pKa values of aqua ligands of platinum (II) anticancer complexes: [1H, 15N] and 195Pt NMR Studies of cis- and trans- [PtCl2 (NH3) (Cyclohexylamine)]

Syntheses and NMR studies are reported of two 15N-labelled Pt(II) complexes of anticancer interest: cis-PtCl2(15NH3)(c-C6H1115NH2), a metabolite of the orally-active Pt(IV) complex cis,trans,cis-[PtCl2(acetate)2(c-C6H11NH2)(NH3), and trans-[PtCl2(15NH3)(c-C6H1115NH2), a reduction product of the active Pt(IV) complex trans,trans,trans-[PtCl2(OH)2(c-C6H11NH2). For cis-[PtCl2(15NH3)(c-C6H1115NH2), hydrolysis was faster for the chloride ligand trans to cyclohexylamine, and the pKa values determined by [1H, 15N NMR spectroscopy for the two cis monoaqua isomers were the same (6.73). The trans monoaqua complex was a stronger acid with pKa of 5.4 (determined by 195Pt NMR). For the cis diaqua complex, pKa values of 5.68 and 7.68 were determined.

Distributed belief revision as applied within a descriptive model of jury deliberations

Belief revision is a well-research topic within AI. We argue that the new model of distributed belief revision as discussed here is suitable for general modelling of judicial decision making, along with extant approach as known from jury research. The new approach to belief revision is of general interest, whenever attitudes to information are to be simulated within a multi-agent environment with agents holding local beliefs yet by interaction with, and influencing, other agents who are deliberating collectively. In the approach proposed, it's the entire group of agents, not an external supervisor, who integrate the different opinions. This is achieved through an election mechanism, The principle of "priority to the incoming information" as known from AI models of belief revision are problematic, when applied to factfinding by a jury. The present approach incorporates a computable model for local belief revision, such that a principle of recoverability is adopted. By this principle, any previously held belief must belong to the current cognitive state if consistent with it. For the purposes of jury simulation such a model calls for refinement. Yet we claim, it constitutes a valid basis for an open system where other AI functionalities (or outer stiumuli) could attempt to handle other aspects of the deliberation which are more specifi to legal narrative, to argumentation in court, and then to the debate among the jurors.

Dirty theory: philosophical enactments after metaphysics

Modern forms of speculative philosophy continue to creep ‘unsuspectingly’ into our understanding of contemporary media/electronic arts, despite (or perhaps even because of) the attempts by Latour, Badiou, or Agamben especially when addressing the zero/one as if a contradictory ‘binary’ rather than as a kind of 'slice’ or (to use Deleuze and Guattari) an immanent plane of immanence. We argue that by playing with and against Neitzsche, Einstein, Godel, and Deleuze, a rather different story of art, not to mention philosophy, can be told. [From conference programme]

The vague, the viral, the parasitic: Piranesi's metropolis

In mid-18th century Giovanni Battista Piranesi’s etchings systematically document the old and new monuments, decrepit buildings and broken down infrastructures of a Rome that continues to inhabit and reinvent its past. His views of Rome offer a devastating account of the blurring of distinctions and articulations that time, use and neglect have imposed on the old differentiations of the urban and the rural, the public and the private, the monumental and the domestic in the 18th century city. Rome becomes for Piranesi the laboratory for a questioning of architecture that places his work well beyond the debate on style and on the origin that dominated the architectural discourse of his time. This paper suggests that Piranesi’s images anticipate the dispersion and sprawl of the city of today, in which the ‘vague’, the ‘viral’ and the ‘parasitic’ become modes of inhabitation and of transient negotiated definition. In the Antichità di Roma, ancient buildings are represented not only in their large scale and magnificence, but also in their decay and reversal to a state of naturalness. These works, together with the acute observations of the Vedute di Roma, provide the materials that are then dislocated, manipulated, cloned and endlessly mutated by Piranesi in the synthesis of the Campo Marzio dell’Antica Roma, in which the historical city is almost entirely dissolved and replaced by an extraordinary congestion of fragments. When they are re-examined on the grounds of contemporary architectural and urban theory, the sites of Piranesi's views reveal anticipations of phenomena that affect the metropolis of today. Political, social and economic conditions have changed dramatically, but the questions asked of architecture in and by these sites challenge the definition of an architecture of style, forms and boundaries - in the 18th century as well as in the 21st -in favour of an architecture of change.

