This thesis focuses on applying one of the rapidly growing non-deterministic optimization algorithms, the ant colony algorithm, for simulating automatic hose/pipe routing with several conflicting objectives. Within the thesis, methods have been developed and applied to single objective hose routing, multi-objective hose routing and multi-hose routing. The use of simulation and optimization in engineering design has been widely applied in all fields of engineering as the computational capabilities of computers has increased and improved. As a result of this, the application of non-deterministic optimization techniques such as genetic algorithms, simulated annealing algorithms, ant colony algorithms, etc. has increased dramatically resulting in vast improvements in the design process. Initially, two versions of ant colony algorithms have been developed based on, respectively, a random network and a grid network for a single objective (minimizing the length of the hoses) and avoiding obstacles in the CAD model. While applying ant colony algorithms for the simulation of hose routing, two modifications have been proposed for reducing the size of the search space and avoiding the stagnation problem. Hose routing problems often consist of several conflicting or trade-off objectives. In classical approaches, in many cases, multiple objectives are aggregated into one single objective function and optimization is then treated as a single-objective optimization problem. In this thesis two versions of ant colony algorithms are presented for multihose routing with two conflicting objectives: minimizing the total length of the hoses and maximizing the total shared length (bundle length). In this case the two objectives are aggregated into a single objective. The current state-of-the-art approach for handling multi-objective design problems is to employ the concept of Pareto optimality. Within this thesis a new Pareto-based general purpose ant colony algorithm (PSACO) is proposed and applied to a multi-objective hose routing problem that consists of the following objectives: total length of the hoses between the start and the end locations, number of bends, and angles of bends. The proposed method is capable of handling any number of objectives and uses a single pheromone matrix for all the objectives. The domination concept is used for updating the pheromone matrix. Among the currently available multi-objective ant colony optimization (MOACO) algorithms, P-ACO generates very good solutions in the central part of the Pareto front and hence the proposed algorithm is compared with P-ACO. A new term is added to the random proportional rule of both of the algorithms (PSACO and P-ACO) to attract ants towards edges that make angles close to the pre-specified angles of bends. A refinement algorithm is also suggested for searching an acceptable solution after the completion of searching the entire search space. For all of the simulations, the STL format (tessellated format) for the obstacles is used in the algorithm instead of the original shapes of the obstacles. This STL format is passed to the C++ library RAPID for collision detection. As a result of using this format, the algorithms can handle freeform obstacles and the algorithms are not restricted to a particular software package.

This master thesis deals with image processing of Petri dishes. The first part is about terms and procedures in laboratory practice. The following part is about devices and algorithms for image analysis of Petri dishes. The second part is about draft and implementation of own colony counting application, which was developed in cooperation with the microbiological laboratory. The application is developed for mobile devices running Android OS. The master thesis also includes the design and creation of two lighting units, which uses as an accessory for better results in the analysis of Petri dishes. In conclusion are presented results, compared lighting units and various types of mobile devices, on which the application was tested.

This diploma thesis deals with ant colony optimization for shortest path problems. In the theoretical part it describes Ant Colony Optimization. In the practical part ant colony optimization algorithms are selected for the design and implementation of shortest path problems in the Java.

This work deals with the issue of swarm intelligence as a subdiscipline of artificial intelligence. It describes biological background of the dilemma briefly and presents the principles of searching paths in ant colonies as well. There is also adduced combinatorial optimization and two selected tasks are defined in detail: Travelling Salesman Problem and Quadratic Assignment Problem. The main part of this work consists of description of swarm intelligence methods for solving mentioned problems and evaluation of experiments that were made on these methods. There were tested Ant System, Ant Colony System, Hybrid Ant System and Max-Min Ant System algorithm. Within the work there were also designed and tested my own method Genetic Ant System which enriches the basic Ant System i.a. with development of unit parameters based on genetical principles. The results of described methods were compared together with the ones of classical artificial intelligence within the frame of both solved problems.

