53 resultados para Récepteur à protéine tyrosine phosphatase-sigma


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The last two decades have seen the application of six sigma methodologies in many manufacturing and also some service industries. Six sigma’s success in manufacturing is well published. But the same cannot be said about its implementation in services. Applying six sigma to services is still limited to only a small number of services. This paper reviews the application of six sigma in service industries. Emphasis is given to application issues such as what are necessary critical success factors and key performance indicators in order for a project to be successful. A pilot study was carried out in order to highlight the issues discussed. Regardless of the service that is provided, a number of guidelines can be commonly applied to varying types of services. The aim of this paper is to help widen the scope of six sigma application in services.

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This paper presents an extensive review on the services, six-sigma, and application of six-sigma in services. In order to improve service quality focus on service process is necessary. Six-sigma is a philosophy which also concentrates on the improvement of process. So, six-sigma if properly applied can be useful for services. This study focuses on the application aspect of six-sigma to wider range of services. The wider applicability of six-sigma depends on identification of key performance indicators(KPIs) for different types of service processes. A case study is conducted in call center services to identify, analyze and compare critical to quality characteristics (CTQs) and KPIs with other types of services available in literature. This study will be helpful to both practitioners and researchers.

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The concept of Six Sigma was initiated in the 1980s by Motorola. Since then it has been implemented in several manufacturing and service organizations. In case of services, health care and finance were major beneficiaries till now. The application of Six Sigma is gradually picking up in other services like; call centers, utilities and public services. This paper provides empirical evidence on Six Sigma implementation in service industries in Singapore. By using a sample size of 50 service organizations (10 responses are from organizations which have implemented Six Sigma), the paper helps in understanding the status of Six Sigma in service organizations in Singapore. The findings confirm the inclusion of critical success factors, critical to quality characteristics, tools and key performance indicators as observed from the literature. The revelation of “not relevant” as a reason for not implementing Six Sigma shows the need for understanding specific requirements of service organizations before its application.

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This paper presents a Six Sigma case study analysis involving three service organizations of Singapore. The organizations are a local hospital, a construction and related engineering service, and a consultancy service. These organizations embarked on their Six Sigma journey around 2003-2004. Though the hospital was slightly ahead than the other two in beginning Six Sigma. These organizations have since achieved significant service improvements through implementation of Six Sigma to their different divisions. Through a series of structured interviews with Six Sigma project champions, team leaders, and members; project reports; public archives; and observations; this study explores the Six Sigma journey of these organizations. The results portray a list of success factors which led to the Six Sigma initiatives, the process of Six Sigma implementation through proper identification of critical-to-quality characteristics, tools and techniques, and the performance indicators which display the improvements due to Six Sigma.

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Six Sigma is considered to be an important management philosophy to obtain satisfied customers. But financial service organisations have been slow to adopt Six Sigma issues so far. Despite the extensive effort that has been invested and benefits that can be obtained, the systematic implementation of Six Sigma in financial service organisations is limited. As a company wide implementation framework is missing so far, this paper tries to fill this gap. Based on theory, a conceptual framework is developed and evaluated by experts from financial institutions. The results show that it is very important to link Six Sigma with the strategic as well as the operations level. Furthermore, although Six Sigma is a very important method for improving quality of processes others such as Lean Management are also used This requires a superior project portfolio management to coordinate resources and projects of Six Sigma with the other methods used. Beside the theoretical contribution, the framework can be used by financial service companies to evaluate their Six Sigma activities. Thus, the framework grounded through literature and empirical data will be a useful guide for sustainable and successful implementation of a Six Sigma initiative in financial service organisations.

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Background: The EphB4 receptor tyrosine kinase has been reported as increased in tumours originating from several different tissues and its expression in a prostate cancer xenograft model has been reported. Methods: RT-PCR, western blotting and immunohistochemical techniques were used to examine EphB4 expression and protein levels in human prostate cancer cell lines LNCaP, DU145 and PC3. Immunohistochemistry was also used to examine localisation of EphB4 in tissue samples from 15 patients with prostate carcinomas. Results: All three prostate cancer cell lines expressed the EphB4 gene and protein. EphB4 immunoreactivity in vivo was significantly greater in human prostate cancers as compared with matched normal prostate epithelium and there appeared to be a trend towards increased expression with higher grade disease. Conclusions: EphB4 is expressed in prostate cancer cell lines with increased expression in human prostate cancers when compared with matched normal tissue. EphB4 may therefore be a useful anti-prostate cancer target. © 2005 Lee et al., licensee BioMed Central Ltd.

