La maladie de Parkinson (MP) est une maladie neurodégénérative caractérisée par trois symptômes moteurs principaux : la bradykinésie, la rigidité et le tremblement de repos. Son diagnostic définitif repose sur l’identification post-mortem d’une importante mort des neurones dopaminergiques de la substance noire (SN) et la présence de corps de Lewy dans les neurones survivants. Cette maladie progresse lentement et les premiers symptômes moteurs n’apparaissent qu’après la dégénérescence de plus de 50% de la SN. Le diagnostic clinique de MP est donc établi tardivement, réduisant ainsi la fenêtre d’action thérapeutique. De plus, les traitements actuels ne soulagent que temporairement les symptômes moteurs. Les défis de la recherche actuelle pour la MP sont donc : 1) d’anticiper le diagnostic de la MP à un stade où la SN est encore suffisamment intacte pour mettre en place des stratégies neuroprotectrices, et 2) d’améliorer les traitements actuels et/ou développer de nouvelles stratégies thérapeutiques pour stopper la progression de la maladie avant que le phénotype moteur ne soit installé. Le stade clinique de la MP est précédé d’une phase prémotrice durant laquelle les patients présentent souvent des symptômes non moteurs tels que l’anosmie, la dépression ou la constipation. Des travaux récents suggèrent que les lésions caractéristiques de la MP pourraient d’abord apparaître dans le système nerveux périphérique puis progresser lentement jusqu’au cerveau. Ces stades précoces de la MP sont cependant mal connus et leurs caractéristiques méritent d’être étudiées dans des modèles expérimentaux appropriés. Ainsi, des études récentes ont montré que la ghréline, un peptide gastro-intestinal, protège les neurones dopaminergiques de la SN contre la mort dans des modèles in vivo et in vitro de syndrome parkinsonien. De plus, dans un modèle animal de syndrome parkinsonien, la ghréline prévient l’aggravation des symptômes gastro intestinaux par la L-DOPA, traitement médicamenteux principal de la MP. Enfin, des altérations des concentrations plasmatiques de ghréline ont également été observées chez les patients aux stades précoces de la maladie. Dans ce contexte, nous avons émis l’hypothèse que la ghréline pourrait jouer un rôle important aux stades précoces de la maladie et donc être utilisée comme biomarqueur et/ou agent neuroprotecteur dans la MP. Ainsi, l’objectif de ma thèse était d’étudier les rôles de la ghréline aux stades précoces de la MP par des approches in vitro et in vivo.La première étape a consisté à déterminer les effets de la ghréline dans des cultures primaires de cellules mésencéphaliques exposées au pesticide roténone, un inhibiteur du complexe I mitochondrial connu pour son association avec la MP. Contrairement aux données de la littérature, nous montrons un effet délétère en fonction de la dose et du temps sur les cellules exposées à la roténone. Nous ne confirmons donc pas l’effet neuroprotecteur de la ghréline dans nos conditions expérimentales. En parallèle, nous avons étudié le potentiel de la ghréline en tant que biomarqueur dans un modèle murin de syndrome parkinsonien reproduisant les stades précoces de la maladie après exposition orale chronique à de faibles doses de roténone. Nous avons d’abord validé ce modèle et confirmé le développement des altérations non motrices et l’absence de mort neuronale au sein de la SN après 1.5 mois de ce régime. En revanche, nos résultats ne montrent pas de modification des taux plasmatiques de ghréline chez les souris exposées 1.5 mois à la roténone. Cependant, des facteurs tels que l’anxiété pourraient avoir affecté les taux de ghréline. Ces données devront donc être confirmées avec des animaux stratifiés selon leur niveau d’anxiété et/ou de plus longues expositions. En conclusion, nos résultats interrogent le rôle neuroprotecteur de la ghréline dans la MP et posent les bases pour de futures recherches sur l’implication de cette hormone orexigène dans la MP. / Parkinson’s disease (PD) is the second most frequent neurodegenerative disease in the world. It is characterized by motor symptoms such as bradykinesia, rigidity and resting tremor. Its definite diagnosis relies on the identification of specific neuropathological hallmarks at autopsy including severe neuronal death within the substantia nigra (SN) and the presence of Lewy bodies in the surviving neurons. PD progresses slowly and the first motor symptoms appear when more than 50% of the SN has degenerated. Therefore, the clinical diagnosis is established late in the course