80 research outputs found

    BH-centroids: A New Efficient Clustering Algorithm

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    The k-means algorithm is one of most widely used method for discovering clusters in data; however one of the main disadvantages to k-means is the fact that you must specify the number of clusters as an input to the algorithm. In this paper we present an improved algorithm for discovering clusters in data by first determining the number of clusters k, allocate the initial centroids, and then clustering data points by assign each data point to one centroid. We use the idea of Gravity, by assuming each data point in the cluster has a gravity that attract the other closest points, this leads each point to move toward the nearest higher gravity toward the nearest higher gravity point to have at the end one point for each cluster, which represent the centroid of that cluster. The measure of gravity of point (X) determined by its weight, which represent the number of points that use point X as the nearest point. Our algorithm employ a distance metric based (eg, Euclidean) similarity measure in order to determine the nearest or the similar point for each point. We conduct an experimental study with real-world as well as synthetic data sets to demonstrate the effectiveness of our techniques

    Purification and Characterization of Flavin-Containing Monooxygenase Isoform 3 from Rat Kidney Microsomes

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    ABSTRACT: Rats are a common animal model for metabolism and toxicity studies. Previously, the enzymatic properties of rat flavin-containing monooxygenase (FMO) 1 purified from hepatic and renal microsomes and that of FMO3 purified from hepatic microsomes were characterized. This study investigated the physical, immunological, and enzymatic properties of FMO3 purified from male rat kidney microsomes and compared the results with those obtained with isolated rat liver FMO3. Renal FMO3 was purified via affinity columns based on the elution of L-methionine (Met) S-oxidase activity and reactivity of the eluted proteins with human FMO3 antibody. In general, Met S-oxidase-specific activity was increased 100-fold through the purification steps. The resulting protein had similar mobility (ϳ56 kDa) as isolated rat liver FMO3 and cDNAexpressed human FMO3 by SDS-polyacrylamide gel electrophoresis. When the isolated kidney protein band was subjected to trypsin digestion and matrix-assisted laser desorption ionization/time of flight mass spectral analysis, 34% of the sequence of rat FMO3 was detected. The apparent K m and V max values for rat kidney FMO3 were determined using the known FMO substrates Met, seleno-L-methionine, S-allyl-L-cysteine (SAC), and methimazole (N-methyl-2-mercaptoimidazole). The stereoselectivity of the reactions with Met and SAC were also examined using high-performance liquid chromatography. The obtained kinetic and stereoselectivity results were similar to those we obtained in the present study, or those previously reported, for rat liver FMO3. Taken together, the results demonstrate many similar properties between rat hepatic and renal FMO3 forms and suggest that renal FMO3 may play an important role in kidney metabolism of xenobiotics containing sulfur and selenium atoms. Flavin-containing monooxygenases (FMOs) are microsomal enzymes that catalyze NADPH-and O 2 -dependent oxidation of compounds with a nucleophilic sulfur, nitrogen, phosphorus, or selenium atom. FMOs have a broad substrate range that includes pharmaceutical drugs, pesticides, industrial chemicals, and endogenous compounds. In general, FMO-mediated metabolites are more readily excreted and are less harmful than the parent compounds; however, with some chemicals, toxic metabolites are formed. Five expressed FMO isoforms (FMO1-FMO5) and six nonexpressed pseudogenes (FMO6P-FMO11P) have been characterized in human

    Alterations of nocturnal activity in rats following subchronic oral administration of the neurotoxin 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline

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    1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) is neurotoxic when administered to the brain and alters motor behaviour following intraperitoneal administration. We have assessed the long-term effects of oral TaClo administration on nocturnal motor behaviour in rats. Two groups of rats received TaClo orally at a dose of either 0.2 or 0.4 mg/kg twice daily for 7 weeks. The control group was given saline. No change in locomotor activity was observed 4–9 days after the end of the 7-week administration of TaClo. In addition, the spontaneous motor activity was altered dose-dependently 9 months after oral TaClo administration, with an increase in the low-dose TaClo group and a decrease in the high-dose group. Oral administration of TaClo in rats may be useful in investigating the hypothesis that in Parkinson’s disease, an unknown pathogenic factor crossing the intestinal mucosa barrier can induce neurodegenerative processes eventually affecting the entire brain

    Purification and Characterization of Flavin-Containing Monooxygenase Isoform 3 from Rat Kidney Microsomes

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    Metabolic activation and detoxication of nephrotoxic cysteine and homocysteine S-conjugates.

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    Differential Localization of Flavin-Containing Monooxygenase (FMO) Isoforms 1, 3, and 4 in Rat Liver and Kidney and Evidence for Expression of FMO4 in Mouse, Rat, and Human Liver and Kidney Microsomes

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    Flavin-containing monooxygenases (FMOs) play significant roles in the metabolism of drugs and endogenous or foreign compounds. In this study, the regional distribution of FMO isoforms 1, 3, and 4 was investigated in male Sprague-Dawley rat liver and kidney using immunohistochemistry (IHC). Rabbit polyclonal antibodies to rat FMO1 and FMO4, developed using anti-peptide technology, and commercial anti-human FMO3 antibody were used; specificities of the antibodies were verified using Western blotting, immunoprecipitation, and IHC. In liver, the highest immunoreactivity for FMO1 and FMO3 was detected in the perivenous region, and immunoreactivity decreased in intensity toward the periportal region. In contrast, FMO4 immunoreactivity was detected with the opposite lobular distribution. In the kidney, the highest immunoreactivity for FMO1, -3, and -4 was detected in the distal tubules. FMO1 and FMO4 immunoreactivity was also detected in the proximal tubules with strong staining in the brush borders, whereas less FMO3 immunoreactivity was detected in the proximal tubules. Immunoreactivity for FMO3 and FMO4 was detected in the collecting tubules in the renal medulla and the glomerulus, whereas little FMO1 immunoreactivity was detected in these regions. The FMO1 antibody did not react with human liver or kidney microsomes. However, the FMO4 antibody reacted with male and female mouse and human tissues. These data provided a compelling visual demonstration of the isoform-specific localization patterns of FMO1, -3, and -4 in the rat liver and kidney and the first evidence for expression of FMO4 at the protein level in mouse and human liver and kidney microsomes
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