Learning wind fields with multiple kernels

This paper presents multiple kernel learning (MKL) regression as an exploratory spatial data analysis and modelling tool. The MKL approach is introduced as an extension of support vector regression, where MKL uses dedicated kernels to divide a given task into sub-problems and to treat them separately in an effective way. It provides better interpretability to non-linear robust kernel regression at the cost of a more complex numerical optimization. In particular, we investigate the use of MKL as a tool that allows us to avoid using ad-hoc topographic indices as covariables in statistical models in complex terrains. Instead, MKL learns these relationships from the data in a non-parametric fashion. A study on data simulated from real terrain features confirms the ability of MKL to enhance the interpretability of data-driven models and to aid feature selection without degrading predictive performances. Here we examine the stability of the MKL algorithm with respect to the number of training data samples and to the presence of noise. The results of a real case study are also presented, where MKL is able to exploit a large set of terrain features computed at multiple spatial scales, when predicting mean wind speed in an Alpine region.

MEPDG Work Plan Task No. 5: Characterization of Unbound Materials (Soils/Aggregates) for Mechanistic-Empirical Pavement Design Guide, 2009

The resilient modulus (MR) input parameters in the Mechanistic-Empirical Pavement Design Guide (MEPDG) program have a significant effect on the projected pavement performance. The MEPDG program uses three different levels of inputs depending on the desired level of accuracy. The primary objective of this research was to develop a laboratory testing program utilizing the Iowa DOT servo-hydraulic machine system for evaluating typical Iowa unbound materials and to establish a database of input values for MEPDG analysis. This was achieved by carrying out a detailed laboratory testing program designed in accordance with the AASHTO T307 resilient modulus test protocol using common Iowa unbound materials. The program included laboratory tests to characterize basic physical properties of the unbound materials, specimen preparation and repeated load triaxial tests to determine the resilient modulus. The MEPDG resilient modulus input parameter library for Iowa typical unbound pavement materials was established from the repeated load triaxial MR test results. This library includes the non-linear, stress-dependent resilient modulus model coefficients values for level 1 analysis, the unbound material properties values correlated to resilient modulus for level 2 analysis, and the typical resilient modulus values for level 3 analysis. The resilient modulus input parameters library can be utilized when designing low volume roads in the absence of any basic soil testing. Based on the results of this study, the use of level 2 analysis for MEPDG resilient modulus input is recommended since the repeated load triaxial test for level 1 analysis is complicated, time consuming, expensive, and requires sophisticated equipment and skilled operators.

Ambulatory assessment of 3D ground reaction force using plantar pressure distribution.

This study aimed to use the plantar pressure insole for estimating the three-dimensional ground reaction force (GRF) as well as the frictional torque (T(F)) during walking. Eleven subjects, six healthy and five patients with ankle disease participated in the study while wearing pressure insoles during several walking trials on a force-plate. The plantar pressure distribution was analyzed and 10 principal components of 24 regional pressure values with the stance time percentage (STP) were considered for GRF and T(F) estimation. Both linear and non-linear approximators were used for estimating the GRF and T(F) based on two learning strategies using intra-subject and inter-subjects data. The RMS error and the correlation coefficient between the approximators and the actual patterns obtained from force-plate were calculated. Our results showed better performance for non-linear approximation especially when the STP was considered as input. The least errors were observed for vertical force (4%) and anterior-posterior force (7.3%), while the medial-lateral force (11.3%) and frictional torque (14.7%) had higher errors. The result obtained for the patients showed higher error; nevertheless, when the data of the same patient were used for learning, the results were improved and in general slight differences with healthy subjects were observed. In conclusion, this study showed that ambulatory pressure insole with data normalization, an optimal choice of inputs and a well-trained nonlinear mapping function can estimate efficiently the three-dimensional ground reaction force and frictional torque in consecutive gait cycle without requiring a force-plate.

Systemic exposure to tobramycin after local antibiotic treatment with calcium sulphate as carrier material.

