Immunohistochemical Evidence from APP-Transgenic Mice for Glutaminyl Cyclase as Drug Target to Diminish pE-Abeta Formation

Oligomeric assemblies of neurotoxic amyloid beta (Abeta) peptides generated by proteolytical processing of the amyloid precursor protein (APP) play a key role in the pathogenesis of Alzheimer's disease (AD). In recent years, a substantial heterogeneity of Abeta peptides with distinct biophysical and cell biological properties has been demonstrated. Among these, a particularly neurotoxic and disease-specific Abeta variant is N-terminally truncated and modified to pyroglutamate (pE-Abeta). Cell biological and animal experimental studies imply the catalysis of this modification by the enzyme glutaminyl cyclase (QC). However, direct histopathological evidence in transgenic animals from comparative brain region and cell type-specific expression of transgenic hAPP and QC, on the one hand, and on the formation of pE-Abeta aggregates, on the other, is lacking. Here, using single light microscopic, as well as triple immunofluorescent, labeling, we report the deposition of pE-Abeta only in the brain regions of APP-transgenic Tg2576 mice with detectable human APP and endogenous QC expression, such as the hippocampus, piriform cortex, and amygdala. Brain regions showing human APP expression without the concomitant presence of QC (the anterodorsal thalamic nucleus and perifornical nucleus) do not display pE-Abeta plaque formation. However, we also identified brain regions with substantial expression of human APP and QC in the absence of pE-Abeta deposition (the Edinger-Westphal nucleus and locus coeruleus). In these brain regions, the enzymes required to generate N-truncated Abeta peptides as substrates for QC might be lacking. Our observations provide additional evidence for an involvement of QC in AD pathogenesis via QC-catalyzed pE-Abeta formation

Externally commercializing technology assets: An examination of different process stages

Besides applying technological knowledge in products and services, firms may externally leverage their technology assets, e.g., by means of technology licensing. Despite its increasing managerial and theoretical importance, outward technology transfer has been relatively neglected in prior research. We use data from 152 industrial companies to analyze how different levels of proficiency in managing different stages of the external technology exploitation process influence a firm's out-licensing performance. With the trend towards open innovation strategies, this research represents an important complement to the large number of success factor studies into new product development.

The role of corporate technology strategy and patent portfolios in low-, medium- and high-technology firms

Previous research into technology strategies and patent portfolios has focused on high-technology firms, whereas low- and medium-technology companies have been relatively neglected. Therefore, we analyze how corporate technology strategy and the size and composition of patent portfolios affect the performance of low-, medium- and high-technology firms. Data from 136 European companies are used to examine four hypotheses relating financial performance to technological diversification, technological aggressiveness, patent portfolio size, and patent portfolio quality. The cross-industry sample allows analyzing the different consequences of these strategic parameters in low-, medium- and high-technology firms by considering technological intensity as a moderator. Our first finding is that the positive impact of technological aggressiveness is limited in low- and medium-technology companies. Secondly, technological diversification has a positive effect in high-technology firms and a negative effect in low-technology firms. Thirdly, patent portfolio size has a positive effect only in high-technology firms. Finally, patent portfolio quality has an equally positive influence on all firms' performance. In part, these results conflict with the findings of previous research into high-technology companies, and they call for rethinking the role of technology strategies and intellectual property portfolios in firms across industries.Low- and medium-technology firms High-technology firms Technology strategy Technological diversification Intellectual property management

Outward knowledge transfer: the impact of project-based organization on performance

Recently, interfirm knowledge transactions have increased although many firms experience major managerial difficulties in outward knowledge transfer, e.g. technology licensing. To reduce the traditional underemphasis on empirical research into corporate outward knowledge transfer, we use data from 152 firms to test four hypotheses relating firms' outward knowledge transfer performance to two types of project-based organization, which complement formal and informal organizational structures: projects that are directed at identifying knowledge transfer opportunities and projects that are directed at implementing outward knowledge transfer. The results underscore the benefits from both types of projects, and their positive interaction further contributes to explaining the discrepancies between some successful firms in managing outward knowledge transfer and many others. Copyright 2010 The Author 2010. Published by Oxford University Press on behalf of Associazione ICC. All rights reserved., Oxford University Press.

Corporate technology out-licensing: Motives and scope

Recently, technology licensing has become a broader trend in many industrial companies. As this increase has not been sufficiently reflected by research, we lack a detailed understanding of the motives for corporate technology out-licensing. Moreover, the insights into the current scope of corporate out-licensing activities are strongly limited. Therefore, this paper presents the results of a questionnaire-based study into the patent and non-patent technology out-licensing activities of 154 European firms across industries. Thus, the present study provides large-scale empirical evidence for the current scope of corporate out-licensing activities. In addition, it deepens our understanding of corporate out-licensing strategies by examining in detail the motives of firms for licensing out technology. After an introduction to the topic, the design of the empirical study is described. Then, the results of the survey are presented, and implications for theory and practice are discussed.Technology licensing Out-licensing External technology commercialization Patent licensing Questionnaire results

Organizing for external technology exploitation in diversified firms

Besides applying technology in their own products, industrial firms increasingly exploit their technologies externally, for example through out-licensing. Earlier studies cannot explain the discrepancies between a few pioneering firms in active technology licensing and the managerial difficulties of many others. In diversified firms, diverging interests of the corporate and business unit level in the keep-or-sell decision constitute a central barrier to active licensing. Therefore, this article examines two essential dimensions of designing the corporate/business unit interface in diversified firms: the centralization of the activities on the corporate level and the alignment between the organizational levels. The study tests three hypotheses regarding the interaction and consequences of these organizational dimensions with data from 152 firms. Consistent with the hypotheses, the data provide support for the benefits from medium levels of corporate centralization and corporate/business unit alignment. The results have implications for technology exploitation, open innovation, markets for technology, and corporate strategy.Technology exploitation Technology licensing Markets for technology Diversified firms