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Potentials recorded on the body surface from the heart are of a spatial and temporal function. The 12-lead electrocardiogram (ECG) provides a useful means of global temporal assessment; however, it yields limited spatial information due to the smoothing effect caused by the volume conductor. In an attempt to circumvent the smoothing problem, researchers have used the five-point method (FPM) to numerically estimate the analytical solution of the Laplacian with an array of monopolar electrodes. Researchers have also developed a bipolar concentric ring electrode system to estimate the analytical Laplacian, and others have used a quasi-bipolar electrode configuration. In a search to find an electrode configuration with a close approximation to the analytical Laplacian, development of a tri-polar concentric ring electrode based on the nine-point method (NPM) was conducted. A comparison of the NPM, FPM, and discrete form of the quasi-bipolar configuration was performed over a 400 x 400 mesh with 1/400 spacing by computer modeling. Different properties of bipolar, quasi-bipolar and tri-polar concentric ring electrodes were evaluated and compared, and verified with tank experiments. One-way analysis of variance (ANOVA) with post hoc t-test and Bonferroni corrections were performed to compare the performance of the various methods and electrode configurations. It was found that the tri-polar electrode has significantly improved accuracy and local sensitivity. This paper also discusses the development of an active sensor using the tri-polar electrode configuration. A 1-cm active Laplacian tri-polar sensor based on the NPM was tested and deemed feasible for acquiring Laplacian cardiac surface potentials.

Predicting the impact of microRNAs (miRNAs) on target proteins is challenging because of their different regulatory effects at the transcriptional and translational levels. In this study, we applied a novel protein lysate microarray (LMA) technology to systematically monitor for target protein levels after high-throughput transfections of 319 pre-miRs into breast cancer cells. We identified 21 miRNAs that downregulated the estrogen receptor-α (ERα), as validated by western blotting and quantitative real time–PCR, and by demonstrating the inhibition of estrogen-stimulated cell growth. Five potent ERα-regulating miRNAs, miR-18a, miR-18b, miR-193b, miR-206 and miR-302c, were confirmed to directly target ERα in 3′-untranslated region reporter assays. The gene expression signature that they repressed highly overlapped with that of a small interfering RNA against ERα, and across all the signatures tested, was most closely associated with the repression of known estrogen-induced genes. Furthermore, miR-18a and miR-18b showed higher levels of expression in ERα-negative as compared with ERα-positive clinical tumors. In summary, we present systematic and direct functional evidence of miRNAs inhibiting ERα signaling in breast cancer, and demonstrate the high-throughput LMA technology as a novel, powerful technique in determining the relative impact of various miRNAs on key target proteins and associated cellular processes and pathways.