Fractional order of poling period for broadly tunable second harmonic generation

We demonstrate the possibility to use a fractional order of poling period of nonlinear crystal waveguides for tunable second harmonic generation. This approach allows one to extend wavelength coverage in the visible spectral range by frequency doubling in a single crystal waveguide.

A methodology for the generation and evaluation of biorefinery process chains, in order to identify the most promising biorefineries for the EU

The topic of bioenergy, biofuels and bioproducts remains at the top of the current political and research agenda. Identification of the optimum processing routes for biomass, in terms of efficiency, cost, environment and socio-economics is vital as concern grows over the remaining fossil fuel resources, climate change and energy security. It is known that the only renewable way of producing conventional hydrocarbon fuels and organic chemicals is from biomass, but the problem remains of identifying the best product mix and the most efficient way of processing biomass to products. The aim is to move Europe towards a biobased economy and it is widely accepted that biorefineries are key to this development. A methodology was required for the generation and evaluation of biorefinery process chains for converting biomass into one or more valuable products that properly considers performance, cost, environment, socio-economics and other factors that influence the commercial viability of a process. In this thesis a methodology to achieve this objective is described. The completed methodology includes process chain generation, process modelling and subsequent analysis and comparison of results in order to evaluate alternative process routes. A modular structure was chosen to allow greater flexibility and allowing the user to generate a large number of different biorefinery configurations The significance of the approach is that the methodology is defined and is thus rigorous and consistent and may be readily re-examined if circumstances change. There was the requirement for consistency in structure and use, particularly for multiple analyses. It was important that analyses could be quickly and easily carried out to consider, for example, different scales, configurations and product portfolios and so that previous outcomes could be readily reconsidered. The result of the completed methodology is the identification of the most promising biorefinery chains from those considered as part of the European Biosynergy Project.

Molecular modelling assisted design and synthesis of cyclothialidine derivatives as DNA gyrase inhibitors

Since cyclothialidine was discovered as the most active DNA gyrase inhibitor in 1994, enormous efforts have been devoted to make it into a commercial medicine by a number of pharmaceutical companies and research groups worldwide. However, no serious breakthrough has been made up to now. An essential problem involved with cyclothialidine is that though it demonstrated the potent inhibition of DNA gyrase, it showed little activity against bacteria. This probably is attributable to its inability to penetrate bacterial cell walls and membranes. We applied the TSAR programme to generate a QSAR equation to the gram-negative organisms. In that equation, LogP is profoundly indicated as the key factor influencing the cyclothialidine activity against bacteria. However, the synthesized new analogues have failed to prove that. In the structure based drug design stage, we designed a group of open chain cyclothialidine derivatives by applying the SPROUT programme and completed the syntheses. Improved activity is found in a few analogues and a 3D pharmacophore of the DNA gyrase B is proposed to lead to synthesis of the new derivatives for development of potent antibiotics.

