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1.
Jun Ogata Kentaro Hirao Kenya Nishioka Arisa Hayashida Yuanzhe Li Hiroyo Yoshino Soichiro Shimizu Nobutaka Hattori Yuzuru Imai 《International journal of molecular sciences》2021,22(7)
Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity. 相似文献
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In this article, we study a linear array of bowtie nanoantennas placed between two metallic strips that can work from 800 to 1420 nm (600 nm linewidth), with an electric field enhancement factor close to 20. We study the dynamical change of the position of the electric field enhancement amongst different elements in the array and, at the same time, the effects of dispersion on the scalability of the array elements. A systematic analysis and methodology to produce an array that can operate over a large bandwidth whilst maintaining the electric field enhancement without significant variation is provided. 相似文献
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The very late antigen-4 (VLA-4) integrin expressed on the surface of lymphocytes and macrophages can regulate their migration to inflammatory sites as well as control cellular activation. The role of VLA-4 in the establishment of autoimmune diabetes is not easily predicted given the multiplicity of adhesion pathways and their differential use by various cell types. The contribution of VLA-4 to insulin-dependent diabetes mellitus was investigated by administration of VLA-4-specific monoclonal antibodies (MoAb) in an adoptive transfer model of disease in NOD mice. This study shows that VLA-4-specific MoAbs profoundly inhibit the development of diabetes with protection sustained by repeated MoAb exposure. Insulitis was completely inhibited during treatment and progressed to a severe degree once MoAb treatment was suspended, yet approximately 40% of treated recipients failed to become diabetic during 1-2 months post-treatment. Although we cannot rule out depletion of a relatively minor subpopulation of cells by prolonged anti-VLA-4 MoAb exposure, this inhibition of diabetes onset by treatment with MoAbs to VLA-4 supports a dependence on VLA-4 for cellular functions leading to diabetes and demonstrates that a significant disease modifying effect can be mediated by targeting the VLA-4 integrin. 相似文献
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Toru Ikegami Hideyuki Negishi Dai Kitamoto Keiji Sakaki Tomohiro Imura Masayoshi Okamoto Yasushi Idemoto Nobuyuki Koura Tsuneji Sano Kenji Haraya Hiroshi Yanagishita 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2005,80(4):381-387
In order to produce highly concentrated bioethanol by pervaporation using an ethanol‐permselective silicalite membrane, techniques to suppress adsorption of succinic acid, which is a chief by‐product of ethanol fermentation and causes the deterioration in pervaporation performance, onto the silicalite crystals was investigated. The amount adsorbed increased as the pH of the aqueous succinic acid solution decreased. The pervaporation performance also decreased with decreasing pH when the ternary mixtures of ethanol/water/succinic acid were separated. Using silicalite membranes individually coated with two types of silicone rubber, pervaporation performance was significantly improved in the pH range of 5 to 7, when compared with that of non‐coated silicalite membranes in ternary mixtures of ethanol/water/succinic acid. Moreover, when using a silicalite membrane double‐coated with the two types of silicone rubber, pervaporation performance was stabilized at lower pH values. In the separation of bioethanol by pervaporation using the double‐coated silicalite membrane, removal of accumulated substances having an ultraviolet absorption maximum at approximately 260 nm from the fermentation broth proved to be vital for efficient pervaporation. Copyright © 2005 Society of Chemical Industry 相似文献
6.
A novel dynamic survivable routing in WDM optical networks with/without sparse wavelength conversion
Vinh Trong Le Xiaohong Jiang Son Hong Ngo Susumu Horiguchi Yasushi Inoguchi 《Optical Switching and Networking》2006,3(3-4):173-190
In this paper, we study the dynamic survivable routing problem, both in optical networks without wavelength conversion and in optical networks with sparse wavelength conversion, and propose a novel hybrid algorithm for it based on the combination of mobile agents technique and genetic algorithms (GA). By keeping a suitable number of mobile agents in the network to cooperatively explore the network states and continuously report cycles (that are formed by two disjoint-link routes) into the routing tables, our new hybrid algorithm can promptly determine the first population of cycles for a new request based on the routing table of its source node, without the time consuming process associated with current GA-based lightpath protection schemes. We further improve the performance of our algorithm by introducing a more advanced fitness function that is suitable for both the above networks. Extensive simulation studies on the ns-2 network simulator show that our hybrid algorithm achieves a significantly lower blocking probability than the conventional survivable routing algorithms for all the cases we studied. 相似文献
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The effect of plasma elongation on the second‐stable spherical tokamak (ST) was numerically studied using the experimentally measured pressure and current profiles of ultrahigh‐beta STs. The maximum beta of ST over 50% was obtained in the TS‐3 ST/CT experiment by applying an external toroidal field to an FRC. It was found that the marginal beta for the ballooning instability increased with the plasma elongation κ of ST. The elongated STs with κ > 2 have the magnetic shear (S)–pressure gradient (α) profiles located in the second‐stable regime for the ballooning mode and the stability margin increased with κ. The close relation between the absolute minimum‐B profile and the second stability was documented. The effect of elongation on maximum beta was observed to saturate when κ exceed 3, indicating that the optimized elongation for high‐beta STs is located around 2 < κ < 3. © 2006 Wiley Periodicals, Inc. Electr Eng Jpn, 155(4): 1–6, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20132 相似文献
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