52 resultados para Carlin-type gold deposit
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A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA – School of Business and Economics
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We show that the waterbed effect, i.e. the pass-through of a change in one price of a firm to its other prices, is much stronger if the latter include subscription rather than only usage fees. In particular, in mobile network competition with a fixed number of customers, the waterbed effect is full under two-part tariffs, while it is only partial under linear tariffs.
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Dissertação para obtenção do Grau de Mestre em Energia e Bioenergia
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Due to the importance and wide applications of the DNA analysis, there is a need to make genetic analysis more available and more affordable. As such, the aim of this PhD thesis is to optimize a colorimetric DNA biosensor based on gold nanoprobes developed in CEMOP by reducing its price and the needed volume of solution without compromising the device sensitivity and reliability, towards the point of care use. Firstly, the price of the biosensor was decreased by replacing the silicon photodetector by a low cost, solution processed TiO2 photodetector. To further reduce the photodetector price, a novel fabrication method was developed: a cost-effective inkjet printing technology that enabled to increase TiO2 surface area. Secondly, the DNA biosensor was optimized by means of microfluidics that offer advantages of miniaturization, much lower sample/reagents consumption, enhanced system performance and functionality by integrating different components. In the developed microfluidic platform, the optical path length was extended by detecting along the channel and the light was transmitted by optical fibres enabling to guide the light very close to the analysed solution. Microfluidic chip of high aspect ratio (~13), smooth and nearly vertical sidewalls was fabricated in PDMS using a SU-8 mould for patterning. The platform coupled to the gold nanoprobe assay enabled detection of Mycobacterium tuberculosis using 3 8l on DNA solution, i.e. 20 times less than in the previous state-of-the-art. Subsequently, the bio-microfluidic platform was optimized in terms of cost, electrical signal processing and sensitivity to colour variation, yielding 160% improvement of colorimetric AuNPs analysis. Planar microlenses were incorporated to converge light into the sample and then to the output fibre core increasing 6 times the signal-to-losses ratio. The optimized platform enabled detection of single nucleotide polymorphism related with obesity risk (FTO) using target DNA concentration below the limit of detection of the conventionally used microplate reader (i.e. 15 ng/μl) with 10 times lower solution volume (3 μl). The combination of the unique optical properties of gold nanoprobes with microfluidic platform resulted in sensitive and accurate sensor for single nucleotide polymorphism detection operating using small volumes of solutions and without the need for substrate functionalization or sophisticated instrumentation. Simultaneously, to enable on chip reagents mixing, a PDMS micromixer was developed and optimized for the highest efficiency, low pressure drop and short mixing length. The optimized device shows 80% of mixing efficiency at Re = 0.1 in 2.5 mm long mixer with the pressure drop of 6 Pa, satisfying requirements for the application in the microfluidic platform for DNA analysis.
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Gene therapy presents an ideal strategy for the treatment of genetic as well as acquired diseases, such as cancer and typically involves the insertion of a functioning gene into cells to correct a cellular dysfunction or to provide a new cellular function. Gene delivery vectors are based in two models: viral and non-viral. Viral vectors have high transfection efficiency but their major barrier is immunogenicity. Since the non-viral vectors have no immunogenicity, these have been widely studied. Gold nanoparticles have been proposed as optimal delivery systems of genetic material, due their small size, high surface-to-volume ratio and the ability to be functionalized with multiple molecules. In the present work, an AuNP-based formulation was developed to deliver a plasmid in a colorectal cancer cell line, containing as reporter gene the gene encoding to EGFP. The delivery system resulted from the functionalization of 14 nm AuNP with a PEG layer (4300114 PEG chains/AuNP), which increases stability and biocompatibility of AuNPs; quaternary ammonium groups which provide positive charges that allow electrostatic binding of plasmid, which is considered the therapeutic agent to be transported into cells. The system developed was characterized by UV-vis spectroscopy, DLS, TEM and by electrophoretic mobility, yielding a formulation with 113.5 nm.Transfection efficiency of the formulation developed was evaluated through PCR and through EGFP expression by fluorescence microscopy and fluorescence spectroscopy. The internalization was observed 3h post transfection; however a low level of EGFP expression was achieved. After 24h of incubation, EGFP expression increases just 3 times compared to non-transfected cells. The commercial system (Lipofectamine) expressed EGFP 5 times more than the system developed AuNP@PEG@R4N+@pEGFP. This difference could be related to lower translocation to the nucleus.
