A holistic approach to model-based testing of Web service compositions

The behavior of composed Web services depends on the results of the invoked services; unexpected behavior of one of the invoked services can threat the correct execution of an entire composition. This paper proposes an event-based approach to black-box testing of Web service compositions based on event sequence graphs, which are extended by facilities to deal not only with service behavior under regular circumstances (i.e., where cooperating services are working as expected) but also with their behavior in undesirable situations (i.e., where cooperating services are not working as expected). Furthermore, the approach can be used independently of artifacts (e.g., Business Process Execution Language) or type of composition (orchestration/choreography). A large case study, based on a commercial Web application, demonstrates the feasibility of the approach and analyzes its characteristics. Test generation and execution are supported by dedicated tools. Especially, the use of an enterprise service bus for test execution is noteworthy and differs from other approaches. The results of the case study encourage to suggest that the new approach has the power to detect faults systematically, performing properly even with complex and large compositions. Copyright © 2012 John Wiley & Sons, Ltd.

Assessment of the initial state of two reserves, Micro áreas Ecoturísticas Litorales (MAEL), in Gran Canaria, Canary Islands

Máster en Oceanografía

Climate impact studies of sediment transport on the Adriatic coastal zone

The study of the impact of climate change on the environment has been based, until very recently, on an global approach, whose interest from a local point of view is very limited. This thesis, on the contrary, has treated the study of the impact of climate change in the Adriatic Sea basin following a twofold strategy of regionalization and integration of numerical models in order to reproduce the present and future scenarios of the system through a more and more realistic and solid approach. In particular the focus of the study was on the impact on the physical environment and on the sediment transport in the basin. This latter is a very new and original issue, to our knowledge still uninvestigated. The study case of the coastal area of Montenegro was particularly studied, since it is characterized by an important supply of sediment through the Buna/Bojana river, second most important in the Adriatic basin in terms of flow. To do this, a methodology to introduce the tidal processes in a baroclinic primitive equations Ocean General Circulation Model was applied and tidal processes were successfully reproduced in the Adriatic Sea, analyzing also the impacts they have on the mean general circulation, on salt and heat transport and on mixing and stratification of the water column in the different seasons of the year. The new hydrodynamical model has been further coupled with a wave model and with a river and sea sediment transport model, showing good results in the reproduction of sediment transport processes. Finally this complex coupled platform was integrated in the period 2001-2030 under the A1B scenario of IPCC, and the impact of climate change on the physical system and on sediment transport was preliminarily evaluated.

Molecular phylogeography of the Woodland Ringlet (Erebia medusa [Denis and Schiffermüller] 1775) in Europe

