This paper presents a 3-Region footloose-entrepreneur new economic geography model. Two symmetric regions are part of an economically integrated area (the Union), while the third region represents an outside trade partner. We explore how the spatial allocation of industrial production and employment within the Union is affected by changes in two aspects of trade liberalisation: regional integration and globalisation. Our main contribution pertains to the analysis of the local and global dynamics of the specified factor mobility process. We show that significant parameter ranges exist for which asymmetric distribution of economic activities is one of the possible long-run outcomes. This is a remarkable result within the NEG literature. We then analyse the impact of international trade liberalisation on the dynamics of agglomeration conditional on the endowments of skilled and unskilled labour of the outside region. (authors' abstract) / Series: Department of Economics Working Paper Series

Company-taxation policies in the Central and East European New Member States (CEE-NMS) have been frequently characterised as tax-cutting strategies in order to attract Foreign Direct Investment (FDI). On the basis of a survey of six empirical studies a median value of the tax-rate elasticities of FDI of -0.22 in CEE-NMS and mediterranean periphery countries is derived. Yet, these tax-rate elasticities probably suffer from a sort of measurement error bias since these studies entirely rely on the host country Statutory tax rate as measure of tax burden. Building on a thorough criticism of FDI as a measure reflecting multinational activity and the Statutory tax rate as a reliable measure of the effective tax burden, 315 effective average bilateral tax rates (BEATR) are calculated for seven home countries and five CEE-NMS for the period 1996-2004, following the approach of Devereux and Griffith (1998). Since our empirical results show substantial differences in the variability of the host country Statutory tax rates and the BEATRs, it is contended that the latter should be used as explanatory variables in empirical studies. / Series: Discussion Papers SFB International Tax Coordination

O presente estudo teve como objetivo avaliar a aplicação de análogo sintético da prostaglandina F2 (PGF2 ) associado à carbetocina ou ocitocina sobre a eficiência na indução ao parto em suínos. Foram analisados o tempo entre aplicação e início do trabalho de parto, duração do parto e percentual de natimortalidade. A indução do parto foi realizada aos 113 dias de gestação através da aplicação do análogo da PGF2 (cloprostenol sódico) via submucosa vulvar (SMV). As ocitocinas foram aplicadas 24 horas após a indução, pela via intramuscular (IM). O experimento 1 contou com 284 fêmeas em 4 tratamentos: T1- cloprostenol sódico; T2- cloprostenol sódico e 0,10 mg de carbetocina; T3- cloprostenol sódico e 10 UI de ocitocina; T4- solução salina 0,9% (NaCl) via SMV. O experimento 2 contou com 276 fêmeas em 4 tratamentos: T1- cloprostenol sódico; T2- cloprostenol sódico e 0,10 mg de carbetocina; T3- cloprostenol sódico e 0,05 mg de carbetocina; T4- cloprostenol sódico e 10 UI de ocitocina. Não houve diferença entre os tratamentos no número de leitões nascidos totais, nascidos vivos e percentual de partos com intervenção obstétrica manual. A sincronização dos partos é maior quando induzidos com cloprostenol comparado ao grupo não induzido. A utilização de cloprostenol associado à carbetocina resulta em menor duração do parto. / The present study aimed the analysis of a synthetic analogue of prostaglandin F2 (PGF2 ) associated to carbetocyn or oxytocin on the efficiency of farrowing induction in swine. The following variables were assessed: time between injections and start of farrowing, farrowing length and stillbirth percentage. Farrowing induction was performed at 113 days of gestation using injection of PGF2 analogue (sodium cloprostenol) by vulvar sub mucosal route (SMV). The oxytocins were used 24 hours after induction, by intra-muscular route (IM). Experiment 1 used 284 females in 4 treatments: T1-sodium cloprostenol; T2- sodium cloprostenol and 0.10 mg of carbetocyn; T3- sodium cloprostenol and 10 UI of oxytocin; T4- saline solution by SMV route. Experiment 2 used 276 females in 4 treatments: T1- sodium cloprostenol; T2- sodium cloprostenol and 0.10 mg of carbetocyn; T3- sodium cloprostenol and 0.05 mg of carbetocyn; T4- sodium cloprostenol and 10 UI of oxytocin. There was no difference between treatments regarding number of total born piglets per farrowing, born alive and percentage of farrowing using manual obstetrical intervention. Farrowing synchronization was higher when induced with cloprostenol when compared to the noninduced group. The use of cloprostenol associated with carbetocyn resulted in a diminished farrowing length.

