Morfologia do funículo espermático em caprinos da raça Bhuj Brasileira

Estudamos em 40 caprinos adultos da raça Bhuj Brasileira os aspectos histológicos do funículo espermático. Observamos que este se acha envolvido por uma cápsula de tecido conjuntivo fibroelástico denso, de espessura variável, pregueada em alguns pontos, e revestida por mesotélio que circunda todo o conjunto vásculo-nervoso, e projeta-se para formar o mesoducto deferente. Em posição subcapsular, verifica- se uma camada de tecido conjuntivo fibroelástico frouxo, de espessura variável, que circunda parcialmente o funículo espermático, isolando nas regiões deferencial e abdeferencial, conjuntos vásculo-nervosos, responsáveis pela nutrição do epidídimo. Na região do mesoducto deferente, o tecido subcapsular acompanhado de tecido adiposo constitui a camada interna deste meso, formando a sua adventícia e abrigando vasos e nervos deferenciais. Na região abdeferencial, pequenos acúmulos de tecido adiposo são vistos de permeio aos vasos e nervos desta região. Entre as artérias, veias e nervos testiculares, bem como entre os vasos das regiões deferencial e abdeferencial, observa-se o tecido conjuntivo denso, intervascular, rico em fibras elásticas, que constitui as adventícias contínuas destes vasos. O arranjo vascular mostra que o segmento da artéria testicular, contido no funículo espermático, apresenta trajeto sinuoso. Estando envolvido pelo plexo venoso pampiniforme, formado por veias testiculares desprovidas de válvulas de calibres variados, apresentando amplas comunicações entre si. As veias responsáveis pela drenagem do epidídimo e ducto deferente estão localizadas em posição subcapsular deferencial e abdeferencial e mostram-se providas de válvulas. O trato das artérias testiculares no funículo espermático apresenta como média e desvio padrão 134,6±38,1cm à direita, e 137,0±33,9cm à esquerda, não existindo diferenças estatisticamente significantes ao nível de 5%, quando comparamos a média do segmento da artéria testicular contida no funículo espermático direito em relação ao esquerdo.

Bicistronic DNA vaccines simultaneously encoding HIV, HSV and HPV antigens promote CD8⁺ T cell responses and protective immunity

Millions of people worldwide are currently infected with human papillomavirus (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunological approaches represents a hope for the eradication of latent infection and/or virus-associated cancer. To date, attempts to develop vaccines against these viruses have been mainly based on a monovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II) that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines mounted antigen-specific CD8⁺ T cell responses, including in vivo cytotoxic responses, against the three antigens. Under experimental conditions, the vaccines conferred protective immunity against challenges with a vaccinia virus expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8⁺ T cell-dependent responses is feasible and may aid in the development of preventive and/or therapeutic approaches for the control of diseases associated with these viruses.

Management of Port Solid Waste Framework

One of contemporary environmental issues refers to progressive and diverse generation of solid waste in urban areas or specific, and requires solutions because the traditional methods of treatment and disposal are becoming unviable over the years and, consequently, a significant contingent of these wastes presents final destination inappropriate. The diversity of solid waste generated as a result of human activities must have the appropriate allocation to specific legislation in force, such as landfill, incineration, among other procedures established by the competent bodies. Thus, also the waste generated in port activities or proceeding vessels require classification and segregation for proper disposal later. This article aims at presenting a methodology for the collection, transportation, treatment and disposal of solid waste port and also application of automation technology that makes possible the implementation of the same.

