A novel and rational approach towards designing aluminium chelators

Aluminium (Al) is known to be neurotoxic and has been associated with the aetiology of Alzheimer's Disease. To date, only desferrioxamine (DFO), a trihydroxamic acid siderophore has been used in the clinical environment for the removal of Al from the body. However, this drug is expensive, orally inactive and is associated with many side effects. These studies employed a theoretical approach, with the use of quantum mechanics (QM) via semi-empirical molecular orbital (MO) calculations, and a practical approach using U87-MG glioblastoma cells as a model for evaluating the influence of potential chelators on the passage of aluminium into cells. Preliminary studies involving the Cambridge Structural Database (CSD) identified that Al prefers binding to bidentate ligands in a 3:1 manner, whereby oxygen was the exclusive donating atom. Statistically significant differences in M-O bond lengths when compared to other trivalent metal ions such as Fe3+ were established and used as an acceptance criterion for subsequent MO calculations. Of the semi-empirical methods parameterised for Al, the PM3 Hamiltonian was found to give the most reliable final optimised geometries of simple 3:1 Al complexes. Consequently the PM3 Hamiltonian was used for evaluating the Hf of 3:1 complexes with more complicated ligands. No correlation exists between published stability constants and individual parameters calculated via PM3 optimisations, although investigation of the dicarboxylates reveals a correlation of 0.961 showing promise for affinity prediction of closely related ligands. A simple and inexpensive morin spectrofluorescence assay has been developed and optimised producing results comparable to atomic absorption spectroscopy methods for the quantitative analysis of Al. This assay was used in subsequent in vitro models, initially on E. coli, which indicated that Al inhibits the antimicrobial action of ciprofloxacin, a potent quinolone antibiotic. Ensuing studies using the second model, U87-MG cells, investigated the influence of chelators on the transmembrane transport of Al, identifying 1,2-diethylhydroxypyridin-4-one as a ligand showing greatest potential for chelating Al in the clinical situation. In conclusion, these studies have explored semi-empirical MO Hamiltonians and an in-vitro U87-MG cell line, both as possible methods for predicting effective chelators of Al.

Using min-sum loopy belief propagation for decentralised supply chain formation

Modern business trends such as agile manufacturing and virtual corporations require high levels of flexibility and responsiveness to consumer demand, and require the ability to quickly and efficiently select trading partners. Automated computational techniques for supply chain formation have the potential to provide significant advantages in terms of speed and efficiency over the traditional manual approach to partner selection. Automated supply chain formation is the process of determining the participants within a supply chain and the terms of the exchanges made between these participants. In this thesis we present an automated technique for supply chain formation based upon the min-sum loopy belief propagation algorithm (LBP). LBP is a decentralised and distributed message-passing algorithm which allows participants to share their beliefs about the optimal structure of the supply chain based upon their costs, capabilities and requirements. We propose a novel framework for the application of LBP to the existing state-of-the-art case of the decentralised supply chain formation problem, and extend this framework to allow for application to further novel and established problem cases. Specifically, the contributions made by this thesis are: • A novel framework to allow for the application of LBP to the decentralised supply chain formation scenario investigated using the current state-of-the-art approach. Our experimental analysis indicates that LBP is able to match or outperform this approach for the vast majority of problem instances tested. • A new solution goal for supply chain formation in which economically motivated producers aim to maximise their profits by intelligently altering their profit margins. We propose a rational pricing strategy that allows producers to earn significantly greater profits than a comparable LBP-based profitmaking approach. • An LBP-based framework which allows the algorithm to be used to solve supply chain formation problems in which goods are exchanged in multiple units, a first for a fully decentralised technique. As well as multiple-unit exchanges, we also model in this scenario realistic constraints such as factory capacities and input-to-output ratios. LBP continues to be able to match or outperform an extended version of the existing state-of-the-art approach in this scenario. • Introduction of a dynamic supply chain formation scenario in which participants are able to alter their properties or to enter or leave the process at any time. Our results suggest that LBP is able to deal easily with individual occurences of these alterations and that performance degrades gracefully when they occur in larger numbers.

The rational design of vaccines

This review provides an insight into the various opportunities for vaccine intervention, analysis of strategies for vaccine development, vaccine ability to modulate immune responses and resultant rational vaccine design. In addition, wider aspects are considered, such as biotechnological advances, advances in immunological understanding and host-pathogen interactions. The key question addressed here is, with all our research and understanding, have we reached a new echelon in vaccine development, that of rational design? ©2005 Elsevier Ltd. All rights reserved.

Tacit collusion, firm asymmetries and numbers:evidence from EC merger cases

This paper estimates the implicit model, especially the roles of size asymmetries and firm numbers, used by the European Commission to identify mergers with coordinated effects. This subset of cases offers an opportunity to shed empirical light on the conditions where a Competition Authority believes tacit collusion is most likely to arise. We find that, for the Commission, tacit collusion is a rare phenomenon, largely confined to markets of two, more or less symmetric, players. This is consistent with recent experimental literature, but contrasts with the facts on ‘hard-core’ collusion in which firm numbers and asymmetries are often much larger.

Tacit vs. overt collusion firm asymmetries and numbers:what's the evidence?

