An der Spitze der Morbiditäts - und Mortalitätsstatistik steht weltweit das Metabolische Syndrom, bestehend aus androider Adipositas, pathologischer Glukosetoleranz, Dyslipidämie und arterieller Hypertonie, verbunden mit einer erhöhten Inzidenz atherosklerotischer Gefäßerkrankungen. Der Replikationsinitiator 1 (Repin1) wurde kürzlich als mögliches Kandidatengen für Adipositas sowie damit verbundene metabolische Funktionsstörungen in kongenen sowie subkongenen Rattenstämmen identifiziert. Ziel der Arbeit war es, den Einfluss von Repin1 auf den Fettzellstoffwechsel zu untersuchen. Hierfür wurde die Expression von Repin1 in 3T3– L1 Präadipozyten und differenzierten 3T3-L1 Adipozyten mittels siRNA Technologie stark vermindert, um so auf mögliche Funktionen des Proteins schließen zu können. Nachfolgend wurden Veränderungen des Zellstoffwechsels mittels Glukosetransport, Palmitataufnahme sowie Triglyceridgehalt der Adipozyten untersucht. Repin1 wird in der 3T3-L1 Zelllinie exprimiert und zeigt eine steigende Expression während der Adipogenese. Der Knockdown von Repin1 resultierte in kleineren Fettzellen mit geringerer basaler, jedoch verstärkter insulinstimulierter Glukoseaufnahme. Auch der Fettstoffwechsel zeigte sich alteriert: Neben einer reduzierten Palmitataufnahme war die Expression verschiedener Schlüsselgene der Fetttropfenfusion, des Glukose-sowie des Fetttransportes verändert. Fazit: Repin1 reguliert die Expression von Genen, die eine Rolle bei der Festlegung der Fettzellgröße und des basalen und Insulin-stimulierten Glukosetransports in Adipozyten spielen.:Inhaltsverzeichnis I Vorbemerkung II Wissenschaftlicher Anteil des Promovenden an der Publikation III Bibliographische Beschreibung IV Abkürzungsverzeichnis V I. Einleitung - Das metabolische Syndrom 1 A. Definition und Prävalenz 1 B. Klinische Relevanz 2 C. Pathophysiologie 3 D. Exogene und genetische Faktoren 7 II. Der Replikationsinitiator 1 9 III. Zielstellung der Arbeit 11 IV. Publikation 12 V. Zusammenfassung 19 VI. Supplemental Materials 24 VII. Literaturverzeichnis 32 VIII. Eigenständigkeitserklärung 38 IX. Curriculum vitae 39 X. Veröffentlichungen im Rahmen dieser Arbeit 41 XI.Danksagung 42

[pt] Com as novas regulamentações ambientais proibindo o uso de fluidos de perfuração que apresentassem em sua composição elementos como óleo diesel, se fez necessário a busca por novos componentes que, além de serem eficazes em sua função, apresentassem característica de biodegradabilidade sendo, assim, menos danoso ao meio ambiente. A base do fluido de perfuração escolhida para se enquadrar as novas regras foi estudada neste trabalho com objetivo de avaliar a sua estabilidade e o seu comportamento reológico. O fluido trabalhado é uma emulsão inversa cuja fase contínua é a olefina e a fase dispersa, salmoura de NaCl, acrescido de um emulsificante primário, Cybermul, e um secundário, Cyberplus. Para retardar o processo de desestabilização, majoritariamente caracterizado pela sedimentação, em um segundo momento, foi adicionada a cal hidratada. Os testes realizados foram divididos em duas etapas: a primeira avaliando emulsões preparadas a 5000 rpm, 7500 rpm e 10000 rpm sem cal em sua composição e a segunda avaliando emulsões preparadas com a mesma velocidade de rotação, entretanto com cal hidratada. A principal variável adotada foi a velocidade de rotação com objetivo de ratificar o conhecimento de que quanto maior a velocidade de agitação durante a emulsificação, menores são as gotas geradas e, consequentemente, mais estável a emulsão. Os testes foram compostos por tensão interfacial, bottle test, distribuição do tamanho de gotas (microscopia e espalhamento dinâmico de luz) e testes de comportamento reológico, que incluem, tensão constante, curva de escoamento e varredura de tensão e tempo. Os resultados obtidos permitiram relacionar o tamanho das gotas geradas com a estabilidade da emulsão e com a sua viscosidade. / [en] Since new environmental regulations were established prohibiting the use of drilling fluids that had elements such as diesel in their composition, it was necessary to search for new components that, besides being effective in their function, had a biodegradability characteristic, thus being less harmful to the environment. The base of the drilling fluid chosen to fit the new rules was studied in this thesis in order to characterize its stability and rheological behavior. The fluid used is an inverse emulsion whose continuous phase is the olefin and the dispersed phase, brine, plus a primary emulsifier, Cybermul, and a secondary one, Cyberplus. To delay the destabilization process, mainly characterized by sedimentation, in a second moment, hydrated lime was added to the emulsion s composition. The tests performed were divided into two stages: the first, emulsions prepared at 5000 rpm, 7500 rpm and 10,000 rpm without lime in their composition were analyzed and the second, emulsions prepared at the same rotation velocities however with hydrated lime in their composition. The main variable adopted was the speed of rotation in order to confirm the knowledge that the higher is the speed of agitation during emulsification, the smaller are the drops generated and, consequently, the more stable is the emulsion. The tests consisted of interfacial tension, bottle test, droplet size distribution (microscopy and dynamic light scattering) and rheological behavior tests, which include, creep tests, flow curve and stress and time sweep tests. The results obtained allowed to relate the size of the drops with the emulsion s stability and with its viscosity.

