Os aços inoxidáveis ferríticos são susceptíveis à corrosão intergranular após resfriamento rápido a partir de 950°C. A teoria de empobrecimento no teor de cromo nas vizinhanças do carboneto e/ou nitreto, precipitados nos contornos de grão, é o mecanismo mais aceito para descrever este fenômeno. O presente trabalho avalia o efeito dos tratamentos isotérmicos na resistência à corrosão intergranular do aço inoxidável ferrítico UNS S43000, utilizando o método de reativação eletroquímica potenciodinâmica na versão ciclo duplo (DL-EPR). As amostras foram solubilizadas a 1200°C e posteriormente tratadas isotermicamente a temperaturas entre 500°C e 700°C, por tempos de 5 minutos a 16 horas. O ensaio DL-EPR foi realizado em solução 0,5M H2SO4 com velocidade de varredura de 1,67 mV/s. As amostras foram examinadas em microscópio óptico e microscópio eletrônico de varredura após ensaio DL-EPR, Práticas W e X da norma ASTM A763 e ataque metalográfico com reagente Vilella. Foram obtidos diferentes valores de grau de sensitização em função do tempo de tratamento isotérmico. Análises por difração de raios X, sobre resíduos extraídos quimicamente identificaram precipitação de nitretos e de carbonetos de cromo, Cr2N e Cr23C6, respectivamente. As temperaturas de 550°C e 600°C mostraram dois máximos de grau de sensitização em função do tempo, por isso este processo de sensitização foi denominado de dupla sensitização. A partir dos resultados obtidos: grau de sensitização DL-EPR, exame microestrutura e difração de raios X, o presente trabalho propõe o seguinte mecanismo para explicar a dupla sensitização: (Etapa 1) no resfriamento da temperatura de solubilização são precipitados nos contornos de grão fases ricas em cromo; (Etapa 2) os tratamentos isotérmicos geram uma fina precipitação de Cr2N nos contornos de grão sobre os precipitados formados na Etapa 1; (Etapa 3) esses precipitados são posteriormente dissolvidos o que permite (Etapa 4) uma nova precipitação de Cr2N e Cr23C6 nos contornos de grão e (Etapa 5) finalmente temse o processo de crescimento, coalescimento e recuperação final. A recuperação total da resistência à corrosão intergranular foi obtida após tratamentos isotérmicos realizados a 650°C por tempos maiores que 20 minutos e a 700°C a partir de 5 minutos. O trabalho confirma que tanto os fenômenos de precipitação, sensitização e recuperação são controlados 5 pela difusão do cromo na ferrita. Tal confirmação foi possível a partir de análises da solução da segunda lei de Fick e gráficos de Arrhenius, construídos a partir do ensaio DL-EPR e dos exames microestruturais, os quais indicaram uma energia de ativação de precipitação com valor de 255 kJ/mol (219 kJ/mol é o valor da energia de ativação para difusão do cromo na ferrita encontrado em literatura (ARAI; TAKEDA; ARATA, 1987; WOLFE; PAXTON, 1964)). / Ferritic stainless steels are prone to intergranular corrosion following quick cooling from 950°C. The explanation based on chromium impoverishment near the carbides and/or nitrides precipitated in the grain boundaries is the most accepted to describe the observations. This work study the effects of heat treatments on the resistance to intergranular corrosion of the UNS S43000 ferritic stainless steel, using the Double Loop Electrochemical Potentiodynamic Reactivation test (DL-EPR). Specimens have been solution annealed at 1200oC followed by isothermical holding at temperatures between 500°C and 700°C, for times of 5min up to 16h. The DL-EPR test was made in a 0,5M H2SO4 solution using scan rate of 1,67 mV/s. The specimens were observed by optical microscope and scanning electron microscope after DLEPR test, Practices W and X (ASTM A763) and metallographic etch with Vilella reagent. Different degrees of sensitization were obtained for different isothermal holding time. X rays diffraction of extracted precipitates identified chromium nitrides and chromium carbides, Cr2N and Cr23C6. The temperatures of 550°C and 600°C produced two maxima in the curves of degree of sensitization as function of time; the process was named double sensitization. From the results of degree of sensitization DL-EPR, microstructural examination and X rays diffraction, this work proposes the following mechanism to explain double sensitization: (1st stage) during cooling from the solution annealing temperature there is grain boundary precipitation of chromium rich phases; (2nd stage) the isothermal treatments produce a fine grain boundary precipitation of Cr2N on the precipitates formed in the 1st stage; (3rd stage) increasing the time, these precipitates are dissolved, allowing for a (4th stage) new grain boundary precipitation of Cr2N e Cr23C6; finally (5th stage) there is growth, coalescence and recovery. Total recovery of intergranular corrosion resistance was achieved, isothermically at 650°C for times longer than 20min and at 700°C for times longer then 5min. Precipitation, sensitization and recovery are controlled by diffusion of chromium in ferrite. This conclusion was based on analysis of solution of Fick’s second law and Arrhenius plots constructed with DL-EPR data and microstructural observations. The calculus of the experimental energy of activation for precipitation produced a value of 255kJ/mol (energy of activation for chromium 7 diffusion in the ferrite reported by Arai, Takeda and Arata (1987) and Wolfe and Paxton (1964) is 219kJ/mol).

Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2016-11-11T13:14:25Z No. of bitstreams: 0 / Made available in DSpace on 2016-11-11T13:14:25Z (GMT). No. of bitstreams: 0 / Os venenos de serpentes são complexas misturas de proteínas e peptídeos que apresentam uma variedade de atividades biológicas. Estudos apontam para uma rica diversidade de moléculas bioativas de baixa massa molecular nos venenos, como a crotamina, miotoxina A, peptídeos potenciadores de bradicinina (BPPs) inibidores do tipo Kunitz de serinopeptidases e tripeptídeos inibidores de metalopeptidases. O interesse nestas moléculas está relacionado ao potencial uso como agentes terapêuticos contra diversas patologias, como distúrbios da coagulação e modulação da atividade de metalopeptidases, moléculas estas envolvidas com tumorigenêse e outros processos patológicos como inflamação crônica e distúrbios neurológicos. O veneno da serpente Bitis gabonica rhinoceros provoca alterações fisiopatológicas como severa desordem na coagulação sanguínea e danos teciduais seguidos de necrose. No presente estudo foram isoladas e caracterizadas metalopeptidases e serinopeptidases, além de componentes de baixa massa molecular como inibidor do tipo Kunitz e BPPs. Estes peptídeos foram testados quanto a sua capacidade inibitória frente as peptidases endógenas e sequenciados por espectrometria de massa. Os nossos dados mostram que as peptidases isoladas degradam caseína e não tem atividade sobre colágeno. A serinopeptidase tem atividade β-fibrinogenolítica e o inibidor tipo Kunitz isolado apresenta maior capacidade de inibir a quimotripsina, com valor de Ki= 0,07 μM, mostrando-se um promissor substituto ao fármaco aprotinina. Este peptídeo apresentou também atividade citotóxica em células B16F10 e tênue atividade antimicrobiana. Dentre os BPPs identificados, o peptídeo que possui sequência não canônica apresentou a capacidade de potencializar a ação da bradicinina tanto em ensaio edematogênico quanto de inibição da atividade enzimática da enzima conversora de angiotensina. Esses resultados indicam o potencial de peptídeos de venenos animais para o desenvolvimento de novos agentes terapêuticos para o tratamento de enfermidades como hipertensão e distúrbios de coagulação. / Tese (Doutorado em Tecnologia Nuclear) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Les études couplant des observations provenant des marges passives actuelles et d’analogues fossiles ont permis de mieux appréhender les mécanismes d’extension de la lithosphère. Néanmoins, l’évolution spatiale et temporelle des processus de rupture continentale et de formation de croûte océanique reste mal contrainte. Le Golfe de Gascogne et les Pyrénées sont utilisés dans ce travail comme laboratoire naturel pour étudier la formation et la réactivation des systèmes de rift. Le développement et l’application d’une approche terre-mer a permis d’identifier, caractériser et cartographier les domaines de rift formés lors de l’ouverture du Golfe de Gascogne et partiellement intégrés à l’orogène Pyrénéenne. Cette cartographie révèle l’architecture complexe de la limite de plaque Ibérie-Europe résultant d’une évolution fortement polyphasée. Plusieurs systèmes de rift spatialement distincts sont préservés à des stades d’évolution différents. Une segmentation importante partiellement héritée de la structuration prérift contrôle la formation des systèmes de rift ce qui a des implications pour la cinématique régionale. Plusieurs étapes de la déformation compressive ont pu être distinguées et mises en relation avec l’architecture héritée du rift. La réactivation est initiée dans le domaine de manteau exhumé. Après lasubduction de croûte hyper-amincie, la collision continentale est contrôlée par les domaines proximaux et de necking qui jouent le rôle de buttoirs. Ces résultats soulignent l’interaction étroite entre l’héritage pré-rift et l’évolution spatiale des systèmes de rift ainsi que l’importance de l’architecture du rift pour comprendre la formation des orogènes. / Knowledge on lithosphere extensional mechanisms has greatly benefited from studies made both at presentday rifted margins and onshore fossil analogues. Nevertheless, the spatial and temporal evolution of the processes leading to continental break-up and oceanic crust formation remains poorly constrained. The Bay of Biscay and Pyrenees is used in this study as a natural laboratory to investigate the formation and reactivation of rift systems. A new offshore-onshore