Measurements of glial metabolic fluxes with C-11-acetate using positron emission and an adapted NMR-based metabolic modeling approach

Objectives: Acetate brain metabolism has the particularity to occur specifically in glial cells. Labeling studies, using acetate labeled either with 13C (NMR) or 11C (PET), are governed by the same biochemical reactions and thus follow the same mathematical principles. In this study, the objective was to adapt an NMR acetate brain metabolism model to analyse [1-11C]acetate infusion in rats. Methods: Brain acetate infusion experiments were modeled using a two-compartment model approach used in NMR.1-3 The [1-11C]acetate labeling study was done using a beta scintillator.4 The measured radioactive signal represents the time evolution of the sum of all labeled metabolites in the brain. Using a coincidence counter in parallel, an arterial input curve was measured. The 11C at position C-1 of acetate is metabolized in the first turn of the TCA cycle to the position 5 of glutamate (Figure 1A). Through the neurotransmission process, it is further transported to the position 5 of glutamine and the position 5 of neuronal glutamate. After the second turn of the TCA cycle, tracer from [1-11C]acetate (and also a part from glial [5-11C]glutamate) is transferred to glial [1-11C]glutamate and further to [1-11C]glutamine and neuronal glutamate through the neurotransmission cycle. Brain poster session: oxidative mechanisms S460 Journal of Cerebral Blood Flow & Metabolism (2009) 29, S455-S466 Results: The standard acetate two-pool PET model describes the system by a plasma pool and a tissue pool linked by rate constants. Experimental data are not fully described with only one tissue compartment (Figure 1B). The modified NMR model was fitted successfully to tissue time-activity curves from 6 single animals, by varying the glial mitochondrial fluxes and the neurotransmission flux Vnt. A glial composite rate constant Kgtg=Vgtg/[Ace]plasma was extracted. Considering an average acetate concentration in plasma of 1 mmol/g5 and the negligible additional amount injected, we found an average Vgtg = 0.08±0.02 (n = 6), in agreement with previous NMR measurements.1 The tissue time-activity curve is dominated by glial glutamate and later by glutamine (Figure 1B). Labeling of neuronal pools has a low influence, at least for the 20 mins of beta-probe acquisition. Based on the high diffusivity of CO2 across the blood-brain barrier; 11CO2 is not predominant in the total tissue curve, even if the brain CO2 pool is big compared with other metabolites, due to its strong dilution through unlabeled CO2 from neuronal metabolism and diffusion from plasma. Conclusion: The two-compartment model presented here is also able to fit data of positron emission experiments and to extract specific glial metabolic fluxes. 11C-labeled acetate presents an alternative for faster measurements of glial oxidative metabolism compared to NMR, potentially applicable to human PET imaging. However, to quantify the relative value of the TCA cycle flux compared to the transmitochondrial flux, the chemical sensitivity of NMR is required. PET and NMR are thus complementary.

Approximation and support theorem for a wave equation in two space dimensions

We prove a characterization of the support of the law of the solution for a stochastic wave equation with two-dimensional space variable, driven by a noise white in time and correlated in space. The result is a consequence of an approximation theorem, in the convergence of probability, for equations obtained by smoothing the random noise. For some particular classes of coefficients, approximation in the Lp-norm for p¿1 is also proved.

Line search multilevel optimization as computational methods for dense optical flow

We evaluate the performance of different optimization techniques developed in the context of optical flow computation with different variational models. In particular, based on truncated Newton methods (TN) that have been an effective approach for large-scale unconstrained optimization, we de- velop the use of efficient multilevel schemes for computing the optical flow. More precisely, we evaluate the performance of a standard unidirectional mul- tilevel algorithm - called multiresolution optimization (MR/OPT), to a bidrec- tional multilevel algorithm - called full multigrid optimization (FMG/OPT). The FMG/OPT algorithm treats the coarse grid correction as an optimiza- tion search direction and eventually scales it using a line search. Experimental results on different image sequences using four models of optical flow com- putation show that the FMG/OPT algorithm outperforms both the TN and MR/OPT algorithms in terms of the computational work and the quality of the optical flow estimation.

