Ce travail présente l’algorithme GARRLiC (Generalized Aerosol Retrieval from Radiometer and Lidar Combined data). Le but de cet algorithme est d’inverser simultanément les mesures co-localisées d’un LiDAR et d’un photomètre solaire. Cet algorithme original permet de déduire un ensemble très complet de paramètres descriptifs de l’aérosol atmosphérique, paramètres à la fois intégrés sur la colonne atmosphérique et résolus verticalement. GARRLiC est basée sur la recherche du meilleur ajustement de données multi-sources avec contraintes a priori. Il est basée sur la recherche de la meilleure solution selon un ensemble de critères statistiques. Les paramètres déduits sont de 2 types. Certains sont des quantités intégrées sur la colonne atmosphériques tandis que d’autres sont fonction de l’altitude comme la concentration en particules pour les deux modes dimensionnels fin et grossier. Une étude de sensibilité a montré que l’ensemble des paramètres peut être restitué avec une bonne précision dans toutes les situations considérées. L’étude indique une précision moins bonne pour le mode fin et qu’en général la précision est moindre à faible épaisseur optique. Elle a également montré que la précision sur l’indice de réfraction pouvait être accrue si l’on prenait en compte la mesure de polarisation issue du photomètre solaire. L’impact de la prise en compte de mesure LiDAR et de bruit sur les mesures a été étudié. GARRLiC a été appliqué à des mesures réelles obtenues à Minsk (Biélorussie) et Lille (France). L’approche employée ici peut être facilement modifiée pour retrouver les propriétés de l’aérosol à partir de multiples combinaisons d’instruments de télédétection passif et actif. / This thesis presents the GARRLiC algorithm (Generalized Aerosol Retrieval from Ra- diometer and Lidar Combined data) that simultaneously inverts co-incident lidar and sun-photometer observations and derives a united set of aerosol parameters that describe both columnar and vertical aerosol properties. GARRLiC searches for the best fit of the multi-source measurements together with a priori constraints on aerosol characteristics through the continuous space of all possi- ble solutions under statistically formulated criteria. It retrieves height independent size distribution, complex refractive index and fraction of spherical particles together with vertically resolved aerosol concentration, all differentiated between fine and coarse aerosol modes. The potential and limitations of the method are demonstrated by sensitivity tests. The tests showed that the complete set of aerosol parameters for each aerosol component can be robustly derived with acceptable accuracy in all considered situations. Limited sen- sitivity to the properties of the fine mode and dependence of retrieval accuracy on the aerosol optical thickness for both modes were found. It was shown that sensitivity to fine mode refractive index could be improved by accounting for polarization data provided by passive instruments. The effects of the presence of lidar data and random noise on aerosol retrievals were studied. The algorithm was also applied to the real lidar and radiometer observations obtained over Minsk (Belarus) and Lille (France) AERONET sites. Suggested approach could be easily modified to retrieve aerosol properties from all possible combinations of existing passive and active remote sensing instruments.

The clonality of a random sample of 102 invasive pneumococcal serotype 3 strains isolated from Gauteng Province during January 2000 to December 2003 was investigated. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) revealed a heterogeneous population with several PFGE clusters and sequence types (STs). The largest PFGE cluster comprised 36/102 (35%) isolates including seven that belonged to ST458, a clone that is not common in other parts of the world. The global clone (ST180) which is common in the United States and other countries was found in a cluster that represented only 14/102 (14%) of isolates examined. The first multidrug-resistant pneumococcal serotype 19A strain that was isolated in South Africa in 1977 was compared with invasive serotype 19A multidrug-resistant strains isolated in South Africa during June 1999 to December 2004. PFGE analysis of these isolates demonstrated clonal diversity among the isolates. MLST of 16 randomly selected isolates revealed several STs, none of which was the same ST as the 1977 clone. Both serotype 3 and 19A were not associated with increased mortality or HIV seropositivity compared to other serotypes.

