Investigation and characterization of polymeric materials are necessary to obtain in-depth understanding of their behavior and properties, which can fuel further development. To illuminate these molecular properties and their coupling to macroscopic behavior, we have performed nuclear magnetic resonance (NMR) studies on a variety of chemical systems. In addition to versatile "traditional" NMR measurements, we took advantage of specialized techniques, such as "rheo-NMR," 2H NMR, and NMR self-diffusion experiments to analyze alignment, orientational order, elaborate rheological behavior, and ion transport in polymer films and complex fluids. We employed self-diffusion and quadrupolar deuterium NMR methods to water-swollen channels in Nafion ionomer films commonly used in fuel cells and actuators. We also correlated water uptake and anisotropic diffusion with differing degrees and types of alignment in Nafion films based on membrane processing methods. Further, we made quantitative measurements of bulk channel alignment in Nafion membranes and determined anisotropic properties such as the biaxiality parameter using these methods. Additionally, our studies made the first direct comparison of directional transport (diffusion) with quantitative orientational order measurements for ionomer membranes. These results lend insight to the importance of water content in ionomer device performance, and showed that increased control over the direction and extent of orientational order of the hydrophilic channels could lead to improved materials design. We used the same techniques, with the addition of "rheo-NMR" and solution rheology measurements, to study the complex rheological behavior of cetyltrimethylammonium bromide wormlike micelle solutions, which behave as nematic liquid crystals at sufficiently high concentration. Amphiphilic solutions of this type are used in myriad applications, from fracturing fluids in oil fields to personal care products. We investigated the phase behavior and dynamics of shear and magnetic field alignment, and made the first observations of a novel bistable shear-activated phase in these solutions. Our first reports of the complex Leslie-Ericksen viscoelastic parameters in wormlike micelles and measurements of diffusion anisotropy show the potential for increased control and understanding of materials used in tissue engineering, oil extraction, personal care products, and advanced lubricants. / Ph. D.

Chez l'humain et la souris, les androgènes retardent la montée de la production de surfactant pulmonaire chez le mâle. L'objectif de ce projet mené chez la souris est de déterminer les moments gestationnels exacts où la production de surfactant augmente chez le mâle et chez la femelle. Pour ce faire, nous avons adapté une technique permettant de quantifier le surfactant pulmonaire à différents moments gestationnels par la mesure des phosphatidylcholines disaturées (DSPC) dans les poumons foetaux. Brièvement, la quantité de DSPC augmente significativement selon l'âge gestationnel chez les deux sexes. Aucune différence sexuelle significative dans la quantité de surfactant n'a pu être détectée. Cela peut être expliqué par une approche de normalisation des résultats non optimale, une puissance statistique insuffisante, une contamination des échantillons par les DSPC membranaires et sanguins ou parce que la différence sexuelle est transitoire et a lieu pendant une courte période précise non étudiée.

Aqueous film-forming foam (AFFF) used for fuel firefighting contains polyfluoroalkyl substances (PFAS) that have been identified as environmentally persistent and bioaccumulative resulting in phase out of AFFF. Currently, there are no environmentally friendly foams available that can perform at the same level as AFFF. Fuel transport has been recognized as a potential mechanism behind poor fire extinguishment, but the key features are yet unidentified. To fill these knowledge gaps, identifying the properties and features of surfactants used in firefighting foam that will prevent the transport of liquid fuel through the surfactant solution was imperative. To achieve that, this research was performed exclusively on single surfactants that have applications in firefighting foam. Impact of single surfactants on fuel transport was evaluated. Thermodynamics of the interaction between single surfactants and fuel; and kinetics of fuel transport through single surfactant solutions was observed. It was hypothesized that the liquid fuel transport would influence microstructure in the bulk of the surfactant solution. Experiments were conducted for different single surfactant structures. Various methods were applied to identify the microstructure and interfacial properties of surfactants with and without exposure to liquid fuel. The factor affecting microstructure, identified through this study was further used to evaluate the firefighting performance of single surfactants through ignition test. The thermodynamics of the interaction between fuel and single surfactants helped us to understand the fuel transport mechanism and role of micelle on fuel transport. Surfactant and fuel interaction has been studied below, at, and above the critical micelle concentration of surfactants. The effect of surfactant concentration, convection, and surfactant types were observed on the fuel transport. Moreover, an ignition test was conducted to evaluate the firefighting performance of single surfactants for various fuel types. Overall, the findings from this study will help design a new type of superefficient, environmentally acceptable surfactant for firefighting foam application. / Doctor of Philosophy / Aqueous film-forming foam (AFFF) used for fuel firefighting contains fluorinated compounds which are environmentally persistent and bioaccumulative. Therefore, AFFF has been phased out. There are no environmentally friendly foams available as efficient as current AFFF. Researchers have found that fuel transport through surfactant foam solution is the reason for foam collapse and poor fire extinguishment performance. However, the key parameters affecting fuel transport through foam solution have not been identified. Therefore, new formulations have become challenging, and it is important to identify the parameters affecting fuel transport through the firefighting foams. Surfactants are the key components of firefighting foam. The liquid fuel transport affects the microstructure of the surfactants in the bulk solution. Through this research microstructural and interfacial properties of single surfactants have been studied with and without exposure to liquid fuel. The factors affecting microstructure and firefighting performance of surfactants have been identified. Moreover, the interaction between fuel and single surfactants has been evaluated. The effect of surfactant concentration and fuel type on fuel transport has been observed. Moreover, the effect of convection (at the foam-fuel interface) on fuel transport has been observed. Overall, an understanding of factors affecting fuel transport of firefighting foam is achieved through this research, which can guide new types of efficient, environmentally friendly surfactant design.

