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1.
Minh Thac Nguyen Ryan Denniston Hien Thi Thu Nguyen Tuan Anh Hoang Hana Ross Anthony D. So 《PloS one》2014,9(1)
Illicit trade carries the potential to magnify existing tobacco-related health care costs through increased availability of untaxed and inexpensive cigarettes. What is known with respect to the magnitude of illicit trade for Vietnam is produced primarily by the industry, and methodologies are typically opaque. Independent assessment of the illicit cigarette trade in Vietnam is vital to tobacco control policy. This paper measures the magnitude of illicit cigarette trade for Vietnam between 1998 and 2010 using two methods, discrepancies between legitimate domestic cigarette sales and domestic tobacco consumption estimated from surveys, and trade discrepancies as recorded by Vietnam and trade partners. The results indicate that Vietnam likely experienced net smuggling in during the period studied. With the inclusion of adjustments for survey respondent under-reporting, inward illicit trade likely occurred in three of the four years for which surveys were available. Discrepancies in trade records indicate that the value of smuggled cigarettes into Vietnam ranges from $100 million to $300 million between 2000 and 2010 and that these cigarettes primarily originate in Singapore, Hong Kong, Macao, Malaysia, and Australia. Notable differences in trends over time exist between the two methods, but by comparison, the industry estimates consistently place the magnitude of illicit trade at the upper bounds of what this study shows. The unavailability of annual, survey-based estimates of consumption may obscure the true, annual trend over time. Second, as surveys changed over time, estimates relying on them may be inconsistent with one another. Finally, these two methods measure different components of illicit trade, specifically consumption of illicit cigarettes regardless of origin and smuggling of cigarettes into a particular market. However, absent a gold standard, comparisons of different approaches to illicit trade measurement serve efforts to refine and improve measurement approaches and estimates. 相似文献
2.
Sharat J. Vayttaden Jacqueline Friedman Tuan M. Tran Thomas C. Rich Carmen W. Dessauer Richard B. Clark 《PLoS computational biology》2010,6(1)
We developed a unified model of the GRK-mediated β2 adrenergic receptor (β2AR) regulation that simultaneously accounts for six different biochemical measurements of the system obtained over a wide range of agonist concentrations. Using a single deterministic model we accounted for (1) GRK phosphorylation in response to various full and partial agonists; (2) dephosphorylation of the GRK site on the β2AR; (3) β2AR internalization; (4) recycling of the β2AR post isoproterenol treatment; (5) β2AR desensitization; and (6) β2AR resensitization. Simulations of our model show that plasma membrane dephosphorylation and recycling of the phosphorylated receptor are necessary to adequately account for the measured dephosphorylation kinetics. We further used the model to predict the consequences of (1) modifying rates such as GRK phosphorylation of the receptor, arrestin binding and dissociation from the receptor, and receptor dephosphorylation that should reflect effects of knockdowns and overexpressions of these components; and (2) varying concentration and frequency of agonist stimulation “seen” by the β2AR to better mimic hormonal, neurophysiological and pharmacological stimulations of the β2AR. Exploring the consequences of rapid pulsatile agonist stimulation, we found that although resensitization was rapid, the β2AR system retained the memory of the previous stimuli and desensitized faster and much more strongly in response to subsequent stimuli. The latent memory that we predict is due to slower membrane dephosphorylation, which allows for progressive accumulation of phosphorylated receptor on the surface. This primes the receptor for faster arrestin binding on subsequent agonist activation leading to a greater extent of desensitization. In summary, the model is unique in accounting for the behavior of the β2AR system across multiple types of biochemical measurements using a single set of experimentally constrained parameters. It also provides insight into how the signaling machinery can retain memory of prior stimulation long after near complete resensitization has been achieved. 相似文献
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Summary The effects of 2deoxycoformycin, a specific inhibitor of adenosine deaminase, on the repair and fixation of potentially lethal damage (PLD) sensitive to treatment with-araA, an adenosine analogue acting via inhibition of DNA polymerases and, have been studied. Given after irradiation deoxycoformycin alone had little effect on cell survival. More damage was nevertheless fixed by a given concentration of-araA in the presence of deoxycoformycin to a degree that 35 µM-araA given simultaneously with 1 µg/ml deoxycoformycin produced the same effect (survival decrease to 20% of the controls) as 90 µM-araA given alone. Maximum potentiation of the-araA effect was observed at 1 µg/ml deoxycoformycin with a slight decrease at higher concentrations.Combined treatment with-araA and deoxycoformycin reduced or eliminated the shoulder from the survival curve without affecting the slope, an effect similar to that observed after treatment of cells with-araA alone. The results indicate the importance of adenosine deaminase in the inactivation of nucleoside analogues and are discussed vis-a-vis the possible practical application of this inhibitor in both experimental and therapeutic applications. 相似文献
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P-815 mastocytoma cells increase the level of pyruvate kinase (PK) expression in response to chloroform-methanol extracts of conditioned media, butyrate, and dibutyryl cyclic AMP (but2cAMP) plus theophylline. The butyrate effect is indomethacin sensitive, suggesting a prostaglandin (PG) is the active signaling factor. Moreover, the chloroform-methanol extracts contain PGE2 and PGF2 alpha and additions of the latter enhance PK activity. PGE2 alone has little or no effect but acts synergistically with PGF2 alpha. These data show that PGF2 alpha can regulate PK levels. On the other hand, other factors may also be active, since the endogeneous and the but2cAMP plus theophylline effects are indomethacin insensitive. Most of the factors that increase PK activity also inhibit cellular growth; however, regulation of PK expression can be uncoupled from growth inhibition. 相似文献
7.
