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| 2. |
- Alijagic, Andi, 1992-, et al.
(författare)
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A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles
- 2023
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.
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| 3. |
- Andersson, Henrik, et al.
(författare)
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T A microarray analysis of the murine macrophage response to infection with Francisella tularensis LVS
- 2006
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Ingår i: Journal of Medical Microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 55:8, s. 1023-1033
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Tidskriftsartikel (refereegranskat)abstract
- The response of cells of the mouse macrophage cell line J774 to infection with Francisella tularensis LVS was analysed by means of a DNA microarray representing approximately 18 500 genes (20 600 clones). The adaptive response was modest at all time points, and at most, 81 clones were differentially regulated from the time point of uptake of bacteria (0 min) up to 240 min later. For all five time points, 229 clones fulfilled the criteria of being differentially regulated, i.e. the ratio between infected versus non-infected cells was at least 1.7-fold up- or down-regulated and P <0.05. It was found that many of the differentially regulated genes are known to respond to stress in general and to oxidative stress specifically. However, at 120 min it was observed that genes that lead to depletion of glutathione were upregulated. Possibly, this was a result of mechanisms induced by F. tularensis. Generally, there was a conspicuous lack of inflammatory responses and, for example, although tumour necrosis factor alpha (TNF-α) was upregulated at 0 min, a significant down-regulation was noted at all subsequent time points. When cells were treated with an inhibitor of inducible nitric oxide synthase (iNOS) or the antioxidant N-acetylcysteine (NAC), the infection-induced cytopathogenic effect was significantly inhibited. Together, the results suggest that F. tularensis LVS infection confers an oxidative stress upon the target cells and that many of the host-defence mechanisms appear to be intended to counteract this stress. The infection is characterized by a very modest inflammatory response.
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| 4. |
- Andersson, L. Robin, et al.
(författare)
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Characterization of Flow Structures Induced by Highly Rough Surface Using Particle Image Velocimetry, Proper Orthogonal Decomposition and Velocity Correlations
- 2018
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Ingår i: Engineering. - : Scientific Research Publishing. - 1947-3931 .- 1947-394X. ; 10, s. 399-416
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Tidskriftsartikel (refereegranskat)abstract
- High Reynolds number flow inside a channel of rectangular cross section is examined using Particle Image Velocimetry. One wall of the channel has been replaced with a surface of a roughness representative to that of real hydropower tunnels, i.e. a random terrain with roughness dimensions typically in the range of ≈10% - 20% of the channels hydraulic radius. The rest of the channel walls can be considered smooth. The rough surface was captured from an existing blasted rock tunnel using high resolution laser scanning and scaled to 1:10. For quantification of the size of the largest flow structures, integral length scales are derived from the auto-correlation functions of the temporally averaged velocity. Additionally, Proper Orthogonal Decomposition (POD) and higher-order statistics are applied to the instantaneous snapshots of the velocity fluctuations. The results show a high spatial heterogeneity of the velocity and other flow characteristics in vicinity of the rough surface, putting outer similarity treatment into jeopardy. Roughness effects are not confined to the vicinity of the rough surface but can be seen in the outer flow throughout the channel, indicating a different behavior than postulated by Townsend’s similarity hypothesis. The effects on the flow structures vary depending on the shape and size of the roughness elements leading to a high spatial dependence of the flow above the rough surface. Hence, any spatial averaging, e.g. assuming a characteristic sand grain roughness factor, for determining local flow parameters becomes less applicable in this case.
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| 5. |
- Bergknut, Magnus, et al.
