Dissertations / Theses on the topic 'Traces of functions'

Interpolating and sampling sequences in spaces of functions are classical subjects in complex and harmonic analysis. A sequence of points is said to be interpolating if, given any collection of values, we can find a function from the space which takes these values on the points of the sequence, and a sequence of points is said to be sampling if it is possible to recover a function from the space knowing the values of the function on the sequence. In Fock spaces these sequences have been characterised in terms of a Beurling type density, that is, interpolating sequences are those sequences whose density is less than a certain critical value, and sampling sequences are those sequences whose density is greater than the same critical value. A critical sequence, that is a sequence whose density is exactly the critical value, is almost an interpolating sequence and almost a sampling sequence. In this thesis we have charaterised completely the trace of functions in these Fock spaces on critical sequences in terms of the discrete Beurling-Ahlfors transform. We also study random point processes in the complex plane and in the unit disc. These random point processes are the zero sets of analytic functions. These functions can be constructed through random linear combinations of elements of a basis for a space of functions. The distribution of the zero set of the function formed by taking a basis for the classical Bargmann-Fock space is well known, and depends on a translation-invariance inherent to the space. We have generalised these ideas to inhomogeneous Fock spaces, where no such invariance exists. In particular we see that the expected number of points is related to a certain measure associated to the space. We also study asymptotic normality and a ‘hole theorem’, that calculates the probability that there are no points in a disc of radius r. We study analogous processes in the unit disc, and on the real line. We calculate the variance of the process in the disc, and we prove a ‘hole theorem’ for large values of the ‘intensity’ of the process. In the real line we study the probability of a large gap for a process that is invariant under translations.<br>Las sucesiones de interpolación y de muestreo en espacios de funciones son temas clásicos en el análisis complejo y armónico. Se dice que una sucesión de puntos es de interpolación si dada una colección de valores podemos hallar una función del espacio que toma estos valores en los puntos de la sucesión y se dice que una sucesión de puntos es de muestreo si se puede recuperar una función cuando se sabe los valores de la función en dicha sucesión. En los espacios de Fock estas sucesiones han sido caracterizadas en términos de una densidad de tipo Beurling, es decir, las sucesiones de interpolación son las que tienen densidad menor que un cierto valor crítico, y las de muestreo son las que tienen densidad mayor que el mismo valor crítico. En esta tesis hemos caracterizado completamente la traza de funciones en estos espacios de Fock sobre sucesiones que tiene densidad igual al valor crítico en términos de la transformada de Beurling-Ahlfors discreta. También estudiamos procesos de puntos aleatorios en el plano complejo y en el disco unidad. Estos procesos de puntos aleatorios son los conjuntos de ceros de funciones analíticas. Se pueden construir dichas funciones mediante sumas aleatorias de funciones que forman una base de un espacio de funciones. La distribución del conjunto de ceros cuando se toma una base del espacio clásico de Bargmann-Fock es bien conocida, y depende de una invariancia por translaciones inherente al espacio. Hemos generalizado estas ideas a espacios de Fock no homogéneos, donde no existe ninguna invariancia. En particular, veamos que la esperanza del número de puntos está relacionada con una medida asociado al espacio. También estudiamos la normalidad asintótica y un ‘teorema del agujero’, que calcula la probabilidad asintótica de que no haya ceros en un disco de radio r. Estudiamos procesos análogos en el disco unidad, y en la recta. Calculamos la variancia de dicho proceso en el disco, y demostramos otro ‘teorema del agujero’, para grandes valores de la ‘intensidad’ del proceso. En la recta estudiamos la probabilidad de un hueco para un proceso que es invariante por translaciones.

Questa tesi fornisce una panoramica sulla teoria delle funzioni Sobolev e BV nel contesto degli spazi metrici con misura. Vengono messe a confronto diverse caratterizzazioni di tali spazi al fine di evidenziarne le interconnessioni e le condizioni che garantiscono l'equivalenza delle definizioni. Dunque, si discute la struttura differenziale introdotta da N. Gigli in un articolo del 2014 per dare una nuova definizione di funzioni BV nel setting RCD(K,\infty) attraverso opportuni campi vettoriali. Di seguito, nel contesto metrico doubling con disuguaglianza di Poincaré, si danno nuove formule di integrazione per parti utilizzando campi a "divergenza-misura" per trattare poi il problema delle tracce delle funzioni BV. Si confronta la teoria delle "rough traces" (riadattata al presente setting, cfr. V. Maz'ya) con l'operatore di traccia definito mediante punti di Lebesgue, trovando le condizioni in cui le due caratterizzazioni coincidono.<br>This thesis offers a survey on the theory of Sobolev and BV functions in the setting of metric measure spaces. We compare different characterizations of such spaces in order to emphasize their relationships along with the conditions which ensure the equivalence of the definitions. Then, we discuss the differential structure introduced by N. Gigli in a paper of 2014 to give a new definition of BV functions in the RCD(K,\infty) setting, making use of suitable vector fileds. Later, in the metric doubling setting with Poincaré inequality, we give new integration by parts formulæ via "divergence-measure" vector fields to attack the issue of traces of BV functions. We compare the theory of "rough traces" (re-adapted to the present setting, cfr. V. Maz'ya) with the trace operator defined via Lebesgue points, finding the conditions under which the two characterizations coincide.

Duke and Jenkins defined a family of linear maps from spaces of weakly holomorphic modular forms of negative integral weight and level 1 into spaces of weakly holomorphic modular forms of half integral weight and level 4 and showed that these lifts preserve the integrality of Fourier coefficients. We show that the generalization of these lifts to modular forms of genus 0 odd prime level also preserves the integrality of Fourier coefficients.

Les sols des friches industrielles sont souvent multi-polluées et représentent des surfaces toujours plus importantes présentant de forts enjeux sociaux-économiques. Leur réhabilitation passe par une bonne compréhension du fonctionnement écologique des sols, qui, en plus d’être pollués, présentent des structures et des teneurs en nutriments souvent inhabituelles. Malgré cela, une recolonisation par la faune, la flore et les microorganismes est généralement observée. La capacité de ces nouvelles communautés à restaurer et maintenir les fonctions clés des sols reste à évaluer, et cela semble indissociable de la mesure d’une ou plusieurs fonctions écosystémiques. La décomposition de la litière est un processus écosystémique clef permettant la réalisation des cycles biogéochimiques du carbone et des nutriments. Les processus de la décomposition dépendent à la fois de ses acteurs (faune et microorganismes) et de la qualité de la litière végétale. De ce fait, la réponse de cette fonction écosystémique à la pollution du sol intègre les effets de cette pollution sur les communautés de plantes, d’animaux, et de microorganismes, ce qui en fait un indicateur potentiellement pertinent pour évaluer les effets de la pollution sur le fonctionnement des écosystèmes du sol. L’objectif central de cette thèse a donc été d’étudier le fonctionnement des friches industrielles en se focalisant sur les effets délétères de la pollution des sols sur la décomposition de la litière de feuilles. L’hypothèse centrale découlant de cet objectif a été que la pollution des sols pouvait impacter la décomposition par deux voies d’action. (1) La première voie, directe, est constituée de l’ensemble des effets délétères que pourraient provoquer les polluants sur les acteurs de la décomposition dont dépend la bonne réalisation de cette fonction. (2) Concernant la deuxième voie d’action, nous avons supposé que la pollution, en entraînant des modifications de la physiologie des plantes, pouvait modifier les paramètres physico-chimiques de la litière et ainsi impacter de façon indirecte la décomposition des litières. Nos résultats ont permis de montrer l’absence de l’effet direct pour huit friches industrielles fortement polluées, et ce malgré des perturbations des communautés d’acteurs, avec notamment une augmentation de l’abondance des détritivores et une modification de la colonisation microbienne des litières sur les sites pollués. Ces résultats plaident en faveur d’une redondance fonctionnelle suffisante au sein de ces communautés, permettant de maintenir le processus de décomposition. Nous avons également montré un effet indirect positif de la pollution sur la décomposition. Cet effet résulte de l’amélioration systématique de la qualité de la litière, entraînant dans certains cas une augmentation de l’activité des acteurs de la décomposition. Par ailleurs, nous avons également montré une accumulation des polluants dans ces mêmes litières, en particulier le Zn et le Cd, polluants pouvant potentiellement produire des effets délétères sur les acteurs de la décomposition. Toutefois, la présence de ces ETM n’a pas semblé influencer la consommation des litières par certains acteurs de la décomposition de la litière. Cependant, ce résultat reste à valider in situ en présence de l’ensemble des communautés de détritivores. De nombreuses perspectives s’ouvrent à la suite de ces travaux. Parmi elles, il reste notamment à déterminer 1) quels sont les mécanismes (physiologiques) qui entrainent une augmentation de la qualité des litières produites sur les sols contaminés ? 2) comment des communautés différentes permettent d’assurer des taux de décomposition similaires ? et 3) quels sont les impacts de la consommation des litières provenant des sites contaminés sur le fonctionnement et la physiologie des détritivores ?<br>Brownfield soils are multi-polluted areas, which cover an increasing surface and thus present serious socio-economical challenges. A better understanding of the ecological functioning of these sites is mandatory for their restoration. In addition to the high pollution found at these sites, brownfields are characterized by a specific soil structure and occasionally also by particular nutrient contents. Despite these constraints, several brownfield are well colonized by plants, fauna and microorganisms. The capacity of these new communities to uphold main ecosystem function remains to be evaluated based on the measurement of one or several ecosystem functions. Leaf litter decomposition is critically important in driving carbon and nutrient biogeochemical cycles. This function depends on decomposition actors (fauna and microorganisms) but also on leaf litter quality. By that, leaf litter decomposition integrates effects of soil pollution on plant, animal and microorganism communities. Thus, leaf litter decomposition is a relevant indicator to evaluate pollution effects on the functioning of soil ecosystems. The main objective of this thesis was to study brownfields soil function by focusing on the impairment of soil pollution on the leaf litter decomposition. The main hypothesis was that soil pollution could negatively affect leaf litter decomposition by two different ways. (1) By direct effects, resulting from adverse effects of soil pollution on decomposition actors, and (2) by indirect effects, assuming that soil pollution will induce modifications of the plant’s physiology, resulting in changes in leaf litter quality and subsequent effects on the decomposition. Our results revealed the absence of direct negative effects for eight highly polluted sites, despite a disturbance of decomposer actors, specifically the increase in abundance of detritivores and a modified microbial colonization of the leaf litter at the polluted sites. These results are in favor of a sufficient functional redundancy of decomposer actors in the local communities, which allowed the maintenance of the decomposition process. We also showed a positive indirect effect of soil pollution on the decomposition. This effect resulted from the improvement of litter quality produced at the polluted sites. This induced, at least for some sites, an increase of the decomposition rate, possibly due to a higher activity of decomposer actors. Furthermore, we also observed pollutants accumulation in these litter, especially Cd and Zn. These pollutants could potentially impair decomposition actors. Whatever, presence of these pollutants in litter did not impair litter consumption by some detritivores. Numerous perspectives can be developed from this study. Among them it seems specifically important to evaluate: 1) which are the (physiological) mechanisms behind the increase in leaf litter quality at polluted sites? 2) How can different communities assure the same decomposition rates at polluted sites? and 3) Are there negative effects observed on the performance and physiology of detritivores when consuming leaf litter from polluted sites ?

