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Sökning: WFRF:(Karlsson Hanna L.)

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1.
  • Ruilope, LM, et al. (författare)
  • Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
  • 2019
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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2.
  • Abramowski, A., et al. (författare)
  • The 2010 very high energy gamma-RAY flare and 10 years of multi-wavelength observations of M 87
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2, s. 151-
  • Tidskriftsartikel (refereegranskat)abstract
    • The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3-6) x 10(9) M-circle dot) provides a unique opportunity to investigate the origin of very high energy (VHE; E > 100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of tau(rise)(d) = (1.69 +/- 0.30) days and tau(decay)(d) = (0.611 +/- 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (similar to day), peak fluxes (Phi(>0.35 TeV) similar or equal to (1-3) x 10(-11) photons cm(-2) s(-1)), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken similar to 3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core (flux increased by factor similar to 2; variability timescale <2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE gamma-ray emission from M 87 are reviewed in the light of the new data.
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3.
  • Acciari, V. A., et al. (författare)
  • Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
  • 2009
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
  • Tidskriftsartikel (refereegranskat)abstract
    • The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.
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4.
  • Abdo, A. A., et al. (författare)
  • Multi-wavelength observations of the flaring gamma-ray blazar 3C 66A in 2008 October
  • 2011
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 726:1, s. 43-
  • Tidskriftsartikel (refereegranskat)abstract
    • The BL Lacertae object 3C 66A was detected in a flaring state by the Fermi Large Area Telescope (LAT) and VERITAS in 2008 October. In addition to these gamma-ray observations, F-GAMMA, GASP-WEBT, PAIRITEL, MDM, ATOM, Swift, and Chandra provided radio to X-ray coverage. The available light curves show variability and, in particular, correlated flares are observed in the optical and Fermi-LAT gamma-ray band. The resulting spectral energy distribution can be well fitted using standard leptonic models with and without an external radiation field for inverse Compton scattering. It is found, however, that only the model with an external radiation field can accommodate the intra-night variability observed at optical wavelengths.
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5.
  • Acciari, V. A., et al. (författare)
  • Discovery of very high energy gamma rays from PKS 1424+240 and multiwavelength constraints on ITS redshift
  • 2010
  • Ingår i: ASTROPHYSICAL JOURNAL LETTERS. - 2041-8205. ; 708:2, s. L100-L106
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the first detection of very high energy(83) (VHE) gamma-ray emission above 140 GeV from PKS 1424+240, a BL Lac object with an unknown redshift. The photon spectrum above 140 GeV measured by VERITAS is well described by a power law with a photon index of 3.8 +/- 0.5(stat) +/- 0.3(syst) and a flux normalization at 200 GeV of (5.1 +/- 0.9(stat) +/- 0.5(syst)) x 10(-11) TeV-1 cm(-2) s(-1), where stat and syst denote the statistical and systematical uncertainties, respectively. The VHE flux is steady over the observation period between MJD 54881 and 55003 (from 2009 February 19 to June 21). Flux variability is also not observed in contemporaneous high-energy observations with the Fermi Large Area Telescope. Contemporaneous X-ray and optical data were also obtained from the Swift XRT and MDM observatory, respectively. The broadband spectral energy distribution is well described by a one-zone synchrotron self-Compton model favoring a redshift of less than 0.1. Using the photon index measured with Fermi in combination with recent extragalactic background light absorption models it can be concluded from the VERITAS data that the redshift of PKS 1424+240 is less than 0.66.
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6.
  • Acciari, V. A., et al. (författare)
  • THE DISCOVERY OF gamma-RAY EMISSION FROM THE BLAZAR RGB J0710+591
  • 2010
  • Ingår i: ASTROPHYSICAL JOURNAL LETTERS. - 2041-8205. ; 715:1, s. L49-L55
  • Tidskriftsartikel (refereegranskat)abstract
    • The high-frequency-peaked BL Lacertae object RGB J0710+591 was observed in the very high-energy (VHE; E > 100 GeV) wave band by the VERITAS array of atmospheric Cherenkov telescopes. The observations, taken between 2008 December and 2009 March and totaling 22.1 hr, yield the discovery of VHE gamma rays from the source. RGB J0710+591 is detected at a statistical significance of 5.5 standard deviations (5.5 sigma) above the background, corresponding to an integral flux of (3.9 +/- 0.8) x 10(-12) cm(-2) s(-1) (3% of the Crab Nebula's flux) above 300 GeV. The observed spectrum can be fit by a power law from 0.31 to 4.6 TeV with a photon spectral index of 2.69 +/- 0.26(stat) +/- 0.20(sys). These data are complemented by contemporaneous multiwavelength data from the Fermi Large Area Telescope, the Swift X-ray Telescope, the Swift Ultra-Violet and Optical Telescope, and the Michigan-Dartmouth-MIT observatory. Modeling the broadband spectral energy distribution (SED) with an equilibrium synchrotron self-Compton model yields a good statistical fit to the data. The addition of an external-Compton component to the model does not improve the fit nor brings the system closer to equipartition. The combined Fermi and VERITAS data constrain the properties of the high-energy emission component of the source over 4 orders of magnitude and give measurements of the rising and falling sections of the SED.
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7.
  • Acciari, V. A., et al. (författare)
  • VERITAS Observations of Gamma-Ray Bursts Detected by Swift
  • 2011
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 743:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of 16 Swift-triggered Gamma-ray burst (GRB) follow-up observations taken with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) telescope array from 2007 January to 2009 June. The median energy threshold and response time of these observations were 260 GeV and 320 s, respectively. Observations had an average duration of 90 minutes. Each burst is analyzed independently in two modes: over the whole duration of the observations and again over a shorter timescale determined by the maximum VERITAS sensitivity to a burst with a t –1.5 time profile. This temporal model is characteristic of GRB afterglows with high-energy, long-lived emission that have been detected by the Large Area Telescope on board the Fermi satellite. No significant very high energy (VHE) gamma-ray emission was detected and upper limits above the VERITAS threshold energy are calculated. The VERITAS upper limits are corrected for gamma-ray extinction by the extragalactic background light and interpreted in the context of the keV emission detected by Swift. For some bursts the VHE emission must have less power than the keV emission, placing constraints on inverse Compton models of VHE emission.
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8.
  • Aliu, E., et al. (författare)
  • VERITAS deep observations of the dwarf spheroidal galaxy Segue 1
  • 2012
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 85:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The VERITAS array of Cherenkov telescopes has carried out a deep observational program on the nearby dwarf spheroidal galaxy Segue 1. We report on the results of nearly 48 hours of good quality selected data, taken between January 2010 and May 2011. No significant γ-ray emission is detected at the nominal position of Segue 1, and upper limits on the integrated flux are derived. According to recent studies, Segue 1 is the most dark matter-dominated dwarf spheroidal galaxy currently known. We derive stringent bounds on various annihilating and decaying dark matter particle models. The upper limits on the velocity-weighted annihilation cross-section are ⟨σv⟩95% CL≲10−23  cm3 s−1, improving our limits from previous observations of dwarf spheroidal galaxies by at least a factor of 2 for dark matter particle masses mχ≳300  GeV. The lower limits on the decay lifetime are at the level of τ95% CL≳1024  s. Finally, we address the interpretation of the cosmic ray lepton anomalies measured by ATIC and PAMELA in terms of dark matter annihilation, and show that the VERITAS observations of Segue 1 disfavor such a scenario.
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9.
  • Arlen, T., et al. (författare)
  • Rapid TeV Gamma-Ray Flaring of BL Lacertae
  • 2013
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 762:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the detection of a very rapid TeV gamma-ray flare from BL Lacertae on 2011 June 28 with the Very Energetic Radiation Imaging Telescope Array System (VERITAS). The flaring activity was observed during a 34.6 minute exposure, when the integral flux above 200 GeV reached (3.4 ± 0.6) × 10–6 photons m–2 s–1, roughly 125% of the Crab Nebula flux measured by VERITAS. The light curve indicates that the observations missed the rising phase of the flare but covered a significant portion of the decaying phase. The exponential decay time was determined to be 13 ± 4 minutes, making it one of the most rapid gamma-ray flares seen from a TeV blazar. The gamma-ray spectrum of BL Lacertae during the flare was soft, with a photon index of 3.6 ± 0.4, which is in agreement with the measurement made previously by MAGIC in a lower flaring state. Contemporaneous radio observations of the source with the Very Long Baseline Array revealed the emergence of a new, superluminal component from the core around the time of the TeV gamma-ray flare, accompanied by changes in the optical polarization angle. Changes in flux also appear to have occurred at optical, UV, and GeV gamma-ray wavelengths at the time of the flare, although they are difficult to quantify precisely due to sparse coverage. A strong flare was seen at radio wavelengths roughly four months later, which might be related to the gamma-ray flaring activities. We discuss the implications of these multiwavelength results.