Les composés organiques volatils (COV) jouent un rôle majeur au sein du système atmosphérique en tant que précurseurs d’ozone troposphérique et d’aérosols organiques (AO) secondaires. En région méditerranéenne, les concentrations en polluants particulaires et gazeux sont généralement plus élevées que dans la plupart des régions d’Europe continentale, en particulier en période estivale. Cependant, la pollution de l’air dans cette région reste difficile à caractériser en raison d’un manque de mesures atmosphériques. Cette thèse permet de mieux comprendre les sources et le devenir des COV en région méditerranéenne orientale. Lors de la campagne de mesure intensive de Mars 2015 réalisée sur un site de fond chypriote, des mesures en continu d’un grand nombre de COV ont permis d’évaluer leurs teneurs, de mieux comprendre leurs principales sources dans la région et de décrire leurs variabilités et leurs origines potentielles. Une analyse factorielle a montré que les sources biogéniques et la pollution de fond régionale étaient les plus importants contributeurs aux concentrations en COV observées sur ce site. Bénéficiant de mesures d’AO en continu, un parallèle entre la composition en aérosol organique et la phase gazeuse a été réalisé. Les interactions des COV biogéniques avec des composés anthropiques peuvent influencer la formation et la croissance de nouvelles particules, induisant un renforcement de la fraction d’AO secondaire. Finalement, des mesures en continu de COV primaires ont été effectuées de Janvier 2015 à Février 2016 afin de mieux caractériser la variation saisonnière des COV et de leurs sources affectant la région méditerranéenne orientale. / Volatile organic compounds (VOCs) play a key role within the atmospheric system acting as precursors of ozone and secondary organic aerosols (OA). In the Mediterranean region, particulate and gaseous concentrations are usually higher than in most continental European regions especially during summertime. However, air pollution in this region remains difficult to characterize because of a lack of atmospheric measurements. This thesis provides a better understanding of the sources and fate of VOCs in the Eastern Mediterranean region. During the intensive field campaign held in March 2015 at a background site of Cyprus, real-time measurements of a large number of VOCs have been performed, allowing the evaluation of their concentration levels in ambient air, improving the understanding of their major sources in the area, and describing their variabilities and their potential origins. A factorial analysis (PMF) showed that the local biogenic sources and the regional background were found to be the largest contributors to the VOC concentrations observed at this site. Benefiting from real-time OA measurements, a parallel between organic aerosol and gas phase composition was conducted. Biogenic VOC interactions with anthropogenic compounds can influence formation and growth of newly particles, inducing a reinforcement of secondary OA fraction. Finally, on-line measurements of primary VOCs were performed from January 2015 to February 2016 to provide a better characterization of the seasonal variation in VOCs and their sources impacting the Eastern Mediterranean region.

