L'urne de Polya est l'exemple typique de processus stochastique avec renforcement. La limite presque sûre (p.s.) en temps existe, est aléatoire et non dégénérée. L'urne de Friedman est une généralisation naturelle dont la limite (proportion asymptotique en temps) n'est plus aléatoire. De nombreux modèles aléatoires sont fondés sur des processus de renforcement comme pour la conception d'essais cliniques au design adaptatif, en économie, ou pour des algorithmes stochastiques à des fins d'optimisation ou d'estimation non paramétrique. Dans ce mémoire, inspirés par de nombreux articles récents, nous introduisons une nouvelle famille de systèmes (finis) de processus de renforcement où l'interaction se traduit par un phénomène de renforcement collectif additif, de type champ moyen. Les deux taux de renforcement (l'un spécifique à chaque composante, l'autre collectif et commun à toutes les composantes) sont possiblement différents. Nous prouvons deux types de résultats mathématiques. Différents régimes de paramètres doivent être considérés : type de la règle (brièvement, Polya/Friedman), taux du renforcement. Nous prouvons l'existence d'une limite p.s. coommune à toutes les composantes du système (synchronisation). La nature de la limite (aléatoire/déterministe) est étudiée en fonction du régime de paramètres. Nous étudions également les fluctuations en prouvant des théorèmes centraux de la limite. Les changements d'échelle varient en fonction du régime considéré. Différentes vitesses de convergence sont ainsi établies. / The Polya urn is the paradigmatic example of a reinforced stochastic process. It leads to a random (non degenerated) almost sure (a.s.) time-limit.The Friedman urn is a natural generalization whose a.s. time-limit is not random anymore. Many stochastic models for applications are based on reinforced processes, like urns with their use in adaptive design for clinical trials or economy, stochastic algorithms with their use in non parametric estimation or optimisation. In this work, in the stream of previous recent works, we introduce a new family of (finite) systems of reinforced stochastic processes, interacting through an additional collective reinforcement of mean field type. The two reinforcement rules strengths (one componentwise, one collective) are tuned through (possibly) different rates. In the case the reinforcement rates are like 1/n, these reinforcements are of Polya or Friedman type as in urn contexts and may thus lead to limits which may be random or not. We state two kind of mathematical results. Different parameter regimes needs to be considered: type of reinforcement rule (Polya/Friedman), strength of the reinforcement. We study the time-asymptotics and prove that a.s. convergence always holds. Moreover all the components share the same time-limit (synchronization). The nature of the limit (random/deterministic) according to the parameters' regime is considered. We then study fluctuations by proving central limit theorems. Scaling coefficients vary according to the regime considered. This gives insights into the different rates of convergence.

No description available.

“Prestige and Prurience: The Decline of the American Art House and the Emergence of Sexploitation, 1957-1972” presents a historical narrative of the art house theatre during the 1960s and its surrounding years, examining the ways in which art theatres transformed into adult theatres during the 1960s and 1970s. Beginning in earnest in the immediate post-war period, art houses in America experienced a short period of growth before stagnating in the middle 1950s. With the release in 1957 of the erotically charged Brigitte Bardot film …And God Created Woman, a new era of art houses followed, one that is characterized by the emergence of sexualized advertising, content and stars. As the 1960s came, sex films like The Immoral Mr. Teas played on art film marketing strategies and even screened in many art houses. Gradually, sexploitation films began to dominate art house programs and replace European art films and Hollywood revivals. In this transitional period, however, sexploitation films used key strategies to emulate many art film characteristics, and likewise art films used sexploitation techniques in order to maintain marketability for American distribution and exhibition. By studying the promotion and programming used by art house theatres during this period, this thesis identifies and announces a number of key trends within the dynamic period for art houses. The period is distinguished by its convergence of practices related to prestigious and prurient signs, merging art and sex in ways unique to the era and to the circumstances by which sex films infiltrated art houses and art films pandered to salacious interests. It presents a new perspective on the history of art houses, art cinema, American exhibition, sexploitation films, hardcore pornography and censorship. / text

