The discovery of transcription factor binding site (TFBS) motifs remains an important and challenging problem in computational biology. This thesis presents MITSU, a novel algorithm for TFBS motif discovery which exploits stochastic methods as a means of both overcoming optimality limitations in current algorithms and as a framework for incorporating relevant prior knowledge in order to improve results. The current state of the TFBS motif discovery field is surveyed, with a focus on probabilistic algorithms that typically take the promoter regions of coregulated genes as input. A case is made for an approach based on the stochastic Expectation-Maximisation (sEM) algorithm; its position amongst existing probabilistic algorithms for motif discovery is shown. The algorithm developed in this thesis is unique amongst existing motif discovery algorithms in that it combines the sEM algorithm with a derived data set which leads to an improved approximation to the likelihood function. This likelihood function is unconstrained with regard to the distribution of motif occurrences within the input dataset. MITSU also incorporates a novel heuristic to automatically determine TFBS motif width. This heuristic, known as MCOIN, is shown to outperform current methods for determining motif width. MITSU is implemented in Java and an executable is available for download. MITSU is evaluated quantitatively using realistic synthetic data and several collections of previously characterised prokaryotic TFBS motifs. The evaluation demonstrates that MITSU improves on a deterministic EM-based motif discovery algorithm and an alternative sEM-based algorithm, in terms of previously established metrics. The ability of the sEM algorithm to escape stable fixed points of the EM algorithm, which trap deterministic motif discovery algorithms and the ability of MITSU to discover multiple motif occurrences within a single input sequence are also demonstrated. MITSU is validated using previously characterised Alphaproteobacterial motifs, before being applied to motif discovery in uncharacterised Alphaproteobacterial data. A number of novel results from this analysis are presented and motivate two extensions of MITSU: a strategy for the discovery of multiple different motifs within a single dataset and a higher order Markov background model. The effects of incorporating these extensions within MITSU are evaluated quantitatively using previously characterised prokaryotic TFBS motifs and demonstrated using Alphaproteobacterial motifs. Finally, an information-theoretic measure of motif palindromicity is presented and its advantages over existing approaches for discovering palindromic motifs discussed.

Pas de résumé en français / It is generally maintained that one of cortex’ functions is the storage of a large number of memories. In this picture, the physical substrate of memories is thought to be realised in pattern and strengths of synaptic connections among cortical neurons. Memory recall is associated with neuronal activity that is shaped by this connectivity. In this framework, active memories are represented by attractors in the space of neural activity. Electrical activity in cortical neurones in vivo exhibits prominent temporal irregularity. A standard way to account for this phenomenon is to postulate that recurrent synaptic excitation and inhibition as well as external inputs are balanced. In the common view, however, these balanced networks do not easily support the coexistence of multiple attractors. This is problematic in view of memory function. Recently, theoretical studies showed that balanced networks with synapses that exhibit short-term plasticity (STP) are able to maintain multiple stable states. In order to investigate whether experimentally obtained synaptic parameters are consistent with model predictions, we developed a new methodology that is capable to quantify both response variability and STP at the same synapse in an integrated and statistically-principled way. This approach yields higher parameter precision than standard procedures and allows for the use of more efficient stimulation protocols. However, the findings with respect to STP parameters do not allow to make conclusive statements about the validity of synaptic theories of balanced working memory. In the second part of this thesis an alternative theory of cortical memory storage is developed. The theory is based on the assumptions that memories are stored in attractor networks, and that memories are not represented by network states differing in their average activity levels, but by micro-states sharing the same global statistics. Different memories differ with respect to their spatial distributions of firing rates. From this the main result is derived: the balanced state is a necessary condition for extensive memory storage. Furthermore, we analytically calculate memory storage capacities of rate neurone networks. Remarkably, it can be shown that crucial properties of neuronal activity and physiology that are consistent with experimental observations are directly predicted by the theory if optimal memory storage capacity is required.

