Recent developments in the synthesis of novel xanthone-1,2,3-triazole dyads

The development of multi-target drugs for treating complex multifactorial diseases constitutes an active research ield. This kind of drugs has gained much importance as alternative strategy to combination therapy (“cocktail drugs”).1 A common way to design them brings together two different pharmacophores in one single molecule (so-called dyads). Following this idea and being aware that xanthones2 and 1,2,3-triazoles3 possess important pharmacological properties, we combined these two heterocycles in one molecule to create new dyads with improved therapeutic potential. In this work, new xanthone-1,2,3-triazole dyads were prepared from novel (E)-2-(4-arylbut-1-en-3-yn-1-yl)chromones by two different approaches to evaluate their eficiency and sustainability. Both methodologies involved Diels-Alder reactions to build the xanthone core, which were optimized using microwave irradiation as alternative heating method, and 1,3-dipolar cycloadditions to insert the 1,2,3-triazole moiety (Figure 1).4 All final and intermediate compounds were fully characterized by 1D and 2D NMR techniques.

Simple texture-based liberation modelling of ores

Mineralogical analysis is often used to assess the liberation properties of particles. A direct method of estimating liberation is to actually break particles and then directly obtain liberation information from applying mineralogical analysis to each size-class of the product. Another technique is to artificially apply random breakage to the feed particle sections to estimate the resultant distribution of product particle sections. This technique provides a useful alternative estimation method. Because this technique is applied to particle sections, the actual liberation properties for particles can only be estimated by applying stereological correction. A recent stereological technique has been developed that allows the discrepancy between the linear intercept composition distribution and the particle section composition distribution to be used as guide for estimating the particle composition distribution. The paper will show results validating this new technique using numerical simulation. (C) 2004 Elsevier Ltd. All rights reserved.

Risks for ross river virus disease in tropical Australia

Background There are no analytical studies of individual risks for Ross River virus (RRV) disease. Therefore, we set out to determine individual risk and protective factors for RRV disease in a high incidence area and to assess the utility of the case-control design applied for this purpose to an arbovirus disease. Methods We used a prospective matched case-control study of new community cases of RRV disease in the local government areas of Cairns, Mareeba, Douglas, and Atherton, in tropical Queensland, from January I to May 31, 1998. Results Protective measures against mosquitoes reduced the risk for disease. Mosquito coils, repellents, and citronella candles each decreased risk by at least 2-fold, with a dose-response for the number of protective measures used. Light-coloured clothing decreased risk 3-fold. Camping increased the risk 8-fold. Conclusions These risks were substantial and statistically significant, and provide a basis for educational programs on individual protection against RRV disease in Australia. Our study demonstrates the utility of the case-control method for investigating arbovirus risks. Such a risk analysis has not been done before for RRV infection, and is infrequently reported for other arbovirus infections.

Determination of Cole parameters in multiple frequency bioelectrical impedance analysis using only the measurement of impedances

Conventional bioimpedance spectrometers measure resistance and reactance over a range of frequencies and, by application of a mathematical model for an equivalent circuit (the Cole model), estimate resistance at zero and infinite frequencies. Fitting of the experimental data to the model is accomplished by iterative, nonlinear curve fitting. An alternative fitting method is described that uses only the magnitude of the measured impedances at four selected frequencies. The two methods showed excellent agreement when compared using data obtained both from measurements of equivalent circuits and of humans. These results suggest that operational equivalence to a technically complex, frequency-scanning, phase-sensitive BIS analyser could be achieved from a simple four-frequency, impedance-only analyser.

