Teses / dissertações sobre o tema "Ghh"

Wachstumshormon (GH) besteht aus 191 Aminosäuren, hat eine Molekülmasse von 22kD und ist essentiell für postnatales Wachstum. Es wird aus der Adenohypophyse freigesetzt. GH bindet an einen GH-Rezeptor (GHR) und aktiviert somit über intrazelluläre Signalvorgänge Zielgene, insbesondere das, welches für die Kodierung von insulin-like growth factor (IGF-1) zuständig ist. IGF-1 vermittelt den Großteil aller GH-Signale. Zusammen mit den bereits bekannten GH Mutanten R77C und D112G ist in dieser Studie der neue GH Mutant d188-190 charakterisiert worden. Alle drei Mutanten wurden in heterozygoter Form in kleinwüchsigen Patienten identifiziert. Diesen Patientendaten zu Folge schien es möglich, dass d188-190 eine GH-antagonistische Wirkung besitzt. Zusätzlich wurde die extrem konservierte C-terminale Disulfidbrücke des GH im Mutanten d188-190 unterbrochen vorgefunden. Die Auswirkung der Unterbrechung wurde durch Substitution einer oder beider involvierter Cysteine durch Alanine untersucht. Alle Mutanten und Wildtypen des GH wurden in menschlichen embryonalen Nierenzellen (HEK-293) angezüchtet und eine Reihe von in vitro Experimenten sind für deren Charakterisierung etabliert worden. Es zeigte sich, dass d188-190 keine GH-antagonistische Wirkung besitzt. Im Vergleich zum Wildtyp weist der Mutant eine verminderte Bindungsaffinität zu GH, schwächere biologische Aktivität und höhere Stabilität auf. R77C und D112G sind dem Wildtyp GH sehr ähnlich. Die Disulfidbrücke ist wichtig für die Rezeptorbindung und für die biologische Aktivität von GH. Wenn ein Cystein entfernt wird vermindert sich die Stabilität des Moleküls. Dieser Effekt kann durch Entfernen des zweiten Cysteins wieder rückgängig gemacht werden. Die in dieser Studie etablierten Experimente können Verwendung finden in der Charakterisierung bislang nicht bekannter GH Mutanten und können darüber hinaus zur Behandlung von Patienten eingesetzt werden.
Growth hormone (GH) is a 22 kD, 191-aa, pituitary-derived peptide hormone that is essential for postnatal growth. GH signals via binding to GH receptor (GHR), which initiates intracellular signal transduction pathways. This leads to activation of target genes, most importantly the one encoding insulin-like growth factor (IGF)-1, which mediates most GH action. In this study a novel GH mutant, d188-190, was characterized along with previously reported GH mutants R77C and D112G. All of these mutants had been identified in heterozygous form in patients with retarded growth. Based on patient data, d188-190 was thought to be a GHR antagonist. Moreover, the extremely conserved C-terminal disulfide bridge of GH was disrupted in mutant d188-190 and its role was studied by substituting one or both of the involved cysteines with alanines. All mutants and wild type (wt) GH were produced in human embryonic kidney (HEK)-293 cells and an array of in vitro experiments was established for their characterization. It turned out that the novel d188-190 mutant is not a GHR antagonist after all. It has a diminished binding affinity to GHR, low biological activity and high stability compared to wt GH. R77C and D112G are rather similar to wt GH. The disulfide bridge is important for receptor binding and biological activity of GH. If one of the cysteines is removed the stability of the molecule drops but this can be reversed by removing both cysteines. If further GH mutants are to be identified, the established array of experiments will be useful for their fast characterization and could even contribute to correct treatment of patients.

A celulose é o biopolímero de maior abundância no mundo e tem potencial para se tornar fonte de energia renovável através de sua transformação em açúcares fermentáveis, que por sua vez serão transformados em etanol. A recalcitrância da celulose, principal dificuldade encontrada no processo, pode ser superada com o auxílio de enzimas (celulases). Ao menos três enzimas celulolíticas são necessárias para a degradação total da celulose, incluindo as celobioidrolases, que hidrolisam as ligações glicosídicas das extremidades redutoras e não redutoras da cadeia, as endoglucanases, que clivam a cadeia de celulose amorfa randomicamente, e as beta-glicosidases, que produzem glicose através dos celo-oligômeros. Mas para que esse processo se torne financeiramente viável é necessário conhecer o funcionamento, otimizar a atividade e aumentar a produção dessas celulases. Com o intuito de avançar na compreensão da função e estrutura dessas enzimas, o presente trabalho teve como objetivo o estudo estrutural de beta-glicosidases da família GH1 e endoglucanases da família GH5. Na primeira parte do trabalho, a expressão da endoglucanase II de Trichoderma reesei não foi alcançada, mesmo utilizando diferentes organismos e condições de expressão. Porém, na segunda etapa, foi obtida a expressão, purificação e os primeiros ensaios de cristalização de 11 beta-glicosidases bacterianas da família GH1 e 8 endoglucanases bacterianas da família GH5. Dentre elas, três beta-glicosidases e uma endoglucanase de Bacillus licheniformis foram cristalizadas e tiveram sua estrutura resolvida. As beta-glicosidases, apesar de possuírem o enovelamente similar, apresentaram variações no tamanho e posição das alças formadoras da fenda catalítica e divergem em relação a um dos aminoácidos importantes para a estabilização do substrato. Essas diferenças podem ajudar a explicar o mecanismo dessas enzimas para reconhecer substratos distintos. A endoglucanase da família GH5, possuindo dois módulos acessórios, foi cristalizada tanto na forma apo quanto complexada ao substrato celotetraose. O segundo módulo acessório possivelmente é um domínio de ligação à celulose (CBM) e seus resíduos aromáticos, que são responsáveis pela interação com o substrato, parecem complementar o sítio catalítico, sendo assim um novo mecanismo de auxílio enzimático de um CBM. O primeiro módulo acessório não possui um aparente sítio de interação com carboidratos e provavelmente funciona como um conector entre domínio catalítico e o CBM. O posicionamento do substrato no sítio de ligação é parecido com outras estruturas já determinadas, porém, suscita algumas dúvidas sobre a função dos resíduos catalíticos que é conservada na família. O carbono anomérico do substrato possui uma densidade eletrônica contínua com o glutamato da fita β4 (que deveria ser o ácido/base) e está mais próximo dele que do glutamato da fita β7 (que deveria ser o nucleófilo).
Cellulose is the most abundant biopolymer in the world and can become a renewable energy source through its transformation in fermentable sugars, which will be converted in bioethanol. The cellulose recalcitrance, main difficulty in the process, can be overcome with the aid of enzymes (cellulases). At least three cellulolytic enzymes are required for complete hydrolysis of cellulose, including cellobiohydrolases for hydrolyzing the glycosidic linkages from the reducing and non-reducing chain ends, endoglucanases for randomly cleaving cellulose chains in the amorphous regions, and beta-glucosidases for producing glucose from the solubilized cello-oligomers. But, to become a financially viable process it is necessary to know the mechanism, optimize the activity and improve the production of these cellulases. In order to advance the understanding of the structure and function of these enzymes, the present work intended to study the structure of beta-glucosidases from family GH1 and endoglucanases from family GH5. In the first part of the work, the expression of endoglucanase II from Trichoderma reesei was not achieved, even using different organisms and expression conditions. However, in the second part, the expression, purification and the crystallization first trials of eleven bacterial beta-glucosidases and eight bacterial endoglucanases were achieved. Among them, three beta-glucosidases and one endoglucanase from Bacillus licheniformis were crystallized and had their structures solved. Beta-glucosidases, although having a similar folding, showed variations in the length and position of the loops that form the catalytic cleft and diverge in relation to one of the amino acids that are important in substrate stabilization. These differences may help explain the mechanism of these enzymes to recognize distinct substrates. The endoglucanase, which has two accessory modules, was crystallized in the apo form and complexed with the substrate celotetraose. The second accessory module probably is a cellulose binding domain (CBM) and its aromatic residues, which are responsible for the substrate interaction, seem to complement the catalytic site. Therefore it can be a new mechanism of CBM assistance in the enzymatic activity. The first accessory module has no apparent interaction site with carbohydrates and probably works as a connector between the catalytic domain and CBM. The positioning of the substrate in the binding site is similar to other structures already solved but raises some questions about the role of the catalytic residues, that are conserved in the family. The anomeric carbon of the substrate has a continuous electron density with glutamate from sheet-β4 (which should be the acid/base) and is closer to it than to glutamate from sheet-β7 (which should be the nucleophile).

Les adénomes hypophysaires sont les tumeurs intracérébrales les plus fréquentes. Les adénomes somatotropes hypersécrètent l’hormone de croissance (GH) et sont traités classiquement par des analogues somatostatinergiques. Une petite moitié des patients acromégales est néanmoins résistante à ces traitements. L’on sait depuis, quelques années, que le récepteur de la ghréline possède une forte activité constitutive et joue un rôle majeur dans la sécrétion de GH. Cette activité constitutive est-elle impliquée dans la tumorigenèse des adénomes somatotropes ? Nos travaux ont montré un niveau de transcrits, codant pour le GHS-R, particulièrement élevé dans ces tumeurs, et l’immunocytochimie révèle un marquage punctiforme localisé à la membrane plasmique. La MSP (agoniste inverse du GHS-R) induit une diminution dose-dépendante de la sécrétion de GH des cultures primaires d’adénomes somatotropes. Cette efficacité de la MSP sur la sécrétion de l’hormone de croissance est particulièrement remarquable sur les patients résistants aux agonistes somatostatinergiques chez qui elle démontre une efficacité relative accrue. Des clones, surexprimant le GHS-R humain (lignées MYST-R), ont été générés à partir de lignées somato-lactotropes tumorales de rat (GH4C1). Sur ces cellules, le ligand endogène du GHS-R induit une augmentation d’IP3 intracellulaire. De façon originale, la MSP induit une diminution du niveau d’IP3 intracellulaire. L’inhibition de l’activité constitutive du GHS-R par un agoniste inverse, tel que la MSP, pourrait permettre de réprimer l’hypersécrétion de GH, faisant de cette molécule une alternative pharmacologique aux traitements actuels des adénomes somatotropes
Pituitary tumors are most usual intracranial tumors. The somatotroph adenomas are characterised by a GH hypersecretion. The current treatments are based on somatostatinergic agonists. Unfortunately, there is steel 50% of patients, which remain insensitive to these treatments. The aim of our work was to find a pharmacological alternative to treat the patients resistant to the current therapies. Ghrelin stimulate pituitary GH release in vivo through GHS-R1a activation. Interestingly, this receptor transduces signal through an unusual high constitutive activity. Noteworthy, human somatotroph adenomas expressed a high level of GHS-R1a at both mRNA and protein level. We actually assess the implication of this constitutive activity in the tumorigenesis of the somatotroph adenomas. Firstly we demonstrated GHS-R1a functionality through its capacity to fixe endogenous ligand. Then we showed that treatment of human somatotroph adenomas primary cultures, with the GHS-R1a inverse agonist (MSP: Modified Substance P), induced a dose dependent decrease of GH secretion. To foremost investigate the transduction mechanisms underlying these results, we developed, from GH4C1 (rat somato-lactotroph tumoral cell line), stable monoclonal cell lines overexpressing human GHS-R1a (named MYST-Rg). Interestingly MYST-Rg cells exhibit relatively high basal activation of the IP3 pathway. GHS-R1a endogenous ligand (ghrelin) strengthens basal IP3 pathway activation of MYST-Rg cells. Noteworthy, the basal IP3 pathway activation can be lessened by MSP treatment. Thus, MSP could be a useful alternative to the current therapies of somatotroph adenomas

