Submitted by Ingritt Moreira (ingritt@gmail.com) on 2019-01-21T20:58:31Z No. of bitstreams: 2 Tese INGRITT CAROLINE MOREIRA.pdf: 2137024 bytes, checksum: 63efdff4c7afd9eeb4db6d7a1a0af110 (MD5) Carta Comprovante Versão Final Tese Ingritt.jpg: 150492 bytes, checksum: 9562c1ad3497c4bc78d70963e45afa55 (MD5) / Approved for entry into archive by Eunice Nunes (eunicenunes6@gmail.com) on 2019-01-22T14:04:13Z (GMT) No. of bitstreams: 2 Tese INGRITT CAROLINE MOREIRA.pdf: 2137024 bytes, checksum: 63efdff4c7afd9eeb4db6d7a1a0af110 (MD5) Carta Comprovante Versão Final Tese Ingritt.jpg: 150492 bytes, checksum: 9562c1ad3497c4bc78d70963e45afa55 (MD5) / Approved for entry into archive by Eunice Nunes (eunicenunes6@gmail.com) on 2019-01-22T14:17:14Z (GMT) No. of bitstreams: 2 Tese INGRITT CAROLINE MOREIRA.pdf: 2137024 bytes, checksum: 63efdff4c7afd9eeb4db6d7a1a0af110 (MD5) Carta Comprovante Versão Final Tese Ingritt.jpg: 150492 bytes, checksum: 9562c1ad3497c4bc78d70963e45afa55 (MD5) / Made available in DSpace on 2019-01-22T14:17:28Z (GMT). No. of bitstreams: 2 Tese INGRITT CAROLINE MOREIRA.pdf: 2137024 bytes, checksum: 63efdff4c7afd9eeb4db6d7a1a0af110 (MD5) Carta Comprovante Versão Final Tese Ingritt.jpg: 150492 bytes, checksum: 9562c1ad3497c4bc78d70963e45afa55 (MD5) Previous issue date: 2018-08-24 / Outra / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / This research focuses on the oxylipins with eighteen carbons, compound derived of polyunsaturated fatty acids, produced by twenty-two species of freshwater algae, one cyanobacteria and three species of plants, with emphasis on green microalgae from the Chlorophyta and Charophyta phylum, and also species of the Selenastraceae family (Chlorophyta, Chlorophyceae, Sphaeropleales). The aim was detected, identified and quantified oxylipins derived from linoleic and linolenic acids produced by microorganisms using High-Performance Liquid Chromatography coupled tandem Mass Spectrometry technique. It was used microalgae from the Culture Collection of Freshwater Microalgae (CCMA-UFSCar), species already classified by classic and / or molecular taxonomy, as well as the species of plants for comparative purposes. For the experiments, the material came from the end of stationary phase. Once the compounds were identified by these techniques, it was tested the possibility of using profiles as diacritical characteristics in a chemotaxonomic approach for formation of hierarchical clusters. The pharmacological potential of these compounds was discussed since they present antibiotic and anti-inflammatory activities. Other possible commercial applications were approached since microalgae revealed their potential value as natural sources of hydroxy fatty acids. No oxylipin was exclusively observed to determinated organism that could represents as species indicator. This condition limits the use of oxylipins derived from C18 PUFAs in the taxonomy of the Selenastraceae family, but even so, these compounds provide complementary information for organisms that may be useful in their identification. There was universality regarding the presence of oxylipins analysed in all the taxonomic groups studied. The strains belonging to Chlorophyta division showed the highest total concentrations of oxylipins. Charophyta algae have a concentration of oxylipins dozens of times lower than Chlorophyta, and similar to concentrations found in plants, which may be related to the evolutionary proximity among plants and Charophyta. / Esta pesquisa tem como foco oxilipinas com dezoito carbonos, substâncias derivadas de ácidos graxos poli-insaturados, produzidas por vinte e duas cepas de algas de água doce, uma cianobactéria e três espécies de plantas, com ênfase em microalgas verdes das divisões Chlorophyta e Charophyta, e também em espécies da família Selenastraceae (Chlorophyta, Chlorophyceae, Sphaeropleales). O objetivo principal foi detectar, identificar e quantificar as oxilipinas derivadas de ácidos linoléico e linolênico produzidas por esses organismos utilizando-se de técnicas de cromatografia líquida acoplada