Les sols des friches industrielles sont souvent multi-polluées et représentent des surfaces toujours plus importantes présentant de forts enjeux sociaux-économiques. Leur réhabilitation passe par une bonne compréhension du fonctionnement écologique des sols, qui, en plus d’être pollués, présentent des structures et des teneurs en nutriments souvent inhabituelles. Malgré cela, une recolonisation par la faune, la flore et les microorganismes est généralement observée. La capacité de ces nouvelles communautés à restaurer et maintenir les fonctions clés des sols reste à évaluer, et cela semble indissociable de la mesure d’une ou plusieurs fonctions écosystémiques. La décomposition de la litière est un processus écosystémique clef permettant la réalisation des cycles biogéochimiques du carbone et des nutriments. Les processus de la décomposition dépendent à la fois de ses acteurs (faune et microorganismes) et de la qualité de la litière végétale. De ce fait, la réponse de cette fonction écosystémique à la pollution du sol intègre les effets de cette pollution sur les communautés de plantes, d’animaux, et de microorganismes, ce qui en fait un indicateur potentiellement pertinent pour évaluer les effets de la pollution sur le fonctionnement des écosystèmes du sol. L’objectif central de cette thèse a donc été d’étudier le fonctionnement des friches industrielles en se focalisant sur les effets délétères de la pollution des sols sur la décomposition de la litière de feuilles. L’hypothèse centrale découlant de cet objectif a été que la pollution des sols pouvait impacter la décomposition par deux voies d’action. (1) La première voie, directe, est constituée de l’ensemble des effets délétères que pourraient provoquer les polluants sur les acteurs de la décomposition dont dépend la bonne réalisation de cette fonction. (2) Concernant la deuxième voie d’action, nous avons supposé que la pollution, en entraînant des modifications de la physiologie des plantes, pouvait modifier les paramètres physico-chimiques de la litière et ainsi impacter de façon indirecte la décomposition des litières. Nos résultats ont permis de montrer l’absence de l’effet direct pour huit friches industrielles fortement polluées, et ce malgré des perturbations des communautés d’acteurs, avec notamment une augmentation de l’abondance des détritivores et une modification de la colonisation microbienne des litières sur les sites pollués. Ces résultats plaident en faveur d’une redondance fonctionnelle suffisante au sein de ces communautés, permettant de maintenir le processus de décomposition. Nous avons également montré un effet indirect positif de la pollution sur la décomposition. Cet effet résulte de l’amélioration systématique de la qualité de la litière, entraînant dans certains cas une augmentation de l’activité des acteurs de la décomposition. Par ailleurs, nous avons également montré une accumulation des polluants dans ces mêmes litières, en particulier le Zn et le Cd, polluants pouvant potentiellement produire des effets délétères sur les acteurs de la décomposition. Toutefois, la présence de ces ETM n’a pas semblé influencer la consommation des litières par certains acteurs de la décomposition de la litière. Cependant, ce résultat reste à valider in situ en présence de l’ensemble des communautés de détritivores. De nombreuses perspectives s’ouvrent à la suite de ces travaux. Parmi elles, il reste notamment à déterminer 1) quels sont les mécanismes (physiologiques) qui entrainent une augmentation de la qualité des litières produites sur les sols contaminés ? 2) comment des communautés différentes permettent d’assurer des taux de décomposition similaires ? et 3) quels sont les impacts de la consommation des litières provenant des sites contaminés sur le fonctionnement et la physiologie des détritivores ?<br>Brownfield soils are multi-polluted areas, which cover an increasing surface and thus present serious socio-economical challenges. A better understanding of the ecological functioning of these sites is mandatory for their restoration. In addition to the high pollution found at these sites, brownfields are characterized by a specific soil structure and occasionally also by particular nutrient contents. Despite these constraints, several brownfield are well colonized by plants, fauna and microorganisms. The capacity of these new communities to uphold main ecosystem function remains to be evaluated based on the measurement of one or several ecosystem functions. Leaf litter decomposition is critically important in driving carbon and nutrient biogeochemical cycles. This function depends on decomposition actors (fauna and microorganisms) but also on leaf litter quality. By that, leaf litter decomposition integrates effects of soil pollution on plant, animal and microorganism communities. Thus, leaf litter decomposition is a relevant indicator to evaluate pollution effects on the functioning of soil ecosystems. The main objective of this thesis was to study brownfields soil function by focusing on the impairment of soil pollution on the leaf litter decomposition. The main hypothesis was that soil pollution could negatively affect leaf litter decomposition by two different ways. (1) By direct effects, resulting from adverse effects of soil pollution on decomposition actors, and (2) by indirect effects, assuming that soil pollution will induce modifications of the plant’s physiology, resulting in changes in leaf litter quality and subsequent effects on the decomposition. Our results revealed the absence of direct negative effects for eight highly polluted sites, despite a disturbance of decomposer actors, specifically the increase in abundance of detritivores and a modified microbial colonization of the leaf litter at the polluted sites. These results are in favor of a sufficient functional redundancy of decomposer actors in the local communities, which allowed the maintenance of the decomposition process. We also showed a positive indirect effect of soil pollution on the decomposition. This effect resulted from the improvement of litter quality produced at the polluted sites. This induced, at least for some sites, an increase of the decomposition rate, possibly due to a higher activity of decomposer actors. Furthermore, we also observed pollutants accumulation in these litter, especially Cd and Zn. These pollutants could potentially impair decomposition actors. Whatever, presence of these pollutants in litter did not impair litter consumption by some detritivores. Numerous perspectives can be developed from this study. Among them it seems specifically important to evaluate: 1) which are the (physiological) mechanisms behind the increase in leaf litter quality at polluted sites? 2) How can different communities assure the same decomposition rates at polluted sites? and 3) Are there negative effects observed on the performance and physiology of detritivores when consuming leaf litter from polluted sites ?

The ability to routinely determine Functional Residual Capacity (FRC) or the ventilation-volume homogeneity of ventilated patients has been a long held goal. Such measures have the potential to greatly improve the treatment of patients by preventing ventilator related lung injuries. Many methods have been proposed, but none have seen routine clinical use. This thesis develops methods of determining such information from tracer gas concentrations, modelling the concentration of the entire expired breath in an attempt to extract more information from the data. A method of using such models to produce a distribution of alveolar volumes, which broadens with an increase in the inhomogeneity of simulated data, was developed. When compared to the Homogeneity Index [Whiteley et al., Respir. Physiol., 124(1):65-83.], the method determines the homogeneity more robustly, particularly when noise is present in the flow signal. In real data from a water-displacement bench lung it also produced tentatively better results. However it did not perform as expected for 25% of the data sets. Investigations into determining FRC, highlighted the need to include mixing within the dead space, which is a move away from traditional dead space models. In human data a dead space with two mixing compartments provided the best FRC results, reducing the mean limits of agreement with plethysmography by 32% when compared to the other practical methods investigated. Compared to data from the literature, this method was no worse than Helium Dilution (the bias and limits of agreement were within the 95% confidence interval) and the limits of agreement were significantly better than for the LUFU device. Thus, if the results are replicated in clinical practice, the method is likely to be robust enough to positively influence patient care. Attempts to correct for time offsets between the flow and concentrations signals did not improve results for humans, despite showing some improvements for a water-displacement bench lung.

In 1973, Combes and Thomas discovered a general technique for showing exponential decay of eigenfunctions. The technique involved proving the exponential decay of the resolvent of the Schrödinger operator localized between two distant regions. Since then, the technique has been been applied to several types of Schrödinger operators. This dissertation will show that the Combes--Thomas method works well with trace, Hilbert--Schmidt and other trace-type norms. The first result we prove shows exponential decay on trace-type norms of a resolvent of a Schrödinger operator localized between two distant regions. We build on this result by applying the Combes--Thomas method again to prove polynomial and sub-exponential decay estimates on functions of Schrödinger operators localized between two distant regions.

Cette thèse porte sur l'étude des points entiers et rationnels de certaines courbes et variétés modulaires. Après une brève introduction décrivant les motivations et le cadre de ce genre d'études ainsi que les résultats principaux de la thèse, le manuscrit se divise en trois parties. Le premier chapitre s'intéresse aux Q-courbes, et aux morphismes Gal(Q/Q) -&gt; PGL2(Fp) qu'on peut leur associer pour tout p premier. Nous montrons que sous de bonnes hypothèses, pour p assez grand par rapport au discriminant du corps de définition de la Q-courbe, ce morphisme est surjectif, ce qui résout un cas particulier du problème d'uniformité de Serre (toujours ouvert en général). Les outils principaux du chapitre sont la méthode de Mazur (basée ici sur des résultats d'Ellenberg), la méthode de Runge et des théorèmes d'isogénie, suivant la structure de preuve de Bilu et Parent. Le second chapitre consiste en des estimations analytiques de sommes pondérées de valeurs de fonctions L de formes modulaires, dans l'esprit de techniques développées par Duke et Ellenberg. La motivation de départ d'un tel résultat est l'application de la méthode de Mazur dans le premier chapitre. Le troisième chapitre est consacré à la recherche de généralisations de la méthode de Runge pour des variétés de dimension supérieure. Nous y redémontrons un résultat de Levin inspiré de cette méthode, avant d'en prouver une forme assouplie dite "de Runge tubulaire", plus largement applicable. Dans l'optique de recherche de points entiers de variétés modulaires, nous en donnons enfin un exemple d'utilisation à la réduction d'une surface abélienne en produit de courbes elliptiques<br>This thesis concerns the study of integral and rational points on some modular curves and varieties. After a brief introduction which describes the motivation and the setting of this topic as well as the main results of this thesis, the manuscript follows a threefold development. The first chapter focuses on Q-curves, and on the morphisms Gal(Q/Q) -&gt; PGL2(Fp) that we can build with a Q-curve for every prime p. We prove that, under good hypotheses, for p large enough with respect to the discriminant of the definition field of the Q-curve, such a morphism is surjective, which solves a particular case of Serre's uniformity problem (still open in general). The main tools of the chapter are Mazur's method (based here on results of Ellenberg), Runge's method, and isogeny theorems, following the strategy of Bilu and Parent. The second chapter covers analytic estimates of weighted sums of L-function values of modular forms, in the fashion of techniques designed by Duke and Ellenberg. The initial goal of such a result is the application of Mazur's method in the first chapter. The third chapter is devoted to the search for generalisations of Runge's method for higherdimensional varieties. Here we prove anew a result of Levin inspired by this method, before proving an enhanced version called "tubular Runge", more generally applicable. In the perspective of studying integral points of modular varieties, we finally give an example of application of this theorem to the reduction of an abelian surface in a product of elliptic curves

