STAT3 differential scanning fluorimetry and differential scanning light scattering assays: Addressing a missing link in the characterization of STAT3 inhibitor interactions

STAT3 protein is an established target for the development of new cancer therapeutic agents. Despite lacking a traditional binding site for small molecule inhibitors, many STAT3 inhibitors have been identified and explored for their anti-cancer activity. Because STAT3 signaling is mediated by protein-protein interactions, indirect methods are often employed to determine if proposed STAT3 inhibitors bind to STAT3 protein. While established STAT3 inhibition assays (such as the fluorescence polarization assay, electrophoretic mobility shift assay and ELISAs) have been used to identify novel inhibitors of STAT3 signaling, methods that directly assess STAT3 protein-inhibitor interactions could facilitate the development of novel inhibitors. In this context, we herein report new STAT3 binding assays based on differential scanning fluorimetry (DSF) and differential scanning light scattering (DSLS) to characterize interactions between STAT3 protein and inhibitors. Several peptide and small molecule STAT3 inhibitors have been evaluated, and new insight into how these compounds may interact with STAT3 is provided

Microstructural and mechanical characterisation of laser-welded high-carbon and stainless steel

The final publication is available at Springer via http://dx.doi.org/10.1007/s00170-015-7111-5Laser welding is becoming an important joining technique for welding of stainless steel to carbon steel and is extensively used across various sectors, including aerospace, transportation, power plants, electronics and other industries. However, welding of stainless steel to high-carbon steel is still at its early stage, predominantly due to the formation of hard brittle phases, which undermine the mechanical strength of the joint. This study reports a scientific investigation on controlling the brittle phase formation during laser dissimilar welding of high-carbon steel to stainless steel. Attempts have been made to tailor the microstructure and phase composition of the fusion zone through influencing the alloying composition and the cooling rate. Results show that the heat-affected zone (HAZ) within the high-carbon steel has significantly higher hardness than the weld area, which severely undermines the weld quality. To reduce the hardness of the HAZ, a new heat treatment strategy was proposed and evaluated using a finite element analysis-based numerical simulation model. A series of experiments has been performed to verify the developed thermo-metallurgical finite element analysis (FEA) model, and a qualitative agreement of predicted martensitic phase distribution is shown to exist

Endometrial cancer and application of proteomics

This work is supported by the Swedish Cancer Foundation, the Swedish Institute and the Swedish Research Council to S.S