L'enseignement du raisonnement clinique infirmier (RCI) est une préoccupation importante des formateurs en sciences infirmières depuis plusieurs années. Les étudiantes en sciences infirmières éprouvent des difficultés à formuler des hypothèses cliniques, à savoir trouver les explications pouvant justifier la coexistence d'une combinaison de données cliniques. Pourtant, la formulation d’hypothèses constitue une étape déterminante du RCI. Dans cette étude qualitative exploratoire, nous avons mis à l'essai une activité d'apprentissage par vignette clinique courte (AVCC) qui fournit aux étudiantes l'occasion d'exercer spécifiquement la formulation d'hypothèses cliniques. L'étude visait à documenter la capacité d'étudiantes de troisième année au baccalauréat en sciences infirmières à formuler des hypothèses cliniques durant l'activité. Dix-sept étudiantes ont été recrutées par convenance et divisées en groupes selon leurs disponibilités. Au total, quatre séances ont eu lieu. Les participantes étaient invitées à réfléchir à une vignette clinique courte et à construire un algorithme qui incluait: 1) leurs hypothèses concernant la nature du problème clinique, 2) les éléments d'informations essentiels à rechercher pour vérifier chaque hypothèse et 3) les moyens pour trouver ces informations. L'observation participante, l'enregistrement audio-vidéo et un questionnaire auto-administré ont servi à collecter les données. Les stratégies de RCI décrites par Fonteyn (1998) ont servi de cadre théorique pour guider l’analyse, sous forme de matrices comprenant des verbatims et des notes de terrain. Les résultats suggèrent que l'AVCC stimule la formulation d'hypothèses cliniques et la réactivation des connaissances antérieures. Cette activité pourrait donc être utile en complément d'autres activités éducatives pour favoriser le développement du RCI chez les étudiantes en sciences infirmières. / Teaching and learning clinical reasoning has been a major concern amongst nurse educators for many years. Hypothesis generation is a critical milestone in clinical nursing reasoning which students are still struggling with at the end of their program. In a qualitative exploratory study, we tested a vignette-based activity to provide to the students an opportunity to specifically practice hypotheses generation. The study aimed at documenting nursing student’s capacity to formulate hypotheses during the activity. Seventeen nursing students in the last semester of their program were recruited by convenience and grouped accordingly to their availability to participate. The activity was held four times. Participants were asked to focus on a brief clinical vignette and to build an algorithm that would include 1) their hypotheses regarding the nature of the problem, 2) the essential pieces of information to collect in order to verify each hypothesis, and 3) the way the information was to be found. The combined methods used for data collection were participative observation, videotaping the activity and a written questionnaire immediately after the activity. Data were then classified in matrices in the form of verbatim and notes using clinical nursing reasoning skills described by Fonteyn (1998) as the theoretical framework. Results suggest that the vignette-based activity does stimulate students to formulate hypotheses. It also stimulates sharing and recollection of knowledge amongst students. This type of activity could therefore be useful in promoting the development of clinical reasoning as a complement to other educative activities used in nursing education programs.

