Installation information system for measuring deviations of the inter-center distance of plates of links of wired circuits with a step of 15,875mm according to GOST 13568-75

В даній дипломній роботі розроблена інформаційна система установки для вимірювання відхилень міжцентрової віддалі пластин привідних ланцюгів. Під час розробки дипломної роботи було сконструйовано вимірювальну установку, розраховано параметри виконавчих пристроїв, які входять до складу даної установки, Також у даній роботі було зроблено розрахунок математичної моделі індуктивного соленоїдного перетворювача. Розроблено систему керування вимірювальною установкою та обґрунтовано вибір її елементів. Установка була сконструйована з урахуванням сучасного рівня автоматизованого керування, таким чином, можна досягнути підвищення швидкодії установи при одночасному покращенні якості вимірювання.In this diploma work the information system of installation for measurement of deviations of intercentral distance of plates of drive chains is developed. During the development of the diploma thesis, a measuring unit was constructed, the parameters of the actuators included in this unit were calculated, and the mathematical model of the inductive solenoid converter was also calculated in this paper. The control system of the measuring installation is developed and the choice of its elements is substantiated. The unit has been designed with the modern level of automated control in mind, so that it can be achieved to improve the performance of the facility while improving the quality of measurement.ВСТУП 1 ДОСЛІДНИЦЬКО-КОНСТРУКТОРСЬКИЙ РОЗДІЛ 1.1Аналіз поставленої задачі 1.2Схема установки вимірювання 1.2.1 Принцип роботи установки 1.3 Вібраційні завантажувальні пристрої 1.4 Вибір ВЗП і його попередній розрахунок 1.5 Розрахунок бункерного пристрою 1.6 Розрахунок похибки установки 1.6.1 Аналіз причин виникнення похибок 1.6.2 Сумарна похибка установки 2 ОСНОВИ НАУКОВИХ ДОСЛІДЖЕНЬ ТА МАТМОДЕЛЮВАННЯ 2.1Аналіз поставленої задачі 2.2 Розрахунок соленоїдного перетворювача індуктивного датчика 3 ЕЛЕКТРОНІКА, МІКРОПРОЦЕСОРНА ТЕХНІКА ТА САПР 3.1 Розробка функціональної схеми 3.1.1 Вимоги до параметрів системи та її функціональності 3.2 Способи реалізації заданих функцій 3.3 Функціональна схема керування 3.4 Створення схеми керування 3.4.1 Оцінка необхідної кількості штифтів мікроконтролера 3.4.2 Використання контролера 3.4.3 Будова мікроконтролера 3.4.4 Вибір рідкокристалічного дисплея 3.4.5 Розрахунок номіналів елементів 3.5 Метрологічний аналіз 3.5.1 Бюджет похибок вимірювального каналу 3.5 .2 Опис алгоритму роботи 4 ОБГРУНТУВАННЯ ЕКОНОМІЧНОЇ ЕФЕКТИВНОСТІ 4.1 Планування технічної підготовки виробництва проектованого приладу 4.1.1 Визначення трудомісткості і обсягу робіт конструкторської підготовки виробництва 4.2.2 Визначення трудомісткості та обсягу робіт технологічної підготовки виробництва 4.2.3 Складання сіткового графіка технічної підготовки виробництва 4.3 Визначення економічної ефективності нового приладу 4.3.1 Розрахунок затрат на виготовлення і використання нового приладу 4.3.1.1 Розрахунок затрат на виготовлення нового приладу 4.3.1.2 Визначення лімітної ціни нового приладу 4.3.1.3Визначення затрат на експлуатацію приладу 4.3.2Розрахунок економічного ефекту від виготовлення і експлуатації приладу 4.3.2.1 Економічний ефект від виготовлення приладу 4.3.2.2. Економічний ефект від експлуатації приладу 4.4 Техніко-економічні показники порівнюваних варіантів 5 ОХОРОНА ПРАЦІ ТА БЕЗПЕКИ В НАДЗВИЧАЙНИХ СИТУАЦІЯХ 5.1 Загальні положення 5.2 Проектування та розрахунок штучного освітлення виробничих примiщень 5.3 Пожежна безпека 5.4 Розроблення заходів підвищення стійкості роботи об'єктів зв’язку, радіомовлення та телебачення в надзвичайних ситуаціях 5.5 Організація оповіщення робітників і службовців підприємства та населення з використанням систем автоматизованого централізованого оповіщення на об’єкті, що проектується 6 ЕКОЛОГІЯ 6.1Організація охорони навколишнього середовища на приладобудівному підприємстві 6.2Забруднення навколишнього середовища при паянні та лудженні ВИСНОВКИ БІБЛІОГРАФІ

