Potent interaction of flavopiridol with MRP1

The multidrug resistance protein 1 (MRP1) is an ATP-dependent transport protein for organic anions, as well as neutral or positively charged anticancer agents. In this study we show that flavopiridol, a synthetic flavonoid currently studied in phase 1 trials for its anti-proliferative characteristics, interacts with MRP1 in a potent way. Flavopiridol, as well as other (iso)flavonoids stimulate the ATPase activity of MRP1 in a dose-dependent way at low micromolar concentrations. A new specific monoclonal antibody against MRP1 (MIB6) inhibits the (iso)flavonoid-induced ATPase activity of plasma membrane vesicles prepared from the MRP1 overexpressing cell line GLC4/ADR. The accumulation of daunorubicin in GLC4/ADR cells is increased by flavopiridol and by other non-glycosylated (iso)flavonoids that interact with MRP1 ATPase activity. However, flavopiridol is the only tested compound that affects the daunorubicin accumulation when present at concentrations below 1 μM. Glycosylated (iso)flavonoids do not affect MRP1-mediated transport or ATPase activity. Finally, MRP1 overexpressing and transfected cells are resistant to flavopiridol, but not to other (iso)flavonoids tested. These findings may be of relevance for the development of anticancer therapies with flavopiridol. © 1999 Cancer Research Campaig

Welcome to the jungle: An orientation guide to the disorder of mathematics education

This introductory chapter builds on the assumption that the sociopolitical dimensions of mathematics education have been gradually recognised as an important part of mathematics education research. We problematise the process of institutionalising these dimensions as a firm strand of mathematics education research just as “philosophy of mathematics (education)”, “history of mathematics (education)”, “modelling and applications” or “geometry”. This leads us to identify and conceptualise “disorder” as the foundation of the sociopolitical dimensions and accordingly to propose a shift from focussing diversity towards focussing disorder. Finally, we illustrate how the chapters of this book contribute to such an alternative self-conception of sociopolitical research in mathematics education

A review of multi-component maintenance models with economic dependence

In this paper we review the literature on multi-component maintenance models with economic dependence. The emphasis is on papers that appeared after 1991, but there is an overlap with Section 2 of the most recent review paper by Cho and Parlar (1991). We distinguish between stationary models, where a long-term stable situation is assumed, and dynamic models, which can take information into account that becomes available only on the short term. Within the stationary models we choose a classification scheme that is primarily based on the various options of grouping maintenance activities: grouping either corrective or preventive maintenance, or combining preventive-maintenance actions with corrective actions. As such, this classification links up with the possibilities for grouped maintenance activities that exist in practice