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My master studies have resulted in the following publication: Martins P, Rosa D, Fernandes AR, Baptista PV. 2014. Nanoparticle Drug Delivery Systems: Recent Patents and Applications in Nanomedicine. Recent Patents in Nanomedicine. 3(2):105-118.
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The main objective of this thesis was the development of a gold nanoparticle-based methodology for detection of DNA adducts as biomarkers, to try and overcome existing drawbacks in currently employed techniques. For this objective to be achieved, the experimental work was divided in three components: sample preparation, method of detection and development of a model for exposure to acrylamide. Different techniques were employed and combined for de-complexation and purification of DNA samples (including ultrasonic energy, nuclease digestion and chromatography), resulting in a complete protocol for sample treatment, prior to detection. The detection of alkylated nucleotides using gold nanoparticles was performed by two distinct methodologies: mass spectrometry and colorimetric detection. In mass spectrometry, gold nanoparticles were employed for laser desorption/ionisation instead of the organic matrix. Identification of nucleotides was possible by fingerprint, however no specific mass signals were denoted when using gold nanoparticles to analyse biological samples. An alternate method using the colorimetric properties of gold nanoparticles was employed for detection. This method inspired in the non-cross-linking assay allowed the identification of glycidamide-guanine adducts and DNA adducts generated in vitro. For the development of a model of exposure, two different aquatic organisms were studies: a goldfish and a mussel. Organisms were exposed to waterborne acrylamide, after which mortality was recorded and effect concentrations were estimated. In goldfish, both genotoxicity and metabolic alterations were assessed and revealed dose-effect relationships of acrylamide. Histopathological alterations were verified primarily in pancreatic cells, but also in hepatocytes. Mussels showed higher effect concentrations than goldfish. Biomarkers of oxidative stress, biotransformation and neurotoxicity were analysed after prolonged exposure, showing mild oxidative stress in mussel cells, and induction of enzymes involved in detoxification of oxygen radicals. A qualitative histopathological screening revealed gonadotoxicity in female mussels, which may present some risk to population equilibrium.
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This thesis reports the work performed in the optimization of deposition parameters of Multi – Walled Carbon Nanotubes (MWCNT) targeting the development of a Field Effect Transistors (FET) on paper substrates. The CNTs were dispersed in a water solution with sodium dodecyl sulphate (SDS) through ultrasonication, ultrasonic bath and a centrifugation to remove the supernatant and have a homogeneous solution. Several deposition tests were performed using different types of CNTs, dis-persants, papers substrates and deposition techniques, such as spray coating and inkjet printing. The characterization of CNTs was made by Scanning Electron Microscopy (SEM) and Hall Effect. The most suitable CNT coatings able to be used as semiconductor in FETs were deposited by spray coat-ing on a paper substrate with hydrophilic nanoporous surface (FS2) at 100 ºC, 4 bar, 10 cm height, 5 second of deposition time and 90 seconds of drying between steps (4 layers of CNTs were deposited). Planar electrolyte gated FETs were produced with these layers using gold-nickel gate, source and drain electrodes. Despite the small current modulation (Ion/Ioff ratio of 1.8) one of these devices have p-type conduction with a field effect mobility of 1.07 cm2/V.s.
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In this paper we analyze the role of deposit insurance in providing the market with liquidity in times of financial turmoil. To do so, we look at the variation in insured and uninsured deposits between 2005Q3 and 2011Q3, controlling for liquidity, solvency and capital adequacy indicators, and find evidence that deposit insurance does provide some confidence in keeping funds in banks in times of turmoil. Additionally we follow an event study methodology to assess the impact of deposit insurance oriented policies on bank holding companies stock market returns, and find a TBTF effect.
