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Deepa Jonnalagadda Debin Wan Jerold Chun Bruce D. Hammock Yasuyuki Kihara 《International journal of molecular sciences》2021,22(9)
Polyunsaturated fatty acids (PUFAs) are essential FAs for human health. Cytochrome P450 oxygenates PUFAs to produce anti-inflammatory and pain-resolving epoxy fatty acids (EpFAs) and other oxylipins whose epoxide ring is opened by the soluble epoxide hydrolase (sEH/Ephx2), resulting in the formation of toxic and pro-inflammatory vicinal diols (dihydroxy-FAs). Pharmacological inhibition of sEH is a promising strategy for the treatment of pain, inflammation, cardiovascular diseases, and other conditions. We tested the efficacy of a potent, selective sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), in an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Prophylactic TPPU treatment significantly ameliorated EAE without affecting circulating white blood cell counts. TPPU accumulated in the spinal cords (SCs), which was correlated with plasma TPPU concentration. Targeted lipidomics in EAE SCs and plasma identified that TPPU blocked production of dihydroxy-FAs efficiently and increased some EpFA species including 12(13)-epoxy-octadecenoic acid (12(13)-EpOME) and 17(18)-epoxy-eicosatrienoic acid (17(18)-EpETE). TPPU did not alter levels of cyclooxygenase (COX-1/2) metabolites, while it increased 12-hydroxyeicosatetraenoic acid (12-HETE) and other 12/15-lipoxygenase metabolites. These analytical results are consistent with sEH inhibitors that reduce neuroinflammation and accelerate anti-inflammatory responses, providing the possibility that sEH inhibitors could be used as a disease modifying therapy, as well as for MS-associated pain relief. 相似文献
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Tindall CI Moore RV Bosley JD Swetnam RD Bowie R De Rudder A 《The Science of the total environment》2006,360(1-3):223-232
The Urban Regeneration and the Environment Research Programme (URGENT) required a system for cataloguing its datasets and enabling its scientific community to discover what data were available to it. This community was multidisciplinary in nature and therefore needed a range of facilities for searching. Of particular importance were facilities to help those unfamiliar with specialist terminology. To meet these needs, four applications were designed and developed: a Metadata Capture Tool for describing datasets in compliance with the National Geospatial Data Framework (NGDF) standard, a Term Entry Tool for creating an ISO compliant thesaurus, a Thesaurus Builder for merging thesauri and a Search Tool. To encourage users to help in cataloguing data, the capture tools were written as stand alone applications, which users could keep and use to build their own metadatabases. The tools contained export and import facilities that allowed the URGENT Data Centre to build a central database and publish it upon the web. During the development work, it was found necessary to extend the NGDF standard as it could not adequately describe time variant or 3-D atmospheric datasets. The four applications met their design objectives. However, a number of ergonomic issues will need to be addressed if the system is to meet the needs of the much larger up coming programmes. The main challenges will be moving from the NGDF standard to the ISO standard, hence bringing the work into line with the recommendations of the INSPIRE Project, and merging the metadatabase with the scientific database, which enable metadata maintenance to be semi-automated. 相似文献
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Exploring laccase and mediators behavior during saccharification and fermentation of steam‐exploded wheat straw for bioethanol production 下载免费PDF全文
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In cloud storage systems, more than 50% of requests are metadata operations, and thus the file system metadata search performance has become increasingly important to different users. With the rapid growth of storage system scales in volume, traditional full-size index trees cannot offer high-performance metadata search due to hierarchical indexing bottleneck. In order to alleviate the long latency and improve the quality-of-service (QoS) in cloud storage service, we proposed a novel provenance based metadata-search system, called PROMES. The metadata search in PROMES is split into three phases: (i) leveraging correlation-aware metadata index tree to identify several files as seeds, most of which can satisfy the query requests, (ii) using the seeds to find the remaining query results via relationship graph search, (iii) continuing to refine and rerank the whole search results, and sending the final results to users. PROMES has the salient features of high query accuracy and low latency, due to files’ tight and lightweight indexing in relationship graph coming from provenance’s analysis. Compared with state-of-the-art metadata searching schemes, PROMES demonstrates its efficiency and efficacy in terms of query accuracy and response latency. 相似文献
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Francesco Losurdo Alessandro Marra Ernesto Cassetta Umberto Monarca Ivano Dileo Vittorio Carlei 《Papers in Regional Science》2019,98(2):737-753
In order to overcome the limitations of defining industrial specializations in digital industries through SIC codes, this paper suggests measuring the specializations and competences of these industries on the basis of the degree of digital technologies present in the products and services supplied. Metadata from CrunchBase are employed, as proxies of firms' specializations and competences which are defined as the fields of activity in which firms are involved. Applying a network analysis, these specializations and competences are linked to the recognition of emerging digital technologies and the strongest combinations of products and services. We tested the proposed methodology on London, a leading centre for the digital economy. 相似文献
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Triclosan (TCS), an antimicrobial agent, is an emerging and persistent environmental pollutant that is often found as a contaminant in surface waters and sediments; hence, knowledge of its degradability is important. In this study we investigated laccase-mediated TCS transformation and detoxification, using laccase (from the fungus Ganoderma lucidum) in the presence and absence of redox mediators. Transformation products were identified using HPLC, ESI-MS and GC-MS, and transformation mechanisms were proposed. In the absence of redox mediator, 56.5% TCS removal was observed within 24 h, concomitant with formation of new products with molecular weights greater than that of TCS. These products were dimers and trimers of TCS, as confirmed by ESI-MS analysis. Among the various mediators tested, 1-hydroxybenzotriazole (HBT) and syringaldehyde (SYD) significantly enhanced TCS transformation (∼90%). The presence of these mediators resulted in products with lower molecular weights than TCS, including 2,4-dichlorophenol (2,4-DCP; confirmed by GC-MS) and dechlorinated forms of 2,4-DCP. When SYD was used as the mediator, dechlorination resulted in 2-chlorohydroquinone (2-CHQ). Bacterial growth inhibition studies revealed that laccase-mediated transformation of TCS effectively decreased its toxicity, with ultimate conversion to less toxic or nontoxic products. Our results confirmed the involvement of two mechanisms of laccase-catalyzed TCS removal: (i) oligomerization in the absence of redox mediators, and (ii) ether bond cleavage followed by dechlorination in the presence of redox mediators. These results suggest that laccase in combination with natural redox mediator systems may be a useful strategy for the detoxification and elimination of TCS from aqueous systems. 相似文献