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1
Costa, Filipa Barbosa da. "Modelo de planeamento – GDH de ambulatório". Master's thesis, FCT - UNL, 2009. http://hdl.handle.net/10362/3384.
Testo completoAbstract (sommario):
Dissertação apresentada na Faculdade de
Ciências e Tecnologia da Universidade Nova de
Lisboa para obtenção do grau de Mestre em
Engenharia BiomédicaA Administração Central do Sistema de Saúde (ACSS), é uma entidade do Sistema Nacional de Saúde que tem como principal missão a gestão dos recursos humanos e financeiros bem como promover a qualidade organizacional das entidades prestadoras de saúde. O Modelo de Planeamento criado pela Siemens SA surge como o sistema de informação que vem colmatar a falta de informação necessária para a ACSS fazer um ajuste adequado dos recursos à procura por parte da população. No entanto, o mercado onde o Modelo se insere caracteriza-se por estar em constante alteração/actualização exigindo ao Modelo a necessidade de se adaptar para continuar a responder adequadamente. No seguimento desta necessidade surge este trabalho com o principal objectivo de adequar o Modelo à recente criação do conceito de Grupo de Diagnóstico Homogéneo (GDH) para Ambulatório. O conceito de GDH surgiu no mercado da saúde como um sistema de classificação de episódios agudos, associados a Internamento, sendo ainda utilizado para definir operacionalmente a produção de um Hospital. A adaptação deste conceito ao Ambulatório surge na consequência da evolução tecnológica permitir, no presente,tratar doentes num período inferior a 24 horas. Pela análise do impacto do conceito no Modelo, realizado no projecto, foi possível confirmar que o problema está no facto de ser a base de dados dos GDHs que alimenta o Internamento no Modelo, levando a que GDHs de Ambulatório fossem introduzidos erradamente nesta linha de produção. Para corrigir esta situação foi crucial estabelecer regras que impedissem a entrada desses episódios em Internamento. Desta forma, a partir da ferramenta Oracle Warehouse Builder, responsável pela manipulação da informação no Modelo, aplicaram-se as regras necessárias para transferir estes dados, considerando o tempo de internamento e o próprio GDH. Para além da actualização do Modelo ao conceito de GDH Ambulatório foi possível trabalhar a outros níveis promovendo um sistema de informação de qualidade, actual e de alta contribuição para quem é responsável pela distribuição e afectação de recursos no sistema de saúde.
2
Leitão, Alexandre Felipe. "Expressão genética de Gase, GSase e GDH em Misgurnus anguillicaudatus". Master's thesis, Universidade de Aveiro, 2009. http://hdl.handle.net/10773/851.
Testo completoAbstract (sommario):
Mestrado em Biologia MarinhaMuitos peixes conseguem sobreviver a elevados níveis de amónia ambiental; entre eles está o Misgurnus anguillicaudatus, este peixe tem também a capacidade invulgar de volatilizar a amónia. Uma dos métodos de tolerar níveis elevados de amónia é através da regulação do metabolismo da glutamina. As reacções de catabólise e anabólise deste metabolismo são catalizadas pela glutaminase (Gase), glutamina sintetase (GSase) e glutamato deshidrogenase (GDH) e permitem o consumo ou síntese de amónia. Estas reacções metabólicas poderão estar à volatilização da amónia no intestino do Misgurnus anguillicaudatus. O objectivo deste trabalho consistia em caracterizar a expressão dos três genes e do seu possível envolvimento na tolerância e volatilização da amónia. A expressão genética foi analisada no decurso de duas experiências. Numa primeira vários tecidos (cérebro, guelra, rim, fígado, e três partes do intestino), de animais controlo, seriam analisados de forma a determinar uma linha base da expressão dos genes. Na segunda experiência os níveis de expressão genética, para os três genes, em duas porções do intestino (intestino anterior e posterior), de animais expostos a elevados níveis de amónia ambiental, seriam quantificados ao longo do tempo para poder determinar possíveis alterações na expressão. Adicionalmente conduzir‐se‐ia a análise das sequências genéticas e comparação filogenética das sequências obtidas no decurso do trabalho. Os resultados da sequenciação mostraram elevada identidade entre as sequências do Misgurnus anguillicaudatus e os seus homólogos noutras espécies, mas na maior parte dos casos também havia distanciação evolutiva entre as sequências das espécies. Os resultados da expressão genética nos vários tecidos mostraram níveis significativamente elevados para a expressão da Gase e GSase no cérebro, estando de acordo com a importância destas enzimas na reciclagem do glutamato e na eliminação de amónia neste órgão. A expressão dos genes no intestino em resposta à exposição à amónia ao longo do tempo n mostraram alterações significativas, isto sugere que o metabolismo da glutamina não é importante para o processo de volatilização ou que regulação não se dá ao nível da transcrição. ABSTRACT: Many fishes are able to cope with high levels of environmental ammonia; among them is the oriental weatherloach (Misgurnus anguillicaudatus), which also has the unusual ability to volatilize ammonia. One proposed method of ammonia tolerance in this species is through the regulation of the glutamine metabolism. Glutaminase (Gase), glutamine synthetase (GSase) and glutamate dehydrogenase (GDH) catalyze reaction in which catabolysis and anabolysis lead to the release or consumption of ammonia, and can possibly be associated with ammonia volatilization in the gut of the weatherloach. This work intended to characterize the expression of these three genes and their possible involvement in ammonia tolerance and ammonia volatilization in the gut of the weatherloach. In order to determine the gene expression levels two experiments were analyzed separately. In one, several tissue samples (brain, gill, liver, kidney and three portions of gut) from control animals would be analyzed in order to determine baseline expression levels of the three genes. In the second experiment gene expression levels for the three genes in two sections of the gut (foregut and hindgut) from animals that had been exposed to high environmental ammonia over time would be analyzed in order to determine possible changes in gene expression. Additionally gene sequence analysis and phylogenic comparison would be carried out on the gene sequences obtained during the work. Sequencing results showed high identity between weatherloach and their homologues in other species for each gene, but in most cases with significant evolutionary branching from other species. The results for gene expression in several tissues showed significantly elevated levels of gene expression for Gase and GSase in the brain, which correlates with the importance of these enzymes in glutamate recycling and ammonia detoxification in this organ. The results for gene expression in gut in response to ammonia exposure over time showed no significant changes suggesting that glutamine metabolism is not important in ammonia volatilization or that regulation is not at the transcriptional level.
3
Heyer, Narinder Isabel. "Glucose dehydrogenase from the hyperthermophilic archaeon Sulfolobus solfataricus". Thesis, University of Bath, 1999. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301967.
Testo completo
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Rose, Andreas. "Analysis of phenolic compounds by dint of GDH-biosensors and immunoassays". Phd thesis, [S.l. : s.n.], 2003. http://pub.ub.uni-potsdam.de/2004/0004/rose.pdf.
Testo completo
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Heid, Erik. "Erste Untersuchungen zur Messung helizitätsabhängiger ([gamma]-N)- Wirkungsquerschnitte [Gamma N Wirkungsquerschnitte] für das GDH-Experiment am MAMI". [S.l. : s.n.], 2000. http://ArchiMeD.uni-mainz.de/pub/2001/0040/diss.pdf.
Testo completo
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Sulkosky, Vincent Anthony. "The spin structure of helium-3 and the neutron at low momentum transfer: A measurement of the generalized GDH integrand". W&M ScholarWorks, 2007. https://scholarworks.wm.edu/etd/1539623521.
Testo completoAbstract (sommario):
Since the 1980's, the study of nucleon (proton or neutron) spin structure has been an active field both experimentally and theoretically. One of the primary goals of this work is to test our understanding of Quantum Chromodynamics (QCD), the fundamental theory of the strong interaction. In the high energy region of asymptotically free quarks, QCD has been verified. However, verifiable predictions in the low energy region are harder to obtain due to the complex interactions between the nucleon's constituents: quarks and gluons. In the non-pertubative regime, low-energy effective field theories such as chiral perturbation theory provide predictions for the spin structure functions in the form of sum rules.;Spin-dependent sum rules such as the Gerasimov-Drell-Hearn (GDH) sum rule are important tools available to study nucleon spin structure. Originally derived for real photon absorption, the Gerasimov-Drell-Hearn (GDH) sum rule was first extended for virtual photon absorption in 1989. The extension of the sum rule provides a unique relation, valid at any momentum transfer ( Q2), that can be used to study the nucleon spin structure and make comparisons between theoretical predictions and experimental data.;Experiment E97-110 was performed at the Thomas Jefferson National Accelerator Facility (Jefferson Lab) to examine the spin structure of the neutron and 3He. The Jefferson Lab longitudinally-polarized electron beam with incident energies between 1.1 and 4.4 GeV was scattered from a longitudinally or transversely polarized 3He gas target in the Hall A end station. Asymmetries and polarized cross-section differences were measured in the quasielastic and resonance regions to extract the spin structure functions g1(x, Q2) and g2(x, Q2) at low momentum transfers (0.02 < Q2 < 0.3 GeV2). The goal of the experiment was to perform a precise measurement of the Q2 dependence of the extended GDH integral and of the moments of the neutron and 3He spin structure functions at low Q2. This Q 2 range allows us to test predictions of chiral perturbation theory and check the GDH sum rule by extrapolating the integral to the real photon point. This thesis will discuss preliminary results from the E97-110 data analysis.
7
Díaz, González Susana. "NAD-glutamato deshidrogenasa de Haloferax mediterranei: clonaje, secuenciación y expresión. Purificación y propiedades de la enzima nativa y recombinante". Doctoral thesis, Universidad de Alicante, 2004. http://hdl.handle.net/10045/1301.
Testo completo
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Barker, Douglas Shaw. "Biochemical characterization of the Pythium ultimum NAD-GDH and genetic analysis of associated genomic regions in Pythium ultimum and Achlya klebsiana". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ32875.pdf.
Testo completo
9
Silva, Priscilla Muniz Ribeiro da. "Caracterização molecular e funcional da enzina glutamato desidrogenase (GDH) em Ilhotas de ratos submetidos à restrição protéica e suplementados com leucina". [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314193.
