1,526 research outputs found

    Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents.

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    HIV latency in resting CD4+ T cell represents a key barrier preventing cure of the infection with antiretroviral drugs alone. Latency reversing agents (LRAs) can activate HIV expression in latently infected cells, potentially leading to their elimination through virus-mediated cytopathic effects, host immune responses, and/or therapeutic strategies targeting cells actively expressing virus. We have recently described several structurally simplified analogs of the PKC modulator LRA bryostatin (termed bryologs) designed to improve synthetic accessibility, tolerability in vivo, and efficacy in inducing HIV latency reversal. Here we report the comparative performance of lead bryologs, including their effects in reducing cell surface expression of HIV entry receptors, inducing proinflammatory cytokines, inhibiting short-term HIV replication, and synergizing with histone deacetylase inhibitors to reverse HIV latency. These data provide unique insights into structure-function relationships between A- and B-ring bryolog modifications and activities in primary cells, and suggest that bryologs represent promising leads for preclinical advancement

    Genome-wide comparison of microRNAs and their targeted transcripts among leaf, flower and fruit of sweet orange

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    BACKGROUND: In plants, microRNAs (miRNAs) regulate gene expression mainly at the post-transcriptional level. Previous studies have demonstrated that miRNA-mediated gene silencing pathways play vital roles in plant development. Here, we used a high-throughput sequencing approach to characterize the miRNAs and their targeted transcripts in the leaf, flower and fruit of sweet orange. RESULTS: A total of 183 known miRNAs and 38 novel miRNAs were identified. An in-house script was used to identify all potential secondary siRNAs derived from miRNA-targeted transcripts using sRNA and degradome sequencing data. Genome mapping revealed that these miRNAs were evenly distributed across the genome with several small clusters, and 69 pre-miRNAs were co-localized with simple sequence repeats (SSRs). Noticeably, the loop size of pre-miR396c was influenced by the repeat number of CUU unit. The expression pattern of miRNAs among different tissues and developmental stages were further investigated by both qRT-PCR and RNA gel blotting. Interestingly, Csi-miR164 was highly expressed in fruit ripening stage, and was validated to target a NAC transcription factor. This study depicts a global picture of miRNAs and their target genes in the genome of sweet orange, and focused on the comparison among leaf, flower and fruit tissues. CONCLUSIONS: This study provides a global view of miRNAs and their target genes in different tissue of sweet orange, and focused on the identification of miRNA involved in the regulation of fruit ripening. The results of this study lay a foundation for unraveling key regulators of orange fruit development and ripening on post-transcriptional level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-695) contains supplementary material, which is available to authorized users

    An Analysis of the Environmental Behavior of the Enterprises in Ningxia

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    科学研究費補助金 研究種目:基盤研究(B)(1) 課題番号:12430008 研究代表者:荒山裕行 研究期間:2000-2002年度research repor

    Deep Quantigraphic Image Enhancement via Comparametric Equations

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    Most recent methods of deep image enhancement can be generally classified into two types: decompose-and-enhance and illumination estimation-centric. The former is usually less efficient, and the latter is constrained by a strong assumption regarding image reflectance as the desired enhancement result. To alleviate this constraint while retaining high efficiency, we propose a novel trainable module that diversifies the conversion from the low-light image and illumination map to the enhanced image. It formulates image enhancement as a comparametric equation parameterized by a camera response function and an exposure compensation ratio. By incorporating this module in an illumination estimation-centric DNN, our method improves the flexibility of deep image enhancement, limits the computational burden to illumination estimation, and allows for fully unsupervised learning adaptable to the diverse demands of different tasks.Comment: Published in ICASSP 2023. For GitHub code, see https://github.com/nttcslab/con
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