Made available in DSpace on 2014-07-29T16:11:46Z (GMT). No. of bitstreams: 1 Dissertacao Wilsione Jose Carneiro.pdf: 729740 bytes, checksum: 371aee359d81ba53af5b532357fc8f09 (MD5) Previous issue date: 2010-03-03 / The venlafaxine, 1-[2-dimethylamino-1-(4-methoxyphenyl)-ethyl] cyclohexanol, is a antidepressant drug of second generation. This is one of the most potent reuptake inhibitor of serotonin and noradrenaline, and its therapeutic effect is attributed to this activity. Venlafaxine is biotransformed in the liver to O-desmethylvenlafaxine (desvenlafaxine), N, O-desmethylvenlafaxine, N-desmethylvenlafaxine. Enzymes CYP2D6, CYP2C19 and CYP2C9 metabolize venlafaxine and major metabolite is the O-desmethylvenlafaxine. This is pharmacologically active and contributes significantly to the pharmacological effect of venlafaxine, as is found in plasma at high concentrations. The investigation of the formation of degradation products is of great importance, because the products formed may be less active, more active or toxic. Bioconversion or the application of microbial models is a strategy to mimic the mammalian metabolism produces significant quantities of metabolites for studies of pharmacological activity and toxicological. This work represents a forced degradation study of venlafaxine extended-release capsules in different stress conditions (acid and alkaline hydrolysis, oxidative and thermal) and select strains of filamentous fungi, to identify those able to metabolize venlafaxine and produce in a semi-preparative major metabolites. The filamentous fungi used were: Aspergillus candidus ATCC 2023, Beauveria bassiana ATCC 7159, Cunninghamella echinulata ATCC 9244, Cunningamella elegans ATCC 6169, Mortierella isabelina ATCC 1757 and Rhizopus arrhizus ATCC 11145. Was developed and validated method stability indicating HPLC using reverse phase for the analysis of venlafaxine in pharmaceutical formulation. The metabolites prepared by bioconversion were used for structural elucidation and later as a reference chemical in the analysis of stability studies and future studies of pharmacological and toxicological activity. The fungus Cunninghamella elegans ATCC 6169 was selected and produced O-desmethylvenlafaxine (desvenlafaxine) and dihydroxy-venlafaxine, similar to those found in mammals, reinforcing the application of microbial models for the study of animal metabolism. The study indicated the stability of the acid condition of venlafaxine, formed two degradation products, the products found were similar to those obtained by bioconversion. The O-desmethylvenlafaxine, corresponds to the active metabolite of venlafaxine in humans and was recently approved for the treatment of major depressive disorder. Those studies, one can get the O-desmethylvenlafaxine in bioconversion reactions by Cunninghamella elegans ATCC 6169 and forced degradation studies of venlafaxine. The method developed and validated HPLC method was considered indicative of stability analysis of venlafaxine extended-release capsules, it is sensitive, specific (interference < 2%), precise (RSD < 2%), linear (r > 0.99), accurate (98.0 to 102.0%) and reproducible (RSD < 2%). / A venlafaxina, (1-[2-dimetilamino)-1-(4-metoxifenil)etil]ciclohexanol), é um fármaco antidepressivo de segunda geração. É um dos mais potentes inibidores da recaptação de serotonina e noradrenalina, e o seu efeito terapêutico é atribuído a esta atividade. A venlafaxina é biotransformada no fígado pelas enzimas CYP2D6, CYP2C19 e CYP2C9 em O-desmetilvenlafaxina ou também chamado de desvenlafaxina (metabólito majoritário), N,O-desmetilvenlafaxina, N-desmetilvenlafaxina. O O-desmetilvenlafaxina é farmacologicamente ativo e contribui significativamente para o efeito farmacológico da venlafaxina, uma vez que é encontrado no plasma em altas concentrações. A investigação da formação de produtos de degradação é de grande importância, pois os produtos formados podem ser menos ativos, mais ativos ou tóxicos. Bioconversão ou a aplicação de modelos microbianos é uma estratégia para mimetizar o metabolismo dos mamíferos produzindo quantidades consideráveis de metabólitos para estudos de atividade farmacológica e toxicológica. Neste trabalho foi realizado um estudo de degradação forçada de venlafaxina em cápsulas de liberação prolongada em diferentes condições de estresse (hidrólise ácida e alcalina, oxidativa e térmica) e