The synthesis of novel nitroxides and their application as small-molecule antioxidants and profluorescent probes for oxidative stress

The detection and potential treatment of oxidative stress in biological systems has been explored using isoindoline-based nitroxide radicals. A novel tetraethyl-fluorescein nitroxide was synthesised for its use as a profluorescent probe for redox processes in biological systems. This tetraethyl system, as well as a tetramethyl-fluorescein nitroxide, were shown to be sensitive and selective probes for superoxide in vitro. The redox environment of cellular systems was also explored using the tetramethylfluorescein species based on its reduction to the hydroxylamine. Flow cytometry was employed to assess the extent of nitroxide reduction, reflecting the overall cellular redox environment. Treatment of normal fibroblasts with rotenone and 2-deoxyglucose resulted in an oxidising cellular environment as shown by the lack of reduction of the fluorescein-nitroxide system. Assessment of the tetraethyl-fluorescein nitroxide system in the same way demonstrated its enhanced resistance to reduction and offers the potential to detect and image biologically relevant reactive oxygen species directly. Importantly, these profluorescent nitroxide compounds were shown to be more effective than the more widely used and commercially available probes for reactive oxygen species such as 2’,7’-dichlorodihydrofluorescein diacetate. Fluorescence imaging of the tetramethyl-fluorescein nitroxide and a number of other rhodamine-nitroxide derivatives was undertaken, revealing the differential cellular localisation of these systems and thus their potential for the detection of redox changes in specific cellular compartments. As well as developing novel methods for the detection of oxidative stress, a number of novel isoindoline nitroxides were synthesised for their potential application as small-molecule antioxidants. These compounds incorporated known pharmacophores into the isoindoline-nitroxide structure in an attempt to increase their efficacy in biological systems. A primary and a secondary amine nitroxide were synthesised which incorporated the phenethylamine backbone of the sympathomimetic amine class of drugs. Initial assessment of the novel primary amine derivative indicated a protective effect comparable to that of 5-carboxy-1,1,3,3- tetramethylisoindolin-2-yloxyl. Methoxy-substituted nitroxides were also synthesised as potential antioxidants for their structural similarity to some amphetamine type stimulants. A copper-catalysed methodology provided access to both the mono- and di-substituted methoxy-nitroxides. Deprotection of the ethers in these compounds using boron tribromide successfully produced a phenolnitroxide, however the catechol moiety in the disubstituted derivative appeared to undergo reaction with the nitroxide to produce quinone-like degradation products. A novel fluoran-nitroxide was also synthesised from the methoxy-substituted nitroxide, providing a pH-sensitive spin probe. An amino-acid precursor containing a nitroxide moiety was also synthesised for its application as a dual-action antioxidant. N-Acetyl protection of the nitroxide radical was necessary prior to the Erlenmeyer reaction with N-acetyl glycine. Hydrolysis and reduction of the azlactone intermediate produced a novel amino acid precursor with significant potential as an effective antioxidant.

Effects of different practice task constraints on fluctuations of player heart rate in small-sided football games

This paper analyzes effects of different practice task constraints on heart rate (HR) variability during 4v4 smallsided football games. Participants were sixteen football players divided into two age groups (U13, Mean age: 12.4±0.5 yrs; U15: 14.6±0.5). The task consisted of a 4v4 sub-phase without goalkeepers, on a 25x15 m field, of 15 minutes duration with an active recovery period of 6 minutes between each condition. We recorded players’ heart rates using heart rate monitors (Polar Team System, Polar Electro, Kempele, Finland) as scoring mode was manipulated (line goal: scoring by dribbling past an extended line; double goal: scoring in either of two lateral goals; and central goal: scoring only in one goal). Subsequently, %HR reserve was calculated with the Karvonen formula. We performed a time-series analysis of HR for each individual in each condition. Mean data for intra-participant variability showed that autocorrelation function was associated with more short-range dependence processes in the “line goal” condition, compared to other conditions, demonstrating that the “line goal” constraint induced more randomness in HR response. Relative to inter-individual variability, line goal constraints demonstrated lower %CV and %RMSD (U13: 9% and 19%; U15: 10% and 19%) compared with double goal (U13: 12% and 21%; U15: 12% and 21%) and central goal (U13: 14% and 24%; U15: 13% and 24%) task constraints, respectively. Results suggested that line goal constraints imposed more randomness on cardiovascular stimulation of each individual and lower inter-individual variability than double goal and central goal constraints.

