134 resultados para Space environment
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The inadequacies and obsolescence of Eurocentric theories based on a binaryand static worldview have become a staple topic of postcolonial studies, and tosome extent also of translation studies. Nonetheless, the literary texts that arecalled upon in order to show the dynamism and hybridity of (post)modern worksbelong for the most part to the languages of the former colonial powers, especiallyEnglish, and remain inserted in a system that construes literatures interms of opposition. As a consequence, there is outside India a doubly misleadingunderstanding of Indian literatures other than those written in English:firstly, that translations of works in Hindi and in the Indian bhāṣā seem to belacking, if not inexistent, and secondly, that these "minor" literatures - as theyare regularly termed - are still often viewed as being highly dependent on theidea of "tradition," in opposition to the "postmodern" hybridity of the literatureswritten in the "dominant" languages, such as English or French. Againstthese views and supported by the analysis of Ajñeya's works in Hindi togetherwith their English translations, this paper aims to show: 1) that translationsfrom Hindi, which are not in fact non-existent, are mainly carried out in India,and 2) that Ajñeya's works, while representing a significant instance of the effectivehybridity present in Indian literatures, help to illustrate the moving spaceof translation. This demonstration effectively invalidates the above-mentionedoppositional standpoint.
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OBJECTIVE: Sleep disordered breathing with central apnea or hypopnea frequently occurs at high altitude and is thought to be caused by a decrease in blood CO(2) level. The aim of this study was to assess the effects of added respiratory dead space on sleep disordered breathing.¦METHODS: Full polysomnographies were performed on 12 unacclimatized swiss mountaineers (11 males, 1 female, mean age 39±12 y.o.) in Leh, Ladakh (3500m). In random order, half of the night was spent with a 500ml increase in dead space through a custom designed full face mask and the other half without it.¦RESULTS: Baseline data revealed two clearly distinct groups: one with severe sleep disordered breathing (n=5, AHI>30) and the other with moderate to no disordered breathing (n=7, AHI<30). DS markedly improved breathing in the first group (baseline vs DS): apnea hypopnea index (AHI) 70.3±25.8 vs 29.4±6.9 (p=0.013), oxygen desaturation index (ODI): 72.9±24.1/h vs 42.5±14.4 (p=0.031), whereas it had no significant effect in the second group or in the total population. Respiratory events were almost exclusively central apnea or hypopnea. Microarousal index, sleep efficiency, and sleep architecture remained unchanged with DS. A minor increase in mean PtcCO(2) (n=3) was observed with DS.¦CONCLUSION: A 500ml increase in dead space through a fitted mask may improve nocturnal breathing in mountaineers with severe altitude-induced sleep disordered breathing.
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The object of this study was to compare the protective action of a new barrier cream (Excipial Protect, Spirig Pharma AG, Egerkingen, Switzerland) to its vehicle in the context of hand irritation of apprentice hairdressers caused by repeated shampooing and exposure to hair-care products. This was a double-blind cross-over comparing Excipial Protect (containing aluminium chlorohydrate 5% as active ingredient) against its vehicle alone. The efficacy of the creams was evaluated taking into account: (1) clinical scores by researchers, (2) biometric measurements, (3) subjective opinions of the subjects. An analysis of variance was performed considering order of application, degree of atopy, and reported number of shampoos. We observed very little difference in efficacy between the protective cream and its vehicle. The presence, however, of aluminium chlorhydrate in the protective cream was shown to have a positive effect against work-related irritation. The cosmetic qualities of the creams seemed, to the participants, to be as important as their real protective and hydrating properties, an important factor in compliance issues.
