Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-05-08T11:13:33Z No. of bitstreams: 1 tatianepinheirolopesnovato.pdf: 844555 bytes, checksum: 0cc711e3cec4e9c6c2686d56ba3c8a39 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-17T13:39:47Z (GMT) No. of bitstreams: 1 tatianepinheirolopesnovato.pdf: 844555 bytes, checksum: 0cc711e3cec4e9c6c2686d56ba3c8a39 (MD5) / Made available in DSpace on 2017-05-17T13:39:47Z (GMT). No. of bitstreams: 1 tatianepinheirolopesnovato.pdf: 844555 bytes, checksum: 0cc711e3cec4e9c6c2686d56ba3c8a39 (MD5) Previous issue date: 2014-10-01 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O presente estudo objetivou avaliar o efeito da combinação entre timol, carvacrol e (E)-cinamaldeido sobre larvas de Amblyomma sculptum e Dermacentor nitens, bem como realizar o primeiro calculo da concentração letal de 50%(CL50) para as espécies alvo e propor adaptações para as categorias qualitativas definidas por Chou (2006) para avaliação de combinações dos compostos ativos. O teste foi realizado por meio da técnica de pacote de larvas modificado e a mortalidade foi avaliada após 24h. Para a determinação da Concentração Letal 50 (CL50) as substâncias foram testadas nas concentrações de 0,62; 1,25; 2,5; 3,75; 5,0 e 7,5 mg/ml, com exceção do teste com o timol sobres larvas de A. sculptum(0,62; 1,25; 2,5; 5,0; 7,5 e 10,0 mg/ml) e nas concentrações de 0,31; 0,62; 1,25; 2,5; 5,0 e 7,5 mg/ml sobre larvas de D. nitens. Após a determinação da CL50, cada substância foi avaliada separadamente e combinada com outra substância na proporção de 1:1 nas concentrações da CL50, 1/2 e 1/4 da CL50. Os grupos foram mantidos em câmara climatizada (27±1°C e UR >80±10%). Para A. sculptum, o menor valor de CL50 foi obtido para o (E)-cinamaldeído 1,40, seguido do timol 2,04 e carvacrol 3,49 mg/ml, sendo observado o mesmo para D. nitens, com valores de 1,68, 2,17 e 3,33 mg/ml, respectivamente. Na avaliação das associações entre as substâncias, para larvas de A. sculptum, apenas a combinação entre carvacrol e timol (CL50) e carvacrol e (E)-cinamaldeído (1/4) apresentaram efeito sinérgico moderado, as demais misturas demonstraram efeito aditivo ou antagônico. Já para larvas de D. nitens as combinações entre timol e carvacrol (1/2 e CL50) apresentaram efeito sinérgico e as demais combinações apresentaram efeito aditivo e antagônico. Conclui-se que as combinações de timol e carvacrol (CL50) têm sinergismo moderado para larvas A. sculptum e timol e carvacrol (1/2 e CL50) tem efeito sinérgico para D. nitens. / The objective of this study was to assess the paired combined effect of thymol, carvacrol and (E)-cinnamaldehyde on Amblyomma sculptum and Dermacentor nitens larvae, as well as to carry out the first calculation of the 50% lethal concentration (LC50) for the target species and propose adaptations to the qualitative categories defined by Chou (2006) for assessment of active compounds combinations. The effects of the treatments were evaluated by the modified larval packet test, to measure the mortality after 24 h. To determine the LC50, the substances were tested individually at concentrations of 0.62, 1.25, 2.5, 3.75, 5.0 and 7.5 mg/ml on A. sculptum larvae, except for the test with thymol (0.62, 1.25, 2.5, 5.0. 7.5 and 10.0 mg/ml). For D. nitens, the concentrations tested were 0.31, 0.62, 1.25, 2.5, 5.0 and 7.5 mg/ml for all substances. After determining the LC50, each substance was evaluated separately and in combination with another substance in a 1:1 proportion at the LC50 concentration and 1/2 and 1/4 of the LC50. The groups were kept in a climate-controlled chamber (27±1 °C and RH >80±10%). For A. sculptum, the lowest LC50 value was obtained for (E)-cinnamaldehyde (1.40), followed by thymol (2.04) and carvacrol (3.49 mg/ml). The same order of effectiveness was observed for D. nitens, with values of 1.68, 2.17 and 3.33 mg/ml, respectively. In the evaluation of the associations of substances against A. sculptum larvae, only the combinations between carvacrol and thymol (LC50) and carvacrol and (E)-cinnamaldehyde (1/4 LC50) presented synergetic effect. The other mixtures demonstrated additive or antagonistic effect. In turn, for D. nitens larvae the combinations between thymol and carvacrol (LC50 and 1/2 LC50) presented synergetic effect, while the others presented additive or antagonistic effect. Therefore, it can be concluded that combinations of thymol and carvacrol (LC50) have a moderate synergetic effect against A. sculptum larvae and thymol combined with carvacrol (LC50 and 1/2 LC50) has a synergetic effect against D. nitens larvae.

