2,579 research outputs found

    Leveraging Semantic Web Service Descriptions for Validation by Automated Functional Testing

    Get PDF
    Recent years have seen the utilisation of Semantic Web Service descriptions for automating a wide range of service-related activities, with a primary focus on service discovery, composition, execution and mediation. An important area which so far has received less attention is service validation, whereby advertised services are proven to conform to required behavioural specifications. This paper proposes a method for validation of service-oriented systems through automated functional testing. The method leverages ontology-based and rule-based descriptions of service inputs, outputs, preconditions and effects (IOPE) for constructing a stateful EFSM specification. The specification is subsequently utilised for functional testing and validation using the proven Stream X-machine (SXM) testing methodology. Complete functional test sets are generated automatically at an abstract level and are then applied to concrete Web services, using test drivers created from the Web service descriptions. The testing method comes with completeness guarantees and provides a strong method for validating the behaviour of Web services

    Genomic Scans Support Repetitive Continental Colonization Events during the Rapid Radiation of Voles (Rodentia: Microtus): the Utility of AFLPs versus Mitochondrial and Nuclear Sequence Markers

    Get PDF
    Single locus studies might not resolve phylogenetic relationships and the evolutionary history of taxa. The analysis of multiple markers promises higher resolution, and congruence among loci may indicate that the phylogenies represent the underlying species history. Here, we examine the utility of a genome-wide approach based on amplified fragment length polymorphisms (AFLP) and several DNA sequence markers in resolving phylogenetic signals in the rapidly radiating rodent genus Microtus which produced about 70 vole species within the last 1.2-2 myr. The current Holarctic distribution of Microtus is assumed to have resulted from three independent colonization events out of Asia to North America, Europe, and northern Asia without subsequent colonization, which would have led to deep splits between species from different continents. We investigated this hypothesis of three single colonization events by reconstructing the phylogenetic relationships among species from all three continents based on data from the first exon of the nuclear arginine vasopressin receptor 1a gene (EXON1), an adjacent noncoding region and the mitochondrial cytochrome b gene. The phylogenetic patterns obtained from these sequence markers are contrasted to genome-wide data on more than 1800 amplified fragment length polymorphisms (AFLP) analyzed for the same samples. Our results show that the single sequence markers partially resolve the phylogenetic relationships within Microtus, but with some incongruence mostly between EXON1 and the other loci. However, deeper nodes of the radiation are only weakly supported and neither the combination of the markers nor additional nuclear sequences improved the resolution significantly. AFLPs provided much stronger support for major continent-specific clades, and show also that reciprocal monophyly of American and European voles is incomplete. Our results demonstrate that Microtus voles colonized the American and European continents each repeatedly in several independent events on similar colonization routes during their radiation. More generally, this study supports the suitability of AFLPs as an alternative to sequence markers to resolve the evolutionary history of rapidly radiating tax

    Genomic scans support repetitive continental colonization events during the rapid radiation of voles (Rodentia: Microtus): the utility of AFLPs versus mitochondrial and nuclear sequence markers

    Get PDF
    Background According to the World Health Organization position paper, immunodeficiency such as human immunodeficiency virus (HIV) infection is a relative contraindication for specific immunotherapy (SIT). Since the introduction of highly active antiretroviral therapy, a significant reconstitution of immune competence in individuals with HIV is possible.Case Report In a 52-year-old man, HIV infection was diagnosed in 1987. Antiretroviral therapy was started in 1998. He presented himself in July 2001 because of an increasingly severe seasonal rhinoconjunctivitis. Symptoms were not sufficiently alleviated by various antiallergic drugs.Results The investigations showed a relevant sensitization to tree pollens. Specific immunotherapy with a tree pollen mix (hazel, birch, ash, and alder, 25% each) was started in November 2001. Viral load at this time was less than 50 copies/mL, the CD4+ cell count was 307/μL. Therapy was given in monthly intervals until mid-April 2005 without any side effects. Viral load and CD4+ cell counts did not change during SIT. Clinically, rhinoconjunctivitis was experienced only intermittently and symptom relief was almost 90%.Conclusions This report indicates that in patients with well-controlled HIV infection on highly active antiretroviral therapy, SIT with pollen extracts is a potential and successful therapeutic option. Keywords: human immunodeficiency virus, pollen allergy, respiratory allergy, allergy treatment, specific immunotherap

    Functional analysis and transcriptional output of the Göttingen minipig genome

    Get PDF
    In the past decade the Göttingen minipig has gained increasing recognition as animal model in pharmaceutical and safety research because it recapitulates many aspects of human physiology and metabolism. Genome-based comparison of drug targets together with quantitative tissue expression analysis allows rational prediction of pharmacology and cross-reactivity of human drugs in animal models thereby improving drug attrition which is an important challenge in the process of drug development.; Here we present a new chromosome level based version of the Göttingen minipig genome together with a comparative transcriptional analysis of tissues with pharmaceutical relevance as basis for translational research. We relied on mapping and assembly of WGS (whole-genome-shotgun sequencing) derived reads to the reference genome of the Duroc pig and predict 19,228 human orthologous protein-coding genes. Genome-based prediction of the sequence of human drug targets enables the prediction of drug cross-reactivity based on conservation of binding sites. We further support the finding that the genome of Sus scrofa contains about ten-times less pseudogenized genes compared to other vertebrates. Among the functional human orthologs of these minipig pseudogenes we found HEPN1, a putative tumor suppressor gene. The genomes of Sus scrofa, the Tibetan boar, the African Bushpig, and the Warthog show sequence conservation of all inactivating HEPN1 mutations suggesting disruption before the evolutionary split of these pig species. We identify 133 Sus scrofa specific, conserved long non-coding RNAs (lncRNAs) in the minipig genome and show that these transcripts are highly conserved in the African pigs and the Tibetan boar suggesting functional significance. Using a new minipig specific microarray we show high conservation of gene expression signatures in 13 tissues with biomedical relevance between humans and adult minipigs. We underline this relationship for minipig and human liver where we could demonstrate similar expression levels for most phase I drug-metabolizing enzymes. Higher expression levels and metabolic activities were found for FMO1, AKR/CRs and for phase II drug metabolizing enzymes in minipig as compared to human. The variability of gene expression in equivalent human and minipig tissues is considerably higher in minipig organs, which is important for study design in case a human target belongs to this variable category in the minipig. The first analysis of gene expression in multiple tissues during development from young to adult shows that the majority of transcriptional programs are concluded four weeks after birth. This finding is in line with the advanced state of human postnatal organ development at comparative age categories and further supports the minipig as model for pediatric drug safety studies.; Genome based assessment of sequence conservation combined with gene expression data in several tissues improves the translational value of the minipig for human drug development. The genome and gene expression data presented here are important resources for researchers using the minipig as model for biomedical research or commercial breeding. Potential impact of our data for comparative genomics, translational research, and experimental medicine are discussed
    corecore