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Ritter, Michaela. "Cytochrom bc1 eine Studie zum Elektronentransfer der bc1-Komplexe des Bakteriums Paracoccus denitrificans und der Hefe Saccharomyces cerevisiae mittels elektrochemisch induzierter Differenzspektroskopie /." [S.l. : s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=971616574.
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Baer, Kimberly Kay. "Protein Coevolution and Coadaptation in the Vertebrate bc1 Complex." Diss., CLICK HERE for online access, 2007. http://contentdm.lib.byu.edu/ETD/image/etd1994.pdf.
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Vallières, Cindy. "Agents antimicrobiens ciblant le complexe III de la chaîne respiratoire mitochondriale : caractérisation de nouveaux inhibiteurs et étude du développement des résistances." Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00840029.
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Des inhibiteurs du complexe bc1 de la chaîne respiratoire mitochondriale ont été développés comme agents antimicrobiens pour lutter contre des pathogènes de l'Homme et de plantes. Ces drogues ciblent les poches catalytiques Qo et Qi formées par le cytochrome b. La comparaison de séquences de cette protéine montre que les sites Qo et Qi sont bien conservés entre les organismes mais qu'il existe toutefois des variations qui pourraient expliquer leur différence de sensibilité aux drogues. A l'aide du modèle levure S. cerevisiae, nous avons étudié les déterminants de la résistance/sensibilité naturelle à deux antipaludiques se liant au site Qo de Plasmodium: l'atovaquone et RCQ06. Nous avons notamment montré que le résidu 275 joue un rôle clé dans ce phénomène. Une approche similaire est actuellement utilisée pour identifier les facteurs de la sensibilité différentielle à deux drogues ciblant le site Qi des oomycètes. Malheureusement, des cas de résistance acquise à ces antimicrobiens ont été rapportés et ont pour origine des mutations dans le cytochrome b. De ce fait, de nouvelles molécules sont requises pour court-circuiter ces résistances. Au cours de ma thèse, nous avons mis au point un test qui permet de cribler des molécules capables d'inhiber la fonction respiratoire. Nous avons ainsi pu identifier un nouvel inhibiteur du complexe bc1 : D12. Nous avons ensuite déterminé le mode de liaison de cette molécule ainsi que celui d'un composé capable d'inhiber la prolifération de Plasmodium, HDQ, grâce à une collection de mutants des poches catalytiques. HDQ s'est avéré être un inhibiteur du site Qi. Il pourrait être utilisé avec un inhibiteur du site Qo afin de limiter l'apparition de mutations de résistance. D12 est un inhibiteur du site Qo qui est capable notamment de court-circuiter la mutation de résistance à des fongicides du site Qo G143A. Cette dernière a été trouvée chez de nombreux phytopathogènes, mais n'est cependant pas apparue chez des champignons possédant un intron immédiatement après le codon codant pour la glycine 143. En utilisant la levure, nous avons montré que la mutation empêche l'épissage de l'intron en altérant la structure exon/intron. Nous avons également identifié des mécanismes de " by-pass " qui permettent de restaurer la fonction respiratoire du mutant et qui pourraient apparaître chez les pathogènes. Les mutants créés au cours de ma thèse pourront aider à identifier, concevoir et caractériser de nouveaux antimicrobiens et à étudier l'apparition de mutations de résistance.
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Gordon, James Alexander. "Design and synthesis of novel cytochrome bc1 inhibitors for the treatment of toxoplasmosis." Thesis, University of Leeds, 2018. http://etheses.whiterose.ac.uk/22638/.
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Toxoplasmosis is a highly prolific and neglected disease, and current treatments fail to adequately address the challenges it presents. As such development of new more efficacious treatments, tailored to the complex nature of the infection, is required. The causative parasite Toxoplasma gondii is a resilient and resourceful organism, adept at invasion, avoidance and survival within its host. The cytochrome bc1 complex has been proven to be a validated target for the treatment of a number of apicomplexan parasitic diseases, including both malaria and toxoplasmosis. Recent work has also identified overexpression of this complex within a strain expressing the difficult to treat bradyzoite phenotype, which supported by findings that treatment with known bc1 inhibitor atovaquone shows reduction in cyst burden, suggests this may be a particularly promising target for an effective systemic parasite treatment. Within discusses the design, synthesis and analysis of a number of cytochrome bc1 inhibitors across several novel scaffolds. Designs focused on improving deficiencies identified in previous inhibitors. Successful synthesis of a number of these designs and biological evaluation identified several submicromolar examples. After preliminary ADMET evaluation of the synthesised scaffolds the tetrahydroquinolone scaffold was selected for further development. Optimisation of the synthesis to the tetrahydroquinolones (THQ's) resulted in access to a library of analogues. From these analogues compound 169 was selected for further analysis, characterisation and ultimately progressed to early stage in vivo assays, in which it demonstrated exceptional potency and efficacy.
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Xue, Vincent. "Modeling and designing Bc1-2 family protein interactions using high-throughput interaction data." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/120446.
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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2018.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 153-164).
Protein-protein interactions (PPIs) play a major role in cellular function, mediating signal processing and regulating enzymatic activity. Understanding how proteins interact is essential for predicting new binding partners and engineering new functions. Mutational analysis is one way to study the determinants of protein interaction. Traditionally, the biophysical study of protein interactions has been limited by the number of mutants that could be made and analyzed, but advances in high-throughput sequencing have enabled rapid assessment of thousands of variants. The Keating lab has developed an experimental protocol that can rank peptides based on their binding affinity for a designated receptor. This technique, called SORTCERY, takes advantage of cell sorting and deep-sequencing technologies to provide more binding data at a higher resolution than has previously been achievable. New computational methods are needed to process and analyze the high-throughput datasets. In this thesis, I show how experimental data from SORTCERY experiments can be processed, modeled, and used to design novel peptides with select specificity characteristics. I describe the computational pipeline that I developed to curate the data and regression models that I constructed from the data to relate protein sequence to binding. I applied models trained on experimental data sets to study the peptide-binding specificity landscape of the Bc1-xL, Mc1-1, and Bf1-1 anti-apoptotic proteins, and I designed novel peptides that selectively bind tightly to only one of these receptors, or to a pre-specified combination of receptors. My thesis illustrates how data-driven models combined with high-throughput binding assays provide new opportunities for rational design.
by Vincent Xue.
Ph. D.
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Pacorel, Benedicte. "Targeting the Hemoglobin Degradation Pathway and the Cytochrome bc1 Complex of Plasmodium Falciparum Malaria." Thesis, University of Liverpool, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.507704.
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Kehrein, Kirsten. "Organization of mitochondrial gene expression in yeast : Specific features of organellar protein synthesis." Doctoral thesis, Stockholms universitet, Institutionen för biokemi och biofysik, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-107568.
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Mitochondria contain their own genetic system, encoding key subunits of the oxidative phosphorylation system. These subunits are expressed by an organelle-specific gene expression machinery. This work revealed a number of fundamental aspects of mitochondrial gene expression and provides evidence that this process is organized in a unique and organelle-specific manner which likely evolved to optimize protein synthesis and assembly in mitochondria. Most importantly, improving the experimental handling of ribosomes we could show that mitochondrial ribosomes are organized in large assemblies that we termed MIOREX complexes. Ribosomes present in these complexes organize gene expression by recruiting multiple factors required for post-transcriptional steps. In addition, we could reveal mechanisms by which ribosome-interactor complexes modulate and coordinate the expression and assembly of the respiratory chain subunits. For example we showed that the Cbp3-Cbp6 complex binds to the ribosome in proximity to the tunnel exit to coordinate synthesis and assembly of cytochrome b. This location perfectly positions Cbp3-Cbp6 for direct binding to newly synthesized cytochrome b and permits Cbp3-Cbp6 to establish a feedback loop that allows modulation of cytochrome b synthesis in response to assembly efficiency. Likewise the interaction of the membrane-anchor proteins Mba1 and Mdm38 with the tunnel exit region enables them to participate in the translation of the two intron-encoding genes COX1 and COB in addition to their role in membrane insertion. In summary, work presented in this thesis shows that mitochondrial gene expression is a highly organized and regulated process. The concepts and technical innovations will facilitate the elucidation of many additional and important aspects and therefore contribute to the general understanding of how proteins are synthesized in mitochondria.At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.
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Davoudi, Cedric-Farhad [Verfasser]. "Regulation and assembly of the cytochrome bc1-aa3 supercomplex in Corynebacterium glutamicum / Cedric-Farhad Davoudi." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2019. http://d-nb.info/1189416115/34.
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ACERO, LUIS FERNANDO JR. "T-CELL HOMEOSTASIS AND THE ROLE OF THE PRO-APOPTOTIC Bc1-2 FAMILY MEMBER Bim." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1126725924.
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Cowley, Robin Neil. "The synthesis and development of novel quinolone antimalarials targeting the bc1 protein complex of Plasmodium falciparum." Thesis, University of Liverpool, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.569047.
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In recent years investigation of the biological mode of action of the antimalarial compound atovaquone has validated the Plasmodium falciparum bC1 protein complex as a target for the development of novel antimalarials. This project is concerned with the design, synthesis and development of quinolone based antimalarial compounds targeting the Qo site of the Plasmodium falciparum bC1 protein complex. -......, ..•. : - A small array of quinolone-based compounds, substituted at the 3 and 7 positions, has been developed utilising the Gould-Jacobs methodology. The synthesised compounds express activity as low as 0.46 nM versus Plasmodium falciparum malaria parasites in vitro. Activity at the bC1 protein complex has been confirmed and selectivity for the parasite protein over the mammalian equivalent has been demonstrated. Poor solubility has been highlighted as a potential issue; however steps have been taken towards the ,/ development of carbamate prod rugs with encouraging results. Docking studies performed in silico, using the crystallised structure of yeast bC1 protein, demonstrate a key role for residues His181 and Glu272 in the recognition of high potency inhibitors and have aided in the rationalisation of the observed biological activities. The orientation of the quinolone group in the active site and interaction of the inhibitors with the hydrophobic channel leading to the active site have both been shown to be of significance for biological potency. Computer lead design of a new chemotype has resulted in the development of a second array of quinolone based compounds synthesised by a divergent method based on the Huisqen 1,3-dipolar cycloaddition. Docking studies predicted the synthesised compounds to be potent inhibitors of Plasmodium falciparum bC1. However, in vitro results for the array proved disappointing, an outcome attributed to a failure to account for membrane permeability and the physical location of the targeted bC1 protein complex.
