DuD Recht

DuD Recht

DuD Recht     

Tracing pathway activities with kinase inhibitors and reverse phase protein arrays

Controlling aberrant protein kinase activity is a promising strategy for a variety of diseases, particularly cancer. Hence, the development of kinase inhibitors is currently a focal point for pharmaceutical research. In this study we utilize a chip-based reverse phase protein array (RPA) platform for profiling of kinase inhibitors in cell-based assays. In combination with the planar wave-guide technology the assay system has an absolute LOD down to the low zeptomole range. A431 cell lysates were analyzed for the activation state of key effectors in the epidermal growth factor (EGF) and insulin signaling pathways to validate this model for compound screening. A microtiter-plate format for growing, treating, and lysing cells was shown to be suitable for this approach, establishing the value of the technology as a screening tool for characterization of large numbers of kinase inhibitors against a wide variety of cellular signaling pathways. Moreover, the reverse array format allows rapid development of site-specific phosphorylation assays, since in contrast to ELISA type systems only a single antigen-specific antibody is required.     

State of the Art of Molecular Visualization in Immersive Virtual Environments

Visualization plays a crucial role in molecular and structural biology. It has been successfully applied to a variety of tasks, including structural analysis and interactive drug design. While some of the challenges in this area can be overcome with more advanced visualization and interaction techniques, others are challenging primarily due to the limitations of the hardware devices used to interact with the visualized content. Consequently, visualization researchers are increasingly trying to take advantage of new technologies to facilitate the work of domain scientists. Some typical problems associated with classic 2D interfaces, such as regular desktop computers, are a lack of natural spatial understanding and interaction, and a limited field of view. These problems could be solved by immersive virtual environments and corresponding hardware, such as virtual reality head-mounted displays. Thus, researchers are investigating the potential of immersive virtual environments in the field of molecular visualization. There is already a body of work ranging from educational approaches to protein visualization to applications for collaborative drug design. This review focuses on molecular visualization in immersive virtual environments as a whole, aiming to cover this area comprehensively. We divide the existing papers into different groups based on their application areas, and types of tasks performed. Furthermore, we also include a list of available software tools. We conclude the report with a discussion of potential future research on molecular visualization in immersive environments.     

Bending impact on the performance of a flexible Li4Ti5O12-based all-solid-state thin-film battery

The growing demand of flexible electronic devices is increasing the requirements of their power sources. The effect of bending in thin-film batteries is still not well understood. Here, we successfully developed a high active area flexible all-solid-state battery as a model system that consists of thin-film layers of Li₄Ti₅O₁₂, LiPON, and Lithium deposited on a novel flexible ceramic substrate. A systematic study on the bending state and performance of the battery is presented. The battery withstands bending radii of at least 14 mm achieving 70% of the theoretical capacity. Here, we reveal that convex bending has a positive effect on battery capacity showing an average increase of 5.5%, whereas concave bending decreases the capacity by 4% in contrast with recent studies. We show that the change in capacity upon bending may well be associated to the Li-ion diffusion kinetic change through the electrode when different external forces are applied. Finally, an encapsulation scheme is presented allowing sufficient bending of the device and operation for at least 500 cycles in air. The results are meant to improve the understanding of the phenomena present in thin-film batteries while undergoing bending rather than showing improvements in battery performance and lifetime.     

Modification of Iron with Degradable Silver Phases Processed via Laser Beam Melting for Implants with Adapted Degradation Rate

In medical technology, implants are used to improve the quality of patients’ lives. The development of materials with adapted properties can further increase the benefit of implants. If implants are only needed temporarily, biodegradable materials are beneficial. In this context, iron-based materials are promising due to their biocompatibility and mechanical properties, but the degradation rate needs to be accelerated. Apart from alloying, the creation of noble phases to cause anodic dissolution of the iron-based matrix is promising. Due to its high electrochemical potential, immiscibility with iron, biocompatibility, and antibacterial properties, silver is suited for the creation of such phases. A suitable technology for processing immiscible material combinations is powder-bed-based procedure like laser beam melting. This procedure offers short exposure times to high temperatures and therefore a limited time for diffusion of alloying elements. As the silver phases remain after the dissolution of the iron matrix, a modification is needed to ensure their degradability. Following this strategy, pure iron with 5 wt% of a degradable silver–calcium–lanthanum alloy is processed via laser beam melting. Investigation of the microstructure yields achievement of the intended microstructure and long-term degradation tests indicates an impact on the degradation, but no increased degradation rate.     

Using Selective Electron Beam Melting to Enhance the High-Temperature Strength and Creep Resistance of NiAl–28Cr–6Mo In Situ Composites

By increasing the density of interfaces in NiAl–CrMo in situ composites, the mechanical properties can be significantly improved compared to conventionally cast material. The refined microstructure is achieved by manufacturing through electron beam powder bed fusion (PBF-EB). By varying the process parameters, an equiaxed or columnar cell morphology can be obtained, exhibiting a plate-like or an interconnected network of the (Cr,Mo) reinforcement phase which is embedded in a NiAl matrix. The microstructure of the different cell morphologies is investigated in detail using scanning electron microscope, transmission electron microscopy, and atom probe tomography. For both morphologies, the mechanical properties at elevated temperatures are analyzed by compression and creep experiments parallel and perpendicular to the building direction. In comparison to cast NiAl and NiAl–(Cr, Mo), the yield strength of the PBF-EB fabricated specimens is significantly improved at temperatures up to 1,027 °C. While the columnar morphology exhibits the best improved mechanical properties at high temperatures, the equiaxial morphology shows nearly ideal isotropic mechanical behavior, which is a substantial advantage over directionally solidified material.     

Combining make to order and make to stock

In inventory control and production planning one is tempted to use one of two strategies: produce all demand to stock or produce all demand to order. The disadvantages are well-known. In the make everything to order case (MTO) the response times may become quite long if the load is high, in the make everything to stock case (MTS) one gets an enormous inventory if the number of different products is large.In this paper we study two simple models which combine MTO and MTS, and investigate the effect of combining MTO and MTS on the production lead times.     

Design rules for an integratable low-power amplifier/filter combination

In this paper design rules for a circuit topology in which there is an inseparable combination of an amplifier and a filter characteristic, are presented. By intentionally using the capacitance of an already present input sensor for the filtering, the total required integrated capacitance is much less than that in circuits, which have a separately designed amplifier and filter function. Consequently, it is possible to have the advantage of a better integratability. Moreover, less complexity in the design is achieved. The presented circuit shows a current-to-voltage conversion and an inherently controllable second-order low-pass filter characteristic. A discrete realization has been designed to test the circuit. This circuit operates down to a 1 V supply voltage and the transfer shows a 1.8 M currentto-voltage conversion with a bandwidth of 6 kHz. Measurement results of this circuit show that a 63 dB dynamic range can be achieved with a total required integrated capacitance of only 31 pF.