INTRODUCTION: Osteoset(®) T is a calcium sulphate void filler containing 4% tobramycin sulphate, used to treat bone and soft tissue infections. Despite systemic exposure to the antibiotic, there are no pharmacokinetic studies in humans published so far. Based on the observations made in our patients, a model predicting tobramycin serum levels and evaluating their toxicity potential is presented. METHODS: Following implantation of Osteoset(®) T, tobramycin serum concentrations were monitored systematically. A pharmacokinetic analysis was performed using a non-linear mixed effects model based on a one compartment model with first-degree absorption. RESULTS: Data from 12 patients treated between October 2006 and March 2008 were analysed. Concentration profiles were consistent with the first-order slow release and single-compartment kinetics, whilst showing important variability. Predicted tobramycin serum concentrations depended clearly on both implanted drug amount and renal function. DISCUSSION AND CONCLUSION: Despite the popularity of aminoglycosides for local antibiotic therapy, pharmacokinetic data for this indication are scarce, and not available for calcium sulphate as carrier material. Systemic exposure to tobramycin after implantation of Osteoset(®) T appears reassuring regarding toxicity potential, except in case of markedly impaired renal function. We recommend in adapting the dosage to the estimated creatinine clearance rather than solely to the patient's weight.

Update on the non-prewhitening model observer in computed tomography for the assessment of the adaptive statistical and model-based iterative reconstruction algorithms.

The state of the art to describe image quality in medical imaging is to assess the performance of an observer conducting a task of clinical interest. This can be done by using a model observer leading to a figure of merit such as the signal-to-noise ratio (SNR). Using the non-prewhitening (NPW) model observer, we objectively characterised the evolution of its figure of merit in various acquisition conditions. The NPW model observer usually requires the use of the modulation transfer function (MTF) as well as noise power spectra. However, although the computation of the MTF poses no problem when dealing with the traditional filtered back-projection (FBP) algorithm, this is not the case when using iterative reconstruction (IR) algorithms, such as adaptive statistical iterative reconstruction (ASIR) or model-based iterative reconstruction (MBIR). Given that the target transfer function (TTF) had already shown it could accurately express the system resolution even with non-linear algorithms, we decided to tune the NPW model observer, replacing the standard MTF by the TTF. It was estimated using a custom-made phantom containing cylindrical inserts surrounded by water. The contrast differences between the inserts and water were plotted for each acquisition condition. Then, mathematical transformations were performed leading to the TTF. As expected, the first results showed a dependency of the image contrast and noise levels on the TTF for both ASIR and MBIR. Moreover, FBP also proved to be dependent of the contrast and noise when using the lung kernel. Those results were then introduced in the NPW model observer. We observed an enhancement of SNR every time we switched from FBP to ASIR to MBIR. IR algorithms greatly improve image quality, especially in low-dose conditions. Based on our results, the use of MBIR could lead to further dose reduction in several clinical applications.

Pharmacokinetic and pharmacodynamic assessment of valganciclovir in solid organ transplant recipients

