Challenges for orchestration and instance selection of composite services in distributed edge clouds

Today's centralized cloud-computing infrastructures have not been designed with geo-localized, personalized, bandwidth/processing-intensive, real-time applications in mind. High network delay and low throughput can have a significant impact on the user experience. Instead, such services could be deployed in distributed service nodes at the edge of the network, closer to the user. In this paper we focus on composite services of which the components are running in different service nodes. We present a two-layer framework that provides service orchestration and instance selection. We present the orchestration mechanisms to enable the flexible re-use of components across different composite services. For the resolution layer of our framework, we present two modes of operation that combine network and service availability information for efficient per-request instance selection among a multitude of service replicas

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

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

Solution of the structure of tetrameric human glucose 6-phosphate dehydrogenase by molecular replacement

Recombinant human glucose 6-phosphate dehydrogenase (G6PD) has been crystallized and its structure solved by molecular replacement. Crystals of the natural mutant R459L grow under similar conditions in space groups P212121 and C2221 with eight or four 515-residue molecules in the asymmetric unit, respectively. A non-crystallographic 222 tetramer was found in the C2221 crystal form using a 4 A resolution data set and a dimer of the large beta + alpha domains of the Leuconostoc mesenteroides enzyme as a search model. This tetramer was the only successful search model for the P212121 crystal form using data to 3 A. Crystals of the deletion mutant DeltaG6PD grow in space group F222 with a monomer in the asymmetric unit; 2.5 A resolution data have been collected. Comparison of the packing of tetramers in the three space groups suggests that the N-terminal tail of the enzyme prevents crystallization with exact 222 molecular symmetry.published_or_final_versio

Service-centric networking

This chapter introduces a new paradigm for service centric networking. Building upon 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 – is discussed. Service-centric networking provides the mechanisms required to deploy replicated service instances across highly distributed networked cloud infrastructures and to route client requests to the closest instance while providing more efficient network infrastructure usage, improved QoS and new business opportunities for application and service providers. </jats:p

Draft Genome Sequence of the Human-Pathogenic Fungus Scedosporium boydii

The opportunistic fungal pathogen Scedosporium boydii is the most common Scedosporium species in French patients with cystic fibrosis. Here we present the first genome report for S. boydii, providing a resource which may enable the elucidation of the pathogenic mechanisms in this species

Cell-Free DNA as a Diagnostic and Prognostic Biomarker in Pediatric Rhabdomyosarcoma.

PURPOSE: Total cell-free DNA (cfDNA) and tumor-derived cfDNA (ctDNA) can be used to study tumor-derived genetic aberrations. We analyzed the diagnostic and prognostic potential of cfDNA and ctDNA, obtained from pediatric patients with rhabdomyosarcoma. METHODS: cfDNA was isolated from diagnostic plasma samples from 57 patients enrolled in the EpSSG RMS2005 study. To study the diagnostic potential, shallow whole genome sequencing (shWGS) and cell-free reduced representation bisulphite sequencing (cfRRBS) were performed in a subset of samples and all samples were tested using droplet digital polymerase chain reaction to detect methylated RASSF1A (RASSF1A-M). Correlation with outcome was studied by combining cfDNA RASSF1A-M detection with analysis of our rhabdomyosarcoma-specific RNA panel in paired cellular blood and bone marrow fractions and survival analysis in 56 patients. RESULTS: At diagnosis, ctDNA was detected in 16 of 30 and 24 of 26 patients using shallow whole genome sequencing and cfRRBS, respectively. Furthermore, 21 of 25 samples were correctly classified as embryonal by cfRRBS. RASSF1A-M was detected in 21 of 57 patients. The presence of RASSF1A-M was significantly correlated with poor outcome (the 5-year event-free survival [EFS] rate was 46.2% for 21 RASSF1A-M‒positive patients, compared with 84.9% for 36 RASSF1A-M‒negative patients [P < .001]). RASSF1A-M positivity had the highest prognostic effect among patients with metastatic disease. Patients both negative for RASSF1A-M and the rhabdomyosarcoma-specific RNA panel (28 of 56 patients) had excellent outcome (5-year EFS 92.9%), while double-positive patients (11/56) had poor outcome (5-year EFS 13.6%, P < .001). CONCLUSION: Analyzing ctDNA at diagnosis using various techniques is feasible in pediatric rhabdomyosarcoma and has potential for clinical use. Measuring RASSF1A-M in plasma at initial diagnosis correlated significantly with outcome, particularly when combined with paired analysis of blood and bone marrow using a rhabdomyosarcoma-specific RNA panel

Draft Genome Sequence of the Pathogenic Fungus Scedosporium apiospermum

This is the final version of the article. Available from the publisher via the DOI in this record.The first genome of one species of the Scedosporium apiospermum complex, responsible for localized to severe disseminated infections according to the immune status of the host, will contribute to a better understanding of the pathogenicity of these fungi and also to the discovery of the mechanisms underlying their low susceptibility to current antifungals.This work was supported by a grant (RF20120600725) from the association Vaincre la Mucoviscidose (France), which is gratefully acknowledged

Genome-wide, high-content siRNA screening identifies the Alzheimer's genetic risk factor FERMT2 as a major modulator of APP metabolism

Genome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer’s disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the “post-GWAS” era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective. We therefore developed a genome-wide, high-content siRNA screening approach and used it to assess the functional impact of gene under-expression on APP metabolism. We found that 832 genes modulated APP metabolism. Eight of these genes were located within AD susceptibility loci. Only FERMT2 (a β3-integrin co-activator) was also significantly associated with a variation in cerebrospinal fluid Aβ peptide levels in 2886 AD cases. Lastly, we showed that the under-expression of FERMT2 increases Aβ peptide production by raising levels of mature APP at the cell surface and facilitating its recycling. Taken as a whole, our data suggest that FERMT2 modulates the AD risk by regulating APP metabolism and Aβ peptide production