This article discusses a typical production structure, describes the theory and terminology. The article also presents theoretical information on presentation of data, knowledge and types of ...knowledge, data formalization and describes the concept of formalization. The problem of automating the assessment of manufacturability of the product design using modern information technologies and data analysis was discussed. An algorithm for typical formalization of information used in the analysis of manufacturability was developed, and an example of its used for an electronic part model was provided.
The paper discusses a typical example of recognizing a sheet metal part containing 2 structural elements. According to the developed recognition algorithm, a software module was implemented for ...automated recognition of structural elements in a 3-dimensional model of parts with the * .stp extension, which allowed working not only with models made in the Siemens NX system, but also, in general, with almost any 3D models exported in this format. The result of recognition can be used to develop systems that design technological processes for the production of mechanical engineering products, including at aircraft production enterprises.
ABSTRACTExpression of cell adhesion molecules (CAM) responsible for leukocyte‐endothelium interactions plays a crucial role in inflammation and atherogenesis. Up‐regulation of vascular CAM‐1 ...(VCAM‐1), intracellular CAM‐1 (ICAM‐1), and E‐selectin expression promotes monocyte recruitment to sites of injury and is considered to be a critical step in atherosclerotic plaque development. Factors that trigger this initial response are not well understood. As platelet activation not only promotes thrombosis but also early stages of atherogenesis, we considered the role of thrombospondin‐1 (TSP‐1), a matricellular protein released in abundance from activated platelets and accumulated in sites of vascular injury, as a regulator of CAM expression. TSP‐1 induced expression of VCAM‐1 and ICAM‐1 on endothelium of various origins, which in turn, resulted in a significant increase of monocyte attachment. This effect could be mimicked by a peptide derived from the C‐terminal domain of TSP‐1 and known to interact with CD47 on the cell surface. The essential role of CD47 in the cellular responses to TSP‐1 was demonstrated further using inhibitory antibodies and knockdown of CD47 with small interfering RNA. Furthermore, we demonstrated that secretion of endogenous TSP‐1 and its interaction with CD47 on the cell surface mediates endothelial response to the major proinflammatory agent, tumor necrosis factor α (TNF‐α). Taken together, this study identifies a novel mechanism regulating CAM expression and subsequent monocyte binding to endothelium, which might influence the development of anti‐atherosclerosis therapeutic strategies.
Background: Kindlin‐3 is a novel integrin activator in hematopoietic cells, and its deficiency leads to immune problems and severe bleeding, known as leukocyte adhesion deficiency III (LAD‐III). Our ...current understanding of Kindlin‐3 function primarily relies on analysis of animal models or cell lines.
Objectives: To understand the functions of Kindlin‐3 in human primary blood cells.
Patients/Methods: We analyzed primary and immortalized hematopoietic cells obtained from a new LAD‐III patient with immune problems, bleeding, a history of anemia, and abnormally shaped red blood cells.
Results: The patient’s white blood cells (WBCs) and platelets showed defects in agonist‐induced integrin activation and botrocetin‐induced platelet agglutination. Primary leukocytes from this patient exhibited abnormal activation of β1 integrin. Integrin activation defects were responsible for the observed deficiency in the botrocetin‐induced platelet response. Analysis of patient genomic DNA revealed a novel mutation in the Kindlin3 gene. The mutation abolished Kindlin‐3 expression in primary WBCs and platelets, owing to abnormal splicing. Kindlin‐3 is expressed in red blood cells (RBCs), and its deficiency is proposed to lead to abnormally shaped RBCs. Immortalized patient WBCs expressed a truncated form of Kindlin‐3 that was not sufficient to support integrin activation. Expression of Kindlin‐3 cDNA in immortalized patient WBCs rescued integrin activation defects, whereas overexpression of the truncated form did not.
Conclusions: Kindlin‐3 deficiency impairs integrin function, including activation of β1 integrin. Abnormalities in glycoprotein Ib–IX function in Kindlin‐3‐deficient platelets are secondary to integrin defects. The region of Kindlin‐3 encoded by exon 11 is crucial for its ability to activate integrins in humans.
The interrelationship between very low density lipoprotein (VLDL) secretion and bile acid production was studied in primary culture of rabbit hepatocytes. Chylomicron remnants (CR) were added to the ...cultures to study their effect on VLDL secretion and bile acid production. After 24 hr preincubation of cells with CR (10-50 micrograms protein/mL), intercellular neutral lipid content was increased 1.5-4-fold in a dose-dependent manner. Neutral lipid accumulation was accompanied by a 70-90% reduction of 14Cacetate incorporation into cholesterol, while no stimulation of 14Coleate incorporation into cholesteryl esters was observed. Incubation of cells with CR increased secretion of free cholesterol, triacylglycerol and apoproteins B and E in VLDL. Stimulation of VLDL cholesterol secretion was accompanied by a reduction of taurocholic acid synthesis. These data demonstrate the existence of an inverse relationship between secretion of VLDL cholesterol and bile acid production under conditions of effective uptake of triacylglycerol-rich CR by hepatocytes.
The main objectives of this study were to compare the effects of dietary commercial cholesterol (containing 5% of oxidized cholesterol derivatives) and purified cholesterol on the secretion rate of ...very low density lipoprotein apolipoproteins and lipids by cultured rabbit hepatocytes and to verify the hypothesis that products of cholesterol autoxidation stimulate the rapid development of hypercholesterolemia. Rabbits fed dietary (old) commercial cholesterol for six weeks showed a fivefold increase in the serum concentration of cholesterol compared with that in purified cholesterol-fed rabbits. The secretion rates of very low density lipoprotein total protein and very low density lipoprotein 3Hapolipoproteins were similar for the hepatocytes of these two cholesterol-fed groups of animals and were two- and threefold greater, respectively, than for cells from control rabbits. Cholesteryl ester content of the hepatocytes from dietary (old) commercial cholesterol-fed rabbits was dramatically increased in comparison with hepatocytes from control and purified cholesterol-fed rabbits. The elevated intracellular cholesteryl ester content is assumed to account for such an increase of very low density lipoprotein-cholesteryl ester secretion by cells prepared from dietary (old) commercial cholesterol-fed rabbits. These effects appear to be caused by activation of cholesterol esterification by oxidized cholesterol derivatives. The rapid development of hypercholesterolemia induced by dietary (old) commercial cholesterol is associated, at least in part, with the stimulated production of hepatic very low density lipoprotein apolipoproteins and cholesteryl esters.
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