978 resultados para inhibitor resistance
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The thermal conductivity of periodic composite media with spherical or cylindrical inclusions embedded in a homogeneous matrix is discussed. Using Green functions, we show that the Rayleigh identity can be generalized to deal with thermal properties ot these systems. A new calculating method for effective conductivity of composite media is proposed. Useful formulae for effective thermal conductivity are derived, and meanings of contact resistance in engineering problems are explained.
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Background -- N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide) is a synthetic retinoid with potent pro-apoptotic activity against several types of cancer, but little is known regarding mechanisms leading to chemoresistance. Ceramide and, more recently, other sphingolipid species (e.g., dihydroceramide and dihydrosphingosine) have been implicated in 4-HPR-mediated tumor cell death. Because sphingolipid metabolism has been reported to be altered in drug-resistant tumor cells, we studied the implication of sphingolipids in acquired resistance to 4-HPR based on an acute lymphoblastic leukemia model. Methods -- CCRF-CEM cell lines resistant to 4-HPR were obtained by gradual selection. Endogenous sphingolipid profiles and in situ enzymatic activities were determined by LC/MS, and resistance to 4-HPR or to alternative treatments was measured using the XTT viability assay and annexin V-FITC/propidium iodide labeling. Results -- No major crossresistance was observed against other antitumoral compounds (i.e. paclitaxel, cisplatin, doxorubicin hydrochloride) or agents (i.e. ultra violet C, hydrogen peroxide) also described as sphingolipid modulators. CCRF-CEM cell lines resistant to 4-HPR exhibited a distinctive endogenous sphingolipid profile that correlated with inhibition of dihydroceramide desaturase. Cells maintained acquired resistance to 4-HPR after the removal of 4-HPR though the sphingolipid profile returned to control levels. On the other hand, combined treatment with sphingosine kinase inhibitors (unnatural (dihydro)sphingosines ((dh)Sph)) and glucosylceramide synthase inhibitor (PPMP) in the presence or absence of 4-HPR increased cellular (dh)Sph (but not ceramide) levels and were highly toxic for both parental and resistant cells. Conclusions -- In the leukemia model, acquired resistance to 4-HPR is selective and persists in the absence of sphingolipid profile alteration. Therapeutically, the data demonstrate that alternative sphingolipid-modulating antitumoral strategies are suitable for both 4-HPR-resistant and sensitive leukemia cells. Thus, whereas sphingolipids may not be critical for maintaining resistance to 4-HPR, manipulation of cytotoxic sphingolipids should be considered a viable approach for overcoming resistance.
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9 p.
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This paper presents a measurement of flow patterns and flow velocities of gas-water two-phase flows based on the technique of electrical resistance tomography (ERT) in a 40m horizontal flow loop. A single-plane and dual-plane ERT sensor on conductive ring technique were used to gather sufficient information for the implementation of flow characteristics particularly flow pattern recognition and air cavity velocity measurement. A fast data collection strategy was applied to the dual-plane ERT sensor and an iterative algorithm was used for image reconstruction. Results, in respect to flow patterns and velocity maps, are reported.
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Ponencia leída en el Foro de Comunicaciones IkasArt II (BEC Barakaldo, 2010.06.17)
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12 p.