Implementing an adaptive TCP fairness while exploiting 802.11e over wireless mesh networks

Purpose: The purpose of this paper is to investigate the use of 802.11e MAC to resolve the transmission control protocol (TCP) unfairness. Design/methodology/approach: The paper shows how a TCP sender may adapt its transmission rate using the number of hops and the standard deviation of recently measured round-trip times to address the TCP unfairness. Findings: Simulation results show that the proposed techniques provide even throughput by providing TCP fairness as the number of hops increases over a wireless mesh network (WMN). Research limitations/implications: Future work will examine the performance of TCP over routing protocols, which use different routing metrics. Other future work is scalability over WMNs. Since scalability is a problem with communication in multi-hop, carrier sense multiple access (CSMA) will be compared with time division multiple access (TDMA) and a hybrid of TDMA and code division multiple access (CDMA) will be designed that works with TCP and other traffic. Finally, to further improve network performance and also increase network capacity of TCP for WMNs, the usage of multiple channels instead of only a single fixed channel will be exploited. Practical implications: By allowing the tuning of the 802.11e MAC parameters that have previously been constant in 802.11 MAC, the paper proposes the usage of 802.11e MAC on a per class basis by collecting the TCP ACK into a single class and a novel congestion control method for TCP over a WMN. The key feature of the proposed TCP algorithm is the detection of congestion by measuring the fluctuation of RTT of the TCP ACK samples via the standard deviation, plus the combined the 802.11e AIFS and CWmin allowing the TCP ACK to be prioritised which allows the TCP ACKs will match the volume of the TCP data packets. While 802.11e MAC provides flexibility and flow/congestion control mechanism, the challenge is to take advantage of these features in 802.11e MAC. Originality/value: With 802.11 MAC not having flexibility and flow/congestion control mechanisms implemented with TCP, these contribute to TCP unfairness with competing flows. © Emerald Group Publishing Limited.

Writing and characterisation methods for UV-photosensitivity based devices and their applications

The underlying work to this thesis focused on the exploitation and investigation of photosensitivity mechanisms in optical fibres and planar waveguides for the fabrication of advanced integrated optical devices for telecoms and sensing applications. One major scope is the improvement of grating fabrication specifications by introducing new writing techniques and the use of advanced characterisation methods for grating testing. For the first time the polarisation control method for advanced grating fabrication has successfully been converted to apodised planar waveguide fabrication and the development of a holographic method for the inscription of chirped gratings at arbitrary wavelength is presented. The latter resulted in the fabrication of gratings for pulse-width suppression and wavelength selection in diode lasers. In co-operation with research partners a number of samples were tested using optical frequency domain and optical low coherence reflectometry for a better insight into the limitations of grating writing techniques. Using a variety of different fabrication methods, custom apodised and chirped fibre Bragg gratings were written for the use as filter elements for multiplexer-demultiplexer devices, as well as for short pulse generation and wavelength selection in telecommunication transmission systems. Long period grating based devices in standard, speciality and tapered fibres are presented, showing great potential for multi-parameter sensing. One particular scope is the development of vectorial curvature and refractive index sensors with potential for medical, chemical and biological sensing. In addition the design of an optically tunable Mach-Zehnder based multiwavelength filter is introduced. The discovery of a Type IA grating type through overexposure of hydrogen loaded standard and Boron-Germanium co-doped fibres strengthened the assumption of UV-photosensitivity being a highly non-linear process. Gratings of this type show a significantly lower thermal sensitivity compared to standard gratings, which makes them useful for sensing applications. An Oxford Lasers copper-vapour laser operating at 255 nm in pulsed mode was used for their inscription, in contrast to previous work using CW-Argon-Ion lasers and contributing to differences in the processes of the photorefractive index change