Scaffolding large units for small group collaborative learning : a case study.

Undergraduates working in teams can be a problematic endeavour, sometimes exacerbated for the student by poor prior experiences, a predisposition to an individual orientation of assessment, and simply the busyness that now typifies the life of a student. But effort in pedagogical design is worthwhile where team work is often a prerequisite in terms of graduate capabilities, robust learning, increased motivation, and indeed in terms of equipping individuals for emergent knowledge-age work practice, often epitomised by collaborative effort in both blended and virtual contexts. Through an iterative approach, based extensively on the established literature, we have developed a successful scaffold which is workable with a large cohort group (n >800), such that it affords students the lived experience of being a part of a learning network. Individuals within teams work together, to develop individual components that are subsequently aggregated and reified to an overall team knowledge artefact. We describe our case and propose a pedagogical model of scaffolding based on three perspectives: conceptual, rule-based and community-driven. This model provides designers with guidelines for producing and refining assessment tasks for team-based learning.

Do programs to improve business performance in small and medium manufacturing enterprise improve opportunity recognition?

Increasing awareness of the benefits of stimulating entrepreneurial behaviour in small and medium enterprises has fostered strong interest in innovation programs. Recently many western countries have invested in design innovation for better firm performance. This research presents some early findings from a study of companies which participated in an holistic approach to design innovation, where the outcomes include better business performance and better market positioning in global markets. Preliminary findings from in-depth semi-structured interviews indicate the importance of firm openness to new ways of working and developing new processes of strategic entrepreneurship. Implications for theory and practice are discussed.

Small, Medium, Large: Theatre Companies and Issues of Scale - A Case Study of a Medium-Sized Company

'Surviving but not thriving.' Tbat is the message about small to mediumsized companies that Ian McRae, Chair ofthe Theatre Board of the Australia Council, has been delivering since 2003. In the Theatre Board Assessment Meeting Report of 2007, McRae strongly urged renewed financial support for this most important sector given the significant decrease over the last 10 years and the consequent decrease in new Australian works being produced. Without such support his prediction is that'considerable damage could be done to the creative infrastructure across Australia resulting in a loss of artistic vibrancy down the track that could be very difficult to recover' (McRae, 2007:3).

The effects of weight loss strategies on gastric emptying and appetite control

The gastrointestinal tract plays an important role in the improved appetite control and weight loss in response to bariatric surgery. Other strategies which similarly alter gastrointestinal responses to food intake could contribute to successful weight management. The aim of this review is to discuss the effects of surgical, pharmacological and behavioural weight loss interventions on gastrointestinal targets of appetite control, including gastric emptying. Gastrointestinal peptides are also discussed because of their integrative relationship in appetite control. This review shows that different strategies exert diverse effects and there is no consensus on the optimal strategy for manipulating gastric emptying to improve appetite control. Emerging evidence from surgical procedures (e.g., sleeve gastrectomy and Roux en-Y gastric bypass) suggests a faster emptying rate and earlier delivery of nutrients to the distal small intestine may improve appetite control. Energy restriction slows gastric emptying, while the effect of exercise-induced weight loss on gastric emptying remains to be established. The limited evidence suggests that chronic exercise is associated with faster gastric emptying which we hypothesise will impact on appetite control and energy balance. Understanding how behavioural weight loss interventions (e.g., diet and exercise) alter gastrointestinal targets of appetite control may be important to improve their success in weight management.

Improving visual noise insensitivity in small vocabulary audio visual speech recognition applications

Visual noise insensitivity is important to audio visual speech recognition (AVSR). Visual noise can take on a number of forms such as varying frame rate, occlusion, lighting or speaker variabilities. The use of a high dimensional secondary classifier on the word likelihood scores from both the audio and video modalities is investigated for the purposes of adaptive fusion. Preliminary results are presented demonstrating performance above the catastrophic fusion boundary for our confidence measure irrespective of the type of visual noise presented to it. Our experiments were restricted to small vocabulary applications.