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| 2. |
- Delhay, J., et al.
(författare)
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Soot volume fraction measurements in aero-engine exhausts using extinction-calibrated backward laser-induced incandescence
- 2009
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Ingår i: Applied Physics B. - : Springer Science and Business Media LLC. - 0946-2171 .- 1432-0649. ; 95:4, s. 825-838
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Tidskriftsartikel (refereegranskat)abstract
- Control and reduction of soot particle emissions from aeronautic turbines requires a monitoring system suitable for quantification of these emissions. Currently, such emissions are estimated using the technique of smoke number. This is an extractive method, which is not sensitive enough for the low emission levels of modern gas turbines. Within a recent European project, AEROTEST, part of the project aimed at investigating an alternative soot monitoring technique, laser-induced incandescence (LII) as an in-situ optical diagnostic for quantification of soot emissions. For aero-engine applications, especially those involving large-scale turbines, it is necessary to perform the measurements at long distance from the turbine. The LII technique is favourable in this respect as it provides for non-intrusive measurements and, by detecting the isotropic LII signal along the same axis as the incoming laser beam (so called backward LII), both the laser and the detector can be built inside one system located several meters from the turbine. The concept was initiated in the previous European projects, AEROJET I and II. This paper describes the modified version of the system and the procedure developed to achieve reliable and quantitative soot volume fraction measurements in the exhausts of aero-engines. Application of the backward LII technique is demonstrated in the exhaust of a military turbojet engine for different engine speeds.
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| 5. |
- Ye, L, et al.
(författare)
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Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1.
- 2003
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Ingår i: Journal of Medicinal Chemistry. ; 24;46:9, s. 1580-8
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Tidskriftsartikel (refereegranskat)abstract
- Endogenous thyroid receptor hormones 3,5,3',5'-tetraiodo-l-thyronine (T(4), 1) and 3,5,3'-triiodo-l-thyronine (T(3), 2) exert a significant effects on growth, development, and homeostasis in mammals. They regulate important genes in intestinal, skeletal, and cardiac muscles, the liver, and the central nervous system, influence overall metabolic rate, cholesterol and triglyceride levels, and heart rate, and affect mood and overall sense of well being. The literature suggests many or most effects of thyroid hormones on the heart, in particular on the heart rate and rhythm, are mediated through the TRalpha(1) isoform, while most actions of the hormones on the liver and other tissues are mediated more through the TRbeta(1) isoform of the receptor. Some effects of thyroid hormones may be therapeutically useful in nonthyroid disorders if adverse effects can be minimized or eliminated. These potentially useful features include weight reduction for the treatment of obesity, cholesterol lowering for treating hyperlipidemia, amelioration of depression, and stimulation of bone formation in osteoporosis. Prior attempts to utilize thyroid hormones pharmacologically to treat these disorders have been limited by manifestations of hyperthyroidism and, in particular, cardiovascular toxicity. Consequently, development of thyroid hormone receptor agonists that are selective for the beta-isoform could lead to safe therapies for these common disorders while avoiding cardiotoxicity. We describe here the synthesis and evaluation of a series of novel TR ligands, which are selective for TRbeta(1) over TRalpha(1). These ligands could potentially be useful for treatment of various disorders as outlined above. From a series of homologous R(1)-substituted carboxylic acid derivatives, increasing chain length was found to have a profound effect on affinity and selectivity in a radioreceptor binding assay for the human thyroid hormone receptors alpha(1) and beta(1) (TRalpha(1) and TRbeta(2)) as well as a reporter cell assay employing CHOK1-cells (Chinese hamster ovary cells) stably transfected with hTRalpha(1) or hTRbeta(1) and an alkaline phosphatase reporter-gene downstream thyroid response element (TRAFalpha(1) and TRAFbeta(1)). Affinity increases in the order formic, acetic, and propionic acid, while beta-selectivity is highest when the R(1) position is substituted with acetic acid. Within this series 3,5-dibromo-4-[(4-hydroxy-3-isopropylphenoxy)phenyl]acetic acid (11a) and 3,5-dichloro-4-[(4-hydroxy-3-isopropylphenoxy)phenyl]acetic acid (15) were found to reveal the most promising in vitro data based on isoform selectivity and were selected for further in vivo studies. The effect of 2, 11a, and 15 in a cholesterol-fed rat model was monitored including potencies for heart rate (ED(15)), cholesterol (ED(50)), and TSH (ED(50)). Potency for tachycardia was significantly reduced for the TRbeta selective compounds 11a and 15 compared with 2, while both 11a and 15 retained the cholesterol-lowering potency of 2. This left an approximately 10-fold therapeutic window between heart rate and cholesterol, which is consistent with the action of ligands that are approximately 10-fold more selective for TRbeta(1). We also report the X-ray crystallographic structures of the ligand binding domains of TRalpha and TRbeta in complex with 15. These structures reveal that the single amino acid difference in the ligand binding pocket (Ser277 in TRalpha or Asn331 in TRbeta) results in a slightly different hydrogen bonding pattern that may explain the increased beta-selectivity of 15.