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10.
  • Collaboration, V E R I T A S, et al. (författare)
  • Detection of Pulsed Gamma Rays Above 100 GeV from the Crab Pulsar
  • 2011
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 334:6052, s. 69-72
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the detection of pulsed gamma rays from the Crab pulsar at energies above 100 giga–electron volts (GeV) with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) array of atmospheric Cherenkov telescopes. The detection cannot be explained on the basis of current pulsar models. The photon spectrum of pulsed emission between 100 mega–electron volts and 400 GeV is described by a broken power law that is statistically preferred over a power law with an exponential cutoff. It is unlikely that the observation can be explained by invoking curvature radiation as the origin of the observed gamma rays above 100 GeV. Our findings require that these gamma rays be produced more than 10 stellar radii from the neutron star.
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11.
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12.
  • Acciari, V. A., et al. (författare)
  • VERITAS Observations of the TeV Binary LS I +61\deg 303 During 2008-2010
  • 2011
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 738:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of observations of the TeV binary LS I +61° 303 with the VERITAS telescope array between 2008 and 2010, at energies above 300 GeV. In the past, both ground-based gamma-ray telescopes VERITAS and MAGIC have reported detections of TeV emission near the apastron phases of the binary orbit. The observations presented here show no strong evidence for TeV emission during these orbital phases; however, during observations taken in late 2010, significant emission was detected from the source close to the phase of superior conjunction (much closer to periastron passage) at a 5.6 standard deviation (5.6σ) post-trials significance. In total, between 2008 October and 2010 December a total exposure of 64.5 hr was accumulated with VERITAS on LS I +61° 303, resulting in an excess at the 3.3σ significance level for constant emission over the entire integrated data set. The flux upper limits derived for emission during the previously reliably active TeV phases (i.e., close to apastron) are less than 5% of the Crab Nebula flux in the same energy range. This result stands in apparent contrast to previous observations by both MAGIC and VERITAS which detected the source during these phases at 10% of the Crab Nebula flux. During the two year span of observations, a large amount of X-ray data were also accrued on LS I +61° 303 by theSwift X-ray Telescope and the Rossi X-ray Timing Explorer Proportional Counter Array. We find no evidence for a correlation between emission in the X-ray and TeV regimes during 20 directly overlapping observations. We also comment on data obtained contemporaneously by the Fermi Large Area Telescope.
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13.
  • Aliu, E., et al. (författare)
  • Discovery of High-energy and Very High Energy γ-Ray Emission from the Blazar RBS 0413
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 750:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the discovery of high-energy (HE; E > 0.1 GeV) and very high energy (VHE; E > 100 GeV) γ-ray emission from the high-frequency-peaked BL Lac object RBS 0413. VERITAS, a ground-based γ-ray observatory, detected VHE γ rays from RBS 0413 with a statistical significance of 5.5 standard deviations (σ) and a γ-ray flux of (1.5 ± 0.6stat ± 0.7syst) × 10–8 photons m–2 s–1 (~1% of the Crab Nebula flux) above 250 GeV. The observed spectrum can be described by a power law with a photon index of 3.18 ± 0.68stat ± 0.30syst. Contemporaneous observations with the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope detected HE γ rays from RBS 0413 with a statistical significance of more than 9σ, a power-law photon index of 1.57 ± 0.12stat +0.11 – 0.12sys, and a γ-ray flux between 300 MeV and 300 GeV of (1.64 ± 0.43stat +0.31 – 0.22sys) × 10–5photons m–2 s–1. We present the results from Fermi-LAT and VERITAS, including a spectral energy distribution modeling of the γ-ray, quasi-simultaneous X-ray (Swift-XRT), ultraviolet (Swift-UVOT), and R-band optical (MDM) data. We find that, if conditions close to equipartition are required, both the combined synchrotron self-Compton/external-Compton and the lepto-hadronic models are preferred over a pure synchrotron self-Compton model.
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14.
  • Aliu, E., et al. (författare)
  • Discovery of TeV Gamma-Ray Emission from CTA 1 by VERITAS
  • 2013
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 764:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery of TeV gamma-ray emission coincident with the shell-type radio supernova remnant (SNR) CTA 1 using the VERITAS gamma-ray observatory. The source, VER J0006+729, was detected as a 6.5 standard deviation excess over background and shows an extended morphology, approximated by a two-dimensional Gaussian of semimajor (semiminor) axis 030 (024) and a centroid 5' from the Fermi gamma-ray pulsar PSR J0007+7303 and its X-ray pulsar wind nebula (PWN). The photon spectrum is well described by a power-law dN/dE = N 0(E/3 TeV)–Γ, with a differential spectral index of Γ = 2.2 ± 0.2stat ± 0.3sys, and normalization N 0 = (9.1 ± 1.3stat ± 1.7sys) × 10–14 cm–2 s–1 TeV–1. The integral flux, F γ = 4.0 ×10–12 erg cm–2 s–1 above 1 TeV, corresponds to 0.2% of the pulsar spin-down power at 1.4 kpc. The energetics, colocation with the SNR, and the relatively small extent of the TeV emission strongly argue for the PWN origin of the TeV photons. We consider the origin of the TeV emission in CTA 1.
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15.
  • Aliu, E., et al. (författare)
  • Discovery of TeV Gamma-Ray Emission toward Supernova Remnant SNR G78.2+2.1
  • 2013
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 770:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery of an unidentified, extended source of very-high-energy gamma-ray emission, VER J2019+407, within the radio shell of the supernova remnant SNR G78.2+2.1, using 21.4 hr of data taken by the VERITAS gamma-ray observatory in 2009. These data confirm the preliminary indications of gamma-ray emission previously seen in a two-year (2007-2009) blind survey of the Cygnus region by VERITAS. VER J2019+407, which is detected at a post-trials significance of 7.5 standard deviations in the 2009 data, is localized to the northwestern rim of the remnant in a region of enhanced radio and X-ray emission. It has an intrinsic extent of  and its spectrum is well-characterized by a differential power law (dN/dE = N 0 × (E/TeV)–Γ) with a photon index of Γ = 2.37 ± 0.14stat ± 0.20sys and a flux normalization of N 0 = 1.5 ± 0.2stat ± 0.4sys × 10–12 photon TeV–1 cm–2 s–1. This yields an integral flux of 5.2 ± 0.8stat ± 1.4sys × 10–12 photon cm–2 s–1above 320 GeV, corresponding to 3.7% of the Crab Nebula flux. We consider the relationship of the TeV gamma-ray emission with the GeV gamma-ray emission seen from SNR G78.2+2.1 as well as that seen from a nearby cocoon of freshly accelerated cosmic rays. Multiple scenarios are considered as possible origins for the TeV gamma-ray emission, including hadronic particle acceleration at the SNR shock.
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16.
  • Aliu, E., et al. (författare)
  • Multiwavelength Observations of the Previously Unidentified Blazar RX J0648.7+1516
  • 2011
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 742:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the VERITAS discovery of very high energy (VHE) gamma-ray emission above 200 GeV from the high-frequency-peaked BL Lac (HBL) object RX J0648.7+1516 (GB J0648+1516), associated with 1FGL J0648.8+1516. The photon spectrum above 200 GeV is fitted by a power law dN/dE = F 0(E/E 0)–Γ with a photon index Γ of 4.4 ± 0.8stat ± 0.3syst and a flux normalization F 0 of (2.3 ± 0.5stat ± 1.2sys) × 10–11 TeV–1 cm–2 s–1 with E 0 = 300 GeV. No VHE variability is detected during VERITAS observations of RX J0648.7+1516 between 2010 March 4 and April 15. Following the VHE discovery, the optical identification and spectroscopic redshift were obtained using the Shane 3 m Telescope at the Lick Observatory, showing the unidentified object to be a BL Lac type with a redshift of z = 0.179. Broadband multiwavelength observations contemporaneous with the VERITAS exposure period can be used to subclassify the blazar as an HBL object, including data from the MDM observatory, Swift-UVOT, and X-Ray Telescope, and continuous monitoring at photon energies above 1 GeV from the FermiLarge Area Telescope (LAT). We find that in the absence of undetected, high-energy rapid variability, the one-zone synchrotron self-Compton (SSC) model overproduces the high-energy gamma-ray emission measured by the Fermi-LAT over 2.3 years. The spectral energy distribution can be parameterized satisfactorily with an external-Compton or lepto-hadronic model, which have two and six additional free parameters, respectively, compared to the one-zone SSC model.
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17.
