Electronic detection of single-base mismatches in DNA with ferrocene-modified probes.

Genotyping and gene-expression monitoring is critical to the study of the association between genetics and drug response (pharmacogenomics) and the association of sequence variation with heritable phenotypes. Recently, we developed an entirely electronic method for the detection of DNA hybridization events by the site-specific incorporation of ferrocenyl derivatives into DNA oligonucleotides. To perform rapid and accurate point mutation detection employing this methodology, two types of metal-containing signaling probes with varying redox potentials are required. In this report we describe a new ferrocene-containing phosphoramidite 9 that provides a range of detectable redox potentials. Using automated DNA/RNA synthesis techniques the two ferrocenyl complexes were inserted at various positions along oligonucleotide probes. Thermal stability analysis of these metal-containing DNA oligonucleotides indicates that incorporation of 9 resulted in no destabilization of the duplex. A mixture of oligonucleotides containing compounds 9 and I was analyzed by alternating current voltammetry (ACV) monitored at the 1st harmonic. The data demonstrate that the two ferrocenyl oligonucleotide derivatives can be distinguished electrochemically. A CMS-DNA array was prepared on an array of gold electrodes on a printed circuit board substrate with a self-assembled mixed monolayer, coupled to an electronic detection system. Experiments for the detection of a single-base match utilizing two signaling probes were carried out. The results demonstrate that rapid and accurate detection of a single-base mismatch can be achieved by using these dual-signaling probes on CMS-DNA chips.     

Research problem: indefinite inner product normal matrices

Several open research problems are formulated concerning normal matrices with respect to indefinite inner products.     

Developing and Maintaining an Equity Index Fund

An index fund is a portfolio of shares designed to replicate the investment performance of a market index. The index represents the behaviour of the market as a whole. This paper describes the selection of an index fund which minimizes expected tracking error. Using a multivariate model of returns on shares, a development of a univariate model by Taylor, the selection problem is formulated as a quadratic programme. The effects of various constraints on tracking error are demonstrated. Several policies for the readjustment of a fund are examined in the context of the differing objectives of fund managers. As a general rule, regular readjustment is shown to be a more expensive policy than irregular updating.     

Stress-intensity factors for a semi-infinite plane crack with a wavy front

The stress-intensity factors for a semi-infinite plane crack with a wavy front are determined when the crack faces are subjected to normal and shearing tractions. The results are derived using asymptotic methods and are valid to O(²) where =A/1; A is the amplitude and is the wavelength of the wavy front. The normal and shearing tractions are in the form of line loads parallel to the crack front.The results are then used to evaluate, in a qualitative manner, the growth characteristics of a semi-infinite plance crack with a wavy front under combined mode loading. This provides a possible explanation of crack front segmentation observed experimentally.     

Synthesis and Evaluation of GdIII‐Based Magnetic Resonance Contrast Agents for Molecular Imaging of Prostate‐Specific Membrane Antigen

Magnetic resonance (MR) imaging is advantageous because it concurrently provides anatomic, functional, and molecular information. MR molecular imaging can combine the high spatial resolution of this established clinical modality with molecular profiling in vivo. However, as a result of the intrinsically low sensitivity of MR imaging, high local concentrations of biological targets are required to generate discernable MR contrast. We hypothesize that the prostate‐specific membrane antigen (PSMA), an attractive target for imaging and therapy of prostate cancer, could serve as a suitable biomarker for MR‐based molecular imaging. We have synthesized three new high‐affinity, low‐molecular‐weight Gd^III‐based PSMA‐targeted contrast agents containing one to three Gd^III chelates per molecule. We evaluated the relaxometric properties of these agents in solution, in prostate cancer cells, and in an in vivo experimental model to demonstrate the feasibility of PSMA‐based MR molecular imaging.     

A Three-Channel Spectrometer for Wide-Field Imaging of Anisotropic Plasmonic Nanoparticles

A three-channel spectrometer (3CS) based on a commercial digital camera was developed to distinguish among tens of large (>100 nm), anisotropic plasmonic particles with various shapes, orientations, and compositions on a surface simultaneously. Using band pass filters and polarizers, the contrast of 3CS images could be enhanced to identify specific orientation and composition characteristics of gold and gold-silver nanopyramids and as well as the direction of the longest arm of gold nanostars.