Inactivation of ethanol-inducible cytochrome P450 and other microsomal P450 isozymes by trans-4-hydroxy-2-nonenal, a major product of membrane lipid peroxidation.

Of the microsomal P450 cytochromes, the ethanol-inducible isoform, P450 2E1, is believed to be predominant in leading to oxidative damage, including the generation of radical species that contribute to lipid peroxidation, and in the reductive beta-scission of lipid hydroperoxides to give hydrocarbons and aldehydes. In the present study, the sensitivity of a series of P450s to trans-4-hydroxy-2-nonenal (HNE), a known toxic product of membrane lipid peroxidation, was determined. After incubation of a purified cytochrome with HNE, the other components of the reconstituted system (NADPH-cytochrome P450 reductase, phosphatidylcholine, and NADPH) were added, and the rate of oxygenation of 1-phenylethanol to yield acetophenone was assayed. Inactivation occurs in a time-dependent and HNE concentration-dependent manner, with P450s 2E1 and 1A1 being the most sensitive, followed by isoforms 1A2, 3A6, and 2B4. At an HNE concentration of 0.24 microM, which was close to the micromolar concentration of the enzyme, four of the isoforms were significantly inhibited, but not P450 2B4. In other experiments, the reductase was shown to be only relatively weakly inactivated by HNE. P450s 2E1 and 2B4 in microsomal membranes from animals induced with acetone or phenobarbital, respectively, are as readily inhibited as the purified forms. Evidence was obtained that the P450 heme is apparently not altered and the sulfur ligand is not displaced, that substrate protects against HNE, and that the inactivation is reversed upon dialysis. Higher levels of reductase or substrate do not restore the activity of inhibited P450 in the catalytic assay. Our results suggest that the observed inhibition of the various P450s is of sufficient magnitude to cause significant changes in the metabolism of foreign compounds such as drugs and chemical carcinogens by the P450 oxygenase system at HNE concentrations that occur in biological membranes. In view of the known activities of P450 2E1 in generating lipid hydroperoxides and in their beta-scission, its inhibition by this product of membrane peroxidation may provide a negative regulatory function.

Citation Methodologies in Eusebius’ Historia ecclesiastica and Other Ancient Historiography

This dissertation examines ancient historiographic citation methodologies in light of Mikhail Bakhtin’s dichotomy between polyphony and monologization. In particular, this dissertation argues that Eusebius of Caesarea’s Historia ecclesiastica (HE) abandons the monologic citation methodology typical of previous Greek and Hellenistic historiography and introduces a polyphonic citation methodology that influences subsequent late-ancient Christian historiography to varying degrees. Whereas Pre-Eusebian Greek and Hellenistic historiographers typically use citations to support the single authorial consciousness of the historiographer, Eusebius uses citations to counterbalance his own shortcomings as a witness to past events. Eusebius allows his citations to retain their own voice, even when they conflict with his. The result is a narrative that transcends the point of view of any single individual and makes multiple witnesses, including the narrator, available to the reader. Post-Eusebian late-ancient Christian historiographers exhibit the influence of Eusebius’ innovation, but they are not as intentional as Eusebius in their use of citation methodologies. Many subsequent Christian historiographers use both monologic and polyphonic citation methodologies. Their tendency to follow Eusebius’ practice of citing numerous lengthy citations sometimes emphasizes points of view that oppose the author’s point of view. When an opposing viewpoint surfaces in enough citations, a polyphonic citation methodology emerges. The reader holds the two different narrative strands in tension as the author continues to give voice to opposing viewpoints. After illustrating the citation methodologies with passages from numerous Greek, Hellenistic, and late ancient Christian historiographers, this dissertation concludes with a short computational analysis that uses natural language processing to reveal some broad trends that highlight the previous findings and suggest a possibility for future research.

