A prova ilícita na investigação de paternidade

A presente dissertação versa sobre a prova ilícita na investigação de paternidade, com a percepção que inexistem direitos e garantias absolutos. Sob esse ponto de vista, propõe-se a demonstrar que tanto o direito à prova quanto a garantia constitucional da inadmissibilidade da prova obtida por meios ilícitos são passíveis de sofrer restrições. Essas restrições, entretanto, não podem implicar na supressão de direitos e garantias fundamentais. Elas devem limitar-se ao estritamente necessário para a salvaguarda de outros direitos constitucionalmente protegidos, à luz de um juízo de ponderação entre os valores conflitantes. Os valores colidentes a serem analisados no presente trabalho são, por um lado, a proteção constitucional dispensada à intimidade, à vida privada, à imagem, à honra, ao sigilo da correspondência, às comunicações telegráficas, aos dados, às comunicações telefônicas e ao domicílio do suposto pai e, por outro, o direito do filho conhecer a sua origem genética e receber do genitor assistência material, educacional e psicológica, além da herança no caso de morte deste. Avultam-se, ainda, os comandos constitucionais da paternidade responsável (CF, o art. 226, § 7º) e da prioridade absoluta que a Constituição Federal confere às questões afetas à criança e ao adolescente. Nessa linha de perspectiva, procura conciliar o direito fundamental ao conhecimento da origem genética com a garantia constitucional que veda a obtenção da prova por meios ilícitos, reduzindo, quando necessário, o alcance de um desses valores contrastantes para que haja a preservação do outro e o restabelecimento do equilíbrio entre eles. Com o intuito de facilitar a compreensão do assunto, o estudo sobre a prova ilícita na investigação de paternidade encontra-se dividido em três capítulos. No primeiro capítulo são estudados o objeto da prova na investigação de paternidade, os fatos a provar, as teorias sobre o objeto da prova, o ônus da prova, a distribuição e a inversão do ônus da prova na investigação de paternidade, o momento da inversão do ônus da prova, o dever de colaboração e a realização do exame de DNA sem o consentimento das partes. Partindo da compreensão da prova como instrumento capaz de propiciar ao juiz o convencimento dos fatos pertinentes, relevantes e controvertidos deduzidos pelas partes como fundamento da ação ou da defesa, sustenta-se que os fatos a provar não são apenas os principais, mas, também, os acessórios que se situem na mesma cadeia deles. Desenvolve-se, outrossim, estudo sobre as teorias utilizadas pela doutrina para explicar o objeto da prova, a saber: a) a teoria clássica; b) a teoria da afirmação; c) a teoria mista. Nesse tópico, merece ênfase o fato das legislações brasileira e portuguesa estarem alicerçadas sob as bases da teoria clássica, em que pesem as divergências doutrinárias sobre o assunto. No item reservado ao ônus da prova, este é concebido como uma atividade e não como uma obrigação, diante da autonomia de vontade que a parte tem para comportar-se da maneira que melhor lhe aprouver para alcançar o resultado pretendido. Embora não traduza um dever jurídico demonstrar a veracidade dos fatos que ensejam a constituição do direito alegado, quem não consegue reunir a prova dos fatos que alega corre o risco de perder a demanda. No que tange à regra de distribuição do ônus da prova, recomenda-se a observação das disposições do art. 333 do CPC, segundo as quais incumbe ao autor comprovar o fato constitutivo do seu direito e ao réu a existência de fato impeditivo, modificativo ou extintivo do direito do autor. Argumenta-se que o CPC brasileiro adota o modelo estático de distribuição do ônus da prova, pois não leva em conta a menor ou maior dificuldade que cada parte tem para produzir a prova que lhe incumbe. Porém, ressalta-se o novo horizonte que se descortina no anteprojeto do novo CPC brasileiro que se encontra no Congresso Nacional, o qual sinaliza no sentido de acolher a distribuição dinâmica do ônus da prova. Esse novo modelo, contudo, não afasta aquele previsto no art. 333 do CPC, mas, sim, o aperfeiçoa ao atribuir o ônus a quem esteja em melhores condições de produzir a prova. Ao tratar do dever de colaboração, idealiza-se a busca descoberta da verdade como finalidade precípua do ordenamento jurídico. E, para se alcançar a justa composição da lide, compreende-se que as partes devem atuar de maneira escorreita, expondo os fatos conforme a verdade e cumprindo com exatidão os provimentos formais. Sob essa ótica, sustenta-se a possibilidade de inversão do ônus da prova, da aplicação da presunção legal de paternidade e até mesmo da condução coercitiva do suposto pai para a realização de exames, caso o mesmo a tanto se recuse ou crie, propositalmente, obstáculo capaz de tornar impossível a colheita da prova. Defende-se que a partir da concepção do nascituro, a autonomia de vontade dos pais fica restringida, de forma que a mãe não pode realizar o aborto e o pai não pode fazer pouco caso da existência do filho, recusando-se, injustificadamente, a submeter-se a exame de DNA e a dar-lhe assistência material, educacional e psicológica. É por essa razão que, em caráter excepcional, se enxerga a possibilidade de condução coercitiva do suposto pai para a coleta de material genético, a exemplo do que ocorre no ordenamento jurídico alemão (ZPO, § 372). Considera-se, outrossim, que a elucidação da paternidade, além de ajudar no diagnóstico, prevenção e tratamento de algumas doenças hereditárias, atende à exigência legal de impedir uniões incestuosas, constituídas entre parentes afins ou consanguíneos com a violação de impedimentos matrimoniais. Nesse contexto, a intangibilidade do corpo não é vista como óbice para a realização do exame de DNA, o qual pode ser feito mediante simples utilização de fios de cabelos com raiz, fragmentos de unhas, saliva e outros meios menos invasivos. O sacrifício a que se submete o suposto pai mostra-se, portanto, ínfimo se comparado com o interesse superior do investigante que se busca amparar. No segundo capítulo, estuda-se o direito fundamental à prova e suas limitações na investigação de paternidade, a prova vedada ou proibida, a distinção entre as provas ilegítima e ilícita, a manifestação e alcance da ilicitude, o tratamento dispensado à prova ilícita no Brasil, nos Estados Unidos da América e em alguns países do continente europeu, o efeito-à-distância das proibições de prova na investigação de paternidade e a ponderação de valores entre os interesses em conflito: prova ilícita x direito ao conhecimento da origem genética. Nesse contexto, o direito à prova é reconhecido como expressão do princípio geral de acesso ao Poder Judiciário e componente do devido processo legal, materializado por meio dos direitos de ação, de defesa e do contraditório. Compreende-se, entretanto, que o direito à prova não pode ser exercido a qualquer custo. Ele deve atender aos critérios de pertinência, relevância e idoneidade, podendo sofrer limitações nos casos expressamente previstos em lei. Constituem exemplos dessas restrições ao direito à prova a rejeição das provas consideradas supérfluas, irrelevantes, ilegítimas e ilícitas. A expressão “provas vedadas ou proibidas” é definida no trabalho como gênero das denominadas provas ilícita e ilegítima, servindo para designar as provas constituídas, obtidas, utilizadas