foram selecionadas cepas de fungos filamentosos com a finalidade de identificar aquelas capazes de metabolizar a venlafaxina e produzir em escala semi-preparativa os principais metabólitos. Os fungos filamentosos utilizados foram: Aspergillus candidus ATCC 2023, Beauveria bassiana ATCC 7159, Cunninghamella echinulata ATCC 9244, Cunningamella elegans ATCC 6169, Mortierella isabelina ATCC 1757 e Rhizopus arrhizus ATCC 11145. Foi desenvolvido e validado um método indicativo de estabilidade por cromatografia líquida de alta eficiência (CLAE) utilizando fase reversa para a análise de venlafaxina na formulação farmacêutica. Os metabólitos preparados por bioconversão foram utilizados para elucidação estrutural e posteriormente serão utilizados como substância química de referência em análises de estudos de estabilidade e futuros estudos de atividade biológica. A cepa Cunninghamella elegans ATCC 6169 foi selecionada e produziu O-desmetilvenlafaxina (desvenlafaxina) e dehidroxi-venlafaxina, similares aos encontrados em mamíferos, reforçando a aplicação dos modelos microbianos para o estudo do metabolismo animal. O estudo indicativo de estabilidade da condição ácida de venlafaxina, formou dois produtos de degradação similares aos obtidos por bioconversão. A O-desmetilvenlafaxina foi recentemente aprovado para o tratamento do transtorno depressivo maior. Como resultado do presente trabalho, foi possível obter a O-desmetilvenlafaxina nas reações de bioconversão por Cunninghamella elegans ATCC 6169 e em estudos de degradação forçada de venlafaxina. O método desenvolvido e validado por CLAE foi considerado método indicativo de estabilidade para análise de venlafaxina em cápsulas de libertação prolongada, pois é sensível/ específico (seletividade < 2%), preciso (D.P.R < 2%), linear (r > 0,99), exato (98,0 - 102,0%) e reprodutível (D.P.R < 2%).

Graphene sheets, one atom thick, two dimensional layers of carbon atoms, have gained enormous importance over the past few years due to their unique attributes - high electronic, thermal conductivities and exceptional mechanical strength. Chemical reduction of graphene oxide (GO) has been considered as a viable route for large scale production of graphene sheets. The reduced graphene oxide (r -GO) sheets although their conductivities are comparatively lower than that of graphene are nevertheless versatile material for applications in thin films and composites. An important consideration in the design of solution processing techniques for the preparation of processable graphene sheets is the dispersibility of GO and r -GO in different solvents, especially aqueous dispersibility. While GO is dispersible in water over a wide range of pH values, r -GO shows poor dispersibility and over a limited range of pH values. Graphene oxide, the oxidized form of graphene, are single atomic layers with lateral dimension that can extend to hundreds of nanometers. The sheets contain a sizable fraction of carbons that are sp3 hybridized and covalently bonded to oxygen in the form of epoxy, carbonyls as well as ionizable hydroxyl and carboxylic functional groups located on the rim of the sheets. The remaining carbons form isolated sp2 graphene like networks. On reduction the oxygen functionalities are removed and the sp2 network partially restored. This thesis focuses on the aqueous dispersibility of GO and r -GO, and describes a strategy to enhance the dispersibility of r -GO by cyclodextrin functionalization. Chapter 1 of the thesis provides a brief review of the synthetic procedures and structure of GO and r -GO while Chapter 2 describes the experimental methods and characterization techniques used in the thesis. The chemistry underlying the aqueous dispersibility of GO and r -GO at different values of pH have been investigated by zeta potential measurements, pH titrations and infrared spectroscopy (Chapter 3). These measurements show that r -GO sheets have ionizable groups with a single pKa value (8.0) while GO sheets have groups that are more acidic (pKa = 4.3), in addition to groups with pKa values of 6.6 and 9.0. Infrared spectroscopy has been used to follow the sequence of ionization events. In both GO and r -GO sheets, it is ionization of the carboxylic groups that is primarily responsible for the build up of charge, but on GO sheets, the presence of phenolic and hydroxyl groups in close proximity to the carboxylic