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- Karlsson, Richard, et al.
(författare)
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Phosphatidylinositol 3-kinase is essential for kit ligand-mediated survival, whereas interleukin-3 and flt3 ligand induce expression of antiapoptotic Bcl-2 family genes
- 2003
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Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 1938-3673 .- 0741-5400. ; 74:5, s. 923-931
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Tidskriftsartikel (refereegranskat)abstract
- Cytokines such as interleukin 3 (IL-3), kit ligand (KL), and flt3 ligand (FL) promote survival of hematopoietic stem cells and myeloid progenitor cells. In many cell types, members of the Bcl-2 gene family are major regulators of survival, but the mediating mechanisms are not fully understood. Using two myeloid progenitor cell lines, FDCP-mix and FDC-P1, as well as primary mouse bone marrow progenitors, we demonstrate that KL-mediated survival is dependent on the activation of phosphatidylinositol-3 (PI-3) kinase. The inhibitor LY294002 was able to completely abolish survival mediated by KL, whereas IL-3 and FL were only partially affected. Although all three cytokines induced phosphorylation of protein kinase B (PKB), only KL required PI-3 kinase activity to elicit survival in hematopoietic progenitors. In contrast, pretreatment of cells with inhibitors to the MAP kinase pathway did not affect the survival. We next established if IL-3 and FL activated antiapoptotic Bcl-2 and the related genes Bcl-X-L and Mcl-1. By RNA protection assay and Western blot analysis, we show that all three genes are induced by IL-3, whereas FL induces Bcl-2 and to some extent Bcl-XL. Importantly, KL could not sustain their expression. Moreover, use of inhibitors implied that IL-3 was mainly exerting its effect on Bcl-2 at the level of transcription. The addition of LY294002 did not affect the expression of Bcl-2 and Bcl-XL, and thus, we conclude that expression of antiapoptotic Bcl-2 family member genes is not dependent on PI-3 kinase activity. Our results indicate that cytokines exert distinct survival effects and that FL and IL-3 are capable of sustaining progenitor survival by upregulating the expression of Bcl-2 and related genes.
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- Maigaard, P, et al.
(författare)
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Homogeneous charge compression ignition engine: A simulation study on the effects of inhomogeneities
- 2003
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Ingår i: Journal of Engineering for Gas Turbines and Power. - : ASME International. - 1528-8919 .- 0742-4795. ; 125:2, s. 466-471
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Tidskriftsartikel (refereegranskat)abstract
- A stochastic model for the HCCI engine is presented The model is based on the PaSPFR-IEM model and accounts for inhomogeneities in the combustion chamber while including a detailed chemical model for natural gas combustion, consisting of 53 chemical species and 590 elementary chemical reactions. The model is able to take any type of inhomogeneities in the initial gas composition into account, such as inhomogeneities in the temperature field, in the air-fuel ratio or in the concentration of the recirculated exhaust gas. With this model the effect of temperature differences caused by the thermal boundary layer and crevices in the cylinder for a particular engine speed and fuel to air ratio is studied. The boundary layer is divided into a viscous sublayer and a turbulent buffer zone. There are also colder zones due to crevices. All zones are modeled by a characteristic temperature distribution. The simulation results are compared with experiments and a previous numerical study employing a PFR model. In all cases the PaSPFR-IEM model leads to a better agreement between simulations and experiment for temperature and pressure. In addition a sensitivity study on the effect of different intensities of turbulent mixing on the combustion is performed. This study reveals that the ignition delay is a Junction of turbulent mixing of the hot bulk and the colder boundary layer.
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