Supersaturating drug delivery systems, such as amorphous solid dispersions (ASDs), have been used extensively to elevate the apparent solubility and oral bioavailability of poorly water-soluble drugs. However, despite the numerous examples of success in increasing solubility and oral bioavailability using ASDs, physical stability challenges remain as formulators seek to employ high drug loading for cost reduction and improved patient compliance. Therefore, stability in both the solid and solution state must be considered for ASDs to be successful. In the solid state, the drug must remain amorphous in the solid matrix throughout the shelf life of the product. Although excipients, such as polymers, have been known to stabilize the amorphous drug in the solid state, stresses encountered during manufacturing and fluctuations in storage conditions may have a detrimental impact on the physical stability of ASDs. Numerous studies have been performed on the impact of each process on ASD stability, yet the relative quantitative impact of each process with respect to the overall energetics landscape is not well understood. Further, ASDs must dissolve after administration and maintain the intended supersaturation in the gastrointestinal (GI) tract during the GI transit time to achieve maximum oral absorption. In solution, the energetics advantage of the amorphous over the crystalline material is a “double-edged sword,” in that it produces not only a high absorption driving force but also an undesirable high crystallization potential. An approach to quantitatively measure the thermodynamic activity of amorphous materials is, thus, desirable. However, it is difficult to measure thermodynamic activity quantitatively, especially due to the speciation process induced by formulation excipients and endogenous materials. Hence, it is often difficult to assess the true enhancement in the absorption for a given ASD and to measure its crystallization tendency in solution. Overall, this dissertation aims to address the following: 1. The relative thermodynamics magnitude of various processes with respect to the crystallization energy associated with amorphous drugs 2. The development of a practical tool to measure the thermodynamic activity of amorphous materials over its crystalline counterpart in solution to assess the enhancement in absorption in the presence of excipients 3. The impact of measured thermodynamic activity on drug crystallization energetics in the presence of excipients

The objective of this work is to optimize high-power low-frequency sonication (US) pretreatment of sludge, and especially to investigate for the first time possible improvements by higher pressure and audible frequency. After a preliminary examination of regular process conditions (sludge conditioning, sludge type, prior alkalization, temperature control, etc), effects of US parameters (power -PUS, intensity -IUS, specific energy input -ES, frequency -FS, etc.) and of hydrostatic pressure (Ph) were specifically looked into, separately and in combination, first under cooling at constant temperature (28°C), then under the progressive temperature rise provoked by sonication. First, it was confirmed that specific energy input (ES) plays a key role in sludge US disintegration (i.e. solubilisation of organic matter) and that temperature rise during adiabatic-like sonication is beneficial through additional effects of thermal hydrolysis and cavitation. At a given ES value, low FS (12 kHz vs. 20 kHz) and high PUS enhance soluble chemical oxygen demand (SCOD) due to more violent cavitation, while hydrostatic pressure gives rise to an optimum value due to its opposite effects on cavitation threshold and intensity. One major result is that optimal pressure depends on IUS (P¬US) as well as temperature profile, but not on ES, FS, nor sludge type. Setting the other parameters at the most favorable conditions expected, i.e. 12 kHz, 360 W , 28 gTS/L, and adiabatic conditions, final optimization was achieved by searching for this pressure optimum and examining sequential procedure to avoid too high temperature dampening cavitation intensity and damaging the transducer. Such conditions with sequential mode and Ph of 3.25 bar being selected succeeded in achieving very high SCOD, but only marginally improved subsequent methanization yield.

