206 research outputs found
Application of lean approaches and techniques in an automotive company
In this paper are applied lean approaches and techniques in an industrial environment at Preh Portugal, Lda., a Company involved in the automotive sector located in Trofa, Portugal. This work makes use of the action-research methodology, aiming to diagnose the production system and to implement lean production procedures in order to optimize the Mizusumashi that supplies several production sections, about plastic Injection, cutting and painting. The results obtained enabled to obtain significant improvements on this Company at several factory management and operational levels.This work was supported by FCT “Fundação para a Ciência e a Tecnologia” under the program: PEst20152020.info:eu-repo/semantics/publishedVersio
Integrated platform for real-time control and production and productivity monitoring and analysis
In this paper is proposed the IndustSystems, which is an integrated platform that aims at controlling and monitoring of production and evaluation of productivity in real time, via web access, using hybrid and scheduling algorithms that allow management and optimized use of production resources and perfect synchronization of production flows.This work was supported by FCT “Fundação para a Ciência e a Tecnologia” under the program: PEst20152020.info:eu-repo/semantics/publishedVersio
PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis
The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al
Application of FMEA for assessment of the polymer composite materials quality
The paper is devoted to developing a methodology for failure mode and effects analysis on the example
of assessment of defects that occur during production and operation of polymer composite materials and industrial
products from them. The paper uses the Ishikawa method to illustrate and further analyze the cause of defects in
reinforced polymer composite material. The Ishikawa diagram was constructed and analyzed using the method of causal
analysis. The types and consequences of failures and defects for polymer composite materials are analyzed. For each
type of defect, the value of the priority number of risks is calculated. For the most critical defect, measures to reduce
potential defects are proposed. Suggestions for improving the detected defective zones in the structures of polymer
composites in the analysis process are given
Parameter Identification of Cutting Forces in Crankshaft Grinding Using Artificial Neural Networks
The intensifying of the manufacturing process and increasing the efficiency of production
planning of precise and non-rigid parts, mainly crankshafts, are the first-priority task in modern
manufacturing. The use of various methods for controlling the cutting force under cylindrical infeed
grinding and studying its impact on crankpin machining quality and accuracy can improve machining
efficiency. The paper deals with developing a comprehensive scientific and methodological approach
for determining the experimental dependence parameters’ quantitative values for cutting-force
calculation in cylindrical infeed grinding. The main stages of creating a method for conducting a
virtual experiment to determine the cutting force depending on the array of defining parameters
obtained from experimental studies are outlined. It will make it possible to get recommendations
for the formation of a valid route for crankpin machining. The research’s scientific novelty lies in
the developed scientific and methodological approach for determining the cutting force, based on
the integrated application of an artificial neural network (ANN) and multi-parametric quasi-linear
regression analysis. In particular, on production conditions, the proposed method allows the rapid
and accurate assessment of the technological parameters’ influence on the power characteristics for
the cutting process. A numerical experiment was conducted to study the cutting force and evaluate
its value’s primary indicators based on the proposed method. The study’s practical value lies in
studying how to improve the grinding performance of the main bearing and connecting rod journals
by intensifying cutting modes and optimizing the structure of machining cycles
Towards an anti-fibrotic therapy for scleroderma: targeting myofibroblast differentiation and recruitment
BACKGROUND: In response to normal tissue injury, fibroblasts migrate into the wound where they synthesize and remodel new extracellular matrix. The fibroblast responsible for this process is called the myofibroblast, which expresses the highly contractile protein alpha-smooth muscle actin (alpha-SMA). In normal tissue repair, the myofibroblast disappears. Conversely, abnormal myofibroblast persistence is a key feature of fibrotic dieases, including scleroderma (systemic sclerosis, SSc). Myofibroblasts can be derived from differentiation of local resident fibroblasts or by recruitment of microvascular pericytes.
CLINICAL PROBLEM ADDRESSED: Controlling myofibroblast differentiation and persistence is crucial for developing anti-fibrotic therapies targeting SSc.
BASIC SCIENCE ADVANCES: Insights have been recently generated into how the proteins transforming growth factor beta (TGFbeta), endothelin-1 (ET-1), connective tissue growth factor (CCN2/CTGF) and platelet derived growth factor (PDGF) contribute to myofibroblast differentiation and pericyte recruitment in general and to the persistent myofibroblast phenotype of lesional SSc fibroblast, specifically.
RELEVANCE TO CLINICAL CARE: This minireview summarizes recent findings pertinent to the origin of myofibroblasts in SSc and how this knowledge might be used to control the fibrosis in this disease.