Chemical modification of smectite clays

Today, speciality use organoclays are being developed for an increasingly large number of specific applications. Many of these, including use in cosmetics, polishes, greases and paints, require that the material be free from abrasive impurities so that the product retains a smooth `feel'. The traditional `wet' method preparation of organoclays inherently removes abrasives naturally present in the parent mineral clay, but it is time-consuming and expensive. The primary objective of this thesis was to explore the alternative `dry' method (which is both quicker and cheaper but which provides no refining of the parent clay) as a process, and to examine the nature of the organoclays produced, for the production of a wide range of commercially usable organophilic clays in a facile way. Natural Wyoming bentonite contains two quite different types of silicate surface (that of the clay mineral montmorillonite and that of a quartz impurity) that may interact with the cationic surfactant added in the `dry' process production of organoclays. However, it is oil shale, and not the quartz, that is chiefly responsible for the abrasive nature of the material, although air refinement in combination with the controlled milling of the bentonite as a pretreatment may offer a route to its removal. Ion exchange of Wyoming bentonite with a long chain quaternary ammonium salt using the `dry' process affords a partially exchanged, 69-78%, organoclay, with a monolayer formation of ammonium ions in the interlayer. Excess ion pairs are sorbed on the silicate surfaces of both the clay mineral and the quartz impurity phases. Such surface sorption is enhanced by the presence of very finely divided, super paramagnetic, Fe2O3 or Fe(O)(OH) contaminating the surfaces of the major mineral components. The sorbed material is labile to washing, and induces a measurable shielding of the 29Si nuclei in both clay and quartz phases in the MAS NMR experiment, due to an anisotropic magnetic susceptibility effect. XRD data for humidified samples reveal the interlamellar regions to be strongly hydrophobic, with the by-product sodium chloride being expelled to the external surfaces. Many organic cations will exchange onto a clay. The tetracationic cyclophane, and multipurpose receptor, cyclobis(paraquat-p-phenylene) undergoes ion exchange onto Wyoming bentonite to form a pillared clay with a very regular gallery height. The major plane of the cyclophane is normal to the silicate surfaces, thus allowing the cavity to remain available for complexation. A series of group VI substituted o-dimethoxybenzenes were introduced, and shown to participate in host/guest interactions with the cyclophane. Evidence is given which suggests that the binding of the host structure to a clay substrate offers advantages, not only of transportability and usability but of stability, to the charge-transfer complex which may prove useful in a variety of commercial applications. The fundamental relationship between particle size, cation exchange capacity and chemical composition of clays was also examined. For Wyoming bentonite the extent of isomorphous substitution increases with decreasing particle size, causing the CEC to similarly increase, although the isomorphous substitution site: edge site ratio remains invarient throughout the particle size range studied.

The behaviour of polymer quenchants

The internationally accepted Wolfson Heat Treatment Centre Engineering Group test was used to evaluate the cooling characteristics of the most popular commercial polymer quenchants: polyalkylene glycols, polyvinylpyrrolidones and polyacrylates. Prototype solutions containing poly(ethyloxazoline) were also examined. Each class of polymer was capable of providing a wide range of cooling rates depending on the product formulation, concentration, temperature, agitation, ageing and contamination. Cooling rates for synthetic quenchants were generally intermediate between those of water and oil. Control techniques, drag-out losses and response to quenching in terms of hardness and residual stress for a plain carbon steel, were also considered. A laboratory scale method for providing a controllable level of forced convection was developed. Test reproducibility was improved by positioning the preheated Wolfson probe 25mm above the geometric centre of a 25mm diameter orifice through which the quenchant was pumped at a velocity of 0.5m/s. On examination, all polymer quenchants were found to operate by the same fundamental mechanism associated with their viscosity and ability to form an insulating polymer-rich-film. The nature of this film, which formed at the vapour/liquid interface during boiling, was dependent on the polymer's solubility characteristics. High molecular weight polymers and high concentration solutions produced thicker, more stable insulating films. Agitation produced thinner more uniform films. Higher molecular weight polymers were more susceptible to degradation, and increased cooling rates, with usage. Polyvinylpyrrolidones can be cross-linked resulting in erratic performance, whilst the anionic character of polyacrylates can lead to control problems. Volatile contaminants tend to decrease the rate of cooling and salts to increase it. Drag-out increases upon raising the molecular weight of the polymer and its solution viscosity. Kinematic viscosity measurements are more effective than refractometer readings for concentration control, although a quench test is the most satisfactory process control method.

