Methods for construction and analysis of computational models in systems biology : applications to the modelling of the heat shock response and the self-assembly of intermediate filaments

Systems biology is a new, emerging and rapidly developing, multidisciplinary research field that aims to study biochemical and biological systems from a holistic perspective, with the goal of providing a comprehensive, system- level understanding of cellular behaviour. In this way, it addresses one of the greatest challenges faced by contemporary biology, which is to compre- hend the function of complex biological systems. Systems biology combines various methods that originate from scientific disciplines such as molecu- lar biology, chemistry, engineering sciences, mathematics, computer science and systems theory. Systems biology, unlike “traditional” biology, focuses on high-level concepts such as: network, component, robustness, efficiency, control, regulation, hierarchical design, synchronization, concurrency, and many others. The very terminology of systems biology is “foreign” to “tra- ditional” biology, marks its drastic shift in the research paradigm and it indicates close linkage of systems biology to computer science. One of the basic tools utilized in systems biology is the mathematical modelling of life processes tightly linked to experimental practice. The stud- ies contained in this thesis revolve around a number of challenges commonly encountered in the computational modelling in systems biology. The re- search comprises of the development and application of a broad range of methods originating in the fields of computer science and mathematics for construction and analysis of computational models in systems biology. In particular, the performed research is setup in the context of two biolog- ical phenomena chosen as modelling case studies: 1) the eukaryotic heat shock response and 2) the in vitro self-assembly of intermediate filaments, one of the main constituents of the cytoskeleton. The range of presented approaches spans from heuristic, through numerical and statistical to ana- lytical methods applied in the effort to formally describe and analyse the two biological processes. We notice however, that although applied to cer- tain case studies, the presented methods are not limited to them and can be utilized in the analysis of other biological mechanisms as well as com- plex systems in general. The full range of developed and applied modelling techniques as well as model analysis methodologies constitutes a rich mod- elling framework. Moreover, the presentation of the developed methods, their application to the two case studies and the discussions concerning their potentials and limitations point to the difficulties and challenges one encounters in computational modelling of biological systems. The problems of model identifiability, model comparison, model refinement, model inte- gration and extension, choice of the proper modelling framework and level of abstraction, or the choice of the proper scope of the model run through this thesis.

Future revenue models: Transformation from textbooks to digital solutions in the educational publishing industry, Case Sanoma Learning

This study was conducted in order to learn how companies’ revenue models will be transformed due to the digitalisation of its products and processes. Because there is still only a limited number of researches focusing solely on revenue models, and particularly on the revenue model change caused by the changes at the business environment, the topic was initially approached through the business model concept, which organises the different value creating operations and resources at a company in order to create profitable revenue streams. This was used as the base for constructing the theoretical framework for this study, used to collect and analyse the information. The empirical section is based on a qualitative study approach and multiple-case analysis of companies operating in learning materials publishing industry. Their operations are compared with companies operating in other industries, which have undergone comparable transformation, in order to recognise either similarities or contrasts between the cases. The sources of evidence are a literature review to find the essential dimensions researched earlier, and interviews 29 of managers and executives at 17 organisations representing six industries. Based onto the earlier literature and the empirical findings of this study, the change of the revenue model is linked with the change of the other dimen-sions of the business model. When one dimension will be altered, as well the other should be adjusted accordingly. At the case companies the transformation is observed as the utilisation of several revenue models simultaneously and the revenue creation processes becoming more complex.

Leptogenesis as the origin of matter-antimatter asymmetry in extra dimensional and supersymmetric models

The Standard Model of particle physics is currently the best description of fundamental particles and their interactions. All particles save the Higgs boson have been observed in particle accelerator experiments over the years. Despite the predictive power the Standard Model there are many phenomena that the scenario does not predict or explain. Among the most prominent dilemmas is matter-antimatter asymmetry, and much effort has been made in formulating scenarios that accurately predict the correct amount of matter-antimatter asymmetry in the universe. One of the most appealing explanations is baryogenesis via leptogenesis which not only serves as a mechanism of producing excess matter over antimatter but can also explain why neutrinos have very small non-zero masses. Interesting leptogenesis scenarios arise when other possible candidates of theories beyond the Standard Model are brought into the picture. In this thesis, we have studied leptogenesis in an extra dimensional framework and in a modified version of supersymmetric Standard Model. The first chapters of this thesis introduce the standard cosmological model, observations made on the photon to baryon ratio and necessary preconditions for successful baryogenesis. Baryogenesis via leptogenesis is then introduced and its connection to neutrino physics is illuminated. The final chapters concentrate on extra dimensional theories and supersymmetric models and their ability to accommodate leptogenesis. There, the results of our research are also presented.

