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Aims/hypothesis. Overwhelming evidence indicates that endothelial cell dysfunction in diabetes is characterised by diminished endothelium-dependent relaxation, but the matter of the underlying molecular mechanism remains unclear. As nitric oxide (NO) production from the endothelium is the major player in endothelium-mediated vascular relaxation, we investigated the effects of high glucose on NO production, and the possible alterations of signalling pathways implicated in this scenario. Methods. NO production and intracellular Ca 2+ levels ([Ca 2+ ] i ) were assessed using the fluorescent probes 4,5-diaminofluorescein diacetate and fura-2 respectively. Results. Exposure of cultured bovine aortic endothelial cells to high glucose for 5 or 10 days significantly reduced NO production induced by bradykinin (but not by Ca 2+ ionophore) in a time-and dose-dependent manner. This was probably due to an attenuation in bradykinin-induced elevations of [Ca 2+ ] i under these conditions, since a close correlation between [Ca 2+ ] i increases and NO generation was observed in intact bovine aortic endothelial cells. Both bradykinin-promoted intracellular Ca 2+ mobilisation and extracellular Ca 2+ entry were affected. Moreover, bradykinin-induced formation of Ins(1,4,5)P 3 , a phospholipase C product leading to increases in [Ca 2+ ] i , was also inhibited following high glucose culture. This abnormality was not attributable to a decrease in inositol phospholipids, but possibly to a reduction in the number of bradykinin receptors. The alterations in NO production, the increases in [Ca 2+ ] i , and the bradykinin receptor number due to high glucose could be largely reversed by protein kinase C inhibitors and D-α-tocopherol (antioxidant). Conclusions/interpretation. Chronic exposure to high glucose reduces NO generation in endothelial cells, probably by impairing phospholipase-C-mediated Ca 2+ signalling due to excess protein kinase C activation. This defect in NO release may contribute to the diminished endothelium-dependent relaxation and thus to the development of cardiovascular diseases in diabetes.

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As the most competitive solution for next-generation network, SDN and its dominant implementation OpenFlow are attracting more and more interests. But besides convenience and flexibility, SDN/OpenFlow also introduces new kinds of limitations and security issues. Of these limitations, the most obvious and maybe the most neglected one is the flow table capacity of SDN/OpenFlow switches. In this paper, we proposed a novel inference attack targeting at SDN/OpenFlow network, which is motivated by the limited flow table capacities of SDN/OpenFlow switches and the following measurable network performance decrease resulting from frequent interactions between data and control plane when the flow table is full. To the best of our knowledge, this is the first proposed inference attack model of this kind for SDN/OpenFlow. We implemented an inference attack framework according to our model and examined its efficiency and accuracy. The evaluation results demonstrate that our framework can infer the network parameters (flow table capacity and usage) with an accuracy of 80% or higher. We also proposed two possible defense strategies for the discovered vulnerability, including routing aggregation algorithm and multilevel flow table architecture. These findings give us a deeper understanding of SDN/OpenFlow limitations and serve as guidelines to future improvements of SDN/OpenFlow.

Objective: Compare immune persistence from one dose of each of 3 different hepatitis A vaccines when given to school-age children: a domestic, live attenuated hepatitis A vaccine (H 2 vaccine); a domestic inactivated hepatitis A vaccine (Healive Ò ); and an imported, inactivated hepatitis A vaccine (Havrix Ò ),. Methods: School-age children were randomized into 1 of 4 groups to receive a single dose of a vaccine: H 2 vaccine, Healive Ò , Havrix Ò , or hepatitis B vaccine [control]. Serum samples were collected 12 and 24 months after vaccination for measurement of anti-HAV IgG using microparticle enzyme immunoassay. Seropositivity was defined as 20 mUI/ml. We compared groups on seropositivity and geometric mean concentration (GMC). Results: Seropositive rates for the H 2 , Healive Ò , Havrix Ò , and control groups were 64%, 94.4%, 73%, and 1.0%, respectively, 12-months post-vaccination; and 63%, 95.6%, 72%, and 1.0%, respectively 24-months post-vaccination. Seropositivity was greater for Healive Ò than for H 2 and Havrix Ò at 12 months (p-values < 0.001) and 24 months (p-values < 0.0001). Average GMCs for the H 2 , Healive Ò , Havrix Ò , and control groups, in mIU/ml, were 29.7, 81.0, 36.4, and 2.9, respectively at 12 months, and 30.9, 112.2, 44.3, and 2.9, respectively, at 24 months. GMCs were greater for Healive Ò than for H 2 and Havrix Ò at 12 months (p-values < 0.0001 and < 0.001, respectively) and 24 months (p-values < 0.001). No statistically significant differences in seropositivity or GMC were found within groups between 12 and 24 months. Conclusion: Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine.