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The circadian oscillator, an internal time-keeping device found in most organisms, enables timely regulation of daily biological activities by maintaining synchrony with the external environment. The mechanistic basis underlying the adjustment of circadian rhythms to changing external conditions, however, has yet to be clearly elucidated. We explored the mechanism of action of nicotinamide in Arabidopsis thaliana , a metabolite that lengthens the period of circadian rhythms, to understand the regulation of circadian period. To identify the key mechanisms involved in the circadian response to nicotinamide, we developed a systematic and practical modeling framework based on the identification and comparison of gene regulatory dynamics. Our mathematical predictions, confirmed by experimentation, identified key transcriptional regulatory mechanisms of circadian period and uncovered the role of blue light in the response of the circadian oscillator to nicotinamide. We suggest that our methodology could be adapted to predict mechanisms of drug action in complex biological systems.

Carotid atherosclerosis is a major reason of stroke, a leading cause of death and disability. In this paper, a segmentation method based on Active Shape Model (ASM) is developed and evaluated to outline common carotid artery (CCA) for carotid atherosclerosis computer-aided evaluation and diagnosis. The proposed method is used to segment both media-adventitia-boundary (MAB) and lumen-intima-boundary (LIB) on transverse views slices from three-dimensional ultrasound (3D US) images. The data set consists of sixty-eight, 17 × 2 × 2, 3D US volume data acquired from the left and right carotid arteries of seventeen patients (eight treated with 80 mg atorvastatin and nine with placebo), who had carotid stenosis of 60% or more, at baseline and after three months of treatment. Manually outlined boundaries by expert are adopted as the ground truth for evaluation. For the MAB and LIB segmentations, respectively, the algorithm yielded Dice Similarity Coefficient (DSC) of 94.4% ± 3.2% and 92.8% ± 3.3%, mean absolute distances (MAD) of 0.26 ± 0.18 mm and 0.33 ± 0.21 mm, and maximum absolute distances (MAXD) of 0.75 ± 0.46 mm and 0.84 ± 0.39 mm. It took 4.3 ± 0.5 mins to segment single 3D US images, while it took 11.7 ± 1.2 mins for manual segmentation. The method would promote the translation of carotid 3D US to clinical care for the monitoring of the atherosclerotic disease progression and regression.

Vascular segmentation plays an important role in medical image analysis. A novel technique for the automatic extraction of vascular trees from 2D medical images is presented, which combines Hessian-based multiscale filtering and a modified level set method. In the proposed algorithm, the morphological top-hat transformation is firstly adopted to attenuate background. Then Hessian-based multiscale filtering is used to enhance vascular structures by combining Hessian matrix with Gaussian convolution to tune the filtering response to the specific scales. Because Gaussian convolution tends to blur vessel boundaries, which makes scale selection inaccurate, an improved level set method is finally proposed to extract vascular structures by introducing an external constrained term related to the standard deviation of Gaussian function into the traditional level set. Our approach was tested on synthetic images with vascular-like structures and 2D slices extracted from real 3D abdomen magnetic resonance angiography (MRA) images along the coronal plane. The segmentation rates for synthetic images are above 95%. The results for MRA images demonstrate that the proposed method can extract most of the vascular structures successfully and accurately in visualization. Therefore, the proposed method is effective for the vascular tree extraction in medical images.

Anoctamin/TMEM16 family members have recently been identified as novel calcium-activated chloride channels, and dysregulation of many family members participates in tumorigenesis and progression. However, the exact role of anoctamin5 (ANO5), one member of this family, in thyroid cancer is still not clarified. In this study, we firstly found that the expression levels of ANO5 was significantly downregulated in thyroid cancer compared to adjacent normal tissue by mining the public GEO database. Subsequently, we further demonstrated that the expression levels of ANO5 was significantly downregulated in 69.5% (57/82) clinical thyroid cancer tissues using real-time PCR assay. Moreover, western blot assay also showed that ANO5 was downregulated in papillary thyroid cancer and follicular thyroid cancer compared to adjacent noncancerous tissues. Furthermore, some biological and functional in vitro experiments proved that ANO5 knockdown promotes thyroid cancer cell migration and invasion but overexpression of ANO5 inhibits these phenotypes. By analyzing gene set enrichment, we found that lower ANO5 expression was positively associated with JAK/STAT3 signaling pathway. Collectively downregulation of ANO5 promotes thyroid cancer cell migration and invasion by affecting JAK/STAT3 pathway.

Carotid atherosclerosis is a major cause of stroke, a leading cause of death and disability. In this paper, we develop and evaluate a new segmentation method for outlining both lumen and adventitia (inner and outer walls) of common carotid artery (CCA) from three-dimensional ultrasound (3D US) images for carotid atherosclerosis diagnosis and evaluation. The data set consists of sixty-eight, 17 × 2 × 2, 3D US volume data acquired from the left and right carotid arteries of seventeen patients (eight treated with 80mg atorvastain and nine with placebo), who had carotid stenosis of 60% or more, at baseline and after three months of treatment. We investigate the use of Active Shape Models (ASMs) to segment CCA inner and outer walls after statin therapy. The proposed method was evaluated with respect to expert manually outlined boundaries as a surrogate for ground truth. For the lumen and adventitia segmentations, respectively, the algorithm yielded Dice Similarity Coefficient (DSC) of 93.6% ± 2.6%, 91.8% ± 3.5%, mean absolute distances (MAD) of 0.28 ± 0.17mm and 0.34 ± 0.19mm, maximum absolute distances (MAXD) of 0.87 ± 0.37mm and 0.74 ± 0.49mm. The proposed algorithm took 4.4 ± 0.6min to segment a single 3D US images, compared to 11.7 ± 1.2min for manual segmentation. Therefore, the method would promote the translation of carotid 3D US to clinical care for the fast, safety and economical monitoring of the atherosclerotic disease progression and regression during therapy.

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