Advancements in the Development of non-BET Bromodomain Chemical Probes

The bromodomain and extra terminal (BET) family of bromodomain-containing proteins (BCPs) have been the subject of extensive research over the past decade, resulting in a plethora of high-quality chemical probes for their tandem bromodomains. In turn, these chemical probes have helped reveal the profound biological role of the BET bromodomains and their role in disease, ultimately leading to a number of molecules in active clinical development. However, the BET subfamily represents just 8/61 of the known human bromodomains, and attention has now expanded to the biological role of the remaining 53 non-BET bromodomains. Rapid growth of this research area has been accompanied by a greater understanding of the requirements for an effective bromodomain chemical probe and has led to a number of new non-BET bromodomain chemical probes being developed. Advances since December 2015 are discussed, highlighting the strengths/caveats of each molecule, and the value they add toward validating the non-BET bromodomains as tractable therapeutic targets.     

A Priori Assessment of Customer Costs in Designing the Life Cycle of Complex Products

The basic stages in the life cycle of a batch of complex engineering products are considered: design, production, operation, and disposal. A priori cost assessment for each stage is discussed. The cost aggregation in the consideration of multiple stages is analyzed. Requirements on the assessment are formulated. Methodological and implementation aspects of the assessment tools are outlined. The conclusion is that it is expedient to predict the costs on the basis of mathematical models of the product batch in an operational environment. The integration of multiple cost estimates is addressed.     

Structure–phase state of the surface layers in rails subjected to differential hardening

A layer-by-layer analysis of the structures, the phase compositions, and the defect substructures of differentially hardened rails has been carried by optical and transmission electron microscopy. It is found that the material volume of the rail head fillet is cooled faster than the volume located along the central axis.     

Multilevel Recording in Ge2Sb2Te5 Thin Films

Semiconductors - The current–voltage characteristics measured on Ge2Sb2Te5 thin films in the current mode are studied. The effect of multilevel recording is established when applying...     

Optimal Placement of Dampers on Multistorey Frames Using Dynamic Analysis

Strength of Materials - The use of a damping system is one of the seismic protection systems that improve the seismic response of structures. The proposed methodology estimates the location (which...     

Effect of the Porous Skeletal Iron Structure on the Infiltration of Aluminum Melts

Powder Metallurgy and Metal Ceramics - The infiltration of aluminum melts into porous metal skeletons produced by powder metallurgy methods, including 3D printing, under a pressure gradient was...