Depuis quelques années, le béton connait une période de mutation. Les tendances actuelles concernant la formulation des bétons à hautes performances et à faibles impacts environnementaux montrent que la fraction volumique solide est de plus en plus élevée. Cette augmentation de la fraction volumique solide est cependant difficilement compatible avec une fluidité importante. La thèse présentée ici a donc pour but de proposer des solutions permettant de contourner le problème de viscosité des ces nouveaux bétons. Nous nous attachons ainsi à identifier les mécanismes d'action de certains polymères à l'origine d'une diminution de la viscosité macroscopique de pâtes de ciment concentrées. Les polymères que nous étudions appartiennent à deux familles différentes : les super plastifiants et les agents entraîneurs d'air. Alors que le chapitre 1 a pour objectif d'expliquer le contexte actuel et de justifier l'intérêt des recherches menées durant cette thèse, le chapitre 2 présente les procédures expérimentales utilisées. Nous proposons des protocoles permettant de faire la distinction entre les effets des polymères étudiés sur la contrainte seuil et leurs effets sur l'autre paramètre du comportement :la viscosité. Dans le chapitre 3, nous mettons en évidence certains mécanismes d'action des polymères adsorbants de type super plastifiants. Nous observons que deux polymères peuvent avoir un effet différent sur la dissipation visqueuse d'une pâte de ciment pour une contrainte seuil donnée. Nous suggérons alors que les molécules de polymère adsorbé modifient l'état de floculation du système, et donc la façon dont le cisaillement se concentre entre les grains. Dans le même temps, les molécules de polymère non adsorbé modifient la viscosité du fluide interstitiel. La viscosité macroscopique résulte alors de la compétition entre ces deux mécanismes. Dans le chapitre 4, nous nous intéressons aux effets des agents entraîneurs d'air. Grâce à des mesures sur pâtes de ciment et mortiers, nous montrons que, suivant la consistance du système étudié, l'entraînement d'air peut diminuer ou non la viscosité. Nous suggérons qu'un tel comportement trouve son origine dans la compétition entre la tension de surface qui tend à empêcher la déformation des bulles et la consistance du système en écoulement qui tend à les déforme / The concrete industry has been undergoing significant change in recent years. Current trends in mix design of high strength and environmentally friendly concretes show that solid volume fraction is progressively increasing. This increase in solid volume fraction is however not compatible with an adequate fluidity. The aim of the work presented here is thus to bring solutions to the high viscosity of these new concretes. We try to identify potential mechanisms of action of some polymers at the origin of a decrease in the macroscopic viscosity of concentrated cement pastes. We focus here on two types of polymers: super plasticizers and air entraining agents. In a first chapter, we explain the current economic, social and industrial situation and justify the need of the research work presented here. In a second chapter, we show the importance of the experimental procedure. We suggest protocols from which the effects of tested polymers on the viscosity parameter can be distinguished from the effects on yield stress. In a third chapter, we show some potential mechanisms of action of adsorbing polymers as super plasticizers. We observe that for the same effect on yield stress, viscous dissipation of cement pastes can be different for the two tested polymers. We suggest that adsorbed polymer molecules modify the flocculation state of the system and thus the way shear concentrates between cement grains. In the same time, non adsorbed polymer molecules modify the viscosity of the interstitial fluid. Therefore, the macroscopic viscosity results from the competition of the two above phenomena. In the fourth chapter, we are interested in the effects of air entraining agents. Thanks to experimental measurements on cement pastes and mortars, we show that according to the system consistency, air entrainment can increase or decrease viscosity. We suggest that such a behaviour finds its origin in the competition between surface tension, which tends to prevent air bubble deformation and the system consistency, which tends to deform the same air bubbles