G-CSF besitzt direkte Effekte auf die Aktivierung bakterizider Eigenschaften neutrophiler Granulozyten und verbessert das Überleben bakteriell infizierter Tiere. Daher wurde in der hier vorliegenden Arbeit der Effekt einer prophylaktischen oder therapeutischen Gabe von G-CSF bei experimenteller Pneumonie durch Klebsiella pneumoniae in Mäusen untersucht. Unerwarteterweise verschlechterte aber eine prophylaktische G-CSF-Gabe das Überleben und führte dosisabhängig zu einer Steigerung der bakteriellen Dissemination von der Lunge in Leber und Milz. Im Gegensatz dazu konnte ein spezifisch gegen K2-Kapselpolysaccharid (K2-KPS) von K. pneumoniae gerichteter monoklonaler Antikörper signifikant die Vermehrung der Bakterien in Lunge, Leber und Milz reduzieren. Die Blockierung von TNF?? durch Pentoxifyllin hingegen verzögerte die Letalität nach Induktion der Pneumonie, verhinderte sie jedoch nicht. In vitro konnte hier nachgewiesen werden, daß G-CSF spezifisch an K. pneumoniae bindet und daß diese Bindung an mehrere Proteine mit einem Molekulargewicht von 41, 25 und 21 kDa erfolgt. Die Bindung von G-CSF an K. pneumoniae führte zu einer signifikant erhöhten Produktion des wichtigsten Virulenzfaktors, K2-KPS. Dies verminderte in vitro signifikant eine Phagozytose der Bakterien durch neutrophile Granulozyten. Damit gelang es zum ersten Mal, die Bindung von G-CSF an ein gram-negatives Bakterium, K. pneumoniae, nachzuweisen und zu zeigen, daß diese Bindung in vitro zu einer erhöhten Produktion des wichtigsten Virulenzfaktors und in vivo zur Verschlechterung einer experimentellen Pneumonie durch erhöhte bakterielle Disseminierung bei prophylaktischer Gabe von G-CSF vor Infektion führt. Die weitere Untersuchung dieser Phänomene hinsichtlich einer möglichen Bindung von G-CSF auch an andere Bakterien könnte zu einer differenzierten supportiven Therapie bakterieller Infektionen mit G-CSF in nicht neutropenischen Patienten führen. / Besides its well-established effects on granulocytopoiesis, granulocyte colony-stimulating factor (G-CSF) has been shown to have direct effects on the recruitment and bactericidal ability of neutrophils, resulting in improved survival of experimentally infected animals. The effect of G-CSF on the course of experimental pneumonia induced by Klebsiella pneumoniae was studied. Using a highly reproducible murine model, the paradoxical finding that mortality from infection was significantly increased when animals received G-CSF before induction of pneumonia could be demonstrated. Administration of G-CSF promoted replication of bacteria in the liver and spleen, thus indicating an impairment rather than an enhancement of antibacterial mechanisms. By contrast, a monoclonal antibody against Klebsiella K2 capsule significantly reduced bacterial multiplication in the lung, liver, and spleen, and abrogated the increased mortality caused by G-CSF. Blocking of TNF-? with pentoxifylline, however, could not prevent increased mortality caused by G-CSF. In vitro studies showed a direct effect of G-CSF on K pneumoniae resulting in inreased capsular polysaccharide (CPS) production. When bacteria were coincubated with therapeutically achievable concentrations of G-CSF, phagocytic uptake and killing by neutrophils was impaired. Western blot analysis showed three binding sites of G-CSF to K pneumoniae. Thus, in this model, the direct effect of G-CSF on a bacterial virulence factor, CPS production, outweighed any beneficial effect of G-CSF on recruitment and stimulation of leukocytes. Further investigations of possible binding of G-CSF to other bacteria might influence a differentiated supportive therapy of bacterial infections in non-neutropenic patients with this growth factor.

