Biophysical analysis of DNA modified by 1,2-diaminocyclohexane platinum(II) complexes.

Modification of DNA and double-stranded deoxyoligonucleotides with antitumour 1,2-diamino-cyclohexanedinitroplatinum(II) (Pt-dach) complexes was investigated with the aid of physico-chemical methods and chemical probes of nucleic acid conformation. The three Pt-dach complexes were used which differed in isomeric forms of the dach nonleaving ligand-Pt(1R,2R-dach), Pt(1S,2S-dach) and Pt(1R,2S-dach) complexes. The latter complex has lower antitumour activity than the other two Pt-dach complexes. Pt(1R,2S-dach) complex exhibits the slowest kinetics of its binding to DNA and of the conversion of monofunctional binding to bifunctional lesions. The anomalously slow electrophoretic mobility of multimers of the platinated and ligated oligomers suggests that bifunctional binding of Pt-dach complexes to a d(GG) site within double-stranded oligonucleotides induces bending of the oligomer. In addition, chemical probing of double-helical deoxyoligonucleotides modified by the Pt-dach complexes at the d(GG) sites reveals that Pt(1R,2S-dach) complex induces more extensive conformational changes in the oligomer than Pt(1R,2R-dach) and Pt(1S,2S-dach) complexes. It is proposed that different effects of the Pt-dach complexes on DNA observed in this work arise mainly from a steric crowding of the axially oriented cyclohexane ring in the DNA adduct of Pt(1R,2S-dach) complex

New visions, old practices: policy and regulation in the internet era

Raymond Williams’ comment applies as much to the media and communication systems of his time as it does to today’s Internet era. As Silverstone (2007: 26) wrote, “mediated connection and interconnection define the dominant infrastructure for the conduct of social, political and economic life across the globe”. The Internet is no more a neutral configuration of technologies than was the earlier media and communication system. If there are forces that are shaping the Internet’s development in ways that are not equitable then there is a case for countering them. This paper offers an assessment of current trends in policy and regulation that bear on the Internet. The aim is to discern whether visions of a post-neoliberal period are visible in policy and regulatory practice in this area. Though some argue that developments in Internet governance are beginning to wrest control of the Internet away from state or private sector influence, I suggest that this is a very one-sided view. In this paper, I argue that the forces influencing Internet developments are not benign because an unregulated Internet is unlikely to maximise the benefits of the Internet for all. This paper focuses on corporate interests in the Internet’s evolution and on the state’s role in regulating various components of the infrastructure and services that employ the Internet. The following section considers the paradoxical alliance between the neoliberal agenda and the advocates of the open unregulated Internet. The impact of the neoliberal agenda on the telecommunication, broadcast and Internet segments of the media and communication industry is then considered briefly, providing a basis for a more in-depth consideration of the incentives encouraging corporate actors to engage in monopolisation strategies as a means of maximising their profits. In the penultimate section, the likelihood of a shift to policy based on a post-neoliberal paradigm is explored through an examination of some recent developments in network infrastructure, broadcast content and radio frequency spectrum policy