Measurement of free drug and clinical end-point by high-performance liquid chromatography-mass spectrometry: Applications and implications for pharmacokinetic and pharmacodynamic studies

Free drug measurement and pharmacodymanic markers provide the opportunity for a better understanding of drug efficacy and toxicity. High-performance liquid chromatography (HPLC)-mass spectrometry (MS) is a powerful analytical technique that could facilitate the measurement of free drug and these markers. Currently, there are very few published methods for the determination of free drug concentrations by HPLC-MS. The development of atmospheric pressure ionisation sources, together with on-line microdialysis or on-line equilibrium dialysis and column switching techniques have reduced sample run times and increased assay efficiency. The availability of such methods will aid in drug development and the clinical use of certain drugs, including anti-convulsants, anti-arrhythmics, immunosuppressants, local anaesthetics, anti-fungals and protease inhibitors. The history of free drug measurement and an overview of the current HPLC-MS applications for these drugs are discussed. Immunosuppressant drugs are used as an example for the application of HPLC-MS in the measurement of drug pharmacodynamics. Potential biomarkers of immunosuppression that could be measured by HPLC-MS include purine nucleoside/nucleotides, drug-protein complexes and phosphorylated peptides. At the proteomic level, two-dimensional gel electrophoresis combined with matrix-assisted laser desorption/ionisation time-of-flight (TOF) MS is a powerful tool for identifying proteins involved in the response to inflammatory mediators. (C) 2003 Elsevier Science B.V. All rights reserved.

Microbial quantification in activated sludge: the hits and misses

Since the implementation of the activated sludge process for treating wastewater, there has been a reliance on chemical and physical parameters to monitor the system. However, in biological nutrient removal (BNR) processes, the microorganisms responsible for some of the transformations should be used to monitor the processes with the overall goal to achieve better treatment performance. The development of in situ identification and rapid quantification techniques for key microorganisms involved in BNR are required to achieve this goal. This study explored the quantification of Nitrospira, a key organism in the oxidation of nitrite to nitrate in BNR. Two molecular genetic microbial quantification techniques were evaluated: real-time polymerase chain reaction (PCR) and fluorescence in situ hybridisation (FISH) followed by digital image analysis. A correlation between the Nitrospira quantitative data and the nitrate production rate, determined in batch tests, was attempted. The disadvantages and advantages of both methods will be discussed.

Synthetic, spectroscopic and X-ray crystallographic structural study of the monomeric [Cu(pysme)(sac)(MeOH)] and dimeric [Cu(6mptsc)(sac)](2) complexes [pysme = anion of the pyridine-2-carboxaldehyde Schiff base of S-methyldithiocarbazate, 6mptsc=the anio

New mixed-ligand copper(II) complexes of empirical formulas [Cu(pysme)(sac) (CH3OH)] and [Cu(6mptsc)(sac)](2) have been synthesized and characterized by conductance, magnetic, IR and electronic spectroscopic techniques. X-ray crystallographic structure analyses of these complexes indicate that in both complexes the copper(II) ions adopt a five-coordinate distorted square-pyramidal geometry with an N3SO donor environment. The Schiff bases are coordinated to the copper(II) ions as tridentate NNS chelates via the pyridine nitrogen atom, the azomethine nitrogen atom and the thiolate sulfur atom. In the monomeric [Cu(pysme)(sac)(MeOH)] complex, the saccharinate anion acts as a monodentate ligand coordinating the copper(II) ion via the imino nitrogen atom whereas in the dimeric [Cu(6mptsc)(sac)](2) complex, the sac anion behaves as a bridging bidentate ligand providing the imino nitrogen donor atom to one of the copper(II) ions and the carbonyl oxygen as a weakly coordinated axial ligand atom to the other Cu(II) ion. In both complexes, the copper(II) ions have distorted square-pyramidal environments. The distortion from an ideal square-pyramidal geometry is attributed to the restricted bite angles of the planar tridentate ligand. (C) 2004 Elsevier Ltd. All rights reserved.

Identifying and discriminating among lucerne cultivars using plant morphological characters

The use of morphological data obtained from field (plot test) and glasshouse trials to identify and discriminate among four Iranian and two New Zealand lucerne (Medicago sativa L.) cultivars was investigated, following guidelines established by the International Union for the Protection of New Varieties of Plants (UPOV) for cultivar registration and the Organisation for Economic Co-operation and Development (OECD) for seed certification. Data were collected for terminal leaflet length, width and ratio, angle of stem growth, date of first flowering, stem height at first flowering, flower colour, cutting recovery height, and disease scores. None of these characters were sufficient to identify or discriminate among the six cultivars. The results indicate a need to find cost-effective and efficient laboratory techniques to enhance the assessment of distinctness of lucerne cultivars (UPOV) and for determining cultivar purity for lucerne seed certification (OECD).

An industry/university collaboration to upgrade software engineering knowledge and skills in industry

This paper describes an ongoing collaboration between Boeing Australia Limited and the University of Queensland to develop and deliver an introductory course on software engineering. The aims of the course are to provide a common understanding of the nature of software engineering for all Boeing Australia's engineering staff, and to ensure they understand the practices used throughout the company. The course is designed so that it can be presented to people with varying backgrounds, such as recent software engineering graduates, systems engineers, quality assurance personnel, etc. The paper describes the structure and content of the course, and the evaluation techniques used to collect feedback from the participants and the corresponding results. The immediate feedback on the course indicates that it has been well received by the participants, but also indicates a need for more advanced courses in specific areas. The long-term feedback from participants is less positive, and the long-term feedback from the managers of the course participants indicates a need to expand on the coverage of the Boeing-specific processes and methods. (C) 2004 Elsevier Inc. All rights reserved.