groups lowers the pKa value by stabilizing the carboxylate anion, resulting in superior water dispersibility. Till recently GO was primarily considered only as an easily available precursor for chemical routes to r -GO but it has now been recognized as an interesting material in its own right. Two such attributes that have attracted wide spread attention are the in- trinsic and tunable fluorescence of GO as well as formation of liquid crystalline phases. Aqueous dispersions of GO exhibit strong pH dependent fluorescence in the visible region that originates, in part, from the oxygenated functionalities present. In Chapter 4, the spectral migration on nanosecond timescales of the pH dependent features in the fluores- cence spectra of GO is described. The changes in the steady state fluorescence spectra with pH have been correlated with the sequence of dissociation events that occur in GO dispersions at different values of pH described in Chapter 3, from time resolved emission spectra (TRES) constructed from the wavelength dependent fluorescence decay curves, it is shown that the migration is associated with excited state proton transfer. Both ‘intramolecular’ and ‘intermolecular’ transfers involving the quasimolecular oxygenated aromatic fragments are observed. Aqueous dispersions of GO constitute a distinctive class of 2D-anisotropic colloids with competing interactions - long range electrostatic repulsion, originating from ionized carboxylic groups located on the rim of the sheets and weak dispersive attractive interactions originating from the un-oxidized sp2 graphitic domains. In Chapter 5, it is shown that, colloidal dispersions of GO are intrinsically frustrated, exhibiting a range of arrested or metastable states, encompassing fluid, glass and gels that coexist with liquid crystalline order. These states can be accessed by varying the relative magnitudes of the repulsive and attractive forces by changing the ionic strength of the medium, by addition of salt and/or the concentration of the dispersion. At low salt concentrations, where long range electrostatic repulsions dominates, the formation of a repulsive Wigner glass is observed while at high salt concentrations, when attractive forces dominate, the formation of gels that exhibits a nematic to columnar liquid crystalline transition. These studies highlights how the chemical structure of GO - hydrophilic ionizable groups and hydrophobic graphitic domains coexisting on a single sheet - gives rise to a rich and complex phase diagram. The poor dispersibility of r -GO in aqueous media limits its use in practical applica- tions. To enhance the dispersibility, r -GO sheets have been functionalized by covalently linking -cyclodextrin ( -CD) cavities to the sheets via an amide linkage (Chapter 6). The functionalized -CD: rGO sheets, in contrast to r -GO, are dispersible over a wide range of pH values (2 - 13). Zeta potential measurements indicate that there is more than one factor responsible for the dispersibility. It is shown that planar aromatic molecules adsorbed on the r -GO sheet as well as nonplanar molecules included in the tethered -CD cavities have their fluorescence effectively quenched by the -CD: rGO sheets. The -CD: rGO sheets combine the hydrophobicity associated with r -GO along with the hydrophobicity of the cyclodextrin cavities in a single water dispersible material. Resonance Raman spectroscopy is a powerful analytical tool for detecting and identi- fying analytes, but the associated strong fluorescence background severely limits the use of the technique. In Chapter 7, it is shown that the cyclodextrin functionalized -CD: rGO sheets, described in Chapter 6, provides a versatile platform for resonance Raman detection. Planar aromatic and dye molecules that adsorb on the r -GO graphitic domains and non-planar molecules included within the tethered -CD cavities have their fluorescence effectively quenched. Using the water dispersible -CD: rGO sheets, it is possible to record the resonance Raman spectra of adsorbed and included organic chromophores directly in aqueous media without having to extract or deposit on a substrate. The Raman signal intensities show a linear dependence with the concentration of analyte present in water. This is significant, as it allows for the identification and estimation of organic analytes present in water by resonance Raman spectroscopy.

