Scalable Inference for Markov Processes with Intractable Likelihoods

Bayesian inference for Markov processes has become increasingly relevant in recent years. Problems of this type often have intractable likelihoods and prior knowledge about model rate parameters is often poor. Markov Chain Monte Carlo (MCMC) techniques can lead to exact inference in such models but in practice can suffer performance issues including long burn-in periods and poor mixing. On the other hand approximate Bayesian computation techniques can allow rapid exploration of a large parameter space but yield only approximate posterior distributions. Here we consider the combined use of approximate Bayesian computation (ABC) and MCMC techniques for improved computational efficiency while retaining exact inference on parallel hardware

Likelihood Free Bayesian Inference for Stochastic Kinetic Models

Ph.D thesisStochastic kinetic models are used to describe a variety of biological, physical and chemical phenomena. One particularly interesting application is computational systems biology, where models are useful for contributing to the quantitative understanding of cellular processes through in{silico experimentation that would otherwise be difficult to undertake in a laboratory. Interest lies in statistical inference for the parameters which govern the dynamics of the system. Likelihood based inference is typically problematic, as discrete time transition kernels for models of this type are intractable in all but the most trivial systems. However, exact realisations can be drawn using a stochastic simulation algorithm. Techniques that rely only on the ability to forward simulate from the model, so called likelihood free inference methods, such as particle Markov chain Monte Carlo and approximate Bayesian computation (ABC) can be leveraged to infer system rate parameters. What is not clear however is how each technique behaves as the nature of the problem changes. This thesis explores the likelihood free methodology applied to stochastic kinetic models in a range of scenarios in order to draw comparisons between the various developments in each. A variety of models and data observation regimes on synthetic data are used to examine the effect of the choice of summary statistics and metrics on the inferred posterior distributions, prevalent questions within the ABC framework. Likelihood free techniques are considered computationally expensive hence it is necessary to consider the relative efficiency of the various approaches. The relative strengths and weaknesses of particle Markov chain Monte Carlo and approximate Bayesian computation are explored and utilised to develop a hybrid technique exploiting the stronger elements of each approach. The thesis concludes with inference of rate parameters for a logistic growth model applied to observations of a uorescent protein in different strains of the gram- positive bacterium, Bacillus subtilis.Engineering and Physical Sciences Research Council (EPSRC)

Prejudice in Venus Traces the Roots of Black Female Iconography

This paper aims to verify how a ‘freak’ show performer named The Venus Hottentot of the early 1800’s in England and in France, came to symbolize the sexualized view of the black female icon today. My thesis production of Suzan-Lori Parks’ play Venus will demonstrate how Eurocentric prejudice in the colonial era shaped the historical facts that permeated around this South African woman’s life and death. In keeping with the play’s revised Afrocentric perspective on these alleged facts, ideas about directorial concepts for this show will validate how this play is relevant to contemporary artists and audiences through Parks’ elegant storytelling. This potential narrative of victimization, that could easily come off as maudlin, will be proven to require a sardonic political edge in order to succeed. The director’s challenges and premise, the writer’s background, the play’s roots in truth and fiction, along with production hurdles to overcome will all be discussed

An assessment of Pant-y-llyn, Wales' only turlough and comparison to Irish sites

Turloughs are ephemeral karst lakes resulting from high rainfall and, accordingly, high groundwater levels in topographic depressions in karstified limestone terrain. The ephemeral nature of turlough hydrology gives rise to a characteristic ecology as such turloughs have been designated as a Priority Habitat in the EU Habitats Directive (92/43/EEC). While there are recorded turloughs in the Republic of Ireland Pant-y Llyn is Wales’ and mainland Britain’s only recorded turlough; it is a key feature of Cernydd Carmel SSSI and SAC. A collaborative investigation was carried out between Environment Agency Wales and Countryside Council for Wales (soon to be Natural Resources Wales). The main aims of this investigation were to: - Improve the hydrogeological conceptual understanding. - Review the water chemistry of Pant-y-Llyn and the surrounding groundwater. - Compare the hydrology of Pant-y-Llyn with that of recorded Irish turloughs. - Use existing data back model the turlough hydrograph. - Provide evidence to confirm its status for the Habitats Directive. The investigation has shown that Pant y Llyn has both a water quality and hydrological cycle. For the first time comparisons with Irish turloughs allow us to put Pant y Llyn into a wider turlough typology

