No description available.

The current research addresses the formability of two magnesium sheet alloys, a conventional AZ31B and a rare earth alloyed ZEK100. Both alloys had a nominal thickness of 1.6 mm. Both Limiting Dome Height (LDH) and Cylindrical Cup Draw experiments were performed between room temperature and 350°C. To examine the effect of sheet directionality and anisotropy, LDH experiments were performed in both the sheet rolling and transverse directions. In addition, strain measurements were performed along both sheet orientations of the cylindrical cup and LDH specimens for which the geometry is symmetric. The LDH tests were used to study the formability of ZEK100 and AZ31B (O and H24 tempers) magnesium alloy sheet between room temperature and 350°C. At room temperature, AZ31B-O and AZ31B-H24 exhibit limited formability, with dome heights of only 11-12 mm prior to the onset of necking. In contrast, the dome heights of ZEK100 at room temperature reached 29 mm (a 140% improvement over AZ31B). Increasing the temperature above 200°C did not affect the relative ranking of the three sheet samples, however it did reduce the magnitude of the difference in dome heights. The rare earth alloyed ZEK100 had pronounced benefits at intermediate temperatures, achieving an LDH of 37 mm at 150°C; this dome height was only reached by AZ31B at a much higher temperature of 250°C. To further characterize the formability of ZEK100, forming limit curves (FLCs) were developed from the LDH tests in both the rolling and transverse directions. Comparisons to AZ31B were made at selected temperatures. Surface strain data was collected with an in situ digital image correlation (DIC) system incorporating two cameras for stereo observation. Results from these experiments further highlighted the enhanced formability relative to AZ31B over the entire temperature range between room temperature and 350°C, with the most dramatic improvements between room temperature and 150°C. The plane strain forming limit (FLC0) for ZEK100 at 150°C was 0.4 which equals that of AZ31B at 250°C. At higher temperatures (300°C), the two alloys exhibited similar performance with both achieving similar dome heights at necking of 37 mm (AZ31B) and 41 mm (ZEK100). To round out the investigation of ZEK100 for industrial applications, cylindrical cup deep drawing experiments were performed on ZEK100 sheet between 25°C and 250°C under isothermal and non-isothermal conditions. Draw ratios of 1.75, 2.00 and 2.25 were considered to examine the effects of draw ratio on draw depth. The effect of sheet anisotropy during deep drawing was investigated by measuring the earring profiles, sheet thickness and strain distribution along both the rolling and transverse directions. Isothermal test results showed enhanced warm temperature drawing performance of ZEK100 over AZ31B sheet; for example, a full draw of 203.2 mm (8”) blanks of ZEK100 was achieved with a tool temperature of 150°C, whereas a tool temperature of 225°C was needed to fully draw AZ31B-O blanks of this diameter. Non-isothermal deep draw experiments showed further improvement in drawability with significantly lower tooling temperatures required for a full cup draw using ZEK100. ZEK100 achieved a full draw of 228.6 mm (9") blanks with a die and blank holder temperature of 150°C and a cooled punch (25°C) while the same size blank of AZ31B required a die and blank holder temperature 225°C and a cooled punch (150°C). Temperature process windows were developed from the isothermal and non-isothermal results to show a direct comparison of drawing behaviour between ZEK100 and AZ31B. Overall, ZEK100 offers significantly improved forming performance compared to AZ31B, particularly at temperatures below 200°C. This lower temperature enhanced formability is attractive since it is less demanding in terms of lubricant requirements and reduces the need for higher temperature tooling.

