Techn. Hochsch., Diss., 2001--Aachen.

Techn. Universiẗat, Diss., 2004--Darmstadt.

Universiẗat, Diss., 2004--Düsseldorf.

Techn. University, Diss., 2005--Darmstadt.

Techn. Universiẗat, Diss., 2004--Dresden.

La formation de structures nanométriques définies dans l'eau demeure un défi pour les chimistes supramoléculaires. L'interaction entre cyclodextrines beta et adamantane a ici été utilisée pour former des polymères supramoléculaires en solution. L'utilisation d'une structure pontée nous a permis d'éviter la formation de l'espèce auto-incluse et d'augmenter la solubilité de nos dérivés. Les polymères supramoléculaires ont été caractérisés par différentes techniques (ROE, ITC, DOSY, SANS), et forment des espèces linéaires en solution allant jusqu'à 26 unités polymérisées. Celles-ci ont été utilisées pour compacter de l'ADN à des concentrations basses en mettant à profit l'association entre monomères. Un deuxième mécanisme, reposant sur des interactions non spécifiques entre cyclodextrines, a aussi été observé. Enfin, les structures synthétisées ont été utilisées dans la transfection d'ADN plasmidique, mais ne sont pas efficaces. Ce comportement pourrait provenir de leur faible densité de charge. / The synthesis of defined nanometric structures in water remains a challenge for supramolecular chemists. The interaction between adamantane and beta cyclodextrin was thus used to build new supramolecular polymers in solution. The use of a bridged structure enabled us to suppress the self-inclusion phenomenon and to enchance the solubility of our compounds. Supramolecular polymers were characterised using several techniques (ROE, ITC, DOSY, SANS), forming linear species up to 26 polymerised units. These structures were used to condense DNA at low concentrations, taking advantage on their host-guest behavior. Another condensation mechanism was discovered, involving non-specific interactions between cyclodextrins. The same structures were used to transfect plasmidic DNA, but were inefficient. This could be due to their low charge density.