La Thérapie par Substitution de Surfactant (TSS), qui opère par instillation d’une solution de surfactant directement dans l’arbre bronchique, est un traitement essentiel chez les nouveau-nés souffrant de syndrome de détresse respiratoire (SDRN). Cette procédure s’est révélée remarquablement efficace chez les grands prématurés, contribuant à la division par cinq de leur mortalité depuis les années 1980. À l’inverse, son utilisation s’est avérée décevante chez l’adulte dans le traitement du syndrome de détresse respiratoire aigu (SDRA), se soldant par un échec après des premiers essais pourtant prometteurs.Dans cette thèse, nous présentons un modèle mathématique et numérique de la propagation de bouchons liquides dans le système pulmonaire aérien de mammifères. Dans ce but, nous commençons par créer des modèles d’arbres trachéobronchiques chez le rat, le cochon ou l’homme. Ces modèles sont définis non seulement par leurs propriétés d’échelle mais également par leur structure tridimensionnelle indispensable à la simulation du transport liquidien. Les géométries ainsi créées sont comparées aux données morphométriques de la littérature.Nous présentons ensuite le modèle mathématique du transport liquidien. La principale propriété de ce modèle réside dans la décomposition de la propagation de bouchons liquides en deux étapes élémentaires fondamentales : (1) le dépôt de liquide sur les parois bronchiques lors de la propagation d’un bouchon, et (2) la division du bouchon liquide à chaque bifurcation de l’arbre. Les équations du processus de séparation sont déduites de la conservation de l’impulsion, pour tout type de bifurcation asymétrique. Cette décomposition en deux étapes élémentaires nous permet de calculer de manière efficace et rapide la propagation du surfactant dans l’intégralité de l’arbre aérien, fournissant ainsi un véritable outil de conception en génie biomédical.Ce modèle numérique est tout d’abord exploité pour calculer l’administration de surfactant chez le rat. Les rôles respectifs du volume initial, du débit et de l’injection multiple sont examinés. Nos résultats de simulations se révèlent être en bon accord avec les données de la littérature. En particulier, nous mettons en évidence le rôle joué par l’architecture monopodiale du rat qui contribue à la faible homogénéité de la distribution finale de surfactant. On observe également la forte non linéarité de la quantité de surfactant distribuée dans les acini en fonction du volume initial, en raison du dépôt d’une fraction de ce volume sur les parois bronchiques (le coût de dépôt). Des simulations de l’administration chez le cochon font apparaître les mêmes propriétés, avec cette fois une sensibilité accrue à la taille du poumon. Les effets respectifs de la gravité et de la tension de surface ne varient en effet pas suivant les mêmes lois d’échelle, ce qui se traduit par une distribution extrêmement inhomogène à bas débit ou à faible volume.Enfin, chez l’homme, notre modèle montre que l’origine de l’échec de la TSS chez l’adulte est possiblement à chercher dans la mécanique des fluides, l’accroissement du coût de dépôt aggravant la non-linéarité de l’administration. Cet effet peut être contré soit en instillant le surfactant à plus faible débit (mais au prix d’une distribution finale fortement inhomogène), soit en augmentant le volume initial. Nos résultats montrent en outre que, même pour des tailles comparables, les géométries très différentes de l’homme et du cochon ne permettent pas de traduire directement pour le premier les résultats obtenus chez le second. Un modèle fiable de l’administration est donc indispensable pour prédire l’efficacité de la TSS à partir de modèles animaux.En conclusion, cette thèse propose un nouvel outil permettant de prédire l’administration de surfactant chez l’animal et chez l’homme, de comprendre le rôle éventuel des modèles animaux, et en définitive de concevoir et d’optimiser de manière individualisée la TSS pour le patient. / Surfactant Replacement Therapy (SRT), which involves instillation of a liquid-surfactant mixture directly into the lung airway tree, is a major therapeutic treatment in neonatal patients with respiratory distress syndrome (NRDS). This procedure has proved to be remarkably effective in premature newborns, contributing to a five-fold decrease of mortality since the 1980s. Disappointingly, its use in adults for treating acute respiratory distress syndrome (ARDS) experienced initial success followed by failures.In this PhD thesis, we present a mathematical and numerical model for the propagation of a liquid plug into the pulmonary airway system of mammals. To that intent, we first create realistic geometrical models