502 research outputs found

    Recognition of paper currencies by hybrid neural network

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    For the recognition of paper currencies by image processing, the two steps data processing approach can yield high performance. The two steps include “recognition” and “verification” steps. In the current recognition machine, a simple statistical test is used as the verification step, where univariate Gaussian distribution is employed. Here we propose the use of the probability density formed by a multivariable Gaussian function, where the input data space is transferred to a lower dimensional subspace. Due to the structure of this model, we refer the total processing system as a hybrid neural network. Since the computation of the verification model only needs the inner product and square, the computational load is very small. In this paper, the method and numerical experimental results are shown by using the real data and the recognition machine</p

    Design of nucleic acid sequences for DNA computing based on a thermodynamic approach

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    We have developed an algorithm for designing multiple sequences of nucleic acids that have a uniform melting temperature between the sequence and its complement and that do not hybridize non-specifically with each other based on the minimum free energy (ΔG(min)). Sequences that satisfy these constraints can be utilized in computations, various engineering applications such as microarrays, and nano-fabrications. Our algorithm is a random generate-and-test algorithm: it generates a candidate sequence randomly and tests whether the sequence satisfies the constraints. The novelty of our algorithm is that the filtering method uses a greedy search to calculate ΔG(min). This effectively excludes inappropriate sequences before ΔG(min) is calculated, thereby reducing computation time drastically when compared with an algorithm without the filtering. Experimental results in silico showed the superiority of the greedy search over the traditional approach based on the hamming distance. In addition, experimental results in vitro demonstrated that the experimental free energy (ΔG(exp)) of 126 sequences correlated well with ΔG(min) (|R| = 0.90) than with the hamming distance (|R| = 0.80). These results validate the rationality of a thermodynamic approach. We implemented our algorithm in a graphic user interface-based program written in Java

    The effect of a child rearing support program, wherein preschoolers interact with children at the kindergarten they intend to enroll in, on parents: An analysis of the written comments of parents of preschool children who participated in the program at their prospective kindergarten

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    In this study, we focused on the period before the transition of children from home to kindergarten life. We aimed to describe the consciousness of the parents of the children, who interacted with the children of the kindergarten into which they were planning to enroll, as part of a child rearing program (hereinafter referred to as “the program”). We also considered the effects of the program and the various considerations of implementing it. The parents were asked for their impressions of the program via a questionnaire, which was analyzed by Steps Coding and Theorization (SCAT). The results indicated that parents were able to confirm the validity of their choice of kindergarten by participating in this program. It also became clear that the parents were able to form and update their views on their own children’s development through comparison with the kindergarten children, and that these experiences were intertwined with their anxiety about their children’s current situation and their expectations of kindergarten life

    Neuropathology and Therapeutic Intervention in Spinal and Bulbar Muscular Atrophy

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    Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). The histopathological finding in SBMA is loss of lower motor neurons in the anterior horn of the spinal cord as well as in the brainstem motor nuclei. Animal studies have revealed that the pathogenesis of SBMA depends on the level of serum testosterone, and that androgen deprivation mitigates neurodegeneration through inhibition of nuclear accumulation of the pathogenic AR. Heat shock proteins, ubiquitin-proteasome system and transcriptional regulation are also potential targets of therapy development for SBMA

    Current Status of Treatment of Spinal and Bulbar Muscular Atrophy

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    Spinal and bulbar muscular atrophy (SBMA) is the first member identified among polyglutamine diseases characterized by slowly progressive muscle weakness and atrophy of the bulbar, facial, and limb muscles pathologically associated with motor neuron loss in the spinal cord and brainstem. Androgen receptor (AR), a disease-causing protein of SBMA, is a well-characterized ligand-activated transcription factor, and androgen binding induces nuclear translocation, conformational change and recruitment of coregulators for transactivation of AR target genes. Some therapeutic strategies for SBMA are based on these native functions of AR. Since ligand-induced nuclear translocation of mutant AR has been shown to be a critical step in motor neuron degeneration in SBMA, androgen deprivation therapies using leuprorelin and dutasteride have been developed and translated into clinical trials. Although the results of these trials are inconclusive, renewed clinical trials with more sophisticated design might prove the effectiveness of hormonal intervention in the near future. Furthermore, based on the normal function of AR, therapies targeted for conformational changes of AR including amino-terminal (N) and carboxy-terminal (C) (N/C) interaction and transcriptional coregulators might be promising. Other treatments targeted for mitochondrial function, ubiquitin-proteasome system (UPS), and autophagy could be applicable for all types of polyglutamine diseases