Orientador: Prof. Dr. Wanius José Garcia da Silva
Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Biotecnociência, 2017.
A hidrolise enzimatica da celulose e realizada pela acao sinergica de pelo menos tres tipos de celulases distintas: endoglucanases, exoglucanases e B.glicosidases. As endoglucanases e celobiohidrolases sao frequentemente inibidas pelo aumento da concentracao de celobiose (dimero de glicose) no meio reacional. As ¿À-glicosidases sao enzimas que clivam celobiose em monomeros de glicose. Portanto, as B-glicosidases sao essenciais ao processo de hidrolise da celulose por impedirem o acumulo de celobiose e, assim, evitar a diminuicao da taxa de hidrolise. Processos de pre-tratamento da biomassa lignocelulosica sao empregados, antes da reacao de hidrolise enzimatica da celulose, a fim de retirar a fracao de lignina e aumentar a taxa de conversao da celulose em glicose. Porem, estes processos de pre-tratamento da biomassa lignocelulosica nao sao 100% eficientes na remocao da lignina. Estudos previos mostraram que a adicao de lignina a celulose pura pode causar a reducao da liberacao de acucar em valores superiores a 60%. Assim, neste estudo, nos caracterizamos a adsorcao nao produtiva da enzima ¿À-glicosidase da familia GH1 da bacteria Thermotoga petrophila (TpBGL1) em ligninas extraidas de diferentes biomassas (cana-de-acucar e eucalipto). Em pH 7 e 6, nossos resultados indicaram que a repulsao eletrostatica enfraquece a adsorcao nao produtiva de TpBGL1 em ligninas. Contudo, em pH 4 a atracao eletrostatica fortalece a adsorcao nao produtiva. Alem disso, o aumento da temperatura de 25 oC para 70 oC nao resultou em um aumento significativo da adsorcao de TpBGL1 em ligninas, provavelmente porque nao ocorre um aumento significativo de regioes hidrofobicas na estrutura da enzima expostas ao solvente. Todas as informacoes obtidas neste estudo poderao ser uteis para aplicacoes biotecnologicas no campo de conversao de polissacarideos estruturais em bioenergia.
The B-glucosidases are a group of important enzymes employed in a large number of industrial applications. In this study, we reported for the first time the photobiosynthesis of stable and functional silver nanoparticles (AgNPs) using two hyperthermostable bacterial â-glucosidases with industrial potential. The syntheses were simple and rapid processes carried out by mixing â-glucosidases and silver solution under irradiation with light (450-600 nm), therefore, compatible with the green chemistry methodology. The synthesized AgNPs were characterized using a series of physical techniques. Absorption spectroscopy showed a strong absorption band at 460 nm due to surface plasmon resonance of the AgNPs. X-ray diffraction analysis showed that the AgNPs were purely crystalline in nature. Electron microscopy showed AgNPs of variable diameter ranging from 20 to 100 nm. In addition, electron microscopy, zeta potential and Fourier transform infrared spectroscopy results confirmed the presence of â-glucosidases coating and stabilizing the AgNPs. The results also showed that the enzymatic activities were maintained in the â-glucosidases assisted AgNPs. The data described in this study should provide a useful basis for future studies of â-glucosidases assisted AgNPs, including biotechnological applications.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Estudo 1 - A ghrelina demonstrou ser um estímulo mais potente do que o GHRP-6 e o GHRH para a secreção de GH em controles e em pacientes com hipertireoidismo. Porém, a resposta do GH após todos os estímulos foi menor na tireotoxicose quando comparada aos indivíduos normais. Portanto, o excesso de hormônios tireoidianos interfere com as vias hipotalâmicas e hipofisárias de liberação de GH ativadas por ghrelina, GHRP-6 e GHRH. Os valores basais de glicemia dos pacientes com hipertireoidismo não foram significativamente diferentes dos observados em controles. A ghrelina promoveu um aumento similar nas concentrações plasmáticas de glicose em ambos os grupos, enquanto que o GHRP-6 não alterou os níveis circulantes de glicose. Portanto, o excesso de hormônios tireoidianos não interfere nos mecanismos de liberação de glicose estimulados pela ghrelina. Estudo 2 - Foi observado um aumento nos valores basais de ACTH e de cortisol nos pacientes com hipertireoidismo comparado com controles, sugerindo que o excesso de hormônios tireoidianos interfere com o eixo hipotálamo-hipófise adrenal. A administração da ghrelina promoveu uma liberação maior de ACTH e de cortisol em ambos os grupos, confirmando que a ghrelina é um estímulo potente para ativação do eixo hipotálamo-hipófise adrenal. A resposta do cortisol à ghrelina e ao GHRP-6 em pacientes com hipertireoidismo foi semelhante a dos controles. A liberação de ACTH após ghrelina na tireotoxicose foi maior que em indivíduos normais, enquanto que com GHRP-6 os valores não alcançaram significância estatística. Nossos dados sugerem que as vias de liberação de ACTH estimuladas pela ghrelina são ativadas pelo excesso de hormônios tireoidianos, porém sem repercussões significativas na resposta adrenocortical..
BV UNIFESP: Teses e dissertações

This report outlines the steps taken to design and develop a 1.2 GHz and 2.4 GHz LEO satellite communication facility at the QUT satellite ground station to allow experimentation and communication links with low earth orbiting (LEO) satellites. The design, setup, construction, testing and installation of the antenna system required by the QUT satellite ground station to operate in the 1.2 GHz and 2.4 GHz frequency bands are described. Existing ground station capabilities and limitations were studied and a complete operational satellite station is suggested for the future to further perform telemetry, tracking and command control. Upgrading the ground station to 1.2 and 2.4 GHz will enable QUT to proceed with investigations and trials on other space related projects.

In dairy cattle, treatment with exogenous growth hormone (GH) affects growth and function of mammary gland. The actions of GH are mediated via interaction with GH receptors (GHR). The first step in signal transduction is homodimerization of two GHR molecules by GH. This step is critical since mutation in either GH or GHR can block dimerization and thus target cell activation. However, association between milk related traits and combination of GH and GHR variations are not known. Accordingly, DNA genotypes in the GH and GHR genes were investigated for association with milk, fat and protein lactation yields in Holsteins. The marker data were obtained on 873 progeny tested bulls by using PCR-RFLP and PCR-SSCP analysis. There were five markers in GH and three in GHR. Estimated breeding values (EBVs) were obtained from Canadian Dairy Network for milk, fat, and protein lactation yields for the 873 genotyped bulls.
There was significant difference among GH6.1 alleles (C-to-G transversion at position 2141) for the milk yield (P < 0.05) and protein yield (p < 0.05). There were significant differences in GHR AluI (A-to-T transversion at -1182) for milk (p < 0.05) and fat (p < 0.05), and GHR StuI (C-to-T transversion at -232) for fat (p < 0.0001) and protein (p < 0.05). Allele frequencies for GH6.1 (C), GHR AluI (A) and GHR StuI (C) alleles in bulls genotyped were 0.95, 0.63 and 0.95, respectively. Bulls with GH6.1 (C/G) genotype had higher milk EBV (p < 0.05) compared to C/C bulls. Bulls with GHR AluI (A/A) genotype had higher milk EBV (p < 0.01) and fat EBVs (p < 0.05). Bulls with StuI (C/C) genotype had higher fat EBV (p < 0.0001) and protein EBV (p < 0.05) compared to StuI (C/T). This study indicates that the combination of GH and GHR markers could serve as a tool to aid in selection for improving milk, fat, and protein production.

A emissão em microondas da Galáxia é um dos principais contaminantes das medidas da Radiação Cósmica de Fundo em microondas (RCFM). Os modelos usuais prevêem três componentes como fontes desta emissão: síncrotron, livre-livre e poeira. No entanto, há evidências de um excesso de emissão nesta região do espectro que estaria aparentemente correlacionado com poeira e que não pode ser explicado pelos modelos de emissão térmica de grãos. Em razão disso, foi proposto mais um mecanismo para explicar este comportamento anômalo da emissão em microondas da Galáxia. Neste trabalho, exploramos as características das emissões galácticas em microondas e do excesso de emissão observado nessa região do espectro. Para isso, usamos os mapas obtidos pelo experimento BEAST em 30 GHz e 41,5 GHz. Aplicamos uma técnica de correlação cruzada entre os mapas BEAST e mapas de referência para as emissões galácticas com o objetivo de estimar a contribuição de cada componente da emissão galáctica nos mapas BEAST. Avaliamos a distribuição espacial das emissões realizando cortes em diferentes latitudes galácticas. Para estudar a emissão difusa da Galáxia e excluir as regiões do Plano Galáctico, aplicamos aos mapas BEAST a máscara Kp2 utilizada nos dados do WMAP. Associando às emissões leis de potência do tipo \textit{T}$\alpha$$\nu$$^\beta$, obtivemos índices espectrais para cada componente galáctica, Analisamos dois ambientes diferentes: as regiões do Plano Galáctico e as regiões difusas que as envolvem. As características espaciais e espectrais de cada componente obtida indicam que: 1) a emissão síncrotron está concentrada no Plano Galáctico, apresentando um índice espectral $\beta$ = -2,9, consistente com o modelo de geração de elétrons no Plano Galáctico; 2) a emissão livre-livre se localiza nas regiões difusas e no Plano Galáctico, apresentando um índice espectral $\beta$ = -1,3, que é menor que o esperado; 3) a emissão de poeira engloba toda a região do Plano Galáctico, apresentando índices que variam entre -2,2 $\textless$$\beta$$\textless$ -1,4; 4) o excesso de emissão na região difusa segue a distribuição da poeira e o índice espectral associado ($\beta$$\sim$-3) é compatível com a emissão de \textit{spinning-dust}. Quando se inclui o Plano Galáctico, o índice espectral ($\beta$$\sim$-1,5) é compatível com o modelo de \textit{spinning-dust} somado à emissão térmica de poeira.
The Galactic microwave emission is one of the main contaminants of the Cosmic Microwave Background (CMB) Radiation measurements. Three components of this foreground are clearly identified: synchrotron, free-free, and dust emission. However, an excess emission in this frequency range has recently been reported, which is apparently correlated with dust emission, and cannot be explained by the usual thermal dust emission model. Several emission mechanisms have been proposed to explain this anomalous behavior of the Galactic microwave emission, including spinning dust emission. In this work, we explore the characteristics of the Galactic microwave emission at 30 GHz and 41.5 GHz using the BEAST experiment data. We used a cross-correlation technique between BEAST maps and Galactic emission templates in order to estimate the contribution of each Galactic microwave emission component to the BEAST maps. The spatial distribution of these emissions is evaluated through Galactic latitude cuts. In order to analyze the Galactic diffuse emission, we apply the WMAP Kp2 mask to the BEAST maps. We obtain spectral indexes for each Galactic microwave emission component (\textit{T}$\alpha$$\nu$$^\beta$). In our analysis, we consider two different environments: the Galactic Plane region and the diffuse region around the Plane. The spatial and spectral characteristics of the Galactic components indicate that the synchrotron emission is concentrated in the Galactic Plane, with spectral index $\beta$= -2,9, which is consistent with the electrons generation model; the free-free emission is located in the diffuse regions and in the Plane, with spectral index $\beta$ = -1,3, which is smaller than the expected one; and the dust emission is present in all the Plane region, with index that varies between -2,2 $\textless$$\beta$$\textless$ -1,4, which is not explained by the thermal dust emission model. The excess emission follows the dust distribution in the diffuse region, with a spectral index ($\beta$$\sim$ -3), which agrees with spinning-dust emission model. When the Galactic Plane is included, the spectral index ($\beta$$\sim$ -1,5) is compatible with a spinning-dust model plus a thermal dust emission model.