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Largueze, Jean-Baptiste. "Modèles membranaires biomimétiques pour l'incorporation du cytochrome bc1 des chaînes de transfert d'électrons photosynthétiques de Rhodobacter sphaeroides." Compiègne, 2011. http://www.theses.fr/2011COMP1927.
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La formation de bicouches lipidiques supportées est réalisée sur la surface des pores d’une électrode d’alumine nanoporeuse. Trois types de modèles membranaires ont été étudiés : une membrane reposant directement sur l’alumine et deux modèles découplés du support, soit par un assemblage biotine/streptavidine, soit par des polymères de PEG2000. La formation au sein des pores des différents modèles passe par l’utilisation de liposomes et une fusion déclenchée par l’emploi d’un agent fusogène. La caractérisation de la membrane est alors suivie par la réduction électrochimique d’ubiquinone incorporée dans les liposomes. L’emploi du modèle supporté par PEG2000 dans l’électrode en tant que biocapteur potentiel est montré pour la détection de molécules membranotropes. Finalement, la reconstitution fonctionnelle du cytochrome bc1 de Rhodobacter sphaeroides dans les modèles supportés a été testéeThe realization of supported lipid bilayers was realized inside the pores of a nanoporous alumina electrode. Three kinds of model membranes were studied: an alumina supported bilayer and a biotine/streptavidin or a PEG2000 tethered bilayer. The bilayer formation inside the pores was accomplished by a PEG8000-triggered fusion of liposomes. The lipid bilayer characterization was then followed by electrochemical reduction of ubiquinone incorporated in the liposomes. The PEG2000 tethered model inside the nanoporous electrode was shown to behave as a biosensor for membranotropic molecules. At last, we tested the reconstitution of the Rhodobacter sphaeroides cytochrome bc1 inside the tethered model
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KANG-PARK, SUKMI. "Etude de la regulation de l'expression de genes hepatocytaires et biliaires dans la lignee cellulaire d'hepatome bc1." Paris 6, 1996. http://www.theses.fr/1996PA066594.
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Le foie presente lors de son developpement de multiples etapes de proliferation et de differenciation sous le controle de differents facteurs de croissances et d'hormones. Si les capacites de regulateur metabolique de l'insuline et desormais egalement d'agent mitogene sont reconnues, il n'en est pas de meme pour son potentiel d'agent de differenciation. Nous avons pu evaluer ce role au niveau de la differenciation hepatocytaire a partir d'une lignee cellulaire originale d'hepatome humain bc1 c. Guguen-guillouzo, inserm u. 49, qui acquiert spontanement un phenotype hepatocytaire au terme de 3 semaines de culture a confluence. Ceci se traduit par une augmentation du taux d'arnm de marqueurs hepatocytaires tels que l'albumine et la transferrine, ainsi que par la secretion accrue de ces proteines dans le milieu de culture. Un traitement chronique par l'insuline (1 m) accelere nettement le processus de differenciation des cellules bc1. Nous avons montre que cet effet positif de l'insuline est parallele a: 1) une variation d'expression des 2 isoformes (+/- exon 11) du recepteur de l'insuline associee a une modification de son affinite de liaison pour l'hormone, 2) une augmentation de la sensibilite a l'insuline pour la synthese de glycogene. Ces resultats montrent pour la premiere fois, que l'insuline peut jouer un role important pour la differenciation hepatocytaire. Dans un deuxieme temps, nous avons utilise les proprietes de cellules progenitrices hepato-biliaires que presentent les cellules bc1 juste a confluecne, pour etudier la regulation du gene cftr (cystic fibrosis transmembrane conductance regulator). Les defauts de cftr, impliques dans la mucoviscidose, sont fortement suspectes d'induire secondairement des desordres au niveau des cellules biliaires ou la proteine est egalement exprimee. Nous avons mis en evidence une regulation post-transcriptionnelle inhibitrice de l'expression de l'arnm de cftr par le pma (phorbol myristate acetate), agent carcinogene connu pour activer a faible concentration la proteine kinase c (pkc). Parmi les 3 isoformes de pkc, alpha, epsilon, et zeta, exprimees dans les cellules bc1, seules alpha et epsilon repondent au pma par une induction de leur translocation membranaire activatrice. La down-regulation de ces isoformes activees presente une cinetique nettement plus lente pour la pkc epsilon, faisant suggerer que l'effet du pma a long-terme sur l'expression de cftr transite par cette isoforme
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Lange, Christian. "Wechselwirkungen des Cytochrom-bc1-Komplexes aus Saccharomyces cerevisiae mit seinen Substraten Cytochrom c und Ubichinon sowie mit Membranlipiden." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=964744287.
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Damadeu, Kouemo Laura. "Assessing the in vitro efficacy of in silico designed compounds targeting the malarial Qi site of cytochrome bc1." Diss., University of Pretoria, 2009. http://hdl.handle.net/2263/67749.
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Plasmodium falciparum is the causative agent of the most commonly fatal form of malaria in Africa with annual deaths of more than 300 000. The rapid development and spread of antimalarial drug resistance by the parasite have stimulated research into the development of new drug classes. Target-based drug discovery have been used as a prominent and efficient tool to identify lead drugs. Reports suggest that selectively inhibiting the parasite mitochondrial electron transport could be a potential treatment effective at multi-stages of the parasite life cycle. Inhibitors of cytochrome bc1 (Cyt bc1), an essential inner mitochondrial membrane protein that drives ATP synthesis in the mitochondria are claimed to be lethal to apicomplexan species including Plasmodium. The emergence of resistance to atovaquone, a Cyt bc1 complex Qo site inhibitor, casts doubt over the long-term efficacy of new drugs targeting these mitochondrial proteins. Many aspects of potential drugs must be investigated to assess the suitability of new emerging drugs targeting the mitochondrion.
In silico target-based drug design methods using Autodock vina were used to design compounds that would theoretically bind to and inhibit the Qi site of Cyt bc1 of the P. falciparum. The potential candidate compounds were selected from compounds defined by Gamo et al., (2010) and tested using in silico docking experiments. Homology models were developed and modified to improve their drug-likeness according to the Lipinski rule, QED parameters and synthesised by Wuxi App Tec. This study assessed the antiproliferative activity of six candidate compounds on P. falciparum parasites in vitro following in silico compound docking and drug likeness assessment. Initial in vitro screening data was obtained for the test compounds at 1 and 5 ?M over 96 h and full dose-response curves was performed for compounds showing >70% proliferation inhibition at 1 ?M against the 3D7 strain. Four of the test compounds, EE1, EE3, EE5 and EE7 gave IC50 values of 89 nM, 664 nM, 64 nM and 249 nM, respectively. The candidate compounds had a marginal >2-fold selectivity towards malaria parasites but did not show cross resistance, with resistance indices of >120. In conclusion, in silico docking using software programs could be utilised as a potential tool for rapidly identifying feasible target-based antimalarial compounds while avoiding high throughput screening. Other possible target sites on the mitochondrion can be used to design new chemotypes. All the designed compounds showed significant antimalarial activity against the asexual stages tested on 3D7 strain with a significant resistance index. However, these compounds showed minimal activity on the gametocyte stage. Finally, compound EE5 showed to be the most potent, more selective and with higher resistance index, hence this can be further optimised for preclinical studies.Dissertation (MSc)--University of Pretoria, 2018.
Pharmacology
MSc
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Lawrenson, Alexandre. "Antimalarial drug design : targeting the Plasmodium falciparum cytochrome bc1 complex through computational modelling, chemical synthesis and biological testing." Thesis, University of Liverpool, 2012. http://livrepository.liverpool.ac.uk/7719/.
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Malaria is a life-threatening disease which is responsible for roughly one million deaths annually. Previous successes in attempting to eradicate the disease have only been short lived, owing to the increased development of resistance in the parasite. There is a continued need for novel compounds which act at novel therapeutic targets, with the Plasmodium falciparum cytochrome bc1 complex (Pfbc1) representing one such target. Its inhibition halts the biochemical generation of ATP, thus resulting in parasite cell death. Work described in this thesis was concerned with utilising molecular modelling, synthesis and biological testing to develop novel antimalarial compounds, which selectively inhibit this target. The structural details of a number of compounds known to be active or inactive against Pfbc1 were used in combination with six different ligand based virtual screening techniques, and applied to the ZINC lead like library of compounds to identify potential chemotypes active against malaria. These methods included fingerprint similarity searching, principal component analysis, and naïve Bayesian classification. The hits from each of these methods were merged and formed part of a consensus analysis in which compounds identified across several methods were deemed of more interest than those which appeared less frequently. Each molecule was given a score based on its occurrence in the virtual screening methods and also its physicochemical properties. Compounds were filtered to remove those with unfavourable chemical properties, or which contained known toxicophores. 19 compounds were ultimately purchased and tested in vitro against the 3D7 strain of the malaria parasite. 5 of the compounds reported single digit µM IC50 values, with each containing novel structural chemotypes. The lead candidate contained a benzothiazole core, and reported an IC50 value against 3D7 of 4.53 ± 1.86 µM. Additional testing showed the compounds to be inactive against bovine bc1, which is promising as strong bovine bc1 inhibition has been shown to be indicative of cardiotoxicity in humans. Molecular docking was extensively employed to rationalise the activity of Pfbc1 inhibitors such as atovaquone and HDQ. A number of quinolone containing compounds were also subject to docking, with key observations made with regard to interactions thought to be crucial to their antimalarial activity. The hits from LBVS were also the focus of docking, further supporting their potential as Pfbc1 inhibitors. QSARs were developed for a series of 4-aminoquinoline compounds which had been tested against both the NF54 and K1 strains of malaria. MLR, PLS and kNN machine learning methods were investigated, with molecular descriptors contained within valid models interpreted. Significant models were identified and shown to have strong predictive abilities for both strains. QSAR models were similarly developed for a series of thiazolide compounds with activity against hepatitis C. SVM was found to give a significant model which was able to predict the cell safety of the thiazolide derivatives. The rational design of the novel pyrroloquinolone chemotype led to the synthesis of 7 synthetic analogues to investigate its SAR, via alkylation and Winterfeldt oxidation reactions. The compounds reported 3D7 activity values between 75 nM and 1.02 µM, with molecular docking supporting their potential for Qo binding and thus Pfbc1 inhibition.
