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The identity of nicotinic receptor subtypes sufficient to elicit both the acute and chronic effects of nicotine dependence is unknown. We engineered mutant mice with a4 nicotinic subunits containing a single point mutation, Leu9' --> Ala9' in the pore-forming M2 domain, rendering a4* receptors hypersensitive to nicotine. Selective activation of a4* nicotinic acetylcholine receptors with low doses of agonist recapitulates nicotine effects thought to be important in dependence, including reinforcement in response to acute nicotine administration, as well as tolerance and sensitization elicited by chronic nicotine administration. These data indicate that activation of a4* receptors is sufficient for nicotine-induced reward, tolerance, and sensitization.  相似文献   
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Recirculating aquaculture system (RAS) is a unique approach that offers total control to culture a wide variety of aquatic species. As capital investment is higher for setting up RAS, it is necessary to conduct an economic feasibility analysis based on real data. A structured questionnaire was used to collect all economic and technical data on two catfish species, viz., Pabda (Ompok pabda) and Shing (Heteropneustes fossilis), cultured in an RAS farm. The ultimate objective was to estimate net cash flow, net present value (NPV), profitability index (PI), payback period, discounted payback period, internal rate of return (IRR), and sensitivity analysis to find out the best profitability indicators. The analysis revealed that the IRR were 4% and 16% for Pabda and Shing production, respectively. However, for Pabda and Shing productions, the payback periods were 15 years and 4 months and 6 years and 2 months, respectively. The NPV value was positive for Shing production and negative for Pabda. On the other hand, the PI was lower than one for Pabda production and higher than one for Shing production. Therefore, the results showed that the Shing production in the RAS facility could be economically feasible; however, Pabda production may not be viable in RAS due to lower production and longer culture period. This study may suggest that by increasing the production capacity of the farm and market price of the product through the proper supply chain and by decreasing the initial investment, cost of fingerlings and feed, profitability can be achieved in RAS in Bangladesh.

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Eight soil profiles were sampled from the upland and lowland components of four glacial-fluvial landforms in the Blue Springs drainage basin, Guelph, Ontario. Sediment stratification in these soils was established at depths where statistically significant changes in the values of the ratios of % total sand/% total silt that are calculated on clay-free and carbonate-free basis take place. Limits of significance for differences between populations of stratified sediments were established from the standard error of determination of the ratios of % total sand/% total silt at the 0.01 probability level. A texturally uniform sediment is characterized by a regression line in which the depth (X) is the independent variable and the value of the ratio of % total sand/% total silt (Y) corresponding to the depth is the dependent variable.  相似文献   
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Bio-guided fractionation of the roots of Paris polyphylla (Trilliaceae), based on inhibition of P-glycoprotein-mediated daunorubicin efflux in K562/R7 cell line, led to isolation and identification of the three saponins 3-O-Rha(1-->2)[Ara(1-->4)]Glc-pennogenine, gracillin and polyphyllin D, and the two ecdysteroids 20-hydroxyecdysone and pinnatasterone. These compounds were tested for multidrug reversion on P-glycoprotein (ABCB1) with both drug-selected and transfected cell lines, and also on Breast Cancer Resistance Protein (BCRP/ABCG2). By contrast to a weak efficiency on BCRP, the three saponins displayed significant effects as inhibitors of P-glycoprotein-mediated drug efflux.  相似文献   
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