(författare)
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Identification of potentially toxic compounds in complex extracts of environmental samples using gas chromatography-mass spectrometry and multivariate data analysis
- 2007
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Ingår i: Environmental Toxicology and Chemistry. - New York : Pergamon. - 0730-7268 .- 1552-8618. ; 26:2, s. 208-217
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we examined 31 samples of varying chemical composition, including samples of soils from gasworks, coke production sites, and sites where wood preservatives were heavily used; ash and soot from municipal solid waste incinerators; antiskid sand; and dust from areas with heavy road traffic. The samples were comprehensively chemically characterized, especially their polycyclic aromatic compound contents, using gas chromatography-time-of-flight mass spectrometry, whereas their biological effects were assessed using dehydrogenase activity, root growth (Hordeum vulgare), reproduction of springtails (Folsomia candida), algal growth (Desmodesmus subspicatus), germinability (Sinapis alba), Vibrio fischeri, DR-CALUX, and Ames Salmonella assays. The number of compounds detected in the samples ranged from 123 to 527. Using the multivariate regression technique of partial-least-squares projections to latent structures, it was possible to find individual compounds that exhibited strong correlations with the different biological responses. Some of the results, however, indicate that a broader chemical characterization may be needed to identify all the compounds that may cause the measured biological responses.
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| 6. |
- Bergknut, Magnus, et al.
(författare)
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Identification of potentially toxic compounds in complex extracts of environmental samples using GC-MS and multivariate data analysis
- 2007
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Ingår i: Environmental Toxicology and Chemistry. - 0730-7268 .- 1552-8618. ; 26:2, s. 208-17
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we examined 31 samples of varying chemical composition, including samples of soils from gasworks, coke production sites, and sites where wood preservatives were heavily used; ash and soot from municipal solid waste incinerators; antiskid sand; and dust from areas with heavy road traffic. The samples were comprehensively chemically characterized, especially their polycyclic aromatic compound contents, using gas chromatography–time-of-flight mass spectrometry, whereas their biological effects were assessed using dehydrogenase activity, root growth (Hordeum vulgare), reproduction of springtails (Folsomia candida), algal growth (Desmodesmus subspicatus), germinability (Sinapis alba), Vibrio fischeri, DR-CALUX, and Ames Salmonella assays. The number of compounds detected in the samples ranged from 123 to 527. Using the multivariate regression technique of partial-least-squares projections to latent structures, it was possible to find individual compounds that exhibited strong correlations with the different biological responses. Some of the results, however, indicate that a broader chemical characterization may be needed to identify all the compounds that may cause the measured biological responses.
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| 7. |
- Bremer, Anders, Docent, 1957-, et al.
(författare)
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Translation and further validation of a global rating scale for the assessment of clinical competence in prehospital emergency care
- 2020
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Ingår i: Nurse Education in Practice. - : Elsevier. - 1471-5953 .- 1873-5223. ; 47:August, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Global rating scales are useful to assess clinical competence at a general level based on specific word dimensions. The aim of this study was to translate and culturally adapt the Paramedic Global Rating Scale, and to contribute validity evidence and instrument usefulness in training results and clinical competence assessments of students undergoing training to become ambulance nurses and paramedics at Swedish and Finnish universities. The study included translation, expert review and inter-rater reliability (IRR) tests. The scale was translated and culturally adapted to clinical and educational settings in both countries. A content validity index (CVI) was calculated using eight experts. IRR tests were performed with five registered nurses working as university lecturers, and with six clinicians working as ambulance nurses. They individually rated the same simulated ambulance assignment. Based on the ratings IRR was calculated with intra-class correlation (ICC). The scale showed excellent CVI for items and scale. The ICC indicated substantial agreement in the group of lecturers and a high degree of agree- ment in the group of clinicians. This study provides validity evidence for a Swedish version of the scale, sup- porting its use in measuring clinical competence among students undergoing training to become ambulance nurses and paramedics.
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| 8. |
- Chew, Michelle S., et al.
