Synthesis, Kinetic Evaluation and Utilization of a Biotinylated Dipeptide Proline Diphenyl Phosphonate for the Disclosure of Dipeptidyl Peptidase IV-like Serine Proteases

In this study, we report on the synthesis, kinetic characterisation, and application of a novel biotinylated and active site-directed inactivator of dipeptidyl peptidase IV (DPP-IV). Thus, the dipeptide-derived proline diphenyl phosphonate NH(2)-Glu(biotinyl-PEG)-Pro(P)(OPh)(2) has been prepared by a combination of classical solution- and solid-phase methodologies and has been shown to be an irreversible inhibitor of porcine DPP-IV, exhibiting an over all second-order rate constant (k(i)/K(i)) for inhibition of 1.57 x 10(3) M(-1) min(-1). This value compares favourably with previously reported rates of inactivation of DPP-IV by dipeptides containing a P(1) proline diphenyl phosphonate grouping [B. Boduszek, J. Oleksyszyn, C.M. Kam, J. Selzler, R.E. Smith, J.C. Powers, Dipeptide phophonates as inhibitors of dipeptidyl peptidase IV, J. Med. Chem. 37 (1994) 3969-3976; B.F. Gilmore, J.F. Lynas, C.J. Scott, C. McGoohan, L. Martin, B. Walker, Dipeptide proline diphenyl phosphonates are potent, irreversible inhibitors of seprase (FAPalpha), Biochem, Biophys. Res. Commun. 346 (2006) 436-446.], thus demonstrating that the incorporation of the side-chain modified (N-biotinyl-3-(2-(2-(3-aminopropyloxy)-ethoxy)-ethoxy)-propyl) glutamic acid residue at the P(2) position is compatible with inhibitor efficacy. The utilisation of this probe for the detection of both purified dipeptidyl peptidase IV and the disclosure of a dipeptidyl peptidase IV-like activity from a clinical isolate of Porphyromonas gingivalis, using established electrophoretic and Western blotting techniques previously developed by our group, is also demonstrated.

Second-Order Training of Adaptive Critics for Online Process Control

A new algorithm for training of nonlinear optimal neuro-controllers (in the form of the model-free, action-dependent, adaptive critic paradigm). Overcomes problems with existing stochastic backpropagation training: need for data storage, parameter shadowing and poor convergence, offering significant benefits for online applications.

Citizenship training in school from the perspective of future primary education teachers

The aim of this paper is to recognize the images that prospective elementary school teachers have about citizenship and citizenship education in school. The qualitative methodology with an ethnographic approach is used for that deep interview of ethnographic kind and analysis of institutional documents, for example, curricula, course syllabus and graduated profi le. The revision of documents helps to a better understanding of discourses. The analysis of the corpus obtained after the application of the paradigm of codifi cation proposed in the established theory. As the principal fi ndings we way point out that the concept of citizens that is common among prospective elementary school teachers is reduced to the school environment because they consider that the promotion of citizenship helps to the incorporation of children to society, thus reproducing a propaedeutic view of education.