of the disease, thus restricting the therapeutic window for clinicians. In addition, the currently available therapeutic options can only temporarily alleviate PD motor symptoms. The challenges of current PD research are: 1) to anticipate the diagnosis and be able to identify the disease as early as possible, when the SN is still intact enough to implement a disease-modifying/neuroprotection strategy to prevent the appearance of motor symptoms, and 2) to improve current medications and/or develop new therapeutic strategies able to stop the disease before the motor phenotype is installed. The decade preceding PD clinical diagnosis is of particular interest since patients often complain about non-motor symptoms such as anosmia, depression or constipation. Moreover, recent evidences suggest that PD-characteristic lesions could first appear in the peripheral nervous system and slowly progress towards the brain. Thus PD earlier stages and their characteristics deserve better investigations using appropriate experimental models. In this regard, recent studies realized in animal and cellular models of advanced parkinsonism have suggested that ghrelin, an orexigenic peptide mainly produced in the stomach, could play a neuroprotective role in PD. Indeed, exposure to ghrelin has shown a protective effect against the neuronal death in animal and cellular models of parkinsonism. In addition, in a rodent model of parkinsonism, ghrelin was shown to alleviate the L-DOPA-induced worsening of gastro-intestinal symptoms, L-DOPA being the current main therapeutic option in PD. Moreover, ghrelin plasma concentrations have shown alterations in early stages of the disease in small cohorts of PD patients. We therefore hypothesized that ghrelin might play an important role in PD early stages and could serve as a biomarker and a neuroprotective agent in PD. In this context, the aim of my PhD was to investigate the roles of ghrelin in PD early stages using both in vitro and in vivo approaches.We first studied the effects of ghrelin in primary mesencephalic cells exposed to the pesticide rotenone, a potent inhibitor of mitochondrial complex I known for its association with PD. Contrary to the data of the literature, we show a dose and time-dependant deleterious effect of ghrelin on mesencephalic cells exposed to rotenone. This does not confirm the neuroprotective potential of ghrelin in our experimental conditions. In parallel, we investigated the potential of ghrelin as a biomarker in a rodent model of parkinsonism mimicking early stages of the disease after chronic oral exposure to low doses of rotenone. We first validated this model in our animal facility and confirmed that mice exposed to such a regimen develop progressive non-motor alterations but no dopaminergic neuronal death in the SN after 1.5 months. Our initial results do not show a modification of plasma ghrelin levels in rotenone-exposed mice at early stages of the pathological condition. However, confounding factors such as anxiety might have altered ghrelin levels. This should therefore be further ascertained in animals stratified for their anxiety levels and/or in longer exposures. In conclusion, these results challenge the suggested role of ghrelin as a disease-modifying agent in PD and set the bases for future investigations of ghrelin in the context of PD.

This diploma thesis deals with problem of design and calculation of membrane structure. Design proces of light and airy structure was demonstrated on conical shaped roof in the finite element analysis program RFEM. The structure was loaded in the virtual wind tunnel in the program RWIND. Results were compared with the values given in the literature. A comprehensive guide for the design of membrane structures has been created. Subsequently, the influence of design stages on the internal forces was demonstrated. Membrane structures are very sensitive to construction stages, because it is not possible to prestress all membrane surfaces at once. Program by DLUBAL software s.r.o. was used for form-finding analysis during construction stages.

Aim of this thesis is the classification of polysomnographic data. The first part of the thesis is a review of mentioned topic and also the statistical analysis of classification features calculated from real EEG, EOG and EMG for evaluating of the features suitability for sleep stages scoring. The second part is focused on the automatic classification of the data using artificial neural networks. All the results are presented and discussed.

