Cancer is the second leading cause of death in the United States and its onset is highly incident in the lungs, with very low long-term survival rates. Chemotherapy plays a significant role for lung cancer treatment, and pulmonary delivery may be a potential route for anticancer drug delivery to treat lung tumors. Coenzyme Q₁₀ (CoQ₁₀) is a poorly-water soluble compound that is being investigated for the treatment of carcinomas. In this work, we hypothesize that formulations of CoQ10 may be developed for pulmonary delivery with a satisfactory pharmacokinetic profile that will have the potential to improve a pharmacodynamic response when treating lung malignancies. The formulation design was to use a vibrating-mesh nebulizer to aerosolize aqueous dispersions of CoQ₁₀ stabilized by phospholipids physiologically found in the lungs. In the first study, a method was developed to measure the surface tension of liquids, a physicochemical property that has been shown to influence the aerosol output characteristics from vibrating-mesh nebulizers. Subsequently, this method was used, together with analysis of particle size distribution, zeta potential, and rheology, to further evaluate the factors influencing the capability of this nebulizer system to continuously and steadily aerosolize formulations of CoQ₁₀ prepared with high pressure homogenization. The aerosolization profile (nebulization performance and in vitro drug deposition of nebulized droplets) of formulations prepared with soybean lecithin, dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC) were evaluated. The rheological behavior of these dispersions was found to be the factor that may be indicative of the aerosolization output profile. Finally, the pulmonary deposition and systemic distribution of CoQ₁₀ prepared as DMPC, DPPC, and DSPC dispersions were investigated in vivo in mice. It was found that high drug amounts were deposited and retained in the mouse lungs for at least 48 hours post nebulization. Systemic distribution was not observed and deposition in the nasal cavity occurred at a lower scale than in the lungs. This body of work provides evidence that CoQ₁₀ may be successfully formulated as dispersions to be aerosolized using vibrating-mesh nebulizers and achieve high drug deposition in the lungs during inhalation. / text

<p>The project was conducted on a small-scale catchment at Goedertrou in the Riebeek- Kasteel district. The focus of this study was to address some of the hydrological processes active in the research catchment, namely infiltration, run-off and sediment mobilisation on different soil types. It was done to investigate the origin of Berg River pollutants. To answer the overall question about what influence the natural salt load of the Berg River, a number of subprojects have been identified, one of which is to understand the hydrological processes in the soil mantle and vadose zone. Hence, the study aimed to answer the research questions mentioned and discussed in section 1.3 of Chapter 1. Considering the results, it could be suggested that decayed root systems from the rows of plants, soil cracks, small channels and openings created by small animals, as well as slope orientation and, therefore, soil composition, all played a major role in influencing the ability of the soil to absorb the simulated rainfall. In this study, the factors that influenced run-off are micro topography, soil moisture, root system, animal activities in soil profile, soil crack dimensions and the hydraulic conductivity. The main factors that played a major role to influence sediments mobilisation are strongly believed to be the micro topography within the ring, slope gradient and length, vegetation cover and rainfall-simulation intensity. After using different techniques, the results show that farmers must be aware that with storm rainfall, particles smaller than 65 &mu / m are subject to mobilisation. It is important to let land-users know that they need proper and appropriate methods for land-use.</p>

Le LiFePO4 est un matériau prometteur pour les cathodes des batteries au lithium. Il possède une bonne stabilité à haute température et les précurseurs utilisés pour la synthèse sont peu couteux. Malheureusement, sa faible conductivité nuit aux performances électrochimiques. Le fait de diminuer la taille des particules ou d’enrober les particules d’une couche de carbone permet d’augmenter la conductivité. Nous avons utilisé une nouvelle méthode appelée « synthèse par voie fondue » pour synthétiser le LiFePO4. Cette synthèse donne des gros cristaux et aucune impureté n’est détectée par analyse Rayon-X. En revanche, la synthèse de LiXFePO4 donne un mélange de LiFePO4 pur et d’impureté à base de lithium ou de fer selon l’excès de fer ou de lithium utilisé. La taille des particules de LiFePO4 est réduite à l’aide d’un broyeur planétaire et plusieurs paramètres de broyage sont étudiés. Une couche de carbone est ensuite déposée sur la surface des particules broyées par un traitement thermique sur le LiFePO4 avec du -lactose. L’influence de plusieurs paramètres comme la température du traitement thermique ou la durée du chauffage sont étudiés. Ces expériences sont réalisées avec un appareil d’analyse thermogravimétrique (ATG) qui donne la quantité de chaleur ainsi que la variation de masse durant le chauffage de l’échantillon. Ce nouveau chauffage pour la couche de carbone donne des échantillons dont les performances électrochimiques sont similaires à celles obtenues précédemment avec la méthode de chauffage pour la couche de carbone utilisant le four tubulaire. / LiFePO4 is a promising cathode material for Lithium-ion batteries. It provides high thermal stability and is synthesized using low cost materials. Unfortunately LiFePO4 suffers from a low electrical conductivity, which is harmful to its electrochemical performance. Decreasing the particle size or coating the particles with carbon increases the conductivity of the material. We have used a new synthetic method called molten synthesis to synthesize LiFePO4. The molten synthesis produces large crystals of LiFePO4 with no impurity detected via X-ray diffraction analysis. Moreover, the synthesis of LiXFePO4 gives a mixture of pure LiFePO4 and Li-based impurities or LiFePO4 and Fe-based impurities whenever there is an excess of lithium or iron used. The particle size of the synthesized material is reduced via a Planetary Mill and numerous milling parameters were investigated. A carbon coating was then deposited on the surface of the milled material by thermally treating LiFePO4 with β-lactose. The influences of several parameters such as heat treatment temperature and/or heating duration were studied. These experiments were performed using a thermogravimetric analysis (TGA), which provides the amount of heat and weight change during the heating of the sample. This new heating method for carbon coating gave rise to samples with similar electrochemical performance data as to the previously established heating method involving a tubular furnace.