Drug administration through the pulmonary route is an ancient technique that evolved from inhaling the smoke of certain leaves as a medicine. The optimum droplet diameter for the pulmonary system deposition has been identified to be in the range from 2 to 3.5 μm, with potential deposition rates of up to 80% of this size range. Currently, the most used aerosol generator methods are the pressurized metered dose inhalers. However, they generally exhibit low deposition efficiency with less than 20 % of the spray reaching the target area of the lungs as most of the drug deposited in the upper airways. This is for the most part due to the droplet size polydispersity that is inherent in these systems. The droplets of the biggest diameter will deposit in the upper airways, and then the deposited medicine will be swallowed and absorbed in the gastrointestinal tract. This can produce adverse medical side effects. Electrospray (ES) or electrohydrodynamic atomization (EHDA) is a promising atomization process due to its ability to produce a spray with monodisperse droplet size. The current study will investigate the feasibility of using electrospray in a pulmonary drug delivery system. Assessments, selection and characterization of suitable biocompatible solvents that can be used as a lung obstruction relief drug were carried out. Tests to identify the electrospray setup necessary to produce droplet sizes in the appropriate range for deposition in the lungs were carried out. The study found that both stable and pulsating cone jet modes can produce the required droplet size and the pulsating mode can produce at least four times higher flow than stable cone jet mode. A low-cost image analysis technique developed for this work gave satisfactory results that could be compared to droplet size scaling laws from the literature. However, it proved to be relatively time consuming and further automation of this technique would make it more suitable for large-scale studies. The image analysis results show a correlation between the cone length, cone angle and the applied voltage. The droplet scaling laws discrepancies such as the solution flow rate exponent and the constant that is used by some scaling laws may be attributed to the droplet evaporation time which is quite short for the water/ ethanol solutions. The emitter diameter and the conductivity effect on the I(Q) power law and the sensitivity of the onset voltage (Vonset) to the liquid flow rate (Q), were demonstrated for solutions of triethylene-glycol (TEG), and for an ethanol-water mixture solution.

No description available.