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This work project (WP) is a study about a clustering strategy for Sport Zone. The general cluster study’s objective is to create groups such that within each group the individuals are similar to each other, but should be different among groups. The clusters creation is a mix of common sense, trial and error and some statistical supporting techniques. Our particular objective is to support category managers to better define the product type to be displayed in the stores’ shelves by doing store clusters. This research was carried out for Sport Zone, and comprises an objective definition, a literature review, the clustering activity itself, some factor analysis and a discriminant analysis to better frame our work. Together with this quantitative part, a survey addressed to category managers to better understand their key drivers, for choosing the type of product of each store, was carried out. Based in a non-random sample of 65 stores with data referring to 2013, the final result was the choice of 6 store clusters (Figure 1) which were individually characterized as the main outcome of this work. In what relates to our selected variables, all were important for the distinction between clusters, which proves the adequacy of their choice. The interpretation of the results gives category managers a tool to understand which products best fit the clustered stores. Furthermore, as a side finding thanks to the clusterization, a STP (Segmentation, Targeting and Positioning) was initiated, being this WP the first steps of a continuous process.
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RESUMO: Introdução: A obstrução da via aérea central (OVAC) refere-se a um processo patológico que conduz a limitação do fluxo de ar ao nível do espaço glótico e subglótico, traqueia e brônquios principais. O seu correcto diagnóstico e tratamento constituem um território de interesse e preocupação para os profissionais de saúde, e requerem um profundo conhecimento da sua etiologia, fisiologia, diagnóstico e opções terapêuticas dado o potencial em originar significativa morbilidade e mortalidade. A avaliação da OVAC abrange múltiplas vertentes, entre as quais se salienta o componente clínico (sinais e sintomas), a repercussão fisiopatológica (função respiratória) e o estudo imagiológico (TC do tórax e broncoscopia). A compilação destes dados associada à etiologia, constituem factores importantes para estabelecer o prognóstico, determinar a necessidade de tratamento ou delinear uma futura intervenção terapêutica. A broncoscopia é o Gold Standard de avaliação desta condição, mas desde há cerca de 40 anos a curva de débito-volume constitui uma ferramenta não invasiva de detecção de OVAC. Apesar deste método ser utilizado até os nossos dias, poucos têm sido os estudos com o objectivo de verificar a sensibilidade e especificidade da curva de débito-volume na detecção de OVAC, bem como averiguar a relação entre as alterações morfológicas e quantitativas da mesma com a localização, o tipo e o grau da obstrução. Material e Métodos: Entre 1 de Novembro de 2009 e 30 de Abril de 2010, os doentes com indicação para a realização de broncoscopia diagnóstica ou terapêutica na Unidade de Técnicas Invasivas Pneumológicas (UTIP) do Centro Hospitalar Lisboa Norte – Hospital Pulido Valente (CHLN – HPV) foram seleccionados de forma consecutiva de acordo com os critérios de inclusão e exclusão. As avaliações (broncoscopia, curva de débito-volume e avaliação da dispneia) realizaram-se com um intervalo de tempo máximo de sete dias. A broncoscopia flexível foi realizada segundo as normas da British Thoracic Society e as curvas de débito-volume segundo as normas da ATS/ERS TaskForce 2005. Para a avaliação da dispneia recorreu-se à escala de dispneia MRC (Medical Research Council). Um painel de peritos realizou a avaliação da morfologia da curva de débito-volume (sugestiva ou não de OVAC) e um elemento independente a verificação dos critérios quantitativos e morfológicos (variáveis intra e extratorácica e fixa) da curva. O estudo foi aprovado pela Comissão de Ética para a Saúde do CHLN e todos os doentes assinaram um consentimento informado de participação. Resultados: Estudaram-se 82 doentes, 36 (44%) dos quais com OVAC. A predominância foi do género masculino, em relação ao feminino. A sensibilidade e especificidade dos critérios quantitativos da curva de débito-volume na detecção de OVAC foi de 91.3% e 88.9% respectivamente. Quando se utilizaram os critérios morfológicos da curva de débito-volume os valores foram de 93.5% e 30.6%. A agregação dos critérios morfológicos e quantitativos permitiu alcançar uma sensibilidade de 95.7% e especificidade de 86.1%. Nesta amostra, o critério quantitativo com maior ocorrência foi o FEF50/FIF50≥1 (83% dos doentes com OVAC). Este mostrou relacionar-se com todas as localizações de obstrução excepto o terço médio da traqueia. Mostrou, ainda, ter uma relação forte e positiva com o grau e tipo de obstrução (intra e extraluminal). O segundo foi o FEV1/PEF≥8, presente em 36% dos casos de OVAC. Relacionou-se com as obstruções no terço inferior da traqueia e brônquio principal direito (BPD). Também apresentou relação forte e positiva com o grau de obstrução e com