Neste trabalho estudamos os type-dependent stochastic spin models propostos por Fernández et al., os que chamaremos de modelos de spins estocástico dependentes de tipo, e que foram usados para modelar redes de sinalização biológica. A modelagem original descreve a evolução macroscópica de um modelo de spin-flip de tamanho finito com k tipos de spins, possuindo um número arbitrário de estados internos, que interagem através de uma dinâmica estocástica não reversível. No limite termodinânico foi provado que, em um intervalo de tempo finito as trajetórias convergem quase certamente para uma trajetória determinística, dada por uma equação diferencial de primeira ordem. Os comportamentos destes sistemas dinâmicos podem incluir bifurcações, relacionadas às transições de fase do modelo. O nosso objetivo principal foi de estender os modelos de spins com dinâmica de Glauber utiliza- dos pelos autores, permitindo trocas múltiplas dos spins. No contexto biológico tentamos incluir situações nas quais moléculas de tipos diferentes trocam simultaneamente os seus estados internos. Utilizando diversas técnicas, como as de grandes desvíos e acoplamento, tem sido possível demonstrar a convergência para o sistema dinâmico associado. / We study type-dependent stochastic spin models proposed by Fernández et al., which were used to model biological signaling networks. The original modeling setup describes the macroscopic evolution of a finite-size spin-flip model with k types of spins with arbitrary number of internal states interacting through a non-reversible stochastic dynamics. In the thermodynamic limit it was proved that, within arbitrary finite time-intervals, the path converges almost surely to a deterministic trajectory determined by a first-order (non-linear) differential equation. The behavior of the associated dynamical system may include bifurcations, associated to phase transitions in the statistical mechanical setting. Our aim is to extend the spin model with Glauber dynamics, to allow multiple spin-flips. In the biological context we included situations in which molecules of different types simultaneously change their internal states. Using several methods, such as large deviations and coupling, we prove the convergence theorem.

Monitoring the mechanical integrity of critical structures is extremely important, as mechanical defects can potentially have adverse impacts on their safe operability throughout their service life. Structural defects can be detected by using active structural health monitoring (SHM) approaches, in which a given structure is excited with harmonic mechanical waves generated by actuators. The response of the structure is then collected using sensor(s) and is analyzed for possible defects, with various active SHM approaches available for analyzing the response of a structure to single- or multi-frequency harmonic excitations. In order to identify the appropriate excitation frequency, however, the majority of such methods require a priori knowledge of the characteristics of the defects under consideration. This makes the whole enterprise of detecting structural defects logically circular, as there is usually limited a priori information about the characteristics and the locations of defects that are yet to be detected. Furthermore, the majority of SHM techniques rely on sensors for response collection, with the very same sensors also prone to structural damage. The Surface Response to Excitation (SuRE) method is a broadband frequency method that has high sensitivity to different types of defects, but it requires a baseline. In this study, initially, theoretical justification was provided for the validity of the SuRE method and it was implemented for detection of internal and external defects in pipes. Then, the Comprehensive Heterodyne Effect Based Inspection (CHEBI) method was developed based on the SuRE method to eliminate the need for any baseline. Unlike traditional approaches, the CHEBI method requires no a priori knowledge of defect characteristics for the selection of the excitation frequency. In addition, the proposed heterodyne effect-based approach constitutes the very first sensor-less smart monitoring technique, in which the emergence of mechanical defect(s) triggers an audible alarm in the structure with the defect. Finally, a novel compact phased array (CPA) method was developed for locating defects using only three transducers. The CPA approach provides an image of most probable defected areas in the structure in three steps. The techniques developed in this study were used to detect and/or locate different types of mechanical damages in structures with various geometries.

No description available.