Vegetable oil methyl esters obtained by transesterification of vegetable oils are considered to be suitable alternative fuels for diesel engines. However, higher viscosity, surface tension and boiling temperatures of biodiesels may adversely affect spray characteristics as compared to those of diesel. Thus, spray characteristics of Jatropha Methyl Ester (JME) are studied by comparing them to those of diesel in a high-pressure chamber with optical access to simulate the actual in-cylinder conditions. Also, the effect of inner-nozzle cavitation on JME and diesel sprays is studied by utilizing two nozzles, one with sharp entry-radius and the other with larger entry-radius. Finally, spray characteristics of surrogate fuels such as n-dodecane and n-hexadecane are also studied. The first part of the work concerning precise measurements of inner-nozzle geometry revealed that one of the nozzles has a hole diameter of 190-µm and entry-radius of around 70-µm, while the other has a hole diameter of 208-µm and entry-radius of around 10-µm. Injection rate-shape and coefficient of discharge for JME and diesel flow through the two nozzles were then measured. It was observed that while the coefficients of discharge (Cd) are almost identical for JME and diesel, the nozzle with entry radius of 10-µm exhibited around 20% lower Cd than that of the entry-radius of 70-µm. This observation coupled with insight from complementary CFD simulations of inner-nozzle flow showed that the lower Cd of the nozzle with entry-radius of 10-µm could be attributed to inner-nozzle cavitation. The second part of the work involved measurement of non-evaporating spray characteristics including spray-tip penetration, spray-cone angle and droplet size measurement under realistic operating conditions using techniques such as Shadowgraphy and Particle/Droplet Imaging Analysis (PDIA). The non-evaporating spray of the fuels are studied by injecting them using a common-rail fuel injection system into the high-pressure chamber maintained at room temperature. Experimental results show that JME is associated with a slightly faster spray-tip penetration and narrow spray-cone angle indicating inferior spray atomization which is confirmed by around 5% larger droplet sizes. Slower spray-tip penetration, wider spray-cone angle and around 5% smaller droplet sizes are observed for the spray from the cavitating nozzle. Thus, the inner nozzle cavitation is observed to improve the atomization of diesel and JME sprays. The differences in spray characteristics of JME and diesel reduce as the injection pressure increases. The spray-tip penetrations of both surrogates are observed to almost match that of diesel. The third part of the work involved measurements of evaporating spray liquid length, vapour penetration and spread angle for JME, diesel and surrogates at conditions of 50 bar chamber pressure and 900 K temperature. It is observed that the JME exhibits around 16% longer liquid length than that of diesel. The liquid length of n-dodecane is significantly lower than that of diesel and liquid length of n-hexadecane is around 20% higher than that of n-dodecane mimicking the trend of JME and diesel. The liquid length of n-hexadecane is very close to that of diesel at all the three test conditions. Interestingly, the vapour penetration and spread angle for all the fuels is observed to be almost identical. As the cold spray and evaporating spray characteristics of n-hexadecane match well with those of diesel, n-hexadecane can be chosen as a pure component surrogate for diesel. Finally, an analytical model for predicting the spray vapour penetration is assessed with the experimentally-observed trends of penetration and spray spread angle. The model indicated that the effect of fuel density variation is compensated by the corresponding variation in injection velocity for a given injection pressure to result in a similar vapour penetration. Overall, the present work, in addition to studying the effect of fuel physical properties and cavitation on sprays, has generated a comprehensive experimental database on non-evaporating and evaporating sprays of biodiesel, diesel, and pure component surrogates, which would aid significantly in validation of CFD simulations.

The extensive growth of nanotechnology has necessitated the development of economical and robust methods for large scale production of nanomaterials. It requires detailed quantitative understanding of lab-scale processes to enable effective scale-up and development of new contacting strategies for their controlled synthesis. In this thesis, attempts are made in both the directions using experimental and modelling approaches for synthesis of different nanoparticles. The two-phase Brust--Schiffrin protocol for the synthesis of gold nanoparticles was investigated first. The mechanism of transfer of reactants from aqueous to organic phase using phase transfer catalyst (PTC) was investigated using the measurement of interfacial tension, viscosity, SLS, SAXS, 1H NMR, DOSY-NMR, and Karl-Fischer titration. The study shows that the reactants are transferred to organic phase through the formation of hydrated complexes between reactants and PTC rather than through the solubilization of reactants in water core of inverse micelles of PTC, proposed recently in the literature. The particle synthesis reactions thus occur in the bulk organic phase. The extensive body of seemingly disparate experimental findings on Brust--Schiffrin protocol were put together next. The emerging picture ruled out both thermodynamic considerations and kinetics based arguments as exemplified by the classical LaMer's mechanism with sequential nucleation growth capping for size control in Brust--Schiffrin protocol. A new model for particle synthesis was developed. The model brought out continued nucleation--growth--capping based size control, an hitherto unknown mechanistic route for the synthesis of monodisperse particles, as the main mechanism. The model not only captured the reported features of the synthesis but also helped to improve the uniformity of the synthesized particles, validated experimentally. The two-step mechanism of Finke--Watzky---first order nucleation from precursor and autocatalytic growth of particles---proposed as an alternative to LaMer model to explain an induction period followed by a sigmoidal decrease in precursor concentration for the synthesis of iridium nanoparticles was investigated next. The mechanism is tested using an equivalent population balance model for its ability to explain the experimentally observed near constant breadth of the evolving size distribution as well. The predictions show that while it captures precursor conversion well, it fails to explain particle synthesis on account of its inability to suppress nucleation. A minimal four-step mechanism with additional steps for nucleation from reduced iridium atoms and their scavenging using particle surface is proposed. The new mechanism when combined with the first or second order nucleation, or classical nucleation with no scavenging of reduced atoms also fails to suppress nucleation. A burst like onset of nuclei formation with homogeneous nucleation and the scavenging of reduced atoms by particles are simultaneously required to explain all the reported features of the synthesis of iridium nanoparticles. A new reactor is proposed for continuous production of CaCO3 nanoparticles in gas-liquid reaction route. The key feature of the new reactor is the control of flow pattern to ensure efficient mixing of reactants. A liquidliquid reaction route for production of CaCO3 nanoparticles is also optimized to produce nanoparticles at high loading. Optimum supersaturation combined with efficient breakup of initial gel-like structure by mechanical agitation and charge control played a crucial role in producing nano sized CaCO3 particles.

