548 research outputs found
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)
- …