Application of stereological methods to estimate post-mortem brain surface area using 3 T MRI

The Cavalieri and Vertical Sections methods of design based stereology were applied in combination with 3 tesla (i.e. 3 T) Magnetic Resonance Imaging (MRI) to estimate cortical and subcortical volume, area of the pial surface, area of the grey–white matter boundary, and thickness of the cerebral cortex. The material comprises eight human cadaveric cerebri which had been separated into sixteen cerebral hemisphere specimens prior to embedding in agar gel. The results from MRI were compared with corresponding ‘gold standard’ values subsequently obtained by application of the same methodology using physical sectioning of the specimens.     

A universal surrogate peptide to enable LC-MS/MS bioanalysis of a diversity of human monoclonal antibody and human Fc-fusion protein drug candidates in pre-clinical animal studies

For the development of human antibody Fc (fraction crystallizable) region-containing therapeutic protein candidates, which can be either monoclonal antibodies (mAbs) or pharmacologically active proteins/peptides fused to the Fc region of human Immunoglobulin G (IgG), reliable quantification of these proteins in animal pharmacokinetic study plasma samples is critical. LC-MS/MS has emerged as a promising assay platform for this purpose. LC-MS/MS assays used for bioanalysis of human antibody Fc region-containing therapeutic protein candidates frequently rely upon quantification of a 'signature' surrogate peptide whose sequence is unique to the protein analyte of interest. One drawback of the signature peptide approach is that a new LC-MS/MS assay must be developed for each new human Fc region-containing therapeutic protein. To address this issue, we propose an alternative 'universal surrogate peptide' approach for the quantification of human antibody Fc region-containing therapeutic protein candidates in plasma samples from all nonclinical species. A single surrogate tryptic peptide was identified in the Fc region of most human antibody Fc-containing therapeutic protein candidates. An LC-MS-MS method based upon this peptide was shown to be capable of supporting bioanalysis of a diversity of human Fc region-containing therapeutic protein candidates in plasma samples of all commonly used animal species.     

Approach to Animated Anthracyclines via an Intramolecular Marschalk Reaction

An anionic cyclization based approach to a novel daunomycin analog is described.     

New high-energy luminescence bands from Co2+ in ZnSe

Three sharp absorption features in the energy range 2.36–2.55 eV have been detected in the transmission spectrum of Co-diffused ZnSe, and a number of luminescence transitions originating from the lowest of these states at 2.361 eV have been observed. Photoluminescence excitation spectra prove that these are high energy excited states of the Co²⁺_Zn impurity, a conclusion confirmed by comparison of measured and predicted luminescence energies. This represents the first identification of luminescence branching from a higher excited state of a transition metal ion in any semiconductor. The sharp, weakly phonon-coupled transitions involve either intra-impurity excitation or transitions from the impurity to localised states split off from a minimum in the conduction band. The implications of these observations for the mechanism of host-impurity energy transfer and for the nature of the excited state wavefunctions are discussed.     

Tautomeric equilibria analysis of β‐ketoamides by mass spectrometry

Mass spectrometric evidence of tautomerism is reported for β‐ketoamides. The most abundant tautomers are ketoamido and Z‐enolamido (both forming internal hydrogen bonds). The influence of temperature on the enol/keto abundance ratios is studied in order to estimate the enthalpy difference for tautomeric equilibria. Theoretical calculations have been done in order to support experimental determinations. There are consistent trends between theoretical and experimental data: Enolization is favored by electron‐withdrawing substiuents, bulky groups in α position and temperature increase. Copyright © 2012 John Wiley & Sons, Ltd.