ou valoradas com afronta a normas de direito material ou processual. A distinção que se faz entre a prova ilícita e a ilegítima leva em consideração a natureza da norma violada. Quando há violação a normas de caráter processual, sem afetar o núcleo essencial dos direitos fundamentais, considera-se a prova ilegítima; ao passo em que havendo infringência à norma de conteúdo material que afete o núcleo essencial do direito fundamental, a prova é tida como ilícita. Esta enseja o desentranhamento da prova dos autos, enquanto aquela demanda a declaração de nulidade do ato sem a observância da formalidade exigida. A vedação da prova ilícita, sob esse aspecto, funciona como garantia constitucional em favor do cidadão e contra arbítrios do poder público e dos particulares. Nessa ótica, o Direito brasileiro não apenas veda a prova obtida por meios ilícitos (CF, art. 5º, X, XI, XII e LVI; CPP, art. 157), como, também, prevê sanções penais e civis para aqueles que desobedeçam à proibição. A análise da prova ilícita é feita à luz de duas concepções doutrinárias, a saber: a) a restritiva - exige que a norma violada infrinja direito ou garantia fundamental; b) a ampla – compreende que a ilicitude afeta não apenas as normas que versem sobre os direitos e garantias fundamentais, mas todas as normas e princípios gerais do direito. A percepção que se tem à luz do art. 157 do CPP é que o ordenamento jurídico brasileiro adotou o conceito amplo de ilicitude, pois define como ilícitas as provas obtidas com violação a normas constitucionais ou legais, sem excluir àquelas de natureza processual nem exigir que o núcleo do direito fundamental seja atingido. Referido dispositivo tem sido alvo de críticas, pois a violação da lei processual pode não implicar na inadmissibilidade da prova e aconselhar o seu desentranhamento dos autos. A declaração de nulidade ou renovação do ato cuja formalidade tenha sido preterida pode ser suficiente para contornar o problema, sem a necessidade de exclusão da prova do processo. Noutra vertente, como a vedação da prova ilícita não pode ser levada às últimas consequências nem se converter em meio facilitador da prática de atos ilícitos e consagrador da impunidade, defende-se a sua admissão nos casos de estado de necessidade, legítima defesa, estrito cumprimento do dever legal e exercício regular de um direito. Assim, entende-se possível a utilização pela vítima de estupro, no processo de investigação de paternidade movido em prol do seu filho, do exame de DNA realizado mediante análise do sêmen deixado em sua vagina por ocasião do ato sexual que resultou na gravidez. Sustenta-se, ainda, a possibilidade de utilização das imagens captadas por circuito interno de câmaras comprobatórias do estupro para fazer prova da paternidade. Ressalta-se, outrossim, que no Brasil a doutrina e a jurisprudência têm admitido a prova ilícita, no processo penal, para comprovar a inocência do acusado e, em favor da vítima, nos casos de extorsão, concussão, sequestro e outros delitos similares. No ponto relativo ao efeito-àdistância das proibições de prova, aduz-se que as experiências americana e alemã da fruit of the poisonous tree doctrine e da fernwirkung são fonte de inspiração para as legislações de vários países. Por força da teoria dos frutos da árvore envenenada, o vício da planta transmite-se aos seus frutos. Ainda no segundo capítulo, estabelece-se breve comparação do tratamento conferido à prova ilícita nos ordenamentos jurídicos brasileiro e português, destacando-se que no regime de controle adotado pela Constituição da República Federativa do Brasil a prova ilícita é tratada como ineficaz e deve ser rejeitada de plano ou desentranhada do processo. Já na Constituição portuguesa adotou-se o regime de nulidade. Após o ingresso da prova ilícita no processo, o juiz declara a sua nulidade. O terceiro capítulo é dedicado ao estudo dos meios de prova e da incidência da ilicitude no processo de investigação de paternidade. Para tanto são eleitos os meios de prova enumerados no art. 212 do Código Civil, quais sejam: a) confissão; b) documento; c) testemunha; d) presunção; e) perícia, além do depoimento pessoal previsto no CPC, analisando a incidência da ilicitude em cada um deles. Má vontade a investigação de paternidade envolva direitos indisponíveis, isso não significa que as declarações das partes não tenham valor probatório, pois o juiz pode apreciá-las como elemento probatório (CC, art. 361º). Por meio do depoimento e confissão da parte são extraídas valiosas informações sobre o tempo, o lugar e a frequência das relações sexuais. Todavia, havendo emprego de métodos proibidos, tais como ameaça, coação, tortura, ofensa à integridade física ou moral, hipnose, utilização de meios cruéis, enganosos ou perturbação da capacidade de memória, a prova será considerada ilícita e não terá validade nem mesmo como elemento probatório a ser livremente apreciado pelo juiz. A prova documental é estudada como a mais vulnerável à incidência da ilicitude, pelo fato de poder expressar-se das mais variadas formas. Essa manifestação da ilicitude pode verificar-se por ocasião da formação da prova documental, no ato da sua obtenção ou no momento da sua exibição em juízo por meio falsificação material do documento público ou particular, da omissão de declaração deveria constar, inserção de declaração falsa ou diversa da que devia ser escrita, alteração de documento verdadeiro, emprego de métodos proibidos de prova para confecção do documento, etc. Na esteira desse raciocínio, em se fazendo constar, por exemplo, da escritura pública ou particular ou do testamento (CC, art. 1.609, II e III) declaração falsa da paternidade, a prova assim constituída é ilícita. Do mesmo modo, é considerada ilícita a prova obtida mediante indevida intromissão na vida privada, com violação de domicílio, emails, sigilos da correspondência, telefônico ou fiscal, realização de gravações, filmagens, etc. Na prova testemunhal entende-se como elemento configurador da ilicitude o emprego de métodos proibidos por parte de agentes públicos ou particulares, tais como tortura, coação, ameaça, chantagem, recursos que impliquem na diminuição ou supressão da capacidade de compreensão, etc, para que a testemunha faça afirmação falsa, negue ou cale a verdade dos fatos. Destaca-se, ainda, como ilícita a prova cujo acesso pela testemunha tenha ocorrido mediante violação à reserva da vida privada. No caso das presunções, vislumbra-se a possibilidade de incidência da ilicitude quando houver ilicitude no fato conhecido, do qual se vale a lei ou o julgador para extraírem as consequências para dedução da existência do fato desconhecido. A troca maliciosa de gametas é citada como meio ilícito de prova para alicerçar a presunção de paternidade no caso de inseminação artificial homóloga. A consecução da prévia autorização do marido, mediante coação, tortura, ameaça, hipnose, etc, na inseminação artificial heteróloga, também é tratada como ação danosa e capaz de viciar e infirmar a presunção legal de paternidade. Enxerga-se, outrossim, no meio de prova pericial, a possibilidade de maculação do resultado do exame por falha humana intencional no processo de coleta, transporte, armazenamento, manipulação ou troca do material genético coletado. Em se verificando essa situação, fica comprometida a credibilidade da prova pericial ante a sua ilicitude.