En raison de leur petite taille, les nanoparticules (NP) (< 100 nm) peuvent coaguler très rapidement ce qui favorise leur pénétration dans l’organisme sous forme d’agglomérats. L’objectif de cette recherche est d’étudier l’influence de l’état d’agglomération de NP de dioxyde de titane (TiO2) de trois tailles de départ différentes, 5, 10-30 ou 50 nm sur la toxicité pulmonaire chez le rat mâle (F344) exposé à des aérosols de 2, 7 ou 20 mg/m3 pendant 6 heures. Dans une chambre d’inhalation, six groupes de rats (n = 6 par groupe) ont été exposés par inhalation aiguë nez-seulement à des aérosols ayant une taille primaire de 5 nm, mais produits sous forme faiblement (< 100 nm) ou fortement (> 100 nm) agglomérée à 2, 7 et 20 mg/m3. De façon similaire, quatre autres groupes de rats ont été exposés à 20 mg/m3 à des aérosols ayant une taille primaire de 10-30 et 50 nm. Les différents aérosols ont été générés par nébulisation à partir de suspensions ou par dispersion à sec. Pour chaque concentration massique, un groupe de rats témoins (n = 6 par groupe) a été exposé à de l’air comprimé dans les mêmes conditions. Les animaux ont été sacrifiés 16 heures après la fin de l’exposition et les lavages broncho-alvéolaires ont permis de doser des marqueurs d’effets inflammatoires, cytotoxiques et de stress oxydant. Des coupes histologiques de poumons ont également été analysées. L’influence de l’état d’agglomération des NP de TiO2 n’a pu être discriminée à 2 mg/m3. Aux concentrations massiques de 7 et 20 mg/m3, nos résultats montrent qu’une réponse inflammatoire aiguë est induite suite à l'exposition aux aérosols fortement agglomérés. En plus de cette réponse, l’exposition aux aérosols faiblement agglomérés à 20 mg/m3 s’est traduite par une augmentation significative de la 8-isoprostane et de la lactate déshydrogénase. À 20 mg/m3, les effets cytotoxiques étaient plus importants suite à l’exposition aux NP de 5 nm faiblement agglomérées. Ces travaux ont montré dans l'ensemble que différents mécanismes de toxicité pulmonaire peuvent être empruntés par les NP de TiO2 en fonction de la taille de départ et de l’état d’agglomération. / Given their small size, nanoparticles (NP) (< 100 nm) can coagulate quickly, which promotes their entry into the body in the form of agglomerates. The objective of this study is to evaluate the influence of the agglomeration state of three different primary particle sizes (5, 10-30 and 50 nm) of titanium dioxide (TiO2) NP on the pulmonary toxicity of male rats (F344) exposed to aerosols at 2, 7 or 20 mg/m3 for 6 hours. In an inhalation chamber, six groups of rats (n = 6 per group) were acutely exposed by nose-only inhalation to aerosols with a 5-nm primary particle size, produced in the form of small agglomerates (< 100 nm) (SA) or large agglomerates (> 100 nm) (LA) at 2, 7 and 20 mg/m3. Similarly, four other groups of rats were exposed to aerosols at 20 mg/m3 with a primary particle size of 10-30 and 50 nm. The different aerosols were generated by nebulization of suspensions or by dry dispersion. For each mass concentration, one group of control rats (n = 6 per group) was exposed to compressed air under the same conditions. The animals were sacrificed 16 hours after the end of exposure, and analysis of the bronchoalveolar lavage fluids was used to measure markers of inflammatory, cytotoxicity and oxidative stress effects. Lung sections were also analyzed for histopathology. The influence of the agglomeration state of TiO2 NP (5 nm) could not be determined at 2 mg/m3. For mass concentrations of 7 and 20 mg/m3, our results showed that an acute inflammatory response was induced following exposure to LA aerosols. In addition to this response, exposure to SA aerosols resulted in a significant increase in 8-isoprostane and lactate dehydrogenase. At 20 mg/m3, the cytotoxic effects were greater after exposure to the 5-nm NP in the SA aerosol. This study showed that TiO2 NP use different mechanisms to induce their pulmonary toxicity as a function of their primary particle size and their agglomeration state.