Euclea natalensis A.DC. belongs to the Ebenaceae family, and is extensively distributed along the eastern coast of southern Africa. Many Euclea species are widely gathered by indigenous people because of their medicinal properties. Roots of these plant species are frequently used to treat respiratory complications such as chest pains, bronchitis, pleurisy and asthma. Ground root powder is topically applied in cases of leprosy and is used by some ethnic groups to treat toothache and headache. The bioactivity encountered is attributable to naphthoquinones, which are common phenolic compounds in the Ebenaceae family. Naphthoquinones isolated from E. natalensis (shinanolone, 7-methyljuglone, diospyrin, isodiospyrin and neodiospyrin) have exhibited a broad spectrum of antimicrobial activity. The demand for these products will escalate due the amount of plant material required to further research. We need to explore techniques that can maximize their productivity. The present study was conducted on E. natalensis, in an attempt to establish if there exists any correlation between the accumulation of naphthoquinones and stages of seedling growth, seasonal fluctuations and application of fertilizers. A possible correlation between seedling growth stages and the accumulation of naphthoquinones (shinanolone, 7-methyljuglone and diospyrin) was investigated in seeds and seedlings of Euclea natalensis. In this study, the seeds represented the first stage, whereas the second seedling stage was defined as the stage when the radicles were about 6 cm long. The lengths of the seedlings at the third, fourth and fifth seedling stages were 9 cm, 12 cm and 16 cm respectively. Plant materials collected from the five seedling stages were separately extracted using chloroform and the naphthoquinones were then quantified by means of High Performance Liquid Chromatography (HPLC). Mobile phase of MeCN: H2O: AcOH (62.5: 32.5: 5) was used as an eluent in an isocratic mode and at a flow rate of 0.8 ml/min. Standard curves of each of the four compounds were obtained by making a series of dilutions in the concentration range of 22.5 µg/ml to 2.25 µg/ml. Ten microlitres of each dilution was injected three times into the HPLC, and the run time for each injection was 20 minutes. Calibration curves were then generated and used for the quantification of each compound. Shinanolone, which was the only naphthoquinone detectible in seeds, accumulated at variable rates (P<0.01) and no trend could be established between its synthesis and seedling growth. The content of shinanolone ranged from 87.5 mg/kg dry weight (dw) in seeds to a high mean value of 1047 mg/kg (dw) during the fourth seedling stage. A significant correlation (P<0.01) was found between the mean concentrations of 7-methyljuglone and seedling growth. 7-Methyljuglone was quantified at a high mean level of 5003 mg/kg during the third seedling stage and was not detected in the seed samples. A positive correlation (P<0.01) was established between the concentration of diospyrin and seedling stages. Diospyrin was detected at an elevated mean concentration of 6182 mg/kg during the fifth seedling stage, which was higher than the other quantified naphthoquinones. Seasonal variation of naphthoquinones (shinanolone, 7-methyljuglone, diospyrin, isodiospyrin and neodiospyrin) was investigated from eleven plants of E. natalensis subsp. natalensis growing in natural populations, over a period of four seasons. The roots were harvested, dried, extracted and analysed as in the previous study. The mean levels of shinanolone and 7-methyljuglone were found to be uniform in all the seasons and no statistically significant variation could be found between seasonal changes and their mean concentrations. Accumulation of isodiospyrin and neodiospyrin varied significantly with seasonal changes (P<0.05). These two bioactive naphthoquinones were detected only in summer and autumn respectively, and not in winter. A statistically significant variation (P<0.05) was established between the levels of diospyrin and seasonal fluctuations. Diospyrin was detected at a mean concentration of 3190 mg/kg (dw) during spring, which was higher than the other naphthoquinones quantified in all four seasons. The effect of NPK fertilizers on growth performance and accumulation of naphthoquinones (shinanolone, 7-methyljuglone, diospyrin, isodiospyrin and neodiospyrin) in seedlings of E. natalensis grown in shade and under field conditions was investigated. Each group was subdivided into four subgroups, which were then subjected to four respective treatments of water-soluble foliar feed (2:1:2 (44) NPK) at three different concentrations. Treatments tested were as follows: Treatment 1 at 40 g/l, Treatment 2 and Treatment 3 at 20 g/l and 10 g/l respectively. The control group received only supplemental water. The first harvest was conducted after 6 months of application of fertilizers and the second one was done after 12 months of treatment. Roots and shoots were harvested and analysed separately. The