Dans ces travaux de thèse, nous proposons un modèle de prévision à court terme des flux de voyageurs basé sur les réseaux bayésiens. Ce modèle est destiné à répondre à des besoins opérationnels divers liés à l'information voyageurs, la régulation des flux ou encore la planification de l'offre de transport. Conçu pour s'adapter à tout type de configuration spatiale, il permet de combiner des sources de données hétérogènes (validations des titres de transport, comptages à bord des trains et offre de transport) et fournit une représentation intuitive des relations de causalité spatio-temporelles entre les flux. Sa capacité à gérer les données manquantes lui permet de réaliser des prédictions en temps réel même en cas de défaillances techniques ou d'absences de systèmes de collecte / In this thesis, we propose a Bayesian network model for short-term passenger flow forecasting. This model is intended to cater for various operational needs related to passenger information, passenger flow regulation or operation planning. As well as adapting to any spatial configuration, it is designed to combine heterogeneous data sources (ticket validation, on-board counts and transport service) and provides an intuitive representation of the causal spatio-temporal relationships between flows. Its ability to deal with missing data allows to make real-time predictions even in case of technical failures or absences of collection systems

One of the main tasks for an industrial robot is to move the end-effector in a predefined path with a specified velocity and acceleration. Different applications have different requirements of the performance. For some applications it is essential that the tracking error is extremely small, whereas other applications require a time optimal tracking. Independent of the application, the controller is a crucial part of the robot system. The most common controller configuration uses only measurements of the motor angular positions and velocities, instead of the position and velocity of the end-effector. The development of new cost optimised robots has introduced unwanted flexibilities in the joints and the links. The consequence is that it is no longer possible to get the desired performance and robustness by only measuring the motor angular positions.  This thesis investigates if it is possible to estimate the end-effector position using Bayesian estimation methods for state estimation, here represented by the extended Kalman filter and the particle filter. The arm-side information is provided by an accelerometer mounted at the end-effector. The measurements consist of the motor angular positions and the acceleration of the end-effector. In a simulation study on a realistic flexible industrial robot, the angular position performance is shown to be close to the fundamental Cramér-Rao lower bound. The methods are also verified in experiments on an ABB IRB4600 robot, where the dynamic performance of the position for the end-effector is significantly improved. There is no significant difference in performance between the different methods. Instead, execution time, model complexities and implementation issues have to be considered when choosing the method. The estimation performance depends strongly on the tuning of the filters and the accuracy of the models that are used. Therefore, a method for estimating the process noise covariance matrix is proposed. Moreover, sampling methods are analysed and a low-complexity analytical solution for the continuous-time update in the Kalman filter, that does not involve oversampling, is proposed.  The thesis also investigates two types of control problems. First, the norm-optimal iterative learning control (ILC) algorithm for linear systems is extended to an estimation-based norm-optimal ILC algorithm where the controlled variables are not directly available as measurements. The algorithm can also be applied to non-linear systems. The objective function in the optimisation problem is modified to incorporate not only the mean value of the estimated variable, but also information about the uncertainty of the estimate. Second, H∞ controllers are designed and analysed on a linear four-mass flexible joint model. It is shown that the control performance can be increased, without adding new measurements, compared to previous controllers. Measuring the end-effector acceleration increases the control performance even more. A non-linear model has to be used to describe the behaviour of a real flexible joint. An H∞-synthesis method for control of a flexible joint, with non-linear spring characteristic, is therefore proposed. / En av de viktigaste uppgifterna för en industrirobot är att förflytta verktyget i en fördefinierad bana med en specificerad hastighet och acceleration. Exempel på användningsområden för en industrirobot är bland annat bågsvetsning eller limning. För dessa typer av applikationer är det viktigt att banföljningsfelet är extremt litet, men även hastighetsprofilen måste följas så att det till exempel inte appliceras för mycket eller för lite lim. Andra användningsområden kan vara punktsvetsning av bilkarosser och paketering av olika varor. För dess applikationer är banföljningen inte det viktiga, istället kan till exempel en tidsoptimal banföljning krävas eller att svängningarna vid en inbromsning minimeras. Oberoende av applikationen är regulatorn en avgörande del av robotsystemet. Den vanligaste regulatorkonfigurationen använder bara mätningar av motorernas vinkelpositioner och -hastigheter, istället för positionen och hastigheten för verktyget, som är det man egentligen vill styra.  