The Critical Turning Points Database : Concept, Methodology and Dataset of an International Transformative Social Innovation Comparison (TRANSIT Working Paper # 10, July 12th 2017)

[Abstract] This working paper presents the TRANSIT open-access online database on Critical Turning Points (CTP) in Transformative Social Innovation. It specifies the contents of the database, comprising qualitative accounts of more than 450 ‘critical’ episodes in the evolution of social innovation initiatives in 27 different countries. Providing the theoretical-methodological context to these data, the paper also describes the theoretical background of the CTP concept and the methodology though which the CTP accounts have been reconstructed through interviews with members of SI initiatives. The paper concludes with reflections on the open access CTP database as a knowledge infrastructure, discussing its significance in terms of mapping, dissemination and framing of social innovation.This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 61316

C4b-binding protein protects coagulation factor Va from inactivation by activated protein C

We investigated the effect of C4BP on APC-mediated inactivation of factor Va (FVa) in the absence and presence of protein S. FVa inactivation was biphasic (k(506) = 4.4 x 10(8) M-1 s(-1), k(306) = 2.7 x 10(7) M-1 s(-1)), and protein S accelerated Arg(306) cleavage approximately 10-fold. Preincubation of protein S with C4BP resulted in a total abrogation of protein S cofactor activity. C4BP also protected FVa from inactivation by APC in the absence of protein S. Control experiments with CLB-PS13, a monoclonal anti-protein S antibody, indicated that inhibition of FVa inactivation by C4BP was not mediated through contaminating traces of protein S in our reaction systems. Protection of FVa was prevented by a monoclonal antibody directed against the C4BP alpha -chain. Recombinant rC4BP alpha comprised of only alpha -chains also protected FVa, but in the presence of protein S, the level of protection was decreased, since rC4BP alpha lacks the beta -chain responsible for C4BP binding to protein S. A truncated C4BP beta -chain (SCR-1+2) inhibited protein S cofactor activity, but had no effect on FVa inactivation by APC in the absence of protein S. In conclusion, C4BP protects FVa from APC-catalyzed cleavage in a protein S-independent way through direct interactions of the alpha -chaims of C4BP with FVa and/or APC