A pipeline approach with spatial information for segmenting multiple sclerosis lesions on brain magnetic resonance imaging

Background: Conventional magnetic resonance imaging (MRI) techniques are highly sensitive to detect multiple sclerosis (MS) plaques, enabling a quantitative assessment of inflammatory activity and lesion load. In quantitative analyses of focal lesions, manual or semi-automated segmentations have been widely used to compute the total number of lesions and the total lesion volume. These techniques, however, are both challenging and time-consuming, being also prone to intra-observer and inter-observer variability.Aim: To develop an automated approach to segment brain tissues and MS lesions from brain MRI images. The goal is to reduce the user interaction and to provide an objective tool that eliminates the inter- and intra-observer variability.Methods: Based on the recent methods developed by Souplet et al. and de Boer et al., we propose a novel pipeline which includes the following steps: bias correction, skull stripping, atlas registration, tissue classification, and lesion segmentation. After the initial pre-processing steps, a MRI scan is automatically segmented into 4 classes: white matter (WM), grey matter (GM), cerebrospinal fluid (CSF) and partial volume. An expectation maximisation method which fits a multivariate Gaussian mixture model to T1-w, T2-w and PD-w images is used for this purpose. Based on the obtained tissue masks and using the estimated GM mean and variance, we apply an intensity threshold to the FLAIR image, which provides the lesion segmentation. With the aim of improving this initial result, spatial information coming from the neighbouring tissue labels is used to refine the final lesion segmentation.Results:The experimental evaluation was performed using real data sets of 1.5T and the corresponding ground truth annotations provided by expert radiologists. The following values were obtained: 64% of true positive (TP) fraction, 80% of false positive (FP) fraction, and an average surface distance of 7.89 mm. The results of our approach were quantitatively compared to our implementations of the works of Souplet et al. and de Boer et al., obtaining higher TP and lower FP values.Conclusion: Promising MS lesion segmentation results have been obtained in terms of TP. However, the high number of FP which is still a well-known problem of all the automated MS lesion segmentation approaches has to be improved in order to use them for the standard clinical practice. Our future work will focus on tackling this issue.

