Worldwide there is an increasing demand of natural resources. In future, non renewable resources get substituted by renewable resources in the energetic sector as well as in the material sector. That implies a stronger usage of renewable resources especially - wood. In 2009 there was a usage of 77 million cubic meters of wood for material applications and a quantity of 55 million cubic meters for energetic applications in Germany alone. Furthermore, there is an increasing demand on wood for energetic purposes. In 2007 this problematic development led to the first supply bottlenecks. To meet the increasing demands of the future, Short Rotation Coppices (SRC) can help to improve the wood provision. An SRC is a planting of fast growing coppice on agricultural areas, which is managed more intensively than usual forestry practices for a quicker production of wooden biomass. With a comparative LCA of conventional wood and wood from SRC the present study evaluates if wood from SRC is reasonable to cover the increasing demand of wood for material and energetic purposes in an environmental friendly way. A comprehensive literature research regarding LCAs of wood and wooden products shows that there are no previous studies comparing the two types of wood. Hence, the present study examines a particleboard production as the material scenario and the combustion of woodchips in a firing system as the energetic scenario to compare the ecological advantages and disadvantages of wood from SRC and conventional wood. The LCA is implemented with the Gabi software designed by PE International. Data is obtained from previous LCA studies evaluating the production of wood, the particleboard production and the combustion of wood. Additionally, data from the Ecoinvent database is used. Functional units are the production of 1m3 particleboard and the production of 1 MJ of thermal energy. The LCIA is implemented with the “Ecoindicator” as endpoint- and “CML 2001” as midpoint approach to cover broad range of environmental issues. Moreover a sensitivity analyses shows the impact of decisive variables on the results of “Ecoindicator” and “CML 2001”. Results reveal that outcomes of the LCIA are dependent of the assessment method and the processed part of trees from conventional forestry. The present study shows, that with an efficient land use, wood from SRC can help to cover the increasing demand of wood for material and energetic purposes in a sustainable way. However, an immediate usage of wood for energetic purposes has to be seen critical. Instead, a cascaded and sustainable utilization of wood is recommendable to counteract climate change and to improve the efficient use of the renew-able resource - “wood”.

The Photovoltaic Industry is at a crossroads for change. Improving the sustainability of this complex system requires a thorough understanding of the entire life cycle of the solar module production. The product life cycle is thereby divided into the value added steps of raw material extraction, outsourced production, in-house production, operation, and recycling. Furthermore, the following report distinguishes between social, ecological, and economic sustainability. The report offers a compacted matrix with all parts of sustainability and each life cycle stage in order toshow companies of the photovoltaic industry the sensible areas. This should be a first step for improving the sustainability in the whole life cycle of a solar module.