  • Aliu, E., et al. (författare)
  • Search for a Correlation between Very-high-energy Gamma Rays and Giant Radio Pulses in the Crab Pulsar
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 760:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of a joint observational campaign between the Green Bank radio telescope and the VERITAS gamma-ray telescope, which searched for a correlation between the emission of very-high-energy (VHE) gamma rays (E γ > 150 GeV) and giant radio pulses (GRPs) from the Crab pulsar at 8.9 GHz. A total of 15,366 GRPs were recorded during 11.6 hr of simultaneous observations, which were made across four nights in 2008 December and in 2009 November and December. We searched for an enhancement of the pulsed gamma-ray emission within time windows placed around the arrival time of the GRP events. In total, eight different time windows with durations ranging from 0.033 ms to 72 s were positioned at three different locations relative to the GRP to search for enhanced gamma-ray emission which lagged, led, or was concurrent with, the GRP event. Furthermore, we performed separate searches on main pulse GRPs and interpulse GRPs and on the most energetic GRPs in our data sample. No significant enhancement of pulsed VHE emission was found in any of the preformed searches. We set upper limits of 5-10 times the average VHE flux of the Crab pulsar on the flux simultaneous with interpulse GRPs on single-rotation-period timescales. On ~8 s timescales around interpulse GRPs, we set an upper limit of 2-3 times the average VHE flux. Within the framework of recent models for pulsed VHE emission from the Crab pulsar, the expected VHE-GRP emission correlations are below the derived limits.
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18.
  • Aliu, E., et al. (författare)
  • VERITAS Observations of Day-scale Flaring of M 87 in 2010 April
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2
  • Tidskriftsartikel (refereegranskat)abstract
    • VERITAS has been monitoring the very-high-energy (VHE; > 100 GeV) gamma-ray activity of the radio galaxy M 87 since 2007. During 2008, flaring activity on a timescale of a few days was observed with a peak flux of (0.70 ± 0.16) × 10–11 cm–2 s–1 at energies above 350 GeV. In 2010 April, VERITAS detected a flare from M 87 with peak flux of (2.71 ± 0.68) × 10–11 cm–2 s–1 forE > 350 GeV. The source was observed for six consecutive nights during the flare, resulting in a total of 21 hr of good-quality data. The most rapid flux variation occurred on the trailing edge of the flare with an exponential flux decay time of 0.90+0.22 –0.15 days. The shortest detected exponential rise time is three times as long, at 2.87+1.65 –0.99 days. The quality of the data sample is such that spectral analysis can be performed for three periods: rising flux, peak flux, and falling flux. The spectra obtained are consistent with power-law forms. The spectral index at the peak of the flare is equal to 2.19 ± 0.07. There is some indication that the spectrum is softer in the falling phase of the flare than the peak phase, with a confidence level corresponding to 3.6 standard deviations. We discuss the implications of these results for the acceleration and cooling rates of VHE electrons in M 87 and the constraints they provide on the physical size of the emitting region.
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19.
  • Aliu, E., et al. (författare)
  • VERITAS Observations of Six Bright, Hard-spectrum Fermi-LAT Blazars
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 759:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on VERITAS very high energy (VHE; E ≥ 100 GeV) observations of six blazars selected from the Fermi Large Area Telescope First Source Catalog (1FGL). The gamma-ray emission from 1FGL sources was extrapolated up to the VHE band, taking gamma-ray absorption by the extragalactic background light into account. This allowed the selection of six bright, hard-spectrum blazars that were good candidate TeV emitters. Spectroscopic redshift measurements were attempted with the Keck Telescope for the targets without Sloan Digital Sky Survey spectroscopic data. No VHE emission is detected during the observations of the six sources described here. Corresponding TeV upper limits are presented, along with contemporaneousFermi observations and non-concurrent Swift UVOT and X-Ray Telescope data. The blazar broadband spectral energy distributions (SEDs) are assembled and modeled with a single-zone synchrotron self-Compton model. The SED built for each of the six blazars shows a synchrotron peak bordering between the intermediate- and high-spectrum-peak classifications, with four of the six resulting in particle-dominated emission regions.
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20.
  • Aliu, E., et al. (författare)
  • VERITAS Observations of the Nova in V407 Cygni
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 754:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on very high energy (E > 100 GeV) gamma-ray observations of V407 Cygni, a symbiotic binary that underwent a nova outburst producing 0.1-10 GeV gamma rays during 2010 March 10-26. Observations were made with the Very Energetic Radiation Imaging Telescope Array System during 2010 March 19-26 at relatively large zenith angles due to the position of V407 Cyg. An improved reconstruction technique for large zenith angle observations is presented and used to analyze the data. We do not detect V407 Cygni and place a differential upper limit on the flux at 1.6 TeV of 2.3 × 10–12 erg cm–2 s–1 (at the 95% confidence level). When considered jointly with data from Fermi-LAT, this result places limits on the acceleration of very high energy particles in the nova.
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21.
  • Aliu, E., et al. (författare)
  • VERITAS Observations of the Unusual Extragalactic Transient Swift J164449.3+573451
  • 2011
  • Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 738:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on very high energy (>100 GeV) gamma-ray observations of Swift J164449.3+573451, an unusual transient object first detected by the Swift Observatory and later detected by multiple radio, optical, and X-ray observatories. A total exposure of 28 hr was obtained on Swift J164449.3+573451 with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) during 2011 March 28-April 15. We do not detect the source and place a differential upper limit on the emission at 500 GeV during these observations of 1.4 × 10–12 erg cm–2 s–1 (99% confidence level). We also present time-resolved upper limits and use a flux limit averaged over the X-ray flaring period to constrain various emission scenarios that can accommodate both the radio-through-X-ray emission detected from the source and the lack of detection by VERITAS.
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22.
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23.
  • Karlsson, Hanna L., et al. (författare)
  • Health hazards of particles in additive manufacturing : a cross-disciplinary study on reactivity, toxicity and occupational exposure to two nickel-based alloys
  • 2023
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The increasing use of additive manufacturing (AM) techniques (e.g., 3D-printing) offers many advantages but at the same time presents some challenges. One concern is the possible exposure and health risk related to metal containing particles of different sizes. Using the nickel-based alloys Hastelloy X (HX) and Inconel 939 (IN939) as a case, the aim of this cross-disciplinary study was to increase the understanding on possible health hazards and exposure. This was done by performing in-depth characterization of virgin, reused and condensate powders, testing in vitro toxicity (cytotoxicity, genotoxicity, oxidative stress), and measuring occupational airborne exposure. The results showed limited metal release from both HX and IN939, and slightly different surface composition of reused compared to virgin powders. No or small effects on the cultured lung cells were observed when tested up to 100 µg/mL. Particle background levels in the printing facilities were generally low, but high transient peaks were observed in relation to sieving. Furthermore, during post processing with grinding, high levels of nanoparticles (> 100,000 particles/cm3) were noted. Urine metal levels in AM operators did not exceed biomonitoring action limits. Future studies should focus on understanding the toxicity of the nanoparticles formed during printing and post-processing.
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24.
  • Alijagic, Andi, 1992-, et al. (författare)
  • Characteristics and health risks of the inhalable fraction of metal additive manufacturing powders
  • 2024
  • Ingår i: Nano Select. - : Wiley-VCH Verlagsgesellschaft. - 2688-4011. ; 5:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Metal additive manufacturing (AM) is gaining traction but raises worker health concerns due to micron-sized powders, including fine inhalable particles. This study explored particle and surface characteristics, electrochemical properties, metal release in artificial lysosomal fluid (ALF), and potential toxicity of virgin and sieved virgin Fe-based powders, stainless steel (316L), Fe, and two tooling steels. Virgin particles ranged in size from 1 to 100μm, while sieved particles were within the respirable size range (<5–10μm). Surface oxide composition differed from bulk composition. The Fe powder showed low corrosion resistance and high metal release due to a lack of protective surface oxide. Sieved particles of 316L, Fe, and one tooling steel released more metals into ALF than virgin particles, with the opposite was observed for the other tooling steel. Sieved particles had no notable impact on cell viability or micronuclei formation in human bronchial epithelial cells. Inflammatory response in human macrophages was generally low, except for the Fe powder and one tooling steel, which induced increased interleukin-8 (IL-8/CXCL-8) and monocyte chemoattractant protein-1 (MCP-1/CCL-2) secretion. This study underscores distinctions between virgin and sieved Fe-based powders and suggests relatively low acute toxicity.
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25.