Vibrational spectroscopic studies of the structure of di-amino acid peptides. Part II: cyclo(L-Asp-L-Asp) in the solid state and in aqueous solution

Solid-state protonated and N,O-deuterated Fourier transform infrared (IR) and Raman scattering spectra together with the protonated and deuterated Raman spectra in aqueous solution of the cyclic di-amino acid peptide cyclo(L-Asp-L-Asp) are reported. Vibrational band assignments have been made on the basis of comparisons with previously cited literature values for diketopiperazine (DKP) derivatives and normal coordinate analyses for both the protonated and deuterated species based upon DFT calculations at the B3-LYP/cc-pVDZ level of the isolated molecule in the gas phase. The calculated minimum energy structure for cyclo(L-Asp-L-Asp), assuming C-2 symmetry, predicts a boat conformation for the DKP ring with both the two L-aspartyl side chains being folded slightly above the ring. The C=O stretching vibrations have been assigned for the side-chain carboxylic acid group (e.g. at 1693 and 1670 cm(-1) in the Raman spectrum) and the cis amide I bands (e.g. at 1660 cm(-1) in the Raman spectrum). The presence of two bands for the carboxylic acid C=O stretching modes in the solid-state Raman spectrum can be accounted for by factor group splitting of the two nonequivalent molecules in a crystallographic unit cell. The cis amide II band is observed at 1489 cm(-1) in the solid-state Raman spectrum, which is in agreement with results for cyclic di-amino acid peptide molecules examined previously in the solid state, where the DKP ring adopts a boat conformation. Additionally, it also appears that as the molecular mass of the substituent on the C-alpha atom is increased, the amide II band wavenumber decreases to below 1500 cm(-1); this may be a consequence of increased strain on the DKP ring. The cis amide II Raman band is characterized by its relatively small deuterium shift (29 cm(-1)), which indicates that this band has a smaller N-H bending contribution than the trans amide II vibrational band observed for linear peptides.

Intracellular fate of bioresponsive poly(amidoamine)s in vitro and in vivo

Linear poly(amidoamine)s (PAAs) have been designed to exhibit minimal non-specific toxicity, display pH-dependent membrane lysis and deliver genes and toxins in vitro. The aim of this study was to measure PAA cellular uptake using ISA1-OG (and as a reference ISA23-OG) in B16F10 cells in vitro and, by subcellular fractionation, quantitate intracellular trafficking of (125)I-labelled ISA1-tyr in liver cells after intravenous (i.v.) administration to rats. The effect of time after administration (0.5-3h) and ISA1 dose (0.04-100mg/kg) on trafficking, and vesicle permeabilisation (N-acetyl-b-D-glucosaminidase (NAG) release from an isolated vesicular fraction) were also studied. ISA1-OG displayed approximately 60-fold greater B16F10 cell uptake than ISA23-OG. Passage of ISA1 along the liver cell endocytic pathway caused a transient decrease in vesicle buoyant density (also visible by TEM). Increasing ISA1 dose from 10mg/kg to 100mg/kg increased both radioactivity and NAG levels in the cytosolic fraction (5-10 fold) at 1h. Moreover, internalised ISA1 provoked NAG release from an isolated vesicular fraction in a dose-dependent manner. These results provide direct evidence, for the first time, of PAA permeabilisation of endocytic vesicular membranes in vivo, and they have important implications for potential efficacy/toxicity of such polymeric vectors.