Mechanisms of vasomotor sympathetic activity generation in the renovascular hypertension in Wistar rats

The renovascular arterial hypertension (AH) is associated with sympathetic hyperactivity and impaired baroreflex sensitivity determined by increase in circulating angiotensin II (Ang II). The aim of this thesis was to evaluate the role of oxidative stress in the generation and maintenance of the AH (2 Kidney – 1 Clip). Five series of experiments were performed in male Wistar. The results showed autonomic cardiovascular control changes characterized by increased sympathetic modulation in blood vessels, impaired baroreflex sensitivity and tachycardia from the fourth week. Furthermore, we observed that Ang II (via AT-1 receptor) and NO (produced by iNOS) in the rostral ventrolateral medulla (RVLM) are involved in the maintenance of AH and renal sympathetic nerve activity in the 2K-1C. Indeed, there is an imbalance between pro-oxidants and antioxidants in the RVL and hypothalamic paraventricular nucleus (PVN) of animals 2K-1C, because the increase in blood pressure (BP) and sympathetic hyperactivity was reversed in response to administration of the antioxidant (Tempol) into the RVLM and PVN. The over expression of CuZnSOD in the RVLM prevented the AH and reduced the production of superoxide in this region in 2K-1C. Furthermore, improved the impaired baroreflex sensitivity and inhibited the tachycardia observed from the fourth week of AH. Chronic Vitamin C treatment decreased BP and sympathetictactivation in hypertensive animals. In addition, reduced gene expression of subunits of NAD (P) H oxidase in the PVN and RVLM, but unchanged the expression of CuZnSOD. Oxidative stress also seems to influence the gene expression of AT-1 receptor, iNOS, nNOS, IL-1 â and Glut-1 in the PVN and RVL regions, because the treatment reduced the expression of these components. Based on our results, we suggest that the angiotensin system, NO and oxidative stress in the PVN and RVLM are involved in the maintenance of sympathetic tone and the AH 2K-1C. Oxidative stress in sympathetic premotor neurons is a major mechanism for the establishment and maintenance of Ang II – dependent hypertension.A Hipertensão arterial (HA) renovascular está associada com uma hiperatividade simpática e prejuízo na sensibilidade reflexa do barorreceptor determinadas por aumento na Angiotensina II (Ang II) circulante. O objetivo da presente Tese foi avaliar o papel do estresse oxidativo na geração e manutenção da HA 2 Rins-1Clipe. Ratos Machos Wistar foram utilizados em cinco séries de experimentos. Os resultados demonstraram uma alteração no controle autonômico cardíaco caracterizado por maior modulação simpática nos vasos, um prejuízo da sensibilidade reflexa do barorreceptor e taquicardia a partir da quarta semana. Além disso, observou-se que Ang II (via receptor AT-1) e o NO (produzido pela iNOS) na região rostro ventrolateral do bulbo (RVL), participam mantendo a HA e a atividade nervosa simpática renal em ratos 2R-1C. Evidenciou-se um desequilíbrio entre próoxidantes e antioxidantes, caracterizando um estado de estresse oxidativo nas regiões RVL e no núcleo paraventricular (PVN) dos animais 2R-1C, visto que o aumento de pressão arterial (PA) e a hiperatividade simpática são revertidos com a administração do antioxidante (Tempol) nessas regiões. A super expressão crônica de CuZnSOD na região RVL preveniu a HA e reduziu a produção de superóxidos nessa região em ratos 2R-1C. Além disso, melhorou a sensibilidade reflexa do barorreceptor e inibiu a taquicardia observada a partir da quarta semana de HA. O tratamento crônico com Vitamina C promoveu queda da PA e simpato-inibição nos animais hipertensos. Além disso, reduziu a expressão gênica das subunidades de NAD(P)H oxidase nas regiões RVL e PVN, mas não interferiu na expressão de CuZnSOD. O estresse oxidativo também parece influenciar na expressão gênica do receptor AT-1, iNOS, nNOS, IL-1 ƒÀ e Glut-1 nas regioes RVL e PVN, visto que o tratamento reduziu a expressao desses componentes. Baseado em nossos resultados, podemos sugerir que o sistema angiotensinergico, nitrergico e o estresse oxidativo nas regioes RVL e PVN estao envolvidos na manutencao do tonus simpatico e da HA 2R-1C. O estresse oxidativo em neuronios pre-motores do simpatico e um mecanismo essencial para o estabelecimento e manutencao da HA Ang II - dependente.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FAPESP: 05/60151-6CAPES/BEX: 3496/07-4TEDEBV UNIFESP: Teses e dissertaçõe

Combination of linear classifiers using score function -- analysis of possible combination strategies

In this work, we addressed the issue of combining linear classifiers using their score functions. The value of the scoring function depends on the distance from the decision boundary. Two score functions have been tested and four different combination strategies were investigated. During the experimental study, the proposed approach was applied to the heterogeneous ensemble and it was compared to two reference methods -- majority voting and model averaging respectively. The comparison was made in terms of seven different quality criteria. The result shows that combination strategies based on simple average, and trimmed average are the best combination strategies of the geometrical combination

Representation in the (Artificial) Immune System

Much of contemporary research in Artificial Immune Systems (AIS) has partitioned into either algorithmic machine learning and optimisation, or, modelling biologically plausible dynamical systems, with little overlap between. We propose that this dichotomy is somewhat to blame for the lack of significant advancement of the field in either direction and demonstrate how a simplistic interpretation of Perelson’s shape-space formalism may have largely contributed to this dichotomy. In this paper, we motivate and derive an alternative representational abstraction. To do so we consider the validity of shape-space from both the biological and machine learning perspectives. We then take steps towards formally integrating these perspectives into a coherent computational model of notions such as life-long learning, degeneracy, constructive representations and contextual recognition—rhetoric that has long inspired work in AIS, while remaining largely devoid of operational definition

Stabilizing weak classifiers: Regularization and combining techniques in discriminant analysis

Applied Science