    Microglia in Alzheimer's Disease: Risk Factors and Inflammation

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    Microglia are resident immune cells in the central nervous system (CNS) that originate from myeloid progenitor cells in the embryonic yolk sac and are maintained independently of circulating monocytes throughout life. In the healthy state, microglia are highly dynamic and control the environment by rapidly extending and retracting their processes. When the CNS is inflamed, microglia can give rise to macrophages, but the regulatory mechanisms underlying this process have not been fully elucidated. Recent genetic studies have suggested that microglial function is compromised in Alzheimer's disease (AD), and that environmental factors such as diet and brain injury also affect microglial activation. In addition, studies of triggering receptor expressed on myeloid cells 2-deficiency in AD mice revealed heterogeneous microglial reactions at different disease stages, complicating the therapeutic strategy for AD. In this paper, we describe the relationship between genetic and environmental risk factors and the roles of microglia in AD pathogenesis, based on studies performed in human patients and animal models. We also discuss the mechanisms of inflammasomes and neurotransmitters in microglia, which accelerate the development of amyloid-β and tau pathology

    高齢夜間頻尿患者における夜間尿産生に対する閉塞性睡眠時無呼吸症候群の影響

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    OBJECTIVE: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on night-time secretion of brain natriuretic peptide (BNP) and antidiuretic hormone (ADH) in older men with nocturia accompanied by nocturnal polyuria. MATERIALS AND METHODS: One hundred six men with nocturia aged ≥ 60 years underwent full-night polysomnography to determine whether they had OSAS. Blood count, standard chemistry panel, BNP, urinary ADH, urinary creatinine (u-Cre), and urinary osmolarity were measured at 6:00 AM, and a frequency volume chart was recorded on the same day that polysomnography was performed. RESULTS: We evaluated 83 patients after excluding 18 with mild OSAS and 5 with nocturnal polyuria index <0.35. Participants with OSAS had higher apnea-hypopnea index (P < .0001) than those without OSAS. Body mass index and systolic blood pressure were higher in OSAS patients than those in the control group. BNP was higher in the OSAS patients than in the control patients (48.6 ± 41.4 vs 30.7 ± 31.5; P = .0006). On urinalysis, OSAS patients showed higher urinary sodium and u-Cre secretion than controls (24.7 ± 11.3 vs 16.2 ± 5.1; P <.0001). Urine osmolarity was also higher in OSAS patients than in the control patients (616 ± 172 vs 516 ± 174; P = .0285). There was no significant difference in urinary ADH and u-Cre (6.7 ± 10.4 vs 6.8 ± 7.8; P = .3617) between the 2 groups. CONCLUSION: Our results indicated that older men with nocturnal polyuria and OSAS did not compensate their fluid imbalance presented with decreased secretion of ADH but increased BNP level.博士(医学)・乙第1349号・平成26年12月3日Copyright © 2014 Elsevier Inc. All rights reserved

    Essential Insight of Direct Electron Transfer-Type Bioelectrocatalysis by Membrane-Bound d-Fructose Dehydrogenase with Structural Bioelectrochemistry

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    電極を基質認識できる酵素の反応メカニズムを解明 --次世代バイオセンシングにつながる基盤技術--. 京都大学プレスリリース. 2023-10-16.Flavin adenine dinucleotide-dependent d-fructose dehydrogenase (FDH) from Gluconobacter japonicus NBRC3260, a membrane-bound heterotrimeric flavohemoprotein capable of direct electron transfer (DET)-type bioelectrocatalysis, was investigated from the perspective of structural biology, bioelectrochemistry, and protein engineering. DET-type reactions offer several benefits in biomimetics (e.g., biofuel cells, bioreactors, and biosensors) owing to their mediator-less configuration. FDH provides an intense DET-type catalytic signal; therefore, extensive research has been conducted on the fundamental principles and applications of biosensors. Structural analysis using cryo-electron microscopy and single-particle analysis has revealed the entire FDH structures with resolutions of 2.5 and 2.7 Å for the reduced and oxidized forms, respectively. The electron transfer (ET) pathway during the catalytic oxidation of d-fructose was investigated by using both thermodynamic and kinetic approaches. Structural analysis has shown the localization of the electrostatic surface charges around heme 2c in subunit II, and experiments using functionalized electrodes with a controlled surface charge support the notion that heme 2c is the electrode-active site. Furthermore, two aromatic amino acid residues (Trp427 and Phe489) were located in a possible long-range ET pathway between heme 2c and the electrode. Two variants (W427A and F489A) were obtained by site-directed mutagenesis, and their effects on DET-type activity were elucidated. The results have shown that Trp427 plays an essential role in accelerating long-range ET and triples the standard rate constant of heterogeneous ET according to bioelectrochemical analysis
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