The work described herein is directed towards the Claisen rearrangements and [3+2] cycloaddition reaction of pyridine N-oxide systems. The pyridine N-oxide molecule is a very versatile and useful synthetic intermediate for the construction of more complex pyridines. Chapter 1 contains a review of work carried out within the group towards Claisen rearrangement of benzene-type systems. The acid catalysed rearrangement of these systems affords a high degree of regioselectivity. A literature survey of the [3+2] cycloaddition reaction of both aliphatic nitrones and aromatic N-oxides with various dipolarophiles is also included. Access to many stereochemically pure products demonstrates that the [3+2] cycloaddition has become a very important ring-forming reaction. Chapter 2 describes development of two Claisen rearrangement precursors and their subsequent attempted Claisen rearrangement is outlined. Chapter 3 details the construction of a range of 3-substituted pyridine N-oxides. Their attempted intermolecular cycloaddition, by thermal means and at high pressure, with mono- and di-activated dipolarophiles is described. Chapter 4 outlines attempts towards and the final synthesis of the ester cycloaddition precursors. Attempted intramolecular [3+2] cycloaddition of these substrates both thermally and under high pressure is summarised. Chapter 5 describes approaches towards [3+2] cycloaddition precursors that contain mono- and di-activated dienophiles. The synthesis of a variety of 3-substituted pyridines is detailed.

This thesis investigates the use of arene chromium complexes as phenyl cation synthons in the synthesis of homochiral N-phenylamino esters, and the dianion formation of a series of complexed aryl ethers. Chapter 1 reviews the properties of arene chromium tricarbonyl complexes and discusses in detail the ability of some of these complexes to undergo nucleophilic aromatic substitution. Chapter 2 outlines the biological importance of homochiral N-phenylamino esters. The N-phenylation of a series of amino alcohols are first investigated both by direct reaction of haloarene complexes with amino alcohols and also via a Smiles rearrangement of an aryl ether derivative. In addition, methodology is developed for the synthesis of a series of homochiral N-phenyl-α-amino esters and N-phenyl-β-amino esters. The synthetic strategy is then applied to the synthesis of some N-phenyl-β-lactams, in particular (+)SCH 48461. Chapter 3 reviews the directed metallation of complexed and uncomplexed arene compounds and discusses the mechanism involved. The generation of dianions in a series of complexed aryl ethers is investigated. Regioselective deprotonation is observed using different alkyllithium bases and the degree of dianion formation is confirmed by electrophilic quench of the dianionic intermediates with CD₃OD and TMSC1.

This thesis describes a study of the substrate selectivity of active site mutants of the monooxygenase cytochrome P450_cam. A range of mutants was constructed which replaced the phenolic side-chain at the Tyr-96 position by various hydrophobic amino acid residues. These 'hydrophobic mutants' were then combined with other mutations around the active site (Val-247, Phe-87, Ile-395 and Phe-193) which altered the space available at different positions in the active site. These mutants were then tested with an in vitro reconstituted P450_cam system with a range of substrates related to diphenylmethane and phenylcylcohexane. All of these large compounds were poor substrates for the wild-type enzyme. It was found that it was necessary to increase both the space available in the active site and the active site hydrophobicity to achieve substrate turnover. The substrates were oxidised preferentially on the aliphatic cyclohexyl ring over the more constrained phenyl ring suggesting that the active site is predisposed to binding the cyclohexyl ring close to the haem. Hydroxylation using the in vitro reconstituted P450_cam system is limited by catalyst lifetime and the need for the expensive cofactor NADH. For P450_cam hydroxylation to become a viable synthetic method it is necessary to find ways to bypass the use of NADH. For this reason various self-sufficient P450_cam system were constructed and expressed in E. coli. The best of these, despite limited protein expression, was found to turnover camphor with the wild-type P450_cam enzyme and other substrates with the Y96A mutant. The in vivo catalytic system was then used to screen many P450_cam mutants for the oxidation of natural products, monoterpenes and sesquiterpenes (e.g. limonene, pinene and valencene). Most of the target substrates are not oxidised by the wild-type enzyme but all are hydroxylated by some if not all of the P450_cam mutants with different degrees of selectivity. Some of the products identified so far are important compounds in the field of flavour and fragrance chemistry (e.g. verbenol and nookatone).