CONCLUSIONS: TGFbeta, ET-1, CCN2 and PDGF are likely to cooperate in driving tissue repair and fibrogenic responses in fibroblasts. TGFbeta, ET-1 and CCN2 appear to contribute to myofibroblast differentiation; PDGF appears to be involved with pericyte recruitment. Thus, different therapeutic strategies may exist for targeting the multisystem fibrotic disorder SSc
Rac Inhibition Reverses the Phenotype of Fibrotic Fibroblasts
Background: Fibrosis, the excessive deposition of scar tissue by fibroblasts, is one of the largest groups of diseases for which there is no therapy. Fibroblasts from lesional areas of scleroderma patients possess elevated abilities to contract matrix and produce alpha-smooth muscle actin (alpha-SMA), type I collagen and CCN2 (connective tissue growth factor, CTGF). The basis for this phenomenon is poorly understood, and is a necessary prerequisite for developing novel, rational anti-fibrotic strategies.Methods and Findings: Compared to healthy skin fibroblasts, dermal fibroblasts cultured from lesional areas of scleroderma (SSc) patients possess elevated Rac activity. NSC23766, a Rac inhibitor, suppressed the persistent fibrotic phenotype of lesional SSc fibroblasts. NSC23766 caused a decrease in migration on and contraction of matrix, and alpha-SMA, type I collagen and CCN2 mRNA and protein expression. SSc fibroblasts possessed elevated Akt phosphorylation, which was also blocked by NSC23766. Overexpression of rac1 in normal fibroblasts induced matrix contraction and alpha-SMA, type I collagen and CCN2 mRNA and protein expression. Rac1 activity was blocked by PI3kinase/Akt inhibition. Basal fibroblast activity was not affected by NSC23766.Conclusion: Rac inhibition may be considered as a novel treatment for the fibrosis observed in SSc
The Role of Perfusion Computed Tomography in the Prediction of Cerebral Hyperperfusion Syndrome
Hyperperfusion syndrome (HPS) following carotid angioplasty with stenting (CAS) is associated with significant morbidity and mortality. At present, there are no reliable parameters to predict HPS. The aim of this study was to clarify whether perfusion computed tomography (CT) is a feasible and reliable tool in predicting HPS after CAS.We performed a retrospective case-control study of 54 patients (11 HPS patients and 43 non-HPS) with unilateral severe stenosis of the carotid artery who underwent CAS. We compared the prevalence of vascular risk factors and perfusion CT parameters including regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and time to peak (TTP) within seven days prior to CAS. Demographic information, risk factors for atherosclerosis, and perfusion CT parameters were evaluated by multivariable logistic regression analysis. The rCBV index was calculated as [(ipsilateral rCBV - contralateral rCBV)/contralateral rCBV], and indices of rCBF and TTP were similarly calculated. We found that eleven patients had HPS, including five with intracranial hemorrhages (ICHs) of whom three died. After a comparison with non-HPS control subjects, independent predictors of HPS included the severity of ipsilateral carotid artery stenosis, 3-hour mean systolic blood pressure (3 h SBP) after CAS, pre-stenting rCBV index >0.15 and TTP index >0.22.The combination of severe ipsilateral carotid stenosis, 3 h SBP after CAS, rCBV index and TTP index provides a potential screening tool for predicting HPS in patients with unilateral carotid stenosis receiving CAS. In addition, adequate management of post-stenting blood pressure is the most important treatable factor in preventing HPS in these high risk patients
CCN2 Is Required for the TGF-β Induced Activation of Smad1 - Erk1/2 Signaling Network
Connective tissue growth factor (CCN2) is a multifunctional matricellular protein, which is frequently overexpressed during organ fibrosis. CCN2 is a mediator of the pro-fibrotic effects of TGF-β in cultured cells, but the specific function of CCN2 in the fibrotic process has not been elucidated. In this study we characterized the CCN2-dependent signaling pathways that are required for the TGF-β induced fibrogenic response. By depleting endogenous CCN2 we show that CCN2 is indispensable for the TGF-β-induced phosphorylation of Smad1 and Erk1/2, but it is unnecessary for the activation of Smad3. TGF-β stimulation triggered formation of the CCN2/β3 integrin protein complexes and activation of Src signaling. Furthermore, we demonstrated that signaling through the αvβ3 integrin receptor and Src was required for the TGF-β induced Smad1 phosphorylation. Recombinant CCN2 activated Src and Erk1/2 signaling, and induced phosphorylation of Fli1, but was unable to stimulate Smad1 or Smad3 phosphorylation. Additional experiments were performed to investigate the role of CCN2 in collagen production. Consistent with the previous studies, blockade of CCN2 abrogated TGF-β-induced collagen mRNA and protein levels. Recombinant CCN2 potently stimulated collagen mRNA levels and upregulated activity of the COL1A2 promoter, however CCN2 was a weak inducer of collagen protein levels. CCN2 stimulation of collagen was dose-dependent with the lower doses (<50 ng/ml) having a stimulatory effect and higher doses having an inhibitory effect on collagen gene expression. In conclusion, our study defines a novel CCN2/αvβ3 integrin/Src/Smad1 axis that contributes to the pro-fibrotic TGF-β signaling and suggests that blockade of this pathway may be beneficial for the treatment of fibrosis
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