RESUME : Valganciclovir (Valcyte®) is an orally administered ester prodrug of the standard anticytomegalovirus (CMV) drug ganciclovir. This drug enabled an important reduction of the burden of CMV morbidity and mortality in solid organ transplant recipients. Prevention of CMV infection and treatment of CMV disease requires drug administration during many weeks. Oral drug administration is therefore convenient. Valganciclovir has been developed to overcome the poor oral availability of ganciclovir, which limits its concentration exposure after oral administration and thus its efficacy. This prodrug crosses efficiently the intestinal barrier, is then hydrolyzed into ganciclovir, providing exposure similar to intravenous ganciclovir. Valganciclovir is now preferred for the prophylaxis and treatment of CMV infection in solid organ transplant recipients. Nevertheless, adequate dosage adjustment is necessary to optimize its use, avoiding either insufficient or exaggerate exposure related to differences in its pharmacokinetic profile between patients. The main goal of this thesis was to better describe the pharmacokinetic and pharmacodynamic profile of valganciclovir in solid organ transplant recipients, to assess their reproducibility and their predictability, and thus to evaluate the current recommendations for valganciclovir dosage adjustment and the potential contribution of routine therapeutic drug monitoring (TDM) to patients' management. A total of 437 ganciclovir plasma concentration data from 65 transplant patients (41 kidney, 12 lung, 10 heart and 2 liver recipients, 58 under oral valganciclovir prophylaxis, 8 under oral valganciclovir treatment and 2 under intravenous ganciclovir) were measured using a validated chromatographic method (HPLC) developed for this study. The results were analyzed by non-linear mixed effect modeling (NONMEM). A two-compartment model with first-order absorption appropriately described the data. Systemic clearance was markedly influenced by GFR, with further differences between graft types and sex (CL/GFR = 1.7 in kidney, 0.9 in heart and 1.2 in lung and liver recipients) with interpatient variability (CV%) of 26% and interoccasion variability of 12%. Body weight and sex influenced central volume of distribution (V1 = 0.34 l/kg in males and 0.27 l/kg in females) with an interpatient variability of 20%. Residual intrapatient variability was 21 %. No significant drug interaction influenced GCV disposition. VGC prophylactic efficacy and tolerability were good, without detectable dependence on GCV profile. In conclusion, this analysis highlights the importance of thorough adjustment of VGC dosage to renal function and body weight. Considering the good predictability and reproducibility of GCV profile after oral VGC in solid organ transplant recipients, routine TDM does not appear to be clinically indicated. However, GCV plasma measurement may still be helpful in specific clinical situations such as documentation of appropriate exposure in patients with potentially compromised absorption, or lack of response to CMV disease treatment, or under renal replacement therapy. RESUME : Le valganciclovir (Valcyte®) est un promédicament oral du ganciclovir qui est un anti-infectieux de référence contre les infections à cytomegalovirus (CMV). Cet antiviral a permis de réduire les effets délétères de cette infection jusqu'ici responsable d'une importante morbidité et mortalité chez les transplantés d'organe. La prévention et le traitement de l'infection à CMV sont donc nécessaires mais requièrent l'administration d'un agent antiviral sur une longue période. Un médicament administré par voie orale représente donc un avantage évident. Le valganciclovir a été développé dans le but d'améliorer la faible absorption orale du ganciclovir, et donc son efficacité. Cet ester valylique du ganciclovir traverse plus facilement la barrière gastro-intestinale, puis est hydrolysé en ganciclovir dans la circulation sanguine, produisant une exposition comparable à celle d'une perfusion intraveineuse de ganciclovir. De ce fait, le valganciclovir est devenu largement utilisé pour la prophylaxie mais aussi le traitement de l'infection à CMV. Néanmoins une utilisation optimale de ce nouveau médicament nécessite de bonnes connaissances sur son profil pharmacocinétique afin d'établir un schéma de dose adapté pour éviter tant une surexposition qu'une sous-exposition résultant des différences d'élimination entre les patients. Le but de cette thèse a été d'étudier le profil pharmacocinétique et pharmacodynamique du valganciclovir chez les transplantés d'organe ainsi que sa reproductibilité et sa prédictibilité. Il s'agissait d'apprécier de manière critique le schéma actuellement recommandé pour l'adaptation des doses de valganciclovir, mais aussi la contribution éventuelle d'un suivi des concentrations sanguines en routine. Un total de 437 taux sanguins de ganciclovir ont été mesurés, provenant de 65 patients transplantés d'organe (41 rénaux, 12 pulmonaires, 10 cardiaques et 2 hépatiques, 58 sous une prophylaxie orale de valganciclovir, 8 sous un traitement de valganciclovir et 2 sous