Dry powder inhalers (DPIs) are commonly used to deliver drugs to the lungs. The drug particles used in these DPIs should possess a number of key properties. These include an aerodynamic particle size < 5μm and particle crystallinity for long term formulation stability. The conventionally used micronization technique to produce inhalation particles offers limited opportunities to control and optimize the particle characteristics. It is also known to induce crystalline disorder in the particles leading to formulation instability. Hence, this research project investigates and optimizes a solvent/anti-solvent crystallization process capable of directly yielding inhalation particles using albuterol sulfate (AS) as a model drug. Further, the feasibility of the process to produce combination particles of AS and ipratropium bromide monohydrate (IB) in predictable proportions and in a size suitable for inhalation is also investigated. The solvent / anti-solvent systems employed were water / ethyl acetate (EA) and water / isopropanol (IPA). Investigation and optimization of the crystallization variables with the water / EA system revealed that particle crystallinity was significantly influenced by an interaction between the drug solution / anti-solvent ratio (Ra ratio), stirring speed and crystal maturation time. Inducing a temperature difference between the drug solution and anti-solvent (Tdrug solution > Tanti-solvent) resulted in smaller particles being formed at a positive temperature difference of 65°C. IPA was shown to be the optimum anti-solvent for producing AS particles (IPA-AS) in a size range suitable for inhalation. In vitro aerosol performance of these IPA-AS particles was found to be superior compared to the conventionally used micronized particles when aerosolized from the Novolizer®. The solvent / anti-solvent systems investigated and optimized for combination particles were water / EA, water / IPA, and water / IPA:EA 1:10 (w/w). IPA was found to be the optimum anti-solvent for producing combination particles of AS and IB with the smallest size. These combination particles showed uniform co-deposition during in vitro aerosol performance testing from the Novolizer®. Pilot molecular modeling studies in conjunction with the analysis of particle interactions using HINT provided an improved understanding of the possible interactions between AS and IB within a combination particle matrix.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

L’interaction dynamique entre le sol et les structures (IDSS) a fait l’objet de nombreuses études sous l’hypothèse de l’élasticité linéaire, bien que les effets de l’IDSS puissent être différents entre un système élastique et un système inélastique. De fait, les méthodologies usuelles développées à partir des études élastiques peuvent ne pas être adaptées aux bâtiments conçus pour dissiper de l’énergie par de l’endommagement lors de séismes sévères. De plus, il est bien connu que la limite d’élasticité du sol est normalement atteinte même pour de séismes relativement faibles. En conséquence, si les effets inélastiques de l’IDSS sont négligés, les études d’endommagement sismique des bâtiments peuvent être très inexactes. L’objectif de ce travail est de développer une stratégie générale pour l’étude du problème de l’IDSS non-linéaire dans le contexte de l’analyse de la vulnérabilité sismique des bâtiments. Ainsi, des modèles d’éléments finis réalistes sont développées et appliquées à des problèmes d’IDSS non-linéaires. Les modèles couvrent une large gamme des conditions pour le sol et des typologies de bâtiments soumis à plusieurs bases de données sismiques. Une stratégie de modélisation a été développée et validée afin de réduire significativement le coût numérique. Pour cela, un modèle 2D équivalent a été développé, implanté dans GEFDyn et utilisé pour effectuer une importante étude paramétrique. De nombreux indicateurs de comportement non-linéaire de la structure et du sol ont été proposés pour synthétiser leur fonctionnement lors du chargement sismique. De surcroît, une stratégie d’évaluation de la vulnérabilité sismique basée sur l’information apportée par une base des données sismiques a été développée. De façon, générale, les résultats ont mis en évidence une réduction de la demande sismique lorsque les effets inélastiques de l’IDSS sont pris en compte. Cette réduction est liée fondamentalement à deux phénomènes : l’amortissement par radiation et l’amortissement hystérétique du sol. Ces deux effets ont lieu simultanément pendant le mouvement sismique. Il est alors très difficile d’isoler l’influence de ces deux phénomènes. En effet, le mouvement effectif transmis à la structure n’est pas le même que celui en champs libre du aux effets d’interaction, ainsi qu’à la modification locale du comportement du sol fortement lié aux poids du bâtiment. Une série de mesures de sévérité sismique et des mécanismes de dissipation d’énergie au niveau du sol et du bâtiment a été introduite dans le but d’analyser ces effets. Cependant, ces résultats sont en général très irréguliers et leur généralisation a été très difficile. Néanmoins, ces