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Dans cette these, nous avons effectue l'analyse des spectres d'absorption a haute resolution de H2S, D2S, HDS et SO2 enregistres pour la premiere fois ou avec une meilleure precision experimentale que les spectres anterieurs. Nous avons developpe une methode originale de "global ftting" qui nous a permis l'analyse de 22 bandes vibrationnelles soit un total de 9700 transitions rovibrationnelles pour la molecule de D2S. Nous avons applique cette meme methode a des molecules de symmetrie Cs, en particulier tout le spectre rovibrationnel de la molecule HDS a ete analyse. La methode SPGF est appliquee aux molecules triatomiques H2S, D2S, HDS. Une procedure originale permettant l'identication des bandes tres peu intenses a ete mise au point pour la premiere fois et appliquee aux bandes chaudes de la molecule SO2. Le formalisme U(p+1) est adapte aux molecules triatomiques non lineaires de symmetrie C2v et les parametres d'un Hamiltonien vibrationnel sont determines dans le cas de la molecule D2S.

In this paper, we present a study of elliptic curves, focusing on theirunderlying mathematical concepts, properties and applications in numbertheory. We begin by introducing elliptic curves and their unique features,discussing their algebraic structure, and exploring their group law, pro-viding examples and geometric interpretations. The core of our studyfocuses on the Elliptic Curve Method (ECM) for integer factorization.We present the motivation behind ECM and compare it to Pollard’s (p-1) method. A discussion on pseudocurves and the choice of an ellipticcurve and bound B is provided. We also address the differences betweenECM and Pollard’s (p-1) method and propose optimization techniques forECM, including the calculation of the least common multiple (LCM) ofthe first B integers using the Sieve of Eratosthenes.

Denna uppsats fokuserar på Haparandas historiska identitet genom att analysera 14 av stadens offentliga skulpturer. Syftet är att presentera en representativ bild av de offentliga skulpturerna och att analysera dess historiska koppling till Haparanda stad. Berättelsen kontrasteras mot en urban syn av Haparandas arkitektur. Det första kapitlet tar upp frågan om makten och identitetsbildningen. Det andra kapitlet diskuterar skulpturernas roll i en viss miljö. I det avslutande tredje kapitlet diskuteras skulpturerna i relation till Haparanda stads historia.  Slutsatsen av min avhandling tyder på att skulpturerna är väl kopplade till Haparandas historia och dess nära relation till tvillingstaden Torneå (Finland). Det är en historia som har en nära koppling till Finlands historia. / This thesis focus on Haparanda's historical identity by analyzing 14 public sculptures in Haparanda. The aim is to present a representative picture of the public sculptures and to analyse its historical connection to Haparanda in realtion to a urban view of Haparanda's architecture. The first chapter adresses the question of power and identity formation. The second chapter discusses the role of sculptures in the collective view of a particular environment. In the concluding third chapter the sculptures are discussed in relation to the history of the city of Haparanda. The conclustion of my thesis suggests that the sculptures are well connected to the history of Haparanda and its close relation to the twin city of Torneå (Finland). It is a story closely connected to Finlands history.

Asthma is the leading chronic illness in children in the United States. Since children in the U.S. spend a majority of their time indoors there is an increased need to understand key sources of daily asthma triggers in the home. Bacterial endotoxin, dust mite allergens and β-D-glucan have been shown to be potent inducers of asthma attacks, and high levels of these allergens in homes can trigger attacks in those with asthma. We aim to better understand the risks to those with asthma that might be associated with evaporative cooler (EC) use in low-income homes. ECs are often promoted because of their low energy consumption and decreased environmental impact compared to central air conditioning (AC). Because of their lower cost, ECs are more widely used in low-income homes. ECs use evaporation to cool the air, which leads to higher indoor relative humidity. This may create an ecological niche for house dust mites in semi-arid climates where they are normally absent. EC sump water also provides an ideal environment for bacteria and fungi to grow, possibly resulting in EC loading the air with more potential asthma triggers than central air conditioning. We sampled low-income homes around Utah county with central air and evaporative cooling and tested them for the presence of dust mite allergens, β-D-glucan and endotoxin. There were significantly higher levels of endotoxins and β-(1→3)-D-glucans in the EC homes compared to the AC homes, with increased odds of dust mite allergen prevalence but not at clinically significant levels. These findings suggest that in semi-arid environments, endotoxin and β-(1→3)-D-glucan levels in homes with evaporative coolers are more elevated than dust mite allergens.