un traitement intraveineux). Une méthode de chromatographie liquide à haute performance a été développée et validée pour cette étude. Les résultats ont été ensuite analysés par modélisation non linéaire à effets mixtes (NONMEM). Un modèle à deux compartiments avec absorption de premier ordre a permis de décrire les données. La clairance systémique était principalement influencée par le débit de filtration glomérulaire (GFR), avec une différence entre les types de greffe et les sexes (CL/GFR = 1.7 chez les greffés rénaux, 0.9 pour les greffés cardiaques et 1.2 pour le groupe des greffés pulmonaires et hépatiques) avec un variabilité inter-individuelle de 26% (CV%) et une variabilité inter-occasion de 12%. Le poids corporel ainsi que le sexe avaient une influence sur le volume central de distribution (V1 = 0.34 l/kg chez les hommes et 0.27 l/kg chez les femmes) avec une variabilité inter-individuelle de 20%. La variabilité intra-individuelle résiduelle était de 21 %. Aucune interaction médicamenteuse n'a montré d'influence sur le profil du ganciclovir. La prophylaxie avec le valganciclovir s'est révélée efficace et bien tolérée. En conclusion, cette analyse souligne l'importance d'une adaptation de la dose du valganciclovir à la fonction rénale et au poids du patient. Au vu de la bonne reproductibilité et prédictibilité du profil pharmacocinétique du ganciclovir chez les patients transplantés recevant du valganciclovir, un suivi des concentrations sanguines en routine ne semble pas cliniquement indiqué. Néanmoins, la mesure des taux plasmatiques de ganciclovir peut être utile dans certaines situations particulières, comme la vérification d'une exposition appropriée chez des patients susceptibles d'absorption insuffisante, ou ne répondant pas au traitement d'une infection à CMV ou encore sous épuration extra-rénale. RESUME LARGE PUBLIC : Le valganciclovir est un précurseur capable de libérer du ganciclovir, récemment développé pour améliorer la faible absorption orale de ce dernier. Une fois le valganciclovir absorbé, le ganciclovir libéré dans la circulation sanguine devient efficace contre les infections à cytomégalovirus. Ce virus largement répandu est responsable de maladies insidieuses et parfois graves chez les personnes présentant une baisse des défenses immunitaires, comme les greffés d'organe recevant un traitement anti-rejet. Le ganciclovir est administré pendant plusieurs mois consécutifs soit pour prévenir une infection après la transplantation, soit pour traiter une infection déclarée. La facilité d'administration du valganciclovir par voie orale représente un avantage sur une administration du ganciclovir par perfusion, qui nécessite une hospitalisation. Toutefois, la voie orale peut être une source supplémentaire de variabilité chez les patients, avec un impact potentiel sur l'efficacité ou la toxicité du médicament. Le but de cette étude a été - de décrire le devenir de ce médicament dans le corps humain (dont l'étude relève de la discipline de la pharmacocinétique) - de définir les facteurs cliniques pouvant expliquer les différences de concentration sanguine observées entre les patients sous une posologie donnée - d'explorer les relations entre les concentrations du médicament dans le sang et son efficacité ou la survenue d'effets indésirables (dont l'étude relève de la discipline de la pharmacodynamie). Cette étude a nécessité le développement et la validation, d'une méthode d'analyse pour mesurer la concentration sanguine du ganciclovir, puis son application à 437 échantillons provenant de 65 patients transplantés d'organe solide (41 rénaux, 12 pulmonaires, 10 cardiaques et 2 hépatiques) recevant du valganciclovir. Les résultats des mesures effectuées ont été analysés à l'aide d'un outil mathématique afin d'élaborer un modèle du devenir du médicament dans le sang chez chaque patient et à chaque occasion. Cette étude a permis d'évaluer chez des patients recevant le valganciclovir, la vitesse à laquelle l'organisme absorbe, distribue, puis élimine le médicament. La vitesse d'élimination dépendait étroitement de la fonction rénale, du type de greffe et du sexe alors que la distribution dépendait du poids et du sexe du patient. La variabilité non expliquée par ces facteurs cliniques était modérée et vraisemblablement sans conséquence clinique évidente soit sur l'efficacité ou la tolérance, qui se révèlent très satisfaisantes chez les patients de l'étude. Les observations n'ont pas révélé de relation entre les concentrations de médicament et l'efficacité thérapeutique ou la survenue d'effets indésirables, confirmant que les doses relativement faibles utilisées dans notre collectif de patients suffisaient à produire une exposition reproductible à des concentrations adéquates. En conclusion, le profil (et par conséquent l'absorption) du valganciclovir chez les patients transplantés semble bien prédictible après une adaptation de la dose à la fonction rénale et au poids du patient. Un contrôle systématique des concentrations sanguines n'est probablement pas indiqué en routine, mais cette mesure peut présenter un intérêt dans certaines conditions particulières.