Trace amines (TAs), tryptamine, tyramine, octopamine, and beta-phenylethylamine, named for their low endogenous concentrations in mammals, are related to the classical monoamine transmitters, but have been understudied and thought of as false transmitters. They share structural, physiological, pharmacological, and metabolic similarities with the monoamines, including synthesis by the aromatic-L-amino acid decarboxylase (AADC) enzyme. In 2001, a new class of receptors preferentially activated by the TAs, termed trace amine-associated receptors (TAARs), was discovered establishing a mechanism for TA actions independent of classic monoaminergic mechanisms. While the TAs and some of their receptors are present in the mammalian central nervous system (CNS), their physiologic role remains uncertain. I hypothesized that the TAs are found intrinsically in the spinal cord, and that they are able to modulate spinal neural networks. Using immunohistochemistry, numerous spinal neurons were identified that express AADC, TAs, and TAARs. Similar results were seen for AADC and TAAR1 with in situ hybridization. The most consistent observation was for labeling D cells associated with the central canal and in motoneurons. Overall, these results provided evidence for the presence of an anatomical substrate onto which the TAs could have intrinsic biological actions in the spinal cord. Using exogenous application of the TAs in the isolated spinal cord in vitro, and in vivo in the mid-thoracic chronically spinalized, I showed that the TAs could induce rhythmic locomotor-like activity. TA injection-induced hindlimb motor rhythms observed in chronic spinalized animals, supports TA spinal actions independent of the descending monoaminergic systems. In the presence of NMDA, TA applications recruited a variety of rhythmic motor patterns in the isolated spinal cord. This ranged from locomotor activity indistinguishable from 5-HT/NMDA induced locomotion to complex patterns including, an episodic form of locomotion where there were locomotor bouts with intervening quiescent periods. TA actions of pattern generating circuits had slower kinetics of activation than 5-HT and NA, were attenuated in the presence of monoamine transport inhibitors, and had increased intracellular labeling when incubated in a nominally Na+-free solution. Together these results suggest that the TAs require transport into neurons to exert their actions, and that transport occurs by Na+-dependent monoamine transporters as well as Na+-independent transporters. Finally, I used the in vitro isolated spinal cord with attached hindlimbs to record electromyographic (EMG) activity from various hindlimb muscles to compare the relationship between the TAs and serotonin (5-HT) evoked motor coordination and to examine the ability of the TAs to modulate ongoing 5-HT and NMDA locomotor-like activity. The TAs produced both the continuous and episodic patterns on muscles as observed in ventral root recordings, but EMG recordings provided more detailed insight into specific muscle actions. The TAs also generally increased both frequency and amplitude of ongoing 5-HT locomotor frequency, with tyramine and octopamine also particularly able to alter 5-HT motor coordination patterns.

Submitted by PPG Ci?ncia da Computa??o (ppgcc@pucrs.br) on 2017-11-24T20:01:50Z No. of bitstreams: 1 Rafael_Anton_Eichelberger_dis.pdf: 5090662 bytes, checksum: 0c27686648c0e4c286c555a921034507 (MD5)<br>Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-12-04T11:49:36Z (GMT) No. of bitstreams: 1 Rafael_Anton_Eichelberger_dis.pdf: 5090662 bytes, checksum: 0c27686648c0e4c286c555a921034507 (MD5)<br>Made available in DSpace on 2017-12-04T11:53:53Z (GMT). No. of bitstreams: 1 Rafael_Anton_Eichelberger_dis.pdf: 5090662 bytes, checksum: 0c27686648c0e4c286c555a921034507 (MD5) Previous issue date: 2017-03-15<br>Service Function Chaining (SFC) ? um importante campo de pesquisa na ?rea de redes de computadores, com v?rias propostas de diferentes m?todos de encapsulamento e encaminhamento de pacotes. Os m?todos de encaminhamento de pacotes usados para implementar SFC podem inviabilizar o uso de ferramentas tradicionais de depura??o de rede, o que dificulta a detec??o de erros de configura??o ou poss?veis degrada??es de desempenho em ambientes SFC. Este trabalho apresenta o SFC Path Tracer, uma ferramenta para detec??o de problemas no dom?nio SFC em ambientes NFV/SDN. Essa ferramenta permite a identifica??o de problemas no dom?nio SFC, atrav?s da gera??o de trace de pacotes e medi??o de atrasos intra-hop a partir de um SFC Path espec?fico. SFC Path Tracer ? agn?stico em rela??o aos mecanismos de encapsulamento e encaminhamento usados para implementar SFC, sendo eficaz na detec??o de grande parte dos problemas em um ambiente SFC.<br>Service Function Chaining (SFC) is an important research field in networking area with many encapsulation and forwarding mechanisms being proposed. To implement SFC, non-standard forwarding methods are used which break the mechanism of regular network troubleshooting tools, challenging the detection of SFC misconfiguration or performance degradation. This work presents the SFC Path Tracer, a tool for roubleshooting SFC in NFV/SDN environments. This tool enables the identification of problems in the SFC environment by generating packet trace and computing intra-hop delays from a specific SFC path. SFC Path Tracer is agnostic regarding the SFC encapsulation and forwarding mechanisms being effective to detect most problems in an SFC environment.

Plusieurs auteurs ont utilisé les champs de contraintes pour résoudre l'équation d’équilibre de la mécanique des milieux continus. Airy (1863) a résolu le cas bidimensionnel, Maxwell (1870) et Morera (1892) ont étudié le cas tridimensionnel. Les solutions obtenues sont des cas particuliers de celles de Beltrami (1892). Gurtin a donné un exemple de solutions ne satisfaisant pas la représentation S = CurlCurlA de Beltrami, ce qui signifie que la représentation précédente est incomplète. De plus, il a montré que si l’ouvert est régulier, alors elle est complète dans l’espace des champs réguliers de contraintes auto-équilibrés.Dans cette thèse intitulée ”Caractérisations de champs de matrices, potentiels matrices et applications aux opérateurs traces”, on s’intéresse à diverses caractérisations de champs de vecteurs, de champs de matrices et spécialement au résultat de Gurtin dans le cas où l’ouvert et les champs de contraintes ne sont pas réguliers.Cette thèse est décomposée en cinq chapitres. Le premier chapitre expose la problématique de recherche traitée dans cette thèse. Il présente également l’origine du sujet de recherche. Dans le deuxième chapitre, on étudie l’opérateur et en particulier l’existence de potentiels vecteurs dans différents cadres fonctionnels.Dans les chapitres 3 et 4, on va montrer quelques versions de la complétude de la représentation de Beltrami et en déduire des décompositions de Helmholtz pour les champs de matrices.Le dernier chapitre est consacré à l’étude de l’image de différents opérateurs traces de fonctions W 2,p (Ω), W 3,p (Ω) lorsque Ω est un ouvert borné de R 2 lipschitzien. L’ingrédient essentiel est donné par la fonction d’Airy ou par la représentation de Beltrami<br>Many authors have used stress fields to solve the equilibrium equation of continuum me- chanics. Airy (1863) solved the two-dimensional case, Maxwell (1870) and Morera (1892) solved the three-dimensional case. The above solutions are special cases of those of Beltrami (1892). Gurtin gave an example of solutions that do not have Beltrami’s S = CurlCurlA representation. He showed that if the domain Ω is regular, then this representation is complete in the class of regular stress fields which are self-equilibrated.My thesis title is ”Characterizations of matrix fields, potential matrices and applications to trace operators”. In this work, we are interested by showing many characterizations ofvector fields, of matrix fields and especially by generalizing the result of Gurtin in the case when the open set and the stress fields are not regular.This thesis consists of five chapters. The first chapter presents the research problem ad- dressed in this thesis. It also presents the origin of the subject of research.In the second chapter, we study the operator . In particular, the existence of potential vectors in different functional frameworks.In Chapters 3 and 4, we will show some versions of Beltrami’s completeness and we deduce some Helmholtz decomopsitions for symmetric matrix fields.The last chapter is devoted to the study of the image of different trace operators of functions W 2,p (Ω), W 3,p (Ω) when Ω is a bounded open of R 2 with Lipschitz boundary. The essential ingredient is given by the Airy’s function or by the Beltrami representation

The main subsect of this thesis is the theory of Lifshits-Krein spectral shift function in semifinite von Neumann algebras and its connection with the theory of spectral flow. Main results are an analogue of the Krein trace formula for semifinite von Neumann algebras, the semifinite analogue of the Birman-Solomyak spectral averaging formula, a connection between the spectral shift function and the spectral flow and a Lidskii type formula for Dixmier traces. In particular, it is established that in the case of operators with compact resolvent, the spectral shift function and the spectral flow are identical notions.

