Track-Etched Membranes for Drug Pharmaceutical Research

Over the last decades, the incorporation of membranes into micro physiological systems used for pharmaceutical research and drug development has grown significantly. One example is the use of microporous track-etched membranes in microfluidic systems like organs-on-a-chip and cell culture inserts for tissue engineering. Tissue-culture treated track-etched membranes serve as excellent support for cell growth and efficient nutrient supply, with the added benefit of precise control of pore parameters, a critical pre-requisite to achieve reproducible results. Here, we provide an overview of track-etched membrane technology in the context of applications in drug discovery and development.     

Field-data-based reliability analysis of power converters in wind turbines: Assessing the effect of explanatory variables

Frequent failures of power converters affect the availability of wind turbines and cause considerable maintenance costs. To enhance the reliability of power converters in wind turbines, the prevailing causes and modes of failures have to be identified. This publication contributes to root-cause analysis of the power-converter failures in wind turbines from a statistical point of view. For this purpose, the failure behavior of power-converters is modeled via lifetime models as well as repairable-system models. By means of regression models, covariates are incorporated, including both design-related and site-specific covariates. The analysis is based on a worldwide extensive field-data collection covering more than 9000 turbines, including different turbine designs, sites, and ages. The results obtained by means of the applied regression models indicate that the location of the power converter within the turbine, the cooling system, the converter rated power, the DC-link voltage, the IGBT-module manufacturer, and the commissioning date of the turbine as design-related covariates have a significant effect on the phase-module failure behavior and with that on converter reliability. Among the site-specific covariates, the analysis results confirm humidity as a likely significant driver of failures.     

Amino Acid Residues Controlling Domain Interaction and Interdomain Electron Transfer in Cellobiose Dehydrogenase

The function of cellobiose dehydrogenase (CDH) in biosensors, biofuel cells, and as a physiological redox partner of lytic polysaccharide monooxygenase (LPMO) is based on its role as an electron donor. Before donating electrons to LPMO or electrodes, an interdomain electron transfer from the catalytic FAD-containing dehydrogenase domain to the electron shuttling cytochrome domain of CDH is required. This study investigates the role of two crucial amino acids located at the dehydrogenase domain on domain interaction and interdomain electron transfer by structure-based engineering. The electron transfer kinetics of wild-type Myriococcum thermophilum CDH and its variants M309A, R698S, and M309A/R698S were analyzed by stopped-flow spectrophotometry and structural effects were studied by small-angle X-ray scattering. The data show that R698 is essential to pull the cytochrome domain close to the dehydrogenase domain and orient the heme propionate group towards the FAD, while M309 is an integral part of the electron transfer pathway – its mutation reducing the interdomain electron transfer 10-fold. Structural models and molecular dynamics simulations pinpoint the action of these two residues on the domain interaction and interdomain electron transfer.