Charakteristisch für Perlcellulose als Regenerat vom Typ Cellulose II sind sphärisch geformte, poröse Partikel mit einer hohen spezifischen Oberfläche und einer guten Bioverträglichkeit. Aufgrund ihrer Eigenschaften sind diese Cellulosemikropartikel besonders gut für medizinische Anwendungen geeignet. Im Mittelpunkt der Arbeit standen Herstellung, Charakterisierung und Modifizierung von Perlcellulosen mit Partikelgrößen von etwa 1 bis10 µm. Im Rahmen der Arbeit wurden zunächst sieben technische Cellulose-2,5-acetate mit vergleichbaren molekularen Eigenschaften auf ihre Eignung zur Herstellung von Perlcellulose nach dem in EP0750007 beschriebenen Acetatverfahren untersucht. Dabei erfolgte der Vergleich verschiedener Eigenschaften. Aus allen untersuchten Celluloseacetaten können Perlcellulosen synthetisiert werden. Als besonders geeignet erwies sich ein Produkt mit einer Molmasse von über 100.000, einem Verhältnis der Molmasse zur numerischen Molmasse von etwa 1,5 und einer guten Löslichkeit in Ethylacetat / Methanol (100:17,5). Die hergestellte Perlcellulose hat eine geringe Partikelgröße und eine relativ enge Größenverteilung. Damit erfüllt dieses Cellulose-2,5-acetat alle Anforderungen für die Synthese von Perlcellulose. Der entscheidende Verfahrensschritt zur Herstellung von Perlcellulose ist das Dispergieren der Emulsion mittels Inline-Ultraturrax. Die Partikelgrößenverteilung hängt im Wesentlichen von den Bedingungen während des Dispergierens ab. Im Rahmen der Arbeit gelang die reproduzierbare Herstellung von Cellulosemicrospheres mit einer Partikelgröße unter 5 µm. Für die Herstellung von Cellulosemikropartikeln mit definierten Eigenschaften ist neben den Synthesebedingungen auch die Charakterisierung der Perlcellulosen von entscheidender Bedeutung. Dafür wurden zunächst etablierte Verfahren verwendet (Partikelgrößenmessung, REM und Quecksilberporosimetrie). Parallel dazu erfolgte die Entwicklung bzw. Einführung neuer Methoden. Im Vordergrund stand die Untersuchung des Sedimentationsverhaltens der Perlcellulosen durch analytisches Zentrifugieren. Davon ausgehend konnte ein Verfahren zur Berechnung der Porosität aus dem Sedimentationsvolumen entwickelt werden. Zum Nachweis der kompletten Deacetylierung der Proben wurde die Ramanspektroskopie genutzt. Durch die Anwendung vorhandener und die Entwicklung neuer Methoden wird die genaue Einstellung von Eigenschaften der Perlcellulosen (z. B. Partikelgröße und deren Verteilung, Morphologie sowie Porosität) ermöglicht und deren Reproduzierbarkeit gewährleistet. Weitere Versuche hatten die Entwicklung von Endotoxinadsorbermaterial auf Basis von Perlcellulose und Polymyxin-B-sulfat (PMB) zum Ziel. Die Kopplung des PMB erfolgte meist nach Aktivierung der Proben mit Epichlorhydrin. Zunächst wurde die eingesetzte Epichlorhydrinmenge variiert, um das Optimum für die Aktivierung der Perlcellulosen zu finden. Weiterhin wurden unterschiedliche Mengen PMB angebunden und die Anbindung an nicht aktivierte Proben untersucht. Die Planung aller Versuche erfolgte jeweils nach Auswertung der an der Donau-Universität Krems durchgeführten Limulus- Amöbocyten- Lysat (LAL)-Tests. Mittels dieser Batchtests wurde die Wirksamkeit des Endotoxinadsorbermaterials sowohl im Vergleich zu unbehandeltem Blutplasma und als auch zu kommerziell erhältlichen Adsorbern auf Polystyrenbasis getestet. Endotoxinadsorber, die bei diesen Tests besonders gut bewertet wurden, konnten in einem up-scale- Versuch erstmals in größeren Mengen synthetisiert werden. Auch die direkte Herstellung von Endotoxinadsorbermaterial aus Perlcelluloseacetat konnte realisiert werden. Bei diesem neu entwickelten Verfahren erfolgen Deacetylierung und Aktivierung in einem Schritt. Damit kann die Herstellung vereinfacht werden. Zur Gewährleistung der Erstfehlersicherheit in extrakorporalen Blutreinigungssystemen sollen magnetisierte Perlcellulosepartikel als bioverträgliche Marker eingesetzt werden. Versuche zur Magnetisierung von Cellulosemikropartikeln während des Herstellungsprozesses zeigten, dass die Einbindung von Magnetit bei Erhalt der sphärischen Partikelstruktur