A modulação da forma e tamanho em órgãos vegetais depende do controle temporal e espacial de divisão e expansão celular. Entretanto, pouco se sabe a respeito dos mecanismos moleculares que regulam este processo durante o desenvolvimento floral. O estudo da via de sinalização de SCI1 (Stigma/style Cell Cycle Inhibitor 1) pode contribuir para o entendimento do processo de crescimento das flores. Este gene produz uma proteína, localizada no nucléolo, que está relacionada à inibição da proliferação celular no estigma e no estilete de Nicotiana tabacum, modulando o tamanho destes órgãos florais. Experimentos feitos para a identificação de parceiros de interação de SCI1 identificaram as proteínas 14-3-3A e 14-3-3D de N. tabacum como candidatas à interação. A família 14-3-3 é composta de proteínas altamente conservadas, que formam dímeros em sua conformação nativa e são responsáveis pela modulação da atividade das mais variadas proteínas em resposta a sinais intracelulares. Por isso, estas proteínas estão associadas à regulação de uma série de processos, incluindo o metabolismo, transcrição, ciclo celular, entre outros. Neste contexto, o presente trabalho teve como objetivo estudar as proteínas 14-3-3A e 14-3-3D de N. tabacum e o seu papel durante o desenvolvimento floral. Os resultados aqui obtidos revelaram que a 14-3-3A possui localização citoplasmática e nuclear, enquanto a 14-3-3D se distribui apenas no citoplasma. Também foi evidenciado que estas proteínas são capazes de formar homodímeros e heterodímeros entre si. Os homodímeros de 14-3-3A estão distribuídos no citoplasma e no núcleo, enquanto os homodímeros de 14-3-3D e heterodímeros se encontram apenas no citoplasma. Adicionalmente, a interação in vivo entre a 14-3-3A e SCI1 foi confirmada por BiFC, apresentando localização nuclear, fora do nucléolo. Análises in silico da sequência de aminoácidos de SCI1 identificaram duas regiões putativas de reconhecimento por proteínas 14-3-3s. Estas regiões estão sendo analisadas funcionalmente por meio de ensaios de BiFC com sequências mutadas de SCI1. A análise deste conjunto de resultados, juntamente com outros resultados obtidos em nosso laboratório, sugere que apenas homodímeros de 14-3-3D e heterodímeros formados entre 14-3-3A e 14-3-3D sejam capazes de interagir com SCI1. Adicionalmente, a localização nuclear dessa interação difere daquelas observadas para SCI1 e para as 14-3-3s individualmente, sugerindo que as 14-3-3s migrem para o núcleo para interagir com SCI1. Nossa hipótese é de que as proteínas 14-3-3s possam modular a localização subnuclear de SCI1. Com o objetivo de levantar dados a respeito das possíveis funções desempenhadas pelas proteínas 14-3-3A e 14-3-3D de N. tabacum, foram identificados os grupos de possíveis ortólogos dessas proteínas em A. thaliana, O. sativa, S. lycopersicum, S. tuberosum e N. benthamiana. Esta análise mostrou que os ortólogos às 14-3-3A e D em Arabidopsis estão associados ao ciclo celular, o que sugere que as proteínas de tabaco possam ter conservado essa função. Além disso, também foram produzidas plantas transgênicas silenciadas para cada uma dessas 14-3-3s de maneira independente. A análise dos fenótipos das plantas transgênicas não levou à elaboração de uma hipótese definitiva sobre a função dessas 14-3-3s no desenvolvimento floral. No entanto, algumas plantas transgênicas apresentaram estruturas menores, especialmente as pétalas, sugerindo que estas proteínas podem estar envolvidas no controle do tamanho de órgãos vegetais. / The modulation of size and shape in plant organs depends on temporal and spatial control of cell division and expansion. However, the molecular mechanisms that regulate this process during floral development are poorly understood. The study of SCI1 (Stigma/style Cell Cycle Inhibitor 1) signaling pathway can contribute to the understanding of the flower growing process. This gene produces a protein which is located in the nucleolus and is related to the inhibition of cell proliferation in the Nicotiana tabacum stigma and style, modulating the size of these organs. Experiments performed to identify SCI1 interaction partners have identified the N. tabacum 14-3-3A and 14-3-3D proteins as interaction candidates. The 14-3-3 family is composed of highly conserved proteins, which form dimers in their native conformation and are responsible to modulate the activity of a large variety of proteins in response to intracellular signals. Therefore, these proteins are associated to the regulation of several processes, including metabolism, transcription, and cell cycle, among others. In this context, the present work aimed to study the N. tabacum 14-3-3A and 14-3-3D proteins and their role during flower development. The results here obtained revealed that 14-3-3A is located in the nucleus and the cytosol, while 14-3-3D protein is distributed only in the cytosol. It was also shown that these proteins can form homodimers and heterodimers with each other. Homodimers of 14-3-3A are distributed in nucleus and cytosol, while 14-3-3D homodimers and heterodimers are located only in the cytosol. Furthermore, the in vivo interaction between SCI1 and 14-3-3A was confirmed by BiFC, showing nuclear localization, outside the nucleolus. In silico analyzes of SCI1 amino acid sequence identified two putative regions of recognition by 14-3-3 proteins. These regions are being evaluated by BiFC assays with SCI1 mutated sequences. The analyses of this set of results, together with other results obtained in our laboratory, suggests that only 14-3-3D homodimers and heterodimers between 14-3-3A and 14-3-3D are capable to interact with SCI1. Moreover, the nuclear localization of this interaction differs from the ones observed for SCI1 and for the 14-3-3s individually, which suggests that the 14-3-3s migrate to the nucleus to interact with SCI1. Our hypothesis is that the 14-3-3 proteins can modulate the subnuclear localization of SCI1. To obtain data concerning the possible roles of the N. tabacum 14-3-3A and 14-3-3D proteins, groups of possible orthologous of these proteins in A. thaliana, O. sativa, S. lycopersicum, S. tuberosum and N. benthamiana were identified. This analysis has shown that the orthologs of 14-3-3A and D in Arabidopsis are associated to the cell cycle, suggesting that the tobacco proteins might have conserved this function. Furthermore, transgenic plants silenced for each of the 14-3-3s independently were also produced. Phenotype analyzes of transgenic plants did not lead to a definitive hypothesis about the function of these 14-3-3s during floral development. However, some transgenic plants exhibited smaller structures, specially petals, which suggests that these proteins may be involved in the size control of plant organs.