Testo completoAbstract (sommario):
Orientador: Everardo Magalhães CarneiroTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-18T10:36:45Z (GMT). No. of bitstreams: 1 Silva_PriscillaMunizRibeiroda_D.pdf: 2752788 bytes, checksum: a2b912ed65ab26f33708f44d094db90a (MD5) Previous issue date: 2011
Resumo: A glutamato desidrogenase (GDH) é uma enzima mitochondrial que cataliza a reação reversível de glutamato a ?-cetoglutarato. Nas ilhotas pancreáticas, está associada com a secreção de insulina por aumentar a concentração de ATP. Ratos alimentados com dieta hipoprotéica apresentam secreção de insulina diminuída. A suplementação com leucina (LEU) aumenta a secreção de insulina em resposta a agentes insulinotrópicos. O presente estudo investigou a influência da suplementação com LEU na expressão da GDH e seu envolvimento com a secreção de insulina em ratos desnutridos e suplementados com LEU. Ratos machos foram alimentados com dietas normo- (17%, NP) ou hipoprotéicas (6%, LP) por oito semanas. Após, foram divididos e suplementados com LEU (1,5%) na água de beber (NPL e LPL) pelas quatro semanas seguintes. O conteúdo protéico de GDH no cérebro, fígado, rim e músculo esquelético não diferiu entre os grupos. Nas ilhotas LP, a expressão da GDH estava diminuída e a suplementação com LEU aumentou a expressão de RNAm restaurando o conteúdo protéico a valores similares a NP. A secreção de insulina estimulada por agentes insulinotrópicos ou inibidores, combinados ou não, estava diminuída em ilhotas LP comparada com NP. A suplementação com LEU aumentou a secreção de insulina a valores similares a NP, exceto quando as ilhotas LPL foram incubadas com EGCG. Ilhotas LP tiveram diminuição na [Ca2+]i quando expostas a GLN+BCH. A suplementação com LEU restaurou esses parâmetros aos valores de NP. Frente a esses resultados, podemos concluir que a diminuição na expressão da GDH induzida pela dieta LP foi central ao pâncreas endócrino e está associada à redução da secreção de insulina observada nas ilhotas LP. A suplementação com LEU foi capaz de restaurar a expressão da GDH, contribuindo para o aumento da secreção de insulina observado nas ilhotas LPL. Além disso, a GDH pode, ainda, estar associada com a secreção de insulina pelo acoplamento estímulo/secreção via regulação da [Ca2+]i
Abstract: Glutamate dehydrogenase (GDH) is a mitochondrial matrix enzyme that catalyzes the reversible reaction of glutamate to ?-ketoglutarate. In the pancreatic islets, this enzyme is associated with insulin secretion by augmenting ATP levels. Protein malnourished rats displayed reduced insulin secretion. Leucine (LEU) supplementation augments the insulin secretion response to insulinotropic agents. The present study investigated the influence of LEU supplementation on GDH expression and its involvement with insulin secretion in malnourished rats supplemented with LEU. Male rats were fed normal- (17%, NP) or low-protein diet (6%, LP) for eight weeks. Half of rats of each group were supplemented with LEU (1.5%) in drinking water for the following four weeks (NPL and LPL groups). GDH protein content in brain, liver, kidney and skeletal muscles was not different in any group. GDH RNAm and protein content was reduced in LP islets and LEU supplementation augmented RNAm expression restoring protein content similar to NP. Insulin secretion was reduced in LP islets compared with NP when stimulated by insulinotropics agents or inhybitors, combinaned or not. LEU supplementation augmented insulin secretion to similar values as NP, an effect that was blunted when LPL islets were incubated with EGCG. LP islets showed lower [Ca2+]i when exposed to GLN+BCH. LEU supplementation augmented these patterns similar to NP. Taken together, we may conclude that diminution in GDH expression induced by LP diet was central to endocrine pancreas and was associated with reduced insulin secretion observed in LP rats. LEU supplementation was able to restore GDH expression and it was capable to restore insulin secretion via GDH restoration. Yet, GDH may contribute to insulin secretion via Ca2+ regulation stimulus/secretion coupling
Doutorado
Fisiologia
Doutor em Biologia Funcional e Molecular
10
Martins, Tânia Sofia Teixeira. "O perfil fármaco terapêutico". Master's thesis, Instituto Superior de Economia e Gestão, 2014. http://hdl.handle.net/10400.5/8592.
Testo completoAbstract (sommario):
Mestrado em Decisão Económica e EmpresarialA insuficiência cardíaca é uma doença associada a altas taxas de mortalidade e de internamentos, que afecta sobretudo a população com mais de 65 anos. A sua prevalência encontra-se em crescimento em diversos países, devido em grande parte ao incremento na esperança de vida e ao desenvolvimento de medicamentos mais eficazes. Diversos estudos sugerem que os internamentos hospitalares constituem o principal fator para o aumento dos custos de tratamento associados a esta patologia e, como tal, seria benéfico a definição de estratégias para a sua redução. O objectivo deste trabalho é comparar o consumo de medicamentos dentro dos mesmos Grupos de Diagnósticos Homogéneos (GDH) em hospitais diferentes, nomeadamente o Hospital Garcia de Orta e o Hospital Prof. Dr. Fernando Fonseca. Para tal, foram utilizados métodos de regressão linear múltipla para investigar a influência de diversas variáveis que descrevem o episódio de internamento sobre o custo com medicamentos. Os resultados sugerem que o consumo de medicamentos nos dois hospitais é similar para um dado GDH, o que é uma das questões fulcrais deste estudo. Após a análise de dados, apurámos através da análise exploratória e ajuste de modelos que os custos com medicamentos aumenta em média com o número de dias de internamento, sendo isso mais notório para o Hospital Garcia da Orta. No entanto, a idade e o sexo não parecem ter um efeito apreciável no custo. Adicionalmente, em algumas regressões foi encontrada evidência de heterocedasticidade, problema que teve de ser solucionado através da estimação robusta de White.
Heart failure is a disease associated with high mortality rates and hospital admissions. It mostly affects the population aged 65 or more and its prevalence is growing in many countries, mainly due to the increase of life expectancy and the development of new and more effective treatments. Previous research suggests that a large proportion of the treatment's cost of this pathology is comprised of hospital internments. Thus, it would be of interest to set out strategies to its reduction. The purpose of the present study is to compare the associated with cost of medication within the same Diagnosis Related Groups (DRG) in different hospitals, namely in Hospital Garcia da Orta and Hospital Prof. Dr. Fernando Fonseca. To do so, we use multiple linear regression methods to select the variables that explain the medicines' cost. The results suggest that a patient of a given DRG uses approximately the same resources regardless of the hospital where (s)he receives medical assistance. Thus, we conclude the cost associated with medication is the same for a given DRG. In addition, we find that the average associated with medication increases with the length of stay. This seems to be particularly true for Hospital Garcia da Orta. On the other hand, explanatory variables such as age and sex do not seem have a significant effect in the medication cost. To correct the standard errors for the presence of heteroskedasticity we used White's robust covariance matrix.
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Msatef, Yamina. "Différenciation des organes agrégés chez le champignon ascomycète sphaerostilbe repens : aspects enzymatiques et moléculaires concernant la synthèse protéique et la régulation de la glutamate deshydrogénase à NADP". Nancy 1, 1990. http://www.theses.fr/1990NAN10459.
Testo completoAbstract (sommario):
Chez sphaérostilbe repens, la GDH à NADP joue le rôle clef dans l'assimilation de l'ammonium. Cette enzyme a une conformation voisine de celle des autres GDH issues d'organismes taxonomiquement proches de sphaerostilbe repens. Les expériences de marquages radiochimiques des protéines montrent que la synthèse de la GDH est faible sur un milieu contenant de l'urée et sa dégradation est plus active. Au contraire, le glutamate favorise la synthèse de l'enzyme. Une forte activité moléculaire de la GDH est enregistrée au moment de la formation des unités agrégées. Par contre, sa quantité dans le thalle est maximale dans le mycélium végétatif. La quantité des ARNM de l'enzyme demeure constante pendant la morphogénèse suggérant que la régulation de l'enzyme s'effectue au niveau traductionnel. La différenciation des organes agrégés s'accompagne d'une stimulation de la synthèse protéique concernant l'ensemble des polypeptides du mycélium végétatif. Cependant, trois polypeptides sont spécifiquement synthétisés pendant la morphogénèse à la suite de l'apparition de leurs ARNM. Une banque D'ADNC a été construite dans le but de vérifier si les ARNM spécifiques sont les produits de gènes exprimés pendant la morphogénèse
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Lang, Michael. "Aufbau des GDH-Experiments und Messung der Helizitätsabhängigkeit von [gamma]p-> pp+p- [gamma p p pi + pi-] von der Schwelle bis 800 MeV". [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=971983550.
Testo completo
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Chalot, Michel. "Assimilation de l'ammonium par les ectomycorhizes d'épicéa (picea excelsa) et par quelques symbiotes fongiques (hebeloma cylindrosporum et laccaria laccata)". Nancy 1, 1992. http://www.theses.fr/1992NAN10056.
Testo completoAbstract (sommario):
Le rôle essentiel de la glutamate déshydrogénase et de la glutamine synthétase dans l'assimilation de l'ammonium par les ectomycorhizes d'épicéa ont été démontré par l'utilisation de l'isotope 15 de l'azote. L'importance du marquage dans les fonctions amide et amine de la glutamine et dans la fonction amine du glutamate en présence ou en absence de méthionine sulfoximine, inhibiteur de la GS, démontre l'intervention de la séquence gdh/gs. La synthèse d'alanine est aussi une voie importante de mobilisation de l'azote exogène dans les ectomycorhizes d'épicéa. L'importance de ces deux enzymes a été confirmée chez les champignons basidiomycètes ectomycorhiziens par l'utilisation d'un mutant déficient en GDH à NADP d'hebeloma cylindrosporum. Les caractéristiques physico-chimiques ainsi que les propriétés fonctionnelles de la GS et de la GDH à NADP ont été étudiées chez laccaria laccata, chez lequel elles ont été purifiées à homogénéité électrophorétiques. L'ensemble de ces résultats accordent un rôle prépondérant à la séquence GDH/GS chez les mycorhizes et leurs symbiotes fongiques
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Sene, Ndiaga. "Implication du métabolisme azoté dans la relation plante-insecte : étude des fluctuations des enzymes glutamine synthétase (GS) et glutamate déshydrogénase (GDH) chez le couple Solanum tuberosum-Myzus persicae". Amiens, 2009. http://www.theses.fr/2009AMIE0119.
