Abstracting Asynchronous Multi-Valued Networks: An Initial Investigation

Multi-valued networks provide a simple yet expressive qualitative state based modelling approach for biological systems. In this paper we develop an abstraction theory for asynchronous multi-valued network models that allows the state space of a model to be reduced while preserving key properties of the model. The abstraction theory therefore provides a mechanism for coping with the state space explosion problem and supports the analysis and comparison of multi-valued networks. We take as our starting point the abstraction theory for synchronous multi-valued networks which is based on the finite set of traces that represent the behaviour of such a model. The problem with extending this approach to the asynchronous case is that we can now have an infinite set of traces associated with a model making a simple trace inclusion test infeasible. To address this we develop a decision procedure for checking asynchronous abstractions based on using the finite state graph of an asynchronous multi-valued network to reason about its trace semantics. We illustrate the abstraction techniques developed by considering a detailed case study based on a multi-valued network model of the regulation of tryptophan biosynthesis in Escherichia coli.Comment: Presented at MeCBIC 201

Psychological aspects of genetic testing for cancer

The aim of this thesis is to explore psychological aspects of genetic testing for cancer, testing theoretical models to determine predictors of intention to have a genetic test. The main study disease is colon cancer, which is a good model for studying psychological aspects of genetic testing. This thesis will address two main themes. The first will explore the associates of intent to have a genetic test for colon cancer in people with a family history, but who are currently asymptomatic. The second theme will explore the generalisability of these results to other groups. In the first study, correlates of intention to have genetic testing were explored within asymptomatic patients at high risk of colon cancer. Specific comparisons assessed the effect of gender on intent to undergo genetic testing and on anticipated emotional outcomes. A year later the stability of the theoretical models used was assessed. The second theme was explored firstly by comparing views of genetic testing held by people at high risk of colon cancer with views held by their partners. In the next study participants with a personal history of cancer were included to explore differences between them and unaffected participants. In the sixth study the enquiry extended to encompass a general population sample, focusing on the influence of objective risk. Finally, comparisons were made between the original sample and women attending a Regional Genetics Service for counselling about breast cancer risk. The studies found high levels of intent to have a genetic test and supported the Theory of Reasoned Action, with the addition of Health Belief Model components. Comparison studies revealed strong similarities between correlates of intent to have genetic testing in people at risk of colon cancer compared with other groups. This supports a general theory of correlates of intention to have any predictive genetic test

Examining the relationship between pubertal stage, adolescent health behaviours and stress

Background. This paper examines the associations between puberty and three important health behavlours (smoking, food intake and exercise) and explores whether these associations are mediated by puberty's relationship to stress and psychological difficulties.Method. Data were taken from the first year of the ongoing, 5-year, Health and Behaviours in Teenagers Study (HABITS). This is a school-based study set in 36 schools in London. In the first year of the study, 4320 students (2578 boys, 1742 girls) in their first year of secondary education took part.Results. Among girls, being more pubertally advanced was associated with a greater likelihood of having tried smoking. Among boys, being more pubertally advanced was associated with a greater likelihood of having tried smoking, a higher intake of high-fat food and higher levels of exercise. More pubertally advanced girls experienced more stress but not more psychological difficulties. There were no associations between puberty and either stress or psychological difficulties in boys. Stress and psychological difficulties were associated with health behaviours in girls and boys, but neither of these factors mediated the relationship between pubertal stage and health behaviours found in girls.Conclusions. These results suggest that the onset of puberty has a marked effect on the development of health behaviours. Puberty was related to an acceleration of the development of unhealthy behaviours, except for exercise behaviour in boys, where advanced puberty was associated with more exercise. These changes were unrelated to adolescent issues of stress and a causal explanation for these associations must be sought elsewhere