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Bruscella, Patrice. "Etude des opérons petI et petII codant pour deux complexes bc1 chez la bactérie acidophile chimioautotrophe stricte Acidithiobacillus ferrooxidans." Aix-Marseille 2, 2004. http://www.theses.fr/2004AIX22086.
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Bincoletto, Claudia. "Autoproliferação celular e expressão do proto-oncogene Bc1-2 em pacientes com leucemia mieloide aguda (LMA) e sindrome mielodisplasica (SMD)." [s.n.], 1998. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314565.
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Orientador: Mary Luci de Souza QueirosTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-07-23T19:13:58Z (GMT). No. of bitstreams: 1 Bincoletto_Claudia_D.pdf: 4247184 bytes, checksum: a0026bf456d6bf0cd05ab5acf14add45 (MD5) Previous issue date: 1998
Resumo: Neste trabalho estudamos o crescimento e diferenciação dos precursores hematopoiéticos da medula óssea, na ausência de fatores estimuladores de colônias (autoproljferação) em vinte e oito pacientes com Leucemia Mielóide Aguda (LMA), doze pacientes com Síndrome Mielodisplásica (SMD) e dezenove controles (indivíduos normais). Os nossos resultados demonstraram que pacientes com LMA e SMD apresentam um aumento autócrino no número de colônias hematopoiéticas que é significativamente superior ao observado em indivíduos normais (p = 0.001). Além disso, verificamos que a presença de autoproliferação celular está associada a um mau prognóstico nas leucemias agudas, pois os pacientes com autoproliferação celular (n = 15) apresentaram uma sobrevida menor em relação aos pacientes com ausência de capacidade autoproliferativa (n = 13), (p = 0.01). O estudo da sobrevida celular, realizado através da caracterização morfológica por microscopia óptica de células apoptóticas, revelou um baixo índice de células apoptóticas em pacientes com LMA (n = 18, P = 0.001) em relação aos controles. Por outro lado, pacientes com SMD apresentaram um alto índice de apoptose celular quando comparado aos indivíduos normais (n = 11, p = 0.001). Em relação à expressão do proto-oncogene bcl-2, verificamos novamente resultados opostos entre os pacientes com LMA e SMD, pois observamos um alto índice de expressão do bcl-2 em células mononucleares de pacientes com LMA (n = 28, P = 0.002) em relação aos controles, e um baixo índice de expressão do proto-oncogene bcl-2 em células mono nucleares de pacientes com SMD (n = 15, p = 0.002). Além disso, verificamos uma correlação linear negativa entre a expressão do proto-oncogene bcl-2 e apoptose celular em pacientes com LMA (rs = - 0.664; P < 0.001). A elevada expressão do bcl-2 verificada nos pacientes com LMA também indica uma interferência deste proto-oncogene na resposta celular à quimioterapia, pois sua expressão estava significativamente maior em pacientes refratário& à quimioterapia (p = 0.03). Sendo assim, os resultados obtidos neste trabalho contribuem para uma melhor compreensão dos mecanismos envolvidos no processo de resistência celular à quimioterapia nos pacientes com LMA e também ajudam a esclarecer, pelo menos em parte, alguns processos envolvidos na hematopoiese desordenada nos casos de SMD
Abstract: In this work we studied the growth and differentiation of early bone marrow progenitor cells in the absence of exogenous growth factors (autonomous proliferation), the bcl-2 expression and the number of apoptotic cells in mononuclear bone marrow cells from patients with confirmed diagnosis of Acute Myeloid Leukaemia (AML) and Myelodysplastic Syndrome (MDS). Bone marrow cells from normal individuals were used as controls. We observed an increased percentage of bcl-2 expression on mononuclear bone marrow cells from AML patients in relation to controls (p = 0.002). Accordingly, the number of apoptotic cells was reduced (p = 0.001) and there was a negative correlation between bcl-2 expression and the number of apoptotic cells (r= - 0.664, P < 0.001) in these patients. In addition, bcl-2 expression was significantly increased in the chemotherapy resistant group in relation to the responsive group (p = 0.03). Survival in the group of AML patients with autonomous proliferation was reduced (p = 0.01). These results suggest that a high bcl-2 expression and the presence of autonomous proliferation are related with a poor prognosis in AML. In the MDS patients, the autonomous proliferation and the percentage of apoptotic cells were also significantly greater when compared to controls (p = 0.001). However, bcl-2 expression was significantly lower on mononuclear bone marrow cells from MDS patients In relation to normal individuals (p = 0.002 - Wilcoxon). These results suggest that the autonomous proliferation observed in these patients is counteracted by the high range of cell death which is probably related to the lower bcl-2 expression
Doutorado
Doutor em Ciências Biológicas
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Gruschke, Steffi. "Early steps in the biogenesis of the bc1 complex in yeast mitochondria : The role of the Cbp3-Cbp6 complex in cytochrome b synthesis and assembly." Doctoral thesis, Stockholms universitet, Institutionen för biokemi och biofysik, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-81033.
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The inner membrane of mitochondria harbors the complexes of the respiratory chain and the ATP synthase, which perform the key metabolic process oxidative phosphorylation. These complexes are composed of subunits from two different genetic origins: the majority of constituents is synthesized on cytosolic ribosomes and imported into mitochondria, but a handful of proteins, which represent core catalytic subunits, are encoded in the organellar DNA and translated on mitochondrial ribosomes. Using yeast as a model organism, I investigated the mitochondrial ribosomal tunnel exit, the region of the ribosome where the nascent chain emerges and that in cytosolic ribosomes serves as a platform to bind biogenesis factors that help the newly synthesized protein to mature. This study provided insights into the structural composition of this important site of mitochondrial ribosomes and revealed the positioning of Cbp3 at the tunnel exit region, a chaperone required specifically for the assembly of the bc1 complex. In my further work I found that Cbp3 structurally and functionally forms a tight complex with Cbp6 and that this complex exhibits fundamental roles in the biogenesis of cytochrome b, the mitochondrially encoded subunit of the bc1 complex. Bound to the ribosome, Cbp3-Cbp6 stimulates translation of the cytochrome b mRNA (COB mRNA). Cbp3-Cbp6 then binds the fully synthesized cytochrome b, thereby stabilizing and guiding it further through bc1 complex assembly. The next steps involve the recruitment of the assembly factor Cbp4 to the Cbp3-Cbp6/cytochrome b complex and presumably acquisition of two redox active heme b cofactors. During further assembly Cbp3-Cbp6 is released from cytochrome b, can again bind to the ribosome and activate further rounds of COB mRNA translation. The dual role of Cbp3-Cbp6 in both translation and assembly allows the complex to act as a regulatory switch to modulate the level of cytochrome b synthesis in response to the bc1 complex assembly process.At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.
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Garcia, Daniel. "Le cytochrome tétrahémique du centre réactionnel de Rhodopseudomonas viridis, sulfoviridis et de Roseobacter denitrificans : structure, fonction et couplage avec le cytochrome BC1." Aix-Marseille 2, 1994. http://www.theses.fr/1994AIX22062.
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Nous avons determine le potentiel de demi-reduction et l'orientation par rapport a la membrane de chaque heme du cytochrome tetrahemique du centre reactionnel de trois bacteries photosynthetiques: rhodopseudomonas sulfoviridis mesophile et thermophile et roseobacter denitrificans. Les resultats obtenus montrent qu'il existe une forte similitude entre le cytochrome des souches de rhodopseudomonas sulfoviridis (h#1: +390 mv, 75 ; h#2: +310 mv, 56 ; l#1: +72 mv, 58 ; l#2: -40 mv, 72,5) et celui de rhodopseudomonas viridis deja bien caracterise (h#1: +380 mv, 75 ; h#2: +310 mv, 55 ; l#1: +20 mv, 60 ; l#2: h#2: -60 mv, 73,5) alors que celui de roseobacter denitrificans est different (h#1: +290 mv, 39 ; +240 mv, 55 ; l#1: +90 mv, 40 ; l#2: +90 mv, 90). L'etude des cinetiques rapides des transferts d'electrons entre les hemes de ce cytochrome et le donneur du centre reactionnel p nous ont permis de conclure que l'arrangement des hemes au sein du cytochrome des deux souches de rhodopseudomonas sulfoviridis est le meme que celui de rhodopseudomonas viridis (l#2-h#2-l#1-h#1-p) alors que celui de roseobacter denitrificans en differe au moins par la position des hemes de haut potentiel (l#2-h#1-l#1-h#2-p). Les hemes de bas potentiel du cytochrome du centre reactionnel de rhodopseudomonas viridis, sulfoviridis et de roseobacter denitrificans ne participent pas a un transfert cyclique d'electrons vers le centre reactionnel meme en conditions fortement reductrices. L'heme de haut potentiel h#2 est couple au cytochrome bc#1 par l'intermediaire d'un cytochrome soluble (c#2 chez rhodopseudomonas viridis et sulfoviridis et c#5#5#1 chez roseobacter denitrificans). Ce cytochrome forme, a l'etat reduit, un complexe electrostatique stable avec le cytochrome du centre reactionnel de rhodopseudomonas viridis et sulfoviridis ce qui n'est pas le cas pour roseobacter denitrificans
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Cedeno, Diana. "Synthesis of UQ10 Analogs, Measurement of their Midpoint Potentials and their Effects on the Activity of WT and T61V bc1 Complexes from Rhodobacter sphaeroides." Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/195424.