Automated synthesis and evaluation of potential new anti-microbial agents

A series of N1-benzylideneheteroarylcarboxamidrazones was prepared in an automated fashion, and tested against Mycobacterium fortuitum in a rapid screen for antimycobacterial activity. Many of the compounds from this series were also tested against Mycobacterium tuberculosis, and the usefulness as M.fortuitum as a rapid, initial screen for anti-tubercular activity evaluated. Various deletions were made to the N1-benzylideneheteroarylcarboxamidrazone structure in order to establish the minimum structural requirements for activity. The N1-benzylideneheteroarylcarbox-amidrazones were then subjected to molecular modelling studies and their activities against M.fortuitum and M.tuberculosis were analysed using quantitative structure-analysis relationship (QSAR) techniques in the computational package TSAR (Oxford Molecular Ltd.). A set of equations predictive of antimycobacterial activity was hereby obtained. The series of N1-benzylidenehetero-arylcarboxamidrazones was also tested against a multidrug-resistant strain of Staphylococcus aureus (MRSA), followed by a panel of Gram-positive and Gram-negative bacteria, if activity was observed for MRSA. A set of antimycobacterial N1-benzylideneheteroarylcarboxamidrazones was hereby discovered, the best of which had MICs against m. fortuitum in the range 4-8μgml-1 and displayed 94% inhibition of M.tuberculosis at a concentration of 6.25μgml-1. The antimycobacterial activity of these compounds appeared to be specific, since the same compounds were shown to be inactive against other classes of organisms. Compounds which were found to be sufficiently active in any screen were also tested for their toxicity against human mononuclear leucocytes. Polyethylene glycol (PEG) was used as a soluble polymeric support for the synthesis of some fatty acid derivatives, containing an isoxazoline group, which may inhibit mycolic acid synthesis in mycobacteria. Both the PEG-bound products and the cleaved, isolated products themselves were tested against M.fortuitum and some low levels of antimycobacterial activity were observed, which may serve as lead compounds for further studies.

Studies in the handling and absorption of biopterin derivatives in man

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Higher-order factor structures and intercorrelations of the 16PF5 and FIRO-B

This study investigated the intercorrelations and the independent and combined factor structures of the Sixteen Personality Factor Questionnaire Fifth Edition (16PF5) and the Fundamental Interpersonal Orientation-Behaviour Scale (FIRO-B). Four thousand four hundred and fourteen U.S. participants completed these measures as part of executive assessments between 1994 and 2003. Exploratory factor analyses supported the five-factor higher-order structure of the 16PF5; however, the three-component structure for the FIRO-B was not supported. A six-factor structure was found to underlie the variance in the measures in combination. Five of these were close to the 16PF5 higher-order structure, but a sixth factor labelled Social Independence also emerged. This new factor consisted of the 16PF5 primaries of Liveliness and Social Boldness, and the FIRO-B Wanted Control scale.

In vitro toxicity and bioactivity of some pyrimethamine derivatives as anti-tuberculosis agents

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Accounting for derivatives:an evaluation of reporting practice by UK banks

In 1998 the Accounting Standards Board (ASB) published FRS 13, ‘Derivatives and other Financial Instruments: Disclosures’. This laid down the requirements for disclosures of an entity’s policies, objectives and strategies in using financial instruments, their impact on its risk, performance and financial condition, and details of how risks are managed. FRS 13 became effective in March 1999, and this paper uses the 1999 annual reports of UK banks to evaluate the usefulness of disclosures from a user’s perspective. Usefulness is measured in terms of the criteria of materiality, relevance, reliability, comparability and understandability as defined in the ASB’s Statement of Principles (ASB, 1999). Our findings suggest that the narrative disclosures are generic in nature, the numerical data incomplete and not always comparable, and that it is difficult for the user to combine both narrative and numerical information in order to assess the banks’ risk profile. Our overall conclusion is therefore that current UK financial reporting practices are of limited help to users wishing to assess the scale of an institution’s financial risk exposure.

