Web caching or web proxy has been considered as the prime vehicle to cope with the ever-increasing demand for information retrieval over the Internet, WWW being a typical example. The existing work on web proxy has primarily focused on content based caching; relatively less attention has been given to the development of proper placement strategies for the potential web proxies in the Internet. This paper investigates the optimal placement policy of web proxies for a target web server in the Internet. The objective is to minimize the overall latency of searching the target web server subject to the network resources and traffic pattern. Specifically, we are interested in finding the optimal placement of multiple web proxies (m) among the potential sites (n) under a given traffic pattern. We model the problem as a Dynamic Programming problem, and we obtain an optimal solution for a linear array topology using O(n 2 m) time.

BackgroundPerineural invasion is a common path for cholangiocarcinoma (CCA) metastasis, and it is highly correlated with postoperative recurrence and poor prognosis. It is often an early event in a disease that is commonly diagnosed in advanced stages, and thus it could offer a timely therapeutic and diagnostic target if better understood. This article systematically reviews the progress of CCA neural invasion-related molecules.MethodsStudies were identified by searching MEDLINE and PubMed databases for articles from January 1990 to December 2009, using the keywords "cholangiocarcinoma," "perineural invasion," "nerve growth factor"(NGF), "neural cell adhesion molecule" (NCAM), "matrix metalloproteinase"(MMP), "neurotransmitter," "acetylcholine" (Ach), and "transforming growth factor" (TGF)." Additional papers and book chapters were identified by a manual search of references from the key articles.ResultsFrom above we found that the molecules NGF, NCAM, MMP, Ach and TGF may have prognostic significance in, and offer clues to the mechanism of CCA neural invasion.ConclusionsCholangiocarcinoma's increasing worldwide incidence is especially poignant in view of both the lacking effective therapies, and the fact that it is commonly diagnosed in advanced stages. As CCA neural invasion often appears early, more complete characterization of its molecular pathology could lead to the identification of targets for the diagnosis and therapy of this devastating malignancy.

Although previous studies showed that the principal oncoprotein encoded by Epstein-Barr virus, latent membrane protein 1(LMP1), could induce the nasopharyngeal carcinoma cells in G2/M phase increased, little is known about the target molecules and mechanisms. The present study demonstrated that LMP1 could induce the accumulation of p53 protein and upregulate its transactivity in a dose dependent manner, which resulted in the decrease of the kinase activity of cdc2/cyclin B complex and inducing arrest at G2/M phase through the activation of NF-κB and AP-1 signaling pathways, and the effect of NF-κB was more obvious than that of AP-1. This study provided some significant evidence for further elucidating the molecular mechanisms that LMP1 had effects on the surveillance mechanism of cell cycle and promoting the survival of transformed cells and tumorigenesis.

Demyelination is a nervous system disease in which the myelin sheaths of neurons are damaged due to inflammatory reactions, inherited abnormalities or trauma. This damage impairs the conduction of signals in the affected nerves, which in turn causes deficiencies in sensation, movement and cognition. Oligodendrocyte precursor cells (OPCs) are able to induce remyelination. However, the remyelination is suboptimal due to the limited migration of OPCs. In the present study, neonatal OPCs were isolated from rats for the investigation of the role of C-X-C motif chemokine ligand 12 (CXCL12), an important chemokine, in mediating the migration ability of OPCs. The present results demonstrated that CXCL12 stimulation markedly promoted the migration of OPCs and activated the dual specificity mitogen-activated protein kinase kinase 1 (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/RAC-α serine/threonine-protein kinase (AKT) pathways. Knockdown of C-X-C motif chemokine receptor 4 (CXCR4; a receptor of CXCL12) reversed the CXCL12-induced migration of OPCs and blocked the MEK/ERK and PI3K/AKT pathways. In addition, specific inhibitors of the MEK/ERK and PI3K/AKT pathways significantly reduced the migration of OPCs. Based on these findings, it was concluded that CXCL12 may induce the migration of OPCs through the CXCR4-activated MEK/ERK and PI3K/AKT pathways. The results of the present study support the manipulation of CXCL12-mediated OPC migration to improve remyelination.

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The use of probiotics has recently become a considerably promising research area. The most advanced fourth-generation probiotics involve beneficial bacteria enclosed in biofilms. However, differences in the effects of probiotics...

Non-small cell lung cancer (NSCLC) is the most common cancer worldwide and is a leading cause of lung cancer mortality due to early stage metastases. Cancer stem-like cells (CSLCs) or tumor-initiating cells (TICs) are rare subpopulation cells that are responsible for maintaining tumor growth and invasion leading to recurrence and metastasis. Previous studies revealed that miR-183 can mediate the invasiveness and growth of NSCLC. However, the exact role of miR-183 in regulating the biological behavior of CSLCs in NSCLC remains unclear. In the present study, we explored the regulation of protein tyrosine phosphatase non-receptor type 4 (PTPN4) by miR-183 in vitro using luciferase reporter assays, and we further analyzed the effects of miR-183 on the invasiveness of CSLCs in vitro and in vivo using transwell and bioluminescence assays. Following our finding that miR-183 binds to PTPN4 messenger RNA (mRNA) to prevent its translation through the 3'-untranslated region (UTR), we found that overexpression of miR-183 in CSLCs decreased PTPN4 protein levels while inhibition of miR-183 increased PTPN4 protein levels. The suppression of PTPN4 levels in CSLCs by miR-183 paralleled with a significant promotion in their motility in vitro and in vivo, while anti-sense miR-183 increased PTPN4 levels in CSLCs, which paralleled with a significant decrease in their invasiveness. Furthermore, correlation analysis between miR-183 and PTPN4 in clinical samples demonstrated a statistically significant inverse correlation between PTPN4 mRNA levels and miR-183. In brief, our data indicate that miR-183 plays a pro-invasive role by inverse regulation of PTPN4, and this axis may be a new therapeutic target for suppressing the metastatic capability of CSLCs in NSCLC.