La leucémie myéloïde chronique (LMC) est une affection hématologique maligne caractérisée par l’apparition dans la moelle osseuse et le sang, d’un nombre important de globules blancs dont certains sont immatures. A l’heure actuelle, le principal traitement est l’Imatinib, commercialisé sous le nom de Glivec®. Ce traitement conduit, chez certains patients, à l'émergence de souches résistantes, ce qui complique la thérapeutique et nécessite un large panel de molécules actives pour contourner les mécanismes de résistance. Par conséquent, la recherche de nouvelles molécules bioactives agissant sur de nouvelles cibles biologiques reste toujours un défi important et d’actualité. Au cours de ce projet de thèse, nous nous sommes intéressés au développement de nouveaux procédés de synthèse pour accéder et découvrir de nouvelles molécules bioactives, en série nucléosidique, pour contourner les mécanismes de résistances dans des modèles de LMC. Nous avons tout d’abord développé une nouvelle méthode de synthèse propre et efficace de nouveaux analogues de C-nucléosides en utilisant une catalyse par le fer. Nous avons ensuite réalisé plusieurs modifications post-synthétiques pour accéder à de nouveaux C-nucléosides hautement fonctionnalisés, en particulier les analogues de la thiophènefurine. Nous avons également développé un nouveau procédé de synthèse d’une famille de O-glycosides, en combinant l’activation par les ultrasons à la catalyse par le fer. Ce procédé a été exploité par la suite pour concevoir et synthétiser les analogues glycosidiques du résvératrol. Enfin, nous avons mis au point une méthode efficace et peu couteuse d’azidation de sucres protégés. / Chronic myeloid leukemia (CML) is a malignant hematological disorder characterized by the formation, in the blood and bone marrow, of an excessive number of white blood cells, some of which are immature. Currently, the main treatment of CML is based on tyrosine-kinase inhibitors, such as Imatinib, the first approved drug of this class of compounds and marketed as Gleevec ®. However, this treatment results, in some patients, to the emergence of resistance, which complicates the treatment and requires a wide range of active molecules to circumvent resistance mechanisms. Therefore, the search for new bioactive molecules featuring new mode of action still remains a challenging.In this thesis project, we were interested in the design and discovery of new bioactive molecules in nucleoside series to circumvent resistance mechanisms in CML models, as well as in the development of new synthetic methods for the preparation of these targeted molecules. We first developed a clean and efficient procedure for the synthesis of new C- nucleoside analogues using iron catalysis. Then, several post-synthetic modifications were carried out, starting from halogenated nucleoside derivatives, to access highly functionalized C- nucleosides, as new analogues of thiophenefurin . We also developed a new procedure for the synthesis of O-glycosides using a cooperative effect of iron catalysis and ultrasound activation. This method has been applied for the synthesis of resveratrol O-glycosides. Finally, we developed an effecient and inexpensive method for anomeric sugar azidation. This method was applied for the synthesis of 1,2,3-triazolyl glycosides using a one-pot azidation-click procedure.

Orientador: Maria Aparecida Custódio Domingues / Resumo: Introdução: A Leucemia Mieloide Crônica (LMC) consiste em uma neoplasia hematopoiética maligna de células-tronco, caracterizada pela aquisição do gene de fusão BCR-ABL1 associado à translocação [t(9;22) (q34;q11)]. O início é insidioso com progressão lenta seguida por uma fase acelerada, que culmina na crise blástica. Os nichos da medula óssea estão relacionados com o microambiente tumoral, afetando a sobrevivência e a proliferação das células-tronco leucêmicas. Objetivos: Análise da quantidade e distribuição de células-tronco hematopoiéticas nos diferentes nichos na LMC em diferentes fases e correlação destes achados com a distribuição de galectina-3 nas fases acelerada e blástica. Material e métodos: Revisão clínico-morfológica de 20 pacientes na fase crônica da LMC, 1 paciente na fase acelerada e 1 paciente na crise blástica. Análise imunofenotípica (CD34, CD31, CD44, CD117 e galectina-3) em Tissue Microarrays para avaliação dos diferentes nichos e sua correlação com a matriz proteica. Resultados: Observou-se aumento na expressão de todos os marcadores na fase crônica quando comparados ao controle. Na fase acelerada há aumento na expressão de CD44 e galectina-3 quando comparado ao controle enquanto que na crise blástica há aumento na expressão de CD44 e CD117. Conclusão: A LMC constitui uma neoplasia mieloproliferativa em que o remodelamento dos nichos malignos favorece a manutenção das células-tronco leucêmicas. O presente estudo demonstrou elevação em todos os marcadores... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Chronic Myeloid Leukemia (CML) is a malignant hematopoietic stem cell neoplasm, characterized by the acquisition of the translocation-associated BCR-ABL1 gene [t(9;22)(q34;q11)]. The onset is insidious with the slow progression followed by an accelerated phase, culminating in the blast crisis. The bone marrow niches are related to the tumor microenvironment, the survival and proliferation of the leukemic stem cells. Objectives: To analyze the amount and distribution of hematopoietic stem cells in different niches in CML in different phases and correlate these findings with the galectin-3 distribution in the accelerated and blastic phases. Material and methods: Clinical-morphological review of 20 patients in CML chronic phase, 1 patient in the accelerated phase and 1 patient in the blast crisis. Immunophenotypic analysis (CD34, CD31, CD44 and galectin-3) in Tissue Microarrays to evaluate the different niches and correlation with the protein matrix. Results: We observed the presence of all markers in the chronic phase when compared to the control. In the accelerated phase there is an increase in expression of CD44 and galectin-3, when compared to control while in blast crisis there is an increase in expression of CD44 and CD117. Conclusion: CML is a myeloproliferative neoplasm in which remodeling of malignant niches favors the maintenance of leukemic stem cells. The present study demonstrated an increase in expression of all immunohistochemical markers at differen... (Complete abstract click electronic access below) / Mestre