Sulla ricerca del minimo dei consumi per vetture sportive

La ricerca oggetto di questa tesi, come si evince dal titolo stesso, è volta alla riduzione dei consumi per vetture a forte carattere sportivo ed elevate prestazioni specifiche. In particolare, tutte le attività descritte fanno riferimento ad un ben definito modello di vettura, ovvero la Maserati Quattroporte. Lo scenario all’interno del quale questo lavoro si inquadra, è quello di una forte spinta alla riduzione dei cosiddetti gas serra, ossia dell’anidride carbonica, in linea con quelle che sono le disposizioni dettate dal protocollo di Kyoto. La necessità di ridurre l’immissione in atmosfera di CO2 sta condizionando tutti i settori della società: dal riscaldamento degli edifici privati a quello degli stabilimenti industriali, dalla generazione di energia ai processi produttivi in senso lato. Nell’ambito di questo panorama, chiaramente, sono chiamati ad uno sforzo considerevole i costruttori di automobili, alle quali è imputata una percentuale considerevole dell’anidride carbonica prodotta ogni giorno e riversata nell’atmosfera. Al delicato problema inquinamento ne va aggiunto uno forse ancor più contingente e diretto, legato a ragioni di carattere economico. I combustibili fossili, come tutti sanno, sono una fonte di energia non rinnovabile, la cui disponibilità è legata a giacimenti situati in opportune zone del pianeta e non inesauribili. Per di più, la situazione socio politica che il medio oriente sta affrontando, unita alla crescente domanda da parte di quei paesi in cui il processo di industrializzazione è partito da poco a ritmi vertiginosi, hanno letteralmente fatto lievitare il prezzo del petrolio. A causa di ciò, avere una vettura efficiente in senso lato e, quindi, a ridotti consumi, è a tutti gli effetti un contenuto di prodotto apprezzato dal punto di vista del marketing, anche per i segmenti vettura più alti. Nell’ambito di questa ricerca il problema dei consumi è stato affrontato come una conseguenza del comportamento globale della vettura in termini di efficienza, valutando il miglior compromesso fra le diverse aree funzionali costituenti il veicolo. Una parte consistente del lavoro è stata dedicata alla messa a punto di un modello di calcolo, attraverso il quale eseguire una serie di analisi di sensibilità sull’influenza dei diversi parametri vettura sul consumo complessivo di carburante. Sulla base di tali indicazioni, è stata proposta una modifica dei rapporti del cambio elettro-attuato con lo scopo di ottimizzare il compromesso tra consumi e prestazioni, senza inficiare considerevolmente queste ultime. La soluzione proposta è stata effettivamente realizzata e provata su vettura, dando la possibilità di verificare i risultati ed operare un’approfondita attività di correlazione del modello di calcolo per i consumi. Il beneficio ottenuto in termini di autonomia è stato decisamente significativo con riferimento sia ai cicli di omologazione europei, che a quelli statunitensi. Sono state inoltre analizzate le ripercussioni dal punto di vista delle prestazioni ed anche in questo caso i numerosi dati rilevati hanno permesso di migliorare il livello di correlazione del modello di simulazione per le prestazioni. La vettura con la nuova rapportatura proposta è stata poi confrontata con un prototipo di Maserati Quattroporte avente cambio automatico e convertitore di coppia. Questa ulteriore attività ha permesso di valutare il differente comportamento tra le due soluzioni, sia in termini di consumo istantaneo, che di consumo complessivo rilevato durante le principali missioni su banco a rulli previste dalle normative. L’ultima sezione del lavoro è stata dedicata alla valutazione dell’efficienza energetica del sistema vettura, intesa come resistenza all’avanzamento incontrata durante il moto ad una determinata velocità. Sono state indagate sperimentalmente le curve di “coast down” della Quattroporte e di alcune concorrenti e sono stati proposti degli interventi volti alla riduzione del coefficiente di penetrazione aerodinamica, pur con il vincolo di non alterare lo stile vettura.

Non-Linear Pricing in Imperfectly Competitive Markets

This thesis is dedicated to the analysis of non-linear pricing in oligopoly. Non-linear pricing is a fairly predominant practice in most real markets, mostly characterized by some amount of competition. The sophistication of pricing practices has increased in the latest decades due to the technological advances that have allowed companies to gather more and more data on consumers preferences. The first essay of the thesis highlights the main characteristics of oligopolistic non-linear pricing. Non-linear pricing is a special case of price discrimination. The theory of price discrimination has to be modified in presence of oligopoly: in particular, a crucial role is played by the competitive externality that implies that product differentiation is closely related to the possibility of discriminating. The essay reviews the theory of competitive non-linear pricing by starting from its foundations, mechanism design under common agency. The different approaches to model non-linear pricing are then reviewed. In particular, the difference between price and quantity competition is highlighted. Finally, the close link between non-linear pricing and the recent developments in the theory of vertical differentiation is explored. The second essay shows how the effects of non-linear pricing are determined by the relationship between the demand and the technological structure of the market. The chapter focuses on a model in which firms supply a homogeneous product in two different sizes. Information about consumers' reservation prices is incomplete and the production technology is characterized by size economies. The model provides insights on the size of the products that one finds in the market. Four equilibrium regions are identified depending on the relative intensity of size economies with respect to consumers' evaluation of the good. Regions for which the product is supplied in a single unit or in several different sizes or in only a very large one. Both the private and social desirability of non-linear pricing varies across different equilibrium regions. The third essay considers the broadband internet market. Non discriminatory issues seem the core of the recent debate on the opportunity or not of regulating the internet. One of the main questions posed is whether the telecom companies, owning the networks constituting the internet, should be allowed to offer quality-contingent contracts to content providers. The aim of this essay is to analyze the issue through a stylized two-sided market model of the web that highlights the effects of such a discrimination over quality, prices and participation to the internet of providers and final users. An overall welfare comparison is proposed, concluding that the final effects of regulation crucially depend on both the technology and preferences of agents.

