Sammanfattning Uppsatsens syfte är att utreda om Mark- och miljööverdomstolen (MÖD) tillgodoser försiktighetsprincipen och EU-rättens krav vid riskbedömningar i Natura 2000-ärenden. Elva svenska rättsfall har analyserats och fyra fall från EU-domstolen. Följande frågor besvaras; -       hänvisar domstolen till begreppet gynnsam bevarandestatus? -       går det att utläsa ur MÖD:s domskäl om försiktighetsprincipen har tillämpats? Natura 2000-regleringen baseras på två EU-direktiv och syftar till att bevara och skydda den biologiska mångfalden inom unionen. Medlemsstaterna åläggs därför att upprätta skyddsområden för de arter och livsmiljöer som är listade i bilagor till direktiven. Medlemsstaterna är skyldiga att inrätta ett förfarande för att pröva verksamheters tillåtlighet inom skyddsområdena. Genom detta förfarande ska de nationella myndigheterna inte tillåta verksamheter som kan skada områdets integritet. Av EU-domstolens rättsfall framgår att tillståndsförfarandet ska tillämpas i ljuset av försiktighetsprincipen. Min analys av rättsfallen visar att MÖD fram till 2011 inte tillgodosett försiktighetsprincipen på ett tillfredställande sätt. Osäkerheter i utredningar angående potentiella skador har förbisetts och i något fall har det inte gått att utläsa om försiktighetsprincipen tillämpats. De två senaste åren har en positiv förändring skett. Domskälen har blivit tydligare, hänvisningar till lagstiftningen har gjorts mer tillfredställande och osäkerheter i utredningarna har lett till att tillstånd inte meddelats. Fortfarande finns dock möjlighet att förtydliga domskälen genom hänvisningar till gynnsam bevarandestatus och bevarandeplaner i aktuella områden.

El nostre laboratori s'ha centrat des de fa anys en l'estudi del gen que codifica per a la Kidney Androgen-regulated Protein (KAP) al ronyó murí, utilitzant-lo com a model d'estudi dels mecanismes moleculars que controlen la regulació de l'expressió gènica mitjançant andrògens al ronyó. Aquest gen, expressat de manera exclussiva per les cèl·lules epitelials del túbul proximal renal, exhibeix un control multihormonal específic en els diferents segments del mateix, amb participació d'andrògens, estrògens i hormona tiroidal. La comparació de seqüències gèniques i de la proteïna deduïda de KAP amb les dipositades en les bases de dades, no revela cap homologia amb altres gens o proteïnes conegudes. Les anàlisis de predicció de dominis funcionals tampoc suggereixen una possible localització o funció per a la KAP. Malgrat això, la relativa abundància del mRNA de la KAP, la seva localització exclussiva a l'epiteli del túbul proximal renal i l'estricte control multihormonal de la seva expressió, suggereixen que es podria tractar d'una proteïna de rellevància en fisiologia renal, i per això l'objectiu d'aquesta tesi ha estat la identificació i caracterització funcional de la proteïna KAP. La producció d'anticossos monoclonals contra dos pèptids sintètics de la KAP ens ha permès identificar la proteïna endògena per immunohistoquímica i Western blot en ronyó murí. La distribució cel·lular i control androgènic es correspon amb la del mRNA i la seva mida aparent és de 20 KDa. La proteïna també ha estat expressada i caracteritzada en sistèmes heteròlegs tals com bacteris i llevat. Assaigs de dobles híbrids en llevat ens han permès observar que la KAP interacciona de manera específica amb el receptor de CsA, la CyPB, havent-se confirmat aquesta interacció mitjançant GST-Pulldown, co-immunoprecipitació i co-localització per microscopia confocal. Malgrat els beneficis de la CsA com a immunosupressor, evitant el rebuig en pacients trasplantats, el seu ús es veu limitat pels greus efectes tòxics que produeix al ronyó, especialment a les cèl·lules del túbul proximal renal. La interacció de KAP amb CyPB ens ha portat a analitzar els efectes de la CsA sobre la interacció KAP-CyPB i sobre la expressió de la KAP. Observem que la CsA no desplaça la interacció entre KAP i CyPB. Hem demostrat que la administració de CsA a ratolins de la soca C57BL/6, disminueix de manera significativa els nivells de proteïna KAP en extractes crus de ronyó. En línies cel·lulars de túbul proximal murí, la presència de CsA augmenta la secreció de la KAP al medi de cultiu. Tanmateix, la transfecció estable de KAP i la seva sobre-expressió controlada per tetraciclina en un sistema cel·lular de túbul proximal, disminueix de forma significativa la toxicitat per CsA. / For years our laboratory has been focused on the gene that codes for the Kidney Androgen-regulated Protein (KAP) as a model to study the molecular mechanisms involved in the hormonal regulation of gene expression, mediated by androgens in mouse kidney. The KAP gene, expressed exclusively in the epithelial cells of proximal convoluted tubules, exhibits a multihormonal control of its expression in the different segments of proximal tubules, mediated by androgens, estrogens and thyroid hormone. Comparison of KAP nucleotide and amino acid sequences with sequences deposited in public databases has revealed that there is no homology with any known sequences that might indicate a possible function of the KAP protein. The relative abundance of the KAP mRNA and its exclusive localization in the epithelial cells of proximal convoluted tubules have suggested that the KAP protein might have a relevant function in kidney physiology. In this scenario, the main objective of this Thesis is the identification and functional characterization of the KAP protein. Production of monoclonal antibodies against two synthetic peptides of the KAP protein has allowed to identify the protein by Western blot and immunohistochemistry analysis in mouse kidney. The cellular distribution and androgenic control of its expression corresponds with that observed for the KAP mRNA and the protein has an apparent molecular weight of 20 kDa in SDS-PAGE gels. The protein has been also expressed and characterized in heterologous systems such as E. coli and Sacharomycces cerevisiae. By using the two-hybrid system in yeast we have been able to demonstrate that KAP interacts in a specific fashion with the Cyclosporin A (CsA) receptor, CypB. This interaction has been also proven by pulldown assays, co-immunoprecipitation and co-location using confocal microscopy. Although CsA is a potent immunosupressor, preventing the graft versus host disease in organ transplantation, its use has been limited by its deleterious side in the kidney, specially in the proximal tubule cells. The interaction between KAP and CypB pointed us to the study of the effects of CsA treatment on KAP-CyPB interaction, and on KAP expression. In our hands, CsA does not compete with KAP for CyPB interaction. We have shown that administration of CsA to C57BL/6 mice significantly diminishes the KAP protein levels in crude kidney extracts. In a cellular model, CsA treatment increases KAP secretion to the culture media. Also, stable transfection of KAP cDNA in a cellular system of proximal tubule cells has shown that overexpression of the KAP protein diminishes significantly the toxic effects of CsA in these cells.