  • Bry, Kristina, 1953, et al. (författare)
  • Communication skills training enhances nurses' ability to respond with empathy to parents' emotions in a neonatal intensive care unit
  • 2016
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 105:4, s. 397-406
  • Tidskriftsartikel (refereegranskat)abstract
    • AimWe quantitatively analysed the effect of a course in communication on the content of nurse-parent encounters and the ability of nurses to respond to the empathic needs of parents in a level III neonatal intensive care unit. MethodsWe evaluated 36 and 45 nurse-parent encounters audio recorded before and after 13 neonatal nurses attended a communication course. The number of empathic opportunities, the nurses' responses to these and the ways they involved parents in their infants' care were studied. ResultsBoth before and after the course, the nurses talked more than the parents during the conversations. This nurse-centredness decreased after the course. The use of empathic or exploring responses to empathic opportunities increased from 19.9 9.0% to 53.8 +/- 8.9% (p = 0.027), whereas ignoring the feelings of the parents or giving inadequate advice decreased from 63.0 +/- 10.0% to 27.5 +/- 8.4% (p = 0.043) after the course. Use of statements expressing caring for the parents and encouragement for parents to participate in the care of their infant increased after the course (p = 0.0034 and p = 0.043, respectively). The nurses felt the course was very useful for their profession. ConclusionA course in communication techniques improved nurses' ability to respond to parents' feelings with empathy.
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26.
  • Cappellini, Francesca, et al. (författare)
  • Dry Generation of CeO2 Nanoparticles and Deposition onto a Co-Culture of A549 and THP-1 Cells in Air-Liquid Interface-Dosimetry Considerations and Comparison to Submerged Exposure
  • 2020
  • Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Relevant in vitro assays that can simulate exposure to nanoparticles (NPs) via inhalation are urgently needed. Presently, the most common method employed is to expose lung cells under submerged conditions, but the cellular responses to NPs under such conditions might differ from those observed at the more physiological air-liquid interface (ALI). The aim of this study was to investigate the cytotoxic and inflammatory potential of CeO2 NPs (NM-212) in a co-culture of A549 lung epithelial cells and differentiated THP-1 cells in both ALI and submerged conditions. Cellular dose was examined quantitatively using inductively coupled plasma mass spectrometry (ICP-MS). The role of serum and LPS-priming for IL-1 beta release was further tested in THP-1 cells in submerged exposure. An aerosol of CeO2 NPs was generated by using the PreciseInhale (R) system, and NPs were deposited on the co-culture using XposeALI (R). No or minor cytotoxicity and no increased release of inflammatory cytokines (IL-1 beta, IL-6, TNF alpha, MCP-1) were observed after exposure of the co-culture in ALI (max 5 mu g/cm(2)) or submerged (max 22 mu g/cm(2)) conditions. In contrast, CeO2 NPs cause clear IL-1 beta release in monocultures of macrophage-like THP-1, independent of the presence of serum and LPS-priming. This study demonstrates a useful approach for comparing effects at various in-vitro conditions.
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27.
  • Cappellini, Francesca, et al. (författare)
  • Mechanistic insight into reactivity and (geno)toxicity of well-characterized nanoparticles of cobalt metal and oxides
  • 2018
  • Ingår i: Nanotoxicology. - : Taylor & Francis. - 1743-5390 .- 1743-5404. ; 12:6, s. 602-620
  • Tidskriftsartikel (refereegranskat)abstract
    • An increasing use of cobalt (Co)-based nanoparticles (NPs) in different applications and exposures at occupational settings triggers the need for toxicity assessment. Improved understanding regarding the physiochemical characteristics of Co metal NPs and different oxides in combination with assessment of toxicity and mechanisms may facilitate decisions for grouping during risk assessment. The aim of this study was to gain mechanistic insights in the correlation between NP reactivity and toxicity of three different Co-based NPs (Co, CoO, and Co3O4) by using various tools for characterization, traditional toxicity assays, as well as six reporter cell lines (ToxTracker) for rapid detection of signaling pathways of relevance for carcinogenicity. The results showed cellular uptake of all NPs in lung cells and induction of DNA strand breaks and oxidative damage (comet assay) by Co and CoO NPs. In-depth studies on the ROS generation showed high reactivity of Co, lower for CoO, and no reactivity of Co3O4 NPs. The reactivity depended on the corrosion and transformation/dissolution properties of the particles and the media highlighting the role of the surface oxide and metal speciation as also confirmed by in silico modeling. By using ToxTracker, Co NPs were shown to be highly cytotoxic and induced reporters related to oxidative stress (Nrf2 signaling) and DNA strand breaks. Similar effects were observed for CoO NPs but at higher concentrations, whereas the Co3O4 NPs were inactive at all concentrations tested. In conclusion, our study suggests that Co and CoO NPs, but not Co3O4, may be grouped together for risk assessment.
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28.
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29.
  • Cronholm, Pontus, et al. (författare)
  • Effect of sonication and serum proteins on copper release from copper nanoparticles and the toxicity towards lung epithelial cells
  • 2011
  • Ingår i: Nanotoxicology. - : Informa UK Limited. - 1743-5390 .- 1743-5404. ; 5:2, s. 269-281
  • Tidskriftsartikel (refereegranskat)abstract
    • Different methodological settings can influence particle characteristics and toxicity in nanotoxicology. The aim of this study was to investigate how serum proteins and sonication of Cu nanoparticle suspensions influence the properties of the nanoparticles and toxicological responses on human lung epithelial cells. This was investigated by using methods for particle characterization (photon correlation spectroscopy and TEM) and Cu release (atomic absorption spectroscopy) in combination with assays for analyzing cell toxicity (MTT-, trypan blue- and Comet assay). The results showed that sonication of Cu nanoparticles caused decreased cell viability and increased Cu release compared to non-sonicated particles. Furthermore, serum in the cell medium resulted in less particle agglomeration and increased Cu release compared with medium without serum, but no clear difference in toxicity was detected. Few cells showed intracellular Cu nanoparticles due to fast release/dissolution processes of Cu. In conclusion; sonication can affect the toxicity of nanoparticles.
  •  
30.
  • Cronholm, Pontus, et al. (författare)
  • Intracellular Uptake and Toxicity of Ag and CuO Nanoparticles : A Comparison Between Nanoparticles and their Corresponding Metal Ions
  • 2013
  • Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 9:7, s. 970-982
  • Tidskriftsartikel (refereegranskat)abstract
    • An increased understanding of nanoparticle toxicity and its impact on human health is essential to enable a safe use of nanoparticles in our society. The aim of this study is to investigate the role of a Trojan horse type mechanism for the toxicity of Ag-nano and CuO-nano particles and their corresponding metal ionic species (using CuCl2 and AgNO3), i.e., the importance of the solid particle to mediate cellular uptake and subsequent release of toxic species inside the cell. The human lung cell lines A549 and BEAS-2B are used and cell death/membrane integrity and DNA damage are investigated by means of trypan blue staining and the comet assay, respectively. Chemical analysis of the cellular dose of copper and silver is performed using atomic absorption spectroscopy. Furthermore, transmission electron microscopy, laser scanning confocal microscopy, and confocal Raman microscopy are employed to study cellular uptake and particle-cell interactions. The results confirm a high uptake of CuO-nano and Ag-nano compared to no, or low, uptake of the soluble salts. CuO-nano induces both cell death and DNA damage whereas CuCl2 induces no toxicity. The opposite is observed for silver, where Ag-nano does not cause any toxicity, whereas AgNO3 induces a high level of cell death. In conclusion: CuO-nano toxicity is predominantly mediated by intracellular uptake and subsequent release of copper ions, whereas no toxicity is observed for Ag-nano due to low release of silver ions within short time periods.
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31.
  • Di Bucchianico, Sebastiano, et al. (författare)
  • Calcium-dependent cyto- and genotoxicity of nickel metal and nickel oxide nanoparticles in human lung cells
  • 2018
  • Ingår i: Particle and Fibre Toxicology. - : BMC. - 1743-8977. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Genotoxicity is an important toxicological endpoint due to the link to diseases such as cancer. Therefore, an increased understanding regarding genotoxicity and underlying mechanisms is needed for assessing the risk with exposure to nanoparticles (NPs). The aim of this study was to perform an in-depth investigation regarding the genotoxicity of well-characterized Ni and NiO NPs in human bronchial epithelial BEAS-2B cells and to discern possible mechanisms. Comparisons were made with NiCl2 in order to elucidate effects of ionic Ni. Methods: BEAS-2B cells were exposed to Ni and NiO NPs, as well as NiCl2, and uptake and cellular dose were investigated by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS). The NPs were characterized in terms of surface composition (X-ray photoelectron spectroscopy), agglomeration (photon cross correlation spectroscopy) and nickel release in cell medium (ICP-MS). Cell death (necrosis/apoptosis) was investigated by Annexin VFITC/PI staining and genotoxicity by cytokinesis-block micronucleus (cytome) assay (OECD 487), chromosomal aberration (OECD 473) and comet assay. The involvement of intracellular reactive oxygen species (ROS) and calcium was explored using the fluorescent probes, DCFH-DA and Fluo-4. Results: NPs were efficiently taken up by the BEAS-2B cells. In contrast, no or minor uptake was observed for ionic Ni from NiCl2. Despite differences in uptake, all exposures (NiO, Ni NPs and NiCl2) caused chromosomal damage. Furthermore, NiO NPs were most potent in causing DNA strand breaks and generating intracellular ROS. An increase in intracellular calcium was observed and modulation of intracellular calcium by using inhibitors and chelators clearly prevented the chromosomal damage. Chelation of iron also protected against induced damage, particularly for NiO and NiCl2. Conclusions: This study has revealed chromosomal damage by Ni and NiO NPs as well as Ni ionic species and provides novel evidence for a calcium-dependent mechanism of cyto- and genotoxicity.
