La stéganographie est l'art de la communication secrète. L'objectif est de dissimuler un message secret dans un médium anodin de sorte qu'il soit indétectable. De nos jours, avec la généralisation d'Internet et l'apparition des supports numériques (fichiers audio, vidéos ou images), plusieurs philosophies de conception de schéma stéganographique ont été proposées. Parmi les méthodes actuelles appliquées aux images numériques naturelles, nous trouvons les méthodes d'insertion adaptative, dont le principe repose sur la modification du médium de couverture avec une garantie d'avoir un certain niveau de sécurité. Ces méthodes représentent une véritable avancée en stéganographie.Dans ce manuscrit, après avoir rappelé les concepts récents de stéganographie adaptative, nous présentons une procédure automatique et complète pour l'insertion adaptative de données secrètes dans des images numériques naturelles. L'approche proposée est une " méta-méthode " basée " oracle ", appelée ASO (Adaptive Steganography by Oracle), qui permet de préserver à la fois la distribution de l'image de couverture et la distribution de la base d'images utilisée par l'émetteur. Notre approche permet d'obtenir des résultats nettement supérieurs aux méthodes actuelles de l'état de l'art, et est donc l'une, si ce n'est la meilleure approche du moment. Par ailleurs, nous définissons également un nouveau paradigme en stéganographie qui est la stéganographie par base, ainsi qu'une nouvelle mesure de sélection pour les images stéganographiées, permettant d'améliorer encore plus les performances de notre schéma d'insertion. Les différentes expérimentations, que nous avons effectuées sur des images réelles, ont confirmé la pertinence de cette nouvelle approche.

Dans cette thèse nous donnons une description complète de la dynamique d'une classe L de fonctions de degré un du cercle, supposées de classe (deux fois dérivable) C^2 à l'exception de deux points où seule la continuité est exigée, et telles qu'elles soient constantes sur un des intervalles délimité par ces derniers. De plus sur des demi-voisinages ouverts de ces points elles s'écrivent sous la forme x^l où l est un nombre réel positif appelé l'exposant critique de la fonction. Dans le chapitre 2 nous montrons pour la sous-classe de L des fonctions dont le nombre de rotation est de type borné, l'existence d'une transition dans la géométrie du système lorsque l'exposant critique traverse 2. Le cas plus général de fonctions en L avec nombre de rotation infinie est considéré dans le chapitre 3. Il devient pourtant plus délicat d'émettre des conjectures ; on rencontre parfois des surprises dues à laprésence de phénomènes paraboliques. De plus, nos résultats sur les applications du cercle nous permettent d'étudier l'intéressante théorie des flots de Cherry (chapitre 4). En particulier, on construit un exemple de tel flot qui a ensemble quasi-minimale métriquement non trivial. Nous donnons également une description complète des mesures physiques sur ce flot. Dans le chapitre 5 nous construisons un contrexemple de Denjoy qui est un difféomorphisme (indéfiniment dérivable) C^∞ partout sauf dans un point qui est demi-critique plat pour la fonction.

Suite aux grands changements politiques, économiques et sociaux que l’Occident a connus depuis plus d’un siècle, de nombreux problèmes ont émergé, de nouveaux défis ont été lancés et plusieurs approches et solutions ont été avancées. L’avènement de la démocratie, un exploit humain inestimable, a plus ou moins règlementé la pluralité idéologique, pour permettre un exercice politique organisé. Aujourd’hui, dans le nouvel ordre mondial, c’est la pluralité morale et religieuse qui a besoin d’être gérée; un défi pour les institutions démocratiques et pour la société civile, afin de réaliser un mieux vivre-ensemble dans le dialogue, la compréhension et le compromis. Or, beaucoup de travail est encore à faire : dans un premier temps, à l’intérieur de chaque tradition religieuse; dans un deuxième temps, entre les différentes traditions; et dans un troisième temps, entre ces traditions et la modernité. Le ‘dogmatisme’ est au cœur de ces débats, qu’il soit d’ordre traditionnel ou moderne, il entrave la raison dans son processus de libération et d’émancipation. La problématique de ce mémoire concerne la gestion de la pluralité morale et religieuse en Occident. Dans ce travail, nous allons essayer de démontrer comment la libération du dogmatisme en général et la libération du ‘dogmatisme’ musulman, en particulier, peuvent contribuer à la réalisation d’un mieux vivre-ensemble en Occident. Pour