| 1. |
- Brunnström, Åsa, et al.
(författare)
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On the biosynthesis of 15-HETE and eoxin C-4 by human airway epithelial cells
- 2015
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Ingår i: Prostaglandins & other lipid mediators. - : Elsevier BV. - 1098-8823 .- 2212-196X. ; 121, s. 83-90
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Tidskriftsartikel (refereegranskat)abstract
- Several lines of evidence indicate that 15-lipoxygenase type 1 (15-LO-1) plays a pathophysiological role in asthma. The aim for this study was to investigate the 15-LO-1 expression and activity in primary human airway epithelial cells cultivated on micro-porous filters at air liquid interface. Incubation of human airway epithelial cells with arachidonic acid led to the formation of 15(S)-hydroxy-eicosatetraenoic acid (15-HETE) and exposing the cells to bacteria or physical injury markedly increased their production of 15-HETE. The cells were also found to convert arachidonic acid to eoxin C-4 (EXC4). Subcellular fractionation revealed that the conversion of EXA(4) to EXC4 was catalyzed by a soluble glutathione transferase (GST). The GST P1-1 enzyme was found to possess the highest activity of the investigated soluble GSTs. Following IL-4 treatment of airway epithelial cells, microarray analysis confirmed high expression of 15-LO-1 and GST P1-1, and immunohistochemical staining of bronchial biopsies revealed co-localization of 15-LO-1 and GST P1-1 in airway epithelial cells. These results indicate that respiratory infection and cell injury may activate the 15-LO pathway in airway epithelial cells. Furthermore, we also demonstrate that airway epithelial cells have the capacity to produce EXC4.
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| 2. |
- Claesson, Erik, 1988-
(författare)
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Carbides in martensitic medium carbon low alloyed tool steels studied with small angle scattering techniques, electron microscopy and atom probe tomography
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Medium carbon low alloyed tool steels are used today in various areas to shape plastics, nonferrous metals, and steels, and they are crucial in the manufacturing industry. To be effective, tool steels must be strong and tough, and have high wear resistance and temperature stability. To achievethe desired properties, materials are alloyed so that secondary phaseparticles precipitate during processing, especially during the tempering of martensitic steels. However, the hardening contribution relates to the size,volume fraction and number density of precipitates, controlled by alloy composition and heat-treating parameters. It is therefore essential to understand how, where, and when the particles nucleate and how the precipitation sequence and kinetics are affected by alloying additions,tempering temperature, and time.This work is aimed to study carbide precipitation in two commercial low-alloy tool steel using small-angle neutron and X-ray scattering. To support these methods, samples were characterized with transmission electronmicroscopy (TEM) and atom probe tomography (APT). With a combination of high-resolution techniques, it was possible to establish the precipitation sequence in these steels. It was also possible with various small angle scattering techniques to determine the evolution of volume fraction and number density of precipitates as a function of tempering parameters.First, small angle neutron scattering (SANS) was used, which is an excellent method for bulk quantification of small precipitates in steel. It was possible with SANS to broadly study the precipitation process depending on annealing temperature and time. However, it is difficult with regular small angle scattering (SAS) to distinguish particle types with overlapping size distributions. To possibly separate the scattering signal from different carbide types, measurements were carried out with polarized small angle neutron scattering (SANSPOL) and anomalous small-angle X-ray scattering(ASAXS). With ASAXS it was possible to isolate the signal from molybdenum-rich carbides from other types of carbides.With SANSPOL, it was possible to follow the enrichment of alloy elements in cementite. The appearance of cementite can be described as an iron-richcore with a chromium-enriched shell. The partitioning of substitutional elements affects the stability of cementite and the alloy carbides. It was also possible with SANSPOL, during heating, to follow the initial precipitation of particles.Results from different experimental methods have been compared with precipitation simulations using thermodynamics-based precipitationmodeling. Equilibrium calculations indicates the possible stability ofdifferent precipitates, and the kinetics are captured with tools such as TCPRISMA to simulate structure evolution during tempering. Hardness measurements were made to correlate structure evolution to mechanical properties.
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| 3. |
- Hagberg, Carolina E, et al.