La spécificité de l’adolescence est la venue au premier plan de la génitalité. Cela entraîne à la fois une métamorphose du corps et un remaniement psychique. À l’adolescence, le corps est aussi un lieu de contradiction que tantôt il attaque, tantôt il embellit dans un érotisme effréné. En effet, la contradiction peut se traduire sous forme symptomatique et manifester l’encombrement que l’adolescent ressent devant son corps qui lui échappe. Il ne sait pas repérer ce qu’il ressent, il ne sait pas le nommer et même il ne sait pas qu’il ne sait pas. Parfois le rapport qu’il entretient avec son corps est suffisamment paradoxal pour qu’il ne puisse pas se l’approprier. C’est cette étrangeté qui va provoquer un clivage chez l’adolescent. Les deux perspectives qui émanent de ces positions sont assez différentes quant à l’avenir du sujet. Ce travail s’inscrit dans la continuité de divers travaux de recherche sur la problématique adolescente. Il vient rendre compte de la mise en place dans un service de Pédiatrie générale d’un groupe thérapeutique à médiation écriture avec des adolescentes qui se scarifient. C’est en considérant ces scarifications comme un langage du corps au coeur de la problématique adolescente et pubertaire, et au regard des difficultés que ces adolescentes ont à mettre des mots sur l’indicible de leur douleur, que le groupe a été créé. La mise en place de celui-ci correspond plus globalement à une réflexion sur le processus d’adolescence, de subjectivation, et le rapport au corps, notamment à travers le travail de symbolisation à l’adolescence. Nous interrogeons également à l’endroit de notre réflexion, la médiation écriture en tant que dépôt d’une trace sur un support, qui au même titre que la rencontre de la lame sur la peau, viendrait comme une butée (Le Breton, 2002) ; la rencontre avec la feuille par analogie au corps viendrait recréer et offrir un contenant à la souffrance psychique. Le groupe quant à lui pourrait être vécu comme espace transitionnel au sens où l'entend Winnicott, au fondement de l’expérience créatrice et rassurante pour l’adolescente. Le corps aurait alors une fonction semblable dans ce qu'il incarnerait une frontière entre un dedans et un dehors. Une des fonctions de la pratique scarificatoire serait alors de restaurer les limites du Soi dans une lutte contre un possible effondrement<br>The specificity of adolescence is the coming to the fore of genitality. This involves both a metamorphosis of the body and a psychic reworking. The body is also a place of contradiction that sometimes attacks, sometimes it embellishes in a frenzied eroticism. Indeed, the contradiction can be translated in symptomatic form and manifest the clutter that the adolescent feels in front of his body that escapes him. He does not know how to identify what he feels, he does not know how to name it and he does not even know he does not know. Sometimes the relationship he has with his body is sufficiently paradoxical that he can't appropriate it. It is this strangeness that will cause a cleavage in the adolescent. The two perspectives that emanate from these positions are quite different as to the future of the subject. This work is a continuation of various research works on the adolescent problem. He reports on the establishment of a therapeutic group in writing in a Pediatric General Service, writing with teenagers who are scarifying themselves. It is by considering these scarifications as a body language at the heart of the adolescent and pubertal problem, and in view of the difficulties that these teenagers have to put words on the indescribable of their pain, that the group was created. The setting up of this one corresponds more generally to a reflection on the process of adolescence, of subjectivation, and the relation with the body, in particular through the work of symbolization in adolescence. We also question the place of our reflection, the mediation writing as a deposit of a trace on a support, which as well as the meeting of the blade on the skin, would come as a stop (Le Breton, 2002); the encounter with the sheet by analogy with the body would come to recreate and offer a container for psychic suffering. The group could be seen as a transitional space in Winnicott's sense, at the root of the creative and reassuring experience for the teenager. The body would then have a similar function in what it would incarnate a border between an inside and an outside. One of the functions of the scarificatory practice would then be to restore the limits of the Self in a fight against a possible collapse

The main focus of my dissertation is the Modified Stochastic Sine-Gordon Equation: utt = 2uxx − ut − sin(|u|^(&gamma)) + b(u, du/dt)dW/dt where &gamma > 0 is the parameter of the power of non-linearity, &delta &ge 0 is the magnitude of non-linearity, &alpha> 0 be the damping parameter, and &sigma the diffusion intensity, on one dimensional domain. We analyze the properties of the solution of the SPDE by the eigenfunctions approach allowing us to truncate the infinite-dimensional stochastic system (i.e the SDEs of Fourier coefficients related to the SPDE), to control its energy, existence, uniqueness, continuity and stability. The analysis relies on the investigation of expected Lyapunov functional of the energy in terms of all system-parameters. We simulate the model with respect to all system-parameters to visualize our conclusions.

This thesis presents SAIF, (Spectral Analysis with Iterative Filter), a SA-based method for the quantification of PET data investigated with irreversible-uptake tracers. SAIF has been designed in order to maintain the main advantages of SA but providing a superior robustness to measurement noise. The final aim was to create a reliable and flexible PET quantification tool, offering a valid alternative to standard methodologies for functional quantitative imaging with PET and irreversible tracers.

The monoamines play important roles as neurotransmitters both centrally and peripherally, and are believed to play a key role in a number of pathological conditions such as Parkinson's disease, schizophrenia, drug addiction, and mood disorders, which has driven many years of research, resulting in a relatively good understanding of the neurochemistry of this group of amines. [n contrast, relatively little is known about the role of a second class of endogenous amines, the 'trace amines, that share substantial overlap with the monoamines. For 30 years the trace amines, have also been thought to be associated with affective behaviour, paranoid chronic schizophrenia and depression. However, until the recent discovery of a novel family Gprotein- coupled receptors (GPCRs), with high affinity for the trace amines, research was restricted. One member of this family, trace amine 1 receptor (TA1) is functional in both rodents and man, and is expressed widely throughout the brain of the mouse, rat and human. The functional role of the TAl receptor in the mammalian brain was therefore the focus of the current project. In order to investigate the function of the TAl receptor, two specific TAl receptor agonists were used, kindly provided by Hoffman La Roche. As the TAl receptor has been implicated in the neuropathophysiology of several psychiatric disorders, such as ADHD and schizophrenia, which are characterised by substantial and debilitating deficits in cognitive performance, initial experiments aimed to assess for any effect of the TAl agonists on cognitive performance in laboratory rodents. In part, the association between the TAl receptor and mental disorders is based on evidence suggesting an interaction with monoamine neurotransmission. However, previously reported findings from in vitro studies do not support a mechanism of interaction comparable with results from in vivo studies. Therefore later experiments investigated the relationship between TAl and monoamine neurotransmission in vivo. Initial experiments focused on the interaction between TAl activation and behaviours induced by psychostimulants known to alter monoamine function, and subsequent investigation examined the possible mechanisms involved using in vivo microdialysis.

This thesis investigates the viability of trace-based just-in-time (JIT) compilation for optimising programs written in the lazy functional programming language Haskell. A trace-based JIT compiler optimises only execution paths through the program, which is in contrast to method-based compilers that optimise complete functions at a time. The potential advantages of this approach are shorter compilation times and more natural interprocedural optimisation. Trace-based JIT compilers have previously been used successfully to optimise programs written in dynamically typed languages such as JavaScript, Python, or Lua, but also statically typed languages like Java or the Common Language Runtime (CLR). Lazy evaluation poses implementation challenges similar to those of dynamic languages, so trace-based JIT compilation promises to be a viable approach. In this thesis we focus on program performance, but having a JIT compiler available can simplify the implementation of features like runtime inspection and mobile code. We implemented Lambdachine, a trace-based JIT compiler which implements most of the pure subset of Haskell. We evaluate Lambdachine's performance using a set of micro-benchmarks and a set of larger benchmarks from the "spectral" category of the Nofib benchmark suite. Lambdachine's performance (excluding garbage collection overheads) is generally about 10 to 20 percent slower than GHC on statically optimised code. We identify the two main causes for this slow-down: trace selection and impeded heap allocation optimisations due to unnecessary thunk updates.

Nous nous intéressons aux opérateurs de Hankel $H_{bar{f}}$ de symbole anti holomorphe $bar{f}$ et regardons l'espace de Dixmier $mathcal{D}^{p}$ associé ($pgeq1$), c'est à dire l'ensemble des $f$ tel que $|H_{bar{f}}|^{p}$ soit dans l'idéal de Macaev $mathcal{S}^{+}_{1}$. Notre approche est de voir l'espace de Dixmier comme une certaine limite des classes de Schatten. Quand $f in mathcal{D}^{p}$, nous étudions $Tr_{omega}(|$H_{bar{f}}$|^{p})$ la trace de Dixmier de $|H_{bar{f}}|^{p}$. Nous redémontrons certains résultats classiques quand $f$ est holomorphe sur le disque alors que nous donnons de nouveaux résultats quand $f$ est entière. Nous utilisons notre méthode pour étudier l'espace de Dixmier du petit opérateur de Hankel, des opérateurs de Toeplitz $T_{varphi}$ ($varphi$ définie sur le disque ou sur le plan complexe tout entier) ainsi que pour l'opérateur de composition<br>We study Hankel operators $H_{bar{f}}$ with anti holomorphic symbol $bar{f}$ and we are interested to the Dixmier space $mathcal{D}^{p}$ ($pgeq1$), the set of functions $f$ such that $|H_{bar{f}}|^{p} in mathcal{S}^{+}_{1}$ the Macaev ideal. We look Dixmier space as a limit of Schatten class. When $f in mathcal{D}^{p}$, we study $Tr_{omega}(|$H_{bar{f}}$|^{p})$ the Dixmier trace of $|H_{bar{f}}|^{p}$. We have different results when $f$ is an entire or a holomorphic function of the unit disk in the complex plan. We study also the Dixmier space of the little Hankel operator, Toeplitz operator and composition operator

The koala is a specialist herbivore thriving on a diet of mainly eucalypts, which contain a toxic cocktail of highly absorbable monoterpenes that can affect health in various ways when ingested in high amounts. Specialist adaptations are required to protect animals from acute intoxication. Koalas apply amongst other strategies high metabolic detoxification capacities to deal with these components but increased exposure to anthropogenic environmental contamination is potentially effecting metabolic detoxification pathways and therefore can reduce food intake in this species. The aim of this thesis is to investigate the systemic exposure of koalas to a range of xenobiotics. The profile of main eucalypt monoterpenes in the ingesta of deceased koalas was investigated and tested for consistencies between animals and regions. A well-balanced monoterpene profile was found when mean profiles of different regions were compared. Blood exposure to selected monoterpenes was found continuous but low compared to other eucalypt feeders. Monoterpene profile in blood was similar to that in ingesta of koalas (but different to the profile of lymphatic tissue) suggesting a feeding behavior that balances toxin exposure in peripheral blood. Accumulation of frequently used pesticides, metal and trace elements were further investigated in koalas from different regions of NSW and Victoria. Hepatic accumulation of pesticides is uncommon in this species, but element exposure of koalas changes significantly with land use and region and less commonly with age and sex of the animals. This study also provides first insight into the effects of eucalypt monoterpenes on the immune function of this species. This study demonstrates that circulating concentrations of monoterpenes have dose dependent inhibitory effects (in vitro) on cytokine expression of koala peripheral blood mononuclear cells, suggesting a potential evolutionary adaptation in this species.

