L’hypertension artérielle pulmonaire (HTAP) correspond à une augmentation des résistances artérielles pulmonaires, avec dans les formes les plus graves, une défaillance cardiaque droite. L’HTAP persistante du nouveau-né (HTAPP) est estimée à 2/100 naissances en France. L’adaptation cardio-respiratoire à la naissance implique le déclenchement simultané de plusieurs phénomènes non complètements compris. Notre travail avait pour but d’approfondir les connaissances sur la régulation pulmonaire périnatale et d’envisager de nouvelles possibilités thérapeutiques. Ainsi, nous avons mis en évidence in vivo une vasoconstriction pulmonaires chez le fœtus lors du tabagisme passif maternel, par blocage de la voie du NO. De même, nous avons pu montrer l’effet vasoconstricteur de l’apeline sur les artères pulmonaires de fœtus de brebis. Cet effet semble dose dépendant, inhibé par l’action des inhibiteurs calciques. Au contraire nous avons mis en évidence un effet vasodilatateur de la Déhydroépiandrostérone (DHEA). Cette action est médiée par la voie du NO. Parallèlement, nous avons montré que les acides gras poly insaturés ω 3 (AGPIω3) entrainaient une vasodilatation pulmonaire, se prolongeant au delà d’une heure après l’arrêt de la perfusion. Cet effet est médié par l’ouverture des canaux potassiques et indépendant de la voie du NO. Parmi les AGPIω3, nous avons établi que l’acide eicosapentaénoïque (EPA) qui induit cette réponse sans effet délétère sur la circulation systémique, ni l’oxygénation tissulaire. Enfin, nous avons établi que l’occlusion trachéale (OT) anténatale, traitement proposé pour certaine hypoplasie pulmonaire malformative, n’altère pas le débit pulmonaire, en favorisant la dilatation pulmonaire. Mais en cas d’OT prolongée, ces effets sont en partie masqués par les effets mécaniques de la pression intraluminale. Ainsi grâce à ces travaux, nous avons avancé dans la compréhension de l’adaptation de la circulation pulmonaire de la vie intra à la vie extra utérine. Ils permettent aussi de proposer de nouvelles thérapeutiques comme la supplémentation en AGPIω 3 des femmes attendant un enfant à risque d’HTAP, et d’envisager de nouvelles voies de recherche thérapeutique comme la voie de l’apeline. / Persistent pulmonary hypertension (PPH) corresponds to an increase in pulmonary arterial resistance, with in the most severe forms, right heart failure. The persistent pulmonary hypertension of the newborn (PPHN) is estimated at 2/100 births in France. The cardiorespiratory adaptation at birth involves the simultaneous triggering of several phenomena including non completions. Our work aimed to increase knowledge on the regulation of perinatal pulmonary and consider new therapeutic possibilities. Thus, we have demonstrated in vivo pulmonary vasoconstriction in the fetus when maternal passive smoking, by blocking the NO pathway. Similarly, we demonstrated the vasoconstrictor effect of apelin infusion on the pulmonary arteries of fetal sheep. This effect appears dose dependent, inhibited by the action of calcium channel blockers. Instead we have shown a vasodilatory effect of dehydroepiandrosterone (DHEA). This action is mediated by the NO pathway. In parallel, we have shown that polyunsaturated fatty acids ω 3 (AGPIω3) would cause pulmonary vasodilation, extending beyond an hour after stopping the infusion. This effect is mediated by the opening of potassium channels and independent of the NO pathway. Among AGPIω3, we found that eicosapentaenoic acid (EPA) that induces this response without deleterious effect on the systemic circulation or tissue oxygenation. Finally, we established that the antenatal tracheal occlusion (TO), treatment proposed for some malformative pulmonary hypoplasia, does not alter pulmonary blood flow, promoting lung expansion. But in case of prolonged OT, these effects are partly masked by the mechanical effects of intraluminal pressure. And through this work, we have made progress in understanding the adaptation of the pulmonary circulation of the intra to extrauterine life. They also suggest new therapeutic, like supplementation as AGPIω for women expecting a child at risk for PAH, and to consider new possibility of therapeutic research like the way of apelin.