Orientador: Luís Geraldo Pedroso Meloni / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação / Made available in DSpace on 2018-08-19T09:59:52Z (GMT). No. of bitstreams: 1 Sousa_EriclesRodrigues_M.pdf: 2046025 bytes, checksum: 14fd32eefec8c8da68e3337d5e033567 (MD5) Previous issue date: 2011 / Resumo: Atualmente, aplicações multimídias exigem grande esforço computacional para manipular dados com elevadas taxas de precisão. Visando otimizar a capacidade de processamento sem elevar demasiadamente o custo do desenvolvimento em sistemas embarcados, este trabalho descreve a proposta de uma arquitetura computacional hibrida, para processamento digital de sinais, baseado-se no uso cooperativo entre DSP (Digital Signal Processor) e FPGA (Field Programmable Gate Array). Neste estudo e realizada uma abordagem sobre o uso de um coprocessador para a acelerar rotinas que demandam grande esforço computacional em um DSP. Também e proposto um modelo matemático capaz de mensurar a eficiência do particionamento de códigos processados de forma descentralizada. Para validação da proposta, foi construído um cenários de testes para a estimação de vetores movimento, um dos principais agentes envolvidos no processo de codificação de vídeo em alta definição. A partir do cenário elaborado foi possível constatar a eficiência da arquitetura proposta. Sendo que, considerando um código de referencia otimizado e baseado na descrição feita em [30], obteve-se mais de 97% de eficiência computacional. Assim, este estudo permite concluir que o uso cooperativo entre DSP e FPGA se mostra muito vantajoso devido a possibilidade de unir em um único sistema as vantagens fornecidas por ambos dispositivos, caracterizando um ambiente de total sinergia e de elevada capacidade de computacional / Abstract: Nowadays, multimedia applications require high computational effort to manipulate data with high precision. In order to optimize the processing power without significantly increasing the cost of development in embedded systems, this work describes the proposal for a hybrid computing architecture applied to digital signal processing, based on the cooperative work between DSP (Digital Signal Processor) and FPGA (Field Programmable Gate Array). An approach about the use of coprocessor able to accelerate a process which requires great computational effort of a DSP is provided by this study. It is also describes a mathematical model able to measure the efficiency of a partitioning code processed in a distributed system. To validate our proposal we developed a tested for calculate the motion estimation vector, which is one of key elements involved on high definition video coding. From the elaborated tested, we could found a high efficiency provided by the architecture proposed. Therefore, considering a optimized reference code based on [30], was possible achieve a computing efficiency around 97%. This study show that cooperative work between DSP and FPGA that provides a very advantageous scenario applied to embedded systems, due to joining the features of both devices, building then, a synergy environment of high computing performance / Mestrado / Telecomunicações e Telemática / Mestre em Engenharia Elétrica

The main purpose of this thesis is to investigate potential synergies between an electronic waybill (e-Waybill) and other Intelligent Transport System (ITS) services. An e-Waybill service, as presented in this thesis, should be able to perform the functions of a paper waybill (which is an important transport document and contains essential information about a consignment) and it should contain at least the information specified in a paper waybill. To investigate synergies between the e-Waybill solutions and ITS services, we present 5 conceptual e-Waybill solutions that differ in where the e-Waybill information is stored, read, and written. These solutions are further investigated for functional and technical requirements (non-functional requirements), which can potentially impose constraints on a potential system that should implement the e-Waybill service. A set of 20 ITS services are considered for synergy analysis in this thesis. These services are mainly for road transport, however most of them are relevant to be considered for utilization in other modes of transport as well. For information synergy analysis, the e-Waybill solutions are assessed based on their synergies with ITS services. For different ITS services, the required input information entities are identified; and if at least one information entity can be provided by an e-Waybill at the right location we regard it to be a synergy. The result from our synergy analysis may support the choice of practical e-Waybill systems, which has the possibility to provide high synergy with ITS services. This may lead to a higher utilization of ITS services and more sustainable transport, e.g., in terms of reduced congestion and emissions. Additionally, a service design method has been proposed for supporting the process of designing new ITS services, which primarily utilizes on functional synergies with already existing ITS services. In order to illustrate the usage of the suggested method, we have applied it for designing a new ITS service, i.e., the Liability Intelligent Transport System (LITS) service. The purpose of the LITS service is to support the process of identifying when, where, and by whom a consignment has been damaged and who was responsible when the consignment was damaged.