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Les infections par Plasmodium induisent des changements importants sur la réponse effectrice et la régulation des cellules B. Ces effets se caractérisent par une suppression de la production d'anticorps contre des antigènes hétérologues et par une activation polyclonale non spécifique des cellules B. Nous avons centré notre attention sur le facteur inhibiteur de la migration des macrophages (MlF), une cytokine secrétée de façon constitutive chez plusieurs types cellulaires et intensifiée durant l'infection par Plasmodium. Le MlF inhibe l'apoptose des cellules B «in vitro» et son rôle dans les altérations des cellules B durant la malaria n'a pas encore été évalué. En utilisant des souris BALB/c infectées avec P. chabaudi adami DK avant et suite à un régime d'immunisation avec de la γ-globuline humaine, nous avons observé que l'infection après l'immunisation réduit significativement les titres d'lgG totaux et IgGI anti-γ-globuline humaine. Le possible rôle du MlF a été vérifié en neutralisant des souris BALB/c (immunisées avec de la γ-globuline humaine) avec anti-MIF. Les résultats démontrent une augmentation significative d'lFN-γ; une diminution de cellules B anexine +; mais aucun effet significatif sur la production d'anticorps. Étant donné que le MlF est présent pendants les infections nous avons neutralisé le MlF avant et après l'infection par P. chabaudi DK. L'inhibition dans les titres d'anticorps spécifiques à la γ-globuline induit par l'infection était comparable chez des souris traitées avec l'anti-MlF, ce qui suggère que le MlF n'y participe pas. Malgré les effets suggérés «in vitro» sur des cellules B, nos études ont démontré une diminution de cellules B, PI+ chez des souris infectées et neutralisées. En conclusion, nous pouvons dire que le MlF ne semble pas participer dans l'activation polyclonale non spécifique des cellules B durant la malaria et nous suggérons d'évaluer le temps de vie des anticorps en évaluant l'expression du récepteur néonatale Fc (FcRn) qu'y est impliqué à la régulation, le rôle des cellules T régulatrices ainsi que la modulation de l'expression du complexe CD74-CD44 durant les infections par Plasmodium. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Malaria, Cellules B, Réponse d'anticorps, MlF, Activation polyclonale.

