The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF receptor-1 knockout mice

5,6-dimethylxanthenone-4-acetic acid, a novel antivascular anticancer drug, has completed Phase I clinical trial. Its actions in mice include tumour necrosis factor induction, serotonin release, tumour blood flow inhibition, and the induction of tumour haemorrhagic necrosis and regression. We have used mice with a targeted disruption of the tumour necrosis factor receptor-1 gene as recipients for the colon 38 carcinoma to determine the role of tumour necrosis factor signalling in the action of 5,6-dimethylxanthenone-4-acetic acid. The pharmacokinetics of 5,6-dimethylxanthenone-4-acetic acid, as well as the degree of induced plasma and tissue tumour necrosis factor, were similar in tumour necrosis factor receptor-1−/− and wild-type mice. However, the maximum tolerated dose of 5,6-dimethylxanthenone-4-acetic acid was considerably higher in tumour necrosis factor receptor-1−/− mice (>100 mg kg−1) than in wild-type mice (27.5 mg kg−1). The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (25 mg kg−1) was strongly attenuated in tumour necrosis factor receptor-1−/− mice. However, the reduced toxicity in tumour necrosis factor receptor-1−/− mice allowed the demonstration that at a higher dose (50 mg kg−1), 5,6-dimethylxanthenone-4-acetic acid was curative and comparable in effect to that of a lower dose (25 mg kg−1) in wild-type mice. The 5,6-dimethylxanthenone-4-acetic acid -induced rise in plasma 5-hydroxyindoleacetic acid, used to reflect serotonin production in a vascular response, was larger in colon 38 tumour bearing than in non-tumour bearing tumour necrosis factor receptor-1−/− mice, but in each case the response was smaller than the corresponding response in wild-type mice. The results suggest an important role for tumour necrosis factor in mediating both the host toxicity and antitumour activity of 5,6-dimethylxanthenone-4-acetic acid, but also suggest that tumour necrosis factor can be replaced by other vasoactive factors in its antitumour action, an observation of relevance to current clinical studies

Real time feedforward active noise control using virtual sensors

Active noise control (ANC) is a potential solution for low frequency tonal noise in vehicular cabin interiors. While ANC can significantly reduce low frequency noise at a microphone error sensor, the zone of attenuation may be so small that a nearby observer might not experience any improvement at all. However, it is also possible to reduce the noise specifically at the observer location, by using a forward prediction 'virtual microphone'. Pressure can be estimated (and hence minimised) at the observer location by extrapolating the signal from a number of remote microphones. Publications by the authors to date have presented the results from either control simulation models or post processed control examples where the potential for control is evaluated mathematically using experimental data. This paper presents the re-sults of real time control using a feedforward controller and two types of 'virtual' error sensor in a free field.http://www.internoise2001.tudelft.nl/Wednesday%20August%2029.htm

Engaging international students through the setting of challenging mini-projects

This paper reflects upon the introduction of a Co-operative Project to the Curriculum for Masters Students studying Advanced Digital Control at the University of Adelaide’s School of Mechanical Engineering. The rationale for the project’s structure is presented and its effectiveness is assessed through consideration of student feedback and the success of the student team in a series of national and international competitions.Steven Grainger, John Judge, Colin Kestell and Antoni Blazewiczhttp://www.aaee.com.au

Virtual error sensing for active noise control in a one-dimensional waveguide: Performance prediction versus measurement (L)

© 2003 Acoustical Society of America.Virtual error sensing is a novel active noise control technique, which is designed to produce a zone of attenuation remote from the physical error sensors. In this letter virtual sensing is investigated for tonal noise (both on and off resonance) in a long narrow duct. The performance of the virtual error sensors using real-time control is compared to the performance determined from an analytical model and the performance determined through the postprocessing of experimental data. Two examples of control using postprocessed experimental transfer function data are presented; the first relied on transfer functions measured using broadband noise and the second relied on transfer functions measured at discrete frequencies. The results highlight the significant errors encountered as a result of using broadband transfer functions in lightly damped enclosures. © 2003 Acoustical Society of America.Jacqueline M. Munn, Ben S. Cazzolato, Colin D. Kestell, and Colin H. Hanse

Higher-order virtual sensing for remote active noise control

Jacqueline M. Munn, Ben S. Cazzolato, Colin H. Hansen and Colin D. Kestel

Primary afferent neurons containing calcitonin gene-related peptide but not substance P in forepaw skin, dorsal root ganglia, and spinal cord of mice

Abstract not availableGarreth R. Kestell, Rebecca L. Anderson, Jennifer N. Clarke, Rainer V. Haberberger, and Ian L. Gibbin

Novel developments in the MOSFET dosemeter for neutron dosimetry applications

The feasibility of large-geometry Metal Oxide Semiconductor Field Effect Transistor (MOSFET) devices has been assessed for both active and passive neutron dosimetry and use in radiotherapy environments. Neutron sensitivity has been enhanced with the use of polymeric cement surrounding the gate region. Neutron activation via nuclear interaction processes is a potential problem with conventionally packaged and fabricated devices. To overcome this problem, a unique low-activation device design is described. Standard Dual in-Line devices, modified with polymeric cement and boron loaded cement have been exposed to gamma rays (60Co) and neutrons (gamma-ray shielded 252Cf) to provide neutron sensitivity estimates. The results show that the neutron sensitivity can be increased by a factor of approximately three by the use of a thin layer of polymeric cement over the gate region. Essentially zero activation is observed in the activation-reduced design compared with 1000 cps in the conventional design MOSFET when both are exposed under identical conditions to a neutron field from a gamma-ray shielded 252Cf isotopic source