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Molecular shape has long been known to be an important property for the process of molecular recognition. Previous studies postulated the existence of a drug-like shape space that could be used to artificially bias the composition of screening libraries, with the aim to increase the chance of success in Hit Identification. In this work, it was analysed to which extend this assumption holds true. Normalized Principal Moments of Inertia Ratios (NPRs) have been used to describe the molecular shape of small molecules. It was investigated, whether active molecules of diverse targets are located in preferred subspaces of the NPR shape space. Results illustrated a significantly stronger clustering than could be expected by chance, with parts of the space unlikely to be occupied by active compounds. Furthermore, a strong enrichment of elongated, rather flat shapes could be observed, while globular compounds were highly underrepresented. This was confirmed for a wide range of small molecule datasets from different origins. Active compounds exhibited a high overlap in their shape distributions across different targets, making a purely shape based discrimination very difficult. An additional perspective was provided by comparing the shapes of protein binding pockets with those of their respective ligands. Although more globular than their ligands, it was observed that binding sites shapes exhibited a similarly skewed distribution in shape space: spherical shapes were highly underrepresented. This was different for unoccupied binding pockets of smaller size. These were on the contrary identified to possess a more globular shape. The relation between shape complementarity and exhibited bioactivity was analysed; a moderate correlation between bioactivity and parameters including pocket coverage, distance in shape space, and others could be identified, which reflects the importance of shape complementarity. However, this also suggests that other aspects are of relevance for molecular recognition. A subsequent analysis assessed if and how shape and volume information retrieved from pocket or respective reference ligands could be used as a pre-filter in a virtual screening approach. ln Lead Optimization compounds need to get optimized with respect to a variety of pararneters. Here, the availability of past success stories is very valuable, as they can guide medicinal chemists during their analogue synthesis plans. However, although of tremendous interest for the public domain, so far only large corporations had the ability to mine historical knowledge in their proprietary databases. With the aim to provide such information, the SwissBioisostere database was developed and released during this thesis. This database contains information on 21,293,355 performed substructural exchanges, corresponding to 5,586,462 unique replacements that have been measured in 35,039 assays against 1,948 molecular targets representing 30 target classes, and on their impact on bioactivity . A user-friendly interface was developed that provides facile access to these data and is accessible at http//www.swissbioisostere.ch. The ChEMBL database was used as primary data source of bioactivity information. Matched molecular pairs have been identified in the extracted and cleaned data. Success-based scores were developed and integrated into the database to allow re-ranking of proposed replacements by their past outcomes. It was analysed to which degree these scores correlate with chemical similarity of the underlying fragments. An unexpectedly weak relationship was detected and further investigated. Use cases of this database were envisioned, and functionalities implemented accordingly: replacement outcomes are aggregatable at the assay level, and it was shawn that an aggregation at the target or target class level could also be performed, but should be accompanied by a careful case-by-case assessment. It was furthermore observed that replacement success depends on the activity of the starting compound A within a matched molecular pair A-B. With increasing potency the probability to lose bioactivity through any substructural exchange was significantly higher than in low affine binders. A potential existence of a publication bias could be refuted. Furthermore, often performed medicinal chemistry strategies for structure-activity-relationship exploration were analysed using the acquired data. Finally, data originating from pharmaceutical companies were compared with those reported in the literature. It could be seen that industrial medicinal chemistry can access replacement information not available in the public domain. In contrast, a large amount of often-performed replacements within companies could also be identified in literature data. Preferences for particular replacements differed between these two sources. The value of combining different endpoints in an evaluation of molecular replacements was investigated. The performed studies highlighted furthermore that there seem to exist no universal substructural replacement that always retains bioactivity irrespective of the biological environment. A generalization of bioisosteric replacements seems therefore not possible. - La forme tridimensionnelle des molécules a depuis longtemps été reconnue comme une propriété importante pour le processus de reconnaissance moléculaire. Des études antérieures ont postulé que les médicaments occupent préférentiellement un sous-ensemble de l'espace des formes des molécules. Ce sous-ensemble pourrait être utilisé pour biaiser la composition de chimiothèques à cribler, dans le but d'augmenter les chances d'identifier