prinzipiell auch auf diesem homogenen Syntheseweg möglich ist. / Bead cellulose is regenerated cellulose II characterized by spherically shaped, porous particles with a high specific surface and a good biocompatibility. Because of their properties these cellulose microspheres are especially suited for medical applications. The focus of this work was the synthesis, characterization and modification of bead cellulose with particle sizes between 1 to 10 µm. In the frame of this work seven technical cellulose-2.5-acetates were investigated with regard to their suitability for making bead cellulose according to the process described in EP0750007. These cellulose acetates have comparable molecular characteristics. Different properties were compared. Bead celluloses can be synthesized from all investigated cellulose acetates. A product with a molecular weight of more than 100,000 and with a ratio between molecular weight and numeric molecular weight of about 1.5 is special suited. This cellulose-2.5-acetate has a good solubility in ethyl acetate / methanol (100:17.5). The bead cellulose made from it has a low particle size and a relative narrow size distribution. Thus this cellulose acetate complies with the requirements for making bead cellulose. The most important process step for making bead cellulose is the dispersing of the emulsion using an inline-ultraturrax. The distribution of particle size depends mainly on the conditions during dispersing. A reproducible synthesis of cellulose microspheres with a particle size range below 5 µm was successfully achieved. In addition to determining conditions for manufacturing bead cellulose the characterization of the microspheres is essential to obtain bead cellulose with well defined properties. At first well-established methods of characterization were used (particle size measurement, SEM and mercury porosimetry). In parallel new methods were developed and implemented. The main focus was the investigation of sedimentation behaviour of bead cellulose using analytical centrifugation. Based on this knowledge of the sedimentation volume a new method to calculate the porosity was designed. Raman spectroscopy was used for detecting the complete deacetylation of the samples. By using well-established and newly developed methods properties of bead cellulose such as particle size and distribution, morphology and porosity can be accurately adjusted. In this way the reproducible synthesis of cellulose microspheres can be ensured. The aim of further experiments was to develop an endotoxin adsorber material based on a coupling of bead cellulose with Polymyxin B sulfate (PMB). The coupling with PMB was carried out after activation of the samples by using epichlorohydrin. At first the added epichlorohydrin amount was diversified in order to find the optimum for the activation of bead cellulose. Later the coupling of different amounts of PMB took place and the linking of PMB to non activated samples was investigated too. The planning of all experiments occurred after evaluation of Limulus amebocyte lysate (LAL) tests at Danube-University Krems. Using these batch tests the effectiveness of the endotoxin adsorber material was tested compared to untreated blood plasma as well as commercial available adsorbers based on polystyrene. Endotoxin adsorbers showing the best adsorption rate were then synthesized for the first time in larger quantities. Also the direct synthesis of endotoxin adsorber material based on bead cellulose acetate could be realized. Using this newly developed method, deacetylation and activation occur during the same step. This means manufacturing process can be simplified. Using magnetized bead cellulose as biocompatible marker particles is planned to achieve first fault safety in case of a membrane rupture during extracorporeal blood purification. Initial tests have shown that the magnetization of cellulose microspheres is possible during the manufacturing process. The incorporation of magnetite can be realized while keeping the spherical shape of the particles using this homogenous synthesis pathway.