Phylogeography is a recent field of biological research that links phylogenetics to biogeography through deciphering the imprint that evolutionary history has left on the genetic structure of extant populations. During the cold phases of the successive ice ages, which drastically shaped species’ distributions since the Pliocene, populations of numerous species were isolated in refugia where many of them evolved into different genetic lineages. My dissertation deals with the phylogeography of the Woodland Ringlet (Erebia medusa [Denis and Schiffermüller] 1775) in Central and Eastern Europe. This Palaearctic butterfly species is currently distributed from central France and south eastern Belgium over large parts of Central Europe and southern Siberia to the Pacific. It is absent from those parts of Europe with mediterranean, oceanic and boreal climates. It was supposed to be a Siberian faunal element with a rather homogeneous population structure in Central Europe due to its postglacial expansion out of a single eastern refugium. An already existing evolutionary scenario for the Woodland Ringlet in Central and Eastern Europe is based on nuclear data (allozymes). To know if this is corroborated by organelle evolutionary history, I sequenced two mitochondrial markers (part of the cytochrome oxydase subunit one and the control region) for populations sampled over the same area. Phylogeography largely relies on the construction of networks of uniparentally inherited haplotypes that are compared to geographic haplotype distribution thanks to recent developed methods such as nested clade phylogeographic analysis (NCPA). Several ring-shaped ambiguities (loops) emerged from both haplotype networks in E. medusa. They can be attributed to recombination and homoplasy. Such loops usually avert the straightforward extraction of the phylogeographic signal contained in a gene tree. I developed several new approaches to extract phylogeographic information in the presence of loops, considering either homoplasy or recombination. This allowed me to deduce a consistent evolutionary history for the species from the mitochondrial data and also adds plausibility for the occurrence of recombination in E. medusa mitochondria. Despite the fact that the control region is assumed to have a lack of resolving power in other species, I found a considerable genetic variation of this marker in E. medusa which makes it a useful tool for phylogeographic studies. In combination with the allozyme data, the mitochondrial genome supports the following phylogeographic scenario for E. medusa in Europe: (i) a first vicariance, due to the onset of the Würm glaciation, led to the formation of several major lineages, and is mirrored in the NCPA by restricted gene flow, (ii) later on further vicariances led to the formation of two sub-lineages in the Western lineage and two sub-lineages in the Eastern lineage during the Last Glacial Maximum or Older Dryas; additionally the NCPA supports a restriction of gene flow with isolation by distance, (iii) finally, vicariance resulted in two secondary sub-lineages in the area of Germany and, maybe, to two other secondary sub-lineages in the Czech Republic. The last postglacial warming was accompanied by strong range expansions in most of the genetic lineages. The scenario expected for a presumably Siberian faunal element such as E. medusa is a continuous loss of genetic diversity during postglacial westward expansion. Hence, the pattern found in this thesis contradicts a typical Siberian origin of E. medusa. In contrast, it corroboratess the importance of multiple extra-Mediterranean refugia for European fauna as it was recently assumed for other continental species.

Export Supply Chain Organization and Food Safety and Quality Standards: a case study of the Moroccan Fruit and Vegetable Sector

Agri-food supply chains extend beyond national boundaries, partially facilitated by a policy environment that encourages more liberal international trade. Rising concentration within the downstream sector has driven a shift towards “buyer-driven” global value chains (GVCs) extending internationally with global sourcing and the emergence of multinational key economic players that compete with increase emphasis on product quality attributes. Agri-food systems are thus increasingly governed by a range of inter-related public and private standards, both of which are becoming a priori mandatory, especially in supply chains for high-value and quality-differentiated agri-food products and tend to strongly affect upstream agricultural practices, firms’ internal organization and strategic behaviour and to shape the food chain organization. Notably, increasing attention has been given to the impact of SPS measures on agri-food trade and notably on developing countries’ export performance. Food and agricultural trade is the vital link in the mutual dependency of the global trade system and developing countries. Hence, developing countries derive a substantial portion of their income from food and agricultural trade. In Morocco, fruit and vegetable (especially fresh) are the primary agricultural export. Because of the labor intensity, this sector (especially citrus and tomato) is particularly important in terms of income and employment generation, especially for the female laborers hired in the farms and packing houses. Hence, the emergence of agricultural and agrifood product safety issues and the subsequent tightening of market requirements have challenged mutual gains due to the lack of technical and financial capacities of most developing countries.

Synthesis of carbolines and analogues via rhodhium-catalyzed [2+2+2] cycloaddition with alkynyl-ynamides : application to the total synthesis of alkaloids

The main research theme of this dissertation is the synthesis of g- and b-carbolines using a metal-catalyzed [2+2+2] cycloaddition strategy of tethered alkynyl-ynamides (diynes) with nitriles. g- and b-carbolines form the core of a large group of natural product and represent important targets for organic chemists. Many of these carbolines showed pharmacological effects ranging from anti-tumor to anxiolytic and anti-HIV activity. A model study with N-Ethynyl-N-tosyl-2-(2-phenylethynyl)aniline and methyl cyanoformate showed that rhodium-based catalysts promote efficiently the reaction. A further optimization showed that the regioselectivity of the reaction can be tuned by the choice of the solvent or by the catalytic system. Application to a larger scope of diynes showed that the regioselectivity strongly depends on the type of substitution of the alkynyl moieties, giving regioselectivities in the range g:b = 1/0 to g:b = 0/1. This [2+2+2] cycloaddition approach for the synthesis of the g- and b-carboline cores was successfully applied to the first total synthesis of Isoperlolyrine and the total synthesis of Perlolyrine. Extension of this strategy to heterocumulenes as cycloaddition partners allowed the synthesis of a g-carbolinone, a thiopyrano[3,4-b]indol-3-imine and thiopyranothiones.