L'analyse multifractale est l'étude des propriétés locales des ensembles de mesures ou de fonctions. Son importance est apparue dans le cadre de la turbulence pleinement développée. Dans ce cadre, l'expérimentateur n'a pas accès à la vitesse en tout point d'un fluide mais il peut mesurer sa valeur en un point en fonction du temps. On ne mesure donc pas directement la fonction vitesse du fluide, mais sa trace. Cette thèse sera essentiellement consacrée à l'étude du comportement local de traces de fonctions d'espaces de Besov : nous déterminerons la dimension de Hausdorff des ensembles de points ayant un exposant de Hölder donné (spectre multifractal). Afin de caractériser facilement l'exposant de Hölder et l'appartenance à un espace de Besov, on utilisera la décomposition de fonctions sur les bases d'ondelettes.Nous n'obtiendrons pas la valeur du spectre de la trace de toute fonction d'un espace de Besov mais sa valeur pour un ensemble générique de fonctions. On fera alors appel à deux notions de généricité différentes : la prévalence et la généricité au sens de Baire. Ces notions ne coïncident pas toujours, mais, ici on obtiendra les mêmes résultats. Dans la dernière partie, afin de déterminer la forme que peut prend un spectre multifractal, on construira une fonction qui est son propre spectre

El sistema enteroendocrí es troba al tracte gastrointestinal i controla la gana i l’activitat pancreàtica endocrina, entre altres funcions. Els compostos bioactius que estimulen aquest sistema són candidats terapèutics per tractar patologies relacionades amb aquestes funcions. Prèviament s’ha identificat que un extracte de proantocianidines de llavors de raïm (GSPE) és antidiabètic per les seves capacitats de millora de la funció de les cèl·lules i la seva capacitat saciant, com a conseqüència en part de l’activació del sistema enteroendocrí. El nostre grup ha relacionat les secrecions enteroendocrines induïdes per polifenols amb l'estimulació de receptors del gust amarg (TAS2R) in vitro, però si això es reflecteix en una ingesta alterada encara és deconegut. Per això, és necessari comprendre millor aquest sistema per poder desenvolupar millors estratègies terapèutiques. Aquesta tesi aborda si les secrecions d’intererohormones induïdes per GSPE modulen la producció de glucagó pancreàtic i si aquestes secrecions es regulen mitjançant l’estimulació específica de TAS2R que condueix a un control diferencial de la ingesta d’aliments. Aquesta hipòtesi s’ha avaluat amb estudis in vivo en rates i estudis ex vivo en mostres intestinals. Hem identificat que el glucagó és més sensible que la insulina a GSPE, fet que es correlaciona amb una secreció il·leal de GLP1 millorada.<br>El sistema enteroendocrino se encuentra en el tracto gastrointestinal y controla el apetito y la actividad pancreática endocrina, entre otras funciones. Los compuestos bioactivos que estimulan este sistema son candidatos terapéuticos para tratar patologías relacionadas con estas funciones. Previamente se identificó que un extracto de proantocianidinas de semillas de uva (GSPE) es antidiabético por sus capacidades de mejora de la función de las células y su capacidad saciante, como consecuencia en parte activar del sistema enteroendocrino. Nuestro grupo relacionó las secreciones enteroendocrinas inducidas por polifenoles con la estimulación de receptores del gusto amargo (TAS2R) in vitro, pero si esto se refleja en una ingesta alterada aún se desconoce. Por esto, es necesario comprender mejor este sistema para poder desarrollar mejores estrategias terapéuticas. Esta tesis aborda si las secreciones enteroendocrinas inducidas por GSPE modulan la producción de glucagón pancreático y si estas se regulan mediante la estimulación específica de TAS2R que conduce a un control diferencial de la ingesta. Esta hipótesis se ha evaluado con estudios in vivo en ratas y estudios ex vivo en muestras intestinales. Hemos identificado que el glucagón es más sensible que la insulina a GSPE, lo que se correlaciona con una secreción ileal de GLP1 mejorada.<br>The enteroendocrine system is located in the gastrointestinal tract and controls appetite and endocrine pancreatic activity, among other functions. Thus, bioactive compounds that stimulate the enteroendocrine system are therapeutic candidates for treating pathologies related to these functions. Previous research has identified a grape-seed proanthocyanidin extract (GSPE) as antidiabetic for its -cell function enhancement abilities and its appetitesuppressing activity at least partly through activating the enteroendocrine system. Moreover, our group has linked the polyphenol-induced enteroendocrine secretions to the stimulation of some bitter taste receptors (TAS2R) in vitro, but whether it results in an altered food intake has not been studied yet. Since little is known of the mechanisms used by polyphenols to stimulate secretory mechanisms of the enteroendocrine system, there is a need to fully comprehend this system to specifically target it with a therapeutic strategy. For this reason, this thesis addressed whether GSPE-induced enterohormone secretions modulate pancreatic glucagon production, and whether these secretions are regulated through the specific stimulation of TAS2R leading to a differential control of food intake. This hypothesis was assessed with in vivo studies in rats and ex vivo studies in intestinal samples.

Cosmic voids are large underdense regions of the Universe that, together with galaxy clusters, filaments and walls, characterise the large-scale structure of the Universe, the so-called cosmic web. Since voids in biased tracers are systematically larger than those identified in the dark matter field, a correction to the dark matter void size function is necessary. The scientific goals of this thesis work are the following: (i) to test the algorithm to clean void catalogues on Λ-cold dark matter (ΛCDM) N-body simulations, (ii) to quantify the accuracy of the theoretical void size function model with dark matter catalogues, (iii) to re-parametrise the theoretical model of the void size function for biased tracers, and (iv) to investigate the cosmological constraining power of cosmic void statistics. For these purposes, we made use of large, high-resolution halo catalogues extracted from ΛCDM N-body simulations. From these catalogues of biased tracers we extracted void catalogues with the Void IDentification and Examination toolkit (VIDE). Then a cleaning procedure is applied to the VIDE void catalogues. In our analyses we found that the theoretical void number density is systematically underpredicted if the effective bias is used to assess the density threshold in the model. We verified this phenomenon by estimating the bias from the ratio between the averaged void density profiles traced by dark matter and biased tracers. In particular, the bias computed with this technique is systematically larger than the linear effective bias of the tracers used to identify the voids. Thus, we used the former to re-parameterise the theoretical size function. Thanks to this new parameterisation, the theoretical void size function is now fully consistent with the result of numerical simulations. Finally, we investigate the effect of varying some of the cosmological parameters used to compute the theoretical void size function.

