In situ synthesis of estrogens is believed to be of great importance for the progression of breast cancer. In postmenopausal women most estrogens are synthesized in peripheral hormone-target tissues from circulating precursor steroids, by the enzymes involved in formation of active estrogens. One of the enzymes involved in this process is 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 1. This enzyme catalyzes the interconversion of estrone (E1) to the biologically more potent estradiol (E2). The gene coding for 17beta-HSD type 1 (HSD17B1) is located at 17q12-21. The aim of this study was to investigate altered gene copy number of HSD17B1 in breast cancer. We used real-time PCR and examined 387 postmenopausal breast tumors for amplification of HSD17B1, and if an increased mRNA level of this enzyme is associated with amplification of the gene. We also investigated whether amplification of HSD17B1 has a prognostic value. There was a significant correlation between gene copy number of HSD17B1 and mRNA expression level (P = 0.00002). ER-positive patients with amplification of HSD17B1 showed lower breast cancer survival than patients without amplification (P = 0.025). Among ER-negative patients there was no significant correlation between increased gene copy number of HSD17B1 and prognosis. Furthermore, we found that amplification of the gene had prognostic significance in multivariate analysis adjusting for other clinicopathological variables.

Ontologies are formal knowledge models that describe concepts and relationships and enable data integration, information search, and reasoning. Ontology Design Patterns (ODPs) are reusable solutions intended to simplify ontology development and support the use of semantic technologies by ontology engineers. ODPs document and package good modelling practices for reuse, ideally enabling inexperienced ontologists to construct high-quality ontologies. Although ODPs are already used for development, there are still remaining challenges that have not been addressed in the literature. These research gaps include a lack of knowledge about (1) which ODP features are important for ontology engineering, (2) less experienced developers' preferences and barriers for employing ODP tooling, and (3) the suitability of the eXtreme Design (XD) ODP usage methodology in non-academic contexts.This dissertation aims to close these gaps by combining quantitative and qualitative methods, primarily based on five ontology engineering projects involving inexperienced ontologists. A series of ontology engineering workshops and surveys provided data about developer preferences regarding ODP features, ODP usage methodology, and ODP tooling needs. Other data sources are ontologies and ODPs published on the web, which have been studied in detail. To evaluate tooling improvements, experimental approaches provide data from comparison of new tools and techniques against established alternatives.The analysis of the gathered data resulted in a set of measurable quality indicators that cover aspects of ODP documentation, formal representation or axiomatisation, and usage by ontologists. These indicators highlight quality trade-offs: for instance, between ODP Learnability and Reusability, or between Functional Suitability and Performance Efficiency. Furthermore, the results demonstrate a need for ODP tools that support three novel property specialisation strategies, and highlight the preference of inexperienced developers for template-based ODP instantiation-neither of which are supported in prior tooling. The studies also resulted in improvements to ODP search engines based on ODP-specific attributes. Finally, the analysis shows that XD should include guidance for the developer roles and responsibilities in ontology engineering projects, suggestions on how to reuse existing ontology resources, and approaches for adapting XD to project-specific contexts.iii Populärvetenskaplig sammanfattningDe senaste två decennierna har användningen av Internet och dess killer app World Wide Web (i dagligt tal webben)ökat explosionsartat, såväl vad gäller antal användare som antal tillgängliga tjänster. Vi surfar inte längre bara på webben för att söka efter information -snarare lever vi i allt högre utsträck-ning våra liv uppkopplade via den. Vi handlar mat och gör bankärenden, vi bokar semestrar och läser böcker, vi delar bilder och videos och minnen med varandra. I de flesta avseenden har webben och dess möjligheter utvecklats långt bortom vad de flesta t...

Abstract:Background: Age related bone loss is widely accepted as related to decreased serum-levels

Ontology engineering is traditionally a complex and timeconsuming process, requiring an intimate knowledge of description logic and predicting non-local effects of different ontological commitments. Pattern-based modular ontology engineering, coupled with a graphical modeling paradigm, can help make ontology engineering accessible to modellers with limited ontology expertise. We have developed CoMo-dIDE, the Comprehensive Modular Ontology IDE, to develop and explore such a modeling approach. In this paper we present an evaluation of the CoModIDE tool, with a set of 21 subjects carrying out some typical modeling tasks. Our findings indicate that using CoModIDE improves task completion rate and reduces task completion time, compared to using standard Protégé. Further, our subjects report higher System Usability Scale (SUS) evaluation scores for CoModIDE, than for Protégé. The subjects also report certain room for improvements in the CoModIDE tool-notably, these comments all concern comparatively shallow UI bugs or issues, rather than limitations inherent in the proposed modeling method itself. We deduce that our modeling approach is viable, and propose some consequences for ontology engineering tool development.

Reusing ontologies for new purposes, or adapting them to new use-cases, is frequently difficult. In our experiences, we have found this to be the case for several reasons: (i) differing representational granularity in ontologies and in use-cases, (ii) lacking conceptual clarity in potentially reusable ontologies, (iii) lack and difficulty of adherence to good modeling principles, and (iv) a lack of reuse emphasis and process support available in ontology engineering tooling. In order to address these concerns, we have developed the Modular Ontology Modeling (MOMo) methodology, and its supporting tooling infrastructure, CoModIDE (the Comprehensive Modular Ontology IDE – “commodity”). MOMo builds on the established eXtreme Design methodology, and like it emphasizes modular development and design pattern reuse; but crucially adds the extensive use of graphical schema diagrams, and tooling that support them, as vehicles for knowledge elicitation from experts. In this paper, we present the MOMo workflow in detail, and describe several useful resources for executing it. In particular, we provide a thorough and rigorous evaluation of CoModIDE in its role of supporting the MOMo methodology’s graphical modeling paradigm. We find that CoModIDE significantly improves approachability of such a paradigm, and that it displays a high usability.