Aggregation invariance in general clustering approaches

General clustering deals with weighted objects and fuzzy memberships. We investigate the group- or object-aggregation-invariance properties possessed by the relevant functionals (effective number of groups or objects, centroids, dispersion, mutual object-group information, etc.). The classical squared Euclidean case can be generalized to non-Euclidean distances, as well as to non-linear transformations of the memberships, yielding the c-means clustering algorithm as well as two presumably new procedures, the convex and pairwise convex clustering. Cluster stability and aggregation-invariance of the optimal memberships associated to the various clustering schemes are examined as well.

Estimating parameters for generalized mass action models using constraint propagation.

As modern molecular biology moves towards the analysis of biological systems as opposed to their individual components, the need for appropriate mathematical and computational techniques for understanding the dynamics and structure of such systems is becoming more pressing. For example, the modeling of biochemical systems using ordinary differential equations (ODEs) based on high-throughput, time-dense profiles is becoming more common-place, which is necessitating the development of improved techniques to estimate model parameters from such data. Due to the high dimensionality of this estimation problem, straight-forward optimization strategies rarely produce correct parameter values, and hence current methods tend to utilize genetic/evolutionary algorithms to perform non-linear parameter fitting. Here, we describe a completely deterministic approach, which is based on interval analysis. This allows us to examine entire sets of parameters, and thus to exhaust the global search within a finite number of steps. In particular, we show how our method may be applied to a generic class of ODEs used for modeling biochemical systems called Generalized Mass Action Models (GMAs). In addition, we show that for GMAs our method is amenable to the technique in interval arithmetic called constraint propagation, which allows great improvement of its efficiency. To illustrate the applicability of our method we apply it to some networks of biochemical reactions appearing in the literature, showing in particular that, in addition to estimating system parameters in the absence of noise, our method may also be used to recover the topology of these networks.

Environmental data mining and modeling based on machine learning algorithms and geostatistics

The paper presents some contemporary approaches to spatial environmental data analysis. The main topics are concentrated on the decision-oriented problems of environmental spatial data mining and modeling: valorization and representativity of data with the help of exploratory data analysis, spatial predictions, probabilistic and risk mapping, development and application of conditional stochastic simulation models. The innovative part of the paper presents integrated/hybrid model-machine learning (ML) residuals sequential simulations-MLRSS. The models are based on multilayer perceptron and support vector regression ML algorithms used for modeling long-range spatial trends and sequential simulations of the residuals. NIL algorithms deliver non-linear solution for the spatial non-stationary problems, which are difficult for geostatistical approach. Geostatistical tools (variography) are used to characterize performance of ML algorithms, by analyzing quality and quantity of the spatially structured information extracted from data with ML algorithms. Sequential simulations provide efficient assessment of uncertainty and spatial variability. Case study from the Chernobyl fallouts illustrates the performance of the proposed model. It is shown that probability mapping, provided by the combination of ML data driven and geostatistical model based approaches, can be efficiently used in decision-making process. (C) 2003 Elsevier Ltd. All rights reserved.

Quantitative modelling of transcription factor binding sites

Abstract One of the most important issues in molecular biology is to understand regulatory mechanisms that control gene expression. Gene expression is often regulated by proteins, called transcription factors which bind to short (5 to 20 base pairs),degenerate segments of DNA. Experimental efforts towards understanding the sequence specificity of transcription factors is laborious and expensive, but can be substantially accelerated with the use of computational predictions. This thesis describes the use of algorithms and resources for transcriptionfactor binding site analysis in addressing quantitative modelling, where probabilitic models are built to represent binding properties of a transcription factor and can be used to find new functional binding sites in genomes. Initially, an open-access database(HTPSELEX) was created, holding high quality binding sequences for two eukaryotic families of transcription factors namely CTF/NF1 and LEFT/TCF. The binding sequences were elucidated using a recently described experimental procedure called HTP-SELEX, that allows generation of large number (> 1000) of binding sites using mass sequencing technology. For each HTP-SELEX experiments we also provide accurate primary experimental information about the protein material used, details of the wet lab protocol, an archive of sequencing trace files, and assembled clone sequences of binding sequences. The database also offers reasonably large SELEX libraries obtained with conventional low-throughput protocols.The database is available at http://wwwisrec.isb-sib.ch/htpselex/ and and ftp://ftp.isrec.isb-sib.ch/pub/databases/htpselex. The Expectation-Maximisation(EM) algorithm is one the frequently used methods to estimate probabilistic models to represent the sequence specificity of transcription factors. We present computer simulations in order to estimate the precision of EM estimated models as a function of data set parameters(like length of initial sequences, number of initial sequences, percentage of nonbinding sequences). We observed a remarkable robustness of the EM algorithm with regard to length of training sequences and the degree of contamination. The HTPSELEX database and the benchmarked results of the EM algorithm formed part of the foundation for the subsequent project, where a statistical framework called hidden Markov model has been developed to represent sequence specificity of the transcription factors CTF/NF1 and LEF1/TCF using the HTP-SELEX experiment data. The hidden Markov model framework is capable of both predicting and classifying CTF/NF1 and LEF1/TCF binding sites. A covariance analysis of the binding sites revealed non-independent base preferences at different nucleotide positions, providing insight into the binding mechanism. We next tested the LEF1/TCF model by computing binding scores for a set of LEF1/TCF binding sequences for which relative affinities were determined experimentally using non-linear regression. The predicted and experimentally determined binding affinities were in good correlation.