Dall'involucro all'invaso. Lo spazio a pianta centrale nell'opera architettonica di Adalberto Libera

An archetype selected over the centuries Adalberto Libera wrote little, showing more inclination to use the project as the only means of verification. This study uses a survey of the project for purely compositional space in relation to the reason that most other returns with continuity and consistency throughout his work. "The fruit of a type selected over centuries", in the words of Libera, is one of the most widely used and repeated spatial archetypes present in the history of architecture, given its nature as defined by a few consolidated elements and precisely defined with characters of geometric precision and absoluteness, the central space is provided, over the course of evolution of architecture, and its construction aspects as well as symbolic, for various uses, from historical period in which it was to coincide with sacred space for excellence, to others in which it lends itself to many different expressive possibilities of a more "secular". The central space was created on assumptions of a constructive character, and the same exact reason has determined the structural changes over the centuries, calling from time to time with advances in technology, the maximum extent possible and the different applications, which almost always have coincided with the reason for the monumental space. But it’s in the Roman world that the reason for the central space is defined from the start of a series of achievements that fix the character in perpetuity. The Pantheon was seen maximum results and, simultaneously, the archetype indispensable, to the point that it becomes difficult to sustain a discussion of the central space that excludes. But the reason the space station has complied, in ancient Rome, just as exemplary, monuments, public spaces or buildings with very different implications. The same Renaissance, on which Wittkower's proving itself once and for all, the nature and interpretation of sacred space station, and thus the symbolic significance of that invaded underlying interpretations related to Humanism, fixing the space-themed drawing it with the study and direct observation by the four-sixteenth-century masters, the ruins that in those years of renewed interest in the classical world, the first big pieces of excavation of ancient Rome brought to light with great surprise of all. Not a case, the choice to investigate the architectural work of Libera through the grounds of the central space. Investigating its projects and achievements, it turns out as the reason invoked particularly evident from the earliest to latest work, crossing-free period of the war which for many authors in different ways, the distinction between one stage and another, or the final miss. The theme and the occasion for Libera always distinct, it is precisely the key through which to investigate her work, to come to discover that the first-in this case the central plan-is the constant underlying all his work, and the second reason that the quota with or at the same time, we will return different each time and always the same Libera, formed on the major works remained from ancient times, and on this building method, means consciously, that the characters of architectural works, if valid, pass the time, and survive the use and function contingent. As for the facts by which to formalize it, they themselves are purely contingent, and therefore available to be transferred from one work to another, from one project to another, using also the loan. Using the same two words-at-issue and it becomes clear now how the theme of this study is the method of Libera and opportunity to the study of the central space in his work. But there is one aspect that, with respect to space a central plan evolves with the progress of the work of Libera on the archetype, and it is the reason behind all the way, just because an area built entirely on reason centric. It 'just the "center" of space that, ultimately, tells us the real progression and the knowledge that over the years has matured and changed in Libera. In the first phase, heavily laden with symbolic superstructure, even if used in a "bribe" from Free-always ill-disposed to sacrifice the idea of architecture to a phantom-center space is just the figure that identifies the icon represents space itself: the cross, the flame or the statue are different representations of the same idea of center built around an icon. The second part of the work of clearing the space station, changed the size of the orders but the demands of patronage, grows and expands the image space centric, celebratory nature that takes and becomes, in a different way, this same symbol . You see, one in all, as the project of "Civiltà Italiana" or symbolic arch are examples of this different attitude. And at the same point of view, you will understand how the two projects formulated on the reuse of the Mausoleum of Augustus is the key to its passage from first to second phase: the Ara Pacis in the second project, making itself the center of the composition "breaks" the pattern of symbolic figure in the center, because it is itself an architecture. And, in doing so, the transition takes place where the building itself-the central space-to become the center of that space that itself creates and determines, by extending the potential and the expressiveness of the enclosure (or cover) that defines the basin centered. In this second series of projects, which will be the apex and the point of "crisis" in the Palazzo dei Congressi all'E42 received and is no longer so, the symbol at the very geometry of space, but space itself and 'action' will be determined within this; action leading a movement, in the case of the Arco simbolico and the "Civiltà Italiana" or, more frequently, or celebration, as in the great Sala dei Recevimenti all’E42, which, in the first project proposal, is represented as a large area populated by people in suits, at a reception, in fact. In other words, in this second phase, the architecture is no longer a mere container, but it represents the shape of space, representing that which "contains". In the next step-determining the knowledge from which mature in their transition to post-war-is one step that radically changes the way centric space, although formally and compositionally Libera continues the work on the same elements, compounds and relationships in a different way . In this last phase Freedom, center, puts the man in human beings, in the two previous phases, and in a latent, were already at the center of the composition, even if relegated to the role of spectators in the first period, or of supporting actors in the second, now the heart of space. And it’s, as we shall see, the very form of being together in the form of "assembly", in its different shades (up to that sacred) to determine the shape of space, and how to relate the parts that combine to form it. The reconstruction of the birth, evolution and development of the central space of the ground in Libera, was born on the study of the monuments of ancient Rome, intersected on fifty years of recent history, honed on the constancy of a method and practice of a lifetime, becomes itself, Therefore, a project, employing the same mechanisms adopted by Libera; the decomposition and recomposition, research synthesis and unity of form, are in fact the structure of this research work. The road taken by Libera is a lesson in clarity and rationality, above all, and this work would uncover at least a fragment.