Synthesis and screening of potential antimicrobial compounds

Tuberculosis (TB), an infection caused by human pathogen Mycobacterium tuberculosis, continues to kill millions each year and is as prevalent as it was in the pre-antimicrobial era. With the emergence of continuously-evolving multi-drug resistant strains (MDR) and the implications of the HIV epidemic, it is crucial that new drugs with better efficacy and affordable cost are developed to treat TB. With this in mind, the first part of this thesis discusses the synthesis of libraries of derivatives of pyridine carboxamidrazones, along with cyclised (1,2,4-triazole and 1,2,4-oxadiazole) and fluorinated analogues. Microbiological screening against M. tuberculosis was carried out at the TAACF, NIAID and IDRI (USA). This confirmed the earlier findings that 2-pyridyl-substituted carboxamidrazones were more active than the 4-pyridyl-substituted carboxamidrazones. Another important observation was that upon cyclisation of these carboxamidrazones, a small number of the triazoles retained their activity while in most of the remaining compounds the activity was diminished. This might be attributed to the significant increase in logP value caused by cyclisation of these linear carboxamidrazones, resulting in high lipophilicity and decreased permeability. Another reason might be that the rigidity conferred upon the compound due to cyclisation, results in failure of the compound to fit into the active site of the putative target enzyme. In order to investigate the potential change to the compounds’ metabolism in the organism and/or host, the most active compounds were selected and a fluorine atom was introduced in the pyridine ring. The microbiological results shows a drastic improvement in the activity of the fluorinated carboxamidrazone amides as compared to their non fluorinated counterpart. This improvement in the activity could possibly be the result of the increased cell permeability caused by the fluorine. In a subsidiary strand, a selection of long-chain , -unsaturated carboxylic esters, -keto, -hydroxy carboxylic esters and -keto, -hydroxy carboxylic esters, structurally similar to mycolic acids, were synthesised. The microbiological data revealed that one of the open chain compound was active against the Mycobacterium tuberculosis H37Rv strain and some resistant isolates. The possible compound activity could be its potential to disrupt mycobacterial cell wall synthesis by interfering with the FAS-II pathway.

The effects of birth order on personality traits and feelings of academic sibling rivalry

The influence of birth order on personality and sibling rivalry is controversial; little research has been conducted into academic sibling rivalry, and none into the connection with personality traits. This study considers the interaction of all three factors. Firstborns (N=22) and lastborns (N=24) completed online personality tests and an Academic Sibling Rivalry Questionnaire. Lastborns were found to experience more academic sibling rivalry: t=2.33, DF=44; p less than 0.05, whereas firstborns are more likely to be conscientious: F(1,44)=3.58; p less than 0.05, and dutiful: F(1,44)=5.39; p less than 0.05. This raises possible implications in domains including education, health and psychotherapy. Further research could be conducted to expand these findings in terms of variables and geographical location. (Contains 2 figures.)

New genre of antioxidants from renewable natural resources:synthesis and characterisation of rosemary plant-derived antioxidants and their performance in polyolefins

Several ester derivatives of rosmarinic acid (rosmarinates) were synthesised, characterised (1D and 2D NMR, UV and FTIR spectroscopy) and tested for their potential use as antioxidants derived from a renewable natural resource. The intrinsic free radical scavenging activity of the rosmarinates was assessed, initially using a modified DPPH (2, 2-diphenyl-1-picrylhydrazyl radical) method, and found to be higher than that of commercial synthetic hindered phenol antioxidants Irganox 1076 and Irganox 1010. The thermal stabilising performance of the rosmarinates in polyethylene (PE) and polypropylene (PP) was subsequently examined and compared to that of samples prepared similarly but in the presence of Irganox 1076 (in PE) and Irganox 1010 (in PP) which are typically used for polyolefin stabilisation in industrial practice. The melt stability and the long-term thermo-oxidative stability (LTTS) of processed polymers containing the antioxidants were assessed by measuring the melt flow index (MFI), melt viscosity, oxidation induction time (OIT) and long-term (accelerated) thermal ageing performance. The results show that both the melt and the thermo-oxidative stabilisation afforded by the rosmarinates, and in particular the stearyl derivative, in both PE and PP, are superior to those of Irganox 1076 and Irganox 1010, hence their potential as effective sustainable bio-based antioxidants for polymers. The rosmarinic acid used for the synthesis of the rosmarinates esters in this study was obtained from commercial rosemary extracts (AquaROX80). Furthermore, a large number of different strains of UK-grown rosemary plants (Rosmarinum officinalis) were also extracted and analysed in order to examine their antioxidant content. It was found that the carnosic and the rosmarinic acids, and to a much lesser extent the carnosol, constituted the main antioxidant components of the UK-plants, with the two acids being present at a ratio of 3:1, respectively.