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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.
Für die Ermittlung der erforderlichen Einspanntiefe von eingespannten Stahlquerschnitten in Betonkonstruktionen existieren verschiedene Bemessungsmodelle. Diese basieren vorwiegend auf Grundlage nationaler Normen wie z. B. DIN 18800 [1] und DIN 1045 [2], die durch die europäische Normung ersetzt wurden. Aus diesem Grund wird in diesem Aufsatz ein Berechnungsmodell für die erforderliche Einspanntiefe von eingespannten Stahlquerschnitten in Betonkonstruktionen auf Grundlage des Eurocodes vorgestellt. Das Grundgerüst für dieses Berechnungsmodell bildet das Verfahren nach Kindmann und Laumann, welches in [3] behandelt wurde. Gleichzeitig werden neue Formeln zur direkten Ermittlung der Mindesteinspanntiefe vorgestellt. Behandelt werden gewalzte I-Profile für einachsige Biegung um die starke Achse (y-y) mit Drucknormalkraft.
Purpose:
MRI plays a leading diagnostic role in assessing the musculoskeletal (MSK) system and is well established for most questions at clinically used field strengths (up to 3 T). However, there are still limitations in imaging early stages of cartilage degeneration, very fine tendons and ligaments, or in locating nerve lesions, for example. 7 T MRI of the knee has already received increasing attention in the current published literature, but there is a strong need to develop new radiofrequency (RF) coils to assess more regions of the MSK system. In this work, an eight-channel transmit/receive RF array was built as a multipurpose coil for imaging some of the thus far neglected regions. An extensive coil characterization protocol and first in vivo results of the human wrist, shoulder, elbow, knee, and ankle imaged at 7 T will be presented.
Methods:
Eight surface loop coils with a dimension ofurn:x-wiley:00942405:media:mp7176:mp7176-math-0001 were machined from FR4 circuit board material. To facilitate easy positioning, two coil clusters, each with four loop elements, were combined to one RF transmit/receive array. An overlapped and shifted arrangement of the coil elements was chosen to reduce the mutual inductance between neighboring coils. A phantom made of body-simulating liquid was used for tuning and matching on the bench. Afterward, the S-parameters were verified on a human wrist, elbow, and shoulder. For safety validation, a detailed compliance test was performed including full wave simulations of the RF field distribution and the corresponding specific absorption rate (SAR) for all joints. In vivo images of four volunteers were assessed with gradient echo and spin echo sequences modified to obtain optimal image contrast, full anatomic coverage, and the highest spatial resolution within a reasonable acquisition time. The performance of the RF coil was additionally evaluated by in vivo B1 mapping.
Results:
A comparison of B1 per unit power, flip angle distribution, and anatomic images showed a fairly homogeneous excitation for the smaller joints (elbow, wrist, and ankle), while for the larger joints, the shoulder and especially the knee, B1 inhomogeneities and limited penetration depth were more pronounced. However, the greater part of the shoulder joint could be imaged.In vivo images rendered very fine anatomic details such as fascicles of the median nerve and the branching of the nerve bundles. High-resolution images of cartilage, labrum, and tendons could be acquired. Additionally, turbo spin echo (TSE) and inversion recovery sequences performed very well.
Conclusions:
This study demonstrates that the concept of two four-channel transmit/receive RF arrays can be used as a multipurpose coil for high-resolutionin vivo MR imaging of the musculoskeletal system at 7 T. Not only gradient echo but also typical clinical and SAR-intensive sequences such as STIR and TSE performed well. Imaging of small structures and peripheral nerves could in particular benefit from this technique.