approach is developed and applied to identify, characterize and map the rift domains inherited from the Bay of Biscay opening and partly integrated into the Pyrenean orogen. This mapping reveals the complex architecture of European-Iberian plate boundary resulting from a strongly polyphased evolution. Several rift systems spatially distinct are preserved at different evolutionary stages. An important segmentation partially inherited from the pre-rift structuration controls the formation of the rift systems, an observation that has important implications for regional kinematic restorations. Several steps in compressional deformation can be distinguished and related to the rift inherited architecture. Reactivation is initiated in the exhumed mantle domain. Following the subduction of hyperthinned crust, continental collision processes are controlled by the proximal and necking domains acting as buttresses. These results emphasize the role of pre-rift inheritance for the spatial evolution of rift systems and the importance of the rift-related architecture to unravel the formation of collisional orogen.

Le but de ce travail est de comprendre les relations entre la déformation et la diagenèse dans les carbonates. Pour cela, l’échelle du m au dam est adéquate car elle permet de séparer les effets matriciels, des fractures et des failles. Celle-ci est sous la résolution de la sismique, donc peu de données géophysiques et diagénétiques spatiale et quantitatives sont disponibles, le plus souvent limitées aux données 1D de puit.Nous avons choisi 4 affleurements présentant des hétérogénéités et des intensités de déformation et de diagenèse diverses. Un protocole multi-échelle et multidisciplinaire a été développé, comprenant de la géophysique à l’échelle du cm au dam, de la diagenèse structurale et de la géochimie sur les ciments de fracture. Nous montrons un fort effet d’échelle entre les Vp en laboratoire et à l’affleurement dû à des hétérogénéités sédimentaire, d’enfouissement et structurale, qui conduisent à différents motifs géostatistiques.Les fractures ont l’effet le plus fort sur les Vp, modulé par leur cimentation, et qui peut entièrement effacer la signature initiale du faciès. La réactivation des fractures induit une anisotropie directionnelle de 10% due à des changements dans le remplissage des fractures, caractérisés par de multiples phases de cimentation, broyage et dissolution.Dans les zones de faille, l’anisotropie sismique est amplifiée, conduisant à un fort affaiblissement de la roche au cisaillement et à une diminution de Vp autour de la faille. Les données géochimiques tracent plusieurs flux de fluides diagénétiques et soulignent les fortes interactions entre l’évolution de la perméabilité, la diagenèse structurale et la signature géophysique des carbonates. / The aim of this work was to understand the relationships between deformations and diagenesis in carbonates. The relevant scale to study it may be the m to dkm scale which allows individualizing fracture, fault and matrix effects. This scale is under the seismic resolution, so few quantitative diagenetic and geophysical spatial data are available, mainly constrained to 1D borehole.Therefore, we selected 4 dkm scale outcrops displaying various heterogeneities and intensities of deformation and diagenesis. We developed a multidisciplinary/multiscale protocol including geophysics from cm to dkm scale along with structural diagenesis study and geochemical measurements on fractures cements. We found a strong scale effect between laboratory and outcrop Vp due to sedimentary, burial and structural heterogeneities that lead to different geostatistical patterns. Fractures have the strongest effect on Vp, being modulated by their cementation and can erase the initial facies acoustic signature. The fracture reactivation induce a 10% Vp directional anisotropy due to microscale changes in the fractures infillings characterized by multiple cementation, crushing and dissolution phases. In fault-zones the seismic anisotropy magnitude is amplified, leading to a strong directional rock shear weakening and a Vp decrease around the fault, caused by higher discontinuities aperture and brecciation. Geochemical data indicate that the Vp signature evolution is linked to different diagenetic fluids flow origins occurring during each deformation phase. This underlines the strong interplay between permeability evolution, structural diagenesis and geophysical signature in carbonates.