of the tracheobronchial trees of mammals, rat, pig, and human, defined not only by their scaling properties but also by their 3D spatial embedding (i.e., branching and rotation angles), a description necessary for simulating liquid transport. The resulting geometries are compared with the available quantitative morphometric measurements found in the literature.We then introduce the mathematical model describing liquid plug transport. The main feature of this model is to decompose the propagation of liquid plugs in two fundamental elementary steps: (1) liquid deposition onto the airway walls during the propagation of a plug into a single airway, and (2) plug splitting at each bifurcation between two consecutive generations. The equations for the splitting process are derived from momentum conservation considerations, for any type of asymmetric bifurcation and any orientation with respect to gravity. The decomposition of the transport of liquid plugs into these essential steps allows us to compute efficiently and rapidly the propagation of surfactant into the entire airway tree, thus creating a truly biomedical engineering design tool.This mathematical and numerical model is first used to compute surfactant delivery into realistic asymmetric conducting airway trees of rat lung. The roles of dose volume, flow rate, and multiple aliquot deliveries are investigated. We find that our simulations of surfactant delivery in rat lungs are in good agreement with experimental data. In particular, we show that the monopodial architecture of the rat airway trees plays a major role in surfactant delivery, contributing to the poor homogeneity of the end distribution of surfactant. We also observe that increasing the initial dose volume increases in a nonlinear way the amount of surfactant delivered to the acini after losing a portion to coating the involved airways, the coating cost volume. Simulations of delivery in pig lungs exhibit the same general features, but our model demonstrates that SRT is very sensitive to the lung size. Surface tension and gravity effects do not scale similarly, and the end distribution can become highly nonhomogeneous at smaller flow rates or small dose volumes.Finally, in the human lung, our model shows that the failure of SRT in adults could, in fact, have a fluid mechanical origin that is potentially reversible. The coating cost is predicted to increase in adult lungs, enhancing the nonlinearity of the delivery process. This effect can be countered either by instilling the surfactant mixture at a smaller flow rate (but then the distribution is highly nonhomogeneous) or by using a larger dose volume. In addition, our results show that, even if sizes are comparable, the very different geometrical structures of pig and human lungs do not permit a direction translation of experimental results in pigs to humans, and that a reliable mathematical model of the delivery is absolutely crucial if one wants to predict the efficacy of SRT from animal models.In conclusion, this thesis provides a tool for predicting surfactant delivery in animals and humans, for understanding how to build animals models of SRT, and finally for engineering and optimizing patient-specific surfactant delivery in complex situations.

Les mutations du gène codant pour la protéine C (SP-C) du surfactant pulmonaire (SFTPC) sont à l’origine de pathologies interstitielles chroniques du nourrisson, de l’enfant mais également de l’adulte. Une importante hétérogénéité phénotypique est cependant observée, y compris au sein d’une même famille. Par un épissage alternatif, le gène SFTPC permet la synthèse de deux isoformes du précurseur protéique de SP-C (proSP-C) pour aboutir à la protéine mature après plusieurs modifications post-traductionnelles. Les conséquences des mutations de SFTPC sur l'homéostasie du surfactant ne sont pas clairement élucidées, mais il semble que le mauvais repliement de la protéine soit une caractéristique commune. A l’issue de nos travaux antérieurs, nous avons mis en évidence un effet de certaines mutations et de polymorphismes sur l’épissage de SFTPC faisant ainsi varier significativement l’expression de chacune des deux isoformes protéiques, sans qu’à l’heure actuelle nous ne connaissions le rôle de chacune dans la synthèse de la protéine SP-C mature. Notre projet, s’inscrivant dans la continuité de mon master 2, a pour but de mieux comprendre les mécanismes physiopathologiques pré et post-transcriptionnels associés aux variations de SFTPC et leurs conséquences sur le développement