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2.
  • Muala, Ala, et al. (författare)
  • Respiratory Tract Deposition of Inhaled Wood Smoke Particles in Healthy Volunteers
  • 2015
  • Ingår i: Journal of Aerosol Medicine. - : Mary Ann Liebert Inc. - 1941-2711 .- 1941-2703. ; 28:4, s. 237-246
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Respiratory tract deposition of air pollution particles is a key to their adverse health effects. This study was aimed to determine the size-resolved deposition fraction (DF) of sooty wood smoke particles in the lungs of healthy subjects. The type of wood smoke investigated is typical for household air pollution from solid fuels, which is among the largest environmental health problems globally.Methods: Twelve healthy volunteers inhaled diluted wood smoke from incomplete soot-rich combustion in a common wood stove. The DF of smoke particles (10–500 nm) was measured during three 15-min exposures in each subject during spontaneous breathing. Lung function was measured using standard spirometry.Results: The total DFs by particle number concentration were 0.34±0.08. This can be compared with DFs of 0.21–0.23 in healthy subjects during previous experiments with wood pellet combustion. For particle mass, the total DFs found in this study were 0.22±0.06. DF and breathing frequency were negatively correlated as expected from model calculations (p<0.01).Conclusions: The DF of the investigated sooty wood smoke particles was higher than for previously investigated particles generated during more efficient combustion of biomass. Together with toxicological studies, which have indicated that incomplete biomass combustion particles rich in soot and polycyclic aromatic hydrocarbons (PAHs) are especially harmful, these data highlight the health risks of inadequate wood combustion.
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3.
  • Ali, Neserin, et al. (författare)
  • Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.
  • 2016
  • Ingår i: Nanotoxicology. - : Taylor & Francis. - 1743-5390 .- 1743-5404. ; 10:2, s. 226-234
  • Tidskriftsartikel (refereegranskat)abstract
    • Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between nasal lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When nasal lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.
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4.
  • Ali, Neserin, et al. (författare)
  • Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix
  • 2018
  • Ingår i: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. Methods: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. Results: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Conclusion: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling. Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.
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5.
  • Blomberg, Sara, et al. (författare)
  • Bimetallic nanoparticles as a model system for an industrial NiMo catalyst
  • 2019
  • Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 12:22
  • Tidskriftsartikel (refereegranskat)abstract
    • An in-depth understanding of the reactionmechanismis required for the further development of Mo-based catalysts for biobased feedstocks. However, fundamental studies of industrial catalysts are challenging, and simplified systems are often used without direct comparison to their industrial counterparts. Here, we report on size-selected bimetallic NiMo nanoparticles as a candidate for a model catalyst that is directly compared to the industrial system to evaluate their industrial relevance. Both the nanoparticles and industrial supported NiMo catalysts were characterized using surface- and bulk-sensitive techniques. We found that the active Ni and Mo metals in the industrial catalyst are well dispersed and well mixed on the support, and that the interaction between Ni and Mo promotes the reduction of the Mo oxide. We successfully produced 25 nm NiMo alloyed nanoparticles with a narrow size distribution. Characterization of the nanoparticles showed that they have a metallic core with a native oxide shell with a high potential for use as a model system for fundamental studies of hydrotreating catalysts for biobased feedstocks. © 2019 by the authors.
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6.
  • Eriksson, Axel, et al. (författare)
  • Diesel soot aging in urban plumes within hours under cold dark and humid conditions
  • 2017
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322.
  • Tidskriftsartikel (refereegranskat)abstract
    • Fresh and aged diesel soot particles have different impacts on climate and human health. While fresh diesel soot particles are highly aspherical and non-hygroscopic, aged particles are spherical and hygroscopic. Aging and its effect on water uptake also controls the dispersion of diesel soot in the atmosphere. Understanding the timescales on which diesel soot ages in the atmosphere is thus important, yet knowledge thereof is lacking. We show that under cold, dark and humid conditions the atmospheric transformation from fresh to aged soot occurs on a timescale of less than five hours. Under dry conditions in the laboratory, diesel soot transformation is much less efficient. While photochemistry drives soot aging, our data show it is not always a limiting factor. Field observations together with aerosol process model simulations show that the rapid ambient diesel soot aging in urban plumes is caused by coupled ammonium nitrate formation and water uptake.
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7.
