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The sequence proline-proline-glycine-proline is highly conserved in cytochrome P450 families 1 and 2, and similar proline rich sequences are found in other cytochromes P450. Since this sequence immediately follows the NH2-terminal hydrophobic membrane insertion signal, it potentially could function as a signal either for retention of cytochrome P450 in the endoplasmic reticulum or for its correct orientation in the membrane. To test this possibility, DNA sequence coding for this tetrapeptide was deleted from cytochrome P450 2C2 cDNA. Translation of the mutated mRNA in a reticulocyte cell-free system containing canine microsomal membranes resulted in the insertion of the protein into the membrane with a topology indistinguishable from that of normal cytochrome P450 2C2. The mutated protein was expressed in COS1 cells and its distribution, assayed by immunofluorescence, was similar to that of cytochrome P450 2C2. Furthermore, if a short peptide containing a potential glycosylation site was fused to the N-terminus of the mutant protein, the new hybrid protein was glycosylated in COS1 cells and the carbohydrate moiety remained sensitive to cleavage by endoglycosidase H. These results indicate that the protein was inserted and retained in the endoplasmic reticulum membrane. Pulse-chase studies showed that the mutated protein was degraded about four times as fast as cytochrome P450 2C2. In contrast to cytochrome P450 2C2, no (omega-1) hydroxylase activity was detected in COS1 cells expressing the mutated protein at similar steady-state levels as the wild-type protein. These results indicate that, although the conserved PPGP tetrapeptide is not required for cellular localization of cytochrome P450 in the endoplasmic reticulum membrane, its deletion decreases the stability of the protein and abolishes enzymatic activity.  相似文献   
996.
In this paper we pursue a twofold aim. First we want to simplify the complexity of the classical Monopoli's scheme, the so-called ‘Augmented error signal control scheme’. Then we also wish to cope with the realistic situation in which the presence of unmodelled dynamics has to be taken into account. This latter problem has been faced in the literature by suitably modifying the adaptation mechanism in order to avoid undesired phenomena as well as to obtain an attractive stability region for the state trajectories starting from any point in a predefined initial condition set. In our case the necessity of introducing any sort of modification in the adaptation mechanism is completely avoided, but we still obtain asymptotic stability of the output error signal.  相似文献   
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The concept of a nonaxisymmetrical X-ray image intensifier is presented in this paper. Instead of cylindrical electrodes, as in the conventional device, this intensifier is equipped with planar electrodes. Each one consists of some number of elementary quadrilateral patches, which are mutually insulated from each other and supplied with the proper voltages. The algorithm for determining potentials which must be supplied to the elementary electrodes is described in the paper. The algorithm has been validated by comparing the electric field distributions in both configurations. Details of the electric field distribution are also helpful in evaluating the optical characteristics of the intensifier  相似文献   
1000.
Spontaneous nasal tumors are rare in mice, and only one adenocarcinoma and two more primary neoplasms of the nose have been observed in our files of long-term feeding studies, which are composed of 3,419 male and 3,521 female CD-1 (Crl:CD-1 (ICR)BR) mice. This adenocarcinoma was a 1-cm-diameter mass observed grossly in the right nasal cavity of a 454-day-old, male CD-1 mouse from a treated group in a bioassay study conducted with 340 males and 340 females. The neoplastic epithelial cells affected the normal nasal architecture on the right side of the nose. Roughly, tumor neoplastic cells of the outer, lateral portion occurred as cuboidal to low columnar cells with basilarily located nuclei and eosinophilic cytoplasm. These cells were arranged in cylindrical profiles and frequently entrapped acini of the glands of the maxillary sinus. Neoplastic epithelial cells of the inner, medial portion appeared as serous acinar or ductular structures circumscribed by multiple lagers of myoepithelial-like cells. Staining failed to demonstrate mucous secretion. The site of origin of this neoplasm appeared to be the serous glands of the maxillary sinus. The adenocarcinoma was believed to be spontaneous.  相似文献   
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