ce faire, nous analyserons les projets de deux penseurs musulmans contemporains : Muhammad Arkoun et Tariq Ramadan. Notre recherche va essentiellement se pencher sur leurs attitudes vis-à-vis de la tradition et de la modernité, car, nous pensons que l’enjeu du ‘dogmatisme’ est lié aux rapports des musulmans à leur tradition et à la modernité. Selon nos deux penseurs, la libération du ‘dogmatisme’ musulman n’est possible qu’à condition de pouvoir changer à la fois notre rapport à la tradition et à la modernité. Arkoun pense que ce changement doit suivre le modèle de la libération occidentale, au moyen d’une critique subversive de la tradition islamique. Cependant, Ramadan opte pour une réforme radicale de la pensée islamique qui vise une critique globale de la tradition, mais, qui épargne les fondements de la foi : le ‘sacré’. / Following the major political, economic and social changes that occurred in the West for over a century, many problems have emerged, new challenges have surfaced, and several approaches and solutions have been proposed. The advent of democracy, an invaluable human achievement, more or less regulated ideological plurality, and allowed the evolution of an organized political exercise. Today, in the new world order, it is the moral and religious diversity that need to be managed. The challenge remains for democratic institutions and civil society to create a better harmonious community through dialogue, understanding and compromise. However, much work is still to be done : first, within each religious tradition, second, between different traditions and third, between tradition and modernity. Dogmatism is at the heart of these debates. An order, whether traditional or modern hampers objectives reasoning in the process of liberation and emancipation. The issue of this paper concerns the management of the moral and religious plurality in the West. In this work, we will try to demonstrate how the relinquishing of ‘dogmatism’ in general and the relinquishing of Muslim ‘dogmatism’ in particular, can contribute to the achievement of a harmonious in a pluralistic West. This will be achieved by shedding light on the projects of two contemporary Muslim thinkers : Muhammad Arkoun and Tariq Ramadan. Our research is mainly to reflect on their attitudes towards tradition versus modernity, as we believe that the issue of dogmatism is linked to Muslims’ attitude towards tradition and modernity. According to these two thinkers, the release of muslims’ ‘dogmatism’ is only possible by changing both our relationship to tradition and modernity. Arkoun thinks this change should follow the model of Western release through a subversive critique of the Islamic tradition. However, Ramadan opts for a radical reform of Islamic thought through a comprehensive critique of the tradition, in order to save the foundation of faith : The ‘sacred’.

In this dissertation, we focus on the uncertainty quantification problems where the goal is to sample the porous media properties given integrated responses. We first introduce a reduced order model using the level set method to characterize the channelized features of permeability fields. The sampling process is completed under Bayesian framework. We hence study the regularity of posterior distributions with respect to the prior measures. The stochastic flow equations that contain both spatial and random components must be resolved in order to sample the porous media properties. Some type of upscaling or multiscale technique is needed when solving the flow and transport through heterogeneous porous media. We propose ensemble-level multiscale finite element method and ensemble-level preconditioner technique for solving the stochastic flow equations, when the permeability fields have certain topology features. These methods can be used to accelerate the forward computations in the sampling processes. Additionally, we develop analysis-of-variance-based mixed multiscale finite element method as well as a novel adaptive version. These methods are used to study the forward uncertainty propagation of input random fields. The computational cost is saved since the high dimensional problem is decomposed into lower dimensional problems. We also work on developing efficient advanced Markov Chain Monte Carlo methods. Algorithms are proposed based on the multi-stage Markov Chain Monte Carlo and Stochastic Approximation Monte Carlo methods. The new methods have the ability to search the whole sample space for optimizations. Analysis and detailed numerical results are presented for applications of all the above methods.