Bei strukturorientierten, aus relativ großen Holzpartikeln aufgebauten Holzwerkstoffen wie z.B. OSB (oriented strand board) addieren sich die gerichteten Festigkeiten der einzelnen Lagen je nach Orientierung der Partikel und der Verteilung ihrer Größenparameter. Wünschenswert wäre eine Messung der Partikelgeometrie und Orientierung möglichst im Prozess, z.B. am Formstrang vor der Presse direkt durch den „Blick auf das Vlies“. Bisher sind regelmäßige on-line-Messungen der Spangeometrie aber nicht möglich, und Einzelspanmessungen werden nicht vorgenommen, weil sie zu aufwändig wären. Um die Partikelkonturen zunächst hinreichend für die Vermessung zu restaurieren und dann zu vermessen, muss ein mehrstufiges Verfahren angewendet werden, das eine Szene mit Strands und mehr oder weniger deutlichen Kanten zunächst als „Grauwertgebirge“ auffasst. Zur Segmentierung reicht ein Watershed-Algorithmus nicht aus. Auch ein zweistufiger Kantendetektor nach Canny liefert allein noch kein ausreichendes Ergebnis, weil sich keine geschlossenen Objektkonturen ergeben. Hinreichend dagegen ist ein komplexes Verfahren auf der Grundlage der Höhenschichtzerlegung und nachfolgenden Synthese: Nach einer Transformation der Grauwerte des Bildes in eine reduzierte, gleichverteilte Anzahl von Höhenschichten werden zwischen diesen die lokalen morphologischen Gradienten berechnet und herangezogen für die Rekonstruktion der ursprünglichen Spankonturen. Diese werden aus den Höhenschichten aufaddiert, wobei allerdings nur Teilflächen innerhalb eines für die gesuchten Spangrößen plausiblen Größenintervalls einbezogen werden, um Störungen zu unterdrücken. Das Ergebnis der Rekonstruktion wird zusätzlich verknüpft mit den bereits durch einen Canny-Operator im Originalbild detektierten deutlichen Kanten und morphologisch bereinigt. Diese erweiterte Höhenschichtanalyse ergibt ausreichend segmentierte Bilder, in denen die Objektgrenzen weitgehend den Spankonturen entsprechen. Bei der nachfolgenden Vermessung der Objekte werden Standard-Algorithmen eingesetzt, wobei sich die Approximation von Spankonturen durch momentengleiche Ellipsen als sinnvoll erwies. Verbliebene Fehldetektionen können bei der Vermessung unterdrückt werden durch Formfaktoren und zusätzliche Größenintervalle. Zur Darstellung und Charakterisierung der Größenverteilungen für die Länge und die Breite wurden die nach der Objektfläche gewichtete, linear skalierte Verteilungsdichte (q2-Verteilung), die Verteilungssumme und verschiedene Quantile verwendet. Zur Umsetzung und Demonstration des Zusammenwirkens der verschiedenen Algorithmen wurde auf der Basis von MATLAB das Demonstrationsprogramm „SizeBulk“ entwickelt, das Bildfolgen verarbeiten kann und mit dem die verschiedenen Varianten der Bildaufbereitung und Parametrierung durchgespielt werden können. Das Ergebnis des Detektionsverfahrens enthält allerdings nur die vollständigen Konturen der ganz oben liegenden Objekte; Objekte unterhalb der Außenlage sind teilweise verdeckt und können daher nur unvollständig vermessen werden. Zum Test wurden daher synthetische Bilder mit vereinzelten und überlagerten Objekten bekannter Größenverteilung erzeugt und dem Detektions- und Messverfahren unterworfen. Dabei zeigte sich, dass die Größenstatistiken durch den Überlagerungseffekt und auch die Spanorientierung zwar beeinflusst werden, dass aber zumindest die Modalwerte der wichtigsten Größenparameter Länge und Breite meist erkennbar bleiben. Als Versuchsmaterial dienten außer den synthetischen Bildern verschiedene Sortimente von OSB-Strands aus Industrie- und Laborproduktion. Sie wurden sowohl manuell vereinzelt als auch zu einem Vlies arrangiert vermessen. Auch bei realen Strands zeigten sich gleiche Einflüsse der Überlagerung auf die Größenverteilungen wie in der Simulation. Es gilt aber auch hier, dass die Charakteristika verschiedener Spankontingente bei gleichen Aufnahmebedingungen und Auswerteparametern gut messbar sind bzw. dass Änderungen in der gemessenen Größenverteilung eindeutig den geometrischen Eigenschaften der Späne zugeordnet werden können. Die Eignung der Verarbeitungsfolge zur Charakterisierung von Spangrößenverteilungen bestätigte sich auch an Bildern, die ausschließlich am Vlies auf einem Formstrang aufgenommen wurden. Zusätzlich wurde nachgewiesen, dass mit der erweiterten Höhenschichtanalyse auch Bilder von Spanplattenoberflächen ausgewertet werden könnten und daraus auf die Größenverteilung der eingesetzten Deckschichtspäne geschlossen werden kann. Das vorgestellte Verfahren ist daher eine gute und neuartige Möglichkeit, prozessnah an Teilflächen von OSB-Vliesen anhand von Grauwertbildern die Größenverteilungen der Strands zu charakterisieren und eignet sich grundsätzlich für den industriellen Einsatz. Geeignete Verfahren waren zumindest für Holzpartikel bisher nicht bekannt. Diese Möglichkeit, Trends in der Spangrößenverteilung automatisch zu erkennen, eröffnet daher neue Perspektiven für die Prozessüberwachung. / The strength of wood-based materials made of several layers of big and oriented particles like OSB (oriented strand board) is a superposition of the strengths of the layers according to the orientation of the particles and depending from their size distribution. It would be desirable to measure particle geometry and orientation close to the production process, e.g. with a “view onto the mat”. Currently, continuous on-line measurements of the particle geometry are not possible, while measurements of separated particles would be too costly and time-consuming. Before measuring particle shapes they have to be reconstructed in a multi-stage procedure which considers an image scene with strands as “gray value mountains”. Segmentation using a watershed algorithm is not sufficient. Also a two-step edge detector according to Canny does