Tikslas: Įvertinti chinoksalino darinių struktūros įtaką jų antimikrobiniam ir priešvėžiniam aktyvumui ir atrinkti perspektyviausius junginius tolimesniems tyrimams. Darbo uždaviniai: 1. Ištirti chinoksalino darinių antimikrobinį (priešgrybelinį ir antibakterinį) aktyvumą in vitro. 2. Ištirti chinoksalino darinių priešvėžinį aktyvumą in vitro. 3. Nustatyti chinoksalino darinių antimikrobinio ir priešvėžinio aktyvumo bei cheminės struktūros ryšio dėsningumus. 4. Įvertinti chinoksalino darinių toksiškumą ir farmakokinetines savybes in silico. 5. Remiantis gautais rezultatais, atrinkti perspektyviausius chinoksalino darinius. Tyrimo metodai. Antimikrobiniam aktyvumui nustatyti naudoti in vitro metodai: skiedimo standžioje ir skystoje terpėse bei difuzijos į agarą metodas. Priešvėžinis aktyvumas įvertintas tiriant ląstelių gyvybingumo slopinimą MTT metodu. Struktūros-aktyvumo ryšys įvertintas analizuojant eksperimentinius duomenis. Junginių toksiškumas ir farmakokinetinės savybės įvertintos in silico, remiantis kompiuterinės programos ACD/I-Lab duomenimis. Tyrimo rezultatai. Aktyviausi chinoksalino dariniai Bacillus ir Staphylococcus genties bakterijų augimą slopino 16 μM koncentracija, grybelio Candida albicans – 22 μM koncentracija. Aktyviausi chinoksalino dariniai žmogaus plaučių karcinomos A549 ir glioblastomos U87 ląsteles veikė 0,5-10 μM koncentracijomis. Nustatyti antimikrobinio poveikio struktūros ryšio dėsningumai: aktyviausi junginiai chinoksalino žiedo antroje padėtyje... [toliau žr. visą tekstą] / The Aim of the Research: To evaluate the structure influence on antimicrobial and anticancer activity of quinoxaline derivatives and identify the most promising compounds for the further development. Objectives: 1. To test antimicrobial (antibacterial and antifungal) activity of quinoxaline derivatives in vitro. 2. To test anticancer activity of quinoxaline derivatives in vitro. 3. To establish relationship between structure and antimicrobial, also anticancer activity. 4. To evaluate toxicity and pharmacokinetic properties of quinoxaline derivatives in silico. 5. To identify the most promising quinoxaline derivatives with reference to experimental results. Methods. Antimicrobial activity was tested in vitro using three different methods: serial dilution in agar, in liquid broth, and diffusion into agar. Anticancer activity was investigated by evaluating cell viability using MTT assay. Structure-activity relationship was evaluated from analysis of experimental data. Toxicity and pharmacokinetic properties were predicted by using ACD/I-Lab program. Results. The most promising quinoxaline derivatives inhibited growth of Bacillus and Staphylococcus genus bacteria with 16 μM concentration, fungus Candida albicans with 22 μM concentration. The most active quinoxaline derivatives were active against human lung carcinoma A549 and glioblastoma U87 cell lines with concentrations of 0.5-10 μM. Some principles of structure – antimicrobial activity relationship were established: the most... [to full text]