We explore the applicability of local polynomial approximation of signals for noise suppression. In the context of data regression, Savitzky and Golay showed that least-squares approximation of data with a polynomial of fixed order, together with a constant window length, is identical to convolution with a finite impulse response filter, whose characteristics depend entirely on two parameters, namely, the order and window length. Schafer’s recent article in IEEE Signal Processing Magazine provides a detailed account of one-dimensional Savitzky-Golay (SG) filters. Drawing motivation from this idea, we present an elaborate study of two-dimensional SG filters and employ them for image denoising by optimizing the filter response to minimize the mean-squared error (MSE) between the original image and the filtered output. The key contribution of this thesis is a method for optimal selection of order and window length of SG filters for denoising images. First, we apply the denoising technique for images contaminated by additive Gaussian noise. Owing to the absence of ground truth in practice, direct minimization of the MSE is infeasible. However, the classical work of C. Stein provides a statistical method to overcome the hurdle. Based on Stein’s lemma, an estimate of the MSE, namely Stein’s unbiased risk estimator (SURE), is derived, and the two critical parameters of the filter are optimized to minimize the cost. The performance of the technique improves when a regularization term, which penalizes fast variations in the estimate, is added to the optimization cost. In the next three chapters, we focus on non-Gaussian noise models. In Chapter 3, image degradation in the presence of a compound noise model, where images are corrupted by mixed Poisson-Gaussian noise, is addressed. Inspired by Hudson’s identity, an estimate of MSE, namely Poisson unbiased risk estimator (PURE), which is analogous to SURE, is developed. Combining both lemmas, Poisson-Gaussian unbiased risk estimator (PGURE) minimization is performed to obtain the optimal filter parameters. We also show that SG filtering provides better lowpass approximation for a multiresolution denoising framework. In Chapter 4, we employ SG filters for reducing multiplicative noise in images. The standard SG filter frequency response can be controlled along horizontal or vertical directions. This limits its ability to capture oriented features and texture that lie at other angles. Here, we introduce the idea of steering the SG filter kernel and perform mean-squared error minimization based on the new concept of multiplicative noise unbiased risk estimation (MURE). Finally, we propose a method to robustify SG filters, robustness to deviation from Gaussian noise statistics. SG filters work on the principle of least-squares error minimization, and are hence compatible with maximum-likelihood (ML) estimation in the context of Gaussian statistics. However, for heavily-tailed noise such as the Laplacian, where ML estimation requires mean-absolute error minimization in lieu of MSE minimization, standard SG filter performance deteriorates. `1 minimization is a challenge since there is no closed-form solution. We solve the problem by inducing the `1-norm criterion using the iteratively reweighted least-squares (IRLS) method. At every iteration, we solve an l`2 problem, which is equivalent to optimizing a weighted SG filter, but, as iterations progress, the solution converges to that corresponding to `1 minimization. The results thus obtained are superior to those obtained using the standard SG filter.

Neste trabalho estudamos os type-dependent stochastic spin models propostos por Fernández et al., os que chamaremos de modelos de spins estocástico dependentes de tipo, e que foram usados para modelar redes de sinalização biológica. A modelagem original descreve a evolução macroscópica de um modelo de spin-flip de tamanho finito com k tipos de spins, possuindo um número arbitrário de estados internos, que interagem através de uma dinâmica estocástica não reversível. No limite termodinânico foi provado que, em um intervalo de tempo finito as trajetórias convergem quase certamente para uma trajetória determinística, dada por uma equação diferencial de primeira ordem. Os comportamentos destes sistemas dinâmicos podem incluir bifurcações, relacionadas às transições de fase do modelo. O nosso objetivo principal foi de estender os modelos de spins com dinâmica de Glauber utiliza- dos pelos autores, permitindo trocas múltiplas dos spins. No contexto biológico tentamos incluir situações nas quais moléculas de tipos diferentes trocam simultaneamente os seus estados internos. Utilizando diversas técnicas, como as de grandes desvíos e acoplamento, tem sido possível demonstrar a convergência para o sistema dinâmico associado. / We study type-dependent stochastic spin models proposed by Fernández et al., which were used to model biological signaling networks. The original modeling setup describes the macroscopic evolution of a finite-size spin-flip model with k types of spins with arbitrary number of internal states interacting through a non-reversible stochastic dynamics. In the thermodynamic limit it was proved that, within arbitrary finite time-intervals, the path converges almost surely to a deterministic trajectory determined by a first-order (non-linear) differential equation. The behavior of the associated dynamical system may include bifurcations, associated to phase transitions in the statistical mechanical setting. Our aim is to extend the spin model with Glauber dynamics, to allow multiple spin-flips. In the biological context we included situations in which molecules of different types simultaneously change their internal states. Using several methods, such as large deviations and coupling, we prove the convergence theorem.