Control of neuronal signalling pathways by CYP46A1, an enzime involved in brain cholesterol homeostasis

Tese de doutoramento, Farmácia (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Farmácia, 2016

A population of HLA-DR+ immature cells accumulates in the blood dendritic cell compartment of patients with different types of cancer

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c(+)) and plasmacytoid (CD123(+)) DC, and a concurrent accumulation of CD11c(-)CD123(-) immature cells that expressed high levels of HLA-DR+ immature cells (DR+IC). Although DR+IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR+IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-gamma secretion by T-lymphocytes. Importantly, increased numbers of DR+IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR+IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR+IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer.

Parasitic infections and storage iron deficiency in children in improverished regions of Mauritius

Using a combination of techniques including relative deprivation index developed by the Government, school performance, household survey and drawing of lots, a sample frame constituting of poverty areas of Mauritius was constructed and four test areas identified. Relevant haematological, parasitological and biochemical parameters of all school-going children living in the four test areas were determined so as to study the possibility of correlation between parasitic infections, plasma ferritin, haemoglobin concentration, white blood cells count, packed cells volume and blood group. It was found that there is a negative correlation between the number of parasites and haemoglobin concentration, packed cells volume of blood and degree of infestation, number of parasites and ferritin and number of parasites and age of subject. It has also been found that, children with blood group 'A' and blood group '0' tend to harbour the most parasites. As regards to storage iron depletion, this is significant only with hookworm infestation. Additionally it has been noted that hookworm infestation is directly related to age contrary to other parasitic infestations.