A intensificaÃÃo da eutrofizaÃÃo nos mananciais à provocada pelas aÃÃes antrÃpicas e tem como predominÃncia as floraÃÃes de cianobactÃrias. Por sua vez, estas floraÃÃes alteram a qualidade da Ãgua para o abastecimento da populaÃÃo, e, ao serem lisadas, podem liberar toxinas (cianotoxinas) causando intoxicaÃÃo. A primeira confirmaÃÃo in loco da morte de seres humanos por intoxicaÃÃo com cianotoxinas no Brasil levou à OMS a publicar rapidamente novas Portarias sobre o monitoramento da qualidade da Ãgua bruta que incorporaram novos indicadores, como a concentraÃÃo das cianobactÃrias e de suas toxinas nos mananciais utilizados para abastecimento de Ãgua potÃvel. Com isso, as tecnologias para o tratamento da Ãgua e para a identificaÃÃo e quantificaÃÃo das cianotoxinas vÃm passando por um processo de aperfeiÃoamento. Neste contexto, o presente trabalho objetivou validar o mÃtodo de cromatografia lÃquida de fase reversa com detector de fluorescÃncia (CLAE-FLD) e derivatizaÃÃo prÃ-coluna para detecÃÃo e quantificaÃÃo das cianotoxinas saxitoxina (STX) e decarbamoil-saxitoxina (dc-STX) proveniente do cultivo da cianobactÃria Cylindrospermopsis raciborskii. Esta validaÃÃo foi realizada para dar credibilidade ao mÃtodo analÃtico e os parÃmetros selecionados foram: seletividade, linearidade, limite de detecÃÃo (LD) e quantificaÃÃo (LQ), exatidÃo, precisÃo e robustez. Os resultados obtidos apresentaram boa seletividade, comprovando que o mÃtodo possuÃa capacidade de medir as toxinas em uma matriz PÃs ExtraÃÃo na presenÃa de outros componentes. As curvas analÃticas foram construÃdas com nove pontos a partir dos padrÃes de STX e dc-STX. O mÃtodo apresentou uma linearidade no intervalo de 4,5 à 150 Âg L-1 para STX e 3,0 à 132 Âg L-1 para dc-STX, e o coeficiente de correlaÃÃo (r) maior que 0,99 para as duas toxinas, mostrando que o mÃtodo tem a capacidade de fornecer resultados diretamente proporcionais à concentraÃÃo dos analitos detectados. A sensibilidade foi medida atravÃs do LD e LQ, obtendo resultados satisfatÃrios para os objetivos do trabalho. O mÃtodo obteve boa precisÃo e exatidÃo, visto que para STX e dc-STX os diferentes nÃveis de concentraÃÃo estavam com valores dentro dos intervalos permitidos pelas normas brasileiras de validaÃÃo, e apresentou-se robusto, pois foi insensÃvel a pequenas variaÃÃes possÃveis de ocorrer durante a anÃlise. Em resumo, pode-se considerar que o mÃtodo utilizado para a detecÃÃo e quantificaÃÃo das cianotoxinas STX e dc-STX apresentou resultados satisfatÃrios, uma vez que os parÃmetros analisados para validÃ-lo estavam em conformidade aos valores aceitos nas normas brasileiras. / The intensification of eutrophication in the watershed is caused by human actions and is the predominant cyanobacteria. In turn, these blooms affecting the quality of the water supply for the population, and, when disrupted, can release toxins (cyanotoxins) causing intoxication. The first in situ confirmation of the death by poisoning of humans with cyanotoxins in Brazil led the WHO to quickly publish new Ordinance on monitoring of raw water quality that incorporate new indicators, as the concentration of the cyanobacteria and their toxins in water sources used for drinking water supply. Thus, technologies for water treatment and for the identification and quantification of cyanotoxins have been going through a process of improvement. In this context, this study aimed to validate the method of reverse phase liquid chromatography with fluorescence detection (HPLC-FLD) and pre-column derivatization for detection and quantification of cyanotoxins saxitoxin (STX) and decarbamoil-saxitoxin (dc-STX) from the cyanobacterium Cylindrospermopsis raciborskii cultivation. This validation was performed to give credibility to the analytical method and the selected parameters were: selectivity, linearity, limit of detection (LOD) and quantification (LOQ), accuracy, precision and robustness. The results showed good selectivity, confirming that the method had the ability to measure the toxins in a Post Extraction matrix in the presence of other components. The analytical curves were constructed with nine points from the patterns of STX and dc-STX. The method showed linearity in the range of 4.5 to 150 mg L-1 for STX and 3.0 to 132 mg L-1 to dc-STX, and the correlation coefficient (r) greater than 0.99 for both toxins, showing that the method has the capacity to deliver results directly proportional to the concentration of analyte detected. The sensitivity was measured by the LD and LQ, obtaining satisfactory for the purposes of work results. The method achieved good precision and accuracy, whereas for STX and dc-STX different concentration levels were with values ​​within the ranges allowed by Brazilian standards for validation, and showed to be robust because it was insensitive to small variations possible to occur during analysis. In summary, one can consider that the method used for the detection and quantification of cyanotoxins STX and dc-STX showed satisfactory results, since the parameters analyzed to validate it were in conformity with the accepted values ​​in Brazilian standards.