It is conventional wisdom that collusion is more likely the fewer firms there are in a market and the more symmetric they are. This is often theoretically justified in terms of a repeated non-cooperative game. Although that model fits more easily with tacit than overt collusion, the impression sometimes given is that ‘one model fits all’. Moreover, the empirical literature offers few stylized facts on the most simple of questions—how few are few and how symmetric is symmetric? This paper attempts to fill this gap while also exploring the interface of tacit and overt collusion, albeit in an indirect way. First, it identifies the empirical model of tacit collusion that the European Commission appears to have employed in coordinated effects merger cases—apparently only fairly symmetric duopolies fit the bill. Second, it shows that, intriguingly, the same story emerges from the quite different experimental literature on tacit collusion. This offers a stark contrast with the findings for a sample of prosecuted cartels; on average, these involve six members (often more) and size asymmetries among members are often considerable. The indirect nature of this ‘evidence’ cautions against definitive conclusions; nevertheless, the contrast offers little comfort for those who believe that the same model does, more or less, fit all.

Tacit collusion, firm asymmetries and numbers:evidence from EC merger cases

The purpose of this paper is to identify empirically the implicit structural model, especially the roles of size asymmetries and concentration, used by the European Commission to identify mergers with coordinated effects (i.e. collective dominance). Apart from its obvious policy-relevance, the paper is designed to shed empirical light on the conditions under which tacit collusion is most likely. We construct a database relating to 62 candidate mergers and find that, in the eyes of the Commission, tacit collusion in this context virtually never involves more than two firms and requires close symmetry in the market shares of the two firms.

Random walks and random numbers from supercontinuum generation

We report a numerical study showing how the random intensity and phase fluctuations across the bandwidth of a broadband optical supercontinuum can be interpreted in terms of the random processes of random walks and Lévy flights. We also describe how the intensity fluctuations can be applied to physical random number generation. We conclude that the optical supercontinuum provides a highly versatile means of studying and generating a wide class of random processes at optical wavelengths. © 2012 Optical Society of America.

Transition of planar Couette flow at infinite Reynolds numbers

An outline of the state space of planar Couette flow at high Reynolds numbers (Re<105) is investigated via a variety of efficient numerical techniques. It is verified from nonlinear analysis that the lower branch of the hairpin vortex state (HVS) asymptotically approaches the primary (laminar) state with increasing Re. It is also predicted that the lower branch of the HVS at high Re belongs to the stability boundary that initiates a transition to turbulence, and that one of the unstable manifolds of the lower branch of HVS lies on the boundary. These facts suggest HVS may provide a criterion to estimate a minimum perturbation arising transition to turbulent states at the infinite Re limit. © 2013 American Physical Society.

Cyberstalking:a matter for community safety but the numbers do not add up

The advent of the internet has led to the new phenomenon of ‘cyberstalking’. This paper examines the extent of this problem. It is argued that all of the estimates commonly cited are flawed because they rely on inaccurate or outdated information or are based on a number of unproven assumptions. Although some estimates suggest that there may be as many as 10 million victims in the United States and Canada alone, available evidence supports a far smaller estimate. It is concluded that additional research is needed to arrive at more accurate and reliable estimates

Rational design of heterogeneous catalysts for biodiesel synthesis

Dwindling oil reserves and growing concerns over carbon dioxide emissions and associated climate change are driving the utilisation of renewable feedstocks as alternative, sustainable fuel sources. Catalysis has a rich history of facilitating energy efficient, selective molecular transformations, and contributes to 90% of current chemical manufacturing processes. In a post-petroleum era, catalysis will be pivotal in overcoming the scientific and engineering barriers to economically feasible bio-fuels. This perspective highlights some recent developments in heterogeneous catalysts for the synthesis of biodiesel from renewable resources, derived from plant and aquatic oil sources. Particular attention will be paid to the importance of catalyst pore architecture, surface polarity and acid and base properties, in meeting the challenge of transforming highly polar and viscous bio-based reactants. © 2012 The Royal Society of Chemistry.

Optimization of Rational Approximations by Continued Fractions

The paper has been presented at the 12th International Conference on Applications of Computer Algebra, Varna, Bulgaria, June, 2006.

On the Asymptotic Behavior of the Ratio between the Numbers of Binary Primitive and Irreducible Polynomials

This work was presented in part at the 8th International Conference on Finite Fields and Applications Fq^8 , Melbourne, Australia, 9-13 July, 2007.

On a Class of Vertex Folkman Numbers

Let a1 , . . . , ar, be positive integers, i=1 ... r, m = ∑(ai − 1) + 1 and p = max{a1 , . . . , ar }. For a graph G the symbol G → (a1 , . . . , ar ) means that in every r-coloring of the vertices of G there exists a monochromatic ai -clique of color i for some i ∈ {1, . . . , r}. In this paper we consider the vertex Folkman numbers F (a1 , . . . , ar ; m − 1) = min |V (G)| : G → (a1 , . . . , ar ) and Km−1 ⊂ G} We prove that F (a1 , . . . , ar ; m − 1) = m + 6, if p = 3 and m ≧ 6 (Theorem 3) and F (a1 , . . . , ar ; m − 1) = m + 7, if p = 4 and m ≧ 6 (Theorem 4).

Complex Hyperbolic Surfaces of Abelian Type

2000 Mathematics Subject Classification: 11G15, 11G18, 14H52, 14J25, 32L07.