| 1. |
- Notarnicola, A., et al.
(författare)
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Autoantibodies against a subunit of mitochondrial respiratory chain complex I in inclusion body myositis
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82, s. 574-574
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Tidskriftsartikel (refereegranskat)abstract
- Background Autoantibodies are found in up to 80% of patients with idiopathic inflammatory myopathies (IIM) and are associated with distinct clinical phenotypes [1]. Autoantibodies targeting cytosolic 5´-nucleotidase 1A (anti-cN1A) are currently the only known serum biomarker for the subgroup inclusion body myositis (IBM) (2), although detected even in other autoimmune diseases.Objectives To identify new autoimmune targets in IIM by antigen bead array assay.Methods In a first cross-sectional exploratory study, 357 antigens representing 268 proteins were incubated with plasma samples from 219 IIM (108 Polymyositis (PM), 80 Dermatomyositis (DM) and 31 IBM) patients, 349 Systemic Lupus Erythematosus (SLE) patients and 306 population controls for screening of IgG reactivity by antigen bead array. All samples were identified in the local biobank of the Rheumatology clinic, Karolinska University Hospital. Interesting results obtained for the IBM subgroup were then validated in an independent larger cohort of 287 patients with IBM followed at nine European rheumatological or neurological centers. IBM serum samples were explored by antigen bead array and results validated by western blot. As controls, serum samples from 30 patients with PM and 30 with DM, HLA-matched with the IBM Swedish cohort, were included. Demographics, laboratory, clinical, and muscle biopsy data of the IBM cohort was retrieved.Results In the exploratory study IgG reactivity towards NADH dehydrogenase 1 α subcomplex 11 (NDUFA11), a subunit of the membrane-bound mitochondrial respiratory chain complex I, was discovered with higher frequency in the IBM (9,7%) than PM (2,8%) and DM samples (2,5%), although the difference was not statistically significant. Anti-NDUFA11 IgG was also found in 2,3% of SLE and 2,6% of population control samples. In the validation study anti-NDUFA11 autoantibodies were detected in 11/287 IBM patients (3,8%), 0/30 PM and 0/30 DM patients. Reactivity against NDUFA11 could be confirmed by western blot (Table 1, Figure 1). The eleven anti-NDUFA11 positive patients showed a trend of lower frequency of wheelchair/walker ever use and higher creatine kinase levels at time of IBM diagnosis compared to the anti-NDUFA11 negative group. Ragged red fibers were significantly more prevalent in anti-NDUFA11 positive than negative patients (p=0.04). Anti-cN1A autoantibodies were detected in 98/287 (34,1%) of IBM, 3/30 (10%) DM and 9/29 (31%) PM patients, p=0.03. Coexistence of anti NDUFA11 and anti-cN1A antibodies was observed in 3 IBM patients.Conclusion Our results reveal a new autoimmune target in the mitochondrial respiratory chain complex I that might be specifically associated with IBM. This is of particular interest as mitochondrial abnormalities are known histological findings in muscle biopsies of IBM patients.References [1]Galindo-Feria AS, Wang G, Lundberg IE. Autoantibodies: Pathogenic or epiphenomenon. Best Pract Res Clin Rheumatol. 2022;36(2):101767.[2]Herbert MK,et al. Disease specificity of autoantibodies to cytosolic 5’-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases. Ann Rheum Dis. 2016;75(4):696-701.
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| 2. |
- Szykowska, Aleksandra, et al.
(författare)
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Selection and structural characterization of anti-TREM2 scFvs that reduce levels of shed ectodomain
- 2021
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 29:11, s. 1241-
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in TREM2, a receptor expressed by microglia in the brain, are associated with an increased risk of neurodegeneration, including Alzheimer's disease. Numerous studies support a role for TREM2 in sensing damaging stimuli and triggering signaling cascades necessary for neuroprotection. Despite its significant role, ligands and regulators of TREM2 activation, and the mechanisms governing TREM2-dependent responses and its cleavage from the membrane, remain poorly characterized. Here, we present phage display generated antibody single-chain variable fragments (scFvs) to human TREM2 immunoglobulin-like domain. Co-crystal structures revealed the binding of two scFvs to an epitope on the TREM2 domain distal to the putative ligand-binding site. Enhanced functional activity was observed for oligomeric scFv species, which inhibited the production of soluble TREM2 in a HEK293 cell model. We hope that detailed characterization of their epitopes and properties will facilitate the use of these renewable binders as structural and functional biology tools for TREM2 research.