MCMC Analysis for Optimization of Stochastic Models

In any decision making under uncertainties, the goal is mostly to minimize the expected cost. The minimization of cost under uncertainties is usually done by optimization. For simple models, the optimization can easily be done using deterministic methods.However, many models practically contain some complex and varying parameters that can not easily be taken into account using usual deterministic methods of optimization. Thus, it is very important to look for other methods that can be used to get insight into such models. MCMC method is one of the practical methods that can be used for optimization of stochastic models under uncertainty. This method is based on simulation that provides a general methodology which can be applied in nonlinear and non-Gaussian state models. MCMC method is very important for practical applications because it is a uni ed estimation procedure which simultaneously estimates both parameters and state variables. MCMC computes the distribution of the state variables and parameters of the given data measurements. MCMC method is faster in terms of computing time when compared to other optimization methods. This thesis discusses the use of Markov chain Monte Carlo (MCMC) methods for optimization of Stochastic models under uncertainties .The thesis begins with a short discussion about Bayesian Inference, MCMC and Stochastic optimization methods. Then an example is given of how MCMC can be applied for maximizing production at a minimum cost in a chemical reaction process. It is observed that this method performs better in optimizing the given cost function with a very high certainty.

ALLOMETRIC MODELS FOR ESTIMATING ABOVEGROUND BIOMASS AND BIOMASS ALLOCATION OF CAPIXINGUI TREES (Croton floribundus Spreng.) IN AN AGRISILVICULTURAL SYSTEM

ABSTRACT The objective of this study was to select allometric models to estimate total and pooled aboveground biomass of 4.5-year-old capixingui trees established in an agrisilvicultural system. Aboveground biomass distribution of capixingui was also evaluated. Single- (diameter at breast height [DBH] or crown diameter or stem diameter as the independent variable) and double-entry (DBH or crown diameter or stem diameter and total height as independent variables) models were studied. The estimated total biomass was 17.3 t.ha-1, corresponding to 86.6 kg per tree. All models showed a good fit to the data (R2ad > 0.85) for bole, branches, and total biomass. DBH-based models presented the best residual distribution. Model lnW = b0 + b1* lnDBH can be recommended for aboveground biomass estimation. Lower coefficients were obtained for leaves (R2ad > 82%). Biomass distribution followed the order: bole>branches>leaves. Bole biomass percentage decreased with increasing DBH of the trees, whereas branch biomass increased.

CFD Modelling of Direct Contact Condensation in Suppression Pools by Applying Condensation Models of Separated Flow