not yield closed object shapes. A multi-step procedure based on threshold decomposition and recombination however is successful: The gray values in the image are transformed into a reduced and uniformly distributed set of threshold levels. The local morphological gradients between these levels are used to re-build the original particle shapes by adding the threshold levels. Only shapes with a plausible size corresponding to real particle shapes are included in order to suppress noise. The result of the reconstruction from threshold levels is then matched with the result of the strong edges in the original image, which had been detected using a Canny operator, and is finally cleaned with morphological operators. This extended threshold analysis produces sufficiently segmented images with object shapes corresponding extensively to the particle shapes. Standard algorithms are used to measure geometric features of the objects. An approximation of particle shapes with ellipses of equal moments of inertia is useful. Remaining incorrectly detected objects are removed by form factors and size intervals. Size distributions for the parameters length and width are presented and characterized as density distribution histograms, weighted by the object area and linearly scaled (q2 distribution), as well as the cumulated distribution and different quantiles. A demonstration software “SizeBulk” based on MATLAB has been developed to demonstrate the computation and the interaction of algorithms. Image sequences can be processed and different variations of image preprocessing and parametrization can be tested. However, the detection procedure yields complete shapes only for those particles in the top layer. Objects in lower layers are partially hidden and cannot be measured completely. Artificial images with separated and with overlaid objects with a known size distribution were generated to study this effect. It was shown that size distributions are influenced by this covering effect and also by the strand orientation, but that at least the modes of the most important size parameters length and width remain in evidence. Artificial images and several samples with OSB strands from industrial and laboratory production were used for testing. They were measured as single strands as well as arrangements similar to an OSB mat. For real strands, the same covering effects to the size distributions revealed as in the simulation. Under stable image acquisition conditions and using similar processing parameters the characteristics of these samples can well be measured, and changes in the size distributions are definitely due to the geometric properties of the strands. The suitability of the processing procedure for the characterization of strand size distributions could also be confirmed for images acquired from OSB mats in a production line. Moreover, it could be shown that the extended threshold analysis is also suitable to evaluate images of particle board surfaces and to draw conclusions about the size distribution of the top layer particles. Therefore, the method presented here is a novel possibility to measure size distributions of OSB strands through the evaluation of partial gray value images of the mat surface. In principle, this method is suitable to be transferred to an industrial application. So far, methods that address the problem of detecting trends of the strand size distribution were not known, and this work shows new perspectives for process monitoring.

Cancer is the second leading cause of death in the United States and its onset is highly incident in the lungs, with very low long-term survival rates. Chemotherapy plays a significant role for lung cancer treatment, and pulmonary delivery may be a potential route for anticancer drug delivery to treat lung tumors. Coenzyme Q₁₀ (CoQ₁₀) is a poorly-water soluble compound that is being investigated for the treatment of carcinomas. In this work, we hypothesize that formulations of CoQ10 may be developed for pulmonary delivery with a satisfactory pharmacokinetic profile that will have the potential to improve a pharmacodynamic response when treating lung malignancies. The formulation design was to use a vibrating-mesh nebulizer to aerosolize aqueous dispersions of CoQ₁₀ stabilized by phospholipids physiologically found in the lungs. In the first study, a method was developed to measure the surface tension of liquids, a physicochemical property that has been shown to influence the aerosol output characteristics from vibrating-mesh nebulizers. Subsequently, this method was used, together with analysis of particle size distribution, zeta potential, and rheology, to further evaluate the factors influencing the capability of this nebulizer system to continuously and steadily aerosolize formulations of CoQ₁₀ prepared with high pressure homogenization. The aerosolization profile (nebulization performance and in vitro drug deposition of nebulized droplets) of formulations prepared with soybean lecithin, dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC) were evaluated. The rheological behavior of these dispersions was found to be the factor that may be indicative of the aerosolization output profile. Finally, the pulmonary deposition and systemic distribution of CoQ₁₀ prepared as DMPC, DPPC, and DSPC dispersions were investigated in vivo in mice. It was found that high drug amounts were deposited and retained in the mouse lungs for at least 48 hours post nebulization. Systemic distribution was not observed and deposition in the nasal cavity occurred at a lower scale than in the lungs. This body of work provides evidence that CoQ₁₀ may be successfully formulated as dispersions to be aerosolized using vibrating-mesh nebulizers and achieve high drug deposition in the lungs during inhalation.