What explains the shift towards greater direct public oversight of financial markets in international financial regulation that has characterized the response to the global financial crisis of 2007-2010? Over this period, the main international financial regulatory bodies have abandoned the market-based mechanisms that had informed their approach towards the regulation of different financial domains in the years before the crisis and significantly expanded the perimeter of state-based regulation. However, the extent and the timing of this shift cannot be regarded only as the by-product of the crisis, nor they can be explained by the existing interpretations of the political determinants of international regulatory policies. This study builds upon existing state-centric explanations of international regulatory policies, but it goes beyond these works by exploring how the preferences of the most influential countries in response to the crisis have been influenced by variations in the degree of public salience of different financial domains. More specifically, this study argues that the lasting increase in the public salience of financial regulatory policies in the US and different European countries since the last quarter of 2008 has created strong incentives for elected officials in these countries to challenge the market-based approach that had emerged in the decade and half before the crisis and to directly interfere in the international regulatory agenda. In order to explain this shift, this study will analyse the evolution in the international governance of three sets of markets and institutions that have occupied an important position in the international regulatory agenda in recent years: 1) OTC derivatives; 2) rating agencies; 3) hedge funds. Besides making an empirical contribution to the literature on the politics of international financial regulation, this study also contributes theoretically to this literature by deepening our understanding of the nexus between international regulatory coordination and domestic public opinion.

The subject of this experimental investigation is to measure the dynamic stability derivatives in roll plane for an oscillating combat aircraft model by using forced oscillation technique. In forced oscillation technique the model is forced to oscillate around the center of gravity according to a harmonic motion of small amplitude and low frequency. The aerodynamic reactions are measured by an internal balance placed inside the model. The thesis presents a brief description of the test rig and the measurement system. The theory of dynamic stability derivatives and forced oscillation technique are also explained. The data is collected and analyzed by using a data acquisition system written with under the Labview programming language. Systematic analysis of the static and dynamic tests results and effect of various parameters (angle of attack, sideslip angle, oscillation frequency and amplitude, wind velocity) on these results are presented. Comparison of the present results with previous results obtained in other test facilities is also given. Design and manufacture process of a new angle of attack mechanism is also given in this thesis.

Numerous authors note failure of private insurance markets to provide affordable and comprehensive crop insurance. Economic logic suggests that index contracts potentially may have some advantages when compared with traditional (farm based) crop insurance. It is also a matter of common knowledge that weather is an important production factor and at the same time one of the greatest sources of risk in agriculture. Hence introduction of crop insurance contracts, based on weather indexes, might be a reasonable approach to mitigate problems, associated with traditional crop insurance products, and possibly lower the cost of insurance for end users. In spite of the fact that before the financial crisis of 2008-09 market for weather derivatives was the fastest growing derivatives market in the USA, agricultural producers didn’t express much interest in application of weather derivatives to management of their systematic risk. There are several reasons for that, but the most important one is the presence of high basis risk, which is represented by its two major components: technological (i.e. goodness of fit between yield and weather index) and geographical basis. Majority of the researchers is focusing either on pricing of weather derivatives or on mitigation of geographical basis risk. At the same time the number of papers researching possible ways to decrease technological basis is quite limited, and always assumes linear dependency between yields and weather variables, while estimating the risk reducing efficiency of weather contracts, which is obviously large deviation from reality. The objective of this study is to estimate the risk reducing efficiency of crop insurance contracts, based on weather derivatives (indexes) in the state of Texas. The distributions of representative farmer’s profits with the proposed contracts are compared to the distributions of profits without a contract. This is done to demonstrate the risk mitigating effect of the proposed contracts. Moreover the study will try to account for a more complex dependency structures between yields and weather variables through usage of copulas, while constructing joint distribution of yields and weather data. Selection of the optimal copula will be implemented in the out-of-sample efficient framework. An effort will be done to identify the most relevant periods of year, when weather has the most significant influence on crop yields, which should be included in the model, and to discover the most effective copula to model joint weather/yield risk. Results suggest that effective insurance of crop yields in the state of Texas by the means of proposed weather derivatives is possible. Besides, usage of data-mining techniques allows for more accurate selection of the time periods to be included in the model than ad hoc procedure previously used in the literature. Finally selection of optimal copula for modeling of joint weather/yield distribution should be crop and county specific, while in general Clayton and Frank copula of Archimedean copula family provide the best out-of-sample metric results.