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32.
  • Elihn, Karine, et al. (författare)
  • Air quality impacts of a large waste fire in Stockholm, Sweden
  • 2023
  • Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 315
  • Tidskriftsartikel (refereegranskat)abstract
    • Fires in waste facilities are a common occurrence. Since many waste facilities are located adjacent to densely populated areas, these fires could potentially expose large populations to the emitted pollutants. However, at the moment there are only few field studies investigating the impact of waste fire emissions on air quality since the unpredictable nature of these events makes them challenging to capture. This study investigated the impact of a large and persistent un-prescribed fire in a waste storage facility in Stockholm county, Sweden, on the local air quality of two residential areas in close proximity to the fire. In-situ measurements of particulate matter, black carbon and nitrogen oxide concentrations were conducted both during open burning and after the fire was fully covered. In addition, filter samples were collected for offline analysis of organic composition, metal content and toxicity. Strongly increased concentrations of PM10, PM2.5 and black carbon were found during the open burning period, especially when the wind was coming from the direction of the fire. In addition, elevated concentrations of particulate heavy metals and polycyclic aromatic hydrocarbons were observed in the air during the open burning period. These results show that waste fires can have a strong impact on the air quality of nearby residential areas.
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33.
  • Elihn, Karine, et al. (författare)
  • Cellular Dose of Partly Soluble Cu Particle Aerosols at the Air-Liquid Interface Using an In Vitro Lung Cell Exposure System
  • 2013
  • Ingår i: Journal of Aerosol Medicine. - : Mary Ann Liebert Inc. - 1941-2711 .- 1941-2703. ; 26:2, s. 84-93
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is currently a need to develop and test in vitro systems for predicting the toxicity of nanoparticles. One challenge is to determine the actual cellular dose of nanoparticles after exposure. Methods: In this study, human epithelial lung cells (A549) were exposed to airborne Cu particles at the air-liquid interface (ALI). The cellular dose was determined for two different particle sizes at different deposition conditions, including constant and pulsed Cu aerosol flow. Results: Airborne polydisperse particles with a geometric mean diameter (GMD) of 180nm [geometric standard deviation (GSD) 1.5, concentration 10(5) particles/mL] deposited at the ALI yielded a cellular dose of 0.4-2.6 mu g/cm(2) at pulsed flow and 1.6-7.6 mu g/cm(2) at constant flow. Smaller polydisperse particles in the nanoregime (GMD 80 nm, GSD 1.5, concentration 10(7) particles/mL) resulted in a lower cellular dose of 0.01-0.05 mu g/cm(2) at pulsed flow, whereas no deposition was observed at constant flow. Exposure experiments with and without cells showed that the Cu particles were partly dissolved upon deposition on cells and in contact with medium. Conclusions: Different cellular doses were obtained for the different Cu particle sizes (generated with different methods). Furthermore, the cellular doses were affected by the flow conditions in the cell exposure system and the solubility of Cu. The cellular doses of Cu presented here are the amount of Cu that remained on the cells after completion of an experiment. As Cu particles were partly dissolved, Cu (a nonnegligible contribution) was, in addition, present and analyzed in the nourishing medium present beneath the cells. This study presents cellular doses induced by Cu particles and demonstrates difficulties with deposition of nanoparticles at the ALI and of partially soluble particles.
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34.
  • Gliga, Anda R., et al. (författare)
  • Cerium oxide nanoparticles inhibit differentiation of neural stem cells
  • 2017
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerium oxide nanoparticles (nanoceria) display antioxidant properties and have shown cytoprotective effects both in vitro and in vivo. Here, we explored the effects of nanoceria on neural progenitor cells using the C17.2 murine cell line as a model. First, we assessed the effects of nanoceria versus samarium (Sm) doped nanoceria on cell viability in the presence of the prooxidant, DMNQ. Both particles were taken up by cells and nanoceria, but not Sm-doped nanoceria, elicited a temporary cytoprotective effect upon exposure to DMNQ. Next, we employed RNA sequencing to explore the transcriptional responses induced by nanoceria or Sm-doped nanoceria during neuronal differentiation. Detailed computational analyses showed that nanoceria altered pathways and networks relevant for neuronal development, leading us to hypothesize that nanoceria inhibits neuronal differentiation, and that nanoceria and Sm-doped nanoceria both interfere with cytoskeletal organization. We confirmed that nanoceria reduced neuron specific beta 3-tubulin expression, a marker of neuronal differentiation, and GFAP, a neuroglial marker. Furthermore, using super-resolution microscopy approaches, we could show that both particles interfered with cytoskeletal organization and altered the structure of neural growth cones. Taken together, these results reveal that nanoceria may impact on neuronal differentiation, suggesting that nanoceria could pose a developmental neurotoxicity hazard.
  •  
35.
  • Gliga, Anda R., et al. (författare)
  • RNA-sequencing reveals long-term effects of silver nanoparticles on human lung cells
  • 2018
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite a considerable focus on the adverse effects of silver nanoparticles (AgNPs) in recent years, studies on the potential long-term effects of AgNPs are scarce. The aim of this study was to explore the effects of AgNPs following repeated low-dose, long-term exposure of human bronchial epithelial cells. To this end, the human BEAS-2B cell line was exposed to 1 mu g/mL AgNPs (10 nm) for 6 weeks followed by RNA-sequencing (RNA-Seq) as well as genome-wide DNA methylation analysis. The transcriptomics analysis showed that a substantial number of genes (1717) were differentially expressed following AgNP exposure whereas only marginal effects on DNA methylation were observed. Downstream analysis of the transcriptomics data identified several affected pathways including the 'fibrosis' and 'epithelial-mesenchymal transition' (EMT) pathway. Subsequently, functional validation studies were performed using AgNPs of two different sizes (10 nm and 75 nm). Both NPs increased collagen deposition, indicative of fibrosis, and induced EMT, as evidenced by an increased invasion index, anchorage independent cell growth, as well as cadherin switching. In conclusion, using a combination of RNA-Seq and functional assays, our study revealed that repeated low-dose, long-term exposure of human BEAS-2B cells to AgNPs is pro-fibrotic, induces EMT and cell transformation.
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36.
  • Gliga, Anda R., et al. (författare)
  • Silver nanoparticles modulate lipopolysaccharide-triggered Toll-like receptor signaling in immune-competent human cell lines
  • 2020
  • Ingår i: Nanoscale Advances. - : ROYAL SOC CHEMISTRY. - 2516-0230. ; 2:2, s. 648-658
  • Tidskriftsartikel (refereegranskat)abstract
    • Silver (Ag) nanoparticles are commonly used in consumer products due to their antimicrobial properties. Here we studied the impact of Ag nanoparticles on immune responses by using cell lines of monocyte/macrophage and lung epithelial cell origin, respectively. Short-term experiments (24 h) showed that Ag nanoparticles reduced the lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines in THP-1 cells under serum-free conditions. ICP-MS analysis revealed that cellular uptake of Ag was higher under these conditions. Long-term exposure (up to 6 weeks) of BEAS-2B cells to Ag nanoparticles also suppressed pro-inflammatory cytokine production following a brief challenge with LPS. Experiments using reporter cells revealed that Ag nanoparticles as well as AgNO3 inhibited LPS-triggered Toll-like receptor (TLR) signaling. Furthermore, RNA-sequencing of BEAS-2B cells indicated that Ag nanoparticles affected TLR signaling pathways. In conclusion, Ag nanoparticles reduced the secretion of pro-inflammatory cytokines in response to LPS, likely as a result of the release of silver ions leading to an interference with TLR signaling. This could have implications for the use of Ag nanoparticles as antibacterial agents. Further in vivo studies are warranted to study this.
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37.