Testo completoAbstract (sommario):
Myzus persicae l’un des ravageurs des cultures de pomme de terre, s’alimente exclusivement aux dépens du compartiment phloémien des végétaux. Le phloème est la voie principale pour la translocation à distance des photoassimilats et sa sève est riche en sucres et particulièrement en saccharose. La sève élaborée est composée aussi de nombreux acides aminés libres dont les concentrations relatives sont fortement déséquilibrées avec en particulier une faible proportion d’acides aminés essentiels. Nous avons, dans un premier temps, montré une augmentation des activités enzymatiques de la Glutamine synthétase (GS) et de la Glutamate déshydrogénase (GDH) au cours du développement qui est confirmée par des westerns-blots et des études immunohistochimiques montrant une présence quasi exclusive des protéines GS1 et GDH dans les cellules compagnes de phloème. A la suite de l’étude du statut de ces enzymes à l’échelle de la plante et au cours du développement, nous avons montré un réel effet de l’infestation par Myzus persicae sur la GS et la GDH qui sont deux des enzymes clés impliquées probablement dans la synthèse des acides aminés et dans le contrôle de la réorientation fine des métabolismes carboné et azoté. L’induction de ces enzymes est uniquement locale comparée aux changements observés des métabolites qui sont affectés aussi bien au niveau locale que systémique. L’ensemble des changements induits par les pucerons laisse penser qu’ils sont capables de modifier la composition nutritionnelle du phloème à leur profit en vue d’une augmentation qualitative et quantitative en acides aminés. Nos observations montrent également qu’une altération du métabolisme azoté, induite par transgénèse ou mutagenèse, a un effet net sur le comportement alimentaire des aphides étudiésMyzus persicae which is one of the potato cultures devastators, feeds exclusively on plants phloem compartment. The phloem is the main route for the long-distance transport of photoassimilates and its sap is rich in sugars, particularly, in sucrose. The elaborated phloem sap is also composed of numerous free amino acids, and the relative concentrations of those are strongly unbalanced, which concerns, in particular, a small proportion of essential amino acids. At first, we have shown an increase in the enzymatic activities of the glutamine synthetase (GS) and the glutamate dehydrogenase (GDH) during the plant development, which has been confirmed by the western-blots and immunohistochemical study. The latter has shown the almost exclusive presence of the GS1 and GDH proteins in phloem companion cells. A study of these enzymes status on the scale of the plant and during plant development has shown a real effect of M. Persicae infection on the GS and GDH, which are two key enzymes probably involved in amino acids synthesis and in the control of fine reorientation of carbon and nitrogenous metabolisms. The induction of these enzymes appears only on the local level as compared to the observed changes of metabolites which are affected on both local and systematic levels. All changes inducted by the aphids suggest that the aphids are able to modify the nutritional composition of phloem in order to gain in qualitative and quantitive increase in amino acids. Our observations have also shown that the change in nitrogenous metabolism, inducted by transgenesis or mutagenesis, has a clear effect on the alimentary habits of the studied aphids
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Castro, Marin Inmaculada. "Nitrate: metabolism and development : characterization of the glutamate dehydrogenase (GDH) family, an enzyme at the cross-roads of carbon-nitrogen interaction metabolites and study of the regulation of flowering by nitrogen". Phd thesis, Universität Potsdam, 2007. http://opus.kobv.de/ubp/volltexte/2008/1882/.
Testo completoAbstract (sommario):
The major aim of this thesis was to study the effect of nitrate on primary metabolism and in development of the model plant Arabidopsis thaliana.
The present work has two separate topics. First, to investigate the GDH family, a small gene family at the interface between nitrogen and carbon metabolisms. Second, to investigate the mechanisms whereby nitrogen is regulating the transition to flowering time in Arabidopsis thaliana.
To gain more insights into the regulation of primary metabolism by the functional characterization of the glutamate dehydrogenase (GDH) family, an enzyme putatively involved in the metabolism of amino acids and thus suggested to play different and essential roles in carbon and nitrogen metabolism in plants, knock out mutants and transgenic plants carrying RNA interference construct were generated and characterized. The effect of silencing GDH on carbon and nitrogen metabolisms was investigated, especially the level of carbohydrates and the amino acid pool were further analysed. It has been shown that GDH expression is regulated by light and/or sugar status therefore, phenotypic and metabolic analysis were developed in plants grown at different points of the diurnal rhythm and in response to an extended night period.
In addition, we are interested in the effect of nutrient availability in the transition from vegetative growth to flowering and especially in nitrate as a metabolite that triggers widespread and coordinated changes in metabolism and development. Nutrient availability has a dramatic effect on flowering time, with a marked delay of flowering when nitrate is supplied (Stitt, 1999).
The use of different mutants and transgenic plants impaired in flowering signalling pathways was crucial to evaluate the impact of different nitrate concentrations on flowering time and to better understand the interaction of nitrate-dependent signals with other main flowering signalling pathways. Plants were grown on glutamine as a constitutive source of nitrogen, and the nitrate supply varied. Low nitrate led to earlier flowering. The response to nitrate is accentuated in short days and in the CONSTANS deficient co2 mutant, whereas long days or overexpression of CONSTANS overrides the nitrate response. These results indicate that nitrates acts downstream of the known flowering signalling pathways for photoperiod, autonomy, vernalization and gibberellic acid.
Global analyses of gene expression of two independent flowering systems, a light impaired mutant (co2tt4) and a constitutive over-expresser of the potent repressor of flowering (35S::FLC), were to be investigated under two different concentrations of nitrate in order to identify candidate genes that may be involved in the regulation of flowering time by nitrate.Das Hauptziel dieser Doktorarbeit war die Untersuchung des Effekts von Stickstoff auf den Primärmetabolisms und auf die Entwicklung der Modellpflanze Arabidopsis thaliana. Die vorliegende Arbeit hat zwei Unterthemen: Auf der einen Seite wurde die GDH Familie untersucht, eine kleine Genfamilie an der Schnittstelle zwischen Stick –und Kohlenstoffmetabolismus. Auf der anderen Seite wurde der Mechanismus, bei dem Stickstoff die Blütezeit in Arabidopsis thaliana kontrolliert, untersucht. Um einen tieferen Einblick in die Regulierung des Primärmetabolismus zu erhalten, wurde eine funktionelle Charakterisierung der Glutamatdehydrogenase-Familie (GDH) mit Hilfe von knock-out Mutanten und transgenen Pflanzen, die ein RNA Interferenzkonstrukt tragen, durchgeführt. GDH ist höchstwahrscheinlich am Aminosäuremetabolismus beteiligt, wobei vermutet wird, dass es verschiedene wichtige Aufgaben im Pflanzenkohlen –und stickstoffmetabolismus übernimmt. Dabei wurde der Effekt des GDH Silencing auf den Kohlen- sowie Stickstoffmetabolismus untersucht und insbesondere die Anteile von Kohlenhydraten und Aminosäuren eingehend analysiert. In vorhergehenden Studien zeigte sich, dass die GDH-Expression durch Licht und/oder die Zuckerverfügbarkeit reguliert wird. Deshalb wurden phenotypische und metabolische Analysen an Pflanzen entwickelt, die zu verschiedenen Zeitpunkten des diurnalen Rhythmus und nach einer längeren Nachtperiode gezüchtet wurden. Ausserdem interesssiert uns der Effekt der Nährstoffverfügbarkeit im Übergang vom vegetativen Wachstum zur Blüte, und vor allen Dingen Nitrat als Metabolit, welches weitreichende und koordinierte Veränderungen im Metabolismus und in der Entwicklung hervorruft. Die Nährstoffverfügbarkeit hat einen dramatischen Effekt auf die Blütezeit, insbesondere führt eine Nitratzugabe zu einer deutlichen Verzögerung der Blüte (Stitt, 1999). Der Einsatz von verschiedenen Mutanten und transgenen Pflanzen, die eine Blockade im Blüte-Signalweg aufwiesen, war ausschlaggebend, um den Einfluss von unterschiedlichen Nitratkonzentrationen auf die Blütezeit zu beurteilen, und um zu einem besserem Verständnis des Zusammenspiels von nitratabhängigen Signalen und anderen Blüte-Signalwegen zu gelangen. Die Pflanzen wuchsen auf Glutamin, das als konstitutive Stickstoffquelle diente, wobei die Nitratversorgung variierte. Niedriger Nitratanteil führte zu einer früheren Blüte. Bei kurzer Tageslänge und bei CONSTANS defizienten Mutanten (co2) ist die Reaktion auf Nitratzugabe erhöht, wohingegen bei fortgeschrittener Tageslänge oder bei Überexpression von CONSTANS die Reaktion auf Nitrat unterbleibt. Diese Ergebnisse verdeutlichen, dass Nitrat unterhalb der bekannten Blüte-Signalwege für Photoperiode, Autonomie, Vernalisierung und Gibberelinsäure fungiert. Globale Expressionsanalysen von zwei unterschiedlichen Blütensystemen, eine licht-unempfindliche Mutante (co2tt4) und eine Mutante mit konstitutiver Expression eines potentiellen Blüte-Repressors (35S::FLC), wurden bei zwei verschiedenen Nitratkonzentrationen durchgeführt, um Kandidatengene zu identifizieren, die eine wichtige Rolle in der Regulation der Blütezeit durch Nitrat spielen könnten.
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Cerato, Evelyne. "Repertoire d'anticorps murins diriges contre les gangliosides gd2 et gd3 : production et caracterisation d'un fragment d'anticorps recombinant colorimetrique anti-gd2". Nantes, 1997. http://www.theses.fr/1997NANT02VS.
Testo completo
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Martins, Juliana. "Caracterização molecular de isolados de Giardia spp. provenientes de amostras fecais de origem humana da Baixada Santista, estado de São Paulo, pela análise de fragmentos do gene codificador da glutamato desidrogenase (gdh) e beta-giardina (bg)". Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/10/10134/tde-14122011-115047/.