Typescript. / Thesis (Ph. D.)--University of Hawaii at Manoa, 1979. / Bibliography: leaves 147-156. / Microfiche. / x, 156 leaves ill. (some col.) 29 cm

In this thesis I present a new numerical scheme for 2.5-D/3-D direct current resistivity modelling in heterogeneous, anisotropic media. This method, named the ‘Gaussian quadrature grid’ (GQG) method, co-operatively combines the solution of the Variational Principle of the partial differential equation, Gaussian quadrature abscissae and local cardinal functions so that it has the main advantages of the spectral element method. The formulation shows that the GQG method is a modification of the spectral element method and does not employ the constant elements and require the mesh generator to match the earth’s surface. This makes it much easier to deal with geological models having a 2-D/3-D complex topography than using traditional numerical methods. The GQG technique can achieve a similar convergence rate to the spectral element method. It is shown that it transforms the 2.5-D/3-D resistivity modelling problem into a sparse and symmetric linear equation system, which can be solved by an iterative or matrix inversion method. Comparison with analytic solutions for homogeneous isotropic and anisotropic models shows that the error depends on the Gaussian quadrature order (abscissae number) and the sub-domain size. The higher order or smaller the subdomain size employed, the more accurate the solution. Several other synthetic examples, both homogeneous and inhomogeneous, incorporating sloping, undulating and severe topography are presented and found to yield results comparable to finite element solutions involving a dense mesh. The thesis also presents for the first time explicit expressions for the Fréchet derivatives or sensitivity functions in resistivity imaging of a heterogeneous and fully anisotropic earth. The formulation involves the Green’s functions and their gradients, and is developed both from a formal perturbation analysis and by means of a numerical (finite element) method. A critical factor in the equations is the derivative of the electrical conductivity tensor with respect to the principal conductivity values and the angles defining the axes of symmetry; these are given analytically. The Fréchet derivative expressions are given for both the 2.5-D and the 3-D problem using both constant point and constant block model parameterisations. Special cases like the isotropic earth and tilted transversely isotropic (TTI) media are shown to emerge from the general solutions. Numerical examples are presented for the various sensitivities as functions of the dip angle and strike of the plane of stratification in uniform TTI media. In addition, analytic solutions are derived for the electric potential, current density and Fréchet derivatives at any interior point within a 3-D transversely isotropic homogeneous medium having a tilted axis of symmetry. The current electrode is assumed to be on the surface of the Earth and the plane of stratification given arbitrary strike and dip. Profiles can be computed for any azimuth. The equipotentials exhibit an elliptical pattern and are not orthogonal to the current density vectors, which are strongly angle dependent. Current density reaches its maximum value in a direction parallel to the longitudinal conductivity direction. Illustrative examples of the Fréchet derivatives are given for the 2.5-D problem, in which the profile is taken perpendicular to strike. All three derivatives of the Green’s function with respect to longitudinal conductivity, transverse resistivity and dip angle of the symmetry axis (dG/dσ₁,dG/dσ₁,dG/dθ₀ ) show a strongly asymmetric pattern compared to the isotropic case. The patterns are aligned in the direction of the tilt angle. Such sensitivity patterns are useful in real time experimental design as well as in the fast inversion of resistivity data collected over an anisotropic earth. / Thesis (Ph.D.) -- University of Adelaide, School of Chemistry and Physics, 2009

Bibliography: leaves 112-140. / xi, 141, [39] leaves, [8] leaves of plates : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The aims of this thesis are to determine the initial cleavage sites of purified pepsin in long-R3-IGF-I and assess whether the resulting cleavages affect biological activity, to design and produce analogues of long-R3-IGF-I which contain amino acid substitutions, to characterise the resulting analogues for pepsin resistance and retention of biological activity and to assess the stability of the long-R3-IGF-I analogues under in vivo conditions using luminal stomach flushings. / Thesis (Ph.D.)--University of Adelaide, Dept. of Biochemistry, 1996