résultats mettent en évidence l’importance de la prise en compte des effets du comportement inélastique du sol. La plupart des cas étudiés ont montré un effet favorable de l’IDSS non-linéaire. Mais, en général, l’IDSS peut augmenter ou diminuer la demande sismique en fonction de la typologie de la structure, des caractéristiques du mouvement sismique et des propriétés du sol. Tout de même, il y a une justification économique pour étudier les effets du comportement non-linéaire du sol sur la réponse sismique. / The dynamic interaction of the soil with a superstructure (DSSI) has been the subject of numerous investigations assuming elasticity of both, superstructure and soil foundation behavior. Nevertheless, the effect of DSSI may differ between elastic and inelastic systems. Thus, the current interaction methodologies based on elastic response studies could not be directly applicable to structures expected to behave inelastically during severe earthquakes. Additionally, the soil is known to exhibit inelastic behavior even for relatively weak to moderate ground motions. Consequently, ignoring these characteristics in studying DSSI could lead to erroneous predictions of structural damage. The main purpose of this work is to develop a general strategy to address the full DSSI problem in the context of the seismic vulnerability analysis of structures. Thus, realistic Finite Elements models are constructed and applied in a practical way to deal with these issues. These models cover a large range of soil conditions and structural typologies under several earthquake databases. Some modelling strategies are introduced and validated in order to reduce the computational cost. Therefore, an equivalent 2D model is developed, implemented in GEFDyn and used in the large parametric study conducted. Several indicators for both structural and soil responses are developed in order to synthesize their behavior under seismic loading. Additionally, a vulnerability assessment strategy is presented in terms of measures of information provided by a ground motion selection. According to the investigation conducted in this work, there is in general a reduction of seismic demand or structural damage when non-linear DSSI phenomenon is included. This reduction can be associated fundamentally to two phenomena: radiative damping and hysteretic damping due to non-linear soil behavior. Both effects take place simultaneously during the dynamic load and it is extremely difficult to separate the contribution of each part in reducing seismic demand. Indeed, effective motion transmitted to the superstructure does not correspond to the free field motion because of the geometrical and inertial interactions as well as the local modification of soil behavior, specially due to the supplementary confinement imposed by the superstructure’s weight. A series of strong-motion severity measures, structural damage measures and energy dissipation indicators have been introduced and studied for this purpose. Nevertheless, results are erratic and consequently, generalization was extremely difficult. Despite these difficulties, the results illustrate the importance of accounting for the inelastic soil behavior. The major part of the studied cases show beneficial effects such as the decrease of the maximum seismic structural demand. However, the non-linear DSSI could increase or decrease the expected structural damage depending on the type of the structure, the input motion, and the dynamic soil properties. Furthermore, there is an economic justification to take into account the modification effects due to inelastic soil behavior.

Consommateurs, chercheurs et industriels cherchent de plus en plus à associer à la valeur nutritionnelle des aliments, un effet bénéfique pour la santé. Les aliments caractérisés par des pouvoirs antioxydants élevés semblent correspondre à cette demande. En effet, plusieurs travaux mentionnent les bénéfices santé de ces aliments. Pour répondre à cette demande les industriels mettent en avant ce critère. La fonctionnalité alimentaire, aux bénéfices prometteurs pour la santé publique, reste un concept néanmoins complexe dans la pratique. Ce travail met l’accent sur le fait que les propriétés fonctionnelles d’un aliment ne sont pas directement liées à la composition en ingrédients. L’évaluation du pouvoir antioxydant d'un aliment est dans la plupart des cas réalisée à partir des valeurs des différents ingrédients avant formulation et mise en œuvre des procédés. Pourtant, plusieurs phénomènes sont susceptibles de modifier le pouvoir antioxydant lors de la durée de vie d'un produit alimentaire. D’un point de vue industriel, il est nécessaire de développer une méthode de prédiction de cette activité. Les objectifs de ce travail étaient d’adapter une méthode reproductible et facile à réaliser de quantification du pouvoir antioxydant sur des aliments complexes et de comparer cet index d'un ensemble de produits contenant une large gamme de matières premières. Enfin, a été discuté l’intérêt que représente, dans le domaine des propriétés anti oxydantes, la quantification de l’index créé. Au