naphthoquinones were quantified as previously described. The bioactivity of root extracts from seedlings was tested against Mycobacterium smegmatis and extracts with lower MIC were further tested on M. tuberculosis. Growth parameters differed between the two groups, with seedlings from the shadehouse showing more plant vigour than the field grown plants. No significant interaction could be established between the measured growth factors and treatment. A significant interaction (P<0.001) was found between Treatment 2 and shadehouse seedlings. Treatment 2 enhanced vegetative performance with the mean values of fresh weight of shoots and roots being twice as much as their respective control mean values. A significantly positive correlation was established between the concentration of shinanolone (P<0.01), isodiospyrin (P<0.05) and neodiospyrin (P<0.05) with fertilization from field-grown seedlings. Application of NPK fertilizers significantly (P<0.05) increased the accumulation of neodiospyrin in seedlings subjected to shadehouse conditions. The most potent naphthoquinone, 7-methyljuglone, was found to be abundant in all the extracts and was quantified at a high mean concentration of 10200 mg/kg from shadehouse seedlings. Root extracts of E. natalensis seedlings grown under field conditions were generally more active against the bacterial strain of M. smegmatis as compared to extracts acquired from roots of seedlings maintained under a shadehouse setting. A lowest minimum inhibitory concentration (MIC) of 0.78mg/ml against M. smegmatis was observed from the second harvest of field-cultivated seedlings of the control and Treatment 1 subgroups. The MIC values for shadehouse seedlings ranged from 1.6 to 6.3 mg/ml. Minimum bactericidal concentration (MBC) values from all the extracts tested were relatively higher than their respective MIC’s. Root extracts of E. natalensis were more active against M. tuberculosis and their MIC values were lower than the tested concentrations. Extracts acquired from field-grown seedlings were more active against M. smegmatis with a lowest MIC value of 0.78 mg/ml. Extracts from the control group and Treatment 1, which had less application of fertilizers were more active against strains of M. tuberculosis with MIC value of 10 µg/ml. This shows the selectivity of E. natalensis against the mycobacterial strain of M. tuberculosis. Based on the findings, synthesis and accumulation of naphthoquinones in E. natalensis is highly variable within individuals of the species investigated. Naphthoquinones accumulate in relatively higher amounts in roots of E. natalensis than in the aboveground structures, which validate their harvest by indigenous people. The concentration of shinanolone varied slightly and its production increased with seedling growth. The synthesis of 7-methyljuglone is independent of fertilisation as its accumulation was enhanced in seedlings subjected to control treatment. Neodiospyrin and isodiospyrin were always present in every sample obtained from the seedlings but they were not detectible in every profile of samples from mature plants. Diospyrin is the only naphthoquinone that was detected in every sample analysed and also quantified in high concentrations from mature plants harvested in spring. The study showed that depending on the requirement of a particular naphthoquinone for research, one could target the seasons and seedling stages recommended from this study. This study also showed that field-cultivated seedlings produced more potent naphthoquinones than the ones subjected to controlled environments. / Dissertation (MSc (Plant Science))--University of Pretoria, 2008. / Plant Production and Soil Science / unrestricted

The work deals with landing facilities in ancient Egypt, both in the Nile Valley and in coastal areas. The aim has been to collect and interpret written, iconographic and archaeological evidence from the Early Dynastic to the Late Periods. The material is presented chronologically and individual groups of sources are arranged by type (written, archaeological and iconographic). The knowledge thus obtained has then been used to form a comprehensive overview of the development, function, importance and organization of harbour/port facilities in ancient Egypt. The main problem of the study of landing facilities in ancient Egypt lies in the extreme fragmentation of sources which makes it impossible to provide a continuous picture of the development of the subject and which raises as many questions as answers. The best preserved group of sources is written evidence, followed by information obtained by archaeology. The least informative is iconographic evidence. Although the majority of these sources are relatively straightforward to interpret, there are cases where interpretation is speculative. A fundamental question has arisen during this study. It is the relationship of the ancient Egyptians themselves to the facilities which undoubtedly played a significant role in the life of the inhabitants of the...