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Cytochrome bc1 (Complex III) is an important enzyme that takes part in the respiratory electron transport chain in vertebrates, yeast, and many bacteria. The complex exists as a dimer, in which each monomer contains three catalytic subunits: cytochrome c1, cytochrome b and the Rieske iron-sulfur protein or ISP. Within the inner mitochondrial membranes of eukaryotes, Complex III catalyzes the transfer of two electrons from ubiquinol (UQH2) to cytochrome c, a water-soluble protein, through a process called the modified Q-cycle mechanism. Under very specific conditions, such as mutations within cytochrome b, disruption of the normal mechanism leads to bypass reactions, including the formation of superoxide and reactive oxygen species. We have sought to restore the activity of a mutant of cytochrome b (T61V) by modifying UQH2, the natural substrate for this enzyme. The structure of the oxidized form, UQ consists of a p-quinone head group and a hydrophobic all-trans polyprenyl unit (tail) that can vary in length, depending on the species in which it is found. The present work highlights modifications to the substituent groups attached to the quinone head and to the all-trans polyprenyl tail. Since the midpoint potentials of these molecules are pH dependent, cyclic voltammetry and spectroelectrochemistry studies in buffered aqueous solutions have been carried out on these molecules (analogs of UQ10). Modifications of the substituent groups attached to the quinone head gave the molecules a different ability to either donate or receive electrons, while modifications to the length of the tail either increased or decreased the solubility of these molecules inside the phospholipid membrane. We examined the normal activity and the production of superoxide in wild-type and (T61V) of bacterial Rhodobacter sphaeroides in the presence of these analogs. We confirmed that to prevent damaging side reactions, normal operation of the Q-cycle requires a fairly narrow window of reduction potentials with respect to the ubiquinol substrate.
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Castellani, Michela [Verfasser], Bernd [Akademischer Betreuer] Ludwig, and Klaas Martinus [Akademischer Betreuer] Pos. "Substrate binding does not only mean catalysis: internal regulation in the cytochrome bc1 complex from Paracoccus denitrificans / Michela Castellani. Gutachter: Bernd Ludwig ; Klaas Martinus Pos." Frankfurt am Main : Univ.-Bibliothek Frankfurt am Main, 2011. http://d-nb.info/104419510X/34.
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Brasseur, Gaël. "Relations structure-fonction du complexe bc1 chez Saccharomyces cerevisiae : étude de mutants affectés au centre QN de réduction des quinones et d'un mutant d'origine nucléaire." Aix-Marseille 1, 1995. http://www.theses.fr/1995AIX11010.
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Les complexes de type bc sont presents dans les chaines de transfert d'electrons a tous les stades de l'evolution. Le cytochrome b joue un role central dans le fonctionnement du complexe bc1. Afin de preciser les relations structure-fonction du cytochrome b membranaire, quatre mutants de deficience respiratoire et dix revertants ont ete analyses. Les mutants du gene du cytochrome b m221k et s206l sont affectes a la fois dans la reduction et l'oxydation de l'heme b562 par le centre n ; l'hypothese retenue est une instabilite de la semiquinone au centre catalytique de reduction des quinones. Les mutants frame-shift 204 et g33d ont un defaut d'assemblage du complexe bc1. Trois revertants issus du mutant s206l sont thermosensibles ; la serine 206 et l'asparagine 208 sont impliquees dans la thermostabilite de la proteine. Les mutations analysees induisent un deplacement du maximum d'absorption de l'heme b562 ce qui suppose une proximite avec l'environnement electronique de cet heme. La position 208 est impliquee dans la fixation de la funiculosine et le site de fixation de cet inhibiteur est tres proche du centre catalytique qn. L'ensemble des resultats montre que la region nh2 terminale du cytochrome b et la boucle reliant les helices transmembranaires 4 et 5 sont proches dans la structure tertiaire de la proteine, au voisinage de l'heme b562 ; ces regions sont impliquees a la fois dans la fixation des inhibiteurs du centre n et dans le centre catalytique de reduction des quinones. Le mutant nucleaire delete-disrupte du gene abc1 est affecte dans les activites de plusieurs complexes de la chaine respiratoire. Le pool de quinones endogenes est fortement diminue. Le profil electrophoretique des proteines mitochondriales est modifie chez ce mutant ; le complexe bc1 est assemble mais son fonctionnement est modifie. Abc1 est implique dans la bioenergetique et dans la biogenese mitochondriale
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Elbehti, Amina. "La chaîne de transfert d'électrons allant de Fe2 au NAD+ chez Thiobacillus ferrooxidans : mise en évidence d'un transfert inverse d'électrons passant par un complexe de type bc1." Aix-Marseille 2, 1996. http://www.theses.fr/1996AIX22014.
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La bacterie thiobacillus ferrooxidans presente un double interet: industriel et fondamental. De point de vue industriel c'est la bacterie la plus utilisee dans l'extraction industrielle de metaux a partir de certains type de minerais en les faisant passer en solution: c'est le biolixiviation. De point de vue fondamental t. Ferrooxidans presente deux caracteristiques importantes: 1- elle est acidophile et constitue un materiel de choix pour tester l'universalite du couplage chimioosmotique ; 2- elle est chimioautotrophe stricte et doit assurer la reduction du nad#+ en nadh necessaire pour la fixation du co#2 (sa seule source de carbone). Notre travail s'est focalise sur l'etude de la chaine de transfert d'electrons allant de fe#2#+ au nad#+ et sur son lien avec la chaine de transfert d'electrons conduisant a l'oxydation de fe#2#+ par l'oxygene. Apres avoir mis en evidence un cytochrome b, de meme que des cytochromes de type c et une cytochrome oxydase, nous avons solubilise et purifie ces divers cytochromes ; nous avons alors mis en evidence trois cytochromes c membranaires, migrant a 46, 30 et 21 kda sur gel sds page. Le cytochrome c a 30 kda a ete purifie jusqu'a l'homogeneite ; la sequence n-terminale et la composition en acides amines du cytochrome de haut poids moleculaire ont ete determinees ; ce cytochrome pourrait etre un cytochrome de type c#1. La mise en evidence, pour la premiere fois chez t. Ferrooxidans, d'une proteine fe-s de type rieske, associee a l'existence de cytochrome de type c et b membranaires, et de la sensibilite de la bacterie aux inhibiteurs des complexes de type bc nous a conduit a conclure a l'existence d'un complexe de type bc#1 chez cet organisme. C'est la premiere fois que ce complexe est mis en evidence chez t. Ferrooxidans. Enfin nous avons montre l'existence d'un transfert inverse d'electrons passant par un complexe de type bc et utilisant l'energie provenant de la force proton motrice etablie en partie par la cytochrome oxydase et en partie par l'hydrolyse de l'atp
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Zeng, Hui [Verfasser], Hartmut [Akademischer Betreuer] Michel, Klaas Martinus [Gutachter] Pos, and Hartmut [Gutachter] Michel. "Structural and functional characterization of cytochrome c oxidase, cytochrome bc1 complex and heme A synthase from Aquifex aeolicus / Hui Zeng ; Gutachter: Klaas Martinus Pos, Hartmut Michel ; Betreuer: Hartmut Michel." Frankfurt am Main : Universitätsbibliothek Johann Christian Senckenberg, 2020. http://d-nb.info/1210555727/34.
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BARRE, PHILIPPE. "Les transferts de genes entre especes de cafeiers diploides : etude des hybrides f1 et bc1 entre c. pseudozanguebariae bridson et c. liberica bull ex. hiern (c. dewevrei de wild et th dur)." Montpellier, ENSA, 1997. http://www.theses.fr/1997ENSA0019.
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Cette etude a pour objet l'evaluation des possibilites de transferts de genes entre deux especes de cafeiers diploides (2n = 2x = 22) phylogenetiquement eloignes : coffea pseudozanguebariae (pse) originaire du kenya et de tanzanie et c. Liberica-dewevrei (dew) originaire d'afrique centrale. Les recombinaisons ont ete etudiees d'une part a l'aide de l'hybridation genomique in situ (hgis) et de la cytometrie en flux et d'autre part a l'aide de marqueurs moleculaires (rflp). De plus, l'heritabilite de la teneur en cafeine, presente chez dew et absente chez pse, a ete etudiee ainsi que la recherche de marqueurs lies a ce caractere. Les hybrides de deuxieme generation ont ete obtenus par fecondation libre des hybrides f1. Les marqueurs rflp associes a des donnees phenotypiques ont permis de caracteriser ces hybrides : 18 proviendraient de backcross sur l'espece pse et 65 proviendraient de backcross sur l'espece dew. L'hgis a permis de determiner la composition genomique d'hybrides f1 et de 7 hybrides de deuxieme generation choisis pour representer la variabilite de la quantite d'adn par noyau entre les parents (2c = 1,13 pg pour pse et 2c = 1,43 pg pour dew). Une relation lineaire a ete mise en evidence entre la taille du genome et le nombre de chromosomes de pse. L'etude de la quantite d'adn par noyau dans les deux backcross et des proportions d'alleles dew a 10 locus rflp independants suggerent que les chromosomes des deux genomes s'associeraient de maniere aleatoire. Une seule carte genetique a ete publiee chez les cafeiers sur c. Canephora ; elle comprend 15 groupes de liaison et une quarantaine de marqueurs rflp. La cartographie de 15 marqueurs rflp sur le croisement pse x dew a mis en evidence deux groupes de liaison et 9 locus independants. La cartographie comparee avec c. Canephora pour deux segments de chromosomes independants indique des taux de recombinaisons equivalents. L'etude de la teneur en cafeine montre qu'elle est sous controle polygenique, avec un fort effet genetique. Cependant, le caractere presence versus absence de cafeine serait controle par un gene majeur avec la presence dominant l'absence. Ce gene explique 41% des variations observees dans le backcross sur pse. La recherche de marqueurs lies a des qtls de la teneur en cafeine a ete realisee dans le backcross sur dew ne comprenant que des individus contenant de la cafeine. Le locus g13 explique 20% des variations de la teneur en cafeine. Ce locus est aussi lie a la duree du cycle de fructification (41% de variance expliquee) : les fortes teneurs en cafeine sont associees a de longs cycles. Ces resultats preliminaires sont encourageants pour le transfert de l'absence de cafeine de pse vers des especes de cafeiers en contenant. En effet, ce caractere semble etre determine par un gene majeur et nous n'avons detecte aucun frein aux recombinaisons.