  • Gliga, Anda R., et al. (författare)
  • Size-dependent cytotoxicity of silver nanoparticles in human lung cells : the role of cellular uptake, agglomeration and Ag release
  • 2014
  • Ingår i: Particle and Fibre Toxicology. - : BioMed Central (BMC). - 1743-8977. ; 11:1, s. 11-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Silver nanoparticles (AgNPs) are currently one of the most manufactured nanomaterials. A wide range of toxicity studies have been performed on various AgNPs, but these studies report a high variation in toxicity and often lack proper particle characterization. The aim of this study was to investigate size-and coating-dependent toxicity of thoroughly characterized AgNPs following exposure of human lung cells and to explore the mechanisms of toxicity. Methods: BEAS-2B cells were exposed to citrate coated AgNPs of different primary particle sizes (10, 40 and 75 nm) as well as to 10 nm PVP coated and 50 nm uncoated AgNPs. The particle agglomeration in cell medium was investigated by photon cross correlation spectroscopy (PCCS); cell viability by LDH and Alamar Blue assay; ROS induction by DCFH-DA assay; genotoxicity by alkaline comet assay and gamma H(2)AX foci formation; uptake and intracellular localization by transmission electron microscopy (TEM); and cellular dose as well as Ag release by atomic absorption spectroscopy (AAS). Results: The results showed cytotoxicity only of the 10 nm particles independent of surface coating. In contrast, all AgNPs tested caused an increase in overall DNA damage after 24 h assessed by the comet assay, suggesting independent mechanisms for cytotoxicity and DNA damage. However, there was no gamma H(2)AX foci formation and no increased production of intracellular reactive oxygen species (ROS). The reasons for the higher toxicity of the 10 nm particles were explored by investigating particle agglomeration in cell medium, cellular uptake, intracellular localization and Ag release. Despite different agglomeration patterns, there was no evident difference in the uptake or intracellular localization of the citrate and PVP coated AgNPs. However, the 10 nm particles released significantly more Ag compared with all other AgNPs (approx. 24 wt% vs. 4-7 wt%) following 24 h in cell medium. The released fraction in cell medium did not induce any cytotoxicity, thus implying that intracellular Ag release was responsible for the toxicity. Conclusions: This study shows that small AgNPs (10 nm) are cytotoxic for human lung cells and that the toxicity observed is associated with the rate of intracellular Ag release, a 'Trojan horse' effect.
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38.
  • Hedberg, Jonas, et al. (författare)
  • The importance of extracellular speciation and corrosion of copper nanoparticles on lung cell membrane integrity
  • 2016
  • Ingår i: Colloids and Surfaces B. - : Elsevier. - 0927-7765 .- 1873-4367. ; 141, s. 291-300
  • Tidskriftsartikel (refereegranskat)abstract
    • Copper nanoparticles (Cu NPs) are increasingly used in various biologically relevant applications and products, e.g., due to their antimicrobial and catalytic properties. This inevitably demands for an improved understanding on their interactions and potential toxic effects on humans. The aim of this study was to investigate the corrosion of copper nanoparticles in various biological media and to elucidate the speciation of released copper in solution. Furthermore, reactive oxygen species (ROS) generation and lung cell (A549 type II) membrane damage induced by Cu NPs in the various media were studied. The used biological media of different complexity are of relevance for nanotoxicological studies: Dulbecco's modified eagle medium (DMEM), DMEM+ (includes fetal bovine serum), phosphate buffered saline (PBS), and PBS + histidine. The results show that both copper release and corrosion are enhanced in DMEM+, DMEM, and PBS + histidine compared with PBS alone. Speciation results show that essentially no free copper ions are present in the released fraction of Cu NPs in neither DMEM+, DMEM nor histidine, while labile Cu complexes form in PBS. The Cu NPs were substantially more membrane reactive in PBS compared to the other media and the NPs caused larger effects compared to the same mass of Cu ions. Similarly, the Cu NPs caused much more ROS generation compared to the released fraction only. Taken together, the results suggest that membrane damage and ROS formation are stronger induced by Cu NPs and by free or labile Cu ions/complexes compared with Cu bound to biomolecules.
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39.
  • Hedberg, Yolanda, et al. (författare)
  • Bioaccessibility, bioavailability and toxicity of commercially relevant iron- and chromium-based particles: in vitro studies with an inhalation perspective
  • 2010
  • Ingår i: Particle and Fibre Toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 7:23
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundProduction of ferrochromium alloys (FeCr), master alloys for stainless steel manufacture, involves casting and crushing processes where particles inevitably become airborne and potentially inhaled. The aim of this study was to assess potential health hazards induced by inhalation of different well-characterized iron- and chromium-based particles, i.e. ferrochromium (FeCr), ferrosiliconchromium (FeSiCr), stainless steel (316L), iron (Fe), chromium (Cr), and chromium(III)oxide (Cr2O3), in different size fractions using in vitro methods. This was done by assessing the extent and speciation of released metals in synthetic biological medium and by analyzing particle reactivity and toxicity towards cultured human lung cells (A549).ResultsThe amount of released metals normalized to the particle surface area increased with decreasing particle size for all alloy particles, whereas the opposite situation was valid for particles of the pure metals. These effects were evident in artificial lysosomal fluid (ALF) of pH 4.5 containing complexing agents, but not in neutral or weakly alkaline biological media. Chromium, iron and nickel were released to very low extent from all alloy particles, and from particles of Cr due to the presence of a Cr(III)-rich protective surface oxide. Released elements were neither proportional to the bulk nor to the surface composition after the investigated 168 hours of exposure. Due to a surface oxide with less protective properties, significantly more iron was released from pure iron particles compared with the alloys. Cr was predominantly released as Cr(III) from all particles investigated and was strongly complexed by organic species of ALF. Cr2O3 particles showed hemolytic activity, but none of the alloy particles did. Fine-sized particles of stainless steel caused however DNA damage, measured with the comet assay after 4 h exposure. None of the particles revealed any significant cytotoxicity in terms of cell death after 24 h exposure.ConclusionIt is evident that particle and alloy characteristics such as particle size and surface composition are important aspects to consider when assessing particle toxicity and metal release from alloy particles compared to pure metal particles. Generated results clearly elucidate that neither the low released concentrations of metals primarily as a result of protective and poorly soluble surface oxides, nor non-bioavailable chromium complexes, nor the particles themselves of occupational relevance induced significant acute toxic response, with exception of DNA damage from stainless steel.
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40.
  • Hedberg, Yolanda, et al. (författare)
  • Surface passivity largely governs the bioaccessibility of nickel-based powder particles at human exposure conditions
  • 2016
  • Ingår i: Regulatory toxicology and pharmacology. - : Elsevier BV. - 0273-2300 .- 1096-0295. ; 81, s. 162-170
  • Tidskriftsartikel (refereegranskat)abstract
    • The European chemical framework REACH requires that hazards and risks posed by chemicals, including alloys and metals, are identified and proven safe for humans and the environment. Therefore, differences in bioaccessibility in terms of released metals in synthetic biological fluids (different pH (1.5-7.4) and composition) that are relevant for different human exposure routes (inhalation, ingestion, and dermal contact) have been assessed for powder particles of an alloy containing high levels of nickel (Inconel 718, 57 wt% nickel). This powder is compared with the bioaccessibility of two nickel-containing stainless steel powders (AISI 316L, 10-12% nickel) and with powders representing their main pure alloy constituents: two nickel metal powders (100% nickel), two iron metal powders and two chromium metal powders. Xray photoelectron spectroscopy, microscopy, light scattering, and nitrogen absorption were employed for the particle and surface oxide characterization. Atomic absorption spectroscopy was used to quantify released amounts of metals in solution. Cytotoxicity (Alamar blue assay) and DNA damage (comet assay) of the Inconel powder were assessed following exposure of the human lung cell line A549, as well as its ability to generate reactive oxygen species (DCFH-DA assay). Despite its high nickel content, the Inconel alloy powder did not release any significant amounts of metals and did not induce any toxic response. It is concluded, that this is related to the high surface passivity of the Inconel powder governed by its chromium-rich surface oxide. Read-across from the pure metal constituents is hence not recommended either for this or any other passive alloy.
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41.