NOx storage-reduction characteristics of Ba-based lean NOx trap catalysts subjected to simulated road aging

In order to study the effect of washcoat composition on lean NOx trap (LNT) aging characteristics, fully formulated monolithic LNT catalysts containing varying amounts of La-stabilized CeO2 (5 wt% La2O3) or CeO2-ZrO2 (Ce:Zr = 70:30) were subjected to accelerated aging on a bench reactor. Subsequent catalyst evaluation revealed that aging resulted in deterioration of the NOx storage, NOx release and NOx reduction functions, whereas the observation of lean phase NO2 slip for all of the aged catalysts indicated that LNT performance was not limited by the kinetics of NO oxidation. After aging, all of the catalysts showed increased selectivity to NH3 in the temperature range 250–450 °C. TEM, H2 chemisorption, XPS and elemental analysis data revealed two main changes which can explain the degradation in LNT performance. First, residual sulfur in the catalysts, present as BaSO4, decreased catalyst NOx storage capacity. Second, sintering of the precious metals in the washcoat was observed, which can be expected to decrease the rate of NOx reduction. Additionally, sintering is hypothesized to result in segregation of the precious metal and Ba phases, resulting in less efficient NOx spillover from Pt to Ba during NOx adsorption, as well as decreased rates of reductant spillover from Pt to Ba and reverse NOx spillover during catalyst regeneration. Spectacular improvement in LNT durability was observed for catalysts containing CeO2 or CeO2-ZrO2 relative to their non-ceria containing analog. This was attributed to (i) the ability of ceria to participate in NOx storage/reduction as a supplement to the main Ba NOx storage component; (ii) the fact that Pt and CeO2(-ZrO2) are not subject to phase segregation; and (iii) the ability of ceria to trap sulfur, resulting in decreased sulfur accumulation on the Ba component.

An investigation of the relationship between antemortem and postmortem drug concentrations in blood

In the field of postmortem toxicology, principles from pharmacology and toxicology are combined in order to determine if exogenous substances contributed to ones death. In order to make this determination postmortem and (whenever available) antemortem blood samples may be analyzed. This project focused on evaluating the relationship between postmortem and antemortem blood drug levels, in order to better define an interpretive framework for postmortem toxicology. To do this, it was imperative to evaluate the differences in antemortem and postmortem drug concentrations, determine the role microbial activity and evaluate drug stability. Microbial studies determined that the bacteria Escherichia coli and Pseudomonas aeruginosa could use the carbon structures of drugs as a source of food. This would suggest prior to sample collection, microbial activity could potentially affect drug levels. This process however would stop before toxicologic evaluation, as at autopsy blood samples are stored in tubes containing the antimicrobial agent sodium fluoride. Analysis of preserved blood determined that under the current storage conditions sodium fluoride effectively inhibited microbial growth. Nonetheless, in many instances inconsistent drug concentrations were identified. When comparing antemortem to postmortem results, diphenhydramine, morphine, codeine and methadone, all showed significantly increased postmortem drug levels. In many instances, increased postmortem concentrations correlated with extended postmortem intervals. Other drugs, such as alprazolam, were likely to have concentration discrepancies when short antemortem to death intervals were coupled with extended postmortem intervals. While still others, such as midazolam followed the expected pattern of metabolism and elimination, which often resulted in decreased postmortem concentrations. The importance of drug stability was displayed when reviewing the clonazepam/ 7-aminoclonazepam data, as the parent drug commonly converted to its metabolite even when stored in the presence of a preservative. In instances of decreasing postmortem drug concentrations the effect of refrigerated storage could not be ruled out. A stability experiment, which contained codeine, produced data that indicated concentrations could continue to decline under the current storage conditions. The cumulative data gathered for this experiment was used to identify concentration trends, which subsequently aided in the development of interpretive considerations for the specific analytes examined in the study.

Piezoelectric energy harvesting using blood-flow-like excitation for implantable devices

The goal of this research is to produce a system for powering medical implants to increase the lifetime of the implanted devices and reduce the battery size. The system consists of a number of elements – the piezoelectric material for generating power, the device design, the circuit for rectification and energy storage. The piezoelectric material is analysed and a process for producing a repeatable high quality piezoelectric material is described. A full width half maximum (FWHM) of the rocking curve X-Ray diffraction (XRD) scan of between ~1.5° to ~1.7° for test wafers was achieved. This is state of the art for AlN on silicon and means devices with good piezoelectric constants can be fabricated. Finite element modelling FEM) was used to design the structures for energy harvesting. The models developed in this work were established to have an accuracy better than 5% in terms of the difference between measured and modelled results. Devices made from this material were analysed for power harvesting ability as well as the effect that they have on the flow of liquid which is an important consideration for implantable devices. The FEM results are compared to experimental results from laser Doppler vibrometry (LDV), magnetic shaker and perfusion machine tests. The rectifying circuitry for the energy harvester was also investigated. The final solution uses multiple devices to provide the power to augment the battery and so this was a key feature to be considered. Many circuits were examined and a solution based on a fully autonomous circuit was advanced. This circuit was analysed for use with multiple low power inputs similar to the results from previous investigations into the energy harvesting devices. Polymer materials were also studied for use as a substitute for the piezoelectric material as well as the substrate because silicon is more brittle.