La catalyse hétérogène est en plein développement pour des raisons économiques, de santé et de protection environnementale. Les travaux de cette thèse s'intéressent à la préparation des silices fonctionnalisées par des sous-structures ioniques pour leur application en catalyse hétérogène. D'abord, des matériaux mésoporeux fonctionnalisés par des entités di-aryl imidazoliums ont été préparés par des réactions de post-greffage. En plus, films de type PMO contenant des entités di-aryl imidazoliums ont été synthétisés en présence d'un surfactant anionique. Ensuite, complexes carbéniques N-hétérocycliques du cuivre et du palladium supportés ont été préparés et appliqués en tant que catalyseurs organométalliques dans des réactions A3 (Cu-NHC) et de couplage de Suzuki (Pd-NHC). Les silices fonctionnalisées avec des entités imidazoliums ont également été utilisées en tant qu'organocatalyseurs des réactions de Henry et dans de cycloaddition du dioxyde de carbone aux époxydes. Des matériaux de type ‘PMO' contenant des entités amines/ammoniums ainsi que des sous-structures zwitterioniques ont été utilisés en réactions organocatalysées de Henry et Biginelli. / Heterogenous catalysis is an area in continuous development due to economical, health and environmental issues. This thesis deals with the preparation of i-silica materials for the posterior application in heterogeneous catalysis. First, di-aryl imidazolium containing silica materials were synthesized by post-grafting reactions on mesoporous SBA-15. Moreover, di-alkyl imidazolium containing PMO films were prepared in presence of an anionic surfactant. Then, supported copper and palladium N-heterocyclic carbenes were synthesized from di-aryl imidazolium silica and applied to A3 reactions (Cu-NHC) and Suzuki cross-coupling reactions (Pd-NHC). Imidazolium functionalized silicas were also utilized as heterogeneous organocatalysts in Henry reactions and in reactions of cycloaddition of carbon dioxide to epoxides. Finally, PMO type materials containing amine/ammonium and zwitterionic substructures were applied to Henry and Biginelli organocatalysed reactions, respectively.

A chemoselective catalyst is preferred in a chemical reaction where protecting groups otherwise are needed. The two lipases Candida antarctica lipase B and Rhizomucor miehei lipase showed large chemoselectivity ratios, defined as (kcat/KM)OH / (kcat/KM)SH, in a transacylation reaction with ethyl octanoate as acyl donor and hexanol or hexanethiol as acyl acceptor (paper I). The chemoselectivity ratio of the uncatalyzed reaction was 120 in favour of the alcohol. Compared to the uncatalyzed reaction, the chemoselectivity was 730 times higher for Candida antarctica lipase B and ten times higher for Rhizomucor miehei lipase. The KM towards the thiol was more than two orders of magnitude higher than the KM towards the corresponding alcohol. This was the dominating contribution to the high chemoselectivity displayed by the two lipases. In a novel approach, Candida antarctica lipase B was used as catalyst for enzymatic synthesis of thiol-functionalized polyesters in a one-pot reaction without using protecting groups (paper II). Poly(e-caprolactone) with a free thiol at one of the ends was synthesized in an enzymatic ring-opening polymerization initiated with mercaptoethanol or terminated with either 3-mercaptopropionic acid or g-thiobutyrolactone.

Polyethylene terephthalate multifilament fabrics used as filtration and operating room textiles possess through-thickness pore channels at the yarn intersections (mesopores). These pore channels pose a risk for the penetration of contaminated fluids and particles. The size of pore channels may be reduced by high-density weaving. However, this leads to reduced drapability and thus to degraded application properties of the fabric. To satisfy the requirements without impeding the physiological properties of the textile, fluid- and particle-tight fabrics are developed. This was realized by partial immobilization of functionalized micro particles into the meso-pores. A reduction of the pore size without complete pore-closure is achieved by establishing a net-like particle structure in the meso-pores. To match the requirements of intensive use, permanent particle-bonding to the fiber surface is necessary. This can be achieved by suitable polyethylene terephthalate fabric surface-modification, dependent on the particle functionalization. The investigations have shown that functionalized particles establish a very good inter particle bonding as well as to the fiber surface. An increased permanent bonding can be realized by a modification of the fabric surface which is tuned to the functionalization of the particle.