des Hits. L'analyse et la validation de cette assertion fait l'objet de cette première partie. Les Ratios de Moments Principaux d'Inertie Normalisés (RPN) ont été utilisés pour décrire la forme tridimensionnelle de petites molécules de type médicament. Il a été étudié si les molécules actives sur des cibles différentes se co-localisaient dans des sous-espaces privilégiés de l'espace des formes. Les résultats montrent des regroupements de molécules incompatibles avec une répartition aléatoire, avec certaines parties de l'espace peu susceptibles d'être occupées par des composés actifs. Par ailleurs, un fort enrichissement en formes allongées et plutôt plates a pu être observé, tandis que les composés globulaires étaient fortement sous-représentés. Cela a été confirmé pour un large ensemble de compilations de molécules d'origines différentes. Les distributions de forme des molécules actives sur des cibles différentes se recoupent largement, rendant une discrimination fondée uniquement sur la forme très difficile. Une perspective supplémentaire a été ajoutée par la comparaison des formes des ligands avec celles de leurs sites de liaison (poches) dans leurs protéines respectives. Bien que plus globulaires que leurs ligands, il a été observé que les formes des poches présentent une distribution dans l'espace des formes avec le même type d'asymétrie que celle observée pour les ligands: les formes sphériques sont fortement sous représentées. Un résultat différent a été obtenu pour les poches de plus petite taille et cristallisées sans ligand: elles possédaient une forme plus globulaire. La relation entre complémentarité de forme et bioactivité a été également analysée; une corrélation modérée entre bioactivité et des paramètres tels que remplissage de poche, distance dans l'espace des formes, ainsi que d'autres, a pu être identifiée. Ceci reflète l'importance de la complémentarité des formes, mais aussi l'implication d'autres facteurs. Une analyse ultérieure a évalué si et comment la forme et le volume d'une poche ou de ses ligands de référence pouvaient être utilisés comme un pré-filtre dans une approche de criblage virtuel. Durant l'optimisation d'un Lead, de nombreux paramètres doivent être optimisés simultanément. Dans ce contexte, la disponibilité d'exemples d'optimisations réussies est précieuse, car ils peuvent orienter les chimistes médicinaux dans leurs plans de synthèse par analogie. Cependant, bien que d'un extrême intérêt pour les chercheurs dans le domaine public, seules les grandes sociétés pharmaceutiques avaient jusqu'à présent la capacité d'exploiter de telles connaissances au sein de leurs bases de données internes. Dans le but de remédier à cette limitation, la base de données SwissBioisostere a été élaborée et publiée dans le domaine public au cours de cette thèse. Cette base de données contient des informations sur 21 293 355 échanges sous-structuraux observés, correspondant à 5 586 462 remplacements uniques mesurés dans 35 039 tests contre 1948 cibles représentant 30 familles, ainsi que sur leur impact sur la bioactivité. Une interface a été développée pour permettre un accès facile à ces données, accessible à http:/ /www.swissbioisostere.ch. La base de données ChEMBL a été utilisée comme source de données de bioactivité. Une version modifiée de l'algorithme de Hussain et Rea a été implémentée pour identifier les Matched Molecular Pairs (MMP) dans les données préparées au préalable. Des scores de succès ont été développés et intégrés dans la base de données pour permettre un reclassement des remplacements proposés selon leurs résultats précédemment observés. La corrélation entre ces scores et la similarité chimique des fragments correspondants a été étudiée. Une corrélation plus faible qu'attendue a été détectée et analysée. Différents cas d'utilisation de cette base de données ont été envisagés, et les fonctionnalités correspondantes implémentées: l'agrégation des résultats de remplacement est effectuée au niveau de chaque test, et il a été montré qu'elle pourrait également être effectuée au niveau de la cible ou de la classe de cible, sous réserve d'une analyse au cas par cas. Il a en outre été constaté que le succès d'un remplacement dépend de l'activité du composé A au sein d'une paire A-B. Il a été montré que la probabilité de perdre la bioactivité à la suite d'un remplacement moléculaire quelconque est plus importante au sein des molécules les plus actives que chez les molécules de plus faible activité. L'existence potentielle d'un biais lié au processus de publication par articles a pu être réfutée. En outre, les stratégies fréquentes de chimie médicinale pour l'exploration des relations structure-activité ont été analysées à l'aide des données acquises. Enfin, les données provenant des compagnies pharmaceutiques ont été comparées à celles reportées dans la littérature. Il a pu être constaté que les chimistes médicinaux dans l'industrie peuvent accéder à des remplacements qui ne sont pas disponibles dans le domaine public. Par contre, un grand nombre de remplacements fréquemment observés dans les données de l'industrie ont également pu être identifiés dans les données de la littérature. Les préférences pour certains remplacements particuliers diffèrent entre ces deux sources. L'intérêt d'évaluer les remplacements moléculaires simultanément selon plusieurs paramètres (bioactivité et stabilité métabolique par ex.) a aussi été étudié. Les études réalisées ont souligné qu'il semble n'exister aucun remplacement sous-structural universel qui conserve toujours la bioactivité quel que soit le contexte biologique. Une généralisation des remplacements bioisostériques ne semble donc pas possible.