<p>The objective of this master thesis was to develop an analytical method for the quantification of the cancer drug Imatinib and its main metabolite CGP74588 in plasma. Imatinib is used in the treatment of chronic myeloid leukemia and gastrointestinal stroma tumors. A quantitative analytical method was developed where reversed-phase columns with different stationary phases were studied and the sensitivity was tested with both UV detectors and a mass spectrometric detection. Since the substances were measured in plasma a solid-phase extraction was developed to purify the samples before analysis. The column chosen for the separation was the Max-RP C12 column (100 x 3 mm, 4 μm particle size) manufactured by Phenomenex with a gradient mobile phase with 1% formic acid in methanol and water. The gradient was as follows; 0 min 15:85, 7 min 60:40, 9 min 60:40 with a total runtime of 13.5 min. The internal standard chosen was Opipramol. Mass spectrometric detection using a sonic spray ionization interface in positive mode proved to be about as sensitive as UV detection at 261 nm. The generated (M+H+)+ ions were isolated and fragmented with the use of three mass spectrometric methods; one for Imatinib (transition 494 —› 394), one for CGP74588 (transition 480 —› 394) and one for Opipramol (transition 364 —› 171). For the purification of the plasma samples an Oasis HLB solid-phase extraction cartridge was selected and the recoveries were close to 100%.</p><p>The developed method was partially validated and showed coefficients of variation (CV) for intra-and inter-day precision between 0.4 and 5.4% with UV detection. The validation results for the mass spectrometer were inconclusive.</p>

The objective of this master thesis was to develop an analytical method for the quantification of the cancer drug Imatinib and its main metabolite CGP74588 in plasma. Imatinib is used in the treatment of chronic myeloid leukemia and gastrointestinal stroma tumors. A quantitative analytical method was developed where reversed-phase columns with different stationary phases were studied and the sensitivity was tested with both UV detectors and a mass spectrometric detection. Since the substances were measured in plasma a solid-phase extraction was developed to purify the samples before analysis. The column chosen for the separation was the Max-RP C12 column (100 x 3 mm, 4 μm particle size) manufactured by Phenomenex with a gradient mobile phase with 1% formic acid in methanol and water. The gradient was as follows; 0 min 15:85, 7 min 60:40, 9 min 60:40 with a total runtime of 13.5 min. The internal standard chosen was Opipramol. Mass spectrometric detection using a sonic spray ionization interface in positive mode proved to be about as sensitive as UV detection at 261 nm. The generated (M+H+)+ ions were isolated and fragmented with the use of three mass spectrometric methods; one for Imatinib (transition 494 —› 394), one for CGP74588 (transition 480 —› 394) and one for Opipramol (transition 364 —› 171). For the purification of the plasma samples an Oasis HLB solid-phase extraction cartridge was selected and the recoveries were close to 100%. The developed method was partially validated and showed coefficients of variation (CV) for intra-and inter-day precision between 0.4 and 5.4% with UV detection. The validation results for the mass spectrometer were inconclusive.

Chronic Myeloid Leukemia is a kind of blood cancer with around 1 incidence per 100 000 persons/year. After the development of an effective treatment, imatinib, in the late 1990:s, the survival percentage has increased drastically. The high survival has turned the attention to different kinds of treatment responses, which in turn are good prognostic factors to future health status. In this thesis, the focus is on whether or not the patient has achieved a so called major molecular response after 12 month, or not. More precisely, the aim is to find prognostic factors to the 12 month response. In order to find prognostic factors for this binary response variable, a multivariate logistic regression analysis is conducted, with the goal of finding a parsimonious logistic model that describes the data. The analysis is done from a merged dataset from three earlier studies. The prognostic factors in the final model are treatment, 3 month response, and enlarged spleen. However, the residual analysis indicates that the model is incomplete, implying that further research needs to be done.