Effects of Heat Acclimation and Acclimatisation on Maximal Aerobic Capacity Compared to Exercise Alone in Both Thermoneutral and Hot Environments: A Meta-Analysis and Meta-Regression

BackgroundHeat acclimation and acclimatisation (HA) is typically used to enhance tolerance to the heat, thereby improving performance. HA might also confer a positive adaptation to maximal oxygen consumption (VO2max), although this has been historically debated and requires clarification via meta-analysis.Objectives(1) To meta-analyse all studies (with and without control groups) that have investigated the effect of HA on VO2max adaptation in thermoneutral or hot environments; (2) Conduct meta-regressions to establish the moderating effect of selected variables on VO2max adaptation following HA.MethodsA search was performed using various databases in May 2020. The studies were screened using search criteria for eligibility. Twenty-eight peer-reviewed articles were identified for inclusion across four separate meta-analyses: (1) Thermoneutral VO2max within-participants (pre-to-post HA); (2) Hot VO2max within-participants (pre-to-post HA); (3) Thermoneutral VO2max measurement; HA vs. control groups; (4) Hot VO2max measurement, HA vs. control groups. Meta-regressions were performed for each meta-analysis based on: isothermal vs. iso-intensity programmes, days of heat exposure, HA ambient temperature (°C), heat index, HA session duration (min), ambient thermal load (HA session x ambient temperature), mean mechanical intensity (W) and the post-HA testing period (days).ResultsThe meta-analysis of pre–post differences in thermoneutral VO2max demonstrated small-to-moderate improvements in VO2max (Hedges’ g = 0.42, 95% CI 0.24–0.59, P < 0.001), whereas moderate improvements were found for the equivalent analysis of hot VO2max changes (Hedges’ g = 0.63, 95% CI 0.26–1.00, P < 0.001), which were positively moderated by the number of days post-testing (P = 0.033, β = 0.172). Meta-analysis of control vs. HA thermoneutral VO2max demonstrated a small improvement in VO2max in HA compared to control (Hedges’ g = 0.30, 95% CI 0.06–0.54, P = 0.014) and this effect was larger for the equivalent hot VO2max analysis where a higher (moderate-to-large) improvement in VO2max was found (Hedges’ g = 0.75, 95% CI 0.22–1.27, P = 0.005), with the number of HA days (P = 0.018; β = 0.291) and the ambient temperature during HA (P = 0.003; β = 0.650) positively moderating this effect.ConclusionHA can enhance VO2max adaptation in thermoneutral or hot environments, with or without control group consideration, by at least a small and up to a moderate–large amount, with the larger improvements occurring in the heat. Ambient heat, number of induction days and post-testing days can explain some of the changes in hot VO2max adaptation

Physiological and thermoregulatory effects of oral taurine supplementation on exercise tolerance during forced convective cooling

We investigated the effects of taurine supplementation on cycling time to exhaustion in cold conditions. Eleven males cycled to exhaustion at a power output equivalent to the mid-point between ventilatory threshold and maximum aerobic power following 15-min rest in the cold (apparent temperature of ∼ 4 °C; air flow of 4.17 m·s-1). Two-hours before, participants ingested taurine (50 mg·kg-1) or placebo beverage. Pulmonary gases, carbohydrate (CHO) and fat oxidation, body temperatures, mean local sweat rate, heart rate, rate of perceived exertion (RPE) and thermal comfort were recorded. Time to exhaustion was not different between trials (taurine = 14.6 ± 4.7 min; placebo = 13.4 ± 5.6 min, P = 0.061, d = 0.27). There were no effects (P > 0.05) of taurine on core temperature, mean skin temperature or local sweat rates. However, the placebo condition showed greater (P < 0.05) reductions in arm-to-finger temperature gradient (i.e. vasodilation) across pre-exercise passive cold exposure and increased CHO oxidation (P < 0.05). Participants also reached a thermally ‘comfortable’ level quicker in the taurine condition (P < 0.05). A 50 mg·kg-1 dose of taurine did not statistically benefit endurance exercise after moderate cold exposure but conferred some potential vascular and metabolic effects