Le but des tokamaks est de produire de l'énergie à partir des réactions de fusion Deutérium-Tritium. Les impuretés dégradant les performances du plasma, par dilution et rayonnement, sont produites par: réactions D-T (Hélium), injection de gaz et interaction plasma-paroi. Dans ITER le divertor sera en Tungstène (W). Les expériences sur JET et ASDEX-Upgrade montrent que W peut pénétrer jusqu'au cœur du plasma et conduire à un effondrement radiatif. La compréhension, la prédiction et le contrôle du transport du W est de fait obligatoire. Collisions et turbulence contribuent au transport d'impuretés. Dans la topologie magnétique du tokamak, les collisions mènent au transport néoclassique. Jusqu'à présent, ces deux canaux de transport sont modélisés séparément, en supposant les flux additifs. Nous avons abordé cette question critique au moyen de simulations gyrocinétiques (GK) 5D avec le code GYSELA. Nous avons construit un nouvel opérateur de collision GK multi-espèces, valable pour toute impureté trace thermique. La version réduite implémentée vérifie les propriétés de conservation des collisions élastiques et la théorie néoclassique. Le coefficient de diffusion et la vitesse de pincement sont en accord avec les prédictions pour tous les régimes de collisionnalité. L'écrantage thermique du W est également retrouvé, mais pas à l'amplitude attendue. Des simulations auto-cohérentes révèlent les synergies entre les transports néoclassiques et turbulents: le flux total de W diffère jusqu'à un facteur 2 de la somme des deux flux obtenu à partir de simulations distinctes. Ceci est partiellement dû à la modification par la turbulence du mode poloïdal m = 1 du potentiel électrique. / Tokamaks aim at producing energy out of Deuterium-Tritium fusion reactions. Impurity degrade performance by diluting the D-T fuel and radiating. They originate from D-T reactions (Helium), or from edge seeding and plasma-wall interaction. In ITER the divertor will be in Tungsten (W). JET and ASDEX-Upgrade experiments have shown that W can penetrate up to the core and lead to radiative collapses. Understanding, predicting and possibly controlling its transport is therefore mandatory. Both collisions and turbulence contribute to impurity transport. In the tokamak magnetic topology, collisions lead to neoclassical transport. So far, these two transport channels are modelled separately, assuming additivity of the fluxes. We have addressed this critical issue by means of 5D gyrokinetic (GK) simulations with the GYSELA code. We have derived a new multi-species GK collision operator, valid for any trace and thermal impurity. The implemented reduced version, adapted to the high performance computing constraints of GYSELA, verifies the conservation properties of elastic collisions and the neoclassical theory. The diffusion coefficient and pinch velocity agree with the predictions in all collisionality regimes. Thermal screening is also recovered for W, although not at the expected magnitude - in link to isotropy and stationarity assumptions. Self-consistent simulations reveal synergies between neoclassical and turbulent transports: the total flux of W differs by up to a factor 2 from the sum of the two, obtained from separate simulations. This is partly due to the modification – magnitude and radial structure – by turbulence of the m=1 poloidal mode of the electric potential.

En fin 2009, les autorités de la concurrence ont accordé une 4ème licence de téléphonie mobile à Free, opérateur français déjà présent dans le fixe et l'internet. Le nouvel opérateur ne disposant pas d'un réseau mobile complet, il a obtenu l'autorisation de signer un contrat d'itinérance avec l'opérateur historique Orange, permettant aux abonnés de Free d'avoir accès au réseau dans les zones non encore couvertes. Vu sa dépendance à Orange, Free peut être considéré comme un opérateur mobile virtuel. Nous utilisons un paramètre qui décrit le niveau d'indépendance de Free et peut prendre trois valeurs possibles. D'abord Free est un opérateur totalement dépendant d'Orange. Ensuite, une partie du trafic de Free passe par son propre réseau. Enfin, Free est un opérateur autonome comme Orange, SFR et Bouygues Telecom. A partir d'une analyse de statique comparative, nous étudions les conséquences de l'octroi de cette licence sous une concurrence à la Cournot. Lorsque Free est un opérateur totalement dépendant d'Orange avec un tarif faible d'accès au réseau d'Orange, son entrée entraîne une baisse du prix, des profits de certains opérateurs titulaires et une hausse du surplus du consommateur. Cependant l'ampleur de la baisse est plus importante quand Free devient plus indépendant. La concurrence à la Stackelberg permet de mieux constater la baisse de prix après l'entrée de Free. Ainsi, l'objectif de cette thèse est de souligner l'importance de la prise en compte du contrat d'itinérance pour analyser les effets de l'entrée de Free. Free a eu des impacts négatifs sur ses concurrents notamment Bouygues Telecom. Pour se maintenir dans le secteur, il existe trois possibilités de fusion. Les fusions avec Free ou SFR-Numéricable se font avec réduction de coûts, tandis que celle avec Orange est sans synergie. L'analyse de ces fusions montre qu'elles sont à la fois rentables et socialement bénéfiques. Ainsi dans cette thèse, nous montrons que toute fusion ne générant aucune synergie, n'est pas forcément anticoncurrentielle. Cependant un dilemme se pose pour Bouygues Telecom, car la fusion acceptée par les autorités de régulation n'est pas celle qui lui procure le profit le plus élevé. / At the end of 2009, the competition authorities have granted a 4th mobile license to Free, French operator already present in the fixed telephony and the Internet. The new operator not having a good coverage, he obtained permission to sign a roaming agreement with the incumbent operator Orange, enabling Free subscribers access to the network in areas not yet covered. Given its dependence on Orange, Free can be seen as a virtual mobile operator. We use a parameter that describes the level of independence of Free and can take three possible values. At first Free is an operator totally dependent on Orange. Then, a part of the traffic of Free passes by its own network. Finally, Free is an independant operator like Orange, SFR and Bouygues Telecom. From a comparative static analysis, we study the consequences of the granting of this license under Cournot competition. When Free is an operator totally dependent on Orange, with a low rate of access to the Orange network, its entry leads to a reduction of price and profits of some incumbent operators with an increase in consumer surplus. However the magnitude of the reduction is greater when Free becomes more independent. Stackelberg competition allows to notice better the price reduction after the entry of Free. Thus, the objective of this thesis is to highlight the importance of the inclusion of the roaming contract to analyze the effects of the entry of Free. Free had negative impacts on his competitors, in particular Bouygues Telecom. To remain in the sector, there are three possibilities of merger. The mergers with Free or SFR-Numericable are made with reduction of costs, whereas that with Orange is without synergy. The analysis of these mergers show that they are at the same time profitable and socially beneficial. Thus in this thesis, we show that any merger creates no synergy, is not necessarily anti-competitive. However a dilemma arises for Bouygues Telecom, because the merger accepted by the authorities of regulation is not the one that gives him the highest profit.

