NAD(P)H:quinone oxidoreductase (NQO1)-mediated detoxification of quinones plays a critical role in cancer prevention. Heavy metals such as mercury (Hg(2+)) alter the carcinogenicity of aryl hydrocarbon receptor ligands, mainly by modifying various xenobiotic-metabolizing enzymes such as NQO1. Therefore, we examined the effect of Hg(2+) on the expression of NQO1 in human hepatoma HepG2 cells. For this purpose HepG2 cells were incubated with various concentrations of Hg(2+) (2.5, 5, and 10μM) in the presence and absence of two NQO1 inducers, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and isothiocyanate sulforaphane (SUL), as bifunctional and monofunctional inducers, respectively. Analysis of the time-dependent effect of Hg(2+) revealed that Hg(2+) increased the expression of NQO1 mRNA in a time-dependent manner. In addition, Hg(2+) increased NQO1 at the mRNA, protein, and activity levels in the presence and absence of both NQO1 inducers, TCDD and SUL, which coincided with increased nuclear accumulation of Nrf2 protein. Investigating the effect of Hg(2+) at the transcriptional level revealed that Hg(2+) significantly induced the antioxidant-responsive element-dependent luciferase reporter gene expression in the absence and the presence of both NQO1 inducers. NQO1 mRNA and protein decay experiments revealed a lack of posttranscriptional and posttranslational mechanisms. Transfecting HepG2 cells with siRNA for Nrf2 significantly decreased the Hg(2+)-mediated induction of NQO1 mRNA and catalytic activity by approximately 90%. In conclusion, we demonstrated that Hg(2+) regulates the expression of the NQO1 gene through a transcriptional mechanism in human hepatoma HepG2 cells. In addition, Nrf2 is involved in the modulation of NQO1 by Hg(2+).

Utility of Nitriles in Organic Synthesis: Synthesis of Poly-Functionaly Substituted Pyridones and Isoquinoline Derivatives. Alex. J. Pharm. Sci.

Aryl hydrocarbon receptor (AhR) ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and metals, such as mercury (Hg(2+)), are environmental co-contaminants and their molecular interaction may disrupt the coordinated regulation of the carcinogen-activating enzyme cytochrome P450 1A1 (CYP1A1). Therefore, we examined the effect of co-exposure to Hg(2+) and TCDD on the expression of the CYP1A1 in HepG2 cells. Our results showed that Hg(2+) significantly inhibited the TCDD-mediated induction of CYP1A1 at the mRNA, protein, and catalytic activity levels. At the transcriptional level, co-exposure to Hg(2+) and TCDD significantly decreased the TCDD-mediated induction of AhR-dependent luciferase reporter gene expression. Moreover, Hg(2+) did not affect CYP1A1 mRNA stability, while decreasing its protein half-life, suggesting the involvement of a posttranslational mechanism. Importantly, Hg(2+) increased the expression of heme oxygenase-1 (HO-1), a rate limiting enzyme in heme degradation, which coincided with further decrease in the CYP1A1 catalytic activity levels. Upon using a competitive HO-1 inhibitor, tin mesoporphyrin, heme precursor, hemin, or transfecting the HepG2 cells with siRNA for HO-1 there was a partial restoration of the inhibition of TCDD-mediated induction of CYP1A1 catalytic activity. In conclusion, we demonstrate that Hg(2+) down-regulates the expression of CYP1A1 at the transcriptional and posttranslational levels in HepG2 cells. In addition, HO-1 is involved in the modulation of CYP1A1 at the posttranslational level.

Positioning systems are one of the key elements required by location-based services (LBS). As global positioning system (GPS) was never intended for indoor environments, indoor positioning systems based on wireless local area networks (WLAN) have been proposed as a viable solution. RADAR algorithm is one of the famous indoor positioning techniques. It uses a database of predetermined fingerprints for selected locations to estimate the location of a mobile user in the signal space. Another new proposed algorithm named the Enhanced Fingerprint (EFP) uses the same principle as RADAR algorithm but with more than one fingerprint per location. In this paper we investigated the location fingerprint based algorithms by taking RADAR and EFP with more details. We evaluated these two algorithms in terms of accuracy, reliability and computation time. Experiment results show that the EFP algorithm gains 1.82 m of accuracy over RADAR algorithm, while the last one saves 75% of computation time. We found that EFP algorithm is more consistent with varying number of training samples.

A web-based online job application has become the most useful tool to access the information about the applicant, and the applicant information is accessible at the press of

a button immediately. Graduates need to work hard to get jobs that may require cost and time. Thus this study proposal to model requirement of UUM Alumni Online Jobs that provide a flexible way to access jobs. The requirement model for the alumni students would provides the alumni with the capability to input, search and receive information of jobs via the online services.

We consider a differentiated duopoly where firms invest in research and development (R&D) to reduce their production cost. The objective of this study is to derive and compare Bertrand and Cournot equilibria, and then examine the robustness of the literature's results, especially those of Qiu (1997). We find that The main results of this study are as follows: (a) Bertrand competition is more efficient if R&D productivity is low, industry spillovers are weak, or products are very different. (b) Cournot competition is more efficient if R&D productivity is high and R&D spillovers and products' degree of substitutability are not very small. (c) Cournot competition may lead to higher Outputs, higher consumer surpluses and lower prices, provided that R&D productivity is very high and spillovers and degree of substitutability of firms' products are moderate to high, (d) Cournot competition results in higher R&D Investments compared to Bertrand's. These results show that the relative efficiencies of Bertrand and Cournot equilibria are sensitive to the suggested specifications, and hence far from being robust.