Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump

Imatinib mesylate (STI571), a potent tyrosine kinase inhibitor, is successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. However, the intended chronic oral administration of imatinib may lead to development of cellular resistance and subsequent treatment failure. Indeed, several molecular mechanisms leading to imatinib resistance have already been reported, including overexpression of the MDR1/ABCB1 drug pump. We examined whether imatinib is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump that is frequently overexpressed in human tumors. Using a panel of well-defined BCRP-overexpressing cell lines, we provide the first evidence that imatinib is a substrate for BCRP, that it competes with mitoxantrone for drug export, and that BCRP-mediated efflux can be reversed by the fumitremorgin C analog Ko-143. Since BCRP is highly expressed in the gastrointestinal tract, BCRP might not only play a role in cellular resistance of tumor cells but also influence the gastrointestinal absorption of imatinib

Stellar Kinematics and Structural Properties of Virgo Cluster Dwarf Early-Type Galaxies from the SMAKCED Project. I. Kinematically Decoupled Cores and Implications for Infallen Groups in Clusters

We present evidence for kinematically decoupled cores (KDCs) in two dwarf early-type (dE) galaxies in the Virgo cluster, VCC 1183 and VCC 1453, studied as part of the SMAKCED stellar absorption-line spectroscopy and imaging survey. These KDCs have radii of 1.8'' (0.14 kpc) and 4.2'' (0.33 kpc), respectively. Each of these KDCs is distinct from the main body of its host galaxy in two ways: (1) inverted sense of rotation; and (2) younger (and possibly more metal-rich) stellar population. The observed stellar population differences are probably associated with the KDC, although we cannot rule out the possibility of intrinsic radial gradients in the host galaxy. We describe a statistical analysis method to detect, quantify the significance of, and characterize KDCs in long-slit rotation curve data. We apply this method to the two dE galaxies presented in this paper and to five other dEs for which KDCs have been reported in the literature. Among these seven dEs, there are four significant KDC detections, two marginal KDC detections, and one dE with an unusual central kinematic anomaly that may be an asymmetric KDC.The frequency of occurence of KDCs and their properties provide important constraints on the formation history of their host galaxies. We discuss different formation scenarios for these KDCs in cluster environments and find that dwarf-dwarf wet mergers or gas accretion can explain the properties of these KDCs. Both of these mechanisms require that the progenitor had a close companion with a low relative velocity. This suggests that KDCs were formed in galaxy pairs residing in a poor group environment or in isolation whose subsequent infall into the cluster quenched star formation.Comment: 14 pages, accepted for publication in Ap

Experimentele afdelingen verbouwd

In een gezamenlijk FOMA-project van het Praktijkonderzoek Varkenshouderij en het IMAG-DLO wordt onderzoek verricht naar emissiearme houderijsystemen. Een deel van dit onderzoek wordt in drie zogenaamde experimentele vleesvarkenafdelingen op het Varkensproefbedrijf in Sterksel uitgevoerd

Deviations from the local field approximation in negative streamer heads

Negative streamer ionization fronts in nitrogen under normal conditions are investigated both in a particle model and in a fluid model in local field approximation. The parameter functions for the fluid model are derived from swarm experiments in the particle model. The front structure on the inner scale is investigated in a 1D setting, allowing reasonable run-time and memory consumption and high numerical accuracy without introducing super-particles. If the reduced electric field immediately before the front is >= 50kV/(cm bar), solutions of fluid and particle model agree very well. If the field increases up to 200kV/(cm bar), the solutions of particle and fluid model deviate, in particular, the ionization level behind the front becomes up to 60% higher in the particle model while the velocity is rather insensitive. Particle and fluid model deviate because electrons with high energies do not yet fully run away from the front, but are somewhat ahead. This leads to increasing ionization rates in the particle model at the very tip of the front. The energy overshoot of electrons in the leading edge of the front actually agrees quantitatively with the energy overshoot in the leading edge of an electron swarm or avalanche in the same electric field.Comment: The paper has 17 pages, including 15 figures and 3 table

Kinetic simulation of an extreme ultraviolet radiation driven plasma near a multilayer mirror

Future generation lithog. tools will use extreme UV radiation to enable the printing of sub-50 nm features on silicon wafers. The extreme UV radiation, coming from a pulsed discharge, photoionizes the low pressure background gas in the tool. A weakly ionized plasma is formed, which will be in contact with the optical components of the lithog. device. In the plasma sheath region ions will be accelerated towards the surfaces of multilayer mirrors. A self-consistent kinetic particle-in-cell model has been applied to describe a radiation driven plasma. The simulations predict the plasma parameters and notably the energy at which ions impact on the plasma boundaries. We have studied the influence of photoelectron emission from the mirror on the sheath dynamics and on the ion impact energy. Furthermore, the ion impact energy distribution has been convoluted with the formula of Yamamura and Tawara [At. Data Nucl. Data Tables 62, 149 (1996)] for the sputter yield to obtain the rate of phys. sputtering. The model predicts that the sputter rate is dominated by the presence of doubly ionized argon ions. [on SciFinder (R)