Evaluator services for optimised service placement in distributed heterogeneous cloud infrastructures

Optimal placement of demanding real-time interactive applications in a distributed heterogeneous cloud very quickly results in a complex tradeoff between the application constraints and resource capabilities. This requires very detailed information of the various requirements and capabilities of the applications and available resources. In this paper, we present a mathematical model for the service optimization problem and study the concept of evaluator services as a flexible and efficient solution for this complex problem. An evaluator service is a service probe that is deployed in particular runtime environments to assess the feasibility and cost-effectiveness of deploying a specific application in such environment. We discuss how this concept can be incorporated in a general framework such as the FUSION architecture and discuss the key benefits and tradeoffs for doing evaluator-based optimal service placement in widely distributed heterogeneous cloud environments

Structural studies of glucose-6-phosphate and NADP+ binding to human glucose-6-phosphate dehydrogenase

Human glucose-6-phosphate dehydrogenase (G6PD) is NADP(+)-dependent and catalyses the first and rate-limiting step of the pentose phosphate shunt. Binary complexes of the human deletion mutant, DeltaG6PD, with glucose-6-phosphate and NADP(+) have been crystallized and their structures solved to 2.9 and 2.5 A, respectively. The structures are compared with the previously determined structure of the Canton variant of human G6PD (G6PD(Canton)) in which NADP(+) is bound at the structural site. Substrate binding in DeltaG6PD is shown to be very similar to that described previously in Leuconostoc mesenteroides G6PD. NADP(+) binding at the coenzyme site is seen to be comparable to NADP(+) binding in L. mesenteroides G6PD, although some differences arise as a result of sequence changes. The tetramer interface varies slightly among the human G6PD complexes, suggesting flexibility in the predominantly hydrophilic dimer-dimer interactions. In both complexes, Pro172 of the conserved peptide EKPxG is in the cis conformation; it is seen to be crucial for close approach of the substrate and coenzyme during the enzymatic reaction. Structural NADP(+) binds in a very similar way in the DeltaG6PD-NADP(+) complex and in G6PD(Canton), while in the substrate complex the structural NADP(+) has low occupancy and the C-terminal tail at the structural NADP(+) site is disordered. The implications of possible interaction between the structural NADP(+) and G6P are considered.published_or_final_versio

Service oriented networking

This paper introduces a new paradigm for service oriented networking being developed in the FUSION project(1). Despite recent proposals in the area of information centric networking, a similar treatment of services - where networked software functions, rather than content, are dynamically deployed, replicated and invoked - has received little attention by the network research community to date. Our approach provides the mechanisms required to deploy a replicated service instance in the network and to route client requests to the closest instance in an efficient manner. We address the main issues that such a paradigm raises including load balancing, resource registration, domain monitoring and inter-domain orchestration. We also present preliminary evaluation results of current work

Impact of cyclosporine dosing regimen and infection on voriconazole pharmacodynamics in an experimental model of cerebral scedosporiosis

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Impact of infection status and cyclosporine on voriconazole pharmacokinetics in an experimental model of cerebral scedosporiosis

Cerebral Scedosporium infections usually occur in lung transplant recipients as well as in immunocompetent patients in the context of near-drowning. Voriconazole is the first-line treatment. The diffusion of voriconazole through the blood-brain barriers in the context of cerebral infection and cyclosporine administration is crucial and remains a matter of debate. To address this issue, the pharmacokinetics of voriconazole were assessed in the plasma, cerebrospinal fluid (CSF), and brain, in an experimental model of cerebral scedosporiosis in rats receiving or not cyclosporine. A single dose of voriconazole (30 mg/kg, i.v.) was administrated to six groups of rats randomized according to the infection status and the cyclosporine dosing regimen (no cyclosporine, a single dose or three doses 15 mg/kg each). Voriconazole concentrations in plasma, CSF, and brain samples were quantified using UPLC-MS/MS and HPLC-UV methods and documented up to 48 hours after administration. Pharmacokinetic parameters were estimated using a non-compartmental approach. Voriconazole pharmacokinetic profiles were similar for plasma, CSF, and the brain in all groups studied. Voriconazole Cmax and AUC0=>48h were significantly higher in the plasma than in the CSF (CSF/plasma ratio, median [range] = 0.5 [0.39-0.55] for AUC0=>48h and 0.47 [0.35 and 0.75] for Cmax). Cyclosporine administration was significantly associated with an increase in voriconazole exposure in the plasma, CSF, and brain. In the plasma but not in the brain, an interaction between the infection and cyclosporine administration reduced the positive impact of cyclosporine on voriconazole exposure. Together these results emphasize the impact of cyclosporine on the brain voriconazole exposure

Ectopic expression of PtaRHE1, encoding a poplar RING-H2 protein with E3 ligase activity, alters plant development and induces defence-related responses

RING (really interesting new gene)-H2 domain-containing proteins are widely represented in plants and play important roles in the regulation of many developmental processes as well as in plant–environment interactions. In the present report, experiments were performed to unravel the role of the poplar gene PtaRHE1, coding for a RING-H2 protein. In vitro ubiquitination assays indicate a functional E3 ligase activity for PtaRHE1 with the specific E2 ubiquitin-conjugating enzyme UbcH5a. The overexpression of PtaRHE1 in tobacco resulted in a pleiotropic phenotype characterized by a curling of the leaves, the formation of necrotic lesions on leaf blades, growth retardation, and a delay in floral transition. The plant gene expression response to PtaRHE1 overexpression provided evidence for the up-regulation of defence- and/or programmed cell death-related genes. Moreover, genes coding for WRKY transcription factors as well as for mitogen-activated protein kinases, such as wound-induced protein kinase (WIPK), were also found to be induced in the transgenic lines as compared with the wild type. In addition, histochemical β-glucuronidase staining showed that the PtaRHE1 promoter is induced by plant pathogens and by elicitors such as salicylic acid and cellulase. Taken together, these results suggest that the E3 ligase PtaRHE1 plays a role in the ubiquitination-mediated regulation of defence response, possibly by acting upstream of WIPK and/or in the activation of WRKY factors