The study felld into three sections. The first section that a liquid chromatography method with fluorescence detection was developed for simultaneous determination of 11 quinolones (QNs; marbofloxacin, norfloxacin, ciprofloxacin, lomefloxacin, danofloxacin, enrofloxacin, sarafloxacin, difloxacin, oxolinic acid, nalidixic acid and flumequine) in chicken, pork, fish and shrimp. The analytes were extracted with 0.3% metaphosphoric acid: acetonitrile (1:1, v/v), followed by a HLB cartridge clean-up procedure. The HPLC separation was carried out on a symmetry column C18 (250 mm x 4.5 mm i.d., 5 £gm) with linear gradient elution of 0.1% formic acid: acetonitrile as mobile phase and programmable fluorescence detection. The method was validated by spiking blank animals tissues at three different levels (25, 50 and 250 ng/g; except 6.25, 12.5 and 62.5 ng/g for DAN) and linearity, detection limit, quantification limit, precision and accuracy were checked. Mean recoveries of 11 QNs from edible animal tissues were 71.7-105.3%. The limits of quantification in different muscle tissues ranged from 5.0 to 28.0 ng/g. The results showed it was simple, rapid, sensitive and suitable for routine test. The second section that a LC-ESI-MS/MS method was developed for determining 18 (fluoro)quinolone (QNs) residues in milk, chicken, pork, fish and shrimp. This method is capable of screening and confirming the presence of 12 amphoteric QNs (marbofloxacin, norfloxacin, enrofloxacin, ciprofloxacin, desethylene ciprofloxacin, lomefloxacin, danofloxacin, sarfloxacin, difloxacin, ofloxacin, orbifloxacin and enoxacin) and 6 acidic QNs (oxolinic acid, nalidixic acid, flumequine, cinoxacin, piromidic acid and pipemidic acid). The drugs were extracted from matrix using acetonitrile with 1% formic acid, diluted in 10% acetonitrile and defatted by extraction with hexane. The LC separation was conducted on a XDB C8 (150 x 4.6 mm, 5£gm) column with gradient elution of 20 mM ammonium formate with 0.1% formic acid¡Vacetonitrile as the mobile phase. Mass spectral acquisition was completed in the positive ion mode by applying multiple reaction mode (MRM). The decision limit (CC£\) and detection capability (CC£]) stated in the Decision No. 2002/657/EC and the ISO standard No.11843, has been calculated in the case of the nonauthorized substance. The values of CC£\ ranged from 0.18 to 0.68 ng/g and CC£] ranged from 0.24 to 0.96 ng/g under specified conditions. The third section that the pharmacokinetics of ENR and its active metabolite (CIP and des-CIP) were estimated in tilapia after intravenous (i.v.) and oral (p.o.) administration of a single dose of 2.5 and 10 mg/kg body weigh, respectively. At prefixed time points, from 0.25 h to 7 days after administration, whole blood and main tissue (liver, kidney, bile and muscle) from 4 individuals in each were collected. The concentration of ENR and its active metabolites in the main tissue were simultaneously detected by LC/MS/MS method. Limited of quantitation (LOQ) of this method were 0.01£gg/g. Pharmacokinetic parameters from both routes were described to have a two- compartment open model with first-order elimination. After i.v. administration, the area under the drug concentration-time (AUC), elimination half-life (t1/2£]), maximum plasma concentration (Cmax ), total body clearance (Cltot) and apparent volume of distribution at steady-state (Vss) of ENR were 109.6 ¡Ó 31.33 £gg.h/mL, 55.17 ¡Ó 22.84 h, 4.70 ¡Ó 0.36 £gg/mL, 14.82 ¡Ó 4.24 L/h/kg, 1105 ¡Ó 223.40 L/kg ,respectively. After oral administration, the AUC , t1/2£], Tmax , Cmax of ENR were 599.42 ¡Ó 76.19£gg.h/mL , 75.95 ¡Ó 12.94 h, 0.601¡Ó0.06h, 9.75 ¡Ó 0.46£gg/mL, respectively. After p.o. administration, CIP could be detected in liver, kidney and bile. Regarding des-CIP, the main active metabolite of CIP, could be detected in 120¡ã168 h bile among tissue. ENR and CIP had significance enterohepatic cycle in Tilapia and easily accumulated in bile. It seems reasonable to explain the phenomenon of ENR and CIP maintenance of high concentration in blood and muscle during the test time.