The effects of multiple-dose gamma irradiation on the shape of survival curves were studied with mouse C3H 10T1/2 cells maintained in contact-inhibited plateau phase. The dose-fractionation intervals included 3, 6, and 24 h. Following three fractionated doses (5 Gy per dose) of exposures, cells responded to further irradiation by displaying a survival curve with a much reduced shoulder width (Dq) compared to that of the survival curve measured in cells irradiated with single-graded doses alone. The effect on the mean lethal dose (D0) was small and appeared to be significant. The effect on reduction of Dq could not be completely overcome by lengthening the fractionation intervals from 3 to 6 h or 24 h, times in which repair of sublethal damage (SLD) measured by simple split-dose scheme and potentially lethal damage (PLD) measured by postirradiation incubation was completed. Other experiments showed that pretreatments of cells with fractionated irradiation appeared to slow down the cellular repair processes of SLD and PLD. Therefore, the observed change in the shape of survival curves after fractionation treatments may be attributed to a reduction of the cells' capacity for damage accumulation by an enhancement of the lethal expression of SLD and PLD. Although the molecular mechanism(s) is not known, the results of this study indicate that the acute graded dose-survival curve cannot be used a priori to extrapolate and reliably predict results of hyperfractionation. It is probable that for a nondividing or slowly dividing cell population, such an extrapolation may lead to an underestimation of cell killing. Furthermore, the findings of this investigation appear to support an interpretation, alternative to the high-linear energy transfer (LET) track-end postulate, for the effects on cell survival seen at low doses or low dose rates. 相似文献
8.
Identification and characterization of a calcium-binding protein in the mouse chorioallantoic placenta.
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Mouse chorioallantoic placenta contains a specific calcium-binding protein (MCaBP). A procedure involving gel filtration and ion-exchange chromatography was developed to purify the MCaBP. The MCaBP activity increased as a function of embryonic gestation and was highly specific for Ca2+. The MCaBP is a monomeric protein of Mr 57000, with pI 4.7. Specific antibodies were prepared against the MCaBP and were used to localize the MCaBP to syncytiotrophoblasts of the chorionic villi of mouse chorioallantoic placenta. These properties suggest that the MCaBP may be involved in transplacental calcium transport. 相似文献
9.
In order to investigate the effect of embryonic calcium deficiency on the cellular differentiation processes in embryonic skeletogenesis, chick embryos were maintained in long-term shell-less cultures in vitro. The absence of the eggshell, which normally provides over 120 mg of calcium to the embryo during the course of development, resulted in severely retarded and anomalous skeletal formation. The pattern of cytodifferentiation in the skeletal elements during development was assessed by examining collagen type synthesis in both endochondral and intramembranous bones of normal and shell-less embryos as a function of developmental age. Skeletal tissues obtained from these embryos at various developmental stages were maintained in short-term organ culture in medium containing [3H]Pro. The metabolically labeled collagen was isolated from these tissues and typed biochemically based on electrophoresis, ion-exchange chromatography, differential salt fractionation, zone precipitation chromatography, and CNBr peptide mapping. The results indicate that, compared to chronologically equivalent normal controls, calcium-deficient skeletal elements from shell-less embryos appeared to fail to mature into complete bony tissues and instead exhibited partial cartilage phenotype with the expression of cartilage-specific type II collagen. 相似文献
10.
Isolation of the nonhistone proteins of rat Walker carcinoma 256 总被引:5,自引:0,他引:5