Testo completoAbstract (sommario):
Giardia duodenalis é um protozoário entérico de distribuição mundial responsável por causar a giardíase em uma grande variedade de mamíferos, incluindo os humanos. É considerada uma espécie complexa, no qual os isolados podem ser classificados em sete agrupamentos genéticos distintos apesar de serem morfologicamente indistinguíveis. O presente trabalho teve como objetivo avaliar a variabilidade genotípica de isolados de G. duodenalis provenientes de humanos naturalmente infectados, residentes em cidades do litoral de São Paulo, na Baixada Santista. A caracterização molecular de 43 isolados pelo seqüenciamento parcial de genes codificadores da enzima glutamato-desidrogenase (gdh) e da proteína beta-giardina (bg) mostrou que o assemblage B da G. duodenalis é o mais freqüente na região litorânea, ocorrendo em 53,5% (n=23) das amostras, sendo o assemblage A identificado em 34,8% (n=15). A maioria das seqüências obtidas pelo gene gdh se mostrou polimórfica, caracterizada por picos duplos de nucleotídeos em algumas posições em cromatograma e quando a análise dos dois genes foi combinada cinco isolados apresentaram identidades diferentes. A esses fenômenos duas explicações são atribuídas, infecção mista ou heterozigose de seqüência alélica. As análises filogenéticas mostraram que o gene bg é mais conservado que o gene gdh, não sendo capaz de discriminar os sub-agrupamentos que constituem os Assemblages do parasita. Com base nos resultados apresentados podemos concluir que a participação de genótipos zoonóticos é relevante na epidemiologia das giardíases nos indivíduos residentes das cidades litorâneas do estado de São Paulo e que estudos de caracterização molecular da G. duodenalis são indispensáveis para melhor conhecimento da epidemiologia desta infecção.Giardia duodenalis is an enteric protozoa of global distribution responsible for causing giardiasis in a wide range of mammals including humans. Is considered complex specie in which the isolates can be classified in different genetic groups despite to be morphologically indistinguishable. The purpose of this study was evaluating the genetic variability of G. duodenalis isolates from humans naturally infected residents in the coast cities of Sao Paulo, in Baixada Santista. The molecular characterization of 43 isolates using the gene encoding glutamate-desidrogenasi enzyme (gdh) and beta-giardin protein (bg) showed that the assemblage B is the most common in the coast region, occurring in 53.5% (n=23) samples, the assemblage A was identified in 34.8% (n=15). Most sequences obtained by the gdh gene showed polymorphism, characterized for double peaks of nucleotides in some chromatogram positions and when the analysis of two genes was combined five isolates were differently identified. For this phenomena can be attributed two explanations, mixed infections or heterozygosis allelic sequence. The phylogenetic analysis showed that bg gene is more conserved than gdh gene, not being able to discriminate the sub-groups of parasite assemblages. Based on the presented results we can conclude the participation of zoonotic genotypes is important in the epidemiology of giardiasis in residents of the coast cities of Sao Paulo state and molecular characterization studies of G. duodenalis are essential for better understanding the epidemiology of this infection.
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Rintala, Jonathan, e Erik Skogetun. "Designing a Mobile User Interface for Crowdsourced Verification of Datasets". Thesis, KTH, Skolan för elektroteknik och datavetenskap (EECS), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-239035.
Testo completoAbstract (sommario):
During the last decade machine learning has spread rapidly in computer science and beyond, and a central issue for machine learning is data quality. This study was carried out in the intersection of business and Human-Computer Interaction, examining how an interface may be developed for crowdsourced verification of datasets.The interface is developed for efficiency and enjoyability through research on areas such as usability, information presentation models and gamification. The interface was developed iteratively, drawing from needs of potential users as well as the machine learning industry. More specifically, the process involved a literature study, expert interviews, a user survey on the Kenyan market and user tests. The study was divided into a conceptual phase and a design phase, each constituting a clearly bounded part of the study with a prototype being developed in each stage. The results of this study give an interesting insight on what usability factors are important when designing a practical tool-type mobile application, while balancing efficiency and enjoyability. The resulting novel interface indicated on a more effective performance than a conventional grid layout and is more enjoyable to use according to the users. In addition, the ‘rapid serial visual presentation’ can be deemed a well-functioning model for tool-type mobile applications which require a high amount of binary decisions on short time. The study highlights the importance of iterative, user-driven processes, allowing a new innovation or idea to merge with the needs and skills of users. The results may be of interest to anyone developing tool-type mobile applications and certainly if binary decision making on images is central.Studien implementerar en utvecklingsprocess inspirerad av design thinking metodologi, och undersöker således gränslandet mellan ekonomi och människa-dator interaktion. Initialt undersöks affärsmöjligheter för mobila crowdsourcing applikationer i en Östafrikansk kontext, och baserat på resultaten av denna förstudie, utvecklas ett interface för mobil crowdsourcing. Interfacet ämnar hantera verifikation av bildbaserade dataset genom att samla in beslut från användarna. Målet var att designa för två huvudkriterier - njutbarhet och effektivitet, vilket uppnåddes genom efterforskning inom användbarhet, speed-reading metodologier och gamificationprinciper. Interfacet utvecklades iterativt, baserat på krav från potentiella användare, såväl som input från maskininlärningsindustrin. Mer specifikt involverade processen en litteraturstudie, expertintervjuer, en användarstudie på den Kenyanska marknaden och iterativa användartester. Den konceptuella fasen handlade om att identifiera problemet och leverera en relevant idé av hur lösningen skulle utformas. Således togs ett novellt ”Touch-Hold-Release”- interface fram. Resultaten av denna studie ger en intressant insikt i vilka usabilityfaktorer som är viktiga vid design av en praktisk arbetsinriktad applikation, samtidigt som effektivitet och njutbarhet balanseras. Det novella interfacet som tagits fram indikerar på en mer effektiv prestanda än den konventionella grid-layouten och är mer njutbar att använda enligt användarna. Dessutom kan ‘rapid serial visual presentation’ anses vara ett väl fungerande modell för arbetsinriktade mobilapplikationer som kräver stora mängder binära beslut på kort tid. Studien understryker vikten av att arbeta iterativt, med användarfokuserade processer som tillåter nya innovationer och idéer att möta användarnas faktiska behov och kunskaper. Resultaten kan vara av intresse för den som utvecklar en arbetsinriktad mobilapplikation och särskilt då binärt beslutsfattande är fundamentalt.
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Jonsson, Sara. "Gender Inequality, GDP per capita and Economic Growth". Thesis, Internationella Handelshögskolan, Högskolan i Jönköping, IHH, Nationalekonomi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-15339.
Testo completoAbstract (sommario):
The purpose of this thesis is to investigate the effects of gender inequality on GDP and GDP per capita. A cross sectional analysis of 177 countries over the time period 1998 to 2008 is undertaken with the use of linear regressions. There are several different factors that contribute to the gender inequality within a country and several ways to measure that disparity. The most well known measurement is the Gender-related Development Index and the components within this composite index have been studied thoroughly, although the index as a whole has not. This thesis then contributes with an overall view of how the gender inequality is important for the GDP and GDP per capita. The findings illustrate how significant equality between the genders is for the economy, irrespective of the human development level within the countries. The implication of this is that gender equality is important for the GDP and GDP per capita, which is in accordance with the theories. One large issue is that there is no way of confirming the way of causality between gender equality and GDP or GDP per capita.
20
Carvalho, Alexandre Faia. "Simultaneous synthesis of diamond on graphene for electronic application". Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/14801.
Testo completoAbstract (sommario):
Mestrado em Engenharia FísicaNeste trabalho é descrito o estudo de estruturas híbridas de grafeno e diamante nano-cristalino (GDH) sintetizadas por deposição química em fase vapor por plasma de micro-ondas (MPCVD) em cobre. Foram investigadas técnicas de controlo da nucleação do diamante nano-cristalino, tendo sido encontrados dois processos com sucesso. Procedeu-se ainda à caracterização estrutural, morfológica e ótica das amostras por análise de SEM, TEM, AFM, EFM, medidas de transmitância UV-Vis e espetroscopia de Raman. A avaliação das propriedades de transporte destes materiais foi efetuada pela medição da curva de transferência de transístores de efeito de campo produzidos para o efeito, sendo os GDHs produzidos o material ativo do canal. Foram observadas baixas mobilidades devido à hidrogenação do grafeno. Em linha com resultados teóricos da literatura, foram encontradas evidências de abertura do hiato energético do grafeno, um potencial desenvolvimento para a aplicação em dispositivos de comutação lógica.
In this work, hybrid structures of graphene and nano-crystalline diamond (GDH) produced by microwave plasma chemical vapor deposition (MPCVD) in copper substrates are studied. The control of the diamond clusters nucleation was investigated, having two different approaches been identified as promising. Structural, morphological and optical characterization was carried out by SEM, TEM, AFM, EFM, UV-Vis transmittance, and Raman spectroscopy. The transport properties of this material were analyzed through the transfer curve of field-effect transistors with GDH channels. Low mobilities were found due to graphene hydrogenation. In line with theoretical studies, evidences were found of graphene band gap opening, a potential breakthrough for the development of logical switching devices.
21
Austin, Dominic. "GDP and post-GDP - A Spurious Divorce". Thesis, Malmö universitet, Fakulteten för kultur och samhälle (KS), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-21130.
Testo completoAbstract (sommario):
Where post-GDP, a socio-ecological substitute of GDP, has become increasingly salient within international relations, its practice at an institutional economic level remains largely marginalised. At a discursive level, however, both GDP and post-GDP appear to be both supplementary and antithetical to one another. This thesis investigates this relationship between GDP and post-GDP discourse, as well as the dependency of economic institutions to exercise such a discourse. Constructivist institutionalism initially frames these economic ideas as both constitutive and antagonistic towards institutional stability. This thesis, however, draws primarily upon institutional poststructuralism, articulating GDP/post-GDP discourse, not the agent, as a mechanism that produces economic knowledge and, by association, the institutions that are shaped by it. A two-part analysis takes place, consisting of an historical genealogy of GDP/post-GDP and a discourse logics analysis between the IMF development committee and the economic departments of India and surrounding countries. The findings show that the formative discourse of GDP and post-GDP had become divorced during the 20th century and that while GDP logics often struggle to reconcile requisite development outcomes, economic institutions exercise the two as a unitary discourse; albeit one that maintains a GDP centre.
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Mattos, Pedro Montero. "Nowcasting Brazilian GDP". reponame:Repositório Institucional do FGV, 2017. http://hdl.handle.net/10438/18775.