des pneumopathies interstitielles. Le premier axe de notre projet repose sur l’étude in vitro (lignées cellulaires) et in vivo (modèle murin, ARN des patients) des variations de chacun des isoformes. Dans un second axe, nous souhaitons poursuivre l'étude de facteurs pouvant influencer le phénotype des patients porteurs de mutations du gène SFTPC, qu'ils soient d'origine externes (infections virales et bactériennes ou environnementaux comme le tabac) ou génétique. Collectivement, ces études nous permettrons de fournir une signature moléculaire pour cette maladie et d’identifier de nouvelles cibles thérapeutiques afin d’en améliorer le pronostic mais également la prise en charge et la qualité de vie des patients. / Surfactant pathologies linked to mutations in the SFTPC gene, via autosomal dominant transmission, are most commonly associated with diffuse interstitial diseases in infants, children and adults, and may also be responsible for acute respiratory distress syndrome in newborns. They are most often accompanied by a high morbidity and mortality rate, thus rendering early diagnosis essential for ideal intervention and support. Mutations in the SFTPC gene lead to alveolar and intracellular accumulation of an abnormal form of the precursor protein SP-C (ProSP-C), which is responsible for the resulting tissue damage. However, the pathophysiological mechanisms are not yet completely deciphered. The gene encodes two isoforms of ProSP-C from three alternative transcripts. The expression level of each is currently unknown and the vast majority of studies evaluating the effect of mutations are performed on only one isoform. Incidentally, our preliminary results on the analysis of RNA extracted from bronchoalveolar washing, both from control subjects and patients harboring a mutation, show that the all three SFTPC transcripts are expressed and that the presence of a mutation is associated with a variation in the expression levels of the transcripts. The aim of my project is to study the expression level of SFTPC transcripts and ProSP-C isoforms from the heterologous expression of the SFTPC gene (exons and introns) in cell lines. I will beanalyzing the post-translational maturation profile of these pro-proteins and evaluating the effect of the mutations on their expression and maturation in both our cellular models and in vivo with two Knock-in mice models.A better understanding of the pathophysiology of genetic abnormalities associated with mutations in the SFTPC gene will not only greatly contribute to earlier management of patients, but also it will help in modifying the progression of lung injury and its prognosis.

There is limited research on High Surfactant Oil Concentrates (HSOC), so studies were conducted for their evaluation. Multiple MSO-based (HSMOC) and POC-based (HSPOC) HSOCs were tested with glyphosate plus dicamba or glyphosate plus tembotrione. The addition of HSMOCs provided greater indicator species control HSPOCs when added to either herbicide tank-mix. When multiple experimental oil to surfactant ratios were added to glyphosate plus dicamba or glyphosate plus tembotrione, there were no differences among experimental HSOC ratios when added to either tank-mix by 28 days after application. Since oil adjuvant rates can be based on either treated area or percent of spray solution, oils were added to either dicamba or tembotrione to evaluate rate methods. There were few differences in species control when oils were added to dicamba. Quinoa and amaranth control were more consistent when using the percent volume-based rates with tembotrione.

No description available.

The sizes of nonionic reverse micelles were investigated as a function of the molecular structure of the surfactant, the type of oil, the total concentration of surfactant [NP], the ratio of NP4 to total surfactant (r), the water to surfactant molar ratio (ω), temperature, salt concentration, and polar phase. The basis of our investigation was nonylphenol polyethoxylates - NP4 and NP7. Micelle sizes were determined using dynamic light scattering (DLS). A central composite experimental design was used to quantitatively model reverse micelle size as a function of ω, [NP], and r. The model has demonstrated the capability of predicting the mean diameter of micelles from 4 to 13 nm with a precision of ± 2 nm as measured by DLS. This quantitative correlation between the size of reverse micelles and the synthetic variables provides the foundation for choosing experimental conditions to control reverse micelle size.