Adaptación de las escalas de actitudes hacia el tabaco, el alcohol y otras drogas en adolescentes portugueses

El presente estudio muestra los resultados de la adaptación de las escalas de actitudes hacia el tabaco (López-Sánchez, Garcia-Rodriguez, Mira y Estévez, 2000), el alcohol (Garcia-Rodriguez y López-Sánchez, 2001) y otras drogas (López-Sánchez et al., 2000) en población portuguesa. Se trata de tres escalas, cada una con trece ítems, de respuesta tipo Likert con cinco opciones de respuesta, que diferencian tres sub-escalas. Para realizar el estudio de adaptación de las escalas a la población portuguesa, se han utilizado dos muestras independientes, constituidas por 329 y 443 adolescentes, alumnos de bachillerato del norte del país, a quienes se administraron los instrumentos. Los datos recogidos, después de ser sometidos a un análisis factorial exploratorio y confirmatorio, permitieron encontrar una solución adecuada para cada una de las escalas, dando como resultando una buena validez y fiabilidad. En la validez concurrente, los resultados sugieren diferencias de género con todas las sub-escalas y una relación negativa con la edad, así como diferencias en las actitudes de acuerdo con la experiencia y el consumo.

Notebook on geography, navigation, mensuration, and other subjects, ca. 1723-1743

This heavily illustrated notebook contains entries on the following topics, among others: geography; mensuration; navigation and the history of navigation; "the use of Gunter's Scale in plain sailing;" compasses; quadrants and their use; "the refraction of the stars observed by the famous Tycho Brahe;" the latitude and longitude of coasts in America, Europe, and Africa; oceans and islands; mountains and "burning mountains" (volcanoes); rivers and lakes; forests and deserts; maps and sea charts; and the uses of geometry and other measurements by carpenters, joiners, painters, glaziers, masons, and bricklayers. Many pages contain navigational problems and their detailed solutions, as well as chronologies of global exploration and lists of all known rivers, mountains, and other geographic features across the world, many with vivid descriptions. The last pages of the notebook contain entries made in December of 1743 regarding celestial measurements Prince took in Stratford, Connecticut, where he was staying with his brother.

Adolescent Illicit Drug Use and Subsequent Academic and Psychosocial Adjustment : an Examination of Socially-Mediated Pathways

Background: Questions remain regarding the consequences of illicit drug use on adolescent adjustment and the nature of mechanisms that may explain these consequences. In this study, we examined whether early-onset illicit drug use predicts subsequent academic and psychosocial adjustment and whether associations are socially-mediated by decreased school engagement and increased peer deviancy. Method: 4885 adolescents were followed throughout secondary school. We used regressions to determine whether illicit drug use in grade 7 predicted academic achievement, school dropout, depressive symptoms, and conduct problems in grades 10–11, adjusting for potential confounders. We used path analysis to test whether significant associations were mediated by school engagement and peer deviancy in grade 8. Results: Illicit drug use predicted conduct problems and school dropout, but not academic achievement and depressive symptoms. The association between illicit drug use and conduct problems was fully mediated by increased peer deviancy. The association between illicit drug use and school dropout was partially mediated by increased peer deviancy, but remained mostly direct. No indirect association via decreased school engagement was found. Examination of reverse pathways revealed that conduct problems and academic achievement in grade 7 predicted drug use in grades 10–11. These associations were mediated by peer deviancy and school engagement (conduct problems only). Conclusion: Adolescent illicit drug use influences the risk of school dropout and conduct problems in part by contributing to deviant peer affiliation. Reciprocal social mediation characterizes the association between drug use and conduct problems. A reverse mechanism best explains the association with academic achievement.

Simulation of Land Use and Investment Behaviour under Different Policy Scenarios: Results of the extended farm/household model. Factor Markets Working Paper No. 27, July 2012

Factor markets are a central issue in analyses of farm development and of agricultural sector vitality. Among the different production factors, land is one of the most studied. Several studies seek to estimate the effect of government policy payments on land value or land rental prices. The studies mostly agree that government payments and other types of policy support are significant in explaining land prices and account for a large share of them. In October 2011, the European Commission published a new policy proposal for the common agricultural policy (CAP) up to 2020. The proposed regulation includes a shift from historical to regional payments. The objective of this paper is to provide an ex ante analysis of the impact of the new CAP policy instruments on the land market. In particular, the effect of the regionalisation of payments in Italy is examined. The analysis is based on the use of a mathematical programming model to simulate the changes in land demand for a farm in Emilia Romagna. The results highlight the relevance of the new policy mechanism in determining a change in land demand. Yet the effect is highly dependent on initial ownership of entitlements under the historical payment scheme.