The condensation rate has to be high in the safety pressure suppression pool systems of Boiling Water Reactors (BWR) in order to fulfill their safety function. The phenomena due to such a high direct contact condensation (DCC) rate turn out to be very challenging to be analysed either with experiments or numerical simulations. In this thesis, the suppression pool experiments carried out in the POOLEX facility of Lappeenranta University of Technology were simulated. Two different condensation modes were modelled by using the 2-phase CFD codes NEPTUNE CFD and TransAT. The DCC models applied were the typical ones to be used for separated flows in channels, and their applicability to the rapidly condensing flow in the condensation pool context had not been tested earlier. A low Reynolds number case was the first to be simulated. The POOLEX experiment STB-31 was operated near the conditions between the ’quasi-steady oscillatory interface condensation’ mode and the ’condensation within the blowdown pipe’ mode. The condensation models of Lakehal et al. and Coste & Lavi´eville predicted the condensation rate quite accurately, while the other tested ones overestimated it. It was possible to get the direct phase change solution to settle near to the measured values, but a very high resolution of calculation grid was needed. Secondly, a high Reynolds number case corresponding to the ’chugging’ mode was simulated. The POOLEX experiment STB-28 was chosen, because various standard and highspeed video samples of bubbles were recorded during it. In order to extract numerical information from the video material, a pattern recognition procedure was programmed. The bubble size distributions and the frequencies of chugging were calculated with this procedure. With the statistical data of the bubble sizes and temporal data of the bubble/jet appearance, it was possible to compare the condensation rates between the experiment and the CFD simulations. In the chugging simulations, a spherically curvilinear calculation grid at the blowdown pipe exit improved the convergence and decreased the required cell count. The compressible flow solver with complete steam-tables was beneficial for the numerical success of the simulations. The Hughes-Duffey model and, to some extent, the Coste & Lavi´eville model produced realistic chugging behavior. The initial level of the steam/water interface was an important factor to determine the initiation of the chugging. If the interface was initialized with a water level high enough inside the blowdown pipe, the vigorous penetration of a water plug into the pool created a turbulent wake which invoked the chugging that was self-sustaining. A 3D simulation with a suitable DCC model produced qualitatively very realistic shapes of the chugging bubbles and jets. The comparative FFT analysis of the bubble size data and the pool bottom pressure data gave useful information to distinguish the eigenmodes of chugging, bubbling, and pool structure oscillations.

Mathematical models to describe the volumetric shrinkage rate of red beans during drying

The present study aimed to determine the volumetric shrinkage rate of bean (Phaseolus vulgaris L.) seeds during air-drying under different conditions of air, temperature and relative humidity, and to adjust several mathematical models to the empiric values observed, and select the one that best represents the phenomenon. Six mathematical models were adjusted to the experimental values to represent the phenomenon. It was determined the degree of adjustment of each model from the value of the coefficient of determination, the behavior of the distribution of the residuals, and the magnitude of the average relative and estimated errors. The rate of volumetric shrinkage that occurred in bean seeds during drying is between 25 and 37%. It basically depends on the final moisture content, regardless of the air conditions during drying. The Modified Bala & Woods' model best represented the process.

Adjust of regression models to estimate the rectal temperature of broilers for the first 14 days of life

The broiler rectal temperature (t rectal) is one of the most important physiological responses to classify the animal thermal comfort. Therefore, the aim of this study was to adjust regression models in order to predict the rectal temperature (t rectal) of broiler chickens under different thermal conditions based on age (A) and a meteorological variable (air temperature - t air) or a thermal comfort index (temperature and humidity index -THI or black globe humidity index - BGHI) or a physical quantity enthalpy (H). In addition, through the inversion of these models and the expected t rectal intervals for each age, the comfort limits of t air, THI, BGHI and H for the chicks in the heating phase were determined, aiding in the validation of the equations and the preliminary limits for H. The experimental data used to adjust the mathematical models were collected in two commercial poultry farms, with Cobb chicks, from 1 to 14 days of age. It was possible to predict the t rectal of conditions from the expected t rectal and determine the lower and superior comfort thresholds of broilers satisfactorily by applying the four models adjusted; as well as to invert the models for prediction of the environmental H for the chicks first 14 days of life.

Comparison between hydrographically conditioned digital elevation models in the morphometric charaterization of watersheds

The aim of this study was to compare the hydrographically conditioned digital elevation models (HCDEMs) generated from data of VNIR (Visible Near Infrared) sensor of ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer), of SRTM (Shuttle Radar Topography Mission) and topographical maps from IBGE in a scale of 1:50,000, processed in the Geographical Information System (GIS), aiming the morphometric characterization of watersheds. It was taken as basis the Sub-basin of São Bartolomeu River, obtaining morphometric characteristics from HCDEMs. Root Mean Square Error (RMSE) and cross validation were the statistics indexes used to evaluate the quality of HCDEMs. The percentage differences in the morphometric parameters obtained from these three different data sets were less than 10%, except for the mean slope (21%). In general, it was observed a good agreement between HCDEMs generated from remote sensing data and IBGE maps. The result of HCDEM ASTER was slightly higher than that from HCDEM SRTM. The HCDEM ASTER was more accurate than the HCDEM SRTM in basins with high altitudes and rugged terrain, by presenting frequency altimetry nearest to HCDEM IBGE, considered standard in this study.