Under terminal water deficit, the impact of stem carbohydrate remobilization has greater significance because post-anthesis assimilation is limited, and grain growth depends on translocation of carbohydrate reserves. The working hypothesis of this thesis is that increases in stem carbohydrates facilitate tolerance to terminal drought in wheat. The goals of this thesis are to examine this hypothesis using physiological and genetic tools; identify genes that are related to QTL for stem carbohydrate; work with wheat and barley breeders to integrate findings into the breeding program of the Department of Agricultural and Food Western Australia. The physiological data of three drought experiments (two years in a glasshouse and one year in the field) suggested the maximum level of stem water soluble carbohydrate (WSC) is not consistently related to grain weight, especially, under water deficit. The patterns of WSC accumulation after anthesis differed depending on variety and suggested that WSC degradation and translocation have different genetic determinants. Most of the carbohydrates in stem WSC in wheat are fructans. Because 1-FEH gene was an important gene in fructan degradation, the three copies of this gene (1-FEH w1, 1-FEH w2 and 1-FEH w3) were isolated from the respective genomes of bread wheat. In addition, the genes were mapped to chromosome locations and coincided with QTL for grain weight. The results of gene expression studies show that 1-FEH w3 had significantly higher levels in the stem and sheath which negatively corresponded to the level of stem WSC in two wheat varieties in both water-deficit and well-watered treatments. Strikingly, the 1-FEH w3 appeared to be activated by water deficit in Westonia but not in Kauz. The results suggest that stem WSC level is not, on its own, a reliable criterion to identify potential grain yield in wheat exposed to water deficit during grain filling. The expression of 1-FEH w3 may provide a better indicator when linked to instantaneous water use efficiency, osmotic potential and green leaf retention, and this requires validation in field grown plants. In view of the location of the contribution to grain filling of stem WSC, this is a potential candidate gene contributing to grain filling. The numerous differences of intron sequences of 1-FEH genes would provide more opportunities to find markers associated with the QTL. A new FEH gene was partially isolated from Chinese Spring and the sequence was closely related to 1-FEH genes. This gene, FEH w4, was mapped to 6AS using Chinese Spring deletion bin lines. The polymorphism of this gene was found between different bread varieties using PCRs and RFLPs, and this allowed the gene to be mapped to two populations of Hanxuan 10 × Lumai 14 and Cranbrook × Halberd. In the population of Hanxuan 10 × Lumai 14, it was close to SSR marker xgwm334 and wmc297 where the QTL of thousand grain weight and grain filling efficiency were located. This result indicated this gene might be another possible candidate gene for grain weight and grain filling in wheat.

Cette étude s'est intéressée à la caractérisation moléculaire du contenu organique de boues résiduaires de stations d'épuration de la région Lorraine. Les quarante huit échantillons collectés proviennent de stations domestiques de différentes tailles (rurales, petites urbaines et urbaines), de stations industrielles (papeteries) et de stations agro-alimentaires (laiteries et fromageries). Le premier volet développé au cours de cette étude a permis de dresser l'inventaire des composés présents dans les boues d'épuration (i) sous forme libre (fraction organique soluble- FOS) et (ii) sous forme liée à la structure macromoléculaire (fraction organique insoluble- FOI). A cette fin, les outils analytiques respectivement utilisés sont la GC-MS d'une part, et la THM-GC-MS et Py-GC-AED d'autre part. Les résultats de l'analyse de la FOS et de la FOI fournissent une information équivalente dans la mesure où ils permettent de différencier les boues selon leur origine (agro-alimentaire, industrielle ou domestique). Une empreinte moléculaire spécifique à chaque type de boues a ainsi pu être définie. Par ailleurs, l'ensemble des boues domestiques est caractérisé par un fonds géochimique pétrolier, témoignant d'une pollution diffuse commune. Une variabilité autour de ce fonds géochimique a également pu être identifiée pour certaines boues domestiques, sans relation avec la taille de la station, ni le degré d'industrialisation de la région. Ces variations, essentiellement observées au niveau de la FOS, peuvent par contre être imputées à des pollutions ponctuelles ou accidentelles dans le système de collecte des eaux usées domestiques. Ce travail a pour but de fournir, à terme, des paramètres moléculaires d'aide au suivi et au contrôle des réseaux de collecte des eaux usées. Le deuxième volet de ce projet s'est intéressé à l'étude des effets de la biodégradation sur le contenu organique des boues. Afin de simuler les processus de dégradation, quatre échantillons ont été incubés à 24°C pendant 140 jours. L'analyse couplée de la FOS et de la FOI des échantillons biodégradés a permis de déterminer les grandes tendances de l'évolution du contenu organique au cours des expérimentations. Un schéma réactionnel global de biodégradation peut ainsi être proposé : l'altération de la structure macromoléculaire de la FOI libère des composés extractibles, dégradés eux-mêmes en composés de plus bas poids moléculaire ou minéralisés. Par ailleurs, cette étude a permis de déterminer des indices de biodégradation ainsi que des marqueurs organiques résistants à cette biodégradation.