El interés industrial por la formabilidad de chapas de aceros de doble fase (DP) se ha incrementado en las últimas décadas, impulsado principalmente por la reciente popularidad de los aceros avanzados de alta resistencia (AHSS) para reducir el peso de partes automotrices. Esto resulta en una fuerte necesidad de determinar la respuesta límite del material frente a solicitaciones típicas de operaciones de conformado y el estudio de los factores que la influencian. La presente Tesis Doctoral aborda el estudio numérico de los factores microestructurales que influyen en el diagrama límite de conformado (FLD) de chapas de acero DP-780. El comportamiento límite del material se modela mediante la técnica de Marciniak-Kuczynski (MK), la cual asume la presencia de una imperfección inicial precursora del proceso de localización; mientras que la descripción constitutiva del material se realiza en el marco de la plasticidad cristalina. El comportamiento anisótropo, la presencia de una distribución preferencial de orientaciones y el efecto de las fases constituyentes – ferrita/martensita – se obtiene mediante una homogeneización autoconsistente de la respuesta viscoplástica a nivel del cristal simple (VPSC). El acople de ambas técnicas (MK-VPSC) permite modelar exitosamente la respuesta límite de las chapas de acero DP-780. Se investiga numéricamente el efecto de parámetros microestructurales típicos de aceros DP, la influencia de la anisotropía y su evolución, así como el efecto del comportamiento del endurecimiento post-estricción en las deformaciones límite. Tanto la fracción en volumen como la plasticidad de la martensita presentan una influencia significativa en la predicción del diagrama FLD, mientras que la evolución de la textura cristalográfica sólo afecta las deformaciones límite bajo solicitaciones biaxiales. El mejor acuerdo con los datos experimentales se encuentra cuando se utiliza una ley de endurecimiento de saturación y cuando la deformación de la martensita es impedida o es retardada hasta el punto de estricción. Un análisis de la actividad de los sistemas de deslizamiento sugiere que, dentro del marco de trabajo del modelo MK-VPSC, la localización ocurre mucho más rápido en la ferrita que en la martensita. Se presenta una extensión del modelo MK-VPSC que permite evitar problemas de convergencia y reducir el costo computacional. Esto se alcanza aplicando directamente las condiciones en velocidad de deformación y tensión, resultantes de las restricciones de equilibrio y compatibilidad, en la banda de inestabilidad del modelo MK. Además, los estados mecánicos dentro y fuera de ésta se resuelven en el marco de referencia de la muestra, evitando rotar las orientaciones cristalográficas y las variables internas a la orientación de la banda para cada incremento, mejorando la eficiencia computacional. Las condiciones de borde generalizadas incorporadas al modelo permiten calcular diagramas FLD basados en trayectorias de carga en deformación (FLDρ) como en tensión (FLDα). / Triggered by the recent popularity of advanced high strength steels (AHSS) for weight-reduction in automotive components, industrial interest in the formability of dual-phase (DP) steel sheets has increased in the last decades. Thus, there is a strong need in the determination of the material’s limit behavior for typical loading conditions in sheet forming operations, as well as the analysis of the influencing factors. This thesis addresses the numerical study of microstructural factors influencing the forming limit diagram (FLD) of DP-780 steel sheets. The material’s limit behavior is modeled by the Marciniak-Kuczynski (MK) model, which assumes an initial imperfection, precursor of the localization