Herbicide resistance modelling: Past, present and future

Computer simulation modelling is an essential aid in building an integrated understanding of how different factors interact to affect the evolutionary and population dynamics of herbicide resistance, and thus in helping to predict and manage how agricultural systems will be affected. In this review, we first discuss why computer simulation modelling is such an important tool and framework for dealing with herbicide resistance. We then explain what questions related to herbicide resistance have been addressed to date using simulation modelling, and discuss the modelling approaches that have been used, focusing first on the earlier, more general approaches, and then on some newer, more innovative approaches. We then consider how these approaches could be further developed in the future, by drawing on modelling techniques that are already employed in other areas, such as individual-based and spatially explicit modelling approaches, as well as the possibility of better representing genetics, competition and economics, and finally the questions and issues of importance to herbicide resistance research and management that could be addressed using these new approaches are discussed. We conclude that it is necessary to proceed with caution when increasing the complexity of models by adding new details, but, with appropriate care, more detailed models will make it possible to integrate more current knowledge in order better to understand, predict and ultimately manage the evolution of herbicide resistance. © 2014 Society of Chemical Industry.

Finite element modelling of lamb wave propagation in prestress concrete and effect of the prestress force on the wave’s characteristic

In order to assess the structural reliability of bridges, an accurate and cost effective Non-Destructive Evaluation (NDE) technology is required to ensure their safe and reliable operation. Over 60% of the Australian National Highway System is prestressed concrete (PSC) bridges according to the Bureau of Transport and Communication Economics (1997). Most of the in-service bridges are more than 30 years old and may experience a heavier traffic load than their original intended level. Use of Ultrasonic waves is continuously increasing for (NDE) and Structural Health Monitoring (SHM) in civil, aerospace, electrical, mechanical applications. Ultrasonic Lamb waves are becoming more popular for NDE because it can propagate long distance and reach hidden regions with less energy loses. The purpose of this study is to numerically quantify prestress force (PSF) of (PSC) beam using the fundamental theory of acoustic-elasticity. A three-dimension finite element modelling approach is set up to perform parametric studies in order to better understand how the lamb wave propagation in PSC beam is affected by changing in the PSF level. Results from acoustic-elastic measurement on prestressed beam are presented, showing the feasibility of the lamb wave for PSF evaluation in PSC bridges.

Large-scale characterization of drought pattern: a continent-wide modelling approach applied to the Australian wheatbelt – spatial and temporal trends

* Plant response to drought is complex, so that traits adapted to a specific drought type can confer disadvantage in another drought type. Understanding which type(s) of drought to target is of prime importance for crop improvement. * Modelling was used to quantify seasonal drought patterns for a check variety across the Australian wheatbelt, using 123 yr of weather data for representative locations and managements. Two other genotypes were used to simulate the impact of maturity on drought pattern. * Four major environment types summarized the variability in drought pattern over time and space. Severe stress beginning before flowering was common (44% of occurrences), with (24%) or without (20%) relief during grain filling. High variability occurred from year to year, differing with geographical region. With few exceptions, all four environment types occurred in most seasons, for each location, management system and genotype. * Applications of such environment characterization are proposed to assist breeding and research to focus on germplasm, traits and genes of interest for target environments. The method was applied at a continental scale to highly variable environments and could be extended to other crops, to other drought-prone regions around the world, and to quantify potential changes in drought patterns under future climates.

Modelling end-of-life care practices: Factors associated with critical care nurse engagement in care provision

Objective To identify factors associated with critical care nurses’ engagement in end-of-life care practices. Methods Multivariable regression modelling was undertaken on 392 responses to an online self-report survey of end-of-life care practices and factors influencing practice by Australian critical care nurses’. Univariate general linear models were built for six end-of-life care practice areas. Results Six statistically significant (p < 0.001) models were developed: Information sharing F(3, 377) = 40.53, adjusted R2 23.8%; Environmental modification F(5, 380) = 19.55, adjusted R2 19.4%; Emotional support F(10, 366) = 12.10, adjusted R2 22.8%; Patient and family centred decision making F(8, 362) = 17.61 adjusted R2 26.4%; Symptom management F(8, 376) = 7.10, adjusted R2 11.3%; and Spiritual support F(9, 367) = 14.66, adjusted R2 24.6%. Stronger agreement with values consistent with a palliative approach, and greater support for patient and family preferences were associated with higher levels of engagement in end-of-life care practices. Higher levels of preparedness and access to opportunities for knowledge acquisition were associated with engagement in the interpersonal practices of patient and family centred decision making and emotional support. Conclusion This study provides evidence for interventions to address factors associated with nurse engagement to increase participation in all end-of-life care practice areas.

Molecular Modelling of Estrogen-Producing Enzymes CYP450 Aromatase and 17beta-Hydroxysteroid Dehydrogenase Type 1