Metodi di ottimizzazione morfologica nel progetto preliminare di propulsori aeronautici avanzati

The aim of this Doctoral Thesis is to develop a genetic algorithm based optimization methods to find the best conceptual design architecture of an aero-piston-engine, for given design specifications. Nowadays, the conceptual design of turbine airplanes starts with the aircraft specifications, then the most suited turbofan or turbo propeller for the specific application is chosen. In the aeronautical piston engines field, which has been dormant for several decades, as interest shifted towards turboaircraft, new materials with increased performance and properties have opened new possibilities for development. Moreover, the engine’s modularity given by the cylinder unit, makes it possible to design a specific engine for a given application. In many real engineering problems the amount of design variables may be very high, characterized by several non-linearities needed to describe the behaviour of the phenomena. In this case the objective function has many local extremes, but the designer is usually interested in the global one. The stochastic and the evolutionary optimization techniques, such as the genetic algorithms method, may offer reliable solutions to the design problems, within acceptable computational time. The optimization algorithm developed here can be employed in the first phase of the preliminary project of an aeronautical piston engine design. It’s a mono-objective genetic algorithm, which, starting from the given design specifications, finds the engine propulsive system configuration which possesses minimum mass while satisfying the geometrical, structural and performance constraints. The algorithm reads the project specifications as input data, namely the maximum values of crankshaft and propeller shaft speed and the maximal pressure value in the combustion chamber. The design variables bounds, that describe the solution domain from the geometrical point of view, are introduced too. In the Matlab® Optimization environment the objective function to be minimized is defined as the sum of the masses of the engine propulsive components. Each individual that is generated by the genetic algorithm is the assembly of the flywheel, the vibration damper and so many pistons, connecting rods, cranks, as the number of the cylinders. The fitness is evaluated for each individual of the population, then the rules of the genetic operators are applied, such as reproduction, mutation, selection, crossover. In the reproduction step the elitist method is applied, in order to save the fittest individuals from a contingent mutation and recombination disruption, making it undamaged survive until the next generation. Finally, as the best individual is found, the optimal dimensions values of the components are saved to an Excel® file, in order to build a CAD-automatic-3D-model for each component of the propulsive system, having a direct pre-visualization of the final product, still in the engine’s preliminary project design phase. With the purpose of showing the performance of the algorithm and validating this optimization method, an actual engine is taken, as a case study: it’s the 1900 JTD Fiat Avio, 4 cylinders, 4T, Diesel. Many verifications are made on the mechanical components of the engine, in order to test their feasibility and to decide their survival through generations. A system of inequalities is used to describe the non-linear relations between the design variables, and is used for components checking for static and dynamic loads configurations. The design variables geometrical boundaries are taken from actual engines data and similar design cases. Among the many simulations run for algorithm testing, twelve of them have been chosen as representative of the distribution of the individuals. Then, as an example, for each simulation, the corresponding 3D models of the crankshaft and the connecting rod, have been automatically built. In spite of morphological differences among the component the mass is almost the same. The results show a significant mass reduction (almost 20% for the crankshaft) in comparison to the original configuration, and an acceptable robustness of the method have been shown. The algorithm here developed is shown to be a valid method for an aeronautical-piston-engine preliminary project design optimization. In particular the procedure is able to analyze quite a wide range of design solutions, rejecting the ones that cannot fulfill the feasibility design specifications. This optimization algorithm could increase the aeronautical-piston-engine development, speeding up the production rate and joining modern computation performances and technological awareness to the long lasting traditional design experiences.

Italia e Francia nell'Ungheria di Trianon (1919-1939): due modelli di penetrazione politico-culturale

Italy and France in Trianon’s Hungary: two political and cultural penetration models During the first post-war, the Danubian Europe was the theatre of an Italian-French diplomatic challenge to gain hegemony in that part of the continent. Because of his geographical position, Hungary had a decisive strategic importance for the ambitions of French and Italian foreign politics. Since in the 1920s culture and propaganda became the fourth dimension of international relations, Rome and Paris developed their diplomatic action in Hungary to affirm not only political and economic influence, but also cultural supremacy. In the 1930, after Hitler’s rise to power, the unstoppable comeback of German political influence in central-eastern Europe determined the progressive decline of Italian and French political and economic positions in Hungary: only the cultural field allowed a survey of Italian-Hungarian and French-Hungarian relations in the contest of a Europe dominated by Nazi Germany during the Second World War. Nevertheless, the radical geopolitical changes in second post-war Europe did not compromise Italian and French cultural presence in the new communist Hungary. Although cultural diplomacy is originally motivated by contingent political targets, it doesn’t respect the short time of politics, but it’s the only foreign politics tool that guarantees preservations of bilateral relations in the long run.

