DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity

Dolly Steering Controller for Enhancing Low-and High-Speed Performance of High Capacity Vehicles

The adaptation of high capacity vehicles (HCVs) into existing commercial vehicle fleets have been considered a potential solution for reducing emissions, operational costs and infrastructure damages. However, due to increased length and number of articulations, there are challenges associated with HCVs with regard to their manoeuvrability at low-speeds and stability at high-speeds. This paper presents a Virtual Rigid Axle Command Steering control strategy for dolly steering, due to which both low- and high-speed performance of HCVs may be improved significantly compared to their conventional version with non-steered dolly. To demonstrate this, two HCVs, namely, A-double (tractor-semitrailer-dolly-semitrailer) and LHV-D (truck-dolly-semitrailer) are considered in this work

EU Tax Law and The Return of the Nation-State

This chapter analyses the European Union’s efforts to counteract the erosion of member states’ corporate tax bases. The author first describes how multinational enterprises, like Apple, have been able to exploit differences between the tax systems in order to pay less taxes. The author then presents the hypothesis that EU member states have managed to defend their interests in protecting their own corporate tax revenues under the pretext of safeguarding national welfare under the mandate of the European Union. However, the Commission’s use of EU rules on state aid to limit tax competition may be viewed as contrary to the Union’s freedom of movement. In view of this trend, the author recommends the EU to agree on a common corporate income tax rule for cross-border transactions reducing member states' initiatives to safeguard their sovereignty through protectionist tax measures