à espectrometria de massas. Utilizou-se cepas de microalgas da coleção de culturas do Laboratório de Ficologia da UFSCar, espécies já classificadas através da taxonomia clássica e/ou molecular, como também espécies de plantas para fins comparativos. Para os experimentos, a biomassa algal foi proveniente do final da fase estacionária. Uma vez identificados estes compostos pelas técnicas acima, testou-se a possibilidade de se utilizar estes perfis como características diacríticas em uma abordagem quimiotaxonômica para a formação de clusters hierárquicos. Também foi discutido o potencial farmacológico destes compostos por apresentarem atividades antibióticas e anti-inflamatórias. Outras possíveis aplicações comerciais também foram abordadas uma vez que as microalgas revelaram seu potencial valor como reservas naturais de hidroxi-ácidos. Não foi observada qualquer oxilipina exclusiva para determinado organismo que pudesse servir como um indicador de espécie. Esta condição limita a utilização de oxilipinas derivadas de PUFAs C18 na taxonomia da família Selenastraceae. Porém, mesmo assim, a quantidade e proporções das oxilipinas nos diversos perfis permitem que estes compostos forneçam informações complementares sobre os organismos que podem ser uteis na sua identificação. Houve universalidade quanto à presença das oxilipinas analisadas em todos os grupos taxonômicos estudados. As cepas pertencentes à divisão Chlorophyta apresentaram as maiores concentrações totais de oxilipinas. As algas Charophyta apresentaram concentrações de oxilipinas dezenas de vezes menor que Chlorophyta e semelhantes às concentrações encontradas em plantas, fato que pode estar relacionado à proximidade evolutiva entre plantas e Charophyta. / CNPQ: 141267/2014-3 / FAPESP: 2011/50054-4

Doctor of Philosophy / Department of Chemistry / Paul Edward Smith / The activity and function of many macromolecules in cellular environments are coupled with the binding of ions such as alkaline earth metal ions and poly oxo anions. These ions are involved in the regulation of important processes such as protein crystallization, nucleic acid and protein stability, enzyme activity, and many others. The exact mechanism of ion specificity is still elusive. In principle, computer simulations can be used to help provide a molecular level understanding of the dynamics of hydrated ions and their interactions with the biomolecules. However, most of the force fields available today often fail to accurately reproduce the properties of ions in aqueous environments. Here we develop a classical non polarizable force field for aqueous alkaline earth metal halides (MX₂) where M = Mg²⁺, Ca²⁺, Sr²⁺, Ba²⁺ and X = Cl⁻, Br⁻, I⁻, and for some biologically important oxo anions which are NO₃⁻, ClO₄⁻, H₂PO₄⁻ and SO₄²⁻, for use in biomolecular simulations. The new force field parameters are developed to reproduce the experimental Kirkwood-Buff integrals. The Kirkwood-Buff integrals can be used to quantify the affinity between molecular species in solution. This helps to capture the fine balance between the interactions of ions and water. Since this new force field can reproduce the experimental Kirkwood-Buff integrals for most concentrations of the respective salts, they are capable of reproduce the experimental activity derivatives, partial molar volumes, and excess coordination numbers. Use of these new models in MD simulations also leads to reasonable diffusion constants and dielectric decrements. Attempts to develop force field parameters for CO₃²⁻, HPO₄²⁻ and PO₄³⁻ ions were unsuccessful due to an excessive aggregation behavior in the simulations. Therefore, in an effort to overcome this aggregation behavior in the simulations, we have investigated scaling the anion to water interaction strength, and also the possibility of using a high frequency permittivity in the simulations. The strategy of increasing relative permittivity of the system to mimic electronic screening effects are particularly promising for decreasing the excessive ion clustering observed in the MD simulations.

