) is one of several novel anthracycline protein kinase C (PKC)-activating agents developed in our laboratories that demonstrates cytotoxic superiority over doxorubicin (Adriamycin; DOX) through its circumvention of multiple mechanisms of drug resistance. This characteristic is attributed at least partly to the principal cellular action of AD 198: PKC activation through binding to the C1b (diacylglycerol binding) regulatory domain. A significant dose-limiting effect of DOX is chronic, dose-dependent, and often irreversible cardiotoxicity ascribed to the generation of reactive oxygen species (ROS) from the semiquinone ring structure of DOX. Despite the incorporation of the same ring structure in AD 198, we hypothesized that AD 198 might also be cardioprotective through its ability to activate PKC-, a key component of protective ischemic preconditioning in cardiomyocytes. Chronic administration of fractional LD 50 doses of DOX and AD 198 to mice results in histological evidence of dose-dependent ventricular damage by DOX but is largely absent from AD 198-treated mice. The absence of significant cardiotoxicity with AD 198 occurs despite the equal ability of DOX and AD 198 to generate ROS in primary mouse cardiomyocytes. Excised rodent hearts perfused with AD 198 prior to hypoxia induced by vascular occlusion are protected from functional impairment to an extent comparable to preconditioning ischemia. AD 198-mediated cardioprotection correlates with increased PKCactivation and is inhibited in hearts from PKC-knockout mice. These results suggest that, despite ROS production, the net cardiac effect of AD 198 is protection through activation of PKC-.

The temperature-dependent microstructure evolution and corresponding mechanical stability of retained austenite in medium-Mn transformation induced plasticity (TRIP) 0.17C-3.1Mn-1.6Al type steel obtained by thermomechanical processing was investigated using scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and X-ray diffraction (XRD) techniques. Specimens were deformed up to rupture in static tensile tests in the temperature range 20–200 °C. It was found that an increase in deformation temperature resulted in the reduced intensity of TRIP effect due to the higher stability of retained austenite. The kinetics of strain-induced martensitic transformation was affected by the carbon content of retained austenite (RA), its morphology, and localization in the microstructure.

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One of the main limitations in application of nanostructured carbide-free bainite as a construction material is the difficulty of joining. This research presents a structural characterization of welded joints of medium carbon 55Si7 grade steel after the welding process with a regeneration technique as well as post welding heat treatment (PWHT). The hardness distribution of the welded joint with regeneration exhibit an overall decrease in hardness when compared to the base material and a significant decrease in hardness was observed in the heat-affected zone (HAZ). Unfavorable hardness distribution was caused by the presence of diffusion-type transformations products (pearlite) in the HAZ and bainite degradation processes. On the other hand, welding with the PWHT promotes the achievement of a comparable level of hardness and structure as in the base material. However, a slight decrease in hardness was observed in the weld zone due to the micro-segregation of the chemical composition caused by the indissoluble solidification structure. Based on the structural analysis, it was found that steel with relatively low hardenability (55Si7) should be welded using PWHT rather than a regeneration technique.

Advanced medium-Mn sheet steels show an opportunity for the development of cost-effective and light-weight automotive parts with improved safety and optimized environmental performance. These steels utilize the strain-induced martensitic transformation of metastable retained austenite to improve the strength–ductility balance. The improvement of mechanical performance is related to the tailored thermal and mechanical stabilities of retained austenite. The mechanical stability of retained austenite was estimated in static tensile tests over a wide temperature range from 20 °C to 200 °C. The thermal stability of retained austenite during heating at elevated temperatures was assessed by means of dilatometry. The phase composition and microstructure evolution were investigated by means of scanning electron microscopy, electron backscatter diffraction, X-ray diffraction and transmission electron microscopy techniques. It was shown that the retained austenite stability shows a pronounced temperature dependence and is also stimulated by the manganese addition in a 3–5% range.