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This article analyzes whether and to what extent the policy environment of civil servants has an impact on their level of Public Service Motivation (PSM). It hypothesizes that public employees working in different policy domains and stages of the policy cycle are diversely motivated by four PSM orientations (Compassion, Commitment to the public interest, Self-sacrifice and Attraction to politics). The empirical results are based on a survey of 6885 Swiss civil servants. They show that those in charge of Welfare State policies are inclined to have higher levels of 'Compassion', whereas those performing core state functions report lower levels. Furthermore, employees whose main tasks are related to policy formulation display high levels of the 'Attraction to politics' dimension of PSM. This study questions the generalization of previous findings on PSM that are based on heterogeneous survey populations.
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The proportion of population living in or around cites is more important than ever. Urban sprawl and car dependence have taken over the pedestrian-friendly compact city. Environmental problems like air pollution, land waste or noise, and health problems are the result of this still continuing process. The urban planners have to find solutions to these complex problems, and at the same time insure the economic performance of the city and its surroundings. At the same time, an increasing quantity of socio-economic and environmental data is acquired. In order to get a better understanding of the processes and phenomena taking place in the complex urban environment, these data should be analysed. Numerous methods for modelling and simulating such a system exist and are still under development and can be exploited by the urban geographers for improving our understanding of the urban metabolism. Modern and innovative visualisation techniques help in communicating the results of such models and simulations. This thesis covers several methods for analysis, modelling, simulation and visualisation of problems related to urban geography. The analysis of high dimensional socio-economic data using artificial neural network techniques, especially self-organising maps, is showed using two examples at different scales. The problem of spatiotemporal modelling and data representation is treated and some possible solutions are shown. The simulation of urban dynamics and more specifically the traffic due to commuting to work is illustrated using multi-agent micro-simulation techniques. A section on visualisation methods presents cartograms for transforming the geographic space into a feature space, and the distance circle map, a centre-based map representation particularly useful for urban agglomerations. Some issues on the importance of scale in urban analysis and clustering of urban phenomena are exposed. A new approach on how to define urban areas at different scales is developed, and the link with percolation theory established. Fractal statistics, especially the lacunarity measure, and scale laws are used for characterising urban clusters. In a last section, the population evolution is modelled using a model close to the well-established gravity model. The work covers quite a wide range of methods useful in urban geography. Methods should still be developed further and at the same time find their way into the daily work and decision process of urban planners. La part de personnes vivant dans une région urbaine est plus élevé que jamais et continue à croître. L'étalement urbain et la dépendance automobile ont supplanté la ville compacte adaptée aux piétons. La pollution de l'air, le gaspillage du sol, le bruit, et des problèmes de santé pour les habitants en sont la conséquence. Les urbanistes doivent trouver, ensemble avec toute la société, des solutions à ces problèmes complexes. En même temps, il faut assurer la performance économique de la ville et de sa région. Actuellement, une quantité grandissante de données socio-économiques et environnementales est récoltée. Pour mieux comprendre les processus et phénomènes du système complexe "ville", ces données doivent être traitées et analysées. Des nombreuses méthodes pour modéliser et simuler un tel système existent et sont continuellement en développement. Elles peuvent être exploitées par le géographe urbain pour améliorer sa connaissance du métabolisme urbain. Des techniques modernes et innovatrices de visualisation aident dans la communication des résultats de tels modèles et simulations. Cette thèse décrit plusieurs méthodes permettant d'analyser, de modéliser, de simuler et de visualiser des phénomènes urbains. L'analyse de données socio-économiques à très haute dimension à l'aide de réseaux de neurones artificiels, notamment des cartes auto-organisatrices, est montré à travers deux exemples aux échelles différentes. Le problème de modélisation spatio-temporelle et de représentation des données est discuté et quelques ébauches de solutions esquissées. La simulation de la dynamique urbaine, et plus spécifiquement du trafic automobile engendré par les pendulaires est illustrée à l'aide d'une simulation multi-agents. Une section sur les méthodes de visualisation montre des cartes en anamorphoses permettant de transformer l'espace géographique en espace fonctionnel. Un autre type de carte, les cartes circulaires, est présenté. Ce type de carte est particulièrement utile pour les agglomérations urbaines. Quelques questions liées à l'importance de l'échelle dans l'analyse urbaine sont également discutées. Une nouvelle approche pour définir des clusters urbains à des échelles différentes est développée, et le lien avec la théorie de la percolation est établi. Des statistiques fractales, notamment la lacunarité, sont utilisées pour caractériser ces clusters urbains. L'évolution de la population est modélisée à l'aide d'un modèle proche du modèle gravitaire bien connu. Le travail couvre une large panoplie de méthodes utiles en géographie urbaine. Toutefois, il est toujours nécessaire de développer plus loin ces méthodes et en même temps, elles doivent trouver leur chemin dans la vie quotidienne des urbanistes et planificateurs.