<p>Date: 6/16/2008</p><p>Institution: School of Sustainable Development of Society and Technology, Mälardalen University, Västerås (Sweden)</p><p>Authors:</p><p>Brüning, Andrea</p><p>830111</p><p>Västerås</p><p>Curtolo,Anna</p><p>820517</p><p>Västerås</p><p>Tutor: Tobias Eltebrandt</p><p>Title: A Study of Switch Pac: what would be the efficient ways for Switch Pac to increase potential demand and capitalize on green attitudes and behavior in the Swedish market?</p><p>Problem: What would be the efficient ways for Switch Pac to increase potential demand and capitalize on green attitudes and behavior in the Swedish market?</p><p>Purpose: The aim of our project is to see the potential of Switch Pac’s oxo-biodegradable plastic bags on the Swedish market by capitalize on green attitudes and behaviour.</p><p>Method: The report is based on primary data collected through questionnaires (end consumer/ B2B customers). For the investigation of Switch Pac’s macro- and microenvironment secondary data was used (books, journals, newspaper and the Internet)</p><p>Conceptual Framework: The conceptual framework consists of certain models to investigate the following topics:</p><p>Consumer behavior</p><p>AIDA-Model</p><p>STP-Model</p><p>Switch Pac´s business environment</p><p>PESTEL</p><p>Conclusion/ Recommendations: In our conclusion based on our frameworks PESTEL, AIDA and STP we concluded that peoples’ awareness regarding environmental friendly plastic bags are not very high based on our questionnaire. The efficient ways for Switch Pac to increase potential demand is to target the customer in the age range from 20 – 49 years and cooperate with supermarkets and (department) stores. Furthermore, Switch Pac needs to position its products in the consumers mind through create brand awareness by using certain elements of the marketing mix model.</p>

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(農学) / 甲第19046号 / 農博第2124号 / 新制||農||1032 / 31997 / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 小川 順, 教授 加納 健司, 教授 植田 充美 / 学位規則第4条第1項該当

Date: 6/16/2008 Institution: School of Sustainable Development of Society and Technology, Mälardalen University, Västerås (Sweden) Authors: Brüning, Andrea 830111 Västerås Curtolo,Anna 820517 Västerås Tutor: Tobias Eltebrandt Title: A Study of Switch Pac: what would be the efficient ways for Switch Pac to increase potential demand and capitalize on green attitudes and behavior in the Swedish market? Problem: What would be the efficient ways for Switch Pac to increase potential demand and capitalize on green attitudes and behavior in the Swedish market? Purpose: The aim of our project is to see the potential of Switch Pac’s oxo-biodegradable plastic bags on the Swedish market by capitalize on green attitudes and behaviour. Method: The report is based on primary data collected through questionnaires (end consumer/ B2B customers). For the investigation of Switch Pac’s macro- and microenvironment secondary data was used (books, journals, newspaper and the Internet) Conceptual Framework: The conceptual framework consists of certain models to investigate the following topics: Consumer behavior AIDA-Model STP-Model Switch Pac´s business environment PESTEL Conclusion/ Recommendations: In our conclusion based on our frameworks PESTEL, AIDA and STP we concluded that peoples’ awareness regarding environmental friendly plastic bags are not very high based on our questionnaire. The efficient ways for Switch Pac to increase potential demand is to target the customer in the age range from 20 – 49 years and cooperate with supermarkets and (department) stores. Furthermore, Switch Pac needs to position its products in the consumers mind through create brand awareness by using certain elements of the marketing mix model.