Πίσω από όλα αυτά τα δεδομένα που υπάρχουν κρύβεται ένας τεράστιος θησαυρός γνώσεων τον οποίο δεν μπορούμε να αντιληφθούμε καθώς η μορφή των πληροφοριών δεν μας το επιτρέπει. Έτσι αναπτύχθηκαν μέθοδοι και τεχνικές που μας βοηθούν να βρούμε την κρυμμένη γνώση και να την αξιοποιήσουμε προς όφελος κυρίως του κοινού και η πιο γνωστή μέθοδος, με την οποία θα ασχοληθούμε και εμείς είναι η Εξόρυξη Γνώσης. Στην εργασία που ακολουθεί θα μιλήσουμε για την χρήση των μεθόδων Εξόρυξης Γνώσης (όπως λέγονται) σε βιοϊατρικά δεδομένα. Στην αρχή θα κάνουμε αναφορά στην Μοριακή Βιολογία και στην Βιοπληροφορική. Ακολούθως θα δουμε την Ανακάλυψη γνώσης από βάσεις δεδομένων. Θα δούμε αναλυτικά την Εξόρυξη γνώσης και πιο πολύ τις μεθόδους κατηγοριοποίησης. Τέλος θα εφαρμόσουμε τους αλγορίθμους σε ιατροβιολογικά δεδομένα και θα δούμε τα συμπεράσματα που προκύπτουν αλλά και μελλοντικές επεκτάσεις. / Behind all these data there is hidden a huge treasure of knowledge which we can not understand . Thus developed methods and techniques that help us find the hidden knowledge and to utilize it for the benefit of the public. The most famous method, which we will study, is Data Mining. In the work that follows we will discuss the use of data mining methods (as they are called) in biomedical data. In the beginning, we will report information about Molecular Biology and Bioinformatics. Then. we will see the knowledge discovery in databases. We will see in detail the Data Mining and the classification methods. Finally we implement the algorithms in biomedical data and see the conclusions and future extensions.

I denna studie har jag genom att observera mig själv utforskat hur jag som blivande musiklärare undervisar vuxna, som har funktionsnedsättningar, i ensemble. Syftet har varit att undersöka vilka semiotiska resurser jag använder mig av då jag undervisar, hur de används och hur de förändras under arbetets gång. Som metod har jag använt mig av videoinspelning och kompletterande loggboksanteckningar. Ensemblegruppen bestod av ca tio vuxna med funktionsnedsättningar och två till fem lärare som vanligtvis arbetar med gruppen. Tillsammans hade vi fyra lektioner där jag undervisade i sång, instrument och ensemblespel. Resultatet presenteras med hjälp av följande teman: Lektion 1, Lektion 2 & 3 och Lektion 4. Vilka resurser jag använder mig av och hur dessa används beror i dessa fall främst på vilka instrument gruppen spelar. Resultatet diskuteras därefter utifrån vilka förutsättningar jag haft, det multimodala perspektivet och tidigare forskning. / In this study I have, by observing myself, analysed how I as a future music teacher educates adults with learning disabilities in ensemble situations. The purpose has been to study which semiotic resources I use during classes, how they are being used and in which way they are changing as the lessons progresses. My method has been video recordings and supplementing logbook notes. The ensemble group consisted of approximately ten adults with learning disabilities and two to five teachers who usually work with the group. Together we had four lessons in which I taught them about singing, instruments and playing in ensemble. In the result I have used the following themes: Lesson 1, Lesson 2 & 3 and Lesson 4. Which resources I use and how they are being used depends in these cases foremost on which instruments the group are playing. The result is discussed subsequently based on preconditions, the multimodal perspective as well as previous research.

abstract: The technology expansion seen in the last decade for genomics research has permitted the generation of large-scale data sources pertaining to molecular biological assays, genomics, proteomics, transcriptomics and other modern omics catalogs. New methods to analyze, integrate and visualize these data types are essential to unveil relevant disease mechanisms. Towards these objectives, this research focuses on data integration within two scenarios: (1) transcriptomic, proteomic and functional information and (2) real-time sensor-based measurements motivated by single-cell technology. To assess relationships between protein abundance, transcriptomic and functional data, a nonlinear model was explored at static and temporal levels. The successful integration of these heterogeneous data sources through the stochastic gradient boosted tree approach and its improved predictability are some highlights of this work. Through the development of an innovative validation subroutine based on a permutation approach and the use of external information (i.e., operons), lack of a priori knowledge for undetected proteins was overcome. The integrative methodologies allowed for the identification of undetected proteins for Desulfovibrio vulgaris and Shewanella oneidensis for further biological exploration in laboratories towards finding functional relationships. In an effort to better understand diseases such as cancer at different developmental stages, the Microscale Life Science Center headquartered at the Arizona State University