Brain surface non-rigid registration in auditory processing

Résumé: Le développement rapide de nouvelles technologies comme l'imagerie médicale a permis l'expansion des études sur les fonctions cérébrales. Le rôle principal des études fonctionnelles cérébrales est de comparer l'activation neuronale entre différents individus. Dans ce contexte, la variabilité anatomique de la taille et de la forme du cerveau pose un problème majeur. Les méthodes actuelles permettent les comparaisons interindividuelles par la normalisation des cerveaux en utilisant un cerveau standard. Les cerveaux standards les plus utilisés actuellement sont le cerveau de Talairach et le cerveau de l'Institut Neurologique de Montréal (MNI) (SPM99). Les méthodes de recalage qui utilisent le cerveau de Talairach, ou celui de MNI, ne sont pas suffisamment précises pour superposer les parties plus variables d'un cortex cérébral (p.ex., le néocortex ou la zone perisylvienne), ainsi que les régions qui ont une asymétrie très importante entre les deux hémisphères. Le but de ce projet est d'évaluer une nouvelle technique de traitement d'images basée sur le recalage non-rigide et utilisant les repères anatomiques. Tout d'abord, nous devons identifier et extraire les structures anatomiques (les repères anatomiques) dans le cerveau à déformer et celui de référence. La correspondance entre ces deux jeux de repères nous permet de déterminer en 3D la déformation appropriée. Pour les repères anatomiques, nous utilisons six points de contrôle qui sont situés : un sur le gyrus de Heschl, un sur la zone motrice de la main et le dernier sur la fissure sylvienne, bilatéralement. Evaluation de notre programme de recalage est accomplie sur les images d'IRM et d'IRMf de neuf sujets parmi dix-huit qui ont participés dans une étude précédente de Maeder et al. Le résultat sur les images anatomiques, IRM, montre le déplacement des repères anatomiques du cerveau à déformer à la position des repères anatomiques de cerveau de référence. La distance du cerveau à déformer par rapport au cerveau de référence diminue après le recalage. Le recalage des images fonctionnelles, IRMf, ne montre pas de variation significative. Le petit nombre de repères, six points de contrôle, n'est pas suffisant pour produire les modifications des cartes statistiques. Cette thèse ouvre la voie à une nouvelle technique de recalage du cortex cérébral dont la direction principale est le recalage de plusieurs points représentant un sillon cérébral. Abstract : The fast development of new technologies such as digital medical imaging brought to the expansion of brain functional studies. One of the methodolgical key issue in brain functional studies is to compare neuronal activation between individuals. In this context, the great variability of brain size and shape is a major problem. Current methods allow inter-individual comparisions by means of normalisation of subjects' brains in relation to a standard brain. A largerly used standard brains are the proportional grid of Talairach and Tournoux and the Montreal Neurological Insititute standard brain (SPM99). However, there is a lack of more precise methods for the superposition of more variable portions of the cerebral cortex (e.g, neocrotex and perisyvlian zone) and in brain regions highly asymmetric between the two cerebral hemipsheres (e.g. planum termporale). The aim of this thesis is to evaluate a new image processing technique based on non-linear model-based registration. Contrary to the intensity-based, model-based registration uses spatial and not intensitiy information to fit one image to another. We extract identifiable anatomical features (point landmarks) in both deforming and target images and by their correspondence we determine the appropriate deformation in 3D. As landmarks, we use six control points that are situated: one on the Heschl'y Gyrus, one on the motor hand area, and one on the sylvian fissure, bilaterally. The evaluation of this model-based approach is performed on MRI and fMRI images of nine of eighteen subjects participating in the Maeder et al. study. Results on anatomical, i.e. MRI, images, show the mouvement of the deforming brain control points to the location of the reference brain control points. The distance of the deforming brain to the reference brain is smallest after the registration compared to the distance before the registration. Registration of functional images, i.e fMRI, doesn't show a significant variation. The small number of registration landmarks, i.e. six, is obvious not sufficient to produce significant modification on the fMRI statistical maps. This thesis opens the way to a new computation technique for cortex registration in which the main directions will be improvement of the registation algorithm, using not only one point as landmark, but many points, representing one particular sulcus.

