-topological insulator-superconductor hybrid junctions, the barrier edge states are expected to be protected against backscattering, to generate unconventional proximity effects, and, possibly, to signal the presence of Majorana fermions. The standards of proximity modes for these types of structures have to be settled for a neat identification of possible new entities. Through a systematic and complete set of measurements of the Josephson properties we find evidence of ballistic transport in coplanar Al-Bi2Se3-Al junctions that we attribute to a coherent transport through the topological edge state. The shunting effect of the bulk only influences the normal transport. This behavior, which can be considered to some extent universal, is fairly independent of the specific features of superconducting electrodes. A comparative study of Shubnikov-de Haas oscillations and scanning tunneling spectroscopy gave an experimental signature compatible with a two-dimensional electron transport channel with a Dirac dispersion relation. A reduction of the size of the Bi2Se3 flakes to the nanoscale is an unavoidable step to drive Josephson junctions in the proper regime to detect possible distinctive features of Majorana fermions.
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| 5. |
- Galletti, L., et al.
(författare)
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Josephson effect in Al/Bi2Se3/Al coplanar hybrid devices
- 2014
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Ingår i: Physica C: Superconductivity and its Applications. - : Elsevier BV. - 0921-4534. ; 503, s. 162-165
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Tidskriftsartikel (refereegranskat)abstract
- The edge states of Topological Insulators (TI) are protected against backscattering, thanks to the topological properties arising from their band structure. Coupling a TI to a superconductor (S) can induce unconventional effects, including the creation of Majorana bound states (MBS). The fabrication of coplanar hybrid devices is a fundamental step to pave the way to the understanding of proximity effects in topologically non-trivial systems, and to a large variety of experiments aimed at the possible detection of MBS. We discuss the feasibility and some relevant properties of Al-Bi2Se3-Al coplanar proximity devices. Special attention is devoted to the design of the junction, aimed at enhancing the coupling between the electrodes and the TI.
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| 6. |
- Michikami, Tatsuhiro, et al.
(författare)
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Three-axial shape distributions of pebbles, cobbles and boulders smaller than a few meters on asteroid Ryugu
- 2022
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Ingår i: Icarus. - : Elsevier. - 0019-1035 .- 1090-2643. ; 381
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Tidskriftsartikel (refereegranskat)abstract
- Over a broad size range, the shapes of impact fragments from catastrophic disruptions are distributed around the mean axial ratio 2: √2: 1, irrespective of experimental conditions and target materials. Although most blocks on asteroids are likely to be impact fragments, there is not enough quantitative data for reliable statistics on their three-axial lengths and/or ratios because it is difficult to precisely estimate the heights of the blocks. In this study, we evaluate the heights of blocks on asteroid Ryugu by measuring their shadows. The three-axial ratios of ~4100 small blocks with diameters from 5.0 cm to 7.6 m in Ryugu's equatorial region are investigated using eight close-up images of narrower localities taken at altitudes below 500 m, i.e. at <5.4 cm/pixel resolution, obtained immediately before the second touch-down of the Hayabusa2 spacecraft. The purpose of this study is to investigate the block shape distribution, which is important for understanding the geological history of asteroid Ryugu. Specifically, the shape distribution is compared to laboratory impact fragments. Our observations indicate that the shape distributions of blocks smaller than 1 m on Ryugu are consistent with laboratory impact fragment shape distributions, implying that the dominant shape-determining process for blocks on Ryugu was impact fragmentation. Blocks several meters in size in the equatorial region seem to be slightly flatter than the rest, suggesting that some blocks are partly buried in a bed of regolith. In conclusion, the shape distributions of blocks from several-cm to several-m in the equatorial region of asteroid Ryugu suggest that these are mainly fragments originating from the catastrophic disruption of their parent body and/or from a later impact.
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| 7. |
- Okochi, Yoshifumi, et al.
(författare)
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The voltage-gated proton channel Hv1/VSOP inhibits neutrophil granule release
- 2016
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Ingår i: Journal of Leukocyte Biology. - 0741-5400 .- 1938-3673. ; 99:1, s. 7-19
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil granule exocytosis is crucial for host defense and inflammation. Neutrophils contain 4 types of granules, the exocytotic release of which is differentially regulated. This exocytosis is known to be driven by diverse mediators, including calcium and nucleotides, but the precise molecular mechanism remains largely unknown. We show in the present study that voltage-gated proton (Hv) channels are necessary for the proper release of azurophilic granules in neutrophils. On activation of NADPH oxidase by PMA and IgG, neutrophils derived from Hvcn1 gene knockout mouse exhibited greater secretion of MPO and elastase than WT cells. In contrast, release of LTF enriched in specific granules was not enhanced in these cells. The excess release of azurophilic granules in Hv1/VSOP-deficient neutrophils was suppressed by inhibiting NADPH oxidase activity and, in part, by valinomycin, a potassium ionophore. In addition, Hv1/VSOP-deficient mice exhibited more severe lung inflammation after intranasal Candida albicans infection than WT mice. These findings suggest that the Hv channel acts to specifically dampen the release of azurophilic granules through, in part, the suppression of increased positive charges at the plasma membrane accompanied by the activation of NADPH oxidase in neutrophils.
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