Testo completoAbstract (sommario):
Submitted by Pedro Montero Mattos (pmattos90@gmail.com) on 2017-09-05T14:09:34Z
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nowcasting-brazilian-gdp-ficha.pdf: 808279 bytes, checksum: 3b790fa6a2be106b618a354ab1f18650 (MD5)Rejected by Joana Martorini (joana.martorini@fgv.br), reason: Prezado Pedro, boa noite, Seu trabalho não condiz com as normas necessárias para aprovação. Favor corrigir para que possamos aceitar o arquivo. Na capa faltou o nome completo da Escola, e ao identificar o local, na parte inferior da página, colocar somente o nome da cidade e o ano, retirar páginas em branco. Dissertação, banca examinadora, data da aprovação, campo de conhecimento devem estar ao lado inferior direito da página e deve haver um resumo em português. No link abaixo, a partir da página 11, tem o modelo dos requisitos necessários que podem auxiliá-lo: http://sistema.bibliotecas-sp.fgv.br/sites/bibliotecas.fgv.br/files/bibnormas1.pdf Se preferir, entre em contato pelo telefone: Thais Oliveira Cursos de Pós-Graduação (55 11) 3799-7764 SRA - Secretaria de Registros Acadêmicos on 2017-09-05T22:51:54Z (GMT)
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Rejected by Joana Martorini (joana.martorini@fgv.br), reason: Prezado, boa tarde. Seu trabalho foi rejeitado pelo seguintes motivos: - O título na capa, contracapa e dissertação devem ser em negrito; - A numeração de páginas começa a partir da Introdução; - As Dissertações, Data da Aprovação e Banca Examinadora devem estar ao lado direito da página. Favor fazer a correção para que possamos aprovar o item. Qualquer dúvida entrar em contato no mestradoprofissional@fgv.br ou ligue 3799-7764 Att. on 2017-09-11T17:59:58Z (GMT)
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Rejected by Joana Martorini (joana.martorini@fgv.br), reason: Prezado Pedro, boa noite. O trabalho está correto, exceto pela numeração de páginas, começa a partir da "Introdução", mas com o número de páginas certo, que no caso do seu arquivo seria "14" contando a partir da folha de rosto. Favor fazer a correção para que possamos aprovar o item. Grata. on 2017-09-11T21:34:20Z (GMT)
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Based on recent surveys on nowcasting methods, we apply the one-step estimation of dynamic factor models to the Brazilian case. Such methodology copes well with the problems of mixed-frequency series, ragged edges, timeliness and high dimensionality of data sets. We use the daily expectation published by the Brazilian Central Bank as a benchmark for our model and we do not find enough evidence to reject that both models have equal predictive accuracy, under non-distressed circumstances.
Baseado em recentes pesquisas em métodos de Nowcasting, foi aplicada a estimação de modelos de fatores dinâmicos em um passo ao caso brasileiro. Esta metodologia lida com os problemas de frequências mistas, amostras recortadas, horizonte temporal e alta dimensão da amostra. Foram utilizadas as expectativas diárias do PIB publicadas pelo Banco Central como um benchmark do modelo. Não foram encontradas evidências que rejeitam a hipótese de igual poder preditivo, para circunstâncias econômicas não estressadas.
23
Pallanca, Jane Emma. "The chemo-enzymic synthesis of GDP-mannose and GDP-mannose analogues". Thesis, University of Exeter, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294003.
Testo completo
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JAZIRI, NOUREDDINE. "Analogues de gdp-mannose : inhibiteurs potentiels de la gdp-mannose deshydrogenase". Paris 6, 1992. http://www.theses.fr/1992PA066661.
Testo completoAbstract (sommario):
Cette these est consacree a la synthese de molecules analogues du gdp-mannose, substrat d'une enzyme specifique de la biosynthese des alginates chez les souches mucoides de pseudomonas aeruginosa: la gdp-mannose deshydrogenase. Dans la premiere partie de ce travail, nous avons choisi une strategie qui consiste en une protection convenable de la guanosine en vue de brancher en position 5 une chaine qui reliera le nucleoside a un derive du mannose. La seconde partie est relative a l'etude de la chimie du ribose au moyen de reactions classiques de protection en positions 1, 2 et 3 et le branchement de differentes chaines en position3 15. Dans la troisieme partie, ont ete mises au point differentes methodes d'activation de la position anomere du mannose ainsi que les conditions de condensation avec les differentes chaines en 5 du ribose. Les methodes de couplage de vorbruggen ont ete utilisees pour la condensation de la guanine et d'autres bases pyrimidiques en position 1 du ribose. La quatrieme partie relate l'ensemble des proprietes biologiques des produits obtenus
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Mäki, Minna. "Conversion of GDP-mannose into various GDP-deoxyhexoses in Gram-negative bacteria". Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/maki/.
Testo completo
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Marczynski, Elaine Sirlei. "Avaliação de membranas hidrocarbônicas não fluoradas para uso como eletrólito em célula a combustível tipo DEFC". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/103831.
Testo completoAbstract (sommario):
Membranas hidrocarbônicas não fluoradas têm sido desenvolvidas para uso em substituição as membranas fluoradas (Nafion®) em células a combustível de eletrólito polimérico (PEMFC), ou em temperaturas superiores a 80 °C, ou em células com adição direta de álcool. Este trabalho teve como objetivo avaliar o desempenho de membranas hidrocarbônicas catiônicas, desenvolvidas para uso em célula a combustível alimentada com etanol (DEFC), e de camadas de difusão gasosa (GDL – Gas Difusion Layer) e eletrodos (GDE – Gas Difusion electrode) preparados para uso com as mesmas. Duas membranas hidrocarbônicas (E-750 e P-730) da empresa FuMATech®/GR foram avaliadas quanto à capacidade de troca iônica e grau de inchamento em água/etanol, quanto a composição química, morfologia, comportamento térmico e visoelástico e condutividade por impedância. As GDLs foram preparadas a partir de uma emulsão aquosa de Teflon® e pó de carbono Vulcan XC-72R®, com e sem agente emulsificante (resina sulfonada), dispersa em ambas as faces do tecido de carbono pelo método de aspersão. Os GDEs foram preparados pela deposição de emulsão catalítica de diferentes eletrocatalisadores sobre as respectivas GDLs do ânodo e catodo. Os GDEs anódico e catódico foram preparados com 1 mg.cm-2 do eletrocatalisador de PtSn/C 20% (75:15) e de Pt/C (20:80), respectivamente, e caracterizados por MEV-EDS. As características fisico-químicas das membranas hidrocarbônicas foram similares às apresentadas pela membrana Nafion®. O desempenho do protótipo de célula unitária DEFC com as membranas FuMATech® foi inferior ao obtido com a membrana Nafion® usando-se GDE comercial. Por outro lado, ensaios com a membrana Nafion® utilizando-se os eletrodos preparados neste trabalho e eletrodos comerciais apresentaram valores de potencial similares.Non-fluorinated hydrocarbon cationic membranes have been developed for use instead of Nafion® in Polymer Electrolyte Membrane Fuel Cells (PEMFCs), or at higher temperatures than 80 ºC, or in fuel cells fed with alcohol. The aim of this work was to evaluate the performance of commercial non-fluorinated hydrocarbon cationic membranes with potential use in direct ethanol fuel cell (DEFC), and also evaluate the Gas Difusion Layer (GDL) and Gas Difusion electrode (GDE) prepared for use with them. Two hydrocarbon membranes (E-750 and P-730) produced by FuMATech®/GR were analyzed according to their ion exchange capacity, water uptake in water/alcohol solution, morphology, chemical composition, thermal and viscoelastic behaviour, and conductivity by impedance. The GDLs were prepared by spraying an aqueous emulsion of Vulcan carbon/Teflon®, with and without emulsifier agent (sulfonated hydrocarbon resin), in both sides of a carbon fabric. The electrodes were prepared by the respective deposition of the electrocatalysts emulsions on the cathode and anode GDLs. The anodic and cathodic GDEs were prepared with 1 mg.cm-2 of the electrocatalyst of PtSn/C 20% (75:15) and of Pt/C (20:80), respectively, which were characterized by SEM-EDS. The physicochemical properties of the hydrocarbon membranes were similar to the Nafion® membrane ones. The potential values obtained in a DEFC prototype unit cell with FuMATech® membranes were lower than those with Nafion-117 membrane. On the other hand, the performance of the DEFC prototype with Nafion-117 membrane was the same if used GDEs commercial or here prepared.
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Nevelsteen, Kim J. L. "GDD as Development Methodology". Thesis, Uppsala University, Department of Information Technology, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-98283.
Testo completoAbstract (sommario):
The Game Design Document is a well defined set of requirements for a game design and a methodology for game development. The most pertinent aspects of the GDD are described and the relative research collected, in order to better the reader's understanding of the concept. This is a work in two parts, theoretical and practical. Research was an ongoing effort while attempting toproduce a game design according to the content prescribed for the GDD. The resultant design was for a fictitious game dubbed Arcane Dominion.
Knowledge gained about the GDD is used to make a comparison and attempt to identify a possible evolution towards existing software engineeringmethodologies. Some differences are brought to light between the GDD and a popular contemporary methodology, Agile Development.
To compliment the research, one aspect of the designed game was implemented in a prototype and thereafter analyzed in order to obtain neededfeedback and be confronted with the complexities of game balancing pertaining to one chosen game strategy.
No knights or soldiers were hurt in the making of this thesis.
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Amaral, Emília. "O leitor segundo G.H". [s.n.], 2001. http://repositorio.unicamp.br/jspui/handle/REPOSIP/251593.
Testo completoAbstract (sommario):
Orientador: Joaquim Brasil FontesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Educação
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Doutorado
29
Brennan, Benjamin. "Essays on Nominal GDP Targeting". Thesis, University of Oregon, 2018. http://hdl.handle.net/1794/23784.
Testo completoAbstract (sommario):
The subject of this dissertation is nominal GDP (NGDP) targeting. In the wake of the Great Recession, some economists have proposed using some form of NGDP target to replace current monetary policy. We evaluate the desirability of NGDP targets based upon their ability to deliver unique and \learnable" equilibria and their welfare gains in the presence of nancial frictions.
In the second chapter, we assess the determinacy and E-stability conditions for simple interest rate rules which respond to NGDP's deviation from target in a simple three-equation New Keynesian model. The rules under consideration target either NGDP level or growth, and can either be contemporaneous, one period ahead, or two periods ahead. We also allow for dierent types of information sets for the agents.
In the third chapter, we compare welfare loss in consumption equivalent terms for NGDP targets with more conventional monetary policy in a New Keynesian model which features nancial frictions.
