Putative tumour-suppressor gene DAB2 is frequently down regulated by promoter hypermethylation in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Human Disabled-2 (DAB2), is a multi-function signalling molecule that it is frequently down-regulated in human cancers. We aimed to investigate the possible tumour suppressor effect of DAB2 in nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>We studied the expression of DAB2 in NPC cell lines, xenografts and primary tumour samples. The status of promoter methylation was assessed by methylation specific PCR and bisulfite sequencing. The functional role of DAB2 in NPC was investigated by re-introducing DAB2 expression into NPC cell line C666-1.</p> <p>Results</p> <p>Decrease or absent of <it>DAB2 </it>transcript was observed in NPC cell lines and xenografts. Loss of DAB2 protein expression was seen in 72% (33/46) of primary NPC as demonstrated by immunohistochemistry. Aberrant <it>DAB2 </it>promoter methylation was detected in 65.2% (30/46) of primary NPC samples by methylation specific PCR. Treatment of the DAB2 negative NPC cell line C666-1 with 5-aza-2'-deoxycytidine resulted in restoration of DAB2 expression in a dose-dependent manner. Overexpression of DAB2 in NPC cell line C666-1 resulted in reduced growth rate and 35% reduction in anchorage-dependent colony formation, and inhibition of serum-induced c-Fos expression compared to vector-transfected controls. Over expression of DAB2 resulted in alterations of multiple pathways as demonstrated by expression profiling and functional network analysis, which confirmed the role of DAB2 as an adaptor molecule involved in multiple receptor-mediated signalling pathways.</p> <p>Conclusions</p> <p>We report the frequent down regulation of DAB2 in NPC and the promoter hypermethylation contributes to the loss of expression of DAB2. This is the first study demonstrating frequent DAB2 promoter hypermethylation in human cancer. Our functional studies support the putative tumour suppressor effect of DAB2 in NPC cells.</p

A Neural Network Modeling Approach to Power amplifiers Taking into Account Temperature Effects

In order to analyze the behavior of PAs at different temperature, this paper propose a neural network modeling approach to predict the temperature dependence of PAs. Three different neural network modeling methods are employed to develop the behavioral models. A 0.1-1.2 GHz CMOS PA is designed and fabricated to verify the effectiveness of the modeling method. Model results agree well with the measurement results. Three different models for the fabricated PA are compared in terms of accuracy. As far as author's knowledge, this is the first time of a temperature dependent behavioral model of CMOS PA is proposed to investigate the temperature effect on the performance of a CMOS PA

Internationalisation and Consolidation of the Container Port Industry: Assessment of Channel Structure and Relationships

The international consolidation of the container port industry is a relatively recent, yet radical trend in international shipping and logistics. Global strategies of vertical and horizontal integration evolving around port ownership and operations are undertaken by a variety of market players, both within and outside the international shipping and logistics markets. However, while much of the available literature on the subject has focused on the bases and various motives behind the change, little work has addressed the impacts on channel structure and relationships, including such aspects as control, power and conflict. By channel, we refer to an organised network of institutions that form the combined physical and non-physical path taken by goods and services as they move from original supplier to final consumer. However, in the context of this paper, the scope of the distribution channel is reduced to active members of the international shipping and logistics industry, that is, shippers, ocean carriers, ports, agents and intermediaries. This paper investigates the extent of channel power, conflict, role, performance and strategic concentration of shipping lines as international container terminal operators. A structural equations model is used to assess the impacts of global factors and consolidation on the container port industry, and test whether the direction of change would result in an increasing or decreasing risk of commoditisation and footloose mobility. Maritime Economics & Logistics (2007) 9, 35–51. doi:10.1057/palgrave.mel.9100170