Abstract. Transient treatment of human adenocarcinoma COLO 205 cells with lipit raft (LR) modulators (MßCD, NY, IMP) was followed by the challenge with metabolic inhibitors and selected anti-cancer drugs. To overturn cholesterol chelation, the MßCD, NY treatment was followed by cholesterol conjugates (CHOL-MßCD or CHOL-PEG). The TNF-·-and P(Ser473)-PKB/Akt1/2-mediated effects initiated at LR were evaluated with regard to cell viability and mitogenicity. Cholesterol chelators reversibly reduced cell survival, whereas some of the tested compounds had weak effects (CIS, CLA), stimulated (EGCG) or reduced (NaB) cell survival. Cellular localizations of LR-associated molecules (ceramides, G ·i-2 heterotrimeric protein, and TNF-R1) in different cellular compartments including the plasma membrane were observed in the respective photographs from TEM and SEM. Evidence from SEM also showed that TNF-R1 is clustered on the surface of COLO 205 cells without presence of cognate ligand but clustering is promoted by TNF-·, while it vanished after IMP treatment. COLO 205 cells remained immune to TNF-·-induced apoptosis unless NaB was added, in which case NaB-induced cell death was further potentiated by TNF-·. Combined NaB and TNF-· treatment was associated with marked changes in the expression of pro-and antiapoptotic proteins. In this study, we demonstrated that initial excess of prosurvival signals could be diminished by cholesterol chelators, whereas LR-independent cell survival could be targeted by NaB. Apparently, lipid rafts do not participate in NaB-dependent cell death.
This paper describes a programming toolkit developed in the PL-Grid project, named QStorMan, which supports storage QoS provisioning for data-intensive applications in distributed environments. QStorMan exploits knowledgeoriented methods for matching storage resources to non-functional requirements, which are defined for a data-intensive application. In order to support various usage scenarios, QStorMan provides two interfaces, such as programming libraries or a web portal. The interfaces allow to define the requirements either directly in an application source code or by using an intuitive graphical interface. The first way provides finer granularity, e.g., each portion of data processed by an application can define a different set of requirements. The second method is aimed at legacy applications support, which source code can not be modified. The toolkit has been evaluated using synthetic benchmarks and the production infrastructure of PL-Grid, in particular its storage infrastructure, which utilizes the Lustre file system.
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