(författare)
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Identification of myocardial injury using perioperative troponin surveillance in major noncardiac surgery and net benefit over the Revised Cardiac Risk Index
- 2022
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Ingår i: British Journal of Anaesthesia. - : Elsevier. - 0007-0912 .- 1471-6771. ; 128:1, s. 26-36
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality.METHODS: Prospective, observational, cohort study in patients ≥50 yr of age undergoing elective major noncardiac surgery at seven hospitals in Sweden. The exposures were hs-cTnT measured before and days 0-3 after surgery. Two previously published thresholds for myocardial injury and two thresholds identified using receiver operating characteristic analyses were evaluated using multivariable logistic regression models and externally validated. The weighted comparison net benefit method was applied to determine the additional value of hs-cTnT thresholds when compared with the Revised Cardiac Risk Index (RCRI). The primary outcome was a composite of 30-day all-cause mortality and MACCE.RESULTS: We included 1291 patients between April 2017 and December 2020. The primary outcome occurred in 124 patients (9.6%). Perioperative increase in hs-cTnT ≥14 ng L-1 above preoperative values provided statistically optimal model performance and was associated with the highest risk for the primary outcome (adjusted odds ratio 2.9, 95% confidence interval 1.8-4.7). Validation in an independent, external cohort confirmed these findings. A net benefit over RCRI was demonstrated across a range of clinical thresholds.CONCLUSIONS: Perioperative increases in hsTnT ≥14 ng L-1 above baseline values identifies acute perioperative myocardial injury and provides a net prognostic benefit when added to RCRI for the identification of patients at high risk of death and MACCE.CLINICAL TRIAL REGISTRATION: NCT03436238.
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| 9. |
- Dracheva, Elena, et al.
(författare)
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In Silico Identification of Potential Thyroid Hormone System Disruptors among Chemicals in Human Serum and Chemicals with a High Exposure Index
- 2022
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:12, s. 8363-8372
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Tidskriftsartikel (refereegranskat)abstract
- Data on toxic effects are at large missing the prevailing understanding of the risks of industrial chemicals. Thyroid hormone (TH) system disruption includes interferences of the life cycle of the thyroid hormones and may occur in various organs. In the current study, high-throughput screening data available for 14 putative molecular initiating events of adverse outcome pathways, related to disruption of the TH system, were used to develop 19 in silico models for identification of potential thyroid hormone system-disrupting chemicals. The conformal prediction framework with the underlying Random Forest was used as a wrapper for the models allowing for setting the desired confidence level and controlling the error rate of predictions. The trained models were then applied to two different databases: (i) an in-house database comprising xenobiotics identified in human blood and ii) currently used chemicals registered in the Swedish Product Register, which have been predicted to have a high exposure index to consumers. The application of these models showed that among currently used chemicals, fewer were overall predicted as active compared to chemicals identified in human blood. Chemicals of specific concern for TH disruption were identified from both databases based on their predicted activity.
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| 10. |
- Hedberg, P. A. Mikael, et al.
(författare)
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Measurements and Simulations of the Flow Distribution in a Down-Scaled Multiple Outlet Spillway with Complex Channel
- 2024
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Ingår i: Water. - : Multidisciplinary Digital Publishing Institute (MDPI). - 2073-4441. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of mass flow through a three-outlet spillway modeled after a scaled-down spillway were conducted. The inlet and channel leading up to the outlets were placed to lead the water toward the outlet at an angle. With this, measurements of the water level at three locations were recorded by magnetostrictive sensors. The volumetric flow rates for each individual outlet were recorded separately to study the differences between them. Additionally, Acoustic Doppler Velocimetry was used to measure water velocities close to the outlets. The conditions changed were the inlet volume flow rate and the flow distribution was measured at 90, 100, 110, and 200 L per second. Differences between the outlets were mostly within the error margin of the instruments used in the experiments with larger differences shown for the 200 L test. The results produced together with a CAD model of the setup can be used for verification of CFD methods. A simulation with the k-epsilon turbulence model is included and compared to earlier experiments and the new experimental results. Larger differences are seen in the new experiments. Differing inlet conditions are assumed as the principal cause for the differences seen.
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