[pt] Reservatórios de petróleo e gás estruturalmente compartimentados por falhas geológicas selantes são encontrados em diversas regiões do mundo. Durante a fase de explotação, a integridade do selo destas falhas pode ser comprometida pelas deformações decorrentes dos processos de depleção e/ou injeção de fluidos. Estas deformações, em conjunto com as propriedades físicas e geométricas das rochas e falhas presentes, podem alterar significativamente o estado de tensões do maciço rochoso fazendo com que uma falha reative e se torne hidraulicamente condutora. A esse fenômeno estão associados riscos de exsudação, perda de integridade de poços e outros potencias problemas geomecânicos. Na literatura, diversas modelagens numéricas têm sido utilizadas a fim de caracterizar e prever os fenômenos de reativação e/ou abertura de falhas geológicas. A maior parte de estas abordagens faz uso de modelos bidimensionais considerando seções críticas na hipótese de estado plano de deformação. Essas simplificações são adotadas a fim de evitar a complexidade geométrica e o alto custo computacional de uma modelagem tridimensional. No entanto, a configuração tridimensional dos planos de falha pode induzir a reativação em direção a zonas mais críticas do que aquelas contidas numa única seção. Neste trabalho apresenta-se uma metodologia para análise de reativação de falhas geológicas e discute-se a importância do uso dos modelos 3D na previsão do comportamento geomecânico de reservatórios compartimentados por falhas geológicas. São apresentados 3 modelos diferentes. O primeiro exemplo traz um modelo bidimensional apresentado na literatura, faz-se uma comparação dos resultados com representação por meio do elemento de interface, por meio do continuo equivalente e por meio de um elemento solido com fraturas embutidas. O segundo exemplo faz-se um comparativo entre a utilização de elementos quadrilaterais e triangulais para a representação da falha em modelos 3D. Para o terceiro modelo foram realizadas simulações numéricas considerando modelos 2D e 3D em um simulador in-house baseado no método dos elementos finitos. Para a representação do meio continuo foram utilizados elementos quadrilaterais para o caso 2D, e elementos hexaédricos e tetraédricos para o caso 3D. Para a representação das falhas geológicas foram utilizados elementos de interface de espessura nula segundo o critério de ruptura de Mohr-Coulomb. Da comparação dos resultados, constata-se que as análises 2D e 3D forneceram previsões de reativação similares. No entanto, as previsões de pressões de abertura foram distintas em ambos os modelos devido às diferentes trajetórias de migração de fluido. Particularmente em modelos com geometria irregular confirma-se a importância do emprego de modelo 3D. / [en] Oil and gas reservoirs that are structurally compartmented by sealing geological faults are common in several areas around the world. During production, the deformations from the processes of fluid depletion and/or injection can compromise the integrity of the seal of the faults. This deformation, together with the physical and geometrical properties from the rocks and faults can significantly change the stress state. Therefore, it might cause fault reactivation, turning it in a hydraulic conduit. Related to this phenomenon, are the exudation, loss of wellbore integrity and other potential geomechanical problems. There are several numerical modelling techniques available in literature to characterize and predict the reactivation and/or opening of geological faults. In most of these modelling approaches, bi-dimensional models are used for critical sections through the assumption of plane strain conditions. The reason for using 2D models is to avoid the geometrical complexity and the high computational costs associated to three-dimensional modeling. On the other hand, the fault planes in the three-dimensional approach can show fault reactivation in a more critical direction e than the one represented by the bi-dimensional model. In this work, a methodology is presented in order to assess geological fault reactivation. In addition, the importance of using 3D models in the prediction of the geomechanical behavior of reservoirs compartmented by geological faults is discussed. Three different models are presented. The first example is based on a two dimensional model from the literature. A comparison between approaches using interface elements, equivalent continuum elements and solid element with fractures is carried out in the first example. The second example brings a comparison between the quadrilateral and triangular elements to represent faults in a 3D model. In addition, an analysis was carried out considering 2D and 3D models using an in house software based on the finite element method. To simulate the continuum medium, quadrilateral elements are used in the 2D case and in the 3D case hexahedral and tetrahedral elements are employed. In addition, to represent the geological faults, interface elements with zero thickness are used in association with the Mohr-Coulomb failure criterion. In the case study, predictions of fault reactivation were similar in the 2D and 3D models. However, fault opening pressures were different in both models, due to the 3D fluid migration path. It also confirmed the importance of using 3D models when simulating irregular geometries.