Indiana University-Purdue University Indianapolis (IUPUI) / The link between volatile organic compounds (VOCs) from breath and various diseases and specific conditions has been identified since long by the researchers. Canine studies and breath sample analysis on Gas chromatography/ Mass Spectroscopy has proven that there are VOCs in the breath that can detect and potentially predict hypoglycemia. This project aims at developing a smart nanosensor system to detect hypoglycemia from human breath. The sensor system comprises of 1-Mercapto-(triethylene glycol) methyl ether functionalized goldnanoparticle (EGNPs) sensors coated with polyetherimide (PEI) and poly(vinylidene fluoride -hexafluoropropylene) (PVDF-HFP) and polymer composite sensor made from PVDF-HFP-Carbon Black (PVDF-HFP/CB), an interface circuit that performs signal conditioning and amplification, and a microcontroller with Bluetooth Low Energy (BLE) to control the interface circuit and communicate with an external personal digital assistant. The sensors were fabricated and tested with 5 VOCs in dry air and simulated breath (a mixture of air, small portion of acetone, ethanol at high humidity) to investigate sensitivity and selectivity. The name of the VOCs is not disclosed herein but these VOCs have been identified in-breath and are identified as potential biomarkers for other diseases as well. The sensor hydrophobicity has been studied using contact angle measurement. The GNPs size was verified using Ultra-Violent-Visible (UV-VIS) Spectroscopy. Field Emission Scanning Electron Microscope (FESEM) image is used to show GNPs embedded in the polymer film. The sensors sensitivity increases by more than 400\% in an environment with relative humidity (RH) of 93\% and the sensors show selectivity towards VOCs of interest. The interface circuit was designed on Eagle PCB and was fabricated using a two-layer PCB. The fabricated interface circuit was simulated with variable resistance and was verified with experiments. The system is also tested at different power source voltages and it was found that the system performance is optimum at more than 5 volts. The sensor fabrication, testing methods, and results are presented and discussed along with interface circuit design, fabrication, and characterization. / 2022-05-8

<p>This thesis highlights the use and significance of surface enhanced Raman spectroscopy (SERS) for forensic applications. Two unique SERS substrates are developed for successful (1) forensic toxicological drug detection in human patient plasma and (2) trace explosive detection.  </p>

I mitt examensarbete undersöker jag hur svensklärare gestaltar genrepedagogik i sin undervisning i ämnet svenska och vilken potential genrepedagogik tillmäts och på vilka grunder. Genrepedagogiken är en stram undervisningsmodell som har sin grund i Australien där undervisningsidealet är synlig undervisning där man namnger språkets delar och lär utdem till eleverna från tidig ålder. I Sverige har genrepedagogiken fått sitt genomslag i ämnet svenska som andraspråk. Där får eleverna möjlighet att skapa texter i olika genrer vilket ger eleverna förutsättningar att förstå och bearbeta olika texttyper. Genom att läraren utför en formaliserad undervisning och anpassar den efter elevernas intresse och behov främjas läroprocessen.Jag har använt mig av kvalitativ metod när jag analyserat svaren från informanterna. Detta är en analysmetod som hjälpt mig att hålla fokus på frågeställningarna, värdera svaren och få tydlighet i analysen. Jag har intervjuat tolv lärare som undervisar på samma skola och precis avslutat en kurs om genrepedagogik.I analys- och resultat delen av mitt examensarbete presenterar jag min empiri som svarar mot mina frågeställningar utifrån olika aspekter beträffande genrepedagogiken och dess påverkan på undervisningen.I min resultatdel kan jag se att lärarna använder sig av genrepedagogik i sin undervisning, dock inte hela tiden utan de delar upp cirkelmodellen och använder sig av de delar de tyckerär det bästa för gruppens och den enskilda individens utveckling. De har utvecklat enförståelse för genrepedagogiken och dess syfte för att utveckla elevernas arbete med olika texttyper, men de vill även fortsätta med en undervisningsmodell som är tydligt funktionaliserad samt ge eleverna möjlighet att utveckla sitt lärande på olika sätt. Nyckelord: Cirkelmodellen, genrepedagogik, inramning, formaliserad undervisning, funktionaliserad undervisning, osynlig undervisning, synlig undervisning