process; whereas the material’s constitutive description is performed within the crystal plasticity framework. The anisotropic behavior, the presence of preferred orientation distributions and the effect of the constituent phases – ferrite/martensite – is obtained by a self-consistent homogenization of the single crystal viscoplastic response (VPSC). The coupled techniques (MK-VPSC) can successfully model the limit response of the DP-780 steel sheet. The effect of typical microstructural parameters of DP steels, the influence of anisotropy and its evolution with deformation, as well as the extrapolated post-necking hardening behavior, on the forming limits is numerically investigated. Both the martensitic volume fraction and plasticity have a significant influence on the FLD prediction, while the evolution of crystallographic texture only affects the limit strains under biaxial deformation. The best agreement with experimentation is found when using the saturation hardening law and when the martensite deformation is either not allowed or retarded to occur after the point of necking. An analysis of the slip systems activity suggests that, within the MK-VPSC framework, localization occurs much faster in the ferritic than in the martensitic phase. An extension to the MK-VPSC model is presented in this thesis in order to avoid convergence problems and reduce the computational cost. This is achieved by directly applying the stress and strain-rate boundary conditions, resulting from the equilibrium and compatibility restrictions, at the MK instability band. Moreover, the mechanical states outside and inside the groove are solved in the sample reference frame. This avoids rotating the crystallographic orientations and the internal variables to the current groove orientation for each increment, improving the computational performance. The generalized boundary conditions in the polycrystal model allow calculating either strain ratio (FLDρ) or stress ratio (FLDα) based FLDs.

<p>Metal forming processes have been widely applied in many industries. With the severe competition in the market, a reliable and robust metal forming process becomes crucial for the manufacturer to reduce product development time and cost. For the purpose of supplying engineers with an effective tool for a reliable and robust design of metal forming process, this research investigates the application of traditional reliability theory and robust design methods in metal forming processes for the ultimate goal of increasing quality and reducing cost in manufacturing.</p> <p> A method to assess the probability of failure of the process based on traditional reliability theory and the forming limit diagram (FLD) is presented. The forming limit of a material is chosen as the failure criteria for analysis of reliability.</p> <p> A study of prediction of forming limit diagrams using finite element simulation without pre-defined geometrical imperfection or material imperfection is presented. A 3D model of the dome test is used to predict the FLD for AA 5182-0. The FE predicted forming limit diagram is in good agreement with the experimental one. The uncertainty sources for the scatter of forming limits are categorized and investigated to see their effects on the shape of FLD.</p> <p>A novel method of improving the reliability of a forming process using the Taguchi method at the design stage is presented. The thickness-thinning ratio is chosen as the failure criteria for the reliability analysis of the process. A Taguchi orthogonal array is constructed to evaluate the effects of design parameters on the thinning ratio. A series of finite element simulations is conducted according to the established orthogonal array. Based on the simulation results, Taguchi S/N analysis and ANOVA analysis are applied to identify the optimal combination of design parameters for minimum thinning ratio, minimum variance of thinning ratio, and maximum expected process reliability.