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| 3. |
- Feroci, M., et al.
(författare)
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Monitoring the hard X-ray sky with SuperAGILE
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 510, s. A9-
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Tidskriftsartikel (refereegranskat)abstract
- Context SuperAGILE is the hard X-ray monitor of the AGILE gamma ray mission, in orbit since 23 April 2007. It is an imaging experiment based on a set of four independent silicon strip detectors, equipped with one-dimensional coded masks, operating in the nominal energy range 18-60 keV. Aims. The main goal of SuperAGILE is the observation of cosmic sources simultaneously with the main gamma-ray AGILE experiment, the Gamma Ray Imaging Detector (GRID). Given its similar to steradian-wide field of view and its similar to 15 mCrab day-sensitivity, SuperAGILE is also well suited to the long-term monitoring of Galactic compact objects and the detection of bright transients. Methods. The SuperAGILE detector properties and design allow for a 6 arcmin angular resolution in each of the two independent orthogonal projections of the celestial coordinates. Photon by photon data are continuously available by means of experiment telemetry, and are used to derive images and fluxes of individual sources, with integration times depending on the source intensity and position in the field of view. Results. We report on the main scientific results achieved by SuperAGILE over its first two years in orbit, until April 2009. The scientific observations started in mid-July 2007, with the science verification phase, continuing during the complete AGILE Cycle 1 and the first similar to half of Cycle 2. Despite the largely non-uniform sky coverage, due to the pointing strategy of the AGILE mission, a few tens of Galactic sources were monitored, sometimes for unprecedently long continuous periods, leading to the detection also of several bursts and outbursts. Approximately one gamma ray burst per month was detected and localized, allowing for prompt multi-wavelength observations. A few extragalactic sources in bright states were occasionally detected as well. The light curves of sources measured by SuperAGILE are made publicly available on the web in almost real-time. To enable a proper scientific use of these, we provide the reader with the relevant scientific and technical background.
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| 4. |
- Hallberg, R. T., et al.
(författare)
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Hydrogen-assisted spark discharge generated metal nanoparticles to prevent oxide formation
- 2018
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 0278-6826 .- 1521-7388. ; 52:3, s. 347-358
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Tidskriftsartikel (refereegranskat)abstract
- There exists a demand for production of metal nanoparticles for today's emerging nanotechnology. Aerosol-generated metal nanoparticles can oxidize during particle formation due to impurities in the carrier gas. One method to produce unoxidized metal nanoparticles is to first generate metal oxides and then reduce them during sintering. Here, we propose to instead prevent oxidation by introducing the reducing agent already at particle formation. We show that by mixing 5% hydrogen into the nitrogen carrier gas, we can generate single crystalline metal nanoparticles by spark discharge from gold, cobalt, bismuth, and tin electrodes. The non-noble nanoparticles exhibit signs of surface oxidation likely formed post-deposition when exposed to air. Nanoparticles generated without hydrogen are found to be primarily polycrystalline and oxidized. To demonstrate the advantages of supplying the reducing agent at generation, we compare to nanoparticles that are generated in nitrogen and sintered in a hydrogen mixture. For bismuth and tin, the crystal quality of the particles after sintering is considerably higher when hydrogen is introduced at particle generation compared to at sintering, whereas for cobalt it is equally effective to only add hydrogen at sintering. We propose that hydrogen present at particle generation prevents the formation of oxide primary particles, thus improving the ability to sinter the nanoparticles to compact and single crystals of metal. This method is general and can be applied to other aerosol generation systems, to improve the generation of size-controlled nanoparticles of non-noble metals with a suitable reducing agent.
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| 5. |
- Marisaldi, M., et al.