Fifty percent of solid cancers are treated with radiation therapy (RT). The dose used in RT is adjusted to the most sensitive individuals so that not more than 5% of the patients will have severe adverse healthy tissue effects. As a consequence, the majority of the patients will receive a suboptimal dose, as they would have tolerated a higher total dose and received a better tumor control. Thus, if RT could be individualized based on radiation sensitivity (RS), more patients would be cured and the most severe adverse reactions could be avoided. At present the mechanisms behind RS are not known. The long term aim of this thesis was to develop diagnostic tools to assess the individual RS of breast cancer patients and to better understand the mechanisms behind the RS and radiation effects after low dose exposures. The approach was based on the hypothesis that biomarkers of individual RS, in terms of acute adverse skin reactions after breast cancer RT, can be found in whole blood that has been stressed by low doses of ionizing radiation (IR).  To reach this goal two different approaches to identify biomarkers of RS have been investigated. A protocol for the analysis of differential protein expression in response to low dose in vitro irradiated whole blood was developed (paper I). This protocol was then used to investigate the proteomic profile of radiation sensitive and normo-sensitive patients, using isotope-coded protein labeled proteomics (ICPL). The results from the ICPL study (paper III) show that the two patient groups have different protein expression profiles both at the basal level and after IR. In paper II the potential biomarker 8-oxo-dG was investigated in serum after IR. The relative levels of IR induced 8-oxo-dG from radiation sensitive patients differ significantly from normo-sensitive patients. This indicates that the sensitive patients differ in their cellular response to IR and that 8-oxo-dG is a potential biomarker for RS. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.</p>

<p>Doktorska disertacija razmatra solubilizaciju holesterola pomoću okso derivata žučnih kiselina, upoređuje okso derivate žučnih&nbsp; kiselina&nbsp; sa hidroksi-derivatima istih u solubilizaciji holesterola i ispituje uticaj okso derivata na vijabilnost ćelijske membrane.&nbsp; Takođe, ispituje pKa vrednost različitih okso-derivata žučnih kiselina sa ciljem da se odredi kiselinska konstanta ovih slabih organskih kiselina. Cilj određivanja pKa vrednosti jeste determinacija rastvorljivosti žučnih kiselina. Kada se primenjuju oralno u raznim farmaceutsko-tehnolo&scaron;kim formulacijama, one se primenjuju u obliku soli, koje su rastvorne u vodi. Međutim, u kiseloj sredini želuca može doći do taloženja žučne kiseline i do daljeg sprečavanja delovanja soli žučne kiseline kao solubilizatora određenih farmacutski aktivnih supstanci. Doktorska disertacija ispituje i kritičnu micelarnu koncentraciju me&scaron;ovitih micela natrijumovih soli 3 žučne kiseline (holne, deoksiholne i 7-oksodeoksiholne kiseline) i natrijum-dodecil-sulfata u različitim molskim udelima na temperaturama od 0 do 50&deg;C pomoću spektrofluorifotometra pirenskom metodom.</p> / <p>The PhD thesis discusses solubilization of cholesterol by using oxo derivatives of bile acids and compares it&nbsp; with the hydroxy-derivatives of the same in the solubilization of cholesterol, and examines the impact of the oxo derivatives to the viability of the cell membrane. Also, the pKa value of different&nbsp; tested oxo-derivatives of&nbsp; bile acids is determined. The aim of determining the pKa values is to determine the solubility of bile acids. When administered orally in various pharmaceutical-technological formulations, they are applied in the form of salts, that are soluble in water. However, the acidic medium of the stomach may cause precipitation of a bile salt and further prevent the action of bile acid salts as a solubilizers of specific pharmaceutically active substances. The PhD&nbsp;&nbsp; thesis examined the the critical micelle concentration of the mixed micelles of sodium salt of 3 bile acid (cholic, deoxycholic, and 7-oksodeoksiholne acid) and sodium dodecyl sulphate at various temperatures, the mole fractions ranging from 0 to 50 &deg;C using the method of spectrofluoriphotometry by pirene as a probe molecule.</p>