moment où les industriels vont être amenés à proposer des allégations liées à l’effet bénéfique de l’aliment choisi parmi un échantillon de plus en plus ample / Consumers, researchers and industrialists try more and more to associate with the nutritional value of food, a beneficial effect for the health. Food characterized by high antioxidant powers seems to correspond to this demand. From an industrial point of view, it is necessary to develop methods of predicting this antioxidant capacity. The objectives of this work were to adapt a method reproducible and easy to realize of quantification of the antioxidant power on complex food and to compare this index of a set of products containing a wide range of raw materials. Until now, it has been considered that the use of raw materials characterized by a high antioxidant capacity also leads to a preparation with a high antioxidant activity. We evaluated many of the factors affecting the antioxidant activity of convenience foods (phenol content, effects of formulation, culinary reheating, and preservation) and to provide data on convenience foods consumed by the French population. The total antioxidant capacity of the ethanolic extracts was evaluated by the method of the equivalent Trolox (TEAC) using the radical cation ABTS•+. The concentration of the total phenolic compounds of the same extracts was determined by the Folin-Ciocalteu method. The results show that the food matrix is an important factor for the modulation of activities of antioxidants. A standardised testing protocol for evaluating antioxidative effects is necessary. Then, we discussed the interest of an index, as the industrialists are going to be brought to claim to the beneficial effect of the food chosen among a more and more ample sample

Aim: The aim of this study is to understand what strategies are used over time by a company facing a transgressional CSR crisis, in order to regain legitimacy, and towards which stakeholder group these strategies are directed. Methods: In order to achieve our aim, Qualitative case study based on secondary data published by Volkswagen as well as news articles were used to identify what strategies the company used over time. Results: To be able to answer our aim, different theoretical lenses were used; SCCT response strategies, legitimization strategies, strategy formulation process and stakeholder theory. Therefore, four main different strategies were identified, minimize attribution, blind adaptation to strategy 2025, US differentiation and internal moral reasoning. The former two were addressed to all stakeholders while the latter two were concerned with specific stakeholder groups. Conclusions: Strategy formulation process during a transgressional CSR crisis is a complex procedure and literature on crisis management should move away from static frameworks towards a more dynamic understanding of how strategies can come to life. Coupled with the complexity of societal expectations in general, a company might have to adopt the paradoxical approach even for one stakeholder. Lastly, an addition to Situational Crisis Communication Theory is proposed.

A pele é o maior tecido do corpo humano e está constantemente exposta a inúmeros agentes nocivos, dentre os quais se destaca a radiação ultravioleta (RUV), que está relacionada aos fotodanos do DNA, geração de espécies reativas de oxigênio (EROs) e ativação de mediadores do processo inflamatório. Nestas circunstâncias, mesmo possuindo um sistema de defesa antioxidante, a pele é submetida ao estresse oxidativo devido ao aumento da concentração de radicais livres, o que rompe o equilíbrio próoxidante/ antioxidante. Neste contexto, as substâncias naturais tem sido frequentemente empregadas como ferramenta para enriquecer o sistema protetor cutâneo endógeno, reduzindo, dessa forma, os danos oxidativos causados pela RUV na pele. Sendo assim, o presente trabalho teve como objetivo avaliar o efeito fotoquimioprotetor in vitro e in vivo da fração de média polaridade de Byrsonima crassifolia (BC) e da (+) catequina (CAT), em cultura de queratinócitos humanos e em camundongos sem pelos submetidos à radiação UVB. Comparado ao extrato purificado, a fração de BC apresentou elevada atividade antioxidante in vitro e maiores teores de polifenóis totais e de compostos fenólicos: (+) catequina (255 ± 3,2mg/g de fração), (-) epigalocatequina-3-galato (26 ± 1,68mg/g de fração) e quercetina 3-O-?