A Bayesian perspective on stochastic neurocontrol

Control design for stochastic uncertain nonlinear systems is traditionally based on minimizing the expected value of a suitably chosen loss function. Moreover, most control methods usually assume the certainty equivalence principle to simplify the problem and make it computationally tractable. We offer an improved probabilistic framework which is not constrained by these previous assumptions, and provides a more natural framework for incorporating and dealing with uncertainty. The focus of this paper is on developing this framework to obtain an optimal control law strategy using a fully probabilistic approach for information extraction from process data, which does not require detailed knowledge of system dynamics. Moreover, the proposed control method framework allows handling the problem of input-dependent noise. A basic paradigm is proposed and the resulting algorithm is discussed. The proposed probabilistic control method is for the general nonlinear class of discrete-time systems. It is demonstrated theoretically on the affine class. A nonlinear simulation example is also provided to validate theoretical development.

A flexible approach for the apodization of planar waveguide Bragg gratings

A novel single-step technique for the apodization of planar waveguide Bragg gratings based on the polarization control method is proposed. First results are presented, showing successful side-lobe suppression in the reflection spectrum of the gratings.

New oil modified acrylic polymer for pH sensitive drug release:experimental results and statistical analysis

We report results of an experimental study, complemented by detailed statistical analysis of the experimental data, on the development of a more effective control method of drug delivery using a pH sensitive acrylic polymer. New copolymers based on acrylic acid and fatty acid are constructed from dodecyl castor oil and a tercopolymer based on methyl methacrylate, acrylic acid and acryl amide were prepared using this new approach. Water swelling characteristics of fatty acid, acrylic acid copolymer and tercopolymer respectively in acid and alkali solutions have been studied by a step-change method. The antibiotic drug cephalosporin and paracetamol have also been incorporated into the polymer blend through dissolution with the release of the antibiotic drug being evaluated in bacterial stain media and buffer solution. Our results show that the rate of release of paracetamol getss affected by the pH factor and also by the nature of polymer blend. Our experimental data have later been statistically analyzed to quantify the precise nature of polymer decay rates on the pH density of the relevant polymer solvents. The time evolution of the polymer decay rates indicate a marked transition from a linear to a strictly non-linear regime depending on the whether the chosen sample is a general copolymer (linear) or a tercopolymer (non-linear). Non-linear data extrapolation techniques have been used to make probabilistic predictions about the variation in weight percentages of retained polymers at all future times, thereby quantifying the degree of efficacy of the new method of drug delivery.

Nanotechnology and microfluidics:formulation design and on-chip manufacture of nanoparticles

Nanoparticles offer an ideal platform for the delivery of small molecule drugs, subunit vaccines and genetic constructs. Besides the necessity of a homogenous size distribution, defined loading efficiencies and reasonable production and development costs, one of the major bottlenecks in translating nanoparticles into clinical application is the need for rapid, robust and reproducible development techniques. Within this thesis, microfluidic methods were investigated for the manufacturing, drug or protein loading and purification of pharmaceutically relevant nanoparticles. Initially, methods to prepare small liposomes were evaluated and compared to a microfluidics-directed nanoprecipitation method. To support the implementation of statistical process control, design of experiment models aided the process robustness and validation for the methods investigated and gave an initial overview of the size ranges obtainable in each method whilst evaluating advantages and disadvantages of each method. The lab-on-a-chip system resulted in a high-throughput vesicle manufacturing, enabling a rapid process and a high degree of process control. To further investigate this method, cationic low transition temperature lipids, cationic bola-amphiphiles with delocalized charge centers, neutral lipids and polymers were used in the microfluidics-directed nanoprecipitation method to formulate vesicles. Whereas the total flow rate (TFR) and the ratio of solvent to aqueous stream (flow rate ratio, FRR) was shown to be influential for controlling the vesicle size in high transition temperature lipids, the factor FRR was found the most influential factor controlling the size of vesicles consisting of low transition temperature lipids and polymer-based nanoparticles. The biological activity of the resulting constructs was confirmed by an invitro transfection of pDNA constructs using cationic nanoprecipitated vesicles. Design of experiments and multivariate data analysis revealed the mathematical relationship and significance of the factors TFR and FRR in the microfluidics process to the liposome size, polydispersity and transfection efficiency. Multivariate tools were used to cluster and predict specific in-vivo immune responses dependent on key liposome adjuvant characteristics upon delivery a tuberculosis antigen in a vaccine candidate. The addition of a low solubility model drug (propofol) in the nanoprecipitation method resulted in a significantly higher solubilisation of the drug within the liposomal bilayer, compared to the control method. The microfluidics method underwent scale-up work by increasing the channel diameter and parallelisation of the mixers in a planar way, resulting in an overall 40-fold increase in throughput. Furthermore, microfluidic tools were developed based on a microfluidics-directed tangential flow filtration, which allowed for a continuous manufacturing, purification and concentration of liposomal drug products.