Information sharing and social network dynamics : a coevolutionary approach

The capacity to interact socially and share information underlies the success of many animal species, humans included. Researchers of many fields have emphasized the evo¬lutionary significance of how patterns of connections between individuals, or the social networks, and learning abilities affect the information obtained by animal societies. To date, studies have focused on the dynamics either of social networks, or of the spread of information. The present work aims to study them together. We make use of mathematical and computational models to study the dynamics of networks, where social learning and information sharing affect the structure of the population the individuals belong to. The number and strength of the relationships between individuals, in turn, impact the accessibility and the diffusion of the shared information. Moreover, we inves¬tigate how different strategies in the evaluation and choice of interacting partners impact the processes of knowledge acquisition and social structure rearrangement. First, we look at how different evaluations of social interactions affect the availability of the information and the network topology. We compare a first case, where individuals evaluate social exchanges by the amount of information that can be shared by the partner, with a second case, where they evaluate interactions by considering their partners' social status. We show that, even if both strategies take into account the knowledge endowments of the partners, they have very different effects on the system. In particular, we find that the first case generally enables individuals to accumulate higher amounts of information, thanks to the more efficient patterns of social connections they are able to build. Then, we study the effects that homophily, or the tendency to interact with similar partners, has on knowledge accumulation and social structure. We compare the case where individuals who know the same information are more likely to learn socially from each other, to the opposite case, where individuals who know different information are instead more likely to learn socially from each other. We find that it is not trivial to claim which strategy is better than the other. Depending on the possibility of forgetting information, the way new social partners can be chosen, and the population size, we delineate the conditions for which each strategy allows accumulating more information, or in a faster way For these conditions, we also discuss the topological characteristics of the resulting social structure, relating them to the information dynamics outcome. In conclusion, this work paves the road for modeling the joint dynamics of the spread of information among individuals and their social interactions. It also provides a formal framework to study jointly the effects of different strategies in the choice of partners on social structure, and how they favor the accumulation of knowledge in the population. - La capacité d'interagir socialement et de partager des informations est à la base de la réussite de nombreuses espèces animales, y compris les humains. Les chercheurs de nombreux domaines ont souligné l'importance évolutive de la façon dont les modes de connexions entre individus, ou réseaux sociaux et les capacités d'apprentissage affectent les informations obtenues par les sociétés animales. À ce jour, les études se sont concentrées sur la dynamique soit des réseaux sociaux, soit de la diffusion de l'information. Le présent travail a pour but de les étudier ensemble. Nous utilisons des modèles mathématiques et informatiques pour étudier la dynamique des réseaux, où l'apprentissage social et le partage d'information affectent la structure de la population à laquelle les individus appartiennent. Le nombre et la solidité des relations entre les individus ont à leurs tours un impact sur l'accessibilité et la diffusion de l'informa¬tion partagée. Par ailleurs, nous étudions comment les différentes stratégies d'évaluation et de choix des partenaires d'interaction ont une incidence sur les processus d'acquisition des connaissances ainsi que le réarrangement de la structure sociale. Tout d'abord, nous examinons comment des évaluations différentes des interactions sociales influent sur la disponibilité de l'information ainsi que sur la topologie du réseau. Nous comparons un premier cas, où les individus évaluent les échanges sociaux par la quantité d'information qui peut être partagée par le partenaire, avec un second cas, où ils évaluent les interactions en tenant compte du statut social de leurs partenaires. Nous montrons que, même si les deux stratégies prennent en compte le montant de connaissances des partenaires, elles ont des effets très différents sur le système. En particulier, nous constatons que le premier cas permet généralement aux individus d'accumuler de plus grandes quantités d'information, grâce à des modèles de connexions sociales plus efficaces qu'ils sont capables de construire. Ensuite, nous étudions les effets que l'homophilie, ou la tendance à interagir avec des partenaires similaires, a sur l'accumulation des connaissances et la structure sociale. Nous comparons le cas où des personnes qui connaissent les mêmes informations sont plus sus¬ceptibles d'apprendre socialement l'une de l'autre, au cas où les individus qui connaissent des informations différentes sont au contraire plus susceptibles d'apprendre socialement l'un de l'autre. Nous constatons qu'il n'est pas trivial de déterminer quelle stratégie est meilleure que l'autre. En fonction de la possibilité d'oublier l'information, la façon dont les nouveaux partenaires sociaux peuvent être choisis, et la taille de la population, nous déterminons les conditions pour lesquelles chaque stratégie permet d'accumuler plus d'in¬formations, ou d'une manière plus rapide. Pour ces conditions, nous discutons également les caractéristiques topologiques de la structure sociale qui en résulte, les reliant au résultat de la dynamique de l'information. En conclusion, ce travail ouvre la route pour la modélisation de la dynamique conjointe de la diffusion de l'information entre les individus et leurs interactions sociales. Il fournit également un cadre formel pour étudier conjointement les effets de différentes stratégies de choix des partenaires sur la structure sociale et comment elles favorisent l'accumulation de connaissances dans la population.

Fate of the herbicide glyphosate and its metabolite AMPA in soils and their transfer to surface waters: A multi-scale approach in the Lavaux vineyards, western Switzerland