O final do período gestacional é marcado por importantes processos que caracterizam a maturação pulmonar fetal, dentre os quais destacam-se alterações estruturais, como a expansão das áreas de troca gasosa; e funcionais, tais como o aumento na produção de surfactante, cuja principal função é reduzir a tensão superficial na interface ar-líquido alveolar, evitando o colapso dos alvéolos na fase final da expiração. Estudos realizados em diferentes espécies animais indicam a influência de fatores endócrinos, incluindo os glicocorticóides, no desenvolvimento pulmonar fetal e transição para a vida extra-uterina. Até o momento, não há estudos na espécie canina, com o objetivo primordial de avaliar a ação da corticoterapia materna na melhora da função pulmonar. Desta forma, são objetivos deste estudo identificar as alterações morfométricas e funcionais pulmonares de neonatos pré-termos e termos submetidos à corticoterapia materna pré-natal e correlacioná-las à melhora da função pulmonar no período neonatal. Para tanto, 25 neonatos da espécie canina, nascidos por cesariana programada, foram alocados aleatoriamente em 2 grupos: Grupo Controle (CONT) (sem corticoterapia materna; n=15) e Grupo Betametasona (BETA) (corticoterapia materna aos 55 dias de gestação; n=10), por aplicação de betametasona (Celestone Soluspan®) em dose única de 0,5 mg/Kg de peso materno, por via de administração intra muscular (IM). No grupo Controle, os neonatos foram avaliados aos 55, 57 e 63 dias de gestação, enquanto no Grupo Betametasona, aos 57 e 58 dias de gestação. Perfez-se a avaliação clínica por escore Apgar, hemogasometria e radiografia pulmonar. Ainda, as modificações pulmonares estruturais e funcionais foram verificadas por análise morfométrica e imunoistoquímica para detecção do número de pneumócitos tipo II produtores da proteína B do surfactante (SP-B) no parênquima pulmonar. Houve melhor evolução clínica nos neonatos pertencentes ao grupo BETA 57 já aos 60 minutos de vida. Os valores de freqüência cardíaca foram estatisticamente maiores nos grupos tratados e controle termo, em comparação ao grupo CONT 57. O escore de freqüência e padrão respiratórios foi estatisticamente superior nos grupos BETA 57 e CONT 63, seguido pelo grupo BETA 58. Valores estatisticamente semelhantes de irritabilidade reflexa foram observados entre os grupos tratados e termo. Do nascimento aos 60 minutos de vida não houve diferença estatística na avaliação do tônus muscular entre os grupos, com valores significativamente superiores aos 240 minutos de vida nos grupos tratados e controle termo. Os neonatos do grupo CONT 63 apresentaram escore de mucosas aparentes da avaliação Apgar estatisticamente superior em relação aos demais grupos ao nascimento, com valores estatisticamente iguais aos grupos tradados e CONT 57 aos 60 minutos de vida. Ao nascimento e após 2 horas de vida, todos os neonatos apresentaram acidemia, com melhor resposta compensatória ao desequilíbrio ácido-básico no grupo BETA 58. Houve maior septação nos grupos tratados e controle termo, em relação aos demais grupos. Um percentual estatisticamente superior de alveolização foi observado no grupo CONT 63, seguido pelo grupo BETA 58. Um menor percentual de sáculos foi identificado no grupo CONT 63 seguido pelos grupos BETA 57 e CONT 55. Não evidenciou-se diferença estatística quanto ao número de pneumócitos tipo II marcados para a proteína SP-B entre os grupos tratados e CONT 57. A avaliação radiográfica mostrou menor percentual de broncograma aéreo, bem como áreas de atelectasia, no grupo BETA 57, associado à melhor visualização do parênquima pulmonar. Em conclusão, a administração de betametasona materna no período pré-natal induz alterações estruturais do parênquima pulmonar, resultando em melhores valores de escore Apgar. Houve melhor resposta compensatória nos grupos tratados, reflexa ao aumento da capacidade de troca gasosa pulmonar. Não foi possível identificar aumento na síntese de surfactante pulmonar entre os grupos, em resposta à administração pré-natal de betametasona. / The final gestational period is marked by an important processes that characterize the lung fetal maturation, like structural changes such as expansion of the areas of gas exchange, and functional changes, such as increased production of surfactant, whose main function is to reduce the surface tension in the air-liquid interface alveolar, preventing the alveoli from collapsing during late expiration. Studies in different species indicate the influence of endocrine factors, including glucocorticoids in fetal lung development and transition to extrauterine life. Up till now, there is not studies in dogs, with the primary objective to evaluate the action of maternal corticosteroid therapy in improving lung function. Thus, the objectives of this study was to identify morphological changes in lung function in preterm and terms neonates submitted to prenatal maternal corticosteroids and correlate them to the improvement in lung function during the neonatal period. For it 25 canine neonates, born by scheduled cesarean section, were randomly divided into 2 groups: control group (CONT) (no maternal corticosteroid therapy, n = 15) and Group betamethasone (BETA) (maternal corticosteroid therapy at 55 days gestation; n = 10), by application of betamethasone (Celestone Chronodose Injection ®) in a single dose of 0.5 mg / kg of maternal weight, route of administration by intra-muscular (IM). Control group neonates were evaluated at 55, 57 and 63 days of