Breast cancer is the most common cancer in women in the western countries. Approximately two-thirds of breast cancer tumours are hormone dependent, requiring estrogens to grow. Estrogens are formed in the human body via a multistep route starting from cholesterol. The final steps in the biosynthesis include the CYP450 aromatase enzyme, converting the male hormones androgens (preferred substrate androstenedione ASD) into estrogens(estrone E1), and the 17beta-HSD1 enzyme, converting the biologically less active E1 into the active hormone 17beta-hydroxyestradiol E2. E2 is bound to the nuclear estrogen receptors causing a cascade of biochemical reactions leading to cell proliferation in normal tissue, and to tumour growth in cancer tissue. Aromatase and 17beta-HSD1 are expressed in or near the breast tumour, locally providing the tissue with estrogens. One approach in treating hormone dependent breast tumours is to block the local estrogen production by inhibiting these two enzymes. Aromatase inhibitors are already on the market in treating breast cancer, despite the lack of an experimentally solved structure. The structure of 17beta-HSD1, on the other hand, has been solved, but no commercial drugs have emerged from the drug discovery projects reported in the literature. Computer-assisted molecular modelling is an invaluable tool in modern drug design projects. Modelling techniques can be used to generate a model of the target protein and to design novel inhibitors for them even if the target protein structure is unknown. Molecular modelling has applications in predicting the activities of theoretical inhibitors and in finding possible active inhibitors from a compound database. Inhibitor binding at atomic level can also be studied with molecular modelling. To clarify the interactions between the aromatase enzyme and its substrate and inhibitors, we generated a homology model based on a mammalian CYP450 enzyme, rabbit progesterone 21-hydroxylase CYP2C5. The model was carefully validated using molecular dynamics simulations (MDS) with and without the natural substrate ASD. Binding orientation of the inhibitors was based on the hypothesis that the inhibitors coordinate to the heme iron, and were studied using MDS. The inhibitors were dietary phytoestrogens, which have been shown to reduce the risk for breast cancer. To further validate the model, the interactions of a commercial breast cancer drug were studied with MDS and ligand–protein docking. In the case of 17beta-HSD1, a 3D QSAR model was generated on the basis of MDS of an enzyme complex with active inhibitor and ligand–protein docking, employing a compound library synthesised in our laboratory. Furthermore, four pharmacophore hypotheses with and without a bound substrate or an inhibitor were developed and used in screening a commercial database of drug-like compounds. The homology model of aromatase showed stable behaviour in MDS and was capable of explaining most of the results from mutagenesis studies. We were able to identify the active site residues contributing to the inhibitor binding, and explain differences in coordination geometry corresponding to the inhibitory activity. Interactions between the inhibitors and aromatase were in agreement with the mutagenesis studies reported for aromatase. Simulations of 17beta-HSD1 with inhibitors revealed an inhibitor binding mode with hydrogen bond interactions previously not reported, and a hydrophobic pocket capable of accommodating a bulky side chain. Pharmacophore hypothesis generation, followed by virtual screening, was able to identify several compounds that can be used in lead compound generation. The visualisation of the interaction fields from the QSAR model and the pharmacophores provided us with novel ideas for inhibitor development in our drug discovery project.

Predictive modelling to aid the regional-scale management of a vertebrate pest

Extensive resources are allocated to managing vertebrate pests, yet spatial understanding of pest threats, and how they respond to management, is limited at the regional scale where much decision-making is undertaken. We provide regional-scale spatial models and management guidance for European rabbits (Oryctolagus cuniculus) in a 260,791 km(2) region in Australia by determining habitat suitability, habitat susceptibility and the effects of the primary rabbit management options (barrier fence, shooting and baiting and warren ripping) or changing predation or disease control levels. A participatory modelling approach was used to develop a Bayesian network which captured the main drivers of suitability and spread, which in turn was linked spatially to develop high resolution risk maps. Policy-makers, rabbit managers and technical experts were responsible for defining the questions the model needed to address, and for subsequently developing and parameterising the model. Habitat suitability was determined by conditions required for warren-building and by above-ground requirements, such as food and harbour, and habitat susceptibility by the distance from current distributions, habitat suitability, and the costs of traversing habitats of different quality. At least one-third of the region had a high probability of being highly suitable (support high rabbit densities), with the model supported by validation. Habitat susceptibility was largely restricted by the current known rabbit distribution. Warren ripping was the most effective control option as warrens were considered essential for rabbit persistence. The anticipated increase in disease resistance was predicted to increase the probability of moderately suitable habitat becoming highly suitable, but not increase the at-risk area. We demonstrate that it is possible to build spatial models to guide regional-level management of vertebrate pests which use the best available knowledge and capture fine spatial-scale processes.

Resting pastures to improve land condition in northern Australia: guidelines based on the literature and simulation modelling

Pasture rest is a possible strategy for improving land condition in the extensive grazing lands of northern Australia. If pastures currently in poor condition could be improved, then overall animal productivity and the sustainability of grazing could be increased. The scientific literature is examined to assess the strength of the experimental information to support and guide the use of pasture rest, and simulation modelling is undertaken to extend this information to a broader range of resting practices, growing conditions and initial pasture condition. From this, guidelines are developed that can be applied in the management of northern Australia’s grazing lands and also serve as hypotheses for further field experiments. The literature on pasture rest is diverse but there is a paucity of data from much of northern Australia as most experiments have been conducted in southern and central parts of Queensland. Despite this, the limited experimental information and the results from modelling were used to formulate the following guidelines. Rest during the growing season gives the most rapid improvement in the proportion of perennial grasses in pastures; rest during the dormant winter period is ineffective in increasing perennial grasses in a pasture but may have other benefits. Appropriate stocking rates are essential to gain the greatest benefit from rest: if stocking rates are too high, then pasture rest will not lead to improvement; if stocking rates are low, pastures will tend to improve without rest. The lower the initial percentage of perennial grasses, the more frequent the rests should be to give a major improvement within a reasonable management timeframe. Conditions during the growing season also have an impact on responses with the greatest improvement likely to be in years of good growing conditions. The duration and frequency of rest periods can be combined into a single value expressed as the proportion of time during which resting occurs; when this is done the modelling suggests the greater the proportion of time that a pasture is rested, the greater is the improvement but this needs to be tested experimentally. These guidelines should assist land managers to use pasture resting but the challenge remains to integrate pasture rest with other pasture and animal management practices at the whole-property scale.