Taking issue with the classical theory of path dependence, we capture the active agency involved in collective efforts aimed at extending a current technological path and, in parallel, at creating a new path in the field of leading-edge international semiconductor manufacturing. We apply structuration theory in order to analyse the practices of path constitution that traditional evolutionary views of lock-in and irreversibility in path processes have neglected. Drawing on 96 interviews since 2003 and extensive secondary sources in the field of semiconductor manufacturing in Europe, Japan and the United States, we perform a qualitative, longitudinal and multi-level case analysis; in this analysis we trace, in particular, the strategic development of a path-extending technological option besides a potentially path-breaking new generation of lithography for chip manufacturing systems. Our results provide deep insights into the collective and collaborative dimension of organizing R&D in processes of technology development. Thereby, we contribute to a theory of technological paths that considers collective embedded agency and takes into account interorganizational forms for an understanding of the innovation dynamics in science-based industries such as semiconductor manufacturing.

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Injection therapy is safe and highly effective (79.7 %). Women were affected by trigger digits more often than men and at a younger age. Surgical release provides a definitive therapeutic option if corticosteroid injection fails.

BackgroundSoft tissue sarcoma (STS) is an anatomically and histologically heterogeneous neoplasia that shares a putative mesenchymal cell origin. The treatment with common chemotherapeutics is still unsatisfying because of association with poor response rates. Although evidence is accumulating for potent oncolytic activity of host defense peptides (HDPs), their potential therapeutic use is often limited by poor bioavailability and inactivation in serum. Therefore, we tested the designer host defense-like lytic D,L-amino acid peptide [D]-K3H3L9 on two STS cell lines in vitro and also in an athymic and syngeneic mouse model. In recent studies the peptide could show selectivity against prostate carcinoma cells and also an active state in serum.Methods In vitro the human synovial sarcoma cell line SW982, the murine fibrosarcoma cell line BFS-1 and primary human fibroblasts as a control were exposed to [D]-K3H3L9, a 15mer D,L-amino acid designer HDP. Cell vitality in physiological and acidic conditions (MTT-assay), cell growth (BrdU) and DNA-fragmentation (TUNEL) were investigated. Membrane damage at different time points could be analyzed with LDH assay. An antibody against the tested peptide and recordings using scanning electron microscopy could give an inside in the mode of action. In vivo [D]-K3H3L9 was administered intratumorally in an athymic and syngeneic (immunocompetent) mouse model with SW982 and BFS-1 cells, respectively. After three weeks tumor sections were histologically analyzed.ResultsThe peptide exerts rapid and high significant cytotoxicity and antiproliferating activity against the malignant cell lines, apparently via a membrane disrupting mode of action. The local intratumoral administration of [D]-K3H3L9 in the athymic and syngeneic mice models significantly inhibited tumor progression. The histological analyses of the tumor sections revealed a significant antiproliferative, antiangiogenic activity of the treatment group.ConclusionThese findings demonstrate the in vitro and in vivo oncolytic activity of [D]-K3H3L9 in athymic and syngeneic mouse models.