Life cycle assessment in construction field: A life cycle cost analysis of reinforcement concrete bridge

The present work is included in the context of the assessment of sustainability in the construction field and is aimed at estimating and analyzing life cycle cost of the existing reinforced concrete bridge “Viadotto delle Capre” during its entire life. This was accomplished by a comprehensive data collection and results evaluation. In detail, the economic analysis of the project is performed. The work has investigated possible design alternatives for maintenance/rehabilitation and end-of-life operations, when structural, functional, economic and also environmental requirements have to be fulfilled. In detail, the economic impact of different design options for the given reinforced concrete bridge have been assessed, whereupon the most economically, structurally and environmentally efficient scenario was chosen. The Integrated Life-Cycle Analysis procedure and Environmental Impact Assessment were also discussed in this work. The scope of this thesis is to illustrate that Life Cycle Cost analysis as part of Life Cycle Assessment approach could be effectively used to drive the design and management strategy of new and existing structures. The final objective of this contribution is to show how an economic analysis can influence decision-making in the definition of the most sustainable design alternatives. The designers can monitor the economic impact of different design strategies in order to identify the most appropriate option.

Drug delivery, entry and intracellular trafficking of polymeric nanoparticles

Polymere Nanopartikel sind kleine Teilchen, die vielseitige Einsatzmöglichkeiten für den Transport von Wirkstoffen bieten. Da Nanomaterialien in diesen biomedizinischen Anwendungen oft mit biologischen Systemen in Berührung kommen, erfordert das eine genaue Untersuchung ihrer gegenseitigen Wechselwirkungen. In diesem speziellen Forschungsgebiet, welches sich auf die Interaktionen von Nanomaterialien mit biologischen Komponenten konzentriert, wurde bereits eine Vielzahl verschiedener Nanopartikel-Zell-Interaktionen (z. B. Nanotoxizität, Wirkstofftransport-mechanismen) analysiert. Bezüglich der Untersuchungen zu nanopartikulären Wirkstofftransport-mechanismen ist es im Allgemeinen akzeptiert, dass ein erfolgreicher zellulärer Transport hauptsächlich von der Aufnahme des Nanotransporters abhängt. Deshalb analysieren wir in dieser Arbeit (1) den Wirkstofftransportmechanismus für biologisch-abbaubare eisenhaltige Poly-L-Milchsäure Nanopartikel (PLLA-Fe-PMI) sowie (2) die Aufnahmemechanismen und die intrazellulären Transportwege von nicht-abbaubaren superparamagnetischen Polystyrolnanopartikeln (SPIOPSN). rnIn dieser Arbeit identifizieren wir einen bisher unbekannten und nicht-invasiven Wirkstoff-transportmechanismus. Dabei zeigt diese Studie, dass der subzelluläre Transport der nanopartikulärer Fracht nicht unbedingt von einer Aufnahme der Nanotransporter abhängt. Der identifizierte Arzneimitteltransportmechanismus basiert auf einem einfachen physikochemischen Kontakt des hydrophoben Poly-L-Milchsäure-Nanopartikels mit einer hydrophoben Oberfläche, wodurch die Freisetzung der nanopartikulären Fracht ausgelöst wird. In Zellexperimenten führt die membranvermittelte Freisetzung der nanopartikulären Fracht zu ihrem sofortigen Transport in TIP47+- und ADRP+- Lipidtröpfchen. Der Freisetzungsmechanismus („kiss-and-run") kann durch die kovalente Einbindung des Frachtmoleküls in das Polymer des Nanopartikels blockiert werden.rnWeiterhin wird in Langzeitversuchen gezeigt, dass die Aufnahme der untersuchten polymeren Nanopartikel von einem Makropinozytose-ähnlichen Mechanismus gesteuert wird. Im Laufe dieser Arbeit werden mehrere Faktoren identifiziert, die in diesem Aufnahmemechanismus eine Rolle spielen. Darunter fallen unter anderem die kleinen GTPasen Rac1 und ARF1, die die Aufnahme von SPIOPSN beeinflussen. Darauffolgend werden die intrazellulären Transportwege der Nanopartikel untersucht. Mit Hilfe eines neuartigen Massenspektrometrieansatzes wird der intrazelluläre Transport von nanopartikelhaltigen endozytotischen Vesikeln rekonstruiert. Intensive Untersuchungen identifizieren Marker von frühen Endosomen, späten Endosomen/ multivesikulären Körpern, Rab11+- Endosomen, Flotillin-Vesikeln, Lysosomen und COP-Vesikeln. Schließlich wird der Einfluss des lysosomalen Milieus auf die Proteinhülle der Nanopartikel untersucht. Hier wird gezeigt, dass die adsorbierte Proteinhülle auf den Nanopartikeln in die Zelle transportiert wird und anschließend im Lysosom abgebaut wird. rnInsgesamt verdeutlicht diese Arbeit, dass die klassische Strategie des nanopartikulären und invasiven Wirkstofftransportmechanismuses überdacht werden muss. Weiterhin lässt sich aus den Daten schlussfolgern, dass polymere Nanopartikel einem atypischen Makropinozytose-ähnlichen Aufnahmemechanismus unterliegen. Dies resultiert in einem intrazellulären Transport der Nanopartikel von Makropinosomen über multivesikuläre Körperchen zu Lysosomen.rn