The regulation of surface tension (ST) by surfactants plays an important role in the human respiratory system but is largely unexplored in brain homeostasis. The aim of this study was to evaluate changes in ST in relation to surfactant proteins (SPs) in children with intraventricular hemorrhage (IVH). CSF samples from 93 patients were analyzed for ST with a force tensiometer and SP-A-D and -G with ELISA assays. Patients belonged to six groups: (i) IVH before primary intervention (PI), (ii) IVH 4–28 days after PI, (iii) IVH 44–357 days after PI, (iv) hydrocephalus, (v) sepsis and (vi) controls. We found indirect correlations and significant differences in ST and SPs (all p < 0.001; except for SP-C, p = 0.007). Post hoc analyses showed significantly decreased ST in IVH patients before PI compared with patients with hydrocephalus, sepsis or controls (p < 0.001), but it increased in IVH patients over time. All SPs were significantly elevated when comparing IVH patients before PI with controls (all p < 0.001; except for SP-C, p = 0.003). Children suffering from IVH displayed an increase in SPs and a decrease in ST as coping mechanisms to preserve CSF flow. The increase in ST over time could serve as prognostic marker for the healing process.

Yes / The structure and dynamics of a single molecule of the nonionic surfactant polysorbate 80 (POE (20) sorbitan monooleate; Tween 80 ) as well as a micelle of polysorbate 80 in water have been investigated by molecular dynamics simulation. In its free state in water the polysorbate 80 molecule samples almost its entire conformational space. The micelle structure is compact and exhibits a prolate ellipsoid shape, with the surface being dominated by the polar terminal groups of the POE chains. The radius of gyration of the micelle was 26.2 A. The physical radius, determined from both the radius of gyration and atomic density, was about 35 A. The estimated diffusion constants for the free molecule (1.8 10 6 cm2 s 1) and the micelle (1.8 10 7 cm2 s 1) were found to be remarkably close to the respective experimental values. The lateral diffusion of the molecules on the micelle surface was estimated to be 1.7 10 7 cm2 s 1, which confirms the highly dynamic nature of the micelle structure. / Tehran University of Medical Sciences & Health Services

No / There is considerable interest, both fundamental and technological, in understanding how additives and impurities influence crystal nucleation, and in the modulation of nucleation in a predictable way by using designer additives. An appropriate additive can promote, retard, or inhibit crystal nucleation and growth, assist in the selective crystallization of a particular enantiomer or polymorphic form, or enable crystals of a desired habit to be obtained.[1¿3] Applications involving additives include the control of the nucleation of proteins,[4] the inhibition of urinary-stone formation[5] and of ice formation in living tissues during cryoprotection,[6] their use as antifreeze agents in Antarctic fish,[7,8] the prevention of blockages in oil and gas pipelines as a result of wax precipitation[9] and gas-hydrate formation,[10] crystal-twin formation,[11] and as a possible basis for the antimalarial activity of some drugs.[12]We report herein the mode of action and explicit (apparently intuitive) rules for designing additive molecules for the modulation of crystal nucleation. The mode of action and the design features have been derived from molecular-dynamics simulations involving simple models.[13] These findings will help to rationalize how known nucleation inhibitors and modulators exert their effect and aid in the identification or design of new additives for the inhibition or promotion of nucleation in specific systems.