</p> <p> A multi-objective optimization approach is presented, which simultaneously maximizes the bulge ratio and minimizes the thinning ratio for a tube hydroforming process. Taguchi method and finite element simulations are used to eliminate the parameters insignificant to the process quality performance. The significant parameters are then optimized to achieve the multiple optimization objectives. The optimization problem is solved by using a goal attainment method. An illustrative case study shows the practicability of this approach and ease of use by product designers and process engineers.</p> / Thesis / Doctor of Philosophy (PhD)

Le déficit familial de LCAT (FLD) est une maladie caractérisée par un défaut de l’activité de l’enzyme lecithin:cholesterol acyltransferase (LCAT). Ce défaut résulte en une concentration plasmatique de C-HDL extrêmement basse, des opacités cornéennes prématurées, la présence d’anémie, de protéinurie et d’insuffisance rénale. Nous avons identifié les premiers patients canadiens-français atteints de déficit familial de LCAT. Deux frères, présentant les signes classiques de FLD étaient homozygotes pour une nouvelle mutation du gène de la LCAT: la mutation c.102delG. Cette mutation se traduit au niveau protéique par un changement du cadre de lecture au niveau du codon His35 et l’insertion d’un codon stop en position 61 entraînant une abolition de l’activité LCAT in vitro et in vivo. La présence de cette mutation cause une réduction importante du C-HDL chez les hétérozygotes (22%) et les homozygotes (88%) ainsi qu’une baisse du C-LDL chez les hétérozygotes (35%) et les homozygotes (58%). De plus, le profil lipidique différait de manière importante entre les deux frères atteints de FLD qui présentaient des génotypes APOE différents. Nous suggérons que APOE est un gène qui modifie le phénotype du FLD et pourrait expliquer l’hétérogénéité des profils lipidiques chez les patients atteints de FLD. Nos résultats suggèrent également que l’association du génotype LCAT-/- a un allèle APOE ε2 est un nouveau mécanisme conduisant à la dysbétalipoproteinemie. Finalement nous avons montré des différences importantes dans les sous-populations des HDL chez les deux sujets atteints de FLD. Le porteur de l’allèle APOE ε2 présentait une proportion beaucoup plus importante de HDL immatures (preβ discoïdaux) par rapport a son frère (77.9% vs. 31.0%). / Familial LCAT deficiency (FLD) is a disease characterized by a defect in the enzyme lecithin:cholesterol acyltransferase (LCAT) resulting in low HDL-C, premature corneal opacities, anaemia as well as proteinuria and renal failure. We have identified the first French Canadian kindred with familial LCAT deficiency. Two brothers, presenting classical signs of FLD, were shown to be homozygous for a novel LCAT mutation. This c.102delG mutation occurs at the codon for His35 and causes a frameshift that stops transcription at codon 61 abolishing LCAT enzymatic activity both in vivo and in vitro. It has a dramatic effect on the lipoprotein profile, with an important reduction of HDL-C in both heterozygotes (22%) and homozygotes (88%) and a significant decrease in LDL-C in heterozygotes (35%) as well as homozygotes (58%). Furthermore, the lipoprotein profile differs markedly between the two affected brothers who had different APOE genotypes. We propose that APOE could be an important modifier gene explaining heterogeneity in lipoprotein profiles observed among FLD patients. Our results suggest that a LCAT-/- genotype associated with an APOE ε2 allele could be a novel mechanism leading to dysbetalipoproteinemia. Finally we have identified major differences in the HDL sub-populations of both subjects affected by FLD. The carrier of the APOE ε2 allele presented a much higher proportion of immature HDL particles (discoid preβ) compared to his brother (77.9% vs. 31.0%).