A unique mechanism of protein oligomerization is domain swapping. It is a feature found in some proteins wherein a dimer or a higher oligomer is formed by the exchange of identical structural segments between protomers. Domain swapping is thought to have played a key role in the evolution of stable oligomeric proteins and in oligomerization of amyloid proteins. This thesis deals with studies to understand the significance of hinges involved in domain swapping for protein oligomerization and function. The stationary phase survival protein SurE from Salmonella typhimurium (StSurE) and Sesbania mosaic virus (SeMV) coat protein have been used as models for studies on domain swapping. This thesis has been divided into eight chapters. Chapter 1 provides a brief introduction to domain swapping, while Chapters 2 to 6 describes the studies carried out on StSurE protein, Chapter 7 deals with studies on SeMV coat protein. The final Chapter 8 provides brief descriptions of various experimental techniques employed during these investigations. Chapter 1 deals with a brief introduction to domain swapping in proteins. Examples where different domains are exchanged are cited. Then it describes physiological relevance of domain swapping in proteins and probable factors which promote swapping. Finally it also discusses the uncertainties that are inevitable in protein structure prediction and design. Chapter 2 describes the structure of Salmonella typhimurium SurE (StSurE; Pappachan et al., 2008) determined at a higher resolution. The chapter also deals with the sequence and structure based comparison of StSurE with other known SurE homolog structures. A comparative analysis of the relative conservation of N- and C-terminal halves of SurE protomer and variations observed in the quaternary structures of SurE homologs are presented. Then a brief introduction is provided on function of StSurE. The conserved active site of StSurE that might be important for its phosphatase activity is described. A plausible mechanism for the phosphatase activity as proposed by Pappachan et al. (2008) is presented. Crystal structures of StSurE bound with AMP, pNPP and pNP that was determined with the view of better understanding the mechanism of enzyme function is presented. These structures provide structural evidence for the mechanism proposed by Pappachan et al. (2008). Finally a substrate entry channel inferred from these structures is discussed. SurE from Salmonella typhimurium (StSurE) was selected for studies on domain swapping as there is at least one homologous structure (Pyrobaculum aerophilum - PaSurE) in which swapping of the C-terminal helices appears to have been avoided without leading to the loss of oligomeric structure or function. It was of interest to examine if an unswapped dimer of StSurE resembling PaSurE dimer could be constructed by mutagenesis. To achieve this objective, a crucial hydrogen bond in the hinge involved in C-terminal helix swapping was abolished by mutagenesis. These mutants were constructed with the intention of increasing the flexibility of the hinge which might bring the C-terminal helices closer to the respective protomer as in PaSurE. Chapter 3 presents a comparative analysis of the hinges involved in C-terminal helix swapping in PaSurE and StSurE. Based on the comparison of structure and sequence, crucial residues important for C-terminal helix swapping in StSurE were identified as D230 and H234. The chapter describes the construction of mutants obtained by substituting D230 and H234 by alanine and their biophysical characterization. Finally it describes structural studies carried out on these mutants. The mutation H234A and D230A/H234A resulted in highly distorted dimers, although helix swapping was not avoided. Comparative analysis of the X-ray crystal structures of native StSurE and mutants H234A and D230A/H234A reveal large structural changes in the mutants relative to the native structure. However the crystal structures do not provide information on the changes in dynamics of the protein resulting from these mutations. To gain better insights into the dynamics involved in the native and mutants H234A and D230A/H234A, MD simulations were carried on using GROMACS 4.0.7. Chapter 4 deals with a brief description of the theory of molecular dynamics, followed by results of simulation studies carried out on monomeric and dimeric forms of StSurE and dimeric forms of its mutants H234A and D230A/H234A. The conformational changes and dynamics of different swapped segments are discussed. Crystal structures of H234A and D230A/H234A mutants reveal that they form highly distorted dimers with altered dimeric interfaces. Chapter 5 focuses on comparison of dimeric interfaces of the native StSurE and