The use of herbicides in agriculture may lead to environmental problems, such as surface water pollution, with a potential risk for aquatic organisms. The herbicide glyphosate is the most used active ingredient in the world and in Switzerland. In the Lavaux vineyards it is nearly the only molecule applied. This work aimed at studying its fate in soils and its transfer to surface waters, using a multi-scale approach: from molecular (10-9 m) and microscopic scales (10-6 m), to macroscopic (m) and landscape ones (103 m). First of all, an analytical method was developed for the trace level quantification of this widely used herbicide and its main by-product, aminomethylphosphonic acid (AMPA). Due to their polar nature, their derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl) was done prior to their concentration and purification by solid phase extraction. They were then analyzed by ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The method was tested in different aqueous matrices with spiking tests and validated for the matrix effect correction in relevant environmental samples. Calibration curves established between 10 and 1000ng/l showed r2 values above 0.989, mean recoveries varied between 86 and 133% and limits of detection and quantification of the method were as low as 5 and 10ng/l respectively. At the parcel scale, two parcels of the Lavaux vineyard area, located near the Lutrive River at 6km to the east of Lausanne, were monitored to assess to which extent glyphosate and AMPA were retained in the soil or exported to surface waters. They were equipped at their bottom with porous ceramic cups and runoff collectors, which allowed retrieving water samples for the growing seasons 2010 and 2011. Results revealed that the mobility of glyphosate and AMPA in the unsaturated zone was likely driven by the precipitation regime and the soil characteristics, such as slope, porosity structure and layer permeability discrepancy. Elevated glyphosate and AMPA concentrations were measured at 60 and 80 cm depth at parcel bottoms, suggesting their infiltration in the upper parts of the parcels and the presence of preferential flow in the studied parcels. Indeed, the succession of rainy days induced the gradual saturation of the soil porosity, leading to rapid infiltration through macropores, as well as surface runoff formation. Furthermore, the presence of more impervious weathered marls at 100 cm depth induced throughflows, the importance of which for the lateral transport of the herbicide molecules was determined by the slope steepness. Important rainfall events (>10 mm/day) were clearly exporting molecules from the soil top layer, as indicated by important concentrations in runoff samples. A mass balance showed that total loss (10-20%) mainly occurred through surface runoff (96%) and, to a minor extent, by throughflows in soils (4%), with subsequent exfiltration to surface waters. Observations made in the Lutrive River revealed interesting details of glyphosate and AMPA dynamics in urbanized landscapes, such as the Lavaux vineyards. Indeed, besides their physical and chemical properties, herbicide dynamics at the catchment level strongly depend on application rates, precipitation regime, land use and also on the presence of drains or constructed channels. Elevated concentrations, up to 4970 ng/l, observed just after the application, confirmed the diffuse export of these compounds from the vineyard area by surface runoff during main rain events. From April to September 2011, a total load of 7.1 kg was calculated, with 85% coming from vineyards and minor urban sources and 15% from arable crops. Small vineyard surfaces could generate high concentrations of herbicides and contribute considerably to the total load calculated at the outlet, due to their steep slopes (~10%). The extrapolated total amount transferred yearly from the Lavaux vineyards to the Lake of Geneva was of 190kg. At the molecular scale, the possible involvement of dissolved organic matter (DOM) in glyphosate and copper transport was studied using UV/Vis fluorescence spectroscopy. Combined with parallel factor (PARAFAC) analysis, this technique allowed characterizing DOM of soil and surface water samples from the studied vineyard area. Glyphosate concentrations were linked to the fulvic-like spectroscopic signature of DOM in soil water samples, as well as to copper, suggesting the formation of ternary complexes. In surface water samples, its concentrations were also correlated to copper ones, but not in a significant way to the fulvic-like signature. Quenching experiments with standards confirmed field tendencies in the laboratory, with a stronger decrease in fluorescence intensity for fulvic-like fluorophore than for more aromatic ones. Lastly, based on maximum concentrations measured in the river, an environmental risk for these compounds was assessed, using laboratory tests and ecotoxicity data from the literature. In our case and with the methodology applied, the risk towards aquatic species was found negligible (RF<1).

