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  • 1
    ISSN: 1432-0924
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract  This paper describes an inverse analysis method using hierarchical neural networks and computational mechanics, and its application to the quantitative nondestructive evaluation with the ultrasonic method. The present method consists of three subprocesses. First, by parametrically changing the location and size of a defect hidden in solid, elastic wave propagation in the solid is calculated with the dynamic finite element method. Second, the back-propagation neural network is trained using the calculated relationships between the defect parameters and the dynamic responses of solid surface. Finally, the trained network is utilized to determine appropriate defect parameters from some measured dynamic responses of solid surface. The accuracy and efficiency of the present method are discussed in detail through the identification of size and location of a defect hidden in solid.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    s.l. ; Stafa-Zurich, Switzerland
    Materials science forum Vol. 196-201 (Nov. 1995), p. 431-436 
    ISSN: 1662-9752
    Source: Scientific.Net: Materials Science & Technology / Trans Tech Publications Archiv 1984-2008
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 39 (1996), S. 1306-1312 
    ISSN: 1432-0428
    Keywords: Keywords Islets of Langerhans ; Fas ; CD95 ; apoptosis ; interleukin-1 ; interferon-γ ; DNA cleavage.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was conducted to investigate the possible involvement of Fas in β-cell death in insulitis of Type 1 (insulin-dependent) diabetes mellitus. Although primary cultured Balb/c mouse islet cells did not express Fas mRNA, 4–12 hours of treatment with 102-105 U/l of mouse interleukin-1 α (IL-1α) induced the expression of Fas mRNA. Surface Fas expression was detected by immunofluorescence flow cytometry using a non-cytolytic anti-Fas monoclonal antibody after 6 or 12 h of incubation with 103 U/l of IL-1α. Primary islet cells were resistant to an agonistic anti-Fas monoclonal antibody. However, 12 h pretreatment with IL-1α sensitized islet cells to its cytolytic effect. Significant cell death was observed 24 h after the addition of anti-Fas, and progressively increased until 72 h, when specific 51Cr release was 72 ± 6 %. Agarose gel electrophoresis of DNA extracted from cells exposed to IL-1α and agonistic anti-Fas showed internucleosomal DNA fragmentation, a hallmark of apoptotic cell death. Since the Fas antibody showed no cross-reactive activity of tumour necrosis factor (TNF), the cytotoxic effect was not mediated by TNF receptors. A protein synthesis inhibitor cycloheximide augmented Fas-mediated islet cell death. The Fas-mediated killing of islet cells was not l-arginine-dependent, or blocked by NG-monomethyl-l-arginine. β-TC1 cells also expressed Fas mRNA when exposed to IL-1α or IL-1α plus interferon-γ. These observations suggest that Fas-mediated apoptosis may be a mechanism of islet cell death in autoimmune insulitis. [Diabetologia (1996) 39: 1306–1312]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Insulin ; insulin receptor substrate-1 ; phosphoinositide 3-kinase ; signal transduction ; phosphotyrosine ; enzyme activation ; conformational change ; Fao cells.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Phosphoinositide 3-kinase (PI3-kinase) plays a crucial role in insulin signal transduction. We studied the molecular mechanism of the insulin-induced activation of PI3-kinase in rat hepatoma Fao cells using an antibody against the 110-kDa catalytic subunit (p110) and two against the 85-kDa regulatory subunit (p85α). PI3-kinase activity increased 1.6-fold in anti-p85 immunoprecipitates after insulin stimulation, whereas it did not increase when cell lysates were first immunoprecipitated with anti-phosphotyrosine or anti-insulin receptor substrate-1 (IRS-1), then with anti-p85, suggesting that the PI3-kinase which associates with tyrosyl phosphoproteins including IRS-1 is responsible for the increase in kinase activity. The activated PI3-kinase molecules constituted 4–6 % of the total PI3-kinase, and their specific activity was 11–14 times higher than that of the basal state. Anti-p110 recognized the catalytically active form of p110, and immunoprecipitated p110 only after exposure to insulin. Hence, the epitope of anti-p110, P200–C215, seems to be included in the portion of p110, the conformation of which is changed by insulin stimulation. We conclude that, in response to insulin stimulation, only a small fraction of p85 in the PI3-kinase pool associates with tyrosyl phosphoproteins including IRS-1, and that the specific activity of p110 is increased presumably through a conformational change including the P200–C215 region. [Diabetologia (1996) 39: 515–522]
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Keywordsβ2-adrenergic receptor gene ; polymorphism ; obesity ; triglyceride ; Type II diabetes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To assess the role of polymorphisms in the β2-adrenergic receptor gene in the development of obesity and obesity-related metabolic disorders, we analysed Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms in 400 non-obese subjects (body mass index 〈 27 kg/m2) and 108 obese subjects (body mass index ≥ 27 kg/m2). The Gln27Glu substitution was twice as common in obese subjects as in non-obese subjects (0.14 vs 0.07, p = 0.001, odds ratio 2.14, 95 % confidence interval 1.35–3.41). The frequency of the Glu27 allele was also higher in patients with Type II (non-insulin-dependent) diabetes mellitus than non-diabetic subjects (0.14 vs 0.07, p = 0.001, odds ratio 2.13, 95 % confidence interval 1.34–3.41). Analysis of variance of multiple variables showed an association between 2-h post-load glucose concentrations and body mass index but not with the Glu27 variant, suggesting that the association with diabetes could be secondary to obesity. Obese subjects carrying the variant allele had higher concentrations of serum triglyceride than obese subjects homozygous for the wild type allele (2.68 ± 1.90 vs 1.18 ± 1.15 mmol/l, p = 0.02). Conversely, the frequency of Gly16 homozygotes was lower in obese women when compared with non-obese women (11 % vs 28 %, p = 0.01, odds ratio 0.30, 95 % confidence interval 0.12–0.75), although the association was not present in male subjects. Thr164Ile substitution was not detected in the subjects of this study. These observations suggest that the amino-terminal polymorphisms of the β2-adrenergic receptor gene could be involved in the molecular pathogenesis of obesity and hypertriglyceridaemia, and thereby the development of Type II diabetes mellitus. [Diabetologia (1999) 42: 98–101]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Keywords Insulin promoter factor 1 ; polymorphism ; mutation ; insulin-dependency.