Muscarinic receptor signaling in the pathophysiology of asthma and COPD

Anticholinergics are widely used for the treatment of COPD, and to a lesser extent for asthma. Primarily used as bronchodilators, they reverse the action of vagally derived acetylcholine on airway smooth muscle contraction. Recent novel studies suggest that the effects of anticholinergics likely extend far beyond inducing bronchodilation, as the novel anticholinergic drug tiotropium bromide can effectively inhibit accelerated decline of lung function in COPD patients. Vagal tone is increased in airway inflammation associated with asthma and COPD; this results from exaggerated acetylcholine release and enhanced expression of downstream signaling components in airway smooth muscle. Vagally derived acetylcholine also regulates mucus production in the airways. A number of recent research papers also indicate that acetylcholine, acting through muscarinic receptors, may in part regulate pathological changes associated with airway remodeling. Muscarinic receptor signalling regulates airway smooth muscle thickening and differentiation, both in vitro and in vivo. Furthermore, acetylcholine and its synthesizing enzyme, choline acetyl transferase (ChAT), are ubiquitously expressed throughout the airways. Most notably epithelial cells and inflammatory cells generate acetylcholine, and express functional muscarinic receptors. Interestingly, recent work indicates the expression and function of muscarinic receptors on neutrophils is increased in COPD. Considering the potential broad role for endogenous acetylcholine in airway biology, this review summarizes established and novel aspects of muscarinic receptor signaling in relation to the pathophysiology and treatment of asthma and COPD

Role of dystrophin in airway smooth muscle phenotype, contraction and lung function

Dystrophin links the transmembrane dystrophin-glycoprotein complex to the actin cytoskeleton. We have shown that dystrophin-glycoprotein complex subunits are markers for airway smooth muscle phenotype maturation and together with caveolin-1, play an important role in calcium homeostasis. We tested if dystrophin affects phenotype maturation, tracheal contraction and lung physiology. We used dystrophin deficient Golden Retriever dogs (GRMD) and mdx mice vs healthy control animals in our approach. We found significant reduction of contractile protein markers: smooth muscle myosin heavy chain (smMHC) and calponin and reduced Ca2+ response to contractile agonist in dystrophin deficient cells. Immunocytochemistry revealed reduced stress fibers and number of smMHC positive cells in dystrophin-deficient cells, when compared to control. Immunoblot analysis of Akt1, GSK3β and mTOR phosphorylation further revealed that downstream PI3K signaling, which is essential for phenotype maturation, was suppressed in dystrophin deficient cell cultures. Tracheal rings from mdx mice showed significant reduction in the isometric contraction to methacholine (MCh) when compared to genetic control BL10ScSnJ mice (wild-type). In vivo lung function studies using a small animal ventilator revealed a significant reduction in peak airway resistance induced by maximum concentrations of inhaled MCh in mdx mice, while there was no change in other lung function parameters. These data show that the lack of dystrophin is associated with a concomitant suppression of ASM cell phenotype maturation in vitro, ASM contraction ex vivo and lung function in vivo, indicating that a linkage between the DGC and the actin cytoskeleton via dystrophin is a determinant of the phenotype and functional properties of ASM. © 2014 Sharma et al

Src mediates cytokine-stimulated gene expression in airway myocytes through ERK MAPK

The p38 and extracellular signal-regulated kinases (ERK) mitogen-activated protein kinases (MAPK) participate in cytokine-stimulated inflammatory gene expression in airway smooth muscle cells. The following study was undertaken to determine whether Src tyrosine kinases are signaling intermediaries upstream of cytokine-stimulated MAPK activation and gene expression. Treating human airway myocytes with interleukin (IL)-1β, tumor necrosis factor (TNF) α and interferon (IFN) γ caused a rapid 1.8-fold increase in Src family tyrosine kinase activity within 1 minute that remained 2.3 to 2.7 fold above basal conditions for 15 minutes. This activity was blocked by addition of 30 μM PP1, a pyrimidine inhibitor specific for Src family tyrosine kinases, in immune-complex assays to confirm that this stimulus activates Src tyrosine kinase. Addition of PP1 also blocked cytokine-stimulated expression of IL-1β, IL-6 and IL-8, while decreasing phosphorylation of ERK, but not p38 MAPK. Since this inflammatory stimulus may activate additional inflammatory signaling pathways downstream of Src, we tested the effects of PP1 on phosphorylation of signal transducers and activators of transcription (STAT). PP1 had no effect on cytokine-stimulated STAT 1 or STAT 3 phosphorylation. These results demonstrate that Src tyrosine kinases participate in the regulation of IL-1β, IL-6 and IL-8 expression and that these effects of Src are mediated through activation of ERK MAPK and not p38 MAPK or STAT1/STAT3 phosphorylation

The laminin β1-competing peptide YIGSR induces a hypercontractile, hypoproliferative airway smooth muscle phenotype in an animal model of allergic asthma