-D-glicopiranosídeo (12 ± 0,09mg/g de fração). A formulação gel adicionada da fração de BC (1%) proporcionou maior liberação dos compostos fenólicos na pele de orelha de porco do que a formulação emulgel e a CAT foi o composto fenólico majoritário quantificado na epiderme viável da pele de orelha de porco (21,72 ± 5,2?g/cm2). Dessa forma, a formulação gel (1%) adicionada da fração de BC ou CAT foi avaliada também quanto à penetração cutânea in vivo. Na epiderme viável da pele dos camundongos sem pelos detectou-se os compostos fenólicos da fração de BC, bem como a CAT. A avaliação fotoquimioprotetora da fração de BC e da CAT em cultura de queratinócitos demonstrou que ambas as amostras foram capazes de inibir a peroxidação lipídica, a secreção da IL-6 e a redução do NF?B/p65 no citoplasma induzidos pela radiação UVB. Em relação à atividade fotoquimioprotetora in vivo, a fração de BC e CAT foram capazes de evitar/diminuir a depleção dos níveis de GSH, o infiltrado inflamatório e a secreção das citocinas IL-1? e IL-6 induzidos pela radiação UVB. Por outro lado, somente a fração de BC foi capaz de inibir a atividade/secreção da metaloproteinase MMP-9, o que demonstra uma potente atividade fotoquimioprotetora e sugere que o efeito da fração vegetal pode ser superior ao do padrão (+) CAT, já que a fração é composta por uma mistura complexa de substâncias capazes de potenciar a ação dos polifenóis. Estes resultados são promissores e apontam para o uso da fração de BC e da CAT na prevenção/tratamento dos danos induzidos pela radiação UVB na pele. / The skin is the largest tissue of the human body and it is constantly exposed to several harmful agents, such as the ultraviolet radiation (UVR), which is related to the DNA photodamage, generation of reactive oxygen species (ROS) and activation of inflammatory mediators. In these circumstances, even having an antioxidant defense system, the skin is exposed to oxidative stress due to the increase of free radicals concentration, which changes the pro oxidant / antioxidant equilibrium. In this context, natural substances have frequently been employed as a tool to improve the skin´s endogenous protective system, which ultimately decreases the oxidative damage caused by UVR on the skin. Therefore, this study aimed to evaluate in vitro and in vivo photochemoprotective effect of Byrsonima crassifolia (BC) fraction and (+) catechin (CAT) in human keratinocytes culture and hairless mouse against UVB radiation. If compared to the extract, BC fraction showed higher in vitro antioxidant activity and higher total polyphenols content and phenolic compounds: (+) catechin (255 ± 3.2 mg / g fraction), (- ) epigallocatechin-3-gallate (26 ± 1.68 mg / g of fraction) and quercetin 3- O-?-D-glucopyranoside (12 ± 0.09 mg / g of fraction). The gel formulation containing to the BC fraction (1%) provided higher release of phenolic compounds on pig ear skin than the emulgel formulation. It was demonstrated that CAT was the major phenolic compound quantified in the viable epidermis (21.72 ± 5,2?g / cm2).Thus, BC fraction or CAT were incorporated the gel formulation (1%) and in vivo skin penetration was evaluated. On the viable epidermis of mice hairless it was detected the phenolic compounds of the BC fraction, as well as CAT compound. Photochemoprotector evaluation in keratinocytes cell culture showed that both BC fraction and CAT were able to inhibit lipid peroxidation and to decrease the secretion of IL-6 and NF?B / p65 transcription in the cytoplasm. Regarding the in vivo functional activity, BC fraction and CAT were able to prevent/reduce the depletion of GSH levels, the inflammatory infiltrate and IL-1? and IL-6 secretion induced by UVB radiation. On the other hand, only the BC fraction was able to inhibit the activity/secretion of matrix metalloproteinase MMP-9, which illustrate its strong photochemoprotector activity and suggests that the plant fraction effect can be superior to the standard. It can be explained by the fact that the fraction is a complex sample in which several substances are present and these substances can enhance the polyphenol activity. These results are promising and suggest the use of BC fraction and CAT in the prevention/treatment of the damages induced by UVB radiation in the skin.

Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) biotype B is a cosmopolitan, devastating insect pest due to their direct damages and transmission of plant viruses. Entomopathogenic fungi comprise the most diverse group of pathogens regulating arthropod pest populations in agroecosystems. Anamorphic fungal entomopathogens, including Beauveria bassiana, Isaria fumosorosea, and Lecanicillium spp., are among the main biocontrol agents of whitefly populations. Advances in research focusing on virulence, mass production, formulation, and storage stability of fungal propagules are imperative for the development of efficient mycopesticides toward whiteflies and other soft-bodied insects. Therefore, this study placed emphasis on screening for virulent fungal strains, enhancement of efficacy using nonionic surfactants in spray tank-mix, development of liquid culture conditions for rapid production and stabilization processes of single-yeast like cells known as blastospores. Firstly, we selected virulent strains of B. bassiana and I. fumosorosea displaying fastest speed of kill and inciting highest mortality levels of whitefly nymphs and adults along with their ability to produce high numbers of conidia on moistened parboiled rice. Secondly, insecticidal performance was enhanced by combining nonionic surfactants with spore suspensions rendering additive or synergistic effects. These surfactants also allowed reducing the volume application rate without altering fungal bioefficacy. Results from liquid fermentation studies using