An Abstraction Theory for Qualitative Models of Biological Systems

Multi-valued network models are an important qualitative modelling approach used widely by the biological community. In this paper we consider developing an abstraction theory for multi-valued network models that allows the state space of a model to be reduced while preserving key properties of the model. This is important as it aids the analysis and comparison of multi-valued networks and in particular, helps address the well-known problem of state space explosion associated with such analysis. We also consider developing techniques for efficiently identifying abstractions and so provide a basis for the automation of this task. We illustrate the theory and techniques developed by investigating the identification of abstractions for two published MVN models of the lysis-lysogeny switch in the bacteriophage lambda.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005

Hydrodynamical models of cometary H ii regions

We have modelled the evolution of cometary H ii regions produced by zero-age main-sequence stars of O and B spectral types, which are driving strong winds and are born off-centre from spherically symmetric cores with power-law (α = 2) density slopes. A model parameter grid was produced that spans stellar mass, age and core density. Exploring this parameter space, we investigated limb-brightening, a feature commonly seen in cometary H ii regions. We found that stars with mass M⋆ ≥ 12 M⊙ produce this feature. Our models have a cavity bounded by a contact discontinuity separating hot shocked wind and ionized ambient gas that is similar in size to the surrounding H ii region. Because of early pressure confinement, we did not see shocks outside of the contact discontinuity for stars with M⋆ ≤ 40 M⊙, but the cavities were found to continue to grow. The cavity size in each model plateaus as the H ii region stagnates. The spectral energy distributions of our models are similar to those from identical stars evolving in uniform density fields. The turn-over frequency is slightly lower in our power-law models as a result of a higher proportion of low-density gas covered by the H ii regions

Ultra-Compact HII Regions

In this thesis I have studied hydrodynamical models of cometary HII regions and distributions of UCHII regions in simulated surveys, for comparison with CORNISH. I present the numerical method used to model the evolution of cometary HII regions produced by ZAMS stars of O and B spectral types, which are driving strong winds and are born off-centre from spherically symmetric cores with power-law (alpha = 2) density slopes. A model parameter grid was produced that spans stellar mass, age and core density. Exploring this parameter space I investigated limb-brightening, a feature commonly seen in cometary HII regions. It was found that all of the models produce this feature. The models have a cavity, bounded by a contact discontinuity separating hot shocked wind and ionised ambient gas, that is similar in size to the surrounding HII region. Due to early pressure confinement, shocks outside of the contact discontinuity were not seen, but the cavities were found to continue to grow. The cavity size in each model plateaus as the expansion of the HII region stagnates, which could be due to the Kelvin-Helmholtz instabilities at the interface mixing in cooler gas. SEDs of the models are similar to those from identical stars evolving in uniform density fields. The turn-over frequency is lower in the power-law models due to a higher proportion of low density gas covered by the HII regions. Following from this I have simulated CORNISH surveys for stars, varying the local density at the location of stellar birth. I have shown that the models used can reproduce the observed size and flux distributions in the CORNISH survey. Higher density environments generally lead to better fits to the observed size and flux distributions. A good match between the overall number of UCHII regions in the simulated surveys for a SFR = 1.5 solar masses per year can be achieved if it is considered that stars are born in a distribution of local densities rather than a single density

Endometrium Cell Surface Abnormalities in the Syrian Hamster as a Result of In Utero Exposure to Diethylstilbestrol

Scanning electron microscopy (SEM) was used to observe changes in the hamster endometrium cell surface following in utero pre- and/or postnatal exposure to diethylstilbestrol (DES). Some of the changes in cell surfaces are associated with alterations in cell sizes and shapes (from columnar to cuboidal and/or squamous) and in microvilli and mucous secretion. In all cases, DES treated uteri show mucosal cell surface pleomorphism, apocrine secretion and cystic accumulation of secretory material. Microvillous pleomorphism and peculiar linkages attaching one microvillus to others were investigated. Although the function and nature of such linkages is unclear, their presence seems to be more prominent in the in utero DES treated hamster endometrium. These infrastructures may provide a support for the microvilli distributed on the mucosal cell surfaces, i.e., a morphological compromise between the single microvillous surface and the microridged structures. These interconnections may represent glycocalyx material or remodeling of cell surfaces toward squamous epithelium