Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Complement proteins and activation products have been found associated with neuropathology in Alzheimer's disease (AD). Recently, a C5a receptor antagonist was shown to suppress neuropathology in two murine models of AD, Tg2576 and 3xTg. Previously, a genetic deficiency of C1q in the Tg2576 mouse model showed an accumulation of fibrillar plaques similar to the complement sufficient Tg2576, but reactive glia were significantly decreased and neuronal integrity was improved suggesting detrimental consequences for complement activation in AD. The goal of this study was to define the role of the classical complement activation pathway in the progression of pathology in the 3xTg mouse that develops tangles in addition to fibrillar plaques (more closely reflecting human AD pathology) and to assess the influence of complement in a model of AD with a higher level of complement hemolytic activity.</p> <p>Methods</p> <p>3xTg mice deficient in C1q (3xTgQ-/-) were generated, and both 3xTg and 3xTgQ-/- were backcrossed to the BUB mouse strain which has higher in vitro hemolytic complement activity. Mice were aged and perfused, and brain sections stained for pathological markers or analyzed for proinflammatory marker expression.</p> <p>Results</p> <p>3xTgQ-/- mice showed similar amounts of fibrillar amyloid, reactive glia and hyperphosphorylated tau as the C1q-sufficient 3xTg at the ages analyzed. However, 3xTg and 3xTgQ-/- on the BUB background developed pathology earlier than on the original 3xTg background, although the presence of C1q had no effect on neuropathological and pro-inflammatory markers. In contrast to that seen in other transgenic models of AD, C1q, C4 and C3 immunoreactivity was undetectable on the plaques of 3xTg in any background, although C3 was associated with reactive astrocytes surrounding the plaques. Importantly, properdin a component of the alternative complement pathway was associated with plaques in all models.</p> <p>Conclusions</p> <p>In contrast to previously investigated transgenic models of AD, development of neuropathology in 3xTg mice, which progresses much slower than other murine models, may not be influenced by fibrillar amyloid mediated activation of the classical complement pathway, suggesting that the alternative complement pathway activation or a C3-independent cleavage of C5 could account for the detrimental effects in these mice that are prevented by the C5a receptor antagonist. Furthermore, the paucity of complement activation may be a factor in the slower kinetics of progression of pathology in the 3xTg model of this disease.</p

CONVERSOR AC-DC EM MODO CONTÍNUO DE CORRENTE COM COMPENSAÇÃO EM FREQUÊNCIA PARA LÂMPADAS LED DE BAIXO CUSTO E ALTA EFICIÊNCIA

Este artigo apresenta uma nova arquitetura de um driver de LEDs de alto brilho, com baixo custo e elevado rendimento. Emprega-se um conversor do tipo CUK em modo contínuo de corrente com compensação em frequência, para alimentação dos LEDs de alto brilho através da rede elétrica, a partir de 85V a 265V, operando em alta frequência com comutação por Modulação por Largura de Pulso (MLP) e conectado a um filtro ressonante LC série para alimentação da carga com proteção contra surto de tensão na entrada. Foram utilizados vinte LEDs de Alta Potência da OSRAM 720-GWPSL e um circuito com corrente constante em modo Off-line. A arquitetura proposta visa apresentar uma proposta de um driver de baixo custo e baixo consumo de corrente. É apresentado o estudo comparativo entre o protótipo deste dispositivo a partir dos gráficos obtidos com os resultados de medições em laboratório

Sonic Boom Propagation with a Nonlinear Geometrical Acoustic Model

A simple analytical model which can predict accurately the sonic boom pressure signature on the ground in the vertical plane below a supersonic aircraft flying at constant horizontal speed in stratified atmosphere is presented. The proposed model employs geometrical acoustics to propagate the boom and combines a nonlinear treatment of its amplitude with a nonlinear calculation of its distortion, supplemented by the ”area rule” for shocks fitting; ray-tracing equations are derived to calculate the rays trajectory and the ray-tube area, considering the standard atmosphere. Although simple, this combined method allows a very efficient and accurate prediction of the boom propagation starting from a given pressure signal in the near-field and can be considered a useful tool for the aerodynamic design and multi-objective optimization of low-boom supersonic aircrafts via CFD methods. Comparisons with recent experimental data and previously published results obtained via well established sonic boom propagation codes are provided

A Nonlinear Geometrical Acoustic Model for Sonic Boom Propagation

A simple analytical model which can predict accurately the sonic boom pressure signature on the ground in the vertical plane below a supersonic aircraft flying at constant horizontal speed in stratified atmosphere is presented. The proposed model employs geometrical acoustics to propagate the boom and combines a nonlinear treatment of its amplitude with a nonlinear calculation of its distortion, supplemented by the ”area rule” for shocks fitting; ray-tracing equations are derived to calculate the rays trajectory and the ray-tube area, considering the standard atmosphere. Although simple, this combined method allows a very efficient and accurate prediction of the boom propagation starting from a given pressure signal in the near-field and can be considered a useful tool for the aerodynamic design and multi-objective optimization of low-boom supersonic aircrafts via CFD methods. Comparisons with recent experimental data and previously published results obtained via well established sonic boom propagation codes are provided

Sonic Boom Propagation Revisited: a Nonlinear Geometrical Acoustic Model

An analytical model which can accurately propagate a near-field sonic boom pressure signature down to the ground in a stratified atmosphere is presented. The pressure perturbations are limited to the vertical plane below a supersonic aircraft flying at constant horizontal speed. The proposed model employs geometrical acoustics to propagate the boom and combines a nonlinear treatment of both its amplitude and distortion, supplemented by the "area rule" for shocks fitting; ray-tracing equations are derived to calculate the ray trajectory and the ray-tube area, considering the Standard Atmosphere. Although simple, this combined method allows a very efficient and accurate prediction of the boom propagation and can be considered a useful tool for the aerodynamic design and multi-objective optimization of low-boom supersonic aircrafts via CFD methods. Whitham's aeroacoustic theory, here proposed in an "inverse mode" formulation, and classical geometrical acoustic theory are recalled and critically compared with the proposed model in order to assess its features and qualities. Comparisons with recent experimental data and previously published results obtained via well established sonic boom propagation codes are also provided and explained

Posterior choanae and choanal polyps

This is a publisher’s version of an article published in Annals of Otology, Rhinology & Laryngology published by Annals Publishing Company. This version is reproduced with permission from Annals Publishing Company. http://www.annals.com/In the literature there are reports of nasal, antrochoanal, ethmochoanal and sphenochoanal polyps. A search, however has not revealed reports of polyps actually arising from the choanae. A report and photograph of a polyp arising from the posterior choana is presented in this paper and it seems logical to refer to this as a choanal polyp