  • Harra, Juha, et al. (författare)
  • Characteristics of nFOG, an aerosol-based wet thin film coating technique
  • 2018
  • Ingår i: JCT Research. - : Springer Science and Business Media LLC. - 1547-0091 .- 2168-8028 .- 1935-3804. ; 15:3, s. 623-632
  • Tidskriftsartikel (refereegranskat)abstract
    • An atmospheric pressure aerosol-based wet thin film coating technique called the nFOG is characterized and applied in polymer film coatings. In the nFOG, a fog of droplets is formed by two air-assist atomizers oriented toward each other inside a deposition chamber. The droplets settle gravitationally and deposit on a substrate, forming a wet film. In this study, the continuous deposition mode of the nFOG is explored. We determined the size distribution of water droplets inside the chamber in a wide side range of 0.1–100 µm and on the substrate using aerosol measurement instruments and optical microscopy, respectively. The droplet size distribution was found to be bimodal with droplets of approximately 30–50 µm contributing the most to the mass of the formed wet film. The complementary measurement methods allow us to estimate the role of different droplet deposition mechanisms. The obtained results suggest that the deposition velocity of the droplets is lower than the calculated terminal settling velocity, likely due to the flow fields inside the chamber. Furthermore, the mass flux of the droplets onto the substrate is determined to be in the order of 1 g/m3s, corresponding to a wet film growth rate of 1 µm/s. Finally, the nFOG technique is demonstrated by preparing polymer films with thicknesses in the range of approximately 0.1–20 µm.
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9.
  • Hemmingsen, Jette Gjerke, et al. (författare)
  • Controlled exposure to diesel exhaust and traffic noise - Effects on oxidative stress and activation in mononuclear blood cells.
  • 2015
  • Ingår i: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 775, s. 66-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Particulate air pollution increases risk of cancer and cardiopulmonary disease, partly through oxidative stress. Traffic-related noise increases risk of cardiovascular disease and may cause oxidative stress. In this controlled random sequence study, 18 healthy subjects were exposed for 3h to diesel exhaust (DE) at 276μg/m(3) from a passenger car or filtered air, with co-exposure to traffic noise at 48 or 75dB(A). Gene expression markers of inflammation, (interleukin-8 and tumor necrosis factor), oxidative stress (heme oxygenase (decycling-1)) and DNA repair (8-oxoguanine DNA glycosylase (OGG1)) were unaltered in peripheral blood mononuclear cells (PBMCs). No significant differences in DNA damage levels, measured by the comet assay, were observed after DE exposure, whereas exposure to high noise levels was associated with significantly increased levels of hOGG1-sensitive sites in PBMCs. Urinary levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine were unaltered. In auxiliary ex vivo experiments whole blood was incubated with particles from the exposure chamber for 3h without effects on DNA damage in PBMCs or intracellular reactive oxygen species production and expression of CD11b and CD62L adhesion molecules in leukocyte subtypes.
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10.
  • Hemmingsen, J. G., et al. (författare)
  • Controlled exposure to particulate matter from urban street air is associated with decreased vasodilation and heart rate variability in overweight and older adults
  • 2015
  • Ingår i: Particle and Fibre Toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Exposure to particulate matter (PM) is generally associated with elevated risk of cardiovascular morbidity and mortality. Elderly and obese subjects may be particularly susceptible, although short-term effects are poorly described. Methods: Sixty healthy subjects 25 males, 35 females, age 55 to 83 years, body mass index > 25 kg/m(2)) were included in a cross-over study with 5 hours of exposure to particle or sham filtered air from a busy street using an exposure-chamber. The sham-versus particle-filtered air had average particle number concentrations of similar to 23.000 versus similar to 1800/cm(3) and PM2.5 levels of 24 versus 3 mu g/m(3), respectively. The PM contained similar fractions of elemental and black carbon (similar to 20-25%) in both exposure scenarios. Reactive hyperemia and nitroglycerin-induced vasodilation in finger arteries and heart rate variability (HRV) measured within 1h after exposure were primary outcomes. Potential explanatory mechanistic variables included markers of oxidative stress (ascorbate/dehydroascorbate, nitric oxide-production cofactor tetrahydrobiopterin and its oxidation product dihydrobiopterin) and inflammation markers (C-reactive protein and leukocyte differential counts). Results: Nitroglycerin-induced vasodilation was reduced by 12% [95% confidence interval: -22%; -1.0%] following PM exposure, whereas hyperemia-induced vasodilation was reduced by 5% [95% confidence interval: -11.6%; 1.6%]. Moreover, HRV measurements showed that the high and low frequency domains were significantly decreased and increased, respectively. Redox and inflammatory status did not change significantly based on the above measures. Conclusions: This study indicates that exposure to real-life levels of PM from urban street air impairs the vasomotor function and HRV in overweight middle-aged and elderly adults, although this could not be explained by changes in inflammation, oxidative stress or nitric oxide-cofactors.
