A CMOS Image Readout Circuit with On-Chip Defective Pixel Detection and Correction.

Images produced by CMOS sensors may contain defective pixels due to noise, manufacturing errors, or device malfunction, which must be detected and corrected at early processing stages in order to produce images that are useful to human users and image-processing or machine-vision algorithms. This paper proposes a defective pixel detection and correction algorithm and its implementation using CMOS analog circuits, which are integrated with the image sensor at the pixel and column levels. During photocurrent integration, the circuit detects defective values in parallel at each pixel using simple arithmetic operations within a neighborhood. At the image-column level, the circuit replaces the defective pixels with the median value of their neighborhood. To validate our approach, we designed a 128×128-pixel imager in a 0.35µm CMOS process, which integrates our defective-pixel detection/correction circuits and processes images at 694 frames per second, according to post-layout simulations. Operating at that frame rate, our proposed algorithm and its CMOS implementation produce better results than current state-of-the-art algorithms: it achieves a Peak Signal to Noise Ratio (PSNR) and Image Enhancement Factor (IEF) of 45 dB and 198.4, respectively, in images with 0.5% random defective pixels, and a PSNR of 44.4 dB and IEF of 194.2, respectively, in images with 1.0% random defective pixels.

Inhibition of CYP21A2 enzyme activity caused by novel missense mutations identified in Brazilian and Scandinavian patients.

BACKGROUND: Most patients with 21-hydroxylase deficiency carry CYP21A1P-derived mutations, but an increasing number of novel and rare mutations have been reported in disease-causing alleles. OBJECTIVE: Functional effects of three novel (p.G56R, p.L107R, p.L142P) and one recurrent (p.R408C) CYP21A2 mutations were investigated. The degree of enzyme impairment caused by p.H62L alone or combined to p.P453S was also analyzed. DESIGN: The study included 10 Brazilian and two Scandinavian patients. To determine the deleterious role of each mutant protein, in vitro assays were performed in transiently transfected COS-1 cells. For a correct genotype-phenotype correlation, the enzymatic activities were evaluated toward the two natural substrates, 17-hydroxyprogesterone and progesterone. RESULTS: Low levels of residual activities obtained for p.G56R, p.L107R, p.L142P, and p.R408C mutants classified them as classical congenital adrenal hyperplasia mutations, whereas the p.H62L showed an activity within the range of nonclassical mutations. Apparent kinetic constants for p.H62L confirmed the nonclassical classification as the substrate binding capacity was within the same magnitude for mutant and normal enzymes. A synergistic effect was observed for the allele bearing the p.H62L+p.P453S combination because it caused a significant reduction in the enzymatic activity. CONCLUSIONS: We describe the functional analysis of five rare missense mutations identified in Brazilian and Scandinavian patients. The p.G56R, p.L107R, and p.L142P are reported for the first time. Most probably these novel mutations are closer to null than the p.I172N, but for the p.G56R, that might not be the case, and the p.H62L is definitely a nonclassical mutation.