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Hogarth, Linda A. "The molecular mechanisms of drug resistance in childhood acute lymphoblastic leukaemia." Thesis, University of Newcastle Upon Tyne, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263034.
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Frolka, Jakub. "BCH kódy." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2012. http://www.nusl.cz/ntk/nusl-219462.
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The work deals with data security using BCH codes. In the work are described BCH codes in binary and non-binary form, and their most important subclass RS codes. Furthermore, this work describes the method of decoding Peterson-Gorenstein-Zierl, Berlekamp- Massey and Euclidean algorithm. For the presentation of encoding and decoding process, the application was created in Matlab, which has two parts – Learning BCH codes and Simulation of BCH codes. Using the generated application performance of BCH codes was compared at the last part of the work.
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Sacharuk, Jasmine. "Late Shang (1200 BCE - 1046 BCE) bronze casting technology and technological behaviour." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/50036.
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This project examines the bronze casting technology of the late Shang Dynasty (1200-1046 BCE). Despite extensive scholarship on the bronzes themselves, the details of the casting process have remained unclear. Considering the relevance of the bronzes in terms of ritual and burial practices, class hierarchy, and royal affiliation, understanding the production behind the bronzes can reveal a great deal about the lives of everyday Shang craftspeople and Shang society as a whole.
This project examines bronze foundry remains from Yinxu, the ruins of the last capital of the Shang Dynasty, in an attempt to uncover more information about the late Shang bronze casting process. Emphasizing the behavioural nature of technology, and the information embedded within technological action, this project undertakes replication experiments to explore how the physical properties of the materials directly influenced the behavioural nature of the bronze casting process.
Scanning electron microscopy (SEM) suggests that the loess used to create bronze molds was processed differently than in other ceramics, with a notably reduced amount of clay. This information is integrated with an experimental program, which concludes that the removal of clay fundamentally facilitates the bronze casting process by minimizing shrinkage, providing structural stability and enabling long-term decoration. This has implications on the labour of the bronze-casting industry, emphasizing an initial process (the removal of clay) in order to facilitate mold construction, decoration and casting at later stages. Examining the ways in which technologies are developed and used, and for what purposes, is a way in which archaeologists can examine past behaviour on both a personal and societal scale. The integration of petrographic analyses with an experimental program highlights how specific behaviours in the late Shang, such as materials processing and labour organization, are reflected in the technological remains of bronze casting. This project concludes that further examination into late Shang bronze casting technology is necessary in order to understand such a politically, socially and spiritually significant industry of the time, offering insight into the daily perspectives of the Shang people due to the inherently behavioural nature of technology.Arts, Faculty of
Anthropology, Department of
Graduate
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Ng, Florence Wai Hung. "Identification and characterization of Bcl-2/Bcl-X¦L interacting protein, p28Bap31." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0015/NQ44531.pdf.
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Liu, Xiaohua. "Spin Excitations in BCC, FCC, HCP Cobalt and BCC Fe1-xCox Alloys /." The Ohio State University, 1996. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487932351057225.
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Gomes, Francisco. "Millennium BCP: precarious environment." Master's thesis, NSBE - UNL, 2013. http://hdl.handle.net/10362/9877.
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Abed, Shahla. "Läkemedel mot Bcl-2 överuttryckande resistenta Prostatatumörer : Läkemedel mot Bcl-2 överuttryckande resistenta Prostatatumörer." Thesis, Umeå universitet, Kemiska institutionen, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-106293.
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Svangren, Henrik. "Konceptstudie av kassadisk B10/B11." Thesis, Jönköping University, JTH, Mechanical Engineering, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-942.
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This master’s thesis report is a summary of the analysis performed together with ITAB Shop Concept located in Jönköping, Sweden. As a last element of the Master’s program at the School of Engineering, this 20 point level D thesis project has been the final work to bring my education to an end.
ITAB Shop Concept expressed an aspiration that the Shop Counter Program B10/B11 should undergo an analysis to point out and possibly lead to improvement.
Through interviews and data collection proposals for possible improvements has been drawn up and the analysis points out current deficiencies. By following the idea generation, proposals to solutions for every individual problem is presented. These proposals are weighted and compared to specified requirements.
The result is built up through a number of changes in the Shop Counter Program, partly by suggestions on reduction of part, but also how the Shop Counter can be re-designed.
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Szafir, Daniel J. "Non-Invasive BCI through EEG." Thesis, Boston College, 2010. http://hdl.handle.net/2345/1208.
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Thesis advisor: Robert SignorileIt has long been known that as neurons fire within the brain they produce measurable electrical activity. Electroencephalography (EEG) is the measurement and recording of these electrical signals using sensors arrayed across the scalp. Though there is copious research in using EEG technology in the fields of neuroscience and cognitive psychology, it is only recently that the possibility of utilizing EEG measurements as inputs in the control of computers has emerged. The idea of Brain-Computer Interfaces (BCIs) which allow the control of devices using brain signals evolved from the realm of science fiction to simple devices that currently exist. BCIs naturally present themselves to many extremely useful applications including prosthetic devices, restoring or aiding in communication and hearing, military applications, video gaming and virtual reality, and robotic control, and have the possibility of significantly improving the quality of life of many disabled individuals. However, current BCIs suffer from many problems including inaccuracies, delays between thought, detection, and action, exorbitant costs, and invasive surgeries. The purpose of this research is to examine the Emotiv EPOC© System as a cost-effective gateway to non-invasive portable EEG measurements and utilize it to build a thought-based BCI to control the Parallax Scribbler® robot. This research furthers the analysis of the current pros and cons of EEG technology as it pertains to BCIs and offers a glimpse of the future potential capabilities of BCI systems
Thesis (BA) — Boston College, 2010
Submitted to: Boston College. College of Arts and Sciences
Discipline: Computer Science Honors Program
Discipline: Computer Science
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Dias, Cleverton Oliveira. "Teoria BCS com efeito Rashba." Universidade Federal do Amazonas, 2015. http://tede.ufam.edu.br/handle/tede/4987.
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This dissertation presents systematically the traditional superconductors, taking into account its discovery, properties that characterize the theory describing and changes taking place in their thermodynamic properties when subject to spin-orbit interaction Rashba. In the rst part are the key topics discussed related to phenomenon of superconductivity. It begins with a chapter 1 approach of the historical evolution of superconductivity and presentation properties that characterize a conventional superconductor, in addition to de ne superconductors Type I (conventional) and type II. The Chapter 2 is intended for an explanation of the microscopic BCS theory whose application is associated with type I superconductors, although this chapter argue about the interaction of electrons with the network, thus forming what is called Cooper pairs. The Chapter 3 is intended to introduce the Rashba model, which can be veri ed in two ways: by spontaneous generation of electric eld the junction interface of two materials or because application of the an external electric eld. In work not take into account the so that will be produced this electric eld. In Chapter 4 it shows the model Hamiltonian that constitutes the junction BCS Hamiltonian with the Hamiltonian of Rashba, from this model it is intended to calculate the e ect of Rashba interaction on the gap energy using the method of canonical transformations, consisting to assess the evolution of the operator concerned by a equation of dynamic evolution, allowing us nd the self energy carriers and their respective eigenvalues and associates them to gaps of energy. As a result of Chapter 4, Chapter 5 determine the gap superconductor function of temperature and the parameter R Rashba and as the thermodynamic properties of the model studied in this chapter also opens a space for comments and discussions. We end with Chapter 6, presenting partial conclusions, Related analytical curve made from certain data numerical, these curves will analyze the variation in thermodynamic properties of superconductors because the e ect Rashba.
A presente dissertação consiste em apresentar de forma sistemática os supercondutores tradicionais, levando em consideração sua descoberta, as propriedades que o caracterizam, a teoria que os descrevem e as mudanças que ocorrem em suas propriedades termodinâmicas quando submetidos a interação spin- orbita de Rashba. Na primeira parte são discutidos os t ópicos fundamentais referentes ao fenômeno da supercondutividade. Inicia-se o capítulo 1 com uma abordagem da evolução hist orica da supercondutividade e a apresentação das propriedades que caracterizam um supercondutor convencional, al em de de nir supercondutores tipo I (convencionais) e tipo II. O cap tulo 2 destina-se a uma explana c~ao da teoria microscópica BCS, cuja aplicação está associada a supercondutores de tipo I, ainda neste capítulo argumenta-se sobre a interação dos elétrons com a rede, formando assim o que chamamos de pares de Cooper. O capiítulo 3 destina-se a apresentar o modelo de Rashba, que pode ser verificado de duas maneiras: por geração espontânea de campo elétrico na interface da junção de dois materiais ou em razão da aplicação de um campo elétrico externo. No trabalho não se levar a em conta a maneira que ser a produzido esse campo elétrico. No capítulo 4 apresenta-se o Hamiltoniano do modelo, que consiste na junção do Hamiltoniano BCS com o Hamiltoniano de Rashba, a partir deste modelo pretende-se calcular o efeito da intera ção de Rashba, sobre os gaps de energia utilizando o m etodo das transforma ções canônicas, que consiste em avaliar a evolu ção temporal do operador em questão por meio de uma equa ção de evolução dinâmica, o que nos permitir a encontrar os autovetores de energia e seus respectivos autovalores e associa-los aos gaps de energia. Como consequência do capítulo 4, no cap tulo 5 determinaremos o gap do supercondutor em fun ção da temperatura e do parâmetro de Rashba R, bem como as propriedades termodinâmicas do modelo estudado, neste cap tulo tamb em abre-se um espa co para comentarios e discussões. Finalizamos com o cap tulo 6, apresentando conclusões parciais, relacionadas a an alise de algumas curvas feitas a partir de dados num ericos, estas curvas permitirão analisar a varia ção nas propriedades termodinâmicas dos supercondutores devido o efeito Rashba.