  • Karlsson, Hanna L, et al. (författare)
  • Comparison of genotoxic and inflammatory effects of particles generated by wood combustion, a road simulator and collected from street and subway
  • 2006
  • Ingår i: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 165:3, s. 203-211
  • Tidskriftsartikel (refereegranskat)abstract
    • The health effects of exposure to airborne particles are of increasing concern in society. In order to protect public health, a clarification of the toxic properties of particles from different sources is of importance. The aim of this study was to investigate and compare the genotoxicity and the ability to induce inflammatory mediators of nine different particle types from wood and pellets combustion, from tire–road wear and collected from an urban street and a subway station. The comet assay was used to assess genotoxicity after exposure of the human lung cell line A549. Inflammatory effects were measured as induction of IL-6, IL-8 and TNF-α after exposure of human macrophages. We found that all particles tested caused DNA damage and those from the subway caused more damage than the other particles (p < 0.001) likely due to redox-active iron. In contrast, particles collected from an urban street were most potent to induce inflammatory cytokines. Particles from tire–road wear collected using a road simulator were genotoxic and able to induce cytokines. Finally, more effective combustion of wood led to less emission of particles, but those emitted did not show less toxicity in this study.
  •  
42.
  • Karlsson, Hanna L., et al. (författare)
  • Mechanism-based genotoxicity screening of metal oxide nanoparticles using the ToxTracker panel of reporter cell lines
  • 2014
  • Ingår i: Particle and Fibre Toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 11, s. 41-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The rapid expansion of manufacturing and use of nano-sized materials fuels the demand for fast and reliable assays to identify their potential hazardous properties and underlying mechanisms. The ToxTracker assay is a recently developed mechanism-based reporter assay based on mouse embryonic stem (mES) cells that uses GFP-tagged biomarkers for detection of DNA damage, oxidative stress and general cellular stress upon exposure. Here, we evaluated the ability of the ToxTracker assay to identify the hazardous properties and underlying mechanisms of a panel of metal oxide-and silver nanoparticles (NPs) as well as additional non-metallic materials (diesel, carbon nanotubes and quartz). Methods: The metal oxide-and silver nanoparticles were characterized in terms of agglomeration and ion release in cell medium (using photon cross correlation spectroscopy and inductively coupled plasma with optical emission spectroscopy, respectively) as well as acellular ROS production (DCFH-DA assay). Cellular uptake was investigated by means of transmission electron microscopy. GFP reporter induction and cytotoxicity of the NPs was simultaneously determined using flow cytometry, and genotoxicity was further tested using conventional assays (comet assay, gamma-H(2)AX and RAD51 foci formation). Results: We show that the reporter cells were able to take up nanoparticles and, furthermore, that exposure to CuO, NiO and ZnO nanoparticles as well as to quartz resulted in activation of the oxidative stress reporter, although only at high cytotoxicity for ZnO. NiO NPs activated additionally a p53-associated cellular stress response, indicating additional reactive properties. Conventional assays for genotoxicity assessment confirmed the response observed in the ToxTracker assay. We show for CuO NPs that the induction of oxidative stress is likely the consequence of released Cu ions whereas the effect by NiO was related to the particles per se. The DNA replication stress-induced reporter, which is most strongly associated with carcinogenicity, was not activated by any of the tested nanoparticles. Conclusions: We conclude that the ToxTracker reporter system can be used as a rapid mechanism-based tool for the identification of hazardous properties of metal oxide NPs. Furthermore, genotoxicity of metal oxide NPs seems to occur mainly via oxidative stress rather than direct DNA binding with subsequent replication stress.
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43.
  • Karlsson, Hanna L., et al. (författare)
  • Toxicity of Metal and Metal Oxide Nanoparticles
  • 2015
  • Ingår i: Handbook on the Toxicology of Metals: Fourth Edition. - : Elsevier BV. ; , s. 75-112
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Engineered nanomaterials hold great potential in many sectors of society, not least in medicine. However, the increasing production and use of engineered nanomaterials also raises concerns about inadvertent exposure and the potential for adverse effects on human health and the environment. This chapter provides an overview of metal and metal oxide nanoparticles, their applications, and the potential for human exposure. This is followed by a discussion of general principles of nanoparticle-induced toxicity and methods for toxicity testing of nanomaterials. Careful assessment of the material properties is required for a full understanding of nanomaterial toxicity; a section of the chapter is therefore devoted to physicochemical characterization. This is followed by a detailed description of the current knowledge concerning 12 of the most important metal and metal oxide nanoparticles, with a systematic evaluation of invitro (cell culture) and invivo (animal) toxicity studies. Ecotoxicological effects are not discussed because the chapter is focused on implications for human health.
  •  
44.
  • Kobayashi, Yumi, et al. (författare)
  • Life-cycle assessment of yeast-based single-cell protein production with oat processing side-stream
  • 2023
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 1879-1026 .- 0048-9697. ; 873
  • Tidskriftsartikel (refereegranskat)abstract
    • Production of fish meal and plant-based feed proteins continues to increase to meet the growing demand for seafood, leading to impacts on marine and terrestrial ecosystems. Microbial proteins such as single-cell proteins (SCPs) have been introduced as feed alternatives since they can replace current fish feed ingredients, e.g., soybean, which are associated with negative environmental impacts. Microbial protein production also enables utilization of grain processing side-streams as feedstock sources. This study assesses the environmental impacts of yeast-based SCP using oat side-stream as feedstock (OS-SCP). Life-cycle assessment with a cradle-to-gate approach was used to quantify global warming, freshwater eutrophication, marine eutrophication, terrestrial acidification, land use, and water consumption of OS-SCP production in Finland. Dried and wet side-streams of oat were compared with each other to identify differences in energy consumption and transportation effects. Sensitivity analysis was performed to examine the difference in impacts at various locations and fermentation times. Benchmarking was used to evaluate the environmental impacts of OS-SCP and other feed products, including both conventional and novel protein products. Results highlight the importance of energy sources in quantifying the environmental performance of OS-SCP production. OS-SCP produced with dried side-streams resulted in higher global warming (16.3 %) and water consumption (7.5 %) than OS-SCP produced from wet side-streams, reflecting the energy and water requirements for the drying process. Compared with conventional products, such as soy protein concentrates, OS-SCP resulted in 61 % less land use, while exacerbating the environmental impacts in all the other categories. OS-SCP had more impact on global warming (205-754 %), water consumption (166-1401 %), freshwater eutrophication (118-333 %), and terrestrial acidification (85-340 %) than other novel products, including yeast protein concentrate, methanotrophic bacterial SCP, and insect meal, while lowering global warming (11 %) and freshwater eutrophication (20 %) compared with dry microalgae biomass.
  •  
45.
  • Latvala, Siiri, et al. (författare)
  • In vitro genotoxicity of airborne Ni-NP in air-liquid interface
  • 2017
  • Ingår i: Journal of Applied Toxicology. - : Wiley. - 0260-437X .- 1099-1263. ; 37:12, s. 1420-1427
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies using advanced toxicological methods enabling in vitro conditions that are more realistic are currently needed for understanding the risks of pulmonary exposure to airborne nanoparticles. Owing to the carcinogenicity of certain nickel compounds, the increased production of nickel nanoparticles (Ni-NPs) raises occupational safety concerns. The aim of this study was to investigate the genotoxicity of airborne Ni-NPs using a recently developed air-liquid interface exposure system. The wild-type Chinese hamster lung fibroblast cell line (V79) was used and cytotoxicity, DNA damage and mutagenicity were studied by testing colony forming efficiency, alkaline DNA unwinding and HPRT mutation assays, respectively. Additionally, co-exposure to a PARP-1 inhibitor was performed to test possible involvement of base excision repair (BER) in repair of Ni-induced DNA damage. The results showed that cell viability was reduced significantly (to 45% and 46%) after 48hours Ni-NP exposure at concentrations of 0.15 and 0.32g cm(-2). DNA damage was significantly increased after Ni-NP exposure in the presence of the BER inhibitor indicating that Ni-NP-induced DNA damages are subsequently repaired by BER. Furthermore, there was no increased HPRT mutation frequency following Ni-NP exposure. In conclusion, this study shows that Ni-NP treatment of lung fibroblasts in an air-liquid interface system that mimics real-life exposure, results in increased DNA strand breaks and reduced cellular viability. These DNA lesions were repaired with BER in an error-free manner without resulting in mutations. This study also underlines the importance of appropriate quantification of the actual exposure concentrations during air-liquid interface exposure studies. The aim of this study was to investigate the genotoxicity of airborne Ni nanoparticles using a recently developed air-liquid interface exposure system that mimics real-life exposure. Cytotoxicity, DNA damage and mutagenicity were in the V79 cell line. Ni nanoparticle exposure of the cells in the air-liquid interface resulted in increased DNA strand breaks and reduced cellular viability at concentrations of 0.15 and 0.32 g cm (-2). These DNA lesions were repaired with BER in an error-free manner without resulting in mutations
  •  
46.
