Multimerization of Peptide Mimotopes for Blocking of Factor VIII Neutralizing Antibodies

About 30 % of patients with severe hemophilia A develop neutralizing antibodies (inhibitors) to coagulation factor VIII (FVIII) upon treatment with exogenous factor preparations. Two peptides, C6 (NPVENMMDRDSQ) and H10 (QSPWQTWFTRAL), that mimic putative inhibitor epitopes (mimotopes), were previously selected by phage display screening of plasma samples from patients with inhibitors. Synthetic peptide mimotopes inhibited IgG binding to FVIII (IC₅₀: 30–50 μM ). This effect was increased by an equimolar combination of both mimotopes. Mimotopes were fused to the C‐terminal multimerization domain of the C4bp α‐chain and expressed as multimers in 293T cells. Multimerized mimotopes showed improved binding to anti‐FVIII IgG and prolonged in vitro half‐life relative to synthetic peptides. The two mimotopes were combined in heteromultimers by co‐transfection of 293T cells with respective vectors, resulting in bi‐specific molecules that almost completely blocked polyclonal antibody binding to FVIII (IC₅₀: 2–3 μM ). This strategy is capable of functionally improving synthetic peptides by multimerization and could provide a basis for novel therapeutic approaches for patients with hemophilia A and inhibitors.     

Contributions to non-identifier based adaptive control in mechatronics

Funnel-Control (FC)–an adaptive (time-varying) MIMO/SISO control strategy–is re-introduced and its applicability introductory for position control of nonlinear, coupled (rigid) robotic systems and for speed control of nonlinear two-mass flexible servo systems is shown. Additionally Error Reference Control (ERC)–a direct derivative of FC–is established. ERC is specially designed with asymmetric boundaries and auxiliary reference, ensuring that the control error evolves within a prespecified tube (a shrinked funnel region, achieving even better tracking performance).FC and hence ERC are based on the high-gain stabilizability of minimum-phase systems with relative degree one and known sign of the high-frequency gain. Although the plant only needs to be known in structure, both concepts assure prescribed transient behavior without identification and/or parameter estimation.As most industrial applications, also the considered robotic and two-mass flexible servo systems, exhibit relative degrees greater than one, FC and ERC cannot directly be applied. Therefore a special state feedback is introduced, reducing the relative degree and retaining the minimum-phase property. The additional implementation of a nominal PI-like extension guarantees good disturbance rejection and asymptotic tracking of (constant) velocity and position reference trajectories.Simulation results for a 6-DOF Manutec r3 robot underpin and compare the achievable position control performance of one overall MIMO Funnel Controller for all joints and one SISO Funnel Controller for each joint (6 controllers). For nonlinear two-mass flexible servo systems, measurement results demonstrate the achievable load speed control performance of FC and ERC in comparison to optimal LQ state feedback.     

Aufzeichnung und Übertragung von Lehrveranstaltungen

Immer mehr Hochschulen gehen dazu über, Lehrveranstaltungen aufzuzeichnen und den Studierenden oder der ?ffentlichkeit zeitgleich oder zeitversetzt zug?nglich zu machen. Der Beitrag untersucht am Beispiel der Rechtslage in Hessen die damit verbundenen Eingriffe in Grundrechte der Hochschullehrenden und Studierenden, deren Rechtfertigung durch die Aufgaben der Hochschulen, die Verpflichtungen der Hochschullehrenden, die datenschutz- und urheberrechtliche Bewertung sowie die M?glichkeiten, diese Fragen durch hochschuleigenes Recht zu regeln.     

Swelling rock behaviour in a tunnel: NATM-support vs. Q-support – A comparison

The Q-system is one of the most applied classification tool in modern tunnelling. After an exact evaluation of the parameters the rock support can be determined via the “Q-support chart”. In an already finished tunnel, mainly driven through limestone, the Q-system was tested under difficult geological conditions (shale–marl). Scope of the appraisal was a comparison of the support suggested by the “Q-support chart” with the real performed support after the NATM, regarding partly massive damages. This article is a contribution referring to the last publication on the topic “fitness of various engineering design tools” from [Palmstrom, A., Stille, H., 2007. Ground behaviour and rock engineering tools for underground excavations. Tunnelling and Underground Space Technology 22, 363–376].     

Imaging of Polarons in Ferromagnetic Bilayered Manganites by Scanning Tunnelling Microscopy

We report scanning tunnelling microscopy images of polaronic charge ordered patch on the layered ferromagnet La_2−2x Sr_1+2x Mn₂O₇, x=0.32. The spectroscopic investigation shows that the material is gapped above and below the critical temperature, where the gap changes from 500 to 800 mV, giving evidence for polaronic transport behaviour. This work has been supported by European Project No. 517039 CoMePhS (Controlling Mesoscopic Phase Separation).     

Vibrations of Layered Beams under Conditions of Damaging and Slipping Interfaces

A nonlinear laminate layerwise beam theory is developed to simulate the effect of inelastic interlayer slip on the stiffness degradation of layered beam structures. Layerwise continuous and linear in-plane displacement fields are implemented. It is shown that by definition of an effective cross-sectional rotation the complex problem reduces to the simpler case of a homogenized shear-deformable beam with effective stiffness and a corresponding set of boundary conditions. Inelastic defects of the interlayer material are equivalent to eigenstrains in an identical but unlimited elastic background structure of the homogenized beam with proper effective virgin stiffness. Cross-sectional resultants of these eigenstrains are defined. Since the incremental response of the background to the given load and to the properly imposed eigenstrain increments is considered to be linear within a given time step, effective solution methods of the linear theory of flexural vibrations become applicable. This revised version was published online in July 2006 with corrections to the Cover Date.     

eIDs und Identitätsmanagement

Zusammenfassung  Mit der Einführung des elektronischen Personalausweises steht in Deutschland eine eID-L?sung mit potentiell sehr weiter Verbreitung vor der Tür. Der Beitrag diskutiert, wie solche L?sungen im Identit?tsmanagement eingesetzt und wie sie in Zukunft verbessert werden k?nnen. Dr. Christoph Sorge Research Scientist, NEC Laboratories Europe, Heidelberg. T?tigkeitsschwerpunkt: Forschung im Bereich der Netzsicherheit, u.a. Identit?tsmanagement Dr. Dirk Westhoff Chief Researcher, NEC Laboratories Europe, Heidelberg. T?tigkeitsschwerpunkt: Forschung in den Bereichen mobile drahtlose Sicherheit, Identit?tsmanagement