Due to the increasing threat of global warming, today’s grid system faces large changes and challenges as more renewable sources are being implemented in the grid. In order to handle these changes and secure future distribution, new technologies and components are necessary. This study investigates the innovation – IT/OT integration and its rate of adoption among potential adopters – Distribution System Operators. Based upon 8 expert interviews, 19 interviews with Swedish DSOs and literature, the study has concluded the following: - Increased micro production in the Swedish electricity grid system is the main drivers for IT/OT integration. IT Security and Swedish Energy Market Inspectorates current pricing model are two of the main inhibitors for IT/OT integration. - Key factors, such as perceived attributes of the innovation and business transformation speed are of high importance when analyzing rate of adoption. - Medium-sized DSOs with high ambition are likely to adopt before other customer segments. Thus, they are potential target customers for suppliers, such as Ericsson. The thesis contributes to literature by providing research of a technical innovation within a complex market. Future research of interest is to apply similar methodology for predicting rate of adoption of IT/OT integration in other nations, since drivers and regulations might differ. / Det ökade hotet från klimatförändringar har medfört att dagens elnätssystem står inför stora förändringar och utmaningar då allt fler förnyelsebara källor implementeras i elnätet. För att hantera denna förändring och säkra framtidens eldistribution krävs att ny teknik och nya komponenter implementeras i elnätet. Denna rapport undersöker innovationen - IT/OT integration och hur denna sprids bland potentiella kunder – elnätsdistributörer. Baserat på 8 expertintervjuer, 19 intervjuer med svenska elnätsdistributörer och litteratur har studien kommit fram till följande slutsatser: - Ökad mikroproduktion i det svenska elnätet är den främsta drivaren för IT/OT integration. IT säkerhet och Energimarknadsinspektionens nuvarande regleringsmodell är idag två av de främsta barriärerna för IT/OT integration. - Huvudfaktorer, så som förväntade uppfattningen av innovationen och företags omvandlingshastighet är av stor betydelse för att uppskatta spridningshastigheten av innovationen. - Mellanstora DSOer med höga ambitioner kommer troligast ta till sig tekniken tidigare än andra kundsegment och bör därför vara potentiell målgrupp för leverantörer, så som Ericsson. Rapporten bidrar till forskningen genom att en teknisk innovation analyserats i en komplex marknad. Vidare undersökningar som kan genomföras är att applicera motsvarande metodik för estimera spridningen av IT/OT integration i andra länder, då drivare och regleringar där kan skilja sig från Sverige.