os tipos de obstrução anteriormente descritos. Quanto à sintomatologia foi possível associar o grau de obstrução com o de dispneia e a presença de estridor com o grau e localização da obstrução na traqueia. Conclusões: Os resultados deste estudo demonstram que os critérios quantitativos da curva de débito-volume têm elevada sensibilidade e especificidade na detecção de OVAC. O critério FEV50/FIF50≥1 tem um bom poder discriminativo na detecção dessa condição, tendo sido relacionado com a localização, o grau e o tipo de obstrução. O critério FEV1/PEF≥8, embora com menor poder discriminativo, também se relaciona com o grau, a localização e o tipo de obstrução. A morfologia da curva tem uma boa sensibilidade mas baixa especificidade na detecção de OVAC, mas a agregação entre os critérios morfológicos e quantitativos aumenta a sensibilidade e especificidade. A dispneia e o estridor foram relacionados com o grau de obstrução e o último com a localização ao nível da traqueia.-------------ABSTRACT: Introduction: Central airway obstruction (CAO) refers to a pathological process that leads to restriction of airflow at the level of the glottis and subglottis, trachea and main bronchi. It’s proper diagnosis and treatment is an area of interest and concern to health professionals, and requires a deep knowledge of its etiology, physiology, diagnosis and treatment options, concerning the potential to cause significant morbidity and mortality. The evaluation of CAO covers multiple aspects: the clinical component (signs and symptoms), the pathophysiological effect (lung function) and the imaging study (bronchoscopy and chest CT). The compilation of this data associated with the etiology, are important for establishing prognosis, determine the need for treatment or outline a future therapeutic intervention. Bronchoscopy is the gold standard for evaluating this condition, but for the last 40 years the flow-volume loop has been used as a noninvasive tool for detecting CAO. Although this method is still in use, only few studies were made in order to verify its sensitivity and specificity in detecting CAO, and investigate the relation between morphological and quantitative changes of the curve to location, type and degree of obstruction. Methods: Between 1st November 2009 and 30th April 2010, patients with indication to perform diagnostic or therapeutic bronchoscopy in Interventional Pulmonology Unit - Hospital Pulido Valente (CHLN - HPV), were selected consecutively according to the inclusion and exclusion criteria. All assessments (bronchoscopy, flow-volume loop and dyspnea) were carried out within a period of seven days. The flexible bronchoscopy was performed according to the standards of the British Thoracic Society and the flow-volume loops in accordance with the standards of the ATS / ERS Taskforce 2005. For the evaluation of dyspnea was used to MRC dyspnea scale (Medical Research Council). A panel of experts evaluated the morphology of flow-volume loop (suggestive or non-suggestive of CAO) and an independent element established the quantitative criteria and morphological (intra and extrathoracic variables and fixed) of the curve. This study was approved by the Ethics Committee for Health CHLN and all the patients signed an informed consent to participate. Results: We’ve studied 82 patients, 36 (44%) of those with CAO. The majority of the patients were males, compared to females. The sensitivity and specificity of the quantitative criteria of the flow-volume curve in detecting CAO was 91.3% and 88.9% respectively. When we used the morphological criteria of flow-volume loop these values were 93.5% and 30.6%. The combination of quantitative and morphological criteria produced values of 95.7% sensitivity and 86.1% specificity. FEF50/FIF50≥1 was the most representative quantitative criterion (83% of patients with CAO) and it was correlated with all sites of obstruction except in the middle third of the trachea. It has shown a strong and positive association with the degree and type of obstruction (intra and extraluminal). The second was the FEV1/PEF ≥ 8, present in 36% of cases of CAO. It could be correlated with the obstruction in the lower third of the trachea and right main bronchus. It also showed a strong positive relation with the degree and types of obstruction described above. Regarding symptoms, we found a link between the degree of obstruction and dyspnea. The presence of stridor was correlated with the location and the degree of obstruction in the trachea. Conclusion: The results of this study demonstrate that the quantitative criteria of the flow-volume loop have a high sensitivity and specificity in detecting CAO. The criterion FEV50/FIF50 ≥ 1 has a good discriminative power to detect this condition and was related to the location, degree and type of obstruction. The criterion FEV1/PEF ≥ 8, although with a weaker discriminative power, also relates to the degree, location and type of obstruction. The morphology of the curve has a good sensitivity but low specificity in detecting CAO although the combination between the morphological and quantitative criteria increases sensitivity and specificity. Dyspnea and stridor were related to the degree of obstruction and the last one with its location in the trachea.
