The evaluation of new and isotopically labeled isoindoline nitroxides and an azaphenalene nitroxide for EPR oximetry

Isoindoline nitroxides are potentially useful probes for viable biological systems, exhibiting low cytotoxicity, moderate rates of biological reduction and favorable Electron Paramagnetic Resonance (EPR) characteristics. We have evaluated the anionic (5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl; CTMIO), cationic (5-(N,N,N-trimethylammonio)-1,1,3,3-tetramethylisoindolin-2-yloxyl iodide, QATMIO) and neutral (1,1,3,3-tetramethylisoindolin-2-yloxyl; TMIO) nitroxides and their isotopically labeled analogs ((2)H(12)- and/or (2)H(12)-(15)N-labeled) as potential EPR oximetry probes. An active ester analogue of CTMIO, designed to localize intracellularly, and the azaphenalene nitroxide 1,1,3,3-tetramethyl-2,3-dihydro-2-azaphenalen-2-yloxyl (TMAO) were also studied. While the EPR spectra of the unlabeled nitroxides exhibit high sensitivity to O(2) concentration, deuteration resulted in a loss of superhyperfine features and a subsequent reduction in O(2) sensitivity. Labeling the nitroxides with (15)N increased the signal intensity and this may be useful in decreasing the detection limits for in vivo measurements. The active ester nitroxide showed approximately 6% intracellular localization and low cytotoxicity. The EPR spectra of TMAO nitroxide indicated an increased rigidity in the nitroxide ring, due to dibenzo-annulation.

Hybrid-Game Strategies for multi-objective design optimization in engineering

A number of Game Strategies (GS) have been developed in past decades. They have been used in the fields of economics, engineering, computer science and biology due to their efficiency in solving design optimization problems. In addition, research in multi-objective (MO) and multidisciplinary design optimization (MDO) has focused on developing robust and efficient optimization methods to produce a set of high quality solutions with low computational cost. In this paper, two optimization techniques are considered; the first optimization method uses multi-fidelity hierarchical Pareto optimality. The second optimization method uses the combination of two Game Strategies; Nash-equilibrium and Pareto optimality. The paper shows how Game Strategies can be hybridised and coupled to Multi-Objective Evolutionary Algorithms (MOEA) to accelerate convergence speed and to produce a set of high quality solutions. Numerical results obtained from both optimization methods are compared in terms of computational expense and model quality. The benefits of using Hybrid-Game Strategies are clearly demonstrated

Glycosaminoglycan and growth factor mediated murine calvarial cell proliferation

Understanding the complex mechanisms underlying bone remodeling is crucial to the development of novel therapeutics. Glycosaminoglycans (GAGs) localised to the extracellular matrix (ECM) of bone are thought to play a key role in mediating aspects of bone development. The influence of isolated GAGs was studied by utilising in vitro murine calvarial monolayer and organ culture model systems. Addition of GAG preparations extracted from the cell surface of human osteoblasts at high concentrations (5 microg/ml) resulted in decreased proliferation of cells and decreased suture width and number of bone lining cells in calvarial sections. When we investigated potential interactions between the growth factors fibroblast growth factor-2 (FGF2), bone morphogenic protein-2 (BMP2) and transforming growth factor-beta1 (TGFbeta1) and the isolated cell surface GAGs, differences between the two model systems emerged. The cell culture system demonstrated a potentiating role for the isolated GAGs in the inhibition of FGF2 and TGFbeta1 actions. In contrast, the organ culture system demonstrated an enhanced stimulation of TFGbeta1 effects. These results emphasise the role of the ECM in mediating the interactions between GAGs and growth factors during bone development and suggest the GAG preparations contain potent inhibitory or stimulatory components able to mediate growth factor activity.

Alone against the crowd: Individual differences in referees' ability to cope under pressure

This paper contributes to the recent debate about the role of referees in the home advantage phenomenon. Specifically, it aims to provide a convincing answer to the newly posed question of the existence of individual differences among referees in terms of the home advantage (Boyko, Boyko, & Boyko, 2007; Johnston, 2008). Using multilevel modelling on a large and representative dataset we find that (1) the home advantage effect differs significantly among referees, and (2) this relationship is moderated by the size of the crowd. These new results suggest that a part of the home advantage is due to the effect of the crowd on the referees, and that some referees are more prone to be influenced by the crowd than others. This provides strong evidence to indicate that referees are a significant contributing factor to the home advantage. The implications of these findings are discussed both in terms of the relevant social psychological research, and with respect to the selection, assessment, and training of referees.