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Non-repudiation techniques are to ensure any communication taking place between two or more parties will be undeniable. Therefore it is crucial to include digital signatures of the involving parties while the communication is taking place. In medical practices, involved parties include; patient(s), doctor(s), pharmacist(s), who are involved in series of visits, diagnosis, prescriptions, and possible operations. To avoid possible conflicts, deploying non-repudiation techniques help immensely. This thesis considers this issue in a wireless medium and studies the Quality of Service (QoS)/Security requirements in terms of network parameters and performance metrics. In terms of research contributions, this thesis embodies a thorough research on layered and cross-layer QoS and security schemes, in particular, featuring an adaptive Forward Error Correction (FEC) at the application layer, adapting to channel conditions. This leads to a cross layer design, which considers various QoS and security parameters export and import to and from various layers with a special focus on the application layer. The aim of this thesis is to consider a practical implementation and associated complexities of a non-repudiation system, including analytical and experimental testbeds and results. The security schemes are based on Suite-B cryptographic algorithms, including: The Elliptic Curve Diffie-Hellman (ECDH) for key agreement, the Advanced Encryption Standard - Galois/Counter Mode (AES-GCM) for encryption and authentication, the Elliptic Curve Digital Signature Algorithm (ECDSA) for digital signatures, and the Secure Hash Algorithm (SHA) for integrity. A key aspect of Suite-B is the deployment of Elliptic Curve Cryptography (ECC). The non-repudiation aspect of this thesis is based on the Suite-B’s digital signature scheme; ECDSA. The digital signature and the hashing function target the entire multimedia data (i.e., text, video, and voice) and the challenge is to offer such extensive security treatment, while guaranteeing certain Quality of Service settings. These settings include: minimum round trip delay, maximum overhead, and minimum bandwidth allocation.

Polycyclic aromatic hydrocarbons (PAH) have been identified as a serious environmental problem. In past research it has been proven that naphthalene, the simplest PAH, could be biodegraded using roller bioreactors and Pseudomonas putida. In this previous work it became apparent that the mass transfer rate of the hydrophobic naphthalene was the rate limiting factor in biodegradation, as the bacteria could degrade the naphthalene as fast as it entered solution. The challenge for the present research was to find a simple, inexpensive method for increasing the mass transfer rates within the framework of the previously successful reactor. <p>After some deliberation, the addition of inert particles (glass beads) was determined to be the preferred option to increase mass transfer. The inert particles visibly increased the turbulence in the reactor and significant increases in both mass transfer and bioremediation rates were achieved. The augmentation of mass transfer rates was found to be dependent on the type, size and relative loading of the particles. Two types of inert particles were investigated to increase mass transfer rates, spherical glass beads and Raschig rings. Glass beads were found to be far superior to Raschig rings for the intended purpose. Three sizes of spherical glass beads were then compared experimentally (1, 3, and 5mm). It was discovered that the 3mm beads were vastly superior to 1mm beads and 5 mm beads were slightly superior to 3mm beads. Different bead loadings (volume of particles / total working volume) were then explored with 10%, 25% and 50% bead loading investigated. Although slight increases in mass transfer were observed at higher bead loadings, the reduction in working volume for biodegradation meant that 50% was accepted as the optimum loading parameter. <p>The optimum conditions for maximum mass transfer occurred using 5 mm spherical glass beads at 50% loading. The increase in mass transfer and biodegradation rates compared to a traditional roller bioreactor were found to be 10 fold and 11 fold, respectively. The optimum mass transfer conditions were then applied to 2-methylnaphthalene with increases in mass transfer and biodegradation equal to 6 fold and 8 fold, respectively. The candidate bacteria used in this study was found incapable of degrading 1,5 dimethylnaphthalene although the mass transfer results demonstrate promise for the developed technology. To determine the effects of scale on the process, two larger reactors were finally studied. They were eight times and twenty-one times the size of the initial bioreactor. The process was shown to speed up at larger scale which shows great promise for future applications. The maximum degradation rate achieved in the larger reactor was 148 mgL-1h-1. This compares very well with the best result found in literature, 119 mgL-1h-1, which was achieved in a much more complex system. Clearly, the bead mill bioreactor designed during the present work is a simple concept that shows superior performance for the bioremediation of PAHs.