Der implizite Bewußtseinsinhalt in der Phänomenologie und der analytischen Philosophie

Die vorliegende Arbeit wurde durch die Erkenntnis motiviert, daß die Theorie der Intentionalität ohne eine Theorie der impliziten Intentionalität unvollständig ist. Die Anlage einer solchen Theorie gründet in der Annahme, daß die impliziten ("ergänzenden oder "mit-bewußten") Erfahrungsinhalte Inhalte intentional wirksam sind: daß sie zur "Konstitution" der intentionalen Objekte – im Sinne vom Husserl und Gurwitsch – beitragen. Die Bedingungen und Umstände dieser Wirksamkeit herauszuarbeiten, ist das Hauptziel der vorliegenden Untersuchungen. Dazu wurde (1) eine phänomenologische Theorie des impliziten Inhalts kritisch expliziert, und (2) diese anhand einiger aktueller Ansätze der analytischen Philosophie auf die Probe gestellt. Im phänomenologischen Teil der Arbeit wurden zuerst die methodologischen Voraussetzungen von Gurwitschs gestalttheoretischer Neuformulierung des Husserlschen Projekts unter Berücksichtigung der sogenannten Konstanzannahme kritisch untersucht. Weiterhin wurden Husserls Noema-Konzeption und seine Horizontlehre aus der Perspektive von Gurwitschs Feldtheorie des Bewußtseins expliziert, und in der Folge Gurwitschs dreifache Gliederung des Bewußtseinsfeldes – das Kopräsenz-Kohärenz-Relevanz-Schema – um die phänomenologischen Begriffe "Potentialität", "Typik" und "Motivation" erweitert. Die Beziehungen, die diesen Begriffen zugrunde liegen, erwiesen sich als "mehr denn bloß kontigent, aber als weniger denn logisch oder notwendig" (Mulligan). An Beispielen aus der analytischen Philosphie der Wahrnehmung (Dretske, Peacocke, Dennett, Kelly) und der Sprache (Sperber, Wilson, Searle) wurde das phänomenologische Konzept des impliziten Inhalts kritisch beurteilt und weiterentwickelt. Hierbei wurde(n) unter anderem (1) der Zusammenhang zwischen dem phänomenologischen Begriff "vorprädikativer Inhalt" und dem analytischen Begriff "nichtkonzeptueller Inhalt" aufgezeigt und (2) Kriterien für die Zuschreibung impliziter Überzeugungen in den typischen Fällen der prädikativen Intentionalität zusammengetragen und systematisiert.

Aspetti di sostenibilità in agricoltura a diverse scale spaziali e temporali. Valutazioni ambientali, economiche ed energetiche.

La Tesi analizza le relazioni tra i processi di sviluppo agricolo e l’uso delle risorse naturali, in particolare di quelle energetiche, a livello internazionale (paesi in via di sviluppo e sviluppati), nazionale (Italia), regionale (Emilia Romagna) e aziendale, con lo scopo di valutare l’eco-efficienza dei processi di sviluppo agricolo, la sua evoluzione nel tempo e le principali dinamiche in relazione anche ai problemi di dipendenza dalle risorse fossili, della sicurezza alimentare, della sostituzione tra superfici agricole dedicate all’alimentazione umana ed animale. Per i due casi studio a livello macroeconomico è stata adottata la metodologia denominata “SUMMA” SUstainability Multi-method, multi-scale Assessment (Ulgiati et al., 2006), che integra una serie di categorie d’impatto dell’analisi del ciclo di vita, LCA, valutazioni costi-benefici e la prospettiva di analisi globale della contabilità emergetica. L’analisi su larga scala è stata ulteriormente arricchita da un caso studio sulla scala locale, di una fattoria produttrice di latte e di energia elettrica rinnovabile (fotovoltaico e biogas). Lo studio condotto mediante LCA e valutazione contingente ha valutato gli effetti ambientali, economici e sociali di scenari di riduzione della dipendenza dalle fonti fossili. I casi studio a livello macroeconomico dimostrano che, nonostante le politiche di supporto all’aumento di efficienza e a forme di produzione “verdi”, l’agricoltura a livello globale continua ad evolvere con un aumento della sua dipendenza dalle fonti energetiche fossili. I primi effetti delle politiche agricole comunitarie verso una maggiore sostenibilità sembrano tuttavia intravedersi per i Paesi Europei. Nel complesso la energy footprint si mantiene alta poiché la meccanizzazione continua dei processi agricoli deve necessariamente attingere da fonti energetiche sostitutive al lavoro umano. Le terre agricole diminuiscono nei paesi europei analizzati e in Italia aumentando i rischi d’insicurezza alimentare giacché la popolazione nazionale sta invece aumentando.