Yes / Inhaled nanoparticles (NPs) are experienced by the first biological barrier inside the alveolus known as lung surfactant (LS), a surface tension reducing agent, consisting of phospholipids and proteins in the form of the monolayer at the air-water interface. The monolayer surface tension is continuously regulated by the alveolus compression and expansion and protects the alveoli from collapsing. Inhaled NPs can reach deep into the lungs and interfere with the biophysical properties of the lung components. The interaction mechanisms of bare gold nanoparticles (AuNPs) with the LS monolayer and the consequences of the interactions on lung function are not well understood. Coarse-grained molecular dynamics simulations were carried out to elucidate the interactions of AuNPs with simplified LS monolayers at the nanoscale. It was observed that the interactions of AuNPs and LS components deform the monolayer structure, change the biophysical properties of LS and create pores in the monolayer, which all interfere with the normal lungs function. The results also indicate that AuNP concentrations >0.1 mol% (of AuNPs/lipids) hinder the lowering of the LS surface tension, a prerequisite of the normal breathing process. Overall, these findings could help to identify the possible consequences of airborne NPs inhalation and their contribution to the potential development of various lung diseases. / University of Technology Sydney (UTS) FEIT Research Scholarship, UTS IRS (S.I.H.), 2018 Blue Sky scheme–Suvash Saha (Activity 2232368), N.S.G is supported by the Vice-Chancellor fellowship funded by QUT.

Yes / Lung surfactant (LS) monolayers that continuously expand and compress during breathing cycles, act as the first line barrier for inhaled nanoparticles. It is known that nanoparticles which adsorb to the surface of the surfactant layer facilitate the rearrangement of lipids and peptides at various stages of the breathing cycle. However, the structural mechanisms for this ability of the lipid rearrangement are not yet fully understood. Coarse-grained molecular dynamics simulations are performed to investigate the role of surfactant protein B (SP-B) segments (SP-B1–25) in modulating the biophysical properties of the surfactant monolayer in the presence of polydisperse gold nanoparticles (AuNPs) at different concentrations. Herein, we observe that the AuNPs significantly alter the inherent structural and dynamical properties of the monolayer and its components in three different breathing states. When adsorbed into the monolayer, the AuNPs inhibit the ability of the monolayer to recover its surface tension and other properties. The presence of SP-B1–25 in the monolayer accelerates the diffusion of the monolayer phospholipids, contrarily to the role of AuNPs on phospholipid diffusion. Also, the AuNPs and the peptides in the monolayer significantly increase their agglomeration in the presence of one another. Overall, the simulations predict that the presence of polydisperse AuNPs hampers the stability and biophysical functions of the LS in contrast to the role of the peptide. This study provides a clear view of the hydrophobic peptide role in the LS monolayer at the interface along with the interactions and the translocation of AuNPs that could have a significant impact to assess the NPs inhalation. / This work was completed with the support of University of Technology Sydney (UTS) FEIT Research Scholarship, UTS IRS (S. I. H.).

The regulation of surface tension (ST) by surfactants plays an important role in the human respiratory system but is largely unexplored in brain homeostasis. The aim of this study was to evaluate changes in ST in relation to surfactant proteins (SPs) in children with intraventricular hemorrhage (IVH). CSF samples from 93 patients were analyzed for ST with a force tensiometer and SP-A-D and -G with ELISA assays. Patients belonged to six groups: (i) IVH before primary intervention (PI), (ii) IVH 4–28 days after PI, (iii) IVH 44–357 days after PI, (iv) hydrocephalus, (v) sepsis and (vi) controls. We found indirect correlations and significant differences in ST and SPs (all p < 0.001; except for SP-C, p = 0.007). Post hoc analyses showed significantly decreased ST in IVH patients before PI compared with patients with hydrocephalus, sepsis or controls (p < 0.001), but it increased in IVH patients over time. All SPs were significantly elevated when comparing IVH patients before PI with controls (all p < 0.001; except for SP-C, p = 0.003). Children suffering from IVH displayed an increase in SPs and a decrease in ST as coping mechanisms to preserve CSF flow. The increase in ST over time could serve as prognostic marker for the healing process.:1. Einführung 3 1.1 Intraventrikuläre Hämorrhagie 3 1.1.1 Allgemeiner Überblick 3 1.1.2 Pathogenese 3 1.1.3 Risikofaktoren und Prävention 4 1.1.4 Klinik 5 1.1.5 Komplikationen 6 1.1.6 Behandlungsoptionen bei IVH und PHVD 7 1.1.6.1 Medikamente 7 1.1.6.2 Interventionen 7 1.2 Surfactant und Surfactant-Proteine 8 1.3 Zusammenfassung der IVH-Problematik und Fragestellungen der Dissertation 11 2. Publikationsmanuskript 13 3. Zusammenfassung der Arbeit 28 4. Literaturverzeichnis 32 5. Abkürzungsverzeichnis 39 6. Anlagen der Originalpublikation 41 7. Darstellung des eigenen Beitrags 48 8. Erklärung über die eigenständige Abfassung der Arbeit 49 9. Lebenslauf 50 10. Publikationen 51 11. Danksagung 52