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11.
  • Hofvander, Jakob, et al. (författare)
  • Frequent low-level mutations of protein kinase D2 in angiolipoma
  • 2017
  • Ingår i: Journal of Pathology. - : WILEY. - 0022-3417 .- 1096-9896. ; 241:5, s. 578-582
  • Tidskriftsartikel (refereegranskat)abstract
    • Tumours displaying differentiation towards normal fat constitute the most common subgroup of soft tissue neoplasms. A series of such tumours was investigated by whole-exome sequencing followed by targeted ultra-deep sequencing. Eighty per cent of angiolipomas, but not any other tumour type, displayed mutations in the protein kinase D2 (PRKD2) gene, typically in the part encoding the catalytic domain. The absence of other aberrations at the chromosome or RNA level suggests that PRKD2 mutations are critical for angiolipoma development. Consistently, the mutated PRKD2 alleles were present at low (3-15%) frequencies, indicating that only a subset of the tumour cells is affected. Indeed, by sequencing mature fat cells and other cells separately, the former typically showed the highest mutation frequencies. Thus, we hypothesize that altered PRKD2 signalling in the adipocytic cells drives tumourigenesis and, in agreement with its pivotal role in angiogenesis, induces the vessel formation that is characteristic for angiolipoma. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley amp; Sons, Ltd.
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12.
  • Holmquist Mengelbier, Linda, et al. (författare)
  • Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer.
  • 2015
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic differences among neoplastic cells within the same tumour have been proposed to drive cancer progression and treatment failure. Whether data on intratumoral diversity can be used to predict clinical outcome remains unclear. We here address this issue by quantifying genetic intratumoral diversity in a set of chemotherapy-treated childhood tumours. By analysis of multiple tumour samples from seven patients we demonstrate intratumoral diversity in all patients analysed after chemotherapy, typically presenting as multiple clones within a single millimetre-sized tumour sample (microdiversity). We show that microdiversity often acts as the foundation for further genome evolution in metastases. In addition, we find that microdiversity predicts poor cancer-specific survival (60%; P=0.009), independent of other risk factors, in a cohort of 44 patients with chemotherapy-treated childhood kidney cancer. Survival was 100% for patients lacking microdiversity. Thus, intratumoral genetic diversity is common in childhood cancers after chemotherapy and may be an important factor behind treatment failure.
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  • Jakobsson, Jonas K F, et al. (författare)
  • Altered deposition of inhaled nanoparticles in subjects with chronic obstructive pulmonary disease
  • 2018
  • Ingår i: BMC Pulmonary Medicine. - : BioMed Central Ltd.. - 1471-2466. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Respiratory tract deposition of airborne particles is a key link to understand their health impact. Experimental data are limited for vulnerable groups such as individuals with respiratory diseases. The aim of this study is to investigate the differences in lung deposition of nanoparticles in the distal lung for healthy subjects and subjects with respiratory disease. Methods: Lung deposition of nanoparticles (50 and 100 nm) was measured after a 10 s breath-hold for three groups: healthy never-smoking subjects (n = 17), asymptomatic (active and former) smokers (n = 15) and subjects with chronic obstructive pulmonary disease (n = 16). Measurements were made at 1300 mL and 1800 mL volumetric lung depth. Each subject also underwent conventional lung function tests, including post bronchodilator FEV1, VC, and diffusing capacity for carbon monoxide, DL,CO. Patients with previously diagnosed respiratory disease underwent a CT-scan of the lungs. Particle lung deposition fraction, was compared between the groups and with conventional lung function tests. Results: We found that the deposition fraction was significantly lower for subjects with emphysema compared to the other subjects (p = 0.001-0.01), but no significant differences were found between healthy never-smokers and smokers. Furthermore, the particle deposition correlated with pulmonary function tests, FEV1%Pred (p < 0.05), FEV1/VC%Pred (p < 0.01) and DL,CO (p < 0.0005) when all subjects were included. Furthermore, for subjects with emphysema, deposition fraction correlated strongly with DL,CO (Pearson's r = 0.80-0.85, p < 0.002) while this correlation was not found within the other groups. Conclusions: Lower deposition fraction was observed for emphysematous subjects and this can be explained by enlarged distal airspaces in the lungs. As expected, deposition increases for smaller particles and deeper inhalation. The observed results have implications for exposure assessment of air pollution and dosimetry of aerosol-based drug delivery of nanoparticles.
