925 research outputs found
Surface flow profiles for dry and wet granular materials by Particle Tracking Velocimetry; the effect of wall roughness
Two-dimensional Particle Tracking Velocimetry (PTV) is a promising technique
to study the behaviour of granular flows. The aim is to experimentally
determine the free surface width and position of the shear band from the
velocity profile to validate simulations in a split-bottom shear cell geometry.
The position and velocities of scattered tracer particles are tracked as they
move with the bulk flow by analyzing images. We then use a new technique to
extract the continuum velocity field, applying coarse-graining with the
postprocessing toolbox MercuryCG on the discrete experimental PTV data. For
intermediate filling heights, the dependence of the shear (or angular) velocity
on the radial coordinate at the free surface is well fitted by an error
function. From the error function, we get the width and the centre position of
the shear band. We investigate the dependence of these shear band properties on
filling height and rotation frequencies of the shear cell for dry glass beads
for rough and smooth wall surfaces. For rough surfaces, the data agrees with
the existing experimental results and theoretical scaling predictions. For
smooth surfaces, particle-wall slippage is significant and the data deviates
from the predictions. We further study the effect of cohesion on the shear band
properties by using small amount of silicon oil and glycerol as interstitial
liquids with the glass beads. While silicon oil does not lead to big changes,
glycerol changes the shear band properties considerably. The shear band gets
wider and is situated further inward with increasing liquid saturation, due to
the correspondingly increasing trend of particles to stick together
Characterization of a clonal human colon adenocarcinoma line intrinsically resistant to doxorubicin.
Intrinsic low-level resistance to anti-cancer drugs is a major problem in the treatment of gastrointestinal malignancies. To address the problem presented by intrinsically resistant tumours, we have isolated two monoclonal lines from LoVo human colon adenocarcinoma cells: LoVo/C7, which is intrinsically resistant to doxorubicin (DOX); and LoVo/C5, which shows the same resistance index for DOX as the mixed parental cell population. For comparison, we have included in the study a LoVo-resistant line selected by continuous exposure to DOX and expressing a typical multidrug resistant (MDR) phenotype. In these cell lines we have studied the expression and/or activity of a number of proteins, including P-glycoprotein 170 (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), glutathione (GSH)-dependent enzymes and protein kinase C (PKC) isoforms, which have been implicated in anti-cancer drug resistance. Intracellular DOX distribution has been assessed by confocal microscopy. The results of the present study indicate that resistance in LoVo/C7 cells cannot be attributed to alterations in P-gp, LRP or GSH/GSH-dependent enzyme levels. Increased expression of MRP, accompanied by alterations in the subcellular distribution of DOX, has been observed in LoVo/C7 cells; changes in PKC isoform pattern have been detected in both intrinsically and pharmacologically resistant cells
Altered MRP is associated with multidrug resistance and reduced drug accumulation in human SW-1573 cells.
We have analysed the contribution of several parameters, e.g. drug accumulation, MDR1 P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and topoisomerase (topo) II, to drug resistance in a large set of drug-resistant variants of the human non-small-cell lung cancer cell line SW-1573 derived by selection with low concentrations of doxorubicin or vincristine. Selection with either drug nearly always resulted in MDR clones. The resistance of these clones could be explained by reduced drug accumulation and was associated with a decrease rather than an increase in the low MDR1 mRNA level. To test whether a decrease in MDR1 mRNA indirectly affected resistance in these cells, we introduced a MDR1-specific hammerhead ribozyme into wild-type SW-1573 cells. Although this led to a substantial reduction in MDR1 mRNA, it did not result in resistance. In all resistant clones we found an altered form of the multidrug resistance-associated protein (MRP), migrating slightly slower during SDS-polyacrylamide gel electrophoresis than MRP in parental cells. This altered MRP was also present in non-P-gp MDR somatic cell hybrids of the SW-1573 cells, demonstrating a clear linkage with the MDR phenotype. Treatment of crude cellular membrane fractions with N-glycanase, endoglycosidase H or neuraminidase showed that the altered migration of MRP on SDS-PAGE is due to a post-translational modification. There was no detectable difference in sialic acid content. In most but not all doxorubicin-selected clones, this MDR phenotype was accompanied by a reduction in topo II alpha mRNA level. No reduction was found in the clones selected with vincristine. We conclude from these results that selection of the SW-1573 cell line for low levels of doxorubicin or vincristine resistance, predominantly results in MDR with reduced drug accumulation associated with the presence of an altered MRP protein. This mechanism can be accompanied by other resistance mechanisms, such as reduced topo II alpha mRNA in case of doxorubicin selection
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