Finally, in the fourth chapter we continue our analysis from chapter one but now allow for strictly positive trend inflation. We present
findings for the relationship between trend inflation and the determinacy and E-stability of the equilibrium when using interest rate rules that target NGPD.
30
(GDV), Gesamtverband der Deutschen Versicherungswirtschaft e. V. "Forschungsberichte / Unfallforschung der Versicherer, GDV". Gesamtverband der Deutschen Versicherungswirtschaft e. V. (GDV), 2021. https://publish.fid-move.qucosa.de/id/qucosa%3A74629.
Testo completo
31
Al-Qahtani, Ahmed. "Development and clinical applications of monoclonal antibodies to human AMH, GDF-9 and GDF-9B". Thesis, Oxford Brookes University, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444326.
Testo completo
32
Naser, Hanan. "An econometric investigation of forecasting GDP, oil prices, and relationships among GDP and energy sources". Thesis, University of Sheffield, 2014. http://etheses.whiterose.ac.uk/7041/.
Testo completoAbstract (sommario):
In order for a policy to be effective, the links between the policy tools and the sub- sequent targets must be known, understandable, stable, and predictable. In this respect, this thesis is composed of three separate yet related empirical studies, that target important macroeconomic variables, which play a central role in the conduct of macroeconomic policies. First, simple regression estimates and a factor-based model are utilized to produce forecasts for Bahrain quarterly GDP growth using quarterly data-set that cover the period from 1995: Q1 to 2008: Q3. To do so, we run a simple regression model using a small data-set including six explanatory variables carefully selected based on in-sample correlation with the target variable. Alternatively, a factor model based on 65 indicators is employed to forecast Bahrain GDP growth. Using simulated out- of-sample experiments we assess and compare the performance of both approaches. The main finding from our forecasting experiment is that the best forecasting performance can be reached using simple regression estimates with a carefully selected small set of variables. In particular, by looking at point and density nowcasts, we find that a simple regression model that use industrial production as an indicator are more accurate than a static factor approach that uses over 65 variables. The official flash estimates of Bahrain quarterly GDP are published with a delay of 90 days after the end of the reference quarter. Our flash estimates, based on simple regression model, reduce the lag to 54 days. Second, we aim to forecast West Texas Intermediate (WTI) crude oil prices using a large monthly data-set that cover the period from March 1983 to December 2011. To achieve this aim, forecasting with factor models offer a usual approach that utilizes large data-sets, however; a forecasting model which simply includes all factors in state space equation and do not allow for time varying may be not suitable with a highly volatile market such as oil market. To overcome these limitations, we employ an approach that accounts both for parameter and model uncertainty. In particular, we implement the the Dynamic Model Averaging (DMA) approach suggested by Koop and Korobilis (2012). The key element of the DMA approach is that it allows both for model and parameter to vary at each point of time. By doing so, the DMA is robust to structural breaks. Empirical findings show that DMA approach outperforms any other alternative model used in the forecasting literature. We show that there is model but not parameter variation. Finally, we find that the DMA approach provides a better proxy of expected spot prices than future prices. Third, the Johansen cointegration technique is used to examine the long-run relationship between oil consumption, nuclear energy consumption, oil price and economic growth for eight countries over the period from 1965 - 2010. The countries investigated are divided into two groups. The first group includes four industrialized countries: USA, Canada, Japan and France, while the second group includes four emerging economies: Russia, China, South Korea and India. Results suggest that there is a long-run relationship between the four variables. Exclusion tests show that at least one energy source enter the cointegration space significantly, which im- plies that energy a long-run impact on economic growth. The emerging economies found to be heavily dependent on both oil and nuclear energy consumption. We also examine the causal linkage between the variables through exogeneity test. There is evidence of a unidirectional causality between energy consumption (oil or nuclear) and economic growth in all investigated countries. Our findings have important pol- icy implications that should be taken into account in designing appropriate energy policies. Energy conservation policies might have drawbacks or damaging repercus- sions on economic growth for this group of countries.
33
Pedak, Martin. "The Effect of Tourism on GDP". Thesis, Internationella Handelshögskolan, Högskolan i Jönköping, IHH, Nationalekonomi, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-41334.
Testo completoAbstract (sommario):
International tourism plays a huge role for many countries in the world. The significance of tourism differs between countries, however increase in tourism tends to lead to gross domestic product growth. The purpose of this paper is to measure those general effects of tourism on gross domestic product per capita. The theory part is focused on determinants of economic growth and GDP and the literature review examines general effects of tourism as well as the effect of tourism on specific countries and regions. The data is cross sectional and was gathered from 111 countries provided by World Bank. The results of this thesis show that international tourism seems to have positive relation with the level of gross domestic product per capita. However, the study also found that tourism specialisation tends to have negative relation on level of gross domestic product per capita and that countries that are most specialised in tourism are quite small states, usually located in the Caribbean Sea.
34
Tomlinson, Dennis Churchill. "Nature and technology in GDR literature". Thesis, University of Bath, 1993. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.332289.
Testo completo
35
(GDV), Gesamtverband der Deutschen Versicherungswirtschaft e. V. "Unfallforschung kompakt / Unfallforschung der Versicherer, GDV". Gesamtverband der Deutschen Versicherungswirtschaft e. V. (GDV), 2021. https://publish.fid-move.qucosa.de/id/qucosa%3A74497.
Testo completo
36
(GDV), Gesamtverband der Deutschen Versicherungswirtschaft e. V. "Unfallforschung kommunal / Unfallforschung der Versicherer, GDV". Gesamtverband der Deutschen Versicherungswirtschaft e. V. (GDV), 2021. https://publish.fid-move.qucosa.de/id/qucosa%3A74743.
Testo completo
37
Björnfot, Fredrik. "GDP Growth Rate Nowcasting and Forecasting". Thesis, Umeå universitet, Institutionen för fysik, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-132951.
Testo completoAbstract (sommario):
The main purpose of this project was to help Swedbank get a better understandingof how gross domestic product growth rate develops in the future froma data set of macroeconomic variables. Since GDP values are released long aftera quarter has ended Swedbank would like to have a model that could predictupcoming GDP from these data sets. This was solved by a combination ofgrowth rate predictions from a dynamic factor model, a vector autoregressivemodel and two machine learning models. The predictions were combined usinga weighting method called system averaging model where the model predictionwith least historical error receives the largest weight in the nal future prediction.In previous work a simple moving average model has been implementedto achieve this eect however there are several aws in a simple moving averagemodel. Most of these defects could in theory be avoided by using an exponentialweighting scheme instead. This resulted in the use of an exponentialweighting method that is used to calculate weights for future predictions. Themain conclusions from this project were that some predictions could get betterwhen removing bad performing models which had too large of a weight. Puttingtoo high weight on a single well performing model is also not optimal since thepredictions could get very unstable because of varying model performance. Theexponential weighting scheme worked well for some predictions however whenthe parameter , that controls how the weight is distributed between recent andhistorical errors, got too small a problem arose. Too few values were used toform the nal weights for the prediction and the estimate got unsteady results.
38
Gregson, Julie. "Engendering the GDR : DEFA cinema 1956-1966". Thesis, University of Nottingham, 2002. http://eprints.nottingham.ac.uk/14353/.
Testo completoAbstract (sommario):
This thesis examines four films made during two key phases in East German film history in the mid-1950s and the mid-1960s which have earned critical acclaim for their challenge to cultural-political orthodoxy and which I read as national narratives offering political, social, cultural and historical constructions of GDR identity. I argue that narrative representations of gender and sexuality serve in the films as a means towards negotiating between affirmation and critique. My analyses are informed by a wide range of other DEFA films. Chapter One sketches broader political and film-historical contexts. Chapter Two examines the role that gender discourse plays in differentiating East from West in the depiction of the frontier city of Berlin in Gerhard Klein's Berlin-Ecke Schonhauser. Chapter Three focuses on Konrad Wolf’s adaptation of Christa Wolfs novel Der geteilte Himmel. It shows how the film articulates competing views of the GDR, but instrumentalizes the female character ultimately to endorse socialist society in a divided Germany, and expresses her attachment to this new society in terms of a family-type relationship. Chapter Four examines how Frank Vogel's Denk bloss nicht, ich heule seeks to mediate between the 'national' past and present, using a triangular family plot. In Chapter Five, the analysis of Frank Beyer's Spur der Steine centres upon the role of a lone female in the film's reforming exploration of the overwhelmingly male collective, but shows how it leaves the status of sexuality - whether for pleasure or for reproductive ends - unresolved. There has been little in-depth study of the way gender representation relates to constructions of the GDR in films of this period. This study remedies this omission, showing how the film-makers frequently rely upon conservative gender paradigms to manage the contradictions implicit in their project and how the endings of the films increasingly come under strain.
39
Chen, Helen Yee-Fang. "Characterization of ganglioside GD3 9-O-Acetylation /". Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2003. http://wwwlib.umi.com/cr/ucsd/fullcit?p3112855.
Testo completo
40
Simon, Bernadett. "Oligodendrocyte cell death induced by Disialoganglioside GD3". [S.l. : s.n.], 2000. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB8879773.
Testo completo
41
Hannafi, Cyrine. "The poverty-GDP per capita-health triangle". Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0573.