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RESUMO: Este trabalho tentou contribuir para a caracterização da fisiopatologia da microcirculação coronária em diferentes formas de patologia com o auxílio da ecocardiografia transtorácica. Com a aplicação da ecocardiografia Doppler transtorácica foi efectuado o estudo da reserva coronária da artéria descendente anterior e com a ecocardiografia de contraste do miocárdio foram analisados parâmetros de perfusão do miocárdio como a velocidade da microcirculação coronária, o volume de sangue miocárdico e a reserva de fluxo miocárdico. Estas técnicas foram utilizadas em diferentes situações fisiopatológicas com particular interesse na hipertrofia ventricular esquerda de diferentes etiologias como a hipertensão arterial, estenose aórtica e cardiomiopatia hipertrófica. Também na diabetes mellitus tipo 2 e na doença coronária aterosclerótica, estudámos as alterações da microcirculação coronária. Com a mesma técnica de ecocardiografia de contraste do miocárdio foi analisada a perfusão do miocárdio num modelo experimental animal sujeito a uma dieta aterogénica. Além das conclusões específicas em relação a cada um dos trabalhos efectuados há a referir como conclusões gerais a sua fácil aplicabilidade e exequibilidade em âmbito clínico, a sua reprodutibilidade e precisão. Quando comparadas com técnicas consideradas de referência mostraram resultados com significativa correlação estatística. Em todos os doentes e nos grupos controle foi possível comprovar e quantificar o gradiente de perfusão transmural em repouso e durante a acção de stress vasodilatador, relevando a importância da perfusão sub-endocárdica na função do ventrículo esquerdo. O estudo da microcirculação coronária no grupo de doentes com hipertrofia ventricular esquerda revelou que no grupo com hipertensão arterial existe disfunção da microcirculação coronária ainda antes de se observar aumento de massa do ventrículo esquerdo, e que esta disfunção é diferente em função da geometria ventricular. Nos doentes com estenose aórtica foi demonstrado que além da disfunção da microcirculação coronária, explicada pelo fenómeno de hipertrofia, existe outro componente extrínseco que depois de corrigido através de cirurgia de substituição valvular, conduziu a uma parcial normalização dos valores de reserva coronária. Na cardiomiopatia hipertrófica observou-se uma grande heterogeneidade de perfusão transmural e foi documentado, em imagens de ecocardiografia de contraste do miocárdio e após análise paramétrica, a ausência de perfusão do miocárdio na região sub-endocárdica durante o stress vasodilatador de reserva coronária diminuídos em fases precoces de evolução da doença. Foi demonstrado que a reserva coronária na DM2 em fases mais avançadas estava significativamente diminuída. Descrevemos também em doentes com DM2 e sem doença coronária angiográfica a existência de disfunção da microcirculação coronária. Durante o stress vasodilatador, observámos e documentámos neste grupo de doentes, a existência de defeitos de perfusão transitórios ou de diminuição da velocidade da microcirculação coronária. No grupo de doentes com doença coronária confirmámos o interesse da avaliação da reserva coronária após intervenção percutânea na definição de prognóstico pós EAM, em termos de recuperação funcional do ventrículo esquerdo. Em doentes com BCRE e de difícil estratificação de risco, foi possível calcular o valor de reserva coronária e estratificar o risco de doença coronária. Num modelo experimental animal demonstrámos a exequibilidade da técnica de ECM, e verificámos que nessas condições experimentais, uma sobrecarga aterogénica na dieta, ao fim de 6 semanas, comprometia severamente a reserva coronária. Estes resultados foram parcialmente reversíveis quando à dieta foi adicionada uma estatina. Estas técnicas pela sua não invasibilidade, fácil acesso, repetibilidade e inocuidade perspectivam-se de grande utilidade na caracterização de doentes com disfunção da microcirculação coronária, nas diferentes áreas de diagnóstico, terapêutica e prevenção. A possibilidade de adaptar a técnica em modelos experimentais animais também nos parece poder vir a ter grande utilidade em investigação.