Accurate diagnosis and prognosis of human cancers by proton MRS and a three-stage classification strategy

Magnetic resonance spectroscopy (MRS) of human biopsy specimens has the potential to become the new gold standard for pathological and, in some organs, clinical characterization of human cancers. MRS can detect small populations of abnormal cells with high accuracy, and identify and subcategorize preinvasive states. In addition, MRS detects changes to cellular chemistry in human tissues prior to these changes being apparent under the light microscope and, hence, discernable by various methods. The development of a classifier for breast biopsy that determines both pathology and nodal involvement is a paradigm shift in the management of breast disease. It remains to be seen if such prognostic information is available in spectra from other organs such as prostate and oesophagus. This new methodology is of clinical importance in identifying the extent of abnormality in preinvasive states, particularly in patients with a predisposition to cancer. The three-stage statistical classification strategy (SCS)-based methodology, which is the focus of this chapter, has been specifically developed for this purpose. The method provides accurate and reliable classification of large amounts of biomedical spectral data, while ensuring that the complete content of the spectrum is considered, spectral identity is retained, and a degree of confidence in a given diagnosis is provided. Furthermore, the use of SCS allows the MRS method to be automated, a step which must precede the routine use of this technology by clinicians

Electrochemical control of a DNA holliday junction nanoswitch by Mg2+ ions

The molecular conformation of a synthetic branched, 4-way DNA Holliday junction (HJ) was electrochemically switched between the open and closed (stacked) conformers. Switching was achieved by electrochemically induced quantitative release of Mg2+ ions from the oxidised poly(N-methylpyrrole) film (PPy), which contained polyacrylate as an immobile counter anion and Mg2+ ions as charge compensating mobile cations. This increase in the Mg2+ concentration screened the electrostatic repulsion between the widely separated arms in the open HJ configuration, inducing switching to the closed conformation. Upon electrochemical reduction of PPy, entrapment of Mg2+ ions back into the PPy film induced the reverse HJ switching from the closed to open state. The conformational transition was monitored using fluorescence resonance energy transfer (FRET) between donor and acceptor dyes each located at the terminus of one of the arms. The demonstrated electrochemical control of the conformation of the used probe-target HJ complex, previously reported as a highly sequence specific nanodevice for detecting of unlabelled target [Buck, A.H., Campbell, C.J., Dickinson, P., Mountford, C.P., Stoquert, H.C., Terry, J.G., Evans, S.A.G., Keane, L., Su, T.J., Mount, A.R., Walton, A.J., Beattie, J.S., Crain, J., Ghazal, P., 2007. Anal. Chem., 79, 4724–4728], allows the development of electronically addressable DNA nanodevices and label-free gene detection assays

Electrochemical deposition of Zn on TiN microelectrode arrays for microanodes

Zn was electrochemically deposited onto square TiN electrodes with edge dimensions of 490 μm and 40 μm. These were fabricated by standard microfabrication techniques, which provide an extremely reproducible electrode for experimentation. Reliable constant-potential electrodeposition of Zn on the TiN was performed at −1.2 V, just below the Zn/Zn2+ redox potential. At more negative potentials, the hydrogen evolution reaction on TiN interfered with bulk metal electrodeposition, resulting in poor quality Zn films. A two-step plating procedure was shown to be most efficient for electrochemical deposition of Zn, with Zn nucleation on the TiN substrate at high cathodic overpotential during the first step and a second step of bulk metal growth on the nucleated layer at low cathodic overpotential. These results were most consistent with 3D progressive nucleation of Zn on the TiN surface. Using this procedure, deposits of Zn on 490 μm TiN electrodes were uniform. In contrast, Zn deposits on 40 μm electrodes formed high-surface area and volume surface structures resulting from preferential growth at the electrode corners due to enhanced hemispherical diffusion at these sites. This should enable the formation of high surface area, high current density Zn anodes on biocompatible TiN microelectrodes, which could find application as improved microanodes for implantable miniature power supplies, e.g., implantable glucose sensors and internal cardioverter defibrillators. Keywords: Titanium nitride, Zinc, Microelectrode arrays, Electrochemical deposition, Microanode

The stability and characteristics of a DNA Holliday junction switch

A Holliday junction (HJ) consists of four DNA double helices, with a branch point discontinuity at the intersection of the component strands. At low ionic strength, the HJ adopts an open conformation, with four widely spaced arms, primarily due to strong electrostatic repulsion between the phosphate groups on the backbones. At high ionic strength, screening of this repulsion induces a switch to a more compact (closed) junction conformation. Fluorescent labelling with dyes placed on the HJ arms allows this conformational switch to be detected optically using fluorescence resonance energy transfer (FRET), producing a sensitive fluorescent output of the switch state. This paper presents a systematic and quantitative survey of the switch characteristics of such a labelled HJ. A short HJ (arm length 8 bp) is shown to be prone to dissociation at low switching ion concentration, whereas an HJ of arm length 12 bp is shown to be stable over all switching ion concentrations studied. The switching characteristics of this HJ have been systematically and quantitatively studied for a variety of switching ions, by measuring the required ion concentration, the sharpness of the switching transition and the fluorescent output intensity of the open and closed states. This stable HJ is shown to have favourable switch characteristics for a number of inorganic switching ions, making it a promising candidate for use in nanoscale biomolecular switch devices

Beeswax rock art from Limmen National Park (Northern Territory), northern Australia: new insights into technique-based patterning and absence in the rock art record

The known geographic distribution of beeswax rock art is largely restricted to the Arnhem Land plateau and Kimberley regions of northern Australia. While considerable research has focussed on the antiquity and meaning of beeswax rock art, much less attention has been directed to the nature and extent of the distribution pattern for this unique motif production technique. In this article, we present details of two beeswax motifs recently discovered in Marra Country at Limmen National Park (southwest Gulf of Carpentaria, Northern Territory). In the first instance, the motifs are explored in the context of their meaning, drawing on ethnography collected in the region over the last 40 years. The motifs are then used as a platform to engage with questions around the low frequency, and in some cases complete absence, of beeswax rock art across other areas of northern Australia. While it is highly unlikely there is one single, homogenous explanation for this in the Gulf country and northeastern Australia, we suggest that exploring the social, cultural and relational understandings of beeswax in these areas offers considerable potential to understand better how people engaged with and inscribed their cultural landscapes