Research shows that the warming of the climate over the last century is extremely likely due to human activities. Furthermore, there is a need for an understanding how business activities counteract or contribute to climate change. In particular, the digitalization industry is often introduced as an important player in climate challenge. However, research also concludes that the digitalization industry’s impact on the climate is ambiguous, since it in some cases contributes to climate change and in other cases counteracts it. In order to understand the interplay between greenhouse gas emissions and digital solutions, it is necessary to outline and quantify the emissions from particular digitalization projects and furthermore the industry itself. The thesis takes off in a single case study at a Swedish digitalization consultancy company in order to investigate how both internal greenhouse gas emissions and greenhouse gas emissions from customer projects can be quantified as accurate and as often as possible. The findings disclose that greenhouse gas (GHG) emissions can be tracked with an extremely short time step, practically continuously, especially if the tracking is integrated with the company’s ERP1 . Furthermore, the findings show that greenhouse gas emissions from customer projects can be quantified if interpreting and implementing the GHG Protocol with a soft system methodology (SSM) approach. The thesis contributes with (1) a general interpretation of the Corporate Standard (part of the GHG Protocol) in the context of digitalization; (2) a specific example of that interpretation and implementation; (3) a practical interpretation and implementation of the Project Protocol in the context of digitalization and its avoided or caused greenhouse gas emissions; and (4) a general and an in-depth analysis on the topic of quantifying a Swedish digitalization company’s greenhouse gas emissions and feasible approaches to assumption making.
Forskning slår fast att uppvärmningen av klimatet under det senaste århundradet med extremt hög sannolikhet är orsakad av människan. Det finns ett behov att förstå hur affärsverksamheter motverkar eller bidrar till klimatförändringarna. En del av denna affärsverksamheten sker inom digitaliseringsindustrin, vilken ofta presenteras som en central spelare i klimatfrågan. Å andra sidan visar forskning även på en osäkerhet gällande digitaliseringsindustrins påverkan på klimatet eftersom den i vissa fall bidrar till klimatförändringar medan den i andra fall motverkar dem. För att förstå samspelet mellan växthusgasutsläpp och digitala lösningar är det nödvändigt att överskåda och kvantifiera utsläpp från specifika digitaliseringsprojekt och, vidare, från själva industrin. Uppsatsen grundar sig i en fallstudie på ett svenskt digitaliseringskonsultbolag för att undersöka hur både interna utsläpp och utsläpp från kundprojekt kan kvantifieras så precist och så frekvent som möjligt. Resultaten pekar på att växthusgasutsläppen kan spåras och följas med extremt kort tidssteg, i stort sett kontinuerligt, i synnerhet om spårningen kan integreras med företagets affärssystem. Dessutom visar resultaten på att växthusgasutsläpp från kundprojekt kan kvantifieras om GHG Protocol tolkas och implementeras med hjälp av en “soft systems” metod (SSM). Uppsatsen bidrar med (1) en generell tolkning av Corporate Standard (en del av GHG Protocol) i en digitaliseringskontext; (2) ett specifikt exempel på en sådan tolkning och implementering; (3) en praktisk tolkning och implementering av Project Prototcol (en del av GHG Protocol) in en kontext av digitaliseringsbranschen och dess undvikta eller orsakade utsläpp; och (4) en generell och djupgående analys angående kvantifiering av ett svenskt digitaliseringsbolags växthusgasutsläpp och gångbara inställningar till att göra antaganden.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Physics, 2015.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 181-185).
Photonic band-gap (PBG) structures are promising candidates for electron accelerators capable of high-gradient operation because they have the inherent damping of high order modes required to avoid beam breakup due to instabilities. A key challenge for PBG structures is high-gradient operation without structure damage due to rf-field-induced breakdowns. This thesis reports theoretical results on the design of PBG structures and the generation of wakefields in such structures. It also reports experimental results on PBG structure breakdown testing at high power at both 11 and 17 GHz. A single-cell photonic band-gap (PBG) structure was designed with an inner row of elliptical rods (PBG-E) to reduce ohmic heating relative to a round-rod structure. The PBG-E structure was built and tested at high power at a 60 Hz repetition rate at X-Band (11.424 GHz) at the SLAC accelerator test stand, achieving a gradient of 128 MV/m at a breakdown probability of 3.6 x 10-3 per pulse per meter at a pulse length of 150 ns. The PBG-E structure showed major improvement in breakdown rate relative to a round-rod PBG structure designed at MIT and previously tested at SLAC. A test stand was designed and built at MIT for testing single-cell structures at 17.1 GHz, a frequency 50% higher than the SLAC frequency. This test stand provides comparable diagnostics to those used at SLAC, adding optical diagnostic access which can be used for open PBG structures. A conventional disc-loaded waveguide structure, MIT-DLWG, was tested at MIT at up to a 2 Hz repetition rate. This structure reached a maximum gradient of 87 MV/m at a breakdown probability of 1.19 x 10-1 per pulse per meter. A round-rod PBG structure, MIT-PBG-2, has also been tested at MIT at up to a 2 Hz repetition rate and 100 ns pulse length, demonstrating operation up to 89 MV/rn at a breakdown probability of 1.09 x 10-1 per pulse per meter. These test results show that a PBG structure can simultaneously operate at high gradients and low breakdown probability, while also providing wakefield damping. This makes PBG structures viable candidates for future collider applications.
by Brian J. Munroe.
Ph. D.

Syfte och frågeställningar: Syftet med studien är att undersöka lärares syn på feedback i lärarutbildningen vid Gymnastik och idrottshögskolan (GIH).  Vilken funktion har feedback enligt lärarna? Hur anser lärarna att de använder feedback i sin undervisning? Hur undervisas det om feedback i lärarutbildningen enligt lärarna?   Metod: I studien har vi använt oss av kvalitativa intervjuer som har varit av halvstrukturerad karaktär. Urvalet bestod utav sex lärarutbildare på GIH som alla undervisar i olika ämnen och kurser. Intervjuerna genomfördes på GIH och spelades in med diktafon. Därefter transkriberades intervjuerna ordagrant för analys och bearbetning.   Resultat: Enligt vår studie tycker lärarna vid GIH att feedbackens funktion är att hjälpa studenter att utvecklas och nå mål. Lärarna anser också att feedback kan användas för att öka självkänslan och motivationen. Samtliga lärare menar att de använder feedback i sin undervisning genom att verbalisera den löpande men också genom att ge skriftliga kommentarer på studenternas inlämnade arbeten. Dessutom använder sig alla lärare av metoden att studenterna får ge varandra feedback i undervisningen. De tycker att studenterna ska hämta inspiration från deras lektionsupplägg och därigenom lära sig om feedback, dock nämner de att de antagligen inte tydliggör detta tillräckligt för studenterna. Merparten av lärarna vi har intervjuat tycker att de undervisar för lite om feedback och anser även att det generellt behandlas för lite i lärarutbildningen vid GIH i Stockholm.   Slutsats Lärarna vid GIH ger studenterna feedback och tror att de undervisar om feedback, men vi anser enligt vår studie att de inte tydliggör undervisningen om feedback i tillräcklig omfattning. Att använda feedback betyder inte att man undervisar om det. Medvetenheten kring feedback vid GIH kan förbättras både för lärare och studenter. Detta skulle kunna göras genom att tydliggöra den och låta feedback bli en viktig del i undervisningen, något som skulle kunna leda till att studenterna, framtidens idrottslärare, är bättre rustade inför sin kommande profession.

De siste årene har det dukket opp stadig nye produkter som inkluderer trådløs bruk. Det er alt fra mobiltelefoner, trådløse hjemmenettverk, pulsmålere og sensorer. For at disse systemene skal bli benyttet er det viktig at den trådløse kommunikasjonen fungerer på en tillitsfull måte. Med så mange nye trådløse produkter som, ofte benytter seg av det samme frekvensområdet, kan det oppstå interferens mellom forskjellige apparater. Da er en måte å løse problemet på å benytte seg av diversitetsteknikker. Denne oppgaven tar utgangspunkt i to spesifikke bruksområder for antennediversitet. En fjernkontroll og et trådløst tastatur som skal benytte seg av to antenner for å potensielt forbedre rekkevidden uten at det går ut over batterilevetid og økonomiske hensyn. Kapittel 2 i denne oppgaven tar for seg teorien rundt antenner og diversitetsløsninger og kapittel 3 tar for seg hvordan simuleringene og målingen er gjennomført. I kapittelene 4 og 5 tar oppgaven for seg resultatene fra simuleringene og målingene som har blitt gjort. Det er også diskutert hva som er årsaken til de resultatene målingene viser. Blant annet hvordan for liten avstand mellom to antenner i en romlig antennediversitet sørger for å forverre egenskapene til applikasjonen. Oppgaven har medført variert arbeid. Det er alt fra simuleringer, fremstilling av antenner, oppkopling i målesituasjoner og behandling av instrumenter og måledata. Det er brukt bilder for å illustrere måleoppsettene.

Orientador: Joaquim Brasil Fontes
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Educação
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Doutorado

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Em pacientes com diabetes mellitus tipo 1 (DM1) foram observadas respostas normais ou aumentadas de GH apos estimulos. O eixo hipotalamo- hipofiseadrenal tem sido menos estudado. A ghrelina e um secretagogo de GH que tambem aumenta os niveis de ACTH e de cortisol, de forma semelhante ao GHRP-6. Nao existem estudos sobre os efeitos da ghrelina em pacientes com DM1. O objetivo do presente trabalho foi avaliar as respostas do GH, ACTH e cortisol a ghrelina e ao GHRP-6 em 9 pacientes com DM1 (HbA1c: 11.7 } 1,3%; media } SE) e em 9 individuos normais. A liberacao de GH induzida por GHRH tambem foi estudada. A media dos niveis basais de GH (ƒÊg/L) foi maior nos pacientes com DM1 (3.5 } 1.2) do que nos controles (0.6 } 0.3). Analisando AASC GH (ƒÊg/L.120min), nao foram observadas diferencas significantes entre os diabeticos (ghrelina: 3.148 } 427; GHRP-6: 1428 } 299; GHRH: 885 } 184) e os controles (ghrelina: 3228 } 1036 ; GHRP-6: 1271 } 217; GHRH: 643 } 178). Em ambos os grupos, a liberacao de GH induzida pela ghrelina foi maior do que apos GHRP-6 e GHRH. Houve uma tendencia (p = 0.055) a elevacao dos niveis de cortisol basal (ƒÊg/dL) nos pacientes com DM1 (11.7 } 1.5) comparado aos controles (8.2 } 0.8). Nao foram observadas diferencas significantes nos valores de AASC cortisol (ƒÊg/dL.90min) entre os grupos apos ghrelina (DM1: 303 } 106; controles: 467 } 86) e GHRP-6 (DM1: 135 } 112; controles: 187 } 73). A media de valores basais de ACTH (pg/mL) foi semelhante nos diabeticos (19.9 } 3.4) e nos controles (14.5 } 2.3). Nao foram observadas diferencas nos valores de AASC ACTH (pg/mL.90min) entre os grupos apos ghrelina (DM1: 1372 } 771; controles: 1394 } 327) e GHRP-6 (DM1: 257 } 291; controles: 423 } 211). Em resumo, os pacientes com DM1 tem resposta normal do GH a ghrelina, GHRP-6 e GHRH. A liberacao de ACTH e cortisol apos ghrelina e GHRP-6 tambem e semelhante aos controles. Nossos resultados sugerem que a hiperglicemia cronica do DM1 nao interfere com a liberacao de GH, ACTH e cortisol estimulada por estes peptideos.
In type 1 diabetes mellitus (T1DM), GH responses to provocative stimuli are normal or exaggerated while the hypothalamic-pituitary-adrenal axis has been less studied. Ghrelin is a GH-secretagogue which also increases ACTH and cortisol levels, similarly to GHRP-6. Ghrelin Ls effects in patients with T1DM have not been evaluated. We, therefore, studied GH, ACTH and cortisol responses to ghrelin and GHRP-6 in 9 patients with T1D1 (HbA1c: 11.7 }1.3%; mean }SE) and 9 control subjects. GHRH- induced GH release was also evaluated. Mean basal GH levels (Rg/L) were higher in T1DM (3.5 }1.2) than in controls (0.6 }0.3). Analyzing ĢAUC GH values (Rg/L.120min), no significant differences were observed in T1DM (ghrelin: 3148 }427; GHRP-6: 1428 }299; GHRH: 885 }184) compared to controls (ghrelin: 3228 }1036; GHRP-6: 1271 }217; GHRH: 643 }178). In both groups, ghrelin-induced GH release was higher than after GHRP-6 and GHRH. There was a trend (p=0.055) to higher mean basal cortisol values (Rg/dL) in T1DM (11.7 }1.5) compared to controls (8.2 }0.8). No significant differences were seen in ĢAUC cortisol values (Rg/dL.90min) in both groups after ghrelin (DM1:303 }106; controls: 467 }86) and GHRP-6 (DM1:135 }112; controls: 187 }73). Mean basal ACTH values (pg/mL) were similar in T1DM (19.9 }3.4) and controls (14.5 }2.3). No differences were seen in ĢAUC ACTH levels (pg/mL.90min) in both groups after ghrelin (DM1:1372 }771; controls: 1394 }327) and GHRP-6 (DM1: 257 }291; controls: 423 }211). In summary, patients with T1DM have normal GH responsiveness to ghrelin, GHRP-6 and GHRH. ACTH and cortisol release after ghrelin and GHRP-6 is also similar to controls. Our results suggest that chronic hyperglycemia of T1DM does not interfere with GH, ACTH and cortisol releasing mechanisms stimulated by these peptides.
TEDE
BV UNIFESP: Teses e dissertações

Sharing a band of frequencies in the radio spectrum among multiple wireless systems has emerged as a viable solution for alleviating the severe capacity crunch in next-generation wireless mobile networks such as 5th generation mobile networks (5G). Spectrum sharing can be achieved by enabling multiple wireless systems to coexist in a single spectrum band. In this dissertation, we discuss the following coexistence problems in spectrum bands that have recently been raising notable research interest: 5G and Fixed Satellite Service (FSS) at 27.5-28.35 GHz (28 GHz); 5G and Fixed Service (FS) at 71-76 GHz (70 GHz); vehicular communications and Wi-Fi at 5.85-5.925 GHz (5.9 GHz); and mobile broadband communications and radar at 3.55-3.7 GHz (3.5 GHz). The results presented in each of the aforementioned parts show comprehensively that the coexistence methods help achieve spectrum sharing in each of the bands, and therefore contribute to achieve appreciable increase of bandwidth efficiency. The proposed techniques can contribute to making spectrum sharing a viable solution for the ever evolving capacity demands in the wireless communications landscape.
Ph. D.

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Neste trabalho são apresentadas diversas análises teóricas de desempenho na determinação das propriedades ópticas do radiotelescópio GEM (Galactic Emission Mapping) feitas com auxílio de programas baseados em óptica geométrica e óptica física, bem como a revisão de conceitos teóricos importantes para o desenvolvimento do trabalho. A óptica do radiotelescópio GEM em 5 GHz e em 10 GHz é do tipo Cassegrain, composta por um refletor primário parabólico de 5,5 m e por um refletor secundário de 80 cm. Em 0,408 GHz, 1,465 GHz e 2,3 GHz, a configuração utilizada apresenta apenas o refletor parabólico. A análise da função de alargamento de ponto (Point Spread Function - PSF) mostra que a aberração do sistema é muito pequena. A análise de frente de onda ao longo do eixo óptico mostra que em 5 GHz o erro PV (pico-a-vale) é igual a 8,6 × 10⁻⁴ e que o erro RMS é 2, 3 × 10⁻⁴. Já em 10 GHz, o erro PV é igual a 1,7 × 10⁻ ³ e o erro RMS é 4,6 × 10⁻⁴. Em um plano deslocado de 250 mm do foco, o raio do diagrama de mancha (spot diagram) é de 49 mm, ao passo que o raio do disco de Airy nessa mesma posição é de 137 mm em 5 GHz e de 69 mm em 10 GHz. Estes resultados serão usados no projeto do receptor do GEM em 10 GHz, que será sensível em intensidade total e polarização.

L'argomento principale di questo elaborato è l'analisi delle proprietà termiche del G.H.A .(Golden Hard Anodizing), ovvero un particolare trattamento di trasformazione superficiale dell'alluminio. Nello specifico è stato studiato tramite confronto con la conducibilità termica, la diffusività e l’emissività termica. Per ottenere tali dati sono state svolte prove sperimentali in modo da avere un chiara visione dell'entità di tali proprietà e metterle a confronto con quelle dell'alluminio base e dell'alluminio anodizzato.

A sepse é a principal causa de morte em unidades de terapia intensiva (UTIs) no mundo. A reduzida disponibilidade do aminoácido mais abundante do organismo, a glutamina contribui para o complicado estado catabólico da sepse. No presente estudo investigamos os efeitos da suplementação oral com L-glutamina e L-alanina (GLN+ALA), ambos na norma livre e como dipeptídeo, L-alanil-L-glutamina (DIP), sobre o eixo glutamina-glutationa (GSH), sistema imune, inflamação, proteínas de choque térmico (HSPs) e expressão de genes envolvidos com vias de sinalização proteica em animais endotoxêmicos. Camundongos C57/B6 foram submetidos à endotoxemia (Escherichia coli LPS, 5 mg.kg-1, grupo LPS) e suplementados por 48 horas com L-glutamina (1 g.kg-1) e L-alanina (0,61 g.kg-1, grupo GLN+ALA-LPS) ou 1,49 g.kg-1 de DIP (grupo DIP-LPS). A endotoxemia promoveu depleção da concentração de glutamina no plasma (71%), músculo esquelético (50%) e fígado (49%), quando comparado ao grupo CTRL, sendo restauradas nos grupos DIP-LPS e GLN+ALA-LPS (P<0,05), fato que atenuou a redução da GSH e o estado redox (taxa GSSG/GSH) em eritrócitos circulantes, musculo e fígado (P<0,05). A suplementação em animais endotoxêmicos resultou em uma upregulation dos genes GSR, GPX1 e GCLC no músculo e fígado. A concentração das citocinas plasmáticasTNF-α, IL-6, IL-1β e IL-10 foi atenuada pelas suplementações, bem como a expressão de mRNAs envolvidos com a resposta inflamatória, ativadas pela via do NF-κB(P<0,05). Concomitantemente, verificou-se aumento da capacidade proliferativa de linfócitos T e B circulantes nos grupos GLN+ALA-LPS e DIP-LPS. A expressão de mRNAs e a concentração de HSPs no tecido muscular foi restabelecida pelas suplementações, contudo, a expressão mRNAs relacionados às vias de síntese e degradação proteica foi somente estimulada no tecido hepático(P<0,05). Os resultados do presente estudo demonstram que a suplementação por via oral com GLN+ALA ou DIP podem ser utilizados clinicamente como métodos nutricionais em reverter o quadro de depressão da disponibilidade de glutamina corporal da sepse induzida por LPS, tendo impacto no eixo glutamina-glutationa, sistema imune e inflamatório.
Sepsis is the leading cause of death inintensive care units (ICUs) in the world.The availability ofthe most abundant amino acid in the body, glutamine, is reduced in this situation, fact that contribute to the complicated catabolic state of sepsis. In the present study, we investigated the effects of oral supplementation with L-glutamine and L-alanine (GLN+ALA), both in their free form and as a dipeptide, L-alanyl-L-glutamine (DIP) on glutamine-glutathione axis (GSH), immune and inflammatory system, heat shock proteins (HSPs) expression and gene expressions involved in protein signaling pathways during endotoxemia. C57/B6 mice were subjected to endotoxemia (Escherichia coli LPS, 5 mg.kg-1, LPS group) and supplemented for 48 hours with L-glutamine (1 g.kg-1) plus L-alanine(0.61 g.kg-1, GLN+ALA-LPS group) or 1.49 g.kg-1of DIP (DIP-LPS group). Endotoxemia promoted depletion glutamine concentration in plasma (71%), skeletal muscle (50%) and liver (49%), when compared to the CTRL group, and was restored in the DIP-LPS e GLN+ALA-LPS (P<0.05), fact that attenuate the reduction of GSH and the redox state (GSSG/GSH rate) in circulating erythrocytes, liver and muscle (P<0.05). Supplementations in endotoxemic mice resulted in upregulation of GSR, GCLC and GPX1 genes in muscle and liver. Plasma concentration of TNF-α, IL-6, IL-1β and IL-10 were attenuated by supplementation as well as the expression of mRNAs involved in the inflammatory response, activated by NFκ-B pathway (P <0.05). At the same time, high proliferative capacity of circulating T and B lymphocytes GLN+ALA-LPS e DIP-LPS were observed. HSPs (protein and mRNAs) and in muscle were restored by the supplements, however, the mRNAs expression related to the synthesis and degradation of protein pathways was only stimulated in the liver (P <0.05). Our results demonstrate that oral supplementation with GLN+ALA or DIP can be used as clinically nutritional methods to reverse the depression of body glutamine availability during sepsis induced by LPS, impacting on the glutamine-glutathione axis, immune and inflammatory system.

This thesis was created in cooperation with company Westfalia. The aim of this work is to analyze the possibility of rationalization of production of end parts for gas tight hoses used in the automotive industry. The thesis includes a study of rationalization of possible production of the second generation of end parts as well as completion of assembly line for the current generation of end parts.

Formålet med denne oppgaven er å designe en Dohertyforsterker. En klasse AB og en klasse C effektforsterker til bruk i denne konfigurasjonen skal designes, simuleres og gjøres målinger på hver for seg. Disse skal så å bli satt sammen til en Dohertyforsterker som skal simuleres og gjøres målinger på. Dohertyforsterkeren skal ha en senterfrekvens på 1.8 GHz og være tilpasset slik at det oppnås best PAE og linearitet. Rapporten omhandler i de første kapitlene litt generell forsterkerteori med hovedtrykk på Dohertykonfigurasjonen og hva som er viktig og tenke på når denne designes. Fordelen med en Dohertyeffektforsterker er at den forbedrer effektiviteten over et større dynamisk område. Dette er spesielt viktig for modulerte signaler som ikke har konstant envelope. Den viktigste delen er design, simulering og praktisk måling av effektforsterkerne som hører med i Dohertykonfigurasjonen. Designet av effektforsterkerene er utført med et designverktøy som heter ADS, Advanced Design Systems. For å designe effektforsterkerene med hensyn på best PAE og linearitet ble det benytte ferdiglagde prosjekter i ADS som fant tilpasningsimpedansene som måtte til for å oppnå dette. Transistorvalget falt på en transistor fra Eudyna som heter FLL120MK. Dette valget ble gjort etter mye testing av en annen transistor, som det viste seg ikke kunne brukes fordi den ikkelineære modellen i ADS var utilstrekkelig. Et firma i Florida hadde en storsignalmodell for denne transistoren som det var mulig å få en lisens til, som kunne brukes under masteroppgaven. En ikkelineær simulering av forsterkerne ble utført i ADS og viktige parametere som karakteriserer forsterkerene er P1dB, gain og PAE. For klasse AB forsterkeren ble $P1dB=19dBm$ inneffekt, $Gain_{P1dB}=9.5 dBm$ og $PAE_{P1dB}=36.7%$. Klasse C forsterkeren ble designet for å være i en Dohertykonfigurasjon og hadde et påslagspunkt på 19 dBm, $Gain_{maks}=9.1 dBm$ og maks PAE på 46% . Disse to forsterkerene ble satt sammen til en Dohertykonfigurasjon som fikk $P1dB=29 dBm$ inneffekt, $Gain_{P1dB}=7.1 dBm$ og $PAE_{P1dB}=48.5%$. For å sammenligne en Doherty og en klasse AB forsterker, er PAE i 6 dB backoff punktet som teller. Forbedringen ble på 20%. Lineariteten i Doherty forsterkeren er meget bra og P1dB økte med 9.5dBm. Gainet hadde gått ned 2.5 dBm, som er en ulempe med Dohertykonfigurasjonen og stemmer bra med teorien. Målingene viste at klasse AB forsterkeren fikk et $P1dB=23 dBm$ inneffekt, $Gain_{P1dB}=5.88$ og $PAE_{P1dB}=35%$. En forskjell på 3 dBm i forhold til klasse AB simuleringene. PAE fikk samme verdi som i simuleringene. Klasse C forsterkeren hadde oscillasjoner ved 160 MHz. Dette fulgte med på Dohertyforsterkeren som hadde samme type oscillasjoner da klasse C forsterkeren begynte å lede. Transistormodellen i ADS er veldig nær opp til den praktiske transistoren, men har ustabilitetsegenskaper som ikke kom fra under simuleringene. Biaseringen og stabilitetsnettverket har skylden i at det ikke ble en stabil klasse C-forsterker.

The aim of this master’s theses was a designing of duplexer working in non license frequency band 5.6GHz. The theses is concerning with selection of suitable concept for a given duplexer, with creating a model in software for simulation of distribution of electromagnetic field and with subsequent implementation of duplexer and verifying its parameters.

PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO
COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR
PROGRAMA DE EXCELENCIA ACADEMICA
A busca constante pela melhoria dos meios de comunicação em banda larga demandou o surgimento de novas tecnologias visando atender a real necessidade de seus usuários. O uso de mobilidade no acesso à internet banda larga como propõem os padrões WiMAX e LTE, impõe a necessidade de se estudar com mais profundidade os parâmetros que caracterizam um canal rádio móvel. Este trabalho objetiva apresentar os resultados experimentais que permitem caracterizar em banda estreita o comportamento do canal de radiopropagação num ambiente urbano. Como resultado das campanhas de medições, são identificados modelos do canal que possibilita ao projetista definir os melhores critérios para a implantação de uma rede móvel de acesso sem fio. Desta forma, são apresentadas duas campanhas de medições, operando nas frequências de 2,5 GHz e 3,5 GHz, destinadas para novos serviços móveis banda larga.
The constant search for improvement of broadband communication systems requires new technologies to attend the increasing needs of the users. The use of mobility in broadband Internet access as proposed in WiMAX and LTE standards, imposes the need to further understand the parameters that characterize a channel mobile radio. This dissertation presents experimental results that allow characterizing the narrow band channel behavior of radio propagation in an urban environment. As a result of measurement campaigns, channel models are identified which allow the designer to define the best criteria to implement a mobile wireless network. The work presents results of two measurement campaigns, at the frequencies of 2.5 GHz and 3.5 GHz, designed for new mobile broadband services.

An extensive radio wave propagation measurement campaign was conducted at 1.3 GHz and 4.0 GHz inside four buildings, including a sports arena, a modern closed-plan office building, and two dissimilar, open-plan factories. Measurements were recorded at 57 locations using base station antenna heights of 1.7 meters and 4.0 meters. Results were obtained for mean and maximum excess delay, rms delay spread, time delay jitter, differential delay jitter, and path loss through analyses of impulse response estimates, which were obtained via repetitive 5 ns probing pulses. The effects of frequency, antenna height, topography (line-of-sight or obstructed direct path), and building environment on delay spread and path loss are quantified. Results indicate that, on average, the frequencies and antenna heights used in this study have minimal impact on rms delay spread and path loss. However, topography and building environment significantly affect these parameters. RMS delay spread values as high as 230 ns were observed in open plan factories. Computed path loss power law exponents are 1.84 and 2.35 for line-of-sight and obstructed topographies, respectively. A second campaign was conducted to determine the effects of antenna directivity and polarization on propagation parameters. On average, line-of-sight indoor channels offer 8 dB of cross-polarization discrimination, whereas obstructed environments offer less than 3 dB. Directional antennas provide a significant reduction in rms delay spread over omni-directional antennas. In line-of-sight environments, circular polarization provides an additional delay spread reduction.
Master of Science

Gross National Happiness (GNH) is an aspirational development philosophy promoted by Bhutan’s 4th King. GNH attracted world attention at the United Nations (UN) when Happiness was declared the 9th Millennium Development Goal in 2012. This dissertation examines how GNH is manifest in tourism policy, planning and development in Bhutan. The study employs a constructivist grounded theory methodology (GTM). Data was collected through a number of qualitative methods, including fieldwork, participant observation, case studies, and semi-structured interviews with tourism stakeholders. The investigation follows the researcher’s journey, navigating through a romanticised notion of GNH, to experiencing the issues and challenges of the implementation of GNH policy in tourism in Bhutan. The GTM led the researcher to Foucault’s governmentality framework, which is used to examine the relationship between tourism development and GNH, in particular the changes in Bhutan’s tourism policy from high value, low volume to high value, low impact, between 2008 and 2012. The study uncovered a number of contradictions in the implementation of GNH; paradox through the change in tourism policy; tensions resulting from the Accelerate Bhutan’s Socio-economic Development (ABSD) Plan’s McKinsey Report; controversy around the Ura-Shinghkar Gold Course Development; and, the concerns of some tourism stakeholders about meeting the demands of increasing tourist numbers whilst maintaining GNH principles. The dissertation has found that the first term democratically elected Bhutanese government (2008 - 2013) prioritised economic benefits over its socio-cultural and environmental integrity through the ABSD Plan, and demonstrates the complexities involved in tourism policy, planning and development. The dissertation concludes that the ‘low impact’ tourism policy is unsustainable and proposes that reverting to ‘low volume’ is better aligned to the GNH value-led and slow-paced development philosophy. The study contributes an increased understanding of the complexities inherent in Bhutan aligning its tourism policy, planning and development with its GNH development philosophy.

Mestrado em Ciências Empresariais
O sucesso num ambiente competitivo de negócios, tal como hoje acontece, é uma possível consequência de uma, cada vez maior, administração eficaz dos Recursos Humanos. Estrutura, tecnologia, recursos financeiros e materiais são, apenas, aspectos físicos e ineficazes que precisam de ser aplicados de forma racional, através das pessoas que compõem a organização. Deste modo, o factor que, efectivamente, constitui a dinâmica das organizações são as pessoas. A Gestão de Recursos Humanos assume, assim, cada vez mais uma maior importância no desenvolvimento de uma cultura organizacional direccionada para a inovação e aprendizagem contínua (Chiavenato, 2004). Este trabalho é a etapa final de um longo percurso académico orientado para a obtenção do grau de mestre em Ciências Empresariais. O seu objectivo consiste em explanar tudo o que pude aprender durante o meu estágio curricular na Pierre Fabre Portugal, Lda. No Capítulo I, será apresentada a componente teórica do trabalho, onde será explanada a evolução da função Recursos Humanos ao longo dos tempos, bem como a relação que pode existir entre a estratégia das organizações e a estratégia da Gestão de Recursos Humanos, de acordo com as características de cada organização. Por fim, serão descritas algumas das técnicas e práticas utilizadas na Gestão de Recursos Humanos. No Capítulo II, será abordada a componente prática, consequência da aprendizagem obtida em tempo de estágio, para que, finalmente, no Capítulo III, se desenvolvam conclusões, fruto do confronto do enquadramento teórico com a componente prática.
Nowadays, the success in a competitive business environment is probably due to the increasing Human Resources effective management. Structures, technologies, financial resources and materials are just physical and ineffective aspects that need to be used in a rational way by the people who make the organization. Therefore, the factor that truly makes up the dynamic of organizations is people. The administration of Human Resources is gradually becoming more important in the development of an organizational culture moving towards innovation and continuous learning (Chiavenato, 2004). This report is the final stage of a long academic path for the title of Master in Management Sciences. Its main purpose is to fully explain everything I learned during my internship at Pierre Fabre Portugal, Lda. Chapter One contains the theory of the evolution of Human Resources through history and the possible connection between the strategies of an organization and the ones in Human Resources Management according to the main characteristics of each organization. Lastly, there is a description of some of the techniques and procedures used in Human Resources Management. In turn, Chapter Two is an approach to the practical elements that were learned during the internship culminating in Chapter Three in the form of conclusions stemming from the comparison between the theoretical and the practical aspects.

Buvo nustatyta, kad redukuoto glutationo koncentraciją pelių kepenyse kadmis padidino po 8 val. 35 proc., o po 14 dienų sumažino 35 proc. Po 8 val., tiek cinkas, tiek selenas taip pat padidino redukuoto glutationo koncentraciją, atitinkamai, 27 proc. ir 17 proc. Įvertinant malondialdehido koncentraciją pelių kepenyse, buvo nustatyta, kad kadmis padidino malondialdehido koncentraciją po 8, 24 val. ir 14 dienų, atitinkamai, 336 proc., 218 proc. ir 182 proc. Veikiant cinkui ir selenui, malondialdehido koncentracija pelių kepenyse padidėjo po 24 val. ir 14 dienų, atitinkamai, 325 proc. ir 437 proc., o po 14 dienų, atitinkamai, 162 proc. ir 288 proc. Taigi, cinkas pajėgus apsaugoti redukuotą glutationą nuo oksidacijos tik 8 val., o po ilgesnio laiko redukuotas glutationas išeikvojamas. Po 8 ir 24 val. tiek cinkas, tiek selenas pelių kepenyse geba apsaugoti lipidus nuo peroksidacijos, o po 14 dienų redukuotą glutationą nuo oksidacijos ir lipidus nuo peroksidacijos apsaugo tik žaliosios arbatos ekstraktas.
It was determined, that after 8 h cadmium increased glutathione concentration by 35 % while after 14 days decreased by 35 %. After 8 h both zinc and selenium also increased reduced glutathione concentration, respectively, 27 % and 17 %. Evaluating malondialdehyde concentration in mice liver, it was established, that cadmium increased malondialdehyde concentration after 8, 24 h and 14 days, respectively, 336 %, 218 % and 182 %. When mice liver were affected with zinc and selenium, malondialdehyde concentration increased after 24 h, respectively, 325 % and 437 % and after 14 days, respectively, 162 % and 288 %. To sum up, zinc can protect reduced glutathione from oxidation in mice liver just for 8 h, and after a longer period reduced glutathione is depleted. After 8, 24 h and 14 days both, zinc and selenium are eager to protect liver from lipid peroxidation and after 14 days reduced glutathione from oxidation. Lipids from peroxidation process can protect only green tea extract.

Prostate cancer is the second most common cause of cancer-related deaths in Western males. Current diagnostic, prognostic and treatment approaches are not ideal and advanced metastatic prostate cancer is incurable. There is an urgent need for improved adjunctive therapies and markers for this disease. GPCRs are likely to play a significant role in the initiation and progression of prostate cancer. Over the last decade, it has emerged that G protein coupled receptors (GPCRs) are likely to function as homodimers and heterodimers. Heterodimerisation between GPCRs can result in the formation of novel pharmacological receptors with altered functional outcomes, and a number of GPCR heterodimers have been implicated in the pathogenesis of human disease. Importantly, novel GPCR heterodimers represent potential new targets for the development of more specific therapeutic drugs. Ghrelin is a 28 amino acid peptide hormone which has a unique n-octanoic acid post-translational modification. Ghrelin has a number of important physiological roles, including roles in appetite regulation and the stimulation of growth hormone release. The ghrelin receptor is the growth hormone secretagogue receptor type 1a, GHS-R1a, a seven transmembrane domain GPCR, and GHS-R1b is a C-terminally truncated isoform of the ghrelin receptor, consisting of five transmembrane domains. Growing evidence suggests that ghrelin and the ghrelin receptor isoforms, GHS-R1a and GHS-R1b, may have a role in the progression of a number of cancers, including prostate cancer. Previous studies by our research group have shown that the truncated ghrelin receptor isoform, GHS-R1b, is not expressed in normal prostate, however, it is expressed in prostate cancer. The altered expression of this truncated isoform may reflect a difference between a normal and cancerous state. A number of mutant GPCRs have been shown to regulate the function of their corresponding wild-type receptors. Therefore, we investigated the potential role of interactions between GHS-R1a and GHS-R1b, which are co-expressed in prostate cancer and aimed to investigate the function of this potentially new pharmacological receptor. In 2005, obestatin, a 23 amino acid C-terminally amidated peptide derived from preproghrelin was identified and was described as opposing the stimulating effects of ghrelin on appetite and food intake. GPR39, an orphan GPCR which is closely related to the ghrelin receptor, was identified as the endogenous receptor for obestatin. Recently, however, the ability of obestatin to oppose the effects of ghrelin on appetite and food intake has been questioned, and furthermore, it appears that GPR39 may in fact not be the obestatin receptor. The role of GPR39 in the prostate is of interest, however, as it is a zinc receptor. Zinc has a unique role in the biology of the prostate, where it is normally accumulated at high levels, and zinc accumulation is altered in the development of prostate malignancy. Ghrelin and zinc have important roles in prostate cancer and dimerisation of their receptors may have novel roles in malignant prostate cells. The aim of the current study, therefore, was to demonstrate the formation of GHS-R1a/GHS-R1b and GHS-R1a/GPR39 heterodimers and to investigate potential functions of these heterodimers in prostate cancer cell lines. To demonstrate dimerisation we first employed a classical co-immunoprecipitation technique. Using cells co-overexpressing FLAG- and Myc- tagged GHS-R1a, GHS-R1b and GPR39, we were able to co-immunoprecipitate these receptors. Significantly, however, the receptors formed high molecular weight aggregates. A number of questions have been raised over the propensity of GPCRs to aggregate during co-immunoprecipitation as a result of their hydrophobic nature and this may be misinterpreted as receptor dimerisation. As we observed significant receptor aggregation in this study, we used additional methods to confirm the specificity of these putative GPCR interactions. We used two different resonance energy transfer (RET) methods; bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET), to investigate interactions between the ghrelin receptor isoforms and GPR39. RET is the transfer of energy from a donor fluorophore to an acceptor fluorophore when they are in close proximity, and RET methods are, therefore, applicable to the observation of specific protein-protein interactions. Extensive studies using the second generation bioluminescence resonance energy transfer (BRET2) technology were performed, however, a number of technical limitations were observed. The substrate used during BRET2 studies, coelenterazine 400a, has a low quantum yield and rapid signal decay. This study highlighted the requirement for the expression of donor and acceptor tagged receptors at high levels so that a BRET ratio can be determined. After performing a number of BRET2 experimental controls, our BRET2 data did not fit the predicted results for a specific interaction between these receptors. The interactions that we observed may in fact represent ‘bystander BRET’ resulting from high levels of expression, forcing the donor and acceptor into close proximity. Our FRET studies employed two different FRET techniques, acceptor photobleaching FRET and sensitised emission FRET measured by flow cytometry. We were unable to observe any significant FRET, or FRET values that were likely to result from specific receptor dimerisation between GHS-R1a, GHS-R1b and GPR39. While we were unable to conclusively demonstrate direct dimerisation between GHS-R1a, GHS-R1b and GPR39 using several methods, our findings do not exclude the possibility that these receptors interact. We aimed to investigate if co-expression of combinations of these receptors had functional effects in prostate cancers cells. It has previously been demonstrated that ghrelin stimulates cell proliferation in prostate cancer cell lines, through ERK1/2 activation, and GPR39 can stimulate ERK1/2 signalling in response to zinc treatments. Additionally, both GHS-R1a and GPR39 display a high level of constitutive signalling and these constitutively active receptors can attenuate apoptosis when overexpressed individually in some cell types. We, therefore, investigated ERK1/2 and AKT signalling and cell survival in prostate cancer the potential modulation of these functions by dimerisation between GHS-R1a, GHS-R1b and GPR39. Expression of these receptors in the PC-3 prostate cancer cell line, either alone or in combination, did not alter constitutive ERK1/2 or AKT signalling, basal apoptosis or tunicamycin-stimulated apoptosis, compared to controls. In summary, the potential interactions between the ghrelin receptor isoforms, GHS-R1a and GHS-R1b, and the related zinc receptor, GPR39, and the potential for functional outcomes in prostate cancer were investigated using a number of independent methods. We did not definitively demonstrate the formation of these dimers using a number of state of the art methods to directly demonstrate receptor-receptor interactions. We investigated a number of potential functions of GPR39 and GHS-R1a in the prostate and did not observe altered function in response to co-expression of these receptors. The technical questions raised by this study highlight the requirement for the application of extensive controls when using current methods for the demonstration of GPCR dimerisation. Similar findings in this field reflect the current controversy surrounding the investigation of GPCR dimerisation. Although GHS-R1a/GHS-R1b or GHS-R1a/GPR39 heterodimerisation was not clearly demonstrated, this study provides a basis for future investigations of these receptors in prostate cancer. Additionally, the results presented in this study and growing evidence in the literature highlight the requirement for an extensive understanding of the experimental method and the performance of a range of controls to avoid the spurious interpretation of data gained from artificial expression systems. The future development of more robust techniques for investigating GPCR dimerisation is clearly required and will enable us to elucidate whether GHS-R1a, GHS-R1b and GPR39 form physiologically relevant dimers.

La ghréline, une hormone peptidique principalement synthétisée au niveau de l'estomac, est le ligand endogène du récepteur des sécrétagogues de l'hormone de croissance appelé GHS-R1a. Elle est impliquée dans de nombreux processus biologiques dont principalement la sécrétion de l'hormone de croissance et la régulation de l'homéostasie énergétique. En raison de ses propriétés orexigènes et adipogènes, la ghréline est un outil puissant pour lutter contre les déséquilibres énergétiques. Développer des antagonistes de son récepteur représente ainsi une stratégie prometteuse pour la découverte de nouvelles pharmacothérapies contre l'obésité.Cette thèse est consacrée au développement d'antagonistes du récepteur de la ghréline dont la structure est basée sur une plateforme peptidomimétique : le 1,2,4-triazole 3,4,5-trisubstitué. Notre objectif est de concilier au mieux l'affinité et l'activité de nos ligands vis-à-vis du GHS-R1a avec des propriétés optimisées permettant de favoriser une bonne biodisponibilité orale. Nous nous sommes basés sur une synthèse rapide et efficace de ces composés pour réaliser des études approfondies de relations structure-activité et structure-propriété. En optimisant successivement les différentes positions autour du motif triazole, des compromis intéressants ont été obtenus. Nous avons ainsi identifié des antagonistes affins du récepteur qui présentent une stabilité microsomale suffisante et une perméabilité membranaire satisfaisante pour envisager des études in vivo
Ghrelin, a peptidic hormone which is mainly synthesized in the stomach, is the endogenous ligand of the growth hormone secretagogue receptor named GHS-R1a. It is involved in numerous biological processes such as the growth hormone secretion and the control of energy homeostasis. Because of its orexigenic and adipogenic properties, ghrelin is a potent tool to control energy imbalance. Developing ghrelin receptor antagonists represents a promising strategy for the discovery of anti-obesity new drugs.This thesis is devoted to the development of ghrelin receptor antagonists based on a peptidomimetic scaffold: the 3,4,5-trisubstituted 1,2,4-triazole. Our aim is to combine ligand affinity and activity towards GHS-R1a with optimized properties which enable to promote a good oral bioavailability. We based our work on a rapid and efficient synthesis of our compounds to carry out detailed structure-activity and structure-property studies. By successively optimizing the different positions around the triazole scaffold, interesting compounds were obtained. We have thus identified receptor antagonists which exhibit sufficient microsomal stability and satisfactory membrane permeability to consider in vivo studies

Thesis (M. Eng. and S.B.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2001.
Includes bibliographical references (leaves 40-41).
A low dispersion 2-GHz comparator is an essential part of the latest automated VLSI tester by Teradyne Inc. With each new and faster CMOS logic VLSI microchips, faster and more precise comparators are needed to verify that the static discipline is being met on the many pins of the integrated circuit. As the error in the comparator is lowered, the VLSI production yield is greatly increased because of greater certainty of the measurements. The comparator described within is designed to test a variety of CMOS logic levels at the expected logic levels and rise-times of the near future. The result is a Si-Ge integrated comparator with 12psec of dispersion by detailed simulation awaiting fabrication. Index Terms-Complementary metal oxide semiconductor transistor technology (CMOS technology), very large scale integration (VLSI), application specific integrated circuit (ASIC), silicon germanium (Si-Ge), integrated circuits (IC), automatic test equipment (ATE), personal computer (PC), digital signal processing (DSP), direct current (DC), alternating current (AC), device under test (DUT), pin electronics (PE), bipolar junction transistors (BJT), complementary metal oxide semiconductor field effect transistor (MOSFET).
by William F. Johnston.
M.Eng.and S.B.

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Engenharia Biomédica
A 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.

On présente l'étude et la réalisation d'une antenne réseau cylindrique directive à 32 GHz. Une approximation simple, dite approximation plane, est développée pour dimensionner le réseau. On démontre la médiocrité d'une solution utilisant la technologie guides à fentes axiales sur le cylindre. Un mode d'alimentation, dite mode simultané, est introduit afin de simplifier le circuit d'alimentation. On démontre sa validité dans le cas d'une réalisation en technologie microruban. Le diagramme d'un élément microruban incliné de 45° sur un cylindre est calculé en utilisant le modelé de la cavité. Le logiciel d'analyse développé est validé par une réalisation d'un réseau cylindre à 12 GHz. Les limitations de 4 types de diviseurs de puissance en technologie microruban sont examinées à travers plusieurs réalisations pratiques. Le réseau cylindrique réalisé à 32 GHz est mesuré et comparé au calcul. Les performances obtenues sont globalement satisfaisantes et quelques axes d'améliorations possibles sont donnés. Une retombée indirecte de cette thèse a été le développement d'une méthode précise pour l'analyse large bande des réseaux plans en guides à fentes

This thesis deals with brief research on problematics of antennas in microwave band for omni-directional applications, own design and assembling of such an antenna. The purpose of the design is to have a best possible radiation patterns and reflection loss of our antenna. Conical monopole is chosen and it is simulated and changed to get the best possible parameters. Two prototypes are manufactured with mechanical changes applied and their parameters measured. Finished antenna is used for experimental channel measurement.

ABSTRACT Mining Merensky reef successfully at Booysendal Mine will require a machine which enhances team efficiencies delivering results on specified operational and quality parameters. The operational objective of the Booysendal Mine trial of the 3108 ADE Roof bolter was to prove that this machine can mine at 1900 mm stoping width and to set a base for KPIs. The purpose of the upgraded 3108 ADE machine was to achieve to drill and install a bolt in 8 minutes translating in 3 bords supported per shift. This machine had to deliver 235m, 1900 m² per month at stoping width of 1900mm translating to 2.55g/ton in terms of head grade. The objective of this study is to assess the use of industrial engineering techniques to expedite the implementation of a roofbolter in the challenging environment at Booysendal Mine. The process of creating a learning environment is one of the important goals in many business improvement frameworks, and underlies the work done here. To deliver on the above mentioned objectives, this research presents a case study in the use of several industrial engineering techniques:  Lean Manufacturing tools were used to draw up effective communication channels for Operators engagement, visible performance data gathering and performance monitoring.  Observational research methods were used to assess and evaluate the impact of 3108a modifications in achieving the set KPIs per shift in a real underground situation.  The A3 report process was used as the framework to communicate the process of the 3108a machine Roll-out to people on the team. Theory suggests that the method of implementation presented here will create a learning environment, which will in turn meet production targets. The implementation team had set itself a number of production targets, primarily a demand for 42 bolts per shift to be installed and stoping width to be controlled to 1900mm. The targets were based both on benchmarks elsewhere and on economic demands at the mine. iii The study shows that through a step-to-step improvement approach the Operators improved from installing less than 19 bolts per shift to move to 19 – 34 bolts per shift. The 1900mm stoping width target was not consistently achieved. In this study, the author played the role of Project Champion, actioning the knowledge acquired when attending the CMMS courses and applied tools/tactics learned from Trackless Mining and Operations Management courses and tools such as Lean Manufacturing, A3 reports and physical observations. The main thrust of this study was to answer this central question: How well will a set of industrial engineering tools work to improve the modified GHH bolter performance to enable the Merensky shaft to efficiently mine at a stoping width of 1900mm consistently? The research shows that detailed improvement approach delivered more bolts drilled and installed per shift. The report goes further and gives practical on-site implementation team actions taken to ensure a machine delivers 3 bords per shift. Where the implementation team identified challenges outside the scope of this study for addressing the stoping width, the team gave recommendations to relevant technical team on-mine. The tools performed well:  The most successful tool was the use of visual indicators and other elements of communication from Lean to engage Operators and encourage the use of gathering data for process improvement because key feature of Lean is its ability to manage a large number and variety of issues simultaneously using visual prompts to assist in communication of issues.  Lean promotes “going to the Gemba” – managers need to see exactly how things really work. The observational tools used in this implementation showed the value of physical observations because even if 8 minutes per installed bolts was not achieved the implementation team knew exactly where the constraints were and how to tackle it.  The A3 methodology was an effective way of structuring and managing the improvement process in the implementation of the Roof bolter. Through the stepped approach in this case study we managed to deliver exceptional production results six months ahead of planned timeframe.
EM2018

