Challenges for the comprehensive management of cloud services in a PaaS framework

The 4CaaSt project aims at developing a PaaS framework that enables flexible definition, marketing, deployment and management of Cloud-based services and applications. The major innovations proposed by 4CaaSt are the blueprint and its lifecycle management, a one stop shop for Cloud services and a PaaS level resource management featuring elasticity. 4CaaSt also provides a portfolio of ready to use Cloud native services and Cloud-aware immigrant technologies

WS-BPEL extension for compliance fragments (BPEL4CFrags), Version 1.0

The Web Services Business Process Execution Language, version 2.0 (WS-BPEL 2.0 or BPEL for brevity) introduces a model for business processes based on Web services. A BPEL process orchestrates interactions among different Web services. The language comprises features required to describe complex control flows, including error handling and compensation behaviour. BPEL for Compliance Fragments (BPEL4CFrags) enables the specification of compliance fragments providing a reusable solution for implementing and meeting compliance requirements. The compliance fragments are not necessarily executable. Providing process modeling support at design time requires the completion of not directly executable compliance fragments, because compliance fragments contain several degrees of freedom, into already existing executable BPEL processes. Moreover, assistance for creation of executable BPEL processes from scratch during IT refinement has to be provided

A Classification of BPEL Extensions

The Business Process Execution Language (BPEL) has emerged as de-facto standard for business processes implementation. This language is designed to be extensible for including additional valuable features in a standardized manner. There are a number of BPEL extensions available. They are, however, neither classified nor evaluated with respect to their compliance to the BPEL standard. This article fills this gap by providing a framework for classifying BPEL extensions, a classification of existing extensions, and a guideline for designing BPEL extensions

An integrated solution for runtime compliance governance

Abstract. In response to recent financial scandals (e.g. those involving Enron, Fortis, Parmalat), new regulations for protecting the society from financial and operational risks of the companies have been introduced. Therefore, companies are required to assure compliance of their operations with those new regulations as well as those already in place. Regulations are only one example of compliance sources modern organizations deal with every day. Other sources of compliance include licenses of business partners and other contracts, internal policies, and international standards. The diversity of compliance sources introduces the problem of compliance governance in an organization. In this paper, we propose an integrated solution for runtime compliance governance in Service-Oriented Architectures (SOAs). We show how the proposed solution supports the whole cycle of compliance management: from modeling compliance requirements in domain-specific languages through monitoring them during process execution to displaying information about the current state of compliance in dashboards. We focus on the runtime part of the proposed solution and describe it in detail. We apply the developed framework in a real case study coming from EU FP7 project COMPAS, and this case study is used through the paper to illustrate our solution

Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke

Background and purpose Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-tage design of discovery and replication. Methods Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 1549 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms (SNPs) in THBD and 22 SNPs in PROCR were evaluated. Following LD pruning (r(2)>= 0.8), we advanced uncorrelated SNPs forward for association analyses. Associated SNPs were evaluated for replication in an early-onset ischemic stroke population (onset-ge Results Among GEOS Caucasians, PROCR rs9574, which was in strong LD with 8 other SNPs, and one additional independent SNP rs2069951, were significantly associated with ischemic stroke (rs9574, OR = 1.33, p = 0.003; rs2069951, OR = 1.80, p = 0.006) using an additive-model adjusting for age, gender and population-structure. Adjusting for risk factors did not change the associations; however, associations were strengthened among those without risk factors. PROCR rs9574 also associated with early-onset ischemic stroke in the replication sample (OR = 1.08, p = 0.015), but not older-onset stroke. There were no PROCR associations in African-Americans, nor were there any THBD associations in either ethnicity. Conclusion PROCR polymorphisms are associated with early-onset ischemic stroke in Caucasians.Peer reviewe

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Peer reviewe

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe