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.

Closing the gap between bandit and full-information online optimization : high-probability regret bound

We demonstrate a modification of the algorithm of Dani et al for the online linear optimization problem in the bandit setting, which allows us to achieve an O( \sqrt{T ln T} ) regret bound in high probability against an adaptive adversary, as opposed to the in expectation result against an oblivious adversary of Dani et al. We obtain the same dependence on the dimension as that exhibited by Dani et al. The results of this paper rest firmly on those of Dani et al and the remarkable technique of Auer et al for obtaining high-probability bounds via optimistic estimates. This paper answers an open question: it eliminates the gap between the high-probability bounds obtained in the full-information vs bandit settings.

On a Syntactic Characterization of Classification with a Mind Change Bound

Most learning paradigms impose a particular syntax on the class of concepts to be learned; the chosen syntax can dramatically affect whether the class is learnable or not. For classification paradigms, where the task is to determine whether the underlying world does or does not have a particular property, how that property is represented has no implication on the power of a classifier that just outputs 1’s or 0’s. But is it possible to give a canonical syntactic representation of the class of concepts that are classifiable according to the particular criteria of a given paradigm? We provide a positive answer to this question for classification in the limit paradigms in a logical setting, with ordinal mind change bounds as a measure of complexity. The syntactic characterization that emerges enables to derive that if a possibly noncomputable classifier can perform the task assigned to it by the paradigm, then a computable classifier can also perform the same task. The syntactic characterization is strongly related to the difference hierarchy over the class of open sets of some topological space; this space is naturally defined from the class of possible worlds and possible data of the learning paradigm.

To bound or not to bound: preliminary Theory of Time Bounds Specification in strategic alliances

This article augments Resource Dependence Theory with Real Options reasoning in order to explain time bounds specification in strategic alliances. Whereas prior work has found about a 50/50 split between alliances that are time bound and those that are open-ended, their substantive differences and antecedents are ill understood. To address this, we suggest that the two alliance modes present different real options trade-offs in adaptation to environmental uncertainty: ceteris paribus, time-bound alliances are likely to provide abandonment options over open-ended alliances, but require additional investments to extend the alliance when this turns out to be desirable after formation. Open-ended alliances are likely to provide growth options over open-ended alliances, but they demand additional effort to abandon the alliance if post-formation circumstances so desire. Therefore, we expect time bounds specification to be a function of environmental uncertainty: organizations in more uncertain environments will be relatively more likely to place time bounds on their strategic alliances. Longitudinal archival and survey data collected amongst 39 industry clusters provides empirical support for our claims, which contribute to the recent renaissance of resource dependence theory by specifying the conditions under which organizations choose different time windows in strategic partnering.

A bound on the maximum strong order of stochastic Runge-Kutta methods for stochastic ordinary differential equations

In Burrage and Burrage [1] it was shown that by introducing a very general formulation for stochastic Runge-Kutta methods, the previous strong order barrier of order one could be broken without having to use higher derivative terms. In particular, methods of strong order 1.5 were developed in which a Stratonovich integral of order one and one of order two were present in the formulation. In this present paper, general order results are proven about the maximum attainable strong order of these stochastic Runge-Kutta methods (SRKs) in terms of the order of the Stratonovich integrals appearing in the Runge-Kutta formulation. In particular, it will be shown that if an s-stage SRK contains Stratonovich integrals up to order p then the strong order of the SRK cannot exceed min{(p + 1)/2, (s - 1)/2), p greater than or equal to 2, s greater than or equal to 3 or 1 if p = 1.

Book Review [White Bound: Nationalists, Antiracists, and the Shared Meanings of Race, by MW Hughey]

Dr Kathy A. Mills provides a critical synthesis and review of the new book by Matthew W. Hughey entitle: White Bound: Nationalists, Antiractists, and the Shared Meanings of Race, published by Standford University Press in 2012. A sample of Dr Mills' review reads: "The author positions race squarely at the center to challenge the shared assumptions of white supremacist logic on both sides of the debate. The clever thesis blurs the boundaries between “good whites” and “bad whites”, rendering the white reader intellectually stimulated, but existentially unchanged – White Bound – as the author ponders: “Perhaps we have met the enemy, and he [it] is us” (p.193)...The unanswered question that remains is: How do we resist the various “shades” of white supremacy to pursue counter-hegemonic practices?"

Parties legally bound to unsigned put and call option

The point at which the parties to a negotiation for the sale of land are legally bound can often be difficult to judge. This is particularly so where the parties have agreed a lawyer is to formalise the agreement between them. When the parties have not agreed all matters relating to the transaction, interesting questions arise as to what terms regulate the relationship. In Moffatt Property Development Group Pty Ltd v Hebron Park Pty Ltd [2009] QCA 60 the Queensland Court of Appeal considered first, whether there was a binding agreement to sell and secondly, how the relationship would be regulated in the absence of express agreement in relation to many of the terms.

Bound to the borders: Representing refugees in the Australian space

This project consists of a novel and an exegesis that explore the use of fiction to counter negative hegemonic representations of refugees in Australia. The possibilities of using Australian spaces, including border spaces, to reveal tensions surrounding refugee belonging and to highlight the reconfiguration of border sites in the Australian imaginary, is a particular focus of this work.