Η αυξητική ορμόνη (GH), πολυλειτουργική ορμόνη που παράγεται από τα σωματοτρόπα κύτταρα του πρόσθιου λοβού της υπόφυσης, προάγει την μεταγεννητική ανάπτυξη σκελετικών και μαλακών ιστών. Επίσης, ασκεί ποικίλες άλλες βιολογικές δράσεις, όπως ρύθμιση του μεταβολισμού των υδατανθράκων, των πρωτεϊνών και του λίπους. Κατά συνέπεια, η ανεπάρκεια της εκτός από αναπτυξιακά μπορεί να προκαλέσει και σοβαρά μεταβολικά προβλήματα. Η GH δρα στους περιφερικούς ιστούς άμεσα αλλά και έμμεσα μέσω του ινσουλινόμορφου αυξητικού παράγοντα IGF-I. Μετά από πρόσδεση της GH στον υποδοχέα της (GHR), ο IGF-I παράγεται στο ήπαρ, όπου απελευθερώνεται στην γενική κυκλοφορία, αλλά παράγεται και τοπικά στους περιφερικούς ιστούς, όπου δρα με αυτοκρινή ή παρακρινή τρόπο. Η έκκριση της GH από την υπόφυση έχει παλμική μορφή και ρυθμίζεται κυρίως μέσω τριών υποφυσιοτρόπων παραγόντων: εκλυτική ορμόνη της GH (GHRH), σωματοστατίνη (SRIF) και γκρελίνη. Η απελευθέρωση της GHRH και της SRIH από τον υποθάλαμο επηρεάζεται και από μια ποικιλία άλλων νευροδιαβιβαστών, νευροορμονών και νευροπεπτιδίων. Έχει υπολογιστεί σε διάφορες μελέτες ότι κοντό ανάστημα συσχετιζόμενο με ανεπάρκεια της αυξητικής ορμόνης (GHD) παρατηρείται με συχνότητα 1 στις 4000 έως 1 στις 10000 γεννήσεις. Παρόλο που οι περισσότερες περιπτώσεις είναι σποραδικές και θεωρούνται αποτέλεσμα περιβαλλοντικών εγκεφαλικών προσβολών ή αναπτυξιακών ανωμαλιών, γενετική αιτιολογία προτείνεται περίπου στο 10% των GHD περιπτώσεων, λόγω του ότι έχει προσβληθεί ένας τουλάχιστον πρώτου βαθμού συγγενής. Η διάγνωση της GHD είναι μια πολύπλευρη διαδικασία που απαιτεί εκτενή κλινική εκτίμηση, αξιολόγηση σωματομετρικών παραμέτρων, βιοχημικές δοκιμασίες του GH-IGF άξονα, και ακτινολογική εκτίμηση. Η GHD μπορεί να παρουσιάζεται είτε ως μεμονωμένο πρόβλημα (IGHD) είτε σε συνδυασμό με πολλαπλές ορμονικές ανεπάρκειες (CPHD). Μοντέλα ζώων έχουν χρησιμοποιηθεί για μελέτη της φυσιολογικής λειτουργίας του υποθαλαμικού-GH άξονα και των πιθανών διαταραχών που οδηγούν σε IGHD/CPHD στους ανθρώπους. Σύμφωνα με τα κλινικά χαρακτηριστικά, τον τρόπο κληρονομικότητας και την ανταπόκριση στην εξωγενή θεραπεία, τέσσερις τύποι οικογενούς IGHD έχουν περιγραφεί στον άνθρωπο. Μεταλλαγές έχουν βρεθεί να συμβαίνουν στο GH γονίδιο (GH1) και στο γονίδιο του υποδοχέα της GHRH (GHRH-R). Πολυμορφισμοί στον υποκινητή του GH1 γονιδίου μειώνουν επίσης την έκφραση του. Πρόσφατα, μεταλλαγές στο γονίδιο του υποδοχέα της γκρελίνης (GHS-R) συσχετίστηκαν με IGHD. Μεταλλαγές σε διακριτά γονίδια μεταγραφικών παραγόντων, που είναι βασικά για την ανάπτυξη και διαφοροποίηση των κυττάρων του πρόσθιου λοβού της υπόφυσης, όπως Pit1/POU1F1, PROP1, HESX1, LHX3, LHX4, έχουν αναγνωρισθεί μέχρι σήμερα σε ανθρώπους με CPHD. Καθώς μεγάλο ποσοστό οικογενών περιπτώσεων IGHD/CPHD δεν οφείλεται σε μεταλλαγές σε κάποιο από τα ήδη γνωστά γονίδια, φαίνεται να εμπλέκονται μεταλλαγές σε επιπρόσθετα υποψήφια γονίδια. Περαιτέρω γενετικές μελέτες μπορούν να συμβάλλουν σε καλύτερη κατανόηση της GHD, σε πρώιμη διάγνωση και βελτίωση της θεραπευτικής αγωγής στα άτομα με GHD.
Growth hormone (GH), a multifunctional hormone which is synthesized in the somatotrope cells of the anterior pituitary gland, promotes postnatal development of skeletal and soft tissues. In addition, GH exerts multiple biological actions, such as regulating the metabolism of carbohydrates, proteins and fat. Consequently, GH deficiency (GHD) apart from causing developmental disorders can also have a deleterious effect on the body’s metabolism. GH acts on peripheral tissues both directly and indirectly, through the mediation of insulin-like growth factor-1 (IGF-1). Upon binding of GH to its receptor (GHR), IGF-1 is produced both in the liver, from where it is released into the general circulation, and locally in the peripheral tissues, such as bone, cartilage, and muscle, where it acts in an autocrine or paracrine fashion. GH is secreted from the pituitary gland in a pulsatile fashion. Major regulatory factors include three hypophysiotropic factors: GH releasing hormone (GHRH), somatostatin (SRIF), and ghrelin. Moreover, GH secretion can be affected by a variety of other neurotransmitters, neurohormones and neuropeptides. The diagnosis of GHD demands detailed clinical, auxological, radiological and biochemical evaluation of the GH-IGF axis. GHD may occur as isolated GHD (IGHD) or in combination with other pituitary hormone deficiencies (Combined Pituitary Hormone Deficiency, CPHD). The physiological actions of the hypothalamic-GH axis and the possible disorders leading to IGHD/CPHD in humans have been extensively studied in animal models. Short stature associated with GHD has been estimated to occur in about 1/4000-1/10000 in various studies. Whereas most cases are sporadic and believed to result from environmental cerebral insults or developmental anomalies, approximately 10% of the affected individuals have a first-degree relative with the same disorder, suggesting a hereditary trend and genetic factors affecting the disorder. Four types of familial IGHD have been described in humans according to clinical characteristics, the mode of inheritance and the response to exogenous therapy. Mutations reducing gene expression have been described in the GH1 gene and in the GHRH receptor (GHRH-R) gene. Polymorphisms found in the promoter of the GH1 gene can also reduce its expression. Recently, mutations in the ghrelin receptor (GHS-R) gene were associated with IGHD. Mutations in discrete genes of transcriptional factors necessary for the development and differentiation of anterior pituitary cells, such as Pit1/POU1F1, PROP1, HESX1, LHX3, LHX4 have been recognized in individuals with CPHD. Considering that a large proportion of familial cases of IGHD/CPHD are not caused by mutations in any of the known genes, mutations in additional candidate genes may be involved. Further genetic studies may contribute to a better understanding of GHD, earlier diagnosis and better therapeutic approaches for this disorder.