----------------ABSTRACT: This work is intended to be a contribution to the study of coronary microcirculation applying new echocardiographic techniques as transthoracic Doppler echocardiography of coronary arteries and myocardial contrast echocardiography. Coronary flow reserve may be assessed by transthoracic Doppler echocardiography, and important functional microcirculation parameters as microcirculation flow velocity, myocardial blood volume and myocardial flow reserve may be evaluated through myocardial contrast echocardiography. Microcirculation was analysed in different pathophysiological settings. We addressed situations with increased left ventricular mass as systemic arterial hypertension, aortic stenosis and hypertrophic cardiomyopathy. Also coronary microcirculation was studied in type 2 Diabetes and in different clinical forms of atherosclerotic coronary artery disease. Specific and detailed conclusions were withdrawn from each experimental work. In the overall it was concluded that these two techniques were important tools to easily assess specific pathophysiological information about coronary microcirculation at bed side which would be difficult to get through other techniques. When compared with gold standard techniques, similar sensibility and specificity was found. Because of their better temporal and spatial resolution it was possible to analyse the importance of transmural perfusion gradients, both in basal and during vasodilatation, and their relation to ischemia, and mechanical wall kinetics, as wall thickening and motion. Coronary microcirculation dysfunction was found in systemic arterial hypertension early evolution stages, also related to different left ventricular geometric patterns. Different etiopathogenical explanations for aortic stenosis coronary microcirculation dysfunction were analysed and compared after aortic valve replacement. Transmural myocardial perfusion heterogeneity pattern was observed in hypertrophic cardiomyopathy which was aggravated during adenosine challenge. Coronary microcirculation dysfunction was diagnosed in type 2 diabetes both with coronary artery disease and with normal angiographic coronary arteries. Dynamic transitory subendocardial perfusion defects with adenosine vasodilatation were visualized in these patients.In patients with left branch block, transthoracic Doppler echocardiography was able to suggest a coronary reserve cut-off value for risk stratification. Also it was possible with this technique to calculate coronary flow reserve and predict restenosis after PTCA Again, in an experimental animal model, applying myocardial contrast echocardiography technique it was possible to study the consequences of an atherogenic diet and statins action on the coronary microcirculation function. Because these techniques are easily performed at bed side, are harmless, use no ionizing radiation and because of their repeatability, reproducibility and accuracythey are promissory tools to assess coronary microcirculation. Both in clinic and research areas these techniques will probably have a role in clinical diagnosis, prevention and therapeutically decision.
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Modern CMOS radio frequency (RF) Receivers have enabled efficient and increasing applications. The main requirement is to have system in a single chip, in order to minimize area and cost. For the purpose it is required the development of inductorless circuits for the key blocks of an RF receiver. Examples of this key blocks are RC oscillators, RF band pass filters, and Low Noise Amplifiers. The present dissertation presents an inductorless wideband MOSFET-only RF Non-Gyrator Type of Active Inductors with low area, low cost, and very low power, capable of covering the whole WMTS, and ISM, band and intended for biomedical applications. The proposed circuit is based on a floating capacitor connected between two controlled current sources. The first current source, which is controlled by the circuit input voltage, has two objectives: supply current to the capacitor (
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This thesis is a study of how heat is transported in non-steady-state conditions from a superconducting Rutherford cable to a bath of superfluid helium (He II). The same type of superconducting cable is used in the dipole magnets of the Large Hadron Collider (LHC). The dipole magnets of the LHC are immersed in a bath of He II at 1.9 K. At this temperature helium has an extremely high thermal conductivity. During operation, heat needs to be efficiently extracted from the dipole magnets to keep their superconducting state. The thermal stability of the magnets is crucial for the operation of the LHC, therefore it is necessary to understand how heat is transported from the superconducting cables to the He II bath. In He II the heat transfer can be described by the Landau regime or by the Gorter-Mellink regime, depending on the heat flux. In this thesis both measurements and numerical simulation have been performed to study the heat transfer in the two regimes. A temperature increase of 8 2 mK of the superconducting cables was successfully measured experimentally. A new numerical model that covers the two heat transfer regimes has been developed. The numerical model has been validated by comparison with existing experimental data. A comparison is made between the measurements and the numerical results obtained with the developed model.