Proteomic analysis of ocular surface components by use of HPLC based mass spectrometric strategies

In der vorliegenden Arbeit wurde eine Top Down (TD) und zwei Bottom Up (BU) MALDI/ESI Massenspektrometrie/HPLC-Methoden entwickelt mit dem Ziel Augenoberfächenkomponenten, d.h. Tränenfilm und Konjunktivalzellen zu analysieren. Dabei wurde ein detaillierter Einblick in die Entwicklungsschritte gegeben und die Ansätze auf Eignung und methodische Grenzen untersucht. Während der TD Ansatz vorwiegend Eignung zur Analyse von rohen, weitgehend unbearbeiteten Zellproben fand, konnten mittels des BU Ansatzes bearbeitete konjunktivale Zellen, aber auch Tränenfilm mit hoher Sensitivität und Genauigkeit proteomisch analysiert werden. Dabei konnten mittels LC MALDI BU-Methode mehr als 200 Tränenproteine und mittels der LC ESI Methode mehr als 1000 Tränen- sowie konjunktivale Zellproteine gelistet werden. Dabei unterschieden sich ESI- and MALDI- Methoden deutlich bezüglich der Quantität und Qualität der Ergebnisse, weshalb differente proteomische Anwendungsgebiete der beiden Methoden vorgeschlagen wurden. Weiterhin konnten mittels der entwickelten LC MALDI/ESI BU Plattform, basierend auf den Vorteilen gegenüber dem TD Ansatz, therapeutische Einflüsse auf die Augenoberfläche mit Fokus auf die topische Anwendung von Taurin sowie Taflotan® sine, untersucht werden. Für Taurin konnten entzündungshemmende Effekte, belegt durch dynamische Veränderungen des Tränenfilms, dokumentiert werden. Außerdem konnten vorteilhafte, konzentrationsabhängige Wirkweisen auch in Studien an konjunktival Zellen gezeigt werden. Für die Anwendung von konservierungsmittelfreien Taflotan® sine, konnte mittels LC ESI BU Analyse eine Regenerierung der Augenoberfläche in Patienten mit Primärem Offenwinkel Glaukom (POWG), welche unter einem “Trockenem Auge“ litten nach einem therapeutischen Wechsel von Xalatan® basierend auf dynamischen Tränenproteomveränderungen gezeigt werden. Die Ergebnisse konnten mittels Microarray (MA) Analysen bestätigt werden. Sowohl in den Taurin Studien, als auch in der Taflotan® sine Studie, konnten charakteristische Proteine der Augenoberfläche dokumentiert werden, welche eine objektive Bewertung des Gesundheitszustandes der Augenoberfläche ermöglichen. Eine Kombination von Taflotan® sine und Taurin wurde als mögliche Strategie zur Therapie des Trockenen Auges bei POWG Patienten vorgeschlagen und diskutiert.