O presente estudo teve como objetivo avaliar a aplicação de análogo sintético da prostaglandina F2 (PGF2 ) associado à carbetocina ou ocitocina sobre a eficiência na indução ao parto em suínos. Foram analisados o tempo entre aplicação e início do trabalho de parto, duração do parto e percentual de natimortalidade. A indução do parto foi realizada aos 113 dias de gestação através da aplicação do análogo da PGF2 (cloprostenol sódico) via submucosa vulvar (SMV). As ocitocinas foram aplicadas 24 horas após a indução, pela via intramuscular (IM). O experimento 1 contou com 284 fêmeas em 4 tratamentos: T1- cloprostenol sódico; T2- cloprostenol sódico e 0,10 mg de carbetocina; T3- cloprostenol sódico e 10 UI de ocitocina; T4- solução salina 0,9% (NaCl) via SMV. O experimento 2 contou com 276 fêmeas em 4 tratamentos: T1- cloprostenol sódico; T2- cloprostenol sódico e 0,10 mg de carbetocina; T3- cloprostenol sódico e 0,05 mg de carbetocina; T4- cloprostenol sódico e 10 UI de ocitocina. Não houve diferença entre os tratamentos no número de leitões nascidos totais, nascidos vivos e percentual de partos com intervenção obstétrica manual. A sincronização dos partos é maior quando induzidos com cloprostenol comparado ao grupo não induzido. A utilização de cloprostenol associado à carbetocina resulta em menor duração do parto. / The present study aimed the analysis of a synthetic analogue of prostaglandin F2 (PGF2 ) associated to carbetocyn or oxytocin on the efficiency of farrowing induction in swine. The following variables were assessed: time between injections and start of farrowing, farrowing length and stillbirth percentage. Farrowing induction was performed at 113 days of gestation using injection of PGF2 analogue (sodium cloprostenol) by vulvar sub mucosal route (SMV). The oxytocins were used 24 hours after induction, by intra-muscular route (IM). Experiment 1 used 284 females in 4 treatments: T1-sodium cloprostenol; T2- sodium cloprostenol and 0.10 mg of carbetocyn; T3- sodium cloprostenol and 10 UI of oxytocin; T4- saline solution by SMV route. Experiment 2 used 276 females in 4 treatments: T1- sodium cloprostenol; T2- sodium cloprostenol and 0.10 mg of carbetocyn; T3- sodium cloprostenol and 0.05 mg of carbetocyn; T4- sodium cloprostenol and 10 UI of oxytocin. There was no difference between treatments regarding number of total born piglets per farrowing, born alive and percentage of farrowing using manual obstetrical intervention. Farrowing synchronization was higher when induced with cloprostenol when compared to the noninduced group. The use of cloprostenol associated with carbetocyn resulted in a diminished farrowing length.