Maintenance of polymorphism : a theoretical approach using multilocus systems

Résumé La thématique de cette thèse peut être résumée par le célèbre paradoxe de biologie évolutive sur le maintien du polymorphisme face à la sélection et par l'équation du changement de fréquence gamétique au cours du temps dû, à la sélection. La fréquence d'un gamète xi à la génération (t + 1) est: !!!Equation tronquée!!! Cette équation est utilisée pour générer des données utlisée tout au long de ce travail pour 2, 3 et 4 locus dialléliques. Le potentiel de l'avantage de l'hétérozygote pour le maintien du polymorphisme est le sujet de la première partie. La définition commune de l'avantage de l'hétérozygote n'etant applicable qu'a un locus ayant 2 allèles, cet avantage est redéfini pour un système multilocus sur les bases de précédentes études. En utilisant 5 définitions différentes de l'avantage de l'hétérozygote, je montre que cet avantage ne peut être un mécanisme général dans le maintien du polymorphisme sous sélection. L'étude de l'influence de locus non-détectés sur les processus évolutifs, seconde partie de cette thèse, est motivée par les travaux moléculaires ayant pour but de découvrir le nombre de locus codant pour un trait. La plupart de ces études sous-estiment le nombre de locus. Je montre que des locus non-détectés augmentent la probabilité d'observer du polymorphisme sous sélection. De plus, les conclusions sur les facteurs de maintien du polymorphisme peuvent être trompeuses si tous les locus ne sont pas détectés. Dans la troisième partie, je m'intéresse à la valeur attendue de variance additive après un goulot d'étranglement pour des traits sélectionés. Une études précédente montre que le niveau de variance additive après goulot d'étranglement augmente avec le nombre de loci. Je montre que le niveau de variance additive après un goulot d'étranglement augmente (comparé à des traits neutres), mais indépendamment du nombre de loci. Par contre, le taux de recombinaison a une forte influence, entre autre en regénérant les gamètes disparus suite au goulot d'étranglement. La dernière partie de ce travail de thèse décrit un programme pour le logiciel de statistique R. Ce programme permet d'itérer l'équation ci-dessus en variant les paramètres de sélection, recombinaison et de taille de populations pour 2, 3 et 4 locus dialléliques. Cette thèse montre qu'utiliser un système multilocus permet d'obtenir des résultats non-conformes à ceux issus de systèmes rnonolocus (la référence en génétique des populations). Ce programme ouvre donc d'intéressantes perspectives en génétique des populations. Abstract The subject of this PhD thesis can be summarized by one famous paradox of evolu-tionary biology: the maintenance of polymorphism in the face of selection, and one classical equation of theoretical population genetics: the changes in gametic frequencies due to selection and recombination. The frequency of gamete xi at generation (t + 1) is given by: !!! Truncated equation!!! This equation is used to generate data on selection at two, three, and four diallelic loci for the different parts of this work. The first part focuses on the potential of heterozygote advantage to maintain genetic polymorphism. Results of previous studies are used to (re)define heterozygote advantage for multilocus systems, since the classical definition is for one diallelic locus. I use 5 different definitions of heterozygote advantage. And for these five definitions, I show that heterozygote advantage is not a general mechanism for the maintenance of polymorphism. The study of the influence of undetected loci on evolutionary processes (second part of this work) is motivated by molecular works which aim at discovering the loci coding for a trait. For most of these works, some coding loci remains undetected. I show that undetected loci increases the probability of maintaining polymorphism under selection. In addition, conclusions about the factor that maintain polymorphism can be misleading if not all loci are considered. This is, therefore, only when all loci are detected that exact conclusions on the level of maintained polymorphism or on the factor(s) that maintain(s) polymorphism could be drawn. In the third part, the focus is on the expected release of additive genetic variance after bottleneck for selected traits. A previous study shows that the expected release of additive variance increases with an increase in the number of loci. I show that the expected release of additive variance after bottleneck increases for selected traits (compared with neutral), but this increase is not a function of the number of loci, but function of the recombination rate. Finally, the last part of this PhD thesis is a description of a package for the statistical software R that implements the Equation given above. It allows to generate data for different scenario regarding selection, recombination, and population size. This package opens perspectives for the theoretical population genetics that mainly focuses on one locus, while this work shows that increasing the number of loci leads not necessarily to straightforward results.

Of flies, mice and men: a systematic approach to understanding the early life origins of chronic lung disease.

Despite intensive research efforts, the aetiology of the majority of chronic lung diseases (CLD) in both, children and adults, remains elusive. Current therapeutic options are limited, providing only symptomatic relief, rather than treating the underlying condition, or preventing its development in the first place. Thus, there is a strong and unmet clinical need for the development of both, novel effective therapies and preventative strategies for CLD. Many studies suggest that modifications of prenatal and/or early postnatal lung development will have important implications for future lung function and risk of CLD throughout life. This view represents a fundamental change of current pathophysiological concepts and treatment paradigms, and holds the potential to develop novel preventative and/or therapeutic strategies. However, for the successful development of such approaches, key questions, such as a clear understanding of underlying mechanisms of impaired lung development, the identification and validation of relevant preclinical models to facilitate translational research, and the development of concepts for correction of aberrant development, all need to be solved. Accordingly, a European Science Foundation Exploratory Workshop was held where clinical, translational and basic research scientists from different disciplines met to discuss potential mechanisms of developmental origins of CLD, and to identify major knowledge gaps in order to delineate a roadmap for future integrative research.