Ante la aparición del virus COVID-19 en China y su propagación por el mundo en el 2020, el sector hotelero afronta una de las crisis más importantes de la historia. Con una reducción aproximada del 90% en transporte aéreo, los hoteles tuvieron que diseñar nuevas estrategias de reactivación para hacerle frente a la reducción de llegada de huéspedes. La presente investigación analiza, de forma académica, los cambios producidos por la crisis de la pandemia del COVID-19 en la industria hotelera mundial y las estrategias implementadas por los hoteles para contrarrestar sus consecuencias en el Perú. Teniendo en cuenta que el fenómeno mencionado se encuentra aún en desarrollo, las investigaciones sobre las acciones tomadas por los hoteles para reactivar sus operaciones aún son escasas; por ello, se aborda la temática de estudio alrededor del mundo, enfocándose en el sector hotelero y su respuesta ante la pandemia del coronavirus. Se utilizó como metodología la revisión bibliográfica descriptiva a partir de fuentes académicas y fuentes primarias como entrevistas a profundidad a expertos hoteleros sobre las estrategias implementadas en los hoteles ante la crisis que trajo la pandemia al Perú. Como resultado se obtuvo que el turismo y la hotelería son de los sectores más afectados por la pandemia, por lo que los hoteles siguen ideando estrategias dirigidas a diseñar nuevos productos que se ajusten a las nuevas exigencias del huésped. La investigación es un aporte a la sistematización y documentación de la gestión en los hoteles y estrategias de reactivación en Lima, Perú. / Faced with the emergence of the COVID-19 virus in China and its spread around the world in 2020, the hotel sector faces one of the most important crises in history. With an approximate 90% reduction in air transport, the hotels had to design new reactivation strategies to cope with the reduction in guest arrivals. This research analyzes, in an academic way, the changes produced by the crisis of the COVID-19 pandemic in the global hotel industry and the strategies implemented by hotels to counteract its consequences in Peru. Taking into account that the aforementioned phenomenon is still under development, investigations into the actions taken by hotels to reactivate their operations are still scarce. For this reason, the subject of study around the world is addressed, focusing on the hotel sector and its response to the coronavirus pandemic. Descriptive bibliographic review from academic sources and primary sources was used as methodology, such as in-depth interviews with hotel experts on the strategies implemented in the hotels in the face of the crisis that the pandemic brought to Peru. As a result, it was obtained that tourism and hotels are among the sectors most affected by the pandemic, so hotels continue to devise strategies aimed at designing new products that meet the new demands of the guest. The research is a contribution to the systematization and documentation of hotel management and reactivation strategies in Lima, Peru. / Trabajo de investigación

This doctoral thesis aimed at better understanding the contribution of sleep, Targeted Memory Reactivation and transcranial Direct Current Stimulation (tDCS) on the consolidation of neutral and emotional memories. In the first part of this work, we found that REM-enriched naps and more specifically rapid eye movement density is associated with the consolidation of sad stories, suggesting a possible implication of Ponto-Geniculo-Occipital (PGO) waves in the consolidation of sad information. In addition, we observed an increase in emotional reactivity during re-exposure to the sad story following a REM-enriched nap. We postulate that REM sleep favored the consolidation of the emotionalsalience of the sad memories, leading to exacerbated emotional reactivity during re-exposure. We also investigated the impact of TMR during NREM sleep on the consolidation of neutral and negative word pairs leanred with a specific sound. We found an equal benefit of the TMR procedure on neutral and emotional material, suggesting that emotion does not modulate the selective enhancing effect of TMR during NREM sleep. In an additional study, we tested the impact of verbatim presentation of the pairs of words during NREM sleep and did not find the memory benefits of TMR. We ascribed the absence of TMR memory benefit to the detrimental effect of the auditory presntation of the second word which impaired the memory reactivation processes initiated by the presentation of the first word. Together, theseresults indicate the crucial role of a sensitive plastic time window necessary for the successful processes of memory reactivation during sleep. Finally, we