Blairgowrie: The Meaning of Place

Defining the meaning of a specific place is difficult. Blairgowrie is a peaceful and naturally protected beach haven on the Nepean Peninsula on the tip of the Mornington Peninsula, in Victoria, Australia. When a major development is perceived as threatening the quality of place, it is perhaps already too late to begin to name its characteristics or particular attributes. The evocative and poetic qualities of Blairgowrie do not reveal themselves immediately. Only over a period of time, and by visiting at various times of the day in all seasons, can one begin to fathom its moods, its soul, its many colours; and to touch its memories. Here sea and sky can meet, or divide, totally unobstructed, depending on climatic conditions, seasonal weather patterns and diurnal changes. It is still possible to get a sense of scale and wide-angle limitless vision. When a Safe Boat Harbour was proposed for Blairgowrie, residents came out in force to voice their objections or their support. A tribunal hearing was put in place. In light of the dismissal of qualitative data, of reflective experiential material, of community opinion, of values of the 'other' in planning tribunal hearings, this paper attempts to build a case for putting into words 'the meaning of place'. The Safe Boat Harbour proposal was the catalyst for this exploration of 'meaning of place', and is not itself primarily the subject of this paper. This very personal paper begins to examine the meaning of this place. Through images, perceptions, and representations; through time; history, topography; flora and fauna: it attempts to find a way of coming to terms with this extraordinary land/seascape. In the long term this project aims to produce relevant, authoritative, and defensible research that provides the context and rationale for the selection and assessment of places of outstanding heritage significance. Further, it will provide a case study in support of new planning regulations for 'place' zones (Mant, 2001) rather than the generic land use zones, which are current in Victoria.     

Recent Changes in U.S. Food and Drug Law: Implications for Drug Development

This paper examines in detail the Waxman/Hatch Act and the NDA Rewrite, from both an implementation point of view and from a world-wide research and development perspective. The central theme of these regulatory changes appears to be consistent with U.S. drug policy of the past two decades, i.e., cost containment, primarily, followed by uniformity and efficiency in the regulatory review process. These recent changes, just as the 1962 Drug Ammendments 22 years earlier, will continue to have profound effects upon the sites at which pharmaceutical research and development is carried out.     

Characteristics of picoliter droplet dried residues as standards for direct analysis techniques

The characteristics of dried residues of picodroplets of single-, two-, and three-element aqueous solutions, which qualify these as reference materials in the direct analysis of single particles, single cells, and other microscopic objects using, e.g., laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOF-MS) and micro-X-ray fluorescence (MXRF), were evaluated. Different single-, two-, and three-element solutions (0.01-1 g/L) were prepared in picoliter volume (around 130 pL) with a thermal inkjet printing technique. An achievable dosing precision of 4-15% was calculated by total reflection X-ray fluorescence (TXRF) determination of the transferred elemental mass of an array of 100 droplets. The size of the dried residues was determined by optical microscopy to be 5-20 microm in diameter depending on the concentration and the surface material. The elemental distribution of the dried residues was determined with synchrotron micro-X-ray fluorescence (SR-MXRF) analyses. The MXRF results show high uniformity for element deposition of every single droplet with an RSTD of 4-6% depending on the concentration of spotted solution. The shape and height profile of dried residues from picoliter droplets were studied using atomic force microscopy (AFM). It was found that these dry to give symmetrical spherical segments with maximum heights of 1.7 microm. The potential of this technique for direct LA-ICP-TOF-MS analysis is shown.     

A new strategy for assessing sensitivities in biochemical models

An integral part of any systems biology approach is the modelling and simulation of the respective system under investigation. However, the values of many parameters of the system have often not been determined or are not identifiable due to technical experimental difficulties or other constraints. Sensitivity analysis is often employed to quantify the importance of each of the model's parameters in the behaviour of the system. This approach can also be useful in identifying those parts of the system that are most sensitive with the potential of becoming drug targets. A problem of the commonly used methods of sensitivity analysis is that they constitute local methods meaning that they depend directly on the exact parameter space, which in turn is not known exactly. One way to circumvent this problem is to carry out sensitivity analysis over a wide range of values for all parameters, but this is handicapped by expensive computations when the systems are high dimensional. Another approach is to employ global sensitivity analysis, which in this context is mostly based on random sampling methods. In this paper we present an efficient approach that involves using numerical optimizing methods that search a wide region of parameter space for a given model to determine the maximum and minimum values of its metabolic control coefficients. A relevant example for drug development is presented to demonstrate the strategy using the software COPASI.     

Real-Time Analysis of Alarm Pheromone Emission by the Pea Aphid (<Emphasis Type="Italic">Acyrthosiphon Pisum</Emphasis>) Under Predation

Upon attack by predators or parasitoids, aphids emit volatile chemical alarm signals that warn other aphids of a potential risk of predation. Release rate of the major constituent of the alarm pheromone in pea aphids (Acyrthosiphon pisum), (E)-b-farnesene (EBF), was measured for all nymphal and the adult stage as aphids were attacked individually by lacewing (Chrysoperla carnae) larvae. Volatilization of EBF from aphids under attack was quantified continuously for 60 min at 2-min intervals with a rapid gas chromatography technique (zNose) to monitor headspace emissions. After an initial burst, EBF volatilization declined exponentially, and detectable amounts were still present after 30 min in most cases. Total emission of EBF averaged 16.33 +/- 1.54 ng and ranged from 1.18 to 48.85 ng. Emission was higher in nymphs as compared to adults. No differences between pea aphid life stages were detected for their speed of alarm signal emission in response to lacewing larvae attack. This is the first time that alarm pheromone emission from single aphids has been reported.     