Utilizing the diverse functionality of amino acids, a new class of amphiphilic graft copolymers has been synthesized, characterized, and explored for applications in biomaterials and nucleic acid delivery. This thesis research focused on the syntheses of oligopeptide-functionalized polyesters and polyolefins. Polyester functionalization was geared towards applications in biomaterials, tissue engineering, and drug delivery by incorporating sequences that promote cell-adhesion. These polyester- graft -oligopeptide materials were prepared by a 1,3-Huisgen cycloaddition reaction, "click" chemistry, of an azide-terminated oligopeptide (prepared by Fmoc-based solid phase peptide synthesis (SPPS)) and alkyne-containing polyester (synthesized by ring-opening polymerization). Following the syntheses of these materials, they were analyzed by nuclear magnetic resonance (NMR) and organic gel permeation chromatography (GPC). The oligopeptide-functionalized polyolefins were designed for nucleic acid complexation, and therefore the oligopeptide sequences were intended to incorporate positively-charged moieties ( e.g. , oligolysine) for DNA and short interfering RNA (siRNA) complexation. These graft copolymers, prepared by SPPS followed by ring-opening metathesis polymerization, have highly tunable structures that enable control over charge density and polymer backbone rigidity. Moreover, non-ionic hydrophilic grafts such as polyethylene glycol were integrated into these polyelectrolytes such that the charges along the polymer backbone are spaced accordingly while maintaining the hydrophilicity of the polymer. While numerous applications for such charged, "bio-tailored" materials can be envisioned, this work is geared towards positively-charged polyelectrolytes for their potential application in nucleic acid therapy, specifically the delivery of plasmid DNA and siRNA. These graft copolymers were characterized ( 1 H, 13 C NMR, organic and aqueous GPC), studied for their solution properties (static and dynamic light scattering), and investigated as polyplexes with plasmid DNA.

<p>  </p> <p>With the surge of interest in the electrification of transportation driven by global climate change, the need for powertrains using non-carbon energy sources has become more urgent than ever. The fuel cell electric vehicles (FCEVs) using polymer electrolyte membrane fuel cells (PEMFCs) have many advantages over the internal combustion engine (ICE) and other renewable energy vehicles such as high efficiency, zero-emission, fast fueling, unique power, and energy scalability (without heavy penalty from the increased mass). After three decades of intensive development, there are only several thousand FCEVs on the road, in contrast to the millions of battery electric vehicles (BEV) in use today. The biggest challenge of the widespread implantation of the PEMFCs is the cost, primarily due to the use of platinum catalysts. The high intrinsic catalyst activity exhibited using a rotating disc electrode (RDE) is rarely realized in the membrane electrode assembly (MEA), which is the core of PEMFC, due to the difference on the electrolyte(ionomer)/catalyst interfaces. Much of my Ph. D research effort is concentrated on how to reduce the Pt usage and improve the stability of catalyst to reduce the operation cost of fuel cells. Several approaches were practiced improving the performance of MEA in a fuel cell, such as optimizing the ink formulation and MEA fabrication method, enhancing proton conductivity of carbon support for catalysts, engineering the ionomer and catalyst interface via surface functionalization. Such studies unraveled the relationship between property, structure, and performance of MEA, and significantly improved the performance of MEA. Further, to reduce the cost of fuel cell operation, approaches that is to improve the stability of catalysts either in reducing Oswald ripening or limiting surface migration were practiced on developing novel catalysts. Such as doping anion into Pt and Ni alloy crystal structure, introducing PANI on catalyst surface. These approaches significantly improve the stability of catalyst and MEA. Finally, same as platinum group metal (PGM) catalysts, PGM-free catalysts as well as their MEAs were studied. A novel method of PGM-free MEA fabrication was developed which significantly reduced the thickness of catalyst layer, thus greatly reduced the mass transfer resistance. Also, a highly stable and active PGM-free catalyst was developed and can be considered as a strong competitor to replace the traditional PGM catalysts in MEA.</p>