A non-reactive model system comprising a highly concentrated and unstable oil-in-water emulsion was used to investigate the retention of oil by the membrane in producing biodiesel with a membrane reactor. Critical flux was identified using the relationship between the permeate flux and transmembrane pressure along with the separation efficiency of the membrane. It was shown that separation efficiencies above 99.5% could be obtained at all operating conditions up to the critical flux. It was observed that the concentration of oil in all collected permeate samples using the oil-water system was below 0.2 wt% when operating at a flux below the critical flux. Studies to date have been limited to the characterization of low concentrated emulsions below 15 vol.%. The average oil droplet size in highly concentrated emulsions was measured as 3200 nm employing direct light scattering (DLS) measurement methods. It was observed that the estimated cake layer thickness of 20 to 80 mm was larger than external diameter of the membrane tube i.e. 6 mm based on a large particle size. Settling of the concentrated emulsion permitted the detection of a smaller particle size distribution (30-100 nm) within the larger particles averaging 3200 nm. It was identified that DLS methods could not efficiently give the droplet size distribution of the oil in the emulsion since large particles interfered with the detection of smaller particles. The content of the smaller particles represented 1% of the total weight of oil at 30°C and 5% at 70°C. This was too low to be detected using DLS measurements but was sufficient to affect ultrafiltration. In order to study the critical flux in the presence of transesterification reaction and the effect of cross flow velocity on separation, various oils were transesterified in another membrane reactor providing higher cross flow velocity. higher cross flow velocity provides better separation by reducing materials deposition on the surface of the membrane due to higher shearing. The oils tested were canola, corn, sunflower and unrefined soy oils (Free Fatty Acids (FFA< 1%)), and waste cooking oil (FFA= 9%). The quality of all biodiesel samples was studied in terms of glycerine, mono-glyceride, di-glyceride and tri-glyceride concentrations. The composition of all biodiesel samples were in the range required by ASTM D6751 and EN 14214 standards. A critical flux based on operating pressure in the reactor was reached for waste cooking and pre-treated corn oils. It was identified that the reaction residence time in the reactor was an extremely important design parameter affecting the operating pressure in the reactor. / Natural Sciences and Engineering Research Council of Canada (NSERC)

Kraft recovery boiler smelt is shattered into small droplets by an impinging steam jet to prevent smelt-water explosions in the dissolving tank. Inadequate shattering increases the likelihood of dissolving tank explosions. While industry has not dedicated much effort to smelt shattering, the safety implications require smelt shattering to be studied in detail. An experimental set-up was constructed to simulate the shattering operation using a water-glycerine solution and air instead of smelt and steam respectively. The objective was to examine how physical properties and flow characteristics affect shattering. It was found that increasing shatter jet velocity greatly reduced droplet mean diameter. Increasing the liquid flow rate greatly increased droplet size, as expected. Shattering was not significantly affected by viscosity, unless a weak shatter jet was used on a highly viscous fluid. Increasing the proximity of the shatter jet nozzle decreased droplet size.