Radiocarbon dating, carbon storage and soil properties of samples from Tulemalu Lake, central Canadian Arctic

We investigated total storage and landscape partitioning of soil organic carbon (SOC) in continuous permafrost terrain, central Canadian Arctic. The study is based on soil chemical analyses of pedons sampled to 1 m depth at 35 individual sites along three transects. Radiocarbon dating of cryoturbated soil pockets, basal peat and fossil wood shows that cryoturbation processes have been occurring since the Middle Holocene and that peat deposits started to accumulate in a forest-tundra environment where spruce was present (~6000 cal yrs BP). Detailed partitioning of SOC into surface organic horizons, cryoturbated soil pockets and non-cryoturbated mineral soil horizons is calculated (with storage in active layer and permafrost calculated separately) and explored using principal component analysis. The detailed partitioning and mean storage of SOC in the landscape are estimated from transect vegetation inventories and a land cover classification based on a Landsat satellite image. Mean SOC storage in the 0-100 cm depth interval is 33.8 kg C/m**2, of which 11.8 kg C/m**2 is in permafrost. Fifty-six per cent of the total SOC mass is stored in peatlands (mainly bogs), but cryoturbated soil pockets in Turbic Cryosols also contribute significantly (17%). Elemental C/N ratios indicate that this cryoturbated soil organic matter (SOM) decomposes more slowly than SOM in surface O-horizons.

Application of battery energy storage in the Québec interconnection

Le Système Stockage de l’Énergie par Batterie ou Batterie de Stockage d’Énergie (BSE) offre de formidables atouts dans les domaines de la production, du transport, de la distribution et de la consommation d’énergie électrique. Cette technologie est notamment considérée par plusieurs opérateurs à travers le monde entier, comme un nouveau dispositif permettant d’injecter d’importantes quantités d’énergie renouvelable d’une part et d’autre part, en tant que composante essentielle aux grands réseaux électriques. De plus, d’énormes avantages peuvent être associés au déploiement de la technologie du BSE aussi bien dans les réseaux intelligents que pour la réduction de l’émission des gaz à effet de serre, la réduction des pertes marginales, l’alimentation de certains consommateurs en source d’énergie d’urgence, l’amélioration de la gestion de l’énergie, et l’accroissement de l’efficacité énergétique dans les réseaux. Cette présente thèse comprend trois étapes à savoir : l’Étape 1 - est relative à l’utilisation de la BSE en guise de réduction des pertes électriques ; l’Étape 2 - utilise la BSE comme élément de réserve tournante en vue de l’atténuation de la vulnérabilité du réseau ; et l’Étape 3 - introduit une nouvelle méthode d’amélioration des oscillations de fréquence par modulation de la puissance réactive, et l’utilisation de la BSE pour satisfaire la réserve primaire de fréquence. La première Étape, relative à l’utilisation de la BSE en vue de la réduction des pertes, est elle-même subdivisée en deux sous-étapes dont la première est consacrée à l’allocation optimale et le seconde, à l’utilisation optimale. Dans la première sous-étape, l’Algorithme génétique NSGA-II (Non-dominated Sorting Genetic Algorithm II) a été programmé dans CASIR, le Super-Ordinateur de l’IREQ, en tant qu’algorithme évolutionniste multiobjectifs, permettant d’extraire un ensemble de solutions pour un dimensionnement optimal et un emplacement adéquat des multiple unités de BSE, tout en minimisant les pertes de puissance, et en considérant en même temps la capacité totale des puissances des unités de BSE installées comme des fonctions objectives. La première sous-étape donne une réponse satisfaisante à l’allocation et résout aussi la question de la programmation/scheduling dans l’interconnexion du Québec. Dans le but de réaliser l’objectif de la seconde sous-étape, un certain nombre de solutions ont été retenues et développées/implantées durant un intervalle de temps d’une année, tout en tenant compte des paramètres (heure, capacité, rendement/efficacité, facteur de puissance) associés aux cycles de charge et de décharge de la BSE, alors que la réduction des pertes marginales et l’efficacité énergétique constituent les principaux objectifs. Quant à la seconde Étape, un nouvel indice de vulnérabilité a été introduit, formalisé et étudié ; indice qui est bien adapté aux réseaux modernes équipés de BES. L’algorithme génétique NSGA-II est de nouveau exécuté (ré-exécuté) alors que la minimisation de l’indice de vulnérabilité proposé et l’efficacité énergétique représentent les principaux objectifs. Les résultats obtenus prouvent que l’utilisation de la BSE peut, dans certains cas, éviter des pannes majeures du réseau. La troisième Étape expose un nouveau concept d’ajout d’une inertie virtuelle aux réseaux électriques, par le procédé de modulation de la puissance réactive. Il a ensuite été présenté l’utilisation de la BSE en guise de réserve primaire de fréquence. Un modèle générique de BSE, associé à l’interconnexion du Québec, a enfin été proposé dans un environnement MATLAB. Les résultats de simulations confirment la possibilité de l’utilisation des puissances active et réactive du système de la BSE en vue de la régulation de fréquence.