Biomass burning started to attract attention since the last decade because of its impacts on the atmosphere and the environmental air quality, as well as significant potential effects on human health and global climate change. Knowledge of particle emission characteristics from biomass burning is crucially important for the quantitative assessment of the potential impacts. This thesis presents the results of study aimed towards comprehensive characterization of particle emissions from biomass burning. The study was conducted both under controlled laboratory conditions, to quantify the particle size distribution and emission factors by taking into account various factors which may affect the particle characteristics, and in the field, to investigate biomass burning processes in the real life situations and to examine vertical profile of particles in the atmosphere. To simulate different environmental conditions, a new technique has been developed for investigating particle emissions from biomass burning in the laboratory. As biomass burning may occur in a field at various wind speeds and burning rates, the technique was designed to allow adjustment of the flow rates of the air introduced into the chamber, in order to control burning under different conditions. In addition, the technique design has enabled alteration of the high particle concentrations, allowing conducting measurements with the instrumentations that had the upper concentration limits exciding the concentrations characteristic to the biomass burning. The technique was applied to characterize particle emissions from burning of several tree species common to Australian forests. The aerosol particles were characterized in terms of size distribution and emission factors, such as PM2.5 particle mass emission factor and particle number emission factor, under various burning conditions. The characteristics of particles over a range of burning phases (e.g., ignition, flaming, and smoldering) were also investigated. The results showed that particle characteristics depend on the type of tree, part of tree, and the burning rate. In particular, fast burning of the wood samples produced particles with the CMD of 60 nm during the ignition phase and 30 nm for the rest of the burning process. Slow burning of the wood samples produced large particles with the CMD of 120 nm, 60 nm and 40 nm for the ignition, flaming and smoldering phases, respectively. The CMD of particles emitted by burning the leaves and branches was found to be 50 nm for the flaming phase and 30 nm for the smoldering phase, under fast burning conditions. Under slow burning conditions, the CMD of particles was found to be between 100 to 200 nm for the ignition and flaming phase, and 50 nm for the smoldering phase. For fast burning, the average particle number emission factors were between 3.3 to 5.7 x 1015 particles/kg for wood and 0.5 to 6.9 x 1015 particles/kg for leaves and branches. The PM2.5 emission factors were between 140 to 210 mg/kg for wood and 450 to 4700 mg/kg for leaves and branches. For slow burning conditions, the average particle number emission factors were between 2.8 to 44.8 x 1013 particles/kg for wood and 0.5 to 9.3 x 1013 particles/kg for leaves and branches, and the PM2.5 emissions factors were between 120 to 480 mg/kg for wood and 3300 to 4900 mg/kg for leaves and branches. The field measurements were conducted to investigate particle emissions from biomass burning in the Northern Territory of Australia over dry seasons. The results of field studies revealed that diameters of particles in ambient air emissions were within the size range observed during laboratory investigations. The laboratory measurements found that the particles released during the controlled burning were of a diameter between 30 and 210 nm, depending on the burning conditions. Under fast burning conditions, smaller particles were produced with a diameter in the range of 30 to 60 nm, whilst larger particles, with a diameter between 60 nm and 210 nm, were produced during slow burning. The airborne field measurements of biomass particles found that most of the particles measured under the boundary layer had a CMD of (83 ± 13) nm during the early dry season (EDS), and (127 ± 6) nm during the late dry season (LDS). The characteristics of ambient particles were found to be significantly different at the EDS and the LDS due to several factors including moisture content of vegetation, location of fires related to the flight paths, intensity of fires, and burned areas. Specifically, the investigations of the vertical profiles of particles in the atmosphere have revealed significant differences in the particle properties during early dry season and late dry season. The characteristics of particle size distribution played a significant role in these differences.