Le risque attribuable est un outil épidémiologique apparu dans les années 1950 aujourd’hui encore assez peu utilisé. Il permet d’estimer la proportion de cas d’une maladie potentiellement évitable par suppression ou réduction de l’exposition d’une population à un facteur de risque. Son principal intérêt réside dans la prise en compte concomitante de l’ampleur d’effet du facteur de risque et de la distribution de ce facteur au sein de la population. Après une présentation des caractéristiques essentielles du risque attribuable et des principes de son estimation à partir d’une étude cas-témoins, nous proposons un cadre conceptuel qui permet d’estimer l’impact d’une intervention de santé publique dans une nouvelle population dont l’exposition à certains facteurs de risque diffère de celle observée dans la population d’étude. Une décomposition du risque attribuable permet alors de prendre en compte l’action combinée, ou synergie, des facteurs de risque dans la survenue de la maladie. Parce qu’il donne une dimension populationnelle à l’estimation de l’effet d’une variable, le risque attribuable est particulièrement intéressant pour quantifier l’importance relative des différentes variables explicatives d’un modèle de régression. La question de l’importance relative des biomarqueurs classiques et de ceux issus des technologies à haut débit dans les modèles diagnostiques est actuellement centrale pour établir les apports respectifs de ces deux niveaux d’information. À partir de simulations, nous montrons comment l’apport des nouvelles technologies, quantifié en termes de risque attribuable, peut être faussé par l’utilisation de méthodologies inadaptées / The attributable risk is an epidemiologic tool that dates back to the fifties but is still relatively seldom used. It estimates the proportion of cases of a given disease that could be avoided if the exposure to a specific risk factor was removed or reduced. Its major interest is that it combines the magnitude of the effect of the risk factor to the distribution of this factor within the population. After a review of the attributable risk main features and the principles of its estimation from case-control studies data, we propose a conceptual framework that allows estimating the impact of a public health intervention in a new population with different exposure to certain risk factors than those observed in the study population. To reach this goal, we used a splitting of the attributable risk that takes into account the combined action –or synergy– of the risk factors on the occurrence of the disease. Because the attributable risk allows estimating the effect of a variable at the population level, it is particularly interesting to quantify the relative importance of the covariates of a regression model. In diagnostic models, the estimation of the relative importance of classic biomarkers and biomarkers obtained from high-throughput technologies is currently crucial in establishing the contribution of each of these two levels of information. Using simulations we have demonstrated the way the role of high-throughput-technologies –quantified in terms of attributable risk– may be wrongly assessed through the use of unsuitable methodology

Hyperthermia is usually used at a sub-lethal level in cancer treatment to potentiate the effects of chemotherapy. The purpose of this study is to investigate the role of heating rate in achieving synergistic cell killing by chemotherapy and hyperthermia. For this purpose, in vitro cell culture experiments with a uterine cancer cell line (MES-SA) and its multidrug resistant (MDR) variant MES-SA/Dx5 were conducted. The cytotoxicitiy, mode of cell death, induction of thermal tolerance and P-gp mediated MDR following the two different modes of heating were studied. Doxorubicin (DOX) was used as the chemotherapy drug. Indocyanine green (ICG), which absorbs near infrared light at 808nm (ideal for tissue penetration), was chosen for achieving rapid rate hyperthermia. A slow rate hyperthermia was provided by a cell culture incubator. The results show that the potentiating effect of hyperthermia to chemotherapy can be maximized by increasing the rate of heating as evident by the results from the cytotoxicity assay. When delivered at the same thermal dose, a rapid increase in temperature from 37 °C to 43 °C caused more cell membrane damage than gradually heating the cells from 37 °C to 43 °C and thus allowed for more intracellular accumulation of the chemotherapeutic agents. Different modes of cell death are observed by the two hyperthermia delivery methods. The rapid rate laser-ICG hyperthermia @ 43 °C caused cell necrosis whereas the slow rate incubator hyperthermia @ 43 °C induced very mild apoptosis. At 43 °C a positive correlation between thermal tolerance and the length of hyperthermia exposure is identified. This study shows that by increasing the rate of heating, less thermal dose is needed in order to overcome P-gp mediated MDR.