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| 7. |
- Alheim, Katarina, et al.
(författare)
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Identification of a functional glucocorticoid response element in the promoter of the cylcin-dependant kinase inhibitor p57(Kip2)
- 2003
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Ingår i: Journal of Molecular Endocrinology. - : Bioscientifica. - 0952-5041 .- 1479-6813. ; 30:3, s. 359-368
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids are known regulators of the cell cycle, normally exerting an anti-proliferative effect. We have previously shown that glucocorticoids stimulate expression of p57(Kip2), a member of the Cip/Kip family of cyclin-dependent kinase inhibitors which, in some cell types, may account for the anti-proliferative responses seen after glucocorticoid treatment. The induction of p57(Kip2) involves primary transcriptional effects where no de novo protein synthesis is necessary, suggesting a direct interaction of the glucocorticoid receptor with the p57(Kip2) gene. In this study we have identified a functional glucocorticoid response element (GRE), located 5 kilo bases (kb) upstream of the transcription start site in the human P57(Kip2) promoter. This GRE was functional also when isolated, suggesting a direct transcriptional effect of the glucocorticoid receptor. Furthermore, mutation of this GRE abolished glucocorticoid induction of the reporter gene, whereas mutation of a nearby Sp1 site did not. Using electrophoretic mobility shift assays, we have shown that the -5 kb p57(Kip2) promoter GRE was able to compete with a well-known GRE for glucocorticoid receptor binding. Sequence comparisons with the mouse genome showed that this GRE is highly conserved, further strengthening the biological importance of this site. All these data emphasize the involvement of this GRE in the glucocorticoid-mediated induction of p57(Kip2) expression.
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| 8. |
- Bladh, Henrik, et al.
(författare)
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Experimental and theoretical comparison of spatially resolved laser-induced incandescence (LII) signals of soot in backward and right-angle configuration
- 2006
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Ingår i: Applied Physics B. - : Springer Science and Business Media LLC. - 0946-2171 .- 1432-0649. ; 83:3, s. 423-433
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Tidskriftsartikel (refereegranskat)abstract
- In-situ measurements of soot volume fraction in the exhausts of jet engines can be carried out using the laser-induced incandescence (LII) technique in backward configuration, in which the signal is detected in the opposite direction of the laser beam propagation. In order to improve backward LII for quantitative measurements, we have in this work made a detailed experimental and theoretical investigation in which backward LII has been compared with the more commonly used right-angle LII technique. Both configurations were used in simultaneous visualization experiments at various pulse energies and gate timings in a stabilized methane diffusion flame. The spatial near-Gaussian laser energy distribution was monitored on-line as well as the time-resolved LII signal. A heat and mass transfer model for soot particles exposed to laser radiation was used to theoretically predict both the temporal and spatial LII signals. Comparison between experimental and theoretical LII signals indicates similar general behaviour, for example the broadening of the spatial LII distribution and the hole-burning effect at centre of the beam due to sublimation for increasing laser pulse energies. However, our comparison also indicates that the current heat and mass transfer model overpredicts signal intensities at higher fluence, and possible reasons for this behaviour are discussed.
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| 9. |
- Bladh, K., et al.
(författare)
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An approach to analyse human reliability during refuelling outage of a nuclear power plant
- 2007
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Ingår i: Proc. of Enlarged Halden Programme Group Meeting.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Human reliability analysis (HRA) constitutes a central role in the probabilistic safety assessment (PSA) for the low power and shutdown period of a nuclear power plant. This is because a large number of operative and maintenance activities take place during a refuelling outage when the plant, to a great extent, is disassembled, maintained, and then reassembled back to operational mode. The paper presents the HRA approach used in the shutdown PSA for Forsmark 1/2 and 3 nuclear power units in Sweden. Challenges of the analysis comprises handling the large scope of activities to be analysed, development and use of a quantification method consistent with the full power PSA, and integration of HRA with the “technical” part of PSA. Experiences from the analysis and results will also be discussed.
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