The Theoretical Framework and Methodology to Estimate the Farm Labour and Other Factor-Derived Demand and Output Supply Systems. Factor Markets Working Document No. 44, May 2013

This paper provides a conceptual framework for the estimation of the farm labour and other factor-derived demand and output supply systems. In order to analyse the drivers of labour demand in agriculture and account for the impact of policies on those decisions, it is necessary to acknowledge the interaction between the different factor markets. For this purpose, we present a review of the theoretical background to primal and dual representations of production and some empirical literature that has made use of derived demand systems. The main focus of the empirical work is to study the effect of market distortions in one market, through inefficient pricing, on the demand for other inputs. Therefore, own-price and cross-price elasticities of demand become key variables in the analysis. The dual cost function is selected as the most appropriate approach, where input prices are assumed to be exogenous. A commonly employed specification – and one that is particularly convenient due to its flexible form – is the translog cost function. The analysis consists of estimating the system of cost-share equations, in order to obtain the derived demand functions for inputs. Thus, the elasticities of factor substitution can be used to examine the complementarity/substitutability between inputs.

Farm/Household-Level Simulation: Results of Testing Policy and Other Scenarios. Factor Markets Working Document No. 54, June 2013

Among the different production factors, land is the one that most often limits farm development and one of the most studied. The connection between policy and other context variables and land markets is at the core of the policy debate, including the present reform of the Common Agricultural Policy. The proposal of the latter has been published in October 2011 and in Italy it will include the switch of the payment regime from an historical to a regional basis. The authors’ objective is to simulate the impact of the proposed policy reform on the land market, particularly on land values and propensity to transaction. They combine insights and data from a farm household investment model revised and extended in order to simulate the demand curve for land in different policy scenarios and a survey of farmers stated intention carried out in the province of Bologna (Italy) in 2012. Based on these results, the authors calibrate a mathematical programming model of land market exchanges for the province of Bologna and use this model form simulation. The results of the model largely corroborate the results from the survey and both hint at a relevant reaction of the land demand and supply to the shift from the historical to the regionalised payments. As effect, the regionalisation would result in increased rental prices and in a tendency to the re-allocation of land.

Land Use and Production 1955-1979. 1980

Community statistics of vegetable products include data relating, on the one hand, to land use, and on the other hand to production, cultivated areas and yields of different products or groups of products, including fodder products, vegetables and fruits.

Adolescent Illicit Drug Use and Subsequent Academic and Psychosocial Adjustment : an Examination of Socially-Mediated Pathways

Background: Questions remain regarding the consequences of illicit drug use on adolescent adjustment and the nature of mechanisms that may explain these consequences. In this study, we examined whether early-onset illicit drug use predicts subsequent academic and psychosocial adjustment and whether associations are socially-mediated by decreased school engagement and increased peer deviancy. Method: 4885 adolescents were followed throughout secondary school. We used regressions to determine whether illicit drug use in grade 7 predicted academic achievement, school dropout, depressive symptoms, and conduct problems in grades 10–11, adjusting for potential confounders. We used path analysis to test whether significant associations were mediated by school engagement and peer deviancy in grade 8. Results: Illicit drug use predicted conduct problems and school dropout, but not academic achievement and depressive symptoms. The association between illicit drug use and conduct problems was fully mediated by increased peer deviancy. The association between illicit drug use and school dropout was partially mediated by increased peer deviancy, but remained mostly direct. No indirect association via decreased school engagement was found. Examination of reverse pathways revealed that conduct problems and academic achievement in grade 7 predicted drug use in grades 10–11. These associations were mediated by peer deviancy and school engagement (conduct problems only). Conclusion: Adolescent illicit drug use influences the risk of school dropout and conduct problems in part by contributing to deviant peer affiliation. Reciprocal social mediation characterizes the association between drug use and conduct problems. A reverse mechanism best explains the association with academic achievement.

The story of the diamond necklace, told in detail for the first time, by the aid of contemporary memoires, original letters, and official and other documents; and comprising a sketch of the life of the Countess de la Motte, pretended confidant of Marie-Antoinette, with particulars of the careers of the other actors in the remarkable drama.

"Authorities referred to in this work": p.ix-xii.

A comparative analysis of policies and other factors which affect the role of the private sector in economic development /

"PN-AAL-031"--Cover.

The Aztec god, and other dramas,

The Aztec god.--Columbus.--Cecil the seer.

Inter-American relations [microform] : a collection of documents, legislation, descriptions of inter-American organizations, and other material pertaining to inter-American affairs /

Reuse of record except for individual research requires license from Congressional Information Service, Inc.

Treaties and other international acts of the United States of America,

Vol. 1 will not appear in final form until all document volumes to which it refers have been published.