Applied evolution: An integrated approach to studying life history traits in response to drug selection

The use of chemical control measures to reduce the impact of parasite and pest species has frequently resulted in the development of resistance. Thus, resistance management has become a key concern in human and veterinary medicine, and in agricultural production. Although it is known that factors such as gene flow between susceptible and resistant populations, drug type, application methods, and costs of resistance can affect the rate of resistance evolution, less is known about the impacts of density-dependent eco-evolutionary processes that could be altered by drug-induced mortality. The overall aim of this thesis was to take an experimental evolution approach to assess how life history traits respond to drug selection, using a free-living dioecious worm (Caenorhabditis remanei) as a model. In Chapter 2, I defined the relationship between C. remanei survival and Ivermectin dose over a range of concentrations, in order to control the intensity of selection used in the selection experiment described in Chapter 4. The dose-response data were also used to appraise curve-fitting methods, using Akaike Information Criterion (AIC) model selection to compare a series of nonlinear models. The type of model fitted to the dose response data had a significant effect on the estimates of LD50 and LD99, suggesting that failure to fit an appropriate model could give misleading estimates of resistance status. In addition, simulated data were used to establish that a potential cost of resistance could be predicted by comparing survival at the upper asymptote of dose-response curves for resistant and susceptible populations, even when differences were as low as 4%. This approach to dose-response modeling ensures that the maximum amount of useful information relating to resistance is gathered in one study. In Chapter 3, I asked how simulations could be used to inform important design choices used in selection experiments. Specifically, I focused on the effects of both within- and between-line variation on estimated power, when detecting small, medium and large effect sizes. Using mixed-effect models on simulated data, I demonstrated that commonly used designs with realistic levels of variation could be underpowered for substantial effect sizes. Thus, use of simulation-based power analysis provides an effective way to avoid under or overpowering a study designs incorporating variation due to random effects. In Chapter 4, I 3 investigated how Ivermectin dosage and changes in population density affect the rate of resistance evolution. I exposed replicate lines of C. remanei to two doses of Ivermectin (high and low) to assess relative survival of lines selected in drug-treated environments compared to untreated controls over 10 generations. Additionally, I maintained lines where mortality was imposed randomly to control for differences in density between drug treatments and to distinguish between the evolutionary consequences of drug treatment versus ecological processes affected by changes in density-dependent feedback. Intriguingly, both drug-selected and random-mortality lines showed an increase in survivorship when challenged with Ivermectin; the magnitude of this increase varied with the intensity of selection and life-history stage. The results suggest that interactions between density-dependent processes and life history may mediate evolved changes in susceptibility to control measures, which could result in misleading conclusions about the evolution of heritable resistance following drug treatment. In Chapter 5, I investigated whether the apparent changes in drug susceptibility found in Chapter 4 were related to evolved changes in life-history of C. remanei populations after selection in drug-treated and random-mortality environments. Rapid passage of lines in the drug-free environment had no effect on the measured life-history traits. In the drug-free environment, adult size and fecundity of drug-selected lines increased compared to the controls but drug selection did not affect lifespan. In the treated environment, drug-selected lines showed increased lifespan and fecundity relative to controls. Adult size of randomly culled lines responded in a similar way to drug-selected lines in the drug-free environment, but no change in fecundity or lifespan was observed in either environment. The results suggest that life histories of nematodes can respond to selection as a result of the application of control measures. Failure to take these responses into account when applying control measures could result in adverse outcomes, such as larger and more fecund parasites, as well as over-estimation of the development of genetically controlled resistance. In conclusion, my thesis shows that there may be a complex relationship between drug selection, density-dependent regulatory processes and life history of populations challenged with control measures. This relationship could have implications for how resistance is monitored and managed if life histories of parasitic species show such eco-evolutionary responses to drug application.

Integrated visual perception architecture for robotic clothes perception and manipulation

This thesis proposes a generic visual perception architecture for robotic clothes perception and manipulation. This proposed architecture is fully integrated with a stereo vision system and a dual-arm robot and is able to perform a number of autonomous laundering tasks. Clothes perception and manipulation is a novel research topic in robotics and has experienced rapid development in recent years. Compared to the task of perceiving and manipulating rigid objects, clothes perception and manipulation poses a greater challenge. This can be attributed to two reasons: firstly, deformable clothing requires precise (high-acuity) visual perception and dexterous manipulation; secondly, as clothing approximates a non-rigid 2-manifold in 3-space, that can adopt a quasi-infinite configuration space, the potential variability in the appearance of clothing items makes them difficult to understand, identify uniquely, and interact with by machine. From an applications perspective, and as part of EU CloPeMa project, the integrated visual perception architecture refines a pre-existing clothing manipulation pipeline by completing pre-wash clothes (category) sorting (using single-shot or interactive perception for garment categorisation and manipulation) and post-wash dual-arm flattening. To the best of the author’s knowledge, as investigated in this thesis, the autonomous clothing perception and manipulation solutions presented here were first proposed and reported by the author. All of the reported robot demonstrations in this work follow a perception-manipulation method- ology where visual and tactile feedback (in the form of surface wrinkledness captured by the high accuracy depth sensor i.e. CloPeMa stereo head or the predictive confidence modelled by Gaussian Processing) serve as the halting criteria in the flattening and sorting tasks, respectively. From scientific perspective, the proposed visual perception architecture addresses the above challenges by parsing and grouping 3D clothing configurations hierarchically from low-level curvatures, through mid-level surface shape representations (providing topological descriptions and 3D texture representations), to high-level semantic structures and statistical descriptions. A range of visual features such as Shape Index, Surface Topologies Analysis and Local Binary Patterns have been adapted within this work to parse clothing surfaces and textures and several novel features have been devised, including B-Spline Patches with Locality-Constrained Linear coding, and Topology Spatial Distance to describe and quantify generic landmarks (wrinkles and folds). The essence of this proposed architecture comprises 3D generic surface parsing and interpretation, which is critical to underpinning a number of laundering tasks and has the potential to be extended to other rigid and non-rigid object perception and manipulation tasks. The experimental results presented in this thesis demonstrate that: firstly, the proposed grasp- ing approach achieves on-average 84.7% accuracy; secondly, the proposed flattening approach is able to flatten towels, t-shirts and pants (shorts) within 9 iterations on-average; thirdly, the proposed clothes recognition pipeline can recognise clothes categories from highly wrinkled configurations and advances the state-of-the-art by 36% in terms of classification accuracy, achieving an 83.2% true-positive classification rate when discriminating between five categories of clothes; finally the Gaussian Process based interactive perception approach exhibits a substantial improvement over single-shot perception. Accordingly, this thesis has advanced the state-of-the-art of robot clothes perception and manipulation.