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Abstract Empirical testing of candidate vaccines has led to the successful development of a number of lifesaving vaccines. The advent of new tools to manipulate antigens and new methods and vectors for vaccine delivery has led to a veritable explosion of potential vaccine designs. As a result, selection of candidate vaccines suitable for large-scale efficacy testing has become more challenging. This is especially true for diseases such as dengue, HIV, and tuberculosis where there is no validated animal model or correlate of immune protection. Establishing guidelines for the selection of vaccine candidates for advanced testing has become a necessity. A number of factors could be considered in making these decisions, including, for example, safety in animal and human studies, immune profile, protection in animal studies, production processes with product quality and stability, availability of resources, and estimated cost of goods. The "immune space template" proposed here provides a standardized approach by which the quality, level, and durability of immune responses elicited in early human trials by a candidate vaccine can be described. The immune response profile will demonstrate if and how the candidate is unique relative to other candidates, especially those that have preceded it into efficacy testing and, thus, what new information concerning potential immune correlates could be learned from an efficacy trial. A thorough characterization of immune responses should also provide insight into a developer's rationale for the vaccine's proposed mechanism of action. HIV vaccine researchers plan to include this general approach in up-selecting candidates for the next large efficacy trial. This "immune space" approach may also be applicable to other vaccine development endeavors where correlates of vaccine-induced immune protection remain unknown.
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With a life expectancy at the age of 65 of around 20 years, damaging health risk behaviours of young-old adults have become a target for preventive actions. Such risk factors necessitate an accurate understanding of the present and past socioeconomic conditions associated with health risk behaviours. The aim of our study is to assess the impact of certain life events as well as economic and environmental factors on health risk behaviours. We included 1309 participants of the Lausanne Cohort Lc65+ aged 65-70 years and employed logistic regression analyses, with individuals nested within areas. The results illustrate the influences of socioeconomic factors from childhood to young-old age. Life experiences in adulthood and economic resources in young-old age are both associated with unfavourable health behaviours. Neighbourhood is a modest determinant as well, particularly regarding alcohol consumption. Therefore, prevention against health risk behaviours should focus on population subgroups defined on the basis of their socioeconomic and living contexts.
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Knowledge of the quantitative genetics of resistance to parasitism is key to appraise host evolutionary responses to parasite selection. Here, we studied effects of common origin (i.e. genetic and pre-hatching parental effects) and common rearing environment (i.e. post-hatching parental effects and other environment effects) on variance in ectoparasite load in nestling Alpine swifts (Apus melba). This colonial bird is intensely parasitized by blood sucking louse-flies that impair nestling development and survival. By cross-fostering half of the hatchlings between pairs of nests, we show strong significant effect of common rearing environment on variance (90.7% in 2002 and 90.9% in 2003) in the number of louse-flies per nestling and no significant effect of common origin on variance in the number of louse-flies per nestling. In contrast, significant effects of common origin were found for all the nestling morphological traits (i.e. body mass, wing length, tail length, fork length and sternum length) under investigation. Hence, our study suggests that genetic and pre-hatching parental effects play little role in the distribution of parasites among nestling Alpine swifts, and thus that nestlings have only limited scope for evolutionary responses against parasites. Our results highlight the need to take into consideration environmental factors, including the evolution of post-hatching parental effects such as nest sanitation, in our understanding of host-parasite relationships.