Cleavage of IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis

Degradation of immunoglobulins is an effective strategy of bacteria to evade the immune system. We have tested whether human IgG is a substrate for gingipain K of Porphyromonas gingivalis and found that the enzyme can hydrolyze subclass 1 and 3 of human IgG. The heavy chain of IgG(1) was cleaved at a single site within the hinge region, generating Fab and Fc fragments. IgG(3) was also cleaved within the heavy chain, but at several sites around the CH2 region. Investigation of the enzyme kinetics of IgG proteolysis by gingipain K, using FPLC- and isothermal titration calorimetry-based assays followed by Hill plots, revealed non-Michaelis-Menten kinetics involving a mechanism of positive cooperativity. In ex vivo studies, it was shown that gingipain K retained its IgG hydrolyzing activity in human plasma despite the high content of natural protease inhibitors; that IgG(1) cleavage products were detected in gingival crevicular fluid samples from patients with severe periodontitis; and that gingipain K treatment of serum samples from patients with high antibody titers against P. gingivalis significantly hindered opsonin-dependent phagocytosis of clinical isolates of P. gingivalis by neutrophils. Altogether, these findings underline a biological function of gingipain K as an IgG protease of pathophysiological importance.

Prediction and prevention of schizophrenia: what has been achieved and where to go next?

In modern medicine, vigorous efforts are being made in the prediction and prevention of diseases. Mental disorders are suitable candidates for the application of this program. The currently known neurobiological and psychosocial risk indicators for schizophrenia do not have a predictive power sufficient for selective prevention in asymptomatic patients at risk. However, once predictive basic and later pre-psychotic high risk symptoms of psychosis develop into the five-year initial prodrome, the impending outbreak of the disease can be predicted with high accuracy. Research findings suggest a differential strategy of indicated prevention with cognitive behavioral therapy in early initial prodromal states and low dosage atypical antipsychotics in late initial prodromal states. The most important future tasks are the improvement of the predictive power by risk enrichment and stratification, as well as the confirmation of the existing and the development of new prevention strategies, with a stronger focus on the etiology of the disorder. In addition, the prediction and prevention approach would benefit from the inclusion of risk symptoms in the DSM-5 criteria.

The Politics of Purchasing Power: Feminist Tourism and Women's Development in Nepal

My purpose in this essay is to explore how ideas about women and development are created and circulated at the moment of consumption of wares produced at a women's development project in Nepal. I analyze the project as an example of the ways that women's development is an object of material and discursive consumption. Artifacts produced and sold by Nepali women, and purchased by tourists from the "first world," become part of an international exchange of power, money, and meaning. Based on a survey of consumers and ethnographic observations, I conclude that feminist tourists forge relations with disempowered "Others" through the pleasurable activity of an alienated market transaction. Consumers of crafts produced at a women's development project assume a position of empowerment and enlightenment, ready to help out their "women" counterparts through their support of an enterprise with circular logic: within the industry of development (although not necessarily for feminist tourists themselves), at least one of the central projects of development is the development project itself. At the same time, feminist tourists locate themselves outside the oppressive structures and ideologies affecting their "third-world sisters." This is a relation of sympathy and imagined empathy, with no sense of differential location within systems of oppression. They fail to examine or articulate the global link between their own purchasing power and local living conditions of Maithil women; the connection is effectively built out of the discourse.