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15.
  • Karlsson, Jenny, et al. (författare)
  • Activation of human telomerase reverse transcriptase through gene fusion in clear cell sarcoma of the kidney.
  • 2015
  • Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 357:2, s. 498-501
  • Tidskriftsartikel (refereegranskat)abstract
    • Clear cell sarcoma of the kidney (CCSK) is a rare tumor type affecting infants and young children. Most CCSKs display few genomic aberrations, and no general underlying mechanism for tumor initiation has yet been identified, although a YWHAE-NUTM2B/NUTM2E fusion gene has been observed in a minority of cases. We performed RNA-sequencing of 22 CCSKs to investigate the presence of additional fusion transcripts. The presence of the YWHAE-NUTM2B/NUTM2E fusion was confirmed in two cases. In addition, a novel IRX2-TERT fusion transcript was identified in one case. SNP-array analyses revealed the underlying event to be an interstitial deletion in the short arm of chromosome 5 (5p15.33). TERT was dramatically upregulated under the influence of the IRX2 promoter. In line with TERT expression being driven by active IRX2 regulatory elements, we found a high expression of IRX2 in CCSKs irrespective of fusion gene status. IRX2 was also expressed in human fetal kidney - the presumed tissue of origin for CCSK. We conclude that in addition to promoter mutations and epigenetic events, TERT can also be activated in tumors via formation of fusion transcripts.
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  • Ludvigsson, Linus, et al. (författare)
  • Carbon Nanotube Emissions from Arc Discharge Production: Classification of Particle Types with Electron Microscopy and Comparison with Direct Reading Techniques.
  • 2016
  • Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 1475-3162 .- 0003-4878. ; 60:4, s. 493-512
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: An increased production and use of carbon nanotubes (CNTs) is occurring worldwide. In parallel, a growing concern is emerging on the adverse effects the unintentional inhalation of CNTs can have on humans. There is currently a debate regarding which exposure metrics and measurement strategies are the most relevant to investigate workplace exposures to CNTs. This study investigated workplace CNT emissions using a combination of time-integrated filter sampling for scanning electron microscopy (SEM) and direct reading aerosol instruments (DRIs). Material and Methods: Field measurements were performed during small-scale manufacturing of multiwalled carbon nanotubes using the arc discharge technique. Measurements with highly time- and size-resolved DRI techniques were carried out both in the emission and background (far-field) zones. Novel classifications and counting criteria were set up for the SEM method. Three classes of CNT-containing particles were defined: type 1: particles with aspect ratio length:width >3:1 (fibrous particles); type 2: particles without fibre characteristics but with high CNT content; and type 3: particles with visible embedded CNTs. Results: Offline sampling using SEM showed emissions of CNT-containing particles in 5 out of 11 work tasks. The particles were classified into the three classes, of which type 1, fibrous CNT particles contributed 37%. The concentration of all CNT-containing particles and the occurrence of the particle classes varied strongly between work tasks. Based on the emission measurements, it was assessed that more than 85% of the exposure originated from open handling of CNT powder during the Sieving, mechanical work-up, and packaging work task. The DRI measurements provided complementary information, which combined with SEM provided information on: (i) the background adjusted emission concentration from each work task in different particle size ranges, (ii) identification of the key procedures in each work task that lead to emission peaks, (iii) identification of emission events that affect the background, thereby leading to far-field exposure risks for workers other than the operator of the work task, and (iv) the fraction of particles emitted from each source that contains CNTs. Conclusions: There is an urgent need for a standardized/harmonized method for electron microscopy (EM) analysis of CNTs. The SEM method developed in this study can form the basis for such a harmonized protocol for the counting of CNTs. The size-resolved DRI techniques are commonly not specific enough to selective analysis of CNT-containing particles and thus cannot yet replace offline time-integrated filter sampling followed by SEM. A combination of EM and DRI techniques offers the most complete characterization of workplace emissions of CNTs today.
