Using a previously developed non-pair-additive model of the water–water hydrogen bond, the relative stabilites of hydrogen ordered and disordered ice Ih, ices VII and VIII are examined. The results are consistent with both the observed hydrogen-ordering in the VII → VIII transition, and the lack of any similar ordering in hexagonal ice I. The symmetry relation between the two sub-lattices of VII and VIII, together with the non-linearity of the energy of the dipole–dipole interaction, suggest such ordering transitions may be favoured only when very special symmetry arrangements result in the cancellation of certain electropole energy terms.
Formulae for calculating the elastic local buckling stresses of doubly-symmetric thin-walled I-section girders subjected to combined shear and direct stresses, accounting for the interaction between the plate elements are presented. The interaction between the plate elements (i.e. the flanges and web) is bounded by a theoretical lower-bound, where there is no interaction and the critical plate is considered to be simply-supported, and a theoretical upper-bound where interaction is strongest and the critical plate is considered to have rotationally fixed edges. The interaction is accounted for by introducing an interaction coefficient ζ that quantifies the relative level of fixity between the aforementioned lower and upper bounds. Expressions to calculate ζ are calibrated using results from finite element analyses generated in Abaqus. Doubly-symmetric I-sections of varying geometric proportions loaded in shear, major axis bending, compression and a full range of combinations thereof are considered. Using the developed formulae, the elastic local buckling stresses of the studied cross-sections are accurately predicted, typically within 5% of the values obtained from FE models; this is a significant improvement over the results determined in the traditional manner in which plate element interaction effects are ignored, where the full cross-section buckling stress is shown to be underestimated by as much as 40%.
I. Introduction Airway pharmacology is concerned with the action of drugs on target cells of the airways and improving our understanding of the mechanism of action of drugs used to treat airway diseases. This should lead to advances in drug development, so that treatment may be more specific and maximizes the beneficial effects. Drugs may also be used as specific probes to analyze pathophysiological processes in airway disease. This chapter concerns the general pharmacological principles of drug action in the airways, with particular emphasis on the application of pharmacology to understanding obstructive airway diseases and their therapy.
In current structural steel design specifications, the stability of members is typically assessed through the use of buckling curves which implicitly consider the influence of both initial geometric imperfections and residual stresses. An alternative and more direct approach is to perform a second order analysis of the member or structure with all imperfections included. For modelling convenience, i.e. to avoid the explicit modelling of residual stresses, so-called 'equivalent' geometric imperfections are typically utilised, which consider the combined influence of both geometric imperfections and residual stresses through an increased geometric imperfection amplitude. For columns and beams, equivalent geometric imperfections for use in design by geometrically and materially nonlinear analysis with imperfections (GMNIA) have recently been developed. However, for beam-columns, which are subjected to combined compression and bending, there are currently no specific provisions. Therefore, equivalent geometric imperfections for application in the stability design of steel and stainless steel beam-columns by GMNIA are developed herein. The proposals are calibrated against the results of benchmark finite element (FE) simulations performed on a large number of steel and stainless steel I-section or hollow section beam-columns, with or without intermediate lateral restraints, subjected to various ratios of axial compression and major and/or minor bending moments. Proposals for the shapes and amplitudes of equivalent geometric imperfections are developed for application with both eigenmode-affine imperfections e0,mod and the direct modelling of sinusoidal bow imperfections e0,bow. Relative to the traditional Eurocode design calculations, employing the developed equivalent geometric imperfections in GMNIA provides more accurate resistance predictions. The reliability analysis of the design provisions shows that partial safety factors of 1.0 for steel and 1.1 for stainless steel can be safely adopted.
Oxidative stress, characterized by an imbalance between increased exposure to free radicals and antioxidant defenses, is a prominent feature of many acute and chronic diseases and even the normal aging process. However, definitive evidence for this association has often been lacking due to recognized shortcomings with methods previously available to assess oxidant stress status in vivo in humans. Several in vitro markers of oxidative stress are available, but most are of limited value in vivo because thay lack sensitivity and/or specificity or require invasive methods. Isoprostanes (IsoPs) are prostaglandin (PG)-like compounds that are produced in vivo independently of cyclooxygenase enzymes, primarily by free radical-induced peroxidation of arachidonic acid. F2-IsoPs are a group of 64 compounds isomeric in structure to cyclooxygenase- derived PGF2α. Other products of the IsoP pathway are also formed in vivo by rearrangement of labile PGH2-like IsoP intermediates including E2- and D2-IsoPs, cyclopentenone-A2- and J2-IsoPs, and highly reactive acyclicketoaldehydes (isoketals). Oxidation of docosahexaenoic acid, an abundant unsaturated fatty acid in the central nervous system, results in the formation of IsoP-like compounds, termed neuroprostanes. Measurement of F2-IsoPs is the most reliable approach to assess oxidative stress status in vivo, providing an important tool to explore the role of oxidative stress in the pathogenesis of human disease. Moreover, F2-IsoPs and other products of the IsoP pathway exert potent biological actions both via receptor-dependent and independent mechanisms and therefore may be pathophysiological mediators of disease. Measurement of F2-IsoPs may provide a uniquely valuable approach to understanding of the clinical pharmacology of antioxidants. Keywords: Isoprostanes, oxidative stress, reactive oxygen species, neuroprostanes, isoketals, eicosanoids, prostaglandins