is pursuing single-cell studies by developing novel technologies. This research arranged and applied a statistical framework that tackled the following challenges: random noise, heterogeneous dynamic systems with multiple states, and understanding cell behavior within and across different Barrett's esophageal epithelial cell lines using oxygen consumption curves. These curves were characterized with good empirical fit using nonlinear models with simple structures which allowed extraction of a large number of features. Application of a supervised classification model to these features and the integration of experimental factors allowed for identification of subtle patterns among different cell types visualized through multidimensional scaling. Motivated by the challenges of analyzing real-time measurements, we further explored a unique two-dimensional representation of multiple time series using a wavelet approach which showcased promising results towards less complex approximations. Also, the benefits of external information were explored to improve the image representation. / Dissertation/Thesis / Ph.D. Industrial Engineering 2011

abstract: In very small electronic devices the alternate capture and emission of carriers at an individual defect site located at the interface of Si:SiO2 of a MOSFET generates discrete switching in the device conductance referred to as a random telegraph signal (RTS) or random telegraph noise (RTN). In this research work, the integration of random defects positioned across the channel at the Si:SiO2 interface from source end to the drain end in the presence of different random dopant distributions are used to conduct Ensemble Monte-Carlo ( EMC ) based numerical simulation of key device performance metrics for 45 nm gate length MOSFET device. The two main performance parameters that affect RTS based reliability measurements are percentage change in threshold voltage and percentage change in drain current fluctuation in the saturation region. It has been observed as a result of the simulation that changes in both and values moderately decrease as the defect position is gradually moved from source end to the drain end of the channel. Precise analytical device physics based model needs to be developed to explain and assess the EMC simulation based higher VT fluctuations as experienced for trap positions at the source side. A new analytical model has been developed that simultaneously takes account of dopant number variations in the channel and depletion region underneath and carrier mobility fluctuations resulting from fluctuations in surface potential barriers. Comparisons of this new analytical model along with existing analytical models are shown to correlate with 3D EMC simulation based model for assessment of VT fluctuations percentage induced by a single interface trap. With scaling of devices beyond 32 nm node, halo doping at the source and drain are routinely incorporated to combat the threshold voltage roll-off that takes place with effective channel length reduction. As a final study on this regard, 3D EMC simulation method based computations of threshold voltage fluctuations have been performed for varying source and drain halo pocket length to illustrate the threshold voltage fluctuations related reliability problems that have been aggravated by trap positions near the source at the interface compared to conventional 45 nm MOSFET. / Dissertation/Thesis / Ph.D. Electrical Engineering 2011

A previsão hidrológica possibilita a identificação antecipada de eventos de cheia potencialmente causadores de inundação, o que é de grande importância para a atuação de entidades como a Defesa Civil. Quando se deseja estender a antecedência no tempo em relação a estes eventos, principalmente nos casos onde a bacia de interesse é relativamente rápida, torna-se necessária a incorporação de previsões quantitativas de precipitação (QPF) na modelagem hidrológica, as quais podem ser obtidas a partir de modelos numéricos de previsão do tempo. Entretanto, a falta de acurácia atribuída a estas previsões de chuva, dadas de forma determinística, vem promovendo sua substituição por sistemas de previsão meteorológica por conjunto (EPS - Ensemble Prediction Systems), cuja finalidade é a geração de possíveis estados futuros da atmosfera para considerar as incertezas associadas ao seu estado inicial e às deficiências na representação física dos modelos de previsão do tempo. Neste contexto, o presente estudo teve por objetivo avaliar uma metodologia de previsão de cheias por conjunto na bacia do Taquari-Antas/RS até a cidade de Encantado (19.000 km²), localizada na região Sul do Brasil. Para tanto, foi utilizado o modelo hidrológico MGB-IPH acoplado a diferentes sistemas de previsão, sendo eles: (i) EPS Regional ETA, de curto prazo (até 72 horas) com 5 membros de diferentes parametrizações; (ii) EPS Global ECMWF de médio prazo (até 10 dias) com 50 membros de condições iniciais perturbadas, incluindo perturbação estocástica nos parâmetros de ajuste do modelo