Using RNA-seq to characterize responses to 4 hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor herbicide resistance in waterhemp (Amaranthus tuberculatus)

Background: Waterhemp (Amaranthus tuberculatus (Moq.) J.D. Sauer) is a problem weed commonly found in the Midwestern United States that can cause crippling yield losses for both maize (Zea mays L.) and soybean (Glycine max L. Merr). In 2011, 4-hydroxyphenylpyruvate-dioxygenase (HPPD, EC 1.13.11.27) inhibitor herbicide resistance was first reported in two waterhemp populations. Since the discovery of HPPD-herbicide resistance, studies have identified the mechanism of resistance and described the inheritance of the herbicide resistance. However, no studies have examined genome-wide gene expression changes in response to herbicide treatment in herbicide resistant and susceptible waterhemp. Results: We conducted RNA-sequencing (RNA-seq) analyses of two waterhemp populations (HPPD-herbicide resistant and susceptible), from herbicide-treated and mock-treated leaf samples at three, six, twelve, and twenty-four hours after treatment (HAT). We performed a de novo transcriptome assembly using all sample sequences. Following assessments of our assembly, individual samples were mapped to the de novo transcriptome allowing us to identify transcripts specific to a genotype, herbicide treatment, or time point. Our results indicate that the response of HPPDherbicide resistant and susceptible waterhemp genotypes to HPPD-inhibiting herbicide is rapid, established as soon as 3 hours after herbicide treatment. Further, there was little overlap in gene expression between resistant and susceptible genotypes, highlighting dynamic differences in response to herbicide treatment. In addition, we used stringent analytical methods to identify candidate single nucleotide polymorphisms (SNPs) that distinguish the resistant and susceptible genotypes. Conclusions: The waterhemp transcriptome, herbicide-responsive genes, and SNPs generated in this study provide valuable tools for future studies by numerous plant science communities. This collection of resources is essential to study and understand herbicide effects on gene expression in resistant and susceptible weeds. Understanding how herbicides impact gene expression could allow us to develop novel approaches for future herbicide development. Additionally, an increased understanding of the prolific traits intrinsic in weed success could lead to crop improvement

Environmental Fit: A Model for Assessing and Treating Problem Behavior Associated with Curricular Difficulties in Children with Autism Spectrum Disorders

Theoretical considerations suggest that problem behavior should increase when a child’s competency does not match the curricular demands of the environment (i.e., when there is poor environmental fit). In the present study, environmental fit was examined for six children with autism spectrum disorders. Results indicated that the children exhibited high rates of problem behavior associated with poor motor or academic competency. Curricular modifications resulted in (a) a decrease in the level of problem behavior, (b) an increase in the percentage of task steps completed correctly, and (c) improved affect. Adults who worked with the children reported ease of intervention techniques. The concept of environmental fit and its usefulness in guiding both assessment of and intervention for problem behavior are discussed

Phenotypic plasticity in chemical defence of butterflies allows usage of diverse host plants.

Host plant specialization is a major force driving ecological niche partitioning and diversification in insect herbivores. The cyanogenic defences of Passiflora plants keep most herbivores at bay, but not the larvae of Heliconius butterflies, which can both sequester and biosynthesize cyanogenic compounds. Here, we demonstrate that both Heliconius cydno chioneus and H. melpomene rosina have remarkable plasticity in their chemical defences. When feeding on Passiflora species with cyanogenic compounds that they can readily sequester, both species downregulate the biosynthesis of these compounds. By contrast, when fed on Passiflora plants that do not contain cyanogenic glucosides that can be sequestered, both species increase biosynthesis. This biochemical plasticity comes at a fitness cost for the more specialist H. m. rosina, as adult size and weight for this species negatively correlate with biosynthesis levels, but not for the more generalist H. c. chioneus. By contrast, H. m rosina has increased performance when sequestration is possible on its specialized host plant. In summary, phenotypic plasticity in biochemical responses to different host plants offers these butterflies the ability to widen their range of potential hosts within the Passiflora genus, while maintaining their chemical defences.UKRI, BBSRC: BB/R007500/1 Horizon 2020 - Marie Curie Actions, grant number: 841230 (Acronym: CyanideEvolution) European Research Council, grant number: 339873 (Acronym: SpeciationGenetics) Danmarks Frie Forskningsfond - FNU: 1323-0008