In this case, players will usually have to manually assign divisions to each front, or they will default to the first front drawn.Īn example of a battle plan would be a major invasion of Italy, north of enemy lines, designed to crush an enemy preoccupied with an engagement from the south.
If desired, different divisions within a single army may be allocated to different battle plans.
Plans do not have to be drawn in order to give divisions orders, but are generally recommended as they reduce micromanagement and improve the flow of gameplay. As such, the aim of this review is to define our current understanding regarding the effect of hemolysis (free heme) on circulating XO levels as well as the subsequent impact of XO-derived oxidants in hemolytic disease processes.A Battle Plan is an important tool that helps players visualize how their divisions will advance, allows the AI to control the player's divisions automatically, and can confer a Planning bonus. While it is known that circulating XO is elevated in hemolytic diseases including sickle cell, malaria and sepsis, little is understood regarding its role in these pathologies. This gap in knowledge stems from several interrelated issues including: 1) lethality of global XO deletion and the absence of tissue-specific XO knockout models have coalesced to relegate proof-of-principle experimentation to pharmacology 2) XO is mobile and thus when upregulated locally can be secreted into the circulation and impact distal vascular beds by high-affinity association to the glycocalyx on the endothelium and 3) endothelial-bound XO is significantly resistant (> 50%) to inhibition by allopurinol, the principle compound used for XO inhibition in the clinic as well as the laboratory. While XO has been studied for over 120 years, much remains unknown regarding specific mechanistic roles for this enzyme in pathologic processes. A key enzymatic source of these reactive species is the purine catabolizing enzyme, xanthine oxidase (XO) as the oxidation of hypoxanthine to xanthine and subsequent oxidation of xanthine to uric acid generates superoxide (O 2 Hemolytic diseases are associated with elevated levels of circulating free heme that can mediate endothelial dysfunction directly via redox reactions with biomolecules or indirectly by upregulating enzymatic sources of reactive species.
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