Untersuchung des Betriebs- und Netzverhaltens bei Netzeinbindung von Windkraftanlagen, deren Einspeiseleistungen den regionalen Energieabfluss uebersteigen Abschlussbericht

The present research programme comprises the following tasks: Computer simulation of the probable network reactions to the fluctuating wind energy supply; verification of the model descriptions; optimisation by computer simulation of the utilisation of the medium high voltage system's capacity; and generally valid statements on the connection of aerogenerators to the electricity network. (HW)Das Forschungsprogramm umfasst folgende Projektaufgaben: - Rechnersimulation der zu erwartenden Netzrueckwirkungen in Abhaengigkeit vom schwankenden Windenergieangebot - Bestaetigung der Richtigkeit der Modellbeschraenkungen -Optimierung der Kapitalauslastung des Mittelspannungsnetzes durch Rechnersimulation - allgemein gueltige Aussagen zur Netzanbindung von Windenergienalagen. (HW)SIGLEAvailable from TIB Hannover: F96B1204+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Cyclotides suppress human T-Lymphocyte proliferation by an interleukin 2-dependent mechanism

Cyclotides are a diverse and abundant group of ribosomally synthesized plant peptides containing a unique cyclic cystine-knotted topology that confers them with remarkable stability. Kalata B1, a representative member of this family of mini-proteins, has been found to inhibit the proliferation of human peripheral blood mononuclear cells. Analysis of T-cell proliferation upon treatment with chemically synthesized kalata B1 mutants revealed a region comprising inter-cysteine loops 1 and 2 of the cyclotide framework to be important for biological activity. Cytokine signaling analysis using an 'active' kalata B1 mutant [T20K], and the reference drug cyclosporin A (CsA) demonstrated that treatment of activated T-lymphocytes with these compounds decreased the expression of the interleukin-2 (IL-2) surface receptor as well as IL-2 cytokine secretion and IL-2 gene expression, whereas the 'inactive' kalata B1 mutant [V10K] did not cause any effects. The anti-proliferative activity of [T20K] kalata B1 was antagonized by addition of exogenous IL-2. Furthermore, treatment with [T20K] kalata B1 led to an initial reduction of the effector function, as indicated by the reduced IFN-gamma and TNF-alpha production, but the levels of both cytokines stabilized over time and returned to their normal levels. On the other hand, the degranulation activity remained reduced. This indicated that cyclotides interfere with T-cell polyfunctionality and arrest the proliferation of immune-competent cells through inhibiting IL-2 biology at more than one site. The results open new avenues to utilize native and synthetically-optimized cyclotides for applications in immune-related disorders and as immunosuppressant peptides