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  • 1
    Publication Date: 2015-04-03
    Description: In this article, we describe an improved method to assign the projection angle for averaged images using tilt-pair images for three-dimensional reconstructions from randomly oriented single-particle molecular images. Our study addressed the so-called ‘initial volume problem’ in the single-particle reconstruction, which involves estimation of projection angles of the particle images. The projected images of the particles in different tilt observations were mixed and averaged for the characteristic views. After the ranking of these group average images in terms of reliable tilt angle information, mutual tilt angles between images are assigned from the constituent tilt-pair information. Then, multiples of the conical tilt series are made and merged to construct a network graph of the particle images in terms of projection angles, which are optimized for the three-dimensional reconstruction. We developed the method with images of a synthetic object and applied it to a single-particle image data set of the purified deacetylase from archaea. With the introduction of low-angle tilt observations to minimize unfavorable imaging conditions due to tilting, the results demonstrated reasonable reconstruction models without imposing symmetry to the structure. This method also guides its users to discriminate particle images of different conformational state of the molecule.
    Print ISSN: 0022-0744
    Electronic ISSN: 1477-9986
    Topics: Electrical Engineering, Measurement and Control Technology , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-09-16
    Description: Purpose: Circulating microRNAs (miRNA) are emerging as promising diagnostic biomarkers for colorectal cancer, but their usefulness for detecting early colorectal neoplasms remains unclear. This study aimed to identify serum miRNA biomarkers for the identification of patients with early colorectal neoplasms. Experimental Design: A cohort of 237 serum samples from 160 patients with early colorectal neoplasms (148 precancerous lesions and 12 cancers) and 77 healthy subjects was analyzed in a three-step approach that included a comprehensive literature review for published biomarkers, a screening phase, and a validation phase. RNA was extracted from sera, and levels of miRNAs were examined by real-time RT-PCR. Results: Nine miRNAs (miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-24, miR-29a, miR-92, and miR-125b) were selected as candidate biomarkers for initial analysis. In the screening phase, serum levels of miR-21, miR-29a, and miR-125b were significantly higher in patients with early colorectal neoplasm than in healthy controls. Elevated levels of miR-21, miR-29a, and miR-125b were confirmed in the validation phase using an independent set of subjects. Area under the curve (AUC) values for serum miR-21, miR-29a, miR-125b, and their combined score in discriminating patients with early colorectal neoplasm from healthy controls were 0.706, 0.741, 0.806, and 0.827, respectively. Serum levels of miR-29a and miR-125b were significantly higher in patients who had only small colorectal neoplasms (≤5 mm) than in healthy subjects. Conclusions: Because serum levels of miR-21, miR-29a, and miR-125b discriminated patients with early colorectal neoplasm from healthy controls, our data highlight the potential clinical use of these molecular signatures for noninvasive screening of patients with colorectal neoplasia. Clin Cancer Res; 21(18); 4234–42. ©2015 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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