In der vorliegenden Arbeit wird die Synthese von Bismut- und Neodymsilanolaten beschrieben. Durch partielle Hydrolyse ausgewählter Bismutsilanolate konnten neue Bismut-oxo-cluster synthetisiert werden. Die Darstellung von heterometallischen Bismut-Neodym-oxo-clustern ausgehend von Bismut- und Neodymsilanolaten wurde untersucht, ergaben jedoch keine definierten Cluster. Das Thermolyseverhalten der Silanolate und Oxo-cluster wurde beschrieben und die erhaltenen Zersetzungsprodukte charakterisiert. Weiterhin wurden in dieser Arbeit Koordinationspolymere von Bismuthalogeniden mit Phosphonsäureestern synthetisiert. Die so erhaltenen ein- und zweidimensionalen Koordinationspolymere wurde in Hinsicht auf ihr Verhalten unter thermischer Belastung untersucht. Das Hauptaugenmerk der vorliegenden Arbeit lag auf der strukturellen Charakterisierung der synthetisierten Verbindungen insbesondere durch Einkristallröntgenstrukturanalysen. Weiter Methoden wie NMR-Spektroskopie in Lösung und im Festkörper, DTA-TG, IR-Spektroskopie, Pulverröntgendiffraktometrie und Elektronenmikroskopie wurden zur Charakterisierung zur Hilfe genommen. / The present thesis deals with the synthesis of bismuth- and neodym silanolates. The partial hydrolysis of selected bismuth silanolates gave a series of novel bismuth-oxo-clusters. The synthesis of heterometallic bismuth-neodymium-oxo-clusters starting from bismuth- and neodymium silanolates has been assayed but did not give defined clusters. In addition the behavior of the silanolates and oxo-clusters towards thermal decomposition has been studied and the decomposition products have been characterized. In the second part of this work the synthesis of coordination polymers starting from bismuth halides and phosphonic acid esters is presented. Several one- and two-dimensional coordination polymers have been synthesized, structurally characterized and analyzed with respect to their thermally induced decomposition. The main focus of this work was to characterize the novel compounds in particular by single crystal X-ray diffraction analysis. Aditionally, NMR spectroscopy in solution and the solid state, DTA-TG, IR spectroscopy, powder X-ray diffraction and SEM-EDX have been used for the characterization of the products.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第19046号 / 農博第2124号 / 新制||農||1032(附属図書館) / 学位論文||H27||N4928(農学部図書室) / 31997 / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 小川 順, 教授 加納 健司, 教授 植田 充美 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

Genomic alterations may initiate cancer development as the consequence of endogenous or exogenous DNA damaging factors. Defects in DNA repair mechanisms may also facilitate cancer progression as well as accumulation of mutations which favor cancer cell survival. However, DNA repair pathways in cancer cells can be considered as their Achilles heel which are possible targets in order to compromise their survival. For instance, it has been demonstrated recently that inhibition of a protein called MTH1 via RNA interference (RNAi) or chemical inhibitors can stop tumor growth and triggers cell death by increasing the load of oxidative DNA damage. MTH1 is a hydrolase which converts 8-oxo-dGTP into 8-oxo-dGMP in order to prevent incorporation of oxidatively damaged nucleotides into DNA. In addition, DNA glycosylases which recognize and remove mismatched or damaged nucleotide pairs in DNA can also participate in repair of 8-oxo-dG, such as MUTYH repairing A:8-oxo-dG pair. The goal of the current study was to investigate the importance of MUTYH activity upon MTH1 depletion. The current study tried to answer whether simultaneous knock-down of MTH1 and MUTYH sensitizes cancer cells to oxidative stress and increases cell death. Both enzymes were simultaneously depleted in T cell acute lymphoblastic leukemia cells using RNAi. Then, we analyzed the efficiency of gene and protein knock-down by quantitative real-time-PCR and western blotting, respectively. Induction of cell death was also assessed by flow cytometric analysis of cell cycle. Afterwards, the effect of the treatments on DNA repair pathways was studied by analysis of gene expression of several DNA glycosylases and DNA polymerases using qRT-PCR. The results showed that concurrent depletion of both enzymes led to synergistic induction of cell death. Down-regulation of NEIL1 DNA glycosylase as well as POLQ and POLH DNA polymerases mRNAs adapted their DNA repair pathways to cope with induced damages under these conditions. Finally, the results of this study suggest that dual suppression of MTH1 and MUTYH may provide a new approach to reduce survival of T cell ALL.