Exposure to thermal stress can negatively impact an animals' overall welfare, resulting in decreased body condition, lower reproductive success, and in severe cases, mortality. The swine industry has prioritized efficient production and as a result has gained rapid improvements in lean growth and increase litter sizes. Unfortunately, modern swine are unable to cope with the negative effects of heat stress. Thus, it is crucial to understand the preferred temperature of swine to create recommendations on when to initiate mitigation strategies to combat the negative effects of thermal stress. However, several different factors contribute to an animals' thermal comfort and thermal preference will differ based on age, reproductive stage, social context, early life thermal stress, and behavior. Thus, making it exceptionally difficult to classify an animal's thermal comfort zone. These studies aim to highlight how those factors influence thermal comfort in pigs and help guide recommendation polices for housing pigs in their preferred temperatures.<br>

Background: Environmental problems are a worrying phenomenon, and there is a call for action. One way to face these problems lies in sustainable entrepreneurship. There is an increase in sustainability-oriented incubators supporting these sustainable entrepreneurs on their entrepreneurial journey, using various support systems. However, there is little research available about the support systems sustainability-oriented incubators offer, the importance of these support systems, and the influence of entrepreneurial stages. Purpose: With our study, we provide sustainability-oriented incubator managers with insights into the importance of different support systems, the frequency in which they are offered and the role of different entrepreneurial stages. This allows sustainability-oriented incubators to support their tenants better and, therefore, positively influence sustainable entrepreneurship.  Method: A single case study method has been applied by using a mixed-method approach of qualitative semi-structured interviews and a quantitative questionnaire which was filled in prior to the interviews by the participants. In total, nine participants were interviewed, consisting of seven incubator tenants and two incubator managers. Conclusion: This research has found a high level of importance and frequency of business model support and market research support, irrespective of the different entrepreneurial stages. This implies a constant reiteration process from sustainable entrepreneurs, demanding a strong-intervention role from the sustainability-oriented incubator. Furthermore, this research has found the shortcomings in using the effectuation model for analysing entrepreneurial stages and suggests a different application.

Coral reef fish are known to have a bipartite life cycle: a dispersive pelagic larval phase (DPL), where larvae ‘travel’ away from their parents to occupy new habitats, and a sedentary reef phase characterized by juveniles and adults. Study of the DPL is an essential prerequisite to understand how persistence, connectivity, and gene flow operate between populations. Clownfish have been the subject of considerably varied fields of research in recent decades, not only due to their economic value, but also because of their ease of maintenance in laboratory settings, regular spawning, and short DPL. Their life cycle is also defined as bipartite, with a DPL lasting around 15 days until settlement, and the fish exhibit a symbiotic relationship with sea anemones. The transitions between phases are associated with a series of morphological, behavioural, genetic, cellular and molecular changes. However, these changes are poorly characterized in some species of clownfish. Therefore, the Red Sea clownfish, Amphiprion bicinctus, was reared to fill the gap in the literature by investigating their i) morphology, ii) swimming abilities, and iii) differential gene expression (DGE) throughout ontogeny. The DPL was characterized in the preflexion, flexion and postflexion stages, according to flexion of the notochord, on 0, 2 and 10 days post hatch (dph), respectively. Metamorphosis was defined by a morphological transition between the DPL and juvenile phases, associated with the appearance of white stripes, on day 10 and until the end of the experiment, on day 14. Additionally, metamorphosis is followed by a behavioural change at 14 dph, called settlement, where larvae transition from free swimming in the water column to associating with the substrate. We also demonstrate that the larvae present active swimming from the moment they hatch, and the swimming speed increases throughout DPL. Overall, the development of A. bicinctus is similar to other clownfish species. This work provides a strong baseline on the development of A. bicinctus, which may open the door to a deeper understanding of the role of dispersal behaviours and enhance our ability to design effective marine reserve networks in the Red Sea.