Geothermal district heating networks: modelling novel operational strategies incorporating heat storage

The value of integrating a heat storage into a geothermal district heating system has been investigated. The behaviour of the system under a novel operational strategy has been simulated focusing on the energetic, economic and environmental effects of the new strategy of incorporation of the heat storage within the system. A typical geothermal district heating system consists of several production wells, a system of pipelines for the transportation of the hot water to end-users, one or more re-injection wells and peak-up devices (usually fossil-fuel boilers). Traditionally in these systems, the production wells change their production rate throughout the day according to heat demand, and if their maximum capacity is exceeded the peak-up devices are used to meet the balance of the heat demand. In this study, it is proposed to maintain a constant geothermal production and add heat storage into the network. Subsequently, hot water will be stored when heat demand is lower than the production and the stored hot water will be released into the system to cover the peak demands (or part of these). It is not intended to totally phase-out the peak-up devices, but to decrease their use, as these will often be installed anyway for back-up purposes. Both the integration of a heat storage in such a system as well as the novel operational strategy are the main novelties of this thesis. A robust algorithm for the sizing of these systems has been developed. The main inputs are the geothermal production data, the heat demand data throughout one year or more and the topology of the installation. The outputs are the sizing of the whole system, including the necessary number of production wells, the size of the heat storage and the dimensions of the pipelines amongst others. The results provide several useful insights into the initial design considerations for these systems, emphasizing particularly the importance of heat losses. Simulations are carried out for three different cases of sizing of the installation (small, medium and large) to examine the influence of system scale. In the second phase of work, two algorithms are developed which study in detail the operation of the installation throughout a random day and a whole year, respectively. The first algorithm can be a potentially powerful tool for the operators of the installation, who can know a priori how to operate the installation on a random day given the heat demand. The second algorithm is used to obtain the amount of electricity used by the pumps as well as the amount of fuel used by the peak-up boilers over a whole year. These comprise the main operational costs of the installation and are among the main inputs of the third part of the study. In the third part of the study, an integrated energetic, economic and environmental analysis of the studied installation is carried out together with a comparison with the traditional case. The results show that by implementing heat storage under the novel operational strategy, heat is generated more cheaply as all the financial indices improve, more geothermal energy is utilised and less fuel is used in the peak-up boilers, with subsequent environmental benefits, when compared to the traditional case. Furthermore, it is shown that the most attractive case of sizing is the large one, although the addition of the heat storage most greatly impacts the medium case of sizing. In other words, the geothermal component of the installation should be sized as large as possible. This analysis indicates that the proposed solution is beneficial from energetic, economic, and environmental perspectives. Therefore, it can be stated that the aim of this study is achieved in its full potential. Furthermore, the new models for the sizing, operation and economic/energetic/environmental analyses of these kind of systems can be used with few adaptations for real cases, making the practical applicability of this study evident. Having this study as a starting point, further work could include the integration of these systems with end-user demands, further analysis of component parts of the installation (such as the heat exchangers) and the integration of a heat pump to maximise utilisation of geothermal energy.

Dynamic model development of adiabatic compressed air energy storage

The share of variable renewable energy in electricity generation has seen exponential growth during the recent decades, and due to the heightened pursuit of environmental targets, the trend is to continue with increased pace. The two most important resources, wind and insolation both bear the burden of intermittency, creating a need for regulation and posing a threat to grid stability. One possibility to deal with the imbalance between demand and generation is to store electricity temporarily, which was addressed in this thesis by implementing a dynamic model of adiabatic compressed air energy storage (CAES) with Apros dynamic simulation software. Based on literature review, the existing models due to their simplifications were found insufficient for studying transient situations, and despite of its importance, the investigation of part load operation has not yet been possible with satisfactory precision. As a key result of the thesis, the cycle efficiency at design point was simulated to be 58.7%, which correlated well with literature information, and was validated through analytical calculations. The performance at part load was validated against models shown in literature, showing good correlation. By introducing wind resource and electricity demand data to the model, grid operation of CAES was studied. In order to enable the dynamic operation, start-up and shutdown sequences were approximated in dynamic environment, as far as is known, the first time, and a user component for compressor variable guide vanes (VGV) was implemented. Even in the current state, the modularly designed model offers a framework for numerous studies. The validity of the model is limited by the accuracy of VGV correlations at part load, and in addition the implementation of heat losses to the thermal energy storage is necessary to enable longer simulations. More extended use of forecasts is one of the important targets of development, if the system operation is to be optimised in future.