Motor vehicles are a major source of gaseous and particulate matter pollution in urban areas, particularly of ultrafine sized particles (diameters < 0.1 µm). Exposure to particulate matter has been found to be associated with serious health effects, including respiratory and cardiovascular disease, and mortality. Particle emissions generated by motor vehicles span a very broad size range (from around 0.003-10 µm) and are measured as different subsets of particle mass concentrations or particle number count. However, there exist scientific challenges in analysing and interpreting the large data sets on motor vehicle emission factors, and no understanding is available of the application of different particle metrics as a basis for air quality regulation. To date a comprehensive inventory covering the broad size range of particles emitted by motor vehicles, and which includes particle number, does not exist anywhere in the world. This thesis covers research related to four important and interrelated aspects pertaining to particulate matter generated by motor vehicle fleets. These include the derivation of suitable particle emission factors for use in transport modelling and health impact assessments; quantification of motor vehicle particle emission inventories; investigation of the particle characteristic modality within particle size distributions as a potential for developing air quality regulation; and review and synthesis of current knowledge on ultrafine particles as it relates to motor vehicles; and the application of these aspects to the quantification, control and management of motor vehicle particle emissions. In order to quantify emissions in terms of a comprehensive inventory, which covers the full size range of particles emitted by motor vehicle fleets, it was necessary to derive a suitable set of particle emission factors for different vehicle and road type combinations for particle number, particle volume, PM1, PM2.5 and PM1 (mass concentration of particles with aerodynamic diameters < 1 µm, < 2.5 µm and < 10 µm respectively). The very large data set of emission factors analysed in this study were sourced from measurement studies conducted in developed countries, and hence the derived set of emission factors are suitable for preparing inventories in other urban regions of the developed world. These emission factors are particularly useful for regions with a lack of measurement data to derive emission factors, or where experimental data are available but are of insufficient scope. The comprehensive particle emissions inventory presented in this thesis is the first published inventory of tailpipe particle emissions prepared for a motor vehicle fleet, and included the quantification of particle emissions covering the full size range of particles emitted by vehicles, based on measurement data. The inventory quantified particle emissions measured in terms of particle number and different particle mass size fractions. It was developed for the urban South-East Queensland fleet in Australia, and included testing the particle emission implications of future scenarios for different passenger and freight travel demand. The thesis also presents evidence of the usefulness of examining modality within particle size distributions as a basis for developing air quality regulations; and finds evidence to support the relevance of introducing a new PM1 mass ambient air quality standard for the majority of environments worldwide. The study found that a combination of PM1 and PM10 standards are likely to be a more discerning and suitable set of ambient air quality standards for controlling particles emitted from combustion and mechanically-generated sources, such as motor vehicles, than the current mass standards of PM2.5 and PM10. The study also reviewed and synthesized existing knowledge on ultrafine particles, with a specific focus on those originating from motor vehicles. It found that motor vehicles are significant contributors to both air pollution and ultrafine particles in urban areas, and that a standardized measurement procedure is not currently available for ultrafine particles. The review found discrepancies exist between outcomes of instrumentation used to measure ultrafine particles; that few data is available on ultrafine particle chemistry and composition, long term monitoring; characterization of their spatial and temporal distribution in urban areas; and that no inventories for particle number are available for motor vehicle fleets. This knowledge is critical for epidemiological studies and exposure-response assessment. Conclusions from this review included the recommendation that ultrafine particles in populated urban areas be considered a likely target for future air quality regulation based on particle number, due to their potential impacts on the environment. The research in this PhD thesis successfully integrated the elements needed to quantify and manage motor vehicle fleet emissions, and its novelty relates to the combining of expertise from two distinctly separate disciplines - from aerosol science and transport modelling. The new knowledge and concepts developed in this PhD research provide never before available data and methods which can be used to develop comprehensive, size-resolved inventories of motor vehicle particle emissions, and air quality regulations to control particle emissions to protect the health and well-being of current and future generations.

[Truncated abstract] Self-filtration is here defined as particle detachment and re-deposition causing re-arrangement of the particles and therefore pore space which affects water flow in soil by decreasing hydraulic conductivity. This is of particular important in soils which are susceptible to structural breakdown. The objective of this thesis was to examine the dynamics of the self-filtration process in sodic sandy soils as affected by ionic strength and soil solution composition. The temporal changes of hydraulic conductivity and the elution of fine particles from soil columns were used as the main criteria to assess selffiltration. Two porous media exhibiting significantly different structural cohesion were examined, one a loamy sand (Balkuling soil) from agricultural land use and the second a mining residue from mineral sands operations . . . The effects of the composition of mixed calcium (Ca) and sodium (Na) ions in solution (sodium adsorption ratio (SAR)) on the exchange behaviour and saturated hydraulic conductivity were examined by carrying out batch binary exchange and saturated column transport experiments. A strong preference for Ca2+ ions in the exchange complex was observed for both soils. Generally K/Ko was found to decrease with increasing sodium adsorption ratio with the more structured Balkuling soil maintaining K/Ko for SARs 3 and 5 at an electrolyte concentration of 100 mmol/L. However measurements at the critical threshold and turbidity concentrations at a SAR of 15 revealed structural breakdown of the pore matrix system attributed to various extents of slaking, swelling, dispersion and decreases of pore radii as a result of selffiltration during leaching. These experiments illustrate the wide range of complex interactions involving clay mineralogy, solution composition and structural factors which can influence the extent of mobilization, transport and re-deposition of colloidal particles during the leaching process in soil profiles.