Percieved Organizational Efficacy in Internationalized Companies: Application of Competing Values Approach and Collective Efficacy

This dissertation focuses on “organizational efficacy”, in particular on employees’ beliefs of organizational capacity to be efficacious. Organizational efficacy is considered from two perspectives – competing values approach and collective efficacy, and evaluated in internationalized companies. The dissertation is composed of three studies. The data were collected in thirteen Italian companies on different stages of internationalization for a total number of respondents is 358. In the first study the factorial validity of the competing values instrument (Rohrbaugh, 1981) was investigated and confirmed. Two scales were used to measure collective efficacy: a general collective efficacy scale (Bohn, 2010), and a specific collective efficacy scale, developed following suggestions of Borgogni et al. (2001), it evaluates employees’ beliefs of efficacy of organizations in the international market. The findings suggest that competing values and collective organizational efficacy instruments may provide a multi-faceted measurement of employees’ beliefs of organizational efficacy. The second study examined the relationship between organizational efficacy and collective work engagement. To measure collective work engagement the UWES-9 (Schaufeli & Bakker, 2003) was adapted at the group level; its factor structure and reliability were similar to the standard UWES-9. The findings suggest that organizational efficacy fully predicts collective work engagement. Also we investigated whether leadership moderates the relationship between organizational efficacy and collective work engagement. We operationalized leadership style with MLQ (Bass & Avolio, 1995); the results suggest that intellectual stimulation and idealized influence (transformational leadership) and contingent reward (transactional leadership) enhance the impact of organizational efficacy on collective work engagement. In the third study we investigated organizational efficacy and collective work engagement in internationalized companies. The findings show that beliefs of organizational efficacy vary across companies in different stages of internationalization, while no significant difference was found for collective work engagement. Limitations, practical implications and future studies are discussed in the conclusion.

Global modeling of pollutant transport and deposition from anthropogenic emission hot spots on global scale

Urban centers significantly contribute to anthropogenic air pollution, although they cover only a minor fraction of the Earth's land surface. Since the worldwide degree of urbanization is steadily increasing, the anthropogenic contribution to air pollution from urban centers is expected to become more substantial in future air quality assessments. The main objective of this thesis was to obtain a more profound insight in the dispersion and the deposition of aerosol particles from 46 individual major population centers (MPCs) as well as the regional and global influence on the atmospheric distribution of several aerosol types. For the first time, this was assessed in one model framework, for which the global model EMAC was applied with different representations of aerosol particles. First, in an approach with passive tracers and a setup in which the results depend only on the source location and the size and the solubility of the tracers, several metrics and a regional climate classification were used to quantify the major outflow pathways, both vertically and horizontally, and to compare the balance between pollution export away from and pollution build-up around the source points. Then in a more comprehensive approach, the anthropogenic emissions of key trace species were changed at the MPC locations to determine the cumulative impact of the MPC emissions on the atmospheric aerosol burdens of black carbon, particulate organic matter, sulfate, and nitrate. Ten different mono-modal passive aerosol tracers were continuously released at the same constant rate at each emission point. The results clearly showed that on average about five times more mass is advected quasi-horizontally at low levels than exported into the upper troposphere. The strength of the low-level export is mainly determined by the location of the source, while the vertical transport is mainly governed by the lifting potential and the solubility of the tracers. Similar to insoluble gas phase tracers, the low-level export of aerosol tracers is strongest at middle and high latitudes, while the regions of strongest vertical export differ between aerosol (temperate winter dry) and gas phase (tropics) tracers. The emitted mass fraction that is kept around MPCs is largest in regions where aerosol tracers have short lifetimes; this mass is also critical for assessing the impact on humans. However, the number of people who live in a strongly polluted region around urban centers depends more on the population density than on the size of the area which is affected by strong air pollution. Another major result was that fine aerosol particles (diameters smaller than 2.5 micrometer) from MPCs undergo substantial long-range transport, with about half of the emitted mass being deposited beyond 1000 km away from the source. In contrast to this diluted remote deposition, there are areas around the MPCs which experience high deposition rates, especially in regions which are frequently affected by heavy precipitation or are situated in poorly ventilated locations. Moreover, most MPC aerosol emissions are removed over land surfaces. In particular, forests experience more deposition from MPC pollutants than other land ecosystems. In addition, it was found that the generic treatment of aerosols has no substantial influence on the major conclusions drawn in this thesis. Moreover, in the more comprehensive approach, it was found that emissions of black carbon, particulate organic matter, sulfur dioxide, and nitrogen oxides from MPCs influence the atmospheric burden of various aerosol types very differently, with impacts generally being larger for secondary species, sulfate and nitrate, than for primary species, black carbon and particulate organic matter. While the changes in the burdens of sulfate, black carbon, and particulate organic matter show an almost linear response for changes in the emission strength, the formation of nitrate was found to be contingent upon many more factors, e.g., the abundance of sulfuric acid, than only upon the strength of the nitrogen oxide emissions. The generic tracer experiments were further extended to conduct the first risk assessment to obtain the cumulative risk of contamination from multiple nuclear reactor accidents on the global scale. For this, many factors had to be taken into account: the probability of major accidents, the cumulative deposition field of the radionuclide cesium-137, and a threshold value that defines contamination. By collecting the necessary data and after accounting for uncertainties, it was found that the risk is highest in western Europe, the eastern US, and in Japan, where on average contamination by major accidents is expected about every 50 years.