The fetus and its placenta, collectively called the conceptus, are semi-allogeneic to the mother, as they express transplantation antigens of paternal origin. Foreign tissues generally experience immunological rejection by the host immune system; however in a normal healthy pregnancy the conceptus does not undergo immune attack. Emerging evidence indicates the conceptus avoids rejection through a number of mechanisms including the induction of active maternal immune tolerance specific for paternal antigens. However, the mechanisms responsible for establishing this tolerance remain undefined, including the timing of the first encounter with paternal antigen and the cellular processes by which paternal antigen is presented to the maternal immune system. Exposure to paternal transplantation antigens occurs in two waves: initially in the context of male seminal fluid at conception, and secondly after placental trophoblast invasion of maternal tissues in mid-gestation pregnancy. Therefore the aim of this research was to evaluate the female immune response to paternal antigens in seminal fluid and those associated with the conceptus. The mechanisms of antigen presentation, the impact of the cytokine environment and the consequences of T cell activation on pregnancy were also investigated. A transgenic system using ovalbumin (OVA) as the model paternal antigen was established. The transgenic Act-mOVA mouse expresses OVA constitutively and ubiquitously under a B-actin promoter and OVA was shown to be present in seminal fluid and in the fetal and placental tissue of sired progeny. The OVA-reactive CD8+ OT-I and CD4+ OT-II T cells were employed to gauge the relative amount of OVA antigen presented, with the strength of the maternal immune response quantified based upon the extent of T cell proliferation, as assessed by CFSE dye-dilution. Utilising bone marrow chimeric mice, it was demonstrated that upon insemination by an Act-mOVA male, seminal fluid-derived OVA was processed and indirectly presented by maternal bone marrow-derived antigen presenting cells to induce activation and proliferation of the CD8+ OT-I T cells within the uterinedraining para-aortic lymph nodes of the female. Likewise, OT-II T cells were responsive to MHC class II-restricted presentation of seminal fluid OVA. Post-implantation conceptus-derived OVA was detected within peripheral lymph nodes and the spleen where it was presented via the MHC class I and class II-restricted pathways to induce systemic proliferation of both OT-I and OT-II T cells. Furthermore, as gestation advanced the extent of OVA presentation and hence T cell proliferation intensified. Conceptus-derived OVA was still presented systemically until 20 days pp. The impact of the uterine cytokine environment was assessed to determine its influence on seminal OVA antigen processing and presentation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a key factor in regulating the leukocyte population of the female reproductive tract. GM-CSF-deficient female mice were unable to process and present seminal fluid OVA as effectively or efficiently as their wildtype counterparts, as assessed by their reduced capacity to drive OT-I and OT-II T cell proliferation following insemination by an Act-mOVA male. Finally, with highly-reactive OVA-specific T cells activated in response to seminal and conceptus OVA antigen, it was of interest to determine the effect of OT-I T cell activation on fetal survival and pregnancy success. It was found that OT-I T cells activated in vivo to paternal OVA antigen in the context of seminal fluid and pregnancy were not deleterious to pregnancy outcomes. However the transfer of cytotoxic OT-I T cells generated in vitro in the presence of an IL-2 into female mice carrying OVA-expressing conceptuses was detrimental to fetal survival. Collectively these experiments demonstrated that the initial exposure to paternal antigen, and hence the first opportunity to develop paternal antigen-specific tolerance, occurs at insemination. Paternal antigen is presented to the maternal T cell repertoire throughout gestation and may play a role in maintaining immune tolerance during pregnancy. The processing and presentation of paternal-derived antigen is chiefly performed by female bone marrow-derived antigen presenting cells. The cytokine environment of the mated female reproductive tract is critical in allowing optimal antigen processing and presentation, to generate an immune response consistent with maternal immune tolerance of the conceptus. / Thesis (Ph.D.) - University of Adelaide, School of Paediatrics and Reproductive Health, 2008

This diploma thesis deals with questions about prospectus assembly for the company GASTROSUN SK, s.r.o with detailed focus on refinement of its prerequisites. The aim of this diploma thesis is to put together the comprehensive and integrated prospectus with the focus on its usability in practice. It’s important so that all assemblage plans in this prospectus reflected the real estate. Partial aim of this diploma thesis is matching other possible kinds of investments with the investment embedded in business by the help of indicator of return on capital employed before taxation.