Dans cette thèse, nous proposons une analyse probabiliste de deux problèmes de biologie moléculaire dans lesquels la stochasticité joue un rôle essentiel : la polymérisation des protéines dans les maladies neurodégénératives ainsi que le raccourcissement des télomères. L’agrégation des protéines en fibrilles amyloïdes est un important phénomène biologique associé à plusieurs maladies humaines telles que les maladies d’Alzheimer, de Huntington ou de Parkinson, ou encore l’amylose ou bien le diabète de type 2. Comme observé au cours des expériences reproduisant les petits volumes des cellules, les courbes d’évolution cinétique de l’agrégation des protéines présentent une phase de croissance exponentielle précédée d’une phase de latence extrêmement fluctuante, liée au temps de nucléation. Après une introduction au problème de polymérisation des protéines dans le chapitre I, nous étudions dans le chapitre II les origines et les propriétés de la variabilité de ladite phase de latence ; pour ce faire, nous proposons un modèle stochastique minimal qui permet de décrire les caractéristiques principales des courbes expérimentales d’agrégation de protéines. On considère alors deux composants chimiques : les monomères et les monomères polymérisés. Au départ, seuls sont présents les monomères ; par suite, ils peuvent polymériser de deux manières différentes : soit deux monomères se rencontrent et for- ment deux monomères polymérisés, soit un monomère se polymérise à la suite d’une collision avec un autre monomère déjà polymérisé. Malgré son efficacité, la simplicité des hypothèses de ce modèle ne lui permet pas de rendre compte de la variabilité observée au cours des expériences. C’est pourquoi dans un second temps, au cours du chapitre III, nous complexifions ce modèle afin de prendre en compte d’autres mécanismes impliqués dans la polymérisation et qui sont susceptibles d’augmenter la variabilité du temps de nucléation. Lors de ces deux chapitres, des résultats asymptotiques incluant diverses échelles de temps sont obtenus pour les processus de Markov correspondants. Une approximation au premier et au second ordre du temps de nucléation sont obtenus à partir de ces théorèmes limites. Ces résultats re- posent sur une renormalisation en temps et en espace du modèle de population, ainsi que sur un principe d’homogénéisation stochastique lié à une version modifiée d’urne d’Ehrenfest. Dans une seconde partie, un modèle stochastique décrivant le raccourcissement des télomères est pro- posé. Les chromosomes des cellules eucaryotes sont raccourcis à chaque mitose à cause des mécanismes de réplication de l’ADN incapables de répliquer les extrémités du chromosome parental. Afin d’éviter une perte de l’information génétique, ces chromosomes possèdent à chaque extrémité des télomères qui n’encodent pas d’information génétique. Au fil des cycles de réplication, ces télomères sont raccourcis jusqu’à rendre la division cellulaire impossible : la cellule entre alors en sénescence réplicative. L’objectif de ce modèle est de remonter aux caractéristiques de la distribution initiale de la taille des télomères à partir de mesures de temps de sénescence. / This PhD dissertation proposes a stochastic analysis of two questions of molecular biology in which randomness is a key feature of the processes involved: protein polymerisation in neurodegenerative diseases on the one hand, and telomere shortening on the other hand. Self-assembly of proteins into amyloid aggregates is an important biological phenomenon associated with human diseases such as prion diseases, Alzheimer’s, Huntington’s and Parkinson’s disease, amyloidosis and type-2 diabetes. The kinetics of amyloid assembly show an exponential growth phase preceded by a lag phase, variable in duration, as seen in bulk experiments and experiments that mimic the small volume of the concerned cells. After an introduction to protein polymerisation in chapter I, we investigate in chapter II the origins and the properties of the observed variability in the lag phase of amyloid assembly. This variability is currently not accounted for by deterministic nucleation-dependent mechanisms. In order to tackle this issue, a stochastic minimal model is proposed, simple, but capable of describing the characteristics of amyloid growth curves. Two populations of chemical components are considered in this model: monomers and polymerised monomers. Initially, there are only monomers and from then, two possible ways of polymerising a monomer: either two monomers collide to combine into two polymerised monomers, or a monomer is polymerised by the encounter of an already polymerised monomer. However efficient, this simple model does not fully explain the variability observed in the experiments, and in chapter III, we extend it in order to take into account other relevant mechanisms of the polymerisation process that may have an impact on fluctuations. In both chapters, asymptotic results involving different time scales are obtained for the corresponding Markov processes. First and second order results for the starting instant of nucleation are derived from these limit theorems. These results rely on a scaling analysis of a population model and the proof of a stochastic averaging principle for a model related to an Ehrenfest urn model. In the second part, a stochastic model for telomere shortening is proposed. In eukaryotic cells, chromosomes are shortened with each occurring mitosis, because the DNA polymerases are unable to replicate the chromosome down to the very end. To prevent potentially catastrophic loss of genetic information, these chromosomes are equipped with telomeres at both ends (repeated sequences that contain no genetic information). After many rounds of replication however, the telomeres are progressively nibbled to the point where the cell cannot divide anymore, a blocked state called replicative senescence. The aim of this model is to trace back to the initial distribution of telomeres from measurements of the time of senescence.

