151 research outputs found

    Process approach: the way to improve the quality of high-tech products

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    В статье представлен процесс регламентации бизнес-процесса «Изготовление источников питания», описанного с использованием методологии IDEF0 и программного продукта Business Studio 4.0 на примере подразделения, которое занимается разработкой и изготовлением сварочных источников тока. При моделировании процесса изготовления источников питания была построена матрица атрибутов, в которой определены цели и задачи процессов, владельцы на каждом этапе процесса, несущие ответственность за ход и за результат, определены входы и выходы (документы) процесса, а также критерии результативности и/или эффективности процесса, для осуществления оперативного управления на всех этапах изготовления конечной продукции. В результате работы был разработан комплект документов, в состав которого вошли: регламент процесса изготовления источников тока, положение о подразделении, должностные инструкции сотрудников, участвующих в процессе. Деятельность по регламентации процесса проводилась в рамках подготовки подразделения к сертификации в соответствии с требованиями стандарта ГОСТ РВ 0015-002-2012 «Система разработки и постановки продукции на производство военной техники. Системы менеджмента качества. Общие требования» в системе добровольной сертификации «Военный регистр»

    5-HT2A receptor signalling through phospholipase D1 associated with its C-terminal tail

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    The 5-HT2AR (5-hydroxytryptamine-2A receptor) is a GPCR (G-protein-coupled receptor) that is implicated in the actions of hallucinogens and represents a major target of atypical antipsychotic agents. In addition to its classical signalling though PLC (phospholipase C), the receptor can activate several other pathways, including ARF (ADP-ribosylation factor)-dependent activation of PLD (phospholipase D), which appears to be achieved through a mechanism independent of heterotrimeric G-proteins. In the present study we show that wild-type and inactive constructs of PLD1 (but not PLD2) respectively facilitate and inhibit ARF-dependent PLD signalling by the 5-HT2AR. Furthermore we demonstrate that PLD1 specifically co-immunoprecipitates with the receptor and binds to a distal site in GST (glutathione transferase) fusion protein constructs of its C-terminal tail which is distinct from the ARF-interaction site, thereby suggesting the existence of a functional ARF-PLD signalling complex directly associated with this receptor. This reveals the spatial co-ordination of an important GPCR, transducer and effector into a physical complex that is likely to reinforce the impact of receptor activation on a heterotrimeric G-protein-independent signalling pathway. Signalling of this receptor through such non-canonical pathways may be important to its role in particular disorders

    The Functions of Auxilin and Rab11 in Drosophila Suggest That the Fundamental Role of Ligand Endocytosis in Notch Signaling Cells Is Not Recycling

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    Notch signaling requires ligand internalization by the signal sending cells. Two endocytic proteins, epsin and auxilin, are essential for ligand internalization and signaling. Epsin promotes clathrin-coated vesicle formation, and auxilin uncoats clathrin from newly internalized vesicles. Two hypotheses have been advanced to explain the requirement for ligand endocytosis. One idea is that after ligand/receptor binding, ligand endocytosis leads to receptor activation by pulling on the receptor, which either exposes a cleavage site on the extracellular domain, or dissociates two receptor subunits. Alternatively, ligand internalization prior to receptor binding, followed by trafficking through an endosomal pathway and recycling to the plasma membrane may enable ligand activation. Activation could mean ligand modification or ligand transcytosis to a membrane environment conducive to signaling. A key piece of evidence supporting the recycling model is the requirement in signaling cells for Rab11, which encodes a GTPase critical for endosomal recycling. Here, we use Drosophila Rab11 and auxilin mutants to test the ligand recycling hypothesis. First, we find that Rab11 is dispensable for several Notch signaling events in the eye disc. Second, we find that Drosophila female germline cells, the one cell type known to signal without clathrin, also do not require auxilin to signal. Third, we find that much of the requirement for auxilin in Notch signaling was bypassed by overexpression of both clathrin heavy chain and epsin. Thus, the main role of auxilin in Notch signaling is not to produce uncoated ligand-containing vesicles, but to maintain the pool of free clathrin. Taken together, these results argue strongly that at least in some cell types, the primary function of Notch ligand endocytosis is not for ligand recycling
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