Monoclonal antibodies (MoAbs) were made to a known insulin sensitivity enhancer (ISE) compound, CS-045. The MoAbs were characterized with respect to binding other known thiazolidinedione ISE ...compounds using a CS-045 labeled with b-phycoerythrin in a competitive particle concentration fluorescence immunoassay (PCFIA). By comparing the rank order of IC
50 values for each compound to its respective potency as an ISE, one MoAb (13E3) was selected for further characterization. This MoAb was also used as a surrogate receptor in a high throughput screen to identify novel compounds that compete for binding to CS-045. Some of the hits were found to have efficacy in reducing blood glucose. Subsequently, another group reported that several compounds with the core thiazolidinedione structure of the ISE compounds bound with high affinity to peroxisome proliferator-activating receptors (PPAR). Therefore, we used the MoAb assay to test these and other compounds that are known to bind to PPARy and noted crossreactivity with some of the compounds.
The integration of photovoltaic (PV) generators in the gird is still an ongoing topic. The peak efficiency of today's power electronics is already above 98%, therefore innovative aspects can grow ...from new ways of grid integration. This paper focuses on the combination of a 5 kW PV-generator with a li-ion battery. The temporal decoupling of the generation and injection of energy into the European low voltage grid is presented. Compared to a classic PV system, an additional bidirectional DC/DC-converter is required to ensure the charge and discharge of the battery. The power management of the system can be controlled by the grid operator or according to the best profit defined in a feed-in tariff law for renewable energy. Special attention has to be paid to the efficiency of this DC/DC-converter, due to the bidirectional energy passing before a grid injection is possible in case of energy buffering. After a brief introduction and system overview, this paper focuses on the DC/DC-Converter.
Based on fundamental investigations of the charge accumulation on the surface of dielectric materials relevant for DC test equipment, it was found that partial discharge (PD) phenomena under DC ...stresses are affected by both local and remote charge generation. With increasing air humidity both charge generation processes are intensified, resulting in an unexpectedly strong reduction of the PD inception voltage. It is therefore concluded that DC test equipment for operating voltages >or approximately=100 kV working in atmospheric air cannot be designed fully PD free at reasonable cost.< >
Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing ...colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