In dynamic Positron Emission Tomography (PET) studies the term "Spectral Analysis" indicates a time-invariant single input/single output model, used for the data quantification [Cunningham and Jones, 1993]. Despite the name and its common use in the engineering field, SA does not indicate an analysis in the frequency domain but, instead, it represents a method from which the radioactivity concentration measured with PET can be related to the underlying physiological processes of the investigated system. SA is so-called, because it provides a “spectrum” of the kinetic components from which it is possible to derive a large variety of physiological parameters, depending on the characteristics of the analyzed tracers. In the last years SA has been widely used with a large number of PET tracers to study brain and non brain tissues, demonstrating to be a very flexible method. Differently from the most used PET quantification approaches, like the compartmental modelling [Godfrey, 1982] or the graphical methods [Patlak, 1983; Logan et al., 1990], SA can be applied to homogeneous as well as to heterogeneous kinetic tissues without any specific compartmental model assumptions. This characteristic makes it a high informative investigative tool especially for the analysis of novel PET tracers. The most critical aspect of SA is related to its sensitivity to the presence of noise in the data. This characteristic makes SA not properly indicated for the application to low signal-to-noise ratio (SNR) data [Turkheimer et al., 1994]. During the past several years, several solutions have been introduced to improve the robustness of SA in the presence of noise. The most famous example is represented by rank-shaping spectral analysis (RS) [Turkheimer et al., 2003]. However, even if RS has been shown to be a precise and accurate quantification method, its applicability is limited to tracers with reversible uptake. This is a severe restriction if we consider that one of the most used PET tracer for clinical research, 18F-Fluorodeoxyglucose ([18F]FDG), is irreversible. In this work we present SAIF, (Spectral Analysis with Iterative Filter), a SA-based method for the quantification of PET data investigated with irreversible-uptake tracers. SAIF has been designed in order to maintain the main advantages of SA but providing a superior robustness to measurement noise. The final aim was to create a reliable and flexible PET quantification tool, offering a valid alternative to standard methodologies for functional quantitative imaging with PET and irreversible tracers. The organization of this thesis is as follows: Chapter 1 offers a brief introduction to PET technique and its quantification methods. A comparison between compartmental modelling approaches and graphical methods is also presented, in order to provide the operative context in which SA is located. Chapter 2 contains the mathematical formalization of the SA model. Standard and filtered SA versions are presented with particular attention to novelty elements introduced by SAIF. In Chapter 3 and Chapter 4, SAIF will be tested with brain and non brain PET data. Several datasets obtained by using different PET tracers are considered. As an example for brain tissue quantification, SAIF application to L-[1-11C]Leucine and [11C]SCH442416 data is presented. For non brain tissues, instead, analysis of three datasets is reported: 1) [18F]FDG PET studies applied to skeletal leg muscle, 2) [18F]FLT PET studies applied to breast cancer patients and 3) [18F]FDG PET studies applied to normal control and acute lung injury patients. For each dataset SAIF results are compared with those provided by already validated methods and used in the literature as reference for the quantification. This analysis allows to compare SAIF performances with those offered by the current state of the art. Chapter 5 investigates the conditioning of the kinetic heterogeneity to PET quantification. The relationship between this problem, the spatial resolution of the imaging technique and the noise level of the data is also considered. This aspect is a critical point for PET quantification because when it is not taken into account it can lead to heavily biased results. Particular attention is given to how SAIF addresses this issue. In Chapter 6 we present SAKE, a software application in-house developed which implements the major SA algorithms. SAKE manages the whole process of PET quantification: from data pre–processing to the result analysis. No other program or additional tool is required. Chapter 7 discusses the most relevant criticalities of the SA approach and of SAIF method in particular. Considerable attention is given to the definition of the setting algorithm as well as to the model assumptions used by SAIF to describe the data. In Chapter 8 an overall discussion is presented with a conclusive summary about strengths and weakness of SAIF method. The appendix of the thesis is dedicated to the some additional works, not directly related to the main argument of this PhD project, but of interest for the PET field. This research concerns 1) the development of voxelwise quantification methods for [11C](R)Rolipram PET data, 2)the use of non linear mixed effects modelling for plasma metabolite correction, and 3) the evaluation of the sensitivity of PET receptor occupancy studies to the experimental design.<br>Negli studi dinamici di Tomografia ad Emissione di Positroni (dall'inglese Positron Emission Tomography, PET) il termine “Analisi Spettrale” (SA) indica un modello tempo-invariante singolo-ingresso/singola-uscita per la descrizione temporale dei dati acquisti dall'esame [Cunningham and Jones, 1993]. Nonostante l'accezione con cui viene comunemente utilizzata all'interno del contesto ingegneristico, SA non fa riferimento ad un'analisi nel dominio delle frequenze quanto, piuttosto, rappresenta un metodo attraverso cui la radioattività misurata durante l'esame PET viene messa in relazione con i processi fisiologici del sistema investigato. Il metodo SA è così chiamato perchè fornisce lo spettro cinetico dell'attità del tracciante nei tessuti, a partire dal quale è possibile derivare una grande varietà di parametri fisiologici relativi al sistema in esame. Come riportato negli studi di Tadokoro (1993), Fujiwara (1996), Richardson (1996), Bertoldo (1998), Hinz (2008), Brooks (2008) e Myers (2012), negli ultimi anni SA è stata ampiamente utilizzata per lo studio dei tessuti cerebrali e non, dimostrando di essere uno strumento adattabile ad una grande varietà di traccianti e processi. Allo stesso tempo SA richiede minime assunzioni per la sua applicazione: differentemente da molti approcci di quantificazione di immagini PET, come la modellistica compartimentale [Godfrey, 1983] o i metodi grafici [Patlak, 1983; Logan et al., 1990], SA può essere applicata ai tessuti omogenei così come ai tessuti eterogenei senza la necessità di ulteriori assunzioni. Questa caratteristica fa della SA uno strumento investigativo altamente informativo specialmente per l'analisi di nuovi traccianti PET in cui le conoscenze a priori risultano limitate. La maggiore criticità della tecnica SA è legata alla sensitività della metodologia alla presenza di rumore nei dati, caratteristica che ne limita l'applicabilità in caso di basso rapporto segnale rumore (SNR) [Turkheimer et al., 1994]. Durante gli anni svariate alternative sono state introdotte per migliorare la robustezza della tecnica alla presenza di rumore. La soluzione di maggior successo è rappresentata dalla rank-shaping spectral analysis (RS) [Turkheimer et al., 2003]. Tuttavia, sebbene sia stato dimostrato come RS rappresenti un preciso e accurato metodo di quantificazione, l'applicabilità della tecnica resta limitata ai soli traccianti con cinetica reversibile. Tale peculiarità costituisce una severa restrizione all'uso della RS se si considera che molti traccianti non rientrano in questa categoria. L'esempio più importante è rappresentato dal [18F]FDG (Fluorodeoxyglucose), il tracciante PET più impiegato al mondo nella ricerca clinica e pratica medica. In questo lavoro viene presentata SAIF (Spectral Analysis with Iterative Filter), un versione filtrata della spectral analysis per la quantificazioni di dati PET ottenuti a partire da traccianti con cinetica irreversibile. SAIF è stata sviluppata per mantenere i principali vantaggi della SA ma allo stesso tempo si propone di offrire una superiore robustezza all'errore di misura. Il contenuto della presente tesi si articola come segue: il capitolo 1 offre una breve introduzione alla tecnica PET e ai principali metodi di quantificazione. Un confronto tra metodi compartimentali e metodi grafici viene presentato in modo da definire le caratteristiche del contesto in cui la tecnica SA si colloca. Il capitolo 2 contiene la formalizzazione matematica della SA. Il metodo standard e le relative versioni filtrate vengono presentante, prestando particolare attenzione agli elementi di novità introdotti dalla tecnica SAIF. Nei capitoli 3 e 4 SAIF viene testata in diversi casi di studio, rispettivamente per esami PET cerebrali e non. Come esempi per la quantificazione dei tessuti cerebrali si presenteranno i casi di applicazione della SAIF ai traccianti L-[1-11C]Leucina e [11C]SCH442416. Relativamente ai tessuti non cerebrali, invece, si prenderanno in considerazione tre casi di interesse: 1) quantificazione di immagini PET ottenuti con tracciante [18F]FDG per lo studio del muscolo scheletrico; 2) quantificazione di immagini PET ottenuti con tracciante [18F]FLT in pazienti oncologici con tumori al seno; 3) quantificazione di immagini PET ottenuti con tracciante [18F]FDG per lo studio dei tessuti polmonari in soggetti sani e in pazienti affetti da sindrome polmonare acuta. Per ogni dataset i risultati ottenuti con il metodo SAIF saranno confrontati con quelli ottenuti da metodi di quantificazione già validati e indicati dalla letteratura come standard di misura. Tali analisi permetteranno di capire le performance della SAIF rispetto al corrente stato dell'arte metodologico. Il capitolo 5 approfondisce il condizionamento della eterogeneità cinetica dei sistemi biologici sulla quantificazione delle immagini PET, analizzando la dipendenza del problema rispetto alla risoluzione spaziale delle immagini e al rumore dei dati. Particolare attenzione verrà riservata a come la metodologia SAIF si approccia al problema. Nel capitolo 6 verrà introdotto SAKE, un'applicazione software sviluppata per implementare i maggiori algoritmi di spectral analysis. Il capitolo 7 propone un'analisi delle criticità degli approcci SA in generale e SAIF in particolare. Verrà discusso come definire il setting applicativo degli algoritmi così come gestire le assunzioni cinetiche dei vari approcci modellistici. In fine verranno presentate le considerazioni complessive dell'intero lavoro, proponendo un riassunto dei punti di forza e debolezza del metodo SAIF. L'appendice della tesi è dedicata ad alcuni lavori addizionali non direttamente collegati all'argomento principale di questa tesi di dottorato, ma di interesse per l'ambito PET. Le ricerche si riferiscono 1) allo sviluppo di metodi voxel-wise per la quantificazione di dati PET ottenuti con tracciante [11C](R)Rolipram, 2) all'uso del metodo non linear mixed effects modelling per la correzione dei metaboliti plasmatici, e 3) alla valutazione della sensitività degli studi recettoriali PET al protocollo sperimentale.

Ce travail de thèse porte sur l'analyse fonctionnelle des assemblages lithiques de la période protoaurignacienne (environ 40 000 – 32 000 BP) dans l'arc méditerranéen, visant à mettre en évidence les comportements techno-économiques de ces groupes humains. L’attention est portée sur deux aspects principaux associés à l’émergence de l’homme moderne en Europe occidentale : la production systématique des lamelles et l’exploitation de la matière dure animale. Plusieurs gisements sont considérés, appartenant à deux aires géographiques majeures : la Zone méditerranéenne (Grotte de l’Observatoire, Esquicho Grapaou, La Laouza) et le Nord de la France (Grotte des Cottés)<br>The Ph.D thesis deals with the Protoaurignacian lithic assemblages (circa 40 000 to 30 000 BP) from Mediterranean area sites via usewear observations, in order to display the techno-economic behaviours of these hunter-gatherer groups.Two major topics are considered, in association with the emergence of the modern Humans in Western Europe: bladelet production and osseous material exploitation. Many sites are concerned by our analysis, from different geographic zones: Mediterranean Area (Observatoire cave, Esquicho Grapaou, La Laouza) and Northern France (Les Cottés cave)

The thesis positions my practice led research within the context of the archive, asking if the documents and artefacts of process might remain as independent artworks in their own right. Focusing on practice as a temporal action through performance practice, research focuses on notion of the trace - those aspects of the archive which might be overlooked, or not conform to traditional notions of the document. By identifying a taxonomy of the performance archive elements such as mythology and repetition have been explored, expanding our consideration of the potential form that the archive may take. Using the methodology of triangulation, the study combines knowledge from contemporary performance practices, the professional practice of the archivist, and theoretical debate around the archival form. In writing the thesis and parallel body of practice led research I have employed selected techniques of the archivist, whilst allowing the voice of the practitioner within the academic structure of the thesis. The study builds on existing research into the archives of performance practice, as an area of artistic activity which has reflected upon its own documentation process. The research answers different questions from those studies which seek to archive contemporary performance in such a way to accurately represent the original, instead, it constructs an archival-artwork which exists as an independent and evolving body of practice. The research produced functions within this structure of the archive due to its fluid nature, just as the traces of a practice are uncertain and open to interpretation, so the body which houses them is one which may exist in multiple contexts. By working with artistic process, rather than only performance events, the research and findings are applicable to a range of interdisciplinary practices, instead of those only engaged in the live action. The study offers methods for approaching the remains of these practices and considering their function in relation to the archive.

