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  • 1
    Keywords: INHIBITOR ; Germany ; human ; IN-VIVO ; MODEL ; VIVO ; CLASSIFICATION ; NETWORK ; NETWORKS ; neural networks ; SUPPORT ; SYSTEM ; MICE ; TIME ; RAT ; animals ; RATS ; VECTOR ; BEHAVIOR ; support vector machines ; RE ; development ; PROFILES ; technique ; function ; EVALUATE ; COMPOUND ; in vivo ; animal ; ENGLAND ; SET ; PROFILE ; German ; ANTIDEPRESSANT ACTIVITY ; automated behavior classification ; forced swimming test ; kernel ; NEURAL-NETWORKS ; support vector machine
    Abstract: The forced swimming test of rats or mice is a frequently used behavioral test to evaluate compounds for antidepressant activity in vivo. The aim of this study was to replace the human observer, needed to score and analyze the behavior of animals, by a fully automated method. For this purpose, in a first step from a video recording of each rat, an activity profile was calculated, from which subsequently a set of meaningful properties was extracted. This set was finally used to train a Support Vector Machine (SVM). Furthermore, specialized kernel functions, namely the so-called time resolved p-spectrum and modified optimal assignment kernels, were developed to calculate the similarity of activity profiles. Our method allows for a very reliable discrimination of animals treated with antidepressants of different classes (tricyclics imipramine and desipramine as well as selective serotonin reuptake inhibitor, SSRI, fluoxetine) versus a vehicle-treated group. Moreover, our technique is able to classify between tricyclic antidepressants and SSRIs. The results of this work enabled the development of an automated and highly accurate behavior classification system. (c) 2007 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 18158234
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  • 2
    Keywords: MOLECULAR CHARACTERIZATION ; COLON-CANCER ; NONPOLYPOSIS COLORECTAL-CANCER ; MISMATCH-REPAIR GENES ; MLH1 ; MSH2 ; epimutation ; ANTISENSE RNA ; GENOMIC DELETIONS ; FREQUENT CAUSE
    Abstract: Recently, we identified 3' end deletions in the EPCAM gene as a novel cause of Lynch syndrome. These truncating EPCAM deletions cause allele-specific epigenetic silencing of the neighboring DNA mismatch repair gene MSH2 in tissues expressing EPCAM. Here we screened a cohort of unexplained Lynch-like families for the presence of EPCAM deletions. We identified 27 novel independent MSH2-deficient families from multiple geographical origins with varying deletions all encompassing the 3' end of EPCAM, but leaving the MSH2 gene intact. Within The Netherlands and Germany, EPCAM deletions appeared to represent at least 2.8% and 1.1% of the confirmed Lynch syndrome families, respectively. MSH2 promoter methylation was observed in epithelial tissues of all deletion carriers tested, thus confirming silencing of MSH2 as the causative defect. In a total of 45 families, 19 different deletions were found, all including the last two exons and the transcription termination signal of EPCAM. All deletions appeared to originate from Alu-repeat mediated recombination events. In 17 cases regions of microhomology around the breakpoints were found, suggesting nonallelic homologous recombination as the most likely mechanism. We conclude that 3' end EPCAM deletions are a recurrent cause of Lynch syndrome, which should be implemented in routine Lynch syndrome diagnostics.
    Type of Publication: Journal article published
    PubMed ID: 21309036
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  • 3
    ISSN: 0173-0835
    Keywords: Identification ; Cyst and root-knot nematodes ; Isoelectric focusing ; Potato ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: To carry out rapid and reliable species identification of Globodera and Meloidogyne specimens, two electrophoretic methods were modified and adapted for an automated electrophoresis system (PhastSystem, Pharmacia). Proteins of individual Globodera cysts were identified using isoelectric focusing and a sensitive silver stain. Proteins of young single Meloidogyne females were separated using polyacrylamide gradient gels and stained for the isozymes esterase and malate dehydrogenase.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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