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

iTesla Power Systems Library (iPSL): A Modelica library for phasor time-domain simulations

The iTesla Power Systems Library (iPSL) is a Modelica package providing a set of power system components for phasor time-domain modeling and simulation. The Modelica language provides a systematic approach to develop models using a formal mathematical description, that uniquely specifies the physical behavior of a component or the entire system. Furthermore, the standardized specification of the Modelica language (Modelica Association [1]) enables unambiguous model exchange by allowing any Modelica-compliant tool to utilize the models for simulation and their analyses without the need of a specific model transformation tool. As the Modelica language is being developed with open specifications, any tool that implements these requirements can be utilized. This gives users the freedom of choosing an Integrated Development Environment (IDE) of their choice. Furthermore, any integration solver can be implemented within a Modelica tool to simulate Modelica models. Additionally, Modelica is an object-oriented language, enabling code factorization and model re-use to improve the readability of a library by structuring it with object-oriented hierarchy. The developed library is released under an open source license to enable a wider distribution and let the user customize it to their specific needs. This paper describes the iPSL and provides illustrative application examples. Keywords: Modelica, Power system, Simulatio