The Pneumocystis carinii carinii DNA content in nuclei of trophic forms and cysts (spore cases) containing 2, 4, or 8 intracystic bodies, were compared using quantitative fluorescence image analysis. The nuclear DNA content was found to be lower than the theoretical limits of Feulgen cytophotometry. Several fluorescent DNA dyes provide brighter staining, but these techniques suffer from nonspecific binding to other cellular components, such as RNA. It was demonstrated that the thick glycocalyx surfaces of trophic forms and the cyst walls of P. carinii organisms, as well as the cell wall of S. cerevisiae, bound all fluorescent dyes tested to varying degrees. Hence in this study, measurements were performed on cells in which the outer surfaces of organisms were first removed with lyticase. Two stains that appeared most specific for DNA, DB181 and 4',6-diamidino-2-phenylindole (DAPI), were used for quantitations; lower deviations of fluorescence intensities were observed with DB181. Haploid wild type Saccharomyces cerevisiae and cdc-28 temperature-sensitive mutant cells, accumulated at the restrictive temperature (37°C), were used as quantitative internal standards for estimating the absolute nuclear DNA content of P. carinii. Haploid wild type and mutant nuclei stained with DAPI had the same relative fluorescence intensities. The P. carinii nuclear DNA content of trophic forms and individual intracystic bodies (spores), regardless of life cycle stage, were not different. The mean values obtained were 6.9 and 6.7 fg DNA/nucleus with DB181 and DAPI, respectively (approximately 9.26 and 8.99 Mbp nucleotides, respectively). Since these would include 2C (G-2 phase) and S-phase nuclei, a 1C population of nuclei was selected by histogram distributions of DB181-stained nuclei. Almost all nuclei analyzed in all life cycle stages fell within this population. The 1C mean of 6.55 fg DNA/nucleus (median, 6.62 fg DNA/nucleus) was estimated as representing 8.79 Mbp nucleotides, assuming only A-T binding of the dye and taking into account the G+C content of S. cerevisiae and P. carinii. A 4C (G-2-phase diploid nuclei) population was not detected in histograms of DB181- or DAPI-stained nuclei. The P. carinii nuclear DNA content values obtained in this study were similar to those independently obtained by calculating the total DNA in the organism's chromosomes resolved by electrophoretic techniques. Together, the data on total chromosome numbers and the estimated DNA content of those chromosomes, with our quantitation of nuclear DNA content of different life-cycle stages demonstrate that P. carinii carinii isolated from infected rat lungs are haploid organisms.

Corn occupies from 25 to 30 percent of the crop land harvested in the United States. In recent years the acreage devoted to corn in this country has been decidedly greater than that devoted to any other cultivated crop. In 1944 its dollar value exceeded the combined values of wheat, barley, rye, grain sorghums, and cotton. Although South Dakota lies on the northwestern fringe of the corn belt, the corn crop is one of the most important in that state. Corn production in that area is somewhat unstable because of drought. Corn often fails to reach full maturity before the first frost in the fall. This is particularly true when frost comes unseasonably early. An irrigation project has been proposed for the James River Basin Area of South Dakota. It is a part of the Missouri River Basin Development Project. The introduction of irrigation into this area can somewhat lessen the dangers of drought and early frost. Moisture requirements of the corn crop can be met by proper water applications. In this way the threat of crop failure as a result of drought can be reduced. The corn maturity can be hastened through correct land management and irrigation practices, thus alleviating the danger of early frost. Very little information is available regarding the management of corn grown under irrigation in the Northern Great Plains Region. The problems associated with corn production are peculiar to that area. More complete information is needed concerning the specific needs of the corn crop in the James River Basin. The work reported here shows some of the relationships between the development and growth of corn and soil moisture supply. The objectives of the study were twofold: to determine the periods of corn development in which abundant moisture is most critical, and to determine the effects of a limited moisture supply at various growth stages upon the development and production of hybrid corn. The results of field and greenhouse studies are reported.