The Networks of Learning in Technological Innovation : The Emergence of Collaboration Across Fields of Expertise

This study addresses four issues concerning technological product innovations. First, the nature of the very early phases or "embryonic stages" of technological innovation is addressed. Second, this study analyzes why and by what means people initiate innovation processes outside the technological community and the field of expertise of the established industry. In other words, this study addresses the initiation of innovation that occurs without the expertise of established organizations, such as technology firms, professional societies and research institutes operating in the technological field under consideration. Third, the significance of interorganizational learning processes for technological innovation is dealt with. Fourth, this consideration is supplemented by considering how network collaboration and learning change when formalized product development work and the commercialization of innovation advance. These issues are addressed through the empirical analysis of the following three product innovations: Benecol margarine, the Nordic Mobile Telephone system (NMT) and the ProWellness Diabetes Management System (PDMS). This study utilizes the theoretical insights of cultural-historical activity theory on the development of human activities and learning. Activity-theoretical conceptualizations are used in the critical assessment and advancement of the concept of networks of learning. This concept was originally proposed by the research group of organizational scientist Walter Powell. A network of learning refers to the interorganizational collaboration that pools resources, ideas and know-how without market-based or hierarchical relations. The concept of an activity system is used in defining the nodes of the networks of learning. Network collaboration and learning are analyzed with regard to the shared object of development work. According to this study, enduring dilemmas and tensions in activity explain the participants' motives for carrying out actions that lead to novel product concepts in the early phases of technological innovation. These actions comprise the initiation of development work outside the relevant fields of expertise and collaboration and learning across fields of expertise in the absence of market-based or hierarchical relations. These networks of learning are fragile and impermanent. This study suggests that the significance of networks of learning across fields of expertise becomes more and more crucial for innovation activities.

Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) : Identification of novel TNFRSF1A mutations and intracellular signalling defects

The systemic autoinflammatory disorders are a group of rare diseases characterized by periodically recurring episodes of acute inflammation and a rise in serum acute phase proteins, but with no signs of autoimmunity. At present eight hereditary syndromes are categorized as autoinflammatory, although the definition has also occasionally been extended to other inflammatory disorders, such as Crohn s disease. One of the autoinflammatory disorders is the autosomally dominantly inherited tumour necrosis factor receptor-associated periodic syndrome (TRAPS), which is caused by mutations in the gene encoding the tumour necrosis factor type 1 receptor (TNFRSF1A). In patients of Nordic descent, cases of TRAPS and of three other hereditary fevers, hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), chronic infantile neurologic, cutaneous and articular syndrome (CINCA) and familial cold autoinflammatory syndrome (FCAS), have been reported, TRAPS being the most common of the four. Clinical characteristics of TRAPS are recurrent attacks of high spiking fever, associated with inflammation of serosal membranes and joints, myalgia, migratory rash and conjunctivitis or periorbital cellulitis. Systemic AA amyloidosis may occur as a sequel of the systemic inflammation. The aim of this study was to investigate the genetic background of hereditary periodically occurring fever syndromes in Finnish patients, to explore the reliability of determining serum concentrations of soluble TNFRSF1A and metalloproteinase-induced TNFRSF1A shedding as helpful tools in differential diagnostics, as well as to study intracellular NF-κB signalling in an attempt to widen the knowledge of the pathomechanisms underlying TRAPS. Genomic sequencing revealed two novel TNFRSF1A mutations, F112I and C73R, in two Finnish families. F112I was the first TNFRSF1A mutation to be reported in the third extracellular cysteine-rich domain of the gene and C73R was the third novel mutation to be reported in a Finnish family, with only one other TNFRSF1A mutation having been reported in the Nordic countries. We also presented a differential diagnostic problem in a TRAPS patient, emphasizing for the clinician the importance of differential diagnostic vigiliance in dealing with rare hereditary disorders. The underlying genetic disease of the patient both served as a misleading factor, which possibly postponed arrival at the correct diagnosis, but may also have predisposed to the pathologic condition, which led to a critical state of the patient. Using a method of flow cytometric analysis modified for the use on fresh whole blood, we studied intracellular signalling pathways in three Finnish TRAPS families with the F112I, C73R and the previously reported C88Y mutations. Evaluation of TNF-induced phosphorylation of NF-κB and p38, revealed low phosphorylation profiles in nine out of ten TRAPS patients in comparison to healthy control subjects. This study shows that TRAPS is a diagnostic possibility in patients of Nordic descent, with symptoms of periodically recurring fever and inflammation of the serosa and joints. In particular in the case of a family history of febrile episodes, the possibility of TRAPS should be considered, if an etiology of autoimmune or infectious nature is excluded. The discovery of three different mutations in a population as small as the Finnish, reinforces the notion that the extracellular domain of TNFRSF1A is prone to be mutated at the entire stretch of its cysteine-rich domains and not only at a limited number of sites, suggesting the absence of a founder effect in TRAPS. This study also demonstrates the challenges of clinical work in differentiating the symptoms of rare genetic disorders from those of other pathologic conditions and presents the possibility of an autoinflammatory disorder as being the underlying cause of severe clinical complications. Furthermore, functional studies of fresh blood leukocytes show that TRAPS is often associated with a low NF-κB and p38 phosphorylation profile, although low phosphorylation levels are not a requirement for the development of TRAPS. The aberrant signalling would suggest that the hyperinflammatory phenotype of TRAPS is the result of compensatory NF-κB-mediated regulatory mechanisms triggered by a deficiency of the innate immune response.