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Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that is highly overexpressed in various cancer cells and antigen-presenting cells. It has emerged as an attractive therapeutic target for cancer immunotherapy, which has prompted high interest in the development of small-molecule inhibitors. To discover novel IDO1 inhibitors, we designed and synthesized a series of N′-hydroxyindazolecarboximidamides. Among the compounds synthesized, compound 8a inhibited both tryptophan depletion and kynurenine production through the IDO1 enzyme. Molecular docking studies revealed that 8a binds to IDO1 with the same binding mode as the analog, epacadostat (INCB24360). Here, we report the synthesis and biological evaluation of these hydroxyindazolecarboximidamides and present the molecular docking study of 8a with IDO1.

This paper deals with secondary cooling in a continuous caster. In particular, it deals with cooling inhomogeneity caused by spray arrangement and segmented rolls used for leading the strand. The cooling section is placed under the mold. Segmented rolls are supported by bearings in several places across the strand. Sprayed water can flow in the gaps between rolls where the bearing pocket is located. The main question that was experimentally studied is how this geometry with segmented rolls can influence homogeneity of cooling. Two experimental approaches developed for this study were applied, and both used full-scale geometrical configuration. The first one was a cold test where water flow and water distribution were observed using a transparent board with the studied surface structures (rollers and bearing pockets) and four spraying nozzles. The second one was a cooling test using a heated steel plate with rolls and bearing pockets. Cooling homogeneity was studied based on the temperature distribution on the rear side of the sample, which was recorded using an infrared camera. Homogeneity of cooling distribution was experimentally studied for three levels of cooling intensity that are used in typical cooling sections in plants. The hot tests showed that the bearing pockets do not provide significant cooling inhomogeneity despite the fact that a large amount of water flows through the gap between the rollers (which has been observed in cold tests).

Particles in molten steel, including argon-gas bubbles, slag droplets, and non-metallic inclusions, are removed into the surface-slag layer or captured by the solidifying steel-shell during continuous steel casting. Captured particles often become serious defects in the final steel product, so understanding particle-capture mechanisms is important for steel quality. Slab casters often have a straight mold and upper-strand prior to a curved lower-strand. The present work investigates particle capture in such a caster using computational modeling with a standard k-ε model for molten-steel flow, a discrete phase model for inclusion transport, and an advanced capture criterion for inclusion entrapment and engulfment into the steel shell. A new postprocessing methodology is presented and applied to predict inclusion-capture rates in commercial cast product. The locations and size distributions of particles captured into the shell, and actual capture rates are quantified. The model predictions are validated with ultrasonic-test plant measurements of the locations of large particles captured in a steel slab. The results reveal how large-inclusion capture accumulates in the beginning of the curved strand, leading to a capture band in the slab inside radius. Finally, the capture fractions and locations due to all capture mechanisms are compared for different inclusion sizes, and the implications are discussed.