O presente estudo teve como objetivo avaliar a aplicação de análogo sintético da prostaglandina F2 (PGF2 ) associado à carbetocina ou ocitocina sobre a eficiência na indução ao parto em suínos. Foram analisados o tempo entre aplicação e início do trabalho de parto, duração do parto e percentual de natimortalidade. A indução do parto foi realizada aos 113 dias de gestação através da aplicação do análogo da PGF2 (cloprostenol sódico) via submucosa vulvar (SMV). As ocitocinas foram aplicadas 24 horas após a indução, pela via intramuscular (IM). O experimento 1 contou com 284 fêmeas em 4 tratamentos: T1- cloprostenol sódico; T2- cloprostenol sódico e 0,10 mg de carbetocina; T3- cloprostenol sódico e 10 UI de ocitocina; T4- solução salina 0,9% (NaCl) via SMV. O experimento 2 contou com 276 fêmeas em 4 tratamentos: T1- cloprostenol sódico; T2- cloprostenol sódico e 0,10 mg de carbetocina; T3- cloprostenol sódico e 0,05 mg de carbetocina; T4- cloprostenol sódico e 10 UI de ocitocina. Não houve diferença entre os tratamentos no número de leitões nascidos totais, nascidos vivos e percentual de partos com intervenção obstétrica manual. A sincronização dos partos é maior quando induzidos com cloprostenol comparado ao grupo não induzido. A utilização de cloprostenol associado à carbetocina resulta em menor duração do parto. / The present study aimed the analysis of a synthetic analogue of prostaglandin F2 (PGF2 ) associated to carbetocyn or oxytocin on the efficiency of farrowing induction in swine. The following variables were assessed: time between injections and start of farrowing, farrowing length and stillbirth percentage. Farrowing induction was performed at 113 days of gestation using injection of PGF2 analogue (sodium cloprostenol) by vulvar sub mucosal route (SMV). The oxytocins were used 24 hours after induction, by intra-muscular route (IM). Experiment 1 used 284 females in 4 treatments: T1-sodium cloprostenol; T2- sodium cloprostenol and 0.10 mg of carbetocyn; T3- sodium cloprostenol and 10 UI of oxytocin; T4- saline solution by SMV route. Experiment 2 used 276 females in 4 treatments: T1- sodium cloprostenol; T2- sodium cloprostenol and 0.10 mg of carbetocyn; T3- sodium cloprostenol and 0.05 mg of carbetocyn; T4- sodium cloprostenol and 10 UI of oxytocin. There was no difference between treatments regarding number of total born piglets per farrowing, born alive and percentage of farrowing using manual obstetrical intervention. Farrowing synchronization was higher when induced with cloprostenol when compared to the noninduced group. The use of cloprostenol associated with carbetocyn resulted in a diminished farrowing length.

No / The pharmacology of bimatoprost, a synthetic prostaglandin-amide, was examined in prostaglandin F2¿ (PGF2¿)-sensitive preparations. Bimatoprost potently contracted the rabbit isolated uterus (pEC50=7.92±0.16). In contrast, bimatoprost exhibited weak excitatory activity in human myometrium from pregnant and nonpregnant donors, mouse uterus, rat uterus, and endothelium-intact rabbit jugular veins, and did not stimulate DNA synthesis in mouse fibroblasts. The possibility that the effects of bimatoprost may reflect partial agonism at prostanoid FP receptors was examined and the contractile effects of full agonists, 17-phenyl PGF2¿ (FP) and U-46619 (TP, a control), were determined in the absence and presence of 1 ¿M bimatoprost on the mouse uterus. Analyses of the agonist¿agonist functional studies showed no antagonism, indicating that bimatoprost is not a partial agonist. Bioassay metabolism studies of bimatoprost and latanoprost (FP receptor agonist prodrug) in the rabbit uterus were conducted using recipient mouse uterus. Results indicated that the potent responses to bimatoprost in the rabbit uterus are produced by the intact molecule and not by its putative free acid metabolite, 17-phenyl PGF2¿. Some hydrolysis of latanoprost to latanoprost free acid appears to have occurred in the rabbit uterus, according to biological detection. The pharmacology of bimatoprost could not be explained by its interaction with known prostanoid FP receptors and was independent of species-, tissue-, or preparation-related factors. The potent contractile effects of bimatoprost in the rabbit uterus provide further pharmacological evidence for the presence of a novel receptor population that preferentially recognises bimatoprost.