B. bassiana and I. fumosorosea revealed that appropriate amounts of inexpensive ingredients, such as cottonseed flour and glucose, are suitable for the rapid production of high yields of blastospores (3 days pre-culture and 2-3 days culture). The resultant blastospores of various strains survived well to desiccation and remained viable for more than one year under refrigeration. Moreover, these air-dried blastospores of both fungal species showed higher virulence against whitefly nymphs when compared with solid-substrate produced conidia. Optimized liquid culture production for B. bassiana blastospores was also achieved through the manipulation of oxygen rates and osmotic pressure in the liquid media. Furthermore, these blastospores produced in highly aerated and hyperosmotic liquid medium containing 140 g glucose L-1 were also more virulent to whitefly nymphs than those cells derived from low-osmotic medium amended with 40 g glucose L-1. These optimal conditions were also scaled up in 5-L bioreactor that yielded 1-2 × 1012 viable blastospores L-1 in 6 days at a cost of US$ 0.19 L-1. These blastospores were formulated with diatomaceous earth for air drying or for spray drying. Formulated blastospores of B. bassiana survived dehydration using both drying methods and showed improved shelf life when stored under vacuumpackaged at 4 °C rather than 28 °C. However, when these blastospores were actively packaged with dual action oxygen-moisture scavenging system, blastospores showed prolonged stability for up to 7 months at 28 °C and still remained virulent to whiteflies. Therefore, this low-cost production and stabilization method for the rapid production of shelf stable, virulent blastospores of B. bassiana and I. fumosorosea may expand the commercial use of mycopesticides for insect control in mainstream agriculture. / A mosca-branca, Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) biótipo B, é uma praga cosmopolita e devastadora devido aos prejuízos oriundos dos seus danos diretos e transmissão de vírus. Fungos entomopatogênicos compreendem um grupo diversificado, que desempenha ação importante na regulação de populações de praga em agroecossistemas. Fungos ascomicetos anamórficos, como Beauveria bassiana, Isaria fumosorosea e Lecanicillium spp., constituem relevantes agentes de biocontrole de moscas-brancas. Avanços na pesquisa focando virulência, produção massal, formulação e estabilização de propágulos fúngicos são fundamentais para o desenvolvimento de micopesticidas eficientes contra moscas-brancas e outros insetos. Desta forma, este trabalho objetivou selecionar isolados fúngicos virulentos à mosca-branca; aumentar a eficácia mediante uso de surfactants não-iônicos em suspensões conidiais; desenvolver meios de cultura para produção rápida e estável por fermentação líquida submersa de células leveduriformes conhecidas por blastosporos. Na primeira etapa, isolados virulentos de B. bassiana e I. fumosorosea foram selecionados pela rápida e elevada atividade inseticida a ninfas e adultos de mosca-branca, bem como alto rendimento de conídios em arroz parboilizado. A adição de surfactantes organosiliconados permitiu a redução do volume de calda aplicado com resultados aditivos ou sinérgicos de controle. Foi ainda verificado que altos rendimentos de blastosporos tanto de B. bassiana como I. fumosorosea foram obtidos em curto tempo de fermentação líquida (3 dias de précultivo e 2-3 dias de cultivo) usando nutrientes de baixo custo, como glucose e farelo de algodão. Esses blastosporos foram tolerantes à dessecação e mantiveram viabilidade por mais de um ano sob refrigeração (4 °C). Os blastosporos foram mais virulentos que conídios aéreos, o que coloca esta estrutura como a mais indicada como ingrediente ativo em bioinseticidas para moscas-brancas. Mediante manipulação nutricional e física do ambiente de fermentação, a produção de blastosporos de B. bassiana foi optimizada mediante aumento da aeração e pressão osmótica do meio líquido. Blastosporos produzidos em meio líquido altamente aerado e hiperosmótico (140 g glucose L-1) mostraram-se mais virulentos à mosca-branca em relação àqueles produzidos em meio hipo-osmótico (40 g glucose L-1). Esse processo foi reproduzido em escala piloto usando biorreator de 5 L resultando numa produção de 1-2 × 1012 blastosporos viáveis L-1 em apenas 3 dias a um custo de US$ 0,19 L-1. Blastosporos de B. bassiana formulados com terra de diatomáceas e secados em fluxo de ar contínuo, ou secados em spray dryer tiveram estabilidade extendida por até 8 meses a 4 °C e superior em relação a 28 °C. Durante empacotamento, o uso de sachês absorventes de oxigênio e umidade prolongou consideravelmente a viabilidade de blastosporos armazenados a 28 °C por até 7 meses sem afetar sua eficiência contra mosca-branca. Em suma, esses resultados demonstram a viabilidade técnica e econômica de produção de blastosporos virulentos de B. bassiana e I. fumosorosea, tolerantes à dessecação e estáveis durante armazenamento. Esta tecnologia é uma nova opção que pode contribuir para expansão comercial de bioinseticidas à base de fungos entomopatogênicos.