The Dynamic Analysis of a Human Skeleton Using the Flexile Multibody Simulation Approach

The human motion study, which relies on mathematical and computational models ingeneral, and multibody dynamic biomechanical models in particular, has become asubject of many recent researches. The human body model can be applied to different physical exercises and many important results such as muscle forces, which are difficult to be measured through practical experiments, can be obtained easily. In the work, human skeletal lower limb model consisting of three bodies in build using the flexible multibody dynamics simulation approach. The floating frame of reference formulation is used to account for the flexibility in the bones of the human lower limb model. The main reason of considering the flexibility inthe human bones is to measure the strains in the bone result from different physical exercises. It has been perceived the bone under strain will become stronger in order to cope with the exercise. On the other hand, the bone strength is considered and important factors in reducing the bone fractures. The simulation approach and model developed in this work are used to measure the bone strain results from applying raising the sole of the foot exercise. The simulation results are compared to the results available in literature. The comparison shows goof agreement. This study sheds the light on the importance of using the flexible multibody dynamic simulation approach to build human biomechanical models, which can be used in developing some exercises to achieve the optimalbone strength.

Monte Carlo Methods in Parameter Estimation of Nonlinear Models

Yksi keskeisimmistä tehtävistä matemaattisten mallien tilastollisessa analyysissä on mallien tuntemattomien parametrien estimointi. Tässä diplomityössä ollaan kiinnostuneita tuntemattomien parametrien jakaumista ja niiden muodostamiseen sopivista numeerisista menetelmistä, etenkin tapauksissa, joissa malli on epälineaarinen parametrien suhteen. Erilaisten numeeristen menetelmien osalta pääpaino on Markovin ketju Monte Carlo -menetelmissä (MCMC). Nämä laskentaintensiiviset menetelmät ovat viime aikoina kasvattaneet suosiotaan lähinnä kasvaneen laskentatehon vuoksi. Sekä Markovin ketjujen että Monte Carlo -simuloinnin teoriaa on esitelty työssä siinä määrin, että menetelmien toimivuus saadaan perusteltua. Viime aikoina kehitetyistä menetelmistä tarkastellaan etenkin adaptiivisia MCMC menetelmiä. Työn lähestymistapa on käytännönläheinen ja erilaisia MCMC -menetelmien toteutukseen liittyviä asioita korostetaan. Työn empiirisessä osuudessa tarkastellaan viiden esimerkkimallin tuntemattomien parametrien jakaumaa käyttäen hyväksi teoriaosassa esitettyjä menetelmiä. Mallit kuvaavat kemiallisia reaktioita ja kuvataan tavallisina differentiaaliyhtälöryhminä. Mallit on kerätty kemisteiltä Lappeenrannan teknillisestä yliopistosta ja Åbo Akademista, Turusta.

A Topological Approach to Fuzzy Sets

This thesis presents a topological approach to studying fuzzy setsby means of modifier operators. Modifier operators are mathematical models, e.g., for hedges, and we present briefly different approaches to studying modifier operators. We are interested in compositional modifier operators, modifiers for short, and these modifiers depend on binary relations. We show that if a modifier depends on a reflexive and transitive binary relation on U, then there exists a unique topology on U such that this modifier is the closure operator in that topology. Also, if U is finite then there exists a lattice isomorphism between the class of all reflexive and transitive relations and the class of all topologies on U. We define topological similarity relation "≈" between L-fuzzy sets in an universe U, and show that the class LU/ ≈ is isomorphic with the class of all topologies on U, if U is finite and L is suitable. We consider finite bitopological spaces as approximation spaces, and we show that lower and upper approximations can be computed by means of α-level sets also in the case of equivalence relations. This means that approximations in the sense of Rough Set Theory can be computed by means of α-level sets. Finally, we present and application to data analysis: we study an approach to detecting dependencies of attributes in data base-like systems, called information systems.

Practical applications of a systematic approach to the chemical abatement of pollutants in water and air