En del av utvecklingsarbetet för nya generationers robotar är att reducera kostnaden men samtidigt förbättra prestandan. Ett sätt att minska kostnaden kan till exempel vara att minska dimensionerna på länkarna eller köpa in billigare växellådor. Den här utvecklingen av kostnadsoptimerade robotar har infört oönskade flexibiliteter i leder och länkar. Det är därför inte längre möjligt att få den önskade prestandan och robustheten genom att bara mäta motorernas vinkelpositioner och -hastigheter. Istället krävs det omfattande matematiska modeller som beskriver dessa oönskade flexibiliteter. Dessa modeller kräver mycket arbete att dels ta fram men även för att identifiera parametrarna. Det finns automatiska metoder för att beräkna modellparametrarna men oftast krävs det en manuell justering för att få bra prestanda.  Den här avhandlingen undersöker möjligheterna att beräkna verktygspositionen med hjälp av bayesianska metoder för tillståndsskattning. De bayesianska skattningsmetoderna beräknar tillstånden för ett system iterativt. Med hjälp av en matematisk modell över systemet predikteras vad tillståndet ska vara vid nästa tidpunkt. Efter att mätningar av systemet vid den nya tidpunkten har genomförts justeras skattningen med hjälp av dessa mätningar. De metoder som har använts i avhandlingen är det så kallade extended Kalman filtret samt partikelfiltret.  Informationen på armsidan av växellådan ges av en accelerometer som är monterad på verktyget. Med hjälp av accelerationen för verktyget och motorernas vinkelpositioner kan en skattning av verktygspositionen beräknas. I en simuleringsstudie för en realistisk vek robot har det visats att skattningsprestandan ligger nära den teoretiska undre gränsen, känd som Raooch mätstörningar som påverkar roboten. För att underlätta trimningen så har en metod för att skatta processbrusets kovariansmatris föreslagits. En annan viktig del som påverkar prestandan är modellerna som används i filtren. Modellerna för en industrirobot är vanligtvis framtagna i kontinuerlig tid medan filtren använder modeller i diskret tid. För att minska felen som uppkommer då de tidskontinuerliga modellerna överförs till diskret tid har olika samplingsmetoder studerats. Vanligtvis används enkla metoder för att diskretisera vilket innebär problem med prestanda och stabilitet. För att hantera dessa problem införs översampling vilket innebär att tidsuppdateringen sker med en mycket kortare sampeltid än vad mätuppdateringen gör. För att undvika översampling kan det motsvarande tidskontinuerliga filtret användas för att prediktera tillstånden vid nästa diskreta tidpunkt. En analytisk lösning med låg beräkningskomplexitet till detta problem har föreslagits.  Vidare innehåller avhandlingen två typer av reglerproblem relaterade till industrirobotar. För det första har den så kallade norm-optimala iterative learning control styrlagen utökats till att hantera fallet då en skattning av den önskade reglerstorheten används istället för en mätning. Med hjälp av skattningen av systemets tillståndsvektor kan metoden nu även användas till olinjära system vilket inte är fallet med standardformuleringen. Den föreslagna metoden utökar målfunktionen i optimeringsproblemet till att innehålla inte bara väntevärdet av den skattade reglerstorheten utan även skattningsfelets kovariansmatris. Det innebär att om skattningsfelet är stort vid en viss tidpunkt ska den skattade reglerstorheten vid den tidpunkten inte påverka resultatet mycket eftersom det finns en stor osäkerhet i var den sanna reglerstorheten befinner sig.  För det andra har design och analys av H∞-regulatorer för en linjär modell av en vek robotled, som beskrivs med fyra massor, genomförts. Det visar sig att reglerprestandan kan förbättras, utan att lägga till fler mätningar än motorns vinkelposition, jämfört med tidigare utvärderade regulatorer. Genom att mäta verktygets acceleration kan prestandan förbättras ännu mer. Modellen över leden är i själva verket olinjär. För att hantera detta har en H∞-syntesmetod föreslagits som kan hantera olinjäriteten i modellen. / Vinnova Excellence Center LINK-SIC

Le changement structurel en agriculture suscite beaucoup d’intérêt de la part des économistes agricoles ainsi que des décideurs politiques. Pour prendre en compte l’hétérogénéité du comportement des agriculteurs, une approche par les modèles de mélange de chaînes de Markov est appliquée pour la première fois en économie agricole pour analyser ce processus. La performance de cette approche est d’abord testée en utilisant une forme simplifiée du modèle, puis sa forme générale est appliquée pour étudier l’impact de certaines mesures de politique agricole. Pour identifier les principaux canaux d’interdépendance entre exploitations voisines dans les processus du changement structurel, une approche de mélange non-Markovienne a été appliquée pour modéliser la survie et l’agrandissement des exploitations agricolesTrois principales conclusions découlent de cette thèse. Tout d’abord, la prise en compte de l’hétérogénéité dans les processus de transition des exploitations agricoles permet de mieux représenter le changement