<p>Lipid peroxidation is thought to be an important factor in the pathophysiology of a number of diseases and in the process of ageing, but its measurement <i>in vivo</i> has been difficult. The aim of this thesis was to evaluate methods for measurement of lipid peroxidation <i>in vivo</i> that are suitable for clinical investigations, and to apply these methods in animal and human studies investigating basal conditions and situations associated with increased lipid peroxidation.</p><p>The ferrous oxidation in xylenol orange assay for quantification of total plasma lipid hydroperoxides was re-evaluated regarding sample handling and storage. It was shown to be a useful tool for analyses of fresh but not stored plasma samples.</p><p>A methodology for measurement of the total amount (sum of free and esterified) of an F₂-isoprostane, 8-iso-prostaglandin F_2α, in tissues using alkaline hydrolysis in combination with an existing radioimmunoassay was developed. High levels of 8-iso-prostaglandin F_2α in rat liver tissue were quantified by this technique both at basal conditions and in an experimental model of increased lipid peroxidation induced by carbon tetrachloride.</p><p>Supplementation with vitamin E to rats decreased both non-enzymatic and enzymatic lipid peroxidation as measured by 8-iso-prostaglandin F_2α and a major prostaglandin F_2α metabolite. This was verified both in the urine at basal conditions, and in the urine and liver tissue after carbon tetrachloride induced lipid peroxidation.</p><p>In a randomised cross-over study in humans, a rapeseed oil-based diet with an increased proportion of easily oxidised polyunsaturated fatty acids was compared to a control diet rich in saturated fats. The rapeseed oil-based diet did not seem to increase the degree of lipid peroxidation in plasma and urine as measured by 8-iso-prostaglandin F_2α, hydroperoxides and malondialdehyde, presumably due to a sufficient content of antioxidants in the rapeseed oil diet.</p><p>In conclusion, the simultaneous measurement of several biomarkers of lipid peroxidation is a promising approach for future studies investigating the possible role of lipid peroxidation <i>in vivo</i> under basal conditions and in the pathology of diseases.</p>

<p>Numerous diseases are associated with reduced antioxidant defence and oxidative stress. The antioxidant defence includes dietary and endogenous antioxidants and involves complex interactions between them. The effects of dietary factors on antioxidant status and oxidative stress of healthy humans were investigated in the studies described in this thesis. Assays of plasma antioxidant capacity encompass interactions between various antioxidants. Although uric acid has an unclear function as an antioxidant, it is a major determinant of antioxidant capacity. We measured antioxidant capacity in the presence and absence of uric acid to provide more information on the application of measures of antioxidant capacity. Individuals with high dietary intakes of various antioxidants and antioxidant rich foods, especially when combined, had higher plasma antioxidant capacities than those with lower antioxidant intakes. However, there were no associations between dietary intake of antioxidants or antioxidant rich foods and the plasma concentration of F₂-isoprostanes, which is considered a reliable biomarker for oxidative stress. Intakes of various doses of a mixture of bilberry juice and black tea, rich in flavonoids for four weeks, increased antioxidant capacity in some groups, but urine levels of F₂-isoprostanes were not affected. There were substantial individual variations in responses to the drinks related to baseline antioxidant capacity. Supplementation with eicosapentaenoic acid and docosahexaenoic acid decreased the plasma levels of F₂-isoprostanes, but not prostaglandin F_2α formation or antioxidant capacity. </p><p>It was concluded that a high intake of foods rich in antioxidants is related to improved antioxidant status. After intake of foods rich in antioxidants, the antioxidant status may increase, but with considerable individual variation in the responses, which warrants further investigation. Lipid peroxidation <i>in vivo</i> is not easily affected by dietary antioxidants in healthy humans. Although n-3 fatty acids are highly unsaturated, they reduce nonenzymatic free radical-catalyzed lipid peroxidation, but not enzymatic lipid peroxidation.</p>