Effets de stresseurs environnementaux sur la fertilite des males chez l'abeille domestique apis mellifera l. en relation avec la fécondite de la reine. Dans un contexte de déclin des colonies d’abeilles mellifères, un appauvrissement de la qualité des reines, se traduisant par une production anormale de couvain et des renouvellements prématurés de reines, a été rapporté par les apiculteurs du monde entier. Partant de ce constat, l’hypothèse avait été émise qu’une atteinte de la fertilité des mâles (faux-bourdons), exposés aux stresseurs environnementaux, pouvait être responsable des défaillances observées chez les reines au sein des ruchers. Dans le but de vérifier cette hypothèse, des approches novatrices pour élever des faux-bourdons, en conditions contrôlées de laboratoire et en conditions semi-contrôlées, ont été développées. Les approches mises en oeuvre ont permis de démontrer que l’insecticide systémique Fipronil, la microsporidie pathogène Nosema ceranae et leur association avaient la capacité de générer des perturbations physiologiques de différents types chez les faux-bourdons incluant des altérations de la qualité des semences. De plus, les effets obtenus après les expositions à ces stresseurs ont montré que la fonction de reproduction de ces individus était particulièrement sensible à l’ensemble des stresseurs étudiés. L’insémination instrumentale de jeunes reines, avec des semences de mâles exposés au Fipronil, a mis en lumière une baisse de leur potentiel reproducteur résultant d’une diminution non seulement du nombre mais aussi de la viabilité des spermatozoïdes stockés dans la spermathèque. Considérant que le contenu de la spermathèque conditionne leur capacité à pondre et leur longévité, ces reines sont donc plus disposées à présenter des signes de défaillance pouvant se répercuter sur le fonctionnement général de leur colonie. Ainsi, les troubles de la reproduction induits par une baisse de la fertilité des mâles, exposés à une multitude de stresseurs environnementaux, pourraient en partie expliquer le déclin des colonies d’abeilles. De ce fait, une évaluation des effets reprotoxiques des substances auxquelles les mâles sont potentiellement exposés, pourrait être envisagée dans un cadre règlementaire à venir. Ainsi, les méthodes et les approches innovantes développées dans le cadre de ce travail pourraient représenter des bases pertinentes pour élaborer de nouveaux tests toxicologiques qui pourraient être utilisés dans la procédure d’enregistrement des pesticides. / In a context of honey bee decline, an impoverishment of queen quality, resulting in abnormal brood production and early queen renewal, has been observed worldwide. Hence, the assumption was made that fertility impairment of drones exposed to environmental stressors could explain the queen failure observed in apiaries. In order to test this assumption, original approaches to rear drones were developed in laboratory and semi-field conditions. These approaches enabled to show that the systemic insecticide Fipronil, the pathogen microsporidia Nosema ceranae and their combination disrupt drone physiology in different ways, including an impairment of the semen quality. In addition, results have highlighted the high sensitivity of the reproductive function of drone to all of these stress factors. The instrumental insemination of young queens with semen of drones exposed to Fipronil has shown a decrease in the reproductive potential of queens that resulted from a lower number and viability of spermatozoa stored in their spermatheca. Consequently, considering that the spermathecal content determines the egg-laying ability and the lifespan of queens, the risk of queen failure and colony dysfunction is higher. Thus, reproductive disorders, linked to a fertility decline of drones continuously exposed to numerous environmental stressors, could explain, at least in part, the phenomenon of honey bee decline. Thereby, an assessment of the reproductive toxicity of pollutants, including pesticides, to which drones are potentially exposed, should be considered in a future regulatory framework. In this way, the innovative methods and approaches developed in the frame of this work could represent pertinent bases to elaborate new toxicological tests that could be used in the registration procedure of pesticides.