Les cellules Natural Killer (NK) sont capables de lyser les cellules tumorales sans la nécessité de reconnaitre un antigène tumoral spécifique. Cette propriété leur confère un avantage par rapport aux lymphocytes T et les rend intéressantes à utiliser en tant que cellules effectrices pour l’immunothérapie adoptive. A ce jour, le potentiel thérapeutique des cellules NK n’a pas été complétement exploré notamment dans le contexte du traitement de la rechute post-allogreffe de cellules souches hématopoïétiques. Actuellement, les patients en rechute post-greffe sont traités avec des injections de lymphocytes du donneur (DLI) parfois issues de petites fractions du greffon de cellules souches hématopoïétiques congelées. Les cellules souches périphériques étant fréquemment utilisées comme source de cellules souches et parfois utilisées comme DLI, nous avons souhaité évaluer l’impact du G-CSF sur le phénotype et les fonctions des cellules NK présentes dans ces fractions. Dans cet objectif, nous avons comparé différentes sources de cellules NK isolées à partir de sang de donneurs sains, de sang mobilisé de donneurs sains ou de patients et observé l’évolution des différentes sous-populations de cellules NK issues de ces prélèvements au décours d’une expansion en présence d’IL-15. Nos résultats ont montré que l’administration de G-CSF diminuait la proportion de cellules NK CD56brightCD16+ au profit d’une population CD16-, diminuait la prolifération des cellules NK lors de l’expansion en culture, et modifiait les propriétés fonctionnelles des cellules NK. / The ability of natural killer (NK) cells to kill tumor cells without the need to recognize a tumor-specific antigen provides advantages over T cells and makes them appealing for a use as effectors for adoptive immunotherapy. However, the full therapeutic potential of NK cell-based immunotherapy has not been fully investigated in the context of leukemic relapse after hematopoietic stem cell transplantation. Today, patients relapsing after hematopoietic stem cell transplantation are often treated with donor lymphocyte infusion (DLI) based on small cell fractions frozen at the time of the stem cell transplantation. Since peripheral blood stem cells are increasingly used as stem cell source and as source of cells for DLI, we aimed to evaluate the impact of G-SCF mobilization on NK cell phenotype and functions. Therefore, we compared the expansion capacity, the phenotype and the function of NK cells from blood for healthy donors, from allogeneic HSCT healthy donors or from autologous HSCT from patients. We also determine the impact of G-CSF on NK cell subset repartition before and after expansion in presence of IL-15. Our results showed that G-CSF administration to patients decreases CD56brightCD16+ NK cell population, proliferation and function. Overcoming this impairment in lymphoid capacity may be important to facilitate post-transplant immunotherapy.

L'amélioration des systèmes énergétiques est considérée comme un levier technologique pour répondre aux défis liés à la croissance de la demande d’électricité et des émissions des gaz à effet de serre. Les futures centrales devraient présenter une intégration thermique plus flexible et des sources de chaleur mixtes possibles. Une des solutions fiables consiste à utiliser un cycle de Brayton au CO2 supercritique (CO2-SC), un tel cycle à haut rendement est théoriquement prometteur pour les applications nucléaires, fossiles et solaires thermiques. Un des principaux obstacles au déploiement du cycle de Brayton au CO2-SC est de justifier sa faisabilité, sa viabilité et son potentiel à l’échelle industrielle. Dans ce contexte deux axes de recherche ont été identifiées : • Une sélection rigoureuse de l’équation d’état qui permet de représenter les propriétés d’intérêt du CO2-SC. • Une nouvelle méthodologie pour l’optimisation des centrales électriques, permettant de sélectionner automatiquement le procédé optimal parmi une grande quantité de