On Modelling, System Identification and Control of Servo-Systems with a Flexible Load

The present study was done with two different servo-systems. In the first system, a servo-hydraulic system was identified and then controlled by a fuzzy gainscheduling controller. The second servo-system, an electro-magnetic linear motor in suppressing the mechanical vibration and position tracking of a reference model are studied by using a neural network and an adaptive backstepping controller respectively. Followings are some descriptions of research methods. Electro Hydraulic Servo Systems (EHSS) are commonly used in industry. These kinds of systems are nonlinearin nature and their dynamic equations have several unknown parameters.System identification is a prerequisite to analysis of a dynamic system. One of the most promising novel evolutionary algorithms is the Differential Evolution (DE) for solving global optimization problems. In the study, the DE algorithm is proposed for handling nonlinear constraint functionswith boundary limits of variables to find the best parameters of a servo-hydraulic system with flexible load. The DE guarantees fast speed convergence and accurate solutions regardless the initial conditions of parameters. The control of hydraulic servo-systems has been the focus ofintense research over the past decades. These kinds of systems are nonlinear in nature and generally difficult to control. Since changing system parameters using the same gains will cause overshoot or even loss of system stability. The highly non-linear behaviour of these devices makes them ideal subjects for applying different types of sophisticated controllers. The study is concerned with a second order model reference to positioning control of a flexible load servo-hydraulic system using fuzzy gainscheduling. In the present research, to compensate the lack of dampingin a hydraulic system, an acceleration feedback was used. To compare the results, a pcontroller with feed-forward acceleration and different gains in extension and retraction is used. The design procedure for the controller and experimental results are discussed. The results suggest that using the fuzzy gain-scheduling controller decrease the error of position reference tracking. The second part of research was done on a PermanentMagnet Linear Synchronous Motor (PMLSM). In this study, a recurrent neural network compensator for suppressing mechanical vibration in PMLSM with a flexible load is studied. The linear motor is controlled by a conventional PI velocity controller, and the vibration of the flexible mechanism is suppressed by using a hybrid recurrent neural network. The differential evolution strategy and Kalman filter method are used to avoid the local minimum problem, and estimate the states of system respectively. The proposed control method is firstly designed by using non-linear simulation model built in Matlab Simulink and then implemented in practical test rig. The proposed method works satisfactorily and suppresses the vibration successfully. In the last part of research, a nonlinear load control method is developed and implemented for a PMLSM with a flexible load. The purpose of the controller is to track a flexible load to the desired position reference as fast as possible and without awkward oscillation. The control method is based on an adaptive backstepping algorithm whose stability is ensured by the Lyapunov stability theorem. The states of the system needed in the controller are estimated by using the Kalman filter. The proposed controller is implemented and tested in a linear motor test drive and responses are presented.

Climate and human forcing of Alpine river flow

River flow in Alpine environments is likely to be highly sensitive to climate change because of the effects of warming upon snow and ice, and hence the intra-annual distribution of river runoff. It is also likely to be influenced strongly by human impacts both upon hydrology (e.g. flow abstraction) and river regulation. This paper compares the river flow and sediment flux of two Alpine drainage basins over the last 5 to 7 decades, one that is largely unimpacted by human activities, one strongly impacted by flow abstraction for hydroelectricity. The analysis shows that both river flow and sediment transport capacity are strongly dependent upon the effects of temperature and precipitation availability upon snow accumulation. As the latter tends to increase annual maximum flows, and given the non-linear form of most sediment transport laws, current warming trends may lead to increased sedimentation in Alpine rivers. However, extension to a system impacted upon by flow abstraction reveals the dominant effect that human activity can have upon river sedimentation but also how human response to sediment management has co-evolved with climate forcing to make disentangling the two very difficult.

Integrability of a linear center perturbed by a fourth degree homogeneous polynomial

In this work we study the integrability of a two-dimensional autonomous system in the plane with linear part of center type and non-linear part given by homogeneous polynomials of fourth degree. We give sufficient conditions for integrability in polar coordinates. Finally we establish a conjecture about the independence of the two classes of parameters which appear in the system; if this conjecture is true the integrable cases found will be the only possible ones.

Integrability of a linear center perturbed by a fifth degree homogeneous polynomial

In this work we study the integrability of two-dimensional autonomous system in the plane with linear part of center type and non-linear part given by homogeneous polynomials of fifth degree. We give a simple characterisation for the integrable cases in polar coordinates. Finally we formulate a conjecture about the independence of the two classes of parameters which appear on the system; if this conjecture is true the integrable cases found will be the only possible ones.