Synaptic transmission alters the strength of the postsynaptic potential, through a process called short-term synaptic plasticity (STP). In this study, endplate potentials (EPPs) from the frog neuromuscular junction were used to resolve and quantify the presynaptic components involved in enhancement and depression of transmitter release during repetitive stimulation under normal quantal release conditions (2 mM Ca2+, 1mM Mg2+). During trains of stimulation given between 10 - 200 Hz, the amplitude of the EPPs first increased then decreased; a maximum increase of 77% was produced after 2-4 stimuli. EPP amplitudes began to increase at ~ 20 Hz, were maximal at ~ 55 Hz, and thereafter, decreased as the rate of stimulation increased. The integrated total release after 25 stimuli was little changed across frequencies between 10 - 100 Hz. EPPs ran down in two phases: a fast phase, attributed to the depletion of a readily releasable pool (RRP) of synaptic vesicles, followed by a slow phase, attributed to the depletion of vesicles from a depot pool (DP). Depletion of the readily releasable pool of synaptic vesicles (RRP) was determined by quantifying release under the fast and slow time rundowns and subtracting the number of vesicles associated with mobilization to the RRP from the total number of vesicles released during stimulation trains of 50 impulses. Impulses were delivered at 12 different rates ranging from 50 to 200 /s. Estimates of the number of vesicles released from the RRP increased with frequency of stimulation until maximal depletion levels of 5500 - 6000 vesicles were reached at stimulation rates between 90-130/s, assuming a control quantal content of 200 vesicles released per impulse. Depletion was less at lower frequencies when the number of stimuli delivered was identical. When the RRP maximally depleted, release was inversely related to stimulation rate, as would be expected if mobilization from the depot pool was the sole determinate of release during the slow phase. An equation constructed from four known components of enhancement and two components of depression - the depletion of vesicles from a readily releasable pool (RRP) and from the depot pool (DP) that refills the RRP, was used to fit and then simulate EPPs obtained during trains using different patterns of stimulation and varying amounts of extracellular Ca2+; the decay time constant parameters of enhancement, numerically derived from the observed data, were fixed at tau ~ 46, 220, 1600, and 20000 ms. The number of components of enhancement necessary to approximate the data decreased, from four in low (0.14 - 0.2mM) extracellular Ca2+, to one (tau ~ 46 ms) in 2.0 mM extracellular Ca2+, but four components of enhancement were necessary to fit the data when the amplitude of the EPP was not depressed below the control amplitude. This model was able to predict within ~ 3 % EPP amplitudes over a 10-fold range of frequency and Ca2+ concentration.

Lipid peroxidation is thought to be an important factor in the pathophysiology of a number of diseases and in the process of ageing, but its measurement in vivo has been difficult. The aim of this thesis was to evaluate methods for measurement of lipid peroxidation in vivo that are suitable for clinical investigations, and to apply these methods in animal and human studies investigating basal conditions and situations associated with increased lipid peroxidation. The ferrous oxidation in xylenol orange assay for quantification of total plasma lipid hydroperoxides was re-evaluated regarding sample handling and storage. It was shown to be a useful tool for analyses of fresh but not stored plasma samples. A methodology for measurement of the total amount (sum of free and esterified) of an F2-isoprostane, 8-iso-prostaglandin F2α, in tissues using alkaline hydrolysis in combination with an existing radioimmunoassay was developed. High levels of 8-iso-prostaglandin F2α in rat liver tissue were quantified by this technique both at basal conditions and in an experimental model of increased lipid peroxidation induced by carbon tetrachloride. Supplementation with vitamin E to rats decreased both non-enzymatic and enzymatic lipid peroxidation as measured by 8-iso-prostaglandin F2α and a major prostaglandin F2α metabolite. This was verified both in the urine at basal conditions, and in the urine and liver tissue after carbon tetrachloride induced lipid peroxidation. In a randomised cross-over study in humans, a rapeseed oil-based diet with an increased proportion of easily oxidised polyunsaturated fatty acids was compared to a control diet rich in saturated fats. The rapeseed oil-based diet did not seem to increase the degree of lipid peroxidation in plasma and urine as measured by 8-iso-prostaglandin F2α, hydroperoxides and malondialdehyde, presumably due to a sufficient content of antioxidants in the rapeseed oil diet. In conclusion, the simultaneous measurement of several biomarkers of lipid peroxidation is a promising approach for future studies investigating the possible role of lipid peroxidation in vivo under basal conditions and in the pathology of diseases.