configurations possibles (dénomme superstructure). Les résultats de la première partie de cette thèse mettent en lumière que l’équation de SW est pertinente pour limiter l’impact de l’imprécision de l’équation d’état sur le dimensionnement du procédé. Dans cette thèse, un simulateur de procédé commercial, ProSimPlus a été combiné avec un solveur type évolutionnaire (MIDACO) afin d’effectuer des optimisations superstructure. Premièrement, le critère d’optimisation est de maximiser le rendement énergétique du procédé. Dans un deuxième temps, on cherche simultanément à minimiser les coûts du procédé. Pour ce faire, des fonctions de coût internes à EDF ont été utilisées afin de permettre l’estimation des coûts d'investissement (CAPEX), des dépenses opérationnelles (OPEX) et du coût actualisé de l'électricité (LCOE) / Efficiency enhancement in power plant can be seen as a key lever in front of increasing energy demand. Nowadays, both the attention and the emphasis are directed to reliable alternatives, i.e., enhancing the energy conversion systems. The supercritical CO2 (SC-CO2) Brayton cycle has recently emerged as a promising solution for high efficiency power production in nuclear, fossil-thermal and solar-thermal applications. Currently, studies on such a thermodynamic power cycle are directed towards the demonstration of its reliability and viability before the possible building of an industrial-scale unit. The objectives of this PhD can be divided in two main parts: • A rigorous selection procedure of an equation of state (EoS) for SC-CO2 which permits to assess influences of thermodynamic model on the performance and design of a SC-CO2 Brayton cycle. • A framework of optimization-based synthesis of energy systems which enables optimizing both system structure and the process parameters. The performed investigations demonstrate that the Span-Wagner EoS is recommended for evaluating the performances of a SC-CO2 Brayton cycle in order to avoid inaccurate predictions in terms of equipment sizing and optimization. By combining a commercial process simulator and an evolutionary algorithm (MIDACO), this dissertation has identified a global feasible optimum design –or at least competitive solutions– for a given process superstructure under different industrial constraints. The carried out optimization firstly base on cycle energy aspects, but the decision making for practical systems necessitates techno-economic optimizations. The establishment of associated techno-economic cost functions in the last part of this dissertation enables to assess the levelized cost of electricity (LCOE). The carried out multi-objective optimization reflects the trade-off between economic and energy criteria, but also reveal the potential of this technology in economic performance.

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-05-10T13:34:32Z No. of bitstreams: 1 julianadeoliveiraaugustin.pdf: 846987 bytes, checksum: 44fe5d4102c2a79c3b44fe3eb961bdd5 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-17T15:06:32Z (GMT) No. of bitstreams: 1 julianadeoliveiraaugustin.pdf: 846987 bytes, checksum: 44fe5d4102c2a79c3b44fe3eb961bdd5 (MD5) / Made available in DSpace on 2017-05-17T15:06:32Z (GMT). No. of bitstreams: 1 julianadeoliveiraaugustin.pdf: 846987 bytes, checksum: 44fe5d4102c2a79c3b44fe3eb961bdd5 (MD5) Previous issue date: 2007-02-22 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Conhecer a biologia e o comportamento de rainhas fundadoras em processo de estabelecimento de novas colônias pode ser útil para se compreender as adaptações evolutivas pelas quais passaram muitos insetos sociais. O presente estudo teve o objetivo de investigar a influência da perda de massa corporal de rainhas de A. sexdens na mortalidade, assim como na produção de ovos, larvas, pupas e operárias, nos períodos de fundação e de crescimento ergonômico, buscando descrever os atos comportamentais executados pelas rainhas mantidas em colônias artificiais. A aferição da