evaluated how the combination of tDCS and TMR procedure during a wakeful rest consolidation interval benefits memory consolidation. We found that TMR alone led to selective memory benefits for cued word pairs. When the TMR procedure was combined with either right-anodal or left anodal tDCS, we observed a significant improved global learning, suggesting that tDCS does not potentiate but overshadows the TMRprocedure. Altogether, these studies offer new perspectives in the field of memory consolidation. More specifically, the application of an alternating current during post-learning sleep concomitantly to a TMR procedure might favor the specific brain oscillations involved in successful memory reactivation, and might enhance the associated memory gains. / Doctorat en Sciences psychologiques et de l'éducation / info:eu-repo/semantics/nonPublished

En el presente trabajo se analizó la importancia que tienen las ferias y mercados itinerantes en Lima – Perú para la reactivación económica frente al desempleo generado por el estado de emergencia debido al COVID-19. Se indagó acerca del desarrollo y el funcionamiento de la industria ferial, así como el nacimiento de diversos emprendimientos por consecuencia del impacto de la pandemia en la sociedad y en el ámbito laboral. Se investigó acerca de las iniciativas relacionadas a ferias y mercados a nivel nacional por parte del estado para brindar apoyo, soluciones y oportunidades a las personas que necesitan espacios para ofrecer y vender sus productos. El trabajo se enfocó en las ferias itinerantes implementadas por municipalidades, específicamente por la Municipalidad de Surco. La investigación y el planteamiento se centró precisamente en el programa llamado "Ferias Itinerantes de Surco Emprende", se buscó información acerca de cómo nacieron, cuál es su funcionamiento y el aporte en la sociedad, detectando los aspectos por mejorar. También se estudió el público objetivo al que están dirigidas estas ferias, con la finalidad de saber, cuales son las necesidades que requieren, para posteriormente utilizar al diseño gráfico como medio para contribuir en el buen funcionamiento de estas, promocionándolas y generando más consumo en ellas, se busca tener como resultado que la afluencia de público sea mayor. Se elaboró un sistema visual integral explorando diferentes materiales y elementos gráficos que permitan crear propuestas pertinentes e innovadoras que se puedan adaptar fácilmente a las necesidades que requiere cada una de ellas y generar mayor impacto. / This study analyzed the roles that itinerant fairs and markets in Lima, Peru play in driving economic recovery in the context of COVID-19. We inquired about the development and functioning of the fair industry and analyzed new ventures that have arisen to respond to market and employment needs during the pandemic. We researched state initiatives related to fairs and markets at a national level to offer support, solutions and opportunities to people who might need a space to sell their products. We focused our work on itinerant fairs at the municipal level, particularly in the Municipality of Surco. Specifically speaking, the research and concept focused on the evolution of"Itinerant Fairs: Surco Emprende". We searched for information regarding how these endeavors got off the ground; how they work; and what they contribute to society. The study also delved into areas for improvement. We also studied the customer pool that these fairs target to determine how they can use graphic design to better promote their product drive sales; and ensure success. Our primary objective is to increase turnout. We prepared a comprehensive visual system that explores the use of diverse materials and graphic elements to create pertinent and innovative proposals that can be easily adapted to generate a larger impact. / Trabajo de Suficiencia Profesional

Toxoplasma gondii est un parasite répandu, ayant un impact médical et vétérinaire. Chez les hôtes intermédiaires, les tachyzoïtes et les bradyzoïtes sont responsables de la toxoplasmose aiguë (TA) et chronique (TC), respectivement. Sous la réponse immunitaire, la TA évolue en TC, se manifestant par des kystes latents dans le cerveau et les muscles squelettiques. De plus, une forte corrélation existe entre la TC et plusieurs neuropathologies et cancers. Chez les patients immunodéprimés, la TC peut être réactivée et conduire à une maladie potentiellement fatale. Les traitements actuels ciblent principalement les TA, et présentent plusieurs effets secondaires. Nous nous sommes concentrés sur la TC et la compréhension de ses mécanismes moléculaires. Nous avons d’abord étudié l’efficacité de l’imiquimod contre la TA et la TC. Au