(författare)
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Detection of terrestrial gamma ray flashes up to 40 MeV by the AGILE satellite
- 2010
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 115:3, s. A00E13-
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Tidskriftsartikel (refereegranskat)abstract
- We report the detection by the Astrorivelatore Gamma a Immagini Leggero (AGILE) satellite of terrestrial gamma ray flashes (TGFs) obtained with the minicalorimeter (MCAL) detector operating in the energy range 0.3-100 MeV. We select events typically lasting a few milliseconds with spectral and directional selections consistent with the TGF characteristics previously reported by other space missions. During the period 1 June 2008 to 31 March 2009 we detect 34 high-confidence events showing millisecond durations and a geographical distribution peaked over continental Africa and Southeast Asia. For the first time, AGILE-MCAL detects photons associated with TGF events up to 40 MeV. We determine the cumulative spectral properties of the spectrum in the range 0.5-40 MeV, which can be effectively described by a Bremsstrahlung spectrum. We find that both the TGF cumulative spectral properties and their geographical distribution are in good agreement with the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) results.
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| 6. |
- Pittori, C., et al.
(författare)
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First AGILE catalog of high-confidence gamma-ray sources
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 506:3, s. 1563-1574
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Tidskriftsartikel (refereegranskat)abstract
- We present the first catalog of high-confidence gamma-ray sources detected by the AGILE satellite during observations performed from July 9, 2007 to June 30, 2008. Cataloged sources were detected by merging all the available data over the entire time period. AGILE, launched in April 2007, is an ASI mission devoted to gamma-ray observations in the 30 MeV-50 GeV energy range, with simultaneous X-ray imaging capability in the 18-60 keV band. This catalog is based on Gamma-Ray Imaging Detector (GRID) data for energies greater than 100 MeV. For the first AGILE catalog, we adopted a conservative analysis, with a high-quality event filter optimized to select gamma-ray events within the central zone of the instrument field of view (radius of 40 degrees). This is a significance-limited (4 sigma) catalog, and it is not a complete flux-limited sample due to the non-uniform first-year AGILE sky coverage. The catalog includes 47 sources, 21 of which are associated with confirmed or candidate pulsars, 13 with blazars (7 FSRQ, 4 BL Lacs, 2 unknown type), 2 with HMXRBs, 2 with SNRs, 1 with a colliding-wind binary system, and 8 with unidentified sources.
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| 7. |
- Shamun, Sam, et al.
(författare)
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Detailed characterization of particulate matter in alcohol exhaust emissions
- 2017
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Ingår i: COMODIA 2017 - 9th International Conference on Modeling and Diagnostics for Advanced Engine Systems. - 2424-2918.
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Konferensbidrag (refereegranskat)abstract
- A way to reduce net CO2 emission and circumvent the high particle emissions from compression ignition (CI) engines, while retaining high efficiency, is by utilizing lighter alcohols in the partially premixed combustion (PPC) process. Methanol and ethanol have a very short carbon chain, and form less soot/particulate matter (PM) during combustion compared to diesel fuel. This study analyzes and compares the characteristics of PM emissions from methanol, ethanol and diesel in terms of soot mass concentration, number concentration and particle size distribution in one cylinder of a six cylinder Scania D13 heavy duty (HD) engine under two operating loads; 6 bar and 10 bar gross mean indicated effective pressure (IMEPG). An electrostatic precipitator (ESP) was used to sample PM on copper grids for transmission electron microscopy (TEM) and energy dispersive X-ray analysis. Also, new and used lubrication oil together with methanol and diesel were analyzed for their sulphur and metal content. Nucleation mode and the majority of accumulation mode particles from methanol and ethanol combustion, showed mainly Ca, S, P and Zn in the energy dispersive X-ray spectrometry (EDX) analysis and were hypothesized to be emitted mainly from the lubrication oil rather than the combustion of the fuel itself. From diesel combustion, the accumulation mode particles were more abundant in comparison with the alcohols and PM/soot emissions measured with the photo-acoustic technique were 3 to 10 times higher than for the alcohols. There were also fewer nucleation mode particles present; although they consisted of the same four abovementioned elements. Utilizing alcohols in CI engines have a great advantage regarding PM, particle number emissions and efficiency. However, the resulting nucleation mode particles need to be reduced to avoid future health concerns.
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