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Goodberry, Benjamin Nathaniel. "Multiparameter BCn-Kostka-Foulkes Polynomials." Thesis, Virginia Tech, 2018. http://hdl.handle.net/10919/83576.
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The Kostka-Foulkes polynomials describe the change of basis between Schur polynomials and Hall-Littlewood polynomials. In this paper, we extend this idea to the family of BCn Macdonald spherical functions, with multiparameter Kostka-Foulkes polynomials acting as the change of basis from the BC_n spherical functions to the type Cn Schur polynomials. We develop a Kato-Lusztig formula that describes the multiparameter BCn-Kostka-Foulkes polynomials.Master of Science
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Lukášová, Pavlína. "Cloud Computing jako nástroj BCM." Master's thesis, Vysoká škola ekonomická v Praze, 2010. http://www.nusl.cz/ntk/nusl-75556.
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This thesis deals with possible interconnections between two concepts playing a big role in contemporary business and IT world. These concepts are Business Continuity Management and Cloud Computing. In the scope of this thesis there are certain areas identified where both concepts are complement, where Cloud Computing brings new opportunities for Business Continuity Management and where could possible problems arise during particular implementation. From the BCM perspective the impact lies on IT services, from the Cloud Computing perspective the thesis deals especially with security aspects. The thesis is also aimed at the characteristics of higher education and basic differences from commercial sphere. Based on defined differences and identified interconnections between BCM and Cloud Computing, the thesis argues for usage of suitable Cloud Computing solution for higher education regarding Business Continuity improvement. The multi-criterion comparison of several Infrastructure-as-a-Service solutions stems from this analysis focusing on technical, financial, and Business Continuity aspects. The result from this comparison together with conclusions from previous chapters serve as an input for subsequent practical proposal of Cloud Computing solution and its verification against Business Continuity improvement in specific conditions on University of Economics in Prague. The proposal is also represented by strategic map.
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Kašpar, Jaroslav. "Zabezpečení přenosu dat BCH kódy." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2008. http://www.nusl.cz/ntk/nusl-217733.
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The thesis Data transmission error-protection with BCH codes deals with a large class of random-error correcting cyclic codes which are able to protect binary data and can be used for example in data storages, high speed modems. Bose, Chaudhuri and Hocquenghem (BCH) codes operate over algebraic structures called Galois fields. The BCH encoding is the same as cyclic encoding and can be done with linear feedback shift register but decoding is more complex and can be done with different algorithms - in this thesis there are two algorithms for decoding Peterson and Berlekam-Massey mentioned. The aim of this thesis is to find BCH code which is able to correct t = 6 independent errors in up to data sequence n = 150 bits, then peruse possible realizations of the codecs and set criteria for the best realization, then design and test this realization. This thesis is split into three main parts. In the first part there are encoding and decoding methods of the BCH code generally described. The second part deals with selecting of the right code and realization. There was chosen BCH (63,30) code and realization with FPGA chip. In the last part is described design of BCH encoder and decoder and compilation in the Altera design software.
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Barrezueta, Luis Fernando Mesias [UNIFESP]. "Imuno-expressão das proteínas da família BCL-2 (BCL-2. BCL-XL, BAX, BAK, BAD) em câncer gátrico, preparados em arranjo em matriz (TMA)." Universidade Federal de São Paulo (UNIFESP), 2009. http://repositorio.unifesp.br/handle/11600/9724.
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Previous issue date: 2009-01-28Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Em casos de carcinoma gástrico, para contribuir ao conhecimento do processo de carcinogênese: Objetivo: Estudar a expressão das proteínas da família Bcl-2 (BcI-2, Bcl-xl, Bak, Bad, Bax). Correlacionar a expressão destas proteínas com 0 índice apoptótico mediante a expressão da proteína Caspase 3 clivada, com 0 índice mit6tico mediante a expressão da proteína Ki-67 e com a expressão da proteína p53. Método: Técnica de arranjo em matriz de amostras teciduais (TMA): em 87 amostras de adenocarcinomas gástricos (grupo teste) e de mucosa gástrica não tumoral (grupo controle) foi avaliada a imuno-expressão das proteínas da família BcI-2 (BeI-2, Bcl-xl, Bak, Bad, Bax), da proteína p53, da proteína caspase 3 e da proteína Ki-67. Resultados: Todas as proteínas examinadas foram observadas nos adenocarcinomas e mucosa não tumoral, porem com diferenças de expressão em relação à porcentagem de positividade e intensidade. Observamos: i) Houve associação entre 0 tamanho do tumor e a proteína p53. ii) Houve associação da proteína Bad no adenocarcinoma com a idade dos pacientes. iii) Associação das proteínas Bax, Bad e Ki-67 com 0 adenocarcinoma de tipo intestinal. iv) As proteínas Bcl-xl, Bak, Bad, p53 e Ki-67 apresentaram diferenças estatisticamente significantes entre a imuno-expressão no tumor e na mucosa não tumoral. v) Associação das proteínas Bax, Bak e Bad na mucosa não tumoral. vi) Não houve correlação da imunoexpressão das proteínas com a sobrevida dos pacientes. Conclusão: A expressão aumentada da proteína Bcl-xl nos adenocarcinomas, com evidente diferença de expressão entre 0 grupo teste e 0 grupo controle, esta relacionada com 0 efeito anti-apoptótico da proteína. A expressão reduzida das proteínas Bak e Bad e a expressão aumentada das proteínas p53 e Ki-67 nos adenocarcinomas demonstram 0 desequilíbrio entre morte e proliferação celular, permitindo 0 crescimento descontrolado das células neoplásicas.
Purpose: To study the immunoexpression of Bcl-2 family proteins (Bcl-2, Bcl-xl, Bax, Bak, Bad) and to evaluate the correlation between the immunoexpression of these proteins with the cleaved caspases 3, Ki-67 and p53 immuno-expression. Methods: A TMA paraffin block was constructed with gastric carcinoma tissue (test group) and normal gastric adjoining mucosa (control group) of 87 patients. The TMA block was submitted to immunohistochemistry for Bcl-2, Bcl-xl, Bax, Bak, Bad, p53 and-cleaved Caspase 3. Results: All studied proteins were present in tumor and normal gastric adjoining mucosa, but with different intensity and amount of positive cells. i) There was an association between tumor size and p53 expression. ii) association between Bad expression in the tumor and patient’s age. iii) Intestinal type adenocarcinoma was positively correlated with the expression of Bax, Bad and Ki-67. iv) The protein Bcl-xl, Bak, Bad, p53 and Ki-67 showed statistically significant differences between the immuno-expression in tumor and normal gastric adjoining mucosa. v) There was an association between the proteins Bax, Bak and Bad expression in the normal gastric adjoining mucosa. vi) No correlation between patient’s survival rates and the expression of the proteins was observed. Conclusions: The higher expression of Bcl-xl protein in adenocarcinoma, the difference of Bcl-xl expression between test group and control group, might be related with the anti-apoptotic effect of this protein. The lower expression of Bak and Bad and the increased expression of p53 protein and Ki-67 protein in adenocarcinomas demonstrate the imbalance between death and cellular proliferation, which allows the uncontrolled tumor cell proliferation.
FAPESP: 04/09932-4
FAPESP: 06/54187-0
TEDE
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Costa, Júnior Abadio de Oliveira da. "Produção de vacina BCG recombinante expressando proteína de fusão CMX e avaliação da indução de células B de memória." Universidade Federal de Goiás, 2014. http://repositorio.bc.ufg.br/tede/handle/tede/7180.
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Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
Tuberculosis is a global public health problem and despite the recent reduction in the incidence of new cases and deaths worldwide, there are still developing countries where these indices are not so optimistic. The only vaccine recommended to TB by WHO is BCG that, although effective against severe forms of childhood TB, has a questionable efficacy against pulmonary tuberculosis in adults. In the pursue for a molecular improvement for BCG and thus enable the development of a widely used method of prophylaxis, a recombinant BCG was produced by electroporation of BCG Moreau, using three different recombinant plasmid constructions (pLA71, pLA73 and pMIP12), all of them containing the fusion protein CMX coding sequence. However, only the pLA71 transformant expressed the CMX fusion protein in the western blot. In order to evaluate the profile of memory B cells, the specific antibodies against CMX and the efficacy of the vaccine, BALB/c mice were immunized with a single dose of BCG or rBCG-CMX or PBS (control). Serum samples were collected from all animals 30, 60 and 90 days after the immunization and the induction of memory B cells was assessed by flow citometry of the splenocytes cell suspensions. Ninety days after the last immunization, animals were challenged with Mtb H37Rv by the intravenous route and forty five days later, lungs were harvested to analyze the bacterial load and the level of inflammation induced by the infection in immunized mice. Even though no specific antibodies against rCMX, rHspX and rMPT-51 proteins were detected, animals immunized with rBCG-CMX showed specific IgG1 (p<0,0001) and IgG2a (p=0,0007) levels against the BCG culture sediment, higher than those induced in the animals vaccinated with BCG. Besides, the rBCG-CMX vaccine was able to induced delayed long lived memory B cells (p=0,0069), reduced the bacterial load in the lungs (p=0,0041) in a similar way as BCG and generated less tissue damage when compared to BCG Moreau. The recombinant BCG vaccine expressing the CMX fusion protein induced specific antibodies for BCG extract and B cell response to stronger memory than BCG, but, the protection induced by both vaccines (BCG and rBCG) were similar.