massa corporal das rainhas e a contagem de ovos, larvas, pupas e operárias foram realizadas semanalmente, mantendo as condições laboratoriais em 25 ± 5°C, 70 a 80 % de umidade relativa e fotoperíodo de 12 horas. Ao final de 168 dias de observações, a mortalidade havia atingido 95,7% das jovens rainhas, principalmente na fase de préoviposição (58,3% de mortalidade). Em média, as rainhas recém-fecundadas e dealadas pesavam 0,7 ± 0,05g após o vôo nupcial, perdendo, em média, 22,5% de massa corporal durante as 11 semanas do período de fundação, e 44,7% nas 11 semanas seguintes, durante o período ergonômico. Quanto à duração das fases de desnvolvimento colonial, verificou-se que as fases de pré-oviposição, embrionária, larval e pupal duraram, respectivamente, 3, 26, 23 e 21 dias. As freqüências médias de ovos reprodutivos, larvas e pupas nos períodos de fundação e ergonômico foram significativamente diferentes entre si. Foram identificados 49 atos comportamentais, os quais puderam ser agrupados em sete categorias, conforme a função biológica aparentemente dedutível. As rainhas recém-fecundadas mostraram-se comparativamente mais ativas durante o período de fundação, em relação ao período ergonômico. Os comportamentos mais freqüentes registrados para rainhas de A. sexdens neste estudo foram aqueles relacionados com a auto limpeza. Este resultado é um forte indício de que a auto-limpeza possivelmente desempenha a função de prevenir a contaminação colonial por parasitas, podendo ter sido de extrema importância no estabelecimento da relação mutualística obrigatória formiga-fungo. Os dados obtidos com a conclusão deste estudo poderão ser utilizados em futuros estudos comparativos entre espécies, auxiliando eventualmente na compreensão de seus processos evolutivos. / Knowing both biology and behavior of newly-mated founding ant queens may be extremely useful for understanding the evolutionary adaptations experienced by many social insect societies. The aim of the present study was to investigate the influence of weight loss of A. sexdens founding queens on the mortality and on the production of eggs, larvae, pupae and workers, during both the founding and ergonomic periods, as well as to describe the behavior repertoire performed by the queens. Individual queen weight and number of eggs, larvae, pupae and workers per colony were taken weekly. Laboratory conditions were kept in 25 ± 5°C, 70 to 80 % of relative umidity and 12 hour fotoperiod. By the end of 168 days, mortality had reached 95,7% of the young queens, mainly in the pre-incubation phase (58,3% of mortality). On average, newly-mated queens weighed 0,7 ± 0,05g after the nuptial flight, losing, on average, 22,5% of weight during the founding period, and 44,7% in the ergonomic period. On average, the pre-incubation, incubation, larval and pupal phases lasted, respectively, 3, 26, 23 and 21 days. The relative frequencies of reproductive eggs, larvae and pupae in the founding period were significantly different from the ergonomic period. Forty-nine behavioral acts were identified and they could be distributed into seven categories, according to their seemingly deducible biological function. The newly-mated queens were found to be comparatively more active during the founding period, in relation to the ergonomic period. Contrary to what one could expect for Attini queens with claustral foundation, the most frequent behaviors registered for A. sexdens queens in this study were those related not to the care with the offspring or to the simbiont fungus, but rather to the self-grooming. This result is a strong indication that self-grooming may function as preventing colony contamination by potential parasites, having been possibly played an important role in the establishment of the obligatory ant-fungus mutualism. Data obtained from the conclusion of this study can be used in comparative studies among ant species, eventually helping in the understanding of their evolutionary processes.