Electricity market price spike forecast with data mining techniques

Electricity market price forecast is a changeling yet very important task for electricity market managers and participants. Due to the complexity and uncertainties in the power grid, electricity prices are highly volatile and normally carry with spikes. which may be (ens or even hundreds of times higher than the normal price. Such electricity spikes are very difficult to be predicted. So far. most of the research on electricity price forecast is based on the normal range electricity prices. This paper proposes a data mining based electricity price forecast framework, which can predict the normal price as well as the price spikes. The normal price can be, predicted by a previously proposed wavelet and neural network based forecast model, while the spikes are forecasted based on a data mining approach. This paper focuses on the spike prediction and explores the reasons for price spikes based on the measurement of a proposed composite supply-demand balance index (SDI) and relative demand index (RDI). These indices are able to reflect the relationship among electricity demand, electricity supply and electricity reserve capacity. The proposed model is based on a mining database including market clearing price, trading hour. electricity), demand, electricity supply and reserve. Bayesian classification and similarity searching techniques are used to mine the database to find out the internal relationships between electricity price spikes and these proposed. The mining results are used to form the price spike forecast model. This proposed model is able to generate forecasted price spike, level of spike and associated forecast confidence level. The model is tested with the Queensland electricity market data with promising results. Crown Copyright (C) 2004 Published by Elsevier B.V. All rights reserved.

The mirror-ball effect: Investigating channels, messages and participation levels

Journalists have always used equipment which has been generally available in the communities in which they worked. This has been a result both of economy and necessity, since they found they had to connect with their audiences using means that were available to the audience, not just to the sender. Newspapers sold on street corners in the very early media days; SMS and email have become the rule for the early 21st century. This development also admits the possibility of the roles of the communication professional and the community merging during the “public journalism” process, and has become most recently evident in the areas around the Bay of Bengal, struck by the tsunami on December 26, 2004, especially in the Indonesian province of Banda Aceh, and in the Andaman and Nicobar Islands, where tiny portable radios, featuring solar panels and hand-cranked dynamos, have suddenly become part of a vital news media channel. In this article participant-observation and personal interview techniques are used to record and compare many of the digital channels used by news and information senders up to 2005. It also investigates the level of genuine participation which these new technologies have brought to the communications process.

Evaluation of the indirect measures of rock brittleness and fracture toughness in rock cutting

Performance prediction models for partial face mechanical excavators, when developed in laboratory conditions, depend on relating the results of a set of rock property tests and indices to specific cutting energy (SE) for various rock types. There exist some studies in the literature aiming to correlate the geotechnical properties of intact rocks with the SE, especially for massive and widely jointed rock environments. However, those including direct and/or indirect measures of rock fracture parameters such as rock brittleness and fracture toughness, along with the other rock parameters expressing different aspects of rock behavior under drag tools (picks), are rather limited. With this study, it was aimed to investigate the relationships between the indirect measures of rock brittleness and fracture toughness and the SE depending on the results of a new and two previous linear rock cutting programmes. Relationships between the SE, rock strength parameters, and the rock index tests have also been investigated in this study. Sandstone samples taken from the different fields around Ankara, Turkey were used in the new testing programme. Detailed mineralogical analyses, petrographic studies, and rock mechanics and rock cutting tests were performed on these selected sandstone specimens. The assessment of rock cuttability was based on the SE. Three different brittleness indices (B1, B2, and B4) were calculated for sandstones samples, whereas a toughness index (T-i), being developed by Atkinson et al.(1), was employed to represent the indirect rock fracture toughness. The relationships between the SE and the large amounts of new data obtained from the mineralogical analyses, petrographic studies, rock mechanics, and linear rock cutting tests were evaluated by using bivariate correlation and curve fitting techniques, variance analysis, and Student's t-test. Rock cutting and rock property testing data that came from well-known studies of McFeat-Smith and Fowell(2) and Roxborough and Philips(3) have also been employed in statistical analyses together with the new data. Laboratory tests and subsequent analyses revealed that there were close correlations between the SE and B4 whereas no statistically significant correlation has been found between the SE and T-i. Uniaxial compressive and Brazilian tensile strengths and Shore scleroscope hardness of sandstones also exhibited strong relationships with the SE. NCB cone indenter test had the greatest influence on the SE among the other engineering properties of rocks, confirming the previous studies in rock cutting and mechanical excavation. Therefore, it was recommended to employ easy-to-use index tests of NCB cone indenter and Shore scleroscope in the estimation of laboratory SE of sandstones ranging from very low to high strengths in the absence of a rock cutting rig to measure it until the easy-to-use universal measures of the rock brittleness and especially the rock fracture toughness, being an intrinsic rock property, are developed.

Developing interdisciplinary research graduates: educational opportunities and dilemmas

Attempting to solve the complex problems of the 21st century requires research graduates that have developed a sophisticated array of interdisciplinary teamwork and communication skills. Although universities, governments, industry and the professions have emphasised the need to break down disciplinary silos in order to produce graduates, who can respond more effectively to the needs of the knowledge economy, much of this work has centred on undergraduate programs. While there are some research higher degree students who choose to work on interdisciplinary research topics, very little has been done to develop interdisciplinary research education systematically. This paper explores the educational opportunities and dilemmas involved in developing systematic programs of interdisciplinary research activities in two research centres at the University of Queensland. Framed by Bruhn's (2000, p. 58) theoretical discourse about interdisciplinary research as 'a philosophy, an art form, an artifact, and an antidote', this paper emphasises the need for such programs to embed the development of students' interdisciplinary research skills and attitudes within their research projects. The two diverse programs also emphasise experiential, active and interactive learning techniques and are centred upon the development of students' reflective practice skills.