In this study, mechanisms of resistance to Imatinib-induced apoptosis in human K562 and Meg-1 chronic myeloid leukemia (CML) cells were examined. Continuous exposure of cells to step-wise increasing concentrations of Imatinib resulted in the selection of 0.2 and 1 &amp / #956 / M imatinib resistant cells. Measurement of endogenous ceramide levels showed that treatment with Imatinib increased the generation of C18-ceramide significantly, which is mainly synthesized by the human longevity assurance gene 1 (hLASS1), in sensitive, but not in resistant cells. Mechanistically, analysis of mRNA and enzyme activity levels of hLASS1 in the absence or presence of Imatinib did not show any significant differences in the resistant cells when compared to its sensitive counterparts, suggesting that accumulation and/or metabolism, but not the synthesis of ceramide, might be altered in resistant cells. iv Indeed, further studies demonstrated that expression levels, and enzyme activity of sphingosine kinase-1 (SK-1), increased significantly in resistant K562 or Meg-1 cells. The expression levels of glucosyl ceramide synthase (GCS) also increased in resistant cells, comparing to the sensitive counterparts, which indicates conversion of pro-apoptotic ceramide to glucosyl ceramide. Expression analyses of BCR-ABL gene demonstrated that expression levels of BCR-ABL gene increased gradually as the cells acquired the resistance. However, Nucleotide sequence analyses of ABL kinase gene revealed that there was no mutation in Imatinib binding region of the gene in resistant cells. There was also an increase in expression levels of MDR1 gene in resistant cells, which transport the toxic substances outside of cells. In conclusion, these data show, for the first time, a role for endogenous ceramide synthesis via hLASS1 in Imatinib-induced apoptosis, and those alterations of the balance between the levels of ceramide and S1P. Mainly the overexpression of SK-1 seems to result in resistance to Imatinib in K562 cells. The cellular resistance may also result from conversion of ceramide to glucosyl ceramide, from overexpression of BCR-ABL and MDR1 genes but not due to mutations in Imatinib binding site of ABL kinase.

Imatinib mesylate is indicated for the treatment of chronic myeloid leukemia (CML) and unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). By the application of this anticancer drug, problems occurs in terms of stability and activity. Computer assisted design (CAD) works showed that the modification of the B and C part molecule can increase the effectivity of the drug. The new derivatives of the drug will be obtained to change some part of the B and C segments. The total synthesis of a new imatinib mesylate will be done and the activity tests are going to be determined in collaboration with other groups.

For robots to operate in human environments they must be able to make their own maps because it is unrealistic to expect a user to enter a map into the robot’s memory; existing floorplans are often incorrect; and human environments tend to change. Traditionally robots have used sonar, infra-red or laser range finders to perform the mapping task. Digital cameras have become very cheap in recent years and they have opened up new possibilities as a sensor for robot perception. Any robot that must interact with humans can reasonably be expected to have a camera for tasks such as face recognition, so it makes sense to also use the camera for navigation. Cameras have advantages over other sensors such as colour information (not available with any other sensor), better immunity to noise (compared to sonar), and not being restricted to operating in a plane (like laser range finders). However, there are disadvantages too, with the principal one being the effect of perspective. This research investigated ways to use a single colour camera as a range sensor to guide an autonomous robot and allow it to build a map of its environment, a process referred to as Simultaneous Localization and Mapping (SLAM). An experimental system was built using a robot controlled via a wireless network connection. Using the on-board camera as the only sensor, the robot successfully explored and mapped indoor office environments. The quality of the resulting maps is comparable to those that have been reported in the literature for sonar or infra-red sensors. Although the maps are not as accurate as ones created with a laser range finder, the solution using a camera is significantly cheaper and is more appropriate for toys and early domestic robots.