A tuberculose (TB) constitui um problema de saúde pública mundial e apesar da recente redução da incidência de novos casos e de mortes em todo mundo ainda há países em desenvolvimento onde estes índices ainda não são tão otimistas. A única vacina indicada pela Organização Mundial de Saúde (OMS) contra a TB é a BCG que embora esta seja eficiente contra as formas graves de TB na infância, apresenta uma eficácia questionável contra a tuberculose pulmonar (TBP) em adultos. Com o objetivo de contribuir para o melhoramento molecular da BCG e possibilitar assim o aprimoramento de um método de profilaxia amplamente utilizado, foram produzidos, por eletroporação da BCG (subcepa Moreau), três recombinantes utilizando diferentes construções plasmidiais (pLA71, pLA73 e pMIP12), ambas, contendo sequência codificadora para a proteína de fusão CMX de Mycobacterium tuberculosis. No entanto, apenas o transformante utilizando o pLA71 apresentou expressão da proteína CMX no imunoblot. Com o objetivo de avaliar o perfil de células B de memória, anticorpos específicos para CMX e a eficácia da vacina, camundongos BALB/c foram imunizados com dose única de BCG ou rBCG-CMX ou PBS (controle). A avaliação do perfil de células B de memória induzido pela imunização foi realizada 30 e 90 dias após a imunização, pela marcação de esplenócitos para citometria de fluxo. Noventa dias após a imunização, os animais foram desafiados, via endovenosa, com Mtb H37Rv e 45 dias após, foram obtidos pulmão dos camundongos para determinação da carga bacilar e do nível de inflamação induzido pela infecção nos camundongos imunizados. Não foram detectados níveis séricos de anticorpos específicos para proteínas rCMX, rHspX e rMPT-51, no entanto, animais vacinados com a rBCG-CMX apresentaram níveis de anticorpos séricos, das classes IgG1 (p<0,0001) e IgG2a (p=0,0007), específicos para extrato de BCG superiores ao induzido em animais vacinados com a BCG. Além disso, a vacina rBCG-CMX mostrou-se capaz de induzir tardiamente células B de memória de vida longa (p=0,0069); reduzir a carga bacilar no pulmão de camundongos infectados com Mtb (p=0,0041), semelhante ao BCG; e promover menor dano tecidual no pulmão de animais vacinados e infectados com Mtb. A vacina BCG recombinante expressando a proteína de fusão CMX mostrou-se capaz de induzir anticorpos específicos para extrato de BCG e resposta de células B de memória mais robustas do que a BCG, entretanto, a proteção induzida por ambas as vacinas (BCG e rBCG) foram semelhantes.
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Bah, Nourdine. "Contrôle du déclenchement de l'apoptose pendant l'arrêt mitotique par l'homologue de Bcl-2, Bcl-xL." Nantes, 2013. http://archive.bu.univ-nantes.fr/pollux/show.action?id=d6222d04-bb86-43e6-810b-21a673a07295.
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Les poisons des microtubules, comme le paclitaxel, sont des composés qui modifient la dynamique des microtubules, et bloquent les cellules en mitose par non-satisfaction du point de contrôle mitotique. La principale cible du point de contrôle mitotique est l'APC/C, une ligase E3 qui régule la dégradation de protéines importantes pour la progression de la mitose. Un de ces substrats est la cycline BI, le cofacteur essentiel à l'activité de Cdk1 , et par conséquent essentiel pour le maintien de la mitose. Sous paclitaxel, le point de contrôle mitotique est actif, et cela aboutit à un blocage en mitose du à l'inhibition d'APC/C via la séquestration de Cdc20. Cet arrêt mitotique peut aboutir à plusieurs devenirs cellulaires, notamment la mort mitotique et l'échappement à l'arrêt mitotique. Nous nous sommes intéressés au rôle de Bcl-xl, dans la réponse cellulaire à l'arrêt mitotique induit par le paclitaxel, et l'extinction de Cdc20, dans des lignées de cancer du sein. Il apparaît que la mort mitotique induite par le paclitaxel ou l'extinction de Cdc20 n'est pas dépendante des caspases, ni de Bax et Bak. L'extinction de Bcl-xl , ou le traitement par l'ABT-737, pendant l'arrêt mitotique induit une conversion de la mort mitotique en une apoptose classique dépendante des caspases et de Bax. Ce « switch » dans l'activité de Bcl-xl (protection/induction de l'apoptose par libération de Bax) est dépendant de sa phosphorylation sur la sérine 62, au cours de l'arrêt mitotique, phosphorylation qui module sa capacité à interagir avec Bax. L'exploitation clinique de ces données (en accord avec d'autres récemment publiées) suggère d'associer ABT-737 (inhibition de Bcl-xl ) et taxanes pour favoriser la réponse des cellules tumorales aux antimitotiques vers une mort mitotique majoritaireAntimitotic agents such as microtubule inhibitors (paclitaxel) are widely used in cancer therapy while new agents blocking mitosis onset are currently in development. All these agents impose a prolonged mitotic arrest in cancer cells that relies on sustained activation of the spindle assembly checkpoint and may lead to subsequent cell death by incompletely understood molecular events. We have investigated the role played by anti-apoptotic Bcl-2 family members in the fate of mitotically arrested mammary tumor cells treated with paclitaxel, or depleted in Cdc20, the activator of the anaphase promoting complex. Under these conditions, a weak and delayed mitotic cell death occurs that is caspase- and Bax/Bak-independent. Moreover, BH3 profiling assays indicate that viable cells during mitotic arrest are primed to die by apoptosis and that Bcl-xL is required to maintain mitochondrial integrity. Consistently, Bcl-xL depletion, or treatment with its inhibitor ABT-737 (but not with the specific Bcl-2 inhibitor ABT-199), during mitotic arrest converts cell response to antimitotics to efficient caspase and Bax-dependent apoptosis. Apoptotic priming under conditions of mitotic arrest relies, at least in part, on the phosphorylation on serine 62 of Bcl- xL, which modulates its interaction with Bax and its sensitivity to ABT-737. The phospho-mimetic S62D-Bcl-xL mutant is indeed less efficient than the corresponding phospho-deficient S62A-Bcl-xL mutant in sequestrating Bax and in protecting cancer cells from mitotic cell death or yeast cells from Bax-induced growth inhibition. Our results provide a rationale for combining Bcl-xL targeting to antimitotic agents to improve clinical efficacy of antimitotic strategy in cancer therapy
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Kuma, Rita Dela. "Paste charaterization of 3rd and 4th millennium BCE ceramics from Arslantepe, Turkey (3350-2800 BCE)." Master's thesis, Universidade de Évora, 2016. http://hdl.handle.net/10174/20855.
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ABSTRACT:
This research aims at defining the main characteristics of technological and
compositional variability of ceramic production at Arslantepe during Periods VIA, VIB1 and
VIB2 (3400-2800BC) in a framework of socioeconomic and political development. The
stereomicroscope in a reflectance mode at a magnification of 1–6.3x was used to analyze a
total number of 158 ceramic samples to identify and characterize the principal inclusions in
the ceramic pastes, their dimensions, shape, color, concentration, distribution, which may be
well-dispersed or clustered, and orientation. The stereomicroscope does not provide detailed
identification of all minerals and rock types, but allows to hypothesize the presence of some
lithic components which should be confirmed under the polarizing microscope. However, the
presence of some inclusions such as chaff, quartz, and mica can be easily distinguished using
the stereomicroscope. The nature of inclusions (lithic and mineral components, chaff, mixed)
and their features (size, proportion, shape and orientation) were the primary variables for
determining compositional and technological variability in the ceramic production of
Arslantepe.
Arslantepe is a high mound in the Malatya plain and was always the dominant center
in its region. In the earliest phases of its history – the Chalcolithic period, Arslantepe had
close links with the Syro-Mesopotamian world with which it shared many cultural features,
structural models, and development trajectories. But in the early centuries of the 3rd
millennium BC, vast changes occurred which halted the development of the Mesopotamiantype
centralized system and reoriented Arslantepe‘s external relations toward Eastern
Anatolia and Transcaucasia.
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Schaller-Schönitz, Michael [Verfasser]. "Der Einfluss von BCR-ABL auf STAT5 in BCR-ABL-positiven Leukämiezellen / Michael Schaller-Schönitz." Hannover : Technische Informationsbibliothek und Universitätsbibliothek Hannover, 2011. http://d-nb.info/1012635929/34.
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Rosa, Larissa Camargo da [UNESP]. "Potencial profilático de estratégias vacinais no diabetes experimental." Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/89956.