Contexte : L’administration de surfactant par méthode minimalement invasive vise à éviter l’exposition à la ventilation mécanique invasive (VMI) chez les nouveau-nés atteints de la maladie des membranes hyalines (MMH). Objectif : L’objectif de cette étude est de tester l’efficacité de l’administration du surfactant par méthode minimalement invasive chez les prématurés de 320/7 à 366/7 semaines d’âge gestationnel (AG) pour prévenir l’exposition à la VMI ainsi que la survenue de pneumothorax. Méthode : Une étude randomisée incluant trois unités néonatales canadiennes a été réalisée. Les patients recevaient l’intervention ou étaient assignés au groupe contrôle. Dans le premier jour de vie, les patients du groupe d’intervention recevaient le surfactant par méthode minimalement invasive immédiatement après la randomisation. La mesure de résultat primaire combinée incluait l’exposition à la VMI et la survenue de pneumothorax nécessitant l’installation d’un drain thoracique. Des critères cliniques d’échec au traitement étaient surveillés puisque l’intervention n’était pas dissimulée. Chaque patient a été analysé selon son groupe d’allocation initiale. Résultats : Parmi 45 patients randomisés, 24 ont été assignés à recevoir l’intervention. Tous les patients ont été inclus dans l’analyse. Huit (33%) patients du groupe d’intervention ont été exposés à la VMI (7) ou ont présenté un pneumothorax (1) alors que 19 (90%) patients du groupe contrôle ont été exposés à la VMI (18) ou ont présenté un pneumothorax (1) (réduction du risque absolu : 0,57, intervalle de confiance à 95% : 0,54-0,60). Aucun patient n’a présenté les critères d’échec au traitement. Conclusion : L’administration de surfactant par méthode minimalement invasive s’est avérée efficace pour réduire la mesure de résultat combinée de l’exposition à la VMI et/ou de la survenue de pneumothorax chez les prématurés de 320/7 à 366/7 semaines atteints de la MMH. / Background: Minimally invasive surfactant therapy (MIST) is used to avoid invasive mechanical ventilation (IMV) in respiratory distress syndrome (RDS) management. Objective: The primary aim of this study was to test MIST in moderate (32 – 33 weeks’ gestational age (GA)) and late preterm (34 - 36 weeks’ GA) infants affected by RDS to avoid IMV exposure and prevent pneumothorax. Methods: This is a randomized controlled trial including three Canadian neonatal intensive care units. Patients were randomized to standard management or to intervention (MIST). In the first day of life, patients from the intervention group received MIST immediately after randomization. The combined primary outcome included either exposure to IMV or occurrence of a pneumothorax requiring a chest tube insertion. Treatment failure criteria were used to prevent bias as the intervention was not blind. The analysis was made by intention to treat approach. Results: Among 45 randomized patients, 24 were assigned to MIST and 21 to the standard management group. All patients were included in the analysis. Eight infants (33%) in the intervention group presented with the primary outcome versus 19 (90%) in the standard management group (absolute risk reduction 0,57, 95% CI: 0,54-0,60). Seven patients from the intervention group reached the primary outcome for being exposed to IMV and one for presenting a pneumothorax. In the control group, 18 patients reached the primary outcome for being exposed to IMV and one for presenting a pneumothorax. In either group, none of the patients have reached the clinical failure criteria. Conclusion: Minimally invasive surfactant therapy was associated with a significant reduction in IMV exposure and pneumothorax occurrence in moderate and late preterm infants affected by RDS.