(författare)
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Vascular endothelial growth factor B controls endothelial fatty acid uptake.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 464:7290, s. 917-21
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Tidskriftsartikel (refereegranskat)abstract
- The vascular endothelial growth factors (VEGFs) are major angiogenic regulators and are involved in several aspects of endothelial cell physiology. However, the detailed role of VEGF-B in blood vessel function has remained unclear. Here we show that VEGF-B has an unexpected role in endothelial targeting of lipids to peripheral tissues. Dietary lipids present in circulation have to be transported through the vascular endothelium to be metabolized by tissue cells, a mechanism that is poorly understood. Bioinformatic analysis showed that Vegfb was tightly co-expressed with nuclear-encoded mitochondrial genes across a large variety of physiological conditions in mice, pointing to a role for VEGF-B in metabolism. VEGF-B specifically controlled endothelial uptake of fatty acids via transcriptional regulation of vascular fatty acid transport proteins. As a consequence, Vegfb(-/-) mice showed less uptake and accumulation of lipids in muscle, heart and brown adipose tissue, and instead shunted lipids to white adipose tissue. This regulation was mediated by VEGF receptor 1 and neuropilin 1 expressed by the endothelium. The co-expression of VEGF-B and mitochondrial proteins introduces a novel regulatory mechanism, whereby endothelial lipid uptake and mitochondrial lipid use are tightly coordinated. The involvement of VEGF-B in lipid uptake may open up the possibility for novel strategies to modulate pathological lipid accumulation in diabetes, obesity and cardiovascular diseases.
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| 4. |
- James, Anna, et al.
(författare)
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The influence of aspirin on release of eoxin C4, leukotriene C4 and 15-HETE, in eosinophilic granulocytes isolated from patients with asthma
- 2013
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 162:2, s. 135-42
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Tidskriftsartikel (refereegranskat)abstract
- Background: The effect of aspirin on the release of key arachidonic acid metabolites in activated eosinophils from subjects with aspirin-intolerant asthma (AIA) has not been investigated previously, despite the characteristic eosinophilia in AIA. Methods: Peripheral blood eosinophils were isolated from four groups of subjects: healthy volunteers (HV; n = 8), mild asthma (MA; n = 8), severe asthma (SA; n = 9) and AIA (n = 7). In the absence or presence of lysine-aspirin, eosinophils were stimulated with arachidonic acid or calcium ionophore to trigger the 15-lipoxygenase-1 (15-LO) and 5-lipoxygenase (5-LO) pathways, respectively. 15(S)-hydroxy-eicosatetraenoic acid (15-HETE) and eoxin C4 (EXC4) were measured as 15-LO products and leukotriene (LT)C4 as a product of the 5-LO pathway. Results: Activated eosinophils from patients with SA and AIA produced approximately five times more 15-HETE than eosinophils from HV or MA patients. In the presence of lysine-aspirin, eosinophils from AIA, MA and SA patients generated higher levels of 15-HETE than in the absence of lysine-aspirin. Furthermore, in the presence of lysine-aspirin, formation of EXC4 was also significantly increased in eosinophils from AIA patients, and LTC4 synthesis was increased both in AIA and SA patients. Conclusions: Taken together, this study shows an increased release of the recently discovered lipid mediator EXC4, as well as the main indicator of 15-LO activity, 15-HETE, in activated eosinophils from severe and aspirin-intolerant asthmatics, and also elevated EXC4 and LTC4 formation in eosinophils from AIA patients after cellular activation in the presence of lysine-aspirin. The findings support a pathophysiological role of the 15-LO pathway in SA and AIA.
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| 5. |
- Johnsson, Anna-Karin, et al.
(författare)
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COX-1 dependent biosynthesis of 15-hydroxyeicosatetraenoic acid in human mast cells
- 2021
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier. - 1388-1981 .- 1879-2618. ; 1866:5
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Tidskriftsartikel (refereegranskat)abstract
- 15-hydroxyeicosatetraenoic acid (15-HETE) is an arachidonic acid derived lipid mediator which can originate both from 15-lipoxygenase (15-LOX) activity and cyclooxygenase (COX) activity. The enzymatic source determines the enantiomeric profile of the 15-HETE formed. 15-HETE is the most abundant arachidonic acid metabolite in the human lung and has been suggested to influence the pathophysiology of asthma. Mast cells are central effectors in asthma, but there are contradictory reports on whether 15-HETE originates from 15-LOX or COX in human mast cells. This prompted the current study where the pathway of 15-HETE biosynthesis was examined in three human mast cell models; the cell line LAD2, cord blood derived mast cells (CBMC) and tissue isolated human lung mast cells (HLMC). Levels and enantiomeric profiles of 15-HETE and levels of the downstream metabolite 15-KETE, were analyzed by UPLC-MS/MS after stimulation with anti-IgE or calcium ionophore A23187 in the presence and absence of inhibitors of COX isoenzymes. We found that 15-HETE was produced by COX-1 in human mast cells under these experimental conditions. Unexpectedly, chiral analysis showed that the 15(R) isomer was predominant and gradually accumulated, whereas the 15(S) isomer was metabolized by the 15hydroxyprostaglandin dehydrogenase. We conclude that during physiological conditions, i.e., without addition of exogenous arachidonic acid, both enantiomers of 15-HETE are produced by COX-1 in human mast cells but that the 15(S) isomer is selectively depleted by undergoing further metabolism. The study highlights that 15-HETE cannot be used as an indicator of 15-LOX activity for cellular studies, unless chirality and sensitivity to pharmacologic inhibition is determined.