cours de la TA, l'imiquimod a entraîné le recrutement de cellules T dans le péritoine et la rate de souris traitées et a considérablement diminué le nombre de kystes cérébraux lors de l'établissement de la TC. Remarquablement, le gavage de souris avec les kystes cérébraux restants chez des souris traitées à l'imiquimod n'a pas pu induire de TC. Après l'établissement de la TC, nous avons démontré que l'imiquimod réduisait considérablement le nombre de kystes cérébraux chez les souris chroniquement infectées et augmentait les récepteurs Toll-Like 11 et 12, qui se lient à une protéine du tachyzoïte, la profiline. Parallèlement, l’expression de TLR-7 augmentait, probablement par son agoniste, l'imiquimod. L'imiquimod induit une interconversion, comme l'indiquent la diminution du taux de protéine P21 et l'augmentation du taux de protéine P30, exprimées exclusivement et respectivement chez les bradyzoïtes et les tachyzoïtes. Les voies en aval de TLR-11/12 ont été activées via la voie MyD88 de signalisation, entraînant une induction ultérieure de la réponse immunitaire. In vitro, l'imiquimod n’affecte pas la souche Toxoplasma dépourvue de profiline, suggérant un rôle via le complexe Profilin/TLR-11/12. Enfin, le traitement par l'imiquimod a régulé positivement les transcrits des ligands 9 (CXCL9) et 10 (CXCL10), connus pour induire le recrutement de lymphocytes T dans des foyers réactivés du Toxoplasme afin d'éliminer l'infection.Ensuite, nous nous sommes concentrés sur les mécanismes moléculaires impliqués dans la TA et particulièrement dans la TC. Nous avons caractérisé P18, un membre de la superfamille SRS. Lorsque nous avons supprimé P18, la virulence était atténuée au cours de la TA, dû à un échappement plus rapide des tachyzoïtes du péritoine de souris, parallèle à un recrutement significatif de cellules dendritiques. De manière concomitante, moins de tachyzoïtes étaient détectés dans la rate, tandis que plus de parasites ont atteint le cerveau de souris infectées. L’élimination de P18 a augmenté le nombre de kystes de bradyzoïtes in vitro et dans le cerveau de souris infectées. Une expression induite de cytokines, notamment CXCL9 et 10, a également été observée. L’immunosuppression de souris KO P18 infectées a retardé la réactivation. L’infection orale de souris immunodéficientes ayant des macrophages fonctionnels a montré un prolongement de survie, contrairement aux souris n’ayant pas de macrophage, soulignant un rôle de l'IFN-g dans l’interconversion. Collectivement, ces données confirment le rôle de P18 dans la modulation de la réponse immunitaire, facilitant le passage des tachyzoïtes dans le cerveau et favorisant la formation de kystes. P18 joue également un rôle central dans la réactivation et la dissémination de parasites de manière dépendante de l'IFN-g. Dans l'ensemble, nous avons montré le potentiel thérapeutique prometteur de l'imiquimod contre la toxoplasmose et caractérisé le rôle de P18 dans l'immunomodulation afin de contrôler la dissémination et l'interconversion. Notre étude ouvre la voie à de nouvelles approches thérapeutiques contre la toxoplasmose, sa persistance et sa réactivation. / Toxoplasma gondii is a prevalent parasite of medical and veterinary impact. In intermediate hosts, tachyzoïtes and bradyzoïtes are responsible for acute and chronic toxoplasmosis (AT and CT), respectively. In immunocompetent patients, AT evolves, due to the host immunity, into a persistent CT, which manifests as latent tissue cysts in the brain and skeletal muscles. CT correlates with several neuro-pathologies and cancers. In immunocompromised patients, CT may reactivate and poses a life threatening condition. Current treatments primarily target AT, are limited to general anti-parasitic/anti-bacterial drugs, and associate with several limitations. Here, we focused on targeting CT and understanding its molecular mechanisms. First, we explored the efficacy of Imiquimod against AT and CT. During AT, Imiquimod led to recruitment of T cells to peritoneum and spleen of treated mice and significantly decreased the number of brain cysts upon establishment of CT. Remarkably, gavage of mice with the remaining brain cysts from Imiquimod treated mice, failed to induce CT. Post-establishment of CT, we demonstrated that Imiquimod sharply reduced the number of brain cysts in chronically infected mice, and significantly increased Toll-Like Receptors 11 and 12. These TLRs are usually expressed by dendritic cells and monocytes, and bind a tachyzoïte actin-binding protein, profilin. Concomitantly, TLR-7 was upregulated, likely by its agonist Imiquimod. Imiquimod induced interconversion as documented by the decreased protein levels of P21, and increased