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17.
  • Löndahl, Jakob, et al. (författare)
  • Skapa bättre luftmiljö för barn
  • 2017
  • Ingår i: Luft & Miljö - Barns hälsa. - 9789162013035 ; , s. 9-11
  • Bokkapitel (populärvet., debatt m.m.)
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18.
  • Magnusson, Linda, et al. (författare)
  • Loss of the tumor suppressor gene AIP mediates the browning of human brown fat tumors
  • 2017
  • Ingår i: Journal of Pathology. - : Wiley. - 0022-3417. ; 243:2, s. 160-164
  • Tidskriftsartikel (refereegranskat)abstract
    • Human brown fat tumors (hibernomas) display concomitant loss of the tumor suppressor genes MEN1 and AIP. In the present study, we hypothesized that the brown fat phenotype is attributed to these mutations. Accordingly, we demonstrate that silencing of AIP in human brown preadipocytic and white fat cell lines results in the induction of the brown fat marker UCP1. In human adipocytic tumors, loss of MEN1 was found both in white (one out of 51 lipomas) and brown fat tumors. In contrast, concurrent loss of AIP was always accompanied by a brown fat morphology. We conclude that this white-to-brown phenotype switch in brown fat tumors is mediated by the loss of AIP.
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19.
  • Minelli, Caterina, et al. (författare)
  • Sticky Measurement Problem : Number Concentration of Agglomerated Nanoparticles
  • 2019
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 35:14, s. 4927-4935
  • Tidskriftsartikel (refereegranskat)abstract
    • Measuring the number concentration of colloidal nanoparticles (NPs) is critical for assessing reproducibility, enabling compliance with regulation, and performing risk assessments of NP-enabled products. For nanomedicines, their number concentration directly relates to their dose. However, the lack of relevant reference materials and established traceable measurement approaches make the validation of methods for NP number concentration difficult. Furthermore, commercial products often exhibit agglomeration, but guidelines for dealing with nonideal samples are scarce. We have compared the performance of five benchtop measurement methods for the measurement of colloidal number concentration in the presence of different levels of agglomeration. The methods are UV-visible spectroscopy, differential centrifugal sedimentation, dynamic light scattering, particle tracking analysis, and single-particle inductively coupled plasma mass spectrometry. We find that both ensemble and particle-by-particle methods are in close agreement for monodisperse NP samples and three methods are within 20% agreement for agglomerated samples. We discuss the sources of measurement uncertainties, including how particle agglomeration affects measurement results. This work is a first step toward validation and expansion of the toolbox of methods available for the measurement of real-world NP products.
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22.
  • Puls, Florian, et al. (författare)
  • PRDM10 -rearranged Soft Tissue Tumor : A Clinicopathologic Study of 9 Cases
  • 2019
  • Ingår i: American Journal of Surgical Pathology. - 0147-5185. ; 43:4, s. 504-513
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene fusion transcripts containing PRDM10 were recently identified in low-grade undifferentiated pleomorphic sarcomas (UPS). Here, we describe the morphologic and clinical features of 9 such tumors from 5 men and 4 women (age: 20 to 61 y). Three cases had previously been diagnosed as UPS, 3 as superficial CD34-positive fibroblastic tumor (SCD34FT), 2 as pleomorphic liposarcoma, and 1 as pleomorphic hyalinizing angiectatic tumor. The tumors were located in the superficial and deep soft tissues of the thigh/knee region (4 cases), shoulder (2 cases), foot, trunk, and perineum (1 case each) ranging in size from 1 to 6 cm. All showed poorly defined cellular fascicles of pleomorphic cells within a fibrous stroma with frequent myxoid change and a prominent inflammatory infiltrate. All displayed highly pleomorphic nuclear features, but a low mitotic count. Most tumors were well circumscribed. One of 9 tumors recurred locally, but none metastasized. Immunohistochemically, all were CD34+ and showed nuclear positivity for PRDM10; focal positivity for cytokeratins was seen in 5/6 cases. PRDM10 immunoreactivity was evaluated in 50 soft tissue tumors that could mimic PRDM10- rearranged tumors, including 4 cases exhibiting histologic features within the spectrum of SCD34FT. Except for 2/6 pleomorphic liposarcomas and 1/4 myxofibrosarcomas, other tumors did not show nuclear positivity but displayed weak to moderate cytoplasmic immunoreactivity. In conclusion, PRDM10-rearranged soft tissue tumor is characterized by pleomorphic morphology and a low mitotic count. Its morphologic spectrum overlaps with SCD34FT. Clinical features of this small series suggest an indolent behavior, justifying its distinction from UPS and other sarcomas.