<p>An immunological mechanism to account for the regulation of peripheral self-reactive T cells, which escape central tolerance in the thymus, during the primary activation of naïve, foreign antigen-specific T cells remains to be established. Contemporary models of primary T cell activation that attempt to describe how this occurs differ significantly in the cellular interactions necessary for naïve CD4+ T helper cell activation. It is generally accepted that most CD8+ T cells are dependent upon CD4+ T helper cells for their activation. </p><p>The Infectious Non-Self and Danger Models of CD4+ T cell activation propose that interaction of a naïve T cell with an appropriately armed dendritic cell is sufficient, whereas the Two-step, Two-signal Model proposes additional cellular interactions are necessary. The major goal of this thesis was to establish and utilize an in vitro experimental system that would allow one to begin to delineate which model most validly describes the cellular interactions required for generation of primary immune responses from naïve T cells. Employing a population of naïve T cells uncontaminated with any partially or fully activated cells is essential for such a study.</p><p>The results presented in this thesis show, that when thymocytes are employed as a source of responding naïve T cells, cellular interactions, in addition to interaction with bone marrow derived dendritic cells, are required for the activation of naïve thymic T cells. The primary activation of thymic T cells to generate CD4+ IL-2 producing cells, and CD8+ IFN-g producing cells and cytotoxic T cells upon stimulation with splenic allogeneic stimulator cells is critically dependent upon the presence of a syngeneic population of radiation resistant, CD4+ T cells found in the spleen of normal mice. Additionally, when such cells are present as a source of help for thymocytes, allogeneic bone marrow derived dendritic cells fail to stimulate the generation of optimal cytotoxic and cytokine responses from naïve thymic T cells. However, they do stimulate thymocytes to cycle and up regulate the ligand for the costimulatory molecule CD40, CD40L.</p><p>The results presented within also show that the optimal activation of naïve thymic T cells to generate CD4+ IL-2 producing cells, and CD8+ IFN-g producing cells and cytotoxic T cells, requires the presence of allo-MHC bearing Ig+ B220+ B cells. The removal of B220+ cells by magnetic cell sorting from the allogeneic spleen reveals that the generation of CD8+ cytotoxic T cells and IFN-g producing cells from thymocytes is markedly reduced compared to unsorted allogeneic spleen cells. However, IL-2 and IL-4 cytokine producing cells are still detectable. Potential reasons for the generation of the latter cytokine producing cells are discussed. The results presented in this thesis have revealed insights into the cellular interactions involved in the activation of naïve thymic T cells.

Nurturing talent inside organizations through the use of Emotional Intelligence could strength businesses competitive advantage. The use of Emotional Intelligence as a tool to create closer liaisons among staff members could provide the connection that employers need to breed their employees, particularly, their B players. Our objective is to study the processes that are built between top managers and B players within the virtual space inside organizations and the viability to elevate their performance through the use of Emotional Intelligence when creating work relationships among them. The study was performed by a cluster of interviews to top managers, practitioners and researchers involved with our object of study and by a series of surveys completed by employees. The main results were connected to verbal language and multicommunicative activities as management of meaning from a leader, intercultural differences, general prevention towards work relationship building, influence from physical space of offices, personal space and personal satisfaction, post modernity in the leadership style, advantages of using Emotional Intelligence, positive effects that interrelations have over businesses general activities and the viability to reinforce business competitive advantage by empowering their human resources. After the termination of this study, we could conclude that communication channels, culture context and local values and beliefs are the main aspects that influence and limit the creation of processes among our both actors and their subsequent success. Furthermore, to create work relationship inside organizations indirectly build the defensive strategy that firms need against competitors and this reinforces their business competitive advantage.

Since our current economic environment is getting more and more competitive, enterprises must continuously improve and strengthen their ability in order to maintain their competitiveness. Therefore, investment activities of firms are the key elements to drive business growth. This article tries to discuss whether three different investment dimensions can help to boost firm¡¦s future growth of profitability. This research uses investment spending of listed firms in domestic electronics industry (including capital expenditure, intangible assets and R&D expenditures) as variable to explore the effects of these three investment expenditures on corporate P/B ratio as well as ROA (Return on Asset). This study attempts to analyze whether firm¡¦s investment activities can impose significantly positive influence on its future profitability. We use panel data to run regression analysis and further divide Taiwan electronics industry into five sectors to analyze the effects of firm¡¦s investment expenditure on P/B and future profitability among different sectors. The empirical results show that investment spending imposes significantly positive effect on firm¡¦s profits, but this relationship exist time lags.