gestation, and the betamethasone group, at 58 and 57 days of gestation. The clinical assessment was made by Apgar score, blood gas and pulmonary radiography. Still, the structural and functional lung changes were verified by morphometric analysis and immunohistochemistry to detect the number of type II pneumocytes producers surfactant protein B (SP-B) in the lung parenchyma. There was better clinical outcome in the groups BETA 57 at 60 minutes of life. The values of heart rate were significantly higher in term treatment and control groups compared to the group CONT 57. The score of respiratory frequency and pattern was statistically higher in groups BETA 57 e 63 followed by the group BETA 58. Statistically similar reflex irritability were observed between the treated groups and term. From birth to 60 minutes of life there was not statistical difference in the assessment of muscle tone between the groups, with significantly higher values at 240 minutes of life in term treatment and control groups. Neonates of CONT 63 has mucous apparent assessment of Apgar statistically superior to other groups at birth, with values statistically equal to tratads and group CONT 57 at 60 minutes of life. At birth and after 2 hours of life, all neonates had acidemia, with better compensatory response to acid-base balance in the group BETA 58. There was an increased septation in treated and control groups comparing other groups. A statistically higher percentage of alveolarization was observed in group CONT 63, followed by the group BETA 58. A lower percentage of saccules was identified in the group CONT 63 followed by groups BETA 57 and CONT 55. There was not statistical differences in the number of type II pneumocytes marked for protein SP-B between the treated groups and CONT 57. The radiographic evaluation showed a lower percentage of air bronchogram, and atelectasis in the group BETA 57, associated with better visualization of the pulmonary parenchyma. In conclusion, maternal administration of betamethasone in prenatally period induced structural changes of the lung parenchyma, resulting in higher values of Apgar score. There was greater compensatory response in the treated groups, the reflex of an increase capacity of pulmonary gas exchange. It was not possible to indentify increases synthesis of surfactant between the groups in response to prenatal administration of betamethasone.

O monocloroacetato de sódio (MCAS) e o dicloroacetato de sódio (DCAS) são compostos tóxicos e irritantes ao ser humano e nocivos ao meio ambiente, sendo impurezas indesejáveis na cocoamido propil betaína (CAPB), que é um surfactante anfótero utilizado em produtos de consumo dos segmentos cosmético e domiciliar. Diante dos requisitos de concentração em nível de mg/kg exigidos pelos órgãos reguladores de saúde do governo, tornou-se mandatório o emprego de metodologia com limite de quantificação, precisão e exatidão adequados aos rígidos controles de processo pelos fabricantes da CAPB, bem como, dispor de técnicas convencionais com poder de resolução e proficiência pelo controle de qualidade e neste contexto inseriu-se a cromatografia a gás. Neste estudo foram estabelecidos os procedimentos analíticos que definiram as melhores condições para identificar e quantificar as impurezas MCAS e DCAS na matriz CAPB por meio da cromatografia a gás. A preparação das amostras consistiu da derivação das impurezas MCAS e DCAS a ésteres etílicos e a extração líquido-líquido em hexano para separar dos demais constituintes da matriz. Os modos de detecção acoplados à cromatografia a gás foram a ionização pela chama (GC/FID), a captura de elétrons (GC/ECD) e a espectrometria de massas (GC/MS). A validação comprovou que as metodologias são lineares entre 4 e 50 mg/kg com recuperação de 70 a 120%, apresentam limites de quantificação inferiores a 10 mg/kg e produziram médias e incertezas similares na amostra examinada, constituindo-se alternativas para a determinação de cloroacetatos em betaínas. / The sodium monochloroacetate (MCAS) and the sodium dichloroacetate (DCAS) are toxic and irritating compounds to humans and harmful to the environment, being undesirable impurities in cocoamidepropyl betaine (CAPB), which is a amphoteric surfactant used in consumer products of cosmetic and household segments. Considering the content requirements at level mg/kg defined by governmental health agency, became mandatory the use of analytical methods with appropriate precision, accuracy and quantification limit to rigid process controls by CAPB manufacturers, as well as, to have available conventional techniques with good resolution and proficiency for quality control staff and in this context was inserted the gas chromatography. In this study, the analytical procedures were established to define the best conditions to identify and quantify the impurities MCAS and DCAS in CAPB matrix by gas chromatography. The sample preparation consisted of MCAS and DCAS derivation to ethyl esters and liquid-liquid extraction in hexane to separate them from the other constituents of matrix. The detection modes coupled to gas chromatography were the flame ionization (GC/FID), electron capture (GC/ECD) and mass spectrometry (GC/MS). The validation ensured that the methodologies are linear between 4 and 50 mg/kg with recovery 70 to 120%, presents quantification limits less than 10 mg/kg and produced similar averages and uncertainties in the examined sample, constituting an alternative for determination of chloroacetates in betaines.