3-iodothyronamine (T1AM) is an endogenous high-affinity ligand for the trace amine-associated receptor 1 (TAAR1) found circulating in mammals and accumulating in many tissues including the brain. Its functional effects are now known to include decrease in heart rate, cardiac output, body temperature, and metabolic rate, as well as stimulation of lipid vs carbohydrate catabolism and neurological effects, including prolearning and antiamnestic action, reduced pain threshold, and reduction of non-REM sleep. The close structural similarity with thyroid hormone (TH) induced to speculate that T1AM might be synthetized from TH through decarboxylation and deiodination, but this hypothesis still requires validation. Notably, in addition to the structural similarities between T1AM and TH, T1AM contains the same arylethylamine scaffold also found in monoamine neurotransmitters, implicating an intriguing role for T1AM as both a neuromodulator and a hormone-like molecule constituting a part of thyroid hormone action. Recent evidence indicates that targeting TAAR1 may provide a new therapeutic approach for the treatment of a range of neuropsychiatric and metabolic disorders. Consistently, T1AM and recently developed halogen free biaryl-methane thyronamine-like TAAR1 agonists, SG-1 and SG-2, have emerged as rapid modulators of behavior and metabolism, with SG-2 showing a potency almost comparable to that of T1AM. To assess the therapeutic potential of TAAR1 agonists for neuroprotection, in the present thesis we investigated whether T1AM and its corresponding halogen free synthetic analogue SG-2 improve learning and memory when systemically administered to mice at submicromolar doses. In addition, since autophagy is key for neuronal plasticity, T1AM and newly developed thyronamine-like TAAR1 agonists SG-1 and SG-2 were evaluated as autophagy inducers in cell lines. T1AM is known to induce pro-learning and anti-amnestic responses when administered icv at very low doses (1.32 to 4 μg.kg-1) to mice, but its effects on memory after systemic administration are currently unknown. To address this point, we evaluated the behavior of CD-1 mice injected i.p. with T1AM or SG-2 (1.32, 4 and 11 μg.kg-1), in the passive avoidance test, while measuring in specific brain areas the activation of typical signalling proteins involved in memory acquisition, including pERK and transcription factor c-fos. The passive avoidance test showed that when administered i.p. at 11 μg.kg-1 either T1AM or SG-2 induced significant memory enhancement. T1AM also significantly increased retention when administered at a lower dosage (4 μg.kg-1). Memory acquisition and storage are typically associated with increased ERK1/2 phosphorylation. After treatment with T1AM and SG-2 at doses of 1.32 μg·kg-1, pERK could be detected, but its levels were not significantly different from those found in vehicle injected mice. However, after treatment with T1AM and SG-2 at doses that proved to be effective on memory acquisition and retention (i.e. 4 and 11 μg·kg-1) pERK turned out to be significantly higher (p<0.01) than that observed in the vehicle group. Similar to pERK, c-fos was not significantly changed in any brain area by treatment with 1.32 μg·kg-1 of T1AM or SG-2. For both compounds, only when injected at the highest dose (i.e. 11μg·kg-1) moderate changes of c-fos expression were observed. At the dosages active on memory, T1AM and SG-2 also proved to have an hyperalgesic effect. In addition, our pain threshold experiments revealed that TA1 and SG-6, the oxidative metabolites of T1AM and SG-2, respectively, seem to play a critical role for the action of the corresponding amine. In fact, at our settings, pretreatment with clorgyline abolished almost completely the effect on pain of T1AM or SG-2 administered i.p. at the highest dosage (i.e., 11 μg/kg). The same effect was also shown to involve the histaminergic system, as it disappeared after pretreatment with the histamine H1-receptor antagonist, pyrilamine. Preliminary results from a LC/MS-MS pharmacokinetic study of TA1 bio-distribution after sistemic administration, indicated that there is a difference in the capacity of clearing the acid by different tissues, with the brain conserving TA1 levels for longer than plasma or liver. Therefore, the brain might represent one important target for TA1 action. Autophagy (ATG) is one of the most important mechanisms of neuroprotection. Inducing autophagy may represent a reasonable strategy to develop therapeutics for the treatment of neurodegenerative diseases, including Alzheimer's disease. Therefore, to explore the possible link between TAAR1 activation and neuroprotection, we investigated the ability of T1AM, SG-1 and SG-2 to induce autophagy in human glioblastoma cell lines (U-87MG) by examining the formation of autophagosomes and autophagic flux. During the process of autophagy, LC3I is converted to its lipidated form LC3II, which is one of the hallmarks of autophagy and essential for the formation of autophagosome. P62 is used as a marker of autophagic flux and inversely correlates with autophagic activity. It binds directly to LC3 and degrades during autophagy. In cultured U-87MG cells exposed to 1μM T1AM, SG-1, SG-2 (for 0.5, 4, 8 and 24h) transmission electron microscopy (TEM) and immunofluorescence (IF) showed a significant (p<0.01) time-dependent increase of autophagy vacuoles and microtubule-associated protein 1 light chain 3 (LC3), with T1AM and SG-1 being the most effective agents. Consistently, western blotting results showed that test compounds increased the conversion of LC3-I to LC3-II while decreasing the levels of P62 in an obvious time-dependent manner. We then proceeded to elucidate which pathway was involved in ATG induction by assessing the effect of our test compounds on the PI3K–AKT–mTOR pathway. We found that 1μM T1AM, SG-1 and SG-2 decreased pAKT/AKT ratio at 0.5 and 4h after treatment (p<0.01), suggesting that these compounds induce autophagy through a reduction of pAkt level. Taking into account the key role played by ATG and/or Ubiquitine-proteasome (UP) in all clearing pathways modulating cell survival and disease mechanisms, and considering their involvement in a wide range of disorders, including neurodegenerative diseases (NDDs), we were also able to prove the ability of T1AM, SG-1 and SG2 to modulate the UP system. Indeed, our TEM analysis showed increased 20S proteasome recruitment to autophagosome in U-87MG cells after treatment with 1μM T1AM, SG-1 and SG-2, suggesting that these compounds might modulate both ATG and UP protein clearing pathways within the autophagoproteasomes. A growing body of evidence has suggested the presence of a strong correlation between obesity and neurodegeneration. NDDs, such as Alzheimer Disease (AD) and Parkinson Disease (PD), are characterized by a progressive loss of memory and cognition, which can ultimately lead to death. This deterioration is majorly a result of inflammation due to aberrant protein deposition, oxidative stress and modification in lipid pathways. Recent studies demonstrated acute and chronic T1AM treatment to have potent effects on shifting whole body macro-nutrient metabolism in mammals. On the basis of these findings, we decided to explore whether T1AM, SG-2 and recently designed synthetic thyronamine/thyroid hormone-hybrid analogs IS25 and TG46 could promote lipolysis in HepG2 cells. Oil Red O staining of HepG2 revealed that all test compounds reduced total lipid accumulation into lipid droplets compared to the control. Moreover, the analysis of free glycerol release confirmed that decreased accumulation of lipids in HepG2 cells observed after Oil Red O staining was caused by increased lipolysis. The involvement of AMPK/ACC modulation was also confirmed by western blot analysis that showed an enhancement of both pAMPK/AMPK and pACC/ACC ratios. AMPK stimulation by test compounds led indeed to the phosphorylation and consequent inactivation of acetyl coenzyme A carboxylase (ACC), the major regulator of fatty acids synthesis. In conclusion, taken together our data displayed that T1AM and thyronamine-like compounds SG-1 and SG-2 have neuroprotective properties, which also involve the induction of autophagy and the regulation of Ubiquitine-Proteasome System. Indirectly, together with newly designed thyronamine/thyroid hormone- hybrid analogs, they could exert a protective action through lipolytic effects. This novel aspect requires further investigation.

Maternal smoking during pregnancy is known to result in an increased incidence of intra-uterine growth retardation. This in part may be due to deleterious effects on the placenta, which is the conduit between the mother and fetus. This study was designed to investigate the effect of maternal smoking on placental function: morphometry, oxygen diffusive capacity, trace element content (zinc and cadmium), microvillous border membrane (MVBM) vesicle zinc and alanine uptake, and placental enzyme activity. The magnitude of maternal smoking and confounding factors were determined twice by questionnaire during pregnancy and confirmed by plasma cotinine; a total of 105 placentae were collected. Morphological changes in membrane thickness, and chrionic villi composition were observed with maternal smoking, however these changes were not great enough to affect the placental oxygen diffusive conductance. Placental cadmium content increased with maternal smoking and also correlated with placental zinc content. There was no correlation for cadmium or zinc with placental metallothionein. MVBM vesicle uptake of zinc exhibited no differences between smoking and non-smoking groups. Similarly, MVBM vesicle sodium-independent alanine uptake exhibited no difference, however sodium-dependent alanine uptake was greater in the smoking group. Placental cytochrome P450 ethoxyresorufin-O-deethylase activity was greater in the smoking group placentae compared to the non-smoking group, however quinone reductase activity was unaffected by maternal smoking. The overall findings of this study extend knowledge regarding the impact of maternal smoking on placental function and support current clinical advice for pregnant mothers to stop smoking during pregnancy.

Cacti (Cactaceae) represent a family of highly specialized angiosperm plants with a native range of distribution restricted to the American continents. Columnar cacti of the sub-family Cactoideae evolved in adaptation to their arid or semi-arid habitats characteristics that distinguish them from most other dicot plants, e.g. the stem succulence with a strongly vascularized storage parenchyma and the presence of the spine wearing areoles. Although cacti have been in cultivation since the discovery of America, some studies even suggest the agricultural use in pre-colombian times, and many scientific investigations were carried out on the functional morphology and anatomy with regard to biomechanical adaptations of the found structures, no research focused on the branch-stem attachment. The most conspicuous features of such a ramification are the pronounced constrictions at the branch-stem junctions that are also present in the lignified vascular structures within the succulent cortex. Based on Finite Element Analyses of ramification models it could be demonstrated that these indentations in the region of high flexural and torsional stresses are not regions of structural weakness, e.g. allowing vegetative propagation. On the contrary, they can be regarded as anatomical adaptations to increase the stability by fine-tuning the stress state and stress directions in the junction along prevalent fiber directions. The development of the woody support structure within the succulent cortex of the parental shoot can be traced back to the leaf and bud traces of the dormant axillary buds. Surprisingly, these initials also develop into another woody structure supporting the flowers of the cacti. As these two support structures differ significantly in their macroscopic and microscopic anatomy and as they develop from the same initial state as leaf/bud traces, another objective of this work was to analyze the secondary growth of the two structures with traditional botanic investigation methods. The results of these investigations reveal a wood dimorphism consisting of an early parenchymatous phase followed later by fibrous wood in both kind of support structure. In vegetative branches, the woody support structures have the typical ringlike arrangement as found in the stele of the parental shoot, whereas the flower support structures have a reticular arrangement of interconnected woody strands. This fundamentally different anatomy of the support structures results from the formation of an interfascicular cambium between the leaf/bud traces when a vegetative branch forms or its absence in the case of a flower. After shedding light on the functional morphology and anatomy of the cactus ramification and their development the question arises if the found load adaptation strategies may serve to improve technical fiber composite structures analogue to the design recommendation developed from the biomechanical analyses of tree ramifications. Such a biomimetic transfer from the cactus ramification as biological role model to a technical implementation and the adaptation of the fine-tuned geometric shape and arrangement of lignified strengthening tissues might contribute to the development of alternative concepts for branched fiber-reinforced composite structures within a limited design space.