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| 6. |
- Sababi, Majid, et al.
(författare)
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Influence of polyaniline and ceria nanoparticle additives on corrosion protection of a UV-cure coating on carbon steel
- 2014
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Ingår i: Corrosion Science. - : Elsevier BV. - 0010-938X .- 1879-0496. ; 84, s. 189-197
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Tidskriftsartikel (refereegranskat)abstract
- Influence of a few percents additives of polyaniline doped with phosphoric acid (PAni-PA) and ceria nanoparticle on corrosion protection of a new ultraviolet (UV)-cure polyester acrylate coating have been studied for coil coating on carbon steel by electrochemical measurements during exposure to a NaCl solution. The results demonstrate that the presence of ceria nanoparticles improves the barrier property and stability of the coating. Adding the PAni-PA results in active corrosion protection for carbon steel due to passivation of the steel, and the combination of both additives greatly enhances the protection property over that of the coating matrix alone.
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| 7. |
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| 8. |
- Andersson, Cecilia, et al.
(författare)
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Mice Lacking 12/15-Lipoxygenase have Attenuated Airway Allergic Inflammation and Remodeling.
- 2008
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Ingår i: American Journal of Respiratory Cell and Molecular Biology. - 1535-4989. ; 39:6, s. 648-656
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Tidskriftsartikel (refereegranskat)abstract
- Arachidonate 15-lipoxygenase (LO)-1 has been implicated in allergic inflammation and asthma. The overall effect of 15-LO in allergic inflammation in vivo is, however, unclear. This study investigates systemic allergen sensitization and local allergic airway inflammation and remodeling in mice lacking the murine 12/15-LO, the ortholog to human 15-LO-1. Upon systemic sensitization with intraperitoneal ovalbumin, 12/15 LO(-/-) mice produced elevated levels of allergen-specific IgE compared to wild type (Wt) controls. However, when challenged with repeated aerosolized allergen sensitized 12/15 LO(-/-) mice had an impaired development of airway allergic inflammation compared to Wt controls, as indicated by reduced BAL fluid leukocytes (eosinophils, lymphocytes macrophages) and Th2 cytokines (IL-4, IL-5, IL-13) as well as tissue eosinophils. Allergen-induced airway epithelial proliferation was also significantly attenuated in 12/15 LO(-/-) mice whereas goblet cell hyperplasia was unaffected. However, 12/15 LO(-/-) mice had significantly reduced luminal mucus secretions compared to Wt controls. The repeated allergen challenges resulted in a dramatic increase of alpha-smooth muscle-actin positive alveolar cells in the peripheral airways, a phenomenon that was significantly less developed in 12/15 LO(-/-) mice. In conclusion, our data suggest that 12/15 LO(-/-) mice, although having a fully developed systemic sensitization, did not establish a fully developed allergic airway inflammation and associated manifestations of central and peripheral airway remodeling. These data suggest that 12/15-LO derived metabolites play an important pathophysiological role in allergen-induced inflammation and remodeling. Hence, pharmacologic targeting of the human 15-LO-1 may represent an attractive therapeutic strategy to control inflammation and remodeling in asthma.
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| 9. |
- Angré, Alexander, et al.
(författare)
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Phase transformation under isostatic pressure in HIP
- 2017
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Ingår i: Powder Metallurgy. - : Informa UK Limited. - 0032-5899 .- 1743-2901. ; 60:3, s. 167-174
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Tidskriftsartikel (refereegranskat)abstract
- The new HIP cooling systems enable very fast cooling rates under isostatic pressure. This does not only enable shorter HIP cycles but also allows complete heat treatment cycles to be performed in one HIP cycle. It has been shown in previous studies that extreme pressures of several thousand bar can push phase transformation towards longer times. The new URQ HIP cooling systems give the opportunity to investigate the impact of pressures up to 2000 bar on phase transformation time dependency. For each of the two materials in this study, a comparison of austenite phase transformation time at 100 and 1700 bar was performed. The study was performed by isothermal heat treatment of specimens for a specific time followed by quenching. To evaluate the influence of pressure on hardenability, the phase fractions were evaluated using grid method on SEM images. The study found significant influence of HIP pressure on hardenability.
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| 10. |
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