Phosphoinositide 3-kinases (PI3Ks) are a family of enzymes that catalyse the synthesis of different lipid second messengers, regulating a plethora of intracellular functions. Deregulation of their signalling pathway has different functional consequences, and it has been associated with a variety of human diseases. The existence of eight distinct isoforms, divided into three classes, has raised in the past many questions on whether and to which extent their role was redundant or overlapping. The study of their intracellular signalling pathways and cellular functions is crucial, because some of these isoforms have been identified as important therapeutic targets. The most investigated PI3Ks belong to the class I subfamily, and they have a well established role in the regulation of cell growth, survival and proliferation. In the past years, attention and research efforts focussed on class I isoforms and alteration of their signalling pathways, one of the most common causes of cancer. More recently, evidence indicated that the least investigated class II PI3Ks have different intracellular roles. This work focussed on the class II isoform PI3K-C2α, the study of its intracellular function(s) in pancreatic β cells and the implications of its inhibition through downregulation in pancreatic β cells homeostasis. It was reported that PI3K-C2α has a crucial role insulin granules exocytosis. This study has demonstrated that this enzyme synthesises the lipid product PtdIns3P specifically at the plasma membrane of pancreatic β cells upon depolarisation of the plasma membrane and stimulation of insulin secretion. Moreover, the data herein presented indicated for the first time that glucose-induced activation of PI3K-C2α is able to protect β cells from cell death induced by nutrients deprivation. Analysis of the intracellular pathways stimulated by glucose indicated that PI3K-C2α is able to modulate the activity of mTOR and its downstream effectors, key regulators of cell proliferation and growth. Importantly, the activation of mTOR pathway upon glucose does not seem to involve the activation of the upstream regulator Akt or class I PI3K, suggesting a novel intracellular pathway stimulated by glucose.

No description available.

Une organisation virtuelle (Virtual Organization, VO) est une organisation avec des éléments et des ressources organisationnelle non co-localisés et qui utilise l’espace virtuel pour les interactions entre ses personnels afin d’atteindre les objectifs organisationnels. L’objectif de cette étude est de développer un modèle d’excellence pour les organisations ainsi définies. A cette fin nous avons choisi comme point de départ le modèle de la «fondation européenne pour la gestion de la qualité » (European Foundation for Quality Management, EFQM) qui peut être considéré comme la plus récente expression du TQM, approche dominante de l’excellence. Pour créer un modèle complet, nous avons conçu tout d’abord un modèle conceptuel basé sur le même état d’esprit que l'EFQM. En seconde étape nous déterminons les facteurs, leurs poids et sous-critères. Nous avons développé le modèle d’Excellence pour l’Organisation Virtuelle en tant que feuille de route des VO pour l’excellence et en même temps pour être une aide aux entrepreneurs en vue de mesurer et améliorer la performance de leur entreprise. Ce modèle pourrait également être un outil pour les experts et analystes de cette nouvelle génération d'organisations. La dernière étape détermine les valeurs fondamentales et le cadre de mesure RADAR. / Purpose – Virtual Organization would be any organization with non-co-located organizational entities and resources, using virtual space for interactions between staff to achieve organizational objectives. The purpose of this thesis is to develop an Excellence model for Virtual Organizations. We chose “European foundation for productivity management model (EFQM)” as the latest expression of TQM which is the dominant approach of Excellence. To create a complete model we first designed a conceptual model in the same culture of EFQM. In the second step we determined factors, their weights and sub-criteria. We developed the Virtual Organization Excellence model as a roadmap for Virtual Organizations to move toward excellence and also being an aid for contractors in measuring and improving their business performance. This model also could be a tool for assessor to analyze this new generation of organizations. Last step was determining the fundamental values and RADAR measuring framework. Design/methodology – This study adopted a pluralist approach including, Extensive literature review, Field experiment, in depth interviews and Survey questionnaire to develop the Virtual Organization excellence model. Findings – The criteria and sub-criteria of the Virtual Organization excellence model were confirmed using empirical data, and the fundamental values and criterion weights were suggested. Value of study – As VOs are the future of firms, main benefit of the Virtual Organization excellence model (VOEM) is that it provides a productivity roadmap for a Virtual firms that developed and evaluated by Virtual Organization experts.