The present dissertation is devoted to the systematic approach to the development of organic toxic and refractory pollutants abatement by chemical decomposition methods in aqueous and gaseous phases. The systematic approach outlines the basic scenario of chemical decomposition process applications with a step-by-step approximation to the most effective result with a predictable outcome for the full-scale application, confirmed by successful experience. The strategy includes the following steps: chemistry studies, reaction kinetic studies in interaction with the mass transfer processes under conditions of different control parameters, contact equipment design and studies, mathematical description of the process for its modelling and simulation, processes integration into treatment technology and its optimisation, and the treatment plant design. The main idea of the systematic approach for oxidation process introduction consists of a search for the most effective combination between the chemical reaction and the treatment device, in which the reaction is supposed to take place. Under this strategy,a knowledge of the reaction pathways, its products, stoichiometry and kinetics is fundamental and, unfortunately, often unavailable from the preliminary knowledge. Therefore, research made in chemistry on novel treatment methods, comprisesnowadays a substantial part of the efforts. Chemical decomposition methods in the aqueous phase include oxidation by ozonation, ozone-associated methods (O3/H2O2, O3/UV, O3/TiO2), Fenton reagent (H2O2/Fe2+/3+) and photocatalytic oxidation (PCO). In the gaseous phase, PCO and catalytic hydrolysis over zero valent ironsare developed. The experimental studies within the described methodology involve aqueous phase oxidation of natural organic matter (NOM) of potable water, phenolic and aromatic amino compounds, ethylene glycol and its derivatives as de-icing agents, and oxygenated motor fuel additives ¿ methyl tert-butyl ether (MTBE) ¿ in leachates and polluted groundwater. Gas-phase chemical decomposition includes PCO of volatile organic compounds and dechlorination of chlorinated methane derivatives. The results of the research summarised here are presented in fifteenattachments (publications and papers submitted for publication and under preparation).

Selective catalytic reduction of nitrogen oxides with ammonia in forced unsteady state reactors - Case based reasoning and mathematical model simulation reasoning

