Selection Of A Novel Aptamer Against Vitronectin Using Capillary Electrophoresis And Next Generation Sequencing

Breast cancer (BC) results in ≃40,000 deaths each year in the United States and even among survivors treatment of the disease may have devastating consequences, including increased risk for heart disease and cognitive impairment resulting from the toxic effects of chemotherapy. Aptamer-mediated drug delivery can contribute to improved treatment outcomes through the selective delivery of chemotherapy to BC cells, provided suitable cancer-specific antigens can be identified. We report here the use of capillary electrophoresis in conjunction with next generation sequencing to develop the first vitronectin (VN) binding aptamer (VBA-01; Kd 405 nmol/l, the first aptamer to vitronectin (VN; Kd = 405 nmol/l), a protein that plays an important role in wound healing and that is present at elevated levels in BC tissue and in the blood of BC patients relative to the corresponding nonmalignant tissues. We used VBA-01 to develop DVBA-01, a dimeric aptamer complex, and conjugated doxorubicin (Dox) to DVBA-01 (7:1 ratio) using pH-sensitive, covalent linkages. Dox conjugation enhanced the thermal stability of the complex (60.2 versus 46.5°C) and did not decrease affinity for the VN target. The resulting DVBA-01-Dox complex displayed increased cytotoxicity to MDA-MB-231 BC cells that were cultured on plasticware coated with VN (1.8 × 10⁻⁶mol/l) relative to uncoated plates (2.4 × 10⁻⁶ mol/l), or plates coated with the related protein fibronectin (2.1 × 10⁻⁶ mol/l). The VBA-01 aptamer was evaluated for binding to human BC tissue using immunohistochemistry and displayed tissue specific binding and apparent association with BC cells. In contrast, a monoclonal antibody that preferentially binds to multimeric VN primarily stained extracellular matrix and vessel walls of BC tissue. Our results indicate a strong potential for using VN-targeting aptamers to improve drug delivery to treat BC

A new accuracy measure based on bounded relative error for time series forecasting

Many accuracy measures have been proposed in the past for time series forecasting comparisons. However, many of these measures suffer from one or more issues such as poor resistance to outliers and scale dependence. In this paper, while summarising commonly used accuracy measures, a special review is made on the symmetric mean absolute percentage error. Moreover, a new accuracy measure called the Unscaled Mean Bounded Relative Absolute Error (UMBRAE), which combines the best features of various alternative measures, is proposed to address the common issues of existing measures. A comparative evaluation on the proposed and related measures has been made with both synthetic and real-world data. The results indicate that the proposed measure, with user selectable benchmark, performs as well as or better than other measures on selected criteria. Though it has been commonly accepted that there is no single best accuracy measure, we suggest that UMBRAE could be a good choice to evaluate forecasting methods, especially for cases where measures based on geometric mean of relative errors, such as the geometric mean relative absolute error, are preferred

Multiband multislab 3D time-of-flight magnetic resonance angiography for reduced acquisition time and improved sensitivity

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Multiband echo-shifted echo planar imaging

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