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rosa_lc_me_botfm.pdf: 636625 bytes, checksum: 4e80c747550326696f8ac42a9a3aed5a (MD5)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Universidade Estadual Paulista (UNESP)
O diabetes tipo I é uma doença causada pela destruição autoimune das células do pâncreas que resulta em deficiência na produção de insulina. O objetivo deste projeto foi, inicialmente, avaliar o potencial profilático de seis estratégias vacinais no controle do diabetes experimental induzido por estreptozotocina (STZ) em camundongos C57BL/6. As três primeiras são específicas e baseadas na imunização com insulina em condições tolerogênicas que incluem associação com alúmen, dexametasona ou Adjuvante Incompleto de Freund (AIF). As outras três são não-específicas e baseadas em estratégias do tipo prime-boost. Neste caso foram testadas as seguintes combinações: BCG/DNAhsp65, BCG/hsp65 e DNAhsp65/BCG. Nos três protocolos iniciais, camundongos C57BL/6 machos foram imunizados e posteriormente inoculados com múltiplas doses de streptozotocina para desencadeamento do diabetes tipo I. Para avaliação inicial do efeito protetor foram determinados os seguintes parâmetros: peso, glicemia, análise histopatológica do pâncreas e perfil de citocinas produzidas por células esplênicas. Dentre todos os protocolos testados com o modelo STZ, os resultados observados no grupo imunizado por priming com BCG seguido de boost com DNAhsp65 forneceu os resultados mais promissores. Neste caso, a hiperglicemia foi menor, ocorreu proteção parcial contra a insulite e produção significativa de IL-10 por células estimuladas in vitro com hsp65. Por último, avaliamos o efeito da estratégia BCG/DNAhsp65 na evolução do diabetes no modelo NOD. Esta imunização determinou maior ganho de peso, proteção contra a hiperglicemia, aumento na produção de citocinas e diminuição na porcentagem de ilhotas inflamadas quando comparado ao grupo de camundongos NOD não imunizados. Esta proteção se mostra promissora e deverá ser confirmada em estudos futuros
Diabetes type I is a disease caused by autoimmune destruction of the beta cells in the pancreas that leads to a deficiency in insulin production. The aim of this project was, initially, to evaluate the prophylactic potential of six different vaccine strategies on diabetes type 1 induced by streptozotocin (STZ) in C57BL/6 mice. The first three strategies were specific for diabetes and based on immunization with insulin in tolerogenic conditions including insulin associated with Incomplete Freund Adjuvant (IFA), alum or dexamethasone. The other three were based on prime-boost strategies involving BCG and the DNAhsp65 vaccine: BCG/DNAhsp65, BCG/hsp65 e DNAhsp65/BCG. In the first three experimental protocols, male C57BL/6 mice were immunized with one of the vaccine strategies and later diabetes was induced with multiple low doses of STZ. The following parameters were analyzed to evaluate the prophylactic potential: body weight, glycemic levels, pancreatic islets histopathological analysis and cytokine production by spleen cells. From all strategies tested in the STZ model, the one with the most promising results was BCG as a primer followed by a booster with DNAhsp65. In this case, we observed protection against weight loss and against hyperglycemia, a decreased islet inflammation and significantly increased production of IL-10 induced by in vitro stimulation with hsp65. As a final point, we evaluated the effect of BCG/DNAhsp65 in the evolution of diabetes in NOD mice. This immunization determined weight gain, protection against hyperglycemia, decreased islet inflammation and higher levels of cytokine production when compared with non-immunized NOD mice. These findings are very interesting and deserve further investigations
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Diniz, Ricardo. "Modelo de bósons interagentes e sua relação com o BCS." Universidade de São Paulo, 1990. http://www.teses.usp.br/teses/disponiveis/43/43131/tde-30042014-152410/.
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Através de um hamiltoniano efetivo baseado no tratamento de NAMBU POT.90 para o BCS, no qual incluímos além do emparelhamento monopolar o emparelhamento quadrupolar, discutimos a relação entre esse modelo e o modelo de bósons interagentes. Uma aplicação e feita a cadeia o (6) do IBM, que corresponde ao limite GAMA-instável do modelo de bohr. As dificuldades encontradas e uma possível generalização para o modelo são discutidas.The nambu mechanism for BCS theory is extended with inclusion of quadrupole pairing in adition to the usual monopole pairing. An effective Hamiltonian is constructed and its relation to the IBM is discussed. We discussed the faced difficulties and a possible generalization of the model.
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Pécot, Jessie. "Dépendance des cellules cancéreuses à BCL-xL : ciblage thérapeutique du réseau d'interactions PUMA, BAX et BCL-xL : effets oncogéniques non canoniques de l'interaction RAS / BCL-xL." Nantes, 2015. https://archive.bu.univ-nantes.fr/pollux/show/show?id=57dfe09c-18e6-4d60-a1e1-cbc567f5cda6.
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La protéine BCL-xL fréquemment surexprimée dans les cancers est impliquée dans la résistance aux chimiothérapies. De nouvelles molécules ciblant cette protéine ont ainsi été développées. Le travail présenté dans le cadre de cette thèse montre que, malgré une spécificité de plus en plus grande de ces molécules, elles restent inefficaces à antagoniser certaines interactions impliquant BCL-xL. Ainsi un traitement au WEHI-539 (ciblant spécifiquement BCL-xL) ne sensibilise pas des cellules surexprimant BCL-xL à une mort dépendante de PUMA, une protéine interagissant avec BCL-xL qui joue un rôle essentiel dans le déclenchement de l'apoptose. Alors que les interactions BAX/BCL-xL répondent au WEHI-539, nos résultats montrent que les interactions PUMA/BCL-xL n'y sont sensibles qu'en dessous d'un certain seuil d'expression de BCL-xL, au-delà duquel la survie des cellules est maintenue par des complexes PUMA/BCL-xL résistants aux BH3-mimétiques. Ces données soulignent l'importance de la compréhension du rôle joué par ce réseau d'interactions impliquant les membres de la famille de BCL-2, en particulier BCL-xL, dans le contexte du développement tumoral. L'autre partie de ce travail est ainsi consacrée à l'étude des conséquences fonctionnelles de l'interaction entre BCL-xL et l'oncogène RAS qui demeurent largement inconnues bien que des travaux lui attribuent des effets oncogéniques. Pour ce faire, nous avons développé des approches de BRET et de pep-scan en vue de mieux caractériser cette interaction d'un point de vue structurel et fonctionnelBCL-xL plays a role in chemoresistance that needs to be overcome. We show here that currently available BH3-mimetics do not efficiently derepress BCL-xL inhibition of BAX-mediated cell death induced by PUMA, a major pro-apoptotic effector of chemotherapy. Live cell measurements of protein-protein interactions reveal that BH3-mimetics readily inhibit BAX interactions with BCL-xL and the effects of BCL-xL on BAX oligomerization but that PUMA interactions with BCL-xL are highly resistant. Thus, PUMA only favors BAX oligomerization/activation and induction of cell death in response to BH3-mimetics when BCL-xL expression is limiting. Mutagenesis studies show that the robustness of PUMA/BCL-xL interactions is due to the avidity of the PUMA BH3 domain for mitochondrial BCL-xL. This has important consequences for the design of strategies combining PUMA-inducing genotoxics and BCL-xL inhibitors, and argues that mitochondrial membranes per se influence treatment outcome. BCL-xL does not only function as guardian of mitochondrial permeability. Non-canonical effects and functions of this protein have been described, as its interaction with the RAS oncogene. Some studies suggest the oncogenic effects of the BCL-xL/RAS interaction. However, its functional consequences remain unknown. So we have used BRET and pep-scan assays in order to structurally and functionally characterize this interaction
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Tidare, Jonatan, and Mattias Bäckström. "A BRAIN-ACTUATED ROBOT CONTROLLER FOR INTUITIVE AND RELIABLE MANOEUVRING." Thesis, Mälardalens högskola, Akademin för innovation, design och teknik, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-31812.
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During this master-thesis a robot controller designed for low-throughput and noisy EEG-data of a Brain Computer Interface (BCI) is implemented. The hypothesis of this master-thesis state that it is possible to design a modular and platform independent BCI-based controller for a mobile robot, which regulates the autonomy of the robot as a function of the user’s will to control. The BCI design is thoroughly described, including both the design choices regarding used brain activity signals and the pre- and post-processing of EEG data. The robot controller is experimentally tested by completing a set of missions in a simulated environment. Both quantitative and qualitative data is derived from the experimental test setup and used to evaluate the controller performance with different levels of induced noise. Additional to the robot control performance result, an offline validation of the BCI performance is depicted. Strength and weaknesses of the system design is presented based on the acquired result, and suggested solutions to improve the over-all performance is given. The produced result show that using the developed controller is a feasible approach for reliable and intuitive manoeuvring of a telepresence robot.
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Suhada, Robert. "The XMM-BCS galaxy cluster survey." Diss., lmu, 2011. http://nbn-resolving.de/urn:nbn:de:bvb:19-132857.
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Al-Zarouni, Mansour. "Expression of recombinant antigen in BCG." Thesis, University of Surrey, 2000. http://epubs.surrey.ac.uk/843308/.
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Little is known about the effect of different modes of expression of an antigen in rBCG on immune response. An appropriate wing of the immune system, with different degrees, is activated upon encounter with a foreign antigen. Knowledge of these responses is vital to the development of future recombinant vaccine. Various E. coli-mycobacterial species shuttle vector constructs were made using a combination of mycobacterial promoters and signal sequences. Thus enabling foreign antigens to be expressed cytoplasmically or secreted outside rBCG as native proteins or membrane-associated lipoproteins. A pivotal study using an E. coli beta-lactamase as a reporter gene is described for the evaluation of the strength of promoter and signal sequence constructs both in vitro and most importantly in vivo using the mouse macrophage cell line J-774. Expression of the diphtheria toxin fragment B as a foreign antigen was detected in vitro with all constructed plasmid vectors in rBCG using a western blot as a means of detection. It was observed that all hsp60 promoter-based constructs exhibited a high frequency with variable degree of plasmid DNA deletions Using three different rBCG substrains, the BCG Tokyo was found to be more stable (P < 0.01) and exhibited less degree of deletion (P < 0.001) compared to either BCG Moreau or BCG Pasteur. Sequence analysis of deleted plasmid DNA revealed a specific region common with nearly all plasmid deletions. Such a region of the DNA was found to correspond to the first transcriptional starting site of the hsp60 promoter. Furthermore no differences were observed in the level of expression among the three-rBCG substrains, retaining plasmid DNA, when detected by immunoblotting.
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Cerrito, Stefano. "Thermodynamics of the BCS-BEC crossover." kostenfrei, 2007. http://mediatum2.ub.tum.de/doc/623023/document.pdf.
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