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin promoter factor 1 (IPF1) is a key factor both for the regulation of insulin gene expression and for the development of the pancreas. In this study 88 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were diagnosed as diabetic at less than 40 years of age, 55 patients with insulin-dependent-diabetes (IDDM), and 67 normal control subjects were analysed for variants in the upstream region of the IPF1 gene by direct sequencing. A novel single nucleotide insertion polymorphism was found in a guanine triplet at 108 bp upstream of the translation start site. The G insertion allele (G4 allele) was found to be common in the Japanese population, at a frequency of 0.50. The prevalence of G3 homozygotes was higher in IDDM patients (35 %) and lower in NIDDM patients (17 %) than in normal control subjects (28 %, p = 0.049). In the NIDDM group, the ratio of insulin treatment tended to be higher in subjects homozygous for the G3 allele, although the genotype was not significantly associated with basal C-peptide levels. The polymorphism is unlikely to be a major contributor to the insulin deficiency of diabetes. However, the polymorphic locus, or an unknown mutation which is in linkage disequilibrium with the polymorphism, could be involved in the pathophysiology of diabetes. The high heterozygosity may be useful for genetic linkage studies of other mutations within and near the IPF1 gene. [Diabetologia (1998) 41: 603–605]
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Insulin ; insulin receptor substrate-1 ; phosphoinositide 3-kinase ; signal transduction ; phosphotyrosine ; enzyme activation ; conformational change ; Fao cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Phosphoinositide 3-kinase (PI3-kinase) plays a crucial role in insulin signal transduction. We studied the molecular mechanism of the insulin-induced activation of PI3-kinase in rat hepatoma Fao cells using an antibody against the 110-kDa catalytic subunit (p110) and two against the 85-kDa regulatory subunit (p85α). PI3-kinase activity increased 1.6-fold in anti-p85 immunoprecipitates after insulin stimulation, whereas it did not increase when cell lysates were first immunoprecipitated with anti-phosphotyrosine or anti-insulin receptor substrate-1 (IRS-1), then with anti-p85, suggesting that the PI3-kinase which associates with tyrosyl phosphoproteins including IRS-1 is responsible for the increase in kinase activity. The activated PI3-kinase molecules constituted 4–6% of the total PI3-kinase, and their specific activity was 11–14 times higher than that of the basal state. Anti-p110 recognized the catalytically active form of p110, and immunoprecipitated p110 only after exposure to insulin. Hence, the epitope of anti-p110, P200-C215, seems to be included in the portion of p110, the conformation of which is changed by insulin stimulation. We conclude that, in response to insulin stimulation, only a small fraction of p85 in the PI3-kinase pool associates with tyrosyl phosphoproteins including IRS-1, and that the specific activity of p110 is increased presumably through a conformational change including the P200-C215 region.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Keywords Fatty acid-binding protein 2 ; intestinal fatty acid binding protein ; insulin resistance ; visceral fat.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alanine to threonine substitution at codon 54 of the fatty acid-binding protein 2 (FABP2) gene was recently shown to be associated with insulin resistance in Pima Indians. It has been hypothesized that the mutation may result in enhanced intestinal uptake of fatty acids, and thereby an impairment of insulin action. We analysed the association of the Ala54Thr substitution with insulin sensitivity and abdominal fat thickness in 395 Japanese men aged 50.5 ± 8.8 years (mean ± SD) with a body mass index of 24.4 ± 3.0 kg/m2. The frequency of the Thr54 allele was 0.34. Although the polymorphism was not significantly associated with diabetes or impaired glucose tolerance, subjects homozygous for the Thr54 allele had higher basal insulin levels. Analysis by homeostasis model assessment showed an association between the amino acid substitution and greater insulin resistance, and slightly higher beta-cell function. Oral glucose tolerance tests performed in 392 subjects without fasting hyperglycaemia showed higher 2-h insulin concentrations in individuals homozygous for the Thr54 allele when compared with heterozygotes or homozygotes for the Ala54 allele. No significant association was obtained between the polymorphism of the FABP2 gene and body mass index. However, ultrasound measurements of abdominal fat thickness revealed a greater accumulation of intra-abdominal fat in subjects homozygous for the Thr54 allele, whereas subcutaneous fat thickness was not associated with the polymorphism. These observations suggest that the Ala54Thr substitution in the FABP2 gene is associated with insulin resistance in Japanese men, and that visceral fat accumulation might be involved in the impaired insulin action associated with the substitution. [Diabetologia (1997) 40: 706–710]
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 41 (1998), S. 125-125 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The developmentally regulated mouse gene Nedd 1 encodes a protein showing similarities with the β-subunit of heterotrimeric GTP-binding proteins and has growth suppressing activity when overexpressed in various cultured cell types. We have mapped the human homolog (NEDD1) of the mouse gene to chromosome 12q22 by fluorescence in situ hybridization using R-banded human (pro)metaphase chromosomes.
    Type of Medium: Electronic Resource
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