  • Latvala, Siiri, et al. (författare)
  • Nickel release, ROS generation and toxicity of Ni and NiO micro- and nanoparticles
  • 2016
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Occupational exposure to airborne nickel is associated with an elevated risk for respiratory tract diseases including lung cancer. Therefore, the increased production of Ni-containing nanoparticles necessitates a thorough assessment of their physical, chemical, as well as toxicological properties. The aim of this study was to investigate and compare the characteristics of nickel metal (Ni) and nickel oxide (NiO) particles with a focus on Ni release, reactive oxygen species (ROS) generation, cellular uptake, cytotoxicity and genotoxicity. Four Ni-containing particles of both nano-size (Ni-n and NiO-n) and micron-size (Ni-m1 and Ni-m2) were tested. The released amount of Ni in solution was notably higher in artificial lysosomal fluid (e.g. 80–100 wt% for metallic Ni) than in cell medium after 24h (ca. 1–3 wt% for all particles). Each of the particles was taken up by the cells within 4 h and they remained in the cells to a high extent after 24 h post-incubation. Thus, the high dissolution in ALF appeared not to reflect the particle dissolution in the cells. Ni-m1 showed the most pronounced effect on cell viability after 48 h (alamar blue assay) whereas all particles showed increased cytotoxicity in the highest doses (20–40 μg cm2) when assessed by colony forming efficiency (CFE). Interestingly an increased CFE, suggesting higher proliferation, was observed for all particles in low doses (0.1 or 1 μg cm-2). Ni-m1 and NiO-n were the most potent in causing acellular ROS and DNA damage. However, no intracellular ROS was detected for any of the particles. Taken together, micron-sized Ni (Ni-m1) was more reactive and toxic compared to the nano-sized Ni. Furthermore, this study underlines that the low dose effect in terms of increased proliferation observed for all particles should be further investigated in future studies.
  •  
47.
  • Lebedova, Jana, et al. (författare)
  • Size-dependent genotoxicity of silver, gold and platinum nanoparticles studied using the mini-gel comet assay and micronucleus scoring with flow cytometry
  • 2018
  • Ingår i: Mutagenesis. - : OXFORD UNIV PRESS. - 0267-8357 .- 1464-3804. ; 33:1, s. 77-85
  • Tidskriftsartikel (refereegranskat)abstract
    • Metallic nanoparticles (NPs) are promising nanomaterials used in different technological solutions as well as in consumer products. Silver (Ag), gold (Au) and platinum (Pt) represent three metallic NPs with current or suggested use in different applications. Pt is also used as vehicle exhaust catalyst leading to a possible exposure via inhalation. Despite their use, there is limited data on their genotoxic potential and possible size-dependent effects, particularly for Pt NPs. The aim of this study was to explore size-dependent genotoxicity of these NPs (5 and 50 nm) following exposure of human bronchial epithelial cells. We characterised the NPs and assessed the viability (Alamar blue assay), formation of DNA strand breaks (mini-gel comet assay) and induction of micronucleus (MN) analysed using flow cytometry (in vitro microflow kit). The results confirmed the primary size (5 and 50 nm) but showed agglomeration of all NPs in the serum free medium used. Slight reduced cell viability (tested up to 50 mu g/ml) was observed following exposure to the Ag NPs of both particle sizes as well as to the smallest (5 nm) Au NPs. Similarly, at non-cytotoxic concentrations, both 5 and 50 nm-sized Ag NPs, as well as 5 nm-sized Au NPs, increased DNA strand breaks whereas for Pt NPs only the 50 nm size caused a slight increase in DNA damage. No clear induction of MN was observed in any of the doses tested (up to 20 mu g/ml). Taken together, by using the comet assay our study shows DNA strand breaks induced by Ag NPs, without any obvious differences in size, whereas effects from Au and Pt NPs were size-dependent in the sense that the 5 nm-sized Au NPs and 50 nm-sized Pt NPs particles were active. No clear induction of MN was observed for the NPs.
  •  
48.
  • Löfdahl, Anna, et al. (författare)
  • Silver nanoparticles alter cell viability ex vivo and in vitro and induce proinflammatory effects in human lung fibroblasts
  • 2020
  • Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 10:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Silver nanoparticles (AgNPs) are commonly used in commercial and medical applications. However, AgNPs may induce toxicity, extracellular matrix (ECM) changes and inflammatory responses. Fibroblasts are key players in remodeling processes and major producers of the ECM. The aims of this study were to explore the effect of AgNPs on cell viability, both ex vivo in murine precision cut lung slices (PCLS) and in vitro in human lung fibroblasts (HFL-1), and immunomodulatory responses in fibroblasts. PCLS and HFL-1 were exposed to AgNPs with different sizes, 10 nm and 75 nm, at concentrations 2 µg/mL and 10 µg/mL. Changes in synthesis of ECM proteins, growth factors and cytokines were analyzed in HFL-1. Ag10 and Ag75 affected cell viability, with significantly reduced metabolic activities at 10 µg/mL in both PCLS and HFL-1 after 48 h. AgNPs significantly increased procollagen I synthesis and release of IL-8, prostaglandin E2, RANTES and eotaxin, whereas reduced IL-6 release was observed in HFL-1 after 72 h. Our data indicate toxic effects of AgNP exposure on cell viability ex vivo and in vitro with altered procollagen and proinflammatory cytokine secretion in fibroblasts over time. Hence, careful characterizations of AgNPs are of importance, and future studies should include timepoints beyond 24 h.
  •  
49.
  • McCarrick, Sarah, et al. (författare)
  • Genotoxicity and inflammatory potential of stainless steel welding fume particles : an in vitro study on standard vs Cr(VI)-reduced flux-cored wires and the role of released metals
  • 2021
  • Ingår i: Archives of Toxicology. - : Springer Nature. - 0340-5761 .- 1432-0738. ; 95:9, s. 2961-2975
  • Tidskriftsartikel (refereegranskat)abstract
    • Welders are daily exposed to various levels of welding fumes containing several metals. This exposure can lead to an increased risk for different health effects which serves as a driving force to develop new methods that generate less toxic fumes. The aim of this study was to explore the role of released metals for welding particle-induced toxicity and to test the hypothesis that a reduction of Cr(VI) in welding fumes results in less toxicity by comparing the welding fume particles of optimized Cr(VI)-reduced flux-cored wires (FCWs) to standard FCWs. The welding particles were thoroughly characterized, and toxicity (cell viability, DNA damage and inflammation) was assessed following exposure to welding particles as well as their released metal fraction using cultured human bronchial epithelial cells (HBEC-3kt, 5-100 mu g/mL) and human monocyte-derived macrophages (THP-1, 10-50 mu g/mL). The results showed that all Cr was released as Cr(VI) for welding particles generated using standard FCWs whereas only minor levels (< 3% of total Cr) were released from the newly developed FCWs. Furthermore, the new FCWs were considerably less cytotoxic and did not cause any DNA damage in the doses tested. For the standard FCWs, the Cr(VI) released in cell media seemed to explain a large part of the cytotoxicity and DNA damage. In contrast, all particles caused rather similar inflammatory effects suggesting different underlying mechanisms. Taken together, this study suggests a potential benefit of substituting standard FCWs with Cr(VI)-reduced wires to achieve less toxic welding fumes and thus reduced risks for welders.
  •  
50.
  • McCarrick, Sarah, et al. (författare)
  • High variability in toxicity of welding fume nanoparticles from stainless steel in lung cells and reporter cell lines : the role of particle reactivity and solubility
  • 2019
  • Ingår i: Nanotoxicology. - : TAYLOR & FRANCIS LTD. - 1743-5390 .- 1743-5404.
  • Tidskriftsartikel (refereegranskat)abstract
    • Millions of people in the world perform welding as their primary occupation resulting in exposure to metal-containing nanoparticles in the fumes generated. Even though health effects including airway diseases are well-known, there is currently a lack of studies investigating how different welding set-ups and conditions affect the toxicity of generated nanoparticles of the welding fume. The aim of this study was to investigate the toxicity of nine types of welding fume particles generated via active gas shielded metal arc welding (GMAW) of chromium-containing stainless steel under different conditions and, furthermore, to correlate the toxicity to the particle characteristics. Toxicological endpoints investigated were generation of reactive oxygen species (ROS), cytotoxicity, genotoxicity and activation of ToxTracker reporter cell lines. The results clearly underline that the choice of filler material has a large influence on the toxic potential. Fume particles generated by welding with the tested flux-cored wire (FCW) were found to be more cytotoxic compared to particles generated by welding with solid wire or metal-cored wire (MCW). FCW fume particles were also the most potent in causing ROS and DNA damage and they furthermore activated reporters related to DNA double- strand breaks and p53 signaling. Interestingly, the FCW fume particles were the most soluble in PBS, releasing more chromium in the hexavalent form and manganese compared to the other fumes. These results emphasize the importance of solubility of different metal constituents of the fume particles, rather than the total metal content, for their acute toxic potential.
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