Le genre Staphylococcus, première étiologie des infections ostéo-articulaires (IOA), est associé à des formes particulièrement difficiles à traiter. Trois mécanismes phénotypiques ont été rattachés à ce fort taux de chronicité et de rechutes, permettant l'adaptation bactérienne à la vie au sein du tissu osseux et un échappement au système immunitaire de l'hôte et à l'action des antibiotiques : la formation de biofilm, la persistance des staphylocoques dans les ostéoblastes, et l'évolution vers le morphotype de small colony variant (SCV). Longtemps considéré comme simple commensal cutanéo-muqueux, S. epidermidis est désormais reconnu comme un agent étiologique majeur des IOA sur matériel. Or, si le portage est universel, l'infection est un phénomène rare. A ce jour, aucun facteur génotypique n'a pu être associé au pouvoir invasif de certaines souches de portage. Notre travail a permis de montrer l'absence de pouvoir discriminant des capacités d'internalisation des ostéoblastes et de formation de biofilm entre souches commensales et invasives. Par ailleurs, un très faible taux d'internalisation de S. epidermidis dans les ostéoblastes a été mis en évidence, suggérant une importance moindre de ce mécanisme dans la physiopathologie des IOA à S. epidermidis par rapport aux IOA à S. aureus. Les principales études ayant porté sur les capacités d'interaction de S. aureus avec les ostéoblastes et de formation de biofilm ont cherché à en explorer les mécanismes à partir de souches de laboratoire ou de souches représentatives de quelques clones de S. aureus résistants à la méticilline (SARM). Dans notre cas, nous avons souhaité étudier une large collection de souches cliniques de S. aureus (n=95) sensible à la méticilline (SASM) responsables d'IOA aiguës ou chroniques. La caractérisation des fonds génétiques de cette collection, puis en élargissant notre étude à des collections de différents villes françaises, a d'abord permis de décrire une forte prévalence du clone émergent de SASM CC398 dans les IOA en France / Pas de résumé en anglais

Les infections en biofilm, notamment de dispositifs médicaux, mettent fréquemment en échec les traitements antibiotiques, imposant le retrait du matériel. Pseudomonas aeruginosa s’est imposé comme le pathogène-type des infections en biofilm. Pour explorer les déterminants de l’échec du traitement antibiotique en biofilm, un modèle de biofilm in vitro à P. aeruginosa exposé à des doses supra-inhibitrices d’antibiotiques a été développé. En culture planctonique, une bithérapie deciprofloxacine et d’amikacine permettait de prévenir la sélection de mutants résistants pour des souches de P. aeruginosa de sensibilité diminuée à la ciprofloxacine ou à l’amikacine par surexpression d’efflux. En biofilm, l’association de la ciprofloxacine et de l’amikacine, administrées simultanément ou séquentiellement, n’était pas supérieure aux monothérapies, permettant une réduction bactérienne, mais pas d’éradication complète du biofilm. Quelles que soient les souches (sauvages ou exprimant un efflux) et l’antibiotique, l’échec microbiologique en biofilm était lié à la sélection de cellules persistantes, tolérantes aux antibiotiques. La ciprofloxacine induisait des modifications importantes de la structure du biofilm avec une réduction considérable des exopolysaccharides, composants majeurs de la matrice. L’étude transcriptomique de gènes potentiellement impliqués dans la persistance suggérait que l’activation précoce de la réponse stringente pourrait être une des voies principales de la tolérance en biofilm sous ciprofloxacine. Enfin, la présence de « small colony variants » au sein du biofilm, dotés d’une capacité accrue de formation de biofilm, témoignait de la diversité des populations en biofilm. Ces travaux participent ainsi à une meilleure compréhension des mécanismes d’échappement aux antibiotiques de P. aeruginosa en biofilm. / Biofilm device-related infections can lead to antibiotic failure requiring frequent removal of medical device. Pseudomonas aeruginosa has emerged as the typical pathogen for biofilm infections. To explore the determinants of antibiotic failure in biofilm, an in vitro P. aeruginosa biofilm model exposed to suprainhibitory antibiotic concentrations was developed. In planktonic culture, the ciprofloxacin and amikacin combination prevented the selection of resistant mutants in ciprofloxacin and amikacinlow-level resistant P. aeruginosa strains overexpressing efflux. In biofilm, the ciprofloxacin and amikacin combination, used simultaneously or sequentially, didn’t show superior effects compared to monotherapies. Despite an initial bacterial reduction, biofilm eradication was not obtained. Regardless of wild-type or efflux strains and antibiotic regimen used, antibiotic failure was related to the selection of antibiotic-tolerant cells named “persisters”. Ciprofloxacin induced significant alterations in the biofilm structure, notably a considerable reduction in the exopolysaccharides of the matrix. The transcriptomic analysis of genes, potentially involved in persistence, suggested that early activation of the stringent response might be one of the main pathways for ciprofloxacin tolerance in biofilm. Finally, the emergence of "small colony variants" within the biofilm, characterized by enhanced ability to form biofilm, attested to biofilm heterogeneity. This work therefore contributes to a better understanding of how P. aeruginosa biofilms escape antibiotic.