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23.
  • Rissler, Jenny, et al. (författare)
  • A set-up for respiratory tract deposition efficiency measurements (15–5000 nm) and first results for a group of children and adults
  • 2017
  • Ingår i: Aerosol and Air Quality Research. - : AAGR Aerosol and Air Quality Research. - 1680-8584 .- 2071-1409. ; 17:6, s. 1244-1255
  • Tidskriftsartikel (refereegranskat)abstract
    • Exposure to airborne particulate matter is associated with a number of negative health effects ranging from respiratorydiseases to systemic effects and cancer. One important factor for understanding the health effects is the individual variationin the respiratory tract deposition of inhaled particles. In this study, we describe an experimental set-up for size-resolvedmeasurements of the lung deposited fraction of airborne particles, covering the diameter range from 15 to 5000 nm. Theset-up includes a system for generating a stable aerosol with a sufficiently broad size distribution. We used a scanningmobility particle sizer and an aerodynamic particle sizer to determine particle number and size. The set-up was used toinvestigate individual differences in the deposition fraction (DF) of particles in the respiratory tract for a group of 67subjects of both sexes aged 7–70 years. The measured DF was applied to two model aerosols, one representing an urbanenvironment and one a rural environment, and the particle deposition rates were derived (i.e., the deposited amount ofparticles per unit time). Furthermore, the deposition rates were normalized to lung surface area and body mass – two dosemeasures that are considered relevant for the health effects of airborne particles. In addition to validation of the set-up, weshow that there is a large individual variation in DF, with some subjects having a DF that is more than twice as high as thatof others. Although we observe differences in the DF between different subgroups, most individual variation wasexplained neither by age nor by gender. When normalizing the deposition rates to lung surface area or body mass, thedeposition rates of children become significantly higher than those of adults. Furthermore, the individual variability islarger for the lung surface area or body mass normalized deposition rates than for DF
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24.
  • Rissler, Jenny, et al. (författare)
  • Deposition efficiency of inhaled particles (15-5000 nm) related to breathing pattern and lung function : An experimental study in healthy children and adults
  • 2017
  • Ingår i: Particle and Fibre Toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Exposure to airborne particles has a major impact on global health. The probability of these particles to deposit in the respiratory tract during breathing is essential for their toxic effects. Observations have shown that there is a substantial variability in deposition between subjects, not only due to respiratory diseases, but also among individuals with healthy lungs. The factors determining this variability are, however, not fully understood. Method: In this study we experimentally investigate factors that determine individual differences in the respiratory tract depositions of inhaled particles for healthy subjects at relaxed breathing. The study covers particles of diameters 15-5000 nm and includes 67 subjects aged 7-70 years. A comprehensive examination of lung function was performed for all subjects. Principal component analyses and multiple regression analyses were used to explore the relationships between subject characteristics and particle deposition. Results: A large individual variability in respiratory tract deposition efficiency was found. Individuals with high deposition of a certain particle size generally had high deposition for all particles <3500 nm. The individual variability was explained by two factors: breathing pattern, and lung structural and functional properties. The most important predictors were found to be breathing frequency and anatomical airway dead space. We also present a linear regression model describing the deposition based on four variables: tidal volume, breathing frequency, anatomical dead space and resistance of the respiratory system (the latter measured with impulse oscillometry). Conclusions: To understand why some individuals are more susceptible to airborne particles we must understand, and take into account, the individual variability in the probability of particles to deposit in the respiratory tract by considering not only breathing patterns but also adequate measures of relevant structural and functional properties.
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25.