A wireless sensor system based on the industrial ZigBee standard for low-rate wireless networking was developed that enables real-time monitoring of gaseous H2O2 during the package sterilization in aseptic food processes. The sensor system consists of a remote unit connected to a calorimetric gas sensor, which was already established in former works, and an external base unit connected to a laptop computer. The remote unit was built up by an XBee radio frequency (RF) module for data communication and a programmable system-on-chip controller to read out the sensor signal and process the sensor data, whereas the base unit is a second XBee RF module. For the rapid H2O2 detection on various locations inside the package that has to be sterilized, a novel read-out strategy of the calorimetric gas sensor was established, wherein the sensor response is measured within the short sterilization time and correlated with the present H2O2 concentration. In an exemplary measurement application in an aseptic filling machinery, the suitability of the new, wireless sensor system was demonstrated, wherein the influence of the gas velocity on the H2O2 distribution inside a package was determined and verified with microbiological tests.
Simulating the electromagnetic‐thermal treatment of thin aluminium layers for adhesion improvement
(2015)
A composite layer material used in packaging industry is made from joining layers of different materials using an adhesive. An important processing step in the production of aluminium-containing composites is the surface treatment and consequent coating of adhesive material on the aluminium surface. To increase adhesion strength between aluminium layer and the adhesive material, the foil is heat treated. For efficient heating, induction heating was considered as state-of-the-art treatment process. Due to the complexity of the heating process and the unpredictable nature of the heating source, the control of the process is not yet optimised. In this work, a finite element analysis of the process was established and various process parameters were studied. The process was simplified and modelled in 3D. The numerical model contains an air domain, an aluminium layer and a copper coil fitted with a magnetic field concentrating material. The effect of changing the speed of the aluminium foil (or rolling speed) was studied with the change of the coil current. Statistical analysis was used for generating a general control equation of coil current with changing rolling speed.
Use of textile structures for reinforcement of pelvic floor structures has to consider mechanical forces to the implant, which are quite different to the tension free conditions of the abdominal wall. Thus, biomechanical analysis of textile devices has to include the impact of strain on stretchability and effective porosity. Prolift® and Prolift + M®, developed for tension free conditions, were tested by measuring stretchability and effective porosity applying mechanical strain. For comparison, we used Dynamesh-PR4®, which was designed for pelvic floor repair to withstand mechanical strain. Prolift® at rest showed moderate porosity with little stretchability but complete loss of effective porosity at strain of 4.9 N/cm. Prolift + M® revealed an increased porosity at rest, but at strain showed high stretchability, with subsequent loss of effective porosity at strain of 2.5 N/cm. Dynamesh PR4® preserved its high porosity even under strain, but as consequence of limited stretchability. Though in tension free conditions Prolift® and Prolift + M® can be considered as large pore class I meshes, application of mechanical strain rapidly lead to collapse of pores. The loss of porosity at mechanical stress can be prevented by constructions with high structural stability. Assessment of porosity under strain was found helpful to define requirements for pelvic floor devices. Clinical studies have to prove whether devices with high porosity as well as high structural stability can improve the patients' outcome.
Unravelling the factors determining the allocation of carbon to various plant organs is one of the great challenges of modern plant biology. Studying allocation under close to natural conditions requires non-invasive methods, which are now becoming available for measuring plants on a par with those developed for humans. By combining magnetic resonance imaging (MRI) and positron emission tomography (PET), we investigated three contrasting root/shoot systems growing in sand or soil, with respect to their structures, transport routes and the translocation dynamics of recently fixed photoassimilates labelled with the short-lived radioactive carbon isotope 11C. Storage organs of sugar beet (Beta vulgaris) and radish plants (Raphanus sativus) were assessed using MRI, providing images of the internal structures of the organs with high spatial resolution, and while species-specific transport sectoralities, properties of assimilate allocation and unloading characteristics were measured using PET. Growth and carbon allocation within complex root systems were monitored in maize plants (Zea mays), and the results may be used to identify factors affecting root growth in natural substrates or in competition with roots of other plants. MRI–PET co-registration opens the door for non-invasive analysis of plant structures and transport processes that may change in response to genomic, developmental or environmental challenges. It is our aim to make the methods applicable for quantitative analyses of plant traits in phenotyping as well as in understanding the dynamics of key processes that are essential to plant performance.