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The Six Sigma technique is one of the quality management strategies and is utilised for improving the quality and productivity in the manufacturing process. It is inspired by the two major project methodologies of Deming’s "Plan – Do – Check – Act (PDCA)" Cycle which consists of DMAIC and DMADV. Those two methodologies are comprised of five phases. The DMAIC project methodology will be comprehensively used in this research. In brief, DMAIC is utilised for improving the existing manufacturing process and it involves the phases Define, Measure, Analyse, Improve, and Control. Mask industry has become a significant industry in today’s society since the outbreak of some serious diseases such as the Severe Acute Respiratory Syndrome (SARS), bird flu, influenza, swine flu and hay fever. Protecting the respiratory system, then, has become the fundamental requirement for preventing respiratory deceases. Mask is the most appropriate and protective product inasmuch as it is effective in protecting the respiratory tract and resisting the virus infection through air. In order to satisfy various customers’ requirements, thousands of mask products are designed in the market. Moreover, masks are also widely used in industries including medical industries, semi-conductor industries, food industries, traditional manufacturing, and metal industries. Notwithstanding the quality of masks have become the prioritisations since they are used to prevent dangerous diseases and safeguard people, the quality improvement technique are of very high significance in mask industry. The purpose of this research project is firstly to investigate the current quality control practices in a mask industry, then, to explore the feasibility of using Six Sigma technique in that industry, and finally, to implement the Six Sigma technique in the case company to develop and evaluate the product quality process. This research mainly investigates the quality problems of musk industry and effectiveness of six sigma technique in musk industry with the United Excel Enterprise Corporation (UEE) Company as a case company. The DMAIC project methodology in the Six Sigma technique is adopted and developed in this research. This research makes significant contribution to knowledge. The main results contribute to the discovering the root causes of quality problems in a mask industry. Secondly, the company was able to increase not only acceptance rate but quality level by utilising the Six Sigma technique. Hence, utilising the Six Sigma technique could increase the production capacity of the company. Third, the Six Sigma technique is necessary to be extensively modified to improve the quality control in the mask industry. The impact of the Six Sigma technique on the overall performance in the business organisation should be further explored in future research.

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Reciprocal interactions between Src family kinases (SFKs) and focal adhesion kinase (FAK) are critical during changes in cell attachment. Recently it has been recognized that another SFK substrate, CUB-domain-containing protein 1 (CDCP1), is differentially phosphorylated during these events. However, the molecular processes underlying SFK-mediated phosphorylation of CDCP1 are poorly understood. Here we identify a novel mechanism in which FAK tyrosine 861 and CDCP1-Tyr-734 compete as SFK substrates and demonstrate cellular settings in which SFKs switch between these sites. Our results show that stable CDCP1 expression induces robust SFK-mediated phosphorylation of CDCP1-Tyr-734 with concomitant loss of p-FAK-Tyr-861 in adherent HeLa cells. SFK substrate switching in these cells is dependent on the level of expression of CDCP1 and is also dependent on CDCP1-Tyr-734 but is independent of CDCP1-Tyr-743 and -Tyr-762. In HeLa CDCP1 cells, engagement of SFKs with CDCP1 is accompanied by an increase in phosphorylation of Src-Tyr-416 and a change in cell morphology to a fibroblastic appearance dependent on CDCP1-Tyr-734. SFK switching between FAK-Tyr-861 and CDCP1-Tyr-734 also occurs during changes in adhesion of colorectal cancer cell lines endogenously expressing these two proteins. Consistently, increased p-FAK-Tyr-861 levels and a more epithelial morphology are seen in colon cancer SW480 cells silenced for CDCP1. Unlike protein kinase Cδ, FAK does not appear to form a trimeric complex with Src and CDCP1. These data demonstrate novel aspects of the dynamics of SFK-mediated cell signaling that may be relevant during cancer progression.

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The concept of Six Sigma was initiated in the 1980s by Motorola. Since then it has been implemented in several manufacturing and service organizations. Till now Six Sigma implementation is mostly limited to healthcare and financial services in private sector. Its implementation is now gradually picking up in services such as call center, education, construction and related engineering etc. in private as well as public sector. Through a literature review, a questionnaire survey, and multiple case study approach the paper develops a conceptual framework to facilitate widening the scope of Six Sigma implementation in service organizations. Using grounded theory methodology, this study develops theory for Six Sigma implementation in service organizations. The study involves a questionnaire survey and case studies to understand and build a conceptual framework. The survey was conducted in service organizations in Singapore and exploratory in nature. The case studies involved three service organizations which implemented Six Sigma. The objective is to explore and understand the issues highlighted by the survey and the literature. The findings confirm the inclusion of critical success factors, critical-to-quality characteristics, and set of tools and techniques as observed from the literature. In case of key performance indicator, there are different interpretations about it in literature and also by industry practitioners. Some literature explain key performance indicator as performance metrics whereas some feel it as key process input or output variables, which is similar to interpretations by practitioners of Six Sigma. The response of not relevant and unknown to us as reasons for not implementing Six Sigma shows the need for understanding specific requirements of service organizations. Though much theoretical description is available about Six Sigma, but there has been limited rigorous academic research on it. This gap is far more pronounced about Six Sigma implementation in service organizations, where the theory is not mature enough. Identifying this need, the study contributes by going through theory building exercise and developing a conceptual framework to understand the issues involving its implementation in service organizations.

