9 research outputs found

    Identification and Functional Analysis of Light-Responsive Unique Genes and Gene Family Members in Rice

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    Functional redundancy limits detailed analysis of genes in many organisms. Here, we report a method to efficiently overcome this obstacle by combining gene expression data with analysis of gene-indexed mutants. Using a rice NSF45K oligo-microarray to compare 2-week-old light- and dark-grown rice leaf tissue, we identified 365 genes that showed significant 8-fold or greater induction in the light relative to dark conditions. We then screened collections of rice T-DNA insertional mutants to identify rice lines with mutations in the strongly light-induced genes. From this analysis, we identified 74 different lines comprising two independent mutant lines for each of 37 light-induced genes. This list was further refined by mining gene expression data to exclude genes that had potential functional redundancy due to co-expressed family members (12 genes) and genes that had inconsistent light responses across other publicly available microarray datasets (five genes). We next characterized the phenotypes of rice lines carrying mutations in ten of the remaining candidate genes and then carried out co-expression analysis associated with these genes. This analysis effectively provided candidate functions for two genes of previously unknown function and for one gene not directly linked to the tested biochemical pathways. These data demonstrate the efficiency of combining gene family-based expression profiles with analyses of insertional mutants to identify novel genes and their functions, even among members of multi-gene families

    Revealing the physical properties of chlorine-substituted poly(acetylene)

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    cis-3,4-Dichlorocyclobutene was synthesized and polymerized using the Grubbs 3(rd) generation catalyst. The corresponding ring-opening metathesis polymerization (ROMP) reaction proceeded in a controlled manner and provided access to narrowly dispersed polymers with tunable molecular weights. Treating poly(3,4-dichlorocyclobutene) with an organic base (e.g., triethylamine) prompted an elimination reaction and afforded poly(chloroethyne-ran-ethyne) in quantitative yield. The electrical conductivity of a film of the chlorine-substituted poly(acetylene) was measured and found to be comparable to values reported for organic semiconductors (10(-5) & omega;(-1) cm(-1)). Higher conductivity (10(-2) & omega;(-1) cm(-1)) values were achieved via p- or n-type doping. A block copolymer that featured a poly(norbornene) segment connected to a chlorine-substituted poly(acetylene) as well as a random copolymer derived from cis-3,4-dichlorocyclobutene and cis-2-ethylhexyl 4-chlorocyclobut-2-ene-1-carboxylate were also synthesized and studied. The copolymers displayed good solubility in organic solvents and valuable electronic properties. The polymers were characterized using various spectroscopic (NMR, FT-IR, UV-vis, XPS, and Raman) and thermal techniques as well as size exclusion chromatography (SEC).11Nsciescopu

    Exploring RNNs for analyzing Zeek HTTP data

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    Cyber vulnerabilities pose a threat across systems in the Department of Defense. Finding ways to analyze network traffic and detect malicious behavior on a network will help keep these systems safe. This poster looks at the data collection techniques, model creation, and results of building a recurrent neural network to classify incoming traffic as normal or malicious. Additionally, it considers how the information will be best portrayed on a GUI to network administrators. The model\u27s initial accuracy is 83.45% when trained on 500,017 connections. With increased accuracy, this tool may be used by the Department of Defense to help defend its networks

    The current state of the osteoarthritis drug development pipeline:a comprehensive narrative review of the present challenges and future opportunities

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    Abstract In this narrative review article, we critically assess the current state of the osteoarthritis (OA) drug development pipeline. We discuss the current state-of-the-art in relation to the development and evaluation of candidate disease-modifying OA drugs (DMOADs) and the limitations associated with the tools and methodologies that are used to assess outcomes in OA clinical trials. We focus on the definition of DMOADs, highlight the need for an updated definition in the form of a consensus statement from all the major stakeholders, including academia, industry, regulatory agencies, and patient organizations, and provide a summary of the results of recent clinical trials of novel DMOAD candidates. We propose that DMOADs should be more appropriately targeted and investigated according to the emerging clinical phenotypes and molecular endotypes of OA. Based on the findings from recent clinical trials, we propose key topics and directions for the development of future DMOADs

    TissueGene-C promotes an anti-inflammatory micro-environment in a rat monoiodoacetate model of osteoarthritis via polarization of M2 macrophages leading to pain relief and structural improvement

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    Abstract Osteoarthritis (OA) is the most common form of arthritis, characterized by cartilage destruction, pain and inflammation in the joints. Existing medications can provide relief from the symptoms, but their effects on the progression of the disease are limited. TissueGene-C (TG-C) is a novel cell and gene therapy for the treatment of OA, comprising a mixture of human allogeneic chondrocytes and irradiated cells engineered to overexpress transforming growth factor-Ξ²1 (TGF-Ξ²1). This study aims to investigate the efficacy and mechanism of action of TG-C in a rat model of OA. Using the monosodium-iodoacetate (MIA) model of OA, we examined whether TG-C could improve OA symptoms and cartilage structure in rats. Our results showed that TG-C provided pain relief and cartilage structural improvement in the MIA OA model over 56 days. In parallel with these long-term effects, cytokine profiles obtained on day 4 revealed increased expression of interleukin-10 (IL-10), an anti-inflammatory cytokine, in the synovial lavage fluid. Moreover, the increased levels of TGF-Ξ²1 and IL-10 caused by TG-C induced the expression of arginase 1, a marker of M2 macrophages, and decreased the expression of CD86, a marker of M1 macrophages. These results suggest that TG-C exerts a beneficial effect on OA by inducing a M2 macrophage-dominant micro-environment. Cell therapy using TG-C may be a promising strategy for targeting the underlying pathogenic mechanisms of OA, reducing pain, improving function, and creating a pro-anabolic micro-environment. This environment supports cartilage structure regeneration and is worthy of further evaluation in future clinical trials
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