hinge mutants H234A and D230A/H234A. Based on the analysis, three sets of interactions were selected to investigate the importance of the interface formed by swapped segments in StSurE mutants H234A and D230A/H234A. One of the selected sites corresponds to a novel interaction involving tetramerization loop in the hinge mutants H234A and D230A/H234A resulting in a salt bridge between E112 – R179’ and E112’ – H180 (prime denotes residue from the other chain of the dimeric protein). This salt bridge seems to stabilize the distorted dimer. It is shown by structural studies that the loss of this salt bridge due to targeted mutation restores symmetry and dimeric organization of the mutants. Loss of a crucial hydrogen bond in the hinge region involved in C-terminal helix swapping in SurE not only leads to large structural changes but also alters the conformation of a loop near the active site. It is of interest to understand functional consequences of these structural changes. StSurE is a phosphatase, and its activity could be conveniently monitored using the synthetic substrate para nitrophenyl phosphate (pNPP) at pH 7 and 25 ºC. Chapter 6 deals with the functional studies carried out with various StSurE mutants. The studies suggest that there is a drastic loss in phosphatase activity in hinge mutants D230A, H234A and D230A/H234A, while in the salt bridge mutants the function seems to have been restored. Few of these mutants also exhibit positive cooperativity, which could probably be due to altered dynamics of domains. Sesbania mosaic virus (SeMV) is a plant virus, belonging to genus sobemovirus. SeMV is a T=3 icosahedral virus (532 symmetry) made up of 180 coat protein (CP) subunits enclosing a positive-sense RNA genome. The asymmetric unit of the icosahedral capsid is composed of chemically identical A, B and C subunits occupying quasi-equivalent environments. Residues 48 – 59 of the N-terminal arms of the C subunits interact at the nearby icosahedral three-fold axes through a network of hydrogen bonds to form a structure called the “β-annulus”. Residues 60 – 73 form the “βA-arm” that connects the N-terminal β-annulus to the rest of the protomer. Various studies on SeMV-CP suggest that different lengths of the N-terminal segments affect the assembly of virus. It might be possible to exploit this flexibility of the N-terminus in SeMV-CP to introduce swapping of this segment between two 2-fold related C subunits as is found in Rice yellow mottle virus (RYMV), another sobemovirus, with which SeMV shares significant sequence similarity. Chapter 7 focuses on attempts made to examine the mutational effects planned to introduce domain swapping. The strategy used for introducing swapping in SeMV-CP was based on the sequence of the βA-arm or the hinge involved in swapping of β-annulus in RYMV. TEM images of the mutant virus like particles obtained suggest that they are heterogeneous. These mutants could not be crystallized, probably due to the heterogeneity. However, the assembly of the expressed proteins to virus like particles was profoundly influenced by the mutations. Chapter 8 discusses various crystallographic, biophysical and biochemical techniques used during these investigations. Finally the thesis concludes with Conclusions and Future perspectives of the various studies reported in the thesis. In summary, I have addressed the importance of amino acid residues and interactions of hinges involved in domain swapping for the quaternary structure and function of proteins.

Philosophiae Doctor - PhD / Tuberculosis is a bacterial infection which is a major cause of death worldwide. TB is a curable disease, however the bacterium can become resistant to the first line treatment against the disease. This leads to a disease called drug resistant TB that is difficult and expensive to treat. It is well-known that TB disease thrives in communities in overcrowded environments with poor ventilation, weak nutrition, inadequate or inaccessible medical care, etc, such as in some prisons or some refugee camps. In particular, the World Health Organization discovered that a number of prisoners come from socio-economic disadvantaged population where the burden of TB disease may be already high and access to medical care may be limited. In this dissertation we propose compartmental models of systems of differential equations to describe the population dynamics of TB disease under conditions of crowding. Such models can be used to make quantitative projections of TB prevalence and to measure the effect of interventions. Indeed we apply these models to specific regions and for specific purposes. The models are more widely applicable, however in this dissertation we calibrate and apply the models to prison populations.