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Since the discovery of the first receptor tyrosine kinase (RTK) proteins in the late 1970s and early 1980s, many scientists have explored the functions of these important cell signaling molecules. The finding that these proteins are often deregulated or mutated in diseases such as cancers and diabetes, together with their potential as clinical therapeutic targets, has further highlighted the necessity for understanding the signaling functions of these important proteins. The mechanisms of RTK regulation and function have been recently reviewed by Lemmon & Schlessinger (2010) but in this review we instead focus on the results of several recent studies that show receptor tyrosine kinases can function from subcellular localisations, including in particular the nucleus, in addition to their classical plasma membrane location. Nuclear localisation of receptor tyrosine kinases has been demonstrated to be important for normal cell function but is also believed to contribute to the pathogenesis of several human diseases.

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Voltammetric techniques have been introduced to monitor the formation of gold nanoparticles produced via the reaction of the amino acid glycyl-L-tyrosine with Au(III) (bromoaurate) in 0.05 M KOH conditions. The alkaline conditions facilitate amino acid binding to Au(III), inhibit the rate of reduction to Au(0), and provide an excellent supporting electrolyte for voltammetric studies. Data obtained revealed that a range of time-dependent gold solution species are involved in gold nanoparticle formation and that the order in which reagents are mixed is critical to the outcome. Concomitantly with voltammetric measurements, the properties of gold nanoparticles formed are probed by examination of electronic spectra in order to understand how the solution environment present during nanoparticle growth affects the final distribution of the nanoparticles. Images obtained by the ex situ transmission electron microscopy (TEM) technique enable the physical properties of the nanoparticles isolated in the solid state to be assessed. Use of this combination of in situ and ex situ techniques provides a versatile framework for elucidating the details of nanoparticle formation.

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Because of increased competition between healthcare providers, higher customer expectations, stringent checks on insurance payments and new government regulations, it has become vital for healthcare organisations to enhance the quality of the care they provide, to increase efficiency, and to improve the cost effectiveness of their services. Consequently, a number of quality management concepts and tools are employed in the healthcare domain to achieve the most efficient ways of using time, manpower, space and other resources. Emergency departments are designed to provide a high-quality medical service with immediate availability of resources to those in need of emergency care. The challenge of maintaining a smooth flow of patients in emergency departments is a global problem. This study attempts to improve the patient flow in emergency departments by considering Lean techniques and Six Sigma methodology in a comprehensive conceptual framework. The proposed research will develop a systematic approach through integration of Lean techniques with Six Sigma methodology to improve patient flow in emergency departments. The results reported in this paper are based on a standard questionnaire survey of 350 patients in the Emergency Department of Aseer Central Hospital in Saudi Arabia. The results of the study led us to determine the most significant variables affecting patient satisfaction with patient flow, including waiting time during patient treatment in the emergency department; effectiveness of the system when dealing with the patient’s complaints; and the layout of the emergency department. The proposed model will be developed within a performance evaluation metric based on these critical variables, to be evaluated in future work within fuzzy logic for continuous quality improvement.

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Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. Results: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma levels (P = .01 for oral dose; P = .0001 for area under the plasma concentration curve at day 2). Patients with a best response of stable disease had a significantly greater reduction in Ki at both day 2 and at the end of cycle 1 compared with progressors (mean difference in % of baseline Ki, 47%, P = .004%; and 51%, P = .006; respectively). The difference in % of baseline Ki remained statistically significant after adjusting for baseline WHO performance status. Conclusion: These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitiors, such as PTK/ZK, for further clinical development. © 2003 by American Society of Clinical Oncology.

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ConA-induced cell surface activation of pro-matrix metalloproteinase-2 (pro-MMP-2) by MDA-MB-231 human breast cancer cells is apparently mediated by up-regulation of membrane type 1 MMP (MT1-MMP) through transcriptional and posttranscriptional mechanisms. Here, we have explored the respective roles of cell surface clustering and protein tyrosine phosphorylation in the ConA- induction effects. Treatment with succinyl-ConA, a variant lacking significant clusterability, partially stimulated MT1-MMP mRNA and protein levels but did not induce MMP-2 activation, suggesting that clustering contributes to the transcriptional regulation by ConA but appears to be critical for the nontranscriptional component. We further found that genistein, an inhibitor of tyrosine phosphorylation, blocked ConA-induced pro-MMP-2 activation and ConA-induced MT1-MMP mRNA level in a dose-dependent manner, implicating tyrosine phosphorylation in the transcriptional aspect. This was confirmed by the dose-dependent promotion of pro-MMP-2 activation by sodium orthovanadate in the presence of suboptimal concentrations of ConA (7.5 μg/ml), with optimal effects seen at 25 μg/g orthovanadate. Genistein did not inhibit the ConA potentiation of MMP-2 activation in MCF-7 cells, in which transfected MT1-MMP is driven by a heterologous promoter, supporting the major implication of phosphotyrosine in the transcriptional component of ConA regulation. These data describe a major signaling event upstream of MT1- MMP induction by ConA and set the stage for further analysis of the nontranscriptional component.