Ergotalkaloide sind sekundäre Stoffwechselprodukte des parasitären Schlauchpilzes Claviceps purpurea der auf Getreide Mutterkörner (Sklerotien) bildet. In Sklerotien sind toxische Ergotalkaloide enthalten. Durch C. purpurea werden vorrangig sechs verschiedene Ergotalkaloid-Epimerenpaare gebildet, die toxischen C8-(R)-Epimere und die biologisch nicht relevanten C8-(S)-Epimere, die ineinander umgewandelt werden können. Das Ziel der Arbeit war es, die Epimerisierung der Ergotalkaloide während der Probenvorbereitung im Vergleich zu bisher bekannten Probenaufarbeitungsverfahren zu minimieren. Dieses gelang durch den Verzicht des Zusatzes starker Säuren oder Basen. Die aufgereinigten Extrakte können bei Raumtemperatur über 96 Stunden epimerisierungsfrei in einer tensidischen Acetonitril-Wasser-Lösung gelagert werden. Die Probenaufarbeitung mit anschließender Auftrennung über die Hochleistungsflüssigchromatographie und fluorimetrischer Detektion (HPLC-FLD) wurde für Roggenmehl und Speiseöl validiert und auf diese Martices angewendet. So konnten erstmals die Ergotalkaloidgehalte auch in Weizenkeimöl quantifiziert werden. Im zweiten Teil der Arbeit wurde das Epimerisierungsverhalten von Ergotalkaloiden bei Backversuchen und in vitro Verdauexperimenten untersucht. Das Backen resultierte in eine Verschiebung des Epimerengleichgewichtes auf die Seite der (S)-Epimere. Das angewendete in vitro Verdaumodell führte für die Ergotalkaloidepimerenpaare Ergotamin und Ergosin zu einer Verschiebung des Epimerengleichgewichtes auf die Seite der toxischen (R)-Epimere. Dagegen zeigten die Ergotalkaloide der Ergotoxingruppe eine Verschiebung des Epimerengleichgewichtes auf die Seite der (S)-Epimere. Der dritte Teil der Arbeit beschäftigt sich mit Ergotalkaloid-Konjugaten, die unter dem Einfluss von UV-Licht entstehen. Es wurden sechs Ergotalkaloid-Fettsäure-Konjugate synthetisiert und in Sklerotien über die HPLC in Verbindung mit massenspektrometrischer Detektion nachgewiesen. / Ergot alkaloids are secondary metabolites of the parasitic fungus Claviceps purpurea that forms sclerotia on cereals. These sclerotia contain toxic ergot alkaloids. C. purpurea forms six epimeric pairs of ergot alkaloids predominantly the toxic C8-(R)-epimers and the biologically inactive C8-(S)-epimers. In view of the fact that both epimeric forms can be transformed into one another, the objective of this work was to develop a novel sample preparation method that minimizes the epimerization rate compared to previously published methods. The presented sample preparation procedure minimizes epimerization of ergot alkaloids, as it operates without the addition of strong acidic or alkaline modifiers for matrix removal. After sample preparation, an ergot alkaloid containing extract in a sodium hexanesulfonate solution is obtained in which no epimerization after 96 hours was observed. Thus, the sample preparation allows extract storage at ambient temperature for prolonged HPLC analysis. This novel sample preparation followed by HPLC-flourescence analysis was validated for the matrices rye flour and wheat germ oil and was applied for food samples. This is the first time that the ergot alkaloid content in wheat germ oil was quantified. The second part of this work was the study of the epimerization behaviour of ergot alkaloids during baking and in vitro digestion. Baking of cookies resulted in a shift of the epimeric ratio towards the (S)-epimers. The in vitro digestion showed an ergot alkaloid specific shift of the epimeric ratio. The initial percentage of the (R)-epimer increased for ergotamine und ergosine. In contrast, ergot alkaloids of the ergotoxine type showed an epimeric shift towards their (S)-epimers. The third part of this work was the study of ergot alkaloid derivatives that are formed in combination with UV-light. Six different ergot alkaloid fatty acid derivates were synthesized and detected in sclerotia using a HPLC-MS/MS method.