Testo completoAbstract (sommario):
Dans le premier chapitre de thèse, nous estimons un système dynamique d’équations simultanées à l’aide de données de panel de pays en développement pour identifier les relations structurelles dynamiques entre la pauvreté, le PIB par habitant et la santé. Pour ce faire, nous utilisons des méthodes économétriques innovantes des données de panel incomplet pour corriger les problèmes d'endogénéité et de sélectivité liés aux données manquantes sur la pauvreté. Dans le deuxième chapitre, nous estimons plutôt les relations de cointégration entre ces trois facteurs, en utilisant des données de panel de pays en développement. Nous effectuons une analyse de cointégration des données de panel afin d'estimer les relations et les tests de causalité de long terme, ainsi qu'un modèle VECM et les fonctions de réponse impulsionnelle (IRFs). Dans le troisième chapitre de thèse, nous étudions les déterminants socio-économiques et religieux / ethniques locaux du conflit syrien actuel. Pour cela, nous fusionnons les données mensuelles de la base de données du panel de martyrs Syriens, à partir de Mars 2011 jusqu'en Avril 2016 au niveau commune, avec des facteurs socio-économiques du Recensement de 2004 et avec les données de lumière géo-localisées depuis l'espace. Nous construisons également des indicateurs ethniques/religieux détaillés par commune. Nous utilisons l'intensité lumineuse nocturne comme proxy pour la population pendant le conflit et examinons la dynamique du conflit en incluant les niveaux passés de la variable dépendanteIn the first chapter, a dynamic system of simultaneous equations is estimated using country-level panel data from developing countries to identify the dynamic causal structural relationships between Poverty, GDP per capita and Health. For this, innovative econometric methods for incomplete panel data are used to correct for endogeneity and the selectivity issues coming from missing data on poverty. In the second chapter, we estimate rather the cointegration relationships between the three factors, using country-level panel data from developing countries. We conduct a panel data cointegration in order to estimate long run relationships and causality tests. We estimate also a VECM model and we compute Impulse response functions. In the third chapter, we investigate socioeconomic and religious/ethnic local determinants of the current Syrian conflict. For this, we match monthly data from the Syrian Martyr panel database from March 2011 to April 2016 at community level with socioeconomic factors from the 2004 Census and with geolocalised luminosity from space. We also construct detailed ethnic/religious indicators. We use nighttime light intensity as a proxy for the population during the conflict and investigate the dynamics of the conflict with including past levels of the dependent variable
42
Solbrig, Jacob H., e Jacob Hagen Solbrig. "Stasi Brainwashing in the GDR 1957 - 1990". ScholarWorks@UNO, 2017. https://scholarworks.uno.edu/td/2431.
Testo completoAbstract (sommario):
This thesis examines the methods used by the Ministerium für Staatssicherheit (MfS), more commonly known as the Stasi, or East German secret police, for extraction of information from citizens of the German Democratic Republic for the purpose of espionage and covert operations inside East Germany, as it pertains to the deliberate brainwashing of East German citizens. As one of the most efficient intelligence agencies to ever exist, the Stasi’s main purpose was to monitor the population, gather intelligence, and collect or turn informants. They used brainwashing techniques to control the people of the GDR, keeping the populace paralyzed with fear and paranoia. By surrounding themselves with a network of informants they prevented actions against the dictatorial communist regime. Using the video testimonies of former prisoners, and former confidential informants who worked closely with and collaborated with Stasi agents, in combination with periodicals and previous historical studies, this work argues that the East German Police State’s brainwashing techniques had long and lasting consequences both for German citizens, and for the psychiatric health of former GDR citizens. The scope and breadth of the techniques and data compiled for use by the Stasi were exhaustive, and the repercussions of their use are still being felt and discovered twenty five years after the fall of the Berlin Wall. This study aims to show the lasting effects brainwashing had on former informants and the Stasi’s victims.
43
Beneš, Vratislav. "Ekonomické modely realizované neuronovou sítí typu GMDH". Master's thesis, Vysoká škola ekonomická v Praze, 2007. http://www.nusl.cz/ntk/nusl-7680.
Testo completoAbstract (sommario):
This diploma thesis is about design and realization of neural network MIA GMDH for ekonomical modelling by inductive method. Models are compared with statistical methods by quallity and usebility degree. An application was developed for verification of functionality on experiments. The same experiments were run in econometrical software. The results were compared. The MIA GMDH is suitable for economic modelling.
44
Ruiz-Alejos, Carlos. "Sustainability Assessment of Scenarios: Beyond GDP growth". Thesis, KTH, Hållbar utveckling, miljövetenskap och teknik, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-220150.
Testo completoAbstract (sommario):
The creation of futures scenarios is a tool to addresschallenges towards sustainability in planning and thebuilt environment. Scenarios in the project BeyondGDP growth explore futures where priority is givento social and environmental aspects and economicgrowth is regarded as uncertain. When futures areused as an input to planning, there has to be anawareness of the possible consequences of those.Sustainability assessment for futures scenarios aimsto give a comprehensive assessment of how differentscenarios can affect relevant aspects. This thesis gives an overview of current methods forsustainability assessment of futures scenarios. It alsoproposes improvements to one of them and tests iton the Beyond GDP growth scenarios. SAFS (SustainabilityAssessment Framework for Scenarios) isthe method selected. SAFS considers environmentaland social aspects providing qualitative results anduses consumption perspective and life cycle approach. Improvements to SAFS are proposed in two directions.First, the Doughnut developed by Raworth(2012) is integrated in the method. It gives a graphicrepresentation, putting each aspect in context withthe others and facilitate the communication of theassessment results. Second, an alternative approachis suggested to evaluate the consequences of environmentaldeprivation on social conditions. Thisalternative approach can also help communicateuncertainties.Att skapa framtidsscenarier är ett verktyg för attadressera utmaningar relaterade till hållbarhet inomsamhällsplanering och samhällsbyggnad. ProjektetBortom BNP-tillväxt utforskar i ett antal scenarierolika framtider där sociala och miljömässiga aspekterfår prioritet och ekonomisk tillväxt betraktas somosäker. När framtidsscenarier används som inputi samhällsplanering behöver det finnas en medvetenhetom dessa framtiders möjliga konsekvenser. Hållbarhetsbedömning av framtida scenarier utgören omfattande utvärdering av hur olika scenarier kanförväntas påverka relevanta aspekter. Den här uppsatsen ger en översikt över befintligametoder för hållbarhetsbedömning av framtidsscenarier,den applicerar en av dessa metoder - SAFS(Sustainability Assessment Framework for Scenarios) -på scenarierna inom Bortom BNP-tillväxt och föreslårförbättringar till metoden. SAFS väljs därför att densom metod tar hänsyn till såväl miljö- som socialaaspekter, ger kvalitativa resultat och utvärderar scenariernaur ett konsumtions- och livscykelperspektiv. Två förbättringar av SAFS föreslås. Den ena är attintegrera Raworths “Doughnut” (2012) eftersomden erbjuder ett sätt att grafiskt representera allautvärderade aspekter tillsammans och underlättaratt kommunicera resultatet från bedömningen. Denandra förbättringen innebär ett annat angreppssättför att utvärdera konsekvenserna av miljöförstöringför sociala aspekter. Det föreslagna angreppssättetkan även underlätta att kommunicera metodens inneboendeosäkerheter gällande resultaten.
Beyond GDP growth
45
Campos, Claúdia Cristina Marinho. "Predicting GDP growth in the Euro Area". Master's thesis, NSBE - UNL, 2013. http://hdl.handle.net/10362/9837.
Testo completoAbstract (sommario):
A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA – School of Business and EconomicsPredicting GDP growth is a concern of several economic agents. The right way to model such variable is far from consensual. This paper’s goal is to compare different models for GDP growth forecasting in the euro area. For comparative purposes, an autoregressive model (which is used as benchmark) and two Autoregressive Distributed Models (ADL), which contain financial and non-financial variables, chosen based on the literature, are used. The main conclusion is that the ADL(2,1,1) considered has superior forecast performance in- and out-of-sample, although in this last case depending on the evaluation metric.
46
Lau, Tak Bun Stephen. "Mechanistic investigation of 3, 5-epimerases / reductases involved in the biosynthesis of GDP-L-Fucose and GDP-L-Galactose". Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/14851.
Testo completoAbstract (sommario):
GDP-fucose synthase (GFS), also known as GDP-4-keto-6-deoxy-mannose 3, 5- epimerase / 4-reductase (GMER), is the key enzyme in the GDP-L-fucose biosynthetic pathway. The pathway begins with a dehydratase that converts GDP-D-mannose into 6-deoxy-4-keto- GDP-D-mannose. Then GFS performs two consecutive epirnerizations, and a final NADPH dependent reduction to generate GDP-L-fucose. The detailed mechanism of GFS has remained a mystery due to limited mechanistic studies as well as the lack of an x-ray crystal structure with any bound GDP-sugar. This thesis investigates the mechanism of the reaction as well as the roles of the active site residues in GFS. The results support a sequential ordered epimerization mechanism where the stereocenter at C-3”is inverted first, followed by the inversion of
stereochemistry at C-5”. This identifies GDP-6-deoxy-D-altrose as a reaction intermediate for the first time. The findings of this thesis also leads to the assignment of the catalytic residue Cys 109,
as the base which deprotonates both epimerization sites, and His179 as the acid which reprotonates the corresponding enol intermediates. GDP-mannose 3, 5-epimerase (GME), is the key enzyme that catalyzes the first committed step of vitamin C biosynthesis in plants. It oxidizes the C-4” position of GDP mannose, then sequentially inverts the stereochemistry at C-5” and C-3”, and finally reduces the C-4” carbonyl to produce GDP-L-galactose. The proposed sequential order of epimerization is based on the observation that GDP-L-gulose (the C-5” epimeric product) is produced whereas GDP-D-altrose (the C-3” epimeric product) is not. Structural studies on GME suggest that Cys145 acts as the catalytic base and Lys 217 acts as the catalytic acid in both epimerization steps. However, very limited mechanistic studies on GME have been performed. This thesis provides mechanistic evidence that supports the proposed sequential epimerization order as well as the assignment of roles for the catalytic residues. It also suggests a model whereby protonated Cys145 is unable to exchange its proton with solvent during the lifetime of the enol(late) intermediate.
47
Hodoroaba, Vasile-Dan. "Wasserstoffeffekt und -analyse in der GDS - Anwendungen in der Werkstoffforschung Hydrogen effect and analysis in GDS - applications in material science /". [S.l. : s.n.], 2003. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB10361088.
Testo completo
48
Lundberg, Otto. "GDP forecasting and nowcasting : Utilizing a system for averaging models to improve GDP predictions for six countries around the world". Thesis, Umeå universitet, Institutionen för matematik och matematisk statistik, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-131718.
