VIZIR: The SEP high resolution laser beam recorder

A means for high density archiving of meteorological data on a photographic film is described. The data are stored on-line under a form accessible to interpretation. The VIZIR thus forms the final link of the receiving system of a ground station

State Aid in the new EU Member States

In the early phase of transition, which began in the 1990s, Central and Eastern European countries (CEECs) pursued economic restructuring that involved massive injections of state support. With reference to the history of state aid in centrally planned economies, we investigate state aid practices of CEECs since attaining full EU membership. We analyse whether their state aid policies during and after transition challenged European state aid legislation, and whether these fit into the EU strategy of ‘less but better targeted aid’. The data-based analysis is complemented with some indicative insights from state aid in the steel industry as well as the financial service sector to suggest that there is today no significant difference in state aid law application between East and West any more – the new EU members have further caught up by better aligning to the objectives of the State Aid Action Plan

Hypoxia-induced modulation of apoptosis and BCL-2 family proteins in different cancer cell types

Hypoxia plays an important role in the resistance of tumour cells to chemotherapy. However, the exact mechanisms underlying this process are not well understood. Moreover, according to the cell lines, hypoxia differently influences cell death. The study of the effects of hypoxia on the apoptosis induced by 5 chemotherapeutic drugs in 7 cancer cell types showed that hypoxia generally inhibited the drug-induced apoptosis. In most cases, the effect of hypoxia was the same for all the drugs in one cell type. The expression profile of 93 genes involved in apoptosis as well as the protein level of BCL-2 family proteins were then investigated. In HepG2 cells that are strongly protected against cell death by hypoxia, hypoxia decreased the abundance of nearly all the pro-apoptotic BCL-2 family proteins while none of them are decreased in A549 cells that are not protected against cell death by hypoxia. In HepG2 cells, hypoxia decreased NOXA and BAD abundance and modified the electrophoretic mobility of BIM(EL). BIM and NOXA are important mediators of etoposide-induced cell death in HepG2 cells and the hypoxia-induced modification of these proteins abundance or post-translational modifications partly account for chemoresistance. Finally, the modulation of the abundance and/or of the post-translational modifications of most proteins of the BCL-2 family by hypoxia involves p53-dependent and -independent pathways and is cell type-dependent. A better understanding of these cell-to-cell variations is crucial in order to overcome hypoxia-induced resistance and to ameliorate cancer therapy

Modified release formulations manufactured by hot-melt extrusion

Hot-melt-extrusion has recently gained interest in pharmaceutical industrial manufacturing due to numerous advantages such as the possibility for continuous manufacturing, low cost of operation or the absence of organic solvents. Hot-melt-extrusion success lies also in its ability to manufacture amorphous solid dispersions, which has been adopted as a method of choice in the pharmaceutical industry to overcome poor drugs water-solubility. Sustained release amorphous solid dispersions are challenging to formulate due to the low extent of supersaturation, the gelation phenomenon around the matrix and recrystallization. Different polymeric carriers for hot-melt-extruded amorphous tablets were evaluated for their ability to provide sustained release. Hydrophilic carriers were able to sustain amorphous drug release in high solubility environment. In lower solubility conditions, drug was trapped in the tablet due to its inability to dissolve and diffuse in the gel layer. In these low solubility conditions, enteric polymers can be used to sustain drug release due to their erosion based release mechanism and the prevention of media penetration. The efficacy of an itraconazole amorphous solid dispersion containing HPMCAS and Vitamin E TPGS was evaluated against invasive fungal infection by Aspergillus fumigatus. This formulation was selected due to its previously demonstrated high bioavailability in rats. Mice infected by Aspergillus fumigatus were treated orally with the formulation, which led to highly variable pharmacokinetic parameters and low efficacy. These were attributed to mice gastro intestinal tract low pH, reduced fluid volumes and low efficacy of itraconazole in mice model. In guinea pigs, high tissue levels were measured with significant decrease in Aspergillus fumigatus fungal burden. Hot-melt-extrusion processing was utilized to manufacture monolithic tablets containing Tramadol HCl and Affinisol™ HPMC. The potential for the tablet to prevent abuse by physical and chemical manipulation was investigated and compared to directly compressed tablet of the same composition. It was demonstrated that hot-melt-extrusion of Affinisol™ HPMC provides high physical strength to the tablets, thus preventing crushing by manual methods. Milling the tablets in a high shear grinder for minutes was necessary to break the tablets. Chemical extraction from milled tablets was also decreased for hotmelt-extruded tablets due to their larger particle sizePharmaceutical Science