The relationship between cisplatin sensitivity and drug uptake into mammalian cells in vitro.

Clonogenic survival of HeLa, Chinese hamster and HaK cells after treatment with a range of cisplatin concentrations and exposure times was determined and cellular platinum concentrations were measured by PIXE. It was demonstrated that cisplatin cytotoxicity of the three cell lines varied considerably as a function of drug exposure dose. These differences are related to differential cellular drug uptake

Radiation-induced transient cisplatin resistance in murine fibrosarcoma cells associated with elevated metallothionein content.

Cisplatin resistant mouse fibrosarcoma cells were isolated after fractionated irradiation in the absence of any drug treatment. Several sublines have been established; clone SSK-rad1 was used for further studies. These cells exhibit unchanged radiosensitivity and are compared to cisplatin resistant sublines, SSK-cis2, previously induced by low dose cisplatin exposure. Both resistant sublines are characterised by reduced CdCl2 sensitivity, indicating enhanced metallothionein content; loss of cisplatin resistance occurs after 10 to 25 generations and correlates with rising CdCl2 toxicity. Increase of MT is demonstrated directly by 109Cd binding to the MT containing region after FPLC. Both sublines differ in GSH level, which is increased only in SSK-rad1 cells, and in cellular platinum content, which is reduced in SSK-cis2 cells compared to the parental SSK cell line. These factors may contribute to cisplatin resistance but are not the main cause responsible for the transient nature of the drug resistance observed. Our results indicate that transient cisplatin resistance in SSK cells can be induced not only by the drug itself but also by gamma-irradiation and is based on the same mechanism of increased cellular MT content

Hypocoercivity for Kolmogorov backward evolution equations and applications

In this article we extend the modern, powerful and simple abstract Hilbert space strategy for proving hypocoercivity that has been developed originally by Dolbeault, Mouhot and Schmeiser. As well-known, hypocoercivity methods imply an exponential decay to equilibrium with explicit computable rate of convergence. Our extension is now made for studying the long-time behavior of some strongly continuous semigroup generated by a (degenerate) Kolmogorov backward operator L. Additionally, we introduce several domain issues into the framework. Necessary conditions for proving hypocoercivity need then only to be verified on some fixed operator core of L. Furthermore, the setting is also suitable for covering existence and construction problems as required in many applications. The methods are applicable to various, different, Kolmogorov backward evolution problems. As a main part, we apply the extended framework to the (degenerate) spherical velocity Langevin equation. The latter can be seen as some kind of an analogue to the classical Langevin equation in case spherical velocities are required. This model is of important industrial relevance and describes the fiber lay-down in the production process of nonwovens. For the construction of the strongly continuous contraction semigroup we make use of modern hypoellipticity tools and pertubation theory

Drivers of grassland loss in Hungary during the post-socialist transformation (1987–1999)

The increase in the speed of land-cover change experienced worldwide is becoming a growing concern. Major socio-economic transitions, such as the breakdown of socialism in Europe, may lead to particularly high rates of landscape transformations. In this paper we examined the loss of semi-natural grasslands in Hungary between 1987 and 1999. We studied the relationship between 9 potential driving forces and the fate of grasslands using logistic GLMs. Grassland loss was found to be very high (1.31 % per year), which is far higher than either before or after this period. The most influential predictors of grassland loss were environmental and landscape characteristics (soil type, area of remnant grassland patches), and the socio-economic context (distance to paved road, and nearest settlement, human population density). Several processes and relationships can only be understood from a historical perspective (e.g. large extent of afforestation, strong decrease of soil water table). Grassland loss during the study period emerged as a consequence of survival strategies of individual farmers seeking adaptation to the changing environmental and socio-economic conditions, and not urbanization and agricultural intensification which are the main underlying drivers for the ongoing landscape transformations in most parts of the developed world. Though globalization increasingly influences local land use decisions , reconstructing and modelling recent landscape changes cannot be done without a proper understanding of local history and culture. Our analysis shows the importance of large-area yet high resolution landscape change research, which may reveal unexpected patterns of land cover change, undetected at coarser scales