Aerosols and clouds provide the largest uncertainty in the atmospheric radiation budget. The main focus of this thesis was to investigate the ability of organic compounds in aerosol particles to form clouds, and more specifically those emitted by living organisms. The cloud forming properties of the highly water-soluble methyltetrols and polyols, which are compounds produced by plants and fungi that are common in aerosol, were studied. All compounds and their salt mixtures have a moderate potential to serve as cloud condensation nuclei (CCN). They are thus not likely to have a significant global impact on cloudiness. The potential presence of surfactants released by microorganisms was investigated for aerosols sampled at different locations. Very low surface tension values were measured for these aerosol extracts (30 mN/m), which implies that these aerosols have good CCN properties and indicate the presence of biosurfactants. Their occurrence in aerosols still needs to be confirmed directly by chemical identification. Reactions of organic compounds in sulfate salt solutions exposed to UV-light were studied and found to produce surface active compounds. Thus, mixed sulfate/organic aerosol could have more favourable CCN properties after exposure to light than when kept in the dark. The surface active compounds were proposed to be long-chained organosulfates with hydrophilic and hydrophobic parts, similar to other amphiphilic surfactants. Mixtures of salt and strong surfactants formed by bacteria were studied using two different techniques for determining their CCN properties. There were inconsistencies between the two methods which could be accounted for by surface partitioning. The studied mixtures were determined to be good potential CCN material in both techniques. All these aspects require further investigation, but if the impact of strong biogenic surfactants on cloud formation is confirmed, a new link between living organisms and climate would be identified. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript.

Atmospheric aerosols may be emitted directly as particles (primary) or formed from gaseous precursors (secondary) from different natural and anthropogenic sources. The highly populated South and East Asia regions are currently in a phase of rapid economic growth to which high emissions of carbonaceous aerosols are coupled. This leads to generally poor air quality and a substantial impact of anthropogenic aerosols on the regional climate. However, the emissions of different carbon aerosol components are still poorly constrained. Water-soluble organic carbon (WSOC) is a large (20-80%) component of carbonaceous aerosols that can absorb solar light and enhance cloud formation, influencing both the direct and indirect climate effects of the aerosols. A novel method for carbon isotope-based studies, including source apportionment, of the WSOC component of ambient aerosols was developed and tested for recovery efficiency and the risk of contamination using both synthetic test substances and ambient aerosols (paper I). The application of this method for the source apportionment of aerosols in South and East Asia shows that fossil fuel input to WSOC is significant in both South Asia (about 17-23%) highly impacted by biomass combustion practices and in East Asia (up to 50%) dominated by fossil energy sources (papers II, III, IV). Fossil fraction in WSOC in the outflow from northern China is considerably larger than what has been measured in South Asia, Europe and USA (paper IV). A trend of enrichment in heavy stable carbon isotopes in WSOC with distance the particles have been transported from the source is observed in the South Asian region (papers II, III). Dual-isotope (Δ14C and δ13C) analysis demonstrates that WSOC is highly influenced by atmospheric aging processes. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Submitted.</p>