structurel et conduit à des prédictions plus précises de la distribution des exploitations, comparé aux modèles généralement utilisés jusqu’ici. Deuxièmement, l’impact des principaux facteurs du changement structurel dépend lui aussi des types non-observables d’exploitations mis en évidence. Enfin, le cadre du modèle de mélange permet également de révéler différents types de relations inobservées entre exploitations voisines qui contribuent au changement structurel observé à un niveau global ou régional. / Structural change in farming has long been the subject of considerable interest among agricultural economists and policy makers. To account for heterogeneity in farmers’ behaviours, a mixture Markov modelling framework is applied to analyse this process for the first time in agricultural economics. The performance of this approach is first investigated using a restrictive form of the model, and its general form is then applied to study the impact of some drivers of structural change, including agricultural policy measures. To identify channels through which interdependency between neighbouring farms arises in this process, the mixture modelling approach is applied to analyse both farm survival and farm growth. The main conclusions of this thesis are threefoldFirstly, accounting for the generally unobserved heterogeneity in the transition process of farms allows better representing structural change in farming and leads to more accurate predictions of farm-size distributions than the models usually used so far. Secondly, the impacts of the main drivers of structural change themselves depend on the specific unobservable farm types which are revealed by the model. Lastly, the mixture modelling approach enables identifying different unobserved relationships between neighbouring farms that contributes to the structural change observed at an aggregate or regional level.

This thesis investigates decision-making in two-player imperfect information games against opponents whose actions can affect our rewards, and whose strategies may be based on memories of interaction, or may be changing, or both. The focus is on modelling these dynamic opponents, and using the models to learn high-reward strategies. The main contributions of this work are: 1. An approach to learn high-reward strategies in small simultaneous-move games against these opponents. This is done by using a model of the opponent learnt from sequence prediction, with (possibly discounted) rewards learnt from reinforcement learning, to lookahead using explicit tree search. Empirical results show that this gains higher average rewards per game than state-of-the-art reinforcement learning agents in three simultaneous-move games. They also show that several sequence prediction methods model these opponents effectively, supporting the idea of using them from areas such as data compression and string matching; 2. An online expectation-maximisation algorithm that infers an agent's hidden information based on its behaviour in imperfect information games; 3. An approach to learn high-reward strategies in medium-size sequential-move poker games against these opponents. This is done by using a model of the opponent learnt from sequence prediction, which needs its hidden information (inferred by the online expectation-maximisation algorithm), to train a state-of-the-art no-regret learning algorithm by simulating games between the algorithm and the model. Empirical results show that this improves the no-regret learning algorithm's rewards when playing against popular and state-of-the-art algorithms in two simplified poker games; 4. Demonstrating that several change detection methods can effectively model changing categorical distributions with experimental results comparing their accuracies to empirical distributions. These results also show that their models can be used to outperform state-of-the-art reinforcement learning agents in two simultaneous-move games. This supports the idea of modelling changing opponent strategies with change detection methods; 5. Experimental results for the self-play convergence to mixed strategy Nash equilibria of the empirical distributions of plays of sequence prediction and change detection methods. The results show that they converge faster, and in more cases for change detection, than fictitious play.

Investors constantly seek information that provides an edge over the market. One of the conventional methods is to find factors which can predict asset returns. In this study we improve the Fama and French Five-Factor model with Regime-Switches, student's t distributions and copula dependencies. We also add price momentum as a sixth factor and add a one-day lag to the factors. The Regime-Switches are obtained from a Hidden Markov Model with conditional Student's t distributions. For the return process we use factor data as input, Student's t distributed residuals, and Student's t copula dependencies. To fit the copulas, we develop a novel approach based on the Expectation-Maximisation algorithm. The results are promising as the quantiles for most of the portfolios show a good fit to the theoretical quantiles. Using a sophisticated Stochastic Programming model, we back-test the predictive power over a 26 year period out-of-sample. Furthermore we analyse the performance of different factors during different market regimes.