生長和繁殖這兩個最主要的生理過程在脊椎動物中是密切相關的。生長主要是由腦-垂體-肝軸，即促生長激素釋放激素/垂體腺苷酸環化酶激活肽（GHRH/ PACAP-生長激素（GH）-胰島素樣生長因子（IGFs）軸所控制。值得一提的是，所有與這個神經內分泌軸相關的基因在卵巢中都有表達。這表明一個有功能的微型軸很可能存在於卵巢中。我們著重研究PACAP，該軸的上游因子，來揭示卵巢中這個微型軸的存在和功能。
PACAP是一種最初從羊的下丘腦純化出來的夠能刺激cAMP分泌的神經肽，研究表明它也存在於如卵巢在內的其它各種外圍組織中。在斑馬魚中，兩種形式的PACAP（PACAP38-1，adcyap1a; PACAP38-2，adcyap1b）和三個 PACAP受體（PAC1-R，adcyap1r1; VPAC1-R，vipr1和VPAC2-R，vipr2）均在卵巢中表達。為了確定PACAP系統在斑馬魚的卵巢中有重要作用，我們首先對 PACAP的配體和三個受體在濾泡中的空間分佈進行了研究。此外，為了研究PACAP系統的潛在作用，我們還分析了PACAP的配體和受體在濾泡發育和成熟時期的表達情況。PACAP系統在濾泡細胞中時空表達的數據顯示，PACAP可能在調節濾泡發育和成熟中發揮雙重作用，這雙重作用是通過PACAP作用於不同的受體上完成的。卵母細胞體外成熟實驗的結果顯示PACAP可以促進完整的濾泡卵母細胞的成熟，但抑制裸露的卵母細胞體外自發成熟，這也進一步支持了我們的假說。
我們以前的研究表明，在原代培養的斑馬魚濾泡細胞中，垂體促性腺激素（HCG）可以顯著提高PACAP（PACAP38-2）的表達。因此，PACAP很可能是垂體促性腺激素控制卵巢功能的下游調節者。我們從幾個方面來驗證我們的假設。首先，由於激活素/結合蛋白系統是公認的垂體促性腺激素（HCG）的下游調節者，我們研究了PACAP對該系統表達的調控。研究結果表明，PACAP不僅能模仿促性腺激素對激活素/結合蛋白系統表達的調控，同時也刺激激活素介導的卵母細胞的成熟。PACAP和hCG選擇同樣的信號通路對激活素/結合蛋白系統進行調控進一步證實 PACAP的下游調節作用。其次，卵巢內源性生長因子，表皮生長因子EGF對PACAP調控激活素/結合蛋白系統表達的影響和其對hCG調控該系統表達的影響是一樣的。表皮生長因子可以作用於其膜上的受體並且使用MEK途徑來調節PACAP對激活素/結合蛋白系統的表達的調控。第三，我們研究了PACAP對激素生成的影響。芳香化酶是激素生成中一個十分重要的酶，它可以將睾酮轉化成雌激素E2。PACAP能刺激斑馬魚濾泡細胞中芳香化酶的表達。cAMP類似物，如forskolin和dbCAMP都可以模仿PACAP對芳香化酶的表達。PKA抑製劑 H89，可以完全抑制 PACAP誘導的芳香化酶的表達，這表明PACAP通過cAMP-PKA依賴性途徑調節芳香化酶的表達。由於促性腺激素也使用相同的cAMP-PKA途徑調節芳香化酶的表達，這進一步證實了PACAP是促性腺激素的下游調節者。
我們還研究了PACAP對該軸的其他因子調控，以便確定卵巢中是否存在一個有功能的GHRH/PACAP-GH-IGF軸。我們使用斑馬魚原代培養的濾泡細胞作為研究體系進行了一系列的基因調控的研究。PACA可以刺激gh及其受體 ghra和ghrb的表達。此外，它還增加了igf1表達，但對igf2a和igf2b的表達沒有明顯的影響。鑑於之前的工作證明重組zfGH可以刺激igf1的表達，我們有理由相信，在斑馬魚卵巢中存在一個有功能的GHRH/PACAP-GH-IGF軸。PACAP對此軸的調節作用也主要是通過cAMP-PKA途徑。
本研究不僅增加了我們對GHRH/PACAP-GH-IGF軸在卵巢中功能的了解，而且還提供了關於魚類生長和繁殖的協調方面有價值的信息，這必將有利於水產養殖。魚脊椎動物中最原始，最多元化的群體，目前的研究結果為其他生物的研究也提供了重要的參考。
Growth and reproduction are two major physiological processes, which have been proven to be closely related in vertebrates. The process of growth is governed by the brain-pituitary-liver axis involving growth hormone releasing hormone/ pituitary adenylate cyclase-activating polypeptide (GHRH/PACAP), growth hormone (GH) and insulin-like growth factors (IGFs). Interestingly, the expression of all the genes involved in this axis has been reported in the ovary, which indicates that a functional mini-axis might exist in the ovary. In this study, we focus on the characterization of PACAP, the upstream element of the axis, to reveal the existence and functional roles of this intraovarian mini-axis.
PACAP is a neuropeptide originally purified from ovine hypothalamus for its potent activity to stimulate cAMP production. However, its presence and actions have also been demonstrated in various peripheral tissues including the ovary. In the zebrafish, two forms of PACAP (PACAP₃₈-1, adcyap1a; and PACAP₃₈-2, adcyap1b) and three PACAP receptors (PAC1-R, adcyap1r1; VPAC1-R, vipr1 and VPAC2-R, vipr2) were all expressed in the ovary. To provide clues to the importance of the PACAP system in the function of zebrafish ovary, we first investigated the spatial distribution of both PACAP ligands and the three potential receptors in the somatic follicle layer and denuded oocytes. We also analyzed the temporal expression profiles of PACAP ligands and receptors during follicle growth and maturation. Spatiotemporal expression data of PACAP system suggested that PACAP might play dual roles in regulating follicle growth and maturation through different receptors located in different compartments. This hypothesis was further supported by the observation that PACAP promoted maturation of follicle-enclosed oocytes but suppressed spontaneous maturation of denuded oocytes in vitro.
As the expression of PACAP (PACAP₃₈-2) was significantly stimulated by pituitary gonadotropins (hCG) in cultured zebrafish follicle cells, PACAP is therefore likely a downstream mediator or modulator of pituitary gonadotropins in controlling ovarian functions. We illustrated from several aspects to verify our hypothesis. Firstly, we tested the regulation of PACAP on the expression of activin/follistatin system for its well characterized roles in mediating pituitary gonadotropins (hCG). According to our results, PACAP could not only mimic gonadotropin-regulated expression of the activin/follistatin system, but also stimulated activin-mediated oocyte maturation. The same cAMP-dependent signal pathways PACAP and hCG chose towards the differential regulation of activin/follistatin system further confirm PACAP’s role as a mediator or even an amplifier. Secondly, EGF, the ovary-derived growth factor, was administrated to study its effects on PACAP regulated expression of activin/follistatin system. Similar with its influences on hCG regulated genes expression of activin system, EGF could work on its membrane receptors using a MEK pathway to regulate the effects of PACAP. Thirdly, the effect of PACAP on steroidogenesis was also studied. PACAP could stimulate the expression of aromatase, one of the steroidogenic enzymes that could convert testosterone to E2, in cultured zebrafish follicle cells. Its effect on aromatase expression could be mimicked by drugs that increase intracellular cAMP levels such as forskolin and db-cAMP. PACAP induced aromatase expression was totally abolished by a PKA inhibitor H89, which indicated that PACAP worked through a cAMP-PKA dependent pathway to regulate aromatase expression. As gonadotropins also use the same cAMP-PKA pathway to regulate the expression of aromatase, it was further confirmed that PACAP could mediate or amplify the effects of gonadotropins, even in steroidogenesis.
We also studied the regulatory effects of PACAP on other components of this mini-axis to find out whether this hypothetical GHRH/PACAP-GH-IGF axis in the ovary work the same way as the systemic somatotrophic one. We carried out a series of regulatory studies using the primary zebrafish follicle cell culture system. Interestingly, PACAP up-regulated the expression of gh and its receptors ghra and ghrb. In addition, it also increased the expression of igf1 but not igf2a and igf2b. Accompanied with the fact that recombinant zfGH could stimulate the expression of igf1, we have reason to believe that a functional intraovarian axis exited in zebrafish ovary. It seems that the regulatory effects of PACAP on this axis also mediated through a cAMP-PKA pathway.
The present study not only increases our understanding of the GHRH/PACAP- GH-IGFs axis and its actions in the ovary, but also provides valuable information on the coordination of growth and reproduction in fish, which will surely benefit the manipulation of fish growth and breeding in aquaculture. Since fish represent the most primitive and diverse group of vertebrates, the information obtained from the present study will serve as important reference for the studies in other organisms.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Zhou, Rui.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2012.
Includes bibliographical references (leaves 127-157).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
Abstract in English --- p.i
Abstract in Chinese --- p.iv
Acknowledgement --- p.vi
Table of content --- p.viii
List of figures and tables --- p.xiii
Symbols and abbreviation --- p.xvi
Chapter Chapter 1 --- General Introduction
Chapter 1.1 --- Ovary --- p.1
Chapter 1.1.1 --- Folliculogenesis --- p.1
Chapter 1.1.2 --- Steroidogenesis --- p.7
Chapter 1.1.3 --- Endocrine, paracrine and autocrine network of ovarian follicles --- p.8
Chapter 1.2 --- GHRH/PACAP-GH-IGF axis --- p.11
Chapter 1.2.1 --- GHRH/PACAP-GH-IGF axis in growth --- p.11
Chapter 1.2.2 --- GHRH/PACAP-GH-IGF axis in reproduction --- p.13
Chapter 1.3 --- Pituitary adenylate cyclase-activating polypeptide (PACAP) family --- p.15
Chapter 1.3.1 --- PACAP ligands --- p.15
Chapter 1.3.2 --- PACAP receptors --- p.17
Chapter 1.3.3 --- Function of PACAP system --- p.21
Chapter 1.4 --- Objective of present study --- p.23
Chapter Chapter 2 --- Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) and Its Receptors in the Zebrafish Ovary - Evidence for Potential Dual Roles of PACAP in Controlling Final Oocyte Maturation
Chapter 2.1 --- Introduction --- p.27
Chapter 2.2 --- Materials and method --- p.30
Chapter 2.2.1 --- Animals and chemicals --- p.30
Chapter 2.2.2 --- Isolation of ovarian follicles --- p.31
Chapter 2.2.3 --- Separation of oocyte and follicle layer --- p.32
Chapter 2.2.4 --- Follicle incubation and oocyte maturation assay --- p.32
Chapter 2.2.5 --- Primary follicle cell culture --- p.33
Chapter 2.2.6 --- RNA extraction and reverse transcription --- p.33
Chapter 2.2.7 --- Semi- quantitative RT-PCR and real-time qPCR --- p.33
Chapter 2.2.8 --- Data analysis --- p.34
Chapter 2.3 --- Results --- p.34
Chapter 2.3.1 --- Spatial distribution of PACAP system within the follicle --- p.34
Chapter 2.3.2 --- Temporal expression profiles of the PACAP system during folliculogenesis --- p.35
Chapter 2.3.3 --- Expression profiles of PACAP system in peri-ovulatory period in vivo --- p.35
Chapter 2.3.4 --- Expression mark change of the PACAP system during in vivo and in vitro maturation --- p.37
Chapter 2.3.5 --- Effects of PACAP on final maturation of intact follicles and denuded oocytes --- p.38
Chapter 2.4 --- Discussion --- p.39
Chapter Chapter 3 --- PACAP Mimics Pituitary Gonadotropin(s) in Regulating Ovarian Activin/Inhibin/Follistatin System
Chapter 3.1 --- Introduction --- p.54
Chapter 3.2 --- Materials and method --- p.57
Chapter 3.2.1 --- Animals and chemicals --- p.57
Chapter 3.2.2 --- Primary culture of ovarian follicle cells --- p.57
Chapter 3.2.3 --- Total RNA isolation and reverse transcription --- p.58
Chapter 3.2.4 --- Real-time polymerase chain reaction --- p.58
Chapter 3.2.5 --- Isolation and incubation of follicles --- p.59
Chapter 3.2.6 --- Data analysis --- p.59
Chapter 3.3 --- Result --- p.61
Chapter 3.3.1 --- PACAP regulation of the expression of activin/inhibin/follistatin system in cultured zebrafish ovarian follicle cells --- p.61
Chapter 3.3.2 --- Involvement of protein kinase A (PKA) in the differential regulation of activin subunits and follistatin by PACAP --- p.61
Chapter 3.3.3 --- Potential role of activin in PACAP-induced oocyte maturation --- p.62
Chapter 3.3.4 --- Interactive effects of EGF and PACAP on the expression of activin subunits and follistatin in the follicle cells --- p.62
Chapter 3.3.5 --- Potential involvement of EGF-EGFR signaling in PACAP-regulated expression of activin subunits and follistatin in the follicle cells --- p.62
Chapter 3.4 --- Discussion --- p.63
Chapter Chapter 4 --- PACAP Regulation of Ovarian GH-IGF System
Chapter 4.1 --- Introduction --- p.78
Chapter 4.2 --- Materials and methods --- p.81
Chapter 4.2.1 --- Animals and chemicals --- p.81
Chapter 4.2.2 --- Primary culture of ovarian follicle cells --- p.81
Chapter 4.2.3 --- Total RNA isolation and reverse transcription --- p.82
Chapter 4.2.4 --- Real-time polymerase chain reaction --- p.82
Chapter 4.2.5 --- Follicle incubation --- p.82
Chapter 4.2.6 --- Data analysis --- p.83
Chapter 4.3 --- Result --- p.83
Chapter 4.3.1 --- PACAP regulation of the expression of growth hormone and growth hormone receptors in cultured zebrafish ovarian follicle cells --- p.83
Chapter 4.3.2 --- PACAP regulation of the expression of insulin-like growth factors and their receptors in cultured zebrafish ovarian follicle cells --- p.84
Chapter 4.3.3 --- Self-regulation of PACAP expression in cultured zebrafish ovarian follicle cells --- p.85
Chapter 4.3.4 --- Evaluation of protein kinase A (PKA) involvement in the PACAP-regulated expression of GH and IGFs family --- p.85
Chapter 4.3.5 --- Interactive effects of PACAP and EGF on expression of zebrafish GH-IGF axis in cultured follicle cells --- p.86
Chapter 4.4 --- Discussion --- p.87
Chapter Chapter 5 --- PACAP regulation of cytochrome P450 aromatase expression in cultured zebrafish ovarian follicle cells
Chapter 5.1 --- Introduction --- p.103
Chapter 5.2 --- Materials and methods --- p.106
Chapter 5.2.1 --- Animals and chemicals --- p.106
Chapter 5.2.2 --- Primary culture of ovarian follicle cells --- p.106
Chapter 5.2.3 --- Total RNA isolation and reverse transcription --- p.107
Chapter 5.2.4 --- Real-time polymerase chain reaction --- p.107
Chapter 5.2.5 --- Data analysis --- p.108
Chapter 5.3 --- Results --- p.108
Chapter 5.3.1 --- PACAP regulation of cyp19a1a expression in cultured zebrafish ovarian follicle cells --- p.108
Chapter 5.3.2 --- Effects of forskolin and db-cAMP on cyp19a1a expression --- p.109
Chapter 5.3.3 --- Involvement of protein kinase A (PKA) in the regulation of cyp19a1a expression by PACAP --- p.109
Chapter 5.4 --- Discussion --- p.109
Chapter Chapter 6 --- General Discussion
Chapter 6.1 --- Potential roles of PACAP in folliculogenesis --- p.120
Chapter 6.2 --- PACAP mediates gonadotropins’ signaling through activin/follistatin system --- p.123
Chapter 6.3 --- PACAP regulation of steroidogenesis --- p.124
Chapter 6.4 --- PACAP regulation of ovarian PACAP-GH-IGF axis --- p.127
Reference

碩士
國立暨南國際大學
電機工程學系
96
This thesis aim is to design ultra wideband low noise amplifiers, 24-GHz and 53-GHz CMOS low noise amplifiers. Study the theme can be divided into three parts： In first part, 3.1 ~ 10.6 GHz low noise amplifier is designed for ultra wideband (UWB). The mainly three types of low noise amplifier were using current-sharing technique to achieve low-power consumption. In order to achieve not only high but also flat gain and small group-delay-variation at the same time, the series and shunt inductive peaking were adopted in the output stage to enhance the frequency of the dominant pole and then expand 3-dB bandwidth of the LNA. In the part of input stage, the R-C negative feedback can achieve impedance matching and reduce chip area. First, we design two types of LNA in standard 0.18 um CMOS technology and use the difference gate inductor of series inductive peaking at the same time. The measured results of the first type LNA (lower gate inductor) show the maximum S21 of 13.5 dB, S11 below -12 dB, S22 below -11.8 dB and flat noise figure of 3.61~ 4.68 dB form 3.1 to 10.6 GHz. The measured results of the second type LNA (larger gate inductor) show the flatter S21 of 12.24±0.62 dB. The S11 and S22 below -8.5 dB and flat noise figure of 3.74 ~ 4.74 dB over 3.1-10.6 GHz while consuming 10.33 mW. In order to pursue better performances of the LNA, the third type of LNA is implemented in standard 0.13 um CMOS technology. The measured results show that the 3-dB bandwidth is 13 GHz, the power gain (S21) of 7.92±0.23 dB, input return loss (S11) and output return loss (S22) below -14 dB, and the group-delay-variation only ±16.7 ps over 3.1-10.6 GHz, minimum noise figure of 2.5 dB is achieved at 10.5 GHz while consuming 10.68 mW. The results show that the LNA is suitable for UWB pulse-radio system applications. In the second part, 21~27 GHz low noise amplifier is implemented in standard TSMC 0.18 um CMOS technology and suitable for radar system. To achieve sufficient gain, this LNA is composed of three cascaded common-source stages and a cascode amplifier. The current-sharing technique with inductive peaking is adopted for bandwidth enhancement in the second and third stage. The measured results show that the 3dB bandwidth is 8.5 GHz, the S21 of 9.3±1.3 dB, S11 and S22 below -8.2 dB, noise figure of 4.9~6.1 dB, and the very small group-delay-variation (±8.1 ps) over 21-27 GHz while consuming 27 mW. The last part, low-power-consumption 53-GHz (V-band) low-noise amplifier (LNA) using standard 0.13 um CMOS technology is reported. To achieve sufficient gain, this LNA is composed of four cascaded common-source stages. Current-sharing technique is adopted in the third and the fourth stage to reduce the power dissipation. The output of each stage is loaded with a LC parallel resonance circuit to maximize the gain at the design frequency. This LNA achieved voltage gain (AV) of 14 dB with very low noise figure (NF) of 6.13 dB, and input referred 1-dB compression point (P1dB-in) of –20 dBm at 53 GHz. It consumed very small dc power of 10.56 mW.

碩士
國立中正大學
電機工程研究所
93
The thesis accomplishes three fractional-N frequenncy synthesizers. Firstly, a new architecture with proposed prescalar and sigma-delta modular controller is presented. The design example of fractional-N frequency synthesizer is accomplished and applied to the Bluetooth system. In addition, a new dual-band franctional-N Frequency Synthesizer architecture is also proposed. This architecture adopts dual-band voltage-controlled oscillator (VCO) with small area due to less inductor rquirement. The whole chip is fabricated and can be applied to Bluetooth system and 802.11a system, respectively. Lastly, Because the low jitter and fast-locking are very important in frequency synthesizer. Therefore, a new phase-and-frequency detecter (PFD), which can adjust the charge-pump current properly, is proposed and applied on the 2.4 GHz franctional-N frequency synthesizer design. The three frequency synthesizers are implemented in TSMC 0.18um 1P6M CMOS process. The measured parts of results show that the tuning range of VCO is 2.298 GHz~2.915 GHz, and phase noise is -98.60 dBc/Hz @100 KHz at power consumption of 19.8 mW. The maximum operation frequency of multi-mode prescaler is 1.6 GHz, at the power consumption of 10.7334 mW.