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Background: Insulin receptor substrate 4 (IRS-4) is an adaptor protein for which new evidence suggests plays a role in tumour promotion.Methods: We described nuclear IRS-4 in RKO colon cancer cell lines in biopsies of patients with colorectal cancer (CRC) (n = 20) and in matched adjacent normal colorectal (MANC) tissue (n = 20).Results: Treatment with physiological doses of IGF-1 promoted nuclear influx of IRS-4 from cellular cytosol in RKO cells. When exogenous IRS-4 was overexpressed in RKO cells, there was an increase in cyclin D1, cyclin E, E2F1, pRB Ser 809/811 and pRB Ser 705 levels compared with the empty vector-transfected cells. Some of these changes returned to control values after wortmannin treatment. Subcellular fractionation showed an overexpression of IRS-4 in the cytoplasm, membrane, and nuclei of tumour samples, whereas the levels of the protein were barely detectable in the three compartments of normal samples. Immunohistochemical studies showed positive nuclear IRS-4 staining in over 74% of the tumour cells. IRS-4 was strongly overexpressed in tumoural tissues from CRC patients compared to MANC tissues. The up-regulation of IRS-4 in CRC samples correlated significantly with the increase of several G1 checkpoint proteins including cyclin D1 (r = 0.6662), Rb (r = 0.7779), pRb Serine 809/811 (r = 0.6864), pRb serine 705 (r = 0.6261) and E2F1 (r = 0.8702).Conclusions: Taken together, our findings suggest that IRS-4 promotes retinoblastoma-cyclin-dependent kinase activation and it may serve as a pharmacological target since its expression is very low in normal tissue, including colonic epithelium. [ABSTRACT FROM AUTHOR]

In the context of the Multiparty Interaction Model, fairness is used to insure that an interaction that is enabled sufficiently often in a concurrent program will eventually be selected for execution. Unfortunately, this notion does not take conspiracies into account, i.e. situations in which an interaction never becomes enabled because of an unfortunate interleaving of independent actions; furthermore, eventual execution is usually too weak for practical purposes since this concept can only be used in the context of infinite executions. In this article, we present a new fairness notion, k-conspiracy-free fairness, that improves on others because it takes finite executions into account, alleviates conspiracies that are not inherent to a program, and k may be set a priori to control its goodness to address the above-mentioned problems. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Current software process models (CMM, SPICE, etc.) strongly recommend the application of statistical control and measure guides to define, implement, and evaluate the effects of different process improvements. However, whilst quantitative modeling has been widely used in other fields, it has not been considered enough in the field of software process improvement. During the last decade software process simulation has been used to address a wide diversity of management problems. Some of these problems are related to strategic management, technology adoption, understanding, training and learning, and risk management, among others. In this work a dynamic integrated framework for software process improvement is presented. This framework combines traditional estimation models with an intensive utilization of dynamic simulation models of the software process. The aim of this framework is to support a qualitative and quantitative assessment for software process improvement and decision making to achieve a higher software development process capability according to the Capability Maturity Model. The concepts underlying this framework have been implemented in a software process improvement tool that has been used in a local software organization. The results obtained and the lessons learned are also presented in this paper. [ABSTRACT FROM AUTHOR]