Unmittelbare, dauerhafte sowie evolutionäre Anpassung an Fremdstoffexpositionen

Eine der Hauptursachen für unerwünschte oder reduzierte Wirkungen von Medikamenten ist die Induktion von Enzymen und Transportern des Medikamentenstoffwechsels. Diese Induktion stellt ursprünglich eine physiologische Reaktion auf die Aufnahme von potentiell schädlichen Fremdstoffen aus der Umwelt dar und sichert so die Gesundheit und Fortpflanzungsfähigkeit von Lebewesen. Beim Menschen sowie anderen Säugetieren werden Fremdstoffe hauptsächlich von den nukleären Rezeptoren PXR und CAR in der Leber und im Dünndarm detektiert. Zu den Medikamenten, welche über PXR und CAR wirken, gehören unter anderem Antikonvulsiva, Statine, antiretrovirale Medikamente, Glucocorticoide sowie Antimykotika. Die durch Fremdstoffe aktivierten Transkriptionsfaktoren PXR und CAR steigern die Menge der Enzyme und Transporter des Fremdstoffmetabolismus. Hierzu zählen vor allem die Cytochrom P450-Enzyme (Cyp-Enzyme) mit breitem Substratspektrum oder der Transporter MDR1, welcher eine Vielzahl von Substraten über Membranen transportiert. Durch die Biotransformation werden die induzierenden, lipophilen Substanzen so modifiziert, dass sie leichter über den Urin oder die Galle ausgeschieden werden können. \r\nDie Dauer der Induktion sollte auf die Zeit der Fremdstoffexposition beschränkt sein, um Störungen des endogenen Stoffwechsels zu vermindern. In dieser Arbeit werden jedoch Hinweise auf dauerhafte und sogar generationsübergreifende Effekte von Medikamenten in Mäusen geliefert. Nachkommen von Müttern, welche bereits vor ihrer Verpaarung einmalig mit TCPOBOP, einem Liganden des murinen CAR, injiziert wurden, hatten eine ungefähr 100-fach gesteigerte Genexpression von Cyp2b10. Auch gab es Expressionsänderungen von Genen, deren Produkte eine Rolle im Lipidstoffwechsel sowie bei Immunkrankheiten spielen. Eine Hochdurchsatz-RNA-Sequenzierung der injizierten Elterngeneration ergab außerdem dauerhafte Expressionsveränderungen anderer Gene des Medikamentenstoffwechsels sowie von Genen mit Verbindung zum Energiemetabolismus. \r\nBerücksichtigt man die enge evolutionäre Verwandtschaft der nukleären Rezeptoren CAR und PXR, sind Langzeitveränderungen auch für PXR möglich und wurden im Verlauf dieser Arbeit ebenfalls untersucht. Eine Hochdurchsatz-Sequenzierung ergab für Mäuse, welche mit dem PXR-Aktivator PCN induziert wurden, dass selbst noch drei Monate nach der Exposition Gene verändert exprimiert waren, welche im Zusammenhang mit Lebernekrosen stehen. Bei Nachkommen von PCN-injizierten Müttern wurden Gene unterschiedlich exprimiert, welche eine Rolle bei der Energiehomöostase sowie im Glukosestoffwechsel spielen. Im Erwachsenenalter sind bei diesen Nachkommen darüber hinaus noch Gene unterschiedlich exprimiert, deren Produkte eine Funktion in der Immunantwort haben. \r\nDa Erwachsene aufgrund ihrer Lebensdauer sowie der absoluten Krankheitshäufigkeit wesentlich öfter Kontakt mit Fremdstoffen haben, war medizinisch von besonderem Interesse, ob anhaltende Genexpressionsänderungen auch bei Erwachsenen zu beobachten sind. So konnte im Rahmen dieser Arbeit gezeigt werden, dass auch einmalig exponierte Adulttiere Gene dauerhaft verändert exprimieren und die Veränderungen im Medikamentenstoffwechsel an die nächste Generation übertrugen. \r\n\r\nBisher sind klinische Studien zur Risikobewertung von Medikamenten (Pharmakovigilanz) nicht generationsübergreifend angelegt. Diese Arbeit gibt Anstöße dafür, dass dies in Zukunft für viel mehr Medikamente notwendig werden könnte. Neben Veränderungen im Medikamentenstoffwechsel ergeben sich Nebenwirkungen von PXR- und CAR-Liganden vor allem aus ihrer Beteiligung an endogenen Stoffwechselwegen. Nach Aktivierung von CAR, welcher viele metabolische Stoffwechselwege steuert, treten beispielsweise Störungen des Energiestoffwechsels auf. Ein tieferes Verständnis der Rezeptoraktivität von CAR samt einer gezielten Modulierung seiner Aktivität würde wichtige Beiträge zum Verständnis der Regulation des Fremdstoffmetabolismus sowie der Entstehung von Nebenwirkungen durch eine Behandlung mit CAR-Liganden leisten. Dauerhafte Veränderungen endogener Stoffwechselwege könnten dann möglicherweise über eine pharmakologische Modulierung der CAR-Aktivität reduziert werden. \r\nZu diesem Zweck wurden im Verlauf dieser Arbeit die CAR-Rezeptoren der Amphibien (Xenopus tropicalis, Xenopus laevis) und Reptilien (Anolis carolinensis) erstmals kloniert, als Proteine exprimiert und charakterisiert. Vergleiche zwischen Tierarten ermöglichen ein besseres Verständnis von humanen Proteinen. Funktionelle Analysen ergaben Ähnlichkeiten des Xenopus laevis-CAR mit dem PXR der Säugetiere: eine niedrige basale Aktivität sowie eine starke Induzierbarkeit durch Liganden. In weiteren funktionellen Analysen wurden die Determinanten der basalen Aktivität des Xenopus laevis-CAR untersucht. Die basale Aktivität war nicht abhängig von der subzellulären Lokalisation, sondern ergab sich aus der Proteinstruktur, welche nur beim CAR der Landvertebraten in einer aktiven Konformation fixiert ist. Ähnlich dem PXR der Säugetiere besitzt CAR der Amphibien eine Aktivierungsdomäne, welche erst durch Ligandenbindung in eine aktive Konformation gebracht wird. Mutationen einzelner Aminosäuren zum jeweils humanen Homolog erhöhten die basale Aktivität des Xenopus laevis-CAR auf die des humanen Rezeptors. Diese Mutanten mit erhöhter basalen Aktivität zeigten eine verstärkte Interaktion mit dem Kofaktor PGC-1a, einem Regulator des Energiestoffwechsels bei Säugetieren. Die hepatischen Zielgene des CAR der Amphibien überlappen zum Teil mit den humanen Zielgenen und spielen ebenfalls eine Rolle im Energiestoffwechsel.

