The effect of tightly-bound water molecules on scaffold diversity in computer-aided de novo ligand design of CDK2 inhibitors

We have determined the effects that tightly bound water molecules have on the de novo design of cyclin-dependent kinase-2 (CDK2) ligands. In particular, we have analyzed the impact of a specific structural water molecule on the chemical diversity and binding mode of ligands generated through a de novo structure-based ligand generation method in the binding site of CDK2. The tightly bound water molecule modifies the size and shape of the binding site and we have found that it also imposed constraints on the observed binding modes of the generated ligands. This in turn had the indirect effect of reducing the chemical diversity of the underlying molecular scaffolds that were able to bind to the enzyme satisfactorily

tRNA structural and functional changes induced by oxidative stress

Oxidatively damaged biomolecules impair cellular functions and contribute to the pathology of a variety of diseases. RNA is also attacked by reactive oxygen species, and oxidized RNA is increasingly recognized as an important contributor to neurodegenerative complications in humans. Recently, evidence has accumulated supporting the notion that tRNA is involved in cellular responses to various stress conditions. This review focuses on the intriguing consequences of oxidative modification of tRNA at the structural and functional level

CypherDB: a novel architecture for outsourcing secure database processing

CypherDB addresses the problem of protecting the confidentiality of database stored externally in a cloud and enabling efficient computation over it to thwart any curious-but-honest cloud computing service provider. It works by encrypting the entire outsourced database and executing queries over the encrypted data using our novel CypherDB secure processor architecture. To optimize computational efficiency, our proposed processor architecture provides tightly-coupled datapaths that avoid information leakage during database access and query execution. Our simulation using a well-known database benchmark TPC-H over a commercial grade Database Management System (SQLite) demonstrates that our proposed architecture incurs an average of about 10 percent overhead when compared with the same set of operations without secure database processing

International opportunity recognition as a critical component for leveraging Internet capabilities and international market performance

Recent research in the field of international entrepreneurship has emphasized the need for a better conceptualization of international opportunity recognition. Further, with advancements in information and communication technologies, such as the Internet, there has been a profound impact on the way in which international business is conducted, for example, enabling entrepreneurial firms to capitalize on the economic opportunities of an Internet environment. In this study, we propose a model, highlighting the importance of international opportunity recognition, as a critical component for leveraging Internet capabilities and international market performance. Through the lens of a resource capabilities approach a quantitative, online survey was used to collect data from Australian, international entrepreneurial firms. Structural equation modelling results indicate that international opportunity recognition plays a central role in explaining how resources and Internet capabilities combine for the firm’s realization of international opportunities, and subsequent international performance. The findings enrich current understanding of how international entrepreneurial firms realize opportunities in Internet-based environments

Iridium-Catalyzed Silylation

In this chapter, homogeneous iridium-catalyzed silylation reactions are reviewed, focusing primarily on their synthetic utility. Additionally, relevant catalytic cycles are commented, paying especial attention to those that are more representative of each type of process. The chapter is divided into two main types of reactions, namely, hydrosilylation and C–H bond silylation. The former deals with the hydrosilylation of polar unsaturated bonds (ketones and imines) and non-polar unsaturated bonds (alkenes and alkynes). The latter covers the directed and non-directed C–H bond silylation of alkenes, alkynes, arenes, and alkanes – mainly comprising dehydrogenative silylation reactions, which may occur in the presence or absence of a hydrogen acceptor.This work was supported by the “Ramón y Cajal” program (RYC2016-20864) (FSE/Agencia Estatal de Investigación) (M. I.) and the Spanish Ministry of Science, Innovation and Universities (RTI2018-099136-A-I00).Peer reviewe