Le mouillage d'un substrat soluble est une situation couramment rencontrée dans la vie de tous les jours les jours. Par exemple, les motivations pratiques de cette étude concernent la préparation de boissons à partir de poudres déshydratées, constituées de substances solubles dans l'eau telles que les glucides. Les modèles hydrodynamiques décrivant le mouillage sur un substrat non soluble ne peuvent pas expliquer les observations expérimentales dans le cas d'un liquide s'étalant sur un substrat soluble. Tay et al.(1) ont émis l'hypothèse que la fraction d'eau à la ligne de contact contrôle la valeur de l'angle de contact et ils ont montré l'importance du processus d'évaporation/condensation du solvant lors du mouillage. Dans cette étude, nous montrons que d'autres transferts de matière doivent être considérés pour améliorer la compréhension du processus de mouillage d'une couche soluble; ainsi la diffusion dans le polymère de l'eau condensée, ou directement depuis la goutte sont des processus qui contribuent à hydrater le substrat et modifier l'angle de contact de la goutte. Nous avons utilisé l'approche suivante pour réaliser cette étude: (i) pour prendre en compte la diffusion dans le substrat, nous avons réalisé des simulations en éléments finis qui permettent de valider nos arguments théoriques, (ii) des expériences d'étalement de goutte sur des couches minces de maltodextrine ont été réalisées afin d'étudier le mouillage et l'hydratation en avant de la ligne de contact. Ce travail nous permet de mettre en avant l'influence de la diffusion dans la couche qui complexifie les profils d'hydratation en avant de la ligne de contact, avec notamment l'apparition d'une région de diffusion où de l'évaporation est observée. Un diagramme de mouillage épaisseur-vitesse (e − U) avec différents régimes est établi. Nous validons ces régimes expérimentalement et plus particulièrement un régime où l'angle de contact est une fonction du produit eU. Par ailleurs, nous montrons l'influence de la transition vitreuse du polymère sur l'angle de contact et l'hydratation. Enfin, une étude préliminaire est réalisée pour comprendre l'influence de la dissolution du polymère lors du mouillage.

Anthraquinone (AQ) derivatives with relatively high reduction potentials have been synthesized to afford good candidates for electron transfer studies in DNA. Electron withdrawing groups on the anthraquinone ring gave derivatives with less negative reduction potentials. The anthraquinone imide (AQI) derivatives had reduction potentials less negative than AQ derivatives. The AQI ring system was subject to base-induced hydrolysis. Water-soluble sulfonated tetraarylporphyrins have been studied in a wide variety of contexts. Herein, we report the first synthesis of a pentasulfonated porphyrin bearing an internal cyclic sulfone ring. Treatment of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS4) with fuming H2SO4 gave a structure consistent with initial sulfonation followed by dehydration to give a sulfone bridge between an ortho-position of one of the phenyl groups and a β-pyrrole position on the porphine ring (TPPS4Sc). The structure was established by ESI-MS and 1HNMR. The Soret absorption is red shifted by about 32 nm compared to that of TPPS4. Streptococcus pyogenes obtains iron by taking up heme from the environment during infection. One of the heme uptake pathways is the Sia or Hts pathway. The initial protein in this pathway is Shr, which has two heme-binding NEAT domains, NEAT1 nearer the N-terminus, and NEAT2 nearer the C-terminus. We report biophysical characteristics of these two NEAT domains. To assess stability of this domain towards heme release, denaturation studies of the Fe(II) and Fe(III) forms were performed. For each domain, both the Fe(II) and the Fe(III) forms behave similarly in thermal denaturation and guanidinium denaturation. Overall, NEAT2 is more stable than NEAT1. Spectral signatures, sequence alignment and homology modeling for both domains suggest that one of the axial ligands is methionine. NEAT2 autoreduces as the pH increases and autooxidizes as the pH decreases. Heme uptake from the host environment is the only iron acquisition pathway in S. pyogenes; inhibition of this pathway might be an approach to infection control. Compounds that might inhibit the heme uptake pathway were selected via virtual screening.