Fosfoetanolamina sintética (Pho-s) é um monoéster análogo à fosfoetanolamina da membrana celular fosforilada artificialmente, com propriedades antiinflamatórias e apoptóticas para vários tipos de células tumorais humanas e murinas. Neste projeto foram avaliados os efeitos antitumorais in vitro da Pho-s e da formulação lipossomal DODAC/Pho-s na linhagem tumoral de leucemia mielóide crônica humana (K-562), em comparação ao modelo resistente a múltiplas drogas K-562 Lucena (MDR+). Os efeitos de citotoxicidade da Pho-s na linhagem tumoral K-562 e K-562 Lucena (MDR+) foram avaliados pela viabilidade celular utilizando o teste da Sulforodamina B, e os valores da IC50% obtidos foram de 43.1 mM e 145.9 mM, respectivamente após 24 horas de tratamento. O tratamento com o carreador DODAC vazio nas células K-562 e K-562 Lucena (MDR+) a IC50% foi de 0,0003mM e 0,008mM respectivamente, e com o tratamento com a formulação lipossomal DODAC/Pho-s a IC50% obtida respectivamente de, 0,56 mM e 0,31 mM. A viabilidade celular foi determinada a exclusão pelo azul de tripan 0,2%, em sistema automatizado Vi-Cell e foram significativas as diminuições da viabilidade celular em comparação ao grupo controle não tratado nas diversas concentrações e em diferentes períodos de tempo de tratamento. As alterações nas distribuições nas populações celulares nas fases do ciclo celular determinadas por citometria de fluxo mostraram aumento do DNA fragmentado (Sub/G1) em 12 e 24 horas de tratamento. Atividade apoptótica das células tumorais pela expressão da Anexina V/PI, no estágio de apoptose inicial, apoptose tardia e necrose foram quantificadas em citometria de fluxo, o tratamento com Pho-s, quando comparado ao grupo controle K-562 (40 e 80 mM) e K-562 Lucena (MDR+) (146 e 292 mM) ocorreu aumento significativo do número de células apoptóticas e em menor percentual o número de células necróticas. O tratamento com a Pho-s em célula leucêmica K-562 e K-562 Lucena (MDR+) tratadas, respectivamente com 40 e 80 mM e 146 e 292 mM mostraram que independente da expressão do fenótipo de resistência há uma redução significativa no potencial elétrico mitocondrial, analisado pelo o ensaio da rodamina-123. Os marcadores de controle e progressão do ciclo celular e da apoptose, mostraram efeitos moduladores da Pho-s dependentes da p53 na expressão da moléculas pró-apoptóticas. Esse conjunto de informações demonstrou os efeitos apoptóticos da Pho-s e da formulação lipossomal nas células tumorais independentemente do perfil molecular de resistência (MDR+), o que possibilita dizer que esse composto possui significativo potencial terapêutico nesse grupo de leucemias / Synthetic phosphoethanolamine (Pho-s) is a monoester analogous to the phosphoethanolamine which composes the membrane of an artificially phosphorylated cell, with anti-inflammatory and apoptotic properties for various types of human and murine tumor cells. In this project, we evaluated in vitro antitumor effects of Pho-s and the DODAC/Pho-s liposomal formulation in the human chronic myeloid leukemia (K-562) tumor line in comparison with the K-562 Lucena (MDR+). The effects of cytotoxicity of Pho-s on K-562 and K-562 Lucena (MDR +) tumor cells lines were evaluated by cell viability using the Sulforhodamine B test, and the IC50% values obtained were 43.1 mM and 145.9 mM after 24 hours of treatment, respectively. Treatment with the empty DODAC carrier on the K-562 and K-562 Lucena (MDR+) at IC50% cells was 0.0003 mM and 0.008 mM, and the treatment with the DODAC/Pho-s liposomal formulation obtained results of 0.56 mM and 0.31 mM, respectively. Cell viability was determined by 0.2% trypan blue exclusion in automated Vi-Cell system and the decreases in cell viability were significant in comparison to the untreated control group at various concentrations and different treatment time periods. Alterations in the distributions of cell populations in the cell cycle phases determined by flow cytometry showed increment of fragmented DNA (Sub/G1) in 12 and 24 hours of treatment. Apoptotic activity of tumor cells by the expression of Annexin V/PI, in the early apoptosis, late apoptosis phase and necrosis