Testo completoAbstract (sommario):
This study was issued by Swedbank because they wanted too improve their GDP growth forecast capabilites. A program was developed and tested on six countries; USA, Sweden, Germany, UK, Brazil and Norway. In this paper I investigate if I can reduce forecasting error for GDP growth by taking a smart average from a variety of models compared to both the best individual models and a random walk. I combine the forecasts from four model groups: Vector autoregression, principal component analysis, machine learning and random walk. The smart average is given by a system that give more weight to the predictions of models with a lower historical error. Different weighting schemas are explored; how far into the past should we look? How much should bad performance be punished? I show that for the six countries studied the smart average outperforms the single best model and that for five out of six countries it beats a random walk by at least 25%.Den här studien beställdes av Swedbank eftersom de ville förbättra sin BNP-prediktionsförmåga. Ett dataprogram utvecklades och testades på sex länder; USA, Sverige, Tyskland, Storbritannien, Brasilien och Norge. I den här rapporten undersöker jag om jag kan minska felmarginalen för BNP-utvecklingsprognoser genom att ta ett smart genomsnitt från flera olika modeller jämfört med både den bästa individuella modellen och en random walk. Jag kombinerar prognoser från fyra modellgrupper: Vektor autoregression, principalkomponentanalys, maskininlärning och random walk. Det smarta genomsnittet skapas genom att ge mer vikt till de modeller som har lägst historiskt felmarginal. Olika viktningsscheman utforskas; hur långt bak i tiden ska vi mäta? Hur hårt ska dåliga prediktioner bestraffas? Jag visar att för de sex länderna i studien presterar det smarta genomsnittet bättre än den enskilt bästa modellen och fem av de sex länderna slår en random walk med mer än 25%.
49
Tong, Wenyong. "Chemistry and biology of tumor-associated ganglioside GD2". Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107647.
Testo completoAbstract (sommario):
Effective therapies typically target diseased tissues without significantly affecting healthy tissues. A tumor-related glycosphingolipid (GSL), such as ganglioside GD2, distinguishes neuroectoderm tumors from their healthy counterparts and is a validated tumor target. GD2 is clinically targeted for diagnosis and immunotherapy. GD2 plays an important functional role in tumor progression and in chemoresistance. It also plays an important functional role in pain; however, the mechanisms that make GD2 important in such phenomena remain unknown.Thus, understanding the structure-activity relationship of GD2, a GSL with two sialic acids, would be helpful. However, such studies on glycolipids are challenging. We employed a chemical biology approach to elucidate the structure and function of GD2 and to further direct the rational design of GD2 ligands and vaccines for GD2-related cancer treatment.The combined use of STD NMR spectroscopy, transferred NOE experiments, and molecular modeling furnished details on the molecular recognition of the ganglioside GD2 by the clinically used anti-GD2 monoclonal antibody 3F8 that can induce apoptosis of GD2 expressing tumours. A binding model that provided the basis for a rational development of GD2 ligands and vaccines was then established. Based on the structural information of GD2-3F8 interactions, small molecule monomeric peptide ligands binding to GD2 were developed. ELISA and NMR experiments demonstrated that peptides selectively bound to GD2 via an induced-fit mechanism. Furthermore, peptidic GD2 ligands, including 3F8, mediated similar biological functions in cell-based assays of activation of NMDA receptor via Src family kinase, calcium fluxe and cAMP. These can explain at least some of the mechanisms associated with tumor progression and pain, where GD2 plays a role. However, current GD2 peptide ligands did not demonstrate any treatment effect in vivo. Hence, we turned to the design of GD2 vaccines as a therapeutic approach. The rigid nature of GD2-oligosaccharides, discovered in our structural study, makes it perfectly suited to drive a structurally convergent immune response. A novel and homogenous tetra-GD2 dendrimer was designed to mimic a clustered GD2 lipid raft. Immunization of mice with tetra-GD2 dendrimer elicited a potent anti-GD2 humoral response. The antibodies (sera or mAbs) thus generated can kill GD2-expressing cells in culture, in the absence of a complement. Tumor growth was significantly delayed in vivo in prophylactic and in therapeutic paradigms. Our research strategy may be expanded to other clinically relevant glycolipids.Typiquement, les thérapies efficaces agissent sur les tissus malades sans toutefois nuire considérablement aux tissus en santé. Un glycosphingolipide (GSL) associé à une tumeur, tel que le ganglioside GD2, peut reconnaître selectivement les tumeurs neuroectodermes malignes et est ainsi validé comme une cible tumorale. Sur le plan clinique, on utilise le GD2 à des fins de diagnostic et d'immunothérapie. D'une part, le GD2 joue un rôle fonctionnel important dans la progression tumorale et la chimiorésistance. D'autre part, le GD2 joue un rôle fonctionnel important dans la douleur, mais les mécanismes qui expliqueraient l'importance du GD2 lors de tels phénomènes demeurent encore inconnus. C'est pourquoi il serait utile de mieux comprendre la relation structure-activité du GD2, un GSL constitué de 2 acides sialiques. Toutefois, entreprendre de telles études sur les glycolipides représente un défi de taille. Nous avons alors utilisé une approche basée sur la biologie chimique pour élucider la structure et la fonction des GD2 et pour mieux concevoir rationnellement des ligands GD2 et des vaccins pour le traitement contre le cancer lié au GD2. En combinant l'utilisation de la spectroscopie RMN DTS, des expériences NOE transférées et des modèles moléculaires, il est possible d'obtenir plus de détails sur la reconnaissance moléculaire du ganglioside GD2 au moyen du 3F8, un anticorps monoclonal anti-GD2 utilisé médicalement et qui peut induire l'apoptose de cellues cancereuses exprimant GD2. Comme point de départ pour le développement rationnel des ligands GD2 et des vaccins, nous avons établi un modèle contraignant. En nous appuyant sur l'information structurelle des interactions GD2-3F8, nous avons développé des petits ligands monomériques peptidiques liés au GD2. Des expériences RMN et ELISA ont démontré que les peptides se lient sélectivement au GD2 via un mécanisme d'ajustement induit. Par ailleurs, les ligands peptidiques GD2, dont le 3F8, deviennent médiateurs de fonctions biologiques similaires dans les essais cellulaires de l'activation des récepteurs NMDA via les kinases de la famille Src, les flux de calcium et cAMP. Ces derniers peuvent au moins expliquer certains des mécanismes associés avec la progression tumorale et la douleur, dans lesquels le GD2 jour un rôle prépondérant. Cependant, les ligands peptidiques GD2 actuels n'ont pas démontré les effets désirés au cours des traitements in vivo. C'est pourquoi nous nous sommes tournés vers le développement de nouveaux vaccins GD2 comme une approche thérapeutique. La nature rigide des oligosaccharides GD2, que nous avons découverte par le biais de notre étude structurale, devient une caractéristique parfaitement adaptée pour favoriser une réponse immunitaire structurellement convergente. Un nouveau dendrimère tetra-GD2 homogène a été conçu de manière à reproduire un radeau lipidique GD2 regroupé. L'immunisation des souris par le dendrimère tetra-GD2 a engendré une puissante réponse humorale anti-GD2. En l'absence d'un complément, les anticorps (sera ou mAbs) ainsi générés peuvent tuer les cellules exprimant le GD2 en culture. La croissance tumorale a été considérablement retardée in vivo dans les paradigmes thérapeutiques et prophylactiques. Notre stratégie de recherche pourrait ainsi être élargie pour inclure d'autres glycolipides pertinents sur le plan clinique.
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Casanova, i. Fernàndez Fèlix. "Magnetocaloric Effect In Gd5(SixGe1-x)4 Alloys". Doctoral thesis, Universitat de Barcelona, 2004. http://hdl.handle.net/10803/1789.
Testo completoAbstract (sommario):
This Ph.D. Thesis has been devoted to the preparation and characterisation of bulk Gd5(SixGe1-x)4 alloys and to the study of the magnetocaloric effect at the first-order magnetostructural transition appearing in these compounds. We summarise the most relevant results from this research:- Bulk Gd5(SixGe1-x)4 samples with 0¡Âx ¡Â0.5 have been prepared by using our home-made arc-melting furnace. Characterisation techniques (SEM, microprobe, XRD, DSC, magnetisation, ac susceptibility) show that the 5:4 phase with the desired x is obtained. Some spread around the nominal value and secondary 5:3 and 1:1 phases are detected. Heat treatment favour the segregation of these secondary phases, but also reduce the spread in the x value. A treatment at 920 ¨¬C for 4 hours in a 10-5 mb vacuum furnace enables a trade-off between phase segregation and removal of x spread.
- A new differential scanning calorimeter (DSC), which operates under applied magnetic fields of up to 5 T and within the temperature range 10-300 K, has been developed. This calorimeter enables an accurate determination of the entropy change associated with a magnetostructural phase transition. The transition can be induced by sweeping either T or H.
- It has been shown that the Clausius-Clapeyron equation and DSC measurements yield the entropy change associated with the first-order magnetostructural transition, ∆S. If the Maxwell relation is evaluated only within the field range over which the transition takes place, the same value is obtained. When the Maxwell relation is evaluated over the whole field range, the T and H dependences of the magnetisation in each phase outside the transition region yield an additional entropy change to that associated with that of the actual first-order transition. The transition temperature Tt must significantly shift with the applied field, in order to achieve a large MCE taking advantage of ∆S.
- DSC under H has been used to measure ∆S for Gd5(SixGe1-x)4, x ¡Â0.5. ∆S scales with Tt, which is a direct consequence of the fact that Tt is tuned by x and H and it is thus expected to be universal for any material showing a field-induced transition. The specific shape of ∆S vs. Tt will depend on the details of the phase diagram, Tt(x). The scaling of ∆S shows the equivalence of magnetovolume and substitution-related effects in Gd5(SixGe1-x)4 alloys.
- The variation of the transition field with the transition temperature, dHt/dTt, has been studied in Gd5(SixGe1-x)4 for 0¡Âx ¡Â0.5. It is shown that dHt/dTt governs the scaling of ∆S with Tt. Two distinct behaviours for dHt/dTt have been found on the two compositional ranges where the magnetostructural transition occurs, showing the difference in the strength of the magnetoelastic coupling in this system.
- It has been shown that an unreported field-induced magnetic phase transition exists from the AFM phase to a phase which presents short-range correlations (SRAFM). The results suggest that the transition results from the breaking of the long-range AFM correlations when a magnetic field is applied, which leads to competing FM and AFM short-range correlations. FM correlations are also relevant in the whole long-range AFM phase. The expected transition from the SRAFM to the PM phase takes place at ~240 K at zero field, being widened and smoothed under applied field. This finding in the Ge-rich Gd5(SixGe1-x)4 alloys arises from the competition between the intraslab FM interactions and the interslab AFM interactions.
- The dynamics of the first-order transition in Gd5(SixGe1-x)4 alloys has been studied by cycling virgin samples. The field-induced entropy change increases during the first cycles, then reaching a stationary value. This behaviour is related to the avalanche distribution, which also evolves with cycling. The structure of avalanches becomes repetitive after a few cycles tending towards a power-law distribution, unveiling the athermal character of the transition.