Nous analysons ici les déterminants du choix de la source d'énergie utilisée pour le chauffage et l'impact de ce choix sur la consommation énergétiques domestiques des ménages en France. Cette thèse est construite en cinq chapitres. Dans le premier, nous mettons en évidence le manque de données relatives à la consommation énergétique domestique et nous présentons un ensemble de statistiques décrivant les niveaux de consommation et de dépense énergétiques domestiques en France.Dans le second, nous décrivons l'utilisation des sources d'énergie pour le chauffage dans le parc résidentiel français et nous recourons à un modèle de choix discret pour déterminer les différents facteurs intervenant dans le choix des équipements de chauffage.Dans le troisième, nous analysons les déterminants de la demande énergétique pour le chauffage et de la dépense énergétique globale dans tous les logements français en estimant une série de modèles économétriques dérivés de Dubin et Mcfadden (1984) pour traiter le biais de sélection. Dans le quatrième, nous nous focalisons sur le secteur locatif afin de déterminer d'une part les singularités qui lui sont propres et de l'autre les particularités qui distinguent le secteur social du secteur libre, tant au niveau des déterminants des choix d'équipements de chauffage qu'au niveau de la consommation et de la dépense énergétiques.Enfin, le dernier chapitre est consacré à poser les bases d'un modèle théorique formalisant le comportement des agents concernés par la facturation collective des frais de chauffage. Notons qu'à ce jour, il n'existe aucun modèle dédié au traitement de cette problématique. / We analyze in this work the determinants of the energy source for heating choice and its impact on the households living in France energy consumption and expenses. This thesis is written in five chapters. In the first we show the lack of data relative to home's energy consumption and we present a set of descriptive statistics showing some features of the energy consumption and expenses in the French dwellings. In the second chapter we describe in details the utilization of energy for heating in the French residential park and we make use of a discrete choice model to determine the factors intervening in the choice of heating equipments.In the third chapter we analyze the determinants of the energy demand for heating and the overall energy expenses in all the French dwellings by estimating a series of econometric models inspired by Dubin and Mcfadden (1984) used to deal with the selection biais.In the fourth chapter we concentrate on the rental sector to determine its singularities on the one hand, and, on the other hand, to find out the features which distinguish the social sector from the private sector concerning the heating equipment choice and the energy consumption and expenses levels. And last but not least, the fifth chapter is dedicated to lay the foundations of a theoretical model formalizing the behavior of all the agents toward energy when the heating bill is collective. It is worth noting that so far, there isn't any model dealing with this question.

The design and development of fluorescent reporters focussed on highly sensitive, specific, and selective imaging of cancer targets is described. These novel optical molecular probes were synthesised with the aim of creating bio-imaging breakthroughs that will aid the clinical analysis of cancer. A specific target of the project was to develop fluorescent reporters for Caspases; intracellular endopeptidases that play an essential role in apoptosis. Lack of activation of the ‘Caspase Cascade’ causes uncontrolled proliferation of cells and has been deemed a ‘Hallmark of Cancer’. In particular, low Caspases-3/7 activities have been associated with a range of cancers, thus molecular detection of Caspases-3/7 activities could therefore lead to advances in oncology. A 14-member FRET library, based upon Caspases-3/7 specific peptide sequences, was initially developed. The cleavage rates and KM values were evaluated for Caspases-3/7, along with the cleavage rates for Cathepsin B, to determine the peptide with the greatest affinity and specificity for Caspase-3. Also developed was a set of internally quenched activity based molecular reporters constructed by attaching fluorophores to a tribranched dendron through the Caspase specific peptide, developed from the FRET Library. The KM values of the dendron probes with Caspase-3 were also evaluated. Furthermore, the dendron reporters were attached to cell penetrating peptides to enable delivery to intracellular Caspase and allow in situ detection of activated Caspase-3 within live cells. In addition, a new labelling moiety was developed enabling dual detection of reporters through fluorescence and MRI imaging. To achieve this, a perfluoro tag (C8F17) was tethered to a Cy5 dye to enable dual detection. The dual 19F-MRI/Cy5 dye was conjugated onto to a cell penetrating peptide to enable in vivo detection of the probe by 19F-MRI and fluorescent imaging.

"October 2003" Bibliography: leaves 190-210. Ch. 1. Literature review -- Ch. 2. A practical approach to increasing intakes of n-3 polyunsaturated fatty acids: use of novel foods enriched with n-3 fats -- Ch. 3. Effects of fatty acids on the incidence of arrhythmias in patients with implanted cardioverter-defibrillators (ICDs) -- Ch. 4. A pilot study to investigate the effects of n-3 fatty acids on inducible, sustained ventricular tachycardia in patients undergoing electrophysiology testing -- Ch. 5. Conclusions and future directions.