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General Summary Although the chapters of this thesis address a variety of issues, the principal aim is common: test economic ideas in an international economic context. The intention has been to supply empirical findings using the largest suitable data sets and making use of the most appropriate empirical techniques. This thesis can roughly be divided into two parts: the first one, corresponding to the first two chapters, investigates the link between trade and the environment, the second one, the last three chapters, is related to economic geography issues. Environmental problems are omnipresent in the daily press nowadays and one of the arguments put forward is that globalisation causes severe environmental problems through the reallocation of investments and production to countries with less stringent environmental regulations. A measure of the amplitude of this undesirable effect is provided in the first part. The third and the fourth chapters explore the productivity effects of agglomeration. The computed spillover effects between different sectors indicate how cluster-formation might be productivity enhancing. The last chapter is not about how to better understand the world but how to measure it and it was just a great pleasure to work on it. "The Economist" writes every week about the impressive population and economic growth observed in China and India, and everybody agrees that the world's center of gravity has shifted. But by how much and how fast did it shift? An answer is given in the last part, which proposes a global measure for the location of world production and allows to visualize our results in Google Earth. A short summary of each of the five chapters is provided below. The first chapter, entitled "Unraveling the World-Wide Pollution-Haven Effect" investigates the relative strength of the pollution haven effect (PH, comparative advantage in dirty products due to differences in environmental regulation) and the factor endowment effect (FE, comparative advantage in dirty, capital intensive products due to differences in endowments). We compute the pollution content of imports using the IPPS coefficients (for three pollutants, namely biological oxygen demand, sulphur dioxide and toxic pollution intensity for all manufacturing sectors) provided by the World Bank and use a gravity-type framework to isolate the two above mentioned effects. Our study covers 48 countries that can be classified into 29 Southern and 19 Northern countries and uses the lead content of gasoline as proxy for environmental stringency. For North-South trade we find significant PH and FE effects going in the expected, opposite directions and being of similar magnitude. However, when looking at world trade, the effects become very small because of the high North-North trade share, where we have no a priori expectations about the signs of these effects. Therefore popular fears about the trade effects of differences in environmental regulations might by exaggerated. The second chapter is entitled "Is trade bad for the Environment? Decomposing worldwide SO2 emissions, 1990-2000". First we construct a novel and large database containing reasonable estimates of SO2 emission intensities per unit labor that vary across countries, periods and manufacturing sectors. Then we use these original data (covering 31 developed and 31 developing countries) to decompose the worldwide SO2 emissions into the three well known dynamic effects (scale, technique and composition effect). We find that the positive scale (+9,5%) and the negative technique (-12.5%) effect are the main driving forces of emission changes. Composition effects between countries and sectors are smaller, both negative and of similar magnitude (-3.5% each). Given that trade matters via the composition effects this means that trade reduces total emissions. We next construct, in a first experiment, a hypothetical world where no trade happens, i.e. each country produces its imports at home and does no longer produce its exports. The difference between the actual and this no-trade world allows us (under the omission of price effects) to compute a static first-order trade effect. The latter now increases total world emissions because it allows, on average, dirty countries to specialize in dirty products. However, this effect is smaller (3.5%) in 2000 than in 1990 (10%), in line with the negative dynamic composition effect identified in the previous exercise. We then propose a second experiment, comparing effective emissions with the maximum or minimum possible level of SO2 emissions. These hypothetical levels of emissions are obtained by reallocating labour accordingly across sectors within each country (under the country-employment and the world industry-production constraints). Using linear programming techniques, we show that emissions are reduced by 90% with respect to the worst case, but that they could still be reduced further by another 80% if emissions were to be minimized. The findings from this chapter go together with those from chapter one in the sense that trade-induced composition effect do not seem to be the main source of pollution, at least in the recent past. Going now to the economic geography part of this thesis, the third chapter, entitled "A Dynamic Model with Sectoral Agglomeration Effects" consists of a short note that derives the theoretical model estimated in the fourth chapter. The derivation is directly based on the multi-regional framework by Ciccone (2002) but extends it in order to include sectoral disaggregation and a temporal dimension. This allows us formally to write present productivity as a function of past productivity and other contemporaneous and past control variables. The fourth chapter entitled "Sectoral Agglomeration Effects in a Panel of European Regions" takes the final equation derived in chapter three to the data. We investigate the empirical link between density and labour productivity based on regional data (245 NUTS-2 regions over the period 1980-2003). Using dynamic panel techniques allows us to control for the possible endogeneity of density and for region specific effects. We find a positive long run elasticity of density with respect to labour productivity of about 13%. When using data at the sectoral level it seems that positive cross-sector and negative own-sector externalities are present in manufacturing while financial services display strong positive own-sector effects. The fifth and last chapter entitled "Is the World's Economic Center of Gravity Already in Asia?" computes the world economic, demographic and geographic center of gravity for 1975-2004 and compares them. Based on data for the largest cities in the world and using the physical concept of center of mass, we find that the world's economic center of gravity is still located in Europe, even though there is a clear shift towards Asia. To sum up, this thesis makes three main contributions. First, it provides new estimates of orders of magnitudes for the role of trade in the globalisation and environment debate. Second, it computes reliable and disaggregated elasticities for the effect of density on labour productivity in European regions. Third, it allows us, in a geometrically rigorous way, to track the path of the world's economic center of gravity.