Implications of FIN 46 for Accruals Quality and Investment Efficiency

The Financial Accounting Standards Board (FASB) issued Interpretation No. 46 (FIN 46), Consolidation of Variable Interest Entities – An Interpretation of ARB No. 51, in January 2003 and revised it in December 2003, with the objective to improve the transparency of financial information. Under FIN 46, companies are required to consolidate variable interest entities (VIEs) on financial statements if they are the primary beneficiaries of the VIEs. This dissertation empirically examines whether the implementation of this new financial reporting guidance affects firms’ accruals quality and investment efficiency. A manually collected sample comprised of firms affected by FIN 46 and firms disclosing no material impact from FIN 46 is used in the empirical analyses.The first part of the dissertation investigates the effects of FIN 46 on accruals quality. By using different accrual quality measures in prior studies, this study found that firms affected by FIN 46 experienced a decrease in accrual quality compared to firms reporting no material impact from FIN 46. Among the firms affected by FIN 46, firms consolidating VIEs were compared with firms terminating or restructuring VIEs. The accruals quality of firms consolidating VIEs was found to be lower than that of firms terminating or restructuring VIEs. These results are consistent in tests using alternative control samples.The second part of this dissertation examines the effects of FIN 46 on investment efficiency. Mixed results were found from using two different proxies used in prior literature. Using the investment-cash flow sensitivity to proxy for investment efficiency, firms affected by FIN 46 experienced a decrease in investment efficiency compared to firms reporting no material impact. It was also found that higher investment-cash flow sensitivity for firms consolidating VIEs during post-FIN 46 periods compared to both the no-impact firms and the matched pair control sample. Contrasting results were found when the deviation from expected investment is used as another proxy for investment efficiency. Empirical analyses show that FIN 46 firms experienced improved investment efficiency measured by the deviation from expected investment after their adoption of FIN 46. This study also provides explanations for the opposite results from the two different proxies.

Natural disasters and university enrolment: Evidence from L’Aquila earthquake

Although there are several studies looking at the effect of natural disasters on economic growth, less attention has been dedicated to their impact on educational outcomes, especially in more developed countries. We use the synthetic control method to examine how the L’Aquila earthquake affected subsequent enrolment at the local university. This issue has wide economic implications as the University of L’Aquila made a large contribution to the local economy before the earthquake. Our results indicate that the earthquake had no statistically significant effect on first-year enrolment at the University of L’Aquila in the three academic years after the disaster. This natural disaster, however, caused a compositional change in the first-year student population, with a substantial increase in the number of students aged 21 or above. This is likely to have been driven by post-disaster measures adopted in order to mitigate the expected negative effects on enrolment triggered by the earthquake.

An efficient parallel MoM to analyze microstrip structures

[EN]The increasing use of microstrip technology require more accurate analysis methods like full wave method of moments. However, this involves a great computational effort. To reduce the computation time, an alternative parallel method to analyze irregular microstrip structures is presented in this paper. This method calculates the unknown surface current on the planar structure trough a irregular rectangular division using basis and weighted functions. The parallel algorithm performs the calculus of a [Z] matrix and then solves the system using current densities as the unknowns. This parallel program was implemented in the IBM-SP2 using MPI library.