The application of forced unsteady-state reactors in case of selective catalytic reduction of nitrogen oxides (NOx) with ammonia (NH3) is sustained by the fact that favorable temperature and composition distributions which cannot be achieved in any steady-state regime can be obtained by means of unsteady-state operations. In a normal way of operation the low exothermicity of the selective catalytic reduction (SCR) reaction (usually carried out in the range of 280-350°C) is not enough to maintain by itself the chemical reaction. A normal mode of operation usually requires supply of supplementary heat increasing in this way the overall process operation cost. Through forced unsteady-state operation, the main advantage that can be obtained when exothermic reactions take place is the possibility of trapping, beside the ammonia, the moving heat wave inside the catalytic bed. The unsteady state-operation enables the exploitation of the thermal storage capacity of the catalyticbed. The catalytic bed acts as a regenerative heat exchanger allowing auto-thermal behaviour when the adiabatic temperature rise is low. Finding the optimum reactor configuration, employing the most suitable operation model and identifying the reactor behavior are highly important steps in order to configure a proper device for industrial applications. The Reverse Flow Reactor (RFR) - a forced unsteady state reactor - corresponds to the above mentioned characteristics and may be employed as an efficient device for the treatment of dilute pollutant mixtures. As a main disadvantage, beside its advantages, the RFR presents the 'wash out' phenomena. This phenomenon represents emissions of unconverted reactants at every switch of the flow direction. As a consequence our attention was focused on finding an alternative reactor configuration for RFR which is not affected by the incontrollable emissions of unconverted reactants. In this respect the Reactor Network (RN) was investigated. Its configuration consists of several reactors connected in a closed sequence, simulating a moving bed by changing the reactants feeding position. In the RN the flow direction is maintained in the same way ensuring uniformcatalyst exploitation and in the same time the 'wash out' phenomena is annulated. The simulated moving bed (SMB) can operate in transient mode giving practically constant exit concentration and high conversion levels. The main advantage of the reactor network operation is emphasizedby the possibility to obtain auto-thermal behavior with nearly uniformcatalyst utilization. However, the reactor network presents only a small range of switching times which allow to reach and to maintain an ignited state. Even so a proper study of the complex behavior of the RN may give the necessary information to overcome all the difficulties that can appear in the RN operation. The unsteady-state reactors complexity arises from the fact that these reactor types are characterized by short contact times and complex interaction between heat and mass transportphenomena. Such complex interactions can give rise to a remarkable complex dynamic behavior characterized by a set of spatial-temporal patterns, chaotic changes in concentration and traveling waves of heat or chemical reactivity. The main efforts of the current research studies concern the improvement of contact modalities between reactants, the possibility of thermal wave storage inside the reactor and the improvement of the kinetic activity of the catalyst used. Paying attention to the above mentioned aspects is important when higher activity even at low feeding temperatures and low emissions of unconverted reactants are the main operation concerns. Also, the prediction of the reactor pseudo or steady-state performance (regarding the conversion, selectivity and thermal behavior) and the dynamicreactor response during exploitation are important aspects in finding the optimal control strategy for the forced unsteady state catalytic tubular reactors. The design of an adapted reactor requires knowledge about the influence of its operating conditions on the overall process performance and a precise evaluation of the operating parameters rage for which a sustained dynamic behavior is obtained. An apriori estimation of the system parameters result in diminution of the computational efforts. Usually the convergence of unsteady state reactor systems requires integration over hundreds of cycles depending on the initial guess of the parameter values. The investigation of various operation models and thermal transfer strategies give reliable means to obtain recuperative and regenerative devices which are capable to maintain an auto-thermal behavior in case of low exothermic reactions. In the present research work a gradual analysis of the SCR of NOx with ammonia process in forced unsteady-state reactors was realized. The investigation covers the presentationof the general problematic related to the effect of noxious emissions in the environment, the analysis of the suitable catalysts types for the process, the mathematical analysis approach for modeling and finding the system solutions and the experimental investigation of the device found to be more suitable for the present process. In order to gain information about the forced unsteady state reactor design, operation, important system parameters and their values, mathematical description, mathematicalmethod for solving systems of partial differential equations and other specific aspects, in a fast and easy way, and a case based reasoning (CBR) approach has been used. This approach, using the experience of past similarproblems and their adapted solutions, may provide a method for gaining informations and solutions for new problems related to the forced unsteady state reactors technology. As a consequence a CBR system was implemented and a corresponding tool was developed. Further on, grooving up the hypothesis of isothermal operation, the investigation by means of numerical simulation of the feasibility of the SCR of NOx with ammonia in the RFRand in the RN with variable feeding position was realized. The hypothesis of non-isothermal operation was taken into account because in our opinion ifa commercial catalyst is considered, is not possible to modify the chemical activity and its adsorptive capacity to improve the operation butis possible to change the operation regime. In order to identify the most suitable device for the unsteady state reduction of NOx with ammonia, considering the perspective of recuperative and regenerative devices, a comparative analysis of the above mentioned two devices performance was realized. The assumption of isothermal conditions in the beginningof the forced unsteadystate investigation allowed the simplification of the analysis enabling to focus on the impact of the conditions and mode of operation on the dynamic features caused by the trapping of one reactant in the reactor, without considering the impact of thermal effect on overall reactor performance. The non-isothermal system approach has been investigated in order to point out the important influence of the thermal effect on overall reactor performance, studying the possibility of RFR and RN utilization as recuperative and regenerative devices and the possibility of achieving a sustained auto-thermal behavior in case of lowexothermic reaction of SCR of NOx with ammonia and low temperature gasfeeding. Beside the influence of the thermal effect, the influence of the principal operating parameters, as switching time, inlet flow rate and initial catalyst temperature have been stressed. This analysis is important not only because it allows a comparison between the two devices and optimisation of the operation, but also the switching time is the main operating parameter. An appropriate choice of this parameter enables the fulfilment of the process constraints. The level of the conversions achieved, the more uniform temperature profiles, the uniformity ofcatalyst exploitation and the much simpler mode of operation imposed the RN as a much more suitable device for SCR of NOx with ammonia, in usual operation and also in the perspective of control strategy implementation. Theoretical simplified models have also been proposed in order to describe the forced unsteady state reactors performance and to estimate their internal temperature and concentration profiles. The general idea was to extend the study of catalytic reactor dynamics taking into account the perspectives that haven't been analyzed yet. The experimental investigation ofRN revealed a good agreement between the data obtained by model simulation and the ones obtained experimentally.

Teaching fundamentals of computing theory: a constructivist approach

A Fundamentals of Computing Theory course involves different topics that are core to the Computer Science curricula and whose level of abstraction makes them difficult both to teach and to learn. Such difficulty stems from the complexity of the abstract notions involved and the required mathematical background. Surveys conducted among our students showed that many of them were applying some theoretical concepts mechanically rather than developing significant learning. This paper shows a number of didactic strategies that we introduced in the Fundamentals of Computing Theory curricula to cope with the above problem. The proposed strategies were based on a stronger use of technology and a constructivist approach. The final goal was to promote more significant learning of the course topics.