Background: Fibroproliferative airway remodelling, including increased airway smooth muscle (ASM) mass and contractility, contributes to airway hyperresponsiveness in asthma. In vitro studies have shown that maturation of ASM cells to a (hyper)contractile phenotype is dependent on laminin, which can be inhibited by the laminin-competing peptide Tyr-Ile-Gly-Ser-Arg (YIGSR). The role of laminins in ASM remodelling in chronic asthma in vivo, however, has not yet been established. Methods: Using an established guinea pig model of allergic asthma, we investigated the effects of topical treatment of the airways with YIGSR on features of airway remodelling induced by repeated allergen challenge, including ASM hyperplasia and hypercontractility, inflammation and fibrosis. Human ASM cells were used to investigate the direct effects of YIGSR on ASM proliferation in vitro. Results: Topical administration of YIGSR attenuated allergen-induced ASM hyperplasia and pulmonary expression of the proliferative marker proliferating cell nuclear antigen (PCNA). Treatment with YIGSR also increased both the expression of sm-MHC and ASM contractility in saline-and allergen-challenged animals; this suggests that treatment with the laminin-competing peptide YIGSR mimics rather than inhibits laminin function in vivo. In addition, treatment with YIGSR increased allergen-induced fibrosis and submucosal eosinophilia. Immobilized YIGSR concentration-dependently reduced PDGF-induced proliferation of cultured ASM to a similar extent as laminin-coated culture plates. Notably, the effects of both immobilized YIGSR and laminin were antagonized by soluble YIGSR. Conclusion: These results indicate that the laminin-competing peptide YIGSR promotes a contractile, hypoproliferative ASM phenotype in vivo, an effect that appears to be linked to the microenvironment in which the cells are exposed to the peptide

Airway Smooth Muscle Inflammation Is Regulated by MicroRNA-145 in COPD.

Chronic obstructive pulmonary disease (COPD) is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease, in part caused by the aberrant function of airway smooth muscle (ASM) cells under the regulation of transforming growth factor (TGF)-β. MicroRNAs are short, non-coding gene transcripts involved in the negative regulation of specific target genes, through their interactions with messenger RNAs. Previous studies have proposed that microRNA-145 (miR-145) may interact with SMAD3, an important downstream signalling molecule of the TGF-β pathway. TGF-β was used to stimulate primary human ASM cells isolated from healthy non-smokers, healthy smokers and COPD patients. This resulted in a TGF-β-dependent increase in CXCL8 and IL-6 release, most notably in the cells from COPD patients. TGF-β stimulation increased SMAD3 expression, only in cells from COPD patients, with a concurrent increased miR-145 expression. Regulation of miR-145 was found to be negatively controlled by pathways involving the MAP kinases, MEK-1/2 and p38 MAPK. Subsequent, overexpression of miR-145 (using synthetic mimics) in ASM cells from patients with COPD suppressed IL-6 and CXCL8 release, to levels comparable to the non-smoker controls. Therefore, this study suggests that miR-145 negatively regulates pro-inflammatory cytokine release from ASM cells in COPD by targeting SMAD3

IL-9 Induces CCL11 Expression via STAT3 Signalling in Human Airway Smooth Muscle Cells

Background: Previous findings support the concept that IL-9 may play a significant role in mediating both pro-inflammatory and changes in airway responsiveness that characterizes the atopic asthmatic state. We previously demonstrated that human airway smooth muscle (ASM) cells express a functional IL-9R that mediate CCL11 expression. However, the signaling pathway governing this effect is not well understood. Methodology/Principal Findings: In this study, we showed that IL-9 mediated CCL11 expression in ASM cells does not rely on STAT6 or STAT5 but on STAT3 pathway. IL-9 induced rapid STAT3 activation in primary ASM cells that was not observed in case of STAT6 or STAT5. STAT3 binding to CCL11 promoter was also observed in vivo upon IL-9 stimulation of ASM cells. Disruption of STAT3 activity with SH2 domain binding inhibitory peptide results in significant reduction of IL-9 mediated CCL11 promoter activity. DN STAT3b over-expression in ASM cells, but not Ser 727 STAT3 or STAT6 DN, abolishes IL-9 mediated CCL11 promoter activity. Finally, STAT3 but not STAT6 silenced ASM cells showed significant reduction in IL-9 mediated CCL11 promoter activity and mRNA expression. Conclusion/Significance: Taken together, our results indicate that IL-9 mediated CCL11 via STAT3 signalling pathway ma

Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors

© 2017 The Author(s). Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness of hTERT immortalisation of human ASM cells as a research tool. Specifically we compared proliferative capacity, inflammatory mediator release and extracellular matrix (ECM) production in hTERT immortalised and parent primary ASM cells from asthmatic and non-asthmatic donors. Our studies revealed no significant differences in proliferation, IL-6 and eotaxin-1 production, or CTGF synthesis between donor-matched parent and hTERT immortalised ASM cell lines. However, deposition of ECM proteins fibronectin and fibulin-1 was significantly lower in immortalised ASM cells compared to corresponding primary cells. Notably, previously reported differences in proliferation and inflammatory mediator release between asthmatic and non-asthmatic ASM cells were retained, but excessive ECM protein deposition in asthmatic ASM cells was lost in hTERT ASM cells. This study shows that hTERT immortalised ASM cells mirror primary ASM cells in proliferation and inflammatory profile characteristics. Moreover, we demonstrate both strengths and weaknesses of this immortalised cell model as a representation of primary ASM cells for future asthma pathophysiological research