Effects of oxidised low density lipoprotein on dendritic cells: a possible immunoregulatory component of the atherogenic micro-environment?

Objective: The objective of this study was to explore the relationship between low density lipoprotein (LDL) and dendritic cell (DC) activation, based upon the hypothesis that reactive oxygen species (ROS)-mediated modification of proteins that may be present in local DC microenvironments could be important as mediators of this activation. Although LDL are known to be oxidised in vivo, and taken up by macrophages during atherogenesis; their effect on DC has not been explored previously. Methods: Human DCs were prepared from peripheral blood monocytes using GM-CSF and IL-4. Plasma LDLs were isolated by sequential gradient centrifugation, oxidised in CuSO4, and oxidation arrested to yield mild, moderate and highly oxidised LDL forms. DCs exposed to these LDLs were investigated using combined phenotypic, functional (autologous T cell activation), morphological and viability assays. Results: Highly-oxidised LDL increased DC HLA-DR, CD40 and CD86 expression, corroborated by increased DC-induced T cell proliferation. Both native and oxidised LDL induced prominent DC clustering. However, high concentrations of highly-oxidised LDL inhibited DC function, due to increased DC apoptosis. Conclusions: This study supports the hypothesis that oxidised LDL are capable of triggering the transition from sentinel to messenger DC. Furthermore, the DC clustering–activation–apoptosis sequence in the presence of different LDL forms is consistent with a regulatory DC role in immunopathogenesis of atheroma. A sequence of initial accumulation of DC, increasing LDL oxidation, and DC-induced T cell activation, may explain why local breach of tolerance can occur. Above a threshold level, however, supervening DC apoptosis limits this, contributing instead to the central plaque core.

Resonance response of electrorheological fluids in vertical oscillation squeeze flow

The resonance effect of microcrystalline cellulose/castor oil electrorheological (ER) suspensions was studied in a compressed oscillatory squeeze flow under external electric fields. The resonance frequency first increases linearly with increasing external held, and then shift to high-field plateau. The amplitudes of resonance peak increase sharply with the applied fields in the range of 0.17-1.67kV/mm. The phase difference of the reduced displacement relative to the excitation force inverses in the case of resonance. A viscoelasticity model of the ER suspensions, which offers both the equivalent stiffness and the viscous damping, should be responsible for the appearance of resonance. The influence of the electric field on the resonance frequency and the resonance hump is consistent qualitatively with the interpretation of our proposed model. Storage modulus G' was presented for the purpose of investigating this influence.

The regulation of cyber warfare under the jus ad bellum

This chapter evaluates the potential for legal regulation of the resort to cyber warfare between states under the ‘jus ad bellum’ (the law on the use of force). Debate in the literature has largely concerned whether cyber warfare falls within the scope of Article 2(4) UNC. The first part of this chapter sets out this debate. It then goes on to argue that the ‘Article 2(4) debate’ often misses the fact that an act of cyber warfare can be considered a breach of a different legal rule: the principle of non-intervention. The chapter further considers some of the issues in applying either the prohibition of the use of force or the principle of non-intervention to cyber warfare, and then concludes by arguing that the debate should be reoriented to focus on another existing international legal obligation: the duty to prevent cyber-attacks.

Breaching the social contract: crises of democratic representation and patterns of extreme right party support

Why has the extreme right Greek Golden Dawn, a party with clear links to fascism experienced a rise defying all theories that claim that such a party is unlikely to win in post-WWII Europe? And, if we accept that economic crisis is an explanation for this, why has such a phenomenon not occurred in other countries that have similar conducive conditions, such as Portugal and Spain? This article addresses this puzzle by (a) carrying out a controlled comparison of Greece, Portugal and Spain and (b) showing that the rise of the extreme right is not a question of intensity of economic crisis. Rather it is the nature of the crisis, i.e. economic versus overall crisis of democratic representation that facilitates the rise of the extreme right. We argue that extreme right parties are more likely to experience an increase in their support when economic crisis culminates into an overall crisis of democratic representation. Economic crisis is likely to become a political crisis when severe issues of governability impact upon the ability of the state to fulfil its social contract obligations. This breach of the social contract is accompanied by declining levels of trust in state institutions, resulting in party system collapse.