e; (iii) Previsão Determinística do Modelo Regional ETA (até 7 dias). A avaliação das previsões consistiu em dois hindcastings distintos, envolvendo uma análise visual de eventos singulares ocorridos em 06/06/2014 e 21/07/2011 além de uma análise estatística no período de Mar/2014 - Nov/2014. Durante a análise visual foi possível identificar, a partir de antecedências de 5 a 6 dias, uma persistência na previsão dada pelo crescente número de membros do conjunto de médio prazo (ECMWF) com superação dos limiares de referência, na medida em que se aproximavam os eventos de cheia. Apesar da grande incerteza na magnitude das previsões hidrológicas para o conjunto de curto prazo, a vazão máxima foi relativamente bem prevista por pelo menos 1 membro em quase todas as antecedências, enquanto que a previsão do timing dos eventos foi considerada de boa confiabilidade. Durante a avaliação estatística foi possível notar uma falta de espalhamento nos conjuntos, com tendência de subestimativa de acordo com o aumento da antecedência. Em uma comparação com previsões determinísticas, as previsões por conjunto demonstraram maior acurácia principalmente até 72 horas de antecedência, com destaque para a maior probabilidade de detecção dos limiares de referência e manutenção de falso alarme a níveis reduzidos. Além disso, verificou-se também que a agregação de previsões efetuadas em tempo anterior naquelas atuais acarreta em ligeira ampliação do espalhamento do conjunto e maiores probabilidades de detecção dos limiares de alerta para os membros mais elevados, apesar da redução no desempenho em termos de acurácia e viés. De forma geral, as previsões por conjunto apresentam potencial para servir como uma informação complementar em sistemas de alerta contra cheias, possibilitando uma melhor preparação dos agentes envolvidos durante a ocorrência destes eventos. / Hydrological forecasting plays an important role for issuing flood warnings, allowing for anticipation and better preparation of authorities at the occurrence of such events. In order to extend lead time in a flood forecast, especially when the catchment response time is relatively fast, it may be useful to couple a hydrological model to quantitative precipitation forecasts (QPF), usually obtained directly from numerical weather prediction (NWP). However, deterministic (i.e. single) QPF are usually referred to many errors and lack of accuracy, mainly caused by uncertainties on initial state of the atmosphere and on physical representation of weather forecasting models. To address these shortcomings, it becomes necessary to take into account the uncertainties associated to rain forecasts, which can be represented by Ensemble Prediction Systems (EPS). The purpose of such systems is to provide different trajectories of the atmosphere by perturbations on its initial condition and on parameterization schemes of the models, generating an ensemble of forecasts that can be used as input to hydrological modelling (HEPS). In this context, the present study aimed to assess a methodology of ensemble flood forecasting on Taquari-Antas basin up to the city of Encantado/RS (19.000 km²), located in southern Brazil. Therefore, the hydrological model MGB-IPH was coupled to different forecasting systems: (i) Short Range EPS ETA (up to 72 hours), a regional model with 5 members of different parameterization schemes; (ii) Medium Range EPS ECMWF (up to 10 days), a global model with 50 members of perturbed initial conditions and stochastic perturbation in the model parameters; (iii) Deterministic ETA Model (up to 7 days). The forecasts were evaluated by two different hindcastings, which includes a visual assessment of singular events occurred on 2011 and 2014 and a statistical analysis for the period between Mar/2014 and Nov/2014. It was possible to identify a forecast persistence on medium-range for the selected events, by the increasing number of members exceeding the reference thresholds from lead times up to 5 - 6 days. On the short range, although large uncertainties in the magnitude of hydrological forecasts were found, the peak discharge was well forecasted - at least for a single member - in nearly all lead times, whereas the prediction of the peak timing was considered reliable. Regarding to statistical evaluation, an inadequate spread in the ensemble was observed from short- to medium-range, with a tendency of underestimation for longer lead times. In a comparison with deterministic forecasts, the ensemble forecasts showed higher accuracy especially up to 72 hours in advance, including highlights on greater probability of detection (POD) above the reference thresholds even with low false alarm rates. It also was found that the a combination of previous forecasts on the recent ones leads to a slight increase of ensemble spread and POD for higher members, despite the performance reduction in terms of accuracy and bias. In summary, the hydrological ensemble forecasts demonstrated a good potential to serve as an additional information within a Flood Alert System.

O antraz é uma doença infecciosa aguda grave, com uma taxa de mortalidade superior a 90% em sua forma respiratória, causada pelo Bacillus anthracis, uma bactéria altamente virulenta, que está desenvolvendo resistência e que tem potencial aplicação como arma biológica e agente de bioterrorismo. Nesse trabalho, a inibição de deidroshikimato desidratase do B. anthracis foi estuda por meio docking, dinâmica molecular e ensemble docking. Essa enzima é responsável por uma etapa chave na biossíntese de petrobactina, molécula através da qual o B. anthracis adquire ferro – micronutriente essencial para seu desenvolvimento e proliferação no hospedeiro. O docking de 25 compostos com ação inibitória conhecida na estrutura cristalográfica da enzima indicou interações importantes com os resíduos His144, His175, Phe211, Tyr217 (ligações de hidrogênio), Arg102 (ponte salina), His144 e Phe255 (interações π-π). Ligantes estruturalmente semelhantes ao cristalográfico (3,4-DHBA) foram docados adequadamente no sítio ativo, enquanto ligantes mais volumosos foram docados na entrada do sítio, resultando em baixa correlação entre as energias livres de ligação experimentais e os escores de docking (R² = 0,1295; R-Pearson = 0,360) e desvios de 23%, em média, frente ao experimental. Simulações de dinâmica molecular mostraram que essa proteína apresenta uma grande rigidez estrutural intrínseca, porém porções do seu sítio ativo, sobretudo da estrutura em forma de laço que o recobre, apresentaram flexibilidade significativa. A presença de ligantes induz a alterações conformacionais que proporcionam o alargamento do sítio e permitem a entrada de ligantes mais volumosos, indicando que o sítio cristalográfico era, de fato, muito restrito. A atividade inibitória aparenta estar relacionada com a formação de uma rede de ligações de hidrogênio entre os ligantes e resíduos do sítio ativo, sendo as principais entre grupos 3-OH do anel aromático dos ligantes e a His175; entre o grupo carboxílico e a Arg102 (ponte salina); entre o grupo 4-OH e a Phe211 e principalmente entre o grupo 5-OH e a His144, um resíduo importante no mecanismo enzimático. O ensemble docking em três estruturas extraídas das simulações de dinâmica molecular permitiu a aprimorar a correlação entre os escores de docking e atividade inibitória experimental, com R² = 0,363 e R-Pearson = 0,602 considerando a totalidade dos ligantes ou com R² = 0,8157 e R-Pearson = 0,903 considerando-se os dez ligantes mais potentes (contra R² = 0,5683 e R-Pearson = 0,754 na estrutura cristalográfica), evidenciando a necessidade de se considerar a flexibilidade do receptor para o docking adequado. Esse modelo linear juntamente com essa compreensão mais profunda dos mecanismos relacionados com a inibição dessa enzima permitirão o desenho e a triagem in silico de novas moléculas com potência e seletividade aprimoradas e com potencial aplicação como uma nova terapia contra o Bacillus anthracis. / Anthrax is a serious acute infectious disease with a mortality rate higher than 90% in its inhalational form. This disease is caused by Bacillus anthracis, a highly virulent bacterium that is developing resistance and which has potential application as a biological weapon and bioterrorism agent. In this work, the inhibition of dehydroshikimate dehydratase from B. anthracis was studied through docking, molecular dynamics and ensemble docking. This enzyme is responsible for a key step in the biosynthetic pathway of petrobactin, a molecule released by B. anthracis to acquire iron, an essential micronutrient for its development and proliferation within the host. Molecular dockings of 25 compounds with known inhibitory activity against dehydroshikimate dehydratase in the crystallographic structure of this enzyme indicated important interactions with the residues His144, His175, Phe211, Tyr217 (hydrogen bonds), Arg102 (salt bridge), His144 and Phe255 (π-π interactions). Ligands structurally similar to the crystallographic (3,4-DHBA) were appropriately docked within the active site, while bulkier ligands were docked at the site's entrance, resulting in a low correlation between the experimental binding free energies and the docking scores (R² = 0,1295; R-Pearson = 0,360), as well as a deviation of 23%, on average, compared to the experimental data. Molecular dynamics simulations showed that this protein has a high structural rigidity, however portions of its active site, especially the loop-like structure that covers it, showed a significant mobility. The presence of ligands induced conformational changes that lead to the widening of the site and allowed bulkier ligands to enter it, what indicates the crystallographic site was, in fact, very restricted. The inhibitory activity appears to be related with the formation of a network of hydrogen bonds between ligands and active site residues, mainly between the 3-OH moiety in the aromatic ring of ligands and His175; between the carboxylic group and Arg102 (salt bridge); between the 4-OH moiety and Phe211 and specially between the 5-OH group and His144, a residue with an important role in the enzymatic mechanism. Ensemble docking with three structures extracted from molecular dynamics simulations allowed to improve the correlation between docking scores and experimental inhibitory activity, with R² = 0,363 and R-Pearson = 0,602, when considering all ligands, and R² = 0,8157 and R-Pearson = 0,903 when considering the ten ligands of higher activity (against the values of R² = 0,5683 and R-Pearson = 0,754 for their docking in the crystallographic structure). This point out the need to account for receptor's flexibility for an appropriate docking. This linear model coupled with this deeper understanding about the mechanisms related with enzymatic inhibition will allow the in silico drug design and screening of new molecules with improved potency and selectivity and with potential application as a new therapy against Bacillus anthracis.