Line bisection in simulated homonymous hemianopia

Hemianopic patients make a systematic error in line bisection, showing a contra-lesional bias towards their blind side, which is the opposite of that in hemineglect patients. This error has been attributed variously to the visual field defect, to long-term strategic adaptation, or to independent effects of damage to extrastriate cortex. To determine if hemianopic bisection error can occur without the latter two factors, we studied line bisection in healthy subjects with simulated homonymous hemianopia using a gaze-contingent display, with different line-lengths, and with or without markers at both ends of the lines. Simulated homonymous hemianopia did induce a contra-lesional bisection error and this was associated with increased fixations towards the blind field. This error was found with end-marked lines and was greater with very long lines. In a second experiment we showed that eccentric fixation alone produces a similar bisection error and eliminates the effect of line-end markers. We conclude that a homonymous hemianopic field defect alone is sufficient to induce both a contra-lesional line bisection error and previously described alterations in fixation distribution, and does not require long-term adaptation or extrastriate damage.

Rapid adaptation of visual search in simulated hemianopia

Patients with homonymous hemianopia have altered visual search patterns, but it is unclear how rapidly this develops and whether it reflects a strategic adaptation to altered perception or plastic changes to tissue damage. To study the temporal dynamics of adaptation alone, we used a gaze-contingent display to simulate left or right hemianopia in 10 healthy individuals as they performed 25 visual search trials. Visual search was slower and less accurate in hemianopic than in full-field viewing. With full-field viewing, there were improvements in search speed, fixation density, and number of fixations over the first 9 trials, then stable performance. With hemianopic viewing, there was a rapid shift of fixation into the blind field over the first 5-7 trials, followed by continuing gradual improvements in completion time, number of fixations, and fixation density over all 25 trials. We conclude that in the first minutes after onset of hemianopia, there is a biphasic pattern of adaptation to altered perception: an early rapid qualitative change that shifts visual search into the blind side, followed by more gradual gains in the efficiency of using this new strategy, a pattern that has parallels in other studies of motor learning.