Le déficit familial de LCAT (FLD) est une maladie caractérisée par un défaut de l’activité de l’enzyme lecithin:cholesterol acyltransferase (LCAT). Ce défaut résulte en une concentration plasmatique de C-HDL extrêmement basse, des opacités cornéennes prématurées, la présence d’anémie, de protéinurie et d’insuffisance rénale. Nous avons identifié les premiers patients canadiens-français atteints de déficit familial de LCAT. Deux frères, présentant les signes classiques de FLD étaient homozygotes pour une nouvelle mutation du gène de la LCAT: la mutation c.102delG. Cette mutation se traduit au niveau protéique par un changement du cadre de lecture au niveau du codon His35 et l’insertion d’un codon stop en position 61 entraînant une abolition de l’activité LCAT in vitro et in vivo. La présence de cette mutation cause une réduction importante du C-HDL chez les hétérozygotes (22%) et les homozygotes (88%) ainsi qu’une baisse du C-LDL chez les hétérozygotes (35%) et les homozygotes (58%). De plus, le profil lipidique différait de manière importante entre les deux frères atteints de FLD qui présentaient des génotypes APOE différents. Nous suggérons que APOE est un gène qui modifie le phénotype du FLD et pourrait expliquer l’hétérogénéité des profils lipidiques chez les patients atteints de FLD. Nos résultats suggèrent également que l’association du génotype LCAT-/- a un allèle APOE ε2 est un nouveau mécanisme conduisant à la dysbétalipoproteinemie. Finalement nous avons montré des différences importantes dans les sous-populations des HDL chez les deux sujets atteints de FLD. Le porteur de l’allèle APOE ε2 présentait une proportion beaucoup plus importante de HDL immatures (preβ discoïdaux) par rapport a son frère (77.9% vs. 31.0%). / Familial LCAT deficiency (FLD) is a disease characterized by a defect in the enzyme lecithin:cholesterol acyltransferase (LCAT) resulting in low HDL-C, premature corneal opacities, anaemia as well as proteinuria and renal failure. We have identified the first French Canadian kindred with familial LCAT deficiency. Two brothers, presenting classical signs of FLD, were shown to be homozygous for a novel LCAT mutation. This c.102delG mutation occurs at the codon for His35 and causes a frameshift that stops transcription at codon 61 abolishing LCAT enzymatic activity both in vivo and in vitro. It has a dramatic effect on the lipoprotein profile, with an important reduction of HDL-C in both heterozygotes (22%) and homozygotes (88%) and a significant decrease in LDL-C in heterozygotes (35%) as well as homozygotes (58%). Furthermore, the lipoprotein profile differs markedly between the two affected brothers who had different APOE genotypes. We propose that APOE could be an important modifier gene explaining heterogeneity in lipoprotein profiles observed among FLD patients. Our results suggest that a LCAT-/- genotype associated with an APOE ε2 allele could be a novel mechanism leading to dysbetalipoproteinemia. Finally we have identified major differences in the HDL sub-populations of both subjects affected by FLD. The carrier of the APOE ε2 allele presented a much higher proportion of immature HDL particles (discoid preβ) compared to his brother (77.9% vs. 31.0%).

Magnesium (Mg) alloy sheets possess several key properties that make them attractive as lightweight replacements for heavier ferrous and non-ferrous alloy sheets. However, Mg alloys need to be formed at elevated temperatures to overcome their limited room-temperature formabilities. For example, commercial forming is presently conducted at 450°C. Deformation behavior of the most commonly used wrought Mg alloy, AZ31B-H24, and two potentially competitive materials, AZ31B-HR and ZEK100 alloy sheets, with weaker crystallographic textures, are studied in uniaxial tension at 450°C and lower temperatures. The underlying physics of deformation including the operating deformation mechanisms, grain growth, normal and planar anisotropy, and strain hardening are used to construct material constitutive models capable of predicting forming for all three Mg alloy sheets at 450°C and 350°C. The material models constructed are implemented in finite-element-method (FEM) simulations and validated using biaxial bulge forming, an independent testing method. Forming limit diagrams are presented for the AZ31B-H24 and ZEK100 alloy sheets at temperatures from 450°C down to 250°C. The results suggest that forming processes at temperatures lower than 450°C are potentially viable for manufacturing complex Mg components. / text