Docosahexaenoic Acid Improves the Nitroso-Redox Balance and Reduces VEGF-Mediated Angiogenic Signaling in Microvascular Endothelial Cells

Purpose. Disturbances to the cellular production of nitric oxide (NO) and superoxide (O2-) can have deleterious effects on retinal vascular integrity and angiogenic signaling. Dietary agents that could modulate the production of these signaling molecules from their likely enzymatic sources, endothelial nitric oxide synthase (eNOS) and NADPH oxidase, would therefore have a major beneficial effect on retinal vascular disease. The effect of ?-3 polyunsaturated fatty acids (PUFAs) on angiogenic signaling and NO/superoxide production in retinal microvascular endothelial cells (RMECs) was investigated.

Methods. Primary RMECs were treated with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) for 48 hours. RMEC migration was determined by scratch-wound assay, proliferation by the incorporation of BrdU, and angiogenic sprouting using a three-dimensional model of in vitro angiogenesis. NO production was quantified by Griess assay, and phospho-eNOS accumulation and superoxide were measured using the fluorescent probe dihydroethidine. eNOS localization to caveolin-rich microdomains was determined by Western blot analysis after subfractionation on a linear sucrose gradient.

Results. DHA treatment increased nitrite and decreased superoxide production, which correlated with the displacement of eNOS from caveolar subdomains and colocalization with the negative regulator caveolin-1. In addition, both ?-3 PUFAs demonstrated reduced responsiveness to VEGF-stimulated superoxide and nitrite release and significantly impaired endothelial wound healing, proliferation, and angiogenic sprout formation.

Conclusions. DHA improves NO bioavailability, decreases O2- production, and blunts VEGF-mediated angiogenic signaling. These findings suggest a role for ?-3 PUFAs, particularly DHA, in maintaining vascular integrity while reducing pathologic retinal neovascularization.

The matrix metalloproteinase-3 (MMP-3) 5A/6A promoter polymorphism is not associated with ischaemic heart disease: Analysis employing a family based approach

Matrix metalloproteinase-3 (MMP-3) has been proposed as an important mediator of the atherosclerotic process. The possible role of the functional -1612(.)5A/6A polymorphism of the MMP-3 gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family based tests of association. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped. Using the combined transmission disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test (PDT), no association between the MMP-3 -1612 5A/6A polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the MMP-3 -1612 5A/6A polymorphism is not associated with IHD.

Inter-Frame Contextual Modelling For Visual Speech Recognition

In this paper, we present a new approach to visual speech recognition which improves contextual modelling by combining Inter-Frame Dependent and Hidden Markov Models. This approach captures contextual information in visual speech that may be lost using a Hidden Markov Model alone. We apply contextual modelling to a large speaker independent isolated digit recognition task, and compare our approach to two commonly adopted feature based techniques for incorporating speech dynamics. Results are presented from baseline feature based systems and the combined modelling technique. We illustrate that both of these techniques achieve similar levels of performance when used independently. However significant improvements in performance can be achieved through a combination of the two. In particular we report an improvement in excess of 17% relative Word Error Rate in comparison to our best baseline system.

Filming and Performing Renaissance History

Over the last one hundred years, many of the events and personalities of the sixteenth and seventeenth centuries have been brought before home, cinema, exhibition, festival and theatrical audiences via a variety of visual media. This collection, for the first time, examines these representations, looking at recent television series, documentaries, feature films, pageantry, theatre and popular culture in a range of cultural and linguistic guises. Filming and Performing Renaissance History opens up wider avenues of interpretive opportunity and substitutes a more generous, nuanced acknowledgement of the ways in which the 'Renaissance' is made to signify across disciplines and in relation to a whole series of events and personalities. Accessing the Renaissance in this fashion generates a genuine sense of the modalities of historical representation, of what the Renaissance 'means' and of how its meanings have been negotiated in modernity.

Fatigue performance of aircraft panels with novel skin buckling containment features

To increase structural efficiency of stiffened panels in an aircraft, it is plausible to introduce skin buckling containment features to increase the local skin stability and thus static strength performance. Introducing buckling containment features may also significantly influence the fatigue crack growth performance of the stiffened panel. This study focuses on the experimental demonstration of panel durability with skin bay buckling containment features. Through a series of fatigue crack growth tests on integrally machined aluminium alloy stiffened panels, the potential to simultaneously improve static strength performance and crack propagation behaviour is demonstrated. The introduction of prismatic buckling containment features which have yielded significant static strength performance gains have herein demonstrated potential fatigue life gains of up to + 63 per cent.