Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases. 相似文献
In this paper we present some preliminary results about the coupling of shallow water equations for free surface flows and Darcy equation for groundwater flows. A suitable set of interface conditions is discussed: the Beavers and Joseph formula for the bottom stress is used. An iterative algorithm to solve the coupled problem is proposed and some numerical results are presented. 相似文献
We used KO mice lacking either TNF receptor 1 (TNFR-1) or receptor 2 (TNFR-2) to determine whether signaling at the start of liver regeneration after partial hepatectomy (PH) involves only one or both TNF receptors and to analyze in more detail the abnormalities caused by lack of TNFR-1 receptor, which is required for the initiation of liver regeneration. Lack of TNFR-2 had little effect on NF-kappaB and STAT3 binding, and no effect in interleukin-6 production after PH, but caused a delay in AP-1 and C/EBP binding and in the expression of c-jun and c-myc messenger RNA (mRNA). In contrast to mice lacking TNFR-1, which had deficient hepatocyte DNA synthesis and massive lipid accumulation in hepatocytes, TNFR-2 KO mice had normal liver structure and similar levels of hepatocyte DNA replication as those of wild type mice. We conclude that TNFR-1, but not TNFR-2, is necessary for liver regeneration, and that NF-kappaB and STAT3 binding are activated by signals transduced by TNFR-1. Inhibition of AP-1 and C/EBP binding and in the expression of c-jun and c-myc mRNA in the first 4 hours after PH, as well as the apparent lack of Fos in AP-1 complexes, had no effect on the timing or extent of DNA replication. 相似文献
The acid activity dependence of pzc for the mercury—perchloric acid aqueous solution interphase was studied, and the results compared with previously reported values. Then, the pzc shift caused by tetraethylammonium (TEA) perchlorate addition to constant activity perchloric acid solutions is reported, and an expression for the Esin—Markov coefficient is given. The need for using activity values is discussed on the basis of quantitive data. 相似文献
The state of the art of searching for non-text data (e.g., images) is to use extracted metadata annotations or text, which might be available as a related information. However, supporting real content-based audiovisual search, based on similarity search on features, is significantly more expensive than searching for text. Moreover, such search exhibits linear scalability with respect to the dataset size, so parallel query execution is needed.In this paper, we present a Distributed Incremental Nearest Neighbor algorithm (DINN) for finding closest objects in an incremental fashion over data distributed among computer nodes, each able to perform its local Incremental Nearest Neighbor (local-INN) algorithm. We prove that our algorithm is optimum with respect to both the number of involved nodes and the number of local-INN invocations. An implementation of our DINN algorithm, on a real P2P system called MCAN, was used for conducting an extensive experimental evaluation on a real-life dataset.The proposed algorithm is being used in two running projects: SAPIR and NeP4B. 相似文献
Motivated by the urgent need to improve the efficiency of similarity queries, approximate similarity retrieval is investigated
in the environment of a metric tree index called the M-tree. Three different approximation techniques are proposed, which
show how to forsake query precision for improved performance. Measures are defined that can quantify the improvements in performance
efficiency and the quality of approximations. The proposed approximation techniques are then tested on various synthetic and
real-life files. The evidence obtained from the experiments confirms our hypothesis that a high-quality approximated similarity
search can be performed at a much lower cost than that needed to obtain the exact results. The proposed approximation techniques
are scalable and appear to be independent of the metric used. Extensions of these techniques to the environments of other
similarity search indexes are also discussed.
Received July 7, 1998 / Accepted October 13, 1998 相似文献
Our goal in this paper is to introduce and motivate a methodology, called Tropos,1 for building agent oriented software systems. Tropos is based on two key ideas. First, the notion of agent and all related mentalistic notions (for instance goals and plans) are used in all phases of software development, from early analysis down to the actual implementation. Second, Tropos covers also the very early phases of requirements analysis, thus allowing for a deeper understanding of the environment where the software must operate, and of the kind of interactions that should occur between software and human agents. The methodology is illustrated with the help of a case study. The Tropos language for conceptual modeling is formalized in a metamodel described with a set of UML class diagrams. 相似文献
Visually impaired individuals often rely on assistive technologies such as white canes for independent navigation. Many electronic enhancements to the traditional white cane have been proposed. However, only a few of these proof-of-concept technologies have been tested with authentic users, as most studies rely on blindfolded non-visually impaired participants or no testing with participants at all. Experiments involving blind users are usually not contrasted with the traditional white cane. This study set out to compare an ultrasound-based electronic cane with a traditional white cane. Moreover, we also compared the performance of a group of visually impaired participants (N = 10) with a group of blindfolded participants without visual impairments (N = 31). The results show that walking speed with the electronic cane is significantly slower compared to the traditional white cane. Moreover, the results show that the performance of the participants without visual impairments is significantly slower than for the visually impaired participants. No significant differences in obstacle detection rates were observed across participant groups and device types for obstacles on the ground, while 79% of the hanging obstacles were detected by the electronic cane. The results of this study thus suggest that electronic canes present only one advantage over the traditional cane, namely in its ability to detect hanging obstacles, at least without prolonged practice. Next, blindfolded participants are insufficient substitutes for blind participants who are expert cane users. The implication of this study is that research into digital white cane enhancements should include blind participants. These participants should be followed over time in longitudinal experiments to document if practice will lead to improvements that surpass the performance achieved with traditional canes.