Developing a comparative photon-proton planning service in Victoria: the experience at Peter MacCallum Cancer Centre.

Proton-beam therapy (PBT) is a cutting-edge radiation therapy modality that is currently not available in Australia. Comparative photon-proton (CPP) planning is required for the medical treatment overseas programme (MTOP) and will be required for access to PBT in Australia in the future. Comparative planning brings professional development benefits to all members of the radiation therapy team. This service was also created to support future proposals for a PBT facility in Victoria. We report our experience developing an in-house CPP service at Peter MacCallum Cancer Centre. A set of resources to support CPP planning was established. Training of relevant staff was undertaken after which an in-house training programme was developed. A standard protocol for PBT planning parameters was established. All CPP plans were reviewed. Future goals for the CPP planning programme were described. In total, 62 cases were comparatively planned over 54 months. Of these, 60% were paediatric cases, 14% were adolescents and young adults (15-25 years) and 26% were adults. The vast majority (over 75%) of patients comparatively planned required irradiation to the central nervous system including brain and cranio-spinal irradiation. A variety of proton plans were reviewed by international PBT experts to confirm their deliverability. Our team at Peter MacCallum Cancer Centre has gained significant experience in CPP planning and will continue to develop this further. Local expertise will help support decentralisation of patient selection for proton treatments in the near future and the PBT business case in Victoria.

The role of loops and cation on the volume of unfolding of G-quadruplexes related to HTel.

In aqueous solutions containing sodium or potassium cations, oligodeoxyribonucleotides (ODNs) rich in guanine form four-stranded DNA structures called G-quadruplexes (G4s). These structures are destabilized by elevated hydrostatic pressure. Here, we use pressure to investigate the volumetric changes arising from the formation of G4 structures. G4s display a great deal of structural heterogeneity that depends on the stabilizing cation as well as the oligonucleotide sequence. Using UV thermal unfolding at different pressures, we have investigated the volume change of the helix-coil equilibrium of a series of ODNs whose sequences are related to the G-rich ODN HTel (d[A(GGGTTA)3GGG]), which contains four repeats of the human telomeric sequence. The experiments are conducted in aqueous buffers containing either 100mM NaCl or KCl at pH7.4. The G4s stabilized by Na+ are less sensitive to pressure perturbation than those stabilized by K+. The overall molar volume changes (ΔVtot) of the unfolding transition for all of the G4s are large and negative. A large fraction of the measured ΔVtot value arises from the re-hydration of the cations released from the interior of the folded structure. However, the differences in the measured ΔVtot values demonstrate that variations in the structure of G4s formed by each ODN, arising from differences in the sequence of the loops, contribute significantly to ΔVtot and presumably the hydration of the folded structures. Depending on the sequence of the loops, the magnitude of the measured ΔVtot can be larger or smaller than that of HTel in solutions containing sodium. However, the magnitude of ΔVtot is smaller than HTel for the unfolding of all G4s that are stabilized by potassium ions.

De novo asymmetric synthesis of 8a-epi-swainsonine.

An enantioselective and diastereocontrolled approach to 8a-epi-d-swainsonine has been developed from achiral furfural. The key step to this synthesis was a one-pot procedure for the hydrogenolytic removal of two protecting groups and two intramolecular reductive amination reactions. The absolute stereochemistry was introduced by asymmetric Noyori reduction of furfuryl ketone. This route relies on diastereoselective palladium-catalyzed glycosylation to install the anomeric bond, and Luche reduction, diastereoselective dihydroxylation to set up the manno-stereochemistry of the indolizidine precursor.

Characterization of a commercialized SERS-active substrate and its application to the identification of intact Bacillus endospores.

Surface-enhanced-Raman-spectroscopy (SERS) can be made an attractive approach for the identification of Raman-active compounds and biological materials (i.e., toxins, viruses, or intact bacterial cells or spores) through development of reproducible, spatially uniform SERS-active substrates. Recently, reproducible (from substrate to substrate), spatially homogeneous (over large areas) SERS-active substrates have been commercialized and are now available in the marketplace. Scanning electron microscopy and high-resolution, tapping-mode atomic force microscopy have been used to analyze these novel plasmonic surfaces for topographical consistency. Additionally, we have assessed, by wavelength-tunable microreflectance spectrometry, the spatial distribution of the localized surface plasmon resonance (LSPR) across a single substrate surface as well as the LSPR lambda(MAX) variance from substrate to substrate. These analyses reveal that these surfaces are topologically uniform with small LSPR variance from substrate to substrate. Further, we have utilized these patterned surfaces to acquire SERS spectral signatures of four intact, genetically distinct Bacillus spore species cultivated under identical growth conditions. Salient spectral signature features make it possible to discriminate among these genetically distinct spores. Additionally, partial least squares, a multivariate calibration method, has been used to develop personal-computer-borne algorithms useful for classification of unknown spore samples based solely on SERS spectral signatures. To our knowledge, this is the first report detailing application of these commercially available SERS-active substrates to identification of intact Bacillus spores.