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During the development process of a complex technical product, one widely used and important technique is accelerated testing where the applied stress on a component is chosen to exceed the reference stress, i.e. the stress encountered in field operation, in order to reduce the time to failure. For that, the reference stress has to be known. Since a complex technical product may fail regarding numerous failure modes, stress in general is highly dimensional rather than scalar. In addition, customers use their products individually, i.e. field operation should be described by a distribution rather than by one scalar stress value. In this paper, a way to span the customer usage space is shown. It allows the identification of worst case reference stress profiles in significantly reduced dimensions with minimal loss of information. The application example shows that even for a complex product like a combustion engine, stress information can be compressed significantly. With low measurement effort it turned out that only three reference stress cycles were sufficient to cover a broad range of customer stress variety.
Bioconjugates containing the GnRH-III hormone decapeptide as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing GnRH receptors, thereby increasing their local efficacy while limiting the peripheral toxicity. However, the number of GnRH receptors on cancer cells is limited and they desensitize under continuous hormone treatment. A possible approach to increase the receptor mediated tumor targeting and consequently the cytostatic effect of the bioconjugates would be the attachment of more than one chemotherapeutic agent to one GnRH-III molecule. Here we report on the design, synthesis and biochemical characterization of multifunctional bioconjugates containing GnRH-III as a targeting moiety and daunorubicin as a chemotherapeutic agent. Two different drug design approaches were pursued. The first one was based on the bifunctional [4Lys]-GnRH-III (Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH2) containing two lysine residues in positions 4 and 8, whose ϵ-amino groups were used for the coupling of daunorubicin. In the second drug design, the native GnRH-III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was used as a scaffold; an additional lysine residue was coupled to the ϵ-amino group of 8Lys in order to generate two free amino groups available for conjugation of daunorubicin. The in vitro stability/degradation of all synthesized compounds was investigated in human serum, as well as in the presence of rat liver lysosomal homogenate. Their cellular uptake was determined on human breast cancer cells and the cytostatic effect was evaluated on human breast, colon and prostate cancer cell lines. Compared with a monofunctional compound, both drug design approaches resulted in multifunctional bioconjugates with increased cytostatic effect.
Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7
(2011)
Suburethral slings as well as different meshes are widely used treating stress urinary incontinence and prolaps in women. With the development of MiniSlings and special meshes using less alloplastic material anchorage systems become more important to keep devices in place and to put some tension especially on the MiniSlings. To date, there are many different systems of MiniSlings of different companies on the market which differ in the structure of the used meshes and anchors. A new objective measurement method to compare different properties of MiniSling systems (mesh and anchor) is presented in this article. Ballistic gelatine acts as soft tissue surrogate. Significant differences in parameters like pull-out strength of anchors or shrinkage of meshes under loading conditions have been determined. The form and size of the anchors as well as the structural stability of the meshes are decisive for a proper integration. The tested anchorings sytems showed markedly different mechanical function at their respective load bearing capacity. As the stable fixation of the device in tissue is a prerequisite for a permanet reinforcement, the proposed test system permits further optimisation of anchor and mesh devices to improve the success of the surgical treatment
A novel scheme for precise diagnostics and effective stabilization of currents in a fuel cell stack
(2010)
A novel scheme for detecting inhomogeneous internal currents in a fuel cell stack is presented. In this paper the scheme is investigated for the case that the flow field plates consist of graphite. Then plates of high conductivity, e.g. aluminium between the flow field plates together with small slits in these plates have three effects: (a) Whenever a local inhomogeneity of the electric current occurs at a particular cell in the stack, this will induce a surface current close to that cell perpendicular to the averaged current. This current can be detected. (b) The plates of high conductivity completely prevent the inhomogeneities from spreading to neighbouring cells. (c) Even at the particular cell the inhomogeneity is suppressed as far as possible. Thus this scheme leads to much better diagnostic possibilities and at the same time reduces electric instabilities to an extent, where they probably become harmless. This scheme will first be explained for a simple model to clarify the idea. However, very precise three dimensional computations using realistic parameters are presented, corroborating the results of the simple model.
A novel tomographic scheme for analysing the state of any single membrane electrode assembly (MEA) in a stack is suggested. Plates of very high conductivity placed between every fuel cell and slitted in an appropriate manner cause surface currents at well-defined locations of the stack. We show that knowing these surface currents, information about anomalies of the currents in a MEA can be obtained using the methods of tomography. The results are mathematically not unique. However, when assuming plausible defect structures, one can exclude improbable deficiencies by applying a special form of simulated annealing. We present numerical calculations of typical examples demonstrating that the essential defects of the MEA in any single cell of the stack can be detected and their extent can be determined.