Transgenic (TG) sorghum genotypes with altered kafirin synthesis were developed by the Africa Biofortified Sorghum Project, employing recombinant DNA technology, with the aim of improving the protein nutritional quality of the grain. In this project, the effects of altered kafirin synthesis on kafirin polymerisation, protein quality, protein body structure and endosperm texture in different TG lines were investigated. The first generation of TG lines were in a type II low-tannin sorghum background. Altered synthesis of different major kafirin sub-classes (α-, γ- and σ-kafirin) was targeted. Some TG lines had improved lysine content (3.17 g/100 g protein) and moderate (55%) to high (74%) cooked in vitro protein digestibility, compared to the parent (2.05 g/100 g protein; 47.4%, respectively). This is of significance as tannins reduce protein digestibility, by complexing with the proline-rich kafirins. Transmission electron microscopy revealed that the improved protein quality traits were associated with floury endosperm texture and irregular protein body structure. Irregular protein bodies were 2-3 ìm in diameter, with few to numerous invaginations, compared to normal protein bodies. The high digestibility TG line also had a unique dense protein matrix, with occasional thick dark-staining inclusions. It appears that reduced kafirin synthesis, specifically γ-kafirin, has a major effect on the protein body structure, which in turn results in changes in protein digestibility and endosperm structure. To further improve the protein quality and poor endosperm texture of the first generation of TG lines, improved non-tannin sorghums were transformed to suppress kafirin synthesis, or they were back-crossed into TG lines with improved protein quality. Co-suppression of the α-, γ- and σ-kafirin sub-classes and removal of the tannin trait, resulted in TG with high cooked protein digestibility (±80%), improved Amino Acid Score (0.8) and Protein Digestibility Corrected Amino Acid Score (0.7) compared to the non-TG null controls (±50%, 0.4 and 0.2, respectively). However, these high-protein quality lines still had a floury endosperm texture. They also had irregular shaped protein body structure, as described previously. When fewer kafirin sub-classes were suppressed (only γ- and σ-kafirin) the endosperm was corneous with normal protein body structure, but the improvement in cooked protein digestibility was less. Apparently, co-suppression of several kafirin sub-classes is required to obtain high-protein quality sorghum, but this seems to result in floury-type grain endosperm. Further work conducted on the high digestible TG line revealed that the proportion of kafirin-1, extracted with 60% tert-butanol alone, was greatly increased. However, the total amount of kafirin remained unchanged. Also, the kafirin was much less polymerised by disulphide bonding, and there was evidence of compensatory synthesis of other kafirin proteins. Hence, the mechanism for the increased protein digestibility of TG lines is probably related to their lower levels of disulphide-bonded kafirins, allowing better access of proteases. This work appears to confirm that disulphide bond formation in kafirin is responsible for the reduced protein digestibility of cooked sorghum. Since grain hardness is an important grain quality attribute, playing a major agronomic role, in sorghum processing and in the end-use quality of sorghum-based foods, further research should focus on transforming sorghum to have both improved protein nutritional quality and good grain endosperm texture. / Thesis (PhD)--University of Pretoria, 2012. / Food Science / unrestricted

No description available.

The health of the transmission power transformers in the power system networks is critical to the reliability of electricity supply. Knowing the precise life expectancy of the transmission power transformer is of vital importance as it permits an optimised asset replacement. The traditionally regarded transmission power transformer’s life expectancy of 40 years is considered dated for the transformers in the UK according to the transformer life data in 2010. In this thesis, it is aimed to investigate the life expectancy of the transmission power transformer in the UK from three aspects: statistical analysis on historic transformer life data, thermal modelling of in-service transformers, and through the in-service transformers’ furan measurements.A detailed statistical analysis shows that deriving the transformer’s reliability at a certain age by calculating the hazard rate is inadequate, as the hazard rate at each age has a statistical range in which the confidence band width is related to the amount of the reliability data. The transformer life data in all ages are grouped together to derive a general hazard rate of 0.27%. It is concluded that the transformer life expectancy could not be derived via statistical approaches due to the limited data available at the older transformer ages.As an alternative approach, regarding the life of insulating paper as the ultimate life of a transformer, the thermal model published by the IEC transformer loading guide 60076-7 is reviewed and extended to estimate a transformer’s thermal lifetime. The model is improved in two aspects, such that Arrhenius equation is adopted to consider the paper’s practical ageing mechanism of oxidation and hydrolysis when calculating the paper’s ageing rate; and the model takes consideration of the paper’s moisture accumulation effect.The developed thermal model is used to reversely derive the generally unknown model input – hot-spot factor, by the means of regarding the scrapped transformer’s degree of polymerisation (DP) predicted thermal lives as a benchmark. Assigning the derived hot-spot factor to the field units with regard to the design family, the thermal lives of 106 in-service transformers have been estimated. To enlarge the life sample, the modelling lives are combined with the 79 scrapped transformers’ DP predicted thermal lives. The thermal life expectancy, defined as the median life of the sample set, is derived as 88 years. A series of sensitivity studies are performed to examine the derived life expectancy’s responses on the variations of load, winding-to-oil gradient, top-oil temperature rise, and the setting of winding temperature indicator.As a non-intrusive approach in transformer’s insulating paper assessment, the correlations between the 2-furaldehyde (2FAL) concentration dissolved in transformer oil and paper’s DP derived by different laboratories are reviewed which are found to differ significantly. As a first-time attempt to derive the 2FAL-DP correlation relationship for the field transformers, the paper’s DP is estimated at the age when oil was sampled using the thermal model, and is plotted with the 2FAL measurement. De Pablo’s equation is found to fit the plot of the DP estimates against the 2FAL measurements better than other function formats. The 2FAL concentrations corresponding to the paper’s critical DP levels are given using the developed 2FAL-DP correlation relationship.