New methodologies for the efficient syntheses of 4,4-difluoro-4-bora-3a,4adiaza- s-indacenes (BODIPYs) and rosamines were developed. A serendipitous discovery led to a new reaction which afforded BODIPYs in high yields. Systematic studies of the kinetics and mechanisms of the new reaction were performed. A series of BODIPYs were successfully prepared using the new approach. A simple and efficient synthesis of rosamines with cyclic-amine substituents was devised. These new rosamines showed interesting anti-tumor activities. Several types of novel fluorescent compounds were prepared. Highly fluorescent GFP-chromophore analogs were designed and synthesized. The correlation between the optical properties and the structures was investigated. New pyronin dyes with mesoheteroatom substituents were efficiently prepared. The fluorescence properties of these compounds were highly dependent on the nature of the meso-substituents. A set of BODIPY dyes that fluoresce brightly above 600 nm were made. They were then used as acceptors to prepare water-soluble through-bond energy transfer cassettes. All the cassettes had complete energy transfer and high quantum yields in MeOH. A few also had good fluorescence properties in aqueous media and even on proteins. The through-bond energy transfer cassettes were used to monitor protein-protein interactions. In order to test our hypothesis, an artificial protein interaction system was built by utilizing the biotin/(strept)avidin interactions. Thus Atto425-BSA-biotin, streptavidin-cassette1 and avidin-cassette2 were prepared. The interactions between Atto425-BSA-biotin and cassette labeled (strept)avidin were successfully detected in vitro and in living cells by fluorescence techniques.

This study investigated the fuel properties, engine performances, and emissions of two biodiesels and diesel. The fuels examined were D100 (ultra-low sulfur diesel), B20 (20% palm biodiesel +80% ultra-low sulfur diesel) and B100 (palm biodiesel). The fuel properties analysis results showed that the benefits of biodiesel were high cetane value, extremely low sulfur and aromatic contents, and good lubricity. While the defects of biodiesel were high pour point. The particulates emitted from the burning of D100, B100, B20 were mainly fine particulates, also known as young aerosols. Particles smaller than 2.5 &#x00B5;m easily enter the trachea and bronchus via the upper respiratory tract, finally deposit on the alveolus, which could cause severe injury to human health. The emission of soluble organic fraction (SOF) from diesel engine using D100, B100 and B20 were 23.2%, 19.9% and 20.2%, respectively. The SOF of D100 is slightly higher than B100 and B20. It suggested that adding biodiesel into diesel can decrease SOF and thus reduce the potential danger to human health. The original total PAHs concentration of tail gas emitted from engines using D100, B100 and B20 were 241, 50.6 and 98.8 &#x00B5;g/m3, respectively. Adding 20% biodiesel into D100 could reduce 59.0% of PAHs emission. Moreover, the original total BaPeq concentration of tail gas emitted from diesel engines using D100, B100 and B20 were 0.714, 0.509 and 0.570 &#x00B5;g/m3, respectively. Adding 20% biodiesel into D100 could also reduce 20.2% of total BaPeq emission. Hence, adding biodiesel into diesel can effectively reduce the emission of PAHs and the potential danger to human health. The emission factors of carbonyl compounds from diesel engines using D100, B100 and B20 were 395, 1,170 and 326 mg/BHP-hr, respectively. carbonyl compounds of B100 were obviously higher than D100 and B20. The results indicated that using pure palm biodiesel in diesel engine can increased the emission of carbonyl compounds. However, adding 20% biodiesel into D100 can effectively reduce 17.5% of carbonyl compounds emission. Keyword: ultra-low sulfur diesel, palm biodiesel, fuel properties¡BThe emission of soluble organic fraction (SOF)¡BPAHs¡Bcarbonyl compounds¡C