Ce travail de thèse propose une démarche méthodologique pour caractériser et anticiper les perturbations organisationnelles dues à l’introduction d’un concept d’offre innovant dans un contexte « business to business ». Elle s’intéresse donc à des produits dont la mise en oeuvre induit conjointement une création de valeur pour le client et une modification des interrelations professionnelles entre métiers de cette entreprise cliente. L’enjeu est de concevoir des nouveaux produits ou services qui soient mieux acceptés par les clients internes des sociétés acheteuses par anticipation et intégration, dans la démarche de conception, de ces impacts. Les apports de cette recherche se positionnent à deux niveaux. D’une part, une démarche méthodologique est proposée. Elle s’intègre au processus de création de l’offre et permet de mieux décrire les opportunités de création de valeur induites par une meilleure définition des structures et attentes des acteurs des organisations clientes. Ces acteurs sont vus comme des individus mais aussi comme un réseau évolutif. D’autre part, une capitalisation des données recueillies auprès des clients est proposée. Ces dernières reposent sur une utilisation revisitée des concepts de « customers concerns » et de personas. Les informations recueillies et interprétées sont la base de nouveaux standards des cahiers des charges concepteurs. La première contribution, d’ordre méthodologique est appelée processus RACCP. Elle a été élaborée à partir d’un cas d’étude : la phase amont d’un processus de conception déployée chez un fournisseur d’automatisme industriel. Elle aide le concepteur à modéliser les évolutions induites par un concept d’offre sur le fonctionnement de tous les acteurs chez son client. Ceci est possible par l’utilisation conjointe de trois modèles opérationnels dès la phase amont d’un processus de conception : le modèle descriptif des problèmes clients, des profils d’acteurs associés à ces problèmes et une représentation des interrelations entre ces acteurs. La seconde contribution est constituée de l’ensemble des trois modèles opérationnels instanciés au cas de la convergence IT OT. Cet apport permet une meilleure compréhension des systèmes humains et techniques liés à ce contexte, riche en opportunités de création de valeur. Cette instanciation apporte également des premiers éléments de preuve d’efficacité du processus RACCP. / This thesis proposes a methodological approach to characterize and anticipate organizational disruptions due to the introduction of an innovative concept offer in a « business to business » context. Therefore, it concerns products whom implementation induced both value creation for the customer and a change of professional interrelationships between trades within the client company. The challenge is to design new products or services that are better accepted wihtin purchasing companies by anticipating and integrating these impacts into the design process. The contributions of this research are positioned at two levels. First, a methodological approach is proposed. It is integrated into the creative process of suppliers. It enables to better describe the value creation opportunities by a better definition of structures and expectations of actors within customer organizations. These actors are seen as individuals but also as a scalable network. Moreover, a capitalization of data collected from customers is proposed. It is based on an adapated use of "customers concerns" and personas concepts. The information collected and interpreted are the basis of new standards for designers’ specifications. The first methodological contribution is a process called RACCP. It was developed from a case study: the upstream phase of a design process used in an industrial automation supplier. It helps the designer to model the changes implied by an offer concept on the operations of all stakeholders within the client company. This is possible by the combined use of three operational models since the upstream phase of the design process: the descriptive model of customer pains, actors profiles involved in these pains and representation of the interrelationships between them. The second contribution consists of an instanciation of all these three operational models in the convergence IT OT context. This contribution enables a better understanding of human and technical systems related to this context, sources of high value creation opportunities. This instantiation also provides the first proof of RACCP process efficiency.

No description available.

I argue that the shift of explanatory burden from the generator to the evaluator in OT syntax – together with the difficulties that arise when we try to formulate a working theory of the interfaces of syntax – leads to a number of assumptions about syntactic structures in OT which are quite different from those typical of minimalist syntax: formal features, as driving forces behind syntactic movement, are useless, and derivational and representational economy are problematic for both empirical and conceptual reasons. The notion of markedness, central in Optimality Theory, is not fully compatible with the idea of synactic economy. Even more so, seemingly obvious cases of blocking by structural economy do not seem to result from grammar proper, but reflect (economical) aspects of language use.

Quasi-Monte Carlo (QMC) methods are playing an increasingly important role in computational finance. This is attributed to the increased complexity of the derivative securities and the sophistication of the financial models. Simple closed-form solutions for the finance applications typically do not exist and hence numerical methods need to be used to approximate their solutions. QMC method has been proposed as an alternative method to Monte Carlo (MC) method to accomplish this objective. Unlike MC methods, the efficiency of QMC-based methods is highly dependent on the dimensionality of the problems. In particular, numerous researches have documented, under the Black-Scholes models, the critical role of the generating matrix for simulating the Brownian paths. Numerical results support the notion that generating matrix that reduces the effective dimension of the underlying problems is able to increase the efficiency of QMC. Consequently, dimension reduction methods such as principal component analysis, Brownian bridge, Linear Transformation and Orthogonal Transformation have been proposed to further enhance QMC. Motivated by these results, we first propose a new measure to quantify the effective dimension. We then propose a new dimension reduction method which we refer as the directional method (DC). The proposed DC method has the advantage that it depends explicitly on the given function of interest. Furthermore, by assigning appropriately the direction of importance of the given function, the proposed method optimally determines the generating matrix used to simulate the Brownian paths. Because of the flexibility of our proposed method, it can be shown that many of the existing dimension reduction methods are special cases of our proposed DC methods. Finally, many numerical examples are provided to support the competitive efficiency of the proposed method.