Epidemiology and genetic architecture of blood pressure: a family based study of Generation Scotland

Hypertension is a major risk factor for cardiovascular disease and mortality, and a growing global public health concern, with up to one-third of the world’s population affected. Despite the vast amount of evidence for the benefits of blood pressure (BP) lowering accumulated to date, elevated BP is still the leading risk factor for disease and disability worldwide. It is well established that hypertension and BP are common complex traits, where multiple genetic and environmental factors contribute to BP variation. Furthermore, family and twin studies confirmed the genetic component of BP, with a heritability estimate in the range of 30-50%. Contemporary genomic tools enabling the genotyping of millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, has transformed hypertension genetics research. This is accompanied by the presence of international consortia that have offered unprecedentedly large sample sizes for genome-wide association studies (GWASs). While GWAS for hypertension and BP have identified more than 60 loci, variants in these loci are associated with modest effects on BP and in aggregate can explain less than 3% of the variance in BP. The aims of this thesis are to study the genetic and environmental factors that influence BP and hypertension traits in the Scottish population, by performing several genetic epidemiological analyses. In the first part of this thesis, it aims to study the burden of hypertension in the Scottish population, along with assessing the familial aggregation and heritialbity of BP and hypertension traits. In the second part, it aims to validate the association of common SNPs reported in the large GWAS and to estimate the variance explained by these variants. In this thesis, comprehensive genetic epidemiology analyses were performed on Generation Scotland: Scottish Family Health Study (GS:SFHS), one of the largest population-based family design studies. The availability of clinical, biological samples, self-reported information, and medical records for study participants has allowed several assessments to be performed to evaluate factors that influence BP variation in the Scottish population. Of the 20,753 subjects genotyped in the study, a total of 18,470 individuals (grouped into 7,025 extended families) passed the stringent quality control (QC) criteria and were available for all subsequent analysis. Based on the BP-lowering treatment exposure sources, subjects were further classified into two groups. First, subjects with both a self-reported medications (SRMs) history and electronic-prescription records (EPRs; n =12,347); second, all the subjects with at least one medication history source (n =18,470). In the first group, the analysis showed a good concordance between SRMs and EPRs (kappa =71%), indicating that SRMs can be used as a surrogate to assess the exposure to BP-lowering medication in GS:SFHS participants. Although both sources suffer from some limitations, SRMs can be considered the best available source to estimate the drug exposure history in those without EPRs. The prevalence of hypertension was 40.8% with higher prevalence in men (46.3%) compared to women (35.8%). The prevalence of awareness, treatment and controlled hypertension as defined by the study definition were 25.3%, 31.2%, and 54.3%, respectively. These findings are lower than similar reported studies in other populations, with the exception of controlled hypertension prevalence, which can be considered better than other populations. Odds of hypertension were higher in men, obese or overweight individuals, people with a parental history of hypertension, and those living in the most deprived area of Scotland. On the other hand, deprivation was associated with higher odds of treatment, awareness and controlled hypertension, suggesting that people living in the most deprived area may have been receiving better quality of care, or have higher comorbidity levels requiring greater engagement with doctors. These findings highlight the need for further work to improve hypertension management in Scotland. The family design of GS:SFHS has allowed family-based analysis to be performed to assess the familial aggregation and heritability of BP and hypertension traits. The familial correlation of BP traits ranged from 0.07 to 0.20, and from 0.18 to 0.34 for parent-offspring pairs and sibling pairs, respectively. A higher correlation of BP traits was observed among first-degree relatives than other types of relative pairs. A variance-component model that was adjusted for sex, body mass index (BMI), age, and age-squared was used to estimate heritability of BP traits, which ranged from 24% to 32% with pulse pressure (PP) having the lowest estimates. The genetic correlation between BP traits showed a high correlation between systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (G: 81% to 94%), but lower correlations with PP (G: 22% to 78%). The sibling recurrence risk ratio (λS) for hypertension and treatment were calculated as 1.60 and 2.04 respectively. These findings confirm the genetic components of BP traits in GS:SFHS, and justify further work to investigate genetic determinants of BP. Genetic variants reported in the recent large GWAS of BP traits were selected for genotyping in GS:SFHS using a custom designed TaqMan® OpenArray®. The genotyping plate included 44 single nucleotide polymorphisms (SNPs) that have been previously reported to be associated with BP or hypertension at genome-wide significance level. A linear mixed model that is adjusted for age, age-squared, sex, and BMI was used to test for the association between the genetic variants and BP traits. Of the 43 variants that passed the QC, 11 variants showed statistically significant association with at least one BP trait. The phenotypic variance explained by these variant for the four BP traits were 1.4%, 1.5%, 1.6%, and 0.8% for SBP, DBP, MAP, and PP, respectively. The association of genetic risk score (GRS) that were constructed from selected variants has showed a positive association with BP level and hypertension prevalence, with an average effect of one mmHg increase with each 0.80 unit increases in the GRS across the different BP traits. The impact of BP-lowering medication on the genetic association study for BP traits has been established, with typical practice of adding a fixed value (i.e. 15/10 mmHg) to the measured BP values to adjust for BP treatment. Using the subset of participants with the two treatment exposure sources (i.e. SRMs and EPRs), the influence of using either source to justify the addition of fixed values in SNP association signal was analysed. BP phenotypes derived from EPRs were considered the true phenotypes, and those derived from SRMs were considered less accurate, with some phenotypic noise. Comparing SNPs association signals between the four BP traits in the two model derived from the different adjustments showed that MAP was the least impacted by the phenotypic noise. This was suggested by identifying the same overlapped significant SNPs for the two models in the case of MAP, while other BP traits had some discrepancy between the two sources

