Computational model validation using a novel multiscale multidimensional spatio-temporal meta model checking approach

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonComputational models of complex biological systems can provide a better understanding of how living systems function but need to be validated before they are employed for real-life (e.g. clinical) applications. One of the most frequently employed in silico approaches for validating such models is model checking. Traditional model checking approaches are limited to uniscale non-spatial computational models because they do not explicitly distinguish between different scales, and do not take properties of (emergent) spatial structures (e.g. density of multicellular population) into account. This thesis defines a novel multiscale multidimensional spatio-temporal meta model checking methodology which enables validating multiscale (spatial) computational models of biological systems relative to how both numeric (e.g. concentrations) and spatial system properties are expected to change over time and across multiple scales. The methodology has two important advantages. First it supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to produce them. Secondly the methodology is generic because it can be automatically reconfigured according to case study specific types of spatial structures and properties using the meta model checking approach. In addition the methodology could be employed for multiple domains of science, but we illustrate its applicability here only against biological case studies. To automate the computational model validation process, the approach was implemented in software tools, which are made freely available online. Their efficacy is illustrated against two uniscale and four multiscale quantitative computational models encoding phase variation in bacterial colonies and the chemotactic aggregation of cells, respectively the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. This novel model checking approach will enable the efficient construction of reliable multiscale computational models of complex systems.Brunel University Londo

Phenolic Compounds and Antifungal Activity of Hedera helix L. (Ivy) Flowers and Fruits

Identification and quantitative analysis of the phenolic compounds from Hedera helix L. (ivy) flower and fruit ethanol extracts by LC/MS, in vitro germination and growth inhibition effects on Aspergillus niger, Botrytis cinerea, Fusarium oxysporum f.sp. tulipae, Penicillium gladioli and Sclerotinia sclerotiorum were performed. In the non-hydrolyzed samples of flower and fruit extracts were determined, in different amounts, five polyphenols (p-coumaric acid, ferulic acid, rutoside, quercetol and kaempferol) while quercitrin was identified only in the ivy flower extract. The hydrolyzed samples of the same ivy extracts indicated four phenolic compounds (p-coumaric acid, ferulic acid, quercetol and kaempferol), in different concentrations, whereas sinapic acid was only detected in the ivy fruit extract. The antifungal activity of the fresh flower extract was stronger than that of the fresh fruit extract and was compared to that of an antimycotic drug

Computational models for inferring biochemical networks

Biochemical networks are of great practical importance. The interaction of biological compounds in cells has been enforced to a proper understanding by the numerous bioinformatics projects, which contributed to a vast amount of biological information. The construction of biochemical systems (systems of chemical reactions), which include both topology and kinetic constants of the chemical reactions, is NP-hard and is a well-studied system biology problem. In this paper, we propose a hybrid architecture, which combines genetic programming and simulated annealing in order to generate and optimize both the topology (the network) and the reaction rates of a biochemical system. Simulations and analysis of an artificial model and three real models (two models and the noisy version of one of them) show promising results for the proposed method.The Romanian National Authority for Scientific Research, CNDI–UEFISCDI, Project No. PN-II-PT-PCCA-2011-3.2-0917

Chemical Composition of Celandine (<i>Chelidonium majus</i> L.) Extract and its Effects on <i>Botrytis tulipae</i> (Lib.) Lind Fungus and the Tulip

In this study, the content of chelidonine and berberine alkaloids, and sterols and phenols in the Chelidonium majus plant extract were analyzed. Subsequently, the effects of the extract on the germination and growth of Botrytis tulipae fungus on nutritive medium were compared to the effects of fluconazole. The plant extract was used at the minimum inhibitory concentration on B. tulipae developed in tulip leaves and the in vivo effects were investigated. The influence of different concentrations of C. majus extract on the physiological processes of the tulip (gas exchange parameters, photosynthetic light use efficiency, and induced chlorophyll fluorescence) were also tested to assess the applicability of the extract for the protection of ornamental plants against fungal infection. Our results demonstrated that 2% celandine extract does not significantly change the gas exchange parameters (transpiration rate, carbon dioxide uptake, and stomatal conductivity) of leaves exposed for 2 h, and does not interfere with the photochemical processes in the leaves. However, in higher concentrations, it increases the transpiration rate and net carbon dioxide influx. At concentrations of 15% and 20%, the extract lowers the potential quantum yield efficiency of photosystem II and the vitality index of the photosynthetic apparatus. Therefore we recommend the use of lower concentrations (≤6%) of celandine extract for the biological protection of tulips against gray mold

Chemical Composition of Celandine (<i>Chelidonium majus</i> L.) Extract and its Effects on <i>Botrytis tulipae</i> (Lib.) Lind Fungus and the Tulip

In this study, the content of chelidonine and berberine alkaloids, and sterols and phenols in the Chelidonium majus plant extract were analyzed. Subsequently, the effects of the extract on the germination and growth of Botrytis tulipae fungus on nutritive medium were compared to the effects of fluconazole. The plant extract was used at the minimum inhibitory concentration on B. tulipae developed in tulip leaves and the in vivo effects were investigated. The influence of different concentrations of C. majus extract on the physiological processes of the tulip (gas exchange parameters, photosynthetic light use efficiency, and induced chlorophyll fluorescence) were also tested to assess the applicability of the extract for the protection of ornamental plants against fungal infection. Our results demonstrated that 2% celandine extract does not significantly change the gas exchange parameters (transpiration rate, carbon dioxide uptake, and stomatal conductivity) of leaves exposed for 2 h, and does not interfere with the photochemical processes in the leaves. However, in higher concentrations, it increases the transpiration rate and net carbon dioxide influx. At concentrations of 15% and 20%, the extract lowers the potential quantum yield efficiency of photosystem II and the vitality index of the photosynthetic apparatus. Therefore we recommend the use of lower concentrations (≤6%) of celandine extract for the biological protection of tulips against gray mold

Cohort profile. the ESC-EORP chronic ischemic cardiovascular disease long-term (CICD LT) registry

The European Society of cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischemic Cardiovascular Disease registry Long Term (CICD) aims to study the clinical profile, treatment modalities and outcomes of patients diagnosed with CICD in a contemporary environment in order to assess whether these patients at high cardiovascular risk are treated according to ESC guidelines on prevention or on stable coronary disease and to determine mid and long term outcomes and their determinants in this population