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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
2.
Navab SinghAuthor Vitae Moitreyee Mukherjee-RoyAuthor VitaeSohan Singh MehtaAuthor Vitae 《Microelectronics Journal》2003,34(4):237-245
The patterning of contact holes by selecting out-of-focus image plane (defocus) using attenuated phase shift masks (APSM) has been studied. Defocus is found to enhance the image modulation at low partial coherence for contact holes with negative local average of mask function. Semi-dense holes up to 130 nm in 8% APSM have been printed by 0.5 μm defocus at a partial coherence of 0.31 using KrF scanner with highest numerical aperture of 0.68. However, these holes were closed with in-focus imaging. Defocus is also found to be beneficial for patterning the pitches that have extensive side lobes with in-focus imaging. 相似文献
3.
M Furuta K Hayakawa S Katano Y Saito Y Nakayama T Takahashi R Imai T Ebara N Mitsuhashi H Niibe 《Canadian Metallurgical Quarterly》1996,26(2):95-98
Vaccination with peptides that induce a specific immune response is a potential prophylactic or therapeutic strategy against viral infections and tumors. Because of the extensive polymorphism of the HLA loci, synthetic peptide vaccines must consist of a cocktail of peptides that bind specifically to different HLA molecules. Such cocktails should be optimized for the target population as each population has its specific HLA gene frequencies. To achieve maximum population coverage with a minimum number of peptides, information is needed on the ranking of the most frequent HLA phenotypes. We introduce the minimal phenotype panel, which is the smallest combination of HLA antigens selected so that the proportion of individuals in a population that express at least one of the antigens in the panel exceeds a desired minimum value. We developed a method for assembling minimal phenotype panels based on known HLA class I gene frequencies. We give an example based on a set of 2446 well-defined HLA-typed, random, healthy, unrelated, Dutch Caucasoid individuals. In addition, we discuss the possibility of assembling minimal phenotype panels based on two-locus haplotypes, which enables the assembly of phenotype panels from the antigens of both loci. 相似文献
4.
This review is written to evaluate the stereoselectivity in cutaneous hydrolysis and transdermal transport of propranolol prodrug. This discussion will be useful in the development of knowledge about stereoselective cutaneous hydrolysis and its influence on stereoselective transdermal transport of many other chiral prodrugs and drugs. Propranolol prodrugs undergo stereoselective hydrolysis in hairless mouse skin homogenate and in excised skin samples during permeation; the stereoselectivity is markedly biased towards hydrolysis of the (R) isomer. Unlike the liver, the esterase activity of the skin is high in its cytosolic fraction. Most of the lipophilic propranolol prodrugs cause stereoselective permeation across hairless mouse skin. A mechanism of stereoselective permeation of propranolol prodrug across the skin has been proposed, which indicates that the stereoselectivity in permeation is resulted from the stereoselective hydrolysis of lipophilic prodrug during permeation. 相似文献
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A stochastic realization problem of a stationary stochastic process is re-visited, and a new stochastically balanced realization algorithm is derived in a Hilbert space generated by second-order stationary processes. The present algorithm computes a stochastically balanced realization by means of the singular value decomposition of a weighted block Hankel matrix derived by a “block LQ decomposition”. Extension to a stochastic subspace identification method explains how the proposed abstract algorithm is implemented in system identification. 相似文献
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8.
Chia-Jung Pai Author Vitae Author Vitae Yu-Ming Liang Author Vitae Author Vitae Sei-Wang Chen Author Vitae 《Pattern recognition》2004,37(5):1025-1034
This paper presents a system that can perform pedestrian detection and tracking using vision-based techniques. A very important issue in the field of intelligent transportation system is to prevent pedestrians from being hit by vehicles. Recently, a great number of vision-based techniques have been proposed for this purpose. In this paper, we propose a vision-based method, which combines the use of a pedestrian model as well as the walking rhythm of pedestrians to detect and track walking pedestrians. Through integrating some spatial and temporal information grabbed by a vision system, we are able to develop a reliable system that can be used to prevent traffic accidents happened at crossroads. In addition, the proposed system can deal with the occlusion problem. Experimental results obtained by executing some real world cases have demonstrated that the proposed system is indeed superb. 相似文献
9.
V. Rodin Author Vitae A. Benzinou Author VitaeAuthor Vitae P. Ballet Author VitaeAuthor Vitae J. Tisseau Author VitaeAuthor Vitae 《Pattern recognition》2004,37(4):631-645
In this article, we present a parallel image processing system based on the concept of reactive agents. Our system lies in the oRis language, which allows to describe finely and simply the agents’ behaviors to detect image features. We also present a method of segmentation using a multi-agent system, and two biological applications made with oRis. The stopping of this multi-agent system is implemented through a technique issued from immunology: the apoptosis. 相似文献
10.