Interrogation of human monoclonal antibodies induced by 4C-MenB to identify protective antigens contained in the OMV component

Neisseria meningitidis is a gram negative human obligated pathogen, mostly found as a commensal in the oropharyngeal mucosa of healthy individuals. It can invade this epithelium determining rare but devastating and fast progressing outcomes, such as meningococcal meningitidis and septicemia, leading to death (about 135000 per year worldwide). Conjugated vaccines for serogroups A, C, W135, X and Y were developed, while for N. meningitidis serogroup B (MenB) the vaccines were based on Outern Membrane Vesicles (OMV). One of them is the 4C-MenB (Bexsero). The antigens included in this vaccine’s formulation are, in addition to the OMV from New Zeland epidemic strain 98/254, three recombinant proteins: NadA, NHBA and fHbp. While the role of these recombinant components was deeply characterized, the vesicular contribution in 4C-MenB elicited protection is mediated mainly by porin A and other unidentified antigens. To unravel the relative contribution of these different antigens in eliciting protective antibody responses, we isolated human monoclonal antibodies (mAbs) from single-cell sorted plasmablasts of 3 adult vaccinees peripheral blood. mAbs have been screened for binding to 4C-MenB components by Luminex bead-based assay. OMV-specific mAbs were purified and tested for functionality by serum bactericidal assay (SBA) on 18 different MenB strains and characterized in a protein microarray containing a panel of prioritized meningococcal proteins. The bactericidal mAbs identified to recognize the outer membrane proteins PorA and PorB, stating the importance of PorB in cross-strain protection. In addition, RmpM, BamE, Hyp1065 and ComL were found as immunogenic components of the 4C-MenB vaccine.

Evidences Of Endocytosis Via Caveolae Following Blood-brain Barrier Breakdown By Phoneutria Nigriventer Spider Venom.

Spider venoms contain neurotoxic peptides aimed at paralyzing prey or for defense against predators; that is why they represent valuable tools for studies in neuroscience field. The present study aimed at identifying the process of internalization that occurs during the increased trafficking of vesicles caused by Phoneutria nigriventer spider venom (PNV)-induced blood-brain barrier (BBB) breakdown. Herein, we found that caveolin-1α is up-regulated in the cerebellar capillaries and Purkinje neurons of PNV-administered P14 (neonate) and 8- to 10-week-old (adult) rats. The white matter and granular layers were regions where caveolin-1α showed major upregulation. The variable age played a role in this effect. Caveolin-1 is the central protein that controls caveolae formation. Caveolar-specialized cholesterol- and sphingolipid-rich membrane sub-domains are involved in endocytosis, transcytosis, mechano-sensing, synapse formation and stabilization, signal transduction, intercellular communication, apoptosis, and various signaling events, including those related to calcium handling. PNV is extremely rich in neurotoxic peptides that affect glutamate handling and interferes with ion channels physiology. We suggest that the PNV-induced BBB opening is associated with a high expression of caveolae frame-forming caveolin-1α, and therefore in the process of internalization and enhanced transcytosis. Caveolin-1α up-regulation in Purkinje neurons could be related to a way of neurons to preserve, restore, and enhance function following PNV-induced excitotoxicity. The findings disclose interesting perspectives for further molecular studies of the interaction between PNV and caveolar specialized membrane domains. It proves PNV to be excellent tool for studies of transcytosis, the most common form of BBB-enhanced permeability.

Nebivolol Reduces Central Blood Pressure In Stage I Hypertensive Patients: Experimental Single Cohort Study.

Assessment of central blood pressure (BP) has grown substantially over recent years because evidence has shown that central BP is more relevant to cardiovascular outcomes than peripheral BP. Thus, different classes of antihypertensive drugs have different effects on central BP despite similar reductions in brachial BP. The aim of this study was to investigate the effect of nebivolol, a β-blocker with vasodilator properties, on the biochemical and hemodynamic parameters of hypertensive patients. Experimental single cohort study conducted in the outpatient clinic of a university hospital. Twenty-six patients were recruited. All of them underwent biochemical and hemodynamic evaluation (BP, heart rate (HR), central BP and augmentation index) before and after 3 months of using nebivolol. 88.5% of the patients were male; their mean age was 49.7 ± 9.3 years and most of them were overweight (29.6 ± 3.1 kg/m2) with large abdominal waist (102.1 ± 7.2 cm). There were significant decreases in peripheral systolic BP (P = 0.0020), diastolic BP (P = 0.0049), HR (P < 0.0001) and central BP (129.9 ± 12.3 versus 122.3 ± 10.3 mmHg; P = 0.0083) after treatment, in comparison with the baseline values. There was no statistical difference in the augmentation index or in the biochemical parameters, from before to after the treatment. Nebivolol use seems to be associated with significant reduction of central BP in stage I hypertensive patients, in addition to reductions in brachial systolic and diastolic BP.