L'intestin est la première barrière de l'organisme contre les contaminants alimentaires, dont les mycotoxines. Le déoxynivalenol (DON) est un contaminant majeur des céréales, souvent retrouvé en association avec d'autres trichothécènes B (TCTs B), le 3- et 15-acétyldéoxynivalénol (3-ADON et 15-ADON), le nivalénol (NIV) et la fusarénone X (FX). Au niveau cellulaire, le DON interagit avec l'ARN ribosomique, bloquant ainsi la synthèse protéique et activant la cascade de la voie de signalisation de MAPKinases impliquée dans des mécanismes de la réponse inflammatoire. Au niveau intestinal, cette mycotoxine pourrait donc perturber le renouvellement continu de l'épithélium, et l'homéostasie de la réponse inflammatoire. On suggère ainsi qu'elle pourrait jouer un rôle dans la pathogénie des maladies inflammatoires chroniques de l'intestin. Si les effets du DON sont relativement connus, ceux du NIV et de leurs dérivés acétylés sont moins bien documentés. De même, peu de données existent quant à la toxicité combinée de ces mycotoxines dont la co-occurrence est avérée. Sur des modèles in vitro de cellules épithéliales intestinales humaines et porcines et sur un modèle ex vivo d'explants de jéjunum de porc, nous avons comparé les toxicités individuelles de cinq TCTs B (DON, 3- et 15-ADON, NIV et FX) et analysé leur toxicité combinée en termes de synergie, additivité ou antagonisme vis-à-vis de l'intestin. Les résultats montrent qu'à des concentrations de l'ordre du micromolaire, les TCTs B inhibent la croissance des cellules épithéliales intestinales par ordre croissant de toxicité 3-ADON, DON, 15-ADON, NIV et FX. Aux faibles doses correspondant à des niveaux d'exposition rencontrés chez le consommateur français ou européen, des synergies d'un facteur 3 à 10 ont été observées. Ces travaux ont également permis de caractériser l'activité pro-inflammatoire au niveau intestinal des TCTs B, et l'analyse benchmark de données de transcriptomique a montré que l'exposition de l'intestin à des doses aussi faibles que 0.04µM de FX, 0.1µM de DON ou 0.1µM de NIV s'accompagne d'une activation significative des mécanismes de l'inflammation. Ces doses sont de l'ordre des concentrations attendues dans le chyle sur la base des valeurs toxicologiques de référence actuelles. En conclusion, ces données montrent que le renouvellement de l'épithélium intestinal et l'activité pro-inflammatoire au niveau intestinal pourraient être des marqueurs très sensibles dans le cadre de l'évaluation de la toxicité individuelle et des interactions entre TCTs B. / As for other food-born contaminants, the gastro-intestinal tract represents the first barrier against deoxynivalenol (DON). This mycotoxin frequently co-occurs with other type B trichothecenes (TCTs B) namely 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX). At the cellular level, DON binding to ribosomal RNA results in the inhibition of protein synthesis and triggers the mitogen-activated protein kinases (MAPKs) pathway that have been linked to immune response mechanisms. Thus, intestinal epithelial cell renewing is considered a putative target in DON toxicity. Moreover, based on the ability of DON to disturb the state of homeostasis of the inflammatory response in the intestine mimicking what is found in inflammatory bowel diseases (IBD), it is proposed that this mycotoxin may play a role in such diseases. However, very few is known about the intestinal toxicity of the other co-occuring TCT B, and their combined effects eventually. By means of in vitro human and porcine intestinal epithelial cells models and an ex vivo porcine jejunal explants model, we assessed the individual toxicity of five TCT B (DON, 3- and 15-ADON, NIV and FX) toward the intestine and we analyzed their combined toxicity in terms of additivity, synergy or antagonism. The tested TCT B significantly impaired the intestinal epithelial cell growth in the micromolar range, in increasing order of potency 3-ADON, DON, 15-ADON, NIV and FX. The toxicity of low doses of TCT B was synergistic. For mycotoxin concentrations corresponding to exposure levels reported for French and European consumers, the amplitude of this synergy ranged between 3 and 10. Benchmark dose analyses of the transcriptional data also showed that the exposure of the intestine to mycotoxin concentrations as low as 0.04µM for FX, 0.1µM for DON and 0.1µM for NIV could be associated to a significant activation of the inflammatory response mechanisms. Taken together, these results suggest that epithelial cell renewing and pro-inflammatory effects at the intestinal level may be consider very sensitive biomarkers for the assessment of the individual toxicity and interactions between the co-occurring TCTs B.

The volume of mergers and acquisitions in 2014 amounted to 3.6 trillion USD. Acquisition activity over the previous year increased by 26 % and the volume of mergers and acquisitions was the third highest in history after 2007 and 2006. The constantly increasing number of mergers and acquisitions and an increase in the volume of capital required for the realization of transactions stand in stark contrast to the high rate of failure. The primary motive for international mergers and acquisitions is the realization of synergies. The paper analyzes in detail the factors that influence the success of international mergers and acquisitions, especially strategic fit, cultural fit and integration. It also analyzes the motives which lead to realization of those transactions and how they relate to the realization of synergies. The results of previous studies are presented in the theoretical part, practical part is focused on a specific acquisition of Anheuser-Busch, which is part of the global brewing group Anheuser-Busch InBev, which in 2014 bought a small Czech brewery - Pivovar Samson.