  • Schavkan, Alexander, et al. (författare)
  • Number concentration of gold nanoparticles in suspension : SAXS and spICPMS as traceable methods compared to laboratory methods
  • 2019
  • Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 9:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The industrial exploitation of high value nanoparticles is in need of robust measurement methods to increase the control over product manufacturing and to implement quality assurance. InNanoPart, a European metrology project responded to these needs by developing methods for the measurement of particle size, concentration, agglomeration, surface chemistry and shell thickness. This paper illustrates the advancements this project produced for the traceable measurement of nanoparticle number concentration in liquids through small angle X-ray scattering (SAXS) and single particle inductively coupled plasma mass spectrometry (spICPMS). It also details the validation of a range of laboratory methods, including particle tracking analysis (PTA), dynamic light scattering (DLS), differential centrifugal sedimentation (DCS), ultraviolet visible spectroscopy (UV-vis) and electrospray-differential mobility analysis with a condensation particle counter (ES-DMA-CPC). We used a set of spherical gold nanoparticles with nominal diameters between 10 nm and 100 nm and discuss the results from the various techniques along with the associated uncertainty budgets.
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26.
  • Svensson, Christian, et al. (författare)
  • Characteristics of airborne gold aggregates generated by spark discharge and high temperature evaporation furnace: Mass-mobility relationship and surface area
  • 2015
  • Ingår i: Journal of Aerosol Science. - : Elsevier BV. - 0021-8502. ; 87, s. 38-52
  • Tidskriftsartikel (refereegranskat)abstract
    • The properties of gas-borne aggregates are important in nano-technology and for potential health effects. Gold aggregates from three generators (one commercial and one custom built spark discharge generator and one high-temperature furnace) have been characterized. The aggregate surface areas were determined using five approaches - based on aggregation theory and/or measured aggregate properties. The characterization included mass-mobility relationships, effective densities (assessed by an Aerosol Particles Mass analyzer), primary particle analysis (based on Transmission Electron Microscopy), as well as total mass and number concentration outputs. The relationships between mass and mobility are well described by power-law functions with exponents of 2.18-2.35. For all generators, the primary particles of the aggregates were fused together by a bridge with a diameter typically similar to 60-70% of the primary particle diameter (5-10 nm). The total mass outputs were 6.1-48.1 mg/m3 and the predicted surface area outputs in the range 0.9 x 10(-3)-17 x 10(-3) cm(2)/cm(3). The aggregate effective densities differed considerably between generators. The difference could partly be explained by the differences in primary particle diameter, but not fully. This in turn may be explained either by a varying primary particle size with aggregate size, or by that there are slight differences in the morphology of the aggregates from the generators. (C) 2015 The Authors. Published by Elsevier Ltd.
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27.
  • Svensson, Christian, et al. (författare)
  • Validation of an air–liquid interface toxicological set-up using Cu, Pd, and Ag well-characterized nanostructured aggregates and spheres
  • 2016
  • Ingår i: Journal of Nanoparticle Research. - : Springer Science and Business Media LLC. - 1388-0764 .- 1572-896X. ; 18:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract: Systems for studying the toxicity of metal aggregates on the airways are normally not suited for evaluating the effects of individual particle characteristics. This study validates a set-up for toxicological studies of metal aggregates using an air–liquid interface approach. The set-up used a spark discharge generator capable of generating aerosol metal aggregate particles and sintered near spheres. The set-up also contained an exposure chamber, The Nano Aerosol Chamber for In Vitro Toxicity (NACIVT). The system facilitates online characterization capabilities of mass mobility, mass concentration, and number size distribution to determine the exposure. By dilution, the desired exposure level was controlled. Primary and cancerous airway cells were exposed to copper (Cu), palladium (Pd), and silver (Ag) aggregates, 50–150 nm in median diameter. The aggregates were composed of primary particles 2, respectively, were achieved. Viability was measured by WST-1 assay, cytokines (Il-6, Il-8, TNF-a, MCP) by Luminex technology. Statistically significant effects and dose response on cytokine expression were observed for SAEC cells after exposure to Cu, Pd, or Ag particles. Also, a positive dose response was observed for SAEC viability after Cu exposure. For A549 cells, statistically significant effects on viability were observed after exposure to Cu and Pd particles. The set-up produced a stable flow of aerosol particles with an exposure and dose expressed in terms of number, mass, and surface area. Exposure-related effects on the airway cellular models could be asserted. Graphical Abstract: [Figure not available: see fulltext.]
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