Favourable prognostic value of antibodies anti-HSP20 in patients with cystic echinococcosis: a differential immunoproteomic approach

Seeking biomarkers reflecting disease development in cystic echinococcosis (CE), we used a proteomic approach linked to immunological characterisation for the identification of respective antigens. Two-dimensional gel electrophoresis (2-DE) of sheep hydatid fluid, followed by immunoblot analysis (IB) with sera from patients with distinct phases of disease, enabled us to identify by mass spectrometry heat shock protein 20 (HSP20) as a potential marker of active CE. Using IB, antibodies specific to the 34 kDa band of HSP20 were detected in sera from 61/95 (64%) patients with CE, but not in sera from healthy subjects. IB revealed anti-HSP20 antibodies in a higher percentage of sera from patients with active disease than in sera from patients with inactive disease (81 vs. 24%; P = 10(-4)). These primary results were confirmed in a long-term follow-up study after pharmacological and surgical treatment. Herewith anti-HSP20 antibody levels significantly decreased over the course of treatment in sera from patients with cured disease, relative to sera from patients with progressive disease (P = 0.017). Thus, during CE, a comprehensive strategy of proteomic identification combined with immunological validation represents a promising approach for the identification of biomarkers useful for the prognostic assessment of treatment of CE patients.

Identification of an African Bacillus anthracis Lineage That Lacks Expression of the Spore Surface-Associated Anthrose-Containing Oligosaccharide

The surfaces of Bacillus anthracis endospores expose a pentasaccharide containing the monosaccharide anthrose, which has been considered for use as a vaccine or target for specific detection of the spores. In this study B. anthracis strains isolated from cattle carcasses in African countries where anthrax is endemic were tested for their cross-reactivity with monoclonal antibodies (MAbs) specific for anthrose-containing oligosaccharides. Unexpectedly, none of the isolates collected in Chad, Cameroon, and Mali were recognized by the MAbs. Sequencing of the four-gene operon encoding anthrose biosynthetic enzymes revealed the presence of premature stop codons in the aminotransferase and glycosyltransferase genes in all isolates from Chad, Cameroon, and Mali. Both immunological and genetic findings suggest that the West African isolates are unable to produce anthrose. The anthrose-deficient strains from West Africa belong to a particular genetic lineage. Immunization of cattle in Chad with a locally produced vaccine based on anthrose-positive spores of the B. anthracis strain Sterne elicited an anti-carbohydrate IgG response specific for a synthetic anthrose-containing tetrasaccharide as demonstrated by glycan microarray analysis. Competition immunoblots with synthetic pentasaccharide derivatives suggested an immunodominant role of the anthrose-containing carbohydrate in cattle. In West Africa anthrax is highly endemic. Massive vaccination of livestock in this area has taken place over long periods of time using spores of the anthrose-positive vaccine strain Sterne. The spread of anthrose-deficient strains in this region may represent an escape strategy of B. anthracis.

Dynamics of Spatial Game Theory Networks with Novel Modifications

Introduction: Advances in biotechnology have shed light on many biological processes. In biological networks, nodes are used to represent the function of individual entities within a system and have historically been studied in isolation. Network structure adds edges that enable communication between nodes. An emerging fieldis to combine node function and network structure to yield network function. One of the most complex networks known in biology is the neural network within the brain. Modeling neural function will require an understanding of networks, dynamics, andneurophysiology. It is with this work that modeling techniques will be developed to work at this complex intersection. Methods: Spatial game theory was developed by Nowak in the context of modeling evolutionary dynamics, or the way in which species evolve over time. Spatial game theory offers a two dimensional view of analyzingthe state of neighbors and updating based on the surroundings. Our work builds upon this foundation by studying evolutionary game theory networks with respect to neural networks. This novel concept is that neurons may adopt a particular strategy that will allow propagation of information. The strategy may therefore act as the mechanism for gating. Furthermore, the strategy of a neuron, as in a real brain, isimpacted by the strategy of its neighbors. The techniques of spatial game theory already established by Nowak are repeated to explain two basic cases and validate the implementation of code. Two novel modifications are introduced in Chapters 3 and 4 that build on this network and may reflect neural networks. Results: The introduction of two novel modifications, mutation and rewiring, in large parametricstudies resulted in dynamics that had an intermediate amount of nodes firing at any given time. Further, even small mutation rates result in different dynamics more representative of the ideal state hypothesized. Conclusions: In both modificationsto Nowak's model, the results demonstrate the network does not become locked into a particular global state of passing all information or blocking all information. It is hypothesized that normal brain function occurs within this intermediate range and that a number of diseases are the result of moving outside of this range.