Methods for construction and analysis of computational models in systems biology : applications to the modelling of the heat shock response and the self-assembly of intermediate filaments

Systems biology is a new, emerging and rapidly developing, multidisciplinary research field that aims to study biochemical and biological systems from a holistic perspective, with the goal of providing a comprehensive, system- level understanding of cellular behaviour. In this way, it addresses one of the greatest challenges faced by contemporary biology, which is to compre- hend the function of complex biological systems. Systems biology combines various methods that originate from scientific disciplines such as molecu- lar biology, chemistry, engineering sciences, mathematics, computer science and systems theory. Systems biology, unlike “traditional” biology, focuses on high-level concepts such as: network, component, robustness, efficiency, control, regulation, hierarchical design, synchronization, concurrency, and many others. The very terminology of systems biology is “foreign” to “tra- ditional” biology, marks its drastic shift in the research paradigm and it indicates close linkage of systems biology to computer science. One of the basic tools utilized in systems biology is the mathematical modelling of life processes tightly linked to experimental practice. The stud- ies contained in this thesis revolve around a number of challenges commonly encountered in the computational modelling in systems biology. The re- search comprises of the development and application of a broad range of methods originating in the fields of computer science and mathematics for construction and analysis of computational models in systems biology. In particular, the performed research is setup in the context of two biolog- ical phenomena chosen as modelling case studies: 1) the eukaryotic heat shock response and 2) the in vitro self-assembly of intermediate filaments, one of the main constituents of the cytoskeleton. The range of presented approaches spans from heuristic, through numerical and statistical to ana- lytical methods applied in the effort to formally describe and analyse the two biological processes. We notice however, that although applied to cer- tain case studies, the presented methods are not limited to them and can be utilized in the analysis of other biological mechanisms as well as com- plex systems in general. The full range of developed and applied modelling techniques as well as model analysis methodologies constitutes a rich mod- elling framework. Moreover, the presentation of the developed methods, their application to the two case studies and the discussions concerning their potentials and limitations point to the difficulties and challenges one encounters in computational modelling of biological systems. The problems of model identifiability, model comparison, model refinement, model inte- gration and extension, choice of the proper modelling framework and level of abstraction, or the choice of the proper scope of the model run through this thesis.

Adult education policy in the European Union during the Lisbon decade : the shift to vocational adult learning and work skills matching

This doctoral dissertation investigates the adult education policy of the European Union (EU) in the framework of the Lisbon agenda 2000–2010, with a particular focus on the changes of policy orientation that occurred during this reference decade. The year 2006 can be considered, in fact, a turning point for the EU policy-making in the adult learning sector: a radical shift from a wide--ranging and comprehensive conception of educating adults towards a vocationally oriented understanding of this field and policy area has been observed, in particular in the second half of the so--called ‘Lisbon decade’. In this light, one of the principal objectives of the mainstream policy set by the Lisbon Strategy, that of fostering all forms of participation of adults in lifelong learning paths, appears to have muted its political background and vision in a very short period of time, reflecting an underlying polarisation and progressive transformation of European policy orientations. Hence, by means of content analysis and process tracing, it is shown that the new target of the EU adult education policy, in this framework, has shifted from citizens to workers, and the competence development model, borrowed from the corporate sector, has been established as the reference for the new policy road maps. This study draws on the theory of governance architectures and applies a post-ontological perspective to discuss whether the above trends are intrinsically due to the nature of the Lisbon Strategy, which encompasses education policies, and to what extent supranational actors and phenomena such as globalisation influence the European governance and decision--making. Moreover, it is shown that the way in which the EU is shaping the upgrading of skills and competences of adult learners is modeled around the needs of the ‘knowledge economy’, thus according a great deal of importance to the ‘new skills for new jobs’ and perhaps not enough to life skills in its broader sense which include, for example, social and civic competences: these are actually often promoted but rarely implemented in depth in the EU policy documents. In this framework, it is conveyed how different EU policy areas are intertwined and interrelated with global phenomena, and it is emphasised how far the building of the EU education systems should play a crucial role in the formation of critical thinking, civic competences and skills for a sustainable democratic citizenship, from which a truly cohesive and inclusive society fundamentally depend, and a model of environmental and cosmopolitan adult education is proposed in order to address the challenges of the new millennium. In conclusion, an appraisal of the EU’s public policy, along with some personal thoughts on how progress might be pursued and actualised, is outlined.

In search of information systems value : a case study of the EHR benefits realisation efforts of three Swedish hospitals.

The Swedish public health care organisation could very well be undergoing its most significant change since its specialisation during the late 19th and early 20th century. At the heart of this change is a move from using manual patient journals to electronic health records (EHR). EHR are complex integrated organisational wide information systems (IS) that promise great benefits and value as well as presenting great challenges to the organisation. The Swedish public health care is not the first organisation to implement integrated IS, and by no means alone in their quest for realising the potential benefits and value that it has to offer. As organisations invest in IS they embark on a journey of value-creation and capture. A journey where a costbased approach towards their IS-investments is replaced with a value-centric focus, and where the main challenges lie in the practical day-to-day task of finding ways to intertwine technology, people and business processes. This has however proven to be a problematic task. The problematic situation arises from a shift of perspective regarding how to manage IS in order to gain value. This is a shift from technology delivery to benefits delivery; from an ISimplementation plan to a change management plan. The shift gives rise to challenges related to the inability of IS and the elusiveness of value. As a response to these challenges the field of IS-benefits management has emerged offering a framework and a process in order to better understand and formalise benefits realisation activities. In this thesis the benefits realisation efforts of three Swedish hospitals within the same county council are studied. The thesis focuses on the participants of benefits analysis projects; their perceptions, judgments, negotiations and descriptions of potential benefits. The purpose is to address the process where organisations seek to identify which potential IS-benefits to pursue and realise, this in order to better understand what affects the process, so that realisation actions of potential IS-benefits could be supported. A qualitative case study research design is adopted and provides a framework for sample selection, data collection, and data analysis. It also provides a framework for discussions of validity, reliability and generalizability. Findings displayed a benefits fluctuation, which showed that participants’ perception of what constituted potential benefits and value changed throughout the formal benefits management process. Issues like structure, knowledge, expectation and experience affected perception differently, and this in the end changed the amount and composition of potential benefits and value. Five dimensions of benefits judgment were identified and used by participants when finding accommodations of potential benefits and value to pursue. Identified dimensions affected participants’ perceptions, which in turn affected the amount and composition of potential benefits. During the formal benefits management process participants shifted between judgment dimensions. These movements emerged through debates and interactions between participants. Judgments based on what was perceived as expected due to one’s role and perceived best for the organisation as a whole were the two dominant benefits judgment dimensions. A benefits negotiation was identified. Negotiations were divided into two main categories, rational and irrational, depending on participants’ drive when initiating and participating in negotiations. In each category three different types of negotiations were identified having different characteristics and generating different outcomes. There was also a benefits negotiation process identified that displayed management challenges corresponding to its five phases. A discrepancy was also found between how IS-benefits are spoken of and how actions of IS benefits realisation are understood. This was a discrepancy between an evaluation and a realisation focus towards IS value creation. An evaluation focus described IS-benefits as well-defined and measurable effects and a realisation focus spoke of establishing and managing an on-going place of value creation. The notion of valuescape was introduced in order to describe and support the understanding of IS value creation. Valuescape corresponded to a realisation focus and outlined a value configuration consisting of activities, logic, structure, drivers and role of IS.