Made available in DSpace on 2014-07-29T16:02:18Z (GMT). No. of bitstreams: 1 Dissertacao_Lucimeire.pdf: 347668 bytes, checksum: 1994a286b451a5d4bd05254e9a5299d8 (MD5) Previous issue date: 2011-04-25 / Let P be a locally finite group of prime exponent p, admitting a finite soluble automorphism group G of order n coprime to p. In this work we study the influence of the centralizers of the automorphisms in G on the structure of P. In this sense we show that if CP(G), the subgroup of fixed points is soluble of derived length d, then P is nilpotent of class bounded in terms of p, n and d. It will be also shown that if a (p-1)-Engel Lie algebra L of characteristic p (or 0) admits a finite soluble automorphism group G of order n coprime to the characteristic of L, such that CL(G), the subalgebra of fixed points, is soluble of derived length d, then the Lie algebra L is nilpotent of class bounded in terms of p, n and d. / Seja P um grupo localmente finito de expoente primo p, admitindo um grupo G de automorfismos solúvel finito de ordem n coprima com p. Neste trabalho estudaremos a influência dos centralizadores dos automorfismos em G sobre a estrutura de P. Nesse sentido, mostraremos que se CP(G), o subgrupo de pontos fixos, é solúvel de comprimento derivado d, então P é nilpotente de classe limitada em termos de p;n e d. Será demonstrado também que se uma álgebra de Lie (p-1)-Engel L, de característica p (ou 0) admite um grupo de automorfismos G solúvel finito de ordem n coprima com a característica de L, tal que CL(G), a subálgebra de pontos fixos, é solúvel de comprimento derivado d, então a álgebra de Lie L é nilpotente de classe limitada em termos de p;n e d.

Les effets anti-allergiques des bactéries lactiques sont suggérés par plusieurs études épidémiologiques, des essais cliniques et des modèles expérimentaux d’allergie. Cependant, les propriétés immunomodulatrices des bactéries lactiques sont sous-exploitées par les stratégies vaccinales développées pour combattre l’allergie et les mécanismes empruntés par ces bactéries pour moduler l’allergie restent peu caractérisés. Dès lors, nous avons caractérisé les propriétés immunomodulatrices qu’exerce Lactobacillus plantarum NCIMB8826, une bactérie lactique modèle, sur la cellule dendritique étant donné le rôle déterminant de cette cellule sur la réponse allergique. Nous montrons que L. plantarum induit une forte sécrétion d’IL-12 p40, d’IL-12 p70, de TNF-a mais une faible production d’IL-10. Cette faculté à induire la sécrétion de cytokines polarisantes dépend de TLR2, de TLR9, de MyD88, de NF-kB, des MAPKs (en particulier JNK, p38 et ERK 1/2), de la composition de l’acide lipotéichoïque de L. plantarum et de CD14. Nous montrons aussi que l’ADN génomique de L. plantarum est un agoniste de TLR9 et que CD14 et CD36 facilitent la liaison de la cellule dendritique avec L. plantarum. Ensuite, nous avons évalué le potentiel vaccinal d’une coadministration L. plantarum + Der p 1 dans un modèle murin d’allergie à Der p 1. Cette formulation vaccinale prévient la production d’IgE Der p 1-spécifique et atténue l’éosinophilie pulmonaire tout en stimulant une forte production d’anticorps IgG2a Der p 1-spécifiques et d’IFN-g par les cellules spléniques. Ces effets bénéfiques nous ont conduit à élaborer une bactérie lactique recombinante dérivée de L. plantarum produisant Der p 1 pour la vaccination contre l’allergie aux acariens. La forme antigénique que nous avons réussi à faire produire par L. plantarum correspond à une protéine de fusion entre la Maltose Binding Protein de E. coli et ProDer p 1 (le zymogène de Der p 1), la présence de ce partenaire de fusion étant indispensable à la production de ProDer p 1. En prophylaxie, la vaccination par cette bactérie recombinante prévient la production d’anticorps IgE-Der p 1-spécifiques et stimule la production d’anticorps IgG2a spécifiques, reproduisant les effets de la coadministration L. plantarum + Der p 1. Elle réduit de manière drastique la production d’IL-5 des cellules spléniques et des cellules ganglionnaires médiastinales et prévient l’éosinophilie pulmonaire mais n’a pas d’effet sur l’hyperréactivité bronchique. Der p 1 étant un des allergènes d’acarien les plus immunodominants, cet ensemble de données montre donc que cette bactérie recombinante constitue un vaccin prophylactique prometteur pour la prévention de l’allergie aux acariens. Des résultats préliminaires obtenus à partir de cellules dendritiques humaines et lymphocytes T autologues montrent la forte capacité de cette bactérie recombinante à induire le développement d’une réponse Th1 fortement polarisée (production d’IFN-g en l’absence de production d’IL-4 et d’IL-5), ce qui suggère que l’utilisation de cette bactérie recombinante pourrait être envisagée pour le traitement de l’allergie chez l’homme.

