The anticancer complexes cisplatin and carboplatin target the DNA major groove, forming intrastrand and interstrand cross-links between guanine bases through their N7 atoms, causing distortion of the DNA helix and apoptotic cell death. A major side effect of these drugs is toxicity, which is caused via binding to many proteins in the body. A range of crystallographic studies have been carried out involving the cocrystallization of hen egg-white lysozyme (HEWL) as a test protein with cisplatin and carboplatin in aqueous and dimethyl sulfoxide (DMSO) conditions. Different cryoprotectants, glycerol and Paratone, were used for each of the cisplatin and carboplatin cocrystallization cases, while silicone oil was used for studies involving N-acetylglucosamine (NAG). Both cisplatin and carboplatin do not bind to HEWL in aqueous media on the timescales of the conditions used here, but upon addition of DMSO two molecules of cisplatin or carboplatin bind either side of His15, which is the only His residue in lysozyme and is assumed to be an imidazolyl anion or a chemical resonance moiety, i.e. both imidazole N atoms are chemically reactive. To identify the platinum-peak positions in the 'with DMSO conditions', anomalous scattering maps were calculated as a cross-check with the F(o) - F(c) OMIT maps. Platinum-occupancy σ values were established using three different software programs in each case. The use of EVAL15 to process all of the diffraction data sets provided a consistent platform for a large ensemble of data sets for the various protein and platinum-compound model refinements with REFMAC5 and then SHELXTL. Overall, this extensive set of crystallization and cryoprotectant conditions allowed a systematic evaluation of cisplatin and carboplatin binding to lysozyme as a test protein via detailed X-ray crystal structure characterizations. DMSO is used as a super-solvent for drug delivery as it is deemed to cause no effect upon drug binding. However, these results show that addition of DMSO causes the platinum anticancer drugs to bind to HEWL. This effect should be considered in toxicity assessments of these drugs and perhaps more widely.

Previous research on the conversation analytic phenomenon of ‘repair’ has focused on its design and function in spoken interaction. Conversely, research on written text or writing rarely focuses on interaction. In this article, we examine repair in written discourse; specifically in online settings. The data corpus comprises one-to-one quasi-synchronous Facebook ‘chat’. First, we show that, as in spoken interaction, repair happens. This basic observation supports conversation analytic arguments that features of talk, like repair and laughter, do not ‘leak randomly’ into interaction but are precision-timed and designed to accomplish action. Second, we report on two types of repair: visible repair which can be seen and oriented to by both participants in the interaction, and message construction repair, which is available only to the message’s writer. While the practice of message construction repair is made possible through the affordances of the online medium, it nevertheless shows how participants in written interaction are oriented to the same basic contingencies as they are in spoken talk: building sequentially organized courses of action and maintaining intersubjectivity. We suggest that assumptions about differences between spoken and online interaction are premature. Rather, we argue that online interaction should be treated as an adaptation of an oral speech-exchange system.

The use of conversation analysis (CA) as a method for analysing the interactional practices of online communication has been growing in recent years (Giles, Stommel, Paulus, Lester & Reed, 2015). A key challenge for analysing online communication is the varied platforms through which interaction can occur. This paper demonstrates how using CA and the concept of affordances (Hutchby, 2001) can provide a lens through which to analyse not only the interaction, but also the technological context of that interaction. A corpus of instant messaging chats, captured from Facebook chat using screen-capture software, is used as a case study to demonstrate how the concept of affordances can be used alongside CA analysis to address the role of technology in the interaction. Two key interactional practices -turn adjacency and openings -are analysed to show the insights that CA can offer for providing an in-depth analysis of online interaction. By using affordances as a lens through which CA analysis can be refracted, scholars using 'digital CA' can better develop an understanding of patterns of interaction across different interactional platforms.

Salt-bridge-p (sb-p) interactions at work: associative interactions of sb-p, p-p and anion-p in Cu(II)malonate-2-aminopyridine-hexafluoridophosphate ternary system3