stage were quantified in flow cytometry, the treatment with Pho-s, when compared to the control group K-562 (40 and 80 mM) and K-562 Lucena (MDR +) (146 and 292 mM) demonstrated that there was a significant increase in the number of apoptotic cells and, in a lower percentage, the number of necrotic cells. Treatments with Pho-s in leukemic cell K-56 with 40 and 80 mM and in K-562 Lucena (MDR+) with 146 and 292 mM showed that independent of the expression of the resistance phenotype there is a significant reduction in the electrical potential of the mitochondrial membrane, analyzed with the rhodamine-123 assay. Control and progression markers of cell cycle and apoptosis showed p53-dependent modulating effects on the expression of pro-apoptotic molecules. This set of information demonstrated the apoptotic effects of Pho-s and liposomal formulation on tumor cells independently of the molecular resistance profile (MDR+), which makes it possible to say that this compound has significant therapeutic potential in this group of leukemias

Este trabalho insere-se no âmbito das formulações não convencionais em elementos finitos. Particularmente, introduzem-se alguns aspectos do método dos elementos finitos generalizados (MEFG) e do clássico refino-p na consagrada formulação híbrida-Trefftz de tensão para a elasticidade bidimensional. A formulação apresentada aproxima diretamente dois campos independentes: o de tensões no domínio dos elementos e o de deslocamentos nas fronteiras dos elementos. Baseado na estrutura de enriquecimento centrada em nuvens, proposta pelo MEFG, podem ser selecionadas oportunamente regiões, formadas por um conjunto de elementos e fronteiras de elementos, onde o espaço da aproximação é adequadamente enriquecido mediante o refino-p. Neste contexto campos auto-equilibrados de tensões, derivados da solução da equação de Navier, são utilizados para compor a aproximação no domínio dos elementos, enquanto nas fronteiras dos elementos o campo de deslocamentos é construído a partir de bases específicas de aproximação; seja a base inicial, formada por funções de forma lineares, ou bases enriquecidas com polinômios hierárquicos, não hierárquicos e funções trigonométricas. Aborda-se também, ainda que preliminarmente, um estudo de painéis com múltiplas fissuras pelo método da partição em formulação híbrida-Trefftz com enriquecimento seletivo. As análises numéricas realizadas revelaram, em geral, uma formulação de ótimo desempenho, caracterizada por uma notável capacidade de aproximação dos campos de tensões e deslocamentos, elevada robustez numérica e reduzido dispêndio computacional. / This work is inserted in the context of unconventional formulations in the finite elements method. Particularly, some aspects of the generalized finite elements method (GFEM) and the classic p-refinement are introduced in the well known hybrid-Trefftz stress formulation for the two dimensional elasticity. The presented formulation approximates two independent fields: the one of stresses in the elements domain and the one of displacements in the boundaries of the elements. Based on the enrichment structure centered in clouds, proposed by the GFEM, some regions, formed by a group of elements and boundaries of elements where the approximation space is adequately enriched by the p-refinement, can be opportunely selected. In this context, self-equilibrated stress fields, derived from the solution of the Navier equation, are used to compose the approximation in the elements domain, whereas the displacements field in the borders of the elements is built from specific approximation bases, that is, the initial base formed by linear shape functions, or, bases enriched with hierarchical polynomials, nonhierarchical ones and trigonometric functions. Also, although preliminarily, a study of the multiple-cracked panels is done using the Splitting Method with a hybrid-Trefftz formulation and a selective enrichment. The numeric analyses done revealed, in general, a high performance formulation characterized by a great capacity of approximation the stress fields and displacements, high numeric robustness and reduced computer expenditure.