In this work we have explored the possibility of using surfactant/polyelectrolyte complexes as templates to synthesize inorganic mesostructured materials mainly with a film morphology. Inorganic species deposit in those regions of the films which are filled with a polymer hydrogel, surrounding the arrays of ordered surfactant micelles. This method produced thick robust films where the inorganic regions are reinforced and functionalized by the polymer, thus these materials are expected to have potential applications in separation, absorption, catalysis and chemical sensing. Initial work involved mixing silicate precursors directly into CTAB/PEI solutions to form highly ordered 2D hexagonal silica films at the air/water interface. Time resolved synchrotron SAXS allowed investigation of processes occurring in solution during the reaction, from which a film growth mechanism was proposed. Films had good thermal properties and after post-synthesis TMOS vapour treatment, retained structure upon template removal. Silica gel monoliths with various mesostructures were also rapidly fabricated in one minute with surfactant/LPEI complexes. Cat-ionic surfactant mixtures with polymers were also employed to template silica films with different cubic mesostructures at the air/water interface. The mesophases of the interfacial films were enriched due to more complicated interactions between the polymers and two surfactants. Polymer molecular weight, total composite concentration, chemical nature of the polymer as well as the cationic-anionic surfactant molar ratio was used to systematically control the silica film mesophase. Robust titania films were also prepared with cat-anionic surfactant mixtures and polymers at the air/water interface. Although the film mesostructure was lost after calcination, the in-situ and dry free-standing films display ordered cubic mesostructures and the films are stable to calcination after post-synthesis treatment. Ordered lamellar iron oxide films templated by SDS/LPEI complexes were also prepared at the air/water interface.

Glioblastoma Multiforme (GBM) is an extremely aggressive grade IV brain tumour that is highly infiltrative and can spread to other parts of the brain quickly. It is the most common primary brain tumour where patients have a median survival of 14.6 months. Symptoms vary depending upon the location of the tumour and include seizures, progressive headaches and focal neurological deficit. The poor prognosis is characterised by deregulation of many key signalling pathways involving survival, growth, apoptosis and evasion of immune surveillance. In this study, we investigated whether complement factor H related protein 5 (CFHR5) from primary GBM cells direct from patients exhibited functional activity similar to factor H. The presence of CFHR5 was validated by western blot and ELISA technique from B30, B31 and B33 primary GBM cells. The functional capacity of CFHR5 was examined through the alternative pathway, co-factor, and decay acceleration assay. We demonstrated that CFHR5 was able to inhibit the alternative pathway through the same mechanism as factor H. Emerging evidence had shown that the innate immune protein surfactant protein D (SP-D) and recombinant human SP-D (rhSP-D) were able to induce apoptosis in eosinophilic leukaemic cells. We studied the ability of rhSP-D to induce apoptosis in U87 GBM cells through apoptotic and viability assays. rhSP-D was unable to mediate cell death and instead increased cell viability. This led us to investigate the expression of SP-D in U87 and B30 GBM cells through western blot, ELISA and immuno-fluorescence detection. We demonstrated novel information about the production of SP-D by GBM cells. To extend our study, we investigated the interaction of THP-1 macrophage with rhSP-D bound U87 cells. We carried out live cell imaging, RT-qPCR, and cell viability assays, to study the changes in cytokine expression and viability of cells. THP-1 did not engulf U87 cells; however, it did reduce the number of cells and decrease the expression of pro-tumourigenic cytokines. This study highlights the ability of primary GBM cells to evade innate immune detection by the secretion of functionally active CFHR5. It also demonstrated the ability of U87 to evade destruction by rhSP-D and THP-1 highlighting the extremely aggressive behaviour of the tumour and lack of new treatment to improve prognosis in over a decade.