This thesis introduces normal factor graphs under a new semantics, namely, the exterior function semantics. Initially, this work was motivated by two distinct lines of research. One line is ``holographic algorithms,'' a powerful approach introduced by Valiant for solving various counting problems in computer science; the other is ``normal graphs,'' an elegant framework proposed by Forney for representing codes defined on graphs. The nonrestrictive normality constraint enables the notion of holographic transformations for normal factor graphs. We establish a theorem, called the generalized Holant theorem, which relates a normal factor graph to its holographic transformation. We show that the generalized Holant theorem on one hand underlies the principle of holographic algorithms, and on the other reduces to a general duality theorem for normal factor graphs, a special case of which was first proved by Forney. As an application beyond Forney's duality, we show that the normal factor graphs duality facilitates the approximation of the partition function for the two-dimensional nearest-neighbor Potts model. In the course of our development, we formalize a new semantics for normal factor graphs, which highlights various linear algebraic properties that enables the use of normal factor graphs as a linear algebraic tool. Indeed, we demonstrate the ability of normal factor graphs to encode several concepts from linear algebra and present normal factor graphs as a generalization of ``trace diagrams.'' We illustrate, with examples, the workings of this framework and how several identities from linear algebra may be obtained using a simple graphical manipulation procedure called ``vertex merging/splitting.'' We also discuss translation association schemes with the aid of normal factor graphs, which we believe provides a simple approach to understanding the subject. Further, under the new semantics, normal factor graphs provide a probabilistic model that unifies several graphical models such as factor graphs, convolutional factor graphs, and cumulative distribution networks.

La structure et l’intensité des interactions ressources-consommateurs qui forment les réseaux trophiques régulent une très grande partie des transferts de biomasse mais aussi de contaminants biologiques et chimiques dans les écosystèmes. L’objectif de la thèse est de développer des modèles permettant d’étudier les mécanismes de transport des contaminants et d’évaluer ainsi d’une part la dynamique des maladies infectieuses et des pollutions chimiques, et d’autre part les réponses des réseaux trophiques soumis à ces contaminations.[...] À l’issue de ces travaux, une quatrième étape de la thèse a été d’intégrer les interactions trophiques, les dynamiques des parasites et les impacts des pollutions dans des méta-écosystèmes (i.e. avec dispersions d’individus entre écosystèmes). En utilisant la théorie des matrices aléatoires nous avons établi des mesures des risques d’émergence de parasites que nous avons évalués en fonction des perturbations extérieures.L’étude a ainsi montré que ces perturbations augmentent les risques épidémiques, mais que ces risques pouvaient être réduits par la dispersion des individus (sains et infectés) sous certaines conditions qui sont,par exemple pour les TTP, un nombre d’espèces plus grand que le nombre d’écosystèmes connectés, et un taux de virulence plus faible que le taux de contagion.Ainsi, dans un contexte planétaire d’augmentation des pressions anthropiques sur les écosystèmes,cette thèse de modélisation apporte un ensemble d’outils et de développements conceptuels permettant d’analyser quantitativement et qualitativement les transferts et les impacts des contaminants sur les écosystèmes<br>Structure and strength of trophic interactions shaping food webs regulate a large part of biomass andenergy transfer in ecosystems, but also the transfer of biological and chemical contaminants. The aim ofthe PhD thesis is to develop models describing the mechanisms of contaminant transmission and using them to study the dynamics of infectious diseases and chemical pollutions, and also the response of trophic networks subject to those contaminations.[...] Following those works, a fourth step of the thesis has been to integrate trophic interactions, parasite dynamics and pollutions effects in order to study the stability of meta community (i.e. spatially connectedcommunities) and the risk of disease outbreaks. To do so, we use the theory of random matrices andwe introduced new criteria of metacommunity stability and of disease outbreak in metacommunity, both under external pressures. The study showed that external perturbations increase the risk of epidemics,but that those risks could be reduced with the dispersal of individuals (susceptible and infectious) underspecific conditions such as, for TTP, a greater number of species than that of connected ecosystems, and a smaller virulence than the contagion rate.In this way, in a context of planetary increase of anthropogenic pressures on ecosystems, this PhD thesis in modeling provides a set of tools and conceptual developments suitable to analyze quantitatively and qualitatively the transfers and impacts of contaminants in ecosystems

Le déoxynivalénol (DON) est une mycotoxine de type trichothécène de type B, principalement produite par le genre Fusarium. C'est l'une des mycotoxines les plus répandues, elle est largement trouvée dans les céréales et les produits dérivés des céréales. Le cadmium est un composant de la croûte terrestre et un polluant environnemental courant. C'est un métal trace non essentiel et toxique pour la santé des humains et des animaux. Bien que la toxicité individuelle du DON et du Cd ait été bien étudiée, leur effet combiné est peu étudié. L'intestin étant le premier organe ciblé par les contaminants alimentaires, le but de cette étude est d'explorer l'effet combiné du DON et du Cd sur la fonction de barrière intestinale à l'aide de modèles in vitro, in vivo et ex vivo. In vitro, des cellules épithéliales intestinales humaines Caco-2 ont été traitées avec une série de concentrations de DON et de Cd (0-30 μM) seules ou en combinaison. La fonction de barrière des cellules Caco-2 a été évaluée par la mesure de la résistance électrique transépithéliale (TEER), de la perméabilité paracellulaire et des protéines jonctionnelles. Le mélange DON, Cd et DON+Cd a diminué le TEER et augmenté la perméabilité paracellulaire de manière dépendante de la concentration. L'abondance des protéines jonctionnelles E-cadhérine et occludine a été considérablement réduite dans les cellules exposées au DON, au Cd et au DON+Cd, tandis que l'expression de ZO-1 et de claudine-3 et -4 est restée inchangée. Le mélange DON Cd a eu des effets légèrement supérieurs ou similaires à ceux du contaminant le plus toxique. In vivo, les rats ont été exposés à des aliments contaminés par du DON (8,2 mg / kg), et à de l'eau de boisson contaminée par du Cd (5 mg / L) ou au mélange DON+Cd pendant 4 semaines. Les résultats n'ont montré aucun effet sur la prise de poids corporel au cours de l'expérience. Des dommages morphologiques légers caractérisés par un oedème au niveau de la lamina propria et un aplatissement et une fusion des villosités ont été découverts chez le rat exposé à chaque contaminant. Le score lésionnel du jéjunum était plus élevé chez tous les animaux traités que chez les animaux témoins. Une diminution significative de la profondeur de la crypte jéjunale a été observée chez les rats exposés au DON, au Cd et au DON+Cd, alors que la hauteur des villosités n'était pas affectée. Une immunomarquage plus faible de l'E-cadhérine dans le jéjunum de rats exposés à des contaminants seuls ou en association a également été observée, alors que l'occludine n'a diminué que chez les rats exposés au DON et au DON+Cd. Comme indiqué in vitro, l'exposition in vivo au DON et au Cd a induit des effets similaires à ceux du contaminant le plus toxique. Des explants jéjunaux de porcs ex vivo ont été exposés au DON (0-24 μM), au Cd (0-96 μM) et à la combinaison de DON+Cd. Le DON seul et le mélange DON Cd ont stimulé la réponse immunitaire chez le jéjunum en régulant positivement l'expression d'ARNm de IL-1, IL-1, IL-8 et TNF- de manière dose-dépendante, tandis que le Cd seul n'a pas affecté ces gènes. L'expression génique des métallothionéines (MT), y compris MT1A et MT2A, était régulée positivement de manière dose-dépendante par le Cd seul et le mélange, mais n'était pas affectée par le DON seul. La régulation à la hausse des gènes de cytokines et de MT induite par le DON+Cd était similaire à celle obtenue par le DON ou le Cd seul. En conclusion, le DON et le Cd modifient tous deux la fonction de barrière intestinale et l'effet combiné est similaire avec leur effet individuel. L'effet du mélange n'a démontré aucune synergie, ce qui suggère que la réglementation sur chaque contaminant protège suffisamment les consommateurs exposés aux mélanges de DON et de Cd<br>Deoxynivalenol (DON) is a type B trichothecene mycotoxin mainly produced by Fusarium genus. It is one of the most prevalent mycotoxins widely found in cereals and cereal-derived products. Cadmium is a component of earth’s crust and also a common environmental pollutant. It is a nonessential trace metal and toxic for humans and animals health. Although the individual toxicity of DON and Cd has been well investigated, their combined effect is poorly studied. As intestine is the first organ targeted by food contaminants, the aim of this study is to explore the combined effect of DON and Cd on the intestinal barrier function using in vitro, in vivo and ex vivo models. In vitro, the human intestinal epithelail cells Caco-2 were treated with a series of concentrations of DON and Cd (0-30 μM) alone or in combination. The barrier function of Caco-2 cells was assessed through the measurement of transepithelial electrical resistance (TEER), paracellular permeability and junctional proteins. DON, Cd and DON+Cd mixture decreased the TEER and increased the paracellular permeability in a concentration-dependent manner. The abundance of junctional proteins E-cadherin and occludin was considerably reduced in cells exposed to DON, Cd and DON+Cd, while the expression of ZO-1, and claudin-3 and -4 remained unchanged. The mixture DON+Cd induced slightly higher or similar effects than the most toxic contaminant. In vivo, rats were exposed to DON-contaminated feed (8.2 mg/kg feed), and Cd-contaminated drinking water (5 mg/L) or to the mixture DON+Cd for 4 weeks. The results showed no effect on body weight gain during the experiment. Mild morphological damage characterized by edema in lamina propria and villi flattening and fusion was found in rat exposed to each contaminant. The lesional score of jejunum was higher in all the treated animals than that in control animals. A significant decrease of jejunal crypt depth was observed in rats exposed to DON, Cd and DON+Cd, whereas villi height remained unaffected. A lower immunostaining of E-cadherin in the jejunum of rats exposed to contaminants alone or in combination was also observed, whereas occludin was only decreased in rats exposed to DON and DON+Cd. As shown in vitro, in vivo exposure to both DON and Cd induced similar effects than the most toxic contaminant. Ex vivo, jejunal explants of pigs were exposed to DON (0-24 μM), Cd (0-96 μM) and in combination DON+Cd. DON alone and mixture DON+Cd stimulated immune response in jejunum by upregulating mRNA expression of IL-1, IL-1, IL- 8 and TNF- in a dose-dependent manner, while Cd alone did not affect these genes. Gene expression of metallothioneins (MTs) including MT1A and MT2A was dose-dependently upregulated by Cd alone and mixture, but not affected by DON alone. The upregulation of cytokine and MTs genes induced by DON+Cd was similar than by DON or Cd alone. In conclusion, both DON and Cd alter intestinal barrier function and the combined effect is similar with their individual effect. The effect of the mixture did not demonstrate any synergy, suggesting that regulation on individual contaminant is protective enough for consumers exposed to DON and Cd mixtures