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  1. Free, publicly-accessible full text available October 12, 2023
  2. A body of studies has proposed to obtain high-quality images from low-dose and noisy Computed Tomography (CT) scans for radiation reduction. However, these studies are designed for population-level data without considering the variation in CT devices and individuals, limiting the current approaches' performance, especially for ultra-low-dose CT imaging. Here, we proposed PIMA-CT, a physical anthropomorphic phantom model integrating an unsupervised learning framework, using a novel deep learning technique called Cyclic Simulation and Denoising (CSD), to address these limitations. We first acquired paired low-dose and standard-dose CT scans of the phantom and then developed two generative neural networks: noise simulator and denoiser. The simulator extracts real low-dose noise and tissue features from two separate image spaces (e.g., low-dose phantom model scans and standard-dose patient scans) into a unified feature space. Meanwhile, the denoiser provides feedback to the simulator on the quality of the generated noise. In this way, the simulator and denoiser cyclically interact to optimize network learning and ease the denoiser to simultaneously remove noise and restore tissue features. We thoroughly evaluate our method for removing both real low-dose noise and Gaussian simulated low-dose noise. The results show that CSD outperforms one of the state-of-the-art denoising algorithms without using anymore »labeled data (actual patients' low-dose CT scans) nor simulated low-dose CT scans. This study may shed light on incorporating physical models in medical imaging, especially for ultra-low level dose CT scans restoration.« less
    Free, publicly-accessible full text available May 25, 2023
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  6. Abstract Maternal-to-filial nutrition transfer is central to grain development and yield. nitrate transporter 1/peptide transporter (NRT1-PTR)-type transporters typically transport nitrate, peptides, and ions. Here, we report the identification of a maize (Zea mays) NRT1-PTR-type transporter that transports sucrose and glucose. The activity of this sugar transporter, named Sucrose and Glucose Carrier 1 (SUGCAR1), was systematically verified by tracer-labeled sugar uptake and serial electrophysiological studies including two-electrode voltage-clamp, non-invasive microelectrode ion flux estimation assays in Xenopus laevis oocytes and patch clamping in HEK293T cells. ZmSUGCAR1 is specifically expressed in the basal endosperm transfer layer and loss-of-function mutation of ZmSUGCAR1 caused significantly decreased sucrose and glucose contents and subsequent shrinkage of maize kernels. Notably, the ZmSUGCAR1 orthologs SbSUGCAR1 (from Sorghum bicolor) and TaSUGCAR1 (from Triticum aestivum) displayed similar sugar transport activities in oocytes, supporting the functional conservation of SUGCAR1 in closely related cereal species. Thus, the discovery of ZmSUGCAR1 uncovers a type of sugar transporter essential for grain development and opens potential avenues for genetic improvement of seed-filling and yield in maize and other grain crops.
    Free, publicly-accessible full text available September 1, 2023
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  10. Naturally occurring enzymes can be a source of unnatural reactivity that can be molded by directed evolution to generate efficient biocatalysts with valuable activities. Owing to the lack of exploitable stereocontrol elements in synthetic systems, steering the absolute and relative stereochemistry of free-radical processes is notoriously difficult in asymmetric catalysis. Inspired by the innate redox properties of first-row transition-metal cofactors, we repurposed cytochromes P450 to catalyze stereoselective atom-transfer radical cyclization. A set of metalloenzymes was engineered to impose substantial stereocontrol over the radical addition step and the halogen rebound step in these unnatural processes, allowing enantio- and diastereodivergent radical catalysis. This evolvable metalloenzyme platform represents a promising solution to tame fleeting radical intermediates for asymmetric catalysis.
    Free, publicly-accessible full text available December 24, 2022