The Fe2+-mediated decomposition, PfATP6 binding, and antimalarial activities of artemisone and other artemisinins: the unlikelihood of C-centered radicals as bioactive intermediates

The results of Fe(2+)-induced decomposition of the clinically used artemisinins, artemisone, other aminoartemisinins, 10-deoxoartemisinin, and the 4-fluorophenyl derivative have been compared with their antimalarial activities and their ability to inhibit the parasite SERCA PfATP6. The clinical artemisinins and artemisone decompose under aqueous conditions to give mixtures of C radical marker products, carbonyl compounds, and reduction products. The 4-fluorophenyl derivative and aminoartemisinins tend to be inert to aqueous iron(II) sulfate and anhydrous iron(II) acetate. Anhydrous iron(II) bromide enhances formation of the carbonyl compounds and provides a deoxyglycal from DHA and enamines from the aminoartemisinins. Ascorbic acid (AA) accelerates the aqueous Fe(2+)-mediated decompositions, but does not alter product distribution. 4-Oxo-TEMPO intercepts C radicals from a mixture of an antimalaria-active trioxolane, 10-deoxoartemisinin, and anhydrous iron(II) acetate to give trapped products in 73 % yield from the trioxolane, and 3 % from the artemisinin. Artemisone provides a trapped product in 10 % yield. Thus, in line with its structural rigidity, only the trioxolane provides a C radical eminently suited for intermolecular trapping. In contrast, the structural flexibility of the C radicals from the artemisinins allows facile extrusion of Fe(2+) and collapse to benign isomerization products. The propensity towards the formation of radical marker products and intermolecular radical trapping have no relationship with the in vitro antimalarial activities of the artemisinins and trioxolane. Desferrioxamine (DFO) attenuates inhibition of PfATP6 by, and antagonizes antimalarial activity of, the aqueous Fe(2+)-susceptible artemisinins, but has no overt effect on the aqueous Fe(2+)-inert artemisinins. It is concluded that the C radicals cannot be responsible for antimalarial activity and that the Fe(2+)-susceptible artemisinins may be competitively decomposed in aqueous extra- and intracellular compartments by labile Fe(2+), resulting in some attenuation of their antimalarial activities. Interpretations of the roles of DFO and AA in modulating antimalarial activities of the artemisinins, and a comparison with antimalarial properties of simple hydroperoxides and their behavior towards thapsigargin-sensitive SERCA ATPases are presented. The general basis for the exceptional antimalarial activities of artemisinins in relation to the intrinsic activity of the peroxide within the uniquely stressed environment of the malaria parasite is thereby adumbrated.     

γ′ Phase Stability and Phase Equilibrium in Ternary Co-Al-W at 900 °C

Phase equilibria at 900 °C in the Co-rich Co-Al-W ternary system are investigated through isothermal annealing of six alloy compositions for times up to 8000 h. The volume fraction of the L1₂-γ′ phase co-existing with disordered FCC-γ, B2 and D0₁₉ phases is found to steadily decrease with increasing annealing time indicating that it is unstable at 900 °C. Additional heat treatments at 850 and 1000 °C further suggest it is a nonequilibrium phase at all temperatures in the ternary system. The L1₂-γ′ phase dissolves slowly with significant amounts remaining in some alloys after 8000 h at 900 °C. However, the present work clearly indicates the microstructure is moving toward a three-phase equilibrium between γ, D0₁₉, and B2. The collected compositional and phase equilibria information provide much needed data for improving the available thermodynamic assessments of the ternary Co-Al-W alloy system.     

Cooling potential of ventilated PV façade and solar air heaters combined with a desiccant cooling machine

Thermal energy collected from a PV-solar air heating system is being used to provide cooling for the Mataro Library, near Barcelona. The system is designed to utilise surplus heat available from the ventilated PV facade and PV shed elements during the summer season to provide building cooling. A desiccant cooling machine was installed on the library roof with an additional solar air collector and connected to the existing ventilated PV façade and PV sheds. The desiccant cooling cycle is a novel open heat driven system that can be used to condition the air supplied to the building interior. Cooling power is supplied to the room space within the building by evaporative cooling of the fresh air supply, and the solar heat from the PV-solar air heating system provides the necessary regeneration air temperature for the desiccant machine. This paper describes the system and gives the main technical details. The cooling performance of the solar powered desiccant cooling system is evaluated by the detailed modelling of the complete cooling process. It is shown that air temperature level of the PV-solar air heating system of 70 °C or more can be efficiently used to regenerate the sorption wheel in the desiccant cooling machine. A solar fraction of 75% can be achieved by such an innovative system and the average COP of the cooling machine over the summer season is approximate 0.518.