The major allergen Der p 1 of the house dust mite Dermatophagoides pteronyssinus is a papain-like cysteine protease (CA1) associated to the development of allergic diseases such as asthma, rhinitis or atopic dermatitis. This allergen is expressed as an inactive precursor, called proDer p 1, formed by a 25 kDa catalytic domain downstream to an 10 kDa N-terminal propeptide, which blocks the active site cleft. The propeptide of Der p 1 exhibits a specific fold, which makes it unique in the CA1 propeptide family as it is characterised by the presence of four alpha helices and the absence of ERFNIN motif. In this study, we investigated the activation steps involved in the maturation of recombinant proDer p 1 expressed in Pichia pastoris under acidic conditions and we studied the influence of acidic pH on the structure of both propeptide and catalytic domain. Therefore, we characterized the interaction between the propeptide and mature Der p 1 at different pH values in terms of activity inhibition, structural stability and proteolytic susceptibility. According to our results, the auto-activation of proDer p 1 is a multistep mechanism, characterized by at least two intermediates (ATFE- and SNGG-) corresponding to the loss of the first and second propeptide alpha helices, respectively. The propeptide strongly inhibits unglycosylated and glycosylated recombinant Der p 1 (KD= 7 nM) at neutral pH. This inhibition is pH dependent, decreasing from pH 7 to pH 4 and can be related to structural changes of the propeptide initiated by the protonation of the aspartate residue of Lys17-Asp51-Tyr19 structural triad presents within the propeptide N-terminal domain. This protonation triggers conformational changes of the first propeptide alpha helix leading to an increase of the propeptide flexibility, an increase of its proteolytic sensitivity and the formation of a molten globule state. In addition, we compare mature protease, zymogen and propeptide pH unfolding and stability and highlights that the presence of the propeptide does not influence the catalytic domain pH unfolding and stability as the propeptide displays a weaker pH stability than the protease domain. These results confirmed that the propeptide unfolding is the key event of the activation process. Finally, we unravel the intermolecular contribution of mature Der p 1 in the activation process and highlights that activation of the precursor can be achieved, under acidic conditions, by intermolecular process but initial auto-activation most probably occurs through an intramolecular process or by the proteolysis by the catalytic domain of another zymogen in which the propeptide is unfolded. According to our results, we proposed that activation of the zymogen at pH 4 reflects a compromise between activity preservation and propeptide unfolding and that the location of the activation sites on the propeptide structure is a compromise between sequence recognition specificity and proteolytic susceptibility of the corresponding area.

Biologically active peptides are important for many physiological functions in the human body and therefore serve as interesting starting points in drug discovery processes. In this work the neuropeptide substance P 1–7 (SP1–7, H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), which has been demonstrated to reduce neuropathic pain and attenuate opioid withdrawal symptoms in animal models, has been addressed in a medicinal chemistry program with the overall aim of transforming this bioactive peptide into more drug-like compounds. Specific binding sites for this neuropeptide have been detected in the brain and the spinal cord. Interestingly, the smaller neuropeptide endomorphin-2 (EM-2, H-Tyr-Pro-Phe-Phe-NH2) also interacts with these binding sites, although 10-fold less efficient. In this work the structure–activity relationship of SP1–7 and EM-2, regarding their affinity to the SP1–7 binding site was elucidated using alanine scans, truncation, and terminal modifications. The C-terminal part of both peptides, and especially the C-terminal phenylalanine, was crucial for binding affinity. Moreover, the C-terminal functional group should preferably be a primary amide. The truncation studies finally resulted in the remarkable discovery of H-Phe-Phe-NH2 as an equally good binder as the heptapeptide SP1–7. This dipeptide amide served as a lead compound for further studies. In order to improve the drug-like properties and to find a plausible bioactive conformation, a set of rigidified and methylated dipeptides of different stereochemistry, and analogs with reduced peptide character, were synthesized and evaluated regarding binding, metabolic stability and absorption. Small SP1–7 analogs with retained affinity and substantially improved permeability and metabolic stability were identified. Beside peptide chemistry the synthetic work included the development of a fast and convenient microwave-assisted protocol for direct arylation of imidazoles. Furthermore, microwave-assisted aminocarbonylation using Mo(CO)6 as a solid carbon monoxide source was investigated in the synthesis of MAP amides and for coupling of imidazoles with amino acids. In a future perspective the present findings, together with the fact that some of the SP1–7 analogs discovered herein have been shown to reproduce the biological effects of SP1-7 in animal studies related to neuropathic pain and opioid dependence, can ultimately have an impact on drug discovery in these two areas.

This work deals with factorization, a decomposition of composite numbers on prime numbers and possibilities of its parallelization. It summarizes also the best known algorithms for factoring and most popular platforms for the implementation of these algorithms on the graphics card. The main part of the thesis deals with the design and implementation of hardware acceleration current fastest algorithm on the graphics card by using the OpenCL framework. Subsequently, the work provides a comparison of speeds accelerated algorithm implemented in this work with other versions of the best known algorithms for factoring, processed serially. In conclusion, the work discussed length of RSA key needed for safe operation without the possibility of breaking in real time interval.