protein levels of P30, exclusively expressed in bradyzoïtes and tachyzoïtes respectively. Pathways downstream from TLR-11/12 were activated, through MyD88 dependent TLR signaling, which resulted in subsequent immune response induction. In vitro, Toxoplasma strain lacking profilin, does not respond to Imiquimod, suggesting a role through Profilin/TLR-11/12. Finally, Imiquimod treatment upregulated the transcript expression levels of Chemokine (C-X-C motif) ligand 9 (CXCL9) and 10 (CXCL10), known to induce T cell recruitment to reactivated Toxoplasma foci to clear the infection.Then, we focused on molecular mechanisms involved in AT and notably CT. We characterized P18, a Surface-Antigen 1 (SAG-1) Related Sequence (SRS) superfamily member. When we deleted P18, the virulence was attenuated during AT. Indeed, P18 depletion led to a faster clearance of the parasites from the peritoneum of mice, paralleled by a substantial recruitment of dendritic cells, presumably a vehicle for tachyzoïte dissemination. Concomitantly, a lower number of tachyzoïtes was detected in the spleens while a higher number of parasites reached the brains of infected mice. P18 depletion increased the number of bradyzoïte cysts, in vitro and in the brains of infected mice. An induced expression of cytokines/chemokines, including CXCL9 and 10 was also observed. Immunosuppression of infected mice with KO P18, delayed reactivation. Oral infection of Severe Combined Immunodeficiency (SCID) (with IFN-g secreting macrophages), and NOD/Shi-scid/IL-2Rgnull (NSG) mice (lacking IFN-g), showed a significant prolonged survival in infected SCID but not NSG mice. This underlines a role for IFN-g in the conversion from bradyzoïtes to tachyzoïtes. Collectively, these data support a role of P18 in orchestrating the immune response, which ultimately facilitates tachyzoïte trafficking to the brain and favors cyst formation. P18 plays also a central role in parasite reactivation and dissemination in an IFN-g dependent fashion.Altogether, we showed the promising therapeutic potential of Imiquimod against toxoplasmosis and characterized P18 role in immunomodulation to control dissemination and interconversion. Our study paves the path towards new therapeutic approaches against toxoplasmosis. It tackled key questions pertaining to establishment, maintenance and reactivation of CT and should result in a comprehensive solution to this endemic disease.

Tras la aparición de la pandemia del COVID-19 y su rápida propagación alrededor del mundo, la industria hotelera ha sufrido la crisis mundial que más la ha afectado, y especialmente el área de alimentos y bebidas ha tenido la mayor cantidad de repercusiones negativas . Es por ello que dicha área se ha visto forzada a aplicar una serie de cambios en su gestión y a diseñar medidas de mejora que le permitan contrarrestar las pérdidas económicas sufridas durante la pandemia y empezar a reactivar progresivamente la funcionalidad del área .La presente investigación tiene como objetivo principal identificar los efectos que ha generado la pandemia COVID-19 en la gestión del área de alimentos y bebidas de los hoteles y las potenciales acciones de mejora que se deben considerar para reactivar el área en el contexto actual. La metodología de investigación utilizada fue la de revisión literaria con enfoque integrador basada en la revisión de diversas fuentes académicas como tesis, libros, y artículos científicos sobre los efectos de la pandemia en la gestión del área de alimentos y bebidas, los cambios en la seguridad alimentaria aplicados en el área y las potenciales medidas de reactivación ante el COVID-19. / Due to the emergence of the COVID-19 pandemic and it’s quick propagation around the world, the hospitality industry has suffered the global crisis that has affected it the most, especially the Food and Beverage area which has suffered a great deal of negative consequences. These consequences have caused the Food and Beverage area to apply a lot of changes in its operations and management and design measurements to soften the huge economic loss during the pandemic, and start to reactivate progressively the area towards a brighter future and recovery. This research paper has as its main objective to identify the effects COVID-19 has caused in the Food and Beverage area of hotels and potential reactivation measurements. The research methodology used in this case is literary review with an integrative approach based on the review of various academic sources such as thesis, books and scientific articles about the effects of the pandemic on the Food and Beverage area, the consequences on food safety and potential reactivation measurements. / Trabajo de investigación