A non-reactive model system comprising a highly concentrated and unstable oil-in-water emulsion was used to investigate the retention of oil by the membrane in producing biodiesel with a membrane reactor. Critical flux was identified using the relationship between the permeate flux and transmembrane pressure along with the separation efficiency of the membrane. It was shown that separation efficiencies above 99.5% could be obtained at all operating conditions up to the critical flux. It was observed that the concentration of oil in all collected permeate samples using the oil-water system was below 0.2 wt% when operating at a flux below the critical flux. Studies to date have been limited to the characterization of low concentrated emulsions below 15 vol.%. The average oil droplet size in highly concentrated emulsions was measured as 3200 nm employing direct light scattering (DLS) measurement methods. It was observed that the estimated cake layer thickness of 20 to 80 mm was larger than external diameter of the membrane tube i.e. 6 mm based on a large particle size. Settling of the concentrated emulsion permitted the detection of a smaller particle size distribution (30-100 nm) within the larger particles averaging 3200 nm. It was identified that DLS methods could not efficiently give the droplet size distribution of the oil in the emulsion since large particles interfered with the detection of smaller particles. The content of the smaller particles represented 1% of the total weight of oil at 30°C and 5% at 70°C. This was too low to be detected using DLS measurements but was sufficient to affect ultrafiltration. In order to study the critical flux in the presence of transesterification reaction and the effect of cross flow velocity on separation, various oils were transesterified in another membrane reactor providing higher cross flow velocity. higher cross flow velocity provides better separation by reducing materials deposition on the surface of the membrane due to higher shearing. The oils tested were canola, corn, sunflower and unrefined soy oils (Free Fatty Acids (FFA< 1%)), and waste cooking oil (FFA= 9%). The quality of all biodiesel samples was studied in terms of glycerine, mono-glyceride, di-glyceride and tri-glyceride concentrations. The composition of all biodiesel samples were in the range required by ASTM D6751 and EN 14214 standards. A critical flux based on operating pressure in the reactor was reached for waste cooking and pre-treated corn oils. It was identified that the reaction residence time in the reactor was an extremely important design parameter affecting the operating pressure in the reactor. / Natural Sciences and Engineering Research Council of Canada (NSERC)

A non-reactive model system comprising a highly concentrated and unstable oil-in-water emulsion was used to investigate the retention of oil by the membrane in producing biodiesel with a membrane reactor. Critical flux was identified using the relationship between the permeate flux and transmembrane pressure along with the separation efficiency of the membrane. It was shown that separation efficiencies above 99.5% could be obtained at all operating conditions up to the critical flux. It was observed that the concentration of oil in all collected permeate samples using the oil-water system was below 0.2 wt% when operating at a flux below the critical flux. Studies to date have been limited to the characterization of low concentrated emulsions below 15 vol.%. The average oil droplet size in highly concentrated emulsions was measured as 3200 nm employing direct light scattering (DLS) measurement methods. It was observed that the estimated cake layer thickness of 20 to 80 mm was larger than external diameter of the membrane tube i.e. 6 mm based on a large particle size. Settling of the concentrated emulsion permitted the detection of a smaller particle size distribution (30-100 nm) within the larger particles averaging 3200 nm. It was identified that DLS methods could not efficiently give the droplet size distribution of the oil in the emulsion since large particles interfered with the detection of smaller particles. The content of the smaller particles represented 1% of the total weight of oil at 30°C and 5% at 70°C. This was too low to be detected using DLS measurements but was sufficient to affect ultrafiltration. In order to study the critical flux in the presence of transesterification reaction and the effect of cross flow velocity on separation, various oils were transesterified in another membrane reactor providing higher cross flow velocity. higher cross flow velocity provides better separation by reducing materials deposition on the surface of the membrane due to higher shearing. The oils tested were canola, corn, sunflower and unrefined soy oils (Free Fatty Acids (FFA< 1%)), and waste cooking oil (FFA= 9%). The quality of all biodiesel samples was studied in terms of glycerine, mono-glyceride, di-glyceride and tri-glyceride concentrations. The composition of all biodiesel samples were in the range required by ASTM D6751 and EN 14214 standards. A critical flux based on operating pressure in the reactor was reached for waste cooking and pre-treated corn oils. It was identified that the reaction residence time in the reactor was an extremely important design parameter affecting the operating pressure in the reactor. / Natural Sciences and Engineering Research Council of Canada (NSERC)