Mechanisms of multidrug resistance: Differences between natural and acquired adriamycin -resistant human colon carcinoma cells

Mechanisms of multidrug resistance (MDR) were studied in two independent MDR sublines (AdR1.2 and SRA1.2) derived from the established human colon carcinoma cell line LoVo. AdR1.2 was developed by long-term continuous exposure of the cells to adriamycin (AdR) in stepwise increments of concentration, while SRA1.2 was selected by repetitive pulse treatments with AdR at a single concentration. In this dissertation, the hypothesis that the mechanism of drug resistance in SRA1.2 is different than that in AdR1.2 is tested. While SRA1.2 demonstrated similar biological characteristics when compared to the parental LoVo, AdR1.2 exhibited remarkable alterations in biological properties. The resistance phenotype of AdR1.2 was reversible when the cells were grown in the drug-free medium whereas SRA1.2 maintained its resistance for at least 10 months under similar conditions. Km and Vmax of carrier-mediated facilitated diffusion AdR transport were similar among the three lines. However, both resistant sublines exhibited an energy-dependent drug efflux. AdR1.2 appeared to possess an activated efflux pump, and a decreased nucleus-binding of AdR, whereas SRA1.2 showed merely a lower affinity in binding of AdR to the nuclei. Southern blot analysis showed no amplification of the MDR1 gene in either of the two resistant subclones. However, Western blot analysis using the C219 monoclonal antibody against P170 glycoprotein detected a Mr 150-kDa plasma protein (P150) in AdR1.2 but not in SRA1.2 or in the parental LoVo. In vitro phosphorylation studies revealed that P150 was a phosphoprotein; its phosphorylation was Mg$\sp{2+}$-dependent and could be enhanced by verapamil, an agent capable of increasing intracellular AdR accumulation in AdR1.2 cells. The phosphorylation studies also revealed elevated phosphorylation of a Mr 66-kDa plasma membrane protein that was detectable in the AdR1.2 revertant and in AdR1.2 when verapamil was present, suggesting that hyperphosphorylation of the Mr 66-kDa protein may be related to the reversal of MDR. SDS-PAGE of the plasma membrane protein demonstrated overproduction of a Mr 130-kDa, MDR-related protein in both the resistant sublines. The Mr 130-kDa, MDR-related protein in both the resistant sublines. The Mr 130-kDa protein was not immunoreactive with C219, but its absence in the AdR1.2 revertant and the parental LoVo suggests that it is an MDR-related plasma membrane protein. In conclusion, the results from this study support the author's hypothesis that the mechanisms responsible for "Acquired" and "Natural" MDR are not identical. ^

Free-Form, High Energy Performance, Transparent Vacuum Envelope

El artículo examina un nuevo sistema envolvente ligero, delgado, con ahorro energético, libre de formas diseñado para su uso en proyectos de arquitectura.

Free-Form, High Energy Performance, Transparent Envelope

This article examines, from the energy viewpoint, a new lightweight, slim, high energy efficient, light-transmitting envelope system, providing for seamless, free-form designs for use in architectural projects. The research was based on envelope components already existing on the market, especially components implemented with granular silica gel insulation, as this is the most effective translucent thermal insulation there is today. The tests run on these materials revealed that there is not one that has all the features required of the new envelope model, although some do have properties that could be exploited to generate this envelope, namely, the vacuum chamber of vacuum insulated panels (VIP), the monolithic aerogel used as insulation in some prototypes, reinforced polyester barriers. By combining these three design components — the high-performance thermal insulation of the vacuum chamber combined with monolithic silica gel insulation, the free-form design potential provided by materials like reinforced polyester and epoxy resins—, we have been able to define and test a new, variable geometry, energy-saving envelope system.

Variable-density jet flows induced by concentrated sources of momentum and energy

The planar and axisymmetric variable-density flows induced in a quiescent gas by a concentrated source of momentum that is simultaneously either a source or a sink of energy are investigated for application to the description of the velocity and temperature far fields in laminar gaseous jets with either large or small values of the initial jet-to-ambient temperature ratio. The source fluxes of momentum and heat are used to construct the characteristic scales of velocity and length in the region where the density differences are of the order of the ambient density, which is slender for the large values of the Reynolds number considered herein. The problem reduces to the integration of the dimensionless boundary-layer conservation equations, giving a solution that depends on the gas transport properties but is otherwise free of parameters. The boundary conditions at the jet exit for integration are obtained by analysing the self-similar flow that appears near the heat source in planar and axisymmetric configurations and also near the heat sink in the planar case. Numerical integrations of the boundary-layer equations with these conditions give solutions that describe accurately the velocity and temperature fields of very hot planar and round jets and also of very cold plane jets in the far field region where the density and temperature differences are comparable to the ambient values. Simple scaling arguments indicate that the point source description does not apply, however, to cold round jets, whose far field region is not large compared with the jet development region, as verified by numerical integrations

Extension of funding and program assistance under the Compact of Free Association : hearing before the Committee on Energy and Natural Resources, United States Senate, One Hundred Seventh Congress, first session, to receive testimony on negotiations on extension of funding and program assistance under the Compact of Free Association, December 6, 2001.

Shipping list no.: 2002-0182-P.

Energy-efficient commercial buildings : the range of possible solutions and their conceptual differences /

"Work Performed Under Contract No. EG-77-C-01-4042."

Results of energy-loss measurements on passenger car tires operating in the free-rolling and braking/traction modes. Final report.

Transportation Systems Center, Cambridge, Mass.