In recent years, a great deal of research on second language (L2) acquisition has been concerned with non-target production of L2 learners, addressing issues such as native language (L1) transfer into L2 and the nature and source of developmental errors. Previous studies have mostly focused on the analysis of discrete L2 segments (Flege 1987, 1999; Major & Kim 1996), rather than on L2 phonological patterns. This study, however, examines the production of sequences of sounds in Russian L1 and L2 from both the phonetic and phonological perspectives.This dissertation investigates native and non-native production of real and nonsense words containing obstruent clusters in which a phonological phenomenon known as regressive voicing assimilation is required. In Russian, forms like lodka `boat' are rendered orthographically with a voiced obstruent which is pronounced as a voiceless one when followed by a voiceless obstruent. The results of the experiments reveal several production patterns in L1 and L2 speech as well as gradiency in devoicing which are further analyzed within the stochastic Optimality Theory framework. Categorical production is accounted for by the re-ranking of L1 and L2 constraints; whereas, gradiency in production is viewed as a result of the re-ranking of constraints within phonetically detailed constraint families.

Komandinis darbas – tai tam tikrą kokybinės brandos lygį pasiekusi komandos narių sąveika, kurioje pagrindiniai darbo principai grindžiami komandos narių bendradarbiavimu, parama, pagarba ir pasitikėjimu, vaidmenų pasiskirstymu bei aukšta motyvacija paremtais tarpusavio santykiais. Atlikus tyrimą, galime spręsti, kad darbuotojai, dirbdami komandinį darbą, susiduria su tam tikromis problemomis. Daugelis teigia, jog komandos nariai labiau siekia savų tikslų, o ne organizacijos, komandos nariai vengia prisiimti atsakomybę. Taip pat įvardijamas nesusikalbėjimas su komandos nariais, aiškaus lyderio nebuvimas, laiko trūkumas. Tyrimas parodė, kad kelionių centro ,,Megaturas“ komanda yra ketvirtajame komandos gyvavimo cikle. Tai yra integracijos etapas, kuriame vyrauja efektyvus komandinis darbas, akcentuojamas tinkamas, produktyvus laiko panaudojimas, problemos sprendžiamos kūrybiškai, vadovavimo funkcijos perduodamos kitiems komandos nariams. Norint patobulinti komandinį darbą kelionių centre „Megaturas“ bei pasiekti brandžios komandos statusą, reiktų gerinti organizacijos klimatą komandoje, didinti komandos bendradarbiavimą, tobulinti vadovavimą, stiprinti komandos normas ir didinti jos vaidmenį bei statusą. / Teamwork - is an interaction between team members of qualitative maturity level. The main working principles are based on team member’s cooperation, support, respect and trust, roles, and high motivation-based relationships. The study showed that the team of travel center “Megaturas” is in the fourth team life cycle. It is in the integration phase, which is dominated by effective teamwork, the emphasis at appropriate, productive use of time. Issues are solved creatively and functions of management are delegated to other team members. A large proportion of workers identified these characteristics as most descriptive of their team. The research suggests that staff members faced with certain problems. Many say that the team members are more likely to reach their own goals, rather than the organization, they avoid taking responsibility. The staff